Lundewilladsen2583
In consistent with in vivo results, SH-SY5Y cells treatment with cholesterol (50 μM, 100 μM) for 48 h culture in vitro demonstrated that pro-apoptotic proteins were enhanced as well. In brief, short-term HFD consumption increases sensitivity to apoptosis, APP and IL-1β production as well as gliosis in cerebral cortex and cerebellum, which may be related to enhancement of ERK1/2 and p38 MAPK activation.The anticancer effect of zinc oxide nanoparticles (ZnO NPs) largely relies on cellular responses such as alteration of gene expression. Although ZnO NPs have been reported to induce transcriptional changes, the potential of ZnO NPs to affect cellular translatome remains largely unknown. Using ribosome profiling, we demonstrated that the transcription of 78 genes and the translation of 1,448 genes are affected during one hour of ZnO NPs exposure in A549 human lung cancer cells. The mitogen-activated protein kinase (MAPK) pathway is up-regulated upon ZnO NP treatment. The upstream open reading frame (uORF) plays a pervasive role in the induction of up-regulated genes, including TLNRD1 and CCNB1IP1. Knockdown of TLNRD1 or CCNB1IP1 reduces ZnO NP-induced cytotoxicity. Together, our study characterizes the landscape of translational alteration under ZnO NPs treatment and provides potential targets to augment the anticancer effect of ZnO NPs.The N-methyl-D-aspartate receptor (NMDAR) plays a crucial role in neurodegenerative diseases such as Alzheimer's disease and in the treatment of major depression by new fast-acting antidepressants such as ketamine. Given their broad implications, GluN2B-containing NMDARs have been of large interest as diagnostic and therapeutic targets. Recently, (R)-11C-Me-NB1 was investigated preclinically and shown to be a promising radioligand for imaging GluN2B subunits. Here, we report on the performance characteristics of this novel radioligand in a first-in-human PET study. Methods Six healthy male subjects were scanned twice on a fully-integrated PET/MR scanner with (R)-11C-Me-NB1 for 120 min. Brain uptake and tracer distribution over time were investigated by standardized uptake values (SUV). Test-retest reliability was assessed with the absolute percentage difference (APD) and the coefficient of variation (COV). Exploratory total volumes of distribution (VT) were computed using an arterial input function and the Lohelp in the selection of appropriate doses of GluN2B-targeting drugs.Background The European Association of Urology (EAU) Prostate Cancer Guidelines Panel recommends risk groups for biochemically recurrent prostate cancer (BCR) to identify men at high risk of progression or metastatic disease. Recent United States Food and Drug Administration approval for 68Ga-PSMA-11 and growing availability of PSMA-directed PET imaging (PSMA PET) will impact disease localization in majority of men with BCR. We determined the rates of local and metastatic disease in recurrent and persistent prostate cancer stratified by EAU BCR risk groups and biochemical persistence (BCP). Patients and Methods Patients with BCR/BCP were enrolled under the same prospective clinical trial protocol conducted at three sites (n = 1777, 91%; UCLA n = 662, NCT02940262; UCSF n = 508, NCT03353740; Michigan, n = 607, NCT03396874); 183 patients with BCP from Universities of Essen, Bologna, and Munich (TUM) were included retrospectively. Patients with BCR had to have sufficient data to determine EAU risk score. Multivark assessment.Introduction Fibroblast activation protein inhibitor positron emission tomography (FAPI-PET) is a new tool in the diagnostic workup of cancer. With growing volume of applications pitfalls and common findings need to be considered for Ga-68-FAPI-PET image interpretation. The aim of this study was to summarize common findings and report pitfalls in Ga-68-FAPI-PET. mTOR inhibitor Methods and materials 91 patients underwent whole-body PET/CT with either FAPI-04 (N = 25) or FAPI-46 (N = 66). Findings were rated in a consensus session of two experienced readers. Pitfalls and common findings were defined as focal or localized uptake above background and categorized as unspecific / non-malignant and grouped into degenerative, muscular, scarring / wound-healing, uterine, mammary glands and head-and-neck findings. Frequency of findings was reported on a per-patient and per-group basis and SUVmax, SUVmean and SUVpeak was measured. Results Non-tumor specific tracer uptake was found in 81.3 % of patients. The most frequent finding was tracer uptake in degenerative lesions (51.6%) with mean SUVmax 7.7 ± 2.9 and head-and-neck (45.1%) findings. Except for salivary glands, the uptake values did not differ between 10 and 60 min p.i. in most findings. Uterine uptake was found in most women (66.7%) with mean SUVmax 12.2 ± 7.3 and uptake correlated negatively with age (SUVmax r = -0.6, p less then 0.01; SUVpeak r = -0.57, p less then 0.01; SUVmean r = -0.58, p less then 0.01). Conclusion Pitfalls include non-tumor specific Ga-68-FAPI uptake in degenerative lesions, muscle, head-and-neck, scarring, mammary glands or uterus. Here we summarize findings to inform readers at centers introducing Ga-68-FAPI-PET to avoid common mistakes.To investigate diagnostic and prognostic value of 18F-FDG PET/CT for surveillance imaging in patients treated for Stage III Merkel cell carcinoma (MCC). Methods This retrospective study included 61 consecutive stage III MCC patients, who were clinically asymptomatic and underwent surveillance FDG-PET/CT. Findings were correlated with either pathology and/or clinical/imaging follow-up. Median follow-up period was 4.8 years. Statistical analyses were performed. Results FDG-PET/CT detected unsuspected recurrences in 33% patients (20/61) with lesion-based sensitivity, specificity, and accuracy of 92%, 93%, and 93%, respectively. Mean±SD SUV for malignant and benign lesions was 7.5±3.9 and 3.8±2.0, respectively. Unknown distant metastases, as first recurrence site, were noted in 12 of 61 patients. Those with positive disease on FDG-PET/CT within one year of definitive treatment had relatively worse overall survival (p less then 0.0001). After adjustment on stage, risk of death increased with higher SUVmax (HR for one unit=1.17;P = 0.006) and with a higher number of positive lesions on FDG-PET/CT (HR for one additional lesion = 1.60;p less then 0.001). Conclusion Post-definitive treatment surveillance FDG-PET/CT scan detects unsuspected recurrences and has prognostic value. Inclusion of FDG-PET/CT within the first 6 months after definitive treatment would be appropriate for surveillance and early detection of recurrence. Our data merits further studies to evaluate the prognostic implications.
Referrals of transgender and gender-diverse (trans) youth to medical clinics for gender-affirming care have increased. We described characteristics of trans youth in Canada at first referral visit.
Baseline clinical and survey data (2017-2019) were collected for Trans Youth CAN!, a 10-clinic prospective cohort of
= 174 pubertal and postpubertal youth <16 years with gender dysphoria, referred for hormonal suppression or hormone therapy, and 160 linked parent-participants. Measures assessed health, demographics, and visit outcome.
Of youth, 137 were transmasculine (assigned female) and 37 transfeminine (assigned male); 69.0% were aged 14 to 15, 18.8% Indigenous, 6.6% visible minorities, 25.7% from immigrant families, and 27.1% low income. Most (66.0%) were gender-aware before age 12. Only 58.1% of transfeminine youth lived in their gender full-time versus 90.1% of transmasculine (
< .001). Although transmasculine youth were more likely than transfeminine youth to report depressive symptoms (21.2% vs 10.8%;
= .03) and anxiety (66.1% vs 33.3%;
< .001), suicidality was similarly high overall (past-year ideation 34.5%, attempts 16.8%). All were in school; 62.0% reported strong parental gender support, with parents the most common support persons (91.9%). Two-thirds of families reported external gender-related stressors. Youth had met with a range of providers (68.5% with a family physician). At clinic visit, 62.4% were prescribed hormonal suppression or hormone therapy, most commonly depot leuprolide acetate.
Trans youth in Canada attending clinics for hormonal suppression or gender-affirming hormones were generally healthy but with depression, anxiety, and support needs.
Trans youth in Canada attending clinics for hormonal suppression or gender-affirming hormones were generally healthy but with depression, anxiety, and support needs.BACKGROUND Irritable bowel syndrome (IBS) is a brain-gut disorder characterized by abdominal pain and altered bowel habits. While the etiology of IBS remains unclear, stress in adulthood or in early life, has been shown to be a significant factor in the development of IBS symptomatology. Evidence suggests that aberrant calcitonin-gene related peptide (CGRP) signaling may be involved in afferent sensitization and visceral organ hypersensitivity. Here, we utilize a monoclonal anti-CGRP F(ab')2 fragment antibody to test the hypothesis that inhibition of peripheral CGRP signaling reverses colonic hypersensitivity induced by either chronic adult stress or early life stress. METHODS A cohort of adult male rats were exposed to repeated water avoidance stress (WAS). Additionally, a second cohort consisting of female rats were exposed to a female-specific neonatal odor-attachment learning paradigm of unpredictable early life stress (ELS). Colonic sensitivity was then assessed in adult animals via behavioral responses early life stress. CGRP targeting antibodies are approved for migraine prevention and our results suggest that targeting CGRP may provide a novel treatment strategy for IBS-related stress-induced visceral pain.
Reflex syncope is the most common subtype of syncope and, despite not being associated with increased mortality, often results in significant morbidity and costly diagnostics. Reflex syncope can be of concern for certain occupational groups and may be exacerbated by some occupations. Reflex syncope in the military is anecdotally common but the extent in the UK Armed Forces (UKAF) is unknown. The aim of this study was to assess the incidence and prevalence of reflex syncope in the UKAF.
A retrospective search of the Defence Medical Information Capability Programme using prespecified read-codes was performed at defence primary healthcare centres over the period of 1 January 2019 to 1 January 2020. Data were obtained on 76 103 service personnel (SP) (53% of the UKAF).
The overall syncope case rate for the UKAF was 10.5 per 1000 person-years (p-yrs). In comparing services there was a significantly increased risk of syncope in the British Army (10.7 per 1000 p-yrs) compared with the Royal Air Force (8.6 per mprove the health and well-being of SP, with economic, logistical and reputational benefits for the UKAF. Further research to identify personnel at risk of future syncopal events may allow for targeted use of countermeasures.
Pediatric hospitalists increasingly provide sedation outside the operating room. Given the large body of safety data available, propofol was identified as a beneficial addition to our hospitalist-run sedation service's medication repertoire. Currently, the training required for hospitalists to provide sedation is defined and determined locally by individual institutions.
We convened a task force to develop and implement training for hospitalists in the use of propofol for deep sedation. After implementing training, we analyzed the outcome of patients receiving propofol for deep sedation for MRI, including the adverse event rate and successful completion rate. An adverse event was defined as a significant desaturation, persistent upper airway obstruction, laryngospasm, administration of neuromuscular blockade, conversion to anesthesia, call for additional backup, or if the procedure was not able to be completed. Successful completion was defined as any patient being able to complete the imaging study or procedure with sedation performed by a hospitalist physician.
