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The most common source was the Internet followed by friends and family members, and health care professionals.

Findings suggest that health information that is disseminated using the Internet needs to be made available in multiple languages to facilitate communication to persons who are not fluent in English nor French. Also, policy makers and health care professionals must increase focus on informal sources of health care information.

Findings suggest that health information that is disseminated using the Internet needs to be made available in multiple languages to facilitate communication to persons who are not fluent in English nor French. Also, policy makers and health care professionals must increase focus on informal sources of health care information.

To develop and evaluate a parent-proxy measure of youth HCT readiness the TR

ANSITION Index-Parent Version.

We recruited parents (77% female) and youth (ages 12 to 25) to complete transition readiness measures during outpatient clinic visits. The TRxANSITION Index-Parent Version contains two domains the Parent Knowledge Domain assessing a parent's knowledge of their youth's illness, and the Parent Proxy Domain, which provides a parental perspective regarding a youth's transition readiness skills. We evaluated the TRxANSITION Index - Parent Version for differences between parent and youth reports of HCT readiness, associations between parent's score and youth's characteristics, and item-category, item-sub-index, and sub-index category correlations.

Data from 93 parents-youth dyads were analyzed. Parents scored significantly higher than youth in the Parent Knowledge Domain and similarly in the Parent Proxy Domain. Parents of daughters had significantly higher scores in the Parent Knowledge Domain than parents of sons and reported similar scores to Parents of sons in the Parent Proxy Domain. Only the self-management sub-index significantly correlated with youth's age. The sub-index-domain, item-sub-index, and item-domain correlations assessed were generally large in magnitude (r>0.5).

The TR

ANSITION Index-Parent Version shows promise as a means of assessing parent knowledge of a youth's illness and may provide an accurate proxy assessment of a youth HCT readiness skills.

Obtaining parental perspective on a youth's HCT readiness may provide useful clinical information during the transition process.

Obtaining parental perspective on a youth's HCT readiness may provide useful clinical information during the transition process.The relationships among the Aurearenophyceae, Phaeothamniophyceae, Phaeophyceae and Xanthophyceae lineages of the Heterokontophyta SI clade are not well known. By adding previously unexamined taxa related to these classes in a five gene phylogeny (SSU rRNA, atpB, psaA, psaB, rbcL), we recovered an assemblage of taxa previously unrecognized. We propose the class Phaeosacciophyceae class. nov., that includes Phaeosaccion collinsii, Phaeosaccion multiseriatum sp. nov., Phaeosaccion okellyi sp. nov., Antarctosaccion applanatum, Tetrasporopsis fuscescens, Tetrasporopsis moei sp. nov., and Psammochrysis cassiotisii gen. & sp. nov. We re-examine the literature for Chrysomeris, Nematochrysis, Chrysowaernella and the invalid name "Giraudyopsis" and conclude some taxa in previous studies are misidentified or misnamed, i.e. Chrysomeris and Chrysowaernella, respectively. We also show that Nematochrysis sessilis var. vectensis and Nematochrysis hieroglyphica may belong in the recently described class Chrysoparadoxophyceae. The phylogenetic relationships of Phaeobotrys solitaria and Pleurochloridella botrydiopsis are not clearly resolved, but they branch near the Xanthophyceae. Here we describe a new class Phaeosacciophyceae, a new order Phaeosacciales, a new family Tetrasporopsidaceae, a new genus Psammochrysis and four new species.Children raised in families with low socioeconomic status (SES) are more likely to exhibit symptoms of psychopathology. However, the strength of this association, the specific indices of SES most strongly associated with childhood psychopathology, and factors moderating the association are strikingly inconsistent across studies. We conducted a meta-analysis of 120 estimates of the association between family SES and child psychopathology in 13 population-representative cohorts of children studied in the US since 1980. Among 26,715 participants aged 3-19 years, we observed small to moderate associations of low family income (g = 0.19), low Hollingshead index (g = 0.21), low subjective SES (g = 0.24), low parental education (g = 0.25), poverty status (g = 0.25), and receipt of public assistance (g = 0.32) with higher levels of childhood psychopathology. Moderator testing revealed that receipt of public assistance showed an especially strong association with psychopathology and that SES was more strongly related to externalizing than internalizing psychopathology. Dispersion in our final, random effects, model suggested that the relation between SES and child psychopathology is likely to vary in different populations of children and in different communities. These findings highlight the need for additional research on the mechanisms of SES-related psychopathology risk in children in order to identify targets for potential intervention.A gap in informatics expertise amongst nursing students, practising staff and faculty has been noted globally, which reduces the potential for nurses to utilise technology to enhance patient care. National nursing education strategies and recommendations from professional associations have identified digital health as an area that needs investment. This case study describes how health informatics is being integrated into a Bachelor of Nursing programme in the United Kingdom. An international collaboration with a US-UK Fulbright Specialist Scholar enabled individual learning units corresponding to key health informatics competencies to be designed and incorporated into a pedagogic framework grounded in the spiral learning approach. This approach is proposed as one way to integrate informatics into nursing education, so students can become competent clinicians that are able to deliver technology enabled care in the health service.Standardisation of clinical teaching practices by nurse educators for undergraduate students is vital, especially within large nursing education institutions distributed over multiple campuses. This quantitative study investigated current clinical teaching practices of nurse educators at a Public College of Nursing in South Africa. A total of n = 68 nurse educators were selected from 5 campuses over a two-month period (April-May 2016), using convenience sampling. Data was collected with a structured questionnaire, the design of which was informed by the Dundee Three Circle Outcomes Model for Clinical Teaching. The results showed that 37% (n = 25) of the nurse educators had above 10 years of clinical teaching experience. Of the 66% (n = 45) who had formal education on clinical teaching practices, 49% (n = 33) received in-service education. Most nurse educators were willing to share amongst colleagues documents they used for clinical teaching, to promote standardisation of teaching practices. Further, they evidenced best clinical practices regarding planning for assessment and clinical placement of students. However, there were significant variations in the majority (seven) of the nine investigated clinical teaching practices among participants. In-service education was positively correlated to best clinical teaching practices (Chi square (d.f. = 2, n = 68) = 7.24; p = .027; V = 0.33 Medium).The persistence of fibres under outdoor conditions is seldom investigated. This research aimed to study simultaneously the influence of several factors (and their cross-interactions) on the persistence of fibres on static textile surfaces. In order to achieve this aim, a design of experiments was successfully implemented under laboratory conditions. Four factors were considered time, inclination of the recipient textile, wind speed, and rainfall. The model obtained by this supervised method was compared with the results collected under actual outdoor conditions near a weather station. The resulting model appears to be reliable as long as the values of the factors are kept within the range used in the study. The results of the laboratory tests showed that wind speed and rainfall significantly influence the persistence of fibres while time and inclination of the recipient textile have been found to be nonsignificant. In general, the observed persistence was high between 90.4 and 100%. This might be attributed to the recipient textile surface possessing abundant protruding fibres which "traps" the transferred fibres. Outdoor experiments usually suffer from a higher variability and result in a higher fibre loss. In outdoor conditions, wind and rainfall have shown an extensive influence on the fibre persistence. Finally, the trend of fibre persistence on static textiles in outdoor conditions is generally linear with time, but extreme meteorological condition will induce exponential losses.Cannabis is classified into two types drug-type cannabis, which is abused worldwide, and fiber-type cannabis, which is used for industrial purposes. The two types are a result of differences in the sequences of tetrahydrocannabinolic acid synthase (THCAS) and cannabidiolic acid synthase (CBDAS) genes. In the present study, we aimed to establish a PCR-based method to distinguish between drug-type and fiber-type cannabis by detecting the differences in the sequences of THCAS and CBDAS. We constructed a single-plex PCR targeting active THCAS, and observed drug-type cannabis-specific amplification when using 10pg to 1ng of DNA; however, amplification was also observed in fiber-type cannabis when the DNA content reached 10ng. Similarly, single-plex PCR targeting active CBDAS showed fiber-type cannabis-specific amplification in 100pg of DNA, as well as in >1ng of drug-type cannabis DNA. Therefore, when an allele-specific duplex PCR system was constructed, in which both primer sets were mixed at an appropriate ratio, unintended nonspecific amplification was suppressed and amplicons of different sizes were observed between the drug-type and fiber-type cannabis, using DNA samples in the range of 1pg to 10ng. When the constructed duplex PCR was performed on DNA extracted from various cannabis seed samples, it was possible to distinguish between the drug-type and the fiber-type as well as detect a hybrid-type with both active THCAS and active CBDAS and a special type with neither. The identification method developed in the present study can quickly and accurately distinguish between drug-type and fiber-type cannabis, and is expected to be used for various purposes such as the detection of genetic contamination of industrial hemp as well as forensic examination of cannabis-related cases.Textile structures are considered as the main component of protective clothing against the penetration of sharp objects. In the current research work, woven fabrics reinforced with metal threads as weft yarn were designed with various weave patterns including Twill, Satin, and Hopsack, and by using a weft-backed weaving structure. The mentioned reinforced samples were produced by altering the diameter and number of metal threads in each fabric structure. Assessment of fabric resistance against bending and sharp object penetration reveals that although the application of metal thread improves the fabric resistance against sharp object penetration, it leads to an increase in the fabric stiffness. According to the results, the influence of the number of metal threads on the penetration resistance was considerably higher than the metal thread diameter. However, more increase in the fabric's bending stiffness was observed with the rise of metal thread's diameter compared to the number of metal threads. According to the obtained outcomes, weave structure is an effective parameter that changes fabric's resistance against penetration. In this regard, weave patterns with more firmness that limit the yarn movement during the indentation of the sharp object present higher protection ability. Furthermore, the increment of fabric density enhances the resistance against penetration. In this study, the resistance of two-layer samples with various orientations angle of 0°/90° and -45°/+45° were probed, as well. Outcomes confirmed that two-layer samples resist better than single-layer sample against sharp object penetration due to the formation of a grid of metal threads. Among two studied fabrics' orientation angles, the sample with the angle of -45°/+45° presents greater penetration resistance.Soil is a very important type of trace evidence. The iron content of soil is of great significance in distinguishing soil types, discriminating among different soils, and tracing soils. However, conventional methods for analyzing the iron content of soil are expensive, laborious, and time-consuming. Previous studies have shown that the color of soil correlates well with its hematite content. This article thus deals with the indirect determination of iron content using soil color as a proxy. Soil color measurements were conducted using microspectrophotometry (MSP), and resulting data were transformed into chromaticity value (L*, a*, and b*). Predictions using the redness index in conjunction with a linear regression model were compared with those using the chromaticity value and a back propagation neural network (BPNN) model. The influences of different modeling conditions on the modeling accuracy were compared, and more accurate predictions were achieved when the iron content was higher than 2.13%. The BPNN model produced predictions with R2 and RMSE values of 0.955 and 0.336%, which were better than the predictions of the linear regression model (R2 0.859, RMSE, 1.07%). We thus demonstrated that MSP can be used for fast, accurate, and non-destructive measurements of soil color and prediction of its iron content. Although the results may not be as precise as conventional laboratory analysis, they still provide more information with acceptable accuracy, which should have promising applications in forensic applications.This paper provides guidance on how to properly analyse data generated from the Home Office fingermark grading scheme. The core of the issue is that it creates ordinal data and should therefore not be analysed using averages. To reduce confusion, it is recommended to label the different degrees of fingermark development as classes rather than numerical scores. Appropriate statistical tests are provided to properly analyse Home Office fingermark grading scheme data, however, not using statistical tests is perfectly acceptable so long as conclusions are worded appropriately and do not exaggerate the significance of the findings. Some guidance is provided on estimating sample size and optimal methods for presenting results.Arsonists may use ignitable liquids to start, accelerate and amplify fires. The sampling of volatiles present on the hands of suspected arsonists is therefore sometimes carried out in the course of the investigation of (possible) deliberate fires. Several collection protocols have been proposed, relying on the concentration of volatiles by the transfer on PVC gloves and further passive headspace extraction with Activated Charcoal Strips (ACS). Previous research findings assessing the use of Activated Carbon Cloth (ACC) - initially developed for the adsorption of gas in military applications - opens the path to new perspectives regarding the extraction and the concentration of ignitable liquid residues in general, and for the sampling on hands in particular. Five alternative methods (four relying on the use of ACC and one on ACS) were considered for the collection of gasoline traces present on the hands and their subsequent analysis by gas chromatography - mass spectrometry. Gasoline was deposited onto the pale or bag (i.e. the headspace volume). This research opens new perspectives for the sampling of ignitable liquid residues through the use of ACC. It corroborates the perceived potential of ACC for the extraction and concentration of volatile compounds, particularly for fire debris analysis purposes. While the experiments were focused on the collection of gasoline on hands, the results provide valuable information in a more general way for the sampling of fire debris.Drugs of abuse are psychoactive substances illicitly distributed and used worldwide. In Rio de Janeiro, Brazil, they represent a public health issue and are directly related to several social problems. The recent increase in appearances of new psychoactive substances (NPS), derived from structural modifications of existing psychoactive substances, poses a threat to public health and forensic laboratories worldwide, as little is known about these substances. This study aimed to chemically and geographically map drugs of abuse from blotter papers seized by the Civil Police of Rio de Janeiro State (PCERJ) between 2006 and 2019. High-performance analytical techniques, such as gas chromatography-mass spectrometry (GC-MS) and Orbitrap mass spectrometry (Orbitrap-MS), combined with statistical analyses, were employed to characterize the seized samples. The most common chemical compounds in NPS found in this study were synthetic phenethylamines, i.e., molecules from the 25I-NBOH (2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol) and 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) families. Prior to 2014, the majority of seized blotter papers contained lysergic acid diethylamide (LSD) and were concentrated in the Metropolitan region. An upsurge in blotter paper seizures was observed from 2014 to 2017; the most common substances during this time were from the NBOMe family. NBOH compounds emerged in 2016 in coastal regions with high tourism, reaching over 1300 items only in 2017. Only one synthetic cannabinoid was found among the blotter papers seized in Rio de Janeiro between 2006 and 2019. The assembled chemical data and statistical analyses allowed the mapping and monitoring of the chemical profiles of the seized blotter papers, providing a strong foundation for the understanding of the origins and movement of these drugs around the RJ State.The present study was designed to investigate the effects of different levels of l-carnitine (LC) on sperm quality factor (SQF), alterations in testis fatty acid profiles, testicular histology and reproductive hormones in young roosters. Eighteen broiler breeders (Ross 308) weighed at 3 months of age. They were randomly classified while each group had six birds. There were three experimental groups based on the LC concentrations (i.e. LC-0, LC-250, LC-500 mg per kg of diet). After two weeks of adaptation, semen samples were collected and evaluated for seminal attributes every two weeks (from week 24 to week 34). At the end of the experiments, four roosters from each treatment group were sacrificed in order to analyze testicular histology, testis fatty acid profiles and reproductive hormones. Supplementing the diet with two of the LC levels for 22 weeks caused significant rise in sperm concentration, viability and SQF compared to that of the control group (P  less then  0.05). Quadratic analysis in terms of nutrations. The concentration of LH in different treatment groups, however, turned out to be similar in response to the different levels of LC. In conclusion, long-term supplementation of rooster diet with LC can have beneficial effects on SQF and testis histology. The benefits include alterations in testicular histology, reproductive hormones and testicular fatty acid profiles.Scrotal heat stress affects spermatogenesis and impairs male fertility by increasing sperm morphological abnormalities, oxidative stress and DNA fragmentation. While sperm morpho-functional changes triggered by scrotal heat stress are well described, sperm molecular alterations remain unknown. Recently, spermatozoa were described as accumulating miRNAs during the last steps of spermatogenesis and through epididymis transit, mainly by communication with small extracellular vesicles (sEVs). Herein, the aim was to investigate the impact of scrotal heat stress in miRNAs profile of sperm, as well as, seminal plasma sEVs. Six Nelore bulls (Bos indicus) were divided into two groups Control (CON; n = 3) and Scrotal Heat Stress (SHS; n = 3; scrotal heat stressed during 96 h by scrotal bags). The day that the scrotal bags were removed from SHS group was considered as D0 (Day zero). Seminal plasma sEVs were isolated from semen samples collected seven days after heat stress (D+7) to evaluate sEVs diameter, concentration,-15a, -18a, -20b, -30a-5p, -30b-5p, -30d, -30e-5p -34b, -34c, -106b, -126-5p, -146a, -191, -192, -200b, -335 and -449a). Thus, the scrotal heat stress probably impacted testicular and epididymis functions by reducing the levels of a substantial proportion of sEVs and sperm miRNAs. Our findings suggest that miR-126-5p was possibly trafficked between sEVs and sperm and provide new insights on the mechanism by which sperm acquire miRNAs in the last stages of spermatogenesis and sperm maturation in cattle.Stress has deleterious impact on semen quality and fertility of roosters. This study was investigated to know whether dietary supplementation of organic selenium (oSe) could improve semen quality and fertility of male broiler breeder under dexamethasone (Dexa) induced stress. Forty broiler breeder roosters (64 week of age) were randomly allotted to four groups (10 roosters/group) and fed a standard diet supplemented with different levels of oSe during 10 successive weeks of the experimental period. To induce stress, the birds received injections of 2 mg/kg BW of Dexa during weeks 5 and 6 of the experiment, in one-day-intervals manner. The roosters were not treated with Dexa and oSe (negative control; NC), or treated with Dexa and different levels of oSe including 0 (positive control; PC), 0.30 (Se30+Dexa) or 0.45 (Se45+Dexa) mg/kg diet. Body weight was measured weekly and semen quality parameters and fertility were evaluated every two weeks. Except for seminal volume and total sperm production which was not affected by the treatment, body weight, semen quality parameters, total antioxidant capacity (TAC) and malondialdehyde (MDA) in seminal plasma were influenced by interactive effect of treatment and time (P less then 0.05). Dexamethasone injection adversely affected semen quality parameters (semen concentration, motility and plasma membrane integrity) in PC group compared to NC group (P less then 0.05); however, dietary supplementation of oSe ameliorated these negative impacts in Dexa-treated roosters (P less then 0.05). Fertility was also improved by dietary supplementation of oSe compared to control groups (P less then 0.05). These results indicate that although induction of stress have negative effects on rooster semen quality parameters, dietary inclusion of oSe may exert beneficial impact on mitigating the harmful effects of stress on semen quality and fertility rate of broiler breeder roosters.

Evaluation of long-term efficacy and safety of various anti-hyperglycaemic agents (AHA) for glycaemic control in NODAT, in stable kidney transplant recipients (KTRs) during 1-year outpatient follow-up.

We collected FPG, PPG, HbA1c, serum creatinine, eGFR, blood tacrolimus level, hypoglycaemia and body weight values from an existing database of KTRs diagnosed to have NODAT. Those newly initiated on AHA over 3 months post-transplant; received standard triple immunosuppressive therapy; and followed up for 1-year after referral, were included.

In ninety-five patients' (Male=65), mean decrease at 1-year from baseline in FPG (185.01±62.11mg/dL), PPG (293.21±85.23mg/dL) and HbA1c (8.48±1.08%) was 67.09, 126.11 and 1.4 respectively (p<0.0001). At 1-year, mean HbA1c was 7.08±0.38%, ninety-one patients achieving HbA1c≤7.5%. Fifty-two patients received oral combination therapy based on linagliptin/metformin/repaglinide/gliclazide, 19 received insulin-based regimen, and 24 received linagliptin monotharapey. Thirty patients reported hypoglycaemia (10 with gliclazide and 15 with insulin) and fifty patients gained body-weight at 1-year. Mean serum creatinine and eGFR significantly improved by 0.29 and 15.77 from baseline of 1.56±0.62mg/dL and 53.95±16.10mL/min/1.73m

respectively.

Significant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.

Significant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.

to understand how undergraduate students with history of suicidal thoughts retrieve information on suicide method.

This is a cross-sectional descriptive study using custom self-rated questionnaires consisting of demographic data, history of previous suicidal thoughts or attempts, current suicidal risks via 8q questionnaires, known methods of suicide and history of suicidal attempt or planning and information on sources of suicide method. Participants were Thai undergraduate students of Mae Fah Luang University who were visiting psychiatric outpatient clinic of the university hospital and had history of suicidal thoughts.

Out of 39 participants, 25 participants reported intentionally searching for information on suicide methods while 31 participants reported unintentionally acquiring information on suicide methods. 19 participants reported that they both intentionally searching for the information and unintentionally acquiring it. The internet was used by all 25 participants who intentionally searched for information on suicide methods, with the second most common way was retrieving information from other suicidal attempters (reported by 11 participants). The most common websites/applications that were purposefully used to search for suicide methods were Google, a local web board and Facebook respectively.

The internet is the most commonly used method to intentionally search for information on suicide methods by undergraduate students of a Northern Thai university who have history of suicidal thoughts. Google and a local web board were the most frequently used websites/applications.

The internet is the most commonly used method to intentionally search for information on suicide methods by undergraduate students of a Northern Thai university who have history of suicidal thoughts. Google and a local web board were the most frequently used websites/applications.The entorhinal cortex is subdivided into anterolateral entorhinal cortex (alERC) and posteromedial entorhinal cortex (pmERC) subregions, which are theorized to support distinct cognitive roles. This distinction is particularly important as the alERC is one of the earliest cortical regions affected by Alzheimer's pathology and related neurodegeneration. The relative associations of alERC/pmERC with neuropsychological test performance have not been examined. We examined how alERC/pmERC volumes differentially relate to performance on 1) the Modified Rey Auditory Learning Test (ModRey), a verbal memory test designed to assess normal/preclinical populations, 2) the Montreal Cognitive Assessment (MoCA), and 3) the National Alzheimer's Coordinating Center neuropsychological battery. We also examined whether alERC/pmERC volumes correlate with Alzheimer's disease cerebrospinal fluid (CSF) biomarkers. In 65 cognitively healthy (CDR = 0) older adults, alERC, but not pmERC, volume was associated with ModRey memory retention. Only alERC volume differentiated between participants who scored above and below the MoCA cutoff score for impairment. Evaluating the MoCA subdomains revealed that alERC was particularly associated with verbal recall. On the National Alzheimer's Coordinating Center battery, both alERC and pmERC volumes were associated with Craft story recall and Benson figure copy, but only alERC volume was associated with Craft story retention and semantic fluency. Neither alERC nor pmERC volume correlated with CSF levels of amyloid or tau, and regression analyses showed that alERC volume and CSF amyloid levels were independently associated with ModRey retention performance. Taken together, these results suggest that the alERC is important for memory performance and that alERC volume differences are related to a pattern of neuropsychological test performance (i.e., impairments in episodic memory and semantic fluency) typically seen in clinical Alzheimer's disease.The recent advances in 3D-printed silicone (PDMS polydimethylsiloxane) implants present prospects for personalized implants with highly accurate anatomical conformity. However, a potential adverse effect, such as granuloma formation due to immune reactions, still exists. One potential way to overcome this problem is to control the implant/host interface using immunomodulatory coatings. In this study, a new cytokine cocktail composed of interleukin-10 and prostaglandin-E2 was designed to decrease adverse immune reactions and promote tissue integration by fixing macrophages into M2 pro-healing phenotype for an extended period of time. In vitro, the cytokine cocktail maintained low levels of pro-inflammatory cytokine (TNF-α and IL-6) secretions and induced the secretion of IL-10 and the upregulation of multifunctional scavenging and sorting receptor stabilin-1, expressed by M2 macrophages. This cocktail was then loaded in a gelatine-based hydrogel to develop an immunomodulatory material that could be used as a cCXCL1 and MCP-1 levels at day 21. The ability of this new immunomodulatory hydrogel to control the level of inflammation once applied to a 3D-printed silicone implant has been demonstrated. Such thin coatings can be applied to any implants or scaffolds used in tissue engineering to diminish the initial immune response, improve the integration and functionality of these materials and decrease potential complications related to their presence.Nanoscale outer membrane vesicles (OMVs) secreted by Gram-negative bacteria are often applied in antibacterial treatment as adjuvants or antigens. Recently, OMVs have also been tested in a few anti-tumor treatment studies, in which OMVs are injected multiple times to achieve certain therapeutic effects, showing risks in repeated cytokine storms. Herein, we propose the use a single low dose of OMVs combined with photothermal therapy (PTT) for effective cancer treatment. It was found that single i. v. injection of OMVs could activate the immune system by boosting the secretion levels of anti-tumor related cytokines. In addition, single i. v. injection of OMVs could also lead to extravasation of red blood cells in the tumor mainly owing to the effect of lipopolysaccharide on the OMVs. Such effect was not observed in other normal organs. As the results, the tumors on OMV-treated mice showed obviously darkened color with greatly increased intratumoral optical absorbance in the near-infrared (NIR) region, further enabling effective photothermal ablation of those tumors by the NIR laser. Without causing obvious adverse responses, bacteria-derived OMVs may be a new type of therapeutic agent for cancer treatment with multiple functions.Immunotherapy has revolutionized cancer treatment; however, only a limited portion of patients show responses to currently available immunotherapy regimens. Here, we demonstrate that RNA interference (RNAi) combined with immunogenic chemotherapy can elicit potent antitumor immunity against melanoma. Specially, we developed cationic polymer-lipid hybrid nanovesicles (P/LNVs) as a new delivery system for doxorubicin and small interfering RNA (siRNA) with extensive cytotoxicity and gene silencing efficiency towards B16 cells. The deployment of doxorubicin-loaded P/LNVs augmented the expression and presentation of endogenous tumor antigens directly in situ by inducing the immunogenic cell death of B16 cells through poly(ADP-ribose) polymerase 1-dependent (PARP1) apoptosis pathway; thereby, eliciting remarkable antitumor immune responses in mice. Leveraging dying B16 cells as a vaccination strategy in combination with RNAi-based programmed cell death ligand 1 (PD-L1) knockdown showed efficacy in both prophylactic and metastasis melanoma settings. Strikingly, PD-L1 blockade synergized with a sub-therapeutic dose of doxorubicin triggered robust therapeutic antitumor T-cell responses and eradicated pre-established tumors in 30% of mice bearing B16 melanoma. Our findings indicated that this combination treatment provided a new powerful immunotherapy modality, characterized by markedly increased infiltration of effector CD8+ T cells and effective alleviation of the immunosuppressive microenvironment in tumors. P/LNVs is a versatile and highly scalable carrier that can enable a broad combination of nanomedicine and RNAi, providing new therapeutic strategies for advanced cancers.Cancer phototherapy has attracted increasing attention for its promising effectiveness and relative non-invasiveness. Over the past years, tremendous efforts have been made to develop better phototherapy strategies with various nano delivery systems. This review introduces cancer phototherapy strategies based on tumor blood vessels for improved therapeutic outcomes from the angle of direct tumor destruction and improved delivery process assisted with nano delivery designs. Latest directions and ideas of cancer phototherapy with translation potential are also discussed. Focusing on the double role of tumor vessels not only as an anti-tumor target but also as part of the delivery process, we highlight the crosstalk between photo-induced extensive effects and the complicated drug delivery process. Due to the heterogeneity of tumors, deeper investigations about the interconnection between tumor vessels and cancer phototherapy remain to be carried out. More delicate and intelligent nano delivery systems are expected to help realize the full potential of this therapeutic strategy.In tasks that extend over time, people tend to exert much effort at the beginning and the end, but not in the middle, exhibiting the stuck-in-the-middle pattern (STIM). To date, little is known about the neural mechanisms underlying this effect. As the supplementary motor area (SMA) was previously implicated in coding prospective task-demands, we tested its role in producing the STIM pattern. Participants first underwent an SMA-localization session in which they tapped their fingers repeatedly while fMRI-scanned. In the next two sessions, before playing a 10-min computer game that measured effort-engagement, participants underwent inhibitory 1-Hz repetitive transcranial magnetic stimulation over the SMA, or over a control precuneus location. Three control experiments and a pretest confirmed that this task yields a STIM, which can be eliminated when the task lacks a salient end-point, or is too short. The results of the main experiment showed a more pronounced STIM following inhibitory SMA stimulation compared to control. A control analysis showed that overall level of effort was similar in both conditions, rendering alternative accounts in terms of motor inhibition unlikely. These findings are consistent with the possibility that the SMA may play a role in moment-to-moment coding of effort value, or in related sub-processes, which can cause effort to be distributed more equally over the course of a task.The application of metal nanoparticles in modern society is growing, but there is insufficient data concerning their influence on reproductive processes and comparison of their biological activity. The present experiments aimed to compare the effects of silver and titanium dioxide nanoparticles (AgNPs and TiO2NPs) on ovarian granulosa cell functions. AgNPs and TiO2NPs were added to culture of porcine granulosa cells at doses 0, 0.01, 0.1, 1 or 10 μg/mL. The mRNAs for proliferating cell nuclear antigen (PCNA), cyclin B1, bax and caspase 3 were quantified by RT-PCR; release of progesterone was analyzed by ELISA. It was shown that both AgNPs and TiO2NPs significantly reduced all the measured parameters. ED50 of the inhibitory influence of AgNPs on the main ovarian cell parameters was higher than ED50 of TiO2NPs. The ability of AgNPs and TiO2NPs to suppress ovarian granulosa cell functions should be taken into account by their application.Cadmium (Cd), prevailing in most of the agricultural lands of the world contaminates food chain, thereby causing several health implications. It has become the main heavy metal contaminant in most of the agricultural lands of Pakistan due to the widespread use of phosphate fertilizers besides application of irrigation water contaminated with industrial and mining effluents. Plant growth promoting bacteria (PGPB) are capable to enhance growth and metal stress tolerance in supplemented plants. Zinc oxide nanoparticles (ZnO-NPs) are capable to alleviate various abiotic stresses when applied to plants. During current research, the efficacy of single and combined application of Bacillus fortis IAGS 223 and ZnO-NPs was evaluated for alleviation of Cd (75 mg kg-1) induced phytotoxicity in Cucumis melo plants. For this purpose, C. melo plants, subjected to Cd stress were treated with B. fortis IAGS 223 and ZnO-NPs (20 mg kg-1), either alone or in combination. The growth relevant characteristics including photosyntheto formulate appropriate combination of ZnO-NPs and B. fortis IAGS-223 to acquire sustainable crop production under Cd stress.Type I interferons (IFNs) play a central role in host defense against viral infection. Multiple posttranslational modifications including ubiquitination and deubiquitination regulate the function of diverse molecules in type I IFN signaling. Many ubiquitin ligase enzymes, such as those of the TRAF and TRIM families, have been shown to participate in the production of type I IFNs and inflammatory cytokines. However, the function of deubiquitinating enzymes (DUBs), a protein family that counteracts the action of protein ubiquitination, on the regulation of antiviral immune responses is not well understood. In this study, we used the broad-spectrum DUB inhibitor G5 to reveal their function in antiviral signaling, and then systematically analyzed mRNA expression of the DUB genes upon poly (IC) treatment in THP-1 cells. Based on this analysis, we cloned some DUB genes whose expression changed and determined their function in antiviral signaling. Taken together, we present a comprehensive DUB gene expression analysis in THP-1 cells, and suggest the involvement of this family of proteins in the regulation of host antiviral activities.

immune checkpoint inhibitors(ICIs) have shown contradictory results in patients with advanced gastro-oesophageal junction/gastric cancer(GOJ/GC).

to identify specific patient subgroups that would derive survival benefit from ICIs.

a subgroup meta-analysis of randomised clinical trials(RCTs) was carried out.

four phase-III-RCTs were identified with data on the following variables primary location(Gastric vs GOJ); age(≤ 65 vs >65); gender(male vs female); ECOG PS(0 vs 1); ethnicity (Asian vs non-Asian), histology(intestinal vs diffuse), PD-L1 expression(≥ 1% vs < 1%). PD-L1 positivity was significantly associated with survival benefit from ICIs (HR 0.82, p 0.047), with a significant interaction between PD-L1 expression and ICI efficacy (interaction HR 1.41, p 0.02). Numerically, the second most relevant interaction was ICI efficacy and gender, with ICI being more effective in males.

The PD-L1 positive patient subgroup derives significant survival benefit from ICI in GOJ/GC, however other predictors are eagerly needed to further refine patient selection.

The PD-L1 positive patient subgroup derives significant survival benefit from ICI in GOJ/GC, however other predictors are eagerly needed to further refine patient selection.Immunotherapy has been a revolution in cancer management in the metastatic setting. This has led to a prompt evaluation of such therapies in earlier stages. This article discusses the still limited amount of data finding the rationale to assess such therapy in this setting and reviews preclinical and clinical data available. Overall, neoadjuvant immunotherapy is a promising approach for the treatment of cancers and the rationale supporting its use is strong. Neoadjuvant immunotherapy resulted, in the majority of clinical trials, in improved pathologic complete response rates with a favorable toxicity profile and no delay in surgery. Various regimens were effective inhibitory immune check-point blockers (IICPB) alone, combination of PD-1 and CTLA-4 inhibitors, combination of chemotherapy (CT) and IICPB, phased CT and IICPB (either IICPB before CT or IICPB after CT). Yet the question whether neoadjuvant immunotherapy will benefit to patients in terms of disease-free and, ultimately, overall survival remains unknown.

PD-1 checkpoint inhibitors are novel therapeutic agents in colorectal cancer (CRC). Immunohistochemical staining for CD274 assessment is standardised in upper GI cancer, but not in CRC.

Methodologies of relevant studies were scrutinized and meta-analysis of survival and CD274/PDCD1 performed. Furthermore, anti-PD-1 therapy clinical trial results in CRC were assessed with particular emphasis on CD274 assessment.

24 studies were included. CD274 on immune cells was associated with good prognosis. CD274 on tumour cells has heterogenous outcomes and does not meet requirements of a prognostic marker. As a marker of response to anti-PD-1 therapy, CD274 assessment is not standardised in CRC.

CD274 does not appear useful as a prognostic marker. As a marker of response to anti-PD-1 therapy, assessment methodology requires standardisation. As the Combined Positive Score (CPS) is used in upper GI cancer, this seems a logical method to adopt. Thresholds for CRC remain to be determined.

CD274 does not appear useful as a prognostic marker. As a marker of response to anti-PD-1 therapy, assessment methodology requires standardisation. As the Combined Positive Score (CPS) is used in upper GI cancer, this seems a logical method to adopt. Thresholds for CRC remain to be determined.Biological materials have length scale dependent structure enabling complex cell-material interactions and driving cellular processes. Synthetic biomaterials are designed to mimic aspects of these biological materials for applications including enhancing cell delivery during wound healing. To mimic native microenvironments, we must understand how cells manipulate their surroundings over several length scales. Our work characterizes length scale dependent rheology in a well-established 3D cell culture platform for human mesenchymal stem cells (hMSCs). hMSCs re-engineer their microenvironment through matrix metalloproteinase (MMP) secretions and cytoskeletal tension. Remodeling occurs across length scales MMPs degrade cross-links on nanometer scales resulting in micrometer-sized paths that hMSCs migrate through, eventually resulting in bulk scaffold degradation. We use multiple particle tracking microrheology (MPT) and bi-disperse MPT to characterize hMSC-mediated length scale dependent pericellular remodeling. MPT measures particle Brownian motion to calculate rheological properties. We use MPT to measure larger length scales with 4.5 µm particles. Bi-disperse MPT simultaneously measures two different length scales (0.5 and 2.0 µm). We measure that hMSCs preferentially remodel larger length scales measured as a higher mobility of larger particles. We inhibit cytoskeletal tension by inhibiting myosin-II and no longer measure this difference in particle mobility. This indicates that cytoskeletal tension is the source of cell-mediated length scale dependent rheological changes. Particle mobility correlates with cell speed across length scales, relating material rheology to cell behavior. These results quantify length scale dependent pericellular remodeling and provide insight into how these microenvironments can be designed into materials to direct cell behavior.In this work, a biocompatible monolithic column based micro-solid-phase extraction (µ-SPE) method was developed for biological fluid analysis. A novel nanoparticle-based polyacrylonitrile monolithic column (C30 NP-PMC) was fabricated by incorporating triacontyl (C30) modified silica nanoparticles (NPs) into the polyacrylonitrile monolithic matrix through thermally induced phase separation. With efficient mass transfer and sorption capacity, C30 NP-PMC exhibited outstanding performance for the extraction of carotenoids and fat-soluble vitamins (FSVs) from human serum samples, superior to commercial C18 cartridges as well as liquid-liquid extraction (LLE) method. Under optimal conditions, the proposed µ-SPE method coupled with high-performance liquid chromatography-diode array detection (HPLC-DAD) achieved satisfactory limits of detection (LODs) (1.5-75.0 ng/mL) and good recoveries (85.0-106.5 %) with relative standard deviations (RSDs) of less than 12.1% by consuming lower sorbent (35.0 mg) and organic solvent (0.8 mL). Successful application of the developed method demonstrated the great potential of such monolithic sorbents for efficient isolation and preconcentration of trace analytes from blood samples.The use of a commercially available short length channel (14 cm length) is proposed to improve the efficiency associated to the separation by asymmetrical flow field-flow fractionation of particles in the nanometer range respect to a standard channel (27 cm length). The effect of channel length on elution times, separation efficiency and resolution have been studied. Polystyrene particles between 50 and 500 nm in size have been used to compare the behavior of both channels. Theoretical aspects based on the different contributions on particle diffusion inside the channel during the separation process have been considered to justify the results obtained. Non-equilibrium diffusion contribution to the efficiency has shown to be the most relevant aspect to be controlled during the separation. The increment of the field strength applied through the cross-flow velocityallows the reduction of diffusion while keep elution times constant. The use of the same cross-flow in a channel with a smaller area is the key factor that justifies the better efficiencies observed along the whole size range studied (improvements that reach factors up to 4.7 in experimental efficiency respect to the standard channel were achieved). The separation of polystyrene particles of 100 and 200 nm was achieved with a resolution of 1.20, whereas a 0.66 value was obtained with the standard channel at the same elution times. Channel recoveries have been also compared under optimized conditions to ensure that no side effects are produced, including the separation of mixtures of TiO2 nanoparticles. Similar or even better values were obtained with the short length channel, with recoveries higher than 85% for all the polystyrene particles tested and 75% recovery for the TiO2 nanoparticle mixture, which justifies its use for the separation of nanoparticles, providing better resolutions without compromise elution times or recoveries.

Accumulating evidence indicates anti-diabetic drug metformin has anti-cancer effect by controlling cancer metabolism. We evaluated whether addition of metformin to chemotherapy improved survival of lung cancer patients.

This randomized phase II study enrolled 164 patients with chemo-native, EGFR-ALK wild-type, stage IIIB/IV non-small-cell lung cancer (NSCLC). Patients were randomized to receive chemotherapy either with metformin (1000 mg twice daily) or alone every 3 weeks for six cycles. The patients received gemcitabine (1000 mg/m

) on days 1 and 8 and carboplatin (5 area under the curve) on day 1. Exploratory studies included serum metabolic panels, positron-emission tomography (PET) imaging, and genetic mutation tests for metabolism-related genes.

Metformin group showed no significant difference in the risk of progression and death compared to control group (progression hazard ratio [HR] = 1.01 [95% confidence interval (CI) = 0.72 - 1.42], P = 0.935; death HR = 0.95 [95% CI = 0.67-1.34], P = 0.757)ded no survival benefit in unselected NSCLC patients. However, it significantly improved the survival of the selected patients with SqCC showing high FDG uptake. It suggests metformin shows the synergistic anti-tumor effect in the tumor which are highly dependent on glucose metabolism.

Little is known about the etiology of pulmonary carcinoids (PC). Associations with other types of cancer may identify shared risk factors but results from earlier studies were inconclusive. The aim of the present study was to explore the association between PC and other primary malignancies for identifying risk factors.

A query of the nationwide Netherlands Cancer Registry generated data about patients diagnosed with PC from 1989 to 2018. The occurrence of second primary malignancies was evaluated separately for year 1 and years 2-30. The expected numbers of second primary malignancies were calculated using incidence reference tables, controlling for age, gender and period. Confidence intervals (95 % CI) for the ratio between observed and expected numbers (SIR standardized incidence ratio) were calculated using Poisson distributions.

In a total of 2933 patients with PC, 425 consecutive primary malignancies were observed in 376 patients. Concomitant diagnoses in the first year mainly comprised lung (n = 59) and renal cancer (n = 14). Metachronous malignancies beyond the first year were most common for breast (n = 50), colorectal (n = 41), prostate (n = 32), and lung cancer (n = 29). Beyond year 1, the overall risk of second primary cancer in patients with PC was similar to the risk within the general population (n = 256, SIR = 1.12, 95 % CI 0.99-1.27). Increased risks were observed for soft tissue sarcoma (n = 5, SIR = 3.52, 95 % CI 1.14-8.22) and GEPNET (n = 4, SIR = 4.30, 95 % CI 1.17-11.01).

Concomitant diagnosis of PC with other cancers is common, reflecting surveillance diagnostics. Apart from MEN-1 family history, no shared risk factors could be identified.

Concomitant diagnosis of PC with other cancers is common, reflecting surveillance diagnostics. Apart from MEN-1 family history, no shared risk factors could be identified.

Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) are the preferred treatment option for patients with advanced/metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations and ALK rearrangements respectively. TKIs can theoretically induce thyroid dysfunction via actions on many levels of the hypothalamic-pituitary-thyroid axis. However, there are no published studies on occurrence of thyroid dysfunction related to use of EGFR/ALK TKIs in lung cancer. The current study aimed to prospectively and comprehensively evaluate incidence of thyroid dysfunction in NSCLC patients treated with EGFR and ALK inhibitors.

This prospective observational study at a tertiary care referral hospital included histologically/cytologically proven advanced/metastatic NSCLC patients treated with EGFR and ALK inhibitors over a period of 15 months. Thyroid function tests (including anti-TPO antibody) were done at baseline and repeated every month for first three months and then every three monthly for 12 months.

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