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  • Further, GTWE inclusion in pork samples (T2 and T3) reduced (p less then 0.05) pH, lipid oxidation and microbial counts, as well as colour loss in meat and bone throughout storage. Chitosan coating with GTWE could be used as an additive for the preservation of pork meat products.The oral cavity of healthy individuals is inhabited by commensals, with species of Streptococcus being the most abundant and prevalent in sites not affected by periodontal diseases. The development of chronic periodontitis is linked with the environmental shift in the oral microbiome, leading to the domination of periodontopathogens. Structure-function studies showed that Streptococcus gordonii employs a "moonlighting" protein glyceraldehyde-3-phosphate dehydrogenase (SgGAPDH) to bind heme, thus forming a heme reservoir for exchange with other proteins. Secreted or surface-associated SgGAPDH coordinates Fe(III)heme using His43. Hemophore-like heme-binding proteins of Porphyromonas gingivalis (HmuY), Prevotella intermedia (PinO) and Tannerella forsythia (Tfo) sequester heme complexed to SgGAPDH. Co-culturing of P. gingivalis with S. gordonii results in increased hmuY gene expression, indicating that HmuY might be required for efficient inter-bacterial interactions. In contrast to the DhmuY mutant strain, the wild type strain acquires heme and forms deeper biofilm structures on blood agar plates pre-grown with S. gordonii. Therefore, our novel paradigm of heme acquisition used by P. gingivalis appears to extend to co-infections with other oral bacteria and offers a mechanism for the ability of periodontopathogens to obtain sufficient heme in the host environment. https://www.selleckchem.com/products/ca3.html Importantly, P. gingivalis is advantaged in terms of acquiring heme, which is vital for its growth survival and virulence.Since the 1980s, molecular biology has been used to investigate medical field mechanisms that still require the use of crude biological materials in order to achieve their necessary goals. Transcription factor-induced pluripotent stem cells are used in regenerative medicine to screen drugs and to support lost tissues. However, these cells insufficiently reconstruct whole organs and require various intact cells, such as damaged livers and diabetic pancreases. For efficient gene transfer in medical use, virally mediated gene transfers are used, although immunogenic issues are investigated. To obtain efficient detective and diagnostic power in intractable diseases, biological tools such as roundworms and zebrafish have been found to be useful for high-throughput screening (HST) and diagnosis. Taken together, this biological approach will help to fill the gaps between medical needs and novel innovations in the field of medicine.Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) ****. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient **** were crossed with TNFtg ****. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient's therapeutic response.Amid the novel coronavirus pandemic, a variety of public health strategies have been implemented by governments worldwide. However, the fact that strict government mandates focus on physical distancing does not mean that social connectedness for voluntary risk communication among citizens should be sacrificed. Furthermore, we lack an understanding of citizens' behaviors regarding the voluntary adoption of public health measures and the control of mental wellbeing in the age of physical distancing. Key variables in the response to the global pandemic are the emergence of risk deliberation networks, voluntary compliance with government guidelines, and the restoration of citizens' subjective health. However, little is known about how citizens' health-related behaviors coevolve with social connections for sharing information and discussing urgent pandemic issues. The findings show that selection and social influence mechanisms coexist by affecting each citizen's health-related behaviors and community-led risk discourses in the face of the urgent health crisis.
    Further, GTWE inclusion in pork samples (T2 and T3) reduced (p less then 0.05) pH, lipid oxidation and microbial counts, as well as colour loss in meat and bone throughout storage. Chitosan coating with GTWE could be used as an additive for the preservation of pork meat products.The oral cavity of healthy individuals is inhabited by commensals, with species of Streptococcus being the most abundant and prevalent in sites not affected by periodontal diseases. The development of chronic periodontitis is linked with the environmental shift in the oral microbiome, leading to the domination of periodontopathogens. Structure-function studies showed that Streptococcus gordonii employs a "moonlighting" protein glyceraldehyde-3-phosphate dehydrogenase (SgGAPDH) to bind heme, thus forming a heme reservoir for exchange with other proteins. Secreted or surface-associated SgGAPDH coordinates Fe(III)heme using His43. Hemophore-like heme-binding proteins of Porphyromonas gingivalis (HmuY), Prevotella intermedia (PinO) and Tannerella forsythia (Tfo) sequester heme complexed to SgGAPDH. Co-culturing of P. gingivalis with S. gordonii results in increased hmuY gene expression, indicating that HmuY might be required for efficient inter-bacterial interactions. In contrast to the DhmuY mutant strain, the wild type strain acquires heme and forms deeper biofilm structures on blood agar plates pre-grown with S. gordonii. Therefore, our novel paradigm of heme acquisition used by P. gingivalis appears to extend to co-infections with other oral bacteria and offers a mechanism for the ability of periodontopathogens to obtain sufficient heme in the host environment. https://www.selleckchem.com/products/ca3.html Importantly, P. gingivalis is advantaged in terms of acquiring heme, which is vital for its growth survival and virulence.Since the 1980s, molecular biology has been used to investigate medical field mechanisms that still require the use of crude biological materials in order to achieve their necessary goals. Transcription factor-induced pluripotent stem cells are used in regenerative medicine to screen drugs and to support lost tissues. However, these cells insufficiently reconstruct whole organs and require various intact cells, such as damaged livers and diabetic pancreases. For efficient gene transfer in medical use, virally mediated gene transfers are used, although immunogenic issues are investigated. To obtain efficient detective and diagnostic power in intractable diseases, biological tools such as roundworms and zebrafish have been found to be useful for high-throughput screening (HST) and diagnosis. Taken together, this biological approach will help to fill the gaps between medical needs and novel innovations in the field of medicine.Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient's therapeutic response.Amid the novel coronavirus pandemic, a variety of public health strategies have been implemented by governments worldwide. However, the fact that strict government mandates focus on physical distancing does not mean that social connectedness for voluntary risk communication among citizens should be sacrificed. Furthermore, we lack an understanding of citizens' behaviors regarding the voluntary adoption of public health measures and the control of mental wellbeing in the age of physical distancing. Key variables in the response to the global pandemic are the emergence of risk deliberation networks, voluntary compliance with government guidelines, and the restoration of citizens' subjective health. However, little is known about how citizens' health-related behaviors coevolve with social connections for sharing information and discussing urgent pandemic issues. The findings show that selection and social influence mechanisms coexist by affecting each citizen's health-related behaviors and community-led risk discourses in the face of the urgent health crisis.
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  • Our investigations enabled us to gain crucial information about the self-assembly of the hydrophobically functionalized poly(acrylic acid) and opened the possibility of understanding and predicting its performance under various conditions.The concept of sentience, how it is characterised and which non-human animals possess it have long been of contention in academic and intellectual debates. Many have argued that there is no way to empirically know that animals have conscious experiences. Yet others argue that consciousness, awareness and sentience in non-human animals can be quite obvious, and can indeed be measured empirically. Most modern declarations of animal sentience from official organisations and governments now include all vertebrate animals as sentient beings, including reptiles and fish. Some declarations also include some invertebrate species. This conceptual, ethical and scientific review first focuses on conceptual components and definitions of consciousness, awareness and sentience. It then specifically discusses how cognitive, neurobiological, ethological and comparative psychological research in non-avian reptiles over the last century has evidenced many capacities that historically were denied to this class of animals. Non-avian reptiles do indeed possess all of the necessary capacities to be declared as sentient beings, at least in the small proportion of reptile species that have actually been empirically investigated so far. It is suggested that **** innovative future research will continue to uncover evidence of capabilities linked to sentience within a wide range of species, including non-avian reptiles, fish and invertebrates.Influences of phosphorus **** from 10% to 50% (by mass) on the setting time and the water requirement of the normal consistency of cement pastes, flowability, resistance to carbonation, and the compressive strength of cement mortars were investigated. The physical activation by improving fineness and the chemical activation by adding the chemical activator were evaluated by the compressive strength of cement mortars with 30% by mass of phosphorus ****. Hydration heat, X-ray diffraction, and scanning electron microscopy were used to study the microstructure of cement pastes and mortars with 30% by mass of phosphorus **** and the chemical activator. Results showed that the setting time of cement pastes was delayed by phosphorus **** from 10% to 50%. Phosphorus **** had nearly no effects on the water requirement of the normal consistency of cement pastes and the flowability of cement mortars. The resistance to carbonation of cement mortars was decreased by phosphorus **** from 10% to 50% according to the acceleration carbonation. The compressive strength of cement mortars was also decreased by phosphorus **** from 10% to 50% and the low activity of phosphorus **** was concluded based on compressive strength of cement mortars. The effect of the chemical activator on the compressive strength of cement mortars with 30% by mass of phosphorus **** was better than improving fineness of phosphorus **** from 300 m2/kg to 450 m2/kg. Both hydration heat and cement hydrates were inhibited by phosphorus **** and could be partly compensated by the chemical activator. Loose morphology and propagations of microcracks were found in cement pastes and mortars with 30% by mass of phosphorus ****.The aim of this study was to compare the efficacy of the intraoperative bending of titanium mesh with the efficacy of pre-contoured "hybrid" patient-specific titanium mesh for the surgical repair of isolated orbital floor fractures. In-house 3D-printed anatomical models were used as bending guides. The main outcome measures were preoperative and postoperative orbital volume and surgery time. We performed a retrospective cohort study including 22 patients who had undergone surgery between May 2016 and November 2018. https://www.selleckchem.com/products/nocodazole.html The first twelve patients underwent conventional reconstruction with intraoperative free-hand bending of an orbital floor mesh plate. The subsequent ten patients received pre-contoured plates based on 3D-printed orbital models that were produced by mirroring the non-fractured orbit of the patient using a medical imaging software. We compared the preoperative and postoperative absolute volume difference (unfractured orbit, fractured orbit), the fracture area, the fracture collapse, and the effective surgery time between the two groups. In comparison to the intraoperative bending of titanium mesh, the application of preformed plates based on a 3D-printed orbital model resulted in a non-significant absolute volume difference in the intervention group (p = 0.276) and statistically significant volume difference in the conventional group (p = 0.002). Further, there was a significant reduction of the surgery time (57.3 ± 23.4 min versus 99.8 ± 28.9 min, p = 0.001). The results of this study suggest that the use of 3D-printed orbital models leads to a more accurate reconstruction and a time reduction during surgery.Light microscopy (LM) is commonly used in the study of biological materials to determine the morphology of cells and tissues. The potential of this technique for studying the structure of food products is also recognized but less known. Especially rare are information regarding LM studies of the supramolecular structure of starch. The aim of the work was to fill this gap by providing data on the possibilities for application of LM in starch studies. It was shown that in spite of an enormous progress in the development of microscopic techniques, including both increase of resolution and improvement of image analysis methods, light microscopy still has a huge potential for starch studies. The advantage of LM over other microscopic techniques is the possibility of differentiating between amylose and amylopectin by iodine staining. That makes LM especially useful in the analysis of the process of gelatinization of starch, the extent of molecular dispersion of its macromolecules, and the changes in its structure caused by modification. Moreover, it can be particularly useful for studying the changes in the supramolecular structure of starch in a food product matrix, providing more information than scanning electron microscopy (SEM)-the most common technique used for these purposes.
    Our investigations enabled us to gain crucial information about the self-assembly of the hydrophobically functionalized poly(acrylic acid) and opened the possibility of understanding and predicting its performance under various conditions.The concept of sentience, how it is characterised and which non-human animals possess it have long been of contention in academic and intellectual debates. Many have argued that there is no way to empirically know that animals have conscious experiences. Yet others argue that consciousness, awareness and sentience in non-human animals can be quite obvious, and can indeed be measured empirically. Most modern declarations of animal sentience from official organisations and governments now include all vertebrate animals as sentient beings, including reptiles and fish. Some declarations also include some invertebrate species. This conceptual, ethical and scientific review first focuses on conceptual components and definitions of consciousness, awareness and sentience. It then specifically discusses how cognitive, neurobiological, ethological and comparative psychological research in non-avian reptiles over the last century has evidenced many capacities that historically were denied to this class of animals. Non-avian reptiles do indeed possess all of the necessary capacities to be declared as sentient beings, at least in the small proportion of reptile species that have actually been empirically investigated so far. It is suggested that much innovative future research will continue to uncover evidence of capabilities linked to sentience within a wide range of species, including non-avian reptiles, fish and invertebrates.Influences of phosphorus slag from 10% to 50% (by mass) on the setting time and the water requirement of the normal consistency of cement pastes, flowability, resistance to carbonation, and the compressive strength of cement mortars were investigated. The physical activation by improving fineness and the chemical activation by adding the chemical activator were evaluated by the compressive strength of cement mortars with 30% by mass of phosphorus slag. Hydration heat, X-ray diffraction, and scanning electron microscopy were used to study the microstructure of cement pastes and mortars with 30% by mass of phosphorus slag and the chemical activator. Results showed that the setting time of cement pastes was delayed by phosphorus slag from 10% to 50%. Phosphorus slag had nearly no effects on the water requirement of the normal consistency of cement pastes and the flowability of cement mortars. The resistance to carbonation of cement mortars was decreased by phosphorus slag from 10% to 50% according to the acceleration carbonation. The compressive strength of cement mortars was also decreased by phosphorus slag from 10% to 50% and the low activity of phosphorus slag was concluded based on compressive strength of cement mortars. The effect of the chemical activator on the compressive strength of cement mortars with 30% by mass of phosphorus slag was better than improving fineness of phosphorus slag from 300 m2/kg to 450 m2/kg. Both hydration heat and cement hydrates were inhibited by phosphorus slag and could be partly compensated by the chemical activator. Loose morphology and propagations of microcracks were found in cement pastes and mortars with 30% by mass of phosphorus slag.The aim of this study was to compare the efficacy of the intraoperative bending of titanium mesh with the efficacy of pre-contoured "hybrid" patient-specific titanium mesh for the surgical repair of isolated orbital floor fractures. In-house 3D-printed anatomical models were used as bending guides. The main outcome measures were preoperative and postoperative orbital volume and surgery time. We performed a retrospective cohort study including 22 patients who had undergone surgery between May 2016 and November 2018. https://www.selleckchem.com/products/nocodazole.html The first twelve patients underwent conventional reconstruction with intraoperative free-hand bending of an orbital floor mesh plate. The subsequent ten patients received pre-contoured plates based on 3D-printed orbital models that were produced by mirroring the non-fractured orbit of the patient using a medical imaging software. We compared the preoperative and postoperative absolute volume difference (unfractured orbit, fractured orbit), the fracture area, the fracture collapse, and the effective surgery time between the two groups. In comparison to the intraoperative bending of titanium mesh, the application of preformed plates based on a 3D-printed orbital model resulted in a non-significant absolute volume difference in the intervention group (p = 0.276) and statistically significant volume difference in the conventional group (p = 0.002). Further, there was a significant reduction of the surgery time (57.3 ± 23.4 min versus 99.8 ± 28.9 min, p = 0.001). The results of this study suggest that the use of 3D-printed orbital models leads to a more accurate reconstruction and a time reduction during surgery.Light microscopy (LM) is commonly used in the study of biological materials to determine the morphology of cells and tissues. The potential of this technique for studying the structure of food products is also recognized but less known. Especially rare are information regarding LM studies of the supramolecular structure of starch. The aim of the work was to fill this gap by providing data on the possibilities for application of LM in starch studies. It was shown that in spite of an enormous progress in the development of microscopic techniques, including both increase of resolution and improvement of image analysis methods, light microscopy still has a huge potential for starch studies. The advantage of LM over other microscopic techniques is the possibility of differentiating between amylose and amylopectin by iodine staining. That makes LM especially useful in the analysis of the process of gelatinization of starch, the extent of molecular dispersion of its macromolecules, and the changes in its structure caused by modification. Moreover, it can be particularly useful for studying the changes in the supramolecular structure of starch in a food product matrix, providing more information than scanning electron microscopy (SEM)-the most common technique used for these purposes.
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  • BACKGROUND AND OBJECTIVE Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (****LD). However, the clinical significance of the positivity of Aspergillus precipitating antibody (APAb), a serodiagnostic test for pulmonary aspergillosis (PA), at the time of ****LD diagnosis is unknown. The objective of this study was to investigate the effects of APAb test results on the clinical outcomes of patients with ****LD. METHODS We retrospectively analyzed patients who were newly diagnosed as having ****LD between 2007 and 2014 in our hospital and checked for APAb at the time of diagnosis. RESULTS We enrolled 131 patients in this study. Of these patients, 20 (15.3%) tested positive for APAb at the diagnosis of ****LD. The APAb-positive patients were more frequently male (70.0% vs. 37.8%, P = 0.013) and more frequently had pulmonary emphysema (60.0% vs. 13.5%, P  less then  0.001) and interstitial pneumonia (15.0% vs. 1.8%, P = 0.025) compared with the APAb-negative patients. During a median follow-up period of 4.0 years, PA developed in 12 of the APAb-positive patients (60.0%, CPA 9 and allergic bronchopulmonary aspergillosis 3) and 12 APAb-negative patients (10.8%, CPA 12) (P  less then  0.001). The APAb-positive patients had a significantly higher rate of mortality than did the APAb-negative patients (P = 0.004). A multivariate analysis indicated that older age, lower albumin, fibrocavitary or fibrocavitary and nodular/bronchiectatic radiographic features, and APAb positivity were negative prognostic factors. CONCLUSIONS APAb-positive patients with ****LD more frequently develop PA and may have an unfavorable prognosis. PURPOSE To investigate the effects of low dose endotoxin on transcriptional activity in intestinal epithelium, and its role in necrotizing enterocolitis (NEC). METHODS Lipopolysaccharides (LPS) were injected into the amniotic cavity of pregnant **** under ultrasound guidance. The effects of LPS on fetal and neonatal intestines were determined. Mouse pups were exposed to low dose LPS (0.01 μg per fetus) prenatally and subjected to experimental NEC after birth. The incidence and severity of NEC, as well as intestinal permeability, NF-κB activation, and IL-6 expression were studied. The signaling pathways in the intestinal epithelial cells (IECs) that were activated by LPS were also investigated. RESULTS Low dose LPS did not increase apoptosis, myeloperoxidase activity, histological injury or NF-κB activity in fetal intestines. However, prenatal low dose LPS exposure disturbed the transient and self-limited activation of NF-κB in neonatal intestines after birth. Importantly, it increased the incidence and severity of experimental NEC in neonatal ****. In primary IECs, low dose LPS induced IRAK-1 expression via activation of GSK3β. Elevated IRAK-1 levels prolonged the activation of IECs upon stimulation by high dose LPS. CONCLUSION Prenatal low dose endotoxin exposure disturbs self-limited postnatal epithelial cell activation and predisposes the neonatal intestine to NEC. LEVEL OF EVIDENCE Not applicable (experimental animal study). BACKGROUND Physician stress impacts patient care and provider wellness. Researchers have largely used reductionist approaches to study stress (e.g. focusing on physiology). This study sought to understand surgeons' subjective experiences of stress in the workplace, using a holistic perspective. METHODS Using a constructivist grounded theory methodology, semi-structured interviews were conducted with 24 staff surgeons at the University of Toronto, purposively sampled for specialties and experience levels. RESULTS The stress experience was reconceptualized as a variable and multidimensional state of fracture, comprised of physiologic, cognitive, emotional, sociocultural, and environmental facets. CONCLUSIONS Reconceptualizing surgeon stress as a multidimensional state of fracture may help surgeons recognize the contributing facets and identify appropriate strategies for promoting wellness and optimizing performance. Two interpretations of similar structures for the same molecular machine illustrate the limits of inferring biochemical mechanism from protein structure. © 2020, Tsai and Hill.Simulations predict a paradoxical effect that should be revealed by patterned stimulation of the cortex. © 2020, Sanzeni and Histed.BACKGROUND Major depressive episodes (MDEs) show diverse cortisol level alterations. Heterogeneity in symptom profiles, symptom severity and cortisol specimens may explain these heterogeneous results. Less severely ill out-patients with a non-melancholic MDE (NM-MDE) may have a variation in the rhythm of cortisol secretion rather than in its concentration. METHOD Cortisol measures were taken (a) over a short-term period (12 h) by measuring daily salivary output using the area under the curve with respect to the ground (AUCg) and (b) over a long-term period (3 months) in hair. Additionally, cortisol reactivity measures in saliva - the cortisol awakening response and the 30 min delta cortisol secretion after awakening (DELTA) - were investigated in 19 patients with a melancholic MDE (M-MDE) and 52 with a NM-MDE, and in 40 matched controls who were recruited from the UK and Chile. Depression severity scores were correlated with different cortisol measures. RESULTS The NM-MDE group showed a decreased AUCg in comparison with controls (P = 0.02), but normal cortisol reactivity and long-term cortisol levels. https://www.selleckchem.com/products/azd6738.html The M-MDE group did not exhibit any significant cortisol alterations nor an association with depression severity scores. Higher Hamilton Rating Scale for Depression score was linked with decreased hair cortisol concentration (HCC, P = 0.05) and higher DELTA (P = 0.04) in NM-MDEs, whereas decreased HCC was the sole alteration associated with out-patients with severe M-MDEs. CONCLUSIONS The contrasting short- and long-term cortisol output results are compatible with an alteration in the rhythm of cortisol secretion in NM-MDEs. This alteration may consist of large and/or intense episodes of hypercortisolaemia in moderate NM-MDEs and frequent, but brief and sharp early-morning DELTAs in its severe form. These changes may reflect the effects of environmental factors or episodes of nocturnal hypercortisolaemia that were not measured by the short-term samples used in this study.
    BACKGROUND AND OBJECTIVE Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). However, the clinical significance of the positivity of Aspergillus precipitating antibody (APAb), a serodiagnostic test for pulmonary aspergillosis (PA), at the time of MAC-LD diagnosis is unknown. The objective of this study was to investigate the effects of APAb test results on the clinical outcomes of patients with MAC-LD. METHODS We retrospectively analyzed patients who were newly diagnosed as having MAC-LD between 2007 and 2014 in our hospital and checked for APAb at the time of diagnosis. RESULTS We enrolled 131 patients in this study. Of these patients, 20 (15.3%) tested positive for APAb at the diagnosis of MAC-LD. The APAb-positive patients were more frequently male (70.0% vs. 37.8%, P = 0.013) and more frequently had pulmonary emphysema (60.0% vs. 13.5%, P  less then  0.001) and interstitial pneumonia (15.0% vs. 1.8%, P = 0.025) compared with the APAb-negative patients. During a median follow-up period of 4.0 years, PA developed in 12 of the APAb-positive patients (60.0%, CPA 9 and allergic bronchopulmonary aspergillosis 3) and 12 APAb-negative patients (10.8%, CPA 12) (P  less then  0.001). The APAb-positive patients had a significantly higher rate of mortality than did the APAb-negative patients (P = 0.004). A multivariate analysis indicated that older age, lower albumin, fibrocavitary or fibrocavitary and nodular/bronchiectatic radiographic features, and APAb positivity were negative prognostic factors. CONCLUSIONS APAb-positive patients with MAC-LD more frequently develop PA and may have an unfavorable prognosis. PURPOSE To investigate the effects of low dose endotoxin on transcriptional activity in intestinal epithelium, and its role in necrotizing enterocolitis (NEC). METHODS Lipopolysaccharides (LPS) were injected into the amniotic cavity of pregnant mice under ultrasound guidance. The effects of LPS on fetal and neonatal intestines were determined. Mouse pups were exposed to low dose LPS (0.01 μg per fetus) prenatally and subjected to experimental NEC after birth. The incidence and severity of NEC, as well as intestinal permeability, NF-κB activation, and IL-6 expression were studied. The signaling pathways in the intestinal epithelial cells (IECs) that were activated by LPS were also investigated. RESULTS Low dose LPS did not increase apoptosis, myeloperoxidase activity, histological injury or NF-κB activity in fetal intestines. However, prenatal low dose LPS exposure disturbed the transient and self-limited activation of NF-κB in neonatal intestines after birth. Importantly, it increased the incidence and severity of experimental NEC in neonatal mice. In primary IECs, low dose LPS induced IRAK-1 expression via activation of GSK3β. Elevated IRAK-1 levels prolonged the activation of IECs upon stimulation by high dose LPS. CONCLUSION Prenatal low dose endotoxin exposure disturbs self-limited postnatal epithelial cell activation and predisposes the neonatal intestine to NEC. LEVEL OF EVIDENCE Not applicable (experimental animal study). BACKGROUND Physician stress impacts patient care and provider wellness. Researchers have largely used reductionist approaches to study stress (e.g. focusing on physiology). This study sought to understand surgeons' subjective experiences of stress in the workplace, using a holistic perspective. METHODS Using a constructivist grounded theory methodology, semi-structured interviews were conducted with 24 staff surgeons at the University of Toronto, purposively sampled for specialties and experience levels. RESULTS The stress experience was reconceptualized as a variable and multidimensional state of fracture, comprised of physiologic, cognitive, emotional, sociocultural, and environmental facets. CONCLUSIONS Reconceptualizing surgeon stress as a multidimensional state of fracture may help surgeons recognize the contributing facets and identify appropriate strategies for promoting wellness and optimizing performance. Two interpretations of similar structures for the same molecular machine illustrate the limits of inferring biochemical mechanism from protein structure. © 2020, Tsai and Hill.Simulations predict a paradoxical effect that should be revealed by patterned stimulation of the cortex. © 2020, Sanzeni and Histed.BACKGROUND Major depressive episodes (MDEs) show diverse cortisol level alterations. Heterogeneity in symptom profiles, symptom severity and cortisol specimens may explain these heterogeneous results. Less severely ill out-patients with a non-melancholic MDE (NM-MDE) may have a variation in the rhythm of cortisol secretion rather than in its concentration. METHOD Cortisol measures were taken (a) over a short-term period (12 h) by measuring daily salivary output using the area under the curve with respect to the ground (AUCg) and (b) over a long-term period (3 months) in hair. Additionally, cortisol reactivity measures in saliva - the cortisol awakening response and the 30 min delta cortisol secretion after awakening (DELTA) - were investigated in 19 patients with a melancholic MDE (M-MDE) and 52 with a NM-MDE, and in 40 matched controls who were recruited from the UK and Chile. Depression severity scores were correlated with different cortisol measures. RESULTS The NM-MDE group showed a decreased AUCg in comparison with controls (P = 0.02), but normal cortisol reactivity and long-term cortisol levels. https://www.selleckchem.com/products/azd6738.html The M-MDE group did not exhibit any significant cortisol alterations nor an association with depression severity scores. Higher Hamilton Rating Scale for Depression score was linked with decreased hair cortisol concentration (HCC, P = 0.05) and higher DELTA (P = 0.04) in NM-MDEs, whereas decreased HCC was the sole alteration associated with out-patients with severe M-MDEs. CONCLUSIONS The contrasting short- and long-term cortisol output results are compatible with an alteration in the rhythm of cortisol secretion in NM-MDEs. This alteration may consist of large and/or intense episodes of hypercortisolaemia in moderate NM-MDEs and frequent, but brief and sharp early-morning DELTAs in its severe form. These changes may reflect the effects of environmental factors or episodes of nocturnal hypercortisolaemia that were not measured by the short-term samples used in this study.
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  • Understanding the different effects of chemical substances on human proteins is fundamental for designing new drugs. It is also important for elucidating the different mechanisms of action of drugs that can cause side-effects. In this context, computational methods for predicting chemical-protein interactions can provide valuable insights on the relation between therapeutic chemical substances and proteins. Their predictions therefore can help in multiple tasks such as drug repurposing, identifying new drug side-effects, etc. Despite their useful predictions, these methods are unable to predict the different implications - such as change in protein expression, abundance, etc, - of chemical - protein interactions. Therefore, In this work, we study the modelling of chemical-protein interactions' effects on proteins activity using computational approaches. We hereby propose using 3D tensors to model chemicals, their target proteins and the effects associated to their interactions. https://www.selleckchem.com/products/SB-431542.html We then use multi-part embedding tensor factorisation to predict the different effects of chemicals on human proteins. We assess the predictive accuracy of our proposed method using a benchmark dataset that we built. We then show by computational experimental evaluation that our approach outperforms other tensor factorisation methods in the task of predicting effects of chemicals on human proteins.Research to support precision medicine for leukemia patients requires integration of biospecimen and clinical data. The Observational Medical Outcomes Partnership common data model (OMOP CDM) and its Specimen table presents a potential solution. Although researchers have described progress and challenges in mapping electronic health record (EHR) data to populate the OMOP CDM, to our knowledge no studies have described populating the OMOP CDM with biospecimen data. Using biobank data from our institution, we mapped 26% of biospecimen records to the OMOP Specimen table. Records failed mapping due to local codes for time point that were incompatible with the OMOP reference terminology. We recommend expanding allowable codes to encompass research data, adding foreign keys to leverage additional OMOP tables with data from other sources or to store additional specimen details, and considering a new table to represent processed samples and inventory.Machine learning methods have recently achieved high-performance in biomedical text analysis. However, a major bottleneck in the widespread application of these methods is obtaining the required large amounts of annotated training data, which is resource intensive and time consuming. Recent progress in self-supervised learning has shown promise in leveraging large text corpora without explicit annotations. In this work, we built a self-supervised contextual language representation model using BERT, a deep bidirectional transformer architecture, to identify radiology reports requiring prompt communication to the referring physicians. We pre-trained the BERT model on a large unlabeled corpus of radiology reports and used the resulting contextual representations in a final text classifier for communication urgency. Our model achieved a precision of 97.0%, recall of 93.3%, and F-measure of 95.1% on an independent test set in identifying radiology reports for prompt communication, and significantly outperformed the previous state-of-the-art model based on word2vec representations.This paper introduces a database derived from Structured Product Labels (SPLs). SPLs are legally mandated snapshots containing information on all drugs released to market in the United States. Since publication is not required for pre-trial findings, we hypothesize that SPLs may contain knowledge absent in the literature, and hence "novel." SemMedDB is an existing database of computable knowledge derived from the literature. If SPL content could be similarly transformed, novel clinically relevant assertions in the SPLs could be identified through comparison with SemMedDB. After we derive a database (containing 4,297,481 assertions), we compare the extracted content with SemMedDB for recent FDA drug approvals. We find that novelty between the SPLs and the literature is nuanced, due to the redundancy of SPLs. Highlighting areas for improvement and future work, we conclude that SPLs contain a wealth of novel knowledge relevant to research and complementary to the literature.This study investigates the use of machine learning methods for classifying and extracting structured information from laboratory reports stored as semi-structured point-form English text. This is a novel data format that has not been evaluated in conjunction with machine learning classifiers in previous literature. Our classifiers achieve human-level predictive accuracy on the binary Test Performed and 4-class Test Outcome labels. We consider symbolic approaches for predicting the highly multi-class Organism Genus and Organism Species labels. Results are discussed from the viewpoint of interpretability and generalizability to new incoming laboratory reports. Code has been made public at https//github.com/enchainingrealm/UbcDssgBccdc-Research/tree/master/src.Seamless sharing between imaging facilities of medical images obtained on the same patient is crucial in providing accurate and efficient care to patients. However, the terminology used to describe semantically similar examinations can vary widely between facilities. Current practice is manual table-based mapping to a standard terminology, which has substantial potential for mislabelled and missing examinations. In this work, we establish several baseline methods for automating the mapping of radiology imaging procedure descriptions to a SNOMED CT based standard terminology. Our best performing baseline, consisting of a bag of words representation and shallow neural network, achieved 96.3% accuracy. In addition, we explore an unsupervised clustering method that explores relevancy matching without the need for an intervening standard. Lastly, we make the procedure name dataset used in this work available to encourage extension of this application.
    Understanding the different effects of chemical substances on human proteins is fundamental for designing new drugs. It is also important for elucidating the different mechanisms of action of drugs that can cause side-effects. In this context, computational methods for predicting chemical-protein interactions can provide valuable insights on the relation between therapeutic chemical substances and proteins. Their predictions therefore can help in multiple tasks such as drug repurposing, identifying new drug side-effects, etc. Despite their useful predictions, these methods are unable to predict the different implications - such as change in protein expression, abundance, etc, - of chemical - protein interactions. Therefore, In this work, we study the modelling of chemical-protein interactions' effects on proteins activity using computational approaches. We hereby propose using 3D tensors to model chemicals, their target proteins and the effects associated to their interactions. https://www.selleckchem.com/products/SB-431542.html We then use multi-part embedding tensor factorisation to predict the different effects of chemicals on human proteins. We assess the predictive accuracy of our proposed method using a benchmark dataset that we built. We then show by computational experimental evaluation that our approach outperforms other tensor factorisation methods in the task of predicting effects of chemicals on human proteins.Research to support precision medicine for leukemia patients requires integration of biospecimen and clinical data. The Observational Medical Outcomes Partnership common data model (OMOP CDM) and its Specimen table presents a potential solution. Although researchers have described progress and challenges in mapping electronic health record (EHR) data to populate the OMOP CDM, to our knowledge no studies have described populating the OMOP CDM with biospecimen data. Using biobank data from our institution, we mapped 26% of biospecimen records to the OMOP Specimen table. Records failed mapping due to local codes for time point that were incompatible with the OMOP reference terminology. We recommend expanding allowable codes to encompass research data, adding foreign keys to leverage additional OMOP tables with data from other sources or to store additional specimen details, and considering a new table to represent processed samples and inventory.Machine learning methods have recently achieved high-performance in biomedical text analysis. However, a major bottleneck in the widespread application of these methods is obtaining the required large amounts of annotated training data, which is resource intensive and time consuming. Recent progress in self-supervised learning has shown promise in leveraging large text corpora without explicit annotations. In this work, we built a self-supervised contextual language representation model using BERT, a deep bidirectional transformer architecture, to identify radiology reports requiring prompt communication to the referring physicians. We pre-trained the BERT model on a large unlabeled corpus of radiology reports and used the resulting contextual representations in a final text classifier for communication urgency. Our model achieved a precision of 97.0%, recall of 93.3%, and F-measure of 95.1% on an independent test set in identifying radiology reports for prompt communication, and significantly outperformed the previous state-of-the-art model based on word2vec representations.This paper introduces a database derived from Structured Product Labels (SPLs). SPLs are legally mandated snapshots containing information on all drugs released to market in the United States. Since publication is not required for pre-trial findings, we hypothesize that SPLs may contain knowledge absent in the literature, and hence "novel." SemMedDB is an existing database of computable knowledge derived from the literature. If SPL content could be similarly transformed, novel clinically relevant assertions in the SPLs could be identified through comparison with SemMedDB. After we derive a database (containing 4,297,481 assertions), we compare the extracted content with SemMedDB for recent FDA drug approvals. We find that novelty between the SPLs and the literature is nuanced, due to the redundancy of SPLs. Highlighting areas for improvement and future work, we conclude that SPLs contain a wealth of novel knowledge relevant to research and complementary to the literature.This study investigates the use of machine learning methods for classifying and extracting structured information from laboratory reports stored as semi-structured point-form English text. This is a novel data format that has not been evaluated in conjunction with machine learning classifiers in previous literature. Our classifiers achieve human-level predictive accuracy on the binary Test Performed and 4-class Test Outcome labels. We consider symbolic approaches for predicting the highly multi-class Organism Genus and Organism Species labels. Results are discussed from the viewpoint of interpretability and generalizability to new incoming laboratory reports. Code has been made public at https//github.com/enchainingrealm/UbcDssgBccdc-Research/tree/master/src.Seamless sharing between imaging facilities of medical images obtained on the same patient is crucial in providing accurate and efficient care to patients. However, the terminology used to describe semantically similar examinations can vary widely between facilities. Current practice is manual table-based mapping to a standard terminology, which has substantial potential for mislabelled and missing examinations. In this work, we establish several baseline methods for automating the mapping of radiology imaging procedure descriptions to a SNOMED CT based standard terminology. Our best performing baseline, consisting of a bag of words representation and shallow neural network, achieved 96.3% accuracy. In addition, we explore an unsupervised clustering method that explores relevancy matching without the need for an intervening standard. Lastly, we make the procedure name dataset used in this work available to encourage extension of this application.
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  • Malnutrition due to persistent food insecurity has been a serious public health issue in Kenya. An unconditional cash transfer programme, the Hunger Safety Net Programme (HSNP), was launched in 2009 in northern Kenya to reduce extreme poverty and to mitigate food insecurity. This study investigates the impact of the HSNP, on expenditure on food, types of food consumed and nutritional intake. Focusing on nutritional intake as well as spending and consumption is important because an unconditional cash transfer, which does not specify how the transferred money must be used, does not guarantee nutritional intake improvement. Converting food consumption data to caloric intake and nutrient content using food consumption databases, we calculate the intake of five macro-nutrients, seven vitamins and seven minerals and then estimate the impacts on nutritional intake 12 and 24 months after treatment exposure. This study finds the increased total expenditure on food items. Specifically, the beneficiary households increased their expenditure on milk and milk products and that on sugar after 12 months and expenditure on roots and tubers after 24 months. For consumption amounts, however, the HSNP did not show significant increases in all food categories except sugar. On the other hand, the HSNP improved the nutritional intakes of some macro- and micro-nutrients. The results show that beneficiary households substantially increased their intake of fat by 25.2% after 24 months and their intake of vitamin B12 by 36.6% and calcium by 34.9% after 12 months. The result does not yield sufficiently strong evidence that poorer households significantly enjoy greater improvements than other households.Musca domestica (Linnaeus, 1758) is a muscoid species that is widespread throughout the world and acts as a mechanical vector of different enteropathogens primarily in underdeveloped countries. The adult and its immature forms are associated with decaying organic matter and can be seen visiting human corpses and animal carcass, and the larvae can also cause an infestation on human and animal wounds, feeding on the tissues. These characteristics make them have a forensic significance and, mainly, a great sanitary importance. This study aimed to analyze and describe morphological aspects of their immature stages of M. domestica, including the eggs, the first-, second-, and third-instar larvae, and the puparium using scanning electron microscopy (SEM). The eggs have standard format that all muscoid flies shared. The exochorion has some modified cells that were used for embryonic respiration. https://www.selleckchem.com/products/chaetocin.html The first-instar larvae present two openings on the posterior spiracle as in the second-instar larvae, but with the last one, we can observe the anterior spiracle structure. The third-instar larvae, as in some other Muscidae species, have a posterior spiracular opening with a sinuous form that is located near the edge of the spiracular plate. The puparium morphology is equal to the third instar with a respiratory structure that helps the breathing during the metamorphosis process. This article supports the need for knowledge over the morphological characteristics of the immature forms of the muscoid Diptera (Linnaeus, 1758) at the same time helping with the correct identification of this insect phase.Background CMV-specific CD8+ T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown. Methods CMV-specific CD8+ T-cell responses were assessed in neonates with cCMV using QuantiFERON®-CMV assay, within day 14th of life (T0) and during the second month of life (T1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON®-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels. Results Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T0 16/30 (53%) subjects had a reactive QuantiFERON®-CMV result and 16/16 (100%) were asymptomatic, while 14/30 (47%) had a non-reactive or indeterminate QuantiFERON®-CMV result and 4/14 (29%) were asymptomatic. At T1, 17/29 (59%) subjects had a reactive QuantiFERON®-CMV result and 17/17 (100%) were asymptomatic, while 12/29 (41%) had a non-reactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T0 and T1 reactive QuantiFERON®-CMV results correlated with lack of symptoms (P=0.0001). At T1 median CMV DNAemia was lower in subjects with reactive QuantiFERON®-CMV results as compared with subjects with non-reactive or indeterminate results (1.82 log IU/mL [1.82-2.89] versus 2.55 log IU/mL [1.82-4.42], P=0.009). No correlation was found between QuantiFERON®-CMV results and gestational age at maternal infection nor with urine CMV DNA levels. Conclusions A detectable CMV-specific CD8+ T-cell response, evaluated using the QuantiFERON®-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemia.In Myotonic Dystrophy Type 1 (DM1), the CUG expansion (CUGexp) in the 3'UTR of the dystrophia myotonica protein kinase (DMPK) mRNAs affects the homeostasis of RNA-binding proteins, causing the multiple symptoms of DM1. We have previously reported that Staufen1 is increased in skeletal muscles from DM1 **** and patients, and that sustained Staufen1 expression in mature mouse muscle causes a progressive myopathy. Here, we hypothesized that the elevated levels of Staufen1 contributes to the myopathic features of the disease. Interestingly, the classic DM1 mouse model HSALR lacks overt atrophy while expressing CUGexp transcripts and elevated levels of endogenous Staufen1, suggesting a lower sensitivity to atrophic signaling in this model. We report that further overexpression of Staufen1 in the DM1 mouse model HSALR, causes a myopathy via inhibition of Akt signaling through an increase in PTEN, leading to the expression of atrogenes. Interestingly, we also show that Staufen1 regulates the expression of MBNL1 and CELF1 in wild-type and DM1 skeletal muscle. Together, data obtained from these new DM1 mouse models provide evidence for the role of Staufen1 as an atrophy-associated gene that impacts progressive muscle wasting in DM1. Accordingly, our findings highlight the potential of Staufen1 as a therapeutic target and biomarker.
    Malnutrition due to persistent food insecurity has been a serious public health issue in Kenya. An unconditional cash transfer programme, the Hunger Safety Net Programme (HSNP), was launched in 2009 in northern Kenya to reduce extreme poverty and to mitigate food insecurity. This study investigates the impact of the HSNP, on expenditure on food, types of food consumed and nutritional intake. Focusing on nutritional intake as well as spending and consumption is important because an unconditional cash transfer, which does not specify how the transferred money must be used, does not guarantee nutritional intake improvement. Converting food consumption data to caloric intake and nutrient content using food consumption databases, we calculate the intake of five macro-nutrients, seven vitamins and seven minerals and then estimate the impacts on nutritional intake 12 and 24 months after treatment exposure. This study finds the increased total expenditure on food items. Specifically, the beneficiary households increased their expenditure on milk and milk products and that on sugar after 12 months and expenditure on roots and tubers after 24 months. For consumption amounts, however, the HSNP did not show significant increases in all food categories except sugar. On the other hand, the HSNP improved the nutritional intakes of some macro- and micro-nutrients. The results show that beneficiary households substantially increased their intake of fat by 25.2% after 24 months and their intake of vitamin B12 by 36.6% and calcium by 34.9% after 12 months. The result does not yield sufficiently strong evidence that poorer households significantly enjoy greater improvements than other households.Musca domestica (Linnaeus, 1758) is a muscoid species that is widespread throughout the world and acts as a mechanical vector of different enteropathogens primarily in underdeveloped countries. The adult and its immature forms are associated with decaying organic matter and can be seen visiting human corpses and animal carcass, and the larvae can also cause an infestation on human and animal wounds, feeding on the tissues. These characteristics make them have a forensic significance and, mainly, a great sanitary importance. This study aimed to analyze and describe morphological aspects of their immature stages of M. domestica, including the eggs, the first-, second-, and third-instar larvae, and the puparium using scanning electron microscopy (SEM). The eggs have standard format that all muscoid flies shared. The exochorion has some modified cells that were used for embryonic respiration. https://www.selleckchem.com/products/chaetocin.html The first-instar larvae present two openings on the posterior spiracle as in the second-instar larvae, but with the last one, we can observe the anterior spiracle structure. The third-instar larvae, as in some other Muscidae species, have a posterior spiracular opening with a sinuous form that is located near the edge of the spiracular plate. The puparium morphology is equal to the third instar with a respiratory structure that helps the breathing during the metamorphosis process. This article supports the need for knowledge over the morphological characteristics of the immature forms of the muscoid Diptera (Linnaeus, 1758) at the same time helping with the correct identification of this insect phase.Background CMV-specific CD8+ T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown. Methods CMV-specific CD8+ T-cell responses were assessed in neonates with cCMV using QuantiFERON®-CMV assay, within day 14th of life (T0) and during the second month of life (T1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON®-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels. Results Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T0 16/30 (53%) subjects had a reactive QuantiFERON®-CMV result and 16/16 (100%) were asymptomatic, while 14/30 (47%) had a non-reactive or indeterminate QuantiFERON®-CMV result and 4/14 (29%) were asymptomatic. At T1, 17/29 (59%) subjects had a reactive QuantiFERON®-CMV result and 17/17 (100%) were asymptomatic, while 12/29 (41%) had a non-reactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T0 and T1 reactive QuantiFERON®-CMV results correlated with lack of symptoms (P=0.0001). At T1 median CMV DNAemia was lower in subjects with reactive QuantiFERON®-CMV results as compared with subjects with non-reactive or indeterminate results (1.82 log IU/mL [1.82-2.89] versus 2.55 log IU/mL [1.82-4.42], P=0.009). No correlation was found between QuantiFERON®-CMV results and gestational age at maternal infection nor with urine CMV DNA levels. Conclusions A detectable CMV-specific CD8+ T-cell response, evaluated using the QuantiFERON®-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemia.In Myotonic Dystrophy Type 1 (DM1), the CUG expansion (CUGexp) in the 3'UTR of the dystrophia myotonica protein kinase (DMPK) mRNAs affects the homeostasis of RNA-binding proteins, causing the multiple symptoms of DM1. We have previously reported that Staufen1 is increased in skeletal muscles from DM1 mice and patients, and that sustained Staufen1 expression in mature mouse muscle causes a progressive myopathy. Here, we hypothesized that the elevated levels of Staufen1 contributes to the myopathic features of the disease. Interestingly, the classic DM1 mouse model HSALR lacks overt atrophy while expressing CUGexp transcripts and elevated levels of endogenous Staufen1, suggesting a lower sensitivity to atrophic signaling in this model. We report that further overexpression of Staufen1 in the DM1 mouse model HSALR, causes a myopathy via inhibition of Akt signaling through an increase in PTEN, leading to the expression of atrogenes. Interestingly, we also show that Staufen1 regulates the expression of MBNL1 and CELF1 in wild-type and DM1 skeletal muscle. Together, data obtained from these new DM1 mouse models provide evidence for the role of Staufen1 as an atrophy-associated gene that impacts progressive muscle wasting in DM1. Accordingly, our findings highlight the potential of Staufen1 as a therapeutic target and biomarker.
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  • 5 (95% CI 0.4-2.6) mm in proximal direction, -0.6 (CI -1.6 to 0.4) in the medial direction and 0.3 (CI 0.0-0.6) in the anterior direction. The mean volume of impacted bone graft was 40 cm³ (CI 28-52). In the graft bone mineral density increased 14% after 6 weeks and 23% after 2 years. There was 1 mechanical failure.Interpretation - Proximal migration of the acetabular component was low and comparable to previous reports. There was a rapid increase of bone mineral density in the bone graft. Low-dose CT scans make migration analysis and bone densitometry measurements possible in the same setting, offering great diagnostic potential for hip arthroplasty patients.A 70-year-old man was referred to our hospital for an abnormal chest shadow. Enhanced computed tomography (CT) revealed 2-humped bronchial artery aneurysms (BAAs) associated with racemose hemangioma. The combined therapy of transcatheter bronchial artery embolization and thoracic endovascular aortic repair was performed. Postoperative CT confirmed the complete exclusion of the aneurysms with no evidence of an endoleak. Our result suggests that this combined therapy is a safe and effective treatment for BAA.Early abortion in ovine toxoplasmosis has had limited investigation. This study evaluated the immune response in the placenta of sheep orally infected with Toxoplasma gondii and euthanized between 2 and 4 weeks postinfection. Toxoplasma infection of the placenta was only found at 4 weeks after infection. Parasitic debris in foci of necrosis were immunolabeled in the maternal caruncle, whereas well-preserved intracellular parasitic vacuole-like structures were found in trophoblasts of fetal cotyledon. Early abortions had increased macrophages in caruncular septa, whereas in later abortions the placentas containing the parasite had an increase of T lymphocytes and macrophages mainly in the fetal cotyledons. This study suggests that the immune response in both the fetal and maternal compartments of the placenta may contribute to the pathogenesis of ovine toxoplasmosis and that these responses differ between early and late presentations of the disease.Ultrasound-guided thrombin injection (UGTI) has emerged as the first-line treatment for moderately sized or persistent pseudoaneurysms (PSAs). https://www.selleckchem.com/products/cordycepin.html Although rare, the most feared complication of UGTI is arterial thrombosis or embolism during the off-label injection of thrombin causing acute limb ischemia requiring emergent surgical intervention. Higher thrombin volume, rapidity of injection, and wide or short-neck PSAs are all thought to increase the risk of arterial thrombosis or embolism during this procedure. For patients with unfavorable PSA anatomy who are high-risk surgical candidates due to their medical comorbidities or active critical illness, balloon-assisted thrombin injection (BATI) has been suggested as a means to potentially reduce the risk of thrombosis or distal embolization associated with UGTI. This minimally invasive technique also decreases the risk of groin wound dehiscence or infection associated with open repair, especially in patients who are morbidly obese or have had prior groin surgery. We report a patient with a complex femoral artery PSA after endovascular intervention who was successfully treated with BATI and describe the procedure in detail.Prolonged or repetitive spine flexion induces creep deformation of posterior spine tissues allowing for increased intervertebral motion beyond 'normal' limits, which may influence sub-regional (intersegmental) spine motion during subsequent manual lifting tasks. Using spine skin-surface kinematics, intersegmental lumbar spine motion was recorded over 20 minutes of prolonged static spine flexion and a subsequent manual lifting task (2 lifts every 3 minutes, 30 minutes total) in 14 participants. Results demonstrated that mid to lower lumbar intersegmental levels (i.e. L2/L3 to L4/L5) experienced the greatest overall creep deformation and range of motion during both prolonged flexion and manual lifting; however, overall range of motion during manual lifting was unaffected. Additionally, creep deformation did not completely recover within 30 minutes. Future work should continue to investigate the influence of this residual creep, as well as how overall creep deformation impacts spine neuromuscular control and stability, and ultimately the development of low **** disorders. Practitioner summary Mid to lower lumbar spine levels (i.e. L2/L3 to L4/L5) experienced the greatest creep deformation and range of motion during both prolonged flexion and manual lifting. Repeated lifting following prolonged flexion may limit creep recovery; however, overall lifting kinematic motion remained unchanged.Background Anterior knee pain (AKP) is often associated with persistent hip muscle weakness and facilitatory interventions may be beneficial for managing patients with AKP (pwAKP). Physiotherapists often employ passive oscillatory hip joint mobilizations to increase hip muscle function. However, there is little information about their effectiveness and the mechanisms of action involved. Objectives To investigate the immediate effects of passive hip joint mobilization on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function. Design A double-blinded, randomized, placebo-controlled crossover design. Method Eighteen patients with AKP participated in two sessions of data collection with one week apart. They received passive hip joint mobilization or placebo mobilization in a randomized order. Eccentric hip muscle strength was measured immediately before and after each intervention using a portable hand-held dynamometer. Results An ANCOVA with the sequence of treatment condition as the independent variable, the within-subject post-treatment differences as the dependent variable and the within-subject pre-treatment differences as the covariate was conducted. Patients showed a significant mean increase in eccentric hip muscle strength of 7.73% (p = 0.001) for the mobilization condition, compared to a mean decrease of 4.22% for the placebo condition. Seventeen out of eighteen participants reported having no pain during any of the strength testing. Conclusion These data suggest that passive hip joint mobilization has an immediate positive effect on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function, even in the absence of current pain.
    5 (95% CI 0.4-2.6) mm in proximal direction, -0.6 (CI -1.6 to 0.4) in the medial direction and 0.3 (CI 0.0-0.6) in the anterior direction. The mean volume of impacted bone graft was 40 cm³ (CI 28-52). In the graft bone mineral density increased 14% after 6 weeks and 23% after 2 years. There was 1 mechanical failure.Interpretation - Proximal migration of the acetabular component was low and comparable to previous reports. There was a rapid increase of bone mineral density in the bone graft. Low-dose CT scans make migration analysis and bone densitometry measurements possible in the same setting, offering great diagnostic potential for hip arthroplasty patients.A 70-year-old man was referred to our hospital for an abnormal chest shadow. Enhanced computed tomography (CT) revealed 2-humped bronchial artery aneurysms (BAAs) associated with racemose hemangioma. The combined therapy of transcatheter bronchial artery embolization and thoracic endovascular aortic repair was performed. Postoperative CT confirmed the complete exclusion of the aneurysms with no evidence of an endoleak. Our result suggests that this combined therapy is a safe and effective treatment for BAA.Early abortion in ovine toxoplasmosis has had limited investigation. This study evaluated the immune response in the placenta of sheep orally infected with Toxoplasma gondii and euthanized between 2 and 4 weeks postinfection. Toxoplasma infection of the placenta was only found at 4 weeks after infection. Parasitic debris in foci of necrosis were immunolabeled in the maternal caruncle, whereas well-preserved intracellular parasitic vacuole-like structures were found in trophoblasts of fetal cotyledon. Early abortions had increased macrophages in caruncular septa, whereas in later abortions the placentas containing the parasite had an increase of T lymphocytes and macrophages mainly in the fetal cotyledons. This study suggests that the immune response in both the fetal and maternal compartments of the placenta may contribute to the pathogenesis of ovine toxoplasmosis and that these responses differ between early and late presentations of the disease.Ultrasound-guided thrombin injection (UGTI) has emerged as the first-line treatment for moderately sized or persistent pseudoaneurysms (PSAs). https://www.selleckchem.com/products/cordycepin.html Although rare, the most feared complication of UGTI is arterial thrombosis or embolism during the off-label injection of thrombin causing acute limb ischemia requiring emergent surgical intervention. Higher thrombin volume, rapidity of injection, and wide or short-neck PSAs are all thought to increase the risk of arterial thrombosis or embolism during this procedure. For patients with unfavorable PSA anatomy who are high-risk surgical candidates due to their medical comorbidities or active critical illness, balloon-assisted thrombin injection (BATI) has been suggested as a means to potentially reduce the risk of thrombosis or distal embolization associated with UGTI. This minimally invasive technique also decreases the risk of groin wound dehiscence or infection associated with open repair, especially in patients who are morbidly obese or have had prior groin surgery. We report a patient with a complex femoral artery PSA after endovascular intervention who was successfully treated with BATI and describe the procedure in detail.Prolonged or repetitive spine flexion induces creep deformation of posterior spine tissues allowing for increased intervertebral motion beyond 'normal' limits, which may influence sub-regional (intersegmental) spine motion during subsequent manual lifting tasks. Using spine skin-surface kinematics, intersegmental lumbar spine motion was recorded over 20 minutes of prolonged static spine flexion and a subsequent manual lifting task (2 lifts every 3 minutes, 30 minutes total) in 14 participants. Results demonstrated that mid to lower lumbar intersegmental levels (i.e. L2/L3 to L4/L5) experienced the greatest overall creep deformation and range of motion during both prolonged flexion and manual lifting; however, overall range of motion during manual lifting was unaffected. Additionally, creep deformation did not completely recover within 30 minutes. Future work should continue to investigate the influence of this residual creep, as well as how overall creep deformation impacts spine neuromuscular control and stability, and ultimately the development of low back disorders. Practitioner summary Mid to lower lumbar spine levels (i.e. L2/L3 to L4/L5) experienced the greatest creep deformation and range of motion during both prolonged flexion and manual lifting. Repeated lifting following prolonged flexion may limit creep recovery; however, overall lifting kinematic motion remained unchanged.Background Anterior knee pain (AKP) is often associated with persistent hip muscle weakness and facilitatory interventions may be beneficial for managing patients with AKP (pwAKP). Physiotherapists often employ passive oscillatory hip joint mobilizations to increase hip muscle function. However, there is little information about their effectiveness and the mechanisms of action involved. Objectives To investigate the immediate effects of passive hip joint mobilization on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function. Design A double-blinded, randomized, placebo-controlled crossover design. Method Eighteen patients with AKP participated in two sessions of data collection with one week apart. They received passive hip joint mobilization or placebo mobilization in a randomized order. Eccentric hip muscle strength was measured immediately before and after each intervention using a portable hand-held dynamometer. Results An ANCOVA with the sequence of treatment condition as the independent variable, the within-subject post-treatment differences as the dependent variable and the within-subject pre-treatment differences as the covariate was conducted. Patients showed a significant mean increase in eccentric hip muscle strength of 7.73% (p = 0.001) for the mobilization condition, compared to a mean decrease of 4.22% for the placebo condition. Seventeen out of eighteen participants reported having no pain during any of the strength testing. Conclusion These data suggest that passive hip joint mobilization has an immediate positive effect on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function, even in the absence of current pain.
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  • nd LPS approaches, that PSS-H may represent a valid alternative to performing total hysterectomy in obese patients. Copyright © 2019 Facts, Views & Vision.Background Gynaecologic pelvic tumours are very common and they can present with a variety of symptoms depending on their size, location, pathophysiology and histogenesis. Infrequently, some pelvic tumours are found in the retroperitoneal space presenting with similar symptoms. Our objective is to present our experience and review of pertinent literature on miscellaneous retroperitoneal tumours. Methods Four women with retroperitoneal tumours (one schwannoma, one granulosa cell tumour and two hindgut (tail gut) cysts)) were encountered during routine laparoscopy (3 cases) and laparotomy (one case). Following multidisciplinary consultation and additional imaging, all tumours were removed by laparotomy with one case provoking litigation due to ureteral and bowel injury. Results Using these four cases, and additional cases from the literature, we highlight the potential pitfalls and provide an algorithm to minimize risks and adverse clinical and legal outcomes associated with unexpected retroperitoneal tumours. The algorithm includes resisting the impulse/temptation to remove or biopsy these tumours, requesting intra-operative consultation(s), obtaining additional detailed imaging to characterize these tumours, providing appropriate counselling to patients, obtaining informed consent, and consulting the appropriate surgical teams. At times, an interdisciplinary approach may prove to be the best course of action in order to optimize treatment and ensure patient safety. Conclusion If a retroperitoneal tumour is unexpectedly encountered, it is imperative to have intra-operative consultation (if available), to not attempt excision or biopsy, and to subsequently obtain post-operative multidisciplinary consultations, specific imaging, and information gathering in order to treat these heterogeneous masses as safely as possible. Copyright © 2019 Facts, Views & Vision.Study question How should surgery for endometriosis be performed? Summary answer This document provides recommendations covering technical aspects of different methods of surgery for deep endometriosis in women of reproductive age. What is known already Endometriosis is highly prevalent and often associated with severe symptoms. Yet compared to equally prevalent conditions it is poorly understood and a challenge to manage. Previously published guidelines have provided recommendations for (surgical) treatment of deep endometriosis, based on the best available evidence, but without technical information and details on how to best perform such treatment in order to be effective and safe. Study design size duration A working group of the European Society for Gynaecological Endoscopy (ESGE), European Society of Human Reproduction and Embryology (ESHRE) and the World Endometriosis Society (WES) collaborated on writing recommendations on the practical aspects of surgery for treatment of deep endometriosis. Participa management of endometriosis and the recommendations for surgical treatment of ovarian endometrioma. Study funding - Competing interests The meetings of the working group were funded by ESGE, ESHRE and WES.Dr. Roman reports personal fees from ETHICON, PLASMASURGICAL, OLYMPUS, and NORDIC PHARMA, outside the submitted work; Dr. Becker reports grants from Bayer AG, Volition Rx, MDNA Life Sciences, and Roche Diagnostics Inc, and other relationships or activities from AbbVie Inc, and Myriad Inc, during the conduct of the study; Dr. Tomassetti reports non-financial support from ESHRE, during the conduct of the study; non-financial support and other from Lumenis, Gedeon-Richter, Ferring Pharmaceuticals, and Merck SA, outside the submitted work. The other authors had nothing to disclose. Copyright © 2019 Facts, Views & Vision.In the recent months, the world was taken by surprise by the outbreak of a coronavirus (SARS-CoV-2) pandemic (COVID-19). The COVID-19 pandemic is a unique opportunity to advance the understanding of the association of respiratory viruses with mood disorders and suicide. In this editorial, we explore three insights to the neuropsychoneuroimmunology of mood disorders that could be taken from the COVID-19 pandemic. © 2020 Published by Elsevier Inc.Traumatic brain injury (TBI) is a major public health concern and remains a leading cause of disability and socio-economic burden. To date, there is no proven therapy that promotes brain repair following an injury to the brain. In this study, we explored the role of an isoform of adenosine kinase expressed in the cell nucleus (ADK-L) as a potential regulator of neural stem cell proliferation in the brain. The rationale for this hypothesis is based on coordinated expression changes of ADK-L during foetal and postnatal murine and human brain development indicating a role in the regulation of cell proliferation and plasticity in the brain. We first tested whether the genetic disruption of ADK-L would increase neural stem cell proliferation after TBI. Three days after TBI, modelled by a controlled cortical impact, transgenic ****, which lack ADK-L (ADKΔneuron) in the dentate gyrus (DG) showed a significant increase in neural stem cell proliferation as evidenced by significant increases in doublecortin and Ki67-pos) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.HIV infection is associated with increased age-related co-morbidities including cognitive deficits, leading to hypotheses of HIV-related premature or accelerated ageing. Impairments in selective attention and the underlying neural dynamics have been linked to HIV-associated neurocognitive disorder; however, the effect of ageing in this context is not yet understood. Thus, the current study aimed to identify the interactive effects of ageing and HIV on selective attention processing. A total of 165 participants (92 controls, 73 participants with HIV) performed a visual selective attention task while undergoing magnetoencephalography and were compared cross-sectionally. Spectrally specific oscillatory neural responses during task performance were imaged and linked with selective attention function. https://www.selleckchem.com/products/SB-431542.html Reaction time on the task and regional neural activity were analysed with analysis of covariance (ANCOVA) models aimed at examining the age-by-HIV interaction term. Finally, these metrics were evaluated with respect to clinical measures such as global neuropsychological performance, duration of HIV infection and medication regimen.
    nd LPS approaches, that PSS-H may represent a valid alternative to performing total hysterectomy in obese patients. Copyright © 2019 Facts, Views & Vision.Background Gynaecologic pelvic tumours are very common and they can present with a variety of symptoms depending on their size, location, pathophysiology and histogenesis. Infrequently, some pelvic tumours are found in the retroperitoneal space presenting with similar symptoms. Our objective is to present our experience and review of pertinent literature on miscellaneous retroperitoneal tumours. Methods Four women with retroperitoneal tumours (one schwannoma, one granulosa cell tumour and two hindgut (tail gut) cysts)) were encountered during routine laparoscopy (3 cases) and laparotomy (one case). Following multidisciplinary consultation and additional imaging, all tumours were removed by laparotomy with one case provoking litigation due to ureteral and bowel injury. Results Using these four cases, and additional cases from the literature, we highlight the potential pitfalls and provide an algorithm to minimize risks and adverse clinical and legal outcomes associated with unexpected retroperitoneal tumours. The algorithm includes resisting the impulse/temptation to remove or biopsy these tumours, requesting intra-operative consultation(s), obtaining additional detailed imaging to characterize these tumours, providing appropriate counselling to patients, obtaining informed consent, and consulting the appropriate surgical teams. At times, an interdisciplinary approach may prove to be the best course of action in order to optimize treatment and ensure patient safety. Conclusion If a retroperitoneal tumour is unexpectedly encountered, it is imperative to have intra-operative consultation (if available), to not attempt excision or biopsy, and to subsequently obtain post-operative multidisciplinary consultations, specific imaging, and information gathering in order to treat these heterogeneous masses as safely as possible. Copyright © 2019 Facts, Views & Vision.Study question How should surgery for endometriosis be performed? Summary answer This document provides recommendations covering technical aspects of different methods of surgery for deep endometriosis in women of reproductive age. What is known already Endometriosis is highly prevalent and often associated with severe symptoms. Yet compared to equally prevalent conditions it is poorly understood and a challenge to manage. Previously published guidelines have provided recommendations for (surgical) treatment of deep endometriosis, based on the best available evidence, but without technical information and details on how to best perform such treatment in order to be effective and safe. Study design size duration A working group of the European Society for Gynaecological Endoscopy (ESGE), European Society of Human Reproduction and Embryology (ESHRE) and the World Endometriosis Society (WES) collaborated on writing recommendations on the practical aspects of surgery for treatment of deep endometriosis. Participa management of endometriosis and the recommendations for surgical treatment of ovarian endometrioma. Study funding - Competing interests The meetings of the working group were funded by ESGE, ESHRE and WES.Dr. Roman reports personal fees from ETHICON, PLASMASURGICAL, OLYMPUS, and NORDIC PHARMA, outside the submitted work; Dr. Becker reports grants from Bayer AG, Volition Rx, MDNA Life Sciences, and Roche Diagnostics Inc, and other relationships or activities from AbbVie Inc, and Myriad Inc, during the conduct of the study; Dr. Tomassetti reports non-financial support from ESHRE, during the conduct of the study; non-financial support and other from Lumenis, Gedeon-Richter, Ferring Pharmaceuticals, and Merck SA, outside the submitted work. The other authors had nothing to disclose. Copyright © 2019 Facts, Views & Vision.In the recent months, the world was taken by surprise by the outbreak of a coronavirus (SARS-CoV-2) pandemic (COVID-19). The COVID-19 pandemic is a unique opportunity to advance the understanding of the association of respiratory viruses with mood disorders and suicide. In this editorial, we explore three insights to the neuropsychoneuroimmunology of mood disorders that could be taken from the COVID-19 pandemic. © 2020 Published by Elsevier Inc.Traumatic brain injury (TBI) is a major public health concern and remains a leading cause of disability and socio-economic burden. To date, there is no proven therapy that promotes brain repair following an injury to the brain. In this study, we explored the role of an isoform of adenosine kinase expressed in the cell nucleus (ADK-L) as a potential regulator of neural stem cell proliferation in the brain. The rationale for this hypothesis is based on coordinated expression changes of ADK-L during foetal and postnatal murine and human brain development indicating a role in the regulation of cell proliferation and plasticity in the brain. We first tested whether the genetic disruption of ADK-L would increase neural stem cell proliferation after TBI. Three days after TBI, modelled by a controlled cortical impact, transgenic mice, which lack ADK-L (ADKΔneuron) in the dentate gyrus (DG) showed a significant increase in neural stem cell proliferation as evidenced by significant increases in doublecortin and Ki67-pos) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.HIV infection is associated with increased age-related co-morbidities including cognitive deficits, leading to hypotheses of HIV-related premature or accelerated ageing. Impairments in selective attention and the underlying neural dynamics have been linked to HIV-associated neurocognitive disorder; however, the effect of ageing in this context is not yet understood. Thus, the current study aimed to identify the interactive effects of ageing and HIV on selective attention processing. A total of 165 participants (92 controls, 73 participants with HIV) performed a visual selective attention task while undergoing magnetoencephalography and were compared cross-sectionally. Spectrally specific oscillatory neural responses during task performance were imaged and linked with selective attention function. https://www.selleckchem.com/products/SB-431542.html Reaction time on the task and regional neural activity were analysed with analysis of covariance (ANCOVA) models aimed at examining the age-by-HIV interaction term. Finally, these metrics were evaluated with respect to clinical measures such as global neuropsychological performance, duration of HIV infection and medication regimen.
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  • Host genetic factors play a fundamental role in regulating humoral immunity to viral infection, including influenza A virus (IAV). Here, we utilize the Collaborative Cross (CC), a mouse genetic reference population, to study genetic regulation of variation in antibody response following IAV infection. CC **** show significant heritable variation in the magnitude, kinetics, and composition of IAV-specific antibody response. We map 23 genetic loci associated with this variation. Analysis of a subset of these loci finds that they broadly affect the antibody response to IAV as well as other viruses. Candidate genes are identified based on predicted variant consequences and haplotype-specific expression patterns, and several show overlap with genes identified in human mapping studies. These findings demonstrate that the host antibody response to IAV infection is under complex genetic control and highlight the utility of the CC in modeling and identifying genetic factors with translational relevance to human health and disease. The underlying mechanisms by which prior immunity to dengue virus (DENV) affords cross-protection against the related flavivirus Zika virus (ZIKV) are poorly understood. Here, we examine the ability of DENV/ZIKV-cross-reactive CD4+ T cells to protect against versus exacerbate ZIKV infection by using a histocompatibility leukocyte antigen (HLA)-DRB1∗0101 transgenic, interferon α/β receptor-deficient mouse model that supports robust DENV and ZIKV replication. By mapping the HLA-DRB1∗0101-restricted T cell response, we identify DENV/ZIKV-cross-reactive CD4+ T cell epitopes that stimulate interferon gamma (IFNγ) and/or tumor necrosis factor (TNF) production. Vaccination of naive HLA-DRB1∗0101 transgenic **** with these peptides induces a CD4+ T cell response sufficient to reduce tissue viral burden following ZIKV infection. Notably, this protective response requires IFNγ and/or TNF secretion but not anti-ZIKV immunoglobulin G (IgG) production. Thus, DENV/ZIKV-cross-reactive CD4+ T cells producing canonical Th1 cytokines can suppress ZIKV replication in an antibody-independent manner. These results may have important implications for increasing the efficacy and safety of DENV/ZIKV vaccines and for developing pan-flavivirus vaccines. Published by Elsevier Inc.Kinetochores are multi-protein machines that form dynamic attachments to microtubules and control chromosome segregation. High fidelity is ensured because kinetochores can monitor attachment status and tension, using this information to activate checkpoints and error-correction mechanisms. To explore how kinetochores achieve this, we used two- and three-color subpixel fluorescence localization to define how proteins from six major complexes (CCAN, MIS12, NDC80, KNL1, RZZ, and SKA) and the checkpoint proteins Bub1, Mad1, and Mad2 are organized in the human kinetochore. This reveals how the outer kinetochore has a high nematic order and is largely invariant to the loss of attachment or tension, except for two mechanical sensors. First, Knl1 unravels to relay tension, and second, NDC80 undergoes jackknifing and loss of nematic order under microtubule detachment, with only the latter wired up to the checkpoint signaling system. This provides insight into how kinetochores integrate mechanical signals to promote error-free chromosome segregation. https://www.selleckchem.com/products/pf-543.html Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus responsible for recent epidemics across the Americas, and it is closely related to dengue virus (DENV). Here, we study samples from 46 DENV-naive and 43 DENV-immune patients with RT-PCR-confirmed ZIKV infection at early-acute, late-acute, and convalescent time points from our pediatric cohort study in Nicaragua. We analyze the samples via RNA sequencing (RNA-seq), CyTOF, and multiplex cytokine/chemokine Luminex to generate a comprehensive, innate immune profile during ZIKV infection. Immunophenotyping and analysis of cytokines/chemokines reveal that CD14+ monocytes play a key role during ZIKV infection. Further, we identify CD169 (Siglec-1) on CD14+ monocytes as a potential biomarker of acute ZIKV infection. Strikingly distinct transcriptomic and immunophenotypic signatures are observed at all three time points. Interestingly, pre-existing dengue immunity has minimal impact on the innate immune response to Zika. Finally, this comprehensive immune profiling and network analysis of ZIKV infection in children serves as a valuable resource. The bacterial cell wall is made of peptidoglycan (PG), a polymer that is essential for the maintenance of cell shape and survival. During growth, bacteria remodel their PG, releasing fragments that are predominantly re-internalized and recycled. Here, we show that Vibrio cholerae recycles PG fragments modified with non-canonical d-amino acids (NCDAA), which lead to the accumulation of cytosolic PG tetrapeptides. We demonstrate that the accumulation of recycled tetrapeptides has two regulatory consequences for the cell wall reduction of d,d-cross-linkage and reduction of PG synthesis. We further demonstrate that l,d-carboxypeptidases from five different species show a preferential activity for substrates containing canonical (d-alanine) versus non-canonical (d-methionine) d-amino acids, suggesting that the accumulation of intracellular tetrapeptides in NCDAA-rich environments is widespread. Collectively, this work reveals a regulatory role of NCDAA linking PG recycling and synthesis to promote optimal cell wall assembly and composition in the stationary phase. The small intestine is responsible for nutrient absorption and one of the most important interfaces between the environment and the body. During aging, changes of the epithelium lead to food malabsorption and reduced barrier function, thus increasing disease risk. The drivers of these alterations remain poorly understood. Here, we compare the proteomes of intestinal crypts from **** across different anatomical regions and ages. We find that aging alters epithelial immunity, metabolism, and cell proliferation and is accompanied by region-dependent skewing in the cellular composition of the epithelium. Of note, short-term dietary restriction followed by refeeding partially restores the epithelium by promoting stem cell differentiation toward the secretory lineage. We identify Hmgcs2 (3-hydroxy-3-methylglutaryl-coenzyme A [CoA] synthetase 2), the rate-limiting enzyme for ketogenesis, as a modulator of stem cell differentiation that responds to dietary changes, and we provide an atlas of region- and age-dependent proteome changes of the small intestine.
    Host genetic factors play a fundamental role in regulating humoral immunity to viral infection, including influenza A virus (IAV). Here, we utilize the Collaborative Cross (CC), a mouse genetic reference population, to study genetic regulation of variation in antibody response following IAV infection. CC mice show significant heritable variation in the magnitude, kinetics, and composition of IAV-specific antibody response. We map 23 genetic loci associated with this variation. Analysis of a subset of these loci finds that they broadly affect the antibody response to IAV as well as other viruses. Candidate genes are identified based on predicted variant consequences and haplotype-specific expression patterns, and several show overlap with genes identified in human mapping studies. These findings demonstrate that the host antibody response to IAV infection is under complex genetic control and highlight the utility of the CC in modeling and identifying genetic factors with translational relevance to human health and disease. The underlying mechanisms by which prior immunity to dengue virus (DENV) affords cross-protection against the related flavivirus Zika virus (ZIKV) are poorly understood. Here, we examine the ability of DENV/ZIKV-cross-reactive CD4+ T cells to protect against versus exacerbate ZIKV infection by using a histocompatibility leukocyte antigen (HLA)-DRB1∗0101 transgenic, interferon α/β receptor-deficient mouse model that supports robust DENV and ZIKV replication. By mapping the HLA-DRB1∗0101-restricted T cell response, we identify DENV/ZIKV-cross-reactive CD4+ T cell epitopes that stimulate interferon gamma (IFNγ) and/or tumor necrosis factor (TNF) production. Vaccination of naive HLA-DRB1∗0101 transgenic mice with these peptides induces a CD4+ T cell response sufficient to reduce tissue viral burden following ZIKV infection. Notably, this protective response requires IFNγ and/or TNF secretion but not anti-ZIKV immunoglobulin G (IgG) production. Thus, DENV/ZIKV-cross-reactive CD4+ T cells producing canonical Th1 cytokines can suppress ZIKV replication in an antibody-independent manner. These results may have important implications for increasing the efficacy and safety of DENV/ZIKV vaccines and for developing pan-flavivirus vaccines. Published by Elsevier Inc.Kinetochores are multi-protein machines that form dynamic attachments to microtubules and control chromosome segregation. High fidelity is ensured because kinetochores can monitor attachment status and tension, using this information to activate checkpoints and error-correction mechanisms. To explore how kinetochores achieve this, we used two- and three-color subpixel fluorescence localization to define how proteins from six major complexes (CCAN, MIS12, NDC80, KNL1, RZZ, and SKA) and the checkpoint proteins Bub1, Mad1, and Mad2 are organized in the human kinetochore. This reveals how the outer kinetochore has a high nematic order and is largely invariant to the loss of attachment or tension, except for two mechanical sensors. First, Knl1 unravels to relay tension, and second, NDC80 undergoes jackknifing and loss of nematic order under microtubule detachment, with only the latter wired up to the checkpoint signaling system. This provides insight into how kinetochores integrate mechanical signals to promote error-free chromosome segregation. https://www.selleckchem.com/products/pf-543.html Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus responsible for recent epidemics across the Americas, and it is closely related to dengue virus (DENV). Here, we study samples from 46 DENV-naive and 43 DENV-immune patients with RT-PCR-confirmed ZIKV infection at early-acute, late-acute, and convalescent time points from our pediatric cohort study in Nicaragua. We analyze the samples via RNA sequencing (RNA-seq), CyTOF, and multiplex cytokine/chemokine Luminex to generate a comprehensive, innate immune profile during ZIKV infection. Immunophenotyping and analysis of cytokines/chemokines reveal that CD14+ monocytes play a key role during ZIKV infection. Further, we identify CD169 (Siglec-1) on CD14+ monocytes as a potential biomarker of acute ZIKV infection. Strikingly distinct transcriptomic and immunophenotypic signatures are observed at all three time points. Interestingly, pre-existing dengue immunity has minimal impact on the innate immune response to Zika. Finally, this comprehensive immune profiling and network analysis of ZIKV infection in children serves as a valuable resource. The bacterial cell wall is made of peptidoglycan (PG), a polymer that is essential for the maintenance of cell shape and survival. During growth, bacteria remodel their PG, releasing fragments that are predominantly re-internalized and recycled. Here, we show that Vibrio cholerae recycles PG fragments modified with non-canonical d-amino acids (NCDAA), which lead to the accumulation of cytosolic PG tetrapeptides. We demonstrate that the accumulation of recycled tetrapeptides has two regulatory consequences for the cell wall reduction of d,d-cross-linkage and reduction of PG synthesis. We further demonstrate that l,d-carboxypeptidases from five different species show a preferential activity for substrates containing canonical (d-alanine) versus non-canonical (d-methionine) d-amino acids, suggesting that the accumulation of intracellular tetrapeptides in NCDAA-rich environments is widespread. Collectively, this work reveals a regulatory role of NCDAA linking PG recycling and synthesis to promote optimal cell wall assembly and composition in the stationary phase. The small intestine is responsible for nutrient absorption and one of the most important interfaces between the environment and the body. During aging, changes of the epithelium lead to food malabsorption and reduced barrier function, thus increasing disease risk. The drivers of these alterations remain poorly understood. Here, we compare the proteomes of intestinal crypts from mice across different anatomical regions and ages. We find that aging alters epithelial immunity, metabolism, and cell proliferation and is accompanied by region-dependent skewing in the cellular composition of the epithelium. Of note, short-term dietary restriction followed by refeeding partially restores the epithelium by promoting stem cell differentiation toward the secretory lineage. We identify Hmgcs2 (3-hydroxy-3-methylglutaryl-coenzyme A [CoA] synthetase 2), the rate-limiting enzyme for ketogenesis, as a modulator of stem cell differentiation that responds to dietary changes, and we provide an atlas of region- and age-dependent proteome changes of the small intestine.
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  • A taste-and-texture questionnaire was collected for suspension-recipients. RESULTS Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable. DISCUSSION Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE. This article is protected by copyright. All rights reserved.PURPOSE This study was undertaken to develop a theoretical framework explaining family caregiving processes for older persons with cognitive impairment recovering from hip fracture surgery. DESIGN AND METHODS In this grounded theory study, data were collected in audio-recorded face-to-face interviews with 21 family caregivers. Among these caregivers, 14 cared for hip-fractured persons with cognitive impairment, and seven cared for those without cognitive impairment. Caregivers were interviewed five times after patients' discharge at 1 week and at 1, 3, 6, and 12 months. Data were analyzed by constant comparative analysis. FINDINGS The core category explaining the family caregiving process for hip-fractured persons with cognitive impairment was "resuming normal life during drip-like recovery." This category captures the slowness of the recovery process, as slow as dripping water. During the early postoperative period, caregivers attempted to gain control of the postoperative situation, using various maintenance and improvement strategies to deal with the chaos in individuals and the family and to protect hip-fractured persons with cognitive impairment from further harm. The goal of recovery was to get **** to their original life. CONCLUSIONS Family caregivers of hip-fractured older persons with cognitive impairment needed to deal with more complex chaotic situations, exerted more efforts to administer safety measures, and required more time to achieve a stable life pattern. CLINICAL RELEVANCE Since postoperative recovery was perceived as extremely slow, family caregivers of hip-fractured older persons with cognitive impairment should be patient regarding recovery and be informed before hospital discharge of different strategies to resume normal life during postoperative recovery. © 2020 Sigma Theta Tau International.BACKGROUND Recently, minimally invasive liver surgery (MILS) has gained wide consensus in the management of hepatocellular carcinoma (HCC). However, its role in the setting of a salvage liver transplantation (SLT) has been poorly investigated. We analyzed the intention-to-treat survival of HCC patients treated with MILS vs. the open approach and eventually waitlisted for SLT. The secondary end-point was identification of risk factors for post-transplant death and tumor recurrence. MATERIALS AND METHODS A multicenter, retrospective analysis was carried out in six Italian centers. A total of 211 HCC patients resected with open surgery (n=167) vs. MILS (n=44) and waitlisted for SLT during the period January 2007 - December 2017 was enrolled. https://www.selleckchem.com/products/sis3.html RESULTS MILS was the most important protective factor for the composite risk of de-listing, post-transplant patient death and HCC recurrence (OR=0.26, 95%CI=0.11-0.63; p=0.003). MILS was also the only independent protective factor for the risk of post-SLT patient death (OR=0.29, 95%CI=0.09-0.93; P=0.04). After propensity score matching, MILS was the only independent protective factor against the risk of de-listing, post-transplant death and HCC recurrence (OR=0.22, 95%CI=0.07-0.75; p=0.02). CONCLUSIONS Based on current analysis, MILS seems protective over open surgery for the risk of de-listing, post-transplant patient death and tumor recurrence. Larger prospective studies balancing liver function and tumor stage are strongly favored to better clarify the beneficial effect of MILS for HCC patients eventually referred to SLT. This article is protected by copyright. All rights reserved.Fusarium oxysporum f. sp. radicis-cucumerinum (Forc) causes severe root rot and wilt in several cucurbit species, including cucumber, melon, and watermelon. Previously, a pathogenicity chromosome, chrRC , was identified in Forc. Strains that were previously nonpathogenic could infect multiple cucurbit species after obtaining this chromosome via horizontal chromosome transfer (HCT). In contrast, F. oxysporum f. sp. melonis (Fom) can only cause disease on melon plants, even though Fom contains contigs that are largely syntenic with chrRC . The aim of this study was to identify the genetic basis underlying the difference in host range between Fom and Forc. First, colonization of different cucurbit species between Forc and Fom strains showed that although Fom did not reach the upper part of cucumber or watermelon plants, it did enter the root xylem. Second, to select candidate genomic regions associated with differences in host range, high-quality genome assemblies of Fom001, Fom005, and Forc016 were compared. One of the Fom contigs that is largely syntenic and highly similar in sequence to chrRC contains the effector gene SIX6. After HCT of the SIX6-containing chromosome from Fom strains to a nonpathogenic strain, the recipient (HCT) strains caused disease on melon plants, but not on cucumber or watermelon plants. These results provide strong evidence that the differences in host range between Fom and Forc are caused by differences between transferred chromosomes of Fom and chrRC , thus narrowing down the search for genes allowing or preventing infection of cucumber and watermelon to genes located on these chromosomes. © 2020 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.AIMS AND OBJECTIVES This study aims to explore nurses' perceptions and experiences regarding pressure injuries caused by medical devices and to understand the perceived challenges and barriers nurses face in preventing medical device-related pressure injuries. BACKGROUND Nurses have a responsibility to prevent pressure injuries and play a major role in their prevention. As there has been a lack of research on medical device-related pressure injuries, not **** is known about nurses' perceptions and experiences. This therefore hinders the establishment of effective and efficient interventions in nurses' education and in the practical environment. DESIGN A descriptive qualitative design was adopted, and the COREQ checklist was employed to report on the current study. METHODS The study was conducted at an acute care hospital in Singapore. Purposive sampling was used, and a total of 21 enrolled and registered nurses who had recent experiences with medical device-related pressure injuries were recruited between August and December 2018.
    A taste-and-texture questionnaire was collected for suspension-recipients. RESULTS Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable. DISCUSSION Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE. This article is protected by copyright. All rights reserved.PURPOSE This study was undertaken to develop a theoretical framework explaining family caregiving processes for older persons with cognitive impairment recovering from hip fracture surgery. DESIGN AND METHODS In this grounded theory study, data were collected in audio-recorded face-to-face interviews with 21 family caregivers. Among these caregivers, 14 cared for hip-fractured persons with cognitive impairment, and seven cared for those without cognitive impairment. Caregivers were interviewed five times after patients' discharge at 1 week and at 1, 3, 6, and 12 months. Data were analyzed by constant comparative analysis. FINDINGS The core category explaining the family caregiving process for hip-fractured persons with cognitive impairment was "resuming normal life during drip-like recovery." This category captures the slowness of the recovery process, as slow as dripping water. During the early postoperative period, caregivers attempted to gain control of the postoperative situation, using various maintenance and improvement strategies to deal with the chaos in individuals and the family and to protect hip-fractured persons with cognitive impairment from further harm. The goal of recovery was to get back to their original life. CONCLUSIONS Family caregivers of hip-fractured older persons with cognitive impairment needed to deal with more complex chaotic situations, exerted more efforts to administer safety measures, and required more time to achieve a stable life pattern. CLINICAL RELEVANCE Since postoperative recovery was perceived as extremely slow, family caregivers of hip-fractured older persons with cognitive impairment should be patient regarding recovery and be informed before hospital discharge of different strategies to resume normal life during postoperative recovery. © 2020 Sigma Theta Tau International.BACKGROUND Recently, minimally invasive liver surgery (MILS) has gained wide consensus in the management of hepatocellular carcinoma (HCC). However, its role in the setting of a salvage liver transplantation (SLT) has been poorly investigated. We analyzed the intention-to-treat survival of HCC patients treated with MILS vs. the open approach and eventually waitlisted for SLT. The secondary end-point was identification of risk factors for post-transplant death and tumor recurrence. MATERIALS AND METHODS A multicenter, retrospective analysis was carried out in six Italian centers. A total of 211 HCC patients resected with open surgery (n=167) vs. MILS (n=44) and waitlisted for SLT during the period January 2007 - December 2017 was enrolled. https://www.selleckchem.com/products/sis3.html RESULTS MILS was the most important protective factor for the composite risk of de-listing, post-transplant patient death and HCC recurrence (OR=0.26, 95%CI=0.11-0.63; p=0.003). MILS was also the only independent protective factor for the risk of post-SLT patient death (OR=0.29, 95%CI=0.09-0.93; P=0.04). After propensity score matching, MILS was the only independent protective factor against the risk of de-listing, post-transplant death and HCC recurrence (OR=0.22, 95%CI=0.07-0.75; p=0.02). CONCLUSIONS Based on current analysis, MILS seems protective over open surgery for the risk of de-listing, post-transplant patient death and tumor recurrence. Larger prospective studies balancing liver function and tumor stage are strongly favored to better clarify the beneficial effect of MILS for HCC patients eventually referred to SLT. This article is protected by copyright. All rights reserved.Fusarium oxysporum f. sp. radicis-cucumerinum (Forc) causes severe root rot and wilt in several cucurbit species, including cucumber, melon, and watermelon. Previously, a pathogenicity chromosome, chrRC , was identified in Forc. Strains that were previously nonpathogenic could infect multiple cucurbit species after obtaining this chromosome via horizontal chromosome transfer (HCT). In contrast, F. oxysporum f. sp. melonis (Fom) can only cause disease on melon plants, even though Fom contains contigs that are largely syntenic with chrRC . The aim of this study was to identify the genetic basis underlying the difference in host range between Fom and Forc. First, colonization of different cucurbit species between Forc and Fom strains showed that although Fom did not reach the upper part of cucumber or watermelon plants, it did enter the root xylem. Second, to select candidate genomic regions associated with differences in host range, high-quality genome assemblies of Fom001, Fom005, and Forc016 were compared. One of the Fom contigs that is largely syntenic and highly similar in sequence to chrRC contains the effector gene SIX6. After HCT of the SIX6-containing chromosome from Fom strains to a nonpathogenic strain, the recipient (HCT) strains caused disease on melon plants, but not on cucumber or watermelon plants. These results provide strong evidence that the differences in host range between Fom and Forc are caused by differences between transferred chromosomes of Fom and chrRC , thus narrowing down the search for genes allowing or preventing infection of cucumber and watermelon to genes located on these chromosomes. © 2020 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.AIMS AND OBJECTIVES This study aims to explore nurses' perceptions and experiences regarding pressure injuries caused by medical devices and to understand the perceived challenges and barriers nurses face in preventing medical device-related pressure injuries. BACKGROUND Nurses have a responsibility to prevent pressure injuries and play a major role in their prevention. As there has been a lack of research on medical device-related pressure injuries, not much is known about nurses' perceptions and experiences. This therefore hinders the establishment of effective and efficient interventions in nurses' education and in the practical environment. DESIGN A descriptive qualitative design was adopted, and the COREQ checklist was employed to report on the current study. METHODS The study was conducted at an acute care hospital in Singapore. Purposive sampling was used, and a total of 21 enrolled and registered nurses who had recent experiences with medical device-related pressure injuries were recruited between August and December 2018.
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  • Vibrio fischeri luminescence inhibition tests revealed that treatment by nanofiltration reduced acute toxicity of all studied effluents.In the study the electrochemical oxidation process for decolorization of Rhodamine-B dye was studied using an anode coated with mixed metal oxides TiO2, RuO2, and IrO2. Batch experimental studies were conducted to assess the effect of four important performance variables, current density, electrolyte concentration, initial pH and electrolysis time, on the decolorization and energy consumption. The process was modeled using an artificial neural network. Response surface methodology using central composite design (CCD) was utilized for optimization of the decolorization process. Based on the experimental design given by CCD, the results obtained by the statistical analysis show that the electrolysis time was the most influential parameter for decolorization whereas the current density had the greatest influence on the energy consumption. According to the optimized results given by the CCD model, maximum color removal of 97% and minimum energy consumption of 1.01 kWh/m3 were predicted in 4.9 minute of electrolysis time, using 0.031 M NaCl concentration at current density 10 mA/cm2 and an initial pH of 3.7. A close conformity was observed between the optimized predicted results and experimental results. The process was found to be efficient and consisted of indirect chemical oxidation producing strong oxidizing agents such as Cl2, HClO and OCl-.Poly-silicate-ferric (PSF) was developed as an heterogeneous UV-Fenton catalyst, which was characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), X-ray fluorescence (XRF), UV-vis diffuse reflectance spectroscopy (DRS), Brunauer-Emmett-Teller (BET) and scanning electron microscopy (SEM). The catalytic process of PSF and generation mechanism of hydroxyl radical based on photo-Fenton system were studied in detail. In the heterogeneous UV-Fenton system, the kapp value of Orange II degradation was as high as 0.268 min-1, which was 1.5 times compared to that with α-FeOOH as catalyst. As a result, the Orange II decolouration and mineralization rates were as high as 99.9% and 92.5% after 40 min treatment, respectively. Moreover, the hydroxyl radical concentration would increase to a peak value of 13.4 μmol/L at about 15 min. The fundamental cause of the high hydroxyl radical generation lay in the high release ability of iron ions from PSF. The peak concentrations of total iron ions and ferrous ions could increase to 4.53 mg/L and 1.57 mg/L at 20 min and 10 min, respectively. After treatment, the re-adsorption of iron ions on the surface of PSF could avoid the additional pollution caused by iron ions. The results confirmed that PSF was a high activity catalyst for an heterogeneous UV-Fenton system.Mass production of nanomaterials to remove pollutants from water still faces many challenges, mainly due to the complexity of the synthesis methods involved and the use of dangerous reagents. The green method of preparation of nanomaterials from plants can effectively solve these problems. Fe,Cu oxide nanocomposites (Fe-Cu-NCs) were synthesized by a green and single-step method using loquat leaf extracts, and were used as an adsorbent for removal of Norfloxacin (NOR) and Ciprofloxacin (CIP) from aqueous solution. The synthesized adsorbent showed excellent adsorption properties for NOR and CIP. The experimental equilibrium data fitted the Redlich-Peterson and Koble-Corrigan models well and the maximum adsorption capacities of Fe-Cu-NCs calculated by the Langmuir model for NOR and CIP were 1.182 mmol/g and 1.103 mmol/g, respectively, at 293 K. Additionally, the morphologies and properties of Fe-Cu-NCs were characterized by transmission electron microscopy (TEM), scanning electron microscopy X-ray energy-dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis and the adsorption mechanism of NOR and CIP onto Fe-Cu-NCs was discussed. Thermodynamic parameters revealed that the adsorption process was spontaneous and endothermic. This study indicated that Fe-Cu-NCs are a potential adsorbent and provide a simple and convenient strategy for the purification of antibiotics-laden wastewater.Intense urbanization results in greater soil sealing and a consequent increase in surface runoff. When high soil sealing rates and high slopes are encountered in small catchments, high volume and short duration precipitation events increase the probability of flash floods. https://www.selleckchem.com/products/Aloxistatin.html This study evaluates the hydrological response of an urban catchment with regard to rainfall-runoff events in the following scenarios current land use, without a detention basin which has been part of the system since the 1970s, with the maximum soil sealing allowed by legislation, and with green infrastructure implantation in 100%, 50% and 10% of the suitable area. Hydrological modelling was performed using the Storm Water Management Model (SWMM). Six level gauges installed along the length of the stream provided the data used in model calibration and validation. The model calibration process provided adequate results the average Nash-Sutcliffe coefficient was 0.72, the mean error of peak flow was 11% and the mean error of the runoff volume was 12%. Rainfall based on 2-, 10-, 50- and 100-year events were simulated for each scenario, as well as two observed events. In the scenario without the detention basin, an average elevation of 10% in the peak flow was observed in the catchment outlet. In the scenario with maximum soil sealing, the catchment outlet peak flow increased by 30% on average. On the other hand, in the scenario with green infrastructure implementation in 100%, 50% and 10% of the available areas, the outlet peak flow was reduced by 60%, 30% and 5%, respectively. Results indicated the efficiency of the detention basin to reduce flooding, the importance of green area preservation to reduce peak flows, as well as the catchment potential of green infrastructure implementation and the hydrological benefits that they can provide, increasing infiltration and reducing runoff volume and peak flow.
    Vibrio fischeri luminescence inhibition tests revealed that treatment by nanofiltration reduced acute toxicity of all studied effluents.In the study the electrochemical oxidation process for decolorization of Rhodamine-B dye was studied using an anode coated with mixed metal oxides TiO2, RuO2, and IrO2. Batch experimental studies were conducted to assess the effect of four important performance variables, current density, electrolyte concentration, initial pH and electrolysis time, on the decolorization and energy consumption. The process was modeled using an artificial neural network. Response surface methodology using central composite design (CCD) was utilized for optimization of the decolorization process. Based on the experimental design given by CCD, the results obtained by the statistical analysis show that the electrolysis time was the most influential parameter for decolorization whereas the current density had the greatest influence on the energy consumption. According to the optimized results given by the CCD model, maximum color removal of 97% and minimum energy consumption of 1.01 kWh/m3 were predicted in 4.9 minute of electrolysis time, using 0.031 M NaCl concentration at current density 10 mA/cm2 and an initial pH of 3.7. A close conformity was observed between the optimized predicted results and experimental results. The process was found to be efficient and consisted of indirect chemical oxidation producing strong oxidizing agents such as Cl2, HClO and OCl-.Poly-silicate-ferric (PSF) was developed as an heterogeneous UV-Fenton catalyst, which was characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), X-ray fluorescence (XRF), UV-vis diffuse reflectance spectroscopy (DRS), Brunauer-Emmett-Teller (BET) and scanning electron microscopy (SEM). The catalytic process of PSF and generation mechanism of hydroxyl radical based on photo-Fenton system were studied in detail. In the heterogeneous UV-Fenton system, the kapp value of Orange II degradation was as high as 0.268 min-1, which was 1.5 times compared to that with α-FeOOH as catalyst. As a result, the Orange II decolouration and mineralization rates were as high as 99.9% and 92.5% after 40 min treatment, respectively. Moreover, the hydroxyl radical concentration would increase to a peak value of 13.4 μmol/L at about 15 min. The fundamental cause of the high hydroxyl radical generation lay in the high release ability of iron ions from PSF. The peak concentrations of total iron ions and ferrous ions could increase to 4.53 mg/L and 1.57 mg/L at 20 min and 10 min, respectively. After treatment, the re-adsorption of iron ions on the surface of PSF could avoid the additional pollution caused by iron ions. The results confirmed that PSF was a high activity catalyst for an heterogeneous UV-Fenton system.Mass production of nanomaterials to remove pollutants from water still faces many challenges, mainly due to the complexity of the synthesis methods involved and the use of dangerous reagents. The green method of preparation of nanomaterials from plants can effectively solve these problems. Fe,Cu oxide nanocomposites (Fe-Cu-NCs) were synthesized by a green and single-step method using loquat leaf extracts, and were used as an adsorbent for removal of Norfloxacin (NOR) and Ciprofloxacin (CIP) from aqueous solution. The synthesized adsorbent showed excellent adsorption properties for NOR and CIP. The experimental equilibrium data fitted the Redlich-Peterson and Koble-Corrigan models well and the maximum adsorption capacities of Fe-Cu-NCs calculated by the Langmuir model for NOR and CIP were 1.182 mmol/g and 1.103 mmol/g, respectively, at 293 K. Additionally, the morphologies and properties of Fe-Cu-NCs were characterized by transmission electron microscopy (TEM), scanning electron microscopy X-ray energy-dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis and the adsorption mechanism of NOR and CIP onto Fe-Cu-NCs was discussed. Thermodynamic parameters revealed that the adsorption process was spontaneous and endothermic. This study indicated that Fe-Cu-NCs are a potential adsorbent and provide a simple and convenient strategy for the purification of antibiotics-laden wastewater.Intense urbanization results in greater soil sealing and a consequent increase in surface runoff. When high soil sealing rates and high slopes are encountered in small catchments, high volume and short duration precipitation events increase the probability of flash floods. https://www.selleckchem.com/products/Aloxistatin.html This study evaluates the hydrological response of an urban catchment with regard to rainfall-runoff events in the following scenarios current land use, without a detention basin which has been part of the system since the 1970s, with the maximum soil sealing allowed by legislation, and with green infrastructure implantation in 100%, 50% and 10% of the suitable area. Hydrological modelling was performed using the Storm Water Management Model (SWMM). Six level gauges installed along the length of the stream provided the data used in model calibration and validation. The model calibration process provided adequate results the average Nash-Sutcliffe coefficient was 0.72, the mean error of peak flow was 11% and the mean error of the runoff volume was 12%. Rainfall based on 2-, 10-, 50- and 100-year events were simulated for each scenario, as well as two observed events. In the scenario without the detention basin, an average elevation of 10% in the peak flow was observed in the catchment outlet. In the scenario with maximum soil sealing, the catchment outlet peak flow increased by 30% on average. On the other hand, in the scenario with green infrastructure implementation in 100%, 50% and 10% of the available areas, the outlet peak flow was reduced by 60%, 30% and 5%, respectively. Results indicated the efficiency of the detention basin to reduce flooding, the importance of green area preservation to reduce peak flows, as well as the catchment potential of green infrastructure implementation and the hydrological benefits that they can provide, increasing infiltration and reducing runoff volume and peak flow.
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  • Ecological data on marine mammal parasites represent an excellent opportunity to expand our understanding of host-parasite systems. In this study, we used a dataset of intestinal helminth parasites on 167 long-finned pilot whales Globicephala melas (Traill, 1809) from seven localities in the Faroe Islands to evaluate the extent to which the host's age and sex influence the occurrence, richness, and nested pattern of helminth parasites and the importance of individual hosts to the helminth community. We found positive effects of age on both the occurrence and richness of helminths. Older host individuals showed an ordered accumulation of parasites, as evidenced by the nested pattern in their composition. Males had a higher occurrence of parasites than females, but the richness of helminths did not differ between sexes. Our findings suggest that differences in host-parasite interactions in long-finned pilot whales result mainly from age-structured variations in biological and behavioral characteristics.Naegleria fowleri causes a deadly infection known as primary amoebic meningoencephalitis (PAM). To our knowledge, there are very few transcriptome studies conducted on these brain-eating amoebae, despite rise in the number of cases. Although the Naegleria genome has been sequenced, currently, it is not well annotated. Transcriptome level studies are needed to help understand the pathology and biology of this fatal parasitic infection. Recently, we showed that nanoparticles loaded with the flavonoid Hesperidin (HDN) are potential novel antimicrobial agents. N. fowleri trophozoites were treated with and without HDN-conjugated with silver nanoparticles (AgNPs) and silver only, and then, 50% minimum inhibitory concentration (MIC) was determined. The results revealed that the ****of HDN-conjugated AgNPs was 12.5 microg/mL when treated for 3 h. As no reference genome exists for N. fowleri, de novo RNA transcriptome analysis using RNA-Seq and differential gene expression analysis was performed using the Trinity software. Analysis revealed that more than 2000 genes were differentially expressed in response to N. fowleri treatment with HDN-conjugated AgNPs. Some of the genes were linked to oxidative stress response, DNA repair, cell division, cell signalling and protein synthesis. The downregulated genes were linked with processes such as protein modification, synthesis of aromatic amino acids, when compared with untreated N. fowleri. Further transcriptome studies will lead to understanding of genetic mechanisms of the biology and pathogenesis and/or the identification of **** needed drug candidates.Giardia and Cryptosporidium infections are common in cats, but knowledge is limited about their clinical importance, risk factors, and the role of cats as a reservoir for human infections. Here, we collected faeces and questionnaire data from 284 cats from shelters and veterinary clinics in the Copenhagen Metropolitan Region (= study population). Additionally, 33 samples were analysed separately from catteries with gastrointestinal clinical signs (= cases). (Oo-)cysts were quantified by immunofluorescence microscopy. All Giardia (n = 34) and Cryptosporidium (n = 29) positive samples were analysed by sequencing of the 18S rRNA, gdh and hsp70 loci, and co-infections were detected by McMaster/inverted microscopy. In the study population, 7.0% and 6.7% were positive for Giardia and Cryptosporidium respectively; 48.5% and 36.4% of the breeder cats (cases) were infected. Increased odds of diarrhoea were demonstrated in Giardia (p = 0.0008) and Cryptosporidium (p = 0.034) positive cats. For Giardia, the odds were positively correlated with infection intensity. Co-infection with Cryptosporidium (OR 12.79; p less then 0.001), parasitic co-infections other than Cryptosporidium (OR 5.22; p = 0.009), no deworming (OR 4.67; p = 0.035), and male sex (OR 3.63; p = 0.025) were risk factors for Giardia. For Cryptosporidium, co-infection with Giardia was the only risk factor (OR 11.93; p less then 0.0001). https://www.selleckchem.com/products/8-bromo-camp.html Genotyping revealed G. duodenalis assemblages A and F, and C. felis, all of them previously detected in humans. In conclusion, excretion of Giardia and Cryptosporidium was associated with clinical disease. Although a public health risk is likely, studies including larger sample sizes, more discriminatory markers and samples from other animals and humans are needed to reveal the full zoonotic potential.Statistical surveys to detect trends in time series are fundamental tools to evaluate farming dynamics of sugarcane and of adaptation plans for possible impacts caused by climate change. This work analyzed the influence of climate change in the cultivation of sugarcane in the state of Paraíba (Northeast Brazil), in order to investigate what are the consequences of temperature increase, air humidity level, and changes in the precipitation regime forecasted for the region in sugarcane farming. Data of temperature, total precipitation, and relative humidity of six meteorological stations kept by the Brazilian National Institute of Meteorology (INMET) spread across the state of Paraíba and data from the area of sugarcane harvesting from the Brazilian Institute of Geography and Statistics (IBGE). Mann-Kendall trend test was employed in order to analyze the existence of trends in each station, separately. The results pointed trends of significant increase in temperature for the stations of Campina Grande, João Pessoa, Monteiro, Patos, and Sousa. The stations of Areia, Campina Grande, and João Pessoa obtained significant precipitation trends. Regarding relative humidity, the stations of João Pessoa, Monteiro, and Patos presented significant decreasing trends, while Sousa showed significant increase trends. The results suggest that these trends may be increasing sugarcane production close to the coast of the region and decreasing production inland.Purpose Patients who receive trastuzumab (T-mab) plus chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer sometimes respond remarkably well and can undergo radical surgery. However, the clinical outcomes of preoperative T-mab combined chemotherapy with radical gastrectomy remain unclear. We conducted this study to investigate the clinical outcomes of this multimodal treatment. Methods From among a total of 199 patients who received T-mab-based chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer between 2011 and 2018, the subjects of this retrospective analysis were 20 patients who subsequently underwent radical gastrectomy. Results Seven patients had gastroesophageal junction cancer and 13 had gastric cancer. Eleven patients had unresectable stage IV cancer and 9 had resectable metastatic disease. Chemotherapy regimens included capecitabine, cisplatin + T-mab (11 patients), and S-1, oxaliplatin + T-mab (nine patients). The median number of chemotherapy cycles before surgery was three (range, 2-62).
    Ecological data on marine mammal parasites represent an excellent opportunity to expand our understanding of host-parasite systems. In this study, we used a dataset of intestinal helminth parasites on 167 long-finned pilot whales Globicephala melas (Traill, 1809) from seven localities in the Faroe Islands to evaluate the extent to which the host's age and sex influence the occurrence, richness, and nested pattern of helminth parasites and the importance of individual hosts to the helminth community. We found positive effects of age on both the occurrence and richness of helminths. Older host individuals showed an ordered accumulation of parasites, as evidenced by the nested pattern in their composition. Males had a higher occurrence of parasites than females, but the richness of helminths did not differ between sexes. Our findings suggest that differences in host-parasite interactions in long-finned pilot whales result mainly from age-structured variations in biological and behavioral characteristics.Naegleria fowleri causes a deadly infection known as primary amoebic meningoencephalitis (PAM). To our knowledge, there are very few transcriptome studies conducted on these brain-eating amoebae, despite rise in the number of cases. Although the Naegleria genome has been sequenced, currently, it is not well annotated. Transcriptome level studies are needed to help understand the pathology and biology of this fatal parasitic infection. Recently, we showed that nanoparticles loaded with the flavonoid Hesperidin (HDN) are potential novel antimicrobial agents. N. fowleri trophozoites were treated with and without HDN-conjugated with silver nanoparticles (AgNPs) and silver only, and then, 50% minimum inhibitory concentration (MIC) was determined. The results revealed that the MIC of HDN-conjugated AgNPs was 12.5 microg/mL when treated for 3 h. As no reference genome exists for N. fowleri, de novo RNA transcriptome analysis using RNA-Seq and differential gene expression analysis was performed using the Trinity software. Analysis revealed that more than 2000 genes were differentially expressed in response to N. fowleri treatment with HDN-conjugated AgNPs. Some of the genes were linked to oxidative stress response, DNA repair, cell division, cell signalling and protein synthesis. The downregulated genes were linked with processes such as protein modification, synthesis of aromatic amino acids, when compared with untreated N. fowleri. Further transcriptome studies will lead to understanding of genetic mechanisms of the biology and pathogenesis and/or the identification of much needed drug candidates.Giardia and Cryptosporidium infections are common in cats, but knowledge is limited about their clinical importance, risk factors, and the role of cats as a reservoir for human infections. Here, we collected faeces and questionnaire data from 284 cats from shelters and veterinary clinics in the Copenhagen Metropolitan Region (= study population). Additionally, 33 samples were analysed separately from catteries with gastrointestinal clinical signs (= cases). (Oo-)cysts were quantified by immunofluorescence microscopy. All Giardia (n = 34) and Cryptosporidium (n = 29) positive samples were analysed by sequencing of the 18S rRNA, gdh and hsp70 loci, and co-infections were detected by McMaster/inverted microscopy. In the study population, 7.0% and 6.7% were positive for Giardia and Cryptosporidium respectively; 48.5% and 36.4% of the breeder cats (cases) were infected. Increased odds of diarrhoea were demonstrated in Giardia (p = 0.0008) and Cryptosporidium (p = 0.034) positive cats. For Giardia, the odds were positively correlated with infection intensity. Co-infection with Cryptosporidium (OR 12.79; p less then 0.001), parasitic co-infections other than Cryptosporidium (OR 5.22; p = 0.009), no deworming (OR 4.67; p = 0.035), and male sex (OR 3.63; p = 0.025) were risk factors for Giardia. For Cryptosporidium, co-infection with Giardia was the only risk factor (OR 11.93; p less then 0.0001). https://www.selleckchem.com/products/8-bromo-camp.html Genotyping revealed G. duodenalis assemblages A and F, and C. felis, all of them previously detected in humans. In conclusion, excretion of Giardia and Cryptosporidium was associated with clinical disease. Although a public health risk is likely, studies including larger sample sizes, more discriminatory markers and samples from other animals and humans are needed to reveal the full zoonotic potential.Statistical surveys to detect trends in time series are fundamental tools to evaluate farming dynamics of sugarcane and of adaptation plans for possible impacts caused by climate change. This work analyzed the influence of climate change in the cultivation of sugarcane in the state of Paraíba (Northeast Brazil), in order to investigate what are the consequences of temperature increase, air humidity level, and changes in the precipitation regime forecasted for the region in sugarcane farming. Data of temperature, total precipitation, and relative humidity of six meteorological stations kept by the Brazilian National Institute of Meteorology (INMET) spread across the state of Paraíba and data from the area of sugarcane harvesting from the Brazilian Institute of Geography and Statistics (IBGE). Mann-Kendall trend test was employed in order to analyze the existence of trends in each station, separately. The results pointed trends of significant increase in temperature for the stations of Campina Grande, João Pessoa, Monteiro, Patos, and Sousa. The stations of Areia, Campina Grande, and João Pessoa obtained significant precipitation trends. Regarding relative humidity, the stations of João Pessoa, Monteiro, and Patos presented significant decreasing trends, while Sousa showed significant increase trends. The results suggest that these trends may be increasing sugarcane production close to the coast of the region and decreasing production inland.Purpose Patients who receive trastuzumab (T-mab) plus chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer sometimes respond remarkably well and can undergo radical surgery. However, the clinical outcomes of preoperative T-mab combined chemotherapy with radical gastrectomy remain unclear. We conducted this study to investigate the clinical outcomes of this multimodal treatment. Methods From among a total of 199 patients who received T-mab-based chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer between 2011 and 2018, the subjects of this retrospective analysis were 20 patients who subsequently underwent radical gastrectomy. Results Seven patients had gastroesophageal junction cancer and 13 had gastric cancer. Eleven patients had unresectable stage IV cancer and 9 had resectable metastatic disease. Chemotherapy regimens included capecitabine, cisplatin + T-mab (11 patients), and S-1, oxaliplatin + T-mab (nine patients). The median number of chemotherapy cycles before surgery was three (range, 2-62).
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