Human Papillomavirus (HPV) Detection in Keratotic Variants of Oral Lichen Planus: Negative Results in a Preliminary Open Study

Background During the last few decades, several researches have been identified HPV genomic sequences in Head Neck Squamous Cell Carcinomas (HNSCC) and in Oral Potentially Malignant Disorders (OPMD) hypothesizing a possible viral etiological role. However, the reported prevalence of HPV-DNA (varying from 0% to 100%) in these lesions result still very discordant. Objective Human papillomavirus (HPV) infection in Oral Lichen Planus (OLP) has been largely investigated but not so extensively with respect to its morphological/histopathological features. The possible influence of hyper-keratosis/parakeratosis in HPV detection for keratotic variants of OLP is here proposed and investigated. Materials and methods A total of 45 individuals with keratotic variants of OLP, clinically and histologically confirmed, were consecutively enrolled, before starting any treatment, and underwent oral brushing for HPV investigation. Viral DNA was extracted from oral brushed cells and HPV DNA researched by the combined use of the INNO-LiPA HPV Genotyping system (Innogenetics) and a PCR assay coupled with genome sequencing. Results None of cytological samples collected resulted HPV-positive. Conclusions In this preliminary study, oral HPV infection, investigated by means of a non-invasive oral sampling procedure and a standardized approach for HPV DNA detection, was not showed in any of the investigated cases. The presence of epithelial hyper-keratosis/parakeratosis in some variants of OLP could be a possible cause of impenetrability and/or difficult detection of the virus. Indeed, in case of keratotic variants of OLP, the possible potential false-negative results of HPV investigation by cytological procedure might be possible; on consequence, an alternative approach for viral detection (i.e. by histological sampling) should be considered

Hydrological control of large hurricane-induced lahars: evidence from rainfall-runoff modeling, seismic and video monitoring

Abstract. The Volcán de Colima, one of the most active volcanoes in Mexico, is commonly affected by tropical rains related to hurricanes that form over the Pacific Ocean. In 2011, 2013 and 2015 hurricanes Jova, Manuel and Patricia, respectively, triggered tropical storms that deposited up to 400 mm of rain in 36 h, with maximum intensities of 50 mm h −1. The effects were devastating, with the formation of multiple lahars along La Lumbre and Montegrande ravines, which are the most active channels in sediment delivery on the south-southwest flank of the volcano. Deep erosion along the river channels and several marginal landslides were observed, and the arrival of block-rich flow fronts resulted in damages to bridges and paved roads in the distal reaches of the ravines. The temporal sequence of these flow events is reconstructed and analyzed using monitoring data (including video images, seismic records and rainfall data) with respect to the rainfall characteristics and the hydrologic response of the watersheds based on rainfall-runoff numerical simulation. For the studied events, lahars occurred 5–6 h after the onset of rainfall, lasted several hours and were characterized by several pulses with block-rich fronts and a maximum flow discharge of 900 m3 s −1. Rainfall-runoff simulations were performer using the SCS-curve number and the Green–Ampt infiltration models, providing a similar result in the detection of simulated maximum watershed peaks discharge. Results show different behavior for the arrival times of the first lahar pulses that correlate with the simulated catchment's peak discharge for La Lumbre ravine and with the peaks in rainfall intensity for Montegrande ravine. This different behavior is related to the area and shape of the two watersheds. Nevertheless, in all analyzed cases, the largest lahar pulse always corresponds with the last one and correlates with the simulated maximum peak discharge of these catchments. Data presented here show that flow pulses within a lahar are not randomly distributed in time, and they can be correlated with rainfall peak intensity and/or watershed discharge, depending on the watershed area and shape. This outcome has important implications for hazard assessment during extreme hydro-meteorological events, as it could help in providing real-time alerts. A theoretical rainfall distribution curve was designed for Volcán de Colima based on the rainfall and time distribution of hurricanes Manuel and Patricia. This can be used to run simulations using weather forecasts prior to the actual event, in order to estimate the arrival time of main lahar pulses, usually characterized by block-rich fronts, which are responsible for most of the damage to infrastructure and loss of goods and lives

Metrological assessment of DC current comparator resistance bridges

Direct-current comparator bridges (DCC) are the working horses of primary resistance metrology in the intermediate resistance range. Having a ratio accuracy reaching 10^-7 or better, they allow the realization of resistance scales and the calibration of artifact standard resistors for customers. In this paper we compare the performances of three commercial DCC bridges, by performing measurements on resistors in decadal ratios (1 Ω to 10 kΩ) of very high stability in a thermostated environment. The results show that the three bridges give mutually compatible results within the manufacturer’s specifications, therefore mutually validating the bridges; nevertheless, the readings time series show quite different statistical behavior, with internal correlations, making an evaluation of the Type A measurement uncertainty not trivial

Chronic Red Bull Consumption during Adolescence: Effect on Mesocortical and Mesolimbic Dopamine Transmission and Cardiovascular System in Adult Rats

Energy drinks are very popular nonalcoholic beverages among adolescents and young adults for their stimulant effects. Our study aimed to investigate the effect of repeated intraoral Red Bull (RB) infusion on dopamine transmission in the nucleus accumbens shell and core and in the medial prefrontal cortex and on cardiac contractility in adult rats exposed to chronic RB consumption. Rats were subjected to 4 weeks of RB voluntary consumption from adolescence to adulthood. Monitoring of in vivo dopamine was carried out by brain microdialysis. In vitro cardiac contractility was studied on biomechanical properties of isolated left-ventricular papillary muscle. The main finding of the study was that, in treated animals, RB increased shell dopamine via a nonadaptive mechanism, a pattern similar to that of drugs of abuse. No changes in isometric and isotonic mechanical parameters were associated with chronic RB consumption. However, a prolonged time to peak tension and half-time of relaxation and a slower peak rate of tension fall were observed in RB-treated rats. It is likely that RB treatment affects left-ventricular papillary muscle contraction. The neurochemical results here obtained can explain the addictive properties of RB, while the cardiovascular investigation findings suggest a hidden papillary contractility impairment

A quick pipeline for the isolation of 3D cell culture-derived extracellular vesicles

Recent advances in cell biology research regarding extracellular vesicles have highlighted an increasing demand to obtain 3D cell culture-derived EVs, because they are considered to more accurately represent EVs obtained in vivo. However, there is still a grave need for efficient and tunable methodologies to isolate EVs from 3D cell cultures. Using nanofibrillar cellulose (NFC) scaffold as a 3D cell culture matrix, we developed a pipeline of two different approaches for EV isolation from cancer spheroids. A batch method was created for delivering high EV yield at the end of the culture period, and a harvesting method was created to enable time-dependent collection of EVs to combine EV profiling with spheroid development. Both these methods were easy to set up, quick to perform, and they provided a high EV yield. When compared to scaffold-free 3D spheroid cultures on ultra-low affinity plates, the NFC method resulted in similar EV production/cell, but the NFC method was scalable and easier to perform resulting in high EV yields. In summary, we introduce here an NFC-based, innovative pipeline for acquiring EVs from 3D cancer spheroids, which can be tailored to support the needs of variable EV research objectives.Peer reviewe

Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab

The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment

Cost effective assay choice for rare disease study designs

High throughput assays tend to be expensive per subject. Often studies are limited not so much by the number of subjects available as by assay costs, making assay choice a critical issue. We have developed a framework for assay choice that maximises the number of true disease causing mechanisms ‘seen’, given limited resources. Although straightforward, some of the ramifications of our methodology run counter to received wisdom on study design. We illustrate our methodology with examples, and have built a website allowing calculation of quantities of interest to those designing rare disease studies.published_or_final_versio