Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson’s disease and addiction. In contrast to the extensive ...studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca2+ elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca2+, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A1 receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A1 receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.
•Astrocytes in the Nucleus Accumbens respond to synaptic dopamine in vivo•Astrocytes mediate the synaptic regulation induced by dopamine and amphetamine•Amphetamine-induced enhancement in locomotion activity is modulated by astrocytes
Corkrum et al. report that astrocyte activity is required for dopamine- and amphetamine-evoked synaptic regulation and amphetamine-induced locomotor effects. Their study reveals astrocytes as active components of dopaminergic signaling and the brain reward system.
Introduction: Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety ...and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single‐institution experience and provide a comprehensive review of the literature. Methods: A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed. Results: A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu‐DOTATATE (73%). The median therapeutic 177Lu‐DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y‐DOTATATE (4.2 GBq) in addition to three infusions of Lu‐177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL. Conclusion: This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.
68 Ga‐DOTATATE PET/CT maximum intensity projection (MIP) images before and after four infusions of peptide receptor radionuclide therapy (PRRT) in a patient with left carotid body paraganglioma. The images show multiple lung, liver, bone and nodal metastases with stable disease on initial follow‐up imaging. The patient had no further treatment following completion of PRRT but proceeded to show delayed partial response on follow‐up imaging at up to 4.5 years post‐PRRT.
Purpose
The aim of this short communication is to outline our experience in policies and processes of a nuclear medicine service during the COVID-19 outbreak in Singapore.
Methods
We describe the key ...considerations of policies and processes that have been implemented in our nuclear medicine service since the first case of COVID-19 was confirmed in Singapore General Hospital on 23 January 2020, up to the present time.
Results
Infection control, screening of patients and visitors, segregation of risk groups, segregation of staff and service continuity plans, communication and staff welfare, using electronic platforms for multi-disciplinary meetings and tele-reporting are discussed.
Conclusion
Since our hospital received the first patient with COVID-19 in Singapore, our centre has managed 16 COVID-19 cases to date. There has not been any healthcare worker in our institution who has contracted COVID-19 through patient contact. We have highlighted for discussion some of the policies and processes to prepare a nuclear medicine service for the COVID-19 threat.
This work deals with the comparison of the morphology of aluminum 6061 splats cold sprayed at various angles between computational finite element modeling predictions and experimental observations. ...Computational modeling of single-splats sprayed at various angles predicted that the highest shear stresses would occur at impact angle of 60-65°, while the highest interfacial equivalent plastic strains would be observed at 50° and both would decrease as the spray angle increases. The amount of interfacial-bonded material was also observed to decrease as the spray angle increases. The computational model was correlated with experimental data from neutron diffraction and x-ray diffraction methods, and experimental tensile adhesive strength test results. From both neutron and x-ray diffraction through-coating measurements, it was also observed that the residual stress profile of the coatings would be increasingly more negative from the coating surface toward the substrate interface, before becoming less negative from that point on. The data also suggested that the coating residual stresses are largely biaxial although there were suggestions of anisotropy for coatings sprayed at oblique angles of 50° and 70°, which was also predicted by the simulation model.
Lumbosacral spine MRI in June, 2010, showed ankylosed sacroiliac joints and hip arthritis that were suggestive of ankylosing spondylitis, but non-steroidal anti-inflammatory drugs and ...disease-modifying antirheumatic drugs gave only modest relief. Oncogenic osteomalacia, an unusual disorder characterised by hypophosphataemia with normal blood calcium, and phosphaturia with normal serum parathyroid hormone from excessive paraneoplastic phosphatonins, was first described by McCance in 1947.2 Most cases are attributable to benign mesenchymal tumours, although giant cell tumours, osteosarcoma, and prostate carcinoma have caused oncogenic osteomalacia.3-5 The disorder is biochemically indistinguishable from inherited forms of hypophosphataemic rickets, so careful family history is essential.
Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than ...40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding
Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.
Background Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced ...hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown. Methods By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial. Results We found that higher tumor mutation burden, NCOR1 mutations and higher expression of interferon gamma pathways occurred more frequently in responders. Meanwhile, non-responders tended to be enriched for a novel Asian-specific transcriptomic subtype (Kaya_P2) with a high frequency of chromosome 16 deletions and upregulated cell cycle pathways. Strikingly, unlike other cancer types, we did not observe any association between T-cell populations and treatment response, but tumors from responders had a higher proportion of CXCL9 + /CXCR3 + macrophages. Moreover, biomarkers discovered in previous immunotherapy trials were not predictive in the current cohort, suggesting a distinctive molecular landscape associated with differential responses to the combination therapy. Conclusions This study unraveled extensive molecular changes underlying distinctive responses to the novel treatment and pinpointed new directions for harnessing combination therapy in patients with advanced HCC.
The importance of routine neck ultrasonography for the detection of unsuspected local or nodal recurrence of thyroid cancer following thyroidectomy (with or without neck dissection) is well ...documented in many journal articles and international guidelines. Herein, we present a pictorial summary of the sonographic features of benign and malignant central neck compartment nodules and cervical lymph nodes via a series of high-quality ultrasonographic images, with a review of the literature.
Epidemiological evidence suggests there are differences in gastroenteropancreatic neuroendocrine neoplasm (GEPNEN) among population groups. We aimed to contribute to the current evidence by ...evaluating the clinicopathological characteristics of GEPNEN in a multi-ethnic Asian group.
This was a retrospective chart review of patients diagnosed with GEPNEN at a tertiary medical institution at Singhealth Outram Campus, Singapore, between 1995 and 2015.
Two hundred ninety-five patients were included in the evaluation, comprising Chinese (74.6%), Malay (4.4%), Indian (9.5%) and other (11.5%) ethnic backgrounds. The median age at diagnosis was 59 years; 52.5% were males. Distribution of disease stage at diagnosis was: localised (42.4%), regional (15.3%) and distant (38.0%). The three most common primary tumour sites were located in the pancreas (38.6%), rectum (19.7%) and stomach (9.5%), which varied significantly with ethnic background and age at diagnosis. Malay patients were younger (median 42 years) at diagnosis than Chinese (60 years). Patients with an appendiceal neuroendocrine neoplasm (NEN) (48 years) were younger compared to oesophageal NEN (66 years). Disease stage correlated with primary tumour site and grade (p < 0.001). Median overall survival (OS) for all GEPNEN was 10.2 years. Age at diagnosis, disease stage and grading were prognostic factors of OS in multivariable analyses.
Our findings correspond with other studies that focus on GEPNEN incidences in Asian countries, with the pancreas, rectum and stomach being the most common primary tumour sites. Our findings suggest racial differences in primary tumour site and age at diagnosis. Further prospective population-based registries are required to understand these epidemiological differences.
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