EBV BMRF-2 facilitates cell-to-cell spread of virus within polarized oral epithelial cells

We previously reported that the Epstein-Barr virus (EBV) BMRF-2 protein plays an important role in EBV infection of polarized oral epithelial cells by interacting with β1 and αv family integrins. Here we show that infection of polarized oral epithelial cells with B27-BMRF-2^low recombinant virus, expressing a low level of BMRF-2, resulted in significantly smaller plaques compared with infection by parental B95-8 virus. BMRF-2 localized in the trans-Golgi network (TGN) and basolateral sorting vesicles and was transported to the basolateral membranes of polarized epithelial cells. Mutation of the tyrosine- and dileucine-containing basolateral sorting signal, YLLV, in the cytoplasmic domain of BMRF-2 led to the failure of its accumulation in the TGN and its basolateral transport. These data show that BMRF-2 may play an important role in promoting the spread of EBV progeny virions through lateral membranes of oral epithelial cells.     

Proton therapy in clinical practice

Radiation dose escalation and acceleration improves local control but also increases toxicity.Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients.Compared with photon therapy,proton therapy spares more critical structures due to its unique physics.The physical properties of a proton beam make it ideal for clinical applications.By modulating the Bragg peak of protons in energy and time,a conformal radiation dose with or without intensity mo...     

Analysis of risk factors for distant metastases in squamous cell carcinoma of the oral cavity

BACKGROUND: The number of patients with oral cavity squamous cell carcinoma (OSCC) is increasing. Because the characteristics of patients with OSCC who develop distant metastases (DM) remain uncertain, the authors analyzed potential risk factors. METHODS: For this report, the authors retrospectively reviewed data from 889 consecutive patients with OSCC who underwent radical surgery from January 1996 to November 2004. Patients were divided into 2 groups according to whether they had either achieved locoregional control (Group A; n = 678 patients) or developed a locoregional recurrence (Group B; n = 211 patients). Cox proportional-hazards models were used to identify independent predictors of the 5-year DM rate. RESULTS: In the entire study cohort, the 5-year DM rate was 9.6% (6.6% for Group A and 21.4% for Group B). In Group A, the number of positive lymph nodes (> or =5; P = .009) and the presence of extracapsular spread (ECS) (P < .001) were independent risk factors for DM. In Group B, the presence of ECS (P = .008), poor differentiation (P = .040), pathological stage > or =III (P = .036), and the presence of neck recurrence (P = .001) were independent prognosticators. CONCLUSIONS: The current results indicated that different risk factor categories according to locoregional control may be used to facilitate the selection of appropriate management for patients with OSCC after they undergo radical surgery.     

Evaluation of spatial resolution of a PET scanner through the simulation and experimental measurement of the recovery coefficient

Purpose: In order to measure spatial resolution of a PET tomograph in clinical conditions, this study describes and validates a method based on the recovery coefficient, a factor required to compensate underestimation in measured radioactivity concentration for small structures.Methods: In a PET image, the recovery factors of radioactive spheres were measured and their comparison with simulated recovery coefficients yielded the tomographic spatial resolution. Following this methodology, resolution was determined in different surrounding media and several conditions for reconstruction, including clinical conditions for brain PET studies. All spatial resolution values were compared with those obtained using classical methods with point and line sources.Results: In each considered condition, spatial resolution of the PET image estimated using the recovery coefficient showed good agreement with classical methods measurements, validating the procedure.Conclusion: Measurement of the recovery coefficient provides an assessment of tomographic spatial resolution, particularly in clinical studies conditions.     

A Recursive Model of the Spread of COVID-19: Modelling Study

BackgroundThe major medical and social challenge of the 21st century is COVID-19, caused by the novel coronavirus SARS-CoV-2. Critical issues include the rate at which the coronavirus spreads and the effect of quarantine measures and population vaccination on this rate. Knowledge of the laws of the spread of COVID-19 will enable assessment of the effectiveness and reasonableness of the quarantine measures used, as well as determination of the necessary level of vaccination needed to overcome this crisis.ObjectiveThis study aims to establish the laws of the spread of COVID-19 and to use them to develop a mathematical model to predict changes in the number of active cases over time, possible human losses, and the rate of recovery of patients, to make informed decisions about the number of necessary beds in hospitals, the introduction and type of quarantine measures, and the required threshold of vaccination of the population.MethodsThis study analyzed the onset of COVID-19 spread in countries such as China, Italy, Spain, the United States, the United Kingdom, Japan, France, and Germany based on publicly available statistical data. The change in the number of COVID-19 cases, deaths, and recovered persons over time was examined, considering the possible introduction of quarantine measures and isolation of infected people in these countries. Based on the data, the virus transmissibility and the average duration of the disease at different stages were evaluated, and a model based on the principle of recursion was developed. Its key features are the separation of active (nonisolated) infected persons into a distinct category and the prediction of their number based on the average duration of the disease in the inactive phase and the concentration of these persons in the population in the preceding days.ResultsSpecific values for SARS-CoV-2 transmissibility and COVID-19 duration were estimated for different countries. In China, the viral transmissibility was 3.12 before quarantine measures were implemented and 0.36 after these measures were lifted. For the other countries, the viral transmissibility was 2.28-2.76 initially, and it then decreased to 0.87-1.29 as a result of quarantine measures. Therefore, it can be expected that the spread of SARS-CoV-2 will be suppressed if 56%-64% of the total population becomes vaccinated or survives COVID-19.ConclusionsThe quarantine measures adopted in most countries are too weak compared to those previously used in China. Therefore, it is not expected that the spread of COVID-19 will stop and the disease will cease to exist naturally or owing to quarantine measures. Active vaccination of the population is needed to prevent the spread of COVID-19. Furthermore, the required specific percentage of vaccinated individuals depends on the magnitude of viral transmissibility, which can be evaluated using the proposed model and statistical data for the country of interest.     

Ovine scrapie: Follow-up of sheep belonging to an endemic scrapie-infected flock

There is a close similarity between the unconventional virus-induced ovine scrapie and human Creutzfeldt-Jakob disease. Since infection might be transmitted orally, the ovine production of an endemically scrapie-infected farm was studied. About 80% of the annual production are sold (50% as butcher-meat, 30% as breeding animals), and scrapie appears in 20% of the sheep kept on the farm. Was the same proportion of butcher-meat animals scrapie-infected? Since the scrapie agent has been detected in “clinically normal” lambs, the same problem occurs with breeding-sheep and “apparently healthy” animals: are they carriers of the pathogenic agent? Are they responsible for the spread of the ovine disease and/or of the human disease?     

An Epizootiological Report of the Re‐emergence and Spread of a Lineage of Virulent Newcastle Disease Virus into Eastern Europe

A number of contemporary outbreaks of Newcastle disease (ND) in Israel, Turkey, Georgia and Bulgaria have all been caused by a very similar viruses related to lineage 5a (genotype VIIa). Comparison with published ND virus (NDV) sequences suggests that this virus strain originated in South‐East Asia and on introduction has circulated widely in backyard poultry in the Middle East and into Eastern Europe. An intracerebral pathogenicity index of 1.9 was obtained for a representative isolate from Bulgaria. In addition, the International Reference Laboratory for ND has characterized a molecular epidemiologically linked virus that has been reported to have caused disease in well‐vaccinated broiler chickens in Pakistan. In the 1990s, another strain from the 5a lineage NDV was introduced into Europe and spread across the continent causing numerous outbreaks up to 1999. Despite improved controls, including good diagnostic tests and widespread vaccination, in commercial poultry, the novel circulating NDV strains described here have been established widely in the region and represent an increased risk for similar disease outbreak events to reoccur within the EU.     

Invasive ductal adenocarcinoma of the pancreas may originate from the larger pancreatic duct: a study of 13 tumors less than 2 cm in diameter

Background/Purpose

We aimed to elucidate the origin/primary site of invasive ductal adenocarcinoma of the pancreas, based on the distribution of intraductal carcinoma components. These components were identified by a mural elastic fiber cuff.

Methods

Thirteen specimens from patients with invasive ductal adenocarcinoma (microscopically, less than 2?cm in diameter) of the pancreas were studied histopathologically. Variants of invasive ductal adenocarcinoma and intraductal papillary-mucinous carcinoma were excluded.

Results

Intraductal carcinoma components of invasive ductal adenocarcinoma were found in 12 of the specimens 13 (92%), and were observed within the tumor mass and/or on its boundary, or outside the tumor mass. Intraductal components were characterized by low papillary projections lacking a fibrovascular core, with/without surrounding tubular structures, or by irregular stratification and pleomorphism of the epithelial cells. Invasive components mostly showed a tubular pattern with desmoplasia. The distribution of the intraductal components in the 12 specimens was as follows: in 9 (75%), they were in both the main pancreatic duct and large branch ducts; and in 3, they were in the smaller branch ducts only.

Conclusions

Invasive ductal adenocarcinomas of the pancreas may originate most frequently from the main pancreatic duct or larger branch ducts, while the smaller ducts are less often the site of cancer origin.