Comparative analysis of tumor capsule thickness and other histologic features in encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

Recent reclassification of a subset of non-invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) tumors as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has led to important changes in the clinical management of patients with these indolent lesions. Although there are established diagnostic criteria to differentiate NIFTP from EFVPTC, our objective was to determine further differences in histological characteristics between NIFTP and noninvasive EFVPTC. Additionally, we sought to identify histological differences between non-invasive and invasive EFVPTC lesions beyond the key finding of invasion. 68 encapsulated follicular lesions with papillary-like nuclear features from patients treated at Thomas Jefferson University Hospital were subcategorized into NIFTP, non-invasive EFVPTC, and invasive EFVPTC based on current diagnostic criteria. Histological characteristics such as capsule thickness, lesion size, fibrosis, and presence of established exclusionary criteria for NIFTP were recorded. Capsule thickness was significantly smaller in NIFTP (

Adrenal Metastases as Sanctuary Sites in Advanced Renal Cancer

Involvement of the adrenal gland in kidney cancer represents a unique site of metastasis with a distinct clinical course. The cases are typically resistant to immune therapy and need local therapy management. A case series of patients with adrenal metastases was reviewed to highlight the nuances of clinical course and therapy. We reviewed renal cancer carcinoma (RCC) cases with adrenal metastases at Karmanos Cancer Center, Detroit MI. Medical records were reviewed to collect relevant case information. Next-generation sequencing, tumor mutation burden testing, and programmed death ligand biomarkers were evaluated in five cases. Twelve cases were reviewed; all were males with a median age of 49.5 years. Three patients presented with adrenal metastases only and were treated with local therapy. Three received interleukin-2 (IL-2). One patient relapsed with bilateral adrenal lesions after 11 years of remission, post-IL-2 therapy. Five cases received immune checkpoint inhibitor (ICI) and one received antivascular therapy. ICI therapy was followed by ablation of residual adrenal metastases in three patients. Genomic profiling was available in five cases. All were BAP1 and PD-L1 negative. Pathogenic mutations in PBRM1, SETD2, and VHL were noted. All patients with residual adrenal metastases responded to antivascular therapies or to local ablation. One patient died 17 years after diagnosis and 11 patients are alive at a median follow-up of 9.5 years. Adrenal metastases in RCC have a distinct clinical course. They can represent a sanctuary site of relapse/residual disease following treatment with immune therapy. Management with local therapy can induce durable remissions. Systemic management with antivascular therapies also demonstrated favorable responses. Further investigation should focus on the unique clinical course and optimal management of adrenal metastases in kidney cancer

Comparing connected language elicitation procedures in persons with aphasia: Concurrent validation of the Story Retell Procedure

Connected language elicitation procedures used to describe and quantify language vary among the many sampling techniques; however, few studies have compared sampling procedures within the same study participants. This study sought to compare the Story Retell Procedure (SRP) to six additional sampling procedures quantifying eight verbal productivity, three verbal disruption, and two syntactic measures. Results from thirteen individuals with aphasia revealed substantial inter-subject variability with high correlation coefficients between the SRP and other language elicitation tasks for the majority of the linguistic measures. The SRP produced either no difference across tasks or significantly greater instances of the dependent variable

Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma.

Basal cell carcinoma (BCC) incidence is increasing, particularly among adults under the age of 40 years. Pigment-related characteristics are associated with BCC in older populations, but epidemiologic studies among younger individuals and analyses of phenotype-genotype interactions are limited. We examined self-reported phenotypes and melanocortin 1 receptor gene (MC1R) variants in relation to early-onset BCC. BCC cases (n=377) and controls with benign skin conditions (n=390) under the age of 40 years were identified through Yale's Dermatopathology database. Factors most strongly associated with early-onset BCC were skin reaction to first summer sun for 1 hour (severe sunburn vs. tan odds ratio (OR)=12.27, 95% confidence interval (CI)=4.08-36.94) and skin color (very fair vs. olive OR=11.06, 95% CI=5.90-20.74). Individuals with two or more MC1R non-synonymous variants were 3.59 times (95% CI=2.37-5.43) more likely to have BCC than those without non-synonymous variants. All host characteristics and MC1R were more strongly associated with multiple BCC case status (37% of cases) than a single BCC case status. MC1R, number of moles, skin reaction to first summer sun for 1 hour, and hair and skin color were independently associated with BCC. BCC risk conferred by MC1R tended to be stronger among those with darker pigment phenotypes, traditionally considered to be at low risk of skin cancer

A comparison of elicitation procedures for connected language analyses in person with aphasia:Concurrent validation of the Story Retell Procedure

Among the elicited and observed procedures used to describe, classify, diagnose, measure change, quantify severity, and plan intervention for persons with aphasia, the measurement of connected spoken language has become a stable and valued procedure for many of these purposes. Although recognized, the most valid, reliable, and efficient methods for sampling connected language has received relatively little experimental attention from clinical and experimental aphasiologists. The recently developed Story Retell Procedure (SRP) (Doyle, et al, 2000) has the unique measurement advantage of predetermined targets for the retold stories; however, it relies on the comprehension as well as the production of the individual for the samples from which linguistic measurements are performed. Its concurrent validation has not been established

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro

The Vehicle, Spring 1984

Vol. 25, No. 2 Table of Contents The OpeningKathy Fordpage 3 PaintThomas B. Waltrippage 3 PhotographLisa Fresepage 4 City as Castigating AnimalJerry McAnultypage 5 LimitsMichelle Mitchellpage 6 In SilenceKeila Tooleypage 6 PhotographLisa Fresepage 7 Indian CreekJerry McAnultypage 8 The Right Idea about RainMichelle Mitchellpage 8 Van Gogh\u27s Young Male PeasantKeila Tooleypage 9 AbigailMaggie Kennedypage 9 CleaningJennifer K. Soulepage 10 Heat WaveJerry McAnultypage 11 VigilJanet Gracepage 11 Hatred of ClownsMichelle Mitchellpage 12 Trees in the YardKeila Tooleypage 13 Lost on Back RoadsToby Mirabellipage 13 The Death of My Father\u27s HandsGina Grillopage 14 Soft LandingMaggie Kennedypage 14 Incident in the Generic AisleMaggie Kennedypage 15 Happy Well-adjusted Individuals, ConsideringJennifer K. Soulepage 16 Old ManGina Grillopage 17 It Doesn\u27t MatterTed Boonepage 18 A Love Poem for Charles DonaldCathy Moepage 18 David Willey at Whitman WharfSue Oiler Millerpage 19 I Am the ArtsBrenda Renee Drummerpage 20 Mothers and DaughtersJennifer K. Soulepage 22 ScratchesMichelle Mitchellpage 26 SedativeStacey Flanniganpage 26 Calloused HandJanet Gracepage 27 Cool CatStacey Flanniganpage 27 For My History Teacher, Miss WilhelmCathy Moepage 28 Short Poem for Chris\u27s EyesBob Zordanipage 28 MissingMichelle Mitchellpage 29 Over ThereGraham Lewispage 30 Strange BedfellowsMaggie Kennedypage 31 Retired PlumberMichelle Mitchellpage 32 Rumors of War DeadKathy Fordpage 33 Night LightsKeila Tooleypage 33 Fish on the Train TracksJerry McAnultypage 34 DaddyKeily Tooleypage 34 A Message to the MessengerAmy Eadespage 35 Dancing AloneKathy Bowerpage 36 HandsMaggie Kennedypage 36 The Key to the Ladies\u27s RoomMichelle Mitchellpage 37 Crashing the BlueStacey Flanniganpage 37 The Cradle will FallMichelle Mitchellpate 38 One IslandKeila Tooleypage 38 Black Walnut PaintSue Oiler Millerpage 39 SerendipityGraham Lewispage 40 Cover ArtLisa Fresehttps://thekeep.eiu.edu/vehicle/1045/thumbnail.jp

Evangelical Christianity and Women’s Changing Lives

Women have outnumbered men as followers of Christianity at least since the transition to industrial capitalist modernity in the West. Yet developments in women's lives in relation to employment, family and feminist values are challenging their Christian religiosity. Building on a new strand of gender analysis in the sociology of religion, this article argues that gender is central to patterns of religiosity and secularization in the West. It then offers a case study of evangelical Christianity in England to illustrate how changes in women's lives are affecting their religiosity. Specifically, it argues that evangelical Christianity continues to be important among women occupying more traditional social positions (as wives and mothers), but adherence is declining among the growing number whose lives do not fit this older model

Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice.

Introduction: Alzheimer\u27s disease (AD) is the most common form of dementia. Beta-secretase (BACE) inhibitors have been proposed as potential therapeutic interventions; however, initiating treatment once disease has significantly progressed has failed to effectively stop or treat disease. Whether BACE inhibition may have efficacy when administered prophylactically in the early stages of AD has been under-investigated. The present studies aimed to evaluate prophylactic treatment of the BACE inhibitor verubecestat in an AD mouse model using the National Institute on Aging (NIA) resources of the Model Organism Development for Late-Onset Alzheimer\u27s Disease (MODEL-AD) Preclinical Testing Core (PTC) Drug Screening Pipeline. Methods: 5XFAD mice were administered verubecestat ad libitum in chow from 3 to 6 months of age, prior to the onset of significant disease pathology. Following treatment (6 months of age), in vivo imaging was conducted with 18F-florbetapir (AV-45/Amyvid) (18F-AV45) and 18-FDG (fluorodeoxyglucose)-PET (positron emission tomography)/MRI (magnetic resonance imaging), brain and plasma amyloid beta (Aβ) were measured, and the clinical and behavioral characteristics of the mice were assessed and correlated with the pharmacokinetic data. Results: Prophylactic verubecestat treatment resulted in dose- and region-dependent attenuations of 18F-AV45 uptake in male and female 5XFAD mice. Plasma Aβ40 and Aβ42 were also dose-dependently attenuated with treatment. Across the dose range evaluated, side effects including coat color changes and motor alterations were reported, in the absence of cognitive improvement or changes in 18F-FDG uptake. Discussion: Prophylactic treatment with verubecestat resulted in attenuated amyloid plaque deposition when treatment was initiated prior to significant pathology in 5XFAD mice. At the same dose range effective at attenuating Aβ levels, verubecestat produced side effects in the absence of improvements in cognitive function. Taken together these data demonstrate the rigorous translational approaches of the MODEL-AD PTC for interrogating potential therapeutics and provide insight into the limitations of verubecestat as a prophylactic intervention for early-stage AD