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Sex Differences in the Neural and Behavioral Effects of Acute High-Dose Edible Cannabis Consumption in Rats [Special Section: Cannabinoid Signaling in Human Health and Disease]

The consumption of 9-tetrahydrocannabinol (THC)- or cannabis-containing edibles has increased in recent years; however, the behavioral and neural circuit effects of such consumption remain unknown, especially in the context of ingestion of higher doses resulting in cannabis intoxication. We examined the neural and behavioral effects of acute high-dose edible cannabis consumption (AHDECC). Sprague-Dawley rats (six males, seven females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Rats were provided access to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg) for 10 minutes, during which they voluntarily consumed all of the provided Nutella and THC mixture. Cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24 hours after exposure. In another cohort (16 males, 15 females), we examined the effects of AHDECC on learning and prepulse inhibition and serum and brain THC and 11-hydroxy-THC concentrations. AHDECC resulted in higher brain and serum THC and 11-hydroxy-THC levels in female rats over 24 hours. AHDECC also produced: 1) Cg, dHipp, and NAc gamma power suppression, with the suppression being greater in female rats, in a time-dependent manner; 2) hypolocomotion, hypothermia, and antinociception in a time-dependent manner; and 3) learning and prepulse inhibition impairments. Additionally, most neural activity and behavior changes appear 2 hours after ingestion, suggesting that interventions around this time might be effective in reversing/reducing the effects of AHDECC.

SIGNIFICANCE STATEMENT

The effects of high-dose edible cannabis on behavior and neural circuitry are poorly understood. We found that the effects of acute high-dose edible cannabis consumption (AHDECC), which include decreased gamma power, hypothermia, hypolocomotion, analgesia, and learning and information processing impairments, are time and sex dependent. Moreover, these effects begin 2 hours after AHDECC and last for at least 24 hours, suggesting that treatments should target this time window in order to be effective.:




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No In Vivo Evidence for Estrogen Receptor Density Changes in Human Neuroendocrine Aging or Their Relationship to Cognition and Menopausal Symptoms




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Correlation of FAPI PET Uptake with Immunohistochemistry in Explanted Lungs from Patients with Advanced Interstitial Lung Disease

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of 68Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis–associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUVmax and SUVmean showed a positive correlation with the immunohistochemical FAP expression score (SUVmax: r = 0.57, P = 0.001; SUVmean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.




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This Month in JNM




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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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Automated Volumetric Software in Dementia: Help or Hindrance to the Neuroradiologist? [RESEARCH]

BACKGROUND AND PURPOSE:

Brain atrophy occurs in the late stage of dementia, yet structural MRI is widely used in the work-up. Atrophy patterns can suggest a diagnosis of Alzheimer disease (AD) or frontotemporal dementia (FTD) but are difficult to assess visually. We hypothesized that the availability of a quantitative volumetric brain MRI report would increase neuroradiologists’ accuracy in diagnosing AD, FTD, or healthy controls compared with visual assessment.

MATERIALS AND METHODS:

Twenty-two patients with AD, 17 with FTD, and 21 cognitively healthy patients were identified from the electronic health systems record and a behavioral neurology clinic. Four neuroradiologists evaluated T1-weighted anatomic MRI studies with and without a volumetric report. Outcome measures were the proportion of correct diagnoses of neurodegenerative disease versus normal aging ("rough accuracy") and AD versus FTD ("exact accuracy"). Generalized linear mixed models were fit to assess whether the use of a volumetric report was associated with higher accuracy, accounting for random effects of within-rater and within-subject variability. Post hoc within-group analysis was performed with multiple comparisons correction. Residualized volumes were tested for an association with the diagnosis using ANOVA.

RESULTS:

There was no statistically significant effect of the report on overall correct diagnoses. The proportion of "exact" correct diagnoses was higher with the report versus without the report for AD (0.52 versus 0.38) and FTD (0.49 versus 0.32) and lower for cognitively healthy (0.75 versus 0.89). The proportion of "rough" correct diagnoses of neurodegenerative disease was higher with the report than without the report within the AD group (0.59 versus 0.41), and it was similar within the FTD group (0.66 versus 0.63). Post hoc within-group analysis suggested that the report increased the accuracy in AD (OR = 2.77) and decreased the accuracy in cognitively healthy (OR = 0.25). Residualized hippocampal volumes were smaller in AD (mean difference –1.8; multiple comparisons correction, –2.8 to –0.8; P < .001) and FTD (mean difference –1.2; multiple comparisons correction, –2.2 to –0.1; P = .02) compared with cognitively healthy.

CONCLUSIONS:

The availability of a brain volumetric report did not improve neuroradiologists’ accuracy over visual assessment in diagnosing AD or FTD in this limited sample. Post hoc analysis suggested that the report may have biased readers incorrectly toward a diagnosis of neurodegeneration in cognitively healthy adults.




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Intra-Aneurysmal High-Resolution 4D MR Flow Imaging for Hemodynamic Imaging Markers in Intracranial Aneurysm Instability [RESEARCH]

BACKGROUND AND PURPOSE:

Prediction of aneurysm instability is crucial to guide treatment decisions and to select appropriate patients with unruptured intracranial aneurysms (IAs) for preventive treatment. High-resolution 4D MR flow imaging and 3D quantification of aneurysm morphology could offer insights and new imaging markers for aneurysm instability. In this cross-sectional study, we aim to identify 4D MR flow imaging markers for aneurysm instability by relating hemodynamics in the aneurysm sac to 3D morphologic proxy parameters for aneurysm instability.

MATERIALS AND METHODS:

In 35 patients with 37 unruptured IAs, a 3T MRA and a 7T 4D MRI flow scan were performed. Five hemodynamic parameters—peak-systolic wall shear stress (WSSMAX) and time-averaged wall shear stress (WSSMEAN), oscillatory shear index (OSI), mean velocity, and velocity pulsatility index—were correlated to 6 3D morphology proxy parameters of aneurysm instability—major axis length, volume, surface area (all 3 size parameters), flatness, shape index, and curvedness—by Pearson correlation with 95% CI. Scatterplots of hemodynamic parameters that correlated with IA size (major axis length) were created.

RESULTS:

WSSMAX and WSSMEAN correlated negatively with all 3 size parameters (strongest for WSSMEAN with volume (r = –0.70, 95% CI –0.83 to –0.49) and OSI positively (strongest with major axis length [r = 0.87, 95% CI 0.76–0.93]). WSSMAX and WSSMEAN correlated positively with shape index (r = 0.61, 95% CI 0.36–0.78 and r = 0.49, 95% CI 0.20–0.70, respectively) and OSI negatively (r = –0.82, 95% CI –0.9 to –0.68). WSSMEAN and mean velocity correlated negatively with flatness (r = –0.35, 95% CI –0.61 to –0.029 and r = –0.33, 95% CI –0.59 to 0.007, respectively) and OSI positively (r = 0.54, 95% CI 0.26–0.74). Velocity pulsatility index did not show any statistically relevant correlation.

CONCLUSIONS:

Out of the 5 included hemodynamic parameters, WSSMAX, WSSMEAN, and OSI showed the strongest correlation with morphologic 3D proxy parameters of aneurysm instability. Future studies should assess these promising new imaging marker parameters for predicting aneurysm instability in longitudinal cohorts of patients with IA.




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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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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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PD-L1+ diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquired PMS2 mutation [RESEARCH REPORT]

We present a unique case of a single patient presenting with two mutationally distinct, PD-L1+ diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired PMS2 mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies.




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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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Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure [RESEARCH REPORT]

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.




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Reclassification of the HPGD p.Ala13Glu variant causing primary hypertrophic osteoarthropathy [VARIANT DISCREPANCY RESOLUTION]

Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the HPGD gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in HPGD was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for HPGD, all provide sufficient evidence to reclassify the HPGD c.38C > A, p.Ala13Glu variant as likely pathogenic.




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Drosophila Cornmeal-Yeast Food




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Selection of Affibody Molecules Using Escherichia coli Display

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for selection via multiple display methods. This protocol describes selection from affibody libraries by Escherichia coli cell surface display. With this method, high-diversity libraries of 1011 can be displayed on the cell surface. The method involves two steps for selection of binders from high-diversity libraries: magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). MACS is used first to enrich the library in target-binding clones and to decrease diversity to a size that can be effectively screened and sorted in the flow cytometer in a reasonable time (typically <107 cells). The protocol is based on methodology using an AIDA-I autotransporter for display on the outer membrane, but the general procedures can also be adjusted and used for other types of autotransporters or alternative E. coli display methods.




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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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Geographic inequalities in need and provision of social prescribing link workers a retrospective study in primary care

BackgroundLong-term health conditions are major challenges for care systems. Social prescribing link workers have been introduced via primary care networks (PCNs) across England since 2019 to address the wider determinants of health by connecting individuals to activities, groups, or services within their local community.AimTo assess whether the rollout of social prescribing link workers was in areas with the highest need.Design and settingA retrospective study of social prescribing link workers in England from 2019 to 2023.MethodWorkforce, population, survey, and area-level data at the PCN-level from April 2020 to October 2023 were combined. Population need before the rollout of link workers was measured using reported lack of support from local services in the 2019 General Practice Patient Survey. To assess if rollout reflected need, linear regression was used to relate provision of link workers (measured by full-time equivalent [FTE] per 10 000 patients) in each quarter to population need for support.ResultsPopulations in urban, more deprived areas and with higher proportions of people from minority ethnic groups had the highest reported lack of support. Geographically these were in the North West and London. Initially, there was no association between need and provision; then from July 2022, this became negative and significant. By October 2023, a 10-percentage point higher need for support was associated with a 0.035 (95% confidence interval = −0.634 to −0.066) lower FTE per 10 000 patients.ConclusionRollout of link workers has not been sufficiently targeted at areas with the highest need. Future deployments should be targeted at those areas.




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Collaborative discussions between GPs and pharmacists to optimise patient medication: a qualitative study within a UK primary care clinical trial

BackgroundThere has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking.AimTo explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice.Design and settingA mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023.MethodAudio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically.ResultsA total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1–6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs.ConclusionThe model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care.




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'The Fellowship is breaking, it has already begun&#x2019;




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Impact of Health Equity Fellowships [Family Medicine Updates]




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Guidance and Resources for Family Medicine Scholarship [Family Medicine Updates]




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Improving Access to Disability Assessment for US Citizenship Applicants in Primary Care: An Embedded Neuropsychological Assessment Innovation [Innovations in Primary Care]




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Using the Electronic Health Record to Facilitate Patient-Physician Relationship While Establishing Care [Innovations in Primary Care]




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Face-to-Face Relationships Still Matter in a Digital Age: A Call for a 5th C in the Core Tenets of Primary Care [Reflections]

We primary care clinicians, scholars, and leaders ascribe value to Barbara Starfield’s core tenets of primary care—the 4 Cs: first contact, comprehensiveness, coordination, and continuity. In today’s era of rapid technological advancements and dwindling resources, what are the implications for face-to-face interactions of patient-clinician relationships? We propose adding a 5th C: "Contiguity." Contiguity—or physical proximity and presence—is a key dimension that not only enables the necessary technical aspects of a physical exam but also authenticates the most human aspects of a relationship and occurs specifically when we are physically vulnerable and responsible for the other before us. This, in turn, may best enable us to bridge difference and nurture trust with our patients. We measure what we value and, thus, naming Contiguity as a core tenet assures that we will not lose sight of this keystone in a patient’s relationship with their personal physician.




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A Cluster-Randomized Study of Technology-Assisted Health Coaching for Weight Management in Primary Care [Original Research]

PURPOSE

We undertook a trial to test the efficacy of a technology-assisted health coaching intervention for weight management, called Goals for Eating and Moving (GEM), within primary care.

METHODS

This cluster-randomized controlled trial enrolled 19 primary care teams with 63 clinicians; 9 teams were randomized to GEM and 10 to enhanced usual care (EUC). The GEM intervention included 1 in-person and up to 12 telephone-delivered coaching sessions. Coaches supported goal setting and engagement with weight management programs, facilitated by a software tool. Patients in the EUC arm received educational handouts. We enrolled patients who spoke English or Spanish, were aged 18 to 69 years, and either were overweight (body mass index 25-29 kg/m2) with a weight-related comorbidity or had obesity (body mass index ≥30 kg/m2). The primary outcome (weight change at 12 months) and exploratory outcomes (eg, program attendance, diet, physical activity) were analyzed according to intention to treat.

RESULTS

We enrolled 489 patients (220 in the GEM arm, 269 in the EUC arm). Their mean (SD) age was 49.8 (12.1) years; 44% were male, 41% Hispanic, and 44% non-Hispanic Black. At 12 months, the mean adjusted weight change (standard error) was –1.4 (0.8) kg in the GEM arm vs –0.8 (1.6) kg in the EUC arm, a nonsignificant difference (P = .48). There were no statistically significant differences in secondary outcomes. Exploratory analyses showed that the GEM arm had a greater change than the EUC arm in mean number of weekly minutes of moderate to vigorous physical activity other than walking, a finding that may warrant further exploration.

CONCLUSIONS

The GEM intervention did not achieve clinically important weight loss in primary care. Although this was a negative study possibly affected by health system resource limitations and disruptions, its findings can guide the development of similar interventions. Future studies could explore the efficacy of higher-intensity interventions and interventions that include medication and bariatric surgery options, in addition to lifestyle modification.




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[PERSPECTIVES] Developmental Dysregulation of Childhood Cancer

Most childhood cancers possess distinct clinicopathological profiles from those seen in adulthood, reflecting their divergent mechanisms of carcinogenesis. Rather than depending on the decades-long, stepwise accumulation of changes within a mature cell that defines adult carcinomas, many pediatric malignancies emerge rapidly as the consequence of random errors during development. These errors—whether they be genetic, epigenetic, or microenvironmental—characteristically block maturation, resulting in phenotypically primitive neoplasms. Only an event that falls within a narrow set of spatiotemporal parameters will forge a malignant clone; if it occurs too soon then the event might be lethal, or negatively selected against, while if it is too late or in an incorrectly primed precursor cell then the necessary intracellular conditions for transformation will not be met. The precise characterization of these changes, through the study of normal tissues and tumors from patients and model systems, will be essential if we are to develop new strategies to diagnose, treat, and perhaps even prevent childhood cancer.




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Des politiques pour mieux soutenir les chirurgiennes enceintes [Commentaire]




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"Steroids in severe community-acquired pneumonia". S. Ananth, A.G. Mathioudakis, J. Hansel. Breathe 2024; 20: 240081.




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Highlights from the Respiratory Failure and Mechanical Ventilation Conference 2024

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.




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The Team Behind Heretic Talks That Ending, The Book of Mormon, and Monopoly



Writer-director partners Scott Beck and Bryan Woods dive into the biggest spoilers of their new Hugh Grant thriller.




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As Rohingya refugees continue to flee from persecution, here’s how you can help

A Rohingya refugee girl poses with a chicken at the Balukhali refugee camp near Cox’s Bazar in Bangladesh. Photo by Jorge Silva/Reuters

More than 500,000 Rohingya Muslims have fled their homes since August to escape systematic violence at the hands of government soldiers in Myanmar. The U.N. has called the actions taken by Myanmar forces against the group “a textbook example of ethnic cleansing.”

A report released by Amnesty International on Wednesday documents widespread rape, killings and burnings of Rohingya across the Rakhine State in Myanmar. The report includes extensive interviews of Rohingya refugees who tell stories of live burnings, sexual violence and mass shootings at the hands of soldiers.

To escape persecution, Rohingya refugees are fleeing in droves to neighboring Bangladesh, a country described by some as a reluctant host for the thousands of refugees behind its borders. Conditions within Bangladesh show refugee camps beyond capacity, as organizations struggle to keep up with humanitarian aid.

Find out more: Rohingya Muslims have been denied citizenship in Myanmar since 1982, though they’ve lived in the area since the 12th century. They are not considered one of the country’s official ethnic groups. As such, their lack of official identity bars them from government services and travel.

Officials from Myanmar, a majority Buddhist state, claim Rohingya are actually immigrants from Bangladesh to justify their exclusion of the group. This most recent burst of violence comes from Myanmar’s crackdown following clashes with the Arakan Rohingya Salvation Army (ARSA). After the government declared ARSA a terrorist organization, the retaliation escalated into hundreds of Rohingya villages.

Where to give: BRAC, a top-ranked NGO based out of Bangladesh, is scaling up humanitarian efforts for clean water, health, sanitation and child care for refugees from Myanmar. You can learn more about their efforts here.

An emergency appeal was made by the Disasters Emergency Committee for immediate crisis relief funds. DEC distributes funds to 13 member aid organizations.
UNHCR, UNICEF and Save the Children have donation pages dedicated to the crisis, as does the International Rescue Committee. CNN’s Public Good page provides a user-friendly resource to find NGOs that match your giving goals.

To give to starvation relief, try Action Against Hunger or the World Food Programme.

Be sure to research organizations receiving your financial contributions, not only to find the best organization aligned with your goals, but also to avoid potential scams. For the latest information on aid organizations and charities, visit GuideStar or Charity Navigator to ensure your donations are going in the right direction.

The post As Rohingya refugees continue to flee from persecution, here’s how you can help appeared first on PBS NewsHour.




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The battle for Mosul is over, but this hidden ISIS danger could lurk for years

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HARI SREENIVASAN: But first: The de facto capital of the Islamic State, Raqqa, in Syria fell yesterday to U.S.-backed forces.

However, the largest city the militants once held was Mosul in Iraq. They were ousted from it in July after a brutal 10-month-long fight that killed thousands.

Now a new major task: finding and destroying the ISIS mines, booby-traps and bombs that litter the city.

Special correspondent Marcia Biggs reports from Iraq.

MARCIA BIGGS, Special Correspondent: It was once a center of learning for over 6,000 students of technology, agriculture, and medicine.

Today, Mosul Technical Institute’s classrooms are burnt to the ground, laboratories reduced to rubble, and books charred and shredded. It’s one of the city’s five universities ravaged by the Islamic State and the battle to oust it.

Now that the battle is over, a new danger looms, the trail of land mines and booby-traps left by ISIS.

So this is the wire, and this is where it was buried.

CHRISTIAN, Team Leader, Janus Global Operations: Yes, they would cut the asphalt, and then they lay the wire in and put the main charge here.

MARCIA BIGGS: We spent the day with Christian, a team leader from Janus Global, a security and risk management firm hired by the U.S. government to sweep and clear major areas of unexploded ordnance and mines.

He’s not allowed to show his face or use his last name, for security reasons.

CHRISTIAN: There’s actually two more on that road before we get to the target building that have to be excavated and/or rendered safe.

MARCIA BIGGS: So, the first building you have to clear, you have got to get rid of the IEDs on the road to that building?

CHRISTIAN: Yes.

MARCIA BIGGS: It’s a long process.

CHRISTIAN: It is, but that’s what makes it interesting.

MARCIA BIGGS: The United States has sunk $30 million this year into clearing former ISIS territories all over Northern Iraq. Under this program, Janus has already cleared 727 buildings, removing 3,000 IEDs, which they say ISIS was producing on assembly lines at an industrial scale.

But State Department officials and experts say the number of unexploded ordnance in Mosul itself is unprecedented.

What’s your first line of attack, in terms of trying to clear Mosul?

CHRISTIAN: Our priority is more the community, rather than the individual, you know, infrastructure. You have got schools, power, sewer, water, so that the area can accept people back into it. And then, once this stabilization phase is over, we can move into the individual homes, so that they can be safer.

MARCIA BIGGS: Clearing Mosul is a process that they say could take years, even decades. So Janus is training local Iraqis to do the job, sending them out as a front-line search team, then investigating and removing any suspicious items themselves.

CHRISTIAN: We’re not going to be here the whole time, so when we — it’s our time to leave, they will have the capacity built from us, and the mentoring we have done, so that they can do it on their own.

MARCIA BIGGS: How are they doing?

CHRISTIAN: They’re — a lot of them are very apt to learn. They’re quick. They’re smart.

MARCIA BIGGS: Fawzi al Nabdi is the team leader for the Iraqi local partner. He’s cleared mines all over Iraq for the last six years.

CHRISTIAN: What you got?

FAWZI AL NABDI, Team Leader, Al Fahad Company (through interpreter): We are ready for this, because it’s my job and I love it. The Americans are here to complete our work and to help us. They have greater experience than we do. If we find any mines, we have to stop and they will investigate it and make a plan to remove it.

MARCIA BIGGS: But he says Mosul is the biggest project he has ever seen, and we’re told it could take at least a month to just get the campus cleared of mines. Only then can they start cleaning it up, so that students can resume classes, this itself a huge task.

ISIS fighters closed the university back in 2014, and used it as a military base. As coalition forces pounded ISIS targets, this seat of higher learning became a battleground.

Ghassan Alubaidy is the institute’s dean.

GHASSAN ALUBAIDY, Dean, Mosul Technical Institute (through interpreter): ISIS used our university to manufacture mines and bombs. For this reason, it was the target of airstrikes in the beginning. They struck the institute nine times, and they struck our workshops, too. Now we can’t use them.

MARCIA BIGGS: The former commander of coalition forces in Iraq, Lieutenant General Stephen Townsend, recently listed 81 locations where bombs were dropped, but had not yet exploded.

Facilities used to make weapons were often on the list of high-value targets for the coalition. So now those places are twice as likely to contain dangerous items.

So, this was once a workshop for electrical engineering students. You can still see the lab tables here. It was hit by an airstrike in 2015. Afterwards, members of the university staff found bomb-making instructions among the rubble. This was likely an ISIS bomb-making factory, and judging by the crater, a high-value target.

Despite the damage, Dean Alubaidy says he will hold classes this fall in alternate buildings, until the campus is ready. He’s expecting registration to be in the thousands, students who lost three years of education during the fighting and don’t want to lose another one.

GHASSAN ALUBAIDY (through interpreter): On our Facebook pages, we found a great number of students posting that they were full of encouragement to come back. For us, it was unbelievable. We couldn’t imagine it, to see how many students wanted to start again, how they were dreaming of the first day of classes, when they could sit in front of teachers again and start to live their lives again.

MARCIA BIGGS: Next door, Mosul University has already started classes. Students even volunteered to help in the cleanup.

But across the river, West Mosul was the site of ISIS’ last stand and bore the brunt of the battle. It’s densely packed Old City, with its flattened buildings, is a challenge for mine-sweeping.

FAWZI AL-NABDI (through interpreter): Most of the homes here were full of mines. And just here in front of us, a man with two kids came back to his home, and when he opened the door, the bomb killed him and his kids.

MARCIA BIGGS: Ahmed Younes fled back in early July with only the clothes on his back. Residents have been virtually banned from returning to his neighborhood on the outskirts of the Old City, but Ahmed said he got special permission, in order to retrieve some personal items.

AHMED YOUNES, Local Resident (through interpreter): We came on our own. We got permission to come, but they are not responsible if anything happens to us.

MARCIA BIGGS: Right now, there is no plan to begin clearing the Old City or even to determine how many mines there are. It is still out of bounds to anyone but the Iraqi security forces.

So the Janus team is focusing on progress in the rest of the city, building by building, bomb by bomb.

CHRISTIAN: Whoever made this device had a set goal. And to allow him to win, people get hurt. So you kind of compete against him to be better than him to take it out before it can do any harm.

MARCIA BIGGS: So, you feel like you’re winning the battle against ISIS?

CHRISTIAN: Yes, one IED at a time.

MARCIA BIGGS: For the PBS NewsHour, I’m Marcia Biggs in Mosul, Iraq.

HARI SREENIVASAN: Tune in later.

Frontline’s latest film, “Mosul,” was on the ground filming the fight as it unfolded street by street and house by house. That’s tonight on PBS.

The post The battle for Mosul is over, but this hidden ISIS danger could lurk for years appeared first on PBS NewsHour.




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Xi Jinping celebrates China’s rising power — and his own

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HARI SREENIVASAN: President Xi Jinping opened China’s twice-per-decade Communist Party Congress today with a lengthy list of his achievements during his first five-year term, and his vision of where he hopes to take his nation.

But beyond the words, Xi is asserting power like no Chinese leader in decades.

William Brangham reports.

WILLIAM BRANGHAM: The applause, the music, it was a reception befitting the commanding role that Xi Jinping has taken since being named party leader five years ago.

He opened today’s proceedings by hailing reforms he’s put in place, and proclaiming a — quote — “new era for China.”

PRESIDENT XI JINPING, China (through interpreter): The Chinese nation has realized a great leap, from declining in modern history to twisting its fate fundamentally and continuously moving to prosperity.

WILLIAM BRANGHAM: Over 3.5 hours, Xi laid out his vision to shape the nation of 1.4 billion people into what he called a — quote — “great modern socialist country” over the next three decades.

PRESIDENT XI JINPING (through interpreter): Achieving the great rejuvenation of the Chinese nation will be no walk in the park, and it will take more than drumbeating and gong-clanging to get there. The whole party must be prepared to make more arduous, strenuous efforts.

WILLIAM BRANGHAM: Susan Shirk is chair of the 21st Century China Center at the University of California, San Diego.

SUSAN SHIRK, University of California, San Diego: Xi Jinping has a vision of China’s role in the world that is much more ambitious than anything we have seen before, talking about China kind of moving toward the center of the world and having a lot more influence than it did before.

WILLIAM BRANGHAM: In his address, Xi largely ignored the question of political reforms in China, and he didn’t mention President Trump or North Korea’s nuclear weapons program.

But in a rare move, he did acknowledge that with global demand weakening, there were challenges facing China’s export-driven economy.

PRESIDENT XI JINPING (through interpreter):  While China’s overall productive forces have significantly improved and in many areas our production capacity leads the world, the more prominent problem is that our development is unbalanced and inadequate.

WILLIAM BRANGHAM: Xi was one of the first foreign leaders to meet with President Trump.

PRESIDENT DONALD TRUMP: The relationship developed by President Xi and myself, I think, is outstanding.

WILLIAM BRANGHAM: That was decidedly warmer than Mr. Trump’s past criticism of China and its economic and trade policies.

But other U.S. officials are more critical of Beijing’s actions.

REX TILLERSON, Secretary of State: China, while rising alongside India, has done so less responsibly.

WILLIAM BRANGHAM: Secretary of State Rex Tillerson today criticized China’s aggressive displays of economic and military power, particularly its expansion on man-made islands in the South China Sea.

REX TILLERSON: We will not shrink from China’s challenges to the rules-based order, and where China subverts the sovereignty of neighboring countries and disadvantages the U.S. and our friends.

SUSAN SHIRK: I think there are things to worry about in Chinese foreign policy that are mostly related to these maritime sovereignty issues and to a kind of bullying in Asia, but the global ambition could turn out to be positive.

WILLIAM BRANGHAM: Susan Shirk says China has filled a vacuum left by the United States’ withdrawal from global agreements like the Trans-Pacific Partnership and the Paris climate accords.

Perhaps the most important thing to watch for in the next few days is who Xi establishes as his likely successor.

SUSAN SHIRK: That is why there is a lot of speculation now that he may be trying, much like Putin, to stay on beyond his normal term or to rule behind the scenes even after he retires.

WILLIAM BRANGHAM: President Trump will be traveling to Beijing to meet Xi next month.

For the PBS NewsHour, I’m William Brangham.

The post Xi Jinping celebrates China’s rising power — and his own appeared first on PBS NewsHour.




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