The Genetic Basis of Primary Myelofibrosis and Its Clinical Relevance

Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, recent data has shed light on the complex and dynamic structure of PMF, that involves competing disease subclones, sequentially acquired genomic events, mostly in genes that are recurrently mutated in several myeloid neoplasms and in clonal hematopoiesis, and biological interactions between clonal hematopoietic stem cells and abnormal bone marrow niches. These observations may contribute to explain the wide heterogeneity in patients’ clinical presentation and prognosis, and support the recent effort to include molecular information in prognostic scoring systems used for therapeutic decision-making, leading to promising clinical translation. In this review, we aim to address the topic of PMF molecular genetics, focusing on four questions: (1) what is the role of mutations on disease pathogenesis? (2) what is their impact on patients’ clinical phenotype? (3) how do we integrate gene mutations in the risk stratification process? (4) how do we take advantage of molecular genetics when it comes to treatment decisions?     

Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.     

Italian multicentre study on microbial environmental contamination in dental clinics: a pilot study

The dental practice is associated with a high risk of infections, both for patients and healthcare operators, and the environment may play an important role in the transmission of infectious diseases. A microbiological environmental investigation was carried out in six dental clinics as a pilot study for a larger multicentre study that will be performed by the Italian SItI (Society of Hygiene, Preventive Medicine and Public Health) working group "Hygiene in Dentistry". Microbial contamination of water, air and surfaces was assessed in each clinic during the five working days of the week, before and during treatments. Air and surfaces were also examined at the end of the daily activity. A wide variation was found in microbial environmental contamination, both within the participating clinics and relative to the different sampling times. Microbial water contamination in Dental Unit Water Systems (DUWS) reached values of up to 26 × 10⁴ cfu/mL (colony forming units per millilitre). P. aeruginosa was found in 33% of the sampled DUWS and Legionella spp. in 50%. A significant decrease in the Total Viable Count (TVC) was recorded during the activity. Microbial air contamination showed the highest levels during dental treatments and tended to decrease at the end of the working activity (p < 0.05). Microbial buildup on surfaces increased significantly during the working hours. As these findings point out, research on microbial environmental contamination and the related risk factors in dental clinics should be expanded and should also be based on larger collections of data, in order to provide the essential knowledge aimed at targeted preventive interventions.     

Wear Performance of Dental Materials: A Comparison of Substructure Ceramics,Veneering Ceramics,and Non‐Precious Alloys

The aim of this in vitro study was to compare the two‐body wear resistance of different dental ceramics and non‐precious alloys. Two‐body wear tests were performed in a chewing simulator with steatite antagonists. A pin‐on‐block design with a vertical load of 50 N for 1.2 × 10⁵ cycles (f = 1.6 Hz; lateral movement: 1 mm, mouth opening: 2 mm) was used for the wear test. Surface roughness R_a (SP6, Perthen‐Feinprüf, G) and wear depth were determined using a 3D‐Profilometer (Laserscan 3D, Willytec, G). Scanning electron microscopy (Quanta FEG 400, FEI, NL) was applied for evaluating wear performance of both, materials and antagonists. Statistics: one‐way ANOVA (α = 0.05). The in vitro wear test showed that the wear performance of dental materials is strongly influenced by the type of material (ceramic, zirconia, or alloy). Zirconia and alloy provided low wear in contrast to glass‐ceramic systems. In contradiction to common expectations, hard zirconia and alloy systems showed even lower antagonistic wear than glass‐ceramics.     

Observations on the electrical resistivity of steel fibre reinforced concrete

Steel fibre reinforced concrete (SFRC) is in many ways a well-known construction material, and its use has gradually increased over the last decades. The mechanical properties of SFRC are well described based on the theories of fracture mechanics. However, knowledge on other material properties, including the electrical resistivity, is sparse. Among others, the electrical resistivity of concrete has an effect on the corrosion process of possible embedded bar reinforcement and transfer of stray current. The present paper provides experimental results concerning the influence of the fibre volume fraction and the moisture content of the SFRC on its electrical resistivity. The electrical resistivity was measured by alternating current (AC) at 126 Hz. Moreover, an analytical model for the prediction of the electrical resistivity of SFRC is presented. The analytical model is capable of predicting the observed correlation between the fibre volume fraction and the electrical resistivity of the composite (the SFRC) for conductive fibres and moisture saturated concrete. This indicates that the steel fibres were conducting when measuring the electrical resistivity by AC at 126 Hz. For partly saturated concrete the model underestimated the influence of the addition of fibres. The results indicate that the addition of steel fibres reduce the electrical resistivity of concrete if the fibres are conductive. This represents a hypothetical case where all fibres are depassivated (corroding) which was created to obtain a conservative estimate on the influence of fibres on the electrical resistivity of concrete. It was observed that within typical ranges of variation the influence of the moisture content on the electrical resistivity was larger than the effect of addition of conductive steel fibres, but also that the relative impact on the electrical resistivity due to conductive steel fibres increased when the moisture content of the concrete was reduced.     

Deficits in emotion-regulation skills predict alcohol use during and after cognitive–behavioral therapy for alcohol dependence.

Objective: As emotion regulation is widely considered to be a primary motive in the misuse of alcohol, our aim in the study was to investigate whether deficits in adaptive emotion-regulation skills maintain alcohol dependence (AD). Method: A prospective study investigated whether emotion-regulation skills were associated with AD and whether these skills predicted alcohol use during and after treatment for AD. Participants were 116 individuals treated for AD with cognitive–behavioral therapy. Emotion regulation and severity of AD symptoms were assessed by self-report. Alcohol use during treatment was assessed by Breathalyzer and urine analysis for ethyl glucuronide; alcohol use during the 3-month follow-up interval was assessed by self-report. Results: Pretreatment emotion-regulation skills predicted alcohol use during treatment, and posttreatment emotion-regulation skills predicted alcohol use at follow-up, even when controlling for other predictors potentially related to emotion regulation. Among a broad range of specific emotion-regulation skills, the ability to tolerate negative emotions was the only skill that negatively predicted subsequent alcohol consumption when controlling for the other skills. Individuals in the AD sample reported significantly larger deficits in emotion-regulation skills than did those in a nonclinical control sample but significantly less than did those in a sample of individuals exclusively meeting criteria for major depressive disorder. Conclusions: Enhancement of general emotion-regulation skills, especially the ability to tolerate negative emotions, appears to be an important target in the treatment of AD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Longitudinal analysis of the formation and realisation of preferences to move into homeownership in the Netherlands

This study investigates how life course characteristics and housing market circumstances affect the formation and realisation of preferences to move into homeownership. Using a data set from the Netherlands in which data from three cross-sectional housing surveys are enriched with longitudinal register data for the period 1998–2008, we follow aspiring homeowners regarding their actual residential behaviour. We find that only 31 % of the aspiring homeowners became homeowners within 2 years, approximately 13 % moved to rental homes, and the vast majority did not move at all. Insufficient socioeconomic resources and a high house price-to-rent ratio hamper the realisation of preferences to move into homeownership. However, these hampering factors are at least as important as the extent to which individuals prefer to move into homeownership. This last finding suggests that housing tenure preferences cannot be viewed as ‘pure’ preferences.