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Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities [75th Anniversary Celebration Collection Special Section]

Both preclinical and clinical studies implicate functional impairments of several neuroactive metabolites of the kynurenine pathway (KP), the major degradative cascade of the essential amino acid tryptophan in mammals, in the pathophysiology of neurologic and psychiatric diseases. A number of KP enzymes, such as tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenases (IDO1 and IDO2), kynurenine aminotransferases (KATs), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3-HAO), and quinolinic acid phosphoribosyltransferase (QPRT), control brain KP metabolism in health and disease and are therefore increasingly considered to be promising targets for the treatment of disorders of the nervous system. Understanding the distribution, cellular expression, and regulation of KP enzymes and KP metabolites in the brain is therefore critical for the conceptualization and implementation of successful therapeutic strategies.

Significance Statement

Studies have implicated the kynurenine pathway of tryptophan in the pathophysiology of neurologic and psychiatric diseases. Key enzymes of the kynurenine pathway regulate brain metabolism in both health and disease, making them promising targets for treating these disorders. Therefore, understanding the distribution, cellular expression, and regulation of these enzymes and metabolites in the brain is critical for developing effective therapeutic strategies. This review endeavors to describe these processes in detail.:




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Seventy-Five Years of Interactions: The Department of Physiology and Pharmacology at Karolinska Institutet and Pharmacological Reviews [75th Anniversary Celebration Collection Special Section-Editorial]




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Low-Field (64 mT) Portable MRI for Rapid Point-of-Care Diagnosis of Dissemination in Space in Patients Presenting with Optic Neuritis [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Low-field 64 mT portable brain MRI has recently shown diagnostic promise for MS. This study aimed to evaluate the utility of portable MRI (pMRI) in assessing dissemination in space (DIS) in patients presenting with optic neuritis and determine whether deploying pMRI in the MS clinic can shorten the time from symptom onset to MRI.

MATERIALS AND METHODS:

Newly diagnosed patients with optic neuritis referred to a tertiary academic MS center from July 2022 to January 2024 underwent both point-of-care pMRI and subsequent 3T conventional MRI (cMRI). Images were evaluated for periventricular (PV), juxtacortical (JC), and infratentorial (IT) lesions. DIS was determined on brain MRI per 2017 McDonald criteria. Test characteristics were computed by using cMRI as the reference. Interrater and intermodality agreement between pMRI and cMRI were evaluated by using the Cohen . Time from symptom onset to pMRI and cMRI during the study period was compared with the preceding 1.5 years before pMRI implementation by using Kruskal-Wallis with post hoc Dunn tests.

RESULTS:

Twenty patients (median age: 32.5 years [interquartile range {IQR}, 28–40]; 80% women) were included, of whom 9 (45%) and 5 (25%) had DIS on cMRI and pMRI, respectively. Median time interval between pMRI and cMRI was 7 days (IQR, 3.5–12.5). Interrater agreement was very good for PV (95%, = 0.89), and good for JC and IT lesions (90%, = 0.69 for both). Intermodality agreement was good for PV (90%, = 0.80) and JC (85%, = 0.63), and moderate for IT lesions (75%, = 0.42) and DIS (80%, = 0.58). pMRI had a sensitivity of 56% and specificity of 100% for DIS. The median time from symptom onset to pMRI was significantly shorter (8.5 days [IQR 7–12]) compared with the interval to cMRI before pMRI deployment (21 days [IQR 8–49], n = 50) and after pMRI deployment (15 days [IQR 12–29], n = 30) (both P < .01). Time from symptom onset to cMRI in those periods was not significantly different (P = .29).

CONCLUSIONS:

In patients with optic neuritis, pMRI exhibited moderate concordance, moderate sensitivity, and high specificity for DIS compared with cMRI. Its integration into the MS clinic reduced the time from symptom onset to MRI. Further studies are warranted to evaluate the role of pMRI in expediting early MS diagnosis and as an imaging tool in resource-limited settings.




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Prevalence of Rathke Cleft and Other Incidental Pituitary Gland Findings on Contrast-Enhanced 3D Fat-Saturated T1 MPRAGE at 7T MRI [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

A cleftlike nonenhancing hypointensity was observed repeatedly in the pituitary gland at the adenohypophysis/neurohypophysis border on contrast-enhanced 3D fat-saturated T1-MPRAGE using clinical 7T MRI. Our primary goal was to assess the prevalence of this finding. The secondary goals were to evaluate the frequency of other incidental pituitary lesions, MRI artifacts, and their effect on pituitary imaging on the contrast-enhanced 3D fat-saturated T1 MPRAGE at 7T.

MATERIALS AND METHODS:

One hundred patients who underwent 7T neuroimaging between October 27, 2021, and August 10, 2023, were included. Each case was evaluated for cleftlike pituitary hypointensity, pituitary masses, and artifacts on contrast-enhanced 3D fat-saturated T1 MPRAGE. Follow-up examinations were evaluated if present. The average prevalence for each finding was calculated, as were descriptive statistics for age and sex.

RESULTS:

A cleftlike hypointensity was present in 66% of 7T MRIs. There were no significant differences between the "cleftlike present" and "cleftlike absent" groups regarding sex (P = .39) and age (P = .32). The cleftlike hypointensity was demonstrated on follow-up MRIs in 3/3 patients with 7T, 1/12 with 3T, and 1/5 with 1.5T. A mass was found in 22%, while 75% had no mass and 3% were indeterminate. A mass was found in 18 (27%) of the cleftlike present and 4 (13%) of the cleftlike absent groups. The most common mass types were Rathke cleft cyst in 7 (31.8%) patients, "Rathke cleft cyst versus entrapped CSF" in 6 (27.3%), and microadenoma in 6 (22.2%) in the cleftlike present group. There were no significant differences in the mass types between the cleftlike present and cleftlike absent groups (P = .23). Susceptibility and/or motion artifacts were frequent using contrast-enhanced 3D fat-saturated T1 MPRAGE (54%). Artifact-free scans were significantly more frequent in the cleftlike present group (P = .03).

CONCLUSIONS:

A cleftlike nonenhancing hypointensity was frequently seen on the contrast-enhanced 3D fat-saturated T1 MPRAGE images at 7T MRI, which most likely represents a normal embryologic Rathke cleft remnant and cannot be seen in lower-field-strength MRIs. Susceptibility and motion artifacts are common in the sella. They may affect image quality, and the artifacts at 7T may lead to an underestimation of the prevalence of the Rathke cleft and other incidental findings.




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An Extended Follow-up of Spinal Instrumentation Rescue with Cement Augmentation [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Percutaneous cement augmentation has been reported as an effective salvage procedure for frail patients with spinal instrumentation failure, such as screw loosening, hardware breakage, cage subsidence, and fractures within or adjacent to stabilized segments. Favorable results were reported during a median follow-up period of 16 months in a retrospective analysis of 31 consecutive procedures performed in 29 patients. In the present study, the long-term effectiveness of this treatment in avoiding or postponing revision surgery is reported.

MATERIALS AND METHODS:

Clinical and radiologic data of our original cohort of patients were retrospectively collected and reviewed to provide an extended follow-up assessment. The need for revision spinal surgery was assessed as the primary outcome, and the radiologic stability of the augmented spinal implants was considered as the secondary outcome.

RESULTS:

An extended radiologic follow-up was available in 27/29 patients with an average of 50.9 months. Overall, 18 of 27 (66.7%) patients, originally candidates for revision surgery, avoided a surgical intervention after a cement augmentation rescue procedure. In the remaining patients, the average interval between the rescue cement augmentation and the revision surgery was 22.5 months. Implant mobilization occurred in 2/27 (7.4%) patients; rod breakage, in 1/27 (3.7%); a new fracture within or adjacent to the instrumented segment occurred in 4/27 (14.8%) patients; and screw loosening at rescued levels occurred in 5/27 (18.5%) patients.

CONCLUSIONS:

In this cohort, cement augmentation rescue procedures were found to be effective in avoiding or postponing revision surgery during long-term follow-up.




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Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

MATERIALS AND METHODS:

The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. Three hundred seventeen patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI data set of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error–corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap maps in Montreal Neurological Institute standard space. The Wilcoxon signed-rank test was used to determine a significant difference in the maximum Dice coefficient for our atlas compared with a meta-analysis-based template with respect to expert-delineated primary language area activations.

RESULTS:

Probabilities of activating the left anterior primary language area and left posterior primary language area in the temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in the left anterior primary language area (0.351 and 0.326, respectively, P < .05) and the left posterior primary language area in the temporal lobe (0.274 and 0.244, respectively, P < .005).

CONCLUSIONS:

Brain tumor patient- and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients compared with the meta-analysis-based template.




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Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

MATERIALS AND METHODS:

Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.

RESULTS:

Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) (P < .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) (P < .001) in the natural history cohort.

CONCLUSIONS:

Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.




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Arterial Spin-Labeling Perfusion Lightbulb Sign: An Imaging Biomarker of Pediatric Posterior Fossa Hemangioblastoma [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a "lightbulb sign" on the arterial spin-labeling (ASL) sequence (diffuse homogeneous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors.

MATERIALS AND METHODS:

In this retrospective comparative observational study, we only included pathology-proved cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proved posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences, including ASL sequence if available. ASL was analyzed for the lightbulb sign. Disagreements between the radiologists were resolved by a third pediatric neuroradiologist. 2 and Fisher exact test were used to analyze the data.

RESULTS:

Ninety-five patients were enrolled in the study; 57 (60%) were boys. The median age at diagnosis was 8 years old (interquartile range: 3–14). Of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n = 31), pilocytic astrocytoma (n = 23), posterior fossa ependymoma type A (n = 16), and other tumors (n = 17). The comparison of hemangioblastoma versus nonhemangioblastoma showed that peripheral edema (P = .02) and T2-flow void (P = .02) favor hemangioblastoma, whereas reduced diffusion (low ADC) (P = .002) and ventricular system extension (P = .001) favor nonhemangioblastoma tumors. Forty-two cases also had ASL perfusion sequences. While high perfusion favors hemangioblastoma (P = .03), the lightbulb sign shows a complete distinction because all the ASL series of hemangioblastoma cases (n = 4) showed the lightbulb sign, whereas none of the nonhemangioblastoma cases (n = 38) showed the sign (P < .001).

CONCLUSIONS:

Lightbulb-like intense and homogeneous hyperperfusion patterns on ASL are helpful in diagnosing posterior fossa hemangioblastoma in children.




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Diffusion Analysis of Intracranial Epidermoid, Head and Neck Epidermal Inclusion Cyst, and Temporal Bone Cholesteatoma [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Intracranial epidermoids temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are typically slow-growing, benign conditions arising from ectodermal tissue. They exhibit increased signal on DWI. While much of the imaging literature describes these lesions as showing diffusion restriction, we investigated these qualitative signal intensities and interpretations of restricted diffusion with respect to normal brain structures. This study aimed to quantitatively evaluate the ADC values and histogram features of these lesions.

MATERIALS AND METHODS:

This retrospective study included children with histologically confirmed diagnoses of intracranial epidermoids, temporal bone cholesteatomas, or head and neck epidermal inclusion cysts. Lesions were segmented, and voxelwise calculation of ADC values was performed along with histogram analysis. ADC calculations were validated with a second analysis software to ensure accuracy. Normal brain ROIs—including the cerebellum, white matter, and thalamus—served as normal comparators. Correlational analysis and Bland-Altman plots assessed agreement among software tools for ADC calculations. Differences in the distribution of values between the lesions and normal brain tissues were assessed using the Wilcoxon rank sum and Kruskal-Wallis tests.

RESULTS:

Forty-eight pathology-proved cases were included in this study. Among them, 13 (27.1%) patients had intracranial epidermoids 14 (29.2%) had head and neck epidermal inclusion cysts, and 21 (43.7%) had temporal bone cholesteatomas. The mean age was 8.67 (SD, 5.30) years, and 27 (56.3%) were female. The intraclass correlation for absolute agreement for lesional ADC between the 2 software tools was 0.997 (95% CI, 0.995–0.998). The intracranial epidermoid head and neck epidermal inclusion cyst, and temporal bone cholesteatoma median ADC values were not significantly different (973.7 versus 875.7 versus 933.2 x 10–6 mm2/s, P = .265). However, the ADCs of the 3 types of lesions were higher than those of 3 normal brain tissue types (933 versus 766, x 10–6 mm2/s, P < .001).

CONCLUSIONS:

The ADC values of intracranial epidermoids, temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are higher than those of normal brain regions. It is not accurate to simply classify these lesions as exhibiting restricted diffusion or reduced diffusivity without considering the tissue used for comparison. The observed hyperintensity on DWI compared with the brain is likely attributable to a relatively higher contribution of the T2 shinethrough effect.




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Utility of Early Postoperative DWI to Assess the Extent of Resection of Adult-Type World Health Organization Grade 2 and 3 Diffuse Gliomas [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

MATERIALS AND METHODS:

A single-center observational cohort study was performed. All patients with histologically confirmed WHO grade 2 and 3 gliomas managed with surgical debulking between January 2015 and December 2020 were identified. Preoperative, early postoperative, and follow-up imaging were reviewed independently by 2 consultant neuroradiologists. The extent of resection was estimated with and without DWI sequences for each case.

RESULTS:

Two hundred twenty-four patients with WHO grade 2 and 3 gliomas were managed with surgical debulking between 2015 and 2020. DWI was not performed on early postoperative MRI in 2 patients. With the use of DWI, the extent of resection was upgraded in 30% of cases (n = 66/222) and classified as "complete" or "supramaximal" in 58% of these patients (n = 38/66). In cases in which the extent of resection was upgraded with the use of DWI, signal abnormality was stable or reduced at follow-up in 78% (n = 49/63). In cases with worsening signal abnormality, 64% were deemed to be secondary to adjuvant radiation therapy (n = 9/14). Eight percent (n = 5/63) of patients with an increased estimated extent of resection using DWI demonstrated signal progression attributed to true disease progression at follow-up.

CONCLUSIONS:

DWI is a helpful and reliable adjunct in differentiating residual tumor from marginal ischemia in early postoperative MRI in WHO grade 2 and 3 diffuse gliomas and increases the accuracy in assessing the extent of resection. It should be used routinely in these cases.




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Comparative Evaluation of Lower Gadolinium Doses for MR Imaging of Meningiomas: How Low Can We Go? [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Gadolinium-based contrast agents are widely used for meningioma imaging; however, concerns exist regarding their side effects, cost, and environmental impact. At the standard gadolinium dose, most meningiomas show avid contrast enhancement, suggesting that administering a smaller dose may be feasible. The purpose of this study was to evaluate the impact of a lower gadolinium dose on the differentiation between meningiomas and adjacent intracranial tissues.

MATERIALS AND METHODS:

One hundred eight patients with presumed or confirmed meningiomas who underwent a brain MRI at multiple doses of gadolinium were included in the study. The patients’ MRIs were categorized into 3 groups based on the gadolinium dose administered: micro (approximately 25% of the standard dose), low (approximately 62% of the standard dose), and standard dose. Multireader qualitative visual assessment and quantitative relative signal differences calculations were performed to evaluate tumor differentiation from the cortex and from the dural venous sinus. The relative signal differences for each dose were analyzed by using ANOVA for quantitative assessment and the McNemar test for qualitative assessment. Additionally, noninferiority testing was used to compare the low and micro doses to the standard dose.

RESULTS:

Decreasing the gadolinium dose to a low dose or micro dose resulted in a statistically significant decrease in signal difference between the tumor and the adjacent brain tissue (P < .02). However, on visual assessment, the low dose was noninferior to the standard dose. The proportion of cases with suboptimal differentiation was significantly higher for the micro dose than for the standard dose, both for the differentiation between the tumor and the cortex (P = .041) and the differentiation between the tumor and the sinus (P < .001).

CONCLUSIONS:

Reducing the gadolinium dose to 62% of the standard level still allows for sufficient visual delineation of meningiomas from surrounding tissues. However, further reduction to 25% substantially compromises the ability to distinguish the tumor from adjacent structures and is, therefore, not advisable.




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Differences in Cervical Spine Fractures in Patients Younger or Older Than 65 Years of Age: Implications for the Canadian C-Spine Rule [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

There has been a distinction made in the 2001 Canadian C-Spine Rule regarding patients 65 and older and younger than 65 years of age as far as indications for cervical spine CT scanning. We sought to determine if there are differences in the symptoms, mechanisms of injury, fracture locations, and types that are still relevant in 2024.

MATERIALS AND METHODS:

The institutional review board approved this retrospective study of cervical spine CT emergency department results from 2 hospitals in our health system after reviewing 5 years of data in patients experiencing trauma. In addition to the primary variable of age (younger than 65 years and 65 years and older), we looked at injury mechanism, fracture types, sites, symptoms, and operative or medical treatments. Because the demographics of our home site is different from most towns in the United States, we provide race/ethnicity data.

RESULTS:

Of 21,986 cervical spine CTs, 190/9455 (2.0%) participants 65 years of age and older and 199/12,531 (1.6%) participants younger than 65 years of age had fractures (total, 389/21,986, 1.8%). There were more cases of falls from standing (106, 55.8%) and falls from a height (46, 4.2%) in those 65 years and older and this mechanism was associated with a higher risk of C1 and C2 fractures (52, 27.4%; and 78, 41.1%, respectively). Among the C1 fractures, anterior and posterior arch fractures predominated (37, 19.5%). For C2 fractures, types 2 and 3 odontoid fractures (39, 20.5%; and 12, 6.3%) were more common in the older cohort. Motor vehicle collisions were more common in the younger cohort (89, 44.7%), and they were associated with more C5–C7 fractures (47, 23.6%; 60, 30.2%; and 66, 33.2%, respectively) including the facets (49, 24.6%), spinous processes (31, 15.6%), and transverse processes (52, 26.1%). Overall, the rates of instability, surgical intervention, and asymptomatic fractures were similar in the 2 age groups.

CONCLUSIONS:

Cervical spine fractures appear in about 1.8% of the CT scans performed in a busy emergency department environment. Fractures in the elderly occur more commonly due to falls, are located at C1 and C2, and may involve ligamentous injuries. Younger patients incur trauma more commonly due to motor vehicle collisions, and they are more likely to affect the posterior elements, especially C5–C7. The differences in trends for fractures in the 65 years of age and older and younger than 65 years of age groups have persisted since the Canadian C-Spine Rule 1996–1998 data were collected.




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Predictors and Outcomes of Periprocedural Intracranial Hemorrhage after Stenting for Symptomatic Intracranial Atherosclerotic Stenosis [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis.

MATERIALS AND METHODS:

We retrospectively analyzed patients with symptomatic intracranial atherosclerotic stenosis stent placement in a prospective cohort at a high-volume stroke center. Clinical, radiologic, and periprocedural characteristics and long-term outcomes were reviewed. Periprocedural intracranial hemorrhage was classified as procedure-related hemorrhage (PRH) and non-procedure-related hemorrhage (NPRH). The long-term outcomes were compared between patients with PRH and NPRH, and the predictors of NPRH were explored.

RESULTS:

Among 1849 patients, 24 (1.3%) had periprocedural intracranial hemorrhage, including PRH (4) and NPRH (20). The postprocedural 30-day mRS was 0–2 in 9 (37.5%) cases, 3–5 in 5 (20.8%) cases, and 6 in 10 (41.7%) cases. For the 14 survivors, the long-term (median of 78 months) mRS were 0–2 in 10 (76.9%) cases and 3–5 in 3 (23.1%) cases. The proportion of poor long-term outcomes (mRS ≥3) in patients with NPRH was significantly higher than those with PRH (68.4% versus 0%, P = .024). Anterior circulation (P = .002), high preprocedural stenosis rate (P < .001), and cerebral infarction within 30 days (P = .006) were independent predictors of NPRH after stent placement.

CONCLUSIONS:

Patients with NPRH had worse outcomes than those with PRH after stent placement for symptomatic ICAS. Anterior circulation, severe preprocedural stenosis, and recent infarction are independent predictors of NPRH.




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Cyclic Aspiration in Mechanical Thrombectomy: Influencing Factors and Experimental Validation [RESEARCH]

BACKGROUND AND PURPOSE:

Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA).

MATERIALS AND METHODS:

StA setup consisted of an aspiration pump connected to pressure transducer. CyA was tested with 5 subsequent iterations: single solenoid valve with air plus saline (i1) or saline alone (i2) as aspiration medium; 2 solenoid valves with air plus saline (i3) as aspiration medium; complete air removal and saline feeding (i4); and pressurized saline feeding (i5). To assess the efficacy of clot ingestion, the pressure transducer was replaced with a distal aspiration catheter. Moderately stiff clot analogs (15 mm) were used to investigate the ingestion quantified as clot relative weight loss. Additionally, the aspiration flow rate was assessed for each setup.

RESULTS:

With CyA i1, the amplitude of the achieved negative pressure waves declined with increasing frequencies but progressively increased with each subsequent iteration, achieving a maximum amplitude of 81 kPa for i5 at 1 Hz. Relative clot weight loss was significantly higher with i5 at 5 Hz than with StA (100% versus 37.8%; P = .05). Aspiration flow rate was lower with CyA than with StA (i5 at 5 Hz: 199.8 mL/min versus StA: 311 mL/min; P < .01).

CONCLUSIONS:

CyA with the appropriate setup may represent an encouraging innovation in mechanical thrombectomy, offering a promising pathway for improving efficacy in clot ingestion and recanalization. The observed benefits warrant confirmation in a clinical setting.




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Stent Retriever AssIsted Lysis Technique with Tirofiban: A Potential Bailout Alternative to Angioplasty and Stenting [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Angioplasty and stent placement have been described as a bailout technique in individuals with failed thrombectomy. We aimed to investigate Stent retriever AssIsted Lysis (SAIL) with tirofiban before angioplasty and stent placement.

MATERIALS AND METHODS:

Patients from 2 comprehensive stroke centers were reviewed (2020–2023). We included patients with failed thrombectomy and/or underlying intracranial stenosis who received SAIL with tirofiban before the intended angioplasty and stent placement. SAIL consisted of deploying a stent retriever through the occluding lesion to create a bypass channel and infuse 10 mL of tirofiban for 10 minutes either intra-arterially or IV. The stent retriever was re-sheathed before retrieval. The primary end points were successful reperfusion (expanded TICI 2b–3) and symptomatic intracerebral hemorrhage. Additional end points included 90-day mRS 0–2 and mortality.

RESULTS:

After a median of 3 (interquartile range, 2–4) passes, 44 patients received the SAIL bridging protocol with tirofiban, and later they were considered potential candidates for angioplasty and stent placement bailout (43.2%, intra-arterial SAIL). Post-SAIL successful reperfusion was obtained in 79.5%. A notable residual stenosis (>50%) after successful SAIL was observed in 45.7%. No significant differences were detected according to post-SAIL: successful reperfusion (intra-arterial SAIL, 80.0% versus IV-SAIL, 78.9%; P = .932), significant stenosis (33.3% versus 55.0%; P = .203), early symptomatic re-occlusion (0% versus 8.0%; P = .207), or symptomatic intracerebral hemorrhage (5.3% versus 8.0%; P = .721). Rescue angioplasty and stent placement were finally performed in 15 (34.1%) patients (intra-arterial SAIL 21.0% versus IV-SAIL 44%; P = .112). At 90 days, mRS 0–2 (intra-arterial SAIL 50.0% versus IV-SAIL 43.5%; P = .086) and mortality (26.3% versus 12.0%; P = .223) were also similar.

CONCLUSIONS:

In patients with stroke in which angioplasty and stent placement are considered, SAIL with tirofiban, either intra-arterial or IV, seems to safely induce sustained recanalization, offering a potential alternative to definitive angioplasty and stent placement.




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Optimal Endovascular Therapy Technique for Isolated Intracranial Atherothrombotic Stroke-Related Large-Vessel Occlusion in the Acute-to-Subacute Stage [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting.

MATERIALS AND METHODS:

We conducted a historical, multicenter registry study at 51 centers that enrolled patients with AT-LVO. We divided the patients into 3 groups based on the endovascular therapy technique: mechanical thrombectomy alone, percutaneous transluminal angioplasty (PTA), and stent deployment. Mechanical thrombectomy alone was classified into the mechanical thrombectomy-only group; PTA and mechanical thrombectomy–PTA, into the PTA group; and mechanical thrombectomy–stent deployment, mechanical thrombectomy–PTA–stent deployment, PTA–stent deployment, and stent deployment–only into the stent group. The primary outcome was incidence of reocclusion of the treated vessels within 90 days of endovascular therapy completion.

RESULTS:

We enrolled 770 patients and analyzed 509 patients. The rates in the mechanical thrombectomy-only, PTA, and stent deployment groups were 40.7%, 44.4%, and 14.9%, respectively. Incidence rate of residual stenosis >70% of final angiography was significantly higher in the mechanical thrombectomy-only group than in the PTA and stent deployment groups (mechanical thrombectomy-only versus PTA versus stent deployment: 34.5% versus 26.3% versus 13.2%, P = .002). Reocclusion rate was significantly lower in the PTA group than in the mechanical thrombectomy-only group (adjusted hazard ratio, 0.48; 95% CI, 0.29–0.80). Of the patients, 83.5% experienced reocclusion within 10 days after endovascular therapy. Alarmingly, a substantial subset (approximately 62.0%) of patients experienced reocclusion within 2 days of endovascular therapy. Incidence of mRS scores of 0–2 ninety days after endovascular therapy was not significantly different among the 3 groups. Incidences of symptomatic intracranial hemorrhage, any other intracranial hemorrhage, and death were not significantly different.

CONCLUSIONS:

Incidence rate of reocclusion was significantly lower in the PTA group than in the mechanical thrombectomy-only group. We found no meaningful difference in reocclusion rates between the stent deployment and mechanical thrombectomy-only groups. In Japan, glycoprotein IIb/IIIa inhibitors are not reimbursed. Therefore, PTA might be the preferred choice for AT-LVOs due to the higher reocclusion risk with mechanical thrombectomy-only. Reocclusion was likely to occur within 10 days, particularly within 2 days post-endovascular therapy.




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Prognosis of Proximal and Distal Vertebrobasilar Artery Stent Placement [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Vertebrobasilar artery stent placement (VBS) is potentially effective in preventing recurrent posterior circulation strokes; however, the incidences of in-stent restenosis and stented-territory ischemic events based on the location of stent placement have rarely been investigated. We aimed to investigate the characteristics and prognosis of VBS between intracranial and extracranial.

MATERIALS AND METHODS:

This study was single-center retrospective cohort study, and we obtained medical records of patients who underwent VBS. We compared clinical and periprocedural factors between extracranial and intracranial VBS. The primary outcomes included the incidence of in-stent restenosis (>50% reduction in lumen diameter) and stented-territory ischemic events. We compared the incidence of in-stent restenosis and stented-territory ischemic events by using Kaplan-Meier curves.

RESULTS:

Of the 105 patients, 41 (39.0%) underwent extracranial VBS, and 64 (61.0%) underwent intracranial VBS. During the follow-up, the incidences of in-stent restenosis and stented-territory ischemic events were 15.2% and 22.9%, respectively. The procedure time was longer (47.7 ± 19.5 minutes versus 74.5 ± 35.2 minutes, P < .001), and the rate of residual stenosis (≥30%) just after VBS was higher (2 [4.9%] versus 24 [37.5%], P < .001) in intracranial VBS than in extracranial VBS. Also, the incidences of in-stent restenosis were significantly higher in intracranial VBS than in extracranial VBS (4.9% versus 21.9%, P = .037). On the other hand, the incidences of stented-territory ischemic events (7.3% versus 32.8%, P < .001) were significantly higher in intracranial VBS than in extracranial VBS. The main mechanisms of stroke were artery-to-artery embolism (2 [66.7%]) in extracranial VBS, and artery-to-artery embolism (9 [42.9%]) and branch atheromatous disease (8 [38.1%]) in intracranial VBS. The Kaplan-Meier curve demonstrated a higher incidence of in-stent restenosis and stented-territory ischemic events in intracranial VBS than in extracranial VBS (P = .008 and P = .002, respectively).

CONCLUSIONS:

During the follow-up, the incidence of in-stent restenosis and stented-territory ischemic events was higher in patients with intracranial VBS than in those with extracranial VBS. The higher rates of postprocedural residual stenosis might have contributed to the increased risk of in-stent restenosis. Furthermore, prolonged procedure time and additional stroke mechanism, including branch atheromatous disease, might be associated with a higher risk of stented-territory ischemic events in intracranial VBS.




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Clinical and Pathophysiologic Correlates of Basilar Artery Measurements in Fabry Disease [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Alterations of the basilar artery (BA) anatomy have been suggested as a possible MRA feature of Fabry disease (FD). Nonetheless, no information about their clinical or pathophysiologic correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD.

MATERIALS AND METHODS:

Brain MRIs of 53 subjects with FD (mean age, 40.7 [SD, 12.4] years; male/female ratio = 23:30) were collected in this single-center study. Mean BA diameter and its tortuosity index were calculated on MRA. Possible correlations between these metrics and clinical, laboratory, and advanced imaging variables of the posterior circulation were tested. In a subgroup of 20 subjects, a 2-year clinical and imaging follow-up was available, and possible longitudinal changes of these metrics and their ability to predict clinical scores were also probed.

RESULTS:

No significant association was found between MRA metrics and any clinical, laboratory, or advanced imaging variable (P values ranging from –0.006 to 0.32). At the follow-up examination, no changes were observed with time for the mean BA diameter (P = .84) and the tortuosity index (P = .70). Finally, baseline MRA variables failed to predict the clinical status of patients with FD at follow-up (P = .42 and 0.66, respectively).

CONCLUSIONS:

Alterations of the BA in FD lack of any meaningful association with clinical, laboratory, or advanced imaging findings collected in this study. Furthermore, this lack of correlation seems constant across time, suggesting stability over time. Taken together, these results suggest that the role of BA dolichoectasia in FD should be reconsidered.




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High-Resolution MRA Cerebrovascular Findings in a Tri-Ethnic Population [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Incidental findings on brain MRI and variations of the circle of Willis (CoW) are relatively common among the general population. Ethnic differences have been described before, but few studies have explored the prevalence of incidental intracranial cerebrovascular findings and CoW variants in the setting of a single multiethnic cohort. The purpose of this investigation was to describe both incidental cerebrovascular findings and the morphology of the CoW on high-resolution 3T TOF-MRA in a UK tri-ethnic population-based cohort and to present updated prevalence estimates and morphologic reference values.

MATERIALS AND METHODS:

We studied participants from the UK Southall and Brent REvisited study who underwent 3T brain MRI between 2014 and 2018. TOF-MRA images were assessed for the presence of incidental cerebrovascular findings and used to determine CoW anatomy.

RESULTS:

Seven hundred fifty participants (mean age, 71.28 [SD, 6.46] years; range, 46–90 years; 337 women), 322 White Europeans, 253 South Asians, and 175 African Caribbeans were included. Incidental cerebrovascular findings were observed in 84 subjects (11.2%, 95% CI, 9.0%–13.7%; 36 women; 42.86%, 95% CI, 32.11%–54.12%), with cerebral aneurysms being the most frequent followed by intracranial arterial stenoses with the highest prevalence among South Asians compared with White European (OR: 2.72; 95% CI, 1.22–6.08; P = .015) and African Caribbean subjects (OR: 2.79; 95% CI, 1.00–7.82; P = .051). Other findings included arteriovenous malformations and infundibula. The CoW was found to be more often complete in women than in men (25.22% compared with 18.41%, P = .024) and in African Caribbean (34.86%) compared with White European (19.19%) and South Asian (14.23%) subjects (P < .001 each).

CONCLUSIONS:

Intracranial arterial stenoses were independently associated with ethnicity after adjusting for vascular risk factors, having the highest prevalence among South Asians. The prevalence of aneurysms was higher than that in previous population-based studies. We observed anatomic differences in the CoW configuration among women, men, and ethnicities.




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Distribution and Disparities of Industry Payments to Neuroradiologists [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Physician-industry relationships can be useful for driving innovation and technologic progress, though little is known about the scale or impact of industry involvement in neuroradiology. The purpose of this study was to assess the trends and distributions of industry payments to neuroradiologists.

MATERIALS AND METHODS:

Neuroradiologists were identified using a previously-validated method based on Work Relative Value Units and Neiman Imaging Types of Service classification. Data on payments from industry were obtained from the Open Payments database from the Centers for Medicare & Medicaid Services, from 2016 to 2021. Payments were grouped into 7 categories, including consulting fees, education, gifts, medical supplies, research, royalties/ownership, and speaker fees. Descriptive statistics were calculated.

RESULTS:

A total of 3019 neuroradiologists were identified in this study. Between 2016 and 2021, 48% (1440/3019) received at least 1 payment from industry, amounting to a total number of 21,967 payments. Each year, among those receiving payments from industry, each unique neuroradiologist received between a mean of 5.49–7.42 payments and a median of 2 payments, indicating a strong rightward skew to the distribution of payments. Gifts were the most frequent payment type made (60%, 13,285/21,967) but accounted for only 4.1% ($689,859/$17,010,546) of payment value. The greatest aggregate payment value came from speaker fees, which made up 36% ($6,127,484/$17,010,546) of the total payment value. The top 5% highest paid neuroradiologists received 42% (9133/21,967) of payments, which accounted for 84% ($14,284,120/$17,010,546) of the total dollar value. Since the start of the coronavirus 2019 (COVID-19) pandemic, the number of neuroradiologists receiving industry payments decreased from a mean of 671 neuroradiologists per year prepandemic (2016–2019) to 411 in the postpandemic (2020–2021) era (P = .030). The total number of payments to neuroradiologists decreased from 4177 per year prepandemic versus 2631 per year postpandemic (P = .011).

CONCLUSIONS:

Industry payments to neuroradiologists are highly concentrated among top earners, particularly among the top 5% of payment recipients. The number of payments decreased during the COVID-19 pandemic, though the dollar value of payments was offset by coincidental increases in royalty payments. Further investigation is needed in subsequent years to determine if the postpandemic changes in industry payment trends continue.




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Ependymal Tumors: Overview of the Recent World Health Organization Histopathologic and Genetic Updates with an Imaging Characteristic [CLINICAL PRACTICE]

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.




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Academic Neuroradiology: 2023 Update on Turnaround Time, Financial Recruitment, and Retention Strategies [CLINICAL PRACTICE]

SUMMARY:

The ASNR Neuroradiology Division Chief Working Group's 2023 survey, with responses from 62 division chiefs, provides insights into turnaround times, faculty recruitment, moonlighting opportunities, and academic funds. In emergency cases, 61% aim for a turnaround time of less than 45–60 minutes, with two-thirds meeting this expectation more than 75% of the time. For inpatient CT and MR imaging scans, 54% achieve a turnaround time of 4–8 hours, with three-quarters meeting this expectation at least 50% of the time. Outpatient scans have an expected turnaround time of 24–48 hours, which is met in 50% of cases. Faculty recruitment strategies included 35% offering sign-on bonuses, with a median of $30,000. Additionally, 23% provided bonuses to fellows during fellowship to retain them in the practice upon completion of their fellowship. Internal moonlighting opportunities for faculty were offered by 70% of divisions, with a median pay of $250 per hour. The median annual academic fund for a full-time neuroradiology faculty member was $6000, typically excluding license fees but including American College of Radiology and American Board of Radiology membership, leaving $4000 for professional expenses. This survey calls for further dialogue on adapting and innovating academic institutions to meet evolving needs in neuroradiology.




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Health supervision for children and adolescents with 16p11.2 deletion syndrome [PRECISION MEDICINE IN PRACTICE]

Rare genetic conditions are challenging for the primary care provider to manage without proper guidelines. This clinical review is designed to assist the pediatrician, family physician, or internist in the primary care setting to manage the complexities of 16p11.2 deletion syndrome. A multidisciplinary medical home with the primary care provider leading the care and armed with up-to-date guidelines will prove most helpful to the rare genetic patient population. A special focus on technology to fill gaps in deficits, review of case studies on novel medical treatments, and involvement with the educational system for advocacy with an emphasis on celebrating diversity will serve the rare genetic syndrome population well.




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The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer [PRECISION MEDICINE IN PRACTICE]

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.




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Analysis of Sleep and Circadian Rhythms from Drosophila Activity-Monitoring Data Using SCAMP

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated and what biological functions it plays. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using beam break counts from Drosophila activity monitors (DAMs). The number of laboratories worldwide studying sleep in Drosophila has grown from only a few 20 years ago to hundreds today. The utility of these studies is limited by the quality of the metrics that can be extracted from the data. Many software options exist to help analyze DAM data; however, these are often expensive or have significant limitations. Therefore, we describe here a method for analyzing DAM-based data using the sleep and circadian analysis MATLAB program (SCAMP). This user-friendly software has an advantage of combining several analyses of both sleep and circadian rhythms in one package and produces graphical outputs as well as spreadsheets of the outputs for further statistical analysis. The version of SCAMP described here is also the first published software package that can analyze data from multibeam DAM5Ms, enabling determination of positional preference over time.




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Analysis of Positional Preference in Drosophila Using Multibeam Activity Monitors

The positional preference of an animal can be very informative regarding the choices it makes about how to interact with its environment. The fruit fly Drosophila melanogaster has been used as a robust system for examining neurobiological mechanisms underlying behavior. Fruit fly positional preference can be gathered from TriKinetics Drosophila activity monitors (DAMs), which contain four infrared beams, allowing for tracking the position of individual flies along the length of a tube. Here, we describe a method for using DAM5Ms to examine food preference. Specifically, we show an example in which circadian changes in food preference are compared between different Drosophila species. More information about the evolution of behavior can be gathered by measuring feeding preference relative to time of day. Noni, fruit from Morinda citrifolia, contains octanoic acid, a chemical toxic to many species of Drosophila. D. melanogaster and D. simulans, both food generalists, show high sensitivity to octanoic acid, whereas D. sechellia, a specialist, can tolerate high concentrations. When two different food substrates are provided at each end of a tube, food preference can be inferred at various times of the day, using the sleep and circadian analysis MATLAB program (SCAMP) to extract and analyze positional data from DAM5Ms. Data gathered from these analyses can be used to compare avoidance or attraction to nutrients, tastants, or odors between species and genotypes or after specific different treatments. Additionally, such data can be examined as a function of time of day.




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Neural Stimulation during Drosophila Activity Monitor (DAM)-Based Studies of Sleep and Circadian Rhythms in Drosophila melanogaster

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated by circadian rhythms, homeostatic sleep drive that builds up with wakefulness, and modifying factors such as hunger or social interactions, as well as about the biological functions of sleep. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using Drosophila activity monitors (DAMs). Here, we describe approaches for the activation of specific neurons of interest using optogenetics (involving genetic modifications that allow for light-based neuronal activation) and thermogenetics (involving genetic modifications that allow for temperature-based neuronal activation) so that researchers can evaluate the roles of those neurons in controlling rest and activity behavior. In this protocol, we describe how to set up a rig for simultaneous optogenetic or thermogenetic stimulation and activity monitoring for analysis of sleep and circadian rhythms in Drosophila, how to raise appropriate flies, and how to perform the experiment. This protocol will allow researchers to assess the causative role in the regulation of sleep and activity rhythms of any genetically tractable subset of cells.




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Activity Monitoring for Analysis of Sleep in Drosophila melanogaster

Sleep is important for survival, and the need for sleep is conserved across species. In the past two decades, the fruit fly Drosophila melanogaster has emerged as a promising system in which to study the genetic, neural, and physiological bases of sleep. Through significant advances in our understanding of the regulation of sleep in flies, the field is poised to address several open questions about sleep, such as how the need for sleep is encoded, how molecular regulators of sleep are situated within brain networks, and what the functions of sleep are. Here, we describe key findings, open questions, and commonly used methods that have been used to inform existing theories and develop new ways of thinking about the function, regulation, and adaptability of sleep behavior.




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General practice should tackle healthcare inequalities but not health inequalities




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Yonder: Improving connections, AI in reflective practice, lung cancer diagnosis, and euthanasia aftercare




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Maternal postnatal care in general practice: steps forward




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PBRNs: Past, Present, and Future: A NAPCRG Report on the Practice-Based Research Network Conference. [Family Medicine Updates]




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Impact of Health Equity Fellowships [Family Medicine Updates]




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Self-Reported PrEP Use and Risk of Bacterial STIs Among Ontarian Men Who Are Gay or Bisexual or Have Sex With Men [Original Research]

PURPOSE

HIV pre-exposure prophylaxis (PrEP) may increase rates of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM) through risk compensation (eg, an increase in condomless sex or number of partners); however, longitudinal studies exploring the time-dependent nature of PrEP uptake and bacterial STIs are limited. We used marginal structural models to estimate the effect of PrEP uptake on STI incidence.

METHODS

We analyzed data from the iCruise study, an online longitudinal study of 535 Ontarian GBM from July 2017 to April 2018, to estimate the effects of PrEP uptake on incidence of self-reported bacterial STIs (chlamydia, gonorrhea, and syphilis) collected with 12 weekly diaries. The incidence rate was calculated as the number of infections per 100 person-months, with evaluation of the STIs overall and individually. We used marginal structural models to account for time-varying confounding and quantitative bias analysis to evaluate the sensitivity of estimates to nondifferential outcome misclassification.

RESULTS

Participating GBM were followed up for a total of 1,623.5 person-months. Overall, 70 participants (13.1%) took PrEP during the study period. Relative to no uptake, PrEP uptake was associated with an increased incidence rate of gonorrhea (incidence rate ratio = 4.00; 95% CI, 1.67-9.58), but not of chlamydia or syphilis, and not of any bacterial STI overall. Accounting for misclassification, the median incidence rate ratio for gonorrhea was 2.36 (95% simulation interval, 1.08-5.06).

CONCLUSIONS

We observed an increased incidence rate of gonorrhea associated with PrEP uptake among Ontarian GBM that was robust to misclassification. Although our findings support current guidelines for integrating gonorrhea screening with PrEP services, additional research should consider the long-term impact of PrEP among this population.

Annals Early Access article




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Family Medicine Resident Scholarly Activity Infrastructure, Output, and Dissemination: A CERA Survey [Original Research]

PURPOSE

Meeting scholarly activity requirements continues to be a challenge in many family medicine (FM) residency programs. Studies comprehensively describing FM resident scholarship have been limited. We sought to identify institutional factors associated with increased scholarly output and meeting requirements of the Accreditation Council for Graduate Medical Education (ACGME).

OBJECTIVES

Our goals were to: (1) describe scholarly activity experiences among FM residents compared with ACGME requirements; (2) classify experiences by Boyer’s domains of scholarship; and (3) associate experiences with residency program characteristics and scholarly activity infrastructure.

METHODS

This was a cross-sectional survey. The survey questions were part of an omnibus survey to FM residency program directors conducted by the Council of Academic Family Medicine Educational Research Alliance (CERA). All ACGME-accredited US FM residency program directors, identified by the Association of Family Medicine Residency Directors, were sampled.

RESULTS

Of the 691 eligible program directors, 298 (43%) completed the survey. The respondents reported that 25% or more residents exceeded ACGME minimum output, 17% reported that 25% or more residents published their work, and 50% reported that 25% or more residents delivered conference presentations. Programs exceeding ACGME scholarship requirements exhibit robust infrastructure characterized by access to faculty mentorship, scholarly activity curricula, Institutional Review Board, medical librarian, and statistician.

CONCLUSIONS

These findings suggest the need for codified ACGME requirements for scholarly activity infrastructure to ensure access to resources in FM residency programs. By fostering FM resident engagement in scholarly activity, programs help to create a culture of inquiry, and address discrepancies in funding and output among FM residency programs.




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Reaction lepreuse de type 1 chez un homme de 50 ans [Pratique]




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Refractory annular erythema in a 58-year-old woman [Practice]




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Necrotizing soft-tissue infections caused by invasive group A Streptococcus [Practice]




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Management of opioid use disorder: 2024 update to the national clinical practice guideline [Guideline]

Background

In an evolving landscape of practices and policies, reviewing and incorporating the latest scientific evidence is necessary to ensure optimal clinical management for people with opioid use disorder. We provide a synopsis of the 2024 update of the 2018 National Guideline for the Clinical Management of Opioid Use Disorder, from the Canadian Research Initiative in Substance Matters.

Methods

For this update, we followed the United States Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines and used the Appraisal of Guidelines Research and Evaluation—Recommendation Excellence tool to ensure guideline quality. We carried out a comprehensive systematic literature review, capturing the relevant literature from Jan. 1, 2017, to Sept. 14, 2023. We drafted and graded recommendations according to the Grading of Recommendations, Assessments, Development and Evaluation approach. A multidisciplinary external national committee, which included people with living or lived experience of opioid use disorder, provided input that was incorporated into the guideline.

Recommendations

From the initial 11 recommendations in the 2018 guideline, 3 remained unchanged, and 8 were updated. Specifically, 4 recommendations were consolidated into a single revised recommendation; 1 recommendation was split into 2; another recommendation was moved to become a special consideration; and 2 recommendations were revised. Key changes have arisen from substantial evidence supporting that methadone and buprenorphine are similarly effective, particularly in reducing opioid use and adverse events, and both are now considered preferred first-line treatment options. Slow-release oral morphine is recommended as a second-line option. Psychosocial interventions can be offered as adjunctive treatment but should not be mandatory. The guideline reaffirms the importance of avoiding withdrawal management as a standalone intervention and of incorporating evidence-based harm reduction services along the continuum of care.

Interpretation

This guideline update presents new recommendations based on the latest literature for standardized management of opioid use disorder. The aim is to establish a robust foundation upon which provincial and territorial bodies can develop guidance for optimal care.




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Can You Really Save a Life? Study Reveals the Impact of Bystander CPR



New research shows that bystander CPR can substantially improve a person's odds of surviving a cardiac arrest while avoiding major brain damage, especially if given immediately.




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Students can be agents of change: Talking about activism in universities with Jade Ho

Jade Ho explains what is possible for university students when they are given opportunities to learn about –and get involved with– social justice and labour issues in their own communities.

The post Students can be agents of change: Talking about activism in universities with Jade Ho appeared first on rabble.ca.






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New research to better understand the biological factors of suicidal behaviour

New research to better understand the biological factors of suicidal behaviour Researchers at the University of Glasgow are embarking on two new PhD projects to better understand the impact that biological factors may have on suicidal behaviour.




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RPG Cast – Episode 601: “Tactical Baking RPG”

Josh and Scotty get into a father-son slap fight. Kelley ascends to divinity playing Picross. Johnathan sees how much his ZHP is worth and has to go make a transaction in a back alley. And Chris tries to justify life without a back button.

The post RPG Cast – Episode 601: “Tactical Baking RPG” appeared first on RPGamer.




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RPG Cast – Episode 604: “Press 5 for More Rune Factory”

It's the RPGCast trio bringing you another week of mild insanity. Kelley struggles because Japanese names are hard. Chris wants to take all the cats camping, but Anna Marie swiftly vetoes the idea. The dad jokes arrive in full force, and everyone's thinking about vacations.

The post RPG Cast – Episode 604: “Press 5 for More Rune Factory” appeared first on RPGamer.




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RPG Cast – Episode 677: “My Parents Thought Final Fantasy Tactics Was a Strategy Guide”

Kelley "accidentally" barbecues her horse. Josh slaps "Trails" onto Horizon: Forbidden West to get Americans to play it. Jason has to go get a tako taco.

The post RPG Cast – Episode 677: “My Parents Thought Final Fantasy Tactics Was a Strategy Guide” appeared first on RPGamer.



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RPG Cast – Episode 725: “Not Every Idea in the Factory Is a Good One”

Ryan slip 'n slides his health away. Robert lives on the side of danger and poor choices in video games. Meanwhile, Chris makes his own bathtub Geralt.

The post RPG Cast – Episode 725: “Not Every Idea in the Factory Is a Good One” appeared first on RPGamer.