FBXO4 loss facilitates carcinogen induced papilloma development in mice

Cyclin D1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC) and is considered a key driver of this disease. Mutations in FBXO4, F-box specificity factor that directs SCF-mediated ubiquitylation of cyclin D1, occur in ESCC with concurrent overexpression of cyclin D1 suggesting a potential tumor suppressor role for FBXO4. To evaluate the contribution of FBXO4-dependent regulation cyclin D1 in esophageal squamous cell homeostasis, we exposed FBXO4 knockout mice to N-nitrosomethylbenzylamine (NMBA), an esophageal carcinogen. Our results revealed that loss of FBXO4 function facilitates NMBA induced papillomas in FBXO4 het (+/−) and null (−/−) mice both by numbers and sizes 11 months after single dose NMBA treatment at 2mg/kg by gavage when compared to that in wt (+/+) mice (P < 0.01). No significant difference was noted between heterozygous or nullizygous mice consistent with previous work. To assess cyclin D1/CDK4 dependence, mice were treated with the CDK4/6 specific inhibitor, PD0332991, for 4 weeks. PD0332991 treatment (150mg/kg daily), reduced tumor size and tumor number. Collectively, our data support a role for FBXO4 as a suppressor of esophageal tumorigenesis.     

The RN-BSN bridge course: transitioning the re-entry learner

BACKGROUND: Although most RN-to-BSN programs offer bridge courses, little can be found in the literature about common course objectives, content, or outcomes. METHOD: This article details course objectives, course content, course implementation, and preliminary outcomes of a primarily distance learning RN-to-BSN bridge course at a northern California university. RESULTS: Preliminary outcome assessments suggested greater than expected increases in role and campus socialization, as well as computer literacy, as a result of RN-to-BSN bridge course implementation. CONCLUSION: The RN-to-BSN bridge course can successfully be used to transition the re-entry student and may be the link allowing RN-to-BSN students to effectively face the concurrent challenges of role socialization and computer literacy while mastering course content and course objectives.     

Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson’s disease

Deep brain stimulation (DBS) has emerged as a viable therapy for Parkinson’s disease (PD). The impact of subthalamic nucleus (STN) lead placement (lateral versus medial) on motor outcome, however, has not been systematically evaluated. Forty-eight patients with PD underwent STN-DBS surgery and were evaluated postoperatively for 48 weeks for motor improvement as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (standardized motor examination) and levodopa equivalent daily dose (LEDD). Postoperative MRI was used to identify the location of the active stimulating contact and motor outcome was analyzed. STN-DBS was associated with significant improvement in motor outcome as determined by a reduction in the UPDRS part III subscore from 34.44 ± 1.29 at baseline to 18.76 ± 1.06 at end visit (p < 0.0001) and a reduction in LEDD from 1721 ± 152 mg/day at baseline to 1134 ± 119 mg/day at end visit (p = 0.0024). Patients with stimulating contacts in the medial STN compared to the lateral STN did not demonstrate any significant differences in motor outcome (UPDRS, p = 0.5811; LEDD, p = 0.7341). No significant differences were found in motor outcome between patients with STN stimulation compared to stimulation of surrounding fiber tracts (p = 0.80). No significant difference in stimulation voltage was noted with respect to lead location. Our study did not find a significant effect for the location of active contact and motor outcome neither within the subregions of the STN nor between the STN and surrounding fibers. Further research is needed to better understand the neurophysiological basis for these results.     

Giant cell (cranial) arteritis: a clinical review

Giant cell arteritis is a disease of the elderly which is more common than previously recognized. It is important to be aware of this condition because treatment effectively relieves symptoms and prevents serious complications. The disease is suggested when an elderly patient complains of constitutional symptoms, headache, jaw claudication, or the musculoskeletal manifestations of polymyalgia rheumatica. Abnormalities in temporal arteries or other cranial arteries, or evidence of large vessel involvement may be detected by physical examination. A markedly elevated sedimentation rate in association with other clinical features of the disease strongly suggests giant cell arteritis, but a biopsy should be performed to confirm the diagnosis. Corticosteroid therapy should be started promptly in high doses in order to prevent blindness. Prolonged treatment with lower dose corticosteroids is generally necessary for up to 1 to 2 years, and sometimes longer, for continued symptomatic relief. Long-term follow-up of treated patients has demonstrated no detectable effect on survivorship.     

SARS-CoV-2 Infection Hospitalization Rate and Infection Fatality Rate Among the Non-Congregate Population in Connecticut

BackgroundInfection fatality rate and infection hospitalization rate, defined as the proportion of deaths and hospitalizations, respectively, of the total infected individuals, can estimate the actual toll of coronavirus disease 2019 (COVID-19) on a community, as the denominator is ideally based on a representative sample of a population, which captures the full spectrum of illness, including asymptomatic and untested individuals.ObjectiveTo determine the COVID-19 infection hospitalization rate and infection fatality rate among the non-congregate population in Connecticut between March 1 and June 1, 2020.MethodsThe infection hospitalization rate and infection fatality rate were calculated for adults residing in non-congregate settings in Connecticut prior to June 2020. Individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were estimated using the seroprevalence estimates from the recently conducted Post-Infection Prevalence study. Information on total hospitalizations and deaths was obtained from the Connecticut Hospital Association and the Connecticut Department of Public Health, respectively.ResultsPrior to June 1, 2020, nearly 113,515 (90% confidence interval [CI] 56,758-170,273) individuals were estimated to have SARS-CoV-2 antibodies, and there were 7792 hospitalizations and 1079 deaths among the non-congregate population. The overall COVID-19 infection hospitalization rate and infection fatality rate were estimated to be 6.86% (90% CI, 4.58%-13.72%) and 0.95% (90% CI, 0.63%-1.90%), respectively, and there was variation in these rate estimates across subgroups; older people, men, non-Hispanic Black people, and those belonging to 2 of the counties had a higher burden of adverse outcomes, although the differences between most subgroups were not statistically significant.ConclusionsUsing representative seroprevalence estimates, the overall COVID-19 infection hospitalization rate and infection fatality rate were estimated to be 6.86% and 0.95%, respectively, among community residents in Connecticut.     

Emerging Role of Human Basophil Biology in Health and Disease

Basophils have emerged in recent years as a small but potent subpopulation of leukocytes capable of bridging innate and adaptive immunity. They can be activated through IgE-dependent and IgE-independent mechanisms to release preformed mediators and to produce Th2 cytokines. In addition to their role in protective immunity to helminths, basophils are major participants in allergic reactions as diverse as anaphylaxis and immediate hypersensitivity reactions, late-phase hypersensitivity reactions, and delayed hypersensitivity reactions. Additionally, basophils have been implicated in the pathophysiology of autoimmune diseases such as lupus nephritis and rheumatoid arthritis, and the modulation of immune responses to bacterial infections, as well as being a feature of myelogenous leukemias. Distinct signals for activation, degranulation, transendothelial migration, and immune regulation are being defined, and demonstrate the important role of basophils in promoting a Th2 microenvironment. These mechanistic insights are driving innovative approaches for diagnostic testing and therapeutic targeting of basophils.