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7 in 2006; and 132.1 in 2017 (p less then 0.01). Congenital and hereditary diseases of the kidney in 1997 accounted for 66% of all CKD causes; in 2006, for 70%; and in 2017, for 79%. In 2017, children with CKD stages 4 or 5 (except transplanted children) had hypertension (87.5%) and anemia (50%) (p less then 0.01). Children under ≤2 years with CKD were at a 3-fold greater risk of having elevated blood pressure (OR = 3.375, 95% CI 1.186-9.904). Conclusions There was no change in the number of children with CKD in Lithuania; however, the prevalence of CKD increased due to reduced pediatric population. CAKUT remains the main cause of CKD at all time periods. Among children with CKD stages 4 or 5, there were more children with hypertension and anemia. In children who were diagnosed with CKD at an early age hypertension developed at a younger age.Pneumoconiosis is an irreversible chronic disease. With functional limitations and an inability to work, pneumoconiosis patients require support from family caregivers. However, the needs of pneumoconiosis caregivers have been neglected. This study aimed to evaluate the effectiveness of a nurse-led education program, which involved four weekly 90-min workshops led by an experienced nurse and guided by Orem's self-care deficit theory. A single-group, repeated-measure study design was adopted. Caregivers' mental health (Hospital Anxiety and Depression Scale, HADS, four single items for stress, worriedness, tiredness, and insufficient support), caregiving burdens (caregiving burden scale, CBS), and unmet direct support and enabling needs (Carer Support Needs Assessment Tool, CSNAT) were measured at the baseline (T0), immediately after (T1), and one month after intervention (T2); 49, 41, and 28 female participants completed the T0, T1, and T2 measurements. Mean age was 65.9 years old (SD 10.08) with a range between 37 and 85 years old. The program improved the caregivers' mental wellbeing, and reduced their caregiving burdens and their unmet support and enabling needs, both immediately (T1) and one-month after the intervention (T2). In particular, the intervention improved the caregivers' mental wellbeing significantly, specifically depression symptoms, stress, and tiredness immediately after the intervention; and reduced most of their unmet support needs and unmet enabling needs one-month after the intervention. This was the first nurse-led program for pneumoconiosis caregivers and should serve as a foundation for further studies to test the program with robust designs.Caralluma europaea (Guss.) N.E.Br. (C. europaea) is a wild medicinal plant belonging to the family Apocynaceae. It is commonly used in traditional medicines for treating several diseases. The present work aims to evaluate the anti-inflammatory, antibacterial, and antifungal potentials of C. europaea fractions including hydro ethanol (ET CE), n-butanol (But CE), and polyphenol (Poly CE). The chemical composition of hydroethanol, n-butanol, and polyphenol-rich fractions from C. europaea were determined using GC-MS after silylation. The anti-inflammatory effect of hydroethanol, n-butanol, and polyphenol-rich fractions was studied by carrageenan-induced paw edema. Antibacterial and antifungal activities of hydroethanol, n-butanol, and polyphenol-rich fractions against Gram-positive bacteria, Gram-negative bacteria, and yeasts were assessed using the disc diffusion and micro-dilution assays. The findings of the chemical characterization affirmed the presence of interesting bioactive compounds in C. europaea fractions. The polyphenol-rich fraction was the best inhibitor of edema by75.68% after 6 h of treatment. The hydroethanol fraction was the most active against both bacteria and yeasts. This study contributes to society as it provides potential bioactive compounds in C. europaea extract, which may help in fighting nosocomial antibiotic-resistant microbes.In this study, self-cleaning polyester (PET) fabrics were prepared using TiOF2 and hexadecyltrimethoxysilane(HDS) treatment. TiOF2 was synthesized via direct fluorination of a precursor TiO2 at various reaction temperatures. The prepared PET fabrics had superior photocatalytic self-cleaning properties compared with anatase TiO2/HDS-treated PET fabrics under UV and sunlight with 98% decomposition of methylene blue. TiOF2/HDS-treated PET fabrics also had superior superhydrophobic self-cleaning properties compared with anatase TiO2/HDS-treated PET fabrics with a 161° water contact angle and 6° roll-off angle. After the self-cleaning tests of the non-dyed TiOF2/HDS-treated PET fabrics, we prepared dyed TiOF2/HDS-treated PET fabrics to test practical aspects of the treatment method. These PET fabrics were barely stained by tomato ketchup; even when stained, they could be self-cleaned within 4 h. These results suggest that practical self-cleaning PET fabrics with superhydrophobicity and photocatalytic degradation could be prepared using TiOF2/HDS-treatment.Background Calcaneal bone cysts rarely occur and most of them are known to be benign. Among them, simple bone cysts (SBCs) third most commonly occur in the calcaneus and of the many surgical treatment options, endoscopic curettage is recently gaining popularity among surgeons due to its advantages of minimal invasiveness and optimal visualization. As for portal placement for endoscopy, two lateral portals are considered a standard technique, but no rationale has been established for SBCs with abnormal geometry. This case report suggests an SBC with secondary aneurysmal change located outside the Ward's triangle, as well as an appropriate endoscopic approach. Case Presentation An 18-year-old male high school student presented with a main complaint of pain at the hind foot level for the past one year, without significant improvement from conservative treatment. An endoscopic curettage through the lesion specific two posterior portals and bone graft using allogeneic cancellous bone were performed. SBC with a secondary aneurysmal bone cyst was diagnosed on pathology. At a one-year follow-up, the patient was painless and had returned to his regular activities. Physical and radiographic examinations revealed that the lesion was completely healed without any evidence of recurrence. Conclusion For calcaneal bone cysts located at the posterior aspect of the calcaneus, eccentrically medial and abnormally long anterior-posteriorly, we suggest an endoscopic procedure using lesion specific portals such as two posterior portals.Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (-)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 Ink4a; EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.Kinetic modeling and degradation study of liquid polysulfide (LPS)/clay nanocomposite is possible through Ozawa-Flynn-Wall (OFW) and Kissinger methods. Comparing the results of these models with experimental data leads to provide an accurate degradation kinetic evaluation of these materials. To this aim, the morphology and distribution of clay nanoparticles (CNPs) within the LPS matrix were investigated using Field Emission Scanning Electron Microscopy (FESEM) and X-ray diffraction (XRD). To evaluate the interaction between the LPS and the CNPs, the Fourier transform infrared (FTIR) identification was utilized. Furthermore, to investigate the kinetics of degradation, the thermal gravimetric analysis (TGA) and derivative thermogravimetry (DTG) of the samples were used in the nitrogen atmosphere with the help of Kissinger and Ozawa-Flynn-Wall (OFW) models. The characterization results confirmed the homogenous dispersion of the CNPs into the LPS matrix. In addition, the presence of CNPs increased the thermal stability and activation energy (Ea) of the samples at different conversion rates. Moreover, the OFW method was highly consistent with the experimental data and provided an appropriate fit for the degradation kinetics.Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is BARD1 (BRCA1 Associated RING Domain 1)-a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on BARD1 significance in childhood cancer is limited. This study determines the expression level of BARD1 and its isoform beta (β) in three different histogenetic groups of pediatric cancer-neuroblastic tumours, and for the first time in chosen germ cell tumours (GCT), and rhabdomyosarcoma (RMS), using the qPCR method. We found higher expression of beta isoform in tumour compared to healthy tissue with no such changes concerning BARD1 full-length. Additionally, differences in expression of BARD1 β between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of BARD1 β characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the TERT (Telomerase Reverse Transcriptase) gene. In two RMS cases we found deep decrease of BARD1 β in post-chemotherapy samples. This work supports the oncogenicity of the beta isoform in pediatric tumours, as well as demonstrates the differences in its expression depending on the histological type of neoplasm, and the level of maturation in neuroblastic tumours.The effect of polyhedral oligomeric silsesquioxane (POSS) on the synthesis and properties of hybrid organic-inorganic ionogels was investigated using octakis(methacryloxypropyl) silsesquioxane (methacryl-POSS). Ionogels were prepared in situ by thiol-ene photopolymerization of triallyl isocyanurate with pentaerythritol tetrakis(3-mercaptopropionate) in a mixture of imidazolium ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMImNTf2) and propylene carbonate (PC). Investigations included the kinetics of hybrid materials formation and selected physical and mechanical properties. The disadvantage of ionogels without the methacryl-POSS modifier is leakage and insufficient mechanical properties. Modifying the thiol-ene matrix by the addition of methacryl-POSS made it possible to obtain non-leaking ionogels with improved mechanical and conductive properties. The steric hindrance of POSS cages and high-density network formation played important roles in ionogel synthesis decrease of polymerization rate (with almost no effect on conversion), as well as dimensions of the formed polymer spheres during dispersion polymerization (highly cross-linked polymer has poorer solubility in polymerizing medium at a similar conversion, and nucleation begins at lower conversion), an increase of glass transition temperature and puncture strength. Hybrid ionogels with high ionic conductivity in the range of 4.0-5.1 mS∙cm-1 with the maximum parameter for 1.5 wt.% addition of the methacryl-POSS were obtained, which can be associated with ion-pair dissociations in ionic liquid clusters caused by methacryl-POSS.The metabolic tumour volume (MTV) is an independent prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, its measurement is not standardised and is subject to wide variations depending on the method used. This study aimed to compare the reproducibility of MTV measurement as well as the thresholds obtained for each method and their prognostic values. The baseline MTV was measured in 239 consecutive patients treated at Henri Becquerel Centre by two blinded evaluators. Eight methods were compared 3 absolute (SUV (standardised uptake value) ≥ 2.5; SUV≥ liver SUVmax; SUV≥ PERCIST SUV), 1 percentage SUV threshold method (SUV ≥ 41% SUVmax) and 4 adaptive methods (Daisne, Nestle, Fitting, Black). The intraclass correlation coefficients were excellent, from 0.91 to 0.96, for the absolute SUV methods, Black and Nestle methods, and good for 41% SUVmax, Fitting and Daisne methods (0.82 to 0.88), with a significantly lower variability with absolute methods compared to 41% SUVmax (p less then 0.04). Thresholds were found to be specific to each segmentation method and ranged from 295 to 552 cm3. There was a strong correlation between the MTV and patient prognosis regardless of the segmentation method used (p = 0.001 for PFS and OS). The largest inter-observer cut-off variability was observed in the 41% SUVmax method, which resulted in more inter-observer disagreements in the classification of patients between high and low MTV groups. MTV measurements based on absolute SUV criteria were found to be significantly more reproducible than those based on 41% SUVmax criteria. The threshold was specific for each of eight segmentation methods, but all predicted prognosis.In eukaryotic cells, lysosomes play a crucial role in the breakdown of a variety of components ranging from small molecules to complex structures, ascertaining the continuous turnover of cellular building blocks. Furthermore, they act as a regulatory hub for metabolism, being crucially involved in the regulation of major signaling pathways. Currently, ~450 lysosomal proteins can be reproducibly identified in a single cell line by mass spectrometry, most of which are low-abundant, restricting their unbiased proteomic analysis to lysosome-enriched fractions. In the current study, we applied two strategies for the targeted investigation of the lysosomal proteome in complex samples data-independent acquisition (DIA) and parallel reaction monitoring (PRM). Using a lysosome-enriched fraction, mouse embryonic fibroblast whole cell lysate, and mouse liver whole tissue lysate, we investigated the capabilities of DIA and PRM to investigate the lysosomal proteome. While both approaches identified and quantified lysosomal proteins in all sample types, and their data largely correlated, DIA identified on average more proteins, especially for lower complex samples and longer chromatographic gradients. For the highly complex tissue sample and shorter gradients, however, PRM delivered a better performance regarding both identification and quantification of lysosomal proteins. All data are available via ProteomeXchange with identifier PXDD023278.The prognosis of late-stage epithelial ovarian cancer (EOC) patients is affected by chemotherapy response and the malignant potential of the tumor cells. In earlier work, we identified hypermethylation of the runt-related transcription factor 3 gene (RUNX3) as a prognostic biomarker and contrary functions of transcript variants (TV1 and TV2) in A2780 and SKOV3 cells. The aim of the study was to further validate these results and to increase the knowledge about RUNX3 function in EOC. New RUNX3 overexpression models of high-grade serous ovarian cancer (HGSOC) were established and analyzed for phenotypic (IC50 determination, migration, proliferation and angiogenesis assay, DNA damage analysis) and transcriptomic consequences (NGS) of RUNX3 TV1 and TV2 overexpression. Platinum sensitivity was affected by a specific transcript variant depending on BRCA background. RUNX3 TV2 induced an increased sensitivity in BRCA1wt cells (OVCAR3), whereas TV1 increased the sensitivity and induced a G2/M arrest under treatment in BRCA1mut cells (A13-2-12). These different phenotypes relate to differences in DNA repair homologous recombination deficient A13-2-12 cells show less γH2AX foci despite higher levels of Pt-DNA adducts. RNA-Seq analyses prove transcript variant and cell-line-specific RUNX3 effects. Pathway analyses revealed another clinically important function of RUNX3-regulation of angiogenesis. This was confirmed by thrombospondin1 analyses, HUVEC spheroid sprouting assays and proteomic profiling. Importantly, conditioned media (CM) from RUNX3 TV1 overexpressing A13-2-12 cells induced an increased HUVEC sprouting. Altogether, the presented data support the hypothesis of different functions of RUNX3 transcript variants related to the clinically relevant processes-platinum resistance and angiogenesis.Electrical properties tomography (EPT) is an imaging method that uses a magnetic resonance (MR) system to non-invasively determine the spatial distribution of the conductivity and permittivity of the imaged object. This manuscript starts by providing clear definitions about the data required for, and acquired in, EPT, followed by comprehensively formulating the physical equations underlying a large number of analytical EPT techniques. This thorough mathematical overview of EPT harmonizes several EPT techniques in a single type of formulation and gives insight into how they act on the data and what their data requirements are. Furthermore, the review describes machine learning-based algorithms. Matlab code of several differential and iterative integral methods is available upon request.In this study, cement minerals, aluminates, and alkali-free accelerators incorporated with steel fiber were used to scrutinize the influence of accelerating agents on the long-term performance of tunneling shotcrete. Performance tests were identified based on the core compressive strength of mix shotcrete specimens with different types of accelerating agents throughout timeframes of 1, 3, 6, and 12 months. Here, 37 kg of steel fiber was incorporated into the cement mineral and aluminate mixes, and 40 kg of steel fiber was incorporated in an alkali-free mix for the shotcrete mix design. The KSF 2784 and ASTM 214 standards were followed for specimen fabrication and core cutting. For all specimens, shotcrete test panels of 250 × 600 × 500 mm were manufactured for core compressive strength tests conducted using 100, 75 and 55 mm diameter cylindrical molds and a length-to-diameter ratio of 2. The 1-month compressive strength of all test variables satisfied the Korea Expressway Co. standard of 21 MPa. The core compressive strength of the shotcrete specimens showed a tendency to increase with age, but a strength reduction occurred in 6 months and increased again at 12 months. Moreover, the impact of the diameter changes in the shotcrete core specimens was analyzed based on the mixing. For 12 months, a large increase in the core compressive strength occurred, particularly in the alkali-free specimens. The comparison also focused on the relative strength compared with a cast concrete mold and shotcrete core specimens. It is necessary to use alkali-free accelerators considering the long-term performance of tunnels and worker safety.Several corrosion mitigation methods are generally applied to pipelines exposed to corrosive environments. However, in the case of pre-buried pipelines, the only option for corrosion inhibition is cathodic protection (CP). To apply CP, the required current should be defined even though the pipeline is covered with various oxide layers. In this study, an electrochemical acceleration test was used to investigate the synthetic soil corrosion of a pre-buried pipeline. Potentiodynamic polarization experiments were first conducted to ascertain the corrosion current density in the environment, and galvanostatic measurements were performed to accelerate corrosion according to the operating time. In addition, corrosion current density and the properties of the rust layer were investigated via potentiodynamic polarization tests and electrochemical impedance spectroscopy (EIS) tests. The variation in surface corrosion was subsequently analyzed via optical microscopy (OM) and X-ray diffraction (XRD) measurements. Finally, an empirical equation for the optimized CP current requirement, according to the pipeline service time, was derived. This equation can be applied to any corroded pipeline.A cryptic sexual reproductive cycle in Leishmania has been inferred through population genetic studies revealing the presence of hybrid genotypes in natural isolates, with attempts made to decipher sexual strategies by studying complex chromosomal inheritance patterns. A more informative approach is to study the products of controlled, laboratory-based experiments where known strains or species are crossed in the sand fly vector to generate hybrid progeny. These hybrids can be subsequently studied through high resolution sequencing technologies and software suites such as PAINT that disclose inheritance patterns including ploidies, parental chromosome contributions and recombinations, all of which can inform the sexual strategy. In this work, we discuss the computational methods in PAINT that can be used to interpret the sexual strategies adopted specifically by aneuploid organisms and summarize how PAINT has been applied to the analysis of experimental hybrids to reveal meiosis-like sexual recombination in Leishmania.

Fascial layers may play an important role in locomotor mechanics. Recent researches have revealed an association between increases of fascia thickness and reduced joint flexibility in patients with chronic pain. The purpose of this study was to measure and compare, through the use of ultrasound imaging, the thickness of the deep/crural fascia in different points of the leg as well as the epimysial fascia thickness at level 2 of anterior compartment of leg, in male basketball players with history of recurrent ankle sprain and in healthy participants.

A cross-sectional study has been performed using ultrasound imaging to measure deep/crural fascia thickness of anterior, lateral and posterior compartment of the leg at different levels with a new protocol in a sample of 30 subjects, 15 basketball players and 15 healthy participants.

Findings of fascial thickness revealed statistically significant differences (

< 0.01) in epimysial fascia thickness and in deep/crural fascia thickness between levels/compartments of the same group and between two groups. Moreover, Post 3 deep/crural fascia thicknesses (

< 0.001) were decreased showing statistically significant difference for the basketball players group respect the healthy participants group.

These findings suggested that the posterior compartment was thicker than anterior compartment, probably due to a postural reason in both groups. Moreover, they showed an increase of thickness of the epimysial fascia in basketball players with previous ankle sprains. This variability underlines the importance to assess the fasciae and to make results comparable.

These findings suggested that the posterior compartment was thicker than anterior compartment, probably due to a postural reason in both groups. Moreover, they showed an increase of thickness of the epimysial fascia in basketball players with previous ankle sprains. This variability underlines the importance to assess the fasciae and to make results comparable.Urea cycle disorders are enzymopathies resulting from inherited deficiencies in any genes of the cycle. In severe cases, currently available therapies are marginally effective, with liver transplantation being the only definitive treatment. Donor liver availability can limit even this therapy. Identification of novel therapeutics for genetic-based liver diseases requires models that provide measurable hepatic functions and phenotypes. Advances in stem cell and genome editing technologies could provide models for the investigation of cell-based genetic diseases, as well as the platforms for drug discovery. This report demonstrates a practical, and widely applicable, approach that includes the successful reprogramming of somatic cells from a patient with a urea cycle defect, their genetic correction and differentiation into hepatic organoids, and the subsequent demonstration of genetic and phenotypic change in the edited cells consistent with the correction of the defect. While individually rare, there is a large number of other genetic-based liver diseases. The approach described here could be applied to a broad range and a large number of patients with these hepatic diseases where it could serve as an in vitro model, as well as identify successful strategies for corrective cell-based therapy.Many studies have shown both the CD28-D80/86 costimulatory pathway and the PD-1-PD-L1/L2 coinhibitory pathway to be important signals in modulating or decreasing the inflammatory profile in ischemia-reperfusion injury (IRI) or in a solid organ transplant setting. The importance of these two opposing pathways and their potential synergistic effect led our group to design a human fusion recombinant protein with CTLA4 and PD-L2 domains named HYBRI. The objective of our study was to determine the HYBRI binding to the postulated ligands of CTLA4 (CD80) and PD-L2 (PD-1) using the Surface Plasmon Resonance technique and to evaluate the in vivo HYBRI effects on two representative kidney inflammatory models-rat renal IRI and allogeneic kidney transplant. The Surface Plasmon Resonance assay demonstrated the avidity and binding of HYBRI to its targets. HYBRI treatment in the models exerted a high functional and morphological improvement. HYBRI produced a significant amelioration of renal function on day one and two after bilateral warm ischemia and on days seven and nine after transplant, clearly prolonging the animal survival in a life-sustaining renal allograft model. In both models, a significant reduction in histological damage and CD3 and CD68 infiltrating cells was observed. HYBRI decreased the circulating inflammatory cytokines and enriched the FoxP3 peripheral circulating, apart from reducing renal inflammation. In conclusion, the dual and opposite costimulatory targeting with that novel protein offers a good microenvironment profile to protect the ischemic process in the kidney and to prevent the kidney rejection, increasing the animal's chances of survival. HYBRI largely prevents the progression of inflammation in these rat models.We determined the properties of fusion between large unilamellar vesicles (LUVs) and the lipid monolayer by measuring the fluorescence intensity of rhodamine-conjugated phospholipids in cell-sized lipid vesicles. The charge of LUVs (containing cationic lipids) and lipid droplets (containing anionic lipids) promoted lipid membrane fusion. We also investigated the formation of cell-sized lipid vesicles with asymmetric lipid distribution using this fusion method. Moreover, cell-sized asymmetric ganglioside vesicles can be generated from the planar lipid bilayer formed at the interface between the lipid droplets with/without LUVs containing ganglioside. The flip-flop dynamics of ganglioside were observed on the asymmetric ganglioside vesicles. This fusion method can be used to form asymmetric lipid vesicles with poor solubility in n-decane or lipid vesicles containing various types of membrane proteins for the development of complex artificial cell models.

It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (

= 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95lceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7-18) versus 9 months (95% CI, 6-16) and 32 (95% CI, 23-49) versus 27 months (95% CI, 16-35), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, less then 3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM.The effects of using a partly curved porous layer on the thermal management and entropy generation features are studied in a ventilated cavity filled with hybrid nanofluid under the effects of inclined magnetic field by using finite volume method. This study is performed for the range of pertinent parameters of Reynolds number (100≤Re≤1000), magnetic field strength (0≤Ha≤80), permeability of porous region (10-4≤Da≤5×10-2), porous layer height (0.15H≤tp≤0.45H), porous layer position (0.25H≤yp≤0.45H), and curvature size (0≤b≤0.3H). The magnetic field reduces the vortex size, while the average Nusselt number of hot walls increases for Ha number above 20 and highest enhancement is 47% for left vertical wall. The variation in the average Nu with permeability of the layer is about 12.5% and 21% for left and right vertical walls, respectively, while these amounts are 12.5% and 32.5% when the location of the porous layer changes. The entropy generation increases with Hartmann number above 20, while there is 22% increase in the entropy generation for the case at the highest magnetic field. The porous layer height reduced the entropy generation for domain above it and it give the highest contribution to the overall entropy generation. When location of the curved porous layer is varied, the highest variation of entropy generation is attained for the domain below it while the lowest value is obtained at yp=0.3H. When the size of elliptic curvature is varied, the overall entropy generation decreases from b=0 to b=0.2H by about 10% and then increases by 5% from b=0.2H to b=0.3H.(1) Background Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results The results here described show that the CFTR scaffolding protein NHERF1 can be up-regulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3'-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-335-5p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine.

The association between long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and prostate cancer (PC) remains unclear.

We compared incident PC rates as a function of the Omega-3 Index [O3I, erythrocyte eicosapentaenoic and docosahexaenoic acids (EPA + DHA)] in 5607 men (40-80 years of age) seen at the Cooper Clinic who were free of PC at baseline. The average follow-up was 5.1 ± 2.8 years until censoring or reporting a new PC diagnosis. Proportional hazards regression was used to model the linear association between baseline O3I and the age-adjusted time to diagnosis. A meta-analysis of n-3 PUFA biomarker-based studies and incident PC was updated with the present findings.

A total of 116 cases of incident PC were identified. When O3I was examined as a continuous variable, the age-adjusted hazard ratio (HR) (95% CI) was 0.98 (0.89, 1.07;

= 0.25) for each 1% increment in the O3I. The updated meta-analysis with 10 biomarker-based studies found no significant relationship between EPA or DHA levels and risk for PC.

We find no evidence in this study nor in a meta-analysis of similar studies that consuming n-3 PUFA-rich fish or using fish oil supplements affects the risk of PC.

We find no evidence in this study nor in a meta-analysis of similar studies that consuming n-3 PUFA-rich fish or using fish oil supplements affects the risk of PC.

Coronary heart disease (CHD) persists as the leading cause of death worldwide. Cardiovascular prevention and rehabilitation (CVPR) has an interdisciplinary focus, and includes not only in physiological components, but it also addresses psycho-social factors.

The study analysed the Spanish psycho-social data collected during the EUROACTION study. In Spain, two hospitals were randomised in the Valencia community. Coronary patients were prospectively and consecutively identified in both hospitals. The intervention hospital carried out a 16-week CVPR programme, which aimed to assess illness perceptions and establish healthy behaviours in patients and their partners.

Illness perceptions were significantly and inversely associated with anxiety and depression. Low levels of anxiety were associated with better self-management of total cholesterol (

= 0.004) and low-density lipoprotein-cholesterol (

= 0.004). There was concordance at one year among patients and partners who participated in the programme related to anxiety (

< 0.001), fruit consumption (

< 0.001), and vegetable consumption (

< 0.001).

The EUROACTION study emphasised the importance of assessing psycho-social factors in a CVPR programme and the inclusion of family as support in patients' changes in behaviour.

The EUROACTION study emphasised the importance of assessing psycho-social factors in a CVPR programme and the inclusion of family as support in patients' changes in behaviour.Excessive inflammation and tissue damage are pathological hallmarks of chronic pulmonary tuberculosis (TB). Despite decades of research, host regulation of these clinical consequences is poorly understood. A sustained effort has been made to understand the contribution of heme oxygenase-1 (HO-1) to this process. HO-1 is an essential cytoprotective enzyme in the host that controls inflammation and oxidative stress in many pathological conditions. While HO-1 levels are upregulated in animals and patients infected with Mycobacterium tuberculosis (Mtb), how it regulates host responses and disease pathology during TB remains unclear. This lack of clarity is due in part to contradictory studies arguing that HO-1 induction contributes to both host resistance as well as disease progression. In this review, we discuss these conflicting studies and the role of HO-1 in modulating myeloid cell functions during Mtb disease progression. We argue that HO-1 is a promising target for host-directed therapy to improve TB immunopathology.Sapovirus is a common cause of acute gastroenteritis in all age groups. Sapovirus infections are seldom investigated in Spain, and its epidemiology in the country is not well known. The use of molecular diagnostic procedures has allowed a more frequent detection of sapoviruses in patients with diarrhea. A total of 2545 stool samples from patients with acute gastroenteritis attended from June 2018 to February 2020 at the Clinic University Hospital in Valencia, Spain, were analyzed by reverse transcription (RT) and real-time multiplex PCR (RT-PCR) to investigate the etiology of enteric infections. Sapovirus was the second enteric virus detected with a positive rate of 8%, behind norovirus (12.2%) and ahead of rotavirus (7.1%), astrovirus (4.9%) and enteric adenoviruses (2.9%). Most sapovirus infections occurred in infants and young children under 3 years of age (74%) with the highest prevalence in autumn and early winter. Coinfections were found in 25% of the patients with sapovirus diarrhea, mainly with other enteric viruses. Genotyping demonstrated the circulation of seven different genotypes during the study period, with a predominance of genotypes GI.1, GI.2, and GII.1. Phylogenetic analysis showed that genogroup GII strains form a cluster separated from genogroup GI and GV, being genotype GV.1 strains related to genotype GI.1 and GI.2 strains.In vivo clinical applications of nanobodies (VHHs) require molecules that induce minimal immunoresponse and therefore possess sequences as similar as possible to the human VH domain. Although the relative sequence variability in llama nanobodies has been used to identify scaffolds with partially humanized signature, the transformation of the Camelidae hallmarks in the framework2 still represents a major problem. We assessed a set of mutants in silico and experimentally to elucidate what is the contribution of single residues to the VHH stability and how their combinations affect the mutant nanobody stability. We described at molecular level how the interaction among residues belonging to different structural elements enabled a model llama nanobody (C8WT, isolated from a naïve library) to be functional and maintain its stability, despite the analysis of its primary sequence would classify it as aggregation-prone. Five chimeras formed by grafting CDRs isolated from different nanobodies into C8WT scaffold were successfully expressed as soluble proteins and both tested clones preserved their antigen binding specificity. We identified a nanobody with human hallmarks that seems suitable for humanizing selected camelid VHHs by grafting heterologous CDRs in its scaffold and could serve for the preparation of a synthetic library of human-like single domains.Anaplasma phagocytophilum (A. phagocytophilum) is a tick-borne pathogen causing disease in both humans and animals. Human granulocytic anaplasmosis (HGA) is an emerging disease, but despite the remarkable prevalence in European ticks and wild animals, human infection appears underdiagnosed. Several genetic variants are circulating in Europe, including the zoonotic ecotype I. This study investigated A. phagocytophilum occurrence in wild ungulates and their ectoparasites in an area where HGA has been reported. Blood samples from wild ungulates and ectoparasites were screened by biomolecular methods targeting the mps2 gene. The groEL gene was amplified and sequenced to perform genetic characterization and phylogenetic analysis. A total of 188 blood samples were collected from different wild ungulates species showing an overall prevalence of 63.8% (88.7% in wild ruminants and 3.6% in wild boars). The prevalence of A. phagocytophilum DNA in ticks (manly Ixodes ricinus), and keds collected from wild ruminants was high, reflecting the high infection rates obtained in their hosts. Among ticks collected from wild boars (Hyalomma marginatum and Dermacentor marginatus) no DNA was detected. Phylogenetic analysis demonstrated the presence of ecotype I and II. To date, this is the first Italian report of ecotype I in alpine chamois, mouflon, and wild boar species. These findings suggest their role in HGA epidemiology, and the high prevalence detected in this study highlights that this human tick-borne disease deserves further attention.Childhood obesity is a worldwide health emergency. In many cases, it is directly linked to inappropriate eating habits and a sedentary lifestyle. During lockdown aimed at containing the coronavirus disease (COVID-19) spread, children have been forced to stay at home. The present study aimed at investigating the lifestyles of outpatients (aged 5-17 years) with complicated obesity enrolled in the day-hospital food education program at the Children's Hospital Bambino Gesù in Rome. A survey was performed based on a structured questionnaire, investigating dietary habits and lifestyles. The questionnaire answers were rated as "yes/no/sometimes" or "often/never/sometimes". Eighty-eight families correctly completed the questionnaire between March and May 2020. The results highlighted that 85.2% (N = 75) of the patients ate breakfast regularly, and 64.3% (N = 72) consumed fruit as an afternoon snack. However, 21.6% (N = 19) did just "often" home workouts, and 50.0% (N = 44) reported an increase of feeling hungry with "sometimes" frequency. There is a significant relationship of feeling hungry with gender (p less then 0.0001) and age (p = 0.048) and, also, between gender with having breakfast (p = 0.020) and cooking (p = 0.006). Living a healthy lifestyle during lockdown was difficult for the outpatients, mainly due to the increase in a sedentary lifestyle and the increase in feeling hungry, but some healthy eating habits were maintained, as advised during the food education program provided before lockdown.Ulcerative colitis (UC), one of the two main types of inflammatory bowel disease, has no effective treatment. Rosmarinic acid (RA) is a polyphenol that, when administered orally, is metabolised in the small intestine, compromising its beneficial effects. We used chitosan/nutriose-coated niosomes loaded with RA to protect RA from gastric degradation and target the colon and evaluated their effect on acute colitis induced by 4% dextran sodium sulphate (DSS) for seven days in mice. RA-loaded nanovesicles (5, 10 and 20 mg/kg) or free RA (20 mg/kg) were orally administered from three days prior to colitis induction and during days 1, 3, 5 and 7 of DSS administration. RA-loaded nanovesicles improved body weight loss and disease activity index as well as increased mucus production and decreased myeloperoxidase activity and TNF-α production. Moreover, RA-loaded nanovesicles downregulated protein expression of inflammasome components such as NLR family pyrin domain-containing 3 (NLRP3), adaptor protein (ASC) and caspase-1, and the consequent reduction of IL-1β levels. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression increased after the RA-loaded nanovesicles treatment However, these mechanistic changes were not detected with the RA-free treatment. Our findings suggest that the use of chitosan/nutriose-coated niosomes to increase RA local bioavailability could be a promising nutraceutical strategy for oral colon-targeted UC therapy.Airway epithelial cell death contributes to the pathogenesis of lung fibrosis. Polyhexamethylene guanidine phosphate (PHMG-p), commonly used as a disinfectant, has been shown to be strongly associated with lung fibrosis in epidemiological and toxicological studies. However, the molecular mechanism underlying PHMG-p-induced epithelial cell death is currently unclear. We synthesized a PHMG-p-fluorescein isothiocyanate (FITC) conjugate and assessed its uptake into lung epithelial A549 cells. To examine intracellular localization, the cells were treated with PHMG-p-FITC; then, the cytoplasmic organelles were counterstained and observed with confocal microscopy. Additionally, the organelle-specific cell death pathway was investigated in cells treated with PHMG-p. PHMG-p-FITC co-localized with the endoplasmic reticulum (ER), and PHMG-p induced ER stress in A549 cells and mice. The ER stress inhibitor tauroursodeoxycholic acid (TUDCA) was used as a pre-treatment to verify the role of ER stress in PHMG-p-induced cytotoxicity. The cells treated with PHMG-p showed apoptosis, which was inhibited by TUDCA. Our results indicate that PHMG-p is rapidly located in the ER and causes ER-stress-mediated apoptosis, which is an initial step in PHMG-p-induced lung fibrosis.A spectroscopic ellipsometry study on as-deposited and annealed non-stoichiometric indium zinc tin oxide thin films of four different compositions prepared by RF magnetron sputtering was conducted. Multi-sample analysis with two sets of samples sputtered onto glass slides and silicon wafers, together with the analysis of the samples onto each substrate separately, was utilized for as-deposited samples. Annealed samples onto the glass slides were also analyzed. Spectroscopic ellipsometry in a wide spectral range (0.2-6 eV) was used to determine optical constants (refractive index n and extinction coefficient k) of these films. Parameterized semiconductor oscillator function, together with Drude oscillator, was used as a model dielectric function. Geometrical parameters (layer thickness and surface roughness) and physical parameters (direct optical bandgap, free carrier concentration, mobility, and specific electrical resistivity) were determined from spectroscopic ellipsometry data modeling. Specific electrical resistivity determined from the Drude oscillator corresponds well with the results from electrical measurements. Change in the optical bandgap, visible especially for annealed samples, corresponds with the change of free carrier concentration (Moss-Burstein effect). Scanning electron microscope did not reveal any noticeable annealing-induced change in surface morphology.An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally modified to generate an attenuated vaccine strain. Alternative approaches for vaccine development are needed to deliver OvHV-2 antigens. Bovine herpesvirus 4 (BoHV-4) has been evaluated as a vaccine vector for several viral antigens with promising results. In this study, we genetically engineered BoHV-4 to express OvHV-2 glycoprotein B (gB) and evaluated its efficacy as an SA-MCF vaccine using a rabbit model. The construction of a viable recombinant virus (BoHV-4-AΔTK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. The immunization of rabbits with BoHV-4-AΔTK-OvHV-2-gB elicited strong humoral responses to OvHV-2 gB, including neutralizing antibodies. Following intra-nasal challenge with a lethal dose of OvHV-2, 42.9% of the OvHV-2 gB vaccinated rabbits were protected against SA-MCF, while all rabbits in the mock-vaccinated group succumbed to SA-MCF. Overall, OvHV-2 gB delivered by the recombinant BoHV-4 was immunogenic and partly protective against SA-MCF in rabbits. These are promising results towards an SA-MCF vaccine; however, improvements are needed to increase protection rates.In contrast with some adult human organs, such as liver or skin, the adult human heart shows very limited self-regeneration capacity, attributed to the negligible presence of resident cardiac stem cells or cardiac progenitors [...].Polydimethylsiloxane (PDMS) is a silicone-based synthetic material used in various biomedical applications due to its properties, including transparency, flexibility, permeability to gases, and ease of use. Though PDMS facilitates and assists the fabrication of complicated geometries at micro- and nano-scales, it does not optimally interact with cells for adherence and proliferation. Various strategies have been proposed to render PDMS to enhance cell attachment. The majority of these surface modification techniques have been offered for a static cell culture system. However, dynamic cell culture systems such as organ-on-a-chip devices are demanding platforms that recapitulate a living tissue microenvironment's complexity. In organ-on-a-chip platforms, PDMS surfaces are usually coated by extracellular matrix (ECM) proteins, which occur as a result of a physical and weak bonding between PDMS and ECM proteins, and this binding can be degraded when it is exposed to shear stresses. This work reports static and dynamic coating methods to covalently bind collagen within a PDMS-based microfluidic device using polydopamine (PDA). These coating methods were evaluated using water contact angle measurement and atomic force microscopy (AFM) to optimize coating conditions. The biocompatibility of collagen-coated PDMS devices was assessed by culturing primary human bronchial epithelial cells (HBECs) in microfluidic devices. It was shown that both PDA coating methods could be used to bind collagen, thereby improving cell adhesion (approximately three times higher) without showing any discernible difference in cell attachment between these two methods. These results suggested that such a surface modification can help coat extracellular matrix protein onto PDMS-based microfluidic devices.

Potential unreported infection might impair and mislead policymaking for COVID-19, and the contemporary spread of COVID-19 varies in different counties of the United States. It is necessary to estimate the cases that might be underestimated based on county-level data, to take better countermeasures against COVID-19. We suggested taking time-varying Susceptible-Infected-Recovered (SIR) models with unreported infection rates (UIR) to estimate factual COVID-19 cases in the United States.

Both the SIR model integrated with unreported infection rates (SIRu) of fixed-time effect and SIRu with time-varying parameters (tvSIRu) were applied to estimate and compare the values of transmission rate (TR), UIR, and infection fatality rate (IFR) based on US county-level COVID-19 data.

Based on the US county-level COVID-19 data from 22 January (T

) to 20 August (T

) in 2020, SIRu was first tested and verified by Ordinary Least Squares (OLS) regression. Further regression of SIRu at the county-level showed that the average values of TR, UIR, and IFR were 0.