• Weinreich Marker opublikował 1 rok, 8 miesięcy temu

    The resveratrol nanoparticles have markedly enhanced its anticancer activity both in vitro and in vivo, thus considering it as a potential strategy to fight various cancers.

    Nanotechnology approaches have been extensively utilized to achieve higher solubility, improved oral bioavailability, enhanced stability, and controlled release of resveratrol. The resveratrol nanoparticles have markedly enhanced its anticancer activity both in vitro and in vivo, thus considering it as a potential strategy to fight various cancers.Quinoxaline (Qx) derivatives are promising building units for efficient photovoltaic polymers owing to their strong light absorption and high charge-transport abilities, but they have been used exclusively in the construction of polymer donors. Herein, for the first time, Qx-based polymer acceptors (PA s) were developed by introducing electron-withdrawing cyano (CN) groups into the Qx moiety (QxCN). A series of QxCN-based PA s, P(QxCN-T2), P(QxCN-TVT), and P(QxCN-T3), were synthesized by copolymerizing the QxCN unit with bithiophene, (E)-1,2-di(thiophene-2-yl)ethene, and terthiophene, respectively. All of the PA s exhibited unipolar n-type characteristics with organic field-effect transistor (OFET) mobilities of around 10-2  cm2  V-1  s-1 . In space-charge-limited current devices, P(QxCN-T2) and P(QxCN-TVT) exhibited electron mobilities greater than 1.0×10-4  cm2  V-1  s-1 , due to the well-ordered structure with tight π-π stacking. When the PA s were applied in all-polymer solar cells (all-PSCs), the highest performance of 5.32 % was achieved in the P(QxCN-T2)-based device. These results demonstrate the significant potential of Qx-based PA s for high-performance all-PSCs and OFETs.We developed a new and injectable poly-dicalcium phosphate dihydrate (P-DCPD) forming cement. The key structural difference between P-DCPD and classical DCPD is that P-DCPD is composed of interconnected P-DCPD crystals by interlocking to the polyphosphate chains. In contrast, DCPD is composed of a package of DCPD crystals with weak mutual ionic bonding. The purpose of this continuing study was to compare the physicochemical properties between P-DCPD and DCPD cement particles. Data collected from SEM, X-ray diffraction, and Raman Spectroscopy approaches demonstrated that P-DCPD has a more stable chemical structure than DCPD as evidenced by much less transformation to hydroxyapatite (HA) during setting. Nanoindentation showed a similar hardness while the elastic modulus of P-DCPD is much lower than DCPD that might be due to the much less HA transformation of P-DCPD. P-DCPD has much lower zeta potential and less hydrophilicity than DCPD because of its entangled and interconnected polyphosphate chains. It is expected that superhydrophilic DCPD undergoes faster dissolution than P-DCPD in an aqueous environment. Another interesting finding is that the pH of eluent from P-DCPD is more neutral (6.6-7.1) than DCPD (5.5-6.5). More extensive experiments are currently underway to further evaluate the potential impacts of the different physiochemical performance observed of P-DCPD and DCPD cement particles on the biocompatibility, degradation behavior and bone defect healing efficacy both in vivo and in vitro.

    Direct-acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)-infected patients. The real-world treatment outcome in Taiwanese patients on a nationwide basis is elusive.

    The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12weeks after end-of-treatment).

    A total of 13951 registered patients with SVR12 data available were analysed (mean age, 63.0years; female, 55.9%; HCV genotype-1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment-naïve noncirrhotic, treatment-naïve cirrhotic, treatment-experienced noncirrhotic and treatment-experienced cirrhotic patients, respectively. The SVR12 rate was>95% acreatment success.

    DAAs are highly effective in treating Taiwanese HCV patients in the real-world setting. Maintaining DAA adherence and selecting highly efficacious regimens are keys to ensure treatment success.

    Bisphenol A (BPA) is a well-recognized endocrine disruptor and is globally used in the manufacture of many plastic items. Multiple studies suggest links between prenatal BPA exposure and alterations in neurodevelopment and behaviors in children, even at lower levels. This study was conducted to reveal the role of astrocyte morphology and Gamma aminobutyric acid (GABA) signaling in BPA induced cognitive defects in the offspring of Wistar albino rats when exposed during the prenatal and postnatal periods.

    Dams of Wistar albino rats were exposed to a dose of 5mg/kg body weight of BPA throughout the pregnancy and lactation period until the third postnatal day (PND). After delivery of pups, cognitive tests were carried out on the 21st, 24th, and 28th PNDs. Blood samples were collected for measurement of serum GABA levels. On the same day as the blood collections, pups were sacrificed and their right frontal cortices were dissected out. Immunohistochemical analysis for glial fibrillar acidic protein + astrocytes was conducted.

    Pre and postnatal BPA exposure led to anxiety like behavior in pups. This exposure also resulted in reduced serum GABA concentrations. Immunohistochemical analysis revealed reduced astrocyte numbers as well as decreased numbers of dendritic spines in the BPA exposed pups.

    BPA exposure during critical periods of development leads to cognitive impairments that correlate with the defects in the GABA signaling pathways and deteriorated morphology of the astrocytes in the offspring of the Wistar rats.

    BPA exposure during critical periods of development leads to cognitive impairments that correlate with the defects in the GABA signaling pathways and deteriorated morphology of the astrocytes in the offspring of the Wistar rats.

    Cisplatin is an extensively used chemotherapy agent for lung cancer, but its drug resistance serves as a huge obstacle for chemotherapy failure of lung cancer patients. Hence, researchers aimed to determine role of sirtuin 3 (SIRT3) considering its action in cisplatin resistance of lung cancer.

    The expression patterns of SIRT3, FOXO3, and CDT1 were determined using RT-qPCR and Immunoblotting in lung cancer. Immunofluorescence and Co-IP were adopted to detect co-localization and interaction of FOXO3 and CDT1. Loss- and gain-function assays were conducted to determine roles of SIRT3, FOXO3, and CDT1 in resulting pathological changes, while biological behavior of cells was determined using a combination of CCK-8, flow cytometry, colony formation, and Transwell assays. The effects of SIRT3 and CDT1 were determined in the nude mice xenografted with the tumor. The proliferation-, angiogenesis-, and apoptosis-associated factors levels were determined using Immunoblotting.

    SIRT3, FOXO3, and CDT1 expression was suppressed in the lung cancer tissues and cells. FOXO3 positively regulates the CDT1 expression pattern and SIRT3 elevation inhibits FOXO3 at the acetylated level, thus, elevating FOXO3 expression. The elevation of SIRT3, FOXO3, or CDT1 inhibited cell cisplatin resistance of lung cancer cells as well as inhibited viability, proliferation, and invasion in vitro. In vivo experiments, SIRT3 depletion elevated Ki-67 and VEGFA levels, but downregulated cleaved caspase 3 level.

    Collectively, overexpressed SIRT3 elevates expression of FOXO3a/CDT1 axis, thus, contributing to enhanced sensitivity of lung cancer cells.

    Collectively, overexpressed SIRT3 elevates expression of FOXO3a/CDT1 axis, thus, contributing to enhanced sensitivity of lung cancer cells.

    Gastric cancer (GC) is a malignant tumor with a significantly high mortality rate, yet, its pathogenesis is not fully understood. Bioinformatics predicted that LINC01224 is highly expressed in stomach adenocarcinoma (STAD), and showed that LINC01224 adsorbed miR-193a-5p to target CDK8. Therefore, this study intended to verify the effect of the LINC01224/miR-193a-5p/CDK8 axis on the biological behavior of gastric cancer.

    Expressions of LINC01224, miR-193a-5p, CDK8, apoptosis-, and EMT-related genes were analyzed using the GEPIA website, RT-qPCR, in situ hybridization, and Western blot as needed. Bioinformatics and dual luciferase assay were used to evaluate the relationship between LINC01224, miR-193a-5p, and CDK8. Functional experiments and rescue experiments (MTT assay, flow cytometry, wound healing assay, and Transwell) were conducted to detect the effects of the above genes on the biological characteristics of GC cells. Tumorigenesis assay was used to verify the results of in vitro experiments.

    LINC01224 adsorbed miR-193a-5p to target and upregulate CDK8. The expressions of LINC01224 and CDK8 were increased, while the expression of miR-193a-5p was decreased in GC. Overexpressed LINC01224 promoted cell viability, migration and invasion, accelerated tumor formation, attenuated apoptosis, inhibited the expressions of apoptosis-related proteins, and promoted the expressions of EMT-related proteins, whereas silenced LINC01224 led to the opposite effect. MiR-193a-5p inhibitor partially offset the effect of silenced LINC01224; interestingly, siCDK8 significantly reversed the effect of miR-193a-5p inhibitor on GC cells.

    LINC01224 affects the biological behavior of gastric cancer by mediating miR-193a-5p to regulate CDK8.

    LINC01224 affects the biological behavior of gastric cancer by mediating miR-193a-5p to regulate CDK8.

    This qualitative study aimed to provide an in-depth understanding of nurses’ experiences with near-miss errors and report omissions known to be direct or indirect causes of medical accidents in hospitals and cited as precursors of serious medical accidents.

    This study collected experiences of research participants through an interview as a qualitative research method and confirmed the meaning through an inductive approach.

    We selected nine nurses with various levels of experience from 27 May to 10 June 2019 for analysis. We adopted phenomenological research methods and procedures proposed by Colaizzi (Existential-phenomenological alternative for psychology, 1978) and established the feasibility and integrity of our results based on narrative studies proposed by Lincoln and Guba (Naturalistic inquiry, 1985).

    This study demonstrated that near-miss errors and report omissions experienced by professional nurses could be merged into the following themes lack of cognitive susceptibility to near-miss errors; confusion about the reporting system for near-miss errors; lack of knowledge about near-miss errors; disappointment with results of reporting near-miss errors; and fear of reporting near-miss errors. These results strongly suggest the need to improve recognition efforts based on a socio-educational viewpoint involving the so-called openness about failures.

    This study demonstrated that near-miss errors and report omissions experienced by professional nurses could be merged into the following themes lack of cognitive susceptibility to near-miss errors; confusion about the reporting system for near-miss errors; lack of knowledge about near-miss errors; disappointment with results of reporting near-miss errors; and fear of reporting near-miss errors. These results strongly suggest the need to improve recognition efforts based on a socio-educational viewpoint involving the so-called openness about failures.The prevalence of Toxoplasma gondii exposure in Inuit living in Nunavut (20%) is twice that of the US (11%); however, routes of exposure for Inuit communities in North America are unclear. Exposure to T. gondii in humans has been linked with consumption of raw or undercooked shellfish that can accumulate environmentally resistant oocysts. Bivalve shellfish, such as clams, are an important, nutritious, affordable and accessible source of food in many Northern Communities. To date, presence of T. gondii in clams in Northern Canada has not been reported. In this study, we tested for T. gondii presence in clams (Mya truncata) that were harvested in Iqaluit, Nunavut over a 1-week period in September 2016. Of 390 clams, eight (2.1%) were confirmed to contain T. gondii DNA (≥99.7% identity), as determined using polymerase chain reaction (PCR) and sequence confirmation. Additionally, three clams (0.8%) were confirmed to contain Neospora caninum-like DNA (≥99.2% identity). While N. caninum is not known to be a zoonotic pathogen, its presence in shellfish indicates contamination of the nearshore with canid faeces, and the potential for marine mammal exposure through marine food webs. Notably, the PCR assay employed in this study does not discriminate between viable and non-viable parasites. These findings suggest a possible route for parasite exposure through shellfish in Iqaluit, Nunavut. Future research employing viability testing will further inform public health messaging on the infectious potential of T. gondii in shellfish.Coxiella burnetii causes coxiellosis in animals and Q fever in humans, a potentially debilitating zoonotic disease commonly transmitted through domestic ruminants. To prevent transboundary spread of C. burnetii, animals may be tested prior to export. In alpacas, this process is complicated by the lack of scientific evidence for C. burnetii infection in the species, and the unique composition of camelid antibodies, which may cause false-positive results in assays developed for ruminants. We evaluated a complement fixation test (CFT; currently recommended for alpacas in New Zealand), an enzyme-linked immunosorbent assay (ELISA) and an immunofluorescence assay (IFA). Positive analytical control samples were generated through vaccination of alpacas with a human Q fever vaccine, whereas negative analytical control samples were sourced from New Zealand (deemed free of C. burnetii). Immunological assays were conducted on 131 alpaca sera submitted for export testing. Test characteristics (sensitivity, specificity, poy alpacas.Vascular liver disease (VLD) presents special challenges in the diagnosis, surveillance, and treatment of hepatocellular carcinoma (HCC). HCC arising in the setting of vascular liver disease is often thought to be due to elevated hepatic arterial blood flow, rather than progressive fibrosis from chronic inflammation as with other chronic liver conditions such as viral hepatitis, autoimmune, and metabolic liver diseases. Vascular alteration inherent in VLD often impedes HCC non-invasive diagnosis and loco-regional treatment that depend on vascular properties found in typical liver environment. Benign and pre-malignant liver nodules such as focal nodular hyperplasia and hepatocellular adenoma are also more common in certain VLDs, further adding to surveillance and diagnostic challenges. In this synopsis, we aimed to review available literature on the epidemiology, surveillance, diagnosis, and management of HCC in patients with VLD and specifically Budd-Chiari syndrome, congenital porto-systemic shunts, Fontan-associated liver disease, hereditary hemorrhagic telangiectasia.The emergence of West Nile virus (WNV) and Usutu virus (USUV) in Europe resulted in significant outbreaks leading to avifauna mortality and human infections. Both viruses have overlapping geographical, host and vector ranges, and are often co-circulating in Europe. In Germany, a nationwide bird surveillance network was established to monitor these zoonotic arthropod-borne viruses in migratory and resident birds. In this framework, co-infections with WNV and USUV were detected in six dead birds collected in 2018 and 2019. Genomic sequencing and phylogenetic analyses classified the detected WNV strains as lineage 2 and the USUV strains as lineages Africa 2 (n = 2), Africa 3 (n = 3) and Europe 2 (n = 1). Preliminary attempts to co-propagate both viruses in vitro failed. However, we successfully cultivated WNV from two animals. Further evidence for WNV-USUV co-infection was obtained by sampling live birds in four zoological gardens with confirmed WNV cases. Three snowy owls had high neutralizing antibody titres against both WNV and USUV, of which two were also positive for USUV-RNA. In conclusion, further reports of co-infections in animals as well as in humans are expected in the future, particularly in areas where both viruses are present in the vector population.’Candidatus Liberibacter asiaticus’ (CLas) is a phloem-limited non-culturable α-proteobacterium associated with citrus Huanglongbing, a highly destructive disease threatening global citrus industry. Research on CLas is challenging due to the current inability to culture CLas in vitro and the low CLas titre in citrus plant. Here, we develop a CLas enrichment system using the holoparasitic dodder plant (Cuscuta campestris) as an amenable host to acquire and enrich CLas from CLas-infected citrus shoots maintained hydroponically. Forty-eight out of fifty-five (87%) dodder plants successfully parasitized CLas-infected citrus shoots with detectable CLas by PCR. Among 48 dodders cultures, 30 showed two- to 419-fold CLas titre increase as compared to the corresponding citrus hosts. The CLas population rapidly increased and reached the highest level in dodder tendrils at 15 days after parasitizing citrus shoot. Genome sequencing and assembly derived from CLas-enriched dodder DNA samples generated a higher resolution than those obtained for CLas from citrus hosts. No genomic variation was detected in CLas after transmission from citrus to dodder during short-term parasitism. Dual RNA-Seq experiments showed similar CLas gene expression profiles in dodder and citrus samples, yet dodder samples generated a higher resolution of CLas transcriptome data. The ability of dodder to support CLas multiplication to high levels, as well as its advantage in CLas genomic and transcriptomic analyses, make it an optimal model for further studies on CLas-host interaction.

    The role of cell death-inducing DFF45-like effector C (CIDEC) in insulin resistance has been established, and it is considered to be an important trigger factor for the progression of diabetic nephropathy (DN). We intend to explore whether CIDEC plays an important role in the regulation of DN and its potential mechanism.

    High-fat diet and low dose streptozotocin were used to establish type 2 diabetic rat model. We investigate the role of CIDEC in the pathogenesis and process of DN through histopathological analysis, western blot and gene silencing. Meanwhile, the effect of CIDEC on renal tubular epithelial cells stimulated by high glucose was also verified.

    DM group exhibited glucose and lipid metabolic disturbance, with hypertrophy of kidneys, damaged renal function, increased apoptosis, decreased autophagy, glomerulosclerosis and interstitial fibrosis. CIDEC gene silencing improved metabolic disorder and insulin resistance, alleviated renal hypertrophy and renal function damage, decreased glomerular and tubular apoptosis, increased autophagy and inhibited renal fibrosis. At the cellular level, high glucose stimulation increased CIDEC expression in renal tubular epithelial cells, accompanied by increased apoptosis and decreased autophagy. CIDEC gene silencing can improve autophagy and reduce apoptosis. At the molecular level, CIDEC gene silencing also decreased the expression of early growth response factor (EGR)1 and increased the expression of adipose triglyceride lipase (ATGL).

    CIDEC gene silencing may delay the progression of DN by restoring autophagy activity and inhibiting apoptosis with the participation of EGR1and ATGL.

    CIDEC gene silencing may delay the progression of DN by restoring autophagy activity and inhibiting apoptosis with the participation of EGR1and ATGL.CLEC10A, (C-type lectin domain family 10, member A), as the member of C-type lectin receptors (CLRs), plays a vital role in modulating innate immunity and adaptive immunity and has shown great potential as an immunotherapy target for cancers. However, there is no functional research of CLEC10A in prognostic risk, immunotherapy or any other treatment of lung adenocarcinoma (LUAD). We performed bioinformatics analysis on LUAD data downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analysed with online databases such as HPA, LinkedOmics, TIMER, ESTIMATE and TISIDB. We found that lower expression of CLEC10A was accompanied with worse outcomes of LUAD patients. Moreover, CLEC10A expression was significantly correlated with a variety of the tumour-infiltrating immune cells (TIICs). As a promising prognosis predictor and potential immunotherapy target, the potential influence and mechanisms of CLEC10A in LUAD deserve further exploring.

    Lateral pelvic lymph node dissection (LPLND) for locally advanced low rectal cancer is a common practice in Japan. However, it is not widely performed in western countries. The aim of this survey study is to assess the current practice and management of lateral pelvic lymph nodes by colorectal surgeons in Australasia.

    The authors developed a survey to assess surgeons’ assessment and management of lateral pelvic lymph nodes in patients with rectal cancer. The survey was run through the online RedCap® platform in 2019. An electronic link and request to complete the survey was sent to specialist surgeons of the Colorectal Surgical Society of Australia and New Zealand (CSSANZ).

    Ninety-two colorectal surgeons completed the online survey (32% response rate). Eighty percent of participants consider malignant lateral pelvic lymph nodes to represent locoregional and resectable disease. In patients with clinically malignant lateral pelvic lymph nodes on preoperative imaging the majority of respondents (92%) recomadequate training and experience with LPLND is limited.First responders often face traumatic and emotionally-taxing incidents in their role. Understanding their mental health and coping capacity is important for wellbeing and continued service delivery. Surf lifesavers and lifeguards are an under researched yet a vital part of the first responder workforce. The recent Senate Report on first responders explored mental health in the leading emergency services personnel in Australia and found a high incidence of mental health difficulties in those who worked or volunteered as emergency responders. However, a significant literature gap exists regarding mental health of surf lifesavers and lifeguards in both the international and Australian context. Here we propose a strategy to address this gap, at the individual, organisational and community level.

    This study aimed to explore the novel biomarkers for immune checkpoint inhibitor (ICI) responses in non-small cell lung cancer (NSCLC) by integrating genomic profiling, tumor mutational burden (TMB), and expression of programmed death receptor 1 ligand (PD-L1).

    Tumor and blood samples from 637 Chinese patients with NSCLC were collected for targeted panel sequencing. Genomic alterations, including single nucleotide variations, insertions/deletions, copy number variations, and gene rearrangements, were assessed and TMB was computed. TMB-high (TMB-H) was defined as ≥10 mutations/Mb. PD-L1 positivity was defined as ≥1% tumor cells with membranous staining. Genomic data and ICI outcomes of 240 patients with NSCLC were derived from cBioPortal.

    EGFR-sensitizing mutations, ALK, RET, and ROS1 rearrangements were associated with lower TMB and PD-L1+/TMB-H proportions, whereas KRAS, ALK, RET, and ROS1 substitutions/indels correlated with higher TMB and PD-L1+/TMB-H proportions than wild-type genotypes. Histone-lysancer (NSCLC); however, only a proportion of patients derive durable responses to this treatment. Biomarkers with greater accuracy are highly needed. In total, 637 Chinese patients with NSCLC were analyzed using next-generation sequencing and IHC to characterize the unique features of genomic alterations and TMB and PD-L1 expression. Our study demonstrated that KMT2C/TP53 co-mutation might be an accurate, cost-effective, and reliable biomarker to predict responses to PD-1 blockade therapy in NSCLC patients and that adding KRAS to the biomarker combination creates a more robust parameter to identify the best responders to ICI therapy.ESBL-/AmpC-producing Escherichia coli from organic fertilizers were previously detected on soil surfaces of arable land and might be emitted by wind erosion. To investigate this potential environmental transmission path, we exposed ESBL-/AmpC-positive chicken litter, incorporated in agricultural soils, to different wind velocities in a wind tunnel and took air samples for microbiological analysis. No data exist concerning the airborne tenacity of ESBL-/AmpC-producing E. coli. Therefore, we explored the tenacity of two ESBL/AmpC E. coli strains and E. coli K12 in aerosol chamber experiments at different environmental conditions. In the wind tunnel, ESBL/AmpC-producing E. coli were detected in none of the air samples (n = 66). Non-resistant E. coli were qualitatively detected in 40.7% of air samples taken at wind velocities exceeding 7.3 m s-1 . Significantly increased emission of total viable bacteria with increasing wind velocity was observed. In the aerosol chamber trials, recovery rates of airborne E. coli ranged from 0.003% to 2.8%, indicating a low airborne tenacity. Concluding, an emission of ESBL/AmpC E. coli by wind erosion in relevant concentrations appears unlikely because of the low concentration in chicken litter compared with non-resistant E. coli and their low airborne tenacity, proven in the aerosol chamber trials.Pseudotorymus jaapiellae is an important ectoparasitoid of the larvae of Gephyraulus lycantha, a serious gall-forming pest that devastates wolfberry, Lycium barbarum, in Northwest China. To provide requisite background for our ongoing research on the mechanisms of P. jaapiellae’s host location and subsequent oviposition, we used scanning electron microscopy to describe the external morphologies and distributions of sensilla on their antennae and ovipositors. The geniculate antennae of both male and female P. jaapiellae were each composed of a scape with a basal radiculum, a pedicel, an anellum and a flagellum. We identified nine morphological sensilla types on the antennae of both sexes, including three sensilla trichodea (ST), one sensillum basiconicum (SB), two sensilla chaetica (SCh), one sensillum placodeum (SP), one sensillum coeloconicum (SCo), and one sensillum campaniformia (SCa). Females had significantly more ST I and SP than males had, but males had more ST III than did females. We observed six types of sensilla on the ovipositor, including three ST, one SB, and two SCa. ST II, ST IV and SB II were on the sheath, whereas ST V and the SCa were on the stylus. Finally, the possible biological functions of these sensilla were discussed according to their morphology and ultrastructure. These results provide an important basis for further study on chemical communication between P. jaapiellae and their host, and contribute to the development of a biological control program for G. lycantha, using the parasitoid, P. jaapiellae.

    Acne vulgaris is a disease of pilosebaceous units and manifests with polymorphic lesions. Vitamin D acts at various stages in its pathogenesis. Recently, vitamin D and metabolic syndrome have shown to be associated with acne vulgaris and its severity.

    To see the effects of serum 25(OH)D3 levels and body mass index on acne vulgaris and their correlation with the severity of acne.

    Fifty patients of acne vulgaris and thirty age- and sex-matched healthy volunteers were recruited. Global Acne Grading System was used to grade the acne severity. Body mass index of all patients and control group was calculated, and serum levels of 25(OH)D3 were measured using chemiluminescence immunoassay.

    Vitamin D deficiency was detected in 28% of patients with acne but only in 6.7% of the healthy controls (p value 0.022). However, there was no significant difference in mean serum 25(OH)D levels in acne patients and controls. Vitamin D deficiency was seen in 60% of the very severe and 33% of the severe acne cases. Eighty percent of patients with very severe acne and 73.33% of severe acne patients had high body mass index. The relationship between severity of acne and body mass index was statistically significant.

    Vitamin D deficiency was more prevalent in acne, and with the increase in severity of acne, an inverse relation between serum levels of vitamin D and body mass index was seen, but statistically significant relation was found only in the very severe cases of acne vulgaris.

    Vitamin D deficiency was more prevalent in acne, and with the increase in severity of acne, an inverse relation between serum levels of vitamin D and body mass index was seen, but statistically significant relation was found only in the very severe cases of acne vulgaris.There is no consensus on the best inhibitory optogenetic tool. Since Gi/o signalling is a native mechanism of neuronal inhibition, we asked whether Lamprey Parapinopsin („Lamplight”), a Gi/o-coupled bistable animal opsin, could be used for optogenetic silencing. We show that short (405 nm) and long (525 nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, respectively, and that combining these wavelengths can be used to achieve intermediate levels of activity. These properties can be applied to produce switchable neuronal hyperpolarisation and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. Expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, with 405 and 525 nm stimuli producing responses of opposite sign in the output neurons of the retina. We conclude that bistable animal opsins can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and reversible.Associations between unmet interpersonal needs and different aspects of suicide have been observed in both Western and non-Western cultures using the Interpersonal Needs Questionnaire (INQ). However, measurement invariance is a prerequisite for comparing differences between culturally different groups, and to date, no studies have examined measurement invariance of INQ across cultures. This study aimed to (a) validate Chinese versions of the INQ, (b) assess measurement invariance across gender for the Chinese INQ, (c) assess measurement invariance across Australian and Chinese cultures for the INQ, and (d) comprehensively assess the association of interpersonal needs with suicide ideation. A sample of 469 Australian undergraduates and a sample of 854 Chinese undergraduates were used in this study. For testing measurement invariance across gender, the sample of Chinese undergraduates was split by gender into the Chinese male and Chinese female samples. Five versions of INQ (10-, 12-, 15-, 18- and 25-item) were tested. The 10- and 15-item Chinese INQ demonstrated adequate psychometric properties through various analyses (i.e., reliability, confirmatory factor analysis, and structural equation modeling) and also demonstrated measurement invariance across gender via multigroup confirmatory factor analysis. The 10-item INQ demonstrated measurement invariance across Australian and Chinese cultures. Of the two interpersonal factors, only perceived burdensomeness was significantly associated with suicide ideation. Multigroup structural equation modeling demonstrated that perceived burdensomeness may be a greater risk factor of suicide among Australian undergraduates than among Chinese undergraduates. Practical and theoretical contributions of this study are discussed.In mouse oocytes, acentriolar MTOCs functionally replace centrosomes and act as microtubule nucleation sites. Microtubules nucleated from MTOCs initially assemble into an unorganized ball-like structure, which then transforms into a bipolar spindle carrying MTOCs at its poles, a process called spindle bipolarization. In mouse oocytes, spindle bipolarization is promoted by kinetochores but the mechanism by which kinetochore-microtubule attachments contribute to spindle bipolarity remains unclear. This study demonstrates that the stability of kinetochore-microtubule attachment is essential for confining MTOC positions at the spindle poles and for limiting spindle elongation. MTOC sorting is gradual and continues even in the metaphase spindle. When stable kinetochore-microtubule attachments are disrupted, the spindle is unable to restrict MTOCs at its poles and fails to terminate its elongation. Stable kinetochore fibers are directly connected to MTOCs and to the spindle poles. These findings suggest a role for stable kinetochore-microtubule attachments in fine-tuning acentrosomal spindle bipolarity.Solid organ transplant recipients have a higher risk of active Mycobacterium tuberculosis infection (TB) compared to the general population. Recognized risk factors are immunosuppressant use, graft dysfunction, diabetes mellitus, liver disease caused by the hepatitis C virus, and co-infections by other opportunists. Most of the active TB cases reported in solid organ transplant recipients occur in kidney transplant patients, especially if they come from M tuberculosis-endemic areas. Extrapulmonary and disseminated TB are among the wide spectrum of clinical presentations found, but the lungs are the most common organ affected. Disseminated disease occurs in up to a third of the affected population, however, multifocal osteoarticular TB with mycobacteremia is unusual. We report the case of a kidney transplant patient with disseminated M tuberculosis infection, who presented with multifocal skeletal TB.Nonsense-mediated mRNA decay (NMD) was identified as a process to degrade flawed cellular messenger RNA (mRNA). Within the last decades it was also shown that NMD carries virus-restricting capacities and thus could be considered a part of the cellular antiviral system. As this was shown to affect primarily positive-sense single stranded RNA ((+)ssRNA) viruses there is only scarce knowledge if this also applies to negative-sense single stranded RNA ((-)ssRNA) viruses. Influenza A viruses (IAVs) harbour a segmented (-)ssRNA genome. During their replication IAVs produce numerous RNA transcripts and simultaneously impair cellular transcription and translation. The viral mRNAs hold several molecular patterns which can elicit NMD and in turn would lead to their degradation. This, in consequence, may mitigate viral propagation. Thus, we examined if a knockdown or a pharmacological inhibition of NMD key components may influence IAV replication. Additionally, we performed similar experiments with respiratory syncytial virus (RSV), another (-)ssRNA virus, but with a non-segmented genome. Although it seemed that a knockdown of up-frameshift protein 1 (UPF1), the central NMD factor, slightly increased viral mRNA and protein levels, no significant alteration of viral replication could be observed, implying that the NMD machinery may not have restricting capacities against (-)ssRNA viruses.

    To identify genes that are related to delayed endolymphatic hydrops (DEH) in patients by RNA-Seq analysis.

    Observational study.

    Eye & ENT Hospital, Fudan University (Shanghai, China).

    We collected the entire vestibular system from four patients with DEH who underwent labyrinthectomy. Three control samples were collected from patients with acoustic neuroma or facial neuroma treated via the translabyrinthine approach. High-throughput RNA-Seq analysis was performed to investigate gene expression in the pathological vestibular system.

    Our bioinformatic analysis identified 17 genes that were upregulated and eight genes that were downregulated in patients with DEH compared with the controls.

    The altered gene expression profile suggested that DEH is closely related to neuropathy and autoimmune disease. In addition, many of the differentially regulated genes were involved in cell adhesion, suggesting a role of cell adhesion in DEH. Immunofluorescence analysis confirmed the expression of PMP2 and CLDN1 analytical tool to characterise the vestibular pathology based on its transcriptome.Previous in vitro and in vivo experiments had demonstrated dose-dependent anti-cancer effects of clinical plasma colchicine concentrations on hepatocellular carcinoma (HCC) cells. This phase IIa trial was to evaluate the potential efficiency and safety of our novel colchicine dosage schedule for the palliative treatment of advanced HCC. The dosage schedule started from oral intake of 1 mg colchicine three times per day for 4 days and discontinuation in the following 3 days (one cycle). The treatment cycle was repeated and the dosage was adjusted ranging from 3 to 1.5 mg/day according to the condition of the participant. The control group was originated from chart review of 86 HCC patients treated by sorafenib for more than 2 months. Fifteen participants signed the inform consent. Two participants were excluded due to screening failure in one and less than four treatment cycles in another. For severe adverse events, the colchicine group demonstrated higher incidence of biliary tract obstruction (p = 0.0184) than the sorafenib group. Comparison grade 1 or 2 adverse events between two groups, the colchicine group had higher incidence of diarrhea (p = 0) and the sorafenib group had higher incidence of palmar-plantar erythrodysesthesia syndrome (p = 0.0045). There was no significant difference in mortality, median survival, and overall survival between two groups (all p > 0.2). In conclusion, our novel colchicine dosage schedule is clinically feasible and has the potential to be applied in the palliative treatment of advanced HCC especially based on the cost-effectiveness consideration.

    Rosacea is a common chronic inflammatory dermatosis with uncertainty of etiology. Although clinical features and risk factors of the disease in Caucasians have been reported, this information in Chinese is largely unavailable.

    To analyze the clinical features and associated risk factors of rosacea in Chinese.

    A questionnaire was given to outpatients with rosacea who visited the dermatology department of the first affiliated hospital of Kunming Medical University from June 2018 to March 2019. Analyses included demographic characteristics of subjects, clinical characteristics, and risk factors of rosacea.

    A total of 254 outpatients completed the questionnaire. The ratio of female to male was 5.681.00. The mean age at onset was 31.18±10.23years. Erythematotelangiectatic subtype accounted for 51.60%, while 39% of the subjects were of papulopustular subtype. The rest were phymatous type (9.40%). Subjects with flushing, persistent facial erythema, and telangiectasia accounted for 91.73%, 90.55%, and 83.07%, respectively. One hundred and thirteen subjects (44.49%) had papules or pustules, and 24 subjects (9.40%) were with phymatous changes. The most commonly involved sites were the cheeks (93.31%), followed by the nose (82.68%), the perioral area (61.42%), and the forehead (51.97%). The clinical symptoms included burning (93.70%), dryness (90.55%), and itching (75.59%). The main risk factors were sun exposure (90.94%), temperature change (87.40%), etc. Fifty-one (20.08%) patients had comorbidities.

    Rosacea mainly affects young females. The common signs and symptoms include flushing, persistent facial erythema, and burning. Sun exposure and temperature changes are the common risk factors. Patients can have comorbidities of systemic disorders.

    Rosacea mainly affects young females. The common signs and symptoms include flushing, persistent facial erythema, and burning. Sun exposure and temperature changes are the common risk factors. Patients can have comorbidities of systemic disorders.

    This study aims to demonstrate the characteristics of late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) imaging in patients with giant cell myocarditis (GCM).

    Six patients histologically diagnosed with GCM were retrospectively recruited in this study. All of them underwent CMR during hospitalization. The distribution and extent of LGE were assessed on both ventricles, and the AHA-17 segment model was used for left ventricular (LV) analysis. Nine case reports with CMR in GCM were reviewed and summarized to investigate the features of LGE further. LGE was detected on both ventricular walls in all subjects. For a detailed analysis of LGE in the LV, the extent ranged from 21.6% to 56%. Among 70 segments (68.6%) involved by LGE, the subendocardial LGE was the most common pattern (46/102, including 24 segments located in the right-sided septum), followed by the subepicardial pattern (23/102). The right-sided septum, the subepicardial anterior wall, and the subendocardial right ventricular (RV) wall were observed in all subjects. To summarize the results of the present study with these case reports, the three most common patterns of LGE are the right-sided septum (73%), the subepicardial anterior wall (60%), and the subendocardial RV wall (53%).

    Extensive LGE seems to be common in GCM, affecting both LV and RV walls. Apart from subepicardial LGE, subendocardial LGE, which was used to be implicated in ischaemic disease, was frequently presented in GCM. The right-sided subendocardial septum, the subepicardial anterior wall, and the subendocardial RV wall might be the vulnerable areas of LGE in GCM.

    Extensive LGE seems to be common in GCM, affecting both LV and RV walls. Apart from subepicardial LGE, subendocardial LGE, which was used to be implicated in ischaemic disease, was frequently presented in GCM. The right-sided subendocardial septum, the subepicardial anterior wall, and the subendocardial RV wall might be the vulnerable areas of LGE in GCM.Reptiles are carriers of Salmonella and can intermittently shed bacteria in their faeces. Contact with snakes and lizards is a source of human salmonellosis. Here, two populations of reptiles, wild and captive were surveyed for Salmonella. One hundred thirty wild-caught reptiles were sampled for Salmonella including 2 turtle, 9 snake and 31 lizard species. Fifty-two of 130 (40%) animals were Salmonella positive one of 5 (20%) turtles, 7 of 14 (50%) snakes and 44 of 111 (39.6%) lizards. One hundred twenty-two reptiles were sampled from a zoo collection including 1 turtle, 6 tortoise, 9 lizard, 14 snake and 1 crocodile species. Forty-two of 122 (34.4%) captive reptiles sampled were Salmonella positive. Salmonella was most commonly isolated from lizards and snakes. Fifteen serotypes were identified from zoo and 19 from wild-caught reptiles and most were members of subspecies enterica (I), salamae (II), arizonae (IIIa) or diarizonae (IIIb). Antimicrobial susceptibility testing was conducted on all Salmonella isolates; only two exhibited resistance, a Salmonella subsp. (II) ser. 21z10 z6 (Wandsbek) isolate cultured from a wild-caught reptile and a Salmonella Typhimurium DT120 isolated from a captive snake. The invasive capacity of reptile-associated Salmonella strains into cultured human intestinal epithelial (Caco2) and mouse macrophages cell lines (J774A.1) was also investigated. All isolates were invasive into both cell lines. Significant (P ≤ 0.001) variability in invasiveness into polarized Caco2 cells was observed. Salmonella Eastbourne exhibited the highest invasiveness into Caco2 cells and Salmonella Chester the lowest, with mean per cent recoveries of 19.99 ± 0.32 and 1.23 ± 0.30, respectively. Invasion into J774A.1 macrophages was also variable but was not significant. Salmonella subsp. II ser. 17g,t- (Bleadon) exhibited the highest invasiveness into J774A.1 with a mean per cent recovery of 10.19 ± 0.19. Thus, reptile-associated Salmonellae are likely to have different capacities to cause disease in humans.Tigecycline has been approved by the US (United States) Food and Drug Administration in a variety of complicated infections due to its broad-spectrum antibiotic activity. Following phase III trials, the product label was revised and acute pancreatitis was listed as an adverse effect. Its safety profile in special groups such as renal transplant patients is not exactly known. We report the first case of unintentional rechallenge of tigecycline induced pancreatitis in a renal transplant patient. Ten days following the renal transplantation, a 35-year-old patient presented to the clinic with acute rejection. He received anti-thymocyte globulin (ATG) and pulse steroid treatments for rejection. Following the treatment, he developed perianal cellulitis and tigecycline was started. Nine days following initiation of tigecycline he received thrombectomy for his incidental cardiac thrombus. One day after thrombectomy, he developed acute pancreatitis (AP). Thrombectomy was suspected to be the cause of AP. During hospitalization for transplant rejection, tigecycline was re-started for a newly developed complicated abdominal infection. On the third day of the tigecycline re-treatment, he developed a second episode of AP. Following tigecycline withdrawal, his symptoms resolved and serum pancreatic enzymes returned to normal, thus AP was ultimately attributed to tigecycline. This lethal side effect should be kept in mind while treating severe infections in renal transplant recipients.

    The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, and death.

    Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011, and October 24, 2018, were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed, and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics, including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death, were collected.

    In increased every year and the most common admissions are for gastrointestinal (30.7%), pulmonary (15/8%), and hepatic (14.2%) events. Readmission rates are high (29% at 30 days, 49% at 180 days) and 64.2% have to permanently discontinue immune checkpoint inhibitor therapy. Importantly, multiple concurrent toxicities were seen in 21.6% (97/450) of irAE admissions and these patients have a fivefold increased risk of inpatient death.Some older adults cannot meaningfully participate in the testing portion of a neuropsychological evaluation due to significant cognitive impairments. There are limited empirical data on this topic. Thus, the current study sought to provide an operational definition for a futile testing profile and examine cognitive severity status and cognitive screening scores as predictors of testing futility at both baseline and first follow-up evaluations. We analysed data from 9,263 older adults from the National Alzheimer’s Coordinating Center Uniform Data Set. Futile testing profiles occurred rarely at baseline (7.40%). There was a strong relationship between cognitive severity status and the prevalence of futile testing profiles, χ2 (4) = 3559.77, p less then .001. Over 90% of individuals with severe dementia were unable to participate meaningfully in testing. Severity range on the Montreal Cognitive Assessment (MoCA) also demonstrated a strong relationship with testing futility, χ2 (3) = 3962.35, p less then .001. The rate of futile testing profiles was similar at follow-up (7.90%). There was a strong association between baseline dementia severity and likelihood of demonstrating a futile testing profile at follow-up, χ2 (4) = 1513.40, p less then .001. Over 90% of individuals with severe dementia, who were initially able to participate meaningfully testing, no longer could at follow-up. Similarly, there was a strong relationship between baseline MoCA score band and likelihood of demonstrating a futile testing profile at follow-up, χ2 (3) = 1627.37, p less then .001. Results can help to guide decisions about optimizing use of limited neuropsychological assessment resources.

    Ocular coherence tomography angiography (OCTA) is available in varying size and resolution. We sought to characterise associations of cardiometabolic factors with retinal microvascular changes using 3 × 3, 6 × 6 and 8 × 8-mm OCTA scans to determine differences in detection with varying scan size.

    Cross-sectional study of 247 cardiovascular patients from a single-centre tertiary-care hospital. Demographic, comorbidity and medication data were obtained. Patients underwent 3 × 3, 6 × 6 and 8 × 8-mm macula OCTA scanning using Carl Zeiss CIRRUS HD-OCT Model 5000. Angioplex and AngioTool software was used to quantify vascular parameters in the superficial capillary plexus.

    Increasing age, hypertension, dyslipidaemia, diabetes, chronic kidney disease, coronary artery disease and peripheral vascular disease were associated with reductions in vessel density, vessel perfusion, average vessel length and/or junction density in 3 × 3-mm OCTA (P < .05 for all). Conversely, smoking was associated with increased vesweakened and progressively attenuated in OCTA scans of larger 6 × 6 and 8 × 8-mm size. These findings advance our understanding of microcirculatory dysfunction and may have future implications for the screening and management of patients with cardiometabolic risk factors. Additional studies are required to further investigate these important associations.

    Opioid use for chronic non-cancer pain (CNCP) is under debate. In the absence of pan-European guidance on this issue, a position paper was commissioned by the European Pain Federation (EFIC).

    The clinical practice recommendations were developed by eight scientific societies and one patient self-help organization under the coordination of EFIC. A systematic literature search in MEDLINE (up until January 2020) was performed.Two categories of guidance are given Evidence-based recommendations (supported by evidence from systematic reviews of randomized controlled trials or of observational studies) and Good Clinical Practice (GCP) statements (supported either by indirect evidence or by case-series, case-control studies and clinical experience). The GRADE system was applied to move from evidence to recommendations. The recommendations and GCP statements were developed by a multiprofessional task force (including nursing, service users, physicians, physiotherapy and psychology) andformal multistep procedures to reach a set of consensus recommendations.

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