Expression of mPGES1 and p16 in feline and human oral squamous cell carcinoma: A comparative oncology approach.

Comparative cancer studies help us determine if discoveries in one species apply to another. Feline and human oral squamous cell carcinoma (FOSCC and HOSCC) are invasive tumours in which inflammation and abnormal p16 expression are reported. Immunohistochemistry was used to determine the expression of p16 and microsomal prostaglandin E2 synthase 1 (mPGES1) in 42 HOSCC and 45 FOSCC samples with known expression of cyclooxygenase 2 (COX2) and cluster of differentiation 147 (CD147). High p16 expression was more common in HOSCC tumour cells compared to adjacent stroma and oral epithelium (p < .05), with a similar but statistically nonsignificant pattern in FOSCC. Interestingly, high mPGES1 expression in FOSCC was more common in the adjacent epithelium compared to the other compartments (p < .05). In HOSCC, mPGES1 was more similar between compartments but was numerically more common in the tumour compartment (p > .05). There were nominal (p > 0.05) differences in marker expression between high and low mPGES1 expressing tumours in both species, including high p16 observed more commonly in high mPGES1 tumours, and COX-2 positive tumours being more common in low mPGES1 tumours. High CD147 HOSCC tumours were more common in the high mPGES1 HOSCC group (p < .05). In the FOSCC cohort, where there was no statistical difference in CD147 expression between high and low mPGES1 tumours, there were numerically higher CD147 cases in the high mPGES1group. Different expression patterns in FOSCC and HOSCC could be related to different risk factors. For example, p16 is a marker of papillomavirus-driven HOSCC, but a causal relationship between papillomaviruses and FOSCC has yet to be definitively demonstrated. The significance of high P16 expression in the absence of papillomavirus infection deserves further study, and the relative contributions of COX2 and mPGES1 to tumour inflammation and progression should be explored. The findings reveal potential similarities in FOSCC and HOSCC biology, while also demonstrating differences that may relate to risk factors and pathogenesis that are unique to each species.

Providing quality employment services to people living with asthma in the vocational rehabilitation program: A model for meeting the needs of an emerging clientele.

BACKGROUND: With incidence and prevalence rates of asthma diagnoses steadily increasing in the United States and worldwide over the past 30 years, people with asthma are an emerging vocational rehabilitation (VR) consumer population. OBJECTIVE: This article describes the job acquisition and return to work considerations facing employees with asthma. METHODS: Following an overview of the etiology, incidence, prevalence, and career development implications of this chronic respiratory disease, the authors present career preparatory and return to work recommendations to meet the needs of Americans with asthma across the phases of the VR process. RESULTS: The importance of access to quality healthcare, lifestyle, and environmental modifications to promote respiratory health, employer consultation, workplace accommodations and universal design, and interface with medical and mental health professionals is emphasized throughout the article. CONCLUSION: Asthma is an emerging disability that disproportionally affects people of color and people who live in poverty. Rehabilitation professionals must be prepared to meet the needs of this growing and diverse clientele as people with asthma seek assistance from the VR program in acquiring, maintaining, and advancing in meaningful, satisfying employment.

A "win-win" perspective on workplace accommodations: RETAIN Kentucky's self-advocacy guide to promote successful return to work and stay at work outcomes for workers with disabilities.

BACKGROUND: Research has long documented the low cost and effectiveness of most workplace accommodations to enable qualified people with disabilities to seek, secure, and maintain employment. OBJECTIVE AND METHOD: RETAIN Kentucky's return to work and stay at work intervention involves focused training for participants on requesting needed accommodations from their employers. RESULTS: In this article, we describe the win-win approach to reasonable accommodations, which serves as the basis for helping Kentuckians with disabilities identify and request on-the-job supports to aid in their efforts to remain in the workforce. CONCLUSIONS: Workers with disabilities are more likely to stay in the workforce and continue making valuable contributions to the national and global economies if they have effective accommodations and other employment supports available to them.

Return to work considerations in the lingering COVID-19 Era: Long COVID, multiple chemical sensitivity, and universal design.

This article discusses how COVID-19 has impacted the American workforce, symptoms of Long COVID syndrome, Multiple Chemical Sensitivity, and ways to avoid triggering its symptoms when sanitizing the workplace and using Universal Design practices to increase accessibility and decrease transmission of COVID-19 among workers. Interface with healthcare providers, rehabilitation professionals, and employers is emphasized.

Educational Case: Antiglomerular Basement Membrane Disease as an Example of Antibody-Mediated Glomerulonephritis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Informing Policy Change: A Study of Rapid Repeat Pregnancy in Adolescents to Increase Access to Immediate Postpartum Contraception.

Background: Rapid repeat pregnancy (RRP) is common among adolescents and is associated with adverse maternal and infant outcomes. Despite evidence that use of long-acting forms of contraception before hospital discharge can help minimize RRP rates, barriers to placement existed within the state of Indiana. We sought to determine state-specific RRP and induced abortion rates for adolescents based on chosen postpartum contraception to inform policy change. Methods: We examined a retrospective cohort of 227 adolescents (ages 12-18 years) who gave birth in Indiana between 2010 and 2012. Demographics, postpartum contraception, and subsequent pregnancies or abortions after the sentinel delivery were obtained. Rates of RRP based on type of immediate postpartum contraception, etonogestrel (ENG) contraceptive implant, depo-medroxyprogesterone acetate (DMPA) injection, and short-acting methods were compared. Bivariate and logistic regression analyses were conducted. Results: RRP rates were 3.7% for those with ENG contraceptive implant, 22.6% for those with DMPA, and 39.1% for those who choose short-acting methods (p = 0.01). Adolescents who did not choose an ENG contraceptive implant were significantly more likely to have an RRP (adjusted odds ratio [aOR] = 11.8, 95% confidence interval: 2.74-110.3), compared with other contraceptive methods, even after adjusting for covariates such as age, prior pregnancies, and postpartum visit attendance. Conclusions: Immediate postpartum receipt of ENG implant was significantly associated with a lower likelihood of RRP in adolescents in Indiana. These data facilitated state policy change regarding insurance reimbursement to improve statewide access for all women, regardless of age, showing how local data can inform policy change.

Educational Case: Lupus Nephritis as an Example of Immune Complex-Mediated Glomerulonephritis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Dysproteinemic Nephropathies: Renal Amyloidosis as an Example.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Cyclooxygenase and CD147 expression in oral squamous cell carcinoma patient samples and cell lines.

OBJECTIVES: In oral squamous cell carcinoma (OSCC), cyclooxygenases (COX-1 and COX-2) contribute to inflammation, and cluster of differentiation factor 147 (CD147) contributes to invasiveness, but their relationship has not been previously examined within a cohort of patients with OSCC or OSCC cell lines. STUDY DESIGN: COX-2 and CD147 expression was determined by using immunohistochemistry on 39 surgical biopsy specimens of OSCC. Expression in tumor cells, stroma, and adjacent oral epithelium was characterized by using a visual grading system. COX-1, COX-2, and CD147 expression was determined in vitro by using OSCC cell lines (SCC25, BHY, and HN) and reverse transcriptase-quantitative polymerase chain reaction. Secretion of prostagladin E2 (PGE2) from OSCC cell lines was determined by using PGE2 enzyme-linked immunosorbent assay. RESULTS: Biopsy specimens showed higher COX-2 expression in tumor cells compared with stroma and adjacent epithelium (P < .05). There was no difference in CD147 expression among the tumor cells, stroma, and adjacent epithelium. In OSCC cell lines, there was a trend for COX-2 and CD147 gene expression to be coordinated. Interestingly, PGE2 secretion was more closely related to COX-1 expression than to COX-2 expression. CONCLUSIONS: COX-1, COX-2, and CD147 appear to be independently regulated in OSCC, potentially representing 2 therapeutic targets for future investigation. COX-1 expression in OSCC deserves further study because it may be an important determinant of PGE2 secretion from OSCC cells.

Introduction.

This article offers an overview of the life and work of Gerald N. Grob. As part of a generation of scholars intent on overturning the old "Whig history" of medicine, Grob pioneered the use of institutional history as an analytical tool. His work on American psychiatry combined a formidable command of archival sources with a strong commitment to putting medical practice in social context. Grob's personal and political views put him at odds with other scholars of the asylum; he conducted some very public feuds with David Rothman and Andrew Scull. At the same time, he showed a more benevolent side to younger historians interested in psychiatry; he took particular pains to encourage women (including the authors of this introduction) to enter a historical specialty then dominated by men. To honor Grob's legacy as a scholar and a person, this special issue features articles written by several generations of scholars influenced and inspired by his work.

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma.

Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but the expression of CD147 in feline OSCC has not been examined. Immunohistochemistry was used to determine if cyclooxygenase 2 (COX-2) and CD147 expression in feline OSCC biopsies was coordinated. Tumor cells were more likely to express COX-2 (22/43 cases or 51%) compared to stroma (8/43 or 19%) and adjacent oral epithelium (9/31 cases or 29%) (p < 0.05). CD147 was also more likely to occur in tumor cells compared to stroma and adjacent mucosa, with 21/43 (49%) of cases having >50% tumor cells with mild or moderate CD147 expression, compared to 9/28 (32%) in adjacent epithelium and only 5/43 (12%) in adjacent stroma (p < 0.05). In feline OSCC cell lines (SCCF1, SCCF2, and SCCF3), CD147 gene expression was more consistently expressed compared to COX-2, which was 60-fold higher in SCCF2 cells compared to SCCF1 cells (p < 0.05). CD147 expression did not correlate with COX-2 expression and prostaglandin E2 (PGE2) secretion, indicating that they may be independently regulated. CD147 potentially represents a novel therapeutic target for the treatment of feline OSCC and further study of CD147 is warranted.

Life Outcomes and Higher Education: The Need for Longitudinal Research Using a Broad Range of Quality of Life Indicators.

Higher education is increasingly becoming an option for young adults with intellectual disability (ID). Although initial evaluations of postsecondary education for this population have been promising, a broader "quality of life" framework needs to be adopted in order to truly understand the impact of these programs. Moreover, researchers and program evaluators must collect longitudinal data that follows former students for multiple years and uses multiple measures. We conducted a pilot evaluation of the life outcomes of students who had attended at least two semesters in Kentucky's supported higher education program for students with ID, collecting data on life status and experiences using measures from the National Core Indicators-Adult Consumer Survey. The findings from this pilot study show better outcomes for young adults who participated in a postsecondary education program compared to young adults who did not, but these findings need to be considered in light of several limitations. In many respects, our data provided more new questions than answers. Recommendations for collecting and evaluating broad-based, longitudinal data to gain insight into the potential benefits of postsecondary education for people with intellectual disability are discussed.

Depletion of MHC class II invariant chain peptide or γ-δ T-cells ameliorates experimental preeclampsia.

Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia (PE); however, the molecular mechanisms involved are unknown. We tested the hypothesis that Toll-like receptor (TLR) activation induces major histocompatibility complex (MHC) class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause PE-like features in mice. Treatment with VG1177, a competitive antagonist peptide for CLIP in the groove of MHC class II, was able to both prevent and treat PE-like features in mice. We then determined that γ-δ T cells are critical for the development of PE-like features in mice since γ-δ T-cell knockout mice, like CLIP deficient mice, are resistant to developing PE-like features. Placentas from women with PE exhibit significantly increased levels of γ-δ T cells. These preclinical data demonstrate that CLIP expression and activated γ-δ T cells are responsible for the development of immunologic PE-like features and that temporarily antagonizing CLIP and/or γ-δ T cells may be a therapeutic strategy for PE.

EUCOLEUS BOEHMI INFECTION IN THE NASAL CONCHAE AND PARANASAL SINUSES OF RED FOX (VULPES VULPES) ON PRINCE EDWARD ISLAND, CANADA.

Eucoleus boehmi (Nematoda: Capillariidae) occurs in the nasal conchae and paranasal sinuses of wild and domestic canids. We surveyed the red fox ( Vulpes vulpes ) on Prince Edward Island, Canada, for E. boehmi infection and characterized the associated histopathology. Nasal capillarid infections were detected based on histologic examination of three coronal sections of the nasal cavity and by centrifugal flotation examination (CFE) of rectal feces. Capillarids were detected in histologic sections in 28 of 36 (78%) foxes; detection occurred most frequently in the caudal section (28 foxes) and least in the rostral section (10 foxes). Adult worm morphology was typical for capillarids (stichosome esophagus, bacillary bands, bipolar plugged eggs); E. boehmi eggs were specifically identified based on the characteristic pitted shell wall surface. Adult worms were detected in histologic sections in all 28 and E. boehmi eggs in 21 of the positive foxes. No eggs of Eucoleus aerophilus were observed in any of the sections. Affected foxes had an eosinophilic and lymphoplasmacytic rhinitis with goblet cell hyperplasia. Eggs of E. aerophilus were detected on CFE in 20 of 36 (56%) foxes; 19 of the histologically positive foxes were coinfected with E. aerophilus. Eggs of E. boehmi were detected on CFE in 26 of 36 (72%) foxes and were consistent in size and morphology with those described from wild canids, but they differed from those reported from cases of infection in dogs. Prevalence based on identification of eggs on histologic section or CFE indicated 27 of 36 (75%) red foxes examined were infected with E. boehmi.

Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice.

Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144-111 mmHg; TLR7 145-106 mmHg; both P<0.05), and also normalized their elevated urinary protein:creatinine ratios (TLR3 5.68-3.72; TLR7 5.57-3.84; both P<0.05). On gestational day 17, aortic endothelium-dependent relaxation responses improved significantly in TLR3-induced and TLR7-induced hypertensive mice that received PLX-PAD cells on gestational day 14 (TLR3 35-65%; TLR7 37-63%; both P<0.05). In addition, markers of systemic inflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX-PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during pregnancy and have a potential therapeutic role in pre-eclampsia treatment.

Congregational Participation of a National Sample of Adults With Intellectual and Developmental Disabilities.

Supporting people with intellectual and developmental disabilities (IDD) to thrive requires careful consideration of multiple avenues of community involvement. Yet little attention has focused on the place of faith community participation in the lives of adults with IDD. We examined attendance at religious services using National Core Indicator data for a sample of 12,706 adults with IDD residing in 24 states. Almost half of adults (48.3%) reported attending a religious service in the past month, and more than one third (34.6%) attended 3 or more times. Religious involvement varied considerably based on a variety of individual (e.g., race, disability type, behavioral support needs, communication mode) and contextual factors (e.g., geographic locale, residential type). Moreover, monthly involvement in religious activities was much less common than participation in other community activities (i.e., exercise, entertainment, eating out, shopping). We offer recommendations for supporting the spiritual lives of adults with IDD, as well as highlight areas for future research and practice.

Students with intellectual disability in higher education: adult service provider perspectives.

Postsecondary education (PSE) is increasingly becoming an option for students with intellectual disability (ID; Grigal & Hart, 2012 ). Postsecondary education offers the promise of pursuing a valued social role (that of college student), enhanced social networks, and, most significantly, increased employment options. To date, research and practice in the area of transition to PSE for students with ID has focused primarily upon the sending (public school systems) and receiving (colleges or universities) agencies ( Oertle & Bragg, 2014 ; Thoma et al., 2011 ). Yet adults with ID often require ongoing supports through state and federally funded developmental disability waivers, and agency providers of waiver services have, for the most part, not been part of this vital conversation. This study represents an exploratory study of directors of developmental disability provider agencies in one midwestern state to assess their knowledge of PSE for individuals with ID. A total of 87 directors responded; quantitative results are presented and, based on these findings, we provide implications for the future.

Clinical signs, pathology and dose-dependent survival of adult wood frogs, Rana sylvatica, inoculated orally with frog virus 3 Ranavirus sp., Iridoviridae.

Amphibian populations suffer massive mortalities from infection with frog virus 3 FV3, genus Ranavirus, family Iridoviridae, a pathogen also involved in mortalities of fish and reptiles. Experimental oral infection with FV3 in captive-raised adult wood frogs, Rana sylvatica Lithobates sylvaticus, was performed as the first step in establishing a native North American animal model of ranaviral disease to study pathogenesis and host response. Oral dosing was successful LD50 was 10(2.93 2.423.44) p.f.u. for frogs averaging 35mm in length. Onset of clinical signs occurred 614days post-infection p.i. median 11 days p.i. and time to death was 1014 days p.i. median 12 days p.i.. Each tenfold increase in virus dose increased the odds of dying by 23-fold and accelerated onset of clinical signs and death by approximately 15. Ranavirus DNA was demonstrated in skin and liver of all frogs that died or were euthanized because of severe clinical signs. Shedding of virus occurred in faeces 710 days p.i. 34.5days before death and skin sheds 10 days p.i. 01.5days before death of some frogs dead from infection. Most common lesions were dermal erosion and haemorrhages haematopoietic necrosis in bone marrow, kidney, spleen and liver and necrosis in renal glomeruli, tongue, gastrointestinal tract and urinary bladder mucosa. Presence of ranavirus in lesions was confirmed by immunohistochemistry. Intracytoplasmic inclusion bodies probably viral were present in the bone marrow and the epithelia of the oral cavity, gastrointestinal tract, renal tubules and urinary bladder. Our work describes a ranaviruswood frog model and provides estimates that can be incorporated into ranavirus disease ecology models.

Estimation of total glomerular number using an integrated disector method in embryonic and postnatal kidneys.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are a polymorphic group of clinical disorders comprising the major cause of renal failure in children. Included within CAKUT is a wide spectrum of developmental malformations ranging from renal agenesis, renal hypoplasia and renal dysplasia (maldifferentiation of renal tissue), each characterized by varying deficits in nephron number. First presented in the Brenner Hypothesis, low congenital nephron endowment is becoming recognized as an antecedent cause of adult-onset hypertension, a leading cause of coronary heart disease, stroke, and renal failure in North America. Genetic mouse models of impaired nephrogenesis and nephron endowment provide a critical framework for understanding the origins of human kidney disease. Current methods to quantitate nephron number include (i) acid maceration (ii) estimation of nephron number from a small number of tissue sections (iii) imaging modalities such as MRI and (iv) the gold standard physical disector/fractionator method. Despite its accuracy, the physical disector/fractionator method is rarely employed because it is labour-intensive, time-consuming and costly to perform. Consequently, less rigourous methods of nephron estimation are routinely employed by many laboratories. Here we present an updated, digitized version of the physical disector/fractionator method using free open source Fiji software, which we have termed the integrated disector method. This updated version of the gold standard modality accurately, rapidly and cost-effectively quantitates nephron number in embryonic and post-natal mouse kidneys, and can be easily adapted for stereological measurements in other organ systems.

Les anomalies congénitales du rein et des voies urinaires (Congenital Anomalies of the Kidney and Urinary Tract, CAKUT) désignent un groupe polymorphe d'entités cliniques qui constitue la cause la plus fréquente d'insuffisance rénale chez l'enfant. Le CAKUT comprend aussi un grand nombre de malformations développementales, dont le syndrome de Potter, l'hypoplasie rénale, ainsi que la dysplasie rénale (maldifférentiation des tissus rénaux), toutes caractérisées par un déficit de néphrons. On reconnaît de plus en plus une masse néphronique congénitale réduite, d'abord présentée dans l'hypothèse de Brenner, comme une cause de l'hypertension chez l'adulte, de coronaropathie, d'AVC, et d'insuffisance rénale en Amérique du Nord. Les modèles génétiques de souris comportant une détérioration de la fonction rénale et de la masse néphronique fournissent un cadre pour permettre la compréhension de l'origine des néphropathies chez l'humain. Les méthodes actuelles de quantification des néphrons comprennent (i) la macération acide (ii) l'estimation du nombre de néphrons à partir d'une petite quantité de tissus sectionnés (iii) les modes d'imagerie tels que l'IRM et (iv) la technique de référence du disecteur et fractionnement. Malgré sa précision, cette dernière méthode n'est employée que rarement, puisqu'elle requiert main-d'œuvre, temps et argent. Par conséquent, plusieurs laboratoires emploient systématiquement des méthodes moins rigoureuses d'estimation du nombre de néphrons. Nous présentons ici une version mise à jour et numérisée de la technique du disecteur et fractionnement, que nous appelons la technique intégrée du disecteur, en utilisant Fiji, un logiciel ouvert et gratuit. Cette version mise à jour de la modalité de référence permet de quantifier les néphrons de manière précise, rapide et rentable dans les reins de souris à l'état embryonnaire ou postnatal, et peut aisément être adaptée aux mesures stéréologiques d'autres organes.

Using research evidence to inform public policy decisions.

The application of scientific data in the development and implementation of sound public policy is a well-established practice, but there appears to be less consensus on the nature of the strategies that can and should be used to incorporate research data into policy decisions. This paper describes the promise and the challenges of using research evidence to inform public policy. Most specifically, we demonstrate how the application of a large-scale data set, the National Core Indicators (NCI), can be systematically used to drive state-level policy decisions, and we describe a case example of one state's application of NCI data to make significant changes to its Intellectual and Developmental Disabilities waiver. The need for continued research in this area is highlighted.