There is rapidly increasing need for palliative care in Greater China because of rapidly aging populations.

This study aimed to systematically review and appraise evidence for palliative care needs, models of care, interventions, and outcomes in Greater China.

Four databases (MEDLINE, EMBASE, CINAHL, and PsycINFO) were searched, with hand searching of local journals and databases. Narrative synthesis was applied to the qualitative and quantitative evidence.

Nineteen qualitative studies and 47 quantitative studies were retained. With respect to care needs, nine themes were synthesized pain control, reduced aggressive end-of-life care, truth telling, physical, emotional, and spiritual supports, and achieving preferred place of care/death. Informal caregivers expressed their needs for education and burden reduction. Health care professionals called for training and national policy support. Twenty-four studies evaluated interventions, mostly among patients with advanced cancer. Positive effects were suggeestablishing culturally appropriate person-centered services.

Antifungal drug resistance in dermatophytes was first reported shortly after the turn of the millennium and has today been reported in Trichophyton and occasionally in Microsporum, but not in Epidermophyton species. Although drug resistance in dermatophytes is not routinely investigated, resistance in Trichophyton spp. is increasingly reported worldwide. The highest rates are observed in India (36% and 68% for terbinafine (MIC ≥4 mg/L) and fluconazole (MICs ≥16 mg/L), respectively), and apparently involve the spread of a unique clade related to the Trichophyton mentagrophytes/Trichophyton interdigitale complex.

The European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST) has released a new method (E.Def 11.0) for antifungal susceptibility testing against microconidia-forming dermatophytes including tentative MIC ranges for quality control strains and tentative breakpoints against Trichophyton rubrum and T.interdigitale. Here, the details ofpropriate therapy. This is important, as resistance is rapidly emerging and largely underdiagnosed.

This standardized procedure with automated end-point reading will allow broader implementation of susceptibility testing of dermatophytes and so facilitate earlier appropriate therapy. This is important, as resistance is rapidly emerging and largely underdiagnosed.The parasitizing stage (trophozoite) of the protozoan parasite Perkinsus olseni progresses to the dormant stage (prezoosporangium) immediately after the death of the host through physiologically and morphologically drastic changes. This development is reproducible in Ray’s fluid thioglycollate medium (RFTM). In this study, supplementation with tissue extract from a host, the Manila clam, significantly improved the efficiency of development, as determined by the numbers and sizes of developed prezoosporangia. Similar results were seen following supplementation with boiled host tissue extract, which indicates that a thermally stable component of the host is required for the parasite’s development. Subsequently, we found that a commercially available lipid concentrate significantly increased prezoosporulation without host tissue, suggesting that the lipids in host tissue enhance prezoosporangia development. Moreover, we determined that yeast extract, sodium thioglycollate, and sodium chloride were the only components of RFTM required for prezoosporulation. Based on these findings, we prepared a simple, host-free medium for P. olseni prezoosporulation-Lipid concentrate Yeast extract Medium (LpcYM)-consisting of yeast extract, lipid concentrate, sodium thioglycollate, and sodium chloride. We confirmed that the prezoosporangia developed in LpcYM produce zoospores that are infectious to Manila clams and that trophozoites of other Perkinsus species (P. marinus, P. honshuensis, and P. chesapeaki) also develop to prezoosporangia in this host-free medium. As LpcYM has the simplest composition of prezoosporulation media available thus far, it enables us to conduct molecular and biochemical studies examining the drastic transformation process of this parasite.COVID-19 is a pandemic that began to spread worldwide caused by SARS-CoV-2. Lung cancer patients are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 enters into the host by the ACE2 receptor. Thus, ACE2 is the key to understand the mechanism of SARS-CoV-2 infection. However, the lack of knowledge about the biomarker of COVID-19 warrants the development of ACE2 biomarkers. The analysis of ACE2 expression in lung cancer was performed using The Cancer Genome Atlas (TCGA). Therefore, we investigated the prognosis, clinical characteristics, and mutational analysis of lung cancer. We also analyzed the shared proteins between the COVID-19 and lung cancer, protein-protein interactions, gene-miRNAs, gene-transcription factors (TFs), and the signaling pathway. Finally, we compared the mRNA expression of ACE2 and its co-expressed proteins using the TCGA. The up-regulation of ACE2 in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) was found irrespective of gender and age. We found the low survival rate in high expression of ACE2 in lung cancer patients and 16 mutational positions. The functional assessment of targeted 12,671, 3107, and 29 positive genes were found in COVID-19 disease, LUAD, and LUSC, respectively. Then, we identified eight common genes that interact with 20 genes, 219 miRNAs, and 16 TFs. The common genes performed the mRNA expression in lung cancer, which proved the ACE2 is the best potential biomarker compared to co-expressed genes. This study uncovers the relationship between COVID-19 disease and lung cancer. We identified ACE2 and also its co-expressed proteins are the potential biomarker and therapy as the current COVID-19 disease and lung cancer.Abnormal environmental conditions induce polyploidization and exacerbate vulnerability to agricultural production. Polyploidization is a pivotal event for plant adaption to stress and the expansion of transcription factors. NACs play key roles in plant stress resistance and growth and development, but the adaptive mechanism of NACs during plant polyploidization remain to be explored. Here, we identified and analyzed NACs from 15 species and found that the expansion of NACs was contributed by polyploidization. The regulatory networks were systematically analyzed based on polyomics. NACs might influence plant phenotypes and were correlated with amino acids acting as nitrogen source, indicating that NACs play a vital role in plant development. More importantly, in quinoa and Arabidopsis thaliana, NACs enabled plants to resist stress by regulating flavonoid pathways, and the universality was further confirmed by the Arabidopsis population. Our study provides a cornerstone for future research into improvement of important agronomic traits by transcription factors in a changing global environment.A multidrug-resistant CTX-M-15-producing Klebsiella pneumoniae (KpP1 strain) was isolated from a native Amazonian fish (Brachyplatystoma filamentosum) at the Brazilian Amazon. The strain was identified by MALDI-TOF. The genome was extracted, purified and a Nextera DNA Flex library was prepared and sequenced by Illumina platform. The sequenced genome was de novo assembled using Unicycler and in silico prediction accomplished by curated bioinformatics tools. The size of the genome is 5.6 Mb with 5715 genes. Whole-genome sequencing analysis revealed the presence of wide resistome, with genes conferring resistance to clinically relevant antibiotics, heavy metals and disinfectants. The KpP1 strain was assigned to the sequence type ST3827, KL111 (wzi113) and O3b locus. Native freshwater fish sold in wet markets of the Amazonian region could be an important vehicle for transmission of multidrug-resistant bacteria to humans. This study may give genomic insights on the spread of critical-priority WHO pathogens in a One Health context.Traditional Chinese Medicine (TCM) is a medical science and cultural heritage empirically applied and reserved by Chinese people for thousands of years. With comprehensive prosperity of China and rapid elaboration of technology, healthcare status of Chinese people has become one of the most crucial concerns of the country. Nearly 30 policies and measures regarding TCM development have been issued since the 18th National Congress of the Communist Party of People’s Republic of China in 2012. This review introduced a detailed evolutionary course of TCM in China with an emphasis on understanding the roadmap of TCM related policies and measures in China.Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide with high prevalence and lethality. The oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is a classic dysregulated pathway involved in the pathogenesis of HCC. However, the underlying mechanism for how PI3K/AKT/mTOR pathway aberrantly activates HCC has not been entirely elucidated. The recognition of the functional roles of long non-coding RNAs (lncRNAs) in PI3K/AKT/mTOR signaling axis sheds light on a new dimension to our understanding of hepatocarcinogenesis. In this review, we comprehensively summarize 67 dysregulated PI3K/AKT/mTOR pathway-related lncRNAs in HCC. Many studies have indicated that the 67 dysregulated lncRNAs show oncogenic or anti-oncogenic effects in HCC by regulation on epigenetic, transcriptional and post-transcriptional levels and they play pivotal roles in the initiation of HCC in diverse biological processes like proliferation, metastasis, drug resistance, radio-resistance, energy metabolism, autophagy and so on. Besides, many of these lncRNAs are associated with clinicopathological features and clinical prognosis in HCC, which may provide a potential future application in the diagnosis and therapy of HCC.Keratoprosthesis (KPro) devices have the remarkable ability to restore vision in patients suffering from corneal blindness who are poor candidates for traditional penetrating keratoplasty. However, eyes with KPro can experience various complications, including the development of retroprosthetic membrane (RPM). RPMs reduce visual acuity in patients due to physical obstruction of the visual axis, but studies have shown that RPM can also lead to a variety of other consequences, from melting of the corneal carrier graft to precipitating retinal detachments. Histopathologic studies have shown that RPMs are composed of elements from both the recipient and donor. The presence of myofibroblasts in RPMs imparts them with contractile properties, which can contribute to their downstream complications, including angle closure, hypotony, and retinal detachment. At present, there are limited treatments to combat the growth of RPM. Future therapies could include anti-metabolites and targeted anti-inflammatory treatments, as well as device coatings or textured device surfaces that can hinder RPM proliferation. The long-term success of KPro depends on devising an effective solution for preventing RPM growth.In recent years, significant progress has been made in the Meibography technique resulting from the use of advanced image analysis methods allowing a quantitative description of the Meibomian gland structures. Many objective measures of gland distortion were previously proposed allowing for user-independent classification of acquired gland images. However, due to the complicated nature of gland deformation, none of the single-valued parameters can fully describe the analyzed gland images. There is a need to increase the number of descriptive factors, selectively sensitive to different gland features. Here we show that global 2D Fourier transform analysis of infra-red gland images provides values of two new such parameters mean gland frequency and anisotropy in gland periodicity. We show that their values correlate with gland dysfunction and can be used to automatically categorize the images into the three subjective classes (healthy, intermediate and unhealthy). We also demonstrated that classification performance can be improved by dimensionality reduction approach using principal component analysis.

Mast cells, historically known for their effector function in the induction of allergic diseases, reside in all vascularized tissues of the body in particular proximity to blood and lymphatic vessels. As neighboring sentinel cells to blood vessels, mast cells have been associated with angiogenesis. Here we assess the direct contribution of mast cells to neovascularization at the ocular surface.

Corneal neovascularization was induced by placing a single figure-of-eight intrastromal suture 1mm from the limbus in mast cell-deficient (cKit

), C57BL/6, and Balb/c mice. Corneas were harvested at 6h post-suture to quantify cKit

FcεR1

mast cells using flow cytometry and tear wash was collected within 6h to measure β-hexosaminidase and tryptase. Neovascularization was assessed using slit-lamp biomicroscope and immunohistochemistry analysis of corneas harvested on day 4 post-suture. To investigate the effects of mast cells on blood vessel growth, mast cells were co-cultured with vascular endothelial cells (VECs), and tube formation and proliferation of VECs were measured. 2% cromolyn was administered locally to inhibit mast cell activation in vivo.

Placement of corneal suture activates ocular surface mast cells, which infiltrate into the cornea adjacent to new vessels. Mast cell-deficient mice develop significantly fewer new vessels following suture placement. Mast cells directly promote VEC proliferation and tube formation, partly through secreting high levels of VEGF-A. Pharmacological inhibition of mast cell activation results in significantly less corneal neovascularization.

Our data demonstrate that ocular surface mast cells are critical to corneal neovascularization, suggesting mast cells as a potential therapeutic target in the treatment of corneal neovascularization.

Our data demonstrate that ocular surface mast cells are critical to corneal neovascularization, suggesting mast cells as a potential therapeutic target in the treatment of corneal neovascularization.

The aim was to develop and evaluate the impact of a new model in which the infectious disease (ID) physician and pharmacist work together to treat diabetic foot infections (DFIs).

A quasi-experimental before-after study was conducted. The medical charts of inpatients with DFI admitted between April 1, 2017 and March 31, 2018 were reviewed retrospectively (control group, n = 30). Inpatients diagnosed with DFI between April 1, 2018 and March 31, 2019 were enrolled prospectively as the intervention group and received treatment through dedicated ID teamwork (intervention group, n = 35).

The distribution of infection severity and levels of metabolic criteria were similar in the two groups. Compared with the control group, the intervention group received adequate initial empirical treatment more frequently (96.8% vs 43.5%, p < 0.001) and had a shorter median duration of fever (1 day vs 7.5 days, p < 0.001). Rates of healing and relapse within 6 months were similar in the two groups, although the intervention group showed more sites of osteomyelitis (p = 0.036) and a higher percentage of polymicrobial infections (48.6% vs 10.0%, p = 0.001).

The early and full participation of ID physicians and pharmacists in the treatment of DFI facilitated targeted antimicrobial treatment and improved patient outcomes.

The early and full participation of ID physicians and pharmacists in the treatment of DFI facilitated targeted antimicrobial treatment and improved patient outcomes.Low- and middle-income countries (LMICs) face many challenges in controlling COVID-19. Healthcare resources are limited and so are ICU beds. RT-PCR testing is conducted on a limited scale and treatment options are few. There is no vaccine. Therefore, what low-cost solutions remain for the prevention, diagnosis, and treatment of SARS-CoV-2? How should these essential health services be delivered in order to reach the most vulnerable in our societies? In this editorial we discuss several important strategies for controlling COVID-19 including vaccination, molecular and serological diagnostics, hygiene and WaSH interventions, and low-cost therapeutics. We also discuss the delivery of such services in order to reach the most in need. The proposed integrated control strategy requires immediate action and political will in order to reduce the widening health inequalities caused by the pandemic.The elongases of very long-chain fatty acids (Elovls) are involved in the rate-limiting of the carbon chain elongation reaction in fatty acid (FA) biosynthesis in vertebrates. One member of the Elovls family, Elovl4, has been regarded as a critical enzyme involved in the biosynthesis pathway of polyunsaturated fatty acids (PUFAs). To explore the role of Elovl4 in PUFA synthesis in Trachinotus ovatus, the cDNA of the Elovl4b gene is cloned from T. ovatus (ToElovl4b). The ORF of ToElovl4b was 918 bp and encoded 305 amino acid (aa) protein sequences. Sequence alignment showed that the deduced amino acids contained significant structural features of the Elovl4 family, such as a histidine box motif (HXXHH), multiple transmembrane domains and an endoplasmic reticulum (ER) retention signal. Moreover, phylogenetic analysis revealed that ToElovl4b was highly conserved with that of Rachycentron canadum Elovl4b. Moreover, heterologous expression in yeast demonstrated that ToElovl4b could efficiently elongate 182n-6, 183n-6 and 205n-3 FAs up to 202n-6, 203n-6 and 225n-3, respectively. Furthermore, the tissue expression profile indicated that mRNA expression of ToElovl4b was higher in the gonads and brain than in other tissues. Additionally, nutritional regulation suggested the highest mRNA levels of ToElovl4b in liver and brain were under feeding with 11 FO-SO (fish oil, FO; soybean oil, SO) and 11 FO-CO (corn oil, CO)), respectively. These new insights were useful for understanding the molecular basis and regulation of LC-PUFA biosynthesis in fish.Cigarette smoking is a major lifestyle factor leading to different human diseases. The DNA repair gene, thymine DNA glycosylase, is important to cell survival because it stops cells from becoming cancerous protecting/preventing DNA. Exposure to CS may induce genetic changes such as single nucleotide polymorphisms in DNA repair genes. Therefore, the purpose of this study was to investigate the genotype and allele distributions of four TDG SNPs with only smoking behavior in normal patients. Four TDG SNPs-rs4135066 (C/T), rs3751209 (A/G), rs1866074 (C/T), and rs1882018 (C/T) were analyzed by genotyping 235 and 239 blood samples collected from cigarette smokers and non-smokers, among the Saudi population. The results showed that TDG rs4135066 has a significant susceptibility effect observed in long-term smokers (>5 years; OR = 4.53; P = 0.0347) but not in short-term smokers (≤5 years) in contrast with non-smokers. Also, in smokers aged less than 29 years, the „CT,” „TT,” and „CT + TT” alleles of rs1882018 increased the risk of developing all diseases related to smoking by approximately 6, 4, and 5 times, respectively, in contrast with the ancestral „CC” homozygous allele. A comparison of the allele distributions of TDG SNPs in a Saudi population with those in other populations represented in the HapMap project showed that the genetic makeup of the Saudi Arabian population appears to differ from that of other ethnicities. Exceptions include the Yoruba people in Ibadan, Nigeria; those of Mexican ancestry in Los Angeles, California; the Luhya population in Webuye, Kenya; Gujarati Indians in Houston, Texas; and the Tuscan population in Italy, which showed similar allelic frequencies for rs3751209 compared to our Saudi population. In this ethnic, we have found a high variation in the distribution of the alleles and genotype frequencies on TDG gene. This variation on TDG SNP’s with smoking could lead to increase the susceptibility to many diseases related to smoking habits in this population.In 2002/2003 there was a pandemic denominate SARS (severe acute respiratory syndrome), caused by the SARS-CoV virus that belongs to the genera Betacoranavirus and the family Coronaviridae, generally responsible for influenza infections. In mid of 2019, a new disease by the coronavirus named by COVID-19 (SARS-CoV-2) emerged, both infections have flu symptoms, however they are infections that variable intensity, being medium to severe. In medium infections individuals have the virus and exhibit symptoms, however hospitalization is not necessary, in severe infections, individuals are hospitalized, have high pathology and in some cases progress to death. The virus is formed by simple positive RNA, enveloped, non-segmented, and presenting the largest genome of viruses constituting 32 Kb, consisting of envelope proteins, membrane, nucleocapsid and spike protein, which is essential in the interaction with the host cells. As for the origin of this virus, research has been intensified to determine this paradox and although the similarity with SARS-CoV, this virus did not has necessarily the same place of origin. As for the immune system, it is currently unknown how this new virus interacts. In this brief review, we demonstrate important considerations about the responses to this infection.This study was designed to evaluate the cross-resistance of Salmonella Typhimurium ATCC 19585 (STWT), ciprofloxacin-resistant S. Typhimurium (STCIP), and clinically isolated S. Typhimurium CCARM 8009 (STCLI) serially exposed to a half MIC of ceftriaxone (CEF), ciprofloxacin (CIP), polymyxin B (POL), or tetracycline (TET), followed by 1 MIC of CEF, CIP, POL, and TET. The viability changes of STWT, STCIP, and STCLI exposed to different classes of antibiotics were measured to evaluate the development of cross-resistance. The relative fitness was also estimated to evaluate the reproductive success of STWT, STCIP, and STCLI consecutively exposed to a half and 1 MIC of CEF, CIP, POL, or TET. The expression levels of efflux pump-related genes (acrA, acrB, mdsA, mdsB, mdtB, and tolC) were evaluated by using a quantitative RT-PCR assay. The MIC of CIP against STCIP was increased by 128-fold compared to STWT. STCLI was highly resistant to POL (MIC = 8 μg/ml) and TET (MIC = 256 μg/ml). STWT exposed to CIP [1/2] was susceptible to POL [1] than CEF [1], CIP [1], and TET [1], STCIP exposed to CIP [1/2] was susceptible to CEF [1] and POL [1], and STCLI exposed to CIP [1/2] was susceptible to POL [1]. STCIP was cross-resistant to CEF [1/2]-CIP [1], CIP [1/2]-CIP [1], POL [1/2]-CIP [1], and TET [1/2]-CIP (Ochoa et al., 2020) [1]. The efflux pump-related genes (acrA, acrB, mdsA, mdsB, mdtB, and tolC) were overexpressed in STWT, STCIP, and STCLI exposed to serial antibiotic treatments, which was related to the development of cross-resistance. The antibiotic susceptibility profiles of STWT, STCIP, and STCLI exposed to serial antibiotic treatments are worth understanding the evolution of antibiotic resistance and developing effective therapeutic regimens against antibiotic-resistant bacteria.Due to the increasing resistance of microorganisms against antibiotics, the use of natural bioactive substances for the prevention of pathogenic bacteria is considered in food products. In this study, thymol, cardamom essential oil, L. plantarum cell-free supernatant (ATCC 14917), and their nanoparticle candies prepared and inhibition activities against S. mutans (ATCC 25175), which is important in causing tooth decay, was investigated. Moisture content, pH, and sensory analyzes of candies measured. Also, SEM and FTIR of treated candy samples were performed. All examined bioactive substances and their nanoparticles showed an inhibitory effect against S. mutans with different minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The prepared candies had pH 5.5 represented a bactericidal effect against S. mutans. SEM and FTIR results approved the antibacterial effects of prepared candies. According to the results, all of the prepared candies significantly decreased S. mutans in saliva compared to the control candy and they are suitable agents for S. mutans growth-inhibiting. Also, cardamom essential oil candy showed the most general acceptance in a sensory analysis by panelists.After sequence comparison, it was found that there are multiple amino acid mutations in pre-M and envelope (E) protein of Japanese encephalitis virus vaccine strain comparison with wild type (WT) strain SA14. It is generally acknowledged it is the mutations that have caused the virulence attenuation of vaccine strain, but lack of sufficient experimental evidences. For a better understanding of the mechanism of attenuation of Japanese encephalitis virus (JEV), in this study, we assessed whether prM/E is critical neurovirulence determinants of JEV with infectious cDNA clones technique. Substitutions prM/E of vaccine strain with that of WT SA14 did significantly increase the virulence of JEV to the similar level of wild type SA14, and simultaneously, replacement prM/E of JEV WT strain SA14 with that of vaccine strain SA14-14-2 decreased the virulence of JEV significantly to the similar level of vaccine stain. The results indicate that the prM/E protein is the crucial virulence determinant of Japanese encephalitis virus, although other proteins take part in the process to some extent.Campylobacter fetus is a gram-negative, motile, spiral or S-shaped bacterium, which induces campylobacteriosis. This disease causes decrease productivity of cattle. Although considerable research has been done on the role of C. fetus on female fertility, little is known about the effect on bulls. The aim of this work was to evaluate the effect of C. fetus subsp. fetus (Cff) and C. fetus subsp. venerealis (Cfv) on bull sperm quality. Samples of frozen semen (n = 29 straws) were each distributed into three groups two of them incubated with the microorganism (Cff, Cfv) and a control group. The proportions of live spermatozoa, with functional membrane and true acrosomal reaction in control group were significantly (P 0.05) were found in sperm chromatin structure among treatments. In adhesion assay, proportions of spermatozoa with adhered Campylobacter were similar for both subspecies. Results confirm that Cff and Cfv have the same ability to bind in an irreversible way to bull spermatozoa and to affect sperm quality. It is proposed that adherence could be considered as the main cause of sperm alterations, and also an important step of pathogenesis and venereal transmission.While serving as environmental reservoir for V. cholerae infection, biofilms are also crucial for intestinal colonization of the pathogen. Triterpenoids, a group of bioactive phytochemicals, have been tested for antibiofilm activity against model biofilm forming bacteria in recent times. In this context, glycyrrhetinic acid (GRA), ursolic acid (UA) and betulinic acid (BA), representing three categorically distinct groups of pentacyclic triterpenoids, are targeted for profiling their impact on Vibrio cholerae C6709 biofilms. The triterpenoids substantially affected biofilm associated attributes like formation, substratum adherence and dispersion from preformed biofilms. Though at variable degree, the compounds decreased cell surface hydrophobicity and composition in terms of macromolecular content. Not only EPS-associated extracellular enzyme activities were estimated to be reduced by triterpenoid exposure, ultra structural analysis also revealed that GRA, UA and BA can affect extracellular polymeric substance (EPS) content. Albeit total extracellular proteolytic activity remained unaffected by the triterpenoids, GRA treatment resulted in considerable reduction of extracellular gelatinase activity. Molecular docking analysis indicated potential interaction with cyclic di-GMP sensor VpsT, autoinducer-2 sensor kinase LuxP-LuxQ and transcriptional activator HapR, components of complex quorum sensing networks modulating biofilm formation. Comprehensive analysis of antibiotic action revealed accentuation of cephalosporin antibiotics with GRA and UA while BA potentiated action of fluoroquinolones against biofilmed bacteria, widening the scope of combinatorial therapeutic strategy.Rhoptry proteins (ROPs) play a significant role in various stages of Toxoplasma gondii (T. gondii) life cycle, being critical for both invasion and intracellular survival. ROP38 is a key manipulator of host gene expression and has a function in tachyzoite to bradyzoite conversion. In this study, we’ve employed various bioinformatics online tools for immunogenicity prediction of ROP38 protein, comprising physico-chemical, antigenic and allergenic profiles, transmembrane domain, subcellular localization, post-translational modification (PTM) sites, secondary and 3D structure, B-cell, MHC-binding and cytotoxic T-lymphocyte (CTL) epitopes. The findings showed 54 PTM sites without a transmembrane domain. Also, ROP38 was proved a non-allergenic and antigenic protein. The protein had Sec signal peptide (Sec/SPI) with 0.8762 likelihood. The secondary structure included 52.68% random coil, 29.57% alpha helix and 17.74% extended strand. Based on Ramachandran plot output for refined model, 95.3%, 3.4%, and 1.4% of amino acid residues were incorporated in the favored, allowed, and outlier regions, respectively. B-cell epitopes TFPGDDIQTSS (67-72) and KAKNKWGRTRYTLQG (207-221) as well as T-cell epitope LSPVGFFTAL (6-15) possessed the highest antigenic index in the protein sequence. This paper is a premise for further researches, and provides insights for the development of a suitable vaccine against toxoplasmosis. More empirical studies are required using the ROP38 alone or in combination with other antigens/epitopes in the future.

Triclosan (TCS) is an extensively used antibacterial agent which has been frequently detected in different environmental compartments. Because of TCS inhibition effect on vast majority of bacterial species, it is important to explore fungal species and their involved enzymes in TCS biodegradation. The aim of this study was to compare the potential of two white rot fungi Pleurotus ostreatus and Trametes versicolor for TCS biodegradation through the whole cell culture of fungi in an aqueous culture medium. Additionally, the changes in ligninolytic enzyme activities and possible correlations and contributions of degradative enzymes during TCS biodegradation process were monitored.

This study was carried out using a factorial experiment with a completely randomized design in three replications. factorial design in The experimental factors included two white rot fungi Pleurotus ostreatus and Trametes versicolor and uninoculated controls which were subjected to five levels of TCS concentrations (0, 5, 10, 20, 3nd biodegradation. Furthermore, laccase and manganese peroxidase (MnP) were determined as more involved enzymes which significantly correlated to TCS biodegradation by T. versicolor and P. ostreatus, respectively.

P. ostreatus might be considered as efficient fungus in biodegradation of high amount of TCS in environmental matrices. The results of the present study might provide insights for future investigations on potential of fungi for applications in bioaugmentation-based strategies to remove TCS from wastewater and activated sludge.

P. ostreatus might be considered as efficient fungus in biodegradation of high amount of TCS in environmental matrices. The results of the present study might provide insights for future investigations on potential of fungi for applications in bioaugmentation-based strategies to remove TCS from wastewater and activated sludge.

Radiotherapy for breast cancer can increase the risks of heart disease. Patient-specific risk assessment may be improved with the inclusion of doses to cardiac substructures. The purpose of this work was to use automatic segmentation to evaluate substructure doses and develop predictive models for these based on the dose to the whole heart.

Automatic segmentation was used to delineate cardiac substructures in a Danish breast cancer trial (DBCG HYPO) dataset comprising over 1500 Danish women treated between 2009 and 2014. Trends in contouring practices and cardiac doses over time were investigated, and models to predict substructure doses from whole heart dose parameters were fit to the data.

Manual contouring consistency improved over the study period when compared with automatic segmentation; systematic differences between automatically and manually defined heart volume decreased from 106cm

to 12.0cm

. Doses to the heart and cardiac substructures also decreased. Mean whole heart doses for left-sided treatments in 2009 and 2014 were 1.94±1.19 Gy and 1.29±0.69 Gy (average ± SD), respectively. Prediction of mean substructure doses is accurate, with R

scores in the range 0.45-0.95 (average 0.77), depending on the particular structure.

This study reports heart and cardiac substructure doses in a large breast cancer cohort. Predictive models generated in this work can be used to estimate mean cardiac substructure doses for datasets where patient imaging and dose distributions are not available, provided the tangential field techniques are consistent with those used in the trial.

This study reports heart and cardiac substructure doses in a large breast cancer cohort. Predictive models generated in this work can be used to estimate mean cardiac substructure doses for datasets where patient imaging and dose distributions are not available, provided the tangential field techniques are consistent with those used in the trial.

We investigated clinical and genetic factors associated with severe radiation-induced lymphopenia (RIL) in a randomized clinical trial of photon vs. proton radiation, with chemotherapy, for non-small cell lung cancer.

XRCC1 rs25487 was genotyped in lymphocytes from serial peripheral blood samples. Severe RIL was defined as absolute lymphocyte count (ALC)<0.3×10

cells/L. Univariate and multivariate analyses were used to identify independent risk factors, which were then used to group patients for risk of severe RIL.

Univariate analysis of the 178 patients in this analysis showed that older age, larger tumors, higher lung V5 and mean lung dose, and higher heart V5 and mean heart dose were associated with severe RIL during treatment (P<0.05). The XRCC1 rs25487 AA genotype was also associated with increased risk of severe RIL during treatment (AA vs. others hazard ratio [HR]=1.665, 95% confidence interval [CI] 1.089-2.500, P=0.018). Multivariate analyses showed that older age (HR=1.031, 95% CI 1.009-1.054, P=0.005), lung V5 (HR=1.039, 95% CI 1.023-1.055, P<0.0001), and AA genotype (AA vs. others, HR=1.768, 95% CI 1.165-2.684, P=0.007) were independently associated with higher incidence of severe RIL. These three risk factors (age≥56years, lung V5≥51% and XRCC1 rs25487 AA) distinguished patients at different risk of developing severe RIL (P<0.0001).

Age, lung V5 and XRCC1 rs25487 AA were all linked with risk of severe RIL. Our predictive risk model may be helpful for identifying patients at high risk of severe RIL so that treatment can be modified.

Age, lung V5 and XRCC1 rs25487 AA were all linked with risk of severe RIL. Our predictive risk model may be helpful for identifying patients at high risk of severe RIL so that treatment can be modified.

Thalictrum minus L., which is widespread across Eurasia, is utilized as a folk medicine for treating dysentery, bedsore, fungal infection and lung inflammation in China, Mongolia and Iran.

A Mongolian folk medicinal plant named Thalictrum minus L. (TML) has been extensively used for the treatment of lung inflammation, bacterial and fungal infection and tuberculosis. Our present study aims to investigate the effectiveness of TML against particulate matter (PM)-induced acute lung injury (ALI) and the potential underlying mechanisms.

Initially, HPLC-Q-TOF was applied for the qualitative analysis and HPLC was used for quantitative analysis of main components in TML. Then, the mice model of ALI was induced by PM via intratracheally instilled with 50mg/kg body weight of Standard Reference Material1648a (SRM1648a), and TML (10, 20, 40mg/kg) were administered orally 1h prior to PM. The efficacy and molecular mechanisms in the presence or absence of TML were elucidated.

Eleven main ingredients were detected in TML attenuated PM-induced ALI through suppressing the release of inflammatory cytokines and alleviating oxidative damage correlated with the AMPK-Nrf2/KEAP signaling pathways, MAPKs-NLRP3/caspase-1 signaling pathways, as well as apoptotic pathways.

These findings indicated that TML attenuated PM-induced ALI through suppressing the release of inflammatory cytokines and alleviating oxidative damage correlated with the AMPK-Nrf2/KEAP signaling pathways, MAPKs-NLRP3/caspase-1 signaling pathways, as well as apoptotic pathways.

Weimaining (WMN) is a condensed Tannin compound extracted from Fagopyrum cymosum (Trevir.) Meisn., which comes from the roots of buckwheat, a type of Chinese herbal medicine, was first recorded in „Bencao Shiyi”. WMN has inhibitory effects on multiple cancer types and is widely used in clinical practice; however, the mechanism underlying the anti-tumor effect of WMN is still unclear.

To investigate the effect of WMN on the cellular activity and apoptosis of mouse breast cancer 4T1-luc2 cells, and caspase-3 and cleaved-caspase-3 expression.

Luciferase-labeled mouse breast cancer 4T1-luc2 cells were inoculated into the mouse breast pad to establish a luciferase-labeled mouse breast cancer cell model. BALB/C-nu mice were randomly divided into model, WMN, and low-molecular-weight heparin (LMWH) groups (n=10). Another 10 mice served as the normal control group (no cancer cell injection). The WMN group was administered WMN 250mg/kg per day for 14 days, the LMWH group was given LMWH (1500 U/kg) daily for 14 dawer than that of the LWMH group on day 14 after administration. Additionally, the AI and expression levels of caspase-3 mRNA, caspase-3, and cleaved-caspase-3 protein of the WMN group were higher than those of the LWMH group.

WMN can effectively suppress the growth of 4T1-luc2 breast cancer xenografts in mice, and promote the apoptosis of breast cancer cells by upregulating the expression of caspase-3.

WMN can effectively suppress the growth of 4T1-luc2 breast cancer xenografts in mice, and promote the apoptosis of breast cancer cells by upregulating the expression of caspase-3.

Lonicerae japonicae flos (LJF, the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.), a typical herbal medicine, targets the lung, heart and stomach meridian with the function of clearing heat and detoxication. It ameliorated inflammatory responses and protected against acute lung inflammation in animal models. Acute lung injury (ALI) is a kind of inflammatory disease in which alveolar cells are damaged. However, a network pharmacology study to thoroughly investigate the mechanisms preventing ALI has not been performed.

In this study, we examined the main active ingredients in LJF and the protective effects of LJF on LPS-induced ALI in rats.

First, the main active ingredients of LJF were screened in the TCMSP database, and the ALI-associated targets were collected from the GeneCards database. Then, we used compound-target and target-pathway networks to uncover the preventive mechanisms of LJF. Furthermore, we assessed the preventive effects of LJF in an LPS-induced rat model with thealysis showed that the DEGs associated with immune response and inflammation signalling pathways and the IL-17 signalling pathway were significantly enriched in LJF. Compared with those in ALI, the expression of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3, which are involved in the IL-17 signalling pathway, were significantly decreased in the LJF group according to the qRT-PCR analyses.

In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF.

In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF.

This study aimed to 1) quantify the evidence-practice gap (EPG) between dental clinical practice and published evidence on Minimal Intervention Dentistry (MID) among dentists in Japan; and 2) examine the hypothesis that dentist characteristics have a significant association with the EPG.

We conducted a cross-sectional study via use of a web-based questionnaire survey of dentists who were affiliated with the Dental Practice-based Research Network Japan (n = 297). To quantify the EPG on MID, we used a questionnaire that included 10 clinical questions or scenarios to assess concordance between dental practice and published evidence on MID. We evaluated concordance by coding responses to each question as consistent or inconsistent with the evidence. An overall concordance was then determined as percent of responses that were consistent with published evidence for 10 questions. Subsequently, multiple logistic regression analysis was conducted to examine the associations between dentist characteristics and highnt-ordinance-designated city”, and „frequently obtaining evidence from the English-language scientific journal articles”.

Despite the establishment and dissemination of the concept of MID, the EPG on MID exists in Japanese dental clinical practices. A high concordance was significantly associated with the following dentist characteristics „female dentist”, „dental clinic location in a government-ordinance-designated city”, and „frequently obtaining evidence from the English-language scientific journal articles”.

This in vitro study explored quantitative outcome measures as clinical indicators of simulated occlusal tooth wear progression.

Ten sound, extracted human premolars were selected and submitted to occlusal tooth wear simulation in 0.5-mm steps (0/0.5/1.0/1.5 mm). At each step, enamel thickness on the buccal cusp tips was evaluated using cross-polarization optical coherence tomography (CP-OCT) and micro-computed tomography (μ-CT). The occlusal surface of each premolar was also scanned at each step using a 3D digital intraoral scanner, followed by morphological characterization using standard topography attributes (Slope, Relief, RFI, OPCr). Repeated measures ANOVA assessed differences in simulated wear levels for the μ-CT and CP-OCT data as well as the topography values. Correlations were also calculated between the μ-CT/CP-OCT and topography data.

Significant differences were observed for enamel thickness at each simulation wear stage, for both CP-OCT (p < 0.001) and μ-CT (p < 0.001), with good agr process.

CP-OCT measures of enamel thickness and dental 3D topographic attributes showed potential as objective outcomes for the clinical monitoring of occlusal tooth wear. Their combination provided a comprehensive understanding of the tooth wear development process.

Toothbrushing and interdental cleaning are critical to maintaining good oral health. Literature is beginning to suggest that these behaviours may be conducted automatically, although the instigation (’deciding to do’) and execution (’doing’) of these behaviours has never been examined separately. The objective of this study was to test a theoretically informed supposition that oral hygiene behaviours in adults are automatic behaviours.

One hundred and fifty participants attending three types of dental providers covering emergency and routine dental services, completed a questionnaire. The self-reported behavioural automaticity index scale (SRBAI) was used to measure behavioural automaticity.

Morning toothbrushing SRBAI scores were higher than evening scores (Z=-3.315, p = 0.001). Automaticity scores for instigating both toothbrushing and interdental cleaning were also higher compared to execution (toothbrushing Z=-2.601, p = 0.009 and interdental cleaning Z=-2.256. p = 0.024). Toothbrushing automaticitys helps inform how behaviour change efforts should be approached.Engineering the membrane of the polymersomes with biologically relevant stimuli-responsive units enables spatial and temporal controlled drug release for effective therapy. Herein, we introduce a new-type of polymersomes featuring reactive oxygen species singlet oxygen (1O2)-labile membrane by employing a versatile stereoregular amphiphilic poly(ethylene glycol)-block-poly(β-aminoacrylate)-block-poly(ethylene glycol) copolymers, which are synthesized through a facile one pot modular amino-alkynoate click polymerization between secondary amines and activated alkynes. These polymersomes readily co-encapsulate an anticancer drug doxorubicin (DOX) and a near infrared (NIR) photosensitizer IR-780 with hydrophobic characteristics in the membrane, and the resulting polymersomes show efficient uptake by the tumor cells. NIR light irradiation on the tumors, following intraperitoneal injection of the IR-780/DOX co-encapsulated polymersomes, facilitates tumor-specific release of DOX through disassembly of the polymersome nanostructure via 1O2-mediated photocleavage of the membrane. Moreover, IR-780 dye can convert NIR light energy into heat in addition to the generation of 1O2, thus allows to realize both photothermal and photodynamic therapy. Accordingly, the NIR light-mediated on demand chemotherapy, in combination with appreciable phototherapy, of IR-780/DOX co-loaded polymersomes demonstrate an efficient tumor suppression in vivo.Here, we report a tannic acid-Fe3+ coordination complex coating that confers magnetic resonance imaging (MRI) theranostic properties to inert nanomaterials. Boron nitride nanosheets (BNS), which lack magnetic field and light responsiveness, were used as a model nonfunctional nanomaterial. Among various catechol derivatives tested (i.e., dopamine, 3,4-dihydroxyphenylacetic acid, gallic acid, and tannic acid), a coating of tannic acid-Fe3+ coordination complex provided the highest magnetic field relaxivity and near infrared (NIR) laser light responsiveness. An in vitro study showed that KB tumor cells treated with tannic acid-Fe3+ coordination complex adsorbed on BNS (TA-Fe/BNS) exhibited higher T1-weighted magnetic resonance contrast compared with plain BNS, and BNS coated with tannic acid or Fe alone. NIR irradiation at 808 nm caused a significant increase in KB tumor cell death after treatment with TA-Fe/BNS compared with other treatments. In vivo MRI imaging revealed tumor accumulation of intravenously administered TA-Fe/BNS. Guided by MRI information, application of focused laser irradiation onto tumor tissues resulted in complete tumor ablation. These results support the potential of TA-Fe/BNS for MRI theranostics. Moreover, this study suggests the wide applicability of TA-Fe noncovalent coating as biocompatible and facile tool for converting nonfunctional early-generation nanomaterials into functional new nanomaterials, opening new opportunities for their use in translational biomedical applications such as MRI theranostics.Due to the rapid changes that have occurred in the field of drug discovery and the recent developments in the early 21st century, the role of drug delivery systems (DDS) has become increasingly more important. For the past 20 years, our laboratory has been developing gene delivery systems based on lipid-based delivery systems. One of our efforts has been directed toward developing a multifunctional envelope-type nano device (MEND) by modifying the particle surface with octaarginine, which resulted in a remarkably enhanced cellular uptake and improved intracellular trafficking of plasmid DNA (pDNA). When we moved to in vivo applications, however, we were faced with the PEG-dilemma and we shifted our strategy to the incorporation of ionizable cationic lipids into our system. This resulted in some dramatic improvements over our original design and this can be attributed to the development of a new lipid library. We have also developed a mitochondrial targeting system based on a membrane fusion mechanism using a MITO-Porter, which can deliver nucleic acids/pDNA into the matrix of mitochondria. After the appearance of antibody medicines, Opdivo, an immune checkpoint inhibitor, has established cancer immunology as the 4th strategy in cancer therapy. Our DDS technologies can also be applied to this new field of cancer therapy to cure cancer by controlling our immune mechanisms. The latest studies are summarized in this review article.

Leadless pacemakers are an established treatment option for bradyarrhythmias. Similar to conventional transvenous pacemakers, satisfying pacing values during implantation are targeted for optimal long-term device function. The objective is to investigate the role of a local injury current (IC) in leadless pacemaker implantations.

The IC, sensing value, capture threshold and impedance were collected in 30 consecutive patients receiving a leadless pacemaker.

39 EGMs were recorded from 30 patients (including 9 device repositions). An IC was detected in 15 cases (38%). At implantation, the presence of an IC was associated with a significantly lower sensing (7.1±3.7mV vs 12.0±4.0mV; P=0.004) and a higher capture threshold (median threshold 1.13V at 0.24ms [0.50-2.00] vs 0.50V at 0.24ms [0.25-0.75]; P=0.002) and with a 26 fold higher likelihood of device repositioning compared to the absence of an IC (OR 26.3 [2.79-248], P<0.001). Patients with an IC in their final implant position had a lower sensing (9.3±4.4mV vs 13.6±4.7mV at implantation, P=0.04), while the initially similar capture threshold was lower after 24h in the IC group. After 2weeks, all parameters were similar between the two groups.

Our study shows that an IC can readily be observed during leadless pacemaker implantation associated with a lower sensing and a higher capture threshold at implantation but with similar to even better values during follow-up.

Our study shows that an IC can readily be observed during leadless pacemaker implantation associated with a lower sensing and a higher capture threshold at implantation but with similar to even better values during follow-up.

Aortic valve area (AVA) is commonly determined from 2-dimensional transthoracic echocardiography (2D TTE) by the continuity equation; however, this method relies on geometric assumptions of the left ventricular outflow tract which may not hold true. This study compared mean differences and correlations for AVA by planimetric (2-dimensional transesophageal echocardiography [2D TEE], 3-dimensional transesophageal echocardiography [3D TEE], 3-dimensional transthoracic echocardiography [3D TTE], multi-detector computed tomography [MDCT], and magnetic resonance imaging [MRI]) with hemodynamic methods (2D TTE and catheterization) using pairwise meta-analysis.

Ovid MEDLINE®, Ovid EMBASE, and The Cochrane Library (Wiley) were queried for studies comparing AVA measurements assessed by planimetric and hemodynamic techniques. Pairwise meta-analysis for mean differences (using random effect model) and for correlation coefficients (r) were performed.

Forty-five studies (3014 patients) were included. Mean differences between planimetric and hemodynamic techniques were 0.