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  • Lung carcinoma is associated with a high mortality worldwide, being the leading cause of cancer death. It is mainly classified into squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, and small cell lung cancer. However, such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment. Therapies can be used in adjuvant and palliative settings. Regarding immunotherapy, it has been widely tested in both first or subsequent palliative lines. In this sense, drugs such as pembrolizumab, nivolumab, atezolizumab, ipilimumab, avelumab, and durvalumab have been assessed in large studies. Some of these trials have also studied these medicines in adjuvant and in maintenance therapy. In recent years, advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed. https://www.selleckchem.com/products/sodium-l-ascorbyl-2-phosphate.html Immunotherapy has increased the overall survival in squamous NSCLC, non-squamous NSCLC, and small cell lung cancer. However, it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support. In order to show how immunotherapy is being applied in the treatment of lung carcinoma, we reviewed the main studies in adjuvant and palliative scenarios. What is the better scheme? What is the better combination? What is the better dose? When should we use immunotherapy? Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency? Some of these questions have already been answered, while others require more investigations.In this era of climate change, novel nature-based solutions, like the daylighting (de-culverting) of streams, that enhance the socio-ecological resilience are gaining prominence. Yet, the growing body of literature on stream daylighting spreads over an array of seemingly disconnected disciplines and lacks consistency in the terminology and the definitions of the practice. Moreover, nearly all the literature review studies on stream daylighting (mostly produced since 2000) underscore, as their point of departure, the daylighting projects rather than a review of the literature's content per se. Therefore, this study reassesses the literature on stream daylighting with a particular focus on its role, as a nature-based solution, for climate change mitigation and adaptation and for socio-environmental justice. We combine the systematic literature review (an all-encompassing review of the available literature on stream daylighting) with the inductive content analysis (an in-depth analysis of this literature's nature). Accordingly, we investigate all the relevant English-language publications since the first peer reviewed article on stream daylighting was published in 1992 until the end of 2018 to analyze four themes the disciplines and sub-disciplines of the literature; the terminologies and synonyms of stream daylighting; the definitions of stream daylighting; and the case studies tackled in the literature.•We develop a method that combines a systematic review of the stream daylighting literature and inductive content analysis.•The method provides insights on the stream daylighting's literature's disciplines, terminologies, synonyms and case studies.•The method is adaptable particularly, to nascent areas of study where sources' numbers range between 100-200.
    To evaluate the effect of double level osteotomy (DLO), a combination of a lateral closed distal femoral osteotomy (LCWDFO) and medial opening wedge high tibial osteotomy (MOWHTO), on patellar height and patellofemoral alignment as compared to those of isolated MOWHTO.

    Twenty-six consecutive knees in 26 patients who underwent DLO (DLO group) constituted the study population. For comparative purpose, a control cohort (N 26) matched for age, sex, and body mass index with the study group were selected from the patients who underwent isolated MOWHTO with an opening gap of more than 10mm during the same period (MOWHTO group). Patellar height and patellofemoral alignment were assessed on radiographs preoperatively and at 2 years after surgery. For the patellar height, following parameters were measured on a lateral radiograph Modified Insall-Salvati Index (mISI), modified Caton-Deschamps Index (mCDI), and modified Blackburne-Peel Index (mBPI). In the assessment of patellofemoral alignment, lateral patellar tiltlt. Those changes in patellar position and orientation were similarly observed in isolated MOWHTO knees. Although DLO is specifically indicated for knees with severe varus deformity, the two surgical options for correction of varus knee deformity exerted similar influences on patellofemoral biomechanics.Lower respiratory infections are the most important cause of death due to a transmissible disease. We present a case of severe influenza and coccidioidomycosis lung coinfection in a 65-year-old Mexican migrant. This case highlights the challenges that respiratory viruses impose on the diagnosis of fungal infections and on the multidisciplinary management of these infections. In addition, this case shows how medical complications and superinfections could be potentially prevented if flu vaccination is provided.In July 2018, the U.S. Department of Housing and Urban Development (HUD) implemented a new Public health Agency rule prohibiting the use of tobacco in and within 25 feet of HUD housing. A convenience sample of 574 residents living in Milwaukee, Wisconsin multi-unit HUD complexes completed a survey from May through July 2019, designed to assess their perceptions of the new policy and its impact. Knowledge of the policy was strong, although continued educational efforts are needed. Attitudes about the policy were generally positive, although smokers held more negative attitudes than non-smokers. Some residents desired more and fairer policy enforcement. Most residents reported that smoke incursions were reduced post policy compared to pre policy, although such incursions still occurred. The policy has had a favorable health impact on smokers; over 80% made at least one positive change in their smoking, including 6.4% who said the policy motivated them to quit. There was no evidence that residents with mobility challenges were differentially affected by the policy.
    Lung carcinoma is associated with a high mortality worldwide, being the leading cause of cancer death. It is mainly classified into squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, and small cell lung cancer. However, such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment. Therapies can be used in adjuvant and palliative settings. Regarding immunotherapy, it has been widely tested in both first or subsequent palliative lines. In this sense, drugs such as pembrolizumab, nivolumab, atezolizumab, ipilimumab, avelumab, and durvalumab have been assessed in large studies. Some of these trials have also studied these medicines in adjuvant and in maintenance therapy. In recent years, advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed. https://www.selleckchem.com/products/sodium-l-ascorbyl-2-phosphate.html Immunotherapy has increased the overall survival in squamous NSCLC, non-squamous NSCLC, and small cell lung cancer. However, it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support. In order to show how immunotherapy is being applied in the treatment of lung carcinoma, we reviewed the main studies in adjuvant and palliative scenarios. What is the better scheme? What is the better combination? What is the better dose? When should we use immunotherapy? Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency? Some of these questions have already been answered, while others require more investigations.In this era of climate change, novel nature-based solutions, like the daylighting (de-culverting) of streams, that enhance the socio-ecological resilience are gaining prominence. Yet, the growing body of literature on stream daylighting spreads over an array of seemingly disconnected disciplines and lacks consistency in the terminology and the definitions of the practice. Moreover, nearly all the literature review studies on stream daylighting (mostly produced since 2000) underscore, as their point of departure, the daylighting projects rather than a review of the literature's content per se. Therefore, this study reassesses the literature on stream daylighting with a particular focus on its role, as a nature-based solution, for climate change mitigation and adaptation and for socio-environmental justice. We combine the systematic literature review (an all-encompassing review of the available literature on stream daylighting) with the inductive content analysis (an in-depth analysis of this literature's nature). Accordingly, we investigate all the relevant English-language publications since the first peer reviewed article on stream daylighting was published in 1992 until the end of 2018 to analyze four themes the disciplines and sub-disciplines of the literature; the terminologies and synonyms of stream daylighting; the definitions of stream daylighting; and the case studies tackled in the literature.•We develop a method that combines a systematic review of the stream daylighting literature and inductive content analysis.•The method provides insights on the stream daylighting's literature's disciplines, terminologies, synonyms and case studies.•The method is adaptable particularly, to nascent areas of study where sources' numbers range between 100-200. To evaluate the effect of double level osteotomy (DLO), a combination of a lateral closed distal femoral osteotomy (LCWDFO) and medial opening wedge high tibial osteotomy (MOWHTO), on patellar height and patellofemoral alignment as compared to those of isolated MOWHTO. Twenty-six consecutive knees in 26 patients who underwent DLO (DLO group) constituted the study population. For comparative purpose, a control cohort (N 26) matched for age, sex, and body mass index with the study group were selected from the patients who underwent isolated MOWHTO with an opening gap of more than 10mm during the same period (MOWHTO group). Patellar height and patellofemoral alignment were assessed on radiographs preoperatively and at 2 years after surgery. For the patellar height, following parameters were measured on a lateral radiograph Modified Insall-Salvati Index (mISI), modified Caton-Deschamps Index (mCDI), and modified Blackburne-Peel Index (mBPI). In the assessment of patellofemoral alignment, lateral patellar tiltlt. Those changes in patellar position and orientation were similarly observed in isolated MOWHTO knees. Although DLO is specifically indicated for knees with severe varus deformity, the two surgical options for correction of varus knee deformity exerted similar influences on patellofemoral biomechanics.Lower respiratory infections are the most important cause of death due to a transmissible disease. We present a case of severe influenza and coccidioidomycosis lung coinfection in a 65-year-old Mexican migrant. This case highlights the challenges that respiratory viruses impose on the diagnosis of fungal infections and on the multidisciplinary management of these infections. In addition, this case shows how medical complications and superinfections could be potentially prevented if flu vaccination is provided.In July 2018, the U.S. Department of Housing and Urban Development (HUD) implemented a new Public health Agency rule prohibiting the use of tobacco in and within 25 feet of HUD housing. A convenience sample of 574 residents living in Milwaukee, Wisconsin multi-unit HUD complexes completed a survey from May through July 2019, designed to assess their perceptions of the new policy and its impact. Knowledge of the policy was strong, although continued educational efforts are needed. Attitudes about the policy were generally positive, although smokers held more negative attitudes than non-smokers. Some residents desired more and fairer policy enforcement. Most residents reported that smoke incursions were reduced post policy compared to pre policy, although such incursions still occurred. The policy has had a favorable health impact on smokers; over 80% made at least one positive change in their smoking, including 6.4% who said the policy motivated them to quit. There was no evidence that residents with mobility challenges were differentially affected by the policy.
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  • The 5' capture scRNAseq analysis of PBMC not only recapitulated previously published reports by detecting virally infected memory and naïve B cells, but also identified cell-associated genomic variants not observed in contemporaneous serum samples. These results demonstrate that oligo(dT) primed 5' capture scRNAseq can detect DENV RNA and quantify virus-infected cells in physiologically relevant conditions, and provides insight into viral sequence variability within infected cells.Terrestrial vegetation removes CO2 from the atmosphere; an important climate regulation service that slows global warming. This 119 Pg C per annum transfer of CO2 into plants-gross primary productivity (GPP)-is the largest land carbon flux globally. While understanding past and anticipated future GPP changes is necessary to support carbon management, the factors driving long-term changes in GPP are largely unknown. Here we show that 1901 to 2010 changes in GPP have been dominated by anthropogenic activity. Our dual constraint attribution approach provides three insights into the spatiotemporal patterns of GPP change. First, anthropogenic controls on GPP change have increased from 57% (1901 decade) to 94% (2001 decade) of the vegetated land surface. Second, CO2 fertilization and nitro gen deposition are the most important drivers of change, 19.8 and 11.1 Pg C per annum (2001 decade) respectively, especially in the tropics and industrialized areas since the 1970's. Third, changes in climate have functioned as fertilization to enhance GPP (1.4 Pg C per annum in the 2001 decade). These findings suggest that, from a land carbon balance perspective, the Anthropocene began over 100 years ago and that global change drivers have allowed GPP uptake to keep pace with anthropogenic emissions.Maternal diet is an important potential factor associated with the risk of preeclampsia. However, it is unclear whether adherence to a Dietary Approaches to Stop Hypertension (DASH)-style diet can reduce the development of preeclampsia. To examine the potential association, we conducted a hospital-based case-control study at the First Affiliated Hospital of Zhengzhou University, China. A total of 449 cases with preeclampsia and 449 controls were studied. Dietary information was collected using a validated food frequency questionnaire (FFQ). DASH scores were calculated according to nutrients/food emphasised or minimised in the DASH diet. The calculated DASH scores ranged from 11 to 38 for all of the participants, and the DASH scores of the cases were significantly lower than those of the controls (23.48 ± 4.58 vs 24.51 ± 4.51; p = 0.001). https://www.selleckchem.com/products/taurocholic-acid-sodium-salt-hydrate.html Participants in the fourth quartile of the DASH score were 45% less likely to have preeclampsia than those in the first quartile in the crude model (Q4 vs Q1, odds ratio [OR] 0.55; 95% confidence interval [CI] 0.38, 0.80; ptrend = 0.001). The relationship remained significant in the model adjusted for multiple confounders, especially for major risk factors of preeclampsia (OR 0.53; 95% CI 0.36, 0.78; ptrend = 0.001). Our findings suggest an inverse relationship between adherence to a DASH-style diet and the odds of preeclampsia. Further larger-scale cohort studies or randomised controlled trials are warranted to confirm these relationships.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Cyst nematodes induce host-plant root cells to form syncytia from which the nematodes feed. Comprehensive histological investigation of these feeding sites is complicated by their variable shape and their positions deep within root tissue. Using tissue clearing and confocal microscopy, we examined thick (up to 150 μm) sections of wheat roots infected by cereal cyst nematodes (Heterodera avenae). This approach provided clear views of feeding sites and surrounding tissues, with resolution sufficient to reveal spatial relationships among nematodes, syncytia and host vascular tissues at the cellular level. Regions of metaxylem vessels near syncytia were found to have deviated from classical developmental patterns. Xylem vessel elements in these regions had failed to elongate but had undergone radial expansion, becoming short and plump rather than long and cylindrical. Further investigation revealed that vessel elements cease to elongate shortly after infection and that they later experience delays in secondary thickening (lignification) of their outer cell walls. Some of these elements were eventually incorporated into syncytial feeding sites. By interfering with a developmental program that normally leads to programmed cell death, H. avenae may permit xylem vessel elements to remain alive for later exploitation by the parasite.Background Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Methods Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. Results Overexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-**** models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine. Conclusions This study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors.
    The 5' capture scRNAseq analysis of PBMC not only recapitulated previously published reports by detecting virally infected memory and naïve B cells, but also identified cell-associated genomic variants not observed in contemporaneous serum samples. These results demonstrate that oligo(dT) primed 5' capture scRNAseq can detect DENV RNA and quantify virus-infected cells in physiologically relevant conditions, and provides insight into viral sequence variability within infected cells.Terrestrial vegetation removes CO2 from the atmosphere; an important climate regulation service that slows global warming. This 119 Pg C per annum transfer of CO2 into plants-gross primary productivity (GPP)-is the largest land carbon flux globally. While understanding past and anticipated future GPP changes is necessary to support carbon management, the factors driving long-term changes in GPP are largely unknown. Here we show that 1901 to 2010 changes in GPP have been dominated by anthropogenic activity. Our dual constraint attribution approach provides three insights into the spatiotemporal patterns of GPP change. First, anthropogenic controls on GPP change have increased from 57% (1901 decade) to 94% (2001 decade) of the vegetated land surface. Second, CO2 fertilization and nitro gen deposition are the most important drivers of change, 19.8 and 11.1 Pg C per annum (2001 decade) respectively, especially in the tropics and industrialized areas since the 1970's. Third, changes in climate have functioned as fertilization to enhance GPP (1.4 Pg C per annum in the 2001 decade). These findings suggest that, from a land carbon balance perspective, the Anthropocene began over 100 years ago and that global change drivers have allowed GPP uptake to keep pace with anthropogenic emissions.Maternal diet is an important potential factor associated with the risk of preeclampsia. However, it is unclear whether adherence to a Dietary Approaches to Stop Hypertension (DASH)-style diet can reduce the development of preeclampsia. To examine the potential association, we conducted a hospital-based case-control study at the First Affiliated Hospital of Zhengzhou University, China. A total of 449 cases with preeclampsia and 449 controls were studied. Dietary information was collected using a validated food frequency questionnaire (FFQ). DASH scores were calculated according to nutrients/food emphasised or minimised in the DASH diet. The calculated DASH scores ranged from 11 to 38 for all of the participants, and the DASH scores of the cases were significantly lower than those of the controls (23.48 ± 4.58 vs 24.51 ± 4.51; p = 0.001). https://www.selleckchem.com/products/taurocholic-acid-sodium-salt-hydrate.html Participants in the fourth quartile of the DASH score were 45% less likely to have preeclampsia than those in the first quartile in the crude model (Q4 vs Q1, odds ratio [OR] 0.55; 95% confidence interval [CI] 0.38, 0.80; ptrend = 0.001). The relationship remained significant in the model adjusted for multiple confounders, especially for major risk factors of preeclampsia (OR 0.53; 95% CI 0.36, 0.78; ptrend = 0.001). Our findings suggest an inverse relationship between adherence to a DASH-style diet and the odds of preeclampsia. Further larger-scale cohort studies or randomised controlled trials are warranted to confirm these relationships.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Cyst nematodes induce host-plant root cells to form syncytia from which the nematodes feed. Comprehensive histological investigation of these feeding sites is complicated by their variable shape and their positions deep within root tissue. Using tissue clearing and confocal microscopy, we examined thick (up to 150 μm) sections of wheat roots infected by cereal cyst nematodes (Heterodera avenae). This approach provided clear views of feeding sites and surrounding tissues, with resolution sufficient to reveal spatial relationships among nematodes, syncytia and host vascular tissues at the cellular level. Regions of metaxylem vessels near syncytia were found to have deviated from classical developmental patterns. Xylem vessel elements in these regions had failed to elongate but had undergone radial expansion, becoming short and plump rather than long and cylindrical. Further investigation revealed that vessel elements cease to elongate shortly after infection and that they later experience delays in secondary thickening (lignification) of their outer cell walls. Some of these elements were eventually incorporated into syncytial feeding sites. By interfering with a developmental program that normally leads to programmed cell death, H. avenae may permit xylem vessel elements to remain alive for later exploitation by the parasite.Background Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Methods Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. Results Overexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-mice models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine. Conclusions This study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors.
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  • The exotoxin TcsL is a major virulence factor in Paeniclostridium (Clostridium) sordellii and responsible for the high lethality rate associated with P. sordellii infection. Here, we present a genome-wide CRISPR-Cas9-mediated screen using a human lung carcinoma cell line and identify semaphorin (SEMA) 6A and 6B as receptors for TcsL. Disrupting SEMA6A/6B expression in several distinct human cell lines and primary human endothelial cells results in reduced TcsL sensitivity, while SEMA6A/6B over-expression increases their sensitivity. TcsL recognizes the extracellular domain (ECD) of SEMA6A/6B via a region homologous to the receptor-binding site in Clostridioides difficile toxin B (TcdB), which binds the human receptor Frizzled. Exchanging the receptor-binding interfaces between TcsL and TcdB switches their receptor-binding specificity. Finally, administration of SEMA6A-ECD proteins protects human cells from TcsL toxicity and reduces TcsL-induced damage to lung tissues and the lethality rate in ****. These findings establish SEMA6A and 6B as pathophysiologically relevant receptors for TcsL. Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin. Genetic mouse studies revealed that dermal adipocytes are necessary to initiate inflammation after injury and promote subsequent repair. We find through histological, ultrastructural, lipidomic, and genetic experiments in **** that adipocytes adjacent to skin injury initiate lipid release necessary for macrophage inflammation. Tamoxifen-inducible genetic lineage tracing of mature adipocytes and single-cell RNA sequencing revealed that dermal adipocytes alter their fate and generate ECM-producing myofibroblasts within wounds. Thus, adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. During early development, extrinsic triggers prompt pluripotent cells to begin the process of differentiation. When and how human embryonic stem cells (hESCs) irreversibly commit to differentiation is a fundamental yet unanswered question. By combining single-cell imaging, genomic approaches, and mathematical modeling, we find that hESCs commit to exiting pluripotency unexpectedly early. We show that bone morphogenetic protein 4 (BMP4), an important differentiation trigger, induces a subset of early genes to mirror the sustained, bistable dynamics of upstream signaling. Induction of one of these genes, GATA3, drives differentiation in the absence of BMP4. Conversely, GATA3 knockout delays differentiation and prevents fast commitment to differentiation. We show that positive feedback at the level of the GATA3-BMP4 axis induces fast, irreversible commitment to differentiation. We propose that early commitment may be a feature of BMP-driven fate choices and that interlinked feedback is the molecular basis for an irreversible transition from pluripotency to differentiation. Introduction Despite growing documentation of the efficacy of telemedicine in diabetes management, racial disparities in telemedicine-facilitated diabetes management remain underexplored. This study examined disparities in diabetes management outcomes between black and white patients with type 2 diabetes (T2D) in a remote monitoring program. Methods The analysis sample included 914 white T2D patients and 365 black T2D patients in Nebraska who completed a 3-month remote patient monitoring and coaching after hospital discharge from 2014 to 2017. Ordinary least squares regression was estimated to examine racial differences in hemoglobin A1c (HbA1c), and logistic regression was used to determine the odds of HbA1c > 9% at the end of the program, controlling for demographics, baseline health conditions, and patient activation and engagement with the program. Results The proportion of white patients with HbA1c > 9% was reduced from 16% at the baseline to 7% at program completion, and the corresponding reduction among black patients was from 30% to 18%. After adjusting for the effects of baseline HbA1c and other covariates, the average HbA1c among black patients at the end of the program was 0.23 points higher than that among white patients (p 9% was 1.68 times that of white patients (95% confidence interval [1.07-2.63]). Discussion The remote patient monitoring and coaching program reduced the absolute gap between black and white T2D patients. However, substantial racial disparities in HbA1c still remained at the end of the program and warranted further research.Background Telemedicine and point-of-care ultrasound have merged to create a field known as teleultrasound (TUS). Real-time TUS involves the transmission of bedside ultrasound (US) images with direct feedback from an US expert. In this review, we summarize the current uses of real-time TUS and discuss its potential future uses. Methods We performed a literature search (PubMed and EMBase) to assess articles related to real-time TUS. Data were extracted using a standardized collection form, and relevant articles were separated into feasibility or clinical studies. Results Our search yielded 45 articles, with most of the reports taking place in resource-constrained settings. A large portion of the studies discussed the use of the focused assessment with sonography in trauma exam. Others included musculoskeletal, vascular, and echocardiography. Conclusion Real-time TUS allows for rapid access to diagnostic imaging in various clinical settings. https://www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html This technology is poised to expand with many uses on the horizon.Mild therapeutic hypothermia is protective against several cellular stresses, but the mechanisms underlying this protection are not completely resolved. In the present study, we used an in vitro model to investigate whether therapeutic hypothermia at 33°C applied following a peroxide-induced oxidative stress would protect PC12 cells. A 1-hour exposure to tert-butyl peroxide increased cell death measured 24 hours later. This cell death was dose-dependent in the range of 100-1000 μM tert-butyl peroxide with ∼50% cell death observed at 24 hours from 500 μM peroxide exposure. Cell survival/death was measured with an alamarBlue viability assay, and propidium iodide/Hoechst imaging for counts of living and dead cells. Therapeutic hypothermia at 33°C applied for 2 hours postperoxide exposure significantly increased cell survival measured 24 hours postperoxide-induced stress. This protection was present even when delayed hypothermia, 15 minutes after the peroxide washout, was applied. Addition of any of the three FDA-approved antioxidants (Tempol, EUK134, Edaravone at 100 μM) in combination with hypothermia improved cell survival.
    The exotoxin TcsL is a major virulence factor in Paeniclostridium (Clostridium) sordellii and responsible for the high lethality rate associated with P. sordellii infection. Here, we present a genome-wide CRISPR-Cas9-mediated screen using a human lung carcinoma cell line and identify semaphorin (SEMA) 6A and 6B as receptors for TcsL. Disrupting SEMA6A/6B expression in several distinct human cell lines and primary human endothelial cells results in reduced TcsL sensitivity, while SEMA6A/6B over-expression increases their sensitivity. TcsL recognizes the extracellular domain (ECD) of SEMA6A/6B via a region homologous to the receptor-binding site in Clostridioides difficile toxin B (TcdB), which binds the human receptor Frizzled. Exchanging the receptor-binding interfaces between TcsL and TcdB switches their receptor-binding specificity. Finally, administration of SEMA6A-ECD proteins protects human cells from TcsL toxicity and reduces TcsL-induced damage to lung tissues and the lethality rate in mice. These findings establish SEMA6A and 6B as pathophysiologically relevant receptors for TcsL. Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin. Genetic mouse studies revealed that dermal adipocytes are necessary to initiate inflammation after injury and promote subsequent repair. We find through histological, ultrastructural, lipidomic, and genetic experiments in mice that adipocytes adjacent to skin injury initiate lipid release necessary for macrophage inflammation. Tamoxifen-inducible genetic lineage tracing of mature adipocytes and single-cell RNA sequencing revealed that dermal adipocytes alter their fate and generate ECM-producing myofibroblasts within wounds. Thus, adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. During early development, extrinsic triggers prompt pluripotent cells to begin the process of differentiation. When and how human embryonic stem cells (hESCs) irreversibly commit to differentiation is a fundamental yet unanswered question. By combining single-cell imaging, genomic approaches, and mathematical modeling, we find that hESCs commit to exiting pluripotency unexpectedly early. We show that bone morphogenetic protein 4 (BMP4), an important differentiation trigger, induces a subset of early genes to mirror the sustained, bistable dynamics of upstream signaling. Induction of one of these genes, GATA3, drives differentiation in the absence of BMP4. Conversely, GATA3 knockout delays differentiation and prevents fast commitment to differentiation. We show that positive feedback at the level of the GATA3-BMP4 axis induces fast, irreversible commitment to differentiation. We propose that early commitment may be a feature of BMP-driven fate choices and that interlinked feedback is the molecular basis for an irreversible transition from pluripotency to differentiation. Introduction Despite growing documentation of the efficacy of telemedicine in diabetes management, racial disparities in telemedicine-facilitated diabetes management remain underexplored. This study examined disparities in diabetes management outcomes between black and white patients with type 2 diabetes (T2D) in a remote monitoring program. Methods The analysis sample included 914 white T2D patients and 365 black T2D patients in Nebraska who completed a 3-month remote patient monitoring and coaching after hospital discharge from 2014 to 2017. Ordinary least squares regression was estimated to examine racial differences in hemoglobin A1c (HbA1c), and logistic regression was used to determine the odds of HbA1c > 9% at the end of the program, controlling for demographics, baseline health conditions, and patient activation and engagement with the program. Results The proportion of white patients with HbA1c > 9% was reduced from 16% at the baseline to 7% at program completion, and the corresponding reduction among black patients was from 30% to 18%. After adjusting for the effects of baseline HbA1c and other covariates, the average HbA1c among black patients at the end of the program was 0.23 points higher than that among white patients (p 9% was 1.68 times that of white patients (95% confidence interval [1.07-2.63]). Discussion The remote patient monitoring and coaching program reduced the absolute gap between black and white T2D patients. However, substantial racial disparities in HbA1c still remained at the end of the program and warranted further research.Background Telemedicine and point-of-care ultrasound have merged to create a field known as teleultrasound (TUS). Real-time TUS involves the transmission of bedside ultrasound (US) images with direct feedback from an US expert. In this review, we summarize the current uses of real-time TUS and discuss its potential future uses. Methods We performed a literature search (PubMed and EMBase) to assess articles related to real-time TUS. Data were extracted using a standardized collection form, and relevant articles were separated into feasibility or clinical studies. Results Our search yielded 45 articles, with most of the reports taking place in resource-constrained settings. A large portion of the studies discussed the use of the focused assessment with sonography in trauma exam. Others included musculoskeletal, vascular, and echocardiography. Conclusion Real-time TUS allows for rapid access to diagnostic imaging in various clinical settings. https://www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html This technology is poised to expand with many uses on the horizon.Mild therapeutic hypothermia is protective against several cellular stresses, but the mechanisms underlying this protection are not completely resolved. In the present study, we used an in vitro model to investigate whether therapeutic hypothermia at 33°C applied following a peroxide-induced oxidative stress would protect PC12 cells. A 1-hour exposure to tert-butyl peroxide increased cell death measured 24 hours later. This cell death was dose-dependent in the range of 100-1000 μM tert-butyl peroxide with ∼50% cell death observed at 24 hours from 500 μM peroxide exposure. Cell survival/death was measured with an alamarBlue viability assay, and propidium iodide/Hoechst imaging for counts of living and dead cells. Therapeutic hypothermia at 33°C applied for 2 hours postperoxide exposure significantly increased cell survival measured 24 hours postperoxide-induced stress. This protection was present even when delayed hypothermia, 15 minutes after the peroxide washout, was applied. Addition of any of the three FDA-approved antioxidants (Tempol, EUK134, Edaravone at 100 μM) in combination with hypothermia improved cell survival.
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  • Acute myocarditis is associated with cardiac arrhythmia in 25% of cases; a third of these arrhythmias are ventricular tachycardia (VT) or ventricular fibrillation (VF). The implantation of a cardiac defibrillator (ICD) following sustained ventricular arrhythmia remains controversial in these patients. We sought to assess the risk of major arrhythmic ventricular events (MAEs) over time in patients implanted with an ICD following sustained VT/VF in the acute phase of myocarditis compared to those implanted for VT/VF occurring on myocarditis sequelae. Our retrospective observational study included patients implanted with an ICD following VT/VF during acute myocarditis or VT/VF on myocarditis sequelae, from 2007 to 2017, in 15 French university hospitals. Over a median follow-up period of 3 years, MAE occurred in 11 (39%) patients of the acute myocarditis group and 24 (60%) patients of the myocarditis sequelae group. Kaplan-Meier MAE rate estimates at one and three years of follow-up were 19% and 45% in the acute group, and 43% and 64% in the sequelae group. Patients who experienced sustained ventricular arrhythmias during acute myocarditis had a very high risk of VT/VF recurrence during follow-up. These results show that the risk of MAE recurrence remains high after resolution of the acute episode.Dating of clay bricks (adobe) and plasters is a relevant topic not only for building historians in the Pannonian region. Especially in vernacular architecture in this region, clay with straw amendments is a dominant construction material. The paper presents the potential of the molecular decay of these amendments to establish prediction tools for age based on infrared spectroscopic measurements. Preliminary results revealed spectral differences between the different plant parts, especially culms, nodes, and ear spindles. Based on these results, a first prediction model is presented including 14 historic samples. https://www.selleckchem.com/products/azd7648.html The coefficient of determination for the validation reached 62.2%, the (RMSE) root mean squared error amounted to 93 years. Taking the limited sample amount and the high material heterogeneity into account, this result can be seen as a promising output. Accordingly, sample size should be increased to a minimum of 100 objects and separate models for the different plant parts should be established.Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2'O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.Adult day care (ADC) provides various services for meeting clients' needs. Based on the mini-Delphi method with 46 ADC staff and the discussions with eight ADC administrators, this study developed and finalized a comprehensive logic model to represent the elements of ADC. For the three basic structures of a logic model-inputs/activities, outputs, and outcomes-the model contained seven core categories and 23 sub-categories. The ADC inputs/activities consisted of two core categories "Place to stay" and "Intervention from staff". These inputs/activities caused two kinds of outputs "Clients' experiences" and "Families' experiences". "Accumulating experiences" with repeated ADC visits was established as the link between the ADC outputs and outcomes, which were "Clients' change" and "Families' change". ADC centers provide various experiences for their clients and their caregivers, ranging from the fulfillment of needs for fundamental care to psychiatric care and self-actualization. Improving various model-related inputs/interventions can produce better experiences and outcomes. The model can guide ADC administrators, policymakers, and researchers in the evaluation of a heterogeneous ADC service program that is community-based, thereby ensuring optimal care for clients with an efficient use of resources.Urban agriculture and gardening provide many health benefits, but the soil is sometimes at risk of heavy metal and metalloid (HMM) contamination. HMM, such as lead and arsenic, can result in adverse health effects for humans. Gardeners may face exposure to these contaminants because of their regular contact with soil and consumption of produce grown in urban areas. However, there is a lack of research regarding whether differential exposure to HMM may be attributed to differential knowledge of exposure sources. In 2018, industrial **** and hazardous levels of soil contamination were detected in West Atlanta. We conducted community-engaged research through surveys and follow-up interviews to understand awareness of ****, HMM in soil, and potential remediation options. Home gardeners were more likely to recognize HMM health effects and to cite health as a significant benefit of gardening than community gardeners. In terms of knowledge, participants were concerned about the potential health effects of contaminants in soil yet unconcerned with produce in their gardens.
    Acute myocarditis is associated with cardiac arrhythmia in 25% of cases; a third of these arrhythmias are ventricular tachycardia (VT) or ventricular fibrillation (VF). The implantation of a cardiac defibrillator (ICD) following sustained ventricular arrhythmia remains controversial in these patients. We sought to assess the risk of major arrhythmic ventricular events (MAEs) over time in patients implanted with an ICD following sustained VT/VF in the acute phase of myocarditis compared to those implanted for VT/VF occurring on myocarditis sequelae. Our retrospective observational study included patients implanted with an ICD following VT/VF during acute myocarditis or VT/VF on myocarditis sequelae, from 2007 to 2017, in 15 French university hospitals. Over a median follow-up period of 3 years, MAE occurred in 11 (39%) patients of the acute myocarditis group and 24 (60%) patients of the myocarditis sequelae group. Kaplan-Meier MAE rate estimates at one and three years of follow-up were 19% and 45% in the acute group, and 43% and 64% in the sequelae group. Patients who experienced sustained ventricular arrhythmias during acute myocarditis had a very high risk of VT/VF recurrence during follow-up. These results show that the risk of MAE recurrence remains high after resolution of the acute episode.Dating of clay bricks (adobe) and plasters is a relevant topic not only for building historians in the Pannonian region. Especially in vernacular architecture in this region, clay with straw amendments is a dominant construction material. The paper presents the potential of the molecular decay of these amendments to establish prediction tools for age based on infrared spectroscopic measurements. Preliminary results revealed spectral differences between the different plant parts, especially culms, nodes, and ear spindles. Based on these results, a first prediction model is presented including 14 historic samples. https://www.selleckchem.com/products/azd7648.html The coefficient of determination for the validation reached 62.2%, the (RMSE) root mean squared error amounted to 93 years. Taking the limited sample amount and the high material heterogeneity into account, this result can be seen as a promising output. Accordingly, sample size should be increased to a minimum of 100 objects and separate models for the different plant parts should be established.Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2'O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.Adult day care (ADC) provides various services for meeting clients' needs. Based on the mini-Delphi method with 46 ADC staff and the discussions with eight ADC administrators, this study developed and finalized a comprehensive logic model to represent the elements of ADC. For the three basic structures of a logic model-inputs/activities, outputs, and outcomes-the model contained seven core categories and 23 sub-categories. The ADC inputs/activities consisted of two core categories "Place to stay" and "Intervention from staff". These inputs/activities caused two kinds of outputs "Clients' experiences" and "Families' experiences". "Accumulating experiences" with repeated ADC visits was established as the link between the ADC outputs and outcomes, which were "Clients' change" and "Families' change". ADC centers provide various experiences for their clients and their caregivers, ranging from the fulfillment of needs for fundamental care to psychiatric care and self-actualization. Improving various model-related inputs/interventions can produce better experiences and outcomes. The model can guide ADC administrators, policymakers, and researchers in the evaluation of a heterogeneous ADC service program that is community-based, thereby ensuring optimal care for clients with an efficient use of resources.Urban agriculture and gardening provide many health benefits, but the soil is sometimes at risk of heavy metal and metalloid (HMM) contamination. HMM, such as lead and arsenic, can result in adverse health effects for humans. Gardeners may face exposure to these contaminants because of their regular contact with soil and consumption of produce grown in urban areas. However, there is a lack of research regarding whether differential exposure to HMM may be attributed to differential knowledge of exposure sources. In 2018, industrial slag and hazardous levels of soil contamination were detected in West Atlanta. We conducted community-engaged research through surveys and follow-up interviews to understand awareness of slag, HMM in soil, and potential remediation options. Home gardeners were more likely to recognize HMM health effects and to cite health as a significant benefit of gardening than community gardeners. In terms of knowledge, participants were concerned about the potential health effects of contaminants in soil yet unconcerned with produce in their gardens.
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  • BACKGROUND There is a high prevalence of work-related musculoskeletal disorders among health care professionals. Posture is an essential point to be addressed for health care professionals with musculoskeletal disorders. Cervical pain can result from several conditions. Treatment should include posture modification and home exercise. OBJECTIVE This study aims to compare a new postural garment (Posture Plus Force; Medi, Bayreuth, Germany) with exercises for women with nonspecific cervical pain. The investigators focus on nurses and allied health professionals due to the importance of posture in work-related musculoskeletal disorders. METHODS This randomized crossover clinical trial has a 3-month treatment sequence and a 3-month washout period. Participants will include nurses and allied health professionals 21 to 55 years of age with cervical pain. Participants are allocated at random to two intervention groups a postural garment (Posture Plus Force) to be worn for 2 to 4 hours per day for 90 days (P+ group) ago Cansado, David Monterde, Josep Romagosa, Elvira Gea. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 16.04.2020.BACKGROUND Leveraging internet-based communication tools (eg, messaging apps, SMS text messaging, and email) may be an effective avenue for delivery of HIV prevention messages to men who have sex with men (MSM) in India, but there are limited models for such internet-based interventions. OBJECTIVE The CHALO! pilot was an online educational and behavioral intervention aimed to determine the feasibility, acceptability, and preliminary impact of a peer-delivered, internet-based messaging intervention for HIV testing and consistent condom use for MSM in India. https://www.selleckchem.com/products/s961.html The messages addressed barriers to HIV testing and condom use and were theoretically based on the information-motivation-behavioral skills model. METHODS Between February and March 2015, we recruited, enrolled, and randomized 244 participants via online advertisements on mobile dating apps and Facebook. Eligible men (18 years or older, sexually active with other men, and self-reported HIV-negative or unknown status) were randomized to receive educational an testing, intentions increased from 32% (16/50) of the sample at baseline to 56% (28/50) of the sample at follow-up (P=.02). Condom use during anal sex did not significantly change from baseline to follow-up. HIV testing and condom use did not significantly differ between approach and avoidance conditions at follow-up. CONCLUSIONS As one of the first studies of an online HIV prevention intervention for Indian MSM, CHALO! was feasible to implement by a community-based organization, was acceptable to participants, and demonstrated potential to improve HIV testing rates. ©Viraj V V Patel, Shruta Rawat, Alpana Dange, Corina Lelutiu-Weinberger, Sarit A Golub. Originally published in JMIR Public Health and Surveillance (http//publichealth.jmir.org), 16.04.2020.BACKGROUND Adults who are homeless are more likely to have alcohol use disorders (AUDs) compared with domiciled adults. Although AUD treatments are commonly available, many factors (eg, transportation limitations and inability to schedule appointments) contribute to low treatment completion rates and low success rates of these interventions among adults experiencing homelessness. Most adults who are homeless own mobile phones; however, no interventions have been developed that use mobile devices to deliver and support AUD interventions for this population. Mobile phone-based AUD interventions may reduce barriers that have limited the use and utility of traditional interventions. OBJECTIVE The aim of this study is to (1) identify variables (eg, affect, stress, geolocation, and cravings) that predict drinking among homeless adults (phase I), (2) develop a mobile intervention that utilizes an algorithm to identify moments of risk for drinking and deliver treatment messages that are tailored to the individual's cected to conclude in 2020. To date, 80 participants have consented to the study, and data analysis for phase I will begin in early 2020. CONCLUSIONS This research will highlight intervention targets and develop a novel intervention for understudied and underserved adults experiencing homelessness with AUD. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/15610. ©Michael S S Businelle, Scott T Walters, Eun-Young Mun, Thomas R Kirchner, Emily T Hébert, Xiaoyin Li. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 16.04.2020.BACKGROUND It is predicted that digital health technologies that incorporate artificial intelligence will transform health care delivery in the next decade. Little research has explored how emerging trends in artificial intelligence-driven digital health technologies may influence the relationship between nurses and patients. OBJECTIVE The purpose of this scoping review is to summarize the findings from 4 research questions regarding emerging trends in artificial intelligence-driven digital health technologies and their influence on nursing practice across the 5 domains outlined by the Canadian Nurses Association framework administration, clinical care, education, policy, and research. Specifically, this scoping review will examine how emerging trends will transform the roles and functions of nurses over the next 10 years and beyond. METHODS Using an established scoping review methodology, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, Cochrane Database of Systematic Reviportunities for action to advance the future of nursing in a technological world and, more specifically, nurses' delivery of compassionate care in the age of artificial intelligence. Results from the symposium will be summarized in the form of a briefing paper and widely disseminated to relevant stakeholders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/17490. ©Christine Buchanan, M Lyndsay Howitt, Rita Wilson, Richard G Booth, Tracie Risling, Megan Bamford. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 16.04.2020.
    BACKGROUND There is a high prevalence of work-related musculoskeletal disorders among health care professionals. Posture is an essential point to be addressed for health care professionals with musculoskeletal disorders. Cervical pain can result from several conditions. Treatment should include posture modification and home exercise. OBJECTIVE This study aims to compare a new postural garment (Posture Plus Force; Medi, Bayreuth, Germany) with exercises for women with nonspecific cervical pain. The investigators focus on nurses and allied health professionals due to the importance of posture in work-related musculoskeletal disorders. METHODS This randomized crossover clinical trial has a 3-month treatment sequence and a 3-month washout period. Participants will include nurses and allied health professionals 21 to 55 years of age with cervical pain. Participants are allocated at random to two intervention groups a postural garment (Posture Plus Force) to be worn for 2 to 4 hours per day for 90 days (P+ group) ago Cansado, David Monterde, Josep Romagosa, Elvira Gea. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 16.04.2020.BACKGROUND Leveraging internet-based communication tools (eg, messaging apps, SMS text messaging, and email) may be an effective avenue for delivery of HIV prevention messages to men who have sex with men (MSM) in India, but there are limited models for such internet-based interventions. OBJECTIVE The CHALO! pilot was an online educational and behavioral intervention aimed to determine the feasibility, acceptability, and preliminary impact of a peer-delivered, internet-based messaging intervention for HIV testing and consistent condom use for MSM in India. https://www.selleckchem.com/products/s961.html The messages addressed barriers to HIV testing and condom use and were theoretically based on the information-motivation-behavioral skills model. METHODS Between February and March 2015, we recruited, enrolled, and randomized 244 participants via online advertisements on mobile dating apps and Facebook. Eligible men (18 years or older, sexually active with other men, and self-reported HIV-negative or unknown status) were randomized to receive educational an testing, intentions increased from 32% (16/50) of the sample at baseline to 56% (28/50) of the sample at follow-up (P=.02). Condom use during anal sex did not significantly change from baseline to follow-up. HIV testing and condom use did not significantly differ between approach and avoidance conditions at follow-up. CONCLUSIONS As one of the first studies of an online HIV prevention intervention for Indian MSM, CHALO! was feasible to implement by a community-based organization, was acceptable to participants, and demonstrated potential to improve HIV testing rates. ©Viraj V V Patel, Shruta Rawat, Alpana Dange, Corina Lelutiu-Weinberger, Sarit A Golub. Originally published in JMIR Public Health and Surveillance (http//publichealth.jmir.org), 16.04.2020.BACKGROUND Adults who are homeless are more likely to have alcohol use disorders (AUDs) compared with domiciled adults. Although AUD treatments are commonly available, many factors (eg, transportation limitations and inability to schedule appointments) contribute to low treatment completion rates and low success rates of these interventions among adults experiencing homelessness. Most adults who are homeless own mobile phones; however, no interventions have been developed that use mobile devices to deliver and support AUD interventions for this population. Mobile phone-based AUD interventions may reduce barriers that have limited the use and utility of traditional interventions. OBJECTIVE The aim of this study is to (1) identify variables (eg, affect, stress, geolocation, and cravings) that predict drinking among homeless adults (phase I), (2) develop a mobile intervention that utilizes an algorithm to identify moments of risk for drinking and deliver treatment messages that are tailored to the individual's cected to conclude in 2020. To date, 80 participants have consented to the study, and data analysis for phase I will begin in early 2020. CONCLUSIONS This research will highlight intervention targets and develop a novel intervention for understudied and underserved adults experiencing homelessness with AUD. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/15610. ©Michael S S Businelle, Scott T Walters, Eun-Young Mun, Thomas R Kirchner, Emily T Hébert, Xiaoyin Li. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 16.04.2020.BACKGROUND It is predicted that digital health technologies that incorporate artificial intelligence will transform health care delivery in the next decade. Little research has explored how emerging trends in artificial intelligence-driven digital health technologies may influence the relationship between nurses and patients. OBJECTIVE The purpose of this scoping review is to summarize the findings from 4 research questions regarding emerging trends in artificial intelligence-driven digital health technologies and their influence on nursing practice across the 5 domains outlined by the Canadian Nurses Association framework administration, clinical care, education, policy, and research. Specifically, this scoping review will examine how emerging trends will transform the roles and functions of nurses over the next 10 years and beyond. METHODS Using an established scoping review methodology, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, Cochrane Database of Systematic Reviportunities for action to advance the future of nursing in a technological world and, more specifically, nurses' delivery of compassionate care in the age of artificial intelligence. Results from the symposium will be summarized in the form of a briefing paper and widely disseminated to relevant stakeholders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/17490. ©Christine Buchanan, M Lyndsay Howitt, Rita Wilson, Richard G Booth, Tracie Risling, Megan Bamford. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 16.04.2020.
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  • A novel nanomaterial of two-dimensional holey CuCo2O4 (2D HCCO) nanosheets was synthesized via a general template-directed method and employed for the first time to construct an effective electrochemical platform for H2O2 sensing with the combination of cerium oxide (CeO2). During the electrocatalytic reduction of H2O2, the synergetic catalysis of CeO2/HCCO/MWCNTs/GCE owing to the naturally holey frameworks and the mediator of CeO2 results in the ultra-sensitive detection of H2O2. The current was greatly enhanced owing to the unique holey structure that can minimize the charge transfer distance and provide more active sites to boost the signals, and the dual oxidation state of Ce3+/Ce4+ on the surface of 2D HCCO nanosheets can promote the in situ production of Cu2+/Cu+ and Cu+/Cu and further amplify the detection signal. The CeO2/HCCO/MWCNTs/GCE showed a wide linear range from 1 μM to 7.31 mM using chronoamperometry at the potential of - 0.25 V and a relatively low detection limit of 0.16 μM in physiological environment, which was also utilized for tracking the trace H2O2 released from Hela cells. This study shows great promise for the emerging application of holey HCCO-based biosensors in bioanalysis and early cancer diagnosis. Graphical abstract.Nowadays, poisoning with metal phosphides, especially aluminum phosphide (ALP), is one of the main health threats in human societies. Patients suffer from significant complications due to this type of poisoning, and the heart is one of the main organs targeted by ALP. Therefore, in this study, we discussed the effect of phosphine on cardiac function. This study is based on data obtained from PubMed, between 2002 and 2020. The key keywords included "Aluminum phosphide," "Oxidative Stress," "Mitochondria," "Cardiovascular disease," and "Treatment." The results showed that ALP produced reactive oxygen species (ROS) due to mitochondrial dysfunction. ROS production leads to red blood cell hemolysis, decreased ATP production, and induction of apoptosis in cardiomyocytes, which eventually results in cardiovascular disease. Since ALP has the most significant effect on cardiomyocytes, the use of appropriate treatment strategies to restore cell function can increase patients' survival.Real-time fluorescence detection of nucleic acid exhibit excellent performance in analytical and diagnostic applications. However, the requirement of laboratory-based instrument and complex nucleic acid extraction greatly limits their application in point-of-care testing (POCT). Herein, a novel integrated silica membrane-based platform incorporating nucleic acid purification, amplification, and detection steps was developed. A universal and portable visualization platform was fabricated by incorporating denaturation bubble-mediated strand exchange amplification (SEA) reaction with silica membrane. The fluorescence signal of SYBR Green I with amplification products was visualized by the naked eye using a simple ultraviolet light on the silica membrane, and significant discrimination between the positive and negative samples could be easily and visually obtained. Besides, chitooligosaccharide-modified silica membrane allows the purification of nucleic acid in a totally aqueous system and enables in situ SEA. With the proposed integrated platform, 102-108 cfu/mL Vibrio parahaemolyticus could be successfully detected and excellent performance was also revealed for gram-positive pathogens. The detection limit of the method for artificially spiked oysters was 103 cfu/g and reached 100 cfu/g after 12 h enrichment. This proof-of-concept method could also be applied to a variety of nucleic acid amplification methods. We believe that the proposed silica membrane-based platform has great potential for the rapid and low-cost detection of nucleic acids especially in low-resource settings. Graphical abstract.MALDI mass spectrometry imaging (MALDI-MSI) is a widely used technique to map the spatial distribution of molecules in sectioned tissue. The technique is based on the systematic generation and analysis of ions from small sample volumes, each representing a single pixel of the investigated sample surface. Subsequently, mass spectrometric images for any recorded ion species can be generated by displaying the signal intensity at the coordinate of origin for each of these pixels. Although easily equalized, these recorded signal intensities, however, are not necessarily a good measure for the underlying amount of analyte and care has to be taken in the interpretation of MALDI-MSI data. Physical and chemical properties that define the analyte molecules' adjacencies in the tissue largely influence the local extraction and ionization efficiencies, possibly leading to strong variations in signal intensity response. Here, we inspect the validity of signal intensity distributions recorded from murine cerebellum as a measure for the underlying molar distributions. Based on segmentation derived from MALDI-MSI measurements, laser microdissection (LMD) was used to cut out regions of interest with a homogenous signal intensity. The molar concentration of six exemplary selected membrane lipids from different lipid classes in these tissue regions was determined using quantitative nano-HPLC-ESI-MS. Comparison of molar concentrations and signal intensity revealed strong deviations between underlying concentration and the distribution suggested by MSI data. Determined signal intensity response factors strongly depend on tissue type and lipid species. https://www.selleckchem.com/products/ipi-549.html Graphical abstract.The potassium ion (K+) plays significant roles in many biological processes. To date, great efforts have been devoted to the development of K+ sensors for colorimetric, fluorescent, and photoacoustic detection of K+ separately. However, the development of molecular K+ probes for colorimetric detection of urinary K+, monitoring K+ fluxes in living cells by fluorescence imaging, and photoacoustic imaging of K+ dynamics in deep tissues still remains an open challenge. Herein, we report the first molecular K+ probe (NK2) for colorimetric, fluorescent, and photoacoustic detection of K+. NK2 is composed of 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) as the chromophore and phenylazacrown-6-lariat ether (ACLE) as the K+ recognition unit. Predominate features of NK2 include a short synthetic procedure, high K+ selectivity, large detection range (5-200 mM), and triple-channel detection manner. NK2 shows good response to K+ with obvious color changes, fluorescence enhancements (about threefold), and photoacoustic intensity changes.
    A novel nanomaterial of two-dimensional holey CuCo2O4 (2D HCCO) nanosheets was synthesized via a general template-directed method and employed for the first time to construct an effective electrochemical platform for H2O2 sensing with the combination of cerium oxide (CeO2). During the electrocatalytic reduction of H2O2, the synergetic catalysis of CeO2/HCCO/MWCNTs/GCE owing to the naturally holey frameworks and the mediator of CeO2 results in the ultra-sensitive detection of H2O2. The current was greatly enhanced owing to the unique holey structure that can minimize the charge transfer distance and provide more active sites to boost the signals, and the dual oxidation state of Ce3+/Ce4+ on the surface of 2D HCCO nanosheets can promote the in situ production of Cu2+/Cu+ and Cu+/Cu and further amplify the detection signal. The CeO2/HCCO/MWCNTs/GCE showed a wide linear range from 1 μM to 7.31 mM using chronoamperometry at the potential of - 0.25 V and a relatively low detection limit of 0.16 μM in physiological environment, which was also utilized for tracking the trace H2O2 released from Hela cells. This study shows great promise for the emerging application of holey HCCO-based biosensors in bioanalysis and early cancer diagnosis. Graphical abstract.Nowadays, poisoning with metal phosphides, especially aluminum phosphide (ALP), is one of the main health threats in human societies. Patients suffer from significant complications due to this type of poisoning, and the heart is one of the main organs targeted by ALP. Therefore, in this study, we discussed the effect of phosphine on cardiac function. This study is based on data obtained from PubMed, between 2002 and 2020. The key keywords included "Aluminum phosphide," "Oxidative Stress," "Mitochondria," "Cardiovascular disease," and "Treatment." The results showed that ALP produced reactive oxygen species (ROS) due to mitochondrial dysfunction. ROS production leads to red blood cell hemolysis, decreased ATP production, and induction of apoptosis in cardiomyocytes, which eventually results in cardiovascular disease. Since ALP has the most significant effect on cardiomyocytes, the use of appropriate treatment strategies to restore cell function can increase patients' survival.Real-time fluorescence detection of nucleic acid exhibit excellent performance in analytical and diagnostic applications. However, the requirement of laboratory-based instrument and complex nucleic acid extraction greatly limits their application in point-of-care testing (POCT). Herein, a novel integrated silica membrane-based platform incorporating nucleic acid purification, amplification, and detection steps was developed. A universal and portable visualization platform was fabricated by incorporating denaturation bubble-mediated strand exchange amplification (SEA) reaction with silica membrane. The fluorescence signal of SYBR Green I with amplification products was visualized by the naked eye using a simple ultraviolet light on the silica membrane, and significant discrimination between the positive and negative samples could be easily and visually obtained. Besides, chitooligosaccharide-modified silica membrane allows the purification of nucleic acid in a totally aqueous system and enables in situ SEA. With the proposed integrated platform, 102-108 cfu/mL Vibrio parahaemolyticus could be successfully detected and excellent performance was also revealed for gram-positive pathogens. The detection limit of the method for artificially spiked oysters was 103 cfu/g and reached 100 cfu/g after 12 h enrichment. This proof-of-concept method could also be applied to a variety of nucleic acid amplification methods. We believe that the proposed silica membrane-based platform has great potential for the rapid and low-cost detection of nucleic acids especially in low-resource settings. Graphical abstract.MALDI mass spectrometry imaging (MALDI-MSI) is a widely used technique to map the spatial distribution of molecules in sectioned tissue. The technique is based on the systematic generation and analysis of ions from small sample volumes, each representing a single pixel of the investigated sample surface. Subsequently, mass spectrometric images for any recorded ion species can be generated by displaying the signal intensity at the coordinate of origin for each of these pixels. Although easily equalized, these recorded signal intensities, however, are not necessarily a good measure for the underlying amount of analyte and care has to be taken in the interpretation of MALDI-MSI data. Physical and chemical properties that define the analyte molecules' adjacencies in the tissue largely influence the local extraction and ionization efficiencies, possibly leading to strong variations in signal intensity response. Here, we inspect the validity of signal intensity distributions recorded from murine cerebellum as a measure for the underlying molar distributions. Based on segmentation derived from MALDI-MSI measurements, laser microdissection (LMD) was used to cut out regions of interest with a homogenous signal intensity. The molar concentration of six exemplary selected membrane lipids from different lipid classes in these tissue regions was determined using quantitative nano-HPLC-ESI-MS. Comparison of molar concentrations and signal intensity revealed strong deviations between underlying concentration and the distribution suggested by MSI data. Determined signal intensity response factors strongly depend on tissue type and lipid species. https://www.selleckchem.com/products/ipi-549.html Graphical abstract.The potassium ion (K+) plays significant roles in many biological processes. To date, great efforts have been devoted to the development of K+ sensors for colorimetric, fluorescent, and photoacoustic detection of K+ separately. However, the development of molecular K+ probes for colorimetric detection of urinary K+, monitoring K+ fluxes in living cells by fluorescence imaging, and photoacoustic imaging of K+ dynamics in deep tissues still remains an open challenge. Herein, we report the first molecular K+ probe (NK2) for colorimetric, fluorescent, and photoacoustic detection of K+. NK2 is composed of 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) as the chromophore and phenylazacrown-6-lariat ether (ACLE) as the K+ recognition unit. Predominate features of NK2 include a short synthetic procedure, high K+ selectivity, large detection range (5-200 mM), and triple-channel detection manner. NK2 shows good response to K+ with obvious color changes, fluorescence enhancements (about threefold), and photoacoustic intensity changes.
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  • We apply density functional theory to estimate the energetics and charge carrier concentrations and, in turn, the resistance across the (210)[001] and (111)[11[combining macron]0] grain boundaries (GBs) in proton conducting Y-doped BaZrO3, assessing four commonly used approximations in space charge modelling. The abrupt core approximation, which models the GB core as a single atomic plane rather than a set of multiple atomic planes, gives an underestimation of the GB resistance with around one order of magnitude for both GBs. The full depletion approximation, which assumes full depletion of effectively positive charge carriers in the space charge layers, has negligible effect on the GB resistance compared to a more accurate model with decaying depletion. Letting protons redistribute in the continuity between atomic planes gives a GB resistance up to 5 times higher than the case where protons are restricted to be located at atomic planes. Finally, neglecting trapping effects between the acceptor doping and the defect charge carriers gives a higher GB resistance with a factor of roughly 2.Recently, the existence of room-temperature ferroelectricity has been experimentally confirmed in a number of two-dimensional (2D) materials. With a switching barrier large enough to be stable against thermal fluctuation, ferroelectricity in even lower dimensions like 1D or 0D may be explored for data storage of higher density, which has been scarcely reported. Here, we show the first-principles design of 0D ferroelectrics/multiferroics based on polar functionalized fullerene. It turns out that the ferroelectric polarization of endohedral metallofullerenes can be reversed with the diffusion of metal ions inside when the fullerene is fixed on a substrate. If its bonding with the substrate is relatively weak, the rotation of fullerene will be more favorable in energy for ferroelectric switching. The switching barriers of both modes, for the candidates with considerable magnetic moments and dipole moments, are all in the ideal range for working under ambient conditions. Moreover, compared with conventional ferroelectrics for data storage, they may be endowed with a high areal density (∼105 Gbit per in2) and high writing speed (∼102 GHz) that are respectively more than 2 and 3 orders of magnitude higher.High-performance Pd-based nanocatalysts for alkaline methanol and formate fuel cells have stimulated widespread attention. Hence, a series of ternary Pd-Au-Ag nanoalloys have been synthesized on carbon nanotubes, which demonstrate promising activity and unexpectedly high stability for the formate oxidation reaction (FOR) in alkaline medium. The ternary Pd3Au3Ag1 nanoalloy catalyst showed an initial mass activity of 4.51 A mgPd-1 and a retained mass activity of 1.32 A mgPd-1 after chronoamperometric measurement for 3600 s, which are superior to the best values for all FOR catalysts reported so far. https://www.selleckchem.com/products/l-nmma-acetate.html The Pd3Au3Ag1 catalyst also showed a good specific activity of 4.32 mA cm-2 for the methanol oxidation reaction. Furthermore, surface reconstruction of the Pd3Au3Ag1 nanoalloy was observed during FOR, where the activity of Pd3Au3Ag1 catalysts increased up to 33% and the cycling durability retained 55% after cyclic voltammetry with the upper potential of 1.7 V. The FOR enhancement is attributed to the formation of mixed oxidation-state Ag sites and the increase in the Pd surface coverage, and provides a new prospect for the design of ternary nanoalloy electrocatalysts for various fuel oxidation reactions.This paper describes chemistry using organocatalysts in hydrocarbon solvents that minimizes solvent waste by using inexpensive, non-volatile, relatively inflammable, and easily recyclable poly(α-olefin)s (PAOs) as hydrocarbon solvents. These studies show that when substrates have limited solubility in PAO solvents, this issue can be addressed by adding a small amount of a cosolvent. Kinetic studies were also carried out and show that reactions carried out in PAOs are kinetically comparable to reactions in conventional non-recyclable hydrocarbon solvents. A range of strategies that separate and isolate products from reactions in PAOs using a polyisobutylene (PIB)-supported DMAP catalyst have been studied using four different catalytic reactions. In the most general procedure, the PAO phase containing a PIB-bound catalyst is separated from products by low energy liquid/liquid gravity separation. This can be accomplished using a minimal amount of a polar solvent. In another example, the product's low solubility leads to it precipitating during the reaction. In this case, a simple filtration recycles the PAO and a PIB-bound DMAP catalyst. We have demonstrated that the PAO phase containing a PIB bound DMAP catalyst can be recycled for at least 10 cycles without loss of activity. Our studies further showed that leaching of the PAO phase into polar solvents was orders of magnitude less than conventional hydrocarbon solvents such as heptane. The result is that the overall solvent waste generation is lower than for the same reaction carried out in conventional solvents.B cell malignancies, such as B cell leukemia and lymphoma, have CD22 overexpression with ∼7% of patients. A short CD22 binding peptide (PV3) with a moderate affinity (Kd ∼ 9 μM) was identified by screening multiple peptide candidates determined through analysis of CD22-epratuzumab complex crystal structure. PV3 binding specificity was confirmed via competitive binding inhibition, then was used as the targeting moiety on CD22-targeted liposomal nanoparticle (TNPPV3) formulations. To maximize the potential therapeutic outcome of TNPPV3 formulation, nanoparticle design parameters, such as peptide hydrophilicity, ethylene glycol linker length, valency, and particle size were optimized for maximum selective cellular uptake by CD22+ malignant cancer cells. The effects of altering design parameters one at a time on TNP uptake were evaluated using flow cytometry, and the optimal parameters for TNPPV3 were determined to be 8% peptide density, EG18 linker, and 3 lysines of 100 nm nanoparticles. This optimally designed TNPPV3 achieved ∼4 and 40-fold enhancement of cellular uptake by CD22+ Raji cells over CD22- Jurkat and MOLT-4 cells, respectively, demonstrating selectivity for malignant cells with CD22 overexpression.
    We apply density functional theory to estimate the energetics and charge carrier concentrations and, in turn, the resistance across the (210)[001] and (111)[11[combining macron]0] grain boundaries (GBs) in proton conducting Y-doped BaZrO3, assessing four commonly used approximations in space charge modelling. The abrupt core approximation, which models the GB core as a single atomic plane rather than a set of multiple atomic planes, gives an underestimation of the GB resistance with around one order of magnitude for both GBs. The full depletion approximation, which assumes full depletion of effectively positive charge carriers in the space charge layers, has negligible effect on the GB resistance compared to a more accurate model with decaying depletion. Letting protons redistribute in the continuity between atomic planes gives a GB resistance up to 5 times higher than the case where protons are restricted to be located at atomic planes. Finally, neglecting trapping effects between the acceptor doping and the defect charge carriers gives a higher GB resistance with a factor of roughly 2.Recently, the existence of room-temperature ferroelectricity has been experimentally confirmed in a number of two-dimensional (2D) materials. With a switching barrier large enough to be stable against thermal fluctuation, ferroelectricity in even lower dimensions like 1D or 0D may be explored for data storage of higher density, which has been scarcely reported. Here, we show the first-principles design of 0D ferroelectrics/multiferroics based on polar functionalized fullerene. It turns out that the ferroelectric polarization of endohedral metallofullerenes can be reversed with the diffusion of metal ions inside when the fullerene is fixed on a substrate. If its bonding with the substrate is relatively weak, the rotation of fullerene will be more favorable in energy for ferroelectric switching. The switching barriers of both modes, for the candidates with considerable magnetic moments and dipole moments, are all in the ideal range for working under ambient conditions. Moreover, compared with conventional ferroelectrics for data storage, they may be endowed with a high areal density (∼105 Gbit per in2) and high writing speed (∼102 GHz) that are respectively more than 2 and 3 orders of magnitude higher.High-performance Pd-based nanocatalysts for alkaline methanol and formate fuel cells have stimulated widespread attention. Hence, a series of ternary Pd-Au-Ag nanoalloys have been synthesized on carbon nanotubes, which demonstrate promising activity and unexpectedly high stability for the formate oxidation reaction (FOR) in alkaline medium. The ternary Pd3Au3Ag1 nanoalloy catalyst showed an initial mass activity of 4.51 A mgPd-1 and a retained mass activity of 1.32 A mgPd-1 after chronoamperometric measurement for 3600 s, which are superior to the best values for all FOR catalysts reported so far. https://www.selleckchem.com/products/l-nmma-acetate.html The Pd3Au3Ag1 catalyst also showed a good specific activity of 4.32 mA cm-2 for the methanol oxidation reaction. Furthermore, surface reconstruction of the Pd3Au3Ag1 nanoalloy was observed during FOR, where the activity of Pd3Au3Ag1 catalysts increased up to 33% and the cycling durability retained 55% after cyclic voltammetry with the upper potential of 1.7 V. The FOR enhancement is attributed to the formation of mixed oxidation-state Ag sites and the increase in the Pd surface coverage, and provides a new prospect for the design of ternary nanoalloy electrocatalysts for various fuel oxidation reactions.This paper describes chemistry using organocatalysts in hydrocarbon solvents that minimizes solvent waste by using inexpensive, non-volatile, relatively inflammable, and easily recyclable poly(α-olefin)s (PAOs) as hydrocarbon solvents. These studies show that when substrates have limited solubility in PAO solvents, this issue can be addressed by adding a small amount of a cosolvent. Kinetic studies were also carried out and show that reactions carried out in PAOs are kinetically comparable to reactions in conventional non-recyclable hydrocarbon solvents. A range of strategies that separate and isolate products from reactions in PAOs using a polyisobutylene (PIB)-supported DMAP catalyst have been studied using four different catalytic reactions. In the most general procedure, the PAO phase containing a PIB-bound catalyst is separated from products by low energy liquid/liquid gravity separation. This can be accomplished using a minimal amount of a polar solvent. In another example, the product's low solubility leads to it precipitating during the reaction. In this case, a simple filtration recycles the PAO and a PIB-bound DMAP catalyst. We have demonstrated that the PAO phase containing a PIB bound DMAP catalyst can be recycled for at least 10 cycles without loss of activity. Our studies further showed that leaching of the PAO phase into polar solvents was orders of magnitude less than conventional hydrocarbon solvents such as heptane. The result is that the overall solvent waste generation is lower than for the same reaction carried out in conventional solvents.B cell malignancies, such as B cell leukemia and lymphoma, have CD22 overexpression with ∼7% of patients. A short CD22 binding peptide (PV3) with a moderate affinity (Kd ∼ 9 μM) was identified by screening multiple peptide candidates determined through analysis of CD22-epratuzumab complex crystal structure. PV3 binding specificity was confirmed via competitive binding inhibition, then was used as the targeting moiety on CD22-targeted liposomal nanoparticle (TNPPV3) formulations. To maximize the potential therapeutic outcome of TNPPV3 formulation, nanoparticle design parameters, such as peptide hydrophilicity, ethylene glycol linker length, valency, and particle size were optimized for maximum selective cellular uptake by CD22+ malignant cancer cells. The effects of altering design parameters one at a time on TNP uptake were evaluated using flow cytometry, and the optimal parameters for TNPPV3 were determined to be 8% peptide density, EG18 linker, and 3 lysines of 100 nm nanoparticles. This optimally designed TNPPV3 achieved ∼4 and 40-fold enhancement of cellular uptake by CD22+ Raji cells over CD22- Jurkat and MOLT-4 cells, respectively, demonstrating selectivity for malignant cells with CD22 overexpression.
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  • A chitinolytic bacterium Chitinophaga sp. S167 producing extracellular chitinases was isolated from a soil sample in India. The extracellular chitinases produced by S167 were concentrated by ammonium sulphate precipitation (AS70) and seven bands corresponding to chitinases were observed by zymography. Optimum temperature and pH of AS70 were between 40 and 45 °C and pH 6.0 respectively with high stability at 20-40 °C and pH 5-7. AS70 inhibited the growth of Fusarium oxysporum, Alternaria alternata and Cladosporium sp. in vitro. The culture conditions for the high level production of extracellular chitinases were optimized resulting in 48-folds higher chitinase production. As the combination of chitinases could be more potent in biocontrol of plant diseases, it was checked if AS70 could control postharvest fungal infection caused by Fusarium oxysporum on tomatoes. AS70 treated tomatoes showed significant lower incidence of infection (11%) by F. oxysporum as compared with 100% in the control at 5 days post inoculation. Further, AS70 caused significant mortality in second stage juveniles of root knot nematode, Meloidogyne incognita, a major agriculture pest responsible for economic losses in agriculture. This study highlights the antifungal and nematicidal activity of chitinases produced by Chitinophaga sp. S167. To the best of our knowledge, this is the first report of the biocontrol potential of the chitinases produced by Chitinophaga sp.Large deletions in the β-globin gene cluster lead to increased HbF levels by delaying the γ- to β-globin switch process. However, these deletions when inherited as a homozygous condition or when co-inherited with β-thalassemia result in variable clinical phenotypes. Individuals or families with a clinically presenting child, where the parents had HbF levels ≥ 10%, were further screened for the presence of large β-globin cluster deletions. Six deletions in the β-globin gene cluster were screened by GAP-PCR, and the uncharacterized deletions were further analyzed by gene dosage or by multiplex ligation-dependent probe amplification (MLPA). Among 192 individuals suspected for the inheritance of large deletions, 138 were heterozygous for large deletions, 45 were compound heterozygous of a large β-globin cluster deletion and β-thalassemia, and 9 were found to be homozygous for deletions. Among the heterozygotes, the Asian Indian inversion-deletion was found to be the most common deletion (39.9%), followed by the HPFH-3 deletion (30.0%). Other deletions 49.3 kb, δβ-thalassemia (21.2%), and 32.6 kb deletion (4.4%) were also found to be prevalent in our population. Patients compound heterozygous or homozygous for HPFH-3 and 32.6 kb deletions showed a milder clinical presentation, as compared with the patients compound heterozygous or homozygous for the Asian Indian inversion-deletion and 49.3 kb δβ-thalassemia. This comprehensive study highlights the mutation spectrum of large β-globin cluster deletions and the clinical heterogeneity in the patients homozygous or compound heterozygous with β-thalassemia, thus asserting the need for molecular characterization of these deletions.Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P less then 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD. In an effort to further delineate the effects of the KLF11-MAOA pathway in anxiety and affective disorders, KLF11 promoter methylation was analyzed via pyrosequencing of sodium bisulfite-treated DNA isolated from human peripheral blood in two independent samples of PD patients with or without comorbid MDD in a case-control design (sample 1 N = 120) as well as MDD patients with and without anxious depression (sample 2 N = 170). Additionally, in sample 1, KLF11 methylation was correlated with **** Depression Inventory (BDI-II) scores. No overall association of KLF11 promoter methylation with PD was detected. However, PD patients with comorbid MDD showed significant hypomethylation relative to both healthy controls (p = 0.010) and PD patients without comorbid MDD (p = 0.008). https://www.selleckchem.com/products/memantine-hydrochloride-namenda.html Furthermore, KLF11 methylation was negatively correlated with BDI-II scores in PD patients (p = 0.013). MDD patients without anxious features showed nominally decreased KLF11 methylation in comparison to MDD patients with anxious depression (p = 0.052). The present results suggest KLF11 promoter hypomethylation as a potential epigenetic marker of MDD comorbidity in PD or of non-anxious depression, respectively, possibly constituting a differential pathomechanism in anxiety and mood disorders.
    A chitinolytic bacterium Chitinophaga sp. S167 producing extracellular chitinases was isolated from a soil sample in India. The extracellular chitinases produced by S167 were concentrated by ammonium sulphate precipitation (AS70) and seven bands corresponding to chitinases were observed by zymography. Optimum temperature and pH of AS70 were between 40 and 45 °C and pH 6.0 respectively with high stability at 20-40 °C and pH 5-7. AS70 inhibited the growth of Fusarium oxysporum, Alternaria alternata and Cladosporium sp. in vitro. The culture conditions for the high level production of extracellular chitinases were optimized resulting in 48-folds higher chitinase production. As the combination of chitinases could be more potent in biocontrol of plant diseases, it was checked if AS70 could control postharvest fungal infection caused by Fusarium oxysporum on tomatoes. AS70 treated tomatoes showed significant lower incidence of infection (11%) by F. oxysporum as compared with 100% in the control at 5 days post inoculation. Further, AS70 caused significant mortality in second stage juveniles of root knot nematode, Meloidogyne incognita, a major agriculture pest responsible for economic losses in agriculture. This study highlights the antifungal and nematicidal activity of chitinases produced by Chitinophaga sp. S167. To the best of our knowledge, this is the first report of the biocontrol potential of the chitinases produced by Chitinophaga sp.Large deletions in the β-globin gene cluster lead to increased HbF levels by delaying the γ- to β-globin switch process. However, these deletions when inherited as a homozygous condition or when co-inherited with β-thalassemia result in variable clinical phenotypes. Individuals or families with a clinically presenting child, where the parents had HbF levels ≥ 10%, were further screened for the presence of large β-globin cluster deletions. Six deletions in the β-globin gene cluster were screened by GAP-PCR, and the uncharacterized deletions were further analyzed by gene dosage or by multiplex ligation-dependent probe amplification (MLPA). Among 192 individuals suspected for the inheritance of large deletions, 138 were heterozygous for large deletions, 45 were compound heterozygous of a large β-globin cluster deletion and β-thalassemia, and 9 were found to be homozygous for deletions. Among the heterozygotes, the Asian Indian inversion-deletion was found to be the most common deletion (39.9%), followed by the HPFH-3 deletion (30.0%). Other deletions 49.3 kb, δβ-thalassemia (21.2%), and 32.6 kb deletion (4.4%) were also found to be prevalent in our population. Patients compound heterozygous or homozygous for HPFH-3 and 32.6 kb deletions showed a milder clinical presentation, as compared with the patients compound heterozygous or homozygous for the Asian Indian inversion-deletion and 49.3 kb δβ-thalassemia. This comprehensive study highlights the mutation spectrum of large β-globin cluster deletions and the clinical heterogeneity in the patients homozygous or compound heterozygous with β-thalassemia, thus asserting the need for molecular characterization of these deletions.Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P less then 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD. In an effort to further delineate the effects of the KLF11-MAOA pathway in anxiety and affective disorders, KLF11 promoter methylation was analyzed via pyrosequencing of sodium bisulfite-treated DNA isolated from human peripheral blood in two independent samples of PD patients with or without comorbid MDD in a case-control design (sample 1 N = 120) as well as MDD patients with and without anxious depression (sample 2 N = 170). Additionally, in sample 1, KLF11 methylation was correlated with Beck Depression Inventory (BDI-II) scores. No overall association of KLF11 promoter methylation with PD was detected. However, PD patients with comorbid MDD showed significant hypomethylation relative to both healthy controls (p = 0.010) and PD patients without comorbid MDD (p = 0.008). https://www.selleckchem.com/products/memantine-hydrochloride-namenda.html Furthermore, KLF11 methylation was negatively correlated with BDI-II scores in PD patients (p = 0.013). MDD patients without anxious features showed nominally decreased KLF11 methylation in comparison to MDD patients with anxious depression (p = 0.052). The present results suggest KLF11 promoter hypomethylation as a potential epigenetic marker of MDD comorbidity in PD or of non-anxious depression, respectively, possibly constituting a differential pathomechanism in anxiety and mood disorders.
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  • The antioxidant activity of PP60 was kept in glutaraldehyde-crosslinked chitosan microspheres before and after their coating, showing an IC50 of 212.3 µg/mL and 154.4 µg/mL, respectively. The potential of chitosan microspheres for the delivery of catechins was illustrated, with limited risk of cytotoxicity as shown in Caco-2 cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The beneficial effects of green tea and its derivatives in the management of metabolic disorders can be exploited using mucoadhesive chitosan microspheres coated with enteric polymers for colonic delivery.Comparative chromosome-painting analysis among highly rearranged karyotypes of Sigmodontinae rodents (Rodentia, Cricetidae) detects conserved syntenic blocks, which are proposed as chromosomal signatures and can be used as phylogenetic markers. In the Akodontini tribe, the molecular topology (Cytb and/or IRBP) shows five low-supported clades (divisions "Akodon", "Bibimys", "Blarinomys", "Oxymycterus", and "Scapteromys") within two high-supported major clades (clade A "Akodon", "Bibimys", and "Oxymycterus"; clade B "Blarinomys" and "Scapteromys"). Here, we examine the chromosomal signatures of the Akodontini tribe by using Hylaeamys megacephalus (HME) probes to study the karyotypes of Oxymycterus amazonicus (2n = 54, FN = 64) and Blarinomys breviceps (2n = 28, FN = 50), and compare these data with those from other taxa investigated using the same set of probes. We strategically employ the chromosomal signatures to elucidate phylogenetic relationships among the Akodontini. When we follow the evolution of chromosomal signature states, we find that the cytogenetic data corroborate the current molecular relationships in clade A nodes. We discuss the distinct events that caused karyotypic variability in the Oxymycterus and Blarinomys genera. In addition, we propose that Blarinomys may constitute a species complex, and that the taxonomy should be revised to better delimit the geographical boundaries and their taxonomic status.Polypharmacy increases the risk of hospitalization but may be reduced by medication review. The study objective is to describe and evaluate a method for conducting medication review in general practice by an interdisciplinary medication team of pharmacists and physicians-in this case conducted by a team from the Department of Clinical Pharmacology-based on information concerning medication, diagnosis, relevant laboratory data and medical history supplied by the general practitioner. We discussed the medication review with the patients' general practitioners and received feedback from them regarding acceptance rates of the recommended changes. Ninety-four patients with a total of 1471 prescriptions were included. A medication change was recommended for nearly half of the prescriptions (48%); at least one change of medication was recommended for all patients. The acceptance rate for recommended medication changes was 55%, corresponding to a mean of 4.2 accepted recommendations per patient. For 18% of all 1471 prescriptions, the general practitioner agreed either to discontinue (stop the medication completely) or reduce the dose of the medication. This method is thorough, but since it requires several healthcare professionals, it is rather time-consuming. There is a need to support medication review in general practice, but although this method may be too time consuming in most cases, it may nevertheless prove to be a useful tool managing the most complicated patients.Background and objectives Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, leading to demyelination of neurons and potentially debilitating physical and mental symptoms. The disease is more prevalent in women than in men. The major histocompatibility complex (MHC) region has been identified as a major genetic determinant for autoimmune diseases, and its role in some neurological disorders including MS was evaluated. An intergenic single-nucleotide polymorphism (SNP), rs9275596, located between the HLA-DQB1 and HLA-DQA2 genes, is in significant association with various autoimmune diseases according to genome-wide association studies (GWASs). A cumulative effect of this SNP with other polymorphisms from this region was revealed. The aim of the study was to verify the data on rs9275596 association in multiple sclerosis in a case/control study of the Latvian population and to evaluate eventual functional significance of allele substitutions. Materials and Methods rs9275596 ns Our results suggest susceptibility of rs9275596 to multiple sclerosis in Latvians.Daylily rust-caused by Puccinia hemerocallidis-was confined to Eastern Asia until the disease was reported in Oceania, Africa, the Americas and Portugal in the 21st century. Although information on rust resistance of American cultivars is available, little is known about the resistance of European bred cultivars, threating the ornamental sector if the fungus spreads to other European countries. Aiming to provide tools to address this, we analyzed the Portuguese pathogens and characterized rust resistance in a selection of cultivars, while optimizing disease rating scales. Morphologic, genetic and cytogenomic characterization of four isolates reveals narrow diversity and raises the question whether the pathogen may have originated in North- or Central America. Daily records of multiple symptomatologic parameters enabled a detailed disease progress analysis, discriminating cultivars according to their resistance levels and revealing susceptibility as the most common state. Among the tested cultivars, 12 out of 17 began to show symptoms between 6-8 dai and were classified as susceptible. https://www.selleckchem.com/products/l-nmma-acetate.html Cultivars 'Stella d'Oro', 'Bitsy' and 'Cherry Tiger' behaved as moderately resistant although the occurrence of late sporulation on leaves suggests incomplete resistance and challenges common rating scales. The identification of resistance sources in European breeding lines is crucial for the sustainable future of daylilies.Flammability and combustion of softwood treated with intumescent coatings were studied in the present work. The formulations applied onto wood surfaces contained different ratios of industrial fillers, titanium dioxide TiO2 and aluminium trihydroxide Al(OH)3, and/or bio-fillers, eggshell and rice husk ash. Combustion behaviours of unprotected and protected wood samples have been examined with the aid of cone calorimetry performed under the varied levels of thermal flux ranging from 30 to 50 kW/m². The char residues obtained after the completion of cone calorimetry test at 40 kW/m² were analysed by the Raman spectroscopy. The fire protective properties of the studied coatings were strongly influenced by the nature of the fillers as well as by the intensity of thermal irradiance. The incorporation of bio-based fillers into the water-based intumescent formulations significantly improved fire resistance of wood substrates. For example, at 30 kW/m², the Effective Heat of Combustion was reduced by more than 40%, whilst the average Peak to Heat Release Rate had dropped from 193.
    The antioxidant activity of PP60 was kept in glutaraldehyde-crosslinked chitosan microspheres before and after their coating, showing an IC50 of 212.3 µg/mL and 154.4 µg/mL, respectively. The potential of chitosan microspheres for the delivery of catechins was illustrated, with limited risk of cytotoxicity as shown in Caco-2 cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The beneficial effects of green tea and its derivatives in the management of metabolic disorders can be exploited using mucoadhesive chitosan microspheres coated with enteric polymers for colonic delivery.Comparative chromosome-painting analysis among highly rearranged karyotypes of Sigmodontinae rodents (Rodentia, Cricetidae) detects conserved syntenic blocks, which are proposed as chromosomal signatures and can be used as phylogenetic markers. In the Akodontini tribe, the molecular topology (Cytb and/or IRBP) shows five low-supported clades (divisions "Akodon", "Bibimys", "Blarinomys", "Oxymycterus", and "Scapteromys") within two high-supported major clades (clade A "Akodon", "Bibimys", and "Oxymycterus"; clade B "Blarinomys" and "Scapteromys"). Here, we examine the chromosomal signatures of the Akodontini tribe by using Hylaeamys megacephalus (HME) probes to study the karyotypes of Oxymycterus amazonicus (2n = 54, FN = 64) and Blarinomys breviceps (2n = 28, FN = 50), and compare these data with those from other taxa investigated using the same set of probes. We strategically employ the chromosomal signatures to elucidate phylogenetic relationships among the Akodontini. When we follow the evolution of chromosomal signature states, we find that the cytogenetic data corroborate the current molecular relationships in clade A nodes. We discuss the distinct events that caused karyotypic variability in the Oxymycterus and Blarinomys genera. In addition, we propose that Blarinomys may constitute a species complex, and that the taxonomy should be revised to better delimit the geographical boundaries and their taxonomic status.Polypharmacy increases the risk of hospitalization but may be reduced by medication review. The study objective is to describe and evaluate a method for conducting medication review in general practice by an interdisciplinary medication team of pharmacists and physicians-in this case conducted by a team from the Department of Clinical Pharmacology-based on information concerning medication, diagnosis, relevant laboratory data and medical history supplied by the general practitioner. We discussed the medication review with the patients' general practitioners and received feedback from them regarding acceptance rates of the recommended changes. Ninety-four patients with a total of 1471 prescriptions were included. A medication change was recommended for nearly half of the prescriptions (48%); at least one change of medication was recommended for all patients. The acceptance rate for recommended medication changes was 55%, corresponding to a mean of 4.2 accepted recommendations per patient. For 18% of all 1471 prescriptions, the general practitioner agreed either to discontinue (stop the medication completely) or reduce the dose of the medication. This method is thorough, but since it requires several healthcare professionals, it is rather time-consuming. There is a need to support medication review in general practice, but although this method may be too time consuming in most cases, it may nevertheless prove to be a useful tool managing the most complicated patients.Background and objectives Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, leading to demyelination of neurons and potentially debilitating physical and mental symptoms. The disease is more prevalent in women than in men. The major histocompatibility complex (MHC) region has been identified as a major genetic determinant for autoimmune diseases, and its role in some neurological disorders including MS was evaluated. An intergenic single-nucleotide polymorphism (SNP), rs9275596, located between the HLA-DQB1 and HLA-DQA2 genes, is in significant association with various autoimmune diseases according to genome-wide association studies (GWASs). A cumulative effect of this SNP with other polymorphisms from this region was revealed. The aim of the study was to verify the data on rs9275596 association in multiple sclerosis in a case/control study of the Latvian population and to evaluate eventual functional significance of allele substitutions. Materials and Methods rs9275596 ns Our results suggest susceptibility of rs9275596 to multiple sclerosis in Latvians.Daylily rust-caused by Puccinia hemerocallidis-was confined to Eastern Asia until the disease was reported in Oceania, Africa, the Americas and Portugal in the 21st century. Although information on rust resistance of American cultivars is available, little is known about the resistance of European bred cultivars, threating the ornamental sector if the fungus spreads to other European countries. Aiming to provide tools to address this, we analyzed the Portuguese pathogens and characterized rust resistance in a selection of cultivars, while optimizing disease rating scales. Morphologic, genetic and cytogenomic characterization of four isolates reveals narrow diversity and raises the question whether the pathogen may have originated in North- or Central America. Daily records of multiple symptomatologic parameters enabled a detailed disease progress analysis, discriminating cultivars according to their resistance levels and revealing susceptibility as the most common state. Among the tested cultivars, 12 out of 17 began to show symptoms between 6-8 dai and were classified as susceptible. https://www.selleckchem.com/products/l-nmma-acetate.html Cultivars 'Stella d'Oro', 'Bitsy' and 'Cherry Tiger' behaved as moderately resistant although the occurrence of late sporulation on leaves suggests incomplete resistance and challenges common rating scales. The identification of resistance sources in European breeding lines is crucial for the sustainable future of daylilies.Flammability and combustion of softwood treated with intumescent coatings were studied in the present work. The formulations applied onto wood surfaces contained different ratios of industrial fillers, titanium dioxide TiO2 and aluminium trihydroxide Al(OH)3, and/or bio-fillers, eggshell and rice husk ash. Combustion behaviours of unprotected and protected wood samples have been examined with the aid of cone calorimetry performed under the varied levels of thermal flux ranging from 30 to 50 kW/m². The char residues obtained after the completion of cone calorimetry test at 40 kW/m² were analysed by the Raman spectroscopy. The fire protective properties of the studied coatings were strongly influenced by the nature of the fillers as well as by the intensity of thermal irradiance. The incorporation of bio-based fillers into the water-based intumescent formulations significantly improved fire resistance of wood substrates. For example, at 30 kW/m², the Effective Heat of Combustion was reduced by more than 40%, whilst the average Peak to Heat Release Rate had dropped from 193.
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  • Conclusions It is proved that a nanosecond pulse laser could be used for LSCI.The role of physician assistant/associate (PA) has expanded from its inception in the United States over 50 years ago, to European countries including Ireland. While there is an increasing body of evidence exploring the role and training of PAs in clinical settings, there is a scarcity of research exploring PA students' perspectives in relation to their experience of anatomy dissection, or how these experiences may contribute to the development of their core professional identity. Students in the first two cohorts of PA Program at the Royal College of Surgeons in Ireland program were invited to interviews which solicited them to reflect and report on their own experiences of anatomical dissection during their course. Participants' responses were analyzed using a thematic inductive approach; common themes and patterns were organized into a hierarchical structure, which generated the final framework of themes. https://www.selleckchem.com/products/s961.html Ten participants took part in the study; only one had previous personal experience of dissection, while two further participants had some familiarity with prosected specimens. The first theme concerned the participants' expectation of anatomical dissection, with sub-themes of preconceptions, smell, and emotions. The second theme involves discussion of coping strategies that the participants used, including talking, viewing the cadaver as their first patient, and naming (or not naming) the cadaver. The third theme includes how the participants' talked about respect and compassion in the dissection room, development of team working skills, and awareness of bereavement and organ donation. A number of recommendations were also made for the experience and orientation of future students in such a program.Objective The objective of this meta-analysis of observational studies was to evaluate the association between simple renal cysts (SRC) and presence of aortic pathology such as aortic aneurysms and dissection. Methods We conducted searches in Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1960 to August 2019 to identify observational studies that examined the association between SRCs and any aortic diseases, including aortic aneurysms and dissection. Two reviewers independently extracted the data and assessed the risk of bias. The meta-analysis was performed by STATA 14.1. Results In total, 11 observational studies with 19 719 participants were included in this meta-analysis. Compared to individuals without SRCs, patients with SRCs had higher odds of abdominal aortic aneurysm (AAA) (adjusted OR = 2.61, 95% CI 2.34-2.91, P less then 0.001, I2 = 0%), ascending thoracic aortic aneurysm (TAA) (adjusted OR = 1.98, 95% CI 1.09-3.63, P = 0.03, I2 = 90.1%), descending TAA (adjusted OR = 3.44, 95% CI, 2.67-4.43, P less then 0.001, I2 = 0%), type A aortic dissection (AD) (adjusted OR = 1.98, 95% CI 1.32-2.96, P = 0.001, I2 = 12.9%), and type B AD (adjusted OR = 2.55, 95% CI, 1.31-4.96, P = 0.006, I2 = 76.2%). There was a higher average in the sum of diameter of SRCs among AAA compared to patients without AAA (WMD = 19.80 mm, 95% CI 13.92-25.67, P less then 0.001, I2 = 63.8%). Conclusion SRC is associated with higher odds of aortic diseases including AAA, ascending and descending TAA, type A and type B dissection even after adjusting for confounders.Planar perovskite solar cells (PSCs), incorporating n-type SnO- 2 , have attracted significant interest because of their excellent photovoltaic performance. However, the film fabrication of SnO 2 is limited by self-aggregation and inhomogeneous growth of the intermediate phase, which produces poor morphology and properties. Herein, a self-controlled SnO 2 layer is successfully fabricated on a direct fluorine-doped tin oxide (FTO) surface via simple and rapid chemical bath deposition. The PSCs, based on this hydrolyzed SnO 2 layer, exhibited an excellent power-conversion efficiency of 20.21% with negligible hysteresis. Analysis of the EIS on the charge transport dynamics indicated that the bias voltage influence both interfacial charge transportation and the ionic double layer under illumination. The hydrolyzed SnO 2 -based PSCs demonstrated a faster ionic charge response time of 2.5 ms in comparison with the 100.5 ms for the hydrolyzed TiO 2 -based hysteric PSCs. The results of quasi-steady-state carrier transportation indicate that a dynamic hysteresis in the J-V curves can be explained by complex ionic-electronic kinetics owing to the slow ionic charge redistribution and hole accumulation caused by electrode polarization, which causes an increase in charge recombination. This study reveals that SnO 2 -based PSCs leads to a stabilized dark depolarization process compared with TiO 2 -based PSCs that are relevant to charge transport dynamics in the high performing planar SnO 2 -based PSCs.Objectives The aim of this study is to compare efficacy, toxicity and cost between oral and intravenous cyclophosphamide (CYC) pulse therapy in inducing remission (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] less then 3) in severe SLE. Methods We retrospectively checked the hospital records of patients between the years 2000 and 2018, who had been administered oral cyclophosphamide pulse and intravenous (IV) cyclophosphamide pulse. SLEDAI at baseline and after 6 months of therapy were noted. The statistical analysis was done using Mann-Whitney U test. The cost was also calculated. Results We included 45 patients in this study, 21 in the oral pulse group and 24 in the IV group. The median age of patients in the oral and IV groups were 29 (interquartile range [IQR] 22-37) and 26 (IQR 19.25-0.75) years respectively. Median SLEDAI at baseline was comparable between the 2 groups (oral 18.0 [IQR 15.0-26.0]; IV 14.5 [IQR 11.0-20.0] P = .151). At the end of 6 months of treatment, it was 0.0 (IQR 0.0-4.0) in the oral group, as against 2.0 (IQR 0.0-5.5) in IV group (P = .676). There was no major adverse event in either group. Oral cyclophosphamide pulse therapy was more economical as compared to IV cyclophosphamide [630 Indian National rupees( INR)/ 8.85 US dollars(USD) in the IV arm and 50 INR/0.7 USD in the oral arm] (P less then .001). Conclusion This study concludes that oral cyclophosphamide pulse therapy is an economical option and there was no difference in efficacy and safety between oral cyclophosphamide pulse therapy and IV pulse cyclophosphamide therapy.
    Conclusions It is proved that a nanosecond pulse laser could be used for LSCI.The role of physician assistant/associate (PA) has expanded from its inception in the United States over 50 years ago, to European countries including Ireland. While there is an increasing body of evidence exploring the role and training of PAs in clinical settings, there is a scarcity of research exploring PA students' perspectives in relation to their experience of anatomy dissection, or how these experiences may contribute to the development of their core professional identity. Students in the first two cohorts of PA Program at the Royal College of Surgeons in Ireland program were invited to interviews which solicited them to reflect and report on their own experiences of anatomical dissection during their course. Participants' responses were analyzed using a thematic inductive approach; common themes and patterns were organized into a hierarchical structure, which generated the final framework of themes. https://www.selleckchem.com/products/s961.html Ten participants took part in the study; only one had previous personal experience of dissection, while two further participants had some familiarity with prosected specimens. The first theme concerned the participants' expectation of anatomical dissection, with sub-themes of preconceptions, smell, and emotions. The second theme involves discussion of coping strategies that the participants used, including talking, viewing the cadaver as their first patient, and naming (or not naming) the cadaver. The third theme includes how the participants' talked about respect and compassion in the dissection room, development of team working skills, and awareness of bereavement and organ donation. A number of recommendations were also made for the experience and orientation of future students in such a program.Objective The objective of this meta-analysis of observational studies was to evaluate the association between simple renal cysts (SRC) and presence of aortic pathology such as aortic aneurysms and dissection. Methods We conducted searches in Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1960 to August 2019 to identify observational studies that examined the association between SRCs and any aortic diseases, including aortic aneurysms and dissection. Two reviewers independently extracted the data and assessed the risk of bias. The meta-analysis was performed by STATA 14.1. Results In total, 11 observational studies with 19 719 participants were included in this meta-analysis. Compared to individuals without SRCs, patients with SRCs had higher odds of abdominal aortic aneurysm (AAA) (adjusted OR = 2.61, 95% CI 2.34-2.91, P less then 0.001, I2 = 0%), ascending thoracic aortic aneurysm (TAA) (adjusted OR = 1.98, 95% CI 1.09-3.63, P = 0.03, I2 = 90.1%), descending TAA (adjusted OR = 3.44, 95% CI, 2.67-4.43, P less then 0.001, I2 = 0%), type A aortic dissection (AD) (adjusted OR = 1.98, 95% CI 1.32-2.96, P = 0.001, I2 = 12.9%), and type B AD (adjusted OR = 2.55, 95% CI, 1.31-4.96, P = 0.006, I2 = 76.2%). There was a higher average in the sum of diameter of SRCs among AAA compared to patients without AAA (WMD = 19.80 mm, 95% CI 13.92-25.67, P less then 0.001, I2 = 63.8%). Conclusion SRC is associated with higher odds of aortic diseases including AAA, ascending and descending TAA, type A and type B dissection even after adjusting for confounders.Planar perovskite solar cells (PSCs), incorporating n-type SnO- 2 , have attracted significant interest because of their excellent photovoltaic performance. However, the film fabrication of SnO 2 is limited by self-aggregation and inhomogeneous growth of the intermediate phase, which produces poor morphology and properties. Herein, a self-controlled SnO 2 layer is successfully fabricated on a direct fluorine-doped tin oxide (FTO) surface via simple and rapid chemical bath deposition. The PSCs, based on this hydrolyzed SnO 2 layer, exhibited an excellent power-conversion efficiency of 20.21% with negligible hysteresis. Analysis of the EIS on the charge transport dynamics indicated that the bias voltage influence both interfacial charge transportation and the ionic double layer under illumination. The hydrolyzed SnO 2 -based PSCs demonstrated a faster ionic charge response time of 2.5 ms in comparison with the 100.5 ms for the hydrolyzed TiO 2 -based hysteric PSCs. The results of quasi-steady-state carrier transportation indicate that a dynamic hysteresis in the J-V curves can be explained by complex ionic-electronic kinetics owing to the slow ionic charge redistribution and hole accumulation caused by electrode polarization, which causes an increase in charge recombination. This study reveals that SnO 2 -based PSCs leads to a stabilized dark depolarization process compared with TiO 2 -based PSCs that are relevant to charge transport dynamics in the high performing planar SnO 2 -based PSCs.Objectives The aim of this study is to compare efficacy, toxicity and cost between oral and intravenous cyclophosphamide (CYC) pulse therapy in inducing remission (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] less then 3) in severe SLE. Methods We retrospectively checked the hospital records of patients between the years 2000 and 2018, who had been administered oral cyclophosphamide pulse and intravenous (IV) cyclophosphamide pulse. SLEDAI at baseline and after 6 months of therapy were noted. The statistical analysis was done using Mann-Whitney U test. The cost was also calculated. Results We included 45 patients in this study, 21 in the oral pulse group and 24 in the IV group. The median age of patients in the oral and IV groups were 29 (interquartile range [IQR] 22-37) and 26 (IQR 19.25-0.75) years respectively. Median SLEDAI at baseline was comparable between the 2 groups (oral 18.0 [IQR 15.0-26.0]; IV 14.5 [IQR 11.0-20.0] P = .151). At the end of 6 months of treatment, it was 0.0 (IQR 0.0-4.0) in the oral group, as against 2.0 (IQR 0.0-5.5) in IV group (P = .676). There was no major adverse event in either group. Oral cyclophosphamide pulse therapy was more economical as compared to IV cyclophosphamide [630 Indian National rupees( INR)/ 8.85 US dollars(USD) in the IV arm and 50 INR/0.7 USD in the oral arm] (P less then .001). Conclusion This study concludes that oral cyclophosphamide pulse therapy is an economical option and there was no difference in efficacy and safety between oral cyclophosphamide pulse therapy and IV pulse cyclophosphamide therapy.
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