Lyme borreliosis (LB) caused by Borrelia burgdorferi spp. is the most common human tick-borne disease in Europe. Although seroprevalence studies are conducted in several countries, rates of seroconversion and seroreversion are lacking, and they are essential to determine the risk of infection. Seropositivity was determined using a two-step approach-first, a serological screening assay, and in the event of a positive or equivocal result, a confirmatory immunoblot assay. Seroconversion and seroreversion rates were assessed from blood samples taken from participants included in two nation-wide population-based surveys. Moreover, the impact of antigen reactivity on seroreversion rates was assessed. The seroprevalence of antibodies reacting against B. burgdorferi spp. in the German population was 8.5% (95% CI 7.5-9.6) in 1997-99 and 9.3% (95% CI 8.3-10.4) in 2008-2011. Seroprevalence increased with age, up to 20% among 70-79 year-olds. The age-standardized seroprevalence remained the same. The yearly seroconversion rate was 0.45% (95% CI 0.37-0.54), and the yearly seroreversion rate was 1.47% (95% CI 1.24-2.17). Lower levels of antibodies were associated with seroreversion. Participants with a strong response against antigen p83 had the lowest odds on seroreversion. Given the yearly seroreversion rate of 1.47% and a seroprevalence up to 20% in the oldest age groups, at least 20% of the German population becomes infected with B. burgdorferi in their lifetime. The slight increase in seroprevalence between the two serosurveys was caused by an aging population.Community pharmacies are the primary entities providing drugs to individual patients in Poland. The pharmacy market has been changing for many years due to significant changes in market regulations. These changes significantly affect the profitability of pharmacies, which may impact the quality of pharmacotherapy. The small number of pharmacies, which resulted from changes in the law in 2017, can influence the level of patient care. The article presents the community pharmacies market in Poland. Particular attention is paid to the legal regulations affecting community pharmacies and the impact of these regulations on the overall shape of the market. The Polish system’s specificity, including the pharmacy market indicators, has been compared with data from other European Union countries.The foot strike pattern performed during running is an important variable for runners, performance practitioners, and industry specialists. Versatile, wearable sensors may provide foot strike information while encouraging the collection of diverse information during ecological running. The purpose of the current study was to predict foot strike angle and classify foot strike pattern from LoadsolTM wearable pressure insoles using three machine learning techniques (multiple linear regression-MR, conditional inference tree-TREE, and random forest-FRST). Model performance was assessed using three-dimensional kinematics as a ground-truth measure. The prediction-model accuracy was similar for the regression, inference tree, and random forest models (RMSE MR = 5.16°, TREE = 4.85°, FRST = 3.65°; MAPE MR = 0.32°, TREE = 0.45°, FRST = 0.33°), though the regression and random forest models boasted lower maximum precision (13.75° and 14.3°, respectively) than the inference tree (19.02°). The classification performance was above 90% for all models (MR = 90.4%, TREE = 93.9%, and FRST = 94.1%). There was an increased tendency to misclassify mid foot strike patterns in all models, which may be improved with the inclusion of more mid foot steps during model training. Ultimately, wearable pressure insoles in combination with simple machine learning techniques can be used to predict and classify a runner’s foot strike with sufficient accuracy.Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on IκB kinase epsilon (IKKε) which has not been investigated in this context before. Therefore, we applied the pan-HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) as well as HDAC-specific siRNA. Administration of HDACi reduced HDAC activity and decreased expression of IKKε although its acetylation was increased. Other pro-inflammatory genes (IL-1β, iNOS, TNFα) also decreased while COX-2 expression increased. HDAC 2, 3 and 4, respectively, might be involved in IKKε and iNOS downregulation with potential participation of NF-κB transcription factor inhibition. Suppression of HDAC 1-3, activation of NF-κB and RNA stabilization mechanisms might contribute to increased COX-2 expression. In conclusion, our results indicate that TSA and SAHA exert a number of histone- and HDAC-independent functions. Furthermore, the data show that different HDAC enzymes fulfill different functions in macrophages and might lead to both pro- and anti-inflammatory effects which have to be considered in therapeutic approaches.The incidence of diabetes mellitus is increasing due to the eating and living habits of modern people. As the disease progresses, the long-term effects of diabetes can cause microvascular disease, causing dysfunction in different parts of the body, which, in turn, leads to different complications, such as diabetic neuropathy, diabetic nephropathy, and diabetic retinopathy (DR). DR is the main cause of vision loss and blindness in diabetic patients. Persistent hyperglycemia may cause damage to the retina, induce the accumulation of inflammatory factors, and destroy the blood-retinal barrier function. Fucoxanthin (Fx) is a marine carotenoid extracted from seaweed. It accounts for more than 10% of the total carotenoids in nature. Fx is mainly found in brown algae and has strong antioxidant properties, due to its unique biologically active structure. This carotenoid also has the effects of reducing lipid peroxidation, reducing DNA damage, and preventing cardiovascular diseases as well as anti-inflammatory and anti-tumor effects. However, there is no relevant research on the protective effect of Fx in DR. Therefore, in this study, we explore the protective effect of Fx on the retina. Human retinal epithelial cells (ARPE-19) are used to investigate the protective effect of Fx on high glucose stress- (glucose 75 mM) and high lipid peroxidation stress (4-hydroxynonenal, 4-HNE (30 μM))-induced DR. The cell viability test shows that Fx recovered the cell damage, and Western blotting shows that Fx reduced the inflammation response and maintained the integrity of the blood-retinal barrier by reducing its apoptosis and cell adhesion factor protein expression. Using an antioxidant enzyme assay kit, we find that the protective effect of Fx may be related to the strong antioxidant properties of Fx, which increases catalase and reduces oxidative stress to produce a protective effect on the retina.Imaging plays a cardinal role in the diagnosis and management of diseases of the pulmonary circulation. Behind the picture itself, every digital image contains a wealth of quantitative data, which are hardly analysed in current routine clinical practice and this is now being transformed by radiomics. Mathematical analyses of these data using novel techniques, such as vascular morphometry (including vascular tortuosity and vascular volumes), blood flow imaging (including quantitative lung perfusion and computational flow dynamics), and artificial intelligence, are opening a window on the complex pathophysiology and structure-function relationships of pulmonary vascular diseases. They have the potential to make dramatic alterations to how clinicians investigate the pulmonary circulation, with the consequences of more rapid diagnosis and a reduction in the need for invasive procedures in the future. Applied to multimodality imaging, they can provide new information to improve disease characterization and increase diagnostic accuracy. These new technologies may be used as sophisticated biomarkers for risk prediction modelling of prognosis and for optimising the long-term management of pulmonary circulatory diseases. These innovative techniques will require evaluation in clinical trials and may in themselves serve as successful surrogate end points in trials in the years to come.The pools of nuclear reactor facilities constitute harsh environments for life, bathed with ionizing radiation, filled with demineralized water and containing toxic radioactive elements. The very few studies published to date have explored water pools used to store spent nuclear fuels. Due to access restrictions and strong handling constraints related to the high radioactivity level, nothing is presently known about life in water pools that directly cool nuclear cores. In this work, we investigated the microbial communities in the cooling pool of the French Osiris nuclear reactor using direct meta-omics approaches, namely, DNA metabarcoding and proteotyping based on 16S ribosomal RNA gene sequencing and on peptide analysis, respectively. We identified 25 genera in the highly radioactive core water supply during operation with radionuclide activity higher than 3 × 109 Bq/m3. The prevailing genera Variovorax and Sphingomonas at operation were supplanted by Methylobacterium, Asanoa, and Streptomyces during shutdown. Variovorax might use dihydrogen produced by water radiolysis as an energy source.The maternal environment modulates immune responses to facilitate embryo development and ensure pregnancy. Unraveling this modulation could improve the livestock breeding systems. Here it is hypothesized that the exposure of the female rabbit reproductive tract to semen, as well as to early embryos, modulates inflammation and angiogenesis among different tissue segments. qPCR analysis of the gene expression changes of the anti-inflammatory interleukin-10 (IL10) and transforming growth factor beta family (TGFβ1-3) and the angiogenesis mediator vascular endothelial growth factor (VEGF-A) were examined in response to mating or insemination with sperm-free seminal plasma (SP). Reproductive tract segment (cervix to infundibulum) samples were obtained in Experiment 1, 20 h after gonadotropin-releasing hormone (GnRH) stimulation (control), natural mating (NM) or vaginal infusion with sperm-free SP (SP-AI). Additionally, segmented samples were also obtained at 10, 24, 36, 68 or 72 h after GnRH-stimulation and natural mating (Experiment 2). The results of gene expression, analyzed by quantitative PCR, showed that NM effects were mainly localized in the uterine tissues, depicting clear temporal variation, while SP-AI effects were restricted to the oviduct. Changes in anti-inflammatory and angiogenesis mediators indicate an early response in the uterus and a late modulation in the oviduct either induced by semen or preimplantation embryos. This knowledge could be used in the implementation of physiological strategies in breeding systems to face the new challenges on rabbit productivity and sustainability.STAT3 and STAT5B (STAT3/STAT5B) mutations are the most common mutations in T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK), but their clinical impact remains unknown. We investigated the frequency and type of STAT3/STAT5B mutations in FACS-sorted populations of expanded T/NK-LGL from 100 (82 clonal; 6 oligoclonal; 12 polyclonal) patients, and its relationship with disease features. Seventeen non-LGL T-CLPD patients and 628 age-matched healthy donors were analyzed as controls. STAT3 (n = 30) and STAT5B (n = 1) mutations were detected in 28/82 clonal T/NK-LGLL patients (34%), while absent (0/18, 0%) among oligoclonal/polyclonal LGL-lymphocytosis. Mutations were found across all diagnostic subgroups TCD8+-LGLL, 36%; CLPD-NK, 38%; TCD4+-LGLL, 7%; Tαβ+DP-LGLL, 100%; Tαβ+DN-LGLL, 50%; Tγδ+-LGLL, 44%. STAT3-mutated T-LGLL/CLPD-NK showed overall reduced (p less then 0.05) blood counts of most normal leukocyte subsets, with a higher rate (vs. nonmutated LGLL) of neutropenia (p = 0.04), severe neutropenia (p = 0.02), and cases requiring treatment (p = 0.0001), together with a shorter time-to-therapy (p = 0.0001), particularly in non-Y640F STAT3-mutated patients. These findings confirm and extend on previous observations about the high prevalence of STAT3 mutations across different subtypes of LGLL, and its association with a more marked decrease of all major blood-cell subsets and a shortened time-to-therapy.A microfluidic assay for the detection of promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) fusion protein was developed. This microfluidic-based system can be used for rapid personalized differential diagnosis of acute promyelocyte leukemia (APL) with the aim of early initiation of individualized therapy. The fusion protein PML-RARα occurs in 95% of acute promyelocytic leukemia cases and is considered as diagnostically relevant. The fusion protein is formed as a result of translocation t(15,17) and is detected in the laboratory by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR). Diagnostic methods require many laboratory steps with specialized staff. The developed microfluidic assay includes a sandwich enzyme-linked immunosorbent assay (ELISA) system for PML-RARα on surface of magnetic microparticles in a microfluidic chip. A rapid detection of PML-RARα in cell lysates is achieved in less than one hour. A biotinylated PML-antibody on the surface of magnetic streptavidin coated microparticles is used as capture antibody. The bound translocation product is detected by a RARα antibody conjugated with horseradish peroxidase and the substrate QuantaRed. The analysis is performed in microfluidic channels which involves automated liquid processing with stringent washing and short incubation times. The results of the developed assay show that cell lysates of PML-RARα-positive cells (NB-4) can be clearly distinguished from PML-RARα-negative cells (HL-60, MV4-11).Background and objectives 339 million people in the world suffer from asthma. Regular physical activity (PA) could help in its control. Therefore, the aim of this research was to determine the level of PA in Spanish people with asthma considering variation by, age, sex, education, marital status, living together, smoking habits, alcohol intake and body mass index (BMI). Materials and Methods 1014 Spanish people from 15 to 69 years were included in the study. Data of the Spanish Health Survey (year 2017) were analysed. PA levels were measure with the international physical activity questionnaire short version (IPAQ-SF). PA was categorized as low, moderate and high, and analyzed by sample characteristics. Mann-Whitney U test, Kruskall Wallis H and crosstabs were used to calculate statistical significance (p less then 0.05). Results On average, Spanish asthmatics engaged in a weekly volume of 2228.9 metabolic equivalent of task (MET)·min/week. Males revealed significantly higher PA than females (2516.8 vs. 201 with lower PA levels.Zinc is a trace metal ion in the central nervous system that plays important biological roles, such as in catalysis, structure, and regulation. It contributes to antioxidant function and the proper functioning of the immune system. In view of these characteristics of zinc, it plays an important role in neurophysiology, which leads to cell growth and cell proliferation. However, after brain disease, excessively released and accumulated zinc ions cause neurotoxic damage to postsynaptic neurons. On the other hand, zinc deficiency induces degeneration and cognitive decline disorders, such as increased neuronal death and decreased learning and memory. Given the importance of balance in this context, zinc is a biological component that plays an important physiological role in the central nervous system, but a pathophysiological role in major neurological disorders. In this review, we focus on the multiple roles of zinc in the brain.Mushrooms can be considered a valuable source of natural bioactive compounds with potential polypharmacological effects due to their proven antimicrobial, antiviral, antitumor, and antioxidant activities. In order to identify new potential anticancer compounds, an in-house chemical database of molecules extracted from both edible and non-edible fungal species was employed in a virtual screening against the isoform 7 of the Histone deacetylase (HDAC). This target is known to be implicated in different cancer processes, and in particular in both breast and ovarian tumors. In this work, we proposed the ibotenic acid as lead compound for the development of novel HDAC7 inhibitors, due to its antiproliferative activity in human breast cancer cells (MCF-7). These promising results represent the starting point for the discovery and the optimization of new HDAC7 inhibitors and highlight the interesting opportunity to apply the „drug repositioning” paradigm also to natural compounds deriving from mushrooms.Autoimmune pancreatitis (AIP) is characterized by enlargement of the pancreas and irregular narrowing of the main pancreatic duct. It is often associated with IgG4-related sclerosing cholangitis (IgG4-SC), in which the bile duct narrows. Although characteristic irregular narrowing of the pancreatic duct caused by endoscopic retrograde cholangiopancreatography is noted in AIP, it is difficult to differentiate between localized AIP and pancreatic carcinoma based on imaging of the pancreatic duct. While stenosis of the bile duct in IgG4-SC is characterized by longer-length stenosis than in cholangiocarcinoma, differentiation based on bile duct imaging alone is challenging. Endoscopic ultrasound (EUS) can characterize hypoechoic enlargement of the pancreas or bile duct wall thickening in AIP and IgG4-SC, and diagnosis using elastography and contrast-enhanced EUS are being evaluated. The utility of EUS-guided fine needle aspiration for the histological diagnosis of AIP has been reported and is expected to improve diagnostic performance for AIP. Findings in the bile duct wall from endoscopic retrograde cholangiopancreatography followed by intraductal ultrasonography are useful in differentiating IgG4-SC from cholangiocarcinoma. Diagnoses based on endoscopic ultrasonography play a central role in the diagnosis of AIP.Melanoma, the most dangerous type of cutaneous neoplasia, contributes to about 75% of all skin cancer-related deaths. Thus, searching for new melanoma treatment options is an important field of study. The current study was designed to assess whether the condition of mild and low-dose UVA radiation augments the lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effect of the drug in melanoma cancer cells through excessive oxidative stress generation. C32 amelanotic and COLO829 melanotic (BRAF-mutant) melanoma cell lines were used as an experimental model system. The combined exposure of cells to both lomefloxacin and UVA irradiation caused higher alterations of redox signalling pathways, as shown by intracellular reactive oxygen species overproduction and endogenous glutathione depletion when compared to non-irradiated but lomefloxacin-treated melanoma cells. The obtained results also showed that lomefloxacin decreased both C32 and COLO829 cells’ viability in a concentration-dependent manner.vative medical treatment option which could improve the effectiveness of therapy. The obtained results also revealed that the redox imbalance intensification mediated by the phototoxic potential of fluoroquinolones may be considered as a more efficient treatment model of malignant melanoma and may constitute the basis for the development of new compounds with a high ability to excessive oxidative stress generation upon UVA radiation in cancer cells.The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the „3 plus 3” dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular degeneration (AMD) in the elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti-VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti-VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia-inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE-19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed VEGF mRNA induction under a CoCl2-induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization.Staphylococcus aureus (S. aureus)-induced acute lung injury (ALI) is a serious disease that has a high risk of death among infants and teenagers. Acetylharpagide, a natural compound of Ajuga decumbens Thunb. (family Labiatae), has been found to have anti-tumor, anti-inflammatory and anti-viral effects. This study investigates the therapeutic effects of acetylharpagide on S. aureus-induced ALI in mice. Here, we found that acetylharpagide alleviated S. aureus-induced lung pathological morphology damage, protected the pulmonary blood-gas barrier and improved the survival of S. aureus-infected mice. Furthermore, S. aureus-induced myeloperoxidase (MPO) activity of lung homogenate and pro-inflammatory factors in bronchoalveolar lavage (BAL) fluid were suppressed by acetylharpagide. Mechanically, acetylharpagide inhibited the interaction between polyubiquitinated receptor interacting protein 1 (RIP1) and NF-κB essential modulator (NEMO), thereby suppressing NF-κB activity. In summary, these results show that acetylharpagide protects mice from S. aureus-induced ALI by suppressing the NF-κB signaling pathway. Acetylharpagide is expected to become a potential treatment for S. aureus-induced ALI.In a wide range of organisms, dolichyl phosphate mannose (DPM) synthase is a complex of tree proteins Dpm1, Dpm2, and Dpm3. However, in the yeast Saccharomyces cerevisiae, it is believed to be a single Dpm1 protein. The function of Dpm3 is performed in S. cerevisiae by the C-terminal transmembrane domain of the catalytic subunit Dpm1. Until present, the regulatory Dpm2 protein has not been found in S. cerevisiae. In this study, we show that, in fact, the Yil102c-A protein interacts directly with Dpm1 in S. cerevisiae and influences its DPM synthase activity. Deletion of the YIL102c-A gene is lethal, and this phenotype is reversed by the dpm2 gene from Trichoderma reesei. Functional analysis of Yil102c-A revealed that it also interacts with glucosylphosphatidylinositol-N-acetylglucosaminyl transferase (GPI-GnT), similar to DPM2 in human cells. Taken together, these results show that Yil102c-A is a functional homolog of DPMII from T. reesei and DPM2 from humans.Enteroviruses (EVs) are positive-sense RNA viruses, with over 50,000 nucleotide sequences publicly available. While most human infections are typically associated with mild respiratory symptoms, several different EV types have also been associated with severe human disease, especially acute flaccid paralysis (AFP), particularly with endemic members of the EV-B species and two pandemic types-EV-A71 and EV-D68-that appear to be responsible for recent widespread outbreaks. Here we review the recent literature on the prevalence, characteristics, and circulation dynamics of different enterovirus types and combine this with an analysis of the sequence coverage of different EV types in public databases (e.g., the Virus Pathogen Resource). This evaluation reveals temporal and geographic differences in EV circulation and sequence distribution, highlighting recent EV outbreaks and revealing gaps in sequence coverage. Phylogenetic analysis of the EV genus shows the relatedness of different EV types. Recombination analysis of the EV-A species provides evidence for recombination as a mechanism of genomic diversification. The absence of broadly protective vaccines and effective antivirals makes human enteroviruses important pathogens of public health concern.Cold shock Y-box binding protein-1 participates in cancer cell transformation and mediates invasive cell growth. It is unknown whether an autoimmune response against cancerous human YB-1 with posttranslational protein modifications or processing develops. We performed a systematic analysis for autoantibody formation directed against conformational and linear epitopes within the protein. Full-length and truncated recombinant proteins from prokaryotic and eukaryotic cells were generated. Characterization revealed a pattern of spontaneous protein cleavage, predominantly with the prokaryotic protein. Autoantibodies against prokaryotic, but not eukaryotic full-length and cleaved human YB-1 protein fragments were detected in both, healthy volunteers and cancer patients. A mapping of immunogenic epitopes performed with truncated E. coli-derived GST-hYB-1 proteins yielded distinct residues in the protein N- and C-terminus. A peptide array with consecutive overlapping 15mers revealed six distinct antigenic regions in cancer patients, however to a lesser extent in healthy controls. Finally, a protein cleavage assay was set up with recombinant pro- and eukaryotic-derived tagged hYB-1 proteins. A distinct cleavage pattern developed, that is retarded by sera from cancer patients. Taken together, a specific autoimmune response against hYB-1 protein develops in cancer patients with autoantibodies targeting linear epitopes.Carbon dots (CDs) are a new type of nanomaterials of the carbon family with unique characteristics, such as their small size (e.g., less then 10 nm), high water solubility, low toxicity, and high metal affinity. Modification of CDs by Nitrogen functional groups (N-CDs) enhances their metal adsorption capacity. This study investigated the influences of pH (4, 6, and 9), ionic strength (1, 50, and 100 mM), and cation valency (Na+ and Ca2+) on the competitive adsorption of Pb to quartz and N-CD surfaces, the transport and retention of N-CDs in saturated porous media, and the capacity of N-CDs to mobilize pre-adsorbed Pb in quartz columns. Pb adsorption was higher on N-CDs than on quartz surfaces and decreased with increases in ionic strength (IS) and divalent cations (Ca2+) concentration. N-CD mobility in quartz columns was highest at pH of 9- and 1-mM monovalent cations (Na+) and decreased with decreases in pH and increases in ionic strength and ion valency. N-CDs mobilized pre-adsorbed Pb from quartz due to the higher adsorption affinity of Pb to N-CD than to quartz surfaces. These findings provide valuable insights into the transport, retention, and risk assessment of lead in the presence of carbon-based engineered nanoparticles.Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the progressive growth of cysts but it is also accompanied by diffuse tissue scarring or fibrosis. A number of recent studies have been published in this area, yet the role of fibrosis in ADPKD remains controversial. Here, we will discuss the stages of fibrosis progression in ADPKD, and how these compare with other common kidney diseases. We will also provide a detailed overview of some key mechanistic pathways to fibrosis in the polycystic kidney. Specifically, the role of the 'chronic hypoxia hypothesis’, persistent inflammation, Transforming Growth Factor beta (TGFβ), Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) and microRNAs will be examined. Evidence for and against a pathogenic role of extracellular matrix during ADPKD disease progression will be provided.The aim of this study was to determine the effect of different drying methods convective (at 50, 60, 70 °C), vacuum-microwave (at 120, 240, 360, 480 W and 360 W with reduction to 120 W) and hybrid (convective pre-drying at 50, 60, 70 °C followed by vacuum-microwave drying at 120 W) on the quality parameters of novel red-fleshed apple fruit snacks (RFAs), such as phenolics, on-line antioxidant capacity, water activity and color. Drying kinetics, including a temperature profile of dried material, and modified Page model were determined. Freeze-drying was used as a control method. The highest content of bioactive compounds in the samples was retained following freeze-drying, then hybrid, vacuum-microwave and finally convection drying. The antioxidant capacity measured by on-line 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), identified anthocyanins, flavan-3-ols and phenolic acid as the main compounds responsible for this activity. Unfavorable changes in color, formation of hydroxymethylfurfural (HMF) and degradation of polyphenolics were noted along with increasing drying temperature and magnetron power. The red-fleshed apple snacks are a promising high-quality dehydrated food product belonging to functional foods category.The PLATZ (plant AT-rich protein and zinc-binding protein) transcription factor family is a class of plant-specific zinc-dependent DNA-binding proteins. PLATZ has essential roles in seed endosperm development, as well as promoting cell proliferation duration in the earlier stages of the crops. In the present study, 62 TaPLATZ genes were identified from the wheat genome, and they were unequally distributed on 15 chromosomes. According to the phylogenetic analysis, 62 TaPLATZ genes were classified into six groups, including two groups that were unique in wheat. Members in the same groups shared similar exon-intron structures. The polyploidization, together with genome duplication of wheat, plays a crucial role in the expansion of the TaPLATZs family. Transcriptome data indicated a distinct divergence expression pattern of TaPLATZ genes that could be clustered into four modules. The TaPLATZs in Module b possessed a seed-specific expression pattern and displayed obvious high expression in the earlier development stage of seeds. Subcellular localization data of TaPLATZs suggesting that they likely perform a function as a conventional transcription factor. This study provides insight into understanding the structure divergence, evolutionary features, expression profiles, and potential function of PLATZ in wheat.The manual muscle test (MMT) is a flexible diagnostic tool, which is used in many disciplines, applied in several ways. The main problem is the subjectivity of the test. The MMT in the version of a „break test” depends on the tester’s force rise and the patient’s ability to resist the applied force. As a first step, the investigation of the reproducibility of the testers’ force profile is required for valid application. The study examined the force profiles of n = 29 testers (n = 9 experiences (Exp), n = 8 little experienced (LitExp), n = 12 beginners (Beg)). The testers performed 10 MMTs according to the test of hip flexors, but against a fixed leg to exclude the patient’s reaction. A handheld device recorded the temporal course of the applied force. The results show significant differences between Exp and Beg concerning the starting force (padj = 0.029), the ratio of starting to maximum force (padj = 0.005) and the normalized mean Euclidean distances between the 10 trials (padj = 0.015). The slope is significantly higher in Exp vs. LitExp (p = 0.006) and Beg (p = 0.005). The results also indicate that experienced testers show inter-tester differences and partly even a low intra-tester reproducibility. This highlights the necessity of an objective MMT-assessment. Furthermore, an agreement on a standardized force profile is required. A suggestion for this is given.The growing demand for new, sophisticated, multifunctional materials has brought natural structural composites into focus, since they underwent a substantial optimization during long evolutionary selection pressure and adaptation processes. Marine biological materials are the most important sources of both inspiration for biomimetics and of raw materials for practical applications in technology and biomedicine. The use of marine natural products as multifunctional biomaterials is currently undergoing a renaissance in the modern materials science. The diversity of marine biomaterials, their forms and fields of application are highlighted in this review. We will discuss the challenges, solutions, and future directions of modern marine biomaterialogy using a thorough analysis of scientific sources over the past ten years.Dactylorhiza hatagirea (Orchidaceae) is a perennial herb inhabiting sub-alpine to alpine regions, ranging at elevations between 2500 and 5000 m.a.s.l. With palmately lobed rhizome and lanceolate leaves having a sheathing leaf base, it bears pink flowers with purple-colored notches and a curved spur. It finds wide use in ayurveda, siddha, unani, and folk medicine in curing disorders of the circulatory, respiratory, nervous, digestive, skeletal, and reproductive systems, besides boosting the immune system to fight infectious diseases. Secondary metabolites such as dactylorhins A-E, dactyloses A-B, and others exhibit a wide spectrum of pharmacological activities (antioxidant, antimicrobial, antiseptic, anticancer, and immune enhancing activities). Its use as a dietary supplement was found to be beneficial in increasing testosterone levels, resulting in improved sexual desire and arousal. Incessant overexploitation of this medicinally important herb has resulted in the dwindling of its populations in the wild, which has resulted in its classification as a critically endangered plant species. Efforts involving mass reproduction through in vitro (through tissue culture) and in vivo (by vegetative propagation) means are currently being made to maintain the germplasm of this critically endangered orchid. Holding immense significance in clinical research and drug discovery, work on the genomic front (transcriptomics) has recently been carried out to discover the wealth of unexplored genetic information for this perennial herb. The present study is aimed at reviewing different aspects of the orchid to present collective (summarized) information on this medicinally important herb in the present, particularly its botany, ethnobotanical uses, phytochemistry, and pharmacognosy, along with the strategies that need to be adopted to prevent its overexploitation in natural habitats.Full Matrix Capture is a multi-channel data acquisition method which enables flexible, high resolution imaging using ultrasound arrays. However, the measurement time and data volume are increased considerably. Both of these costs can be circumvented via compressed sensing, which exploits prior knowledge of the underlying model and its sparsity to reduce the amount of data needed to produce a high resolution image. In order to design compression matrices that are physically realizable without sophisticated hardware constraints, structured subsampling patterns are designed and evaluated in this work. The design is based on the analysis of the Cramér-Rao Bound of a single scatterer in a homogeneous, isotropic medium. A numerical comparison of the point spread functions obtained with different compression matrices and the Fast Iterative Shrinkage/Thresholding Algorithm shows that the best performance is achieved when each transmit event can use a different subset of receiving elements and each receiving element uses a different section of the echo signal spectrum. Such a design has the advantage of outperforming other structured patterns to the extent that suboptimal selection matrices provide a good performance and can be efficiently computed with greedy approaches.Muscular dystrophies are a group of more than 160 different human neuromuscular disorders characterized by a progressive deterioration of muscle mass and strength. The causes, symptoms, age of onset, severity, and progression vary depending on the exact time point of diagnosis and the entity. Congenital myopathies are rare muscle diseases mostly present at birth that result from genetic defects. There are no known cures for congenital myopathies; however, recent advances in gene therapy are promising tools in providing treatment. This review gives an overview of the mouse models used to investigate the most common muscular dystrophies and congenital myopathies with emphasis on their potentials and limitations in respect to human applications.This paper reports an Alkali-Activated Materials (AAM) using two different precursors, metakaolin and a metallurgical slag with photocatalytic zinc oxide nanoparticles, as novel photocatalytic composites. The photodegradation performance of the composites using methylene blue (MB) dye as a wastewater model was investigated by ultraviolet radiations (UV-vis) spectroscopy. Adsorption in dark conditions and photodegradation under UV irradiation are the mechanisms for removing MB dye. The pseudo-first-order kinetic and pseudo-second-order kinetic models were employed, and the experimental data agreed with the pseudo-second-order model in both cases with UV and without UV irradiations. As new photocatalytic materials, these composites offer an alternative for environmental applications.We report the first case of non-dermatophytic onychomycosis of the toenail described in Kazakhstan caused by Candida parapsilosis. The biological properties of the strain were studied. C. parapsilosis forms white creamy colonies, smooth with focal wrinkles, and the reversum is light-yellow. The culture of C. parapsilosis is represented by a yeast form, characterized by the presence of round or cylindrical yeast cells with active budding. The strain has a high saccharolytic and urease activity and is indifferent to the sucrose and maltose. The C. parapsilosis strain was sensitive to polyene and azole antifungal agents. The highest sensitivity was found to ketoconazole, itraconazole and nystatin.When the first- and second-line therapeutics used to treat neuropathic pain (NP) fail to induce efficient analgesia-which is estimated to relate to more than half of the patients-opioid drugs are prescribed. Still, the pathological changes following the nerve tissue injury, i.a. pronociceptive neuropeptide systems activation, oppose the analgesic effects of opiates, enforcing the use of relatively high therapeutic doses in order to obtain satisfying pain relief. In parallel, the repeated use of opioid agonists is associated with burdensome adverse effects due to compensatory mechanisms that arise thereafter. Rational design of hybrid drugs, in which opioid ligands are combined with other pharmacophores that block the antiopioid action of pronociceptive systems, delivers the opportunity to ameliorate the NP-oriented opioid treatment via addressing neuropathological mechanisms shared both by NP and repeated exposition to opioids. Therewith, the new dually acting drugs, tailored for the specificity of NP, can gain in efficacy under nerve injury conditions and have an improved safety profile as compared to selective opioid agonists. The current review presents the latest ideas on opioid-comprising hybrid drugs designed to treat painful neuropathy, with focus on their biological action, as well as limitations and challenges related to this therapeutic approach.In order to meet the demand for high-quality fruit and vegetable (F&V) products, a wide variety of novel non-thermal processing (NTP) technologies are under development. This study used a qualitative focus group approach to investigate consumers’ perception and attitudes towards non-thermally processed F&V products among young (18-30 years old) and middle-aged (45-60 y.o.) consumers across six European countries Denmark, Germany, Italy, Serbia, Spain, and the Netherlands. Findings show that the expected benefits and social concerns are important factors which affect consumers’ attitudes toward non-thermally processed F&V. Extending shelf-life, being healthier and more nutritious, and better hygiene and safety were important benefits, whilst impacts on product quality, safety risks, higher price and environmental costs were the concerns most often mentioned by participants. However, due to a lack of knowledge and trustworthy information sources, consumers have difficulties in assessing relevant benefits and risks. Targeted communication that could explicitly and efficiently reveal benefits and risks is highly recommended to enhance consumer awareness and trust. This may especially be needed to reach middle-aged consumers who showed less confidence in NTP, compared to young consumers. Consumers from Spain, Denmark, and the Netherlands appeared more interested in consuming NTP F&V, compared to Italy, Serbia, and Germany. These findings are expected to provide recommendations to better communicate non-thermally processed F&V with consumers in the EU.Calcific aortic valve disease (CAVD), a degenerative disease characterized by inflammation, fibrosis and calcification, is accelerated in diabetes. Hyperglycemia contributes to this process by mechanisms that still need to be uncovered. We have recently developed a 3D model of the human aortic valve based on gelatin methacrylate and revealed that high glucose (HG) induced osteogenic molecules and increased calcium deposits in a pro-osteogenic environment. To further understand the events leading to calcification in diabetic conditions in CAVD, we analyzed here the inflammatory and remodeling mechanisms induced by HG in our 3D model. We exposed valvular endothelial cells (VEC) and interstitial cells (VIC) to normal glucose (NG) or HG for 7 and 14 days, then we isolated and separated the cells by anti-CD31 immunomagnetic beads. The changes induced by HG in the 3D model were investigated by real-time polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. Our results showed that HG induced expression of different cytokines, cell adhesion molecules and matrix metalloproteinases in VEC and VIC. In addition, protein kinase C was increased in VEC and VIC, indicating molecular mechanisms associated with HG induced inflammation and remodeling in both valvular cells. These findings may indicate new biomarkers and targets for therapy in diabetes associated with CAVD.The aim of this study was to analyze the main leisure habits of students at the University of Huelva and the relationship with perceived health by grouping the various activities into components whilst also evaluating possible gender differences. The sample was selected through random cluster sampling and was composed of 903 students from various courses and degrees. Of the sample, 73.8% were female and 26.2% were male, with a mean age of 20.82 years. The participants responded to items measuring perceived health and the inventory of leisure activities extracted from the INJUVE (Spanish Youth Observatory) survey. The results obtained offered a solution of four components, grouping the activities into passive leisure, festive leisure, sports-competitive leisure and cultural leisure. Passive leisure was the most practiced and cultural leisure the least practiced. Statistically significant differences were observed between men and women in terms of the sports-competitive component and in the perception of health. In addition, a direct relationship was found between the sports-competitive dimension and health perception. These results support the existence of a „techno-active” profile in males and should be considered in the creation of university policies linked to health promotion or the prevention of risk behaviors.Oysters and clams are important for food security and of commercial value worldwide. They are affected by anthropogenic changes and opportunistic pathogens and can be indicators of changes in ocean environments. Therefore, studies into biomarker discovery are of considerable value. This study aimed at assessing extracellular vesicle (EV) signatures and post-translational protein deimination profiles of hemolymph from four commercially valuable Mollusca species, the blue mussel (Mytilus edulis), soft shell clam (Mya arenaria), Eastern oyster (Crassostrea virginica), and Atlantic jacknife clam (Ensis leei). EVs form part of cellular communication by transporting protein and genetic cargo and play roles in immunity and host-pathogen interactions. Protein deimination is a post-translational modification caused by peptidylarginine deiminases (PADs), and can facilitate protein moonlighting in health and disease. The current study identified hemolymph-EV profiles in the four Mollusca species, revealing some species ee of the Bivalvia species under study (e.g., EP protein, C1q domain containing protein, histone H2B, tubulin, elongation factor 1-alpha, dominin, extracellular superoxide dismutase). Protein interaction network analysis for the deiminated protein hits revealed major pathways relevant for immunity and metabolism, providing novel insights into post-translational regulation via deimination. The study contributes to EV characterization in diverse taxa and understanding of roles for PAD-mediated regulation of immune and metabolic pathways throughout phylogeny.Extensive microbial colonization of the infant gastrointestinal tract starts after parturition. There are several parallel mechanisms by which early life microbiome acquisition may proceed, including early exposure to maternal vaginal and fecal microbiota, transmission of skin associated microbes, and ingestion of microorganisms present in breast milk. The crucial role of vertical transmission from the maternal microbial reservoir during vaginal delivery is supported by the shared microbial strains observed among mothers and their babies and the distinctly different gut microbiome composition of caesarean-section born infants. The healthy infant colon is often dominated by members of the keystone genus Bifidobacterium that have evolved complex genetic pathways to metabolize different glycans present in human milk. In exchange for these host-derived nutrients, bifidobacteria’s saccharolytic activity results in an anaerobic and acidic gut environment that is protective against enteropathogenic infection. Interference with early-life microbiota acquisition and development could result in adverse health outcomes. Compromised microbiota development, often characterized by decreased abundance of Bifidobacterium species has been reported in infants delivered prematurely, delivered by caesarean section, early life antibiotic exposure and in the case of early life allergies. Various microbiome modulation strategies such as probiotic, prebiotics, synbiotics and postbiotics have been developed that are able to generate a bifidogenic shift and help to restore the microbiota development. This review explores the evolutionary ecology of early-life type Bifidobacterium strains and their symbiotic relationship with humans and discusses examples of compromised microbiota development in which stimulating the abundance and activity of Bifidobacterium has demonstrated beneficial associations with health.Current trends suggest that adolescent obesity is an on-going and recurrent decimal that is still on the rise in Australia and the social burden associated with it can significantly cause low self-esteem and lack of confidence in personal body image in adulthood. Nonetheless, evidence-based prevention programs are not widely implemented in schools, even though they are commonplace for easy access to adolescents. The primary objective of this systematic review was to assess the scope and efficacy of adolescent obesity intervention strategies in Australian schools, to guide future research. Seven electronic databases were searched for peer-reviewed school-based intervention articles written in the English language and targeting 12-18-year-old adolescents. Intervention characteristics were extracted, and quality, efficacy and outcome measures were assessed utilizing thirteen studies that met the inclusion criteria for this review. Most of the Australian adolescent obesity research emanated from the State of New South Wales and none were nationwide. Five studies successfully met all the requirements in all measured outcomes, four met at least one measured outcome and the remaining four were unsuccessful. Despite the weak evidence of intervention efficacy for most of the reviewed studies, school-based interventions with multi-component combinations of physical activity, nutrition and alignment to a theory yielded promising results. Our findings point to the need for future research to assess the perceptions of school stakeholders in relation to the barriers and enablers to establishing school-based prevention and intervention programs for adolescents.