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Crisaborole, a nonsteroidal phosphodiesterase 4 inhibitor, represents the first nonsteroidal medication approved for the treatment of atopic dermatitis in over a decade. In this work, crisaborole skin permeation and retention was studied in vitro from a 2% ointment using porcine skin as barrier. Crisaborole was also characterized in terms of thermal behavior, solubility, and logP. Control experiments were performed also on tape stripped skin to clarify the role of stratum corneum in drug partitioning and permeation across the skin. The results obtained indicate that crisaborole accumulates into the skin in considerable amounts after application of a topical lipophilic ointment. Crisaborole shows more affinity for the dermis compared to the epidermis despite its relatively high value of partition coefficient; stratum corneum analysis revealed a low affinity of the drug for this skin layer. Skin penetration across hair follicles or sebaceous glands can be a reason for the high dermis retention and is worth further investigation. The comparison with data obtained from a solution in acetonitrile suggests that the formulation plays a certain role in determining the relative distribution of crisaborole in the skin layers and in the receptor compartment.This research work analyses the influence of the use of by-products from a fluorite mine to replace the fine fraction of natural aggregates, on the properties of Ultra-High-Performance Fibre-Reinforced Concrete (UHPFRC). Replacing natural aggregates for different kinds of wastes is becoming common in concrete manufacturing and there are a number of studies into the use of waste from the construction sector in UHPFRC. However, there is very little work concerning the use of waste from the mining industry. Furthermore, most of the existing studies focus on granite wastes. So, using mining sand waste is an innovative alternative to replace natural aggregates in the manufacture of UHPFRC. The substitutions in this study are of 50%, 70% and 100% by volume of 0-0.5 mm natural silica sand. The results obtained show that the variations in the properties of consistency, compressive strength, modulus of elasticity and tensile strength, among others, are acceptable for substitutions of up to 70%. Therefore, fluorite mining sand waste is proved to be a viable alternative in the manufacturing of UHPFRC.The field of multiple myeloma (MM) imaging has evolved. The International Myeloma Working Group recently recommended performing 18F-fluorodeoxyglucose glucose (18FDG) positron emission tomography/computed tomography (PET/CT) with the aim of staging MM patients at baseline and evaluating response to therapy. Novel oncological radiotracers such as 11C-Choline and 18F-Fluorocholine, have been studied in comparison with 18FDG, mostly in MM patients presenting with refractory disease or suspected relapse. Choline-based tracers may overcome some limitations of 18FDG, which include a lack of sensitivity in depicting skull lesions and the fact that 10% of MM patients are FDG-negative. The majority of MM lesions display a higher uptake of Choline than FDG. Amprenavir HIV Protease inhibitor Also, in many situations, Choline may offer better lesion visualization, with a higher tumor to background ratio; however, various patterns of Choline and FDG uptake have been observed in MM and some limitations, notably as regards liver lesions, should be recognized. Overall, Choline may provide additional detection of up to 75% more lesions. This article aims to provide a comprehensive review of the potential role of Choline in multiple myeloma, as compared to FDG, encompassing Choline physiopathology as well as data from clinical studies.Obesity is defined by the World Health Organization (WHO) as a body mass index (BMI) ≥ 30 Kg/m2. This study aimed to test the validity of this BMI cut-off point for adiposity in a weight management clinical setting in Lebanon. This cross-sectional study of 442 adults of mixed gender, categorized by the WHO BMI classification, included 66 individuals of normal weight, 110 who were overweight and 266 with obesity. The clinical sample was referred to the Outpatient Clinic in the Department of Nutrition and Dietetics at Beirut Arab University (BAU) in Lebanon. All participants underwent anthropometric evaluation. The gold standard for defining obesity was based on the National Institutes of Health (NIH)/WHO guidelines for total body fat percentage (BF%). The best sensitivity and specificity were attained to predict obesity, according to the receiver operating characteristic curve (ROC) analysis. The BMI cut-off point for predicting obesity in the clinical sample was nearly 31.5 Kg/m2, and more than 90% of individuals with obesity and cardiometabolic disease were above this cut-off point. In conclusion, this new BMI cut-off point, an obesity definition higher than suggested in Western populations, was demonstrated to have clinical usefulness. Obesity guidelines in Lebanon, therefore, need revising.Sessile serrated adenoma/polyp with dysplasia (SSA/P-D) is an SSA/P with cellular dysplasia and has a higher risk of progressing to colon carcinogenesis. Previously, we reported that tight junction impairment by Clostridium perfringens enterotoxin (CPE) leads to activation of the transcriptional co-activator yes-associated protein (YAP) in oral squamous cell carcinoma. Here, we investigated whether CPE activates YAP to promote the malignant progression of SSA/P. E-cadherin expression was lower in the 12 cases with SSA/P-D examined than that in normal mucosa, SSA/P, or tubular adenoma (TA). Furthermore, intracellular translocation of claudin-4 (CLDN4) and nuclear translocation of YAP were observed. The CPE gene was detected in DNA extracted from SSA/P-D lesions, but not in SSA/P or TA. link2 Treatment of the rat intestinal epithelial cell line IEC6 with low-dose CPE resulted in intracellular translocation of CLDN4 to the cytoplasmic membrane. Cytoplasmic CLDN4 showed co-precipitation with transcriptional co-activatoOur findings further highlight the importance of controlling intestinal flora using probiotics or antibiotics.Targeted agents have improved the efficacy of chemotherapy for cancer patients, however, there remains a lack of understanding of how these therapies affect the unsuspecting bystanders of the stromal microenvironment. Cetuximab, a monoclonal antibody therapy targeting the epidermal growth factor receptor (EGFR), is given in combination with chemotherapy as the standard of care for a subset of metastatic colorectal cancer patients. The overall response to this treatment is underwhelming and, while genetic mutations that confer resistance have been identified, it is still not known why this drug is ineffective for some patients. We discovered that cancer-associated fibroblasts (CAFs), a major cellular subset of the tumor stroma, can provide a source of cancer cell resistance. Specifically, we observed that upon treatment with cetuximab, CAFs increased their secretion of EGF, which was sufficient to render neighboring cancer cells resistant to cetuximab treatment through sustained mitogen-activated protein kinases (MAPK) signaling. Furthermore, we show the cetuximab-induced EGF secretion to be specific to CAFs and not to cancer cells or normal fibroblasts. Altogether, this work emphasizes the importance of the tumor microenvironment and considering the potential unintended consequences of therapeutically targeting cancer-driving proteins on non-tumorigenic cell types.Human cytomegalovirus (HCMV) is a widespread virus that can establish life-long latent infection in large populations. The establishment of latent infection prevents HCMV from being cleared by host cells, and HCMV reactivation from latency can cause severe disease and death in people with immature or compromised immune systems. To establish persistent and latent infection in healthy individuals, HCMV encodes a large array of proteins that can modulate different components and pathways of host cells. It has been reported that pUL138 encoded by the UL133-UL138 polycistronic locus promotes latent infection in primary CD34+ hematopoietic progenitor cells (HPCs) infected in vitro. link3 In this study, recombinant HCMV HanUL138del was constructed by deleting the UL138 locus of Han, a clinical HCMV strain. Then, a comparative quantitative proteomic analysis of Han- and HanUL138del-infected MRC5 cells was performed to study the effect of pUL138 on host cells in the context of HCMV infection. Our results indicated that, during the early phase of HCMV infection, the innate immune response was differentially activated, while during the late phase of HCMV infection, multiple host proteins were differentially expressed between Han- and HanUL138del-infected cells, and these proteins are involved in the oxidation-reduction process, ER to Golgi vesicle-mediated transport, and extracellular matrix organization. Among these proteins, STEAP3, BORCS7, FAM172A, RELL1, and WDR48 were further demonstrated to affect HCMV infection. Our study provides a systematic view of the effect of pUL138 on the host cell proteome and highlights the proposition that multiple biological processes or host factors may be involved in the overall role of the UL133-UL138 polycistronic locus in HCMV persistence.Large oil shale resources are found in Eastern Estonia, where the mineral resource is mined, excavated, and used for electricity generation and shale oil extraction. During industrial activities in the last 100 years, pollutants have been emitted in large amounts, some of which are toxic and carcinogenic. The current study aims to analyse time trends in cancer incidence in the oil shale industry-affected areas and compare them with overall cancer incidence rates and trends in Estonia. We analysed Estonian Cancer Registry data on selected cancer sites that have been previously indicated to have relationships with industrial activities like oil shale extraction. We included lung cancer, kidney cancer, urinary bladder cancer, leukaemia, breast cancer, and non-Hodgkin's lymphoma. A statistically significantly higher lung cancer age-standardized incidence rate (ASIR) was found during the study period (1992-2015) only in males in the oil shale areas as compared to males in Estonia overall 133.6 and 95.5 per 100,000, respectively. However, there appeared to be a statistically significant (p less then 0.05) decrease in the lung cancer ASIR in males in the oil shale areas (overall decrease 28.9%), whereas at the same time, there was a significant increase (p less then 0.05) in non-oil shale areas (13.3%) and in Estonia overall (1.5%). Other cancer sites did not show higher ASIRs in the oil shale industrial areas compared to other areas in Estonia. Possible explanations could be improved environmental quality, socio-economic factors, and other morbidities.Polymers with embedded metal-organic frameworks (MOFs) have been of interest in research for advanced applications in gas separation, catalysis and sensing due to their high porosity and chemical selectivity. In this study, we utilize specific MOFs with high thermal stability and non-centrosymmetric crystal structures (zeolitic imidazolate framework, ZIF-8) in order to give an example of MOF-polymer composite applications in nonlinear optics. The synthesized MOF-based polymethyl methacrylate (PMMA) composite (ZIF-8-PMMA) demonstrates the possibility of the visualization of near-infrared laser beams in the research lab. The resulting ZIF-8-PMMA composite is exposed to a laser under extreme conditions and exhibits enhanced operating limits, much higher than that of the widely used inorganic materials in optics. Overall, our findings support the utilization of MOFs for synthesis of functional composites for optical application.