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  • While some diseases reduce fibrinogen concentration, others increase the amount of this clotting factor in the blood. Some studies have shown that the fibrinogen concentration in the blood is related to the stiffness of the formed clot. Hence, the aim of this study was to employ an ultrasonic method based on impulsive acoustic radiation force (IARF) to identify the fibrinogen concentration (coagulation factor I) in a plasma sample by means of peak-displacement (PD), time of peak-displacement (TPD), and shear modulus (μ) as well as to identify the change of plasma samples during the clot formation process. The IARF-based ultrasonic system transmitted bursts with a frequency of 2.03 MHz, duration of 246.31 µs, amplitude of 118 VPP, and pulse with 1.25 Hz repetition frequency to generate an IARF on a glass sphere (2.99 mm in diameter and 2500 kg/m3 in density) embedded in a plasma sample, causing a displacement that was monitored by a pulse-echo system with a center frequency of 4.89 MHz. The values of the shear moduli were 124.14 ± 3.02, 556.99 ± 11.76, and 670.39 ± 9.77 Pa, for fibrinogen concentrations of 1.2, 2.4, and 3.6 g/L 20 to 36 min after the beginning of the coagulation process. The TPD values obtained in the same period were 5.28 ± 0.09, 3.03 ± 0.02, and 2.83 ± 0.01 s. The results indicate that an IARF-based ultrasonic system can be used clinically because it uses small amounts of plasma and has the ability to detect differences in PD, TPD, and μ as a function of fibrinogen concentrations.In spite of extensive work, inconsistent findings and lack of specificity in most neuroimaging techniques used to examine age- and gender-related patterns in brain tissue microstructure indicate the need for additional research. Here, we performed the largest Multi-component T2 relaxometry cross-sectional study to date in healthy adults (N = 145, 18-60 years). Five quantitative microstructure parameters derived from various segments of the estimated T2 spectra were evaluated, allowing a more specific interpretation of results in terms of tissue microstructure. We found similar age-related myelin water fraction (MWF) patterns in men and women but we also observed differential male related results including increased MWF content in a few white matter tracts, a faster decline with age of the intra- and extra-cellular water fraction and its T2 relaxation time (i.e. steeper age related negative slopes) and a faster increase in the free and quasi-free water fraction, spanning the whole grey matter. Such results point to a sexual dimorphism in brain tissue microstructure and suggest a lesser vulnerability to age-related changes in women.Chemokines are a group of cytokines with low molecular weight that principally direct chemotaxis of target cells. They have prominent roles in the pathogenesis systemic lupus erythematosus (SLE) and related complications particularly lupus nephritis. These molecules not only induce autoimmune responses in the organs of patients, but also can amplify the induced inflammatory responses. Although chemokine family has at least 46 identified members, the role of a number of these molecules have been more clarified in SLE patients or animal models of this disorder. In the current paper, we review the role of CCL2, CCL3, CCL4, CCL11, CCL20, CXCL1, CXCL2, CXCL8, CXCL10, CXCL12 and CXCL13 in the pathogenesis of SLE.Many attempts have been made to search for safer immunomodulatory agents that enhance the immune response and reduce the number and severity of infections in at-risk populations. The use of postbiotics, non-viable microbial cells or cell fractions that confer a health benefit to the consumer, represents a safe and attractive way to modulate and enhance the immune function in order to improve human health. Therefore, the aim of this work is to evaluate the immunoregulatory effect of Lactobacillus rhamnosus CRL1505 postbiotics in a complex culture system using human intestinal epithelial cells (IECs) and dendritic cells (DCs) differentiated from peripheral blood mononuclear cells. First, we demonstrated that L. rhamnosus CRL1505 differentially modulate human IECs and DCs after the challenge with the TLR4 agonist LPS. The CRL1505 strain down-regulated CD40, CD80 and CD86 expression in DCs, and increased their production of TNF-α, IL-1β, IL-6 and IL-10. Interestingly, the non-viable strain was able to modulate the immune response of both types of human cells. Then, we showed that cell wall (CW1505) and peptidoglycan (PG1505) from L. rhamnosus CRL1505 modulated TLR4-triggered immune response in IECs and DCs. Of interest, CW1505 showed a strong stimulatory effect while the PG1505 presented immune characteristics that were more similar to viable and non-viable CRL1505. To date, several molecules of immunobiotics were identified, that can be connected to specific host-responses. We hereby demonstrated that peptidoglycan of L. rhamnosus CRL1505 is a key molecule for the immunobiotic properties of this strain in human IECs and DCs. Likewise, the result of these studies could provide predictive tools for the in vivo efficacy of postbiotics and the scientific basis for their future applications in immunocompromised patients.In response to DNA damage, most factors involved in damage recognition and repair are tightly regulated to ensure proper repair pathway choice. Histone acetylation at DNA double strand breaks (DSBs) by p300 histone acetyltransferase (HAT) is critical for the recruitment of DSB repair proteins to chromatin. https://www.selleckchem.com/pharmacological_epigenetics.html Here, we show that phosphorylation of Sp1 by ATM increases its interaction with p300 and that Sp1-dependent recruitment of p300 to DSBs is necessary to modify the histones associated with p300 activity and NHEJ repair factor recruitment and repair. p300 is known to acetylate multiple residues on histones H3 and H4 necessary for NHEJ. Acetylation of H3K18 by p300 is associated with the recruitment of the SWI/SNF chromatin remodeling complex and Ku70 to DSBs for NHEJ repair. Depletion of Sp1 results in decreased acetylation of lysines on histones H3 and H4. Specifically, cells depleted of Sp1 display defects in the acetylation of H3K18, resulting in defective SWI/SNF and Ku70 recruitment to DSBs. These results shed light on mechanisms by which chromatin remodelers are regulated to ensure activation of the appropriate DSB repair pathway.
    While some diseases reduce fibrinogen concentration, others increase the amount of this clotting factor in the blood. Some studies have shown that the fibrinogen concentration in the blood is related to the stiffness of the formed clot. Hence, the aim of this study was to employ an ultrasonic method based on impulsive acoustic radiation force (IARF) to identify the fibrinogen concentration (coagulation factor I) in a plasma sample by means of peak-displacement (PD), time of peak-displacement (TPD), and shear modulus (μ) as well as to identify the change of plasma samples during the clot formation process. The IARF-based ultrasonic system transmitted bursts with a frequency of 2.03 MHz, duration of 246.31 µs, amplitude of 118 VPP, and pulse with 1.25 Hz repetition frequency to generate an IARF on a glass sphere (2.99 mm in diameter and 2500 kg/m3 in density) embedded in a plasma sample, causing a displacement that was monitored by a pulse-echo system with a center frequency of 4.89 MHz. The values of the shear moduli were 124.14 ± 3.02, 556.99 ± 11.76, and 670.39 ± 9.77 Pa, for fibrinogen concentrations of 1.2, 2.4, and 3.6 g/L 20 to 36 min after the beginning of the coagulation process. The TPD values obtained in the same period were 5.28 ± 0.09, 3.03 ± 0.02, and 2.83 ± 0.01 s. The results indicate that an IARF-based ultrasonic system can be used clinically because it uses small amounts of plasma and has the ability to detect differences in PD, TPD, and μ as a function of fibrinogen concentrations.In spite of extensive work, inconsistent findings and lack of specificity in most neuroimaging techniques used to examine age- and gender-related patterns in brain tissue microstructure indicate the need for additional research. Here, we performed the largest Multi-component T2 relaxometry cross-sectional study to date in healthy adults (N = 145, 18-60 years). Five quantitative microstructure parameters derived from various segments of the estimated T2 spectra were evaluated, allowing a more specific interpretation of results in terms of tissue microstructure. We found similar age-related myelin water fraction (MWF) patterns in men and women but we also observed differential male related results including increased MWF content in a few white matter tracts, a faster decline with age of the intra- and extra-cellular water fraction and its T2 relaxation time (i.e. steeper age related negative slopes) and a faster increase in the free and quasi-free water fraction, spanning the whole grey matter. Such results point to a sexual dimorphism in brain tissue microstructure and suggest a lesser vulnerability to age-related changes in women.Chemokines are a group of cytokines with low molecular weight that principally direct chemotaxis of target cells. They have prominent roles in the pathogenesis systemic lupus erythematosus (SLE) and related complications particularly lupus nephritis. These molecules not only induce autoimmune responses in the organs of patients, but also can amplify the induced inflammatory responses. Although chemokine family has at least 46 identified members, the role of a number of these molecules have been more clarified in SLE patients or animal models of this disorder. In the current paper, we review the role of CCL2, CCL3, CCL4, CCL11, CCL20, CXCL1, CXCL2, CXCL8, CXCL10, CXCL12 and CXCL13 in the pathogenesis of SLE.Many attempts have been made to search for safer immunomodulatory agents that enhance the immune response and reduce the number and severity of infections in at-risk populations. The use of postbiotics, non-viable microbial cells or cell fractions that confer a health benefit to the consumer, represents a safe and attractive way to modulate and enhance the immune function in order to improve human health. Therefore, the aim of this work is to evaluate the immunoregulatory effect of Lactobacillus rhamnosus CRL1505 postbiotics in a complex culture system using human intestinal epithelial cells (IECs) and dendritic cells (DCs) differentiated from peripheral blood mononuclear cells. First, we demonstrated that L. rhamnosus CRL1505 differentially modulate human IECs and DCs after the challenge with the TLR4 agonist LPS. The CRL1505 strain down-regulated CD40, CD80 and CD86 expression in DCs, and increased their production of TNF-α, IL-1β, IL-6 and IL-10. Interestingly, the non-viable strain was able to modulate the immune response of both types of human cells. Then, we showed that cell wall (CW1505) and peptidoglycan (PG1505) from L. rhamnosus CRL1505 modulated TLR4-triggered immune response in IECs and DCs. Of interest, CW1505 showed a strong stimulatory effect while the PG1505 presented immune characteristics that were more similar to viable and non-viable CRL1505. To date, several molecules of immunobiotics were identified, that can be connected to specific host-responses. We hereby demonstrated that peptidoglycan of L. rhamnosus CRL1505 is a key molecule for the immunobiotic properties of this strain in human IECs and DCs. Likewise, the result of these studies could provide predictive tools for the in vivo efficacy of postbiotics and the scientific basis for their future applications in immunocompromised patients.In response to DNA damage, most factors involved in damage recognition and repair are tightly regulated to ensure proper repair pathway choice. Histone acetylation at DNA double strand breaks (DSBs) by p300 histone acetyltransferase (HAT) is critical for the recruitment of DSB repair proteins to chromatin. https://www.selleckchem.com/pharmacological_epigenetics.html Here, we show that phosphorylation of Sp1 by ATM increases its interaction with p300 and that Sp1-dependent recruitment of p300 to DSBs is necessary to modify the histones associated with p300 activity and NHEJ repair factor recruitment and repair. p300 is known to acetylate multiple residues on histones H3 and H4 necessary for NHEJ. Acetylation of H3K18 by p300 is associated with the recruitment of the SWI/SNF chromatin remodeling complex and Ku70 to DSBs for NHEJ repair. Depletion of Sp1 results in decreased acetylation of lysines on histones H3 and H4. Specifically, cells depleted of Sp1 display defects in the acetylation of H3K18, resulting in defective SWI/SNF and Ku70 recruitment to DSBs. These results shed light on mechanisms by which chromatin remodelers are regulated to ensure activation of the appropriate DSB repair pathway.
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  • Colorectal cancer is the third most common cancer, and surgery is the most common treatment. Several surgical options are available, but each is associated with a range of potential complications. The timely and efficient identification of these complications is vital for effective clinical management of these patients in order to minimise their morbidity and mortality. This review aims to describe the range of commonly performed surgical treatments for colorectal surgery. In addition, frequent post-surgical complications are explored with investigative options explained and illustrated.The overgrowth syndromes related to phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) are grouped under the concept of PROS (PIK3CA-related overgrowth spectrum). It is a heterogeneous group of diseases, considered a rare disease (ORPHA 530313), which combines the presence of vascular malformations with segmental overgrowth of some parts of the body. All these diseases are caused by mutations in the gene that encodes for the alpha subunit of PI3K. These mutations are somatic and take place during the embryonic stage. Depending on the stage of embryonic development and the affected germ layers, the phenotype will be very different, from syndromes with extensive involvement to isolated forms. Although there are clinical criteria, identification of the mutation by biopsy, although complex, confirms the diagnosis. The objective of the present study is to review the pathophysiological, clinical, diagnostic, and therapeutic aspects of PROS, in order to optimize its identification.
    Sublobar resection is frequently offered to patients with small, peripheral lung cancers, despite the lack of outcome data from ongoing randomized clinical trials. Sublobar resection may be a particularly attractive surgical strategy for screen-detected lung cancers, which have been suggested to be less biologically aggressive than cancers detected by other means. Using prospective data collected from patients undergoing surgery in the National Lung Screening Trial, we sought to determine whether extent of resection affected survival for patients with screen-detected lung cancer.

    The National Lung Screening Trial database was queried for patients who underwent surgical resection for confirmed lung cancer. Propensity score matching analysis (lobectomy vs sublobar resection) was done (nearest neighbor, 11, matching with no replacement, caliper 0.2). Demographics, clinicopathologic and perioperative outcomes, and long-term survival were compared in the entire cohort and in the propensity-matched groups. Multresection may provide distinct advantages in a screened patient cohort.
    The accurate preoperative diagnosis of periprosthetic joint infection (PJI) is critical. The aim of this study was to evaluate the diagnostic accuracy and performance of the 2018 International Consensus Meeting (ICM) preoperative minor criteria for the diagnosis of chronic PJI in total hip and knee arthroplasty.

    We retrospectively reviewed 260 patients that underwent a revision knee or hip arthroplasty at our institution between 2015 and 2017. All major and minor 2018 ICM criteria (except erythrocyte sedimentation rate, D-dimer) were available for all patients included. Cases with at least 1 major criterion were considered as infected. Receiver operative characteristic curve analysis was performed for preoperative minor criteria.

    The diagnostic performance of the preoperative minor criteria ranked as per the area under the curve was PMN% (0.926), alpha defensin (0.922), white blood cell count (0.916), leukocyte esterase (0.861), and serum C-reactive protein (0.860). Increasing the PMN % cutoff from 70% to 77.8% improves the diagnostic accuracy (86.5% vs 90.8%). The highest diagnostic performance was achieved by combining all 5 preoperative parameters, and at current ICM thresholds, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive were 93.5%, 95.4%, 92.1%, 89.7%, and 96.5%, respectively.

    The diagnostic performance of preoperative minor criteria was outstanding (PMN%, alpha defensin, white blood cell count) or excellent (leukocyte esterase, serum C-reactive protein). PMN% showed the best diagnostic utility (area under the curve) and should have an increased weight-adjusted score in the ICM scoring system.
    The diagnostic performance of preoperative minor criteria was outstanding (PMN%, alpha defensin, white blood cell count) or excellent (leukocyte esterase, serum C-reactive protein). PMN% showed the best diagnostic utility (area under the curve) and should have an increased weight-adjusted score in the ICM scoring system.Investment in action is vital to confront the challenges associated with chronic diseases and disability facing European health systems. Although relevant policy responses are being increasingly developed, most of them fail to recognize the role of rehabilitation services in achieving public health and social goals. Comprehensive guidance is thus urgently needed to support rehabilitation policy development and expand access to rehabilitation care to meet population needs effectively. This paper describes a framework to guide policy action for rehabilitation in Europe. https://www.selleckchem.com/products/nms-p937-nms1286937.html The framework was developed in collaboration with the European Academy of Rehabilitation Medicine based on a focused literature review and expert consultations. A review in PubMed and grey literature sources identified 458 references and resulted in 135 relevant documents published between 2006 and 2019. Thematic analysis of extracted information helped summarize the findings and develop the draft policy action framework. This was circulated to a wider group of experts and discussed in three workshops in 2018-2019. The framework was revised according to their feedback. The proposed framework contains 48 options for policy action organized in six domains and twelve subdomains that address several areas of health programming. The proposed framework provides a structure to understand the policy terrain related to rehabilitation in Europe and the measures required for translating aspirational political pronouncements into targeted programmatic action and tangible health and social outcomes.
    Colorectal cancer is the third most common cancer, and surgery is the most common treatment. Several surgical options are available, but each is associated with a range of potential complications. The timely and efficient identification of these complications is vital for effective clinical management of these patients in order to minimise their morbidity and mortality. This review aims to describe the range of commonly performed surgical treatments for colorectal surgery. In addition, frequent post-surgical complications are explored with investigative options explained and illustrated.The overgrowth syndromes related to phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) are grouped under the concept of PROS (PIK3CA-related overgrowth spectrum). It is a heterogeneous group of diseases, considered a rare disease (ORPHA 530313), which combines the presence of vascular malformations with segmental overgrowth of some parts of the body. All these diseases are caused by mutations in the gene that encodes for the alpha subunit of PI3K. These mutations are somatic and take place during the embryonic stage. Depending on the stage of embryonic development and the affected germ layers, the phenotype will be very different, from syndromes with extensive involvement to isolated forms. Although there are clinical criteria, identification of the mutation by biopsy, although complex, confirms the diagnosis. The objective of the present study is to review the pathophysiological, clinical, diagnostic, and therapeutic aspects of PROS, in order to optimize its identification. Sublobar resection is frequently offered to patients with small, peripheral lung cancers, despite the lack of outcome data from ongoing randomized clinical trials. Sublobar resection may be a particularly attractive surgical strategy for screen-detected lung cancers, which have been suggested to be less biologically aggressive than cancers detected by other means. Using prospective data collected from patients undergoing surgery in the National Lung Screening Trial, we sought to determine whether extent of resection affected survival for patients with screen-detected lung cancer. The National Lung Screening Trial database was queried for patients who underwent surgical resection for confirmed lung cancer. Propensity score matching analysis (lobectomy vs sublobar resection) was done (nearest neighbor, 11, matching with no replacement, caliper 0.2). Demographics, clinicopathologic and perioperative outcomes, and long-term survival were compared in the entire cohort and in the propensity-matched groups. Multresection may provide distinct advantages in a screened patient cohort. The accurate preoperative diagnosis of periprosthetic joint infection (PJI) is critical. The aim of this study was to evaluate the diagnostic accuracy and performance of the 2018 International Consensus Meeting (ICM) preoperative minor criteria for the diagnosis of chronic PJI in total hip and knee arthroplasty. We retrospectively reviewed 260 patients that underwent a revision knee or hip arthroplasty at our institution between 2015 and 2017. All major and minor 2018 ICM criteria (except erythrocyte sedimentation rate, D-dimer) were available for all patients included. Cases with at least 1 major criterion were considered as infected. Receiver operative characteristic curve analysis was performed for preoperative minor criteria. The diagnostic performance of the preoperative minor criteria ranked as per the area under the curve was PMN% (0.926), alpha defensin (0.922), white blood cell count (0.916), leukocyte esterase (0.861), and serum C-reactive protein (0.860). Increasing the PMN % cutoff from 70% to 77.8% improves the diagnostic accuracy (86.5% vs 90.8%). The highest diagnostic performance was achieved by combining all 5 preoperative parameters, and at current ICM thresholds, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive were 93.5%, 95.4%, 92.1%, 89.7%, and 96.5%, respectively. The diagnostic performance of preoperative minor criteria was outstanding (PMN%, alpha defensin, white blood cell count) or excellent (leukocyte esterase, serum C-reactive protein). PMN% showed the best diagnostic utility (area under the curve) and should have an increased weight-adjusted score in the ICM scoring system. The diagnostic performance of preoperative minor criteria was outstanding (PMN%, alpha defensin, white blood cell count) or excellent (leukocyte esterase, serum C-reactive protein). PMN% showed the best diagnostic utility (area under the curve) and should have an increased weight-adjusted score in the ICM scoring system.Investment in action is vital to confront the challenges associated with chronic diseases and disability facing European health systems. Although relevant policy responses are being increasingly developed, most of them fail to recognize the role of rehabilitation services in achieving public health and social goals. Comprehensive guidance is thus urgently needed to support rehabilitation policy development and expand access to rehabilitation care to meet population needs effectively. This paper describes a framework to guide policy action for rehabilitation in Europe. https://www.selleckchem.com/products/nms-p937-nms1286937.html The framework was developed in collaboration with the European Academy of Rehabilitation Medicine based on a focused literature review and expert consultations. A review in PubMed and grey literature sources identified 458 references and resulted in 135 relevant documents published between 2006 and 2019. Thematic analysis of extracted information helped summarize the findings and develop the draft policy action framework. This was circulated to a wider group of experts and discussed in three workshops in 2018-2019. The framework was revised according to their feedback. The proposed framework contains 48 options for policy action organized in six domains and twelve subdomains that address several areas of health programming. The proposed framework provides a structure to understand the policy terrain related to rehabilitation in Europe and the measures required for translating aspirational political pronouncements into targeted programmatic action and tangible health and social outcomes.
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  • r reflect how segmentation quality affects dose distribution and related tumor control and toxicity.
    This study shows a low correlation between segmentation metrics and dosimetric changes for OARs in brain tumor patients. Results suggest that the current metrics for image segmentation in RT, as well as deep learning systems employing such metrics, need to be revisited towards clinically oriented metrics that better reflect how segmentation quality affects dose distribution and related tumor control and toxicity.In current biological and medical research, statistical shape modeling (SSM) provides an essential framework for the characterization of anatomy/morphology. Such analysis is often driven by the identification of a relatively small number of geometrically consistent features found across the samples of a population. These features can subsequently provide information about the population shape variation. Dense correspondence models can provide ease of computation and yield an interpretable low-dimensional shape descriptor when followed by dimensionality reduction. However, automatic methods for obtaining such correspondences usually require image segmentation followed by significant preprocessing, which is taxing in terms of both computation as well as human resources. In many cases, the segmentation and subsequent processing require manual guidance and anatomy specific domain expertise. This paper proposes a self-supervised deep learning approach for discovering landmarks from images that can directly be used as a shape descriptor for subsequent analysis. We use landmark-driven image registration as the primary task to force the neural network to discover landmarks that register the images well. We also propose a regularization term that allows for robust optimization of the neural network and ensures that the landmarks uniformly span the image domain. The proposed method circumvents segmentation and preprocessing and directly produces a usable shape descriptor using just 2D or 3D images. In addition, we also propose two variants on the training loss function that allows for prior shape information to be integrated into the model. We apply this framework on several 2D and 3D datasets to obtain their shape descriptors. We analyze these shape descriptors in their efficacy of capturing shape information by performing different shape-driven applications depending on the data ranging from shape clustering to severity prediction to outcome diagnosis.
    In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March - mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP).

    PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life.

    2653 PwP were included 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group.

    The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .
    The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .
    The previously observed effects of nonpolar additives on the scission energy and rheological properties of surfactant wormlike micelles can be explained in terms of the spatial distribution of the additive within the micelles. The dependence of the scission energy with the molecular organization of the system can be analyzed with a molecular theory capable of describing the thermodynamics and structure of the micelles.

    A new theoretical method to determine the scission energy of surfactant wormlike micelles is introduced. This methodology is based on a molecular theory that explicitly considers molecular details of all components of the micelles, and their inter- and intramolecular interactions without the use of fitting and/or empirical macroscopic parameters.

    The predicted effects of the concentration, molecular structure and hydrophobicity of the additive on the scission energy of cetyltrimethylammonium bromide (CTAB) wormlike micelles are found to be in qualitative agreement with previous experimental observations. In particular, our theory captures the decrease of micellar length with increasing content of highly hydrophobic additives and the non-monotonic dependence of the viscosity with additive hydrophobicity. The latter effect arises because highly and mildly hydrophobic additives affect the scission energy of wormlike micelles via markedly different molecular mechanisms.
    The predicted effects of the concentration, molecular structure and hydrophobicity of the additive on the scission energy of cetyltrimethylammonium bromide (CTAB) wormlike micelles are found to be in qualitative agreement with previous experimental observations. In particular, our theory captures the decrease of micellar length with increasing content of highly hydrophobic additives and the non-monotonic dependence of the viscosity with additive hydrophobicity. https://www.selleckchem.com/ The latter effect arises because highly and mildly hydrophobic additives affect the scission energy of wormlike micelles via markedly different molecular mechanisms.
    r reflect how segmentation quality affects dose distribution and related tumor control and toxicity. This study shows a low correlation between segmentation metrics and dosimetric changes for OARs in brain tumor patients. Results suggest that the current metrics for image segmentation in RT, as well as deep learning systems employing such metrics, need to be revisited towards clinically oriented metrics that better reflect how segmentation quality affects dose distribution and related tumor control and toxicity.In current biological and medical research, statistical shape modeling (SSM) provides an essential framework for the characterization of anatomy/morphology. Such analysis is often driven by the identification of a relatively small number of geometrically consistent features found across the samples of a population. These features can subsequently provide information about the population shape variation. Dense correspondence models can provide ease of computation and yield an interpretable low-dimensional shape descriptor when followed by dimensionality reduction. However, automatic methods for obtaining such correspondences usually require image segmentation followed by significant preprocessing, which is taxing in terms of both computation as well as human resources. In many cases, the segmentation and subsequent processing require manual guidance and anatomy specific domain expertise. This paper proposes a self-supervised deep learning approach for discovering landmarks from images that can directly be used as a shape descriptor for subsequent analysis. We use landmark-driven image registration as the primary task to force the neural network to discover landmarks that register the images well. We also propose a regularization term that allows for robust optimization of the neural network and ensures that the landmarks uniformly span the image domain. The proposed method circumvents segmentation and preprocessing and directly produces a usable shape descriptor using just 2D or 3D images. In addition, we also propose two variants on the training loss function that allows for prior shape information to be integrated into the model. We apply this framework on several 2D and 3D datasets to obtain their shape descriptors. We analyze these shape descriptors in their efficacy of capturing shape information by performing different shape-driven applications depending on the data ranging from shape clustering to severity prediction to outcome diagnosis. In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March - mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP). PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life. 2653 PwP were included 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group. The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. . The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. . The previously observed effects of nonpolar additives on the scission energy and rheological properties of surfactant wormlike micelles can be explained in terms of the spatial distribution of the additive within the micelles. The dependence of the scission energy with the molecular organization of the system can be analyzed with a molecular theory capable of describing the thermodynamics and structure of the micelles. A new theoretical method to determine the scission energy of surfactant wormlike micelles is introduced. This methodology is based on a molecular theory that explicitly considers molecular details of all components of the micelles, and their inter- and intramolecular interactions without the use of fitting and/or empirical macroscopic parameters. The predicted effects of the concentration, molecular structure and hydrophobicity of the additive on the scission energy of cetyltrimethylammonium bromide (CTAB) wormlike micelles are found to be in qualitative agreement with previous experimental observations. In particular, our theory captures the decrease of micellar length with increasing content of highly hydrophobic additives and the non-monotonic dependence of the viscosity with additive hydrophobicity. The latter effect arises because highly and mildly hydrophobic additives affect the scission energy of wormlike micelles via markedly different molecular mechanisms. The predicted effects of the concentration, molecular structure and hydrophobicity of the additive on the scission energy of cetyltrimethylammonium bromide (CTAB) wormlike micelles are found to be in qualitative agreement with previous experimental observations. In particular, our theory captures the decrease of micellar length with increasing content of highly hydrophobic additives and the non-monotonic dependence of the viscosity with additive hydrophobicity. https://www.selleckchem.com/ The latter effect arises because highly and mildly hydrophobic additives affect the scission energy of wormlike micelles via markedly different molecular mechanisms.
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  • Carrying out bibliometric reports is one of the common tasks performed by librarians and practitioners within the framework of their professional duties. The emergence of novel data sources, the need to measure new research activities and the growing demand for fairer and more equitable evaluation within the framework of the Responsible Metrics movement has led to calls for a review of the traditional approaches to these types of reports. The main goal of this study is to outline a series of recommendations for bibliometricians, consultants and research support librarians when drafting bibliometric reports in their institutions. These best practices can significantly enhance the quality and utility of bibliometric reports, posing their practitioners as key players in the science management process.We deal with a heterogeneous pharmaceutical knowledge-graph containing textual information built from several databases. The knowledge graph is a heterogeneous graph that includes a wide variety of concepts and attributes, some of which are provided in the form of textual pieces of information which have not been targeted in the conventional graph completion tasks. To investigate the utility of textual information for knowledge graph completion, we generate embeddings from textual descriptions given to heterogeneous items, such as drugs and proteins, while learning knowledge graph embeddings. We evaluate the obtained graph embeddings on the link prediction task for knowledge graph completion, which can be used for drug discovery and repurposing. We also compare the results with existing methods and discuss the utility of the textual information.[This corrects the article DOI 10.18502/ijrm.v19i3.8574.].
    Small supernumerary marker chromosomes (sSMCs) are chromosomal fragments with abnormal structures found in patients with fertility problems and developmental delay. They may be detected in amniotic cell karyotypes. sSMCs are categorized as hereditary or de novo. Here, we describe a case of prenatal de novo 4q11q12 sSMC and its molecular cytogenetic features which had no apparent phenotypic abnormality.

    The fetus of a 36-yr-old pregnant woman was detected positive for Down's syndrome (trisomy 21) at the 16




    th


    wk of gestation. Quantitative fluorescent polymerase chain reaction technique was applied for the rapid detection of numerical aneuploidy of chromosomes X, Y, 13, 18, and 21 microsatellites. Array comparative genomic hybridization (array CGH) technique was also conducted following the karyotype analysis of amniotic cells. The karyotype analysis was also done for the parents. Quantitative fluorescent polymerase chain reaction result revealed a male fetus with a normal chromosomal pattern, while the amniocentesis karyotype analysis identified a male fetus with a marker chromosome (47, XY, +mar), and the sSMC were existing in 100% of amniocyte metaphase spreads. The parents' normal karyotypes indicated that the sSMC was de novo. Array CGH analysis revealed a 6.48-Mb duplication at 4q11q12. Eventually, the parents decided to terminate the pregnancy by legal abortion.

    Our study highlights the importance of the application of array CGH in combination with karyotype analysis for rapid and precise prenatal diagnosis of partial aneuploidy region.
    Our study highlights the importance of the application of array CGH in combination with karyotype analysis for rapid and precise prenatal diagnosis of partial aneuploidy region.
    Clomiphene citrate is an estrogen receptor ligand with mixed agonistic-antagonistic properties used for the treatment of female and male infertility. Various visual disturbances and several irreversible visual outcomes have been associated with clomiphene citrate. In this report, we present a patient with presumed clomiphene-induced optic neuropathy.

    A 33-yr-old man with acute visual loss of the right eye was referred to Amiralmomenin Hospital, Rasht, Iran in November 2018. His only medication was clomiphene citrate 100 mg daily, taken for 2 wk for fertility issues. The patient presented with a sudden decrease of visual acuity in the right eye on the 14




    th


    day of starting the treatment and subsequently developed complete loss of inferior visual field within a few days. On examination, the visual acuity was 6/20 in the right and 20/20 in the left eyes, with a right relative afferent pupillary defect and decreased red color saturation. The fundus examination revealed optic discc anterior ischemic optic neuropathy and those experiencing visual symptoms while taking clomiphene be examined promptly for evidence of optic nerve injury.
    The prevalence of infertility is increasing worldwide and the treatment is one of the important issues.

    This study aimed to evaluate the effect of local endometrial scratching on pregnancy outcomes in women with previous failure of intrauterine insemination.

    This non-randomized clinical trial study was performed on 336 women referred to the infertility clinic of Ali ebn-e Abitaleb Hospital of Zahedan (between May and November 2019). Women were divided into two groups endometrial scratch as case and a control group. In the case group (n = 173), endometrial scratching was performed on days 8-9 of the menstrual cycle in addition to routine infertility treatments, while in the control group (n = 163), only routine treatment was performed. Chi-square test was used to compare the frequency of male factor severity and the percentage of successful pregnancies between both groups and was used to investigate the effect of male factor on the fertility rate in each group (moderate male factor and mild male factor).

    The mean age of the women was 28.4


    ±

    5.2 yr. The success rate of pregnancy in the case group was 12.3% and in the control group 11%, which were not statistically significant (p = 0.697).

    Overall, the results of this study showed that endometrial scratching had no effect on the pregnancy rate.
    Overall, the results of this study showed that endometrial scratching had no effect on the pregnancy rate.
    Endometrial scratch injury is considered controversial in increasing the success rate of assisted reproductive technology.

    To compare the pregnancy outcomes in women undergoing intrauterine insemination with and without an endometrial scratch.

    In this randomized clinical trial, 150 women referred to the Fatemieh Hospital, Hamadan, Iran who were candidates for IUI between December 2017 and December 2018 were randomly assigned into two groups (n = 75/each) with or without an endometrial scratch (as case and control groups, respectively). https://www.selleckchem.com/GSK-3.html Women in both groups were in proper and identical protocol for IUI. Chemical and clinical pregnancies, abortion, and live birth rate, also pregnancy complications were compared between the groups.

    Chemical and clinical pregnancy rates were higher in the case than the control group (p = 0.25, p = 0.54, respectively). In the case group, the abortion and multiple gestation rates were 14.3% and 4.3%, respectively, while it was 5% in the control group (p = 0.60, p = 0.54 respectively).
    Carrying out bibliometric reports is one of the common tasks performed by librarians and practitioners within the framework of their professional duties. The emergence of novel data sources, the need to measure new research activities and the growing demand for fairer and more equitable evaluation within the framework of the Responsible Metrics movement has led to calls for a review of the traditional approaches to these types of reports. The main goal of this study is to outline a series of recommendations for bibliometricians, consultants and research support librarians when drafting bibliometric reports in their institutions. These best practices can significantly enhance the quality and utility of bibliometric reports, posing their practitioners as key players in the science management process.We deal with a heterogeneous pharmaceutical knowledge-graph containing textual information built from several databases. The knowledge graph is a heterogeneous graph that includes a wide variety of concepts and attributes, some of which are provided in the form of textual pieces of information which have not been targeted in the conventional graph completion tasks. To investigate the utility of textual information for knowledge graph completion, we generate embeddings from textual descriptions given to heterogeneous items, such as drugs and proteins, while learning knowledge graph embeddings. We evaluate the obtained graph embeddings on the link prediction task for knowledge graph completion, which can be used for drug discovery and repurposing. We also compare the results with existing methods and discuss the utility of the textual information.[This corrects the article DOI 10.18502/ijrm.v19i3.8574.]. Small supernumerary marker chromosomes (sSMCs) are chromosomal fragments with abnormal structures found in patients with fertility problems and developmental delay. They may be detected in amniotic cell karyotypes. sSMCs are categorized as hereditary or de novo. Here, we describe a case of prenatal de novo 4q11q12 sSMC and its molecular cytogenetic features which had no apparent phenotypic abnormality. The fetus of a 36-yr-old pregnant woman was detected positive for Down's syndrome (trisomy 21) at the 16 th wk of gestation. Quantitative fluorescent polymerase chain reaction technique was applied for the rapid detection of numerical aneuploidy of chromosomes X, Y, 13, 18, and 21 microsatellites. Array comparative genomic hybridization (array CGH) technique was also conducted following the karyotype analysis of amniotic cells. The karyotype analysis was also done for the parents. Quantitative fluorescent polymerase chain reaction result revealed a male fetus with a normal chromosomal pattern, while the amniocentesis karyotype analysis identified a male fetus with a marker chromosome (47, XY, +mar), and the sSMC were existing in 100% of amniocyte metaphase spreads. The parents' normal karyotypes indicated that the sSMC was de novo. Array CGH analysis revealed a 6.48-Mb duplication at 4q11q12. Eventually, the parents decided to terminate the pregnancy by legal abortion. Our study highlights the importance of the application of array CGH in combination with karyotype analysis for rapid and precise prenatal diagnosis of partial aneuploidy region. Our study highlights the importance of the application of array CGH in combination with karyotype analysis for rapid and precise prenatal diagnosis of partial aneuploidy region. Clomiphene citrate is an estrogen receptor ligand with mixed agonistic-antagonistic properties used for the treatment of female and male infertility. Various visual disturbances and several irreversible visual outcomes have been associated with clomiphene citrate. In this report, we present a patient with presumed clomiphene-induced optic neuropathy. A 33-yr-old man with acute visual loss of the right eye was referred to Amiralmomenin Hospital, Rasht, Iran in November 2018. His only medication was clomiphene citrate 100 mg daily, taken for 2 wk for fertility issues. The patient presented with a sudden decrease of visual acuity in the right eye on the 14 th day of starting the treatment and subsequently developed complete loss of inferior visual field within a few days. On examination, the visual acuity was 6/20 in the right and 20/20 in the left eyes, with a right relative afferent pupillary defect and decreased red color saturation. The fundus examination revealed optic discc anterior ischemic optic neuropathy and those experiencing visual symptoms while taking clomiphene be examined promptly for evidence of optic nerve injury. The prevalence of infertility is increasing worldwide and the treatment is one of the important issues. This study aimed to evaluate the effect of local endometrial scratching on pregnancy outcomes in women with previous failure of intrauterine insemination. This non-randomized clinical trial study was performed on 336 women referred to the infertility clinic of Ali ebn-e Abitaleb Hospital of Zahedan (between May and November 2019). Women were divided into two groups endometrial scratch as case and a control group. In the case group (n = 173), endometrial scratching was performed on days 8-9 of the menstrual cycle in addition to routine infertility treatments, while in the control group (n = 163), only routine treatment was performed. Chi-square test was used to compare the frequency of male factor severity and the percentage of successful pregnancies between both groups and was used to investigate the effect of male factor on the fertility rate in each group (moderate male factor and mild male factor). The mean age of the women was 28.4 ± 5.2 yr. The success rate of pregnancy in the case group was 12.3% and in the control group 11%, which were not statistically significant (p = 0.697). Overall, the results of this study showed that endometrial scratching had no effect on the pregnancy rate. Overall, the results of this study showed that endometrial scratching had no effect on the pregnancy rate. Endometrial scratch injury is considered controversial in increasing the success rate of assisted reproductive technology. To compare the pregnancy outcomes in women undergoing intrauterine insemination with and without an endometrial scratch. In this randomized clinical trial, 150 women referred to the Fatemieh Hospital, Hamadan, Iran who were candidates for IUI between December 2017 and December 2018 were randomly assigned into two groups (n = 75/each) with or without an endometrial scratch (as case and control groups, respectively). https://www.selleckchem.com/GSK-3.html Women in both groups were in proper and identical protocol for IUI. Chemical and clinical pregnancies, abortion, and live birth rate, also pregnancy complications were compared between the groups. Chemical and clinical pregnancy rates were higher in the case than the control group (p = 0.25, p = 0.54, respectively). In the case group, the abortion and multiple gestation rates were 14.3% and 4.3%, respectively, while it was 5% in the control group (p = 0.60, p = 0.54 respectively).
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  • p21-deficient CAIA **** are susceptible to RA phenotype alterations, including joint cartilage destruction and severe synovitis. Therefore, p21 may have a regulatory role in inflammatory cytokine production including IL-1β, IL-6, and TNF-α.Adipose tissue and adipokine concentrations change markedly during pregnancy, but the effects of physical activity on these changes are rarely studied. We aimed to assess physical activity levels in pregnant women of normal-weight (NW) or with obesity (OB), and to determine the relation with changes in fat mass and adipokines. In each trimester, pregnant women (136 NW, 51 OB) were interviewed about their physical activity and had their body composition, leptin, soluble leptin receptor (sOB-R) and adiponectin determined. NW reported higher activity and more aerobic exercise than OB during early pregnancy. Both groups maintained training frequency but reduced overall activity as pregnancy progressed. NW women reporting aerobic and/or resistance exercise and OB women reporting aerobic exercise had greater sOB-R increases (independent of BMI or gestational weight gain). In NW, exercise also associated with lower fat mass and leptin increases. Higher activity levels associated with lower gestational weight gain in both groups. The relationship between physical activity and adiponectin differed between NW and OB. https://www.selleckchem.com/ Maternal exercise may partly mediate its beneficial effects through regulation of leptin bioavailability, by enhancing pregnancy-induced increases in sOB-R. This could be of particular importance in OB with pre-gestational hyperleptinemia and leptin resistance.Patients with severe acute liver injury (SLI) usually recover spontaneously. However, some SLI patients progress to acute liver failure with varying degrees of hepatic encephalopathy. Acute liver failure is associated with high mortality and can be substantially reduced by liver transplantation. Therefore, distinguishing SLI patients who might progress to acute liver failure and are at a risk of death is important when evaluating patients needing liver transplantation. The present study aimed to determine whether technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) scintigraphy can predict the prognosis of patients with SLI. This prospective observational study included 69 SLI patients. The accuracy of Tc-99m GSA for predicting death or liver transplantation for 6 months was assessed. Between the two groups of patients stratified based on the cut-off values from the receiver operating characteristic curves, 6-month transplant-free survival was compared. Sixteen (23.2%) patients died or underwent liver transplantation from admission (poor outcome). The hepatic accumulation index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest at 15 min (i.e., LHL15). The LHL15 in the 16 patients (0.686) was significantly lower than that in survivors (0.836; P  less then  0.0001). The optimal LHL15 cut-off for distinguishing poor outcome and survival was 0.737 with a sensitivity of 81.3%, specificity of 88.7%, and area under the curve of 0.907 (95% CI, 0.832-0.981). When patients were divided into two groups based on the LHL15 cut-off value, the 6-month transplant-free survival was significantly lower in patients with an LHL15 level ≤ 0.737. Tc-99m GSA scintigraphy may help predict the prognosis of patients with SLI.The western Arctic Ocean (WAO) has experienced increased heat transport into the region, sea-ice reduction, and changes to the WAO nitrous oxide (N2O) cycles from greenhouse gases. We investigated WAO N2O dynamics through an intensive and precise N2O survey during the open-water season of summer 2017. The effects of physical processes (i.e., solubility and advection) were dominant in both the surface (0-50 m) and deep layers (200-2200 m) of the northern Chukchi Sea with an under-saturation of N2O. By contrast, both the surface layer (0-50 m) of the southern Chukchi Sea and the intermediate (50-200 m) layer of the northern Chukchi Sea were significantly influenced by biogeochemically derived N2O production (i.e., through nitrification), with N2O over-saturation. During summer 2017, the southern region acted as a source of atmospheric N2O (mean + 2.3 ± 2.7 μmol N2O m-2 day-1), whereas the northern region acted as a sink (mean - 1.3 ± 1.5 μmol N2O m-2 day-1). If Arctic environmental changes continue to accelerate and consequently drive the productivity of the Arctic Ocean, the WAO may become a N2O "hot spot", and therefore, a key region requiring continued observations to both understand N2O dynamics and possibly predict their future changes.Cyclic dominance of competing species is an intensively used working hypothesis to explain biodiversity in certain living systems, where the evolutionary selection principle would dictate a single victor otherwise. Technically the May-Leonard models offer a mathematical framework to describe the mentioned non-transitive interaction of competing species when individual movement is also considered in a spatial system. Emerging rotating spirals composed by the competing species are frequently observed character of the resulting patterns. But how do these spiraling patterns change when we vary the external environment which affects the general vitality of individuals? Motivated by this question we suggest an off-lattice version of the tradition May-Leonard model which allows us to change the actual state of the environment gradually. This can be done by introducing a local carrying capacity parameter which value can be varied gently in an off-lattice environment. Our results support a previous analysis obtained in a more intricate metapopulation model and we show that the well-known rotating spirals become evident in a benign environment when the general density of the population is high. The accompanying time-dependent oscillation of competing species can also be detected where the amplitude and the frequency show a scaling law of the parameter that characterizes the state of the environment. These observations highlight that the assumed non-transitive interaction alone is insufficient condition to maintain biodiversity safely, but the actual state of the environment, which characterizes the general living conditions, also plays a decisive role on the evolution of related systems.
    p21-deficient CAIA mice are susceptible to RA phenotype alterations, including joint cartilage destruction and severe synovitis. Therefore, p21 may have a regulatory role in inflammatory cytokine production including IL-1β, IL-6, and TNF-α.Adipose tissue and adipokine concentrations change markedly during pregnancy, but the effects of physical activity on these changes are rarely studied. We aimed to assess physical activity levels in pregnant women of normal-weight (NW) or with obesity (OB), and to determine the relation with changes in fat mass and adipokines. In each trimester, pregnant women (136 NW, 51 OB) were interviewed about their physical activity and had their body composition, leptin, soluble leptin receptor (sOB-R) and adiponectin determined. NW reported higher activity and more aerobic exercise than OB during early pregnancy. Both groups maintained training frequency but reduced overall activity as pregnancy progressed. NW women reporting aerobic and/or resistance exercise and OB women reporting aerobic exercise had greater sOB-R increases (independent of BMI or gestational weight gain). In NW, exercise also associated with lower fat mass and leptin increases. Higher activity levels associated with lower gestational weight gain in both groups. The relationship between physical activity and adiponectin differed between NW and OB. https://www.selleckchem.com/ Maternal exercise may partly mediate its beneficial effects through regulation of leptin bioavailability, by enhancing pregnancy-induced increases in sOB-R. This could be of particular importance in OB with pre-gestational hyperleptinemia and leptin resistance.Patients with severe acute liver injury (SLI) usually recover spontaneously. However, some SLI patients progress to acute liver failure with varying degrees of hepatic encephalopathy. Acute liver failure is associated with high mortality and can be substantially reduced by liver transplantation. Therefore, distinguishing SLI patients who might progress to acute liver failure and are at a risk of death is important when evaluating patients needing liver transplantation. The present study aimed to determine whether technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) scintigraphy can predict the prognosis of patients with SLI. This prospective observational study included 69 SLI patients. The accuracy of Tc-99m GSA for predicting death or liver transplantation for 6 months was assessed. Between the two groups of patients stratified based on the cut-off values from the receiver operating characteristic curves, 6-month transplant-free survival was compared. Sixteen (23.2%) patients died or underwent liver transplantation from admission (poor outcome). The hepatic accumulation index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest at 15 min (i.e., LHL15). The LHL15 in the 16 patients (0.686) was significantly lower than that in survivors (0.836; P  less then  0.0001). The optimal LHL15 cut-off for distinguishing poor outcome and survival was 0.737 with a sensitivity of 81.3%, specificity of 88.7%, and area under the curve of 0.907 (95% CI, 0.832-0.981). When patients were divided into two groups based on the LHL15 cut-off value, the 6-month transplant-free survival was significantly lower in patients with an LHL15 level ≤ 0.737. Tc-99m GSA scintigraphy may help predict the prognosis of patients with SLI.The western Arctic Ocean (WAO) has experienced increased heat transport into the region, sea-ice reduction, and changes to the WAO nitrous oxide (N2O) cycles from greenhouse gases. We investigated WAO N2O dynamics through an intensive and precise N2O survey during the open-water season of summer 2017. The effects of physical processes (i.e., solubility and advection) were dominant in both the surface (0-50 m) and deep layers (200-2200 m) of the northern Chukchi Sea with an under-saturation of N2O. By contrast, both the surface layer (0-50 m) of the southern Chukchi Sea and the intermediate (50-200 m) layer of the northern Chukchi Sea were significantly influenced by biogeochemically derived N2O production (i.e., through nitrification), with N2O over-saturation. During summer 2017, the southern region acted as a source of atmospheric N2O (mean + 2.3 ± 2.7 μmol N2O m-2 day-1), whereas the northern region acted as a sink (mean - 1.3 ± 1.5 μmol N2O m-2 day-1). If Arctic environmental changes continue to accelerate and consequently drive the productivity of the Arctic Ocean, the WAO may become a N2O "hot spot", and therefore, a key region requiring continued observations to both understand N2O dynamics and possibly predict their future changes.Cyclic dominance of competing species is an intensively used working hypothesis to explain biodiversity in certain living systems, where the evolutionary selection principle would dictate a single victor otherwise. Technically the May-Leonard models offer a mathematical framework to describe the mentioned non-transitive interaction of competing species when individual movement is also considered in a spatial system. Emerging rotating spirals composed by the competing species are frequently observed character of the resulting patterns. But how do these spiraling patterns change when we vary the external environment which affects the general vitality of individuals? Motivated by this question we suggest an off-lattice version of the tradition May-Leonard model which allows us to change the actual state of the environment gradually. This can be done by introducing a local carrying capacity parameter which value can be varied gently in an off-lattice environment. Our results support a previous analysis obtained in a more intricate metapopulation model and we show that the well-known rotating spirals become evident in a benign environment when the general density of the population is high. The accompanying time-dependent oscillation of competing species can also be detected where the amplitude and the frequency show a scaling law of the parameter that characterizes the state of the environment. These observations highlight that the assumed non-transitive interaction alone is insufficient condition to maintain biodiversity safely, but the actual state of the environment, which characterizes the general living conditions, also plays a decisive role on the evolution of related systems.
    0 Commentarios 0 Acciones 2 Views 0 Vista previa

  • In the past decade, the Korean smoking rate has only decreased by 3%, despite several smoking control policies. There is a need for such policies to take smokers' psychological characteristics into account. Depression is a well-known contributor to failed smoking cessation. This study aimed to examine the effect of smokers' depression status changes on their daily cigarette smoking amount (DCA).

    This study used a sample drawn from the Korea Welfare Panel Study (KoWePS) waves 3 (2008) to 13 (2018). The DCA refers to the number of the cigarettes smoked per day at the time of the survey. Depression was measured using an 11-item version of the Center for Epidemiologic Studies Depression Scale (CESD-11). A generalized estimating equation (GEE) model was employed to analyse the effect of change of depression status on DCA.

    The 2008 baseline included a total of 1821 participants 1645 males and 176 females. The Yes→No male depression status group had lower DCA (β = - 0.631, p-value = 0.0248) than the No→No grou when treating people participating in smoking cessation programs, counsellors should check for depression symptoms and encourage individuals to pursue depression treatment simultaneously.
    Limb-shaking transient ischaemic attacks (TIAs) are an under recognised presentation of severe cerebrovascular disease resulting from cerebral hypoperfusion. https://www.selleckchem.com/products/abt-199.html Patients present with jerking, transitory limb movements precipitated by change in position or exercise that are often confused with seizure. Cerebral perfusion imaging studies are an important tool available to aid diagnosis.

    We present the case of a young female who developed limb-shaking TIA in the context of progressive severe intracranial atherosclerotic disease (ICAD). Previous cortical infarction raised suspicion for seizure as a cause of her symptoms. However, single photon emission CT (SPECT) with CT acetazolamide challenge identified severe left hemisphere cerebral hypoperfusion and a diagnosis of limb-shaking TIA was made. Symptoms improved with maximal medical management.

    This case highlights the importance of cerebral perfusion imaging for diagnostic confirmation as well as therapeutic options available to alleviate symptoms and reduce stroke risk in patients with limb-shaking TIA.
    This case highlights the importance of cerebral perfusion imaging for diagnostic confirmation as well as therapeutic options available to alleviate symptoms and reduce stroke risk in patients with limb-shaking TIA.
    Rheumatic Heart Disease (RHD) is a disease of poverty that is neglected in developing countries, including South Africa. Lack of adequate evidence regarding the cost of RHD care has hindered national and international actions to prevent RHD related deaths. The objective of this study was to estimate the cost of RHD-related health services in a tertiary hospital in the Western Cape, South Africa.

    The primary data on service utilisation were collected from a randomly selected sample of 100 patient medical records from the Global Rheumatic Heart Disease Registry (the REMEDY study) - a registry of individuals living with RHD. Patient-level clinical data, including, prices and quantities of medications and laboratory tests, were collected from the main tertiary hospital providing RHD care. All annual costs from a health system perspective were estimated in 2017 (base year) in South African **** (ZAR) using a combination of ingredients and step-down costing approaches and later converted to United States dollarrimary health centers in order to reduce future tertiary care costs. The study could also inform resource allocation efforts and provide cost estimates for future studies of intervention cost-effectiveness.
    RHD-related healthcare consumes significant tertiary hospital resources in South Africa, with annual per-patient costs higher than many other non-communicable and infectious diseases. This analysis supports the scaling up of primary and secondary prevention programmes at primary health centers in order to reduce future tertiary care costs. The study could also inform resource allocation efforts and provide cost estimates for future studies of intervention cost-effectiveness.
    The Coronavirus Disease 2019 (COVID-19) pandemic has led to a significant decline in Non Communicable Diseases (NCD) screening and early detection activities, especially Cardiovascular Disease (CVD). This study aims to assess the potential of community-based self-screening of CVD risk through the mhealth application.

    This is operational research by actively involving the community to carry out self-screening through the mHealth application. Community health workers were recruited as facilitators who encourage the community to carry out self-screening. To evaluate the potential of community-based self-screening of CVD risk, we use several indicators responses rate, level of CVD risk, and community acceptance.

    Of the 846 individuals reached by the cadres, 53% or 442 individuals carried out self-screening. Based on the results of self-screening of CVD risk, it is known that around 21.3% are at high risk of developing CVD in the next 10 years. The results of the evaluation of semi-structured questions showe policies and community activities.
    The outbreak of Coronavirus Disease 2019(COVID-19) caused psychological stress in Chinese adults population. But we are unaware of whether the pandemic causes psychological stress on children.

    We used the Children's Impact of Event Scale questionnaire (CRIES-13) to investigate the degree of Post-traumatic Stress (PTSD) symptoms caused by the pandemic in students selected from schools in Sichuan, Jiangsu, Henan, Yunnan, and Chongqing provinces of China.

    A total of 7769 students(3692 male and 4077 female), aged 8-18 years, were enrolled in the study, comprising 1214 in primary schools, 2799 in junior high schools and 3756 in senior high schools. A total of 1639 students (21.1%) had severe psychological stress reactions. A large proportion of senior high school students (23.3%) experienced severe psychological stress, and they had the highest median total CRIES-13 score. Female students were more likely to experience severe psychological stress and had higher median CRIES-13 total scores than males.

    COVID-19 has placed psychological stresses on primary and secondary school students in China.
    In the past decade, the Korean smoking rate has only decreased by 3%, despite several smoking control policies. There is a need for such policies to take smokers' psychological characteristics into account. Depression is a well-known contributor to failed smoking cessation. This study aimed to examine the effect of smokers' depression status changes on their daily cigarette smoking amount (DCA). This study used a sample drawn from the Korea Welfare Panel Study (KoWePS) waves 3 (2008) to 13 (2018). The DCA refers to the number of the cigarettes smoked per day at the time of the survey. Depression was measured using an 11-item version of the Center for Epidemiologic Studies Depression Scale (CESD-11). A generalized estimating equation (GEE) model was employed to analyse the effect of change of depression status on DCA. The 2008 baseline included a total of 1821 participants 1645 males and 176 females. The Yes→No male depression status group had lower DCA (β = - 0.631, p-value = 0.0248) than the No→No grou when treating people participating in smoking cessation programs, counsellors should check for depression symptoms and encourage individuals to pursue depression treatment simultaneously. Limb-shaking transient ischaemic attacks (TIAs) are an under recognised presentation of severe cerebrovascular disease resulting from cerebral hypoperfusion. https://www.selleckchem.com/products/abt-199.html Patients present with jerking, transitory limb movements precipitated by change in position or exercise that are often confused with seizure. Cerebral perfusion imaging studies are an important tool available to aid diagnosis. We present the case of a young female who developed limb-shaking TIA in the context of progressive severe intracranial atherosclerotic disease (ICAD). Previous cortical infarction raised suspicion for seizure as a cause of her symptoms. However, single photon emission CT (SPECT) with CT acetazolamide challenge identified severe left hemisphere cerebral hypoperfusion and a diagnosis of limb-shaking TIA was made. Symptoms improved with maximal medical management. This case highlights the importance of cerebral perfusion imaging for diagnostic confirmation as well as therapeutic options available to alleviate symptoms and reduce stroke risk in patients with limb-shaking TIA. This case highlights the importance of cerebral perfusion imaging for diagnostic confirmation as well as therapeutic options available to alleviate symptoms and reduce stroke risk in patients with limb-shaking TIA. Rheumatic Heart Disease (RHD) is a disease of poverty that is neglected in developing countries, including South Africa. Lack of adequate evidence regarding the cost of RHD care has hindered national and international actions to prevent RHD related deaths. The objective of this study was to estimate the cost of RHD-related health services in a tertiary hospital in the Western Cape, South Africa. The primary data on service utilisation were collected from a randomly selected sample of 100 patient medical records from the Global Rheumatic Heart Disease Registry (the REMEDY study) - a registry of individuals living with RHD. Patient-level clinical data, including, prices and quantities of medications and laboratory tests, were collected from the main tertiary hospital providing RHD care. All annual costs from a health system perspective were estimated in 2017 (base year) in South African Rand (ZAR) using a combination of ingredients and step-down costing approaches and later converted to United States dollarrimary health centers in order to reduce future tertiary care costs. The study could also inform resource allocation efforts and provide cost estimates for future studies of intervention cost-effectiveness. RHD-related healthcare consumes significant tertiary hospital resources in South Africa, with annual per-patient costs higher than many other non-communicable and infectious diseases. This analysis supports the scaling up of primary and secondary prevention programmes at primary health centers in order to reduce future tertiary care costs. The study could also inform resource allocation efforts and provide cost estimates for future studies of intervention cost-effectiveness. The Coronavirus Disease 2019 (COVID-19) pandemic has led to a significant decline in Non Communicable Diseases (NCD) screening and early detection activities, especially Cardiovascular Disease (CVD). This study aims to assess the potential of community-based self-screening of CVD risk through the mhealth application. This is operational research by actively involving the community to carry out self-screening through the mHealth application. Community health workers were recruited as facilitators who encourage the community to carry out self-screening. To evaluate the potential of community-based self-screening of CVD risk, we use several indicators responses rate, level of CVD risk, and community acceptance. Of the 846 individuals reached by the cadres, 53% or 442 individuals carried out self-screening. Based on the results of self-screening of CVD risk, it is known that around 21.3% are at high risk of developing CVD in the next 10 years. The results of the evaluation of semi-structured questions showe policies and community activities. The outbreak of Coronavirus Disease 2019(COVID-19) caused psychological stress in Chinese adults population. But we are unaware of whether the pandemic causes psychological stress on children. We used the Children's Impact of Event Scale questionnaire (CRIES-13) to investigate the degree of Post-traumatic Stress (PTSD) symptoms caused by the pandemic in students selected from schools in Sichuan, Jiangsu, Henan, Yunnan, and Chongqing provinces of China. A total of 7769 students(3692 male and 4077 female), aged 8-18 years, were enrolled in the study, comprising 1214 in primary schools, 2799 in junior high schools and 3756 in senior high schools. A total of 1639 students (21.1%) had severe psychological stress reactions. A large proportion of senior high school students (23.3%) experienced severe psychological stress, and they had the highest median total CRIES-13 score. Female students were more likely to experience severe psychological stress and had higher median CRIES-13 total scores than males. COVID-19 has placed psychological stresses on primary and secondary school students in China.
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  • Mutation is the source of genetic variation and the fundament of evolution. Temperature has long been suggested to have a direct impact on realized spontaneous mutation rates. If mutation rates vary in response to environmental conditions, such as the variation of the ambient temperature through space and time, they should no longer be described as species-specific constants. By combining mutation accumulation with whole-genome sequencing in a multicellular organism, we provide empirical support to reject the null hypothesis of a constant, temperature-independent mutation rate. Instead, mutation rates depended on temperature in a U-shaped manner with increasing rates toward both temperature extremes. This relation has important implications for mutation-dependent processes in molecular evolution, processes shaping the evolution of mutation rates, and even the evolution of biodiversity as such.Gut microbial communities can respond to antibiotic perturbations by rapidly altering their taxonomic and functional composition. However, little is known about the strain-level processes that drive this collective response. Here, we characterize the gut microbiome of a single individual at high temporal and genetic resolution through a period of health, disease, antibiotic treatment, and recovery. We used deep, linked-read metagenomic sequencing to track the longitudinal trajectories of thousands of single nucleotide variants within 36 species, which allowed us to contrast these genetic dynamics with the ecological fluctuations at the species level. We found that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. These genetic changes were frequently observed in species without obvious changes in species abundance, emphasizing the importance of monitoring diversity below the species level. We also found that many sweeping variants quickly reverted to their baseline levels once antibiotic treatment had concluded, demonstrating that the ecological resilience of the microbiota can sometimes extend all the way down to the genetic level. Our results provide new insights into the population genetic forces that shape individual microbiomes on therapeutically relevant timescales, with potential implications for personalized health and disease.A wealth of genetic information is available describing single-nucleotide variants in the human population that appear to be well-tolerated and in and of themselves do not confer disease. These variant data sets contain signatures about the protein structure-function relationships and provide an unbiased view of various protein functions in the context of human health. This information can be used to determine regional intolerance to variation, defined as the missense tolerance ratio (MTR), which is an indicator of stretches of the polypeptide chain that can tolerate changes without compromising protein function in a manner that impacts human health. This approach circumvents the lack of comprehensive data by averaging the data from adjacent residues on the polypeptide chain. We reasoned that many motifs in proteins consist of nonadjacent residues, but together function as a unit. We therefore developed an approach to analyze nearest neighbors in three-dimensional space as determined by crystallography rather than on the polypeptide chain. We used members of the GRIN gene family that encode subunits of NMDA-type ionotropic glutamate receptors (iGluRs) to exemplify the differences between these methods. Our method, 3DMTR, provides new information about regions of intolerance within iGluRs, allows consideration of protein-protein interfaces in multimeric proteins, and moves this important research tool from one-dimensional analysis to a structurally relevant tool. We validate the improved 3DMTR score by showing that it more accurately classifies the functional consequences of a set of newly measured and published point mutations of Grin family genes than existing methods.Susumu Ohno proposed that the gene content of the mammalian X Chromosome should remain highly conserved due to dosage compensation. X Chromosome linkage (gene order) conservation is widespread in placental mammals but does not fall within the scope of Ohno's prediction and may be an indirect result of selection on gene content or selection against rearrangements that might disrupt X-Chromosome inactivation (XCI). Previous comparisons between the human and mouse X Chromosome sequences have suggested that although single-copy X Chromosome genes are conserved between species, most ampliconic genes were independently acquired. https://www.selleckchem.com/products/epacadostat-incb024360.html To better understand the evolutionary and functional constraints on X-linked gene content and linkage conservation in placental mammals, we aligned a new, high-quality, long-read X Chromosome reference assembly from the domestic cat (incorporating 19.3 Mb of targeted ****clone sequence) to the pig, human, and mouse assemblies. A comprehensive analysis of annotated X-linked orthologs in public databases demonstrated that the majority of ampliconic gene families were present on the ancestral placental X Chromosome. We generated a domestic cat Hi-C contact map from an F1 domestic cat/Asian leopard cat hybrid and demonstrated the formation of the bipartite structure found in primate and rodent inactivated X Chromosomes. Conservation of gene order and recombination patterns is attributable to strong selective constraints on three-dimensional genomic architecture necessary for superloop formation. Species with rearranged X Chromosomes retain the ancestral order and relative spacing of loci critical for superloop formation during XCI, with compensatory inversions evolving to maintain these long-range physical interactions.Direct comparison of bulk gene expression profiles is complicated by distinct cell type mixtures in each sample which obscure whether observed differences are actually due to changes in expression levels themselves or simply due to differing cell type compositions. Single-cell technology has made it possible to measure gene expression in individual cells, achieving higher resolution at the expense of increased noise. If carefully incorporated, such single-cell data can be used to deconvolve bulk samples to yield accurate estimates of the true cell type proportions, thus enabling one to disentangle the effects of differential expression and cell type mixtures. Here, we propose a generative model and a likelihood-based inference method that uses asymptotic statistical theory and a novel optimization procedure to perform deconvolution of bulk RNA-seq data to produce accurate cell type proportion estimates. We demonstrate the effectiveness of our method, called RNA-Sieve, across a diverse array of scenarios involving real data and discuss extensions made uniquely possible by our probabilistic framework, including a demonstration of well-calibrated confidence intervals.
    Mutation is the source of genetic variation and the fundament of evolution. Temperature has long been suggested to have a direct impact on realized spontaneous mutation rates. If mutation rates vary in response to environmental conditions, such as the variation of the ambient temperature through space and time, they should no longer be described as species-specific constants. By combining mutation accumulation with whole-genome sequencing in a multicellular organism, we provide empirical support to reject the null hypothesis of a constant, temperature-independent mutation rate. Instead, mutation rates depended on temperature in a U-shaped manner with increasing rates toward both temperature extremes. This relation has important implications for mutation-dependent processes in molecular evolution, processes shaping the evolution of mutation rates, and even the evolution of biodiversity as such.Gut microbial communities can respond to antibiotic perturbations by rapidly altering their taxonomic and functional composition. However, little is known about the strain-level processes that drive this collective response. Here, we characterize the gut microbiome of a single individual at high temporal and genetic resolution through a period of health, disease, antibiotic treatment, and recovery. We used deep, linked-read metagenomic sequencing to track the longitudinal trajectories of thousands of single nucleotide variants within 36 species, which allowed us to contrast these genetic dynamics with the ecological fluctuations at the species level. We found that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. These genetic changes were frequently observed in species without obvious changes in species abundance, emphasizing the importance of monitoring diversity below the species level. We also found that many sweeping variants quickly reverted to their baseline levels once antibiotic treatment had concluded, demonstrating that the ecological resilience of the microbiota can sometimes extend all the way down to the genetic level. Our results provide new insights into the population genetic forces that shape individual microbiomes on therapeutically relevant timescales, with potential implications for personalized health and disease.A wealth of genetic information is available describing single-nucleotide variants in the human population that appear to be well-tolerated and in and of themselves do not confer disease. These variant data sets contain signatures about the protein structure-function relationships and provide an unbiased view of various protein functions in the context of human health. This information can be used to determine regional intolerance to variation, defined as the missense tolerance ratio (MTR), which is an indicator of stretches of the polypeptide chain that can tolerate changes without compromising protein function in a manner that impacts human health. This approach circumvents the lack of comprehensive data by averaging the data from adjacent residues on the polypeptide chain. We reasoned that many motifs in proteins consist of nonadjacent residues, but together function as a unit. We therefore developed an approach to analyze nearest neighbors in three-dimensional space as determined by crystallography rather than on the polypeptide chain. We used members of the GRIN gene family that encode subunits of NMDA-type ionotropic glutamate receptors (iGluRs) to exemplify the differences between these methods. Our method, 3DMTR, provides new information about regions of intolerance within iGluRs, allows consideration of protein-protein interfaces in multimeric proteins, and moves this important research tool from one-dimensional analysis to a structurally relevant tool. We validate the improved 3DMTR score by showing that it more accurately classifies the functional consequences of a set of newly measured and published point mutations of Grin family genes than existing methods.Susumu Ohno proposed that the gene content of the mammalian X Chromosome should remain highly conserved due to dosage compensation. X Chromosome linkage (gene order) conservation is widespread in placental mammals but does not fall within the scope of Ohno's prediction and may be an indirect result of selection on gene content or selection against rearrangements that might disrupt X-Chromosome inactivation (XCI). Previous comparisons between the human and mouse X Chromosome sequences have suggested that although single-copy X Chromosome genes are conserved between species, most ampliconic genes were independently acquired. https://www.selleckchem.com/products/epacadostat-incb024360.html To better understand the evolutionary and functional constraints on X-linked gene content and linkage conservation in placental mammals, we aligned a new, high-quality, long-read X Chromosome reference assembly from the domestic cat (incorporating 19.3 Mb of targeted BAC clone sequence) to the pig, human, and mouse assemblies. A comprehensive analysis of annotated X-linked orthologs in public databases demonstrated that the majority of ampliconic gene families were present on the ancestral placental X Chromosome. We generated a domestic cat Hi-C contact map from an F1 domestic cat/Asian leopard cat hybrid and demonstrated the formation of the bipartite structure found in primate and rodent inactivated X Chromosomes. Conservation of gene order and recombination patterns is attributable to strong selective constraints on three-dimensional genomic architecture necessary for superloop formation. Species with rearranged X Chromosomes retain the ancestral order and relative spacing of loci critical for superloop formation during XCI, with compensatory inversions evolving to maintain these long-range physical interactions.Direct comparison of bulk gene expression profiles is complicated by distinct cell type mixtures in each sample which obscure whether observed differences are actually due to changes in expression levels themselves or simply due to differing cell type compositions. Single-cell technology has made it possible to measure gene expression in individual cells, achieving higher resolution at the expense of increased noise. If carefully incorporated, such single-cell data can be used to deconvolve bulk samples to yield accurate estimates of the true cell type proportions, thus enabling one to disentangle the effects of differential expression and cell type mixtures. Here, we propose a generative model and a likelihood-based inference method that uses asymptotic statistical theory and a novel optimization procedure to perform deconvolution of bulk RNA-seq data to produce accurate cell type proportion estimates. We demonstrate the effectiveness of our method, called RNA-Sieve, across a diverse array of scenarios involving real data and discuss extensions made uniquely possible by our probabilistic framework, including a demonstration of well-calibrated confidence intervals.
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  • Mass spectrometry has increasingly been used as a tool to complement studies of sphingolipid metabolism and biological functions in plants and other eukaryotes. https://www.selleckchem.com/products/LBH-589.html Mass spectrometry is now essential for comprehensive sphingolipid analytical profiling because of the huge diversity of sphingolipid classes and molecular species in eukaryotes, particularly in plants. This structural diversity arises from large differences in polar head group glycosylation as well as carbon-chain lengths of fatty acids and desaturation and hydroxylation patterns of fatty acids and long-chain bases that together comprise the ceramide hydrophobic backbone of glycosphingolipids. The standard methods for liquid chromatography-mass spectrometry (LC-MS)-based analyses of Arabidopsis thaliana leaf sphingolipids profile >200 molecular species of four sphingolipid classes and free long-chain bases and their phosphorylated forms. While these methods have proven valuable for A. thaliana based sphingolipid research, we have recently adapted them for use with ultraperformance liquid chromatography separations of molecular species and to profile aberrant sphingolipid forms in pollen, transgenic lines, and mutants. This chapter provides updates to standard methods for LC-MS profiling of A. thaliana sphingolipids to expand the utility of mass spectrometry for plant sphingolipid research.The plant lipidome is highly complex and changes dynamically under the influence of various biotic and abiotic stresses. Targeted analyses based on mass spectrometry enable the detection and characterization of the plant lipidome. It can be analyzed in plant tissues of different developmental stages and from isolated cellular organelles and membranes. Here, we describe a sensitive method to establish the relative abundance of molecular lipid species belonging to three lipid categories glycerolipids, sphingolipids, and sterol lipids. The method is based on a monophasic lipid extraction and includes the derivatization of a few rare and low-abundant lipid classes. The molecular lipid species are resolved by lipid class-specific reverse-phase liquid chromatography and detected by nanoelectrospray ionization coupled with tandem mass spectrometry. The triple quadrupole analyzer is used for detection with multiple reaction monitoring (MRM). Mass transition lists are constructed based on the knowledge of organism-specific lipid building blocks. They are initially determined by classical lipid analytical methods and then used for combinative assembly of all possible lipid structures. The targeted analysis enables detailed and comprehensive profiling of the entire lipid content and composition of plants.Total acyl lipid collision-induced dissociation time-of-flight (TAL-CID-TOF) mass spectrometry uses a quadrupole time-of-flight (QTOF) mass spectrometer to rapidly provide a comprehensive fatty acid composition of a biological lipid extract. Samples are infused into a QTOF instrument, operated in negative mode, and the quadrupole is used to transfer all, or a wide mass range of, precursor ions to the collision cell for fragmentation. Time-of-flight-acquired mass spectra provide mass accuracy and resolution sufficient for chemical formula determination of fatty acids in the complex mixture. Considering the limited number of reasonable CHO variants in fatty acids, one can discern acyl anions with the same nominal mass but different chemical formulas. An online application, LipidomeDB Data Calculation Environment, is employed to process the mass spectral output data and match identified fragments to target fragments at a resolution specified by the user. TAL-CID-TOF methodology is a useful discovery or screening tool to identify and compare fatty acid profiles of biological samples.Direct infusion or "shotgun" mass spectrometry provides a fast strategy to measure different classes of lipids, combining rapid analysis and short idle time. In contrast to liquid chromatography-mass spectrometry (LC-MS), the lipids are infused into the mass spectrometer without prior separation by liquid chromatography. Ions are separated in the quadrupole of a tandem mass spectrometer, and after collision-induced dissociation fragments are quantified relative to internal standards in the third quadrupole or in the time-of-flight mass analyzer of a triple quadrupole or quadrupole time of flight (Q-TOF) mass spectrometer. Abundant lipids, that is, galactolipids and phospholipids in leaves, are measured in crude lipid extracts, while less abundant lipids can be measured after enrichment by solid-phase extraction. Here we describe protocols for the quantification of the major plant glycerolipids (galactolipids, phospholipids, diacylglycerol, and triacylglycerol) using nanospray direct infusion mass spectrometry. This provides a strategy for comprehensive, highly sensitive, high-throughput lipidomic analyses.Algae are ecologically important organisms and are widely used for basic research, with a focus on for example photosynthesis, evolution, and lipid metabolism. Many biosynthetic pathways of algal lipids have been deciphered using available genomic information. Here we describe methods for lipid analyses from three representative algae, including Archaeplastida, the SAR lineage (Stramenopiles, Alveolata, Rhizaria), and Excavata. Archaeplastida acquired their plastids by primary endosymbiosis, and the others by secondary endosymbiosis with a Rhodophyceae-type plastid in SAR and a Chlorophyceae-type plastid in Excavata (Euglenozoa). Analytical methods for these algae are described for membrane lipids and neutral lipids including triacylglycerol and wax esters.Lipids are produced through a dynamic metabolic network involving branch points, cycles, reversible reactions, parallel reactions in different subcellular compartments, and distinct pools of the same lipid class involved in different parts of the network. For example, diacylglycerol (DAG) is a biosynthetic and catabolic intermediate of many different lipid classes. Triacylglycerol can be synthesized from DAG assembled de novo, or from DAG produced by catabolism of membrane lipids, most commonly phosphatidylcholine. Quantification of lipids provides a snapshot of the lipid abundance at the time they were extracted from the given tissue. However, quantification alone does not provide information on the path of carbon flux through the metabolic network to synthesize each lipid. Understanding lipid metabolic flux requires tracing lipid metabolism with isotopically labeled substrates over time in living tissue. [14C]acetate and [14C]glycerol are commonly utilized substrates to measure the flux of nascent fatty acids and glycerol backbones through the lipid metabolic network in vivo.
    Mass spectrometry has increasingly been used as a tool to complement studies of sphingolipid metabolism and biological functions in plants and other eukaryotes. https://www.selleckchem.com/products/LBH-589.html Mass spectrometry is now essential for comprehensive sphingolipid analytical profiling because of the huge diversity of sphingolipid classes and molecular species in eukaryotes, particularly in plants. This structural diversity arises from large differences in polar head group glycosylation as well as carbon-chain lengths of fatty acids and desaturation and hydroxylation patterns of fatty acids and long-chain bases that together comprise the ceramide hydrophobic backbone of glycosphingolipids. The standard methods for liquid chromatography-mass spectrometry (LC-MS)-based analyses of Arabidopsis thaliana leaf sphingolipids profile >200 molecular species of four sphingolipid classes and free long-chain bases and their phosphorylated forms. While these methods have proven valuable for A. thaliana based sphingolipid research, we have recently adapted them for use with ultraperformance liquid chromatography separations of molecular species and to profile aberrant sphingolipid forms in pollen, transgenic lines, and mutants. This chapter provides updates to standard methods for LC-MS profiling of A. thaliana sphingolipids to expand the utility of mass spectrometry for plant sphingolipid research.The plant lipidome is highly complex and changes dynamically under the influence of various biotic and abiotic stresses. Targeted analyses based on mass spectrometry enable the detection and characterization of the plant lipidome. It can be analyzed in plant tissues of different developmental stages and from isolated cellular organelles and membranes. Here, we describe a sensitive method to establish the relative abundance of molecular lipid species belonging to three lipid categories glycerolipids, sphingolipids, and sterol lipids. The method is based on a monophasic lipid extraction and includes the derivatization of a few rare and low-abundant lipid classes. The molecular lipid species are resolved by lipid class-specific reverse-phase liquid chromatography and detected by nanoelectrospray ionization coupled with tandem mass spectrometry. The triple quadrupole analyzer is used for detection with multiple reaction monitoring (MRM). Mass transition lists are constructed based on the knowledge of organism-specific lipid building blocks. They are initially determined by classical lipid analytical methods and then used for combinative assembly of all possible lipid structures. The targeted analysis enables detailed and comprehensive profiling of the entire lipid content and composition of plants.Total acyl lipid collision-induced dissociation time-of-flight (TAL-CID-TOF) mass spectrometry uses a quadrupole time-of-flight (QTOF) mass spectrometer to rapidly provide a comprehensive fatty acid composition of a biological lipid extract. Samples are infused into a QTOF instrument, operated in negative mode, and the quadrupole is used to transfer all, or a wide mass range of, precursor ions to the collision cell for fragmentation. Time-of-flight-acquired mass spectra provide mass accuracy and resolution sufficient for chemical formula determination of fatty acids in the complex mixture. Considering the limited number of reasonable CHO variants in fatty acids, one can discern acyl anions with the same nominal mass but different chemical formulas. An online application, LipidomeDB Data Calculation Environment, is employed to process the mass spectral output data and match identified fragments to target fragments at a resolution specified by the user. TAL-CID-TOF methodology is a useful discovery or screening tool to identify and compare fatty acid profiles of biological samples.Direct infusion or "shotgun" mass spectrometry provides a fast strategy to measure different classes of lipids, combining rapid analysis and short idle time. In contrast to liquid chromatography-mass spectrometry (LC-MS), the lipids are infused into the mass spectrometer without prior separation by liquid chromatography. Ions are separated in the quadrupole of a tandem mass spectrometer, and after collision-induced dissociation fragments are quantified relative to internal standards in the third quadrupole or in the time-of-flight mass analyzer of a triple quadrupole or quadrupole time of flight (Q-TOF) mass spectrometer. Abundant lipids, that is, galactolipids and phospholipids in leaves, are measured in crude lipid extracts, while less abundant lipids can be measured after enrichment by solid-phase extraction. Here we describe protocols for the quantification of the major plant glycerolipids (galactolipids, phospholipids, diacylglycerol, and triacylglycerol) using nanospray direct infusion mass spectrometry. This provides a strategy for comprehensive, highly sensitive, high-throughput lipidomic analyses.Algae are ecologically important organisms and are widely used for basic research, with a focus on for example photosynthesis, evolution, and lipid metabolism. Many biosynthetic pathways of algal lipids have been deciphered using available genomic information. Here we describe methods for lipid analyses from three representative algae, including Archaeplastida, the SAR lineage (Stramenopiles, Alveolata, Rhizaria), and Excavata. Archaeplastida acquired their plastids by primary endosymbiosis, and the others by secondary endosymbiosis with a Rhodophyceae-type plastid in SAR and a Chlorophyceae-type plastid in Excavata (Euglenozoa). Analytical methods for these algae are described for membrane lipids and neutral lipids including triacylglycerol and wax esters.Lipids are produced through a dynamic metabolic network involving branch points, cycles, reversible reactions, parallel reactions in different subcellular compartments, and distinct pools of the same lipid class involved in different parts of the network. For example, diacylglycerol (DAG) is a biosynthetic and catabolic intermediate of many different lipid classes. Triacylglycerol can be synthesized from DAG assembled de novo, or from DAG produced by catabolism of membrane lipids, most commonly phosphatidylcholine. Quantification of lipids provides a snapshot of the lipid abundance at the time they were extracted from the given tissue. However, quantification alone does not provide information on the path of carbon flux through the metabolic network to synthesize each lipid. Understanding lipid metabolic flux requires tracing lipid metabolism with isotopically labeled substrates over time in living tissue. [14C]acetate and [14C]glycerol are commonly utilized substrates to measure the flux of nascent fatty acids and glycerol backbones through the lipid metabolic network in vivo.
    0 Commentarios 0 Acciones 7 Views 0 Vista previa

  • When measured as intractable beliefs, only stronger belief in suicide as a solution to a problem predicted delayed reductions in stress following ideation. Increased intensity of negative emotions immediately following suicidal ideation suggests a potential vicious cycle of heightened emotion intensity and suicidality.We assessed the effects of the COVID19 lockdown on the mental health of transgender and gender non-conforming (TGN) youth (n = 18) vs cisgender youth (29 males; 29 females). Coronavirus Health Impact Survey (CRISIS) and Emotion Regulation Questionnaire were used in an online study. No group differences were found in demographic variables and exposure to COVID19. Negative emotions/feeling increased for all groups. Cisgender youth reported using more adaptive emotion regulation strategies than TGN youth. While the lockdown similarly affected TGN and cisgender youth, the former showed elevated levels of symptomatology and fewer adaptive emotional regulation strategies.Given the prolonged nature of the COVID-19 pandemic, the purpose of this study was to examine the association between posttraumatic growth (PTG) among young adults during the COVID-19 pandemic and their psychosocial characteristics, specifically distress tolerance; resilience; family connectedness; depression, anxiety, and PTSD symptoms; and COVID-19-related worry. The study utilized data from 805 U.S. young adults (18-30 years) who completed online surveys during the COVID-19 pandemic across two waves (April-August 2020 and September 2020-March 2021). Overall, young adults reported low PTG scores. PTSD symptoms and COVID-19-related worry significantly predicted higher levels of PTG, while their depression symptoms predicted lower levels of PTG. Resilience and family connectedness significantly predicted higher levels of PTG, and distress tolerance significantly predicted lower levels of PTG after accounting for sociodemographic characteristics and negative influential factors. Compared to Whites, Asians were less likely to report PTG. In general, young adults have not perceived personal growth from the pandemic; however, young adults with certain psychosocial factors appear to be predisposed to such PTG. This study highlights the importance of exploring and elucidating the potential positive trajectories following the adversity of the COVID-19 pandemic.
    Commuting exposes millions of people to carcinogens from traffic-related air pollution (TRAP) but is seldomly considered in epidemiologic studies of lung cancer. In the prospective United Kingdom (UK) Biobank cohort study, we investigated associations between commute patterns, residential nitrogen dioxide concentrations (NO
    ; a surrogate for TRAP), and lung cancer risk.

    We analyzed 234,124 employed participants at baseline (2006-2010). There were 493 incident lung cancer cases diagnosed over an average 7-year follow-up. Subjects were cross-classified into exclusive categories of commute mode (automobile, public transportation, walking, cycling, active mixture, and other mixture) and frequency (regular 1-4, often ≥5 work-bound trips/week). Annual average residential NO
    concentrations in 2005-2007 were estimated with land use regression. Multivariable Cox regression was used to estimate associations between commute patterns, NO
    quartiles, and incident lung cancer. We conducted analyses stratified by NOlung cancer risk compared to regular automobile users. These results warrant investigations into which component(s) of public transportation contribute to the observed association with increased lung cancer risk.Pharmaceutically active compounds (PhACs) have been shown to accumulate in aquatic and riparian food-webs. Yet, our understanding of how temperature, a key environmental factor in nature, affects uptake, biotransformation, and the subsequent accumulation of PhACs in aquatic organisms is limited. In this study, we tested to what extent bioconcentration of an anxiolytic drugs (temazepam and oxazepam) is affected by two temperature regimes (10 and 20 °C) and how the temperature affects the temazepam biotransformation and subsequent accumulation of its metabolite (oxazepam) in aquatic organisms. We used European perch (Perca fluviatilis) and dragonfly larvae (Sympetrum sp.), which represent predator and prey species of high ecological relevance in food chains of boreal and temperate aquatic ecosystems. Experimental organisms were exposed to target pharmaceuticals at a range of concentrations (0.2-6 µg L-1) to study concentration dependent differences in bioconcentration and biotransformation. https://www.selleckchem.com/JAK.html We found that the bioconcentration of temazepam in perch was significantly reduced at higher temperatures. Also, temperature had a strong effect on temazepam biotransformation in the fish, with the production and subsequent accumulation of its metabolite (oxazepam) being two-fold higher at 20 °C compared to 10 °C. In contrast, we found no temperature dependency for temazepam bioconcentration in dragonfly larvae and no detectable biotransformation of the parent compound that would result in measurable concentrations of oxazepam in this organism. Our results highlight that while organisms may share the same aquatic ecosystem, their exposure to PhACs may change differently across temperature gradients in the environment.Urban areas in the Brazilian Amazon have grown at an unprecedented rate during the last years. About 90% of the wastewater produced by these urban areas are discharged untreated into Amazonian freshwater ecosystems, constituting a potential environmental pathway for pharmaceuticals and other chemicals consumed by modern societies (e.g. psychostimulants, personal-care products, hormones). The distribution of these chemicals into the Amazon River and their potential risks for freshwater biodiversity have not been evaluated so far. Here, we show the results of the largest chemical monitoring campaign conducted in the Amazon region. We assessed exposure patterns for 43 pharmaceuticals and other urban contaminants in 40 sampling sites distributed along the Amazon River, three major tributaries (Negro, Tapajós and Tocantins Rivers), and four large cities of the Brazilian Amazon (Manaus, Santarém, Macapá, Belém). We assessed risks for freshwater biodiversity using species sensitivity distributions and mixture toxicity approaches.
    When measured as intractable beliefs, only stronger belief in suicide as a solution to a problem predicted delayed reductions in stress following ideation. Increased intensity of negative emotions immediately following suicidal ideation suggests a potential vicious cycle of heightened emotion intensity and suicidality.We assessed the effects of the COVID19 lockdown on the mental health of transgender and gender non-conforming (TGN) youth (n = 18) vs cisgender youth (29 males; 29 females). Coronavirus Health Impact Survey (CRISIS) and Emotion Regulation Questionnaire were used in an online study. No group differences were found in demographic variables and exposure to COVID19. Negative emotions/feeling increased for all groups. Cisgender youth reported using more adaptive emotion regulation strategies than TGN youth. While the lockdown similarly affected TGN and cisgender youth, the former showed elevated levels of symptomatology and fewer adaptive emotional regulation strategies.Given the prolonged nature of the COVID-19 pandemic, the purpose of this study was to examine the association between posttraumatic growth (PTG) among young adults during the COVID-19 pandemic and their psychosocial characteristics, specifically distress tolerance; resilience; family connectedness; depression, anxiety, and PTSD symptoms; and COVID-19-related worry. The study utilized data from 805 U.S. young adults (18-30 years) who completed online surveys during the COVID-19 pandemic across two waves (April-August 2020 and September 2020-March 2021). Overall, young adults reported low PTG scores. PTSD symptoms and COVID-19-related worry significantly predicted higher levels of PTG, while their depression symptoms predicted lower levels of PTG. Resilience and family connectedness significantly predicted higher levels of PTG, and distress tolerance significantly predicted lower levels of PTG after accounting for sociodemographic characteristics and negative influential factors. Compared to Whites, Asians were less likely to report PTG. In general, young adults have not perceived personal growth from the pandemic; however, young adults with certain psychosocial factors appear to be predisposed to such PTG. This study highlights the importance of exploring and elucidating the potential positive trajectories following the adversity of the COVID-19 pandemic. Commuting exposes millions of people to carcinogens from traffic-related air pollution (TRAP) but is seldomly considered in epidemiologic studies of lung cancer. In the prospective United Kingdom (UK) Biobank cohort study, we investigated associations between commute patterns, residential nitrogen dioxide concentrations (NO ; a surrogate for TRAP), and lung cancer risk. We analyzed 234,124 employed participants at baseline (2006-2010). There were 493 incident lung cancer cases diagnosed over an average 7-year follow-up. Subjects were cross-classified into exclusive categories of commute mode (automobile, public transportation, walking, cycling, active mixture, and other mixture) and frequency (regular 1-4, often ≥5 work-bound trips/week). Annual average residential NO concentrations in 2005-2007 were estimated with land use regression. Multivariable Cox regression was used to estimate associations between commute patterns, NO quartiles, and incident lung cancer. We conducted analyses stratified by NOlung cancer risk compared to regular automobile users. These results warrant investigations into which component(s) of public transportation contribute to the observed association with increased lung cancer risk.Pharmaceutically active compounds (PhACs) have been shown to accumulate in aquatic and riparian food-webs. Yet, our understanding of how temperature, a key environmental factor in nature, affects uptake, biotransformation, and the subsequent accumulation of PhACs in aquatic organisms is limited. In this study, we tested to what extent bioconcentration of an anxiolytic drugs (temazepam and oxazepam) is affected by two temperature regimes (10 and 20 °C) and how the temperature affects the temazepam biotransformation and subsequent accumulation of its metabolite (oxazepam) in aquatic organisms. We used European perch (Perca fluviatilis) and dragonfly larvae (Sympetrum sp.), which represent predator and prey species of high ecological relevance in food chains of boreal and temperate aquatic ecosystems. Experimental organisms were exposed to target pharmaceuticals at a range of concentrations (0.2-6 µg L-1) to study concentration dependent differences in bioconcentration and biotransformation. https://www.selleckchem.com/JAK.html We found that the bioconcentration of temazepam in perch was significantly reduced at higher temperatures. Also, temperature had a strong effect on temazepam biotransformation in the fish, with the production and subsequent accumulation of its metabolite (oxazepam) being two-fold higher at 20 °C compared to 10 °C. In contrast, we found no temperature dependency for temazepam bioconcentration in dragonfly larvae and no detectable biotransformation of the parent compound that would result in measurable concentrations of oxazepam in this organism. Our results highlight that while organisms may share the same aquatic ecosystem, their exposure to PhACs may change differently across temperature gradients in the environment.Urban areas in the Brazilian Amazon have grown at an unprecedented rate during the last years. About 90% of the wastewater produced by these urban areas are discharged untreated into Amazonian freshwater ecosystems, constituting a potential environmental pathway for pharmaceuticals and other chemicals consumed by modern societies (e.g. psychostimulants, personal-care products, hormones). The distribution of these chemicals into the Amazon River and their potential risks for freshwater biodiversity have not been evaluated so far. Here, we show the results of the largest chemical monitoring campaign conducted in the Amazon region. We assessed exposure patterns for 43 pharmaceuticals and other urban contaminants in 40 sampling sites distributed along the Amazon River, three major tributaries (Negro, Tapajós and Tocantins Rivers), and four large cities of the Brazilian Amazon (Manaus, Santarém, Macapá, Belém). We assessed risks for freshwater biodiversity using species sensitivity distributions and mixture toxicity approaches.
    0 Commentarios 0 Acciones 29 Views 0 Vista previa
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