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Frontiers in Psychiatry 2023Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This... (Review)
Review
BACKGROUND
Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics may alter markers associated with synaptic density, and that these changes may underlie effects such as sensitization, conditioned place preference, drug self-administration, and verbal memory performance. In this scoping review, we examined studies that measured synaptic markers in animals and humans after exposure to ketamine and/or psychedelics.
METHODS
A systematic search was conducted following PRISMA guidelines, through PubMed, EBSCO, Scopus, and Web of Science, based on a published protocol (Open Science Framework, DOI: 10.17605/OSF.IO/43FQ9). Both and studies were included. Studies on the following synaptic markers were included: dendritic structural changes, PSD-95, synapsin-1, synaptophysin-1, synaptotagmin-1, and SV2A.
RESULTS
Eighty-four studies were included in the final analyses. Seventy-one studies examined synaptic markers following ketamine treatment, nine examined psychedelics, and four examined both. Psychedelics included psilocybin/psilocin, lysergic acid diethylamide, N,N-dimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine, and ibogaine/noribogaine. Mixed findings regarding synaptic changes in the hippocampus and prefrontal cortex (PFC) have been reported when ketamine was administered in a single dose under basal conditions. Similar mixed findings were seen under basal conditions in studies that used repeated administration of ketamine. However, studies that examined animals during stressful conditions found that a single dose of ketamine counteracted stress-related reductions in synaptic markers in the hippocampus and PFC. Repeated administration of ketamine also counteracted stress effects in the hippocampus. Psychedelics generally increased synaptic markers, but results were more consistently positive for certain agents.
CONCLUSION
Ketamine and psychedelics can increase synaptic markers under certain conditions. Heterogeneous findings may relate to methodological differences, agents administered (or different formulations of the same agent), sex, and type of markers. Future studies could address seemingly mixed results by using meta-analytical approaches or study designs that more fully consider individual differences.
PubMed: 37435405
DOI: 10.3389/fpsyt.2023.1197890 -
Folia Medica Cracoviensia Apr 2023Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of...
Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of oncologic patients, but the survival time varies from 6 weeks to 5 months. The diagnostics should begin with a clinical evaluation and basic laboratory tests. For CUP placed in head and neck the positron emission tomography - computed tomography is recommended; pancreatic or lung neoplasms are diagnosed with the computed tomography as well. Recently, the magnetic resonance, especially whole-body diffusion-weighted imaging has been introduced to the imaging panel. The lesion obtained during surgically removed metastases or biopsy material should be histopathological and molecularly examined to define the type of tumor. The basic immunoexpression panel should include cytokeratin-5/6, -7 and -20, EMA, synaptophysin, chromogranin, vimentin and GATA3 and molecular expression of ERBB2, PIK3CA, NF1, NF2, BRAF, IDH1, PTEN, FGFR2, EGFR, MET and CDK6. During the accurate diagnostics enable to classify malignancy of undefined primary origin as provisional CUP or finally confirmed CUP in which the primary place of tumor remains undetectable. The detailed diagnostics should be performed in highly specified centers to establish an accurate diagnosis and to initiate personalized treatment. Majority of patients are diagnosed with adenocarcinoma (70%), undifferentiated carcinoma (20%), squamous cell or transitional cell/uroepithelial carcinoma (5-10%), neuroendocrine tumor (5%) and with minor incidence other histological types, including melanoma.
Topics: Humans; Neoplasms, Unknown Primary; Carcinoma; Adenocarcinoma; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Head and Neck Neoplasms
PubMed: 37406274
DOI: 10.24425/fmc.2023.145427 -
Pediatric Ectopic Cushing Syndrome Caused by Hepatic Neoplasms: A Case Report and Systematic Review.Cureus Mar 2023Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an...
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an adolescent boy who presented with Cushingoid features and had endogenous ACTH-dependent hypercortisolism on hormonal evaluation. Abdominal ultrasound and CT revealed a hepatic lesion with characteristics suggestive of hemangioma, whereas the lesion was tracer non-avid on Ga-DOTANOC positron emission tomography/CT. A regional sampling of ACTH was done to confirm the hepatic lesion as the source of EAS, and a definitive ACTH gradient was observed between the hepatic vein and the right internal jugular vein. Further, a preoperative biopsy of the lesion revealed a small round cell tumor with positive immunostaining for ACTH and synaptophysin, suggestive of a neuroendocrine tumor. The patient was managed with partial hepatectomy, resulting in hormonal and clinical remission of Cushing syndrome. In a systematic review of pediatric EAS due to primary hepatic tumors (n = 11), calcifying nested stromal epithelial cell tumors were the most common. EAS-associated hepatic tumors were larger (≥10 cm) except benign primary hepatic neuroendocrine tumors (PHNET). The latter were misdiagnosed as hemangioma in two cases by anatomical imaging but correctly diagnosed by somatostatin receptor scintigraphy. Hepatic tumors causing EAS in children required extensive resection, except benign PHNET. Nevertheless, all benign tumors with an uncomplicated perioperative course demonstrated disease-free survival over a median follow-up period of two years.
PubMed: 37123777
DOI: 10.7759/cureus.36852 -
Journal of Gastrointestinal and Liver... Dec 2022Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von...
BACKGROUND AND AIMS
Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von Recklinghausen's disease. The aims of this study were to systematically review the literature regarding SAV and to highlight the clinicopathological characteristics and optimal therapeutic management of this rare entity.
METHODS
A systematic search of the literature in PubMed/Medline and Scopus databases was performed by two independent investigators, including all case reports and case series concerning SAVs from 1980 until September 2021.
RESULTS
In total, 37 articles were retrieved, including 43 patients, with a male to female ratio of 1.8:1 and a mean age of 46.8 ± 11.3 years (mean, SD). For 23 out of 43 patients (53.5%), Von Recklinghausen's disease was proved. The main clinical manifestations were abdominal pain (41.9%), jaundice (27.9%), weight loss (20.9%) and bowel disorders (20.9%). Typical histological findings included psammoma bodies, nests or clusters of epithelial cells with eosinophilic cytoplasm, while somatostatin staining was positive in 35 patients (81.4%), chromogranin-A in 21 patients (48.8%) and synaptophysin in 18 patients (41.9%). Surgery was the initial therapeutic approach in 34 patients (79.1%), whereas Whipple's procedure was the preferred surgical approach in 23 patients (53.4%). The longest survival among included patients was 13 years and only two postoperative deaths (4.7%) were reported.
CONCLUSIONS
Somatostatinomas of the ampulla of Vater are rare malignancies that require increased physicians' suspicion and accurate surgical approach in order to achieve optimal therapeutic results.
Topics: Humans; Male; Female; Adult; Middle Aged; Somatostatinoma; Neurofibromatosis 1; Ampulla of Vater; Duodenal Neoplasms; Pancreatic Neoplasms
PubMed: 36535044
DOI: 10.15403/jgld-4383 -
Frontiers in Endocrinology 2022Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a...
Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Carcinoma, Neuroendocrine; Adenocarcinoma; Neuroendocrine Tumors; Tumor Microenvironment
PubMed: 36440195
DOI: 10.3389/fendo.2022.1012005 -
Archivio Italiano Di Urologia,... Dec 2021Ectopic adrenal tissue in the kidney, including "Ectopic adrenal tissue" and "Adrenal-renal fusion", is a rare event with a specific behavior which may be difficult to...
INTRODUCTION
Ectopic adrenal tissue in the kidney, including "Ectopic adrenal tissue" and "Adrenal-renal fusion", is a rare event with a specific behavior which may be difficult to distinguish clinically from renal neoplasms. We performed a systematic review on ectopic adrenal tissue variants reported in the literature underlining its clinical aspects.
METHODS
Manuscripts which presented a case report or case series of ectopic adrenal tissue in the kidney were included even if published in original articles, reviews, or letters to the editor. A specific search on SCOPUS®, PubMed®, and Web of Science® database was performed. Only English language papers published in a period ranging between August 1991 and April 2020 were considered. Additionally, a case we had at our institution is described, and its characteristics are included. Data on clinical presentation, type of adrenal anomaly, location, anatomopathological and immune-histotype characteristics were collected.
RESULTS
We identified 888 manuscripts. Among these 29 were included in this systematic review. Overall, 39 patients with renal adrenal fusion or adrenal ectopia were considered. In most cases, the diagnosis was made incidentally, or following investigation for flank pain, abdominal pain, or endocrinological disorders. CT scan frequently identified a solid vascularized lesion that was difficult to distinguish from renal neoplasm. Adrenal fusion was mostly located at the level of the upper pole. Adrenal rest was found in the renal parenchyma, renal hilum, or retroperitoneum in close proximity to the renal peduncle. Often these ectopic adrenal tissue lesions follow a benign behavior and can be classified as functioning or non-functioning adenomas. Rarely, they may experience neoplastic degeneration. The most frequently positive markers were inhibin, vimentin, melan-A, synaptophysin and anti-p450 scc.
CONCLUSIONS
Ectopic adrenal tissue in the kidney is a rare event with specific clinical characteristics that need to be identified in order to arrive at a correct diagnosis and carry out appropriate treatment management.
Topics: Adenoma; Choristoma; Humans; Kidney; Kidney Neoplasms; Tomography, X-Ray Computed
PubMed: 34933527
DOI: 10.4081/aiua.2021.4.481 -
Frontiers in Neurology 2021Gray matter pathology plays a central role in the progression of multiple sclerosis (MS). The occurrence of synaptic loss appears to be important but, to date, still...
Gray matter pathology plays a central role in the progression of multiple sclerosis (MS). The occurrence of synaptic loss appears to be important but, to date, still poorly investigated aspect of MS pathology. In this systematic review, we drew from the recent knowledge about synaptic loss in human post-mortem studies. We conducted a systematic search with PubMed to identify relevant publications. Publications available from15 June 2021 were taken into account. We selected human post-mortem studies that quantitatively assessed the synapse number in MS tissue. We identified 14 relevant publications out of which 9 reported synaptic loss in at least one investigated subregion. The most commonly used synaptic marker was synaptophysin; non-etheless, we found substantial differences in the methodology and the selection of reference tissue. Investigated regions included the cortex, the hippocampus, the cerebellum, the thalamus, and the spinal cord. Synaptic loss seems to take place throughout the entire central nervous system. However, the results are inconsistent, probably due to differences in the methodology. Moreover, synaptic loss appears to be a dynamic process, and thus the nature of this pathology might be captured using synaptic density measurements.
PubMed: 34912290
DOI: 10.3389/fneur.2021.782599 -
International Journal of Molecular... Mar 2021Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on...
BACKGROUND
Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis.
METHODS
We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD.
RESULTS
In additional to Aβ and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls.
CONCLUSIONS
Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.
Topics: Aged; Alzheimer Disease; Biomarkers; Chromatography, High Pressure Liquid; Diagnosis, Computer-Assisted; Female; Humans; Machine Learning; Middle Aged
PubMed: 33803217
DOI: 10.3390/ijms22052761 -
Scientific Reports Sep 2020Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a highly invasive cervical cancer. The immunohistochemical criteria is an important aspect for assistant... (Meta-Analysis)
Meta-Analysis
Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a highly invasive cervical cancer. The immunohistochemical criteria is an important aspect for assistant diagnosis of SCNECC. However, which markers can be appropriate selection for diagnosing SCNECC were not determined. The aim was to systematically evaluate expression levels of four neuroendocrine markers (containing synaptophysin (Syn), neural cell adhesion molecules (CD56), neuron-specific enolase (NSE) and chromograninA (CgA)) and to find out the appropriate selection for diagnosing SCNECC. Four English and three Chinese libraries were retrieved between 1984 and 2020. 23 studies about NSE, 36 studies about Syn, 23 studies about CD56 and 36 studies about CgA (all studies containing 581 patients) were eligible for meta-analyses. The pooled positive expression percentages (95% CI; I) were as follows: 84.84% (79.41-90.27%; 76.7%) for Syn, 84.53% (79.43-89.96%; 37.5%) for CD56, 77.94% (69.13-86.76%; 83.5%) for NSE, and 72.90% (67.40-78.86%; 59.7%) for CgA. The positive proportions (95% CI; I) ranked top three of simultaneous expressions of two markers were 87.75% (82.03-93.87%, 33.3%) for Syn and CD56, 70.92% (50.50-87.68%, 82.7%) for Syn and NSE, 65.65% (53.33-76.98%, 73.5%) for Syn and CgA. This confirms that Syn and CD56 are reliable indicators for diagnosing SCNECC.
Topics: Biomarkers, Tumor; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Female; Humans; Neoplasm Proteins; Uterine Cervical Neoplasms
PubMed: 32917946
DOI: 10.1038/s41598-020-72055-x