end Girls Lose Friends for Having Sex But Boys Don't, Study Shows By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Girls Lose Friends for Having Sex But Boys Don't, Study ShowsCategory: Health NewsCreated: 8/24/2015 12:00:00 AMLast Editorial Review: 8/24/2015 12:00:00 AM Full Article
end Oldest Sister at Greater Risk of Obesity, Study Contends By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Oldest Sister at Greater Risk of Obesity, Study ContendsCategory: Health NewsCreated: 8/26/2015 12:00:00 AMLast Editorial Review: 8/27/2015 12:00:00 AM Full Article
end Medical Groups Endorse Early Exposure to Peanut Products for High-Risk Infants By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Medical Groups Endorse Early Exposure to Peanut Products for High-Risk InfantsCategory: Health NewsCreated: 8/26/2015 12:00:00 AMLast Editorial Review: 8/27/2015 12:00:00 AM Full Article
end Family Trumps Friends in Extending Seniors' Lives By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Family Trumps Friends in Extending Seniors' LivesCategory: Health NewsCreated: 8/21/2016 12:00:00 AMLast Editorial Review: 8/22/2016 12:00:00 AM Full Article
end Teen Cyberbullies More Apt to Be Friends Than Strangers By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Teen Cyberbullies More Apt to Be Friends Than StrangersCategory: Health NewsCreated: 8/20/2016 12:00:00 AMLast Editorial Review: 8/22/2016 12:00:00 AM Full Article
end 'Pretend Mommy' Program Doesn't Deter Teen Pregnancy By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: 'Pretend Mommy' Program Doesn't Deter Teen PregnancyCategory: Health NewsCreated: 8/25/2016 12:00:00 AMLast Editorial Review: 8/26/2016 12:00:00 AM Full Article
end School Kids Need Supervision After Classes End By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: School Kids Need Supervision After Classes EndCategory: Health NewsCreated: 8/26/2018 12:00:00 AMLast Editorial Review: 8/27/2018 12:00:00 AM Full Article
end Hearing Persists at End of Life, Brain Waves of Hospice Patients Show By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Hearing Persists at End of Life, Brain Waves of Hospice Patients ShowCategory: Health NewsCreated: 8/26/2020 12:00:00 AMLast Editorial Review: 8/27/2020 12:00:00 AM Full Article
end President Trump Promises a COVID Vaccine Before the End of the Year By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: President Trump Promises a COVID Vaccine Before the End of the YearCategory: Health NewsCreated: 8/28/2020 12:00:00 AMLast Editorial Review: 8/28/2020 12:00:00 AM Full Article
end Toppling TVs, Furniture Sending Many Young Children to ERs By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Toppling TVs, Furniture Sending Many Young Children to ERsCategory: Health NewsCreated: 8/27/2021 12:00:00 AMLast Editorial Review: 8/27/2021 12:00:00 AM Full Article
end U.S. Government Extends Baby Formula Waivers, Rebates for WIC Families By www.medicinenet.com Published On :: Sat, 27 Aug 2022 00:00:00 PDT Title: U.S. Government Extends Baby Formula Waivers, Rebates for WIC FamiliesCategory: Health NewsCreated: 8/25/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
end Wendy's Pulls Lettuce Due to E. Coli Outbreak By www.medicinenet.com Published On :: Mon, 22 Aug 2022 00:00:00 PDT Title: Wendy's Pulls Lettuce Due to E. Coli OutbreakCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
end 84 People Now Sickened in E. Coli Outbreak Tied to Wendy's Restaurant Lettuce By www.medicinenet.com Published On :: Fri, 26 Aug 2022 00:00:00 PDT Title: 84 People Now Sickened in E. Coli Outbreak Tied to Wendy's Restaurant LettuceCategory: Health NewsCreated: 8/26/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
end FDA Warns Amazon, Other Vendors About Sale of Skin Tag Removal Products By www.medicinenet.com Published On :: Wed, 10 Aug 2022 00:00:00 PDT Title: FDA Warns Amazon, Other Vendors About Sale of Skin Tag Removal ProductsCategory: Health NewsCreated: 8/10/2022 12:00:00 AMLast Editorial Review: 8/10/2022 12:00:00 AM Full Article
end Stay Independent of Asthma, Allergies This July 4th By www.medicinenet.com Published On :: Fri, 1 Jul 2022 00:00:00 PDT Title: Stay Independent of Asthma, Allergies This July 4thCategory: Health NewsCreated: 7/1/2022 12:00:00 AMLast Editorial Review: 7/1/2022 12:00:00 AM Full Article
end Kidneys' Resilience May Depend on Your Gender, Study Finds By www.medicinenet.com Published On :: Mon, 22 Aug 2022 00:00:00 PDT Title: Kidneys' Resilience May Depend on Your Gender, Study FindsCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
end Re: Friendship as Medicine By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Full Article
end NEAT1 promotes genome stability via m6A methylation-dependent regulation of CHD4 [Research Papers] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 Long noncoding (lnc)RNAs emerge as regulators of genome stability. The nuclear-enriched abundant transcript 1 (NEAT1) is overexpressed in many tumors and is responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear. Here, we investigate the expression, modification, localization, and structure of NEAT1 in response to DNA double-strand breaks (DSBs). DNA damage increases the levels and N6-methyladenosine (m6A) marks on NEAT1, which promotes alterations in NEAT1 structure, accumulation of hypermethylated NEAT1 at promoter-associated DSBs, and DSB signaling. The depletion of NEAT1 impairs DSB focus formation and elevates DNA damage. The genome-protective role of NEAT1 is mediated by the RNA methyltransferase 3 (METTL3) and involves the release of the chromodomain helicase DNA binding protein 4 (CHD4) from NEAT1 to fine-tune histone acetylation at DSBs. Our data suggest a direct role for NEAT1 in DDR. Full Article
end Dysregulating mTORC1-4E-BP2 signaling in GABAergic interneurons impairs hippocampus-dependent learning and memory [RESEARCH PAPERS] By learnmem.cshlp.org Published On :: 2024-10-28T08:52:55-07:00 Memory formation is contingent on molecular and structural changes in neurons in response to learning stimuli—a process known as neuronal plasticity. The initiation step of mRNA translation is a gatekeeper of long-term memory by controlling the production of plasticity-related proteins in the brain. The mechanistic target of rapamycin complex 1 (mTORC1) controls mRNA translation, mainly through phosphorylation of the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks). mTORC1 signaling decreases throughout brain development, starting from the early postnatal period. Here, we discovered that in mice, the age-dependent decrease in mTORC1 signaling occurs selectively in excitatory but not inhibitory neurons. Using a gene conditional knockout (cKO) strategy, we demonstrate that either up- or downregulating the mTORC1-4E-BP2 axis in GAD65 inhibitory interneurons, but not excitatory neurons, results in long-term object recognition and object location memory deficits. Our data indicate that the mTORC1 pathway in inhibitory but not excitatory neurons plays a key role in memory formation. Full Article
end A worldwide perspective of long COVID management: how can we END-COVID? By beta.openres.ersjournals.com Published On :: 2024-11-11T01:50:25-08:00 Extract As of 15 May 2024, >775 million confirmed cases of COVID-19 and >7 million deaths have been reported to the World Health Organization [1]. Although most patients with COVID-19 survive, survivors are at risk of long COVID, the sequelae of the viral infection affecting multiple organ systems [2]. Long COVID poses a substantial burden to individuals and society, even with a conservative estimate of 10% prevalence among COVID-19 survivors [3–5]. However, as the symptoms of long COVID vary substantially, ranging from respiratory symptoms, such as dyspnoea and cough, to fatigue and cognitive impairment [6], developing a standard set of investigations and management protocols for patients with long COVID is challenging. Full Article
end A worldwide look into long COVID-19 management: an END-COVID survey By beta.openres.ersjournals.com Published On :: 2024-11-11T01:50:25-08:00 Background Long COVID is a heterogeneous clinical syndrome characterised by a variety of reported symptoms and signs. Its clinical management is expected to differ significantly worldwide. Methods A survey-based study investigating long COVID-related standard operating procedures (SOPs) has been conducted by the European Respiratory Society (ERS) END-COVID clinical research collaboration with the support of other international societies (ALAT, APSR, CHEST, ESCMID and PATS). A global analysis of the results is provided here, alongside sub-population analysis based on continents, national income levels, type of involved healthcare professional and inclusion or exclusion of paediatric patients. Findings 1015 healthcare professionals from 110 different countries worldwide participated in this study, the majority of them being respiratory physicians (60.6%). A dedicated long COVID programme was present in 55.4% of the investigated institutions, with hospital admission during the acute infection being the main inclusion criteria to access them. Consistent differences in long COVID-related procedures were identified among centres, mainly regarding the multidisciplinary approach, the availability of telemedicine and psychological support, the type of requested exams and the total amount of visits in the centre. Interpretation Long COVID management shows important differences related to geographical areas and national income levels. SOPs were significantly different when centres were managed by a pulmonologist or when paediatric patients were included. Full Article
end Characterization and Prediction of Organic Anion Transporting Polypeptide 1B Activity in Prostate Cancer Patients on Abiraterone Acetate Using Endogenous Biomarker Coproporphyrin I [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We used OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant (Ki) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our nine metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3-mediated, but not OATP1B1-mediated, uptake of CP-I in vitro, with an estimated Ki of 3.93 μM. Baseline CP-I concentrations were simulated to be 0.81 ± 0.26 ng/ml and determined to be 0.72 ± 0.16 ng/ml among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low. SIGNIFICANCE STATEMENT The authors used the endogenous biomarker coproporphyrin I (CP-I) and identified abiraterone as a moderate inhibitor of organic anion transporting polypeptide (OATP) 1B3 in vitro. Subsequent physiologically based pharmacokinetic (PBPK) simulations and clinical observations suggested an absence of OATP1B-mediated interaction between abiraterone and CP-I among prostate cancer patients. This multipronged study concluded that the interaction risk between abiraterone acetate and substrates of OATP1Bs is low, demonstrating the application of PBPK-CP-I modeling in predicting OATP1B-mediated interaction implicating abiraterone. Full Article
end Assessing Trends in Cytokine-CYP Drug Interactions and Relevance to Drug Dosing [Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part II-Minireview] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 The regulation of drug-metabolizing enzymes and transporters by cytokines has been extensively studied in vitro and in clinic. Cytokine-mediated suppression of cytochrome P450 (CYP) or drug transporters may increase or decrease the systemic clearance of drug substrates that are primarily cleared via these pathways; neutralization of cytokines by therapeutic proteins may thereby alter systemic exposures of such drug substrates. The Food and Drug Administration recommends evaluating such clinical drug interactions during clinical development and has provided labeling recommendations for therapeutic proteins. To determine the clinical relevance of these drug interactions to dose adjustments, trends in steady-state exposures of CYP-sensitive substrates coadministered with cytokine modulators as reported in the University of Washington Drug Interaction Database were extracted and examined for each of the CYPs. Coadministration of cytochrome P450 family 3 subfamily A (CYP3A) (midazolam/simvastatin), cytochrome P450 subfamily 2C19 (omeprazole), or cytochrome P450 subfamily 1A2 (caffeine/tizanidine) substrates with anti-interleukin-6 and with anti-interleukin-23 therapeutics led to changes in systemic exposures of CYP substrates ranging from ~ –58% to ~35%; no significant trends were observed for cytochrome P450 subfamily 2D6 (dextromethorphan) and cytochrome P450 subfamily 2C9 (warfarin) substrates. Although none of these changes in systemic exposures have been reported as clinically meaningful, dose adjustment of midazolam for optimal sedation in acute care settings has been reported. Simulated concentration-time profiles of midazolam under conditions of elevated cytokine levels when coadministered with tocilizumab, suggest a ~six- to sevenfold increase in midazolam clearance, suggesting potential implications of cytokine–CYP drug interactions on dose adjustments of sensitive CYP3A substrates in acute care settings. Additionally, this article also provides a brief overview of nonclinical and clinical assessments of cytokine–CYP drug interactions in drug discovery and development. SIGNIFICANCE STATEMENT There has been significant progress in understanding cytokine-mediated drug interactions for CYP-sensitive substrates. This article provides an overview of the progress in this field, including a trend analysis of systemic exposures of CYP-sensitive substrates coadministered with anti-interleukin therapeutics. In addition, the review also provides a perspective of current methods used to assess these drug interactions during drug development and a focus on individualized medicine, particularly in acute care settings. Full Article
end Ghrelin Modulates Voltage-Gated Ca2+ Channels through Voltage-Dependent and Voltage-Independent Pathways in Rat Gastric Vagal Afferent Neurons [Article] By molpharm.aspetjournals.org Published On :: 2024-10-17T05:12:59-07:00 The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca2+ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca2+ currents were inhibited with a log (Ic50) = –2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca2+ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca2+ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca2+ current inhibition was mediated by the Gαi/o or Gαq/11 family of subunits. Treatment with both PTX (Ca2+ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin’s effects on Ca2+ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gαi/o and Gαq/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca2+ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin’s regulation of gastric vagal afferents. SIGNIFICANCE STATEMENT This study demonstrated that in gastric vagal afferent neurons, activation of GHSR1a by ghrelin inhibits voltage-gated Ca2+ channels through both voltage-dependent and voltage-independent signaling pathways. These results provide necessary insights into the cellular mechanism underlying ghrelin regulation of gastric vagal afferent activity, which may benefit future studies investigating ghrelin mimetics to treat gastric motility disorders. Full Article
end Simplified Method for Kinetic and Thermodynamic Screening of Cardiotonic Steroids through the K+-Dependent Phosphatase Activity of Na+/K+-ATPase with Chromogenic pNPP Substrate [Article] By molpharm.aspetjournals.org Published On :: 2024-10-17T05:12:59-07:00 The antitumor effect of cardiotonic steroids (CTS) has stimulated the search for new methods to evaluate both kinetic and thermodynamic aspects of their binding to Na+/K+-ATPase (IUBMB Enzyme Nomenclature). We propose a real-time assay based on a chromogenic substrate for phosphatase activity (pNPPase activity), using only two concentrations with an inhibitory progression curve, to obtain the association rate (kon), dissociation rate (koff), and equilibrium (Ki) constants of CTS for the structure-kinetics relationship in drug screening. We show that changing conditions (from ATPase to pNPPase activity) resulted in an increase of Ki of the cardenolides digitoxigenin, essentially due to a reduction of kon. In contrast, the Ki of the structurally related bufadienolide bufalin increased much less due to the reduction of its koff partially compensating the decrease of its kon. When evaluating the kinetics of 15 natural and semisynthetic CTS, we observed that both kon and koff correlated with Ki (Spearman test), suggesting that differences in potency depend on variations of both kon and koff. A rhamnose in C3 of the steroidal nucleus enhanced the inhibitory potency by a reduction of koff rather than an increase of kon. Raising the temperature did not alter the koff of digitoxin, generating a H (koff) of –10.4 ± 4.3 kJ/mol, suggesting a complex dissociation mechanism. Based on a simple and inexpensive methodology, we determined the values of kon, koff, and Ki of the CTS and provided original kinetics and thermodynamics differences between CTS that could help the design of new compounds. SIGNIFICANCE STATEMENT This study describes a fast, simple, and cost-effective method for the measurement of phosphatase pNPPase activity enabling structure-kinetics relationships of Na+/K+-ATPase inhibitors, which are important compounds due to their antitumor effect and endogenous role. Using 15 compounds, some of them original, this study was able to delineate the kinetics and/or thermodynamics differences due to the type of sugar and lactone ring present in the steroid structure. Full Article
end Regulation of Cannabinoid and Opioid Receptor Levels by Endogenous and Pharmacological Chaperones [Special Section: Cannabinoid Signaling in Human Health and Disease] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Cannabinoid and opioid receptor activities can be modulated by a variety of post-translational mechanisms including the formation of interacting complexes. This study examines the involvement of endogenous and exogenous chaperones in modulating the abundance and activity of cannabinoid CB1 receptor (CB1R), opioid receptor (DOR), and CB1R-DOR interacting complexes. Focusing on endogenous protein chaperones, namely receptor transporter proteins (RTPs), we examined relative mRNA expression in the mouse spinal cord and found RTP4 to be expressed at higher levels compared with other RTPs. Next, we assessed the effect of RTP4 on receptor abundance by manipulating RTP4 expression in cell lines. Overexpression of RTP4 causes an increase and knock-down causes a decrease in the levels of CB1R, DOR, and CB1R-DOR interacting complexes; this is accompanied by parallel changes in signaling. The ability of small molecule lipophilic ligands to function as exogenous chaperones was examined using receptor-selective antagonists. Long-term treatment leads to increases in receptor abundance and activity with no changes in mRNA supporting a role as pharmacological chaperones. Finally, the effect of cannabidiol (CBD), a small molecule ligand and a major active component of cannabis, on receptor abundance and activity in mice was examined. We find that CBD administration leads to increases in receptor abundance and activity in mouse spinal cord. Together, these results highlight a role for chaperones (proteins and small molecules) in modulating levels and activity of CB1R, DOR, and their interacting complexes potentially through mechanisms including receptor maturation and trafficking. SIGNIFICANCE STATEMENT This study highlights a role for chaperones (endogenous and small membrane-permeable molecules) in modulating levels of cannabinoid CB1 receptor, delta opioid receptor, and their interacting complexes. These chaperones could be developed as therapeutics for pathologies involving these receptors. Full Article
end Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics [Special Section: Cannabinoid Signaling in Human Health and Disease-Minireview] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Targeting the endocannabinoid (eCB) signaling system for pain relief is an important treatment option that is only now beginning to be mechanistically explored. In this review, we focus on two recently appreciated cannabinoid-based targeting strategies, treatments with cannabidiol (CBD) and α/β-hydrolase domain containing 6 (ABHD6) inhibitors, which have the exciting potential to produce pain relief through distinct mechanisms of action and without intoxication. We review evidence on plant-derived cannabinoids for pain, with an emphasis on CBD and its multiple molecular targets expressed in pain pathways. We also discuss the function of eCB signaling in regulating pain responses and the therapeutic promises of inhibitors targeting ABHD6, a 2-arachidonoylglycerol (2-AG)-hydrolyzing enzyme. Finally, we discuss how the novel cannabinoid biosensor GRABeCB2.0 may be leveraged to enable the discovery of targets modulated by cannabinoids at a circuit-specific level. SIGNIFICANCE STATEMENT Cannabis has been used by humans as an effective medicine for millennia, including for pain management. Recent evidence emphasizes the therapeutic potential of compounds that modulate endocannabinoid signaling. Specifically, cannabidiol and inhibitors of the enzyme ABHD6 represent promising strategies to achieve pain relief by modulating endocannabinoid signaling in pain pathways via distinct, nonintoxicating mechanisms of action. Full Article
end No In Vivo Evidence for Estrogen Receptor Density Changes in Human Neuroendocrine Aging or Their Relationship to Cognition and Menopausal Symptoms By jnm.snmjournals.org Published On :: 2024-11-01T04:25:31-07:00 Full Article
end Routine Use of [64Cu]Cu-DOTATATE PET/CT in a Neuroendocrine Tumor Center: Referral Patterns and Image Results of 2,249 Consecutive Scans By jnm.snmjournals.org Published On :: 2024-11-01T04:25:31-07:00 The role of somatostatin receptor (SSTR) PET/CT, using 68Ga-based tracers or [64Cu]Cu-DOTATATE (64Cu-DOTATATE), in the management of patients with neuroendocrine neoplasm (NEN) is guided by appropriate use criteria (AUC). In this study, we performed systematic analyses of referral patterns and image findings of routine 64Cu-DOTATATE PET/CT scans to support AUC development. Methods: We included all clinical routine 64Cu-DOTATATE PET/CT scans performed between April 10, 2018 (start of clinical use), and May 2, 2022, at Copenhagen University Hospital–Rigshospitalet. We reviewed the referral text and image report of each scan and classified the indication according to clinical scenarios as listed in the AUC. Results: In total, 1,290 patients underwent 2,249 64Cu-DOTATATE PET/CT scans. Monitoring of patients with NEN seen both on conventional imaging and on SSTR PET without clinical evidence of progression was the most common indication (defined as "may be appropriate" in the AUC) and accounted for 703 (31.3%) scans. Initial staging after NEN diagnosis ("appropriate" in the AUC) and restaging after curative-intent surgery ("may be appropriate" in the AUC) accounted for 221 (9.8%) and 241 (10.7%) scans, respectively. Selection of patients eligible for peptide receptor radionuclide therapy ("appropriate" in the AUC) and restaging after peptide receptor radionuclide therapy completion ("appropriate" in the AUC) accounted for 95 (4.2%) and 115 (5.1%) scans, respectively. The number of scans performed for indications not defined in the AUC was 371 (16.5%). Image result analysis revealed no disease in 669 scans (29.7%), stable disease in 582 (25.9%), and progression in 461 (20.5%). In 99 of the 461 (21.5%) scans, progression was detected on PET but not on CT. Conclusion: Our study provided real-life data that may contribute to support development of 64Cu-DOTATATE/SSTR PET/CT guidelines including AUC. Some scenarios listed as "may be appropriate" in the current AUC were frequent in our data. Monitoring of patients with NEN without clinical evidence of progression was the most frequent indication for 64Cu-DOTATATE PET/CT, in which disease progression was detected in more than one third, and a large proportion was visible by PET only. We therefore conclude that this scenario could potentially be classified as appropriate. Full Article
end Cardiac Neuroendocrine Tumor Metastases on 68Ga-DOTATATE PET/CT: Identification and Prognostic Significance By jnm.snmjournals.org Published On :: 2024-11-01T04:25:31-07:00 Neuroendocrine tumor (NET) metastases to the heart are found in 1%–4% of NET patients and have been reported primarily in the form of individual cases. We investigated the prevalence, clinical characteristics, imaging features, and outcomes of NET patients with cardiac metastases on 68Ga-DOTATATE PET/CT. Methods: 68Ga-DOTATATE PET/CT of 490 consecutive patients from a single institution were retrospectively reviewed for sites of metastases. The cumulative cardiovascular event rate and overall survival of patients with cardiac NET metastases (CNMs) were compared with those of a control group of metastatic NET patients without cardiac metastases. In patients with CNMs, the cardiac SUVmax with and without normalization to the myocardial background uptake was compared with a separate cohort of 11 patients with active cardiac sarcoidosis who underwent 68Ga-DOTATATE PET/CT for research purposes. Results: In total, 270 patients with metastatic NETs were identified, 9 (3.3%) of whom had CNMs. All 9 patients had grade 1–2 gastroenteropancreatic NETs, most commonly from the small intestine (7 patients). The control group consisted of 140 patients with metastatic grade 1–2 gastroenteropancreatic NETs. On Kaplan–Meier analysis, there was no significant difference in the risk of cardiovascular adverse events (P = 0.91 on log-rank test) or mortality (P = 0.83) between the metastatic NET patients with and without cardiac metastases. The degree of cardiac DOTATATE uptake was significantly higher in CNMs than in patients with cardiac sarcoidosis without overlap, in terms of both cardiac SUVmax (P = 0.027) and SUVmax–to–myocardial background ratio (P = 0.021). Conclusion: Routine 68Ga-DOTATATE PET/CT can be used to identify CNMs in 3% of patients with metastatic NETs. CNMs do not confer added cardiovascular or mortality risk. A distinguishing feature of CNMs is their high degree of DOTATATE uptake compared with focal myocardial inflammation. Full Article
end An Extended Follow-up of Spinal Instrumentation Rescue with Cement Augmentation [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
end Optimal Endovascular Therapy Technique for Isolated Intracranial Atherothrombotic Stroke-Related Large-Vessel Occlusion in the Acute-to-Subacute Stage [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
end Ependymal Tumors: Overview of the Recent World Health Organization Histopathologic and Genetic Updates with an Imaging Characteristic [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
end Deep molecular tracking over the 12-yr development of endometrial cancer from hyperplasia in a single patient [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Although the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-yr development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially designed 58-gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic/likely pathogenic mutations in seven genes, APC, ARID1A, CTNNB1, CDKN2A, KRAS, PTEN, and TP53, were identified. A PTEN nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this PTEN mutation, the only other recurrent mutation was KRAS G12D, which was present in six biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The PTEN p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%), and, notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single PTEN mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance toward medical and nonsurgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease PTEN mutant allele fractions to precancerous levels. Full Article
end Weight trends among adults with diabetes or hypertension during the COVID-19 pandemic: an observational study using OpenSAFELY By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 BackgroundCOVID-19 pandemic restrictions may have influenced behaviours related to weight.AimTo describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic.Design and settingAn observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP.MethodClinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression.ResultsData were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = −0.1 kg/m2/year [interquartile range {IQR} −0.7–0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60–69 years versus 18–29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR −0.6–0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D.ConclusionAmong adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions. Full Article
end Deep End Kawasaki/Yokohama: A New Challenge for GPs in Deprived Areas in Japan [Innovations in Primary Care] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
end Roadside serendipity: an accident can lead to a rare diagnosis By breathe.ersjournals.com Published On :: 2024-11-12T00:25:08-08:00 Full Article
end Small cell lung cancer and neuroendocrine tumours By breathe.ersjournals.com Published On :: 2024-11-12T00:25:08-08:00 Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership. Full Article
end The Team Behind Heretic Talks That Ending, The Book of Mormon, and Monopoly By gizmodo.com Published On :: Tue, 12 Nov 2024 17:00:26 +0000 Writer-director partners Scott Beck and Bryan Woods dive into the biggest spoilers of their new Hugh Grant thriller. Full Article Movies Bryan Woods Heretic Scott Beck
end Deepfakes and gender based violence By rabble.ca Published On :: Tue, 07 Nov 2023 18:39:49 +0000 Deepfakes can be close to indistinguishable from authentic video, and are now being used to perpetrate gender based abuse. The post Deepfakes and gender based violence appeared first on rabble.ca. Full Article Feminism Human Rights Deepfakes gender based violence Woman Abuse Prevention Month
end Iraqi, Kurdish forces in standoff, weeks after Kurdish vote for independence By www.pbs.org Published On :: Sun, 15 Oct 2017 20:33:23 +0000 Watch Video | Listen to the AudioHARI SREENIVASAN: The desire of the Kurds along Iraq’s northern border to govern themselves is receiving more resistance from Iraq’s central government. Iraqi army forces are demanding Kurdish troops withdraw from oil fields and military bases around Kirkuk, a city in the Kurdistan region that voted for independence last month. Kirkuk also has 10% of Iraq’s known oil reserves. Washington Post’s Loveday Morris is in Baghdad covering this standoff joins me now via Skype. First of all the significance of this. Why is it so important? LOVEDAY MORRIS: There’s been a longtime conflict between Baghdad and Kurdistan over these disputed territories. Most significant of which is Kirkuk because of the oil reserves. But the referendum last month has really sharpened these disputes because you have Baghdad opposing independence and so it feels like they have to restate its territorial claims these areas. So that’s why we’re seeing a lot of tension right now. HARI SREENIVASAN: And just to give people a little bit of a brief timeline – Iraqi forces control this area for a while and then in June ISIS took over the area and now it’s kind of back in Kurdish hands? LOVEDAY MORRIS: Right. So in June 2014 Iraq lost control of a lot of the areas and we have this huge collapse in the face of an ISIS offensive. Over 100,000 soldiers fled and Kurdish forces moved in some of these areas – some of them maybe took from ISIS and others just moved into into the vacuum. And so Iraqi forces have been in these areas since June 2014. And that’s their main demand that they return to the areas. HARI SREENIVASAN: What’s the likelihood that this standoff right now turns violent? Into some sort of a civil war? LOVEDAY MORRIS:: I think at this point both sides don’t want violence. Al-Abadi, the prime minister, is really trying to defuse the situation by saying there’s going to be no military attack. But at the same time there is this buildup of forces so that I think they are trying to, in a way, intimidate the Kurds to withdraw from some areas but they don’t want to see a fight per say. But in this really tense situation there can be a small spark and things can turn violent quite easily. HARI SREENIVASAN: Thank you. The post Iraqi, Kurdish forces in standoff, weeks after Kurdish vote for independence appeared first on PBS NewsHour. Full Article iraq Kurdistan middle east NewsHour Weekend
end Sarwar: Scottish Government must follow Chancellor and extend rates relief By www.heraldscotland.com Published On :: Tue, 12 Nov 2024 17:43:29 +0000 Ministers must follow the UK Government and extend rates relief for businesses in Scotland, Anas Sarwar has said. Full Article
end RPG Cast – Episode 588: “Nintendo Leaked Themselves” By rpgamer.com Published On :: Sat, 12 Jun 2021 19:28:07 +0000 On this week's show, Chris is going through his failed Kickstarters; Anna Marie is off banging a ghost, which was fun; Kelley is collecting wheels of cheese in Skyrim; Josh is lookin' fly in his Yakuza shoes; and Alex wonders why he didn't just skip this week and write more E3 stories. The post RPG Cast – Episode 588: “Nintendo Leaked Themselves” appeared first on RPGamer. Full Article News Podcasts RPG Cast Edge of Eternity Final Fantasy VII Remake Final Fantasy XIV: Stormblood The Elder Scrolls Online
end RPG Cast – Episode 595: “I’m With the PS5, I Don’t Like Your Range Extender” By rpgamer.com Published On :: Sat, 07 Aug 2021 18:49:33 +0000 Kelley's cat tosses a coin to The Witcher. Chris finds out there's just too many pigs. And Josh goes to Reddit, but all he finds is a meme. The post RPG Cast – Episode 595: “I’m With the PS5, I Don’t Like Your Range Extender” appeared first on RPGamer. Full Article News Podcasts RPG Cast Disgaea 6 Fuga: Melodies of Steel
end RPG Cast – Episode 667: “Nintendo Has an Animal Crossing Jail?” By rpgamer.com Published On :: Sat, 04 Mar 2023 20:47:31 +0000 Kelley is the master of the hunting horn. Chris is too old to play Solid Snake. Robert only steals from old people. And Ryan stuffs all the kids into the cannon. The post RPG Cast – Episode 667: “Nintendo Has an Animal Crossing Jail?” appeared first on RPGamer. Full Article News Podcasts RPG Cast 8-Bit Adventures 2 Fuga: Melodies of Steel Pokémon Scarlet / Violet The Legend of Heroes: Trails in the Sky Theatrhythm Final Bar Line Valkyrie Profile
end RPG Cast – Episode 674: “Stop Sending Dragons, I Have Things to Do” By rpgamer.com Published On :: Sat, 29 Apr 2023 20:02:26 +0000 Jason and Robert have a weeb-off. Kelley dies for two days and wakes up in her own sweat. Chris goes to a store that's half comics, half anime, and half body pillows. Bullseye! The post RPG Cast – Episode 674: “Stop Sending Dragons, I Have Things to Do” appeared first on RPGamer. Full Article News Podcasts RPG Cast Final Fantasy Pixel Remaster Skyrim Yakuza Zero
end RPG Cast – Episode 676: “Sending All Our Love to the Korok Down the Well” By rpgamer.com Published On :: Sat, 13 May 2023 20:31:14 +0000 Sam brings the sexy back to RPG Cast. Chris goes down the rabbit hole of Skyrim Mods. Kelley's cannon stuffs kids into itself. And Josh collects a series of progressively larger vegetables. The post RPG Cast – Episode 676: “Sending All Our Love to the Korok Down the Well” appeared first on RPGamer. Full Article News Podcasts RPG Cast Fuga: Melodies of Steel 2 Like a Dragon: Ishin! Skyrim The Legend of Heroes: Trails from Zero The Legend of Zelda: Tears of the Kingdom
end RPG Cast – Episode 692: “Vending Machine Isekai” By rpgamer.com Published On :: Sat, 23 Sep 2023 20:19:14 +0000 Josh learns that despite Bethesda's best efforts, Starfield is not Fallout 76. Robert learns the taste of Amiibo blood. Chris is just here to ask, "kink-why?" And Kelley is obsessed with Red XIII on a chocobo. The post RPG Cast – Episode 692: “Vending Machine Isekai” appeared first on RPGamer. Full Article News Podcasts RPG Cast Disgaea 7 Sea of Stars Starfield The Legend of Nayuta: Boundless Trails Xenoblade Chronicles 3
end RPG Cast – Episode 745: “The Shipwreck Ending” By rpgamer.com Published On :: Sat, 26 Oct 2024 19:52:40 +0000 Chris eats around dirty grapes. Kelley plays the goose class of Monster Hunter. Ryan runs out of disc space until he deletes a Rogue Trader save file. Don't get distracted by salsa. The post RPG Cast – Episode 745: “The Shipwreck Ending” appeared first on RPGamer. Full Article News Podcasts RPG Cast Diablo IV Metaphor: ReFantazio Ys X: Nordics
end The Vinyl Factory: Reverb exhibition extended until 22 December By www.factmag.com Published On :: Wed, 18 Sep 2024 12:18:58 +0000 Reverb features new works by Es Devlin and Theaster Gates, plus Devon Turnbull's Listening Room. The post The Vinyl Factory: Reverb exhibition extended until 22 December appeared first on Fact Magazine. Full Article Exhibitions Featured Stories Featured Top Reverb