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  • 13 log 10 (MPN+1)/100ml. Salmonella isolates were resistant to nalidixic acid and tetracycline. The results from this study highlight the need for further training on mitigation strategies to reduce contamination of animal products and fresh produce by foodborne pathogens.Context Developing low-cost assessment tools to quantify ankle biomechanics in a clinical setting may improve rehabilitation for patients with chronic ankle instability (CAI). Objective To determine whether a crossline laser can predict peak plantar pressure during walking. Design Descriptive laboratory study. Setting Laboratory. Patients or other participants Twenty-five participants with CAI (9 men, 16 women; age = 20.8 ± 2.3 years, height = 170.4 ± 10.4 cm, mass = 78.9 ± 22.4 kg). Intervention(s) Participants completed 30 seconds of treadmill walking with a crossline laser fixed to their shoe while, simultaneously, a video camera recorded the laser projection on the wall and an in-shoe plantar-pressure system measured plantar pressure. Main outcome measure(s) Peak laser rotation and peak plantar pressure of the lateral midfoot and forefoot. Results With respect to peak plantar pressure, peak rotation of the laser during walking explained 57% of the variance in the lateral midfoot and 64% in the lateral forefoot. Conclusions The crossline laser may be a valuable clinical tool for predicting lateral peak plantar pressure in patients with CAI during walking.Background The response to adrenocorticotropic hormone (ACTH) is poorly characterized in old-old adults and may provide insight into the physiologic response to stress. Methods We performed a standard 250 mcg ACTH stimulation test in a home-based substudy of 51 women aged 85-96 years enrolled in the Women's Health and Aging Study II who were not taking corticosteroids. We examined the cortisol and dehydroepiandrosterone (DHEA) responses at 0, 30, 60, and 120 minutes, overall and by frailty status. Results The peak cortisol response to ACTH could not be determined, with the highest levels at the 120 minute time point. Pre- and post-ACTH stimulated cortisol levels did not differ by frailty status over this time frame, with no difference in the characteristics of the dose-response curves. Pre- and post-ACTH stimulated DHEA levels also did not differ by frailty status, though the dose-response curves suggested divergence after stimulation, with a more rapid DHEA response with increasing frailty. Conclusions Our data demonstrate a robust cortisol response to ACTH challenge testing, but inadequate negative feedback in old-old women, resulting in prolonged exposure to cortisol. Future studies should examine dynamic cortisol and DHEA responses in this age group, using a less potent ACTH stimulus and longer collection period.Summary Experimental laboratory management and data-driven science require centralized software for sharing information such as lab collections or genomic sequencing datasets. Although database servers such as PostgreSQL can store such information with multiple-user access, they lack user-friendly graphical and programmatic interfaces for easy data access and inputting. We developed LabxDB, a versatile open-source solution for organizing and sharing structured data. We provide several out-of-the-box databases for deployment in the cloud including simple mutant or plasmid collections and purchase-tracking databases. We also developed a high-throughput sequencing (HTS) database, LabxDB seq, dedicated to storage of hierarchical sample annotations. Scientists can import their own or publicly available HTS data into LabxDB seq to manage them from production to publication. Using LabxDB's programmatic access (REST API), annotations can be easily integrated into bioinformatics pipelines. LabxDB is modular, offering a flexible framework that scientists can leverage to build new database interfaces adapted to their needs. Availability LabxDB is available at https//gitlab.com/vejnar/labxdb and https//labxdb.vejnar.org for documentation. LabxDB is licensed under the terms of the Mozilla Public License 2.0. Supplementary information Supplementary data are available at Bioinformatics online.Motivation Large-scale sequencing studies have created a need to succinctly visualize genomic characteristics of patient cohorts linked to widely variable phenotypic information. This is often done by visualizing the co-occurrence of variants with comutation plots. Current tools lack the ability to create highly customizable and publication quality comutation plots from arbitrary user data. Results We developed CoMut, a stand-alone, object-oriented Python package that creates comutation plots from arbitrary input data, including categorical data, continuous data, bar graphs, side bar graphs, and data that describes relationships between samples. Availability and implementation The CoMut package is open source and is available at https//github.com/vanallenlab/comut under the MIT License, along with documentation and examples. A no installation, easy-to-use implementation is available on Google Colab (see GitHub).Phylogenetic species of Paracoccidioides brasiliensis complex (S1a and S1b, PS2, PS3, and PS4) and Paracoccidioides lutzii are agents of paracoccidioidomycosis, an endemic fungal disease in Latin America. https://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html P. restrepiensis (PS3 genotype) was classified as monophyletic and geographically restricted to Colombia and neighboring territories. BAT (or Pb-327B) was isolated from a patient living in the southeast region of Brazil but with genotype similar to Colombian Paracoccidioides spp. strains. This study aimed to define the phylogenetic species of BAT isolate by using additional genotyping methods, as well as reviewing the epidemiological and clinical studies related to P. restrepiensis isolates. Genomic DNA of BAT isolate and reference strains of P. brasiliensis sensu stricto (S1b), P. americana (PS2), P. restrepiensis (PS3), and P. lutzii were analyzed by conventional polymerase chain reaction (PCR) of partial gp43 exon 2 loci, by PCR-RFLP technique of tub1 gene, and by sequencing of the whole gp43 exon 2 loci. Here, we show that BAT isolate belongs to P. restrepiensis species, which is an unusual identification in southeastern Brazil, where P. brasiliensis sensu stricto is the prevalent genotype. This identification has relevance for geographical distribution and propagation of the genus Paracoccidioides in South America.
    13 log 10 (MPN+1)/100ml. Salmonella isolates were resistant to nalidixic acid and tetracycline. The results from this study highlight the need for further training on mitigation strategies to reduce contamination of animal products and fresh produce by foodborne pathogens.Context Developing low-cost assessment tools to quantify ankle biomechanics in a clinical setting may improve rehabilitation for patients with chronic ankle instability (CAI). Objective To determine whether a crossline laser can predict peak plantar pressure during walking. Design Descriptive laboratory study. Setting Laboratory. Patients or other participants Twenty-five participants with CAI (9 men, 16 women; age = 20.8 ± 2.3 years, height = 170.4 ± 10.4 cm, mass = 78.9 ± 22.4 kg). Intervention(s) Participants completed 30 seconds of treadmill walking with a crossline laser fixed to their shoe while, simultaneously, a video camera recorded the laser projection on the wall and an in-shoe plantar-pressure system measured plantar pressure. Main outcome measure(s) Peak laser rotation and peak plantar pressure of the lateral midfoot and forefoot. Results With respect to peak plantar pressure, peak rotation of the laser during walking explained 57% of the variance in the lateral midfoot and 64% in the lateral forefoot. Conclusions The crossline laser may be a valuable clinical tool for predicting lateral peak plantar pressure in patients with CAI during walking.Background The response to adrenocorticotropic hormone (ACTH) is poorly characterized in old-old adults and may provide insight into the physiologic response to stress. Methods We performed a standard 250 mcg ACTH stimulation test in a home-based substudy of 51 women aged 85-96 years enrolled in the Women's Health and Aging Study II who were not taking corticosteroids. We examined the cortisol and dehydroepiandrosterone (DHEA) responses at 0, 30, 60, and 120 minutes, overall and by frailty status. Results The peak cortisol response to ACTH could not be determined, with the highest levels at the 120 minute time point. Pre- and post-ACTH stimulated cortisol levels did not differ by frailty status over this time frame, with no difference in the characteristics of the dose-response curves. Pre- and post-ACTH stimulated DHEA levels also did not differ by frailty status, though the dose-response curves suggested divergence after stimulation, with a more rapid DHEA response with increasing frailty. Conclusions Our data demonstrate a robust cortisol response to ACTH challenge testing, but inadequate negative feedback in old-old women, resulting in prolonged exposure to cortisol. Future studies should examine dynamic cortisol and DHEA responses in this age group, using a less potent ACTH stimulus and longer collection period.Summary Experimental laboratory management and data-driven science require centralized software for sharing information such as lab collections or genomic sequencing datasets. Although database servers such as PostgreSQL can store such information with multiple-user access, they lack user-friendly graphical and programmatic interfaces for easy data access and inputting. We developed LabxDB, a versatile open-source solution for organizing and sharing structured data. We provide several out-of-the-box databases for deployment in the cloud including simple mutant or plasmid collections and purchase-tracking databases. We also developed a high-throughput sequencing (HTS) database, LabxDB seq, dedicated to storage of hierarchical sample annotations. Scientists can import their own or publicly available HTS data into LabxDB seq to manage them from production to publication. Using LabxDB's programmatic access (REST API), annotations can be easily integrated into bioinformatics pipelines. LabxDB is modular, offering a flexible framework that scientists can leverage to build new database interfaces adapted to their needs. Availability LabxDB is available at https//gitlab.com/vejnar/labxdb and https//labxdb.vejnar.org for documentation. LabxDB is licensed under the terms of the Mozilla Public License 2.0. Supplementary information Supplementary data are available at Bioinformatics online.Motivation Large-scale sequencing studies have created a need to succinctly visualize genomic characteristics of patient cohorts linked to widely variable phenotypic information. This is often done by visualizing the co-occurrence of variants with comutation plots. Current tools lack the ability to create highly customizable and publication quality comutation plots from arbitrary user data. Results We developed CoMut, a stand-alone, object-oriented Python package that creates comutation plots from arbitrary input data, including categorical data, continuous data, bar graphs, side bar graphs, and data that describes relationships between samples. Availability and implementation The CoMut package is open source and is available at https//github.com/vanallenlab/comut under the MIT License, along with documentation and examples. A no installation, easy-to-use implementation is available on Google Colab (see GitHub).Phylogenetic species of Paracoccidioides brasiliensis complex (S1a and S1b, PS2, PS3, and PS4) and Paracoccidioides lutzii are agents of paracoccidioidomycosis, an endemic fungal disease in Latin America. https://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html P. restrepiensis (PS3 genotype) was classified as monophyletic and geographically restricted to Colombia and neighboring territories. BAT (or Pb-327B) was isolated from a patient living in the southeast region of Brazil but with genotype similar to Colombian Paracoccidioides spp. strains. This study aimed to define the phylogenetic species of BAT isolate by using additional genotyping methods, as well as reviewing the epidemiological and clinical studies related to P. restrepiensis isolates. Genomic DNA of BAT isolate and reference strains of P. brasiliensis sensu stricto (S1b), P. americana (PS2), P. restrepiensis (PS3), and P. lutzii were analyzed by conventional polymerase chain reaction (PCR) of partial gp43 exon 2 loci, by PCR-RFLP technique of tub1 gene, and by sequencing of the whole gp43 exon 2 loci. Here, we show that BAT isolate belongs to P. restrepiensis species, which is an unusual identification in southeastern Brazil, where P. brasiliensis sensu stricto is the prevalent genotype. This identification has relevance for geographical distribution and propagation of the genus Paracoccidioides in South America.
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  • As the prevalence of metabolic syndrome (MetS) in children and young adults is increasing, a better understanding of genetics that underlie MetS will provide critical insights into the origin of the disease. We examined associations of common genetic variants and repeated MetS score from early childhood to adolescence in a pan-European, prospective IDEFICS/I.Family cohort study with baseline survey and follow-up examinations after two and six years. We tested associations in 3067 children using a linear mixed model and confirmed the results with meta-analysis of identified SNPs. With a stringent Bonferroni adjustment for multiple comparisons we obtained significant associations(p  0.85) in the 16q12.2 non-coding intronic chromosomal region of FTO gene with strongest association observed for rs8050136 (effect size(β) = 0.31, pWald = 1.52 × 10-5). We also observed a strong association of rs708272 in CETP with increased HDL (p = 5.63 × 10-40) and decreased TRG (p = 9.60 × 10-5) levels. These findings along with meta-analysis advance etiologic understanding of childhood MetS, highlighting that genetic predisposition to MetS is largely driven by genes of obesity and lipid metabolism. Inclusion of the associated genetic variants in polygenic scores for MetS may prove to be fundamental for identifying children and subsequently adults of the high-risk group to allow earlier targeted interventions.Anaemia among children under 5, is a public health problem of serious concern. In Ghana, an estimated 8 out of every 10 children are anaemic. This study employed a novel approach to investigate the determinants of normal haemoglobin (Hb) concentration among children aged 6 to 59 months, using data from the Ghana Demographic and Health Surveys. The results showed that maternal schooling was positively associated with normal Hb concentration among children. Children of non-anaemic mothers were 1.67 (CI = 1.32, 2.10; P  less then  0.001) times more likely to have normal Hb concentration relative to children of anaemic mothers. Compared to mothers who had less than 4 antenatal care (ANC) visits, mothers who had at least 4 ANC visits increased the odds of their children having a normal Hb concentration by 1.62 (CI = 1.09, 2.40; P  less then  0.018). Children living in middle and rich households had respectively 1.48 (CI = 1.06, 2.07; p  less then  0.021) and 1.59 (CI = 1.08, 2.33; p  less then  0.018) increased odds of having a normal Hb concentration relative to those living in poor households. https://www.selleckchem.com/products/heptadecanoic-acid.html Maternal education, anaemia, ANC attendance, and household wealth index are strong determinants of normal Hb concentration among children in Ghana. Strategies aimed at addressing childhood anaemia should take into account maternal anaemia, education, poverty and ANC attendance.Medical radiation exposure is a significant concern for interventional cardiologists (IC). This study was aimed at estimating the radiation exposure of IC operators and assistants in real clinical practice. The radiation exposure of the operator and assistant was evaluated by conducting two types of procedures via coronary angiography (CAG) and percutaneous coronary intervention (PCI) on 1090 patients in 11-cardiovascular centers in Korea. Radiation exposure was measured using an electronic personal dosimeter (EPD). EPD were attached at 3 points on each participant on the apron on the left anterior chest (A1), under the apron on the sternum (A2), and on the thyroid shield (T). Average radiation exposure (ARE) of operators at A1, A2, and T was 19.219 uSv, 4.398 uSv, and 16.949 uSv during CAG and 68.618 uSv, 15.213 uSv, and 51.197 uSv during PCI, respectively. ARE of assistants at A1, A2, and T was 4.941 uSv, 0.860 uSv, and 5.232 uSv during CAG and 20.517 uSv, 4.455 uSv, and 16.109 uSv during PCI, respectively. AED of operator was 3.4 times greater during PCI than during CAG.Although isolated Champsosaurus remains are common in Upper Cretaceous sediments of North America, the braincase of these animals is enigmatic due to the fragility of their skulls. Here, two well-preserved specimens of Champsosaurus (CMN 8920 and CMN 8919) are CT scanned to describe their neurosensory structures and infer sensory capability. The anterior portion of the braincase was poorly ossified and thus does not permit visualization of a complete endocast; however, impressions of the olfactory stalks indicate that they were elongate and likely facilitated good olfaction. The posterior portion of the braincase is ossified and morphologically similar to that of other extinct diapsids. The absence of an otic notch and an expansion of the pars inferior of the inner ear suggests Champsosaurus was limited to detecting low frequency sounds. Comparison of the shapes of semicircular canals with lepidosaurs and archosauromorphs demonstrates that the semicircular canals of Champsosaurus are most similar to those of aquatic reptiles, suggesting that Champsosaurus was well adapted for sensing movement in an aquatic environment. This analysis also demonstrates that birds, non-avian archosauromorphs, and lepidosaurs possess significantly different canal morphologies, and represents the first morphometric analysis of semicircular canals across Diapsida.Quantum walk is a key operation in quantum computing, simulation, communication and information. Here, we report for the first time the demonstration of quantum walks and localized quantum walks in a new type of optical fibers having a ring of cores constructed with both periodic and quasiperiodic Fibonacci sequences, respectively. Good agreement between theoretical and experimental results has been achieved. The new multicore ring fibers provide a new platform for experiments of quantum effects in low-loss optical fibers which is critical for scalability of real applications with large-size problems. Furthermore, our new quasiperiodic Fibonacci multicore ring fibers provide a new class of quasiperiodic photonics lattices possessing both on- and off-diagonal deterministic disorders for realizing localized quantum walks deterministically. The proposed Fibonacci fibers are simple and straightforward to fabricate and have a rich set of properties that are of potential use for quantum applications. Our simulation and experimental results show that, in contrast with randomly disordered structures, localized quantum walks in new proposed quasiperiodic photonics lattices are highly controllable due to the deterministic disordered nature of quasiperiodic systems.
    As the prevalence of metabolic syndrome (MetS) in children and young adults is increasing, a better understanding of genetics that underlie MetS will provide critical insights into the origin of the disease. We examined associations of common genetic variants and repeated MetS score from early childhood to adolescence in a pan-European, prospective IDEFICS/I.Family cohort study with baseline survey and follow-up examinations after two and six years. We tested associations in 3067 children using a linear mixed model and confirmed the results with meta-analysis of identified SNPs. With a stringent Bonferroni adjustment for multiple comparisons we obtained significant associations(p  0.85) in the 16q12.2 non-coding intronic chromosomal region of FTO gene with strongest association observed for rs8050136 (effect size(β) = 0.31, pWald = 1.52 × 10-5). We also observed a strong association of rs708272 in CETP with increased HDL (p = 5.63 × 10-40) and decreased TRG (p = 9.60 × 10-5) levels. These findings along with meta-analysis advance etiologic understanding of childhood MetS, highlighting that genetic predisposition to MetS is largely driven by genes of obesity and lipid metabolism. Inclusion of the associated genetic variants in polygenic scores for MetS may prove to be fundamental for identifying children and subsequently adults of the high-risk group to allow earlier targeted interventions.Anaemia among children under 5, is a public health problem of serious concern. In Ghana, an estimated 8 out of every 10 children are anaemic. This study employed a novel approach to investigate the determinants of normal haemoglobin (Hb) concentration among children aged 6 to 59 months, using data from the Ghana Demographic and Health Surveys. The results showed that maternal schooling was positively associated with normal Hb concentration among children. Children of non-anaemic mothers were 1.67 (CI = 1.32, 2.10; P  less then  0.001) times more likely to have normal Hb concentration relative to children of anaemic mothers. Compared to mothers who had less than 4 antenatal care (ANC) visits, mothers who had at least 4 ANC visits increased the odds of their children having a normal Hb concentration by 1.62 (CI = 1.09, 2.40; P  less then  0.018). Children living in middle and rich households had respectively 1.48 (CI = 1.06, 2.07; p  less then  0.021) and 1.59 (CI = 1.08, 2.33; p  less then  0.018) increased odds of having a normal Hb concentration relative to those living in poor households. https://www.selleckchem.com/products/heptadecanoic-acid.html Maternal education, anaemia, ANC attendance, and household wealth index are strong determinants of normal Hb concentration among children in Ghana. Strategies aimed at addressing childhood anaemia should take into account maternal anaemia, education, poverty and ANC attendance.Medical radiation exposure is a significant concern for interventional cardiologists (IC). This study was aimed at estimating the radiation exposure of IC operators and assistants in real clinical practice. The radiation exposure of the operator and assistant was evaluated by conducting two types of procedures via coronary angiography (CAG) and percutaneous coronary intervention (PCI) on 1090 patients in 11-cardiovascular centers in Korea. Radiation exposure was measured using an electronic personal dosimeter (EPD). EPD were attached at 3 points on each participant on the apron on the left anterior chest (A1), under the apron on the sternum (A2), and on the thyroid shield (T). Average radiation exposure (ARE) of operators at A1, A2, and T was 19.219 uSv, 4.398 uSv, and 16.949 uSv during CAG and 68.618 uSv, 15.213 uSv, and 51.197 uSv during PCI, respectively. ARE of assistants at A1, A2, and T was 4.941 uSv, 0.860 uSv, and 5.232 uSv during CAG and 20.517 uSv, 4.455 uSv, and 16.109 uSv during PCI, respectively. AED of operator was 3.4 times greater during PCI than during CAG.Although isolated Champsosaurus remains are common in Upper Cretaceous sediments of North America, the braincase of these animals is enigmatic due to the fragility of their skulls. Here, two well-preserved specimens of Champsosaurus (CMN 8920 and CMN 8919) are CT scanned to describe their neurosensory structures and infer sensory capability. The anterior portion of the braincase was poorly ossified and thus does not permit visualization of a complete endocast; however, impressions of the olfactory stalks indicate that they were elongate and likely facilitated good olfaction. The posterior portion of the braincase is ossified and morphologically similar to that of other extinct diapsids. The absence of an otic notch and an expansion of the pars inferior of the inner ear suggests Champsosaurus was limited to detecting low frequency sounds. Comparison of the shapes of semicircular canals with lepidosaurs and archosauromorphs demonstrates that the semicircular canals of Champsosaurus are most similar to those of aquatic reptiles, suggesting that Champsosaurus was well adapted for sensing movement in an aquatic environment. This analysis also demonstrates that birds, non-avian archosauromorphs, and lepidosaurs possess significantly different canal morphologies, and represents the first morphometric analysis of semicircular canals across Diapsida.Quantum walk is a key operation in quantum computing, simulation, communication and information. Here, we report for the first time the demonstration of quantum walks and localized quantum walks in a new type of optical fibers having a ring of cores constructed with both periodic and quasiperiodic Fibonacci sequences, respectively. Good agreement between theoretical and experimental results has been achieved. The new multicore ring fibers provide a new platform for experiments of quantum effects in low-loss optical fibers which is critical for scalability of real applications with large-size problems. Furthermore, our new quasiperiodic Fibonacci multicore ring fibers provide a new class of quasiperiodic photonics lattices possessing both on- and off-diagonal deterministic disorders for realizing localized quantum walks deterministically. The proposed Fibonacci fibers are simple and straightforward to fabricate and have a rich set of properties that are of potential use for quantum applications. Our simulation and experimental results show that, in contrast with randomly disordered structures, localized quantum walks in new proposed quasiperiodic photonics lattices are highly controllable due to the deterministic disordered nature of quasiperiodic systems.
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  • upport was safe or effective for the treatment of transient tachypnea of the newborn. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.This analysis developed a population pharmacokinetic (PK) model for odanacatib, characterized demographic and concomitant medication covariates effect, and provided odanacatib exposure estimates for subjects in phase 2/3 studies. Data from multiple phase 1 (P005, P025, and P014), phase 2b (P004 and P022), and phase 3 (Long-Term Odanacatib Fracture Trial; P018) studies were pooled to create a data set of 1280 postmenopausal women aged 45 to 91 years (102 from phase 1, 514 from phase 2b, and 664 from phase 3) who received weekly oral odanacatib doses ranging from 3 to 100 mg. A 1-compartment model with first-order absorption, dose-dependent relative bioavailability (F1), and first-order elimination best described odanacatib PK. F1 decreased from the 100% reference bioavailability for a 3-mg oral dose to 24.5% for a 100-mg dose. Eight statistically significant covariates were included in the final PK model body weight, age, race, and concomitant cytochrome P450 (CYP)3A inhibitors on apparent clearance; body weight on apparent central volume of distribution; and concomitant hydrochlorothiazide, high-fat breakfast, and a study effect on F1. All fixed- and random-effects parameters were estimated with good precision (%standard error of the mean ≤29.5%). This population PK analysis provides insights into intrinsic- and extrinsic-factor effects on odanacatib exposure in postmenopausal and elderly women with osteoporosis. The magnitude of the intrinsic-factor effects was generally modest (odanacatib exposure geometric mean ratios, 0.80-1.21) even in subjects aged >80 years, or in subsets with multiple combinations of factors. © 2020, The American College of Clinical Pharmacology.BACKGROUND The R-DHAP regimen (rituximab, cisplatin, dexamethasone, high-dose cytarabine) is standardly used to treat relapsed Non-Hodgkin lymphoma (NHL). Despite scarce data, cisplatin is frequently substituted with oxaliplatin (R-DHAOx) to avoid nephrotoxicity. We compared nephrotoxicity of cisplatin and oxaliplatin based on creatinine-based trajectory modelling. METHODS All patients with NHL treated by R-DHAP or R-DHAOx in Angers hospital between 2007/01/01 and 2014/12/31 were included. Patients received cisplatin 100 mg/m2 or oxaliplatin 130 mg/m2 (d1) with cytarabine (2000 mg/m2, two doses, d2), dexamethasone (40 mg, d1-4), rituximab (375mg/m2, d1). Creatinine levels were recorded before each cycle. Individual profiles of trajectories were clustered to detect homogeneous patterns of evolution. RESULTS 22 patients received R-DHAP, 35 R-DHAOx, 6 switched from R-DHAP to R-DHAOx due to nephrotoxicity. Characteristics of patients were similar between two groups. Patients receiving R-DHAP experienced more severe renal injury than patients receiving R-DHAOx (68% vs. 7.7%, p less then 0.001). Two homogeneous clusters appeared cluster A, with a majority of R-DHAOx (32, 91.4%), was less nephrotoxic than B, with a majority of R-DHAP (19, 86.4%), with a decreased average serum creatinine level (p less then 0.0001). There were no other differences between clusters. CONCLUSIONS Our study confirms that R-DHAOx regimen causes less nephrotoxicity than R-DHAP regimen. This article is protected by copyright. All rights reserved.I do not believe that this manuscript type (Medical Education Adaptations Really Good Stuff for Educational Transition during a Pandemic) includes an abstract. This article is protected by copyright. All rights reserved.OBJECTIVE Pegylated IFN α2a has been reported in two case reports as being efficacious in treating CDA-I patients. This study aims to assess its efficacy on a series of CDA-I patients. METHODS Study sample consisted of seven CDA type 1 transfusion-dependent patients. They received pegylated interferon alfa 2a at an initial dose of 90-180mcg once a week, tapered according to clinical response and side effects. Good response was defined as Hb ≥ 10gr/dL for ≥ three months, Partial response was defined as 7≤Hb less then 10gr/dL for ≥ three months, and no response was defined as HB less then 7g/dL for over three months on treatment. Time to response was defined as the time needed to achieve hemoglobin levels ≥ 10g/dL without transfusion. Patients were evaluated periodically by abdominal ultrasounds to rule out liver adenomas. RESULTS Five patients (71%) had a good response to treatment. One patient stopped treatment due to side effects. One patient had partial response. One patient, with more severe phenotype and poor compliance, had poor response to treatment. No abnormal findings were found in ultrasound examination. No effect on serum ferritin level could be established. CONCLUSION Pegylated interferon α2a therapy is efficacious in CDA-I patients with a reasonable safety profile. This article is protected by copyright. All rights reserved.The use of left ventricular assist devices (LVADs) as a treatment method for heart failure patients has been steadily increasing; however, pathological studies showed presence of thrombi around the HeartWare ventricular assist device inflow cannula (IC) in more than 95% of patients after device explantation. Flow fields around the IC might trigger thrombus formation and require further investigation. https://www.selleckchem.com/products/riluzole-hydrochloride.html In this study flow dynamics parameters were evaluated for different patient geometries using computational fluid dynamics (CFD) simulations. Left ventricular (LV) models of two LVAD patients were obtained from CT scans. The LV volumes of Patient 1 (P1) and Patient 2 (P2) were 264 and 114 cm3 with an IC angle of 20° and 9° from the mitral-IC tip axis at the coronal plane. The IC insertion site at the apex was central for P1, whereas it was lateral for P2. Transient CFD simulations were performed over 9 cardiac cycles. The wedge area was defined from the cannula tip to the wall of the LV apex. Mean velocity magnitude and blood stagnation region (volume with mean velocity less then 5 mm/s) as well as the wall shear stress (WSS) at the IC surface were calculated. Cardiac support resulted in a flow mainly crossing the ventricle from the mitral valve to the LVAD cannula for P2, while the main inflow jet deviated toward the septal wall in P1. Lower WSS at the IC surface and consequently larger stagnation volumes were observed for P2 (P1 0.17, P2 0.77 cm3 ). Flow fields around an LVAD cannula can be influenced by many parameters such as LV size, IC angle, and implantation site. Careful consideration of influencing parameters is essential to get reliable evaluations of the apical flow field and its connection to apical thrombus formation. Higher blood washout and lower stagnation were observed for a central implantation of the IC at the apex. © 2020 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.
    upport was safe or effective for the treatment of transient tachypnea of the newborn. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.This analysis developed a population pharmacokinetic (PK) model for odanacatib, characterized demographic and concomitant medication covariates effect, and provided odanacatib exposure estimates for subjects in phase 2/3 studies. Data from multiple phase 1 (P005, P025, and P014), phase 2b (P004 and P022), and phase 3 (Long-Term Odanacatib Fracture Trial; P018) studies were pooled to create a data set of 1280 postmenopausal women aged 45 to 91 years (102 from phase 1, 514 from phase 2b, and 664 from phase 3) who received weekly oral odanacatib doses ranging from 3 to 100 mg. A 1-compartment model with first-order absorption, dose-dependent relative bioavailability (F1), and first-order elimination best described odanacatib PK. F1 decreased from the 100% reference bioavailability for a 3-mg oral dose to 24.5% for a 100-mg dose. Eight statistically significant covariates were included in the final PK model body weight, age, race, and concomitant cytochrome P450 (CYP)3A inhibitors on apparent clearance; body weight on apparent central volume of distribution; and concomitant hydrochlorothiazide, high-fat breakfast, and a study effect on F1. All fixed- and random-effects parameters were estimated with good precision (%standard error of the mean ≤29.5%). This population PK analysis provides insights into intrinsic- and extrinsic-factor effects on odanacatib exposure in postmenopausal and elderly women with osteoporosis. The magnitude of the intrinsic-factor effects was generally modest (odanacatib exposure geometric mean ratios, 0.80-1.21) even in subjects aged >80 years, or in subsets with multiple combinations of factors. © 2020, The American College of Clinical Pharmacology.BACKGROUND The R-DHAP regimen (rituximab, cisplatin, dexamethasone, high-dose cytarabine) is standardly used to treat relapsed Non-Hodgkin lymphoma (NHL). Despite scarce data, cisplatin is frequently substituted with oxaliplatin (R-DHAOx) to avoid nephrotoxicity. We compared nephrotoxicity of cisplatin and oxaliplatin based on creatinine-based trajectory modelling. METHODS All patients with NHL treated by R-DHAP or R-DHAOx in Angers hospital between 2007/01/01 and 2014/12/31 were included. Patients received cisplatin 100 mg/m2 or oxaliplatin 130 mg/m2 (d1) with cytarabine (2000 mg/m2, two doses, d2), dexamethasone (40 mg, d1-4), rituximab (375mg/m2, d1). Creatinine levels were recorded before each cycle. Individual profiles of trajectories were clustered to detect homogeneous patterns of evolution. RESULTS 22 patients received R-DHAP, 35 R-DHAOx, 6 switched from R-DHAP to R-DHAOx due to nephrotoxicity. Characteristics of patients were similar between two groups. Patients receiving R-DHAP experienced more severe renal injury than patients receiving R-DHAOx (68% vs. 7.7%, p less then 0.001). Two homogeneous clusters appeared cluster A, with a majority of R-DHAOx (32, 91.4%), was less nephrotoxic than B, with a majority of R-DHAP (19, 86.4%), with a decreased average serum creatinine level (p less then 0.0001). There were no other differences between clusters. CONCLUSIONS Our study confirms that R-DHAOx regimen causes less nephrotoxicity than R-DHAP regimen. This article is protected by copyright. All rights reserved.I do not believe that this manuscript type (Medical Education Adaptations Really Good Stuff for Educational Transition during a Pandemic) includes an abstract. This article is protected by copyright. All rights reserved.OBJECTIVE Pegylated IFN α2a has been reported in two case reports as being efficacious in treating CDA-I patients. This study aims to assess its efficacy on a series of CDA-I patients. METHODS Study sample consisted of seven CDA type 1 transfusion-dependent patients. They received pegylated interferon alfa 2a at an initial dose of 90-180mcg once a week, tapered according to clinical response and side effects. Good response was defined as Hb ≥ 10gr/dL for ≥ three months, Partial response was defined as 7≤Hb less then 10gr/dL for ≥ three months, and no response was defined as HB less then 7g/dL for over three months on treatment. Time to response was defined as the time needed to achieve hemoglobin levels ≥ 10g/dL without transfusion. Patients were evaluated periodically by abdominal ultrasounds to rule out liver adenomas. RESULTS Five patients (71%) had a good response to treatment. One patient stopped treatment due to side effects. One patient had partial response. One patient, with more severe phenotype and poor compliance, had poor response to treatment. No abnormal findings were found in ultrasound examination. No effect on serum ferritin level could be established. CONCLUSION Pegylated interferon α2a therapy is efficacious in CDA-I patients with a reasonable safety profile. This article is protected by copyright. All rights reserved.The use of left ventricular assist devices (LVADs) as a treatment method for heart failure patients has been steadily increasing; however, pathological studies showed presence of thrombi around the HeartWare ventricular assist device inflow cannula (IC) in more than 95% of patients after device explantation. Flow fields around the IC might trigger thrombus formation and require further investigation. https://www.selleckchem.com/products/riluzole-hydrochloride.html In this study flow dynamics parameters were evaluated for different patient geometries using computational fluid dynamics (CFD) simulations. Left ventricular (LV) models of two LVAD patients were obtained from CT scans. The LV volumes of Patient 1 (P1) and Patient 2 (P2) were 264 and 114 cm3 with an IC angle of 20° and 9° from the mitral-IC tip axis at the coronal plane. The IC insertion site at the apex was central for P1, whereas it was lateral for P2. Transient CFD simulations were performed over 9 cardiac cycles. The wedge area was defined from the cannula tip to the wall of the LV apex. Mean velocity magnitude and blood stagnation region (volume with mean velocity less then 5 mm/s) as well as the wall shear stress (WSS) at the IC surface were calculated. Cardiac support resulted in a flow mainly crossing the ventricle from the mitral valve to the LVAD cannula for P2, while the main inflow jet deviated toward the septal wall in P1. Lower WSS at the IC surface and consequently larger stagnation volumes were observed for P2 (P1 0.17, P2 0.77 cm3 ). Flow fields around an LVAD cannula can be influenced by many parameters such as LV size, IC angle, and implantation site. Careful consideration of influencing parameters is essential to get reliable evaluations of the apical flow field and its connection to apical thrombus formation. Higher blood washout and lower stagnation were observed for a central implantation of the IC at the apex. © 2020 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.
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  • 001). Spirituality was very important to 39.9% and religiosity to 31.7% of patients, and unimportant to 30.6% and 39.5%, respectively. Following diagnosis, patients prayed (p less then 0.001) and meditated (p less then 0.001) more, seeking more time, strength and acceptance. Attendance at religious services decreased with frailty (p less then 0.001), while engagement in other religious activities increased (p=0.017). Patients who received some level of spiritual/religious support from external religious/faith communities and moderate to complete spiritual/religious needs met by the hospitals reported greater total FACIT-SP-12 spirituality scores (p less then 0.001). Conclusion Respectful inquiry into patients spiritual/religious needs in hospitals allows for an attuned approach to addressing such care needs while considerately accommodating those disinterested in such support.Objectives To examine the effects of nurse-led interventions on the health-related quality of life, symptom burden and self-management/behavioural outcomes in women with breast cancer. Methods Cochrane Controlled Register of Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline and Embase databases were searched (January 1999 to May 2019) to identify randomised controlled trials (RCTs) and controlled before-and-after studies of interventions delivered by nurses with oncology experience for women with breast cancer. Risk of bias was evaluated using the revised Cochrane risk-of-bias tool for randomised trials. Intervention effects were synthesised by cancer trajectory using The Omaha System Intervention Classification Scheme. Results Thirty-one RCTs (4651 participants) were included. All studies were at risk of bias mainly due to inherent limitations such as lack of blinding and self-report data. Most studies (71%; n=22) reported at least one superior intervention effect. e International Prospective Register of Systematic Reviews (PROSPERO) CRD42020134914).Background Refractory angina can have a significant effect on quality of life. Non-invasive interventions have been suggested but there are few guidelines on management. https://www.selleckchem.com/products/remdesivir.html Our aim was to systematically review all studies that reported non-invasive interventions for refractory angina and report on their effectiveness and safety. Methods We performed a literature search of six databases and a grey literature search. Treatments considered first line or second line according to the European Society of Cardiology were excluded, as were interventions that had undergone review within the last 3 years. Design, setting and outcomes were extracted and quality was assessed. A narrative synthesis was undertaken, including an analysis of adverse effects. Results 4476 studies were screened, 14 studies were included in our analysis. Interventions were specialist multidisciplinary programmes, transcutaneous electrical nerve stimulation (TENS), perhexiline, medical optimisation, morphine and intranasal alfentanil. The effects of specialist programmes and perhexiline treatment were mixed. Positive effects were reported with TENS, opioids and medical optimisation, with improvements in symptoms, exercise capacity and quality of life. No major adverse effects were noted in any of the treatments. Conclusion There are non-invasive treatments for refractory angina that are overlooked by current guidelines. While the quality of these studies varies, positive changes have been reported in symptoms, exercise tolerance and quality of life with few adverse effects. There is a need for further research into these treatments which could be useful within the contexts of cardiology and palliative care.During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/telophase is required for posttranscriptional activation and may play a role in the establishment of topologically associating domains (TADs). Together, our results suggest that the genome is reorganized in a sequential order, in which histone methylations occur first in prometaphase, histone acetylation, and CTCF in anaphase/telophase, transcription in cytokinesis, and long-range chromatin interactions in early G1. We thus provide insights into the histone modification landscape that allows faithful reestablishment of the transcriptional program and TADs during cell division.Hematopoietic stem cell (HSC) ontogeny is accompanied by dynamic changes in gene regulatory networks. We performed RNA-seq and histone mark ChIP-seq to define the transcriptomes and epigenomes of cells representing key developmental stages of HSC ontogeny in ****. The five populations analyzed were embryonic day 10.5 (E10.5) endothelium and hemogenic endothelium from the major arteries, an enriched population of prehematopoietic stem cells (pre-HSCs), fetal liver HSCs, and adult bone marrow HSCs. Using epigenetic signatures, we identified enhancers for each developmental stage. Only 12% of enhancers are primed, and 78% are active, suggesting the vast majority of enhancers are established de novo without prior priming in earlier stages. We constructed developmental stage-specific transcriptional regulatory networks by linking enhancers and predicted bound transcription factors to their target promoters using a novel computational algorithm, target inference via physical connection (TIPC). TIPC predicted known transcriptional regulators for the endothelial-to-hematopoietic transition, validating our overall approach, and identified putative novel transcription factors, including the broadly expressed transcription factors SP3 and MAZ.
    001). Spirituality was very important to 39.9% and religiosity to 31.7% of patients, and unimportant to 30.6% and 39.5%, respectively. Following diagnosis, patients prayed (p less then 0.001) and meditated (p less then 0.001) more, seeking more time, strength and acceptance. Attendance at religious services decreased with frailty (p less then 0.001), while engagement in other religious activities increased (p=0.017). Patients who received some level of spiritual/religious support from external religious/faith communities and moderate to complete spiritual/religious needs met by the hospitals reported greater total FACIT-SP-12 spirituality scores (p less then 0.001). Conclusion Respectful inquiry into patients spiritual/religious needs in hospitals allows for an attuned approach to addressing such care needs while considerately accommodating those disinterested in such support.Objectives To examine the effects of nurse-led interventions on the health-related quality of life, symptom burden and self-management/behavioural outcomes in women with breast cancer. Methods Cochrane Controlled Register of Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline and Embase databases were searched (January 1999 to May 2019) to identify randomised controlled trials (RCTs) and controlled before-and-after studies of interventions delivered by nurses with oncology experience for women with breast cancer. Risk of bias was evaluated using the revised Cochrane risk-of-bias tool for randomised trials. Intervention effects were synthesised by cancer trajectory using The Omaha System Intervention Classification Scheme. Results Thirty-one RCTs (4651 participants) were included. All studies were at risk of bias mainly due to inherent limitations such as lack of blinding and self-report data. Most studies (71%; n=22) reported at least one superior intervention effect. e International Prospective Register of Systematic Reviews (PROSPERO) CRD42020134914).Background Refractory angina can have a significant effect on quality of life. Non-invasive interventions have been suggested but there are few guidelines on management. https://www.selleckchem.com/products/remdesivir.html Our aim was to systematically review all studies that reported non-invasive interventions for refractory angina and report on their effectiveness and safety. Methods We performed a literature search of six databases and a grey literature search. Treatments considered first line or second line according to the European Society of Cardiology were excluded, as were interventions that had undergone review within the last 3 years. Design, setting and outcomes were extracted and quality was assessed. A narrative synthesis was undertaken, including an analysis of adverse effects. Results 4476 studies were screened, 14 studies were included in our analysis. Interventions were specialist multidisciplinary programmes, transcutaneous electrical nerve stimulation (TENS), perhexiline, medical optimisation, morphine and intranasal alfentanil. The effects of specialist programmes and perhexiline treatment were mixed. Positive effects were reported with TENS, opioids and medical optimisation, with improvements in symptoms, exercise capacity and quality of life. No major adverse effects were noted in any of the treatments. Conclusion There are non-invasive treatments for refractory angina that are overlooked by current guidelines. While the quality of these studies varies, positive changes have been reported in symptoms, exercise tolerance and quality of life with few adverse effects. There is a need for further research into these treatments which could be useful within the contexts of cardiology and palliative care.During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/telophase is required for posttranscriptional activation and may play a role in the establishment of topologically associating domains (TADs). Together, our results suggest that the genome is reorganized in a sequential order, in which histone methylations occur first in prometaphase, histone acetylation, and CTCF in anaphase/telophase, transcription in cytokinesis, and long-range chromatin interactions in early G1. We thus provide insights into the histone modification landscape that allows faithful reestablishment of the transcriptional program and TADs during cell division.Hematopoietic stem cell (HSC) ontogeny is accompanied by dynamic changes in gene regulatory networks. We performed RNA-seq and histone mark ChIP-seq to define the transcriptomes and epigenomes of cells representing key developmental stages of HSC ontogeny in mice. The five populations analyzed were embryonic day 10.5 (E10.5) endothelium and hemogenic endothelium from the major arteries, an enriched population of prehematopoietic stem cells (pre-HSCs), fetal liver HSCs, and adult bone marrow HSCs. Using epigenetic signatures, we identified enhancers for each developmental stage. Only 12% of enhancers are primed, and 78% are active, suggesting the vast majority of enhancers are established de novo without prior priming in earlier stages. We constructed developmental stage-specific transcriptional regulatory networks by linking enhancers and predicted bound transcription factors to their target promoters using a novel computational algorithm, target inference via physical connection (TIPC). TIPC predicted known transcriptional regulators for the endothelial-to-hematopoietic transition, validating our overall approach, and identified putative novel transcription factors, including the broadly expressed transcription factors SP3 and MAZ.
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  • Atmospheric new particle formation (NPF), which is observed in many environments globally, is an important source of boundary-layer aerosol particles and cloud condensation nuclei, which affect both the climate and human health. To better understand the mechanisms behind NPF, chamber experiments can be used to simulate this phenomenon under well-controlled conditions. Recent advancements in instrumentation have made it possible to directly detect the first steps of NPF of molecular clusters (~1-2 nm in diameter) and to calculate quantities such as the formation and growth rates of these clusters. Whereas previous studies reported particle formation rates as the flux of particles across a specified particle diameter or calculated them from measurements of larger particle sizes, this protocol outlines methods to directly quantify particle dynamics for cluster sizes. Here, we describe the instrumentation and analysis methods needed to quantify particle dynamics during NPF of sub-3-nm aerosol particles in chamber experiments. The methods described in this protocol can be used to make results from different chamber experiments comparable. The experimental setup, collection and post-processing of the data, and thus completion of this protocol, take from months up to years, depending on the chamber facility, experimental plan and level of expertise. Use of this protocol requires engineering capabilities and expertise in data analysis.Genome replication follows a defined temporal programme that can change during cellular differentiation and disease onset. DNA replication results in an increase in DNA copy number that can be measured by high-throughput sequencing. Here we present a protocol to determine genome replication dynamics using DNA copy-number measurements. Cell populations can be obtained in three variants of the method. First, sort-seq reveals the average replication dynamics across S phase in an unperturbed cell population; FACS is used to isolate replicating and non-replicating subpopulations from asynchronous cells. Second, sync-seq measures absolute replication time at specific points during S phase using a synchronized cell population. Third, marker frequency analysis can be used to reveal the average replication dynamics using copy-number analysis in any proliferating asynchronous cell culture. These approaches have been used to reveal genome replication dynamics in prokaryotes, archaea and a wide range of eukaryotes, including yeasts and mammalian cells. We have found this approach straightforward to apply to other organisms and highlight example studies from across the three domains of life. Here we present a Saccharomyces cerevisiae version of the protocol that can be performed in 7-10 d. It requires basic molecular and cellular biology skills, as well as a basic understanding of Unix and R.This protocol describes the use of 9-fluorenone as a cheap and non-toxic photocatalyst for the oxidation of non-activated alcohols performed under the irradiation of a blue light-emitting diode. It also describes the use of the similarly cheap and non-toxic photocatalyst rose bengal for the selective α-oxygenation of tertiary amines to produce the corresponding amides in a selective way using the same light source. We have provided detailed instructions on how to assemble the light-emitting diode equipment and set up the photocatalytic reaction, where an oxygen atmosphere is created with an O2-filled balloon. Further details are provided using four example reactions that illustrate how this system works alcohol oxidation to prepare terephthlalaldehyde and androstanedione, and amine oxidation to make 2-phenyl-3,4-dihydroisoquinolin-1(2H)-one and (4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)m-tolyl)methanone. The times needed to perform these photocatalytic reactions are 18, 76, 22 and 54 h, respectively. https://www.selleckchem.com/products/Staurosporine.html We believe that this protocol represents a robust methodology for the late-stage modification of amines and the selective oxidation of steroids.During DNA replication, the genetic information of a cell is copied. Subsequently, identical genetic information is segregated reliably to the two daughter cells through cell division. Meanwhile, DNA replication is intrinsically linked to the process of chromatin duplication, which is required for regulating gene expression and establishing cell identities. Understanding how chromatin is established, maintained or changed during DNA replication represents a fundamental question in biology. Recently, we developed a method to directly visualize chromatin components at individual replication forks undergoing DNA replication. This method builds upon the existing chromatin fiber technique and combines it with cell type-specific chromatin labeling and superresolution microscopy. In this method, a short pulse of nucleoside analog labels replicative regions in the cells of interest. Chromatin fibers are subsequently isolated and attached to a glass slide, after which a laminar flow of lysis buffer extends the lysed chromatin fibers parallel with the direction of the flow. Fibers are then immunostained for different chromatin-associated proteins and mounted for visualization using superresolution microscopy. Replication foci, or 'bubbles,' are identified by the presence of the incorporated nucleoside analog. For researchers experienced in molecular biology and superresolution microscopy, this protocol typically takes 2-3 d from sample preparation to data acquisition, with an additional day for data processing and quantification.Methods developed to capture protein-anchored chromatin interactions (chromatin interaction analysis by paired-end tag sequencing and HiChIP) have yielded tremendous insights into the 3D folding principles of the genome, but are normalized by sequencing depth and therefore unable to accurately measure global changes in chromatin interactions and contact domain organization. We herein describe the protocol for absolute quantification of chromatin architecture (AQuA)-HiChIP, an advance that allows the absolute differences in protein-anchored chromatin interactions between samples to be determined. With our method, defined ratios of mouse and human fixed nuclei are mixed and subjected to endonuclease digestion. Chromatin contacts are captured by biotin-dATP incorporation and proximity ligation, followed by gentle shearing, ChIP, biotin capture and paired-end sequencing. 3D contacts are counted from paired-end tags (PETs) from the human genome and are normalized to the total PETs from the mouse genome. As orthogonal normalization allows observation of global changes, the approach will enable more quantitative insights into the topological determinants of transcriptional control and tissue-specific epigenetic memory.
    Atmospheric new particle formation (NPF), which is observed in many environments globally, is an important source of boundary-layer aerosol particles and cloud condensation nuclei, which affect both the climate and human health. To better understand the mechanisms behind NPF, chamber experiments can be used to simulate this phenomenon under well-controlled conditions. Recent advancements in instrumentation have made it possible to directly detect the first steps of NPF of molecular clusters (~1-2 nm in diameter) and to calculate quantities such as the formation and growth rates of these clusters. Whereas previous studies reported particle formation rates as the flux of particles across a specified particle diameter or calculated them from measurements of larger particle sizes, this protocol outlines methods to directly quantify particle dynamics for cluster sizes. Here, we describe the instrumentation and analysis methods needed to quantify particle dynamics during NPF of sub-3-nm aerosol particles in chamber experiments. The methods described in this protocol can be used to make results from different chamber experiments comparable. The experimental setup, collection and post-processing of the data, and thus completion of this protocol, take from months up to years, depending on the chamber facility, experimental plan and level of expertise. Use of this protocol requires engineering capabilities and expertise in data analysis.Genome replication follows a defined temporal programme that can change during cellular differentiation and disease onset. DNA replication results in an increase in DNA copy number that can be measured by high-throughput sequencing. Here we present a protocol to determine genome replication dynamics using DNA copy-number measurements. Cell populations can be obtained in three variants of the method. First, sort-seq reveals the average replication dynamics across S phase in an unperturbed cell population; FACS is used to isolate replicating and non-replicating subpopulations from asynchronous cells. Second, sync-seq measures absolute replication time at specific points during S phase using a synchronized cell population. Third, marker frequency analysis can be used to reveal the average replication dynamics using copy-number analysis in any proliferating asynchronous cell culture. These approaches have been used to reveal genome replication dynamics in prokaryotes, archaea and a wide range of eukaryotes, including yeasts and mammalian cells. We have found this approach straightforward to apply to other organisms and highlight example studies from across the three domains of life. Here we present a Saccharomyces cerevisiae version of the protocol that can be performed in 7-10 d. It requires basic molecular and cellular biology skills, as well as a basic understanding of Unix and R.This protocol describes the use of 9-fluorenone as a cheap and non-toxic photocatalyst for the oxidation of non-activated alcohols performed under the irradiation of a blue light-emitting diode. It also describes the use of the similarly cheap and non-toxic photocatalyst rose bengal for the selective α-oxygenation of tertiary amines to produce the corresponding amides in a selective way using the same light source. We have provided detailed instructions on how to assemble the light-emitting diode equipment and set up the photocatalytic reaction, where an oxygen atmosphere is created with an O2-filled balloon. Further details are provided using four example reactions that illustrate how this system works alcohol oxidation to prepare terephthlalaldehyde and androstanedione, and amine oxidation to make 2-phenyl-3,4-dihydroisoquinolin-1(2H)-one and (4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)m-tolyl)methanone. The times needed to perform these photocatalytic reactions are 18, 76, 22 and 54 h, respectively. https://www.selleckchem.com/products/Staurosporine.html We believe that this protocol represents a robust methodology for the late-stage modification of amines and the selective oxidation of steroids.During DNA replication, the genetic information of a cell is copied. Subsequently, identical genetic information is segregated reliably to the two daughter cells through cell division. Meanwhile, DNA replication is intrinsically linked to the process of chromatin duplication, which is required for regulating gene expression and establishing cell identities. Understanding how chromatin is established, maintained or changed during DNA replication represents a fundamental question in biology. Recently, we developed a method to directly visualize chromatin components at individual replication forks undergoing DNA replication. This method builds upon the existing chromatin fiber technique and combines it with cell type-specific chromatin labeling and superresolution microscopy. In this method, a short pulse of nucleoside analog labels replicative regions in the cells of interest. Chromatin fibers are subsequently isolated and attached to a glass slide, after which a laminar flow of lysis buffer extends the lysed chromatin fibers parallel with the direction of the flow. Fibers are then immunostained for different chromatin-associated proteins and mounted for visualization using superresolution microscopy. Replication foci, or 'bubbles,' are identified by the presence of the incorporated nucleoside analog. For researchers experienced in molecular biology and superresolution microscopy, this protocol typically takes 2-3 d from sample preparation to data acquisition, with an additional day for data processing and quantification.Methods developed to capture protein-anchored chromatin interactions (chromatin interaction analysis by paired-end tag sequencing and HiChIP) have yielded tremendous insights into the 3D folding principles of the genome, but are normalized by sequencing depth and therefore unable to accurately measure global changes in chromatin interactions and contact domain organization. We herein describe the protocol for absolute quantification of chromatin architecture (AQuA)-HiChIP, an advance that allows the absolute differences in protein-anchored chromatin interactions between samples to be determined. With our method, defined ratios of mouse and human fixed nuclei are mixed and subjected to endonuclease digestion. Chromatin contacts are captured by biotin-dATP incorporation and proximity ligation, followed by gentle shearing, ChIP, biotin capture and paired-end sequencing. 3D contacts are counted from paired-end tags (PETs) from the human genome and are normalized to the total PETs from the mouse genome. As orthogonal normalization allows observation of global changes, the approach will enable more quantitative insights into the topological determinants of transcriptional control and tissue-specific epigenetic memory.
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  • Conclusion The timely intervention of the RRS in EOLC facilitates an objective assessment of the patient's medical conditions, the limitation of treatments that may be minimally beneficial to the patient, and the choice of a higher quality of care. The EOLC decision using the legal process defined in the relevant Korean Act has advantages, wherein patients can clarify their preference, the family can prioritize the patient's preference for EOLC decisions, and physicians can make transparent EOLC decisions based on medical evidence and informed patient consent.Background Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps muscle weakness that limits their successful return to play and are also at an increased risk of developing knee osteoarthritis (OA). Human growth hormone (HGH) has been shown to prevent muscle atrophy and weakness in various models of disuse and disease but has not been evaluated in patients undergoing ACLR. Hypothesis Compared with placebo treatment, a 6-week perioperative treatment course of HGH would protect against muscle atrophy and weakness in patients undergoing ACLR. Study design Randomized controlled trial; Level of evidence, 2. Methods A total of 19 male patients (aged 18-35 years) scheduled to undergo ACLR were randomly assigned to the placebo (n = 9) or HGH (n = 10) group. Patients began placebo or HGH treatment twice daily 1 week before surgery and continued through 5 weeks after surgery. Knee muscle strees in muscle volume or patient-reported outcome scores. Conclusion HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR. On the basis of this pilot study, further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients undergoing ACLR are warranted. Registration NCT02420353 ( ClinicalTrials.gov identifier).Health risks in an extremely cold environment make warm retention equipment highly desirable. However, creating materials with a high warm retention performance and robust mechanical property to durably prevent against the harsh conditions is highly challenging. Herein, we report on a one-step and facile strategy to fabricate stretchable and superelastic fibrous sponges by creating unique "stiff-soft" polymer networks within fibers and bonding architecture among fibers. https://www.selleckchem.com/products/Staurosporine.html The premise of this design is that stiff polystyrene can endow materials with rigidity and soft polyurethane can absorb energy during mechanical deformation. Benefiting from this systematic tailoring for the polymer and assembling networks, the resultant fibrous sponges exhibit a unique tensile recovery property, a large breaking elongation of 70%, and an outstanding resilience for resisting 100 cyclic compressions with 50% strain under -50 °C. Moreover, the fibrous sponges possess dramatic characteristics of high porosity (∼99.31%), ultralight property (volume density = 7.68 mg cm-3), and effective warmth retention (thermal conductivity = 27.6 mW m-1 K-1), as well as technical features of the simple assembly process to scale up easily. The preparation of fibrous sponges provides a new vision for developing ultralight and efficient warmth retention materials.As effective light absorbers in solar cells, CsPbI3 all-inorganic perovskite quantum dots (QDs) have received increasing attention, benefitting from their suitable optical band gap and thermal stability. However, the easy cubic to yellow orthorhombic phase transition hinders their further application in stable photovoltaic devices. CsPbBr3 QDs have been targeted as a promising material for ultrahigh voltage and stable solar cells. In this work, we first develop a simple yet efficient post-treatment method using guanidinium thiocyanate (GASCN), which is able to exchange the native capping ligands of CsPbBr3 QDs, thus improving the carrier transport properties through enhanced electrical coupling between QDs. Additionally, the morphology and crystalline properties of solid QD films are also improved. Therefore, simultaneously improved open-circuit voltage (Voc), short-circuit current density (Jsc), and fill factor (FF) were obtained in the corresponding CsPbBr3 QD devices. Finally, the QD solar cells based on optimal hole-transporting layers delivered the highest efficiency exceeding 5% together with an ultrahigh Voc of 1.65 V, representing the most efficient CsPbBr3 QD solar cells to date. More importantly, the CsPbBr3 perovskite QD solar cells developed here exhibit excellent stability, ultrahigh voltage, and high transparency over the entire visible spectrum region, demonstrating their great potential in applications like solar windows of greenhouse and hydrogen generation driven by perovskite solar cells.In this study, we proposed a ratiometric electrochemiluminescent (ECL)/electrochemical (EC) biosensor based on duplex-specific nuclease (DSN)-assisted target recycling and multilayer catalytic hairpin assembly (CHA) amplification cascades for the detection of microRNA (miRNA). The DSN-assisted target recycling transformed miRNAs into a large number of ssDNA, which then catalyzed a multilayer CHA amplification cascade to produce numerous long dsDNA duplexes Hn/Hn+1 (n = 2, 4, 6, ...). Then the Hn/Hn+1 displaced the ferrocene (Fc)-labeled ssDNA (Sx+1, x = 1, 3, 5, ...) to hybridize with the Sx sequence on the gold electrode surface. Consequently, a great number of long Sx/Hn/Hn+1 duplexes were immobilized for binding Ru(phen)32+ to obtain an amplified ECL signal. Meanwhile, the EC signal of Fc was reduced, and the quenching effect of Fc to ECL signal also decreased. By measuring the ratio of the ECL signal of Ru(phen)32+ to the EC signal of Fc, quantitative analysis of miRNA-499 with high accuracy and reproducibility was obtained. The ratiometric biosensor shows high sensitivity and a wide linear range of 6 orders of magnitude. With the help of DSN-assisted target recycling, this strategy can be easily extended to detect other miRNAs without redesigning the CHA cascade system. The proposed "hybrid" ratiometric ECL/EC strategy enriches the ratiometric sensors and can find extensive applications in bioanalysis, especially for multiplex detection.
    Conclusion The timely intervention of the RRS in EOLC facilitates an objective assessment of the patient's medical conditions, the limitation of treatments that may be minimally beneficial to the patient, and the choice of a higher quality of care. The EOLC decision using the legal process defined in the relevant Korean Act has advantages, wherein patients can clarify their preference, the family can prioritize the patient's preference for EOLC decisions, and physicians can make transparent EOLC decisions based on medical evidence and informed patient consent.Background Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps muscle weakness that limits their successful return to play and are also at an increased risk of developing knee osteoarthritis (OA). Human growth hormone (HGH) has been shown to prevent muscle atrophy and weakness in various models of disuse and disease but has not been evaluated in patients undergoing ACLR. Hypothesis Compared with placebo treatment, a 6-week perioperative treatment course of HGH would protect against muscle atrophy and weakness in patients undergoing ACLR. Study design Randomized controlled trial; Level of evidence, 2. Methods A total of 19 male patients (aged 18-35 years) scheduled to undergo ACLR were randomly assigned to the placebo (n = 9) or HGH (n = 10) group. Patients began placebo or HGH treatment twice daily 1 week before surgery and continued through 5 weeks after surgery. Knee muscle strees in muscle volume or patient-reported outcome scores. Conclusion HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR. On the basis of this pilot study, further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients undergoing ACLR are warranted. Registration NCT02420353 ( ClinicalTrials.gov identifier).Health risks in an extremely cold environment make warm retention equipment highly desirable. However, creating materials with a high warm retention performance and robust mechanical property to durably prevent against the harsh conditions is highly challenging. Herein, we report on a one-step and facile strategy to fabricate stretchable and superelastic fibrous sponges by creating unique "stiff-soft" polymer networks within fibers and bonding architecture among fibers. https://www.selleckchem.com/products/Staurosporine.html The premise of this design is that stiff polystyrene can endow materials with rigidity and soft polyurethane can absorb energy during mechanical deformation. Benefiting from this systematic tailoring for the polymer and assembling networks, the resultant fibrous sponges exhibit a unique tensile recovery property, a large breaking elongation of 70%, and an outstanding resilience for resisting 100 cyclic compressions with 50% strain under -50 °C. Moreover, the fibrous sponges possess dramatic characteristics of high porosity (∼99.31%), ultralight property (volume density = 7.68 mg cm-3), and effective warmth retention (thermal conductivity = 27.6 mW m-1 K-1), as well as technical features of the simple assembly process to scale up easily. The preparation of fibrous sponges provides a new vision for developing ultralight and efficient warmth retention materials.As effective light absorbers in solar cells, CsPbI3 all-inorganic perovskite quantum dots (QDs) have received increasing attention, benefitting from their suitable optical band gap and thermal stability. However, the easy cubic to yellow orthorhombic phase transition hinders their further application in stable photovoltaic devices. CsPbBr3 QDs have been targeted as a promising material for ultrahigh voltage and stable solar cells. In this work, we first develop a simple yet efficient post-treatment method using guanidinium thiocyanate (GASCN), which is able to exchange the native capping ligands of CsPbBr3 QDs, thus improving the carrier transport properties through enhanced electrical coupling between QDs. Additionally, the morphology and crystalline properties of solid QD films are also improved. Therefore, simultaneously improved open-circuit voltage (Voc), short-circuit current density (Jsc), and fill factor (FF) were obtained in the corresponding CsPbBr3 QD devices. Finally, the QD solar cells based on optimal hole-transporting layers delivered the highest efficiency exceeding 5% together with an ultrahigh Voc of 1.65 V, representing the most efficient CsPbBr3 QD solar cells to date. More importantly, the CsPbBr3 perovskite QD solar cells developed here exhibit excellent stability, ultrahigh voltage, and high transparency over the entire visible spectrum region, demonstrating their great potential in applications like solar windows of greenhouse and hydrogen generation driven by perovskite solar cells.In this study, we proposed a ratiometric electrochemiluminescent (ECL)/electrochemical (EC) biosensor based on duplex-specific nuclease (DSN)-assisted target recycling and multilayer catalytic hairpin assembly (CHA) amplification cascades for the detection of microRNA (miRNA). The DSN-assisted target recycling transformed miRNAs into a large number of ssDNA, which then catalyzed a multilayer CHA amplification cascade to produce numerous long dsDNA duplexes Hn/Hn+1 (n = 2, 4, 6, ...). Then the Hn/Hn+1 displaced the ferrocene (Fc)-labeled ssDNA (Sx+1, x = 1, 3, 5, ...) to hybridize with the Sx sequence on the gold electrode surface. Consequently, a great number of long Sx/Hn/Hn+1 duplexes were immobilized for binding Ru(phen)32+ to obtain an amplified ECL signal. Meanwhile, the EC signal of Fc was reduced, and the quenching effect of Fc to ECL signal also decreased. By measuring the ratio of the ECL signal of Ru(phen)32+ to the EC signal of Fc, quantitative analysis of miRNA-499 with high accuracy and reproducibility was obtained. The ratiometric biosensor shows high sensitivity and a wide linear range of 6 orders of magnitude. With the help of DSN-assisted target recycling, this strategy can be easily extended to detect other miRNAs without redesigning the CHA cascade system. The proposed "hybrid" ratiometric ECL/EC strategy enriches the ratiometric sensors and can find extensive applications in bioanalysis, especially for multiplex detection.
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  • Background Accidents and injuries are the leading cause of childhood morbidity and mortality. This study aimed to investigate the incidences of different causes of accidents in children under 6 years old. Methods This population-based cross-sectional study was carried out in one year (2016-2017) on a sample of 6000 children in Southern Iran with a multistage sampling method using a standard checklist for comprehensive child health monitoring. Results The annual incidence rate of accidents was 16% and the mean age of accident victims was 2.5±1.5 years. Of these, 17.3% and 14.8% were male and female, respectively. 25% of the children suffered from more than one accident. The most common causes of accidents were burns (16%), falls (14%), and accidents involving objects (10%). In multivariate analysis, a higher number of male children in the family and lower child age significantly increased the likelihood of accidents (p less than 0.05). Conclusions This study was a direct survey of the population, and showed that the incidence rate of accidents in children in southern Iran was in line with that of other regions of Iran, but less than the world average. There was no significant difference in accident etiology and only trends in etiology were found compared to studies using existing data.Bovine leukemia virus (BLV) belongs to the genus, Deltaretrovirus of the family, Retroviridae and it is the causative agent of enzootic bovine leukosis. The prevalence of BLV in three provinces in the Red River Delta Region in the North of Vietnam, Hanoi, Vinhphuc and Bacninh was studied from April 2017 to June 2018. A total of 275 blood samples collected from cattle were used for serum isolation and DNA extraction. Of these samples, 266 sera were subjected to ELISA test for detecting antibody against BLV gp51 protein and 152 DNA samples were used to detect the 444 bp fragment corresponding to a part of the gp51 region of the env by nested PCR. The results showed that 16.5% (n=44) and 21.1% (n=32) of samples were positive for BLV gp51 antibody and BLV proviral DNA, respectively. Phylogenetic analysis of the partial (423 bp) and complete (913 bp) BLV env-gp51 gene indicated that Vietnamese strains were clustered into genotypes 1, 6 and 10 (G1, G6 and G10). Of those genotypes, G1 genotype was dominant; G6 strains were designated as G6e and G6f subgenotypes; the existence of genotype 10 was confirmed for the first time in Vietnam. The present study provides important information regarding the prevalence of BLV infection and genetic characteristics of BLV strains identified in Vietnam, contributing to promote the establishment of disease control and eradication strategies in Vietnam.The errors in the following list appeared in the article titled "Characteristics of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Anticentriole Autoantibodies" by Hisataka Maki, Kana Kubota, Masaru Hatano, Shun Minatsuki, Eisuke Amiya, Ayumi Yoshizaki, Yoshihide Asano, Hiroyuki Morita, Shinichi Sato, Issei Komuro (Vol 61, No.2, 413-418, 2020).Influenza (flu) is a prominent infectious disease that worsens the general prognosis of older adults. We herein report a case of a clinically odd and rare reaction on an instant diagnostic kit for influenza. An 81-year-old man with a fever and rhinorrhea consulted our hospital. He had a history of dementia of Alzheimer's type and rheumatoid arthritis and had been treated with oral prednisolone (10 mg/day). Instant diagnostic test kit A using exudation from the upper pharynx showed positivity for antigen of flu A virus, and computed tomography indicated acute pneumonia. https://www.selleckchem.com/ Immediately after the diagnosis, 150 mg/day of oseltamivir was started for 5 days. However, a high fever over 38.0°C persisted, and flu A antigen from the upper pharynx was repeatedly detected using test kit A. Despite subsequent oral treatment with 100 mg/day of amantadine and single venous infusion of 300 mg/day of peramivir, the high fever continued, and the detection of C-reactive protein in the serum as well as flu A antigen in the upper pharynx persisted. We suspected test failure, and the results of another test kit (kit B) were indeed negative. Furthermore, polymerase chain reaction performed by two independent laboratories failed to detect flu gene fragments. We concluded that the patient did not have the flu, and results of test kit A had been a false positive. The patient was successfully treated with ABPC/SBT infusions. We should consider the implications of diagnosing flu using instant test kits.Aim To verify the clinical utility of instrumental activities of daily life evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG-IC) as a screening tool for patients with early-phase cognitive impairment, including mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Methods We recruited healthy subjects from our community-based cohort and consecutive subjects with MCI and AD from our clinic. The TMIG-IC was investigated in all participants and their family members. The total and subscale scores were compared among all groups. We then statistically determined the accuracy of the differentiation of MCI and AD. Results We registered 187 normal controls (NC), 39 participants with MCI, 50 AD patients with functional assessment staging (FAST) 4, and 19 AD patients with ≥5 FAST. The family-report score was significantly lower in MCI patients than in others, followed by AD patients. The total score was able to differentiate MCI and AD with a sensitivity of 85.7% and a specificity of 90.9% (area under the curve [AUC]=0.913). Differentiation of MCI alone had a low accuracy (AUC=0.787). However, the AUC was 0.847 when only the items with inconsistent responses between self and family reports were used as indices. Conclusions The TMIG-IC is a useful tool for evaluating the severity of AD, including early AD. These findings suggest that family-report scores can differentiate MCI and AD from cognitive normal aging with a sufficient degree of accuracy. It was also suggested that inconsistencies between self and family reports were higher when differentiating MCI than the self- and family-reports.
    Background Accidents and injuries are the leading cause of childhood morbidity and mortality. This study aimed to investigate the incidences of different causes of accidents in children under 6 years old. Methods This population-based cross-sectional study was carried out in one year (2016-2017) on a sample of 6000 children in Southern Iran with a multistage sampling method using a standard checklist for comprehensive child health monitoring. Results The annual incidence rate of accidents was 16% and the mean age of accident victims was 2.5±1.5 years. Of these, 17.3% and 14.8% were male and female, respectively. 25% of the children suffered from more than one accident. The most common causes of accidents were burns (16%), falls (14%), and accidents involving objects (10%). In multivariate analysis, a higher number of male children in the family and lower child age significantly increased the likelihood of accidents (p less than 0.05). Conclusions This study was a direct survey of the population, and showed that the incidence rate of accidents in children in southern Iran was in line with that of other regions of Iran, but less than the world average. There was no significant difference in accident etiology and only trends in etiology were found compared to studies using existing data.Bovine leukemia virus (BLV) belongs to the genus, Deltaretrovirus of the family, Retroviridae and it is the causative agent of enzootic bovine leukosis. The prevalence of BLV in three provinces in the Red River Delta Region in the North of Vietnam, Hanoi, Vinhphuc and Bacninh was studied from April 2017 to June 2018. A total of 275 blood samples collected from cattle were used for serum isolation and DNA extraction. Of these samples, 266 sera were subjected to ELISA test for detecting antibody against BLV gp51 protein and 152 DNA samples were used to detect the 444 bp fragment corresponding to a part of the gp51 region of the env by nested PCR. The results showed that 16.5% (n=44) and 21.1% (n=32) of samples were positive for BLV gp51 antibody and BLV proviral DNA, respectively. Phylogenetic analysis of the partial (423 bp) and complete (913 bp) BLV env-gp51 gene indicated that Vietnamese strains were clustered into genotypes 1, 6 and 10 (G1, G6 and G10). Of those genotypes, G1 genotype was dominant; G6 strains were designated as G6e and G6f subgenotypes; the existence of genotype 10 was confirmed for the first time in Vietnam. The present study provides important information regarding the prevalence of BLV infection and genetic characteristics of BLV strains identified in Vietnam, contributing to promote the establishment of disease control and eradication strategies in Vietnam.The errors in the following list appeared in the article titled "Characteristics of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Anticentriole Autoantibodies" by Hisataka Maki, Kana Kubota, Masaru Hatano, Shun Minatsuki, Eisuke Amiya, Ayumi Yoshizaki, Yoshihide Asano, Hiroyuki Morita, Shinichi Sato, Issei Komuro (Vol 61, No.2, 413-418, 2020).Influenza (flu) is a prominent infectious disease that worsens the general prognosis of older adults. We herein report a case of a clinically odd and rare reaction on an instant diagnostic kit for influenza. An 81-year-old man with a fever and rhinorrhea consulted our hospital. He had a history of dementia of Alzheimer's type and rheumatoid arthritis and had been treated with oral prednisolone (10 mg/day). Instant diagnostic test kit A using exudation from the upper pharynx showed positivity for antigen of flu A virus, and computed tomography indicated acute pneumonia. https://www.selleckchem.com/ Immediately after the diagnosis, 150 mg/day of oseltamivir was started for 5 days. However, a high fever over 38.0°C persisted, and flu A antigen from the upper pharynx was repeatedly detected using test kit A. Despite subsequent oral treatment with 100 mg/day of amantadine and single venous infusion of 300 mg/day of peramivir, the high fever continued, and the detection of C-reactive protein in the serum as well as flu A antigen in the upper pharynx persisted. We suspected test failure, and the results of another test kit (kit B) were indeed negative. Furthermore, polymerase chain reaction performed by two independent laboratories failed to detect flu gene fragments. We concluded that the patient did not have the flu, and results of test kit A had been a false positive. The patient was successfully treated with ABPC/SBT infusions. We should consider the implications of diagnosing flu using instant test kits.Aim To verify the clinical utility of instrumental activities of daily life evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG-IC) as a screening tool for patients with early-phase cognitive impairment, including mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Methods We recruited healthy subjects from our community-based cohort and consecutive subjects with MCI and AD from our clinic. The TMIG-IC was investigated in all participants and their family members. The total and subscale scores were compared among all groups. We then statistically determined the accuracy of the differentiation of MCI and AD. Results We registered 187 normal controls (NC), 39 participants with MCI, 50 AD patients with functional assessment staging (FAST) 4, and 19 AD patients with ≥5 FAST. The family-report score was significantly lower in MCI patients than in others, followed by AD patients. The total score was able to differentiate MCI and AD with a sensitivity of 85.7% and a specificity of 90.9% (area under the curve [AUC]=0.913). Differentiation of MCI alone had a low accuracy (AUC=0.787). However, the AUC was 0.847 when only the items with inconsistent responses between self and family reports were used as indices. Conclusions The TMIG-IC is a useful tool for evaluating the severity of AD, including early AD. These findings suggest that family-report scores can differentiate MCI and AD from cognitive normal aging with a sufficient degree of accuracy. It was also suggested that inconsistencies between self and family reports were higher when differentiating MCI than the self- and family-reports.
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  • ©Copyright the Author(s), 2019.This paper reports on HIV related stigma based on results from an HIV legal environment assessment (LEA) within the Churches Health Association of Zambia HIV/AIDS program. We conducted 9 Focus Group Discussions and 20 Key Informant Interviews with key HIV/AIDS stakeholders that included representatives from network of Zambian people living with HIV. We administered a Survey Questionnaire to 337 people living with HIV (PLHIV) and 233 health workers. Quantitative data were analyzed using SAS v9.4; qualitative data was analyzed using QRS NVIVO version 11.0 Pro. Internalized stigma ranged between 20.8% and 31.8% of PLHIV; more among females than males. About one third (31%, n=104)) of the 337 participants reported that they were aware of being gossiped once, a few times, or often; more among females than males. 62.3%, 63.1%, and 55.1% of the 233 health workers said it was somewhat true or certainly true that in their catchment areas, PLHIV struggle to have an HIV test because of stigma, were hesitant to start ART due to stigma; told them that they had challenges taking their ARVs because of stigma respectively. ©Copyright the Author(s), 2019.Background Multiple sclerosis is an immune mediated disease targeting the central nervous system. Association of non-human leukocyte antigen gene, CD58, with multiple sclerosis has been reported in several populations but is unclear among Southeast Asians. This pilot study was conducted to explore the association between CD58 polymorphism and multiple sclerosis among the Malay population in Malaysia. Methods Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals. All patients were tested negative for anti-aquaporin 4. DNA was extracted from the blood and genotyped for 3 single nucleotide polymorphisms rs12044852, rs2300747 and rs1335532 of gene CD58 by real-time PCR. Results The majority of multiple sclerosis patients were female (85.2%). https://www.selleckchem.com/products/opn-expression-inhibitor-1.html The general mean age of onset was 30.5 years. Genotyping results showed that frequencies of the alleles were between 40 and 50% for MS patients and healthy individuals. Association (allelic model) between multiple sclerosis and CD58 gene polymorphism alleles rs12044852 (p = 0.410), rs2300747 (p = 0.881) and rs1335532 (p = 0.407) were indistinct. Conclusions The impact of the CD58 gene polymorphism was not prominent in this pilot study, implying that genetic composition contributing to multiple sclerosis may be different between different populations, thus results in a heterogeneity of disease manifestation and distribution. © The Author(s) 2019.Background Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Methods Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients through real time PCR. Results HERV-K was overexpressed only in moderately affected individuals but HERV-W showed no difference. Conclusions This is the first report about HERV-K differential expression in moderate ME/CFS. Although the relationship between HERVs and ME/CFS has yet to be proven, the observation of this phenomenon deserves further attention. © The Author(s) 2019.Background The human monoclonal autoantibody K1-70™ binds to the TSH receptor (TSHR) with high affinity and blocks TSHR cyclic AMP stimulation by TSH and thyroid stimulating autoantibodies. Methods The preclinical toxicology assessment following weekly intravenous (IV) or intramuscular (IM) administration of K1-70™ in rats and cynomolgus monkeys for 29 days was carried out. An assessment of delayed onset toxicity and/or reversibility of toxicity was made during a further 4 week treatment free period. The pharmacokinetic parameters of K1-70™ and the effects of different doses of K1-70™ on serum thyroid hormone levels in the study animals were determined in rats and primates after IV and IM administration. Results Low serum levels of T3 and T4 associated with markedly elevated levels of TSH were observed in the study animals following IV and IM administration of K1-70™. The toxicological findings were attributed to the pharmacology of K1-70™ and were consistent with the hypothyroid state. The no observable adverse effect level (NOAEL) could not be established in the rat study while in the primate study it was 100 mg/kg/dose for both males and females. Conclusions The toxicology, pharmacodynamic and pharmacokinetic data in this preclinical study were helpful in designing the first in human study with K1-70™ administered to subjects with Graves' disease. © The Author(s) 2019.Background Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years. Methods 327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50-7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (É£GT) and ELF score were measured by automated methods. Results Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.
    ©Copyright the Author(s), 2019.This paper reports on HIV related stigma based on results from an HIV legal environment assessment (LEA) within the Churches Health Association of Zambia HIV/AIDS program. We conducted 9 Focus Group Discussions and 20 Key Informant Interviews with key HIV/AIDS stakeholders that included representatives from network of Zambian people living with HIV. We administered a Survey Questionnaire to 337 people living with HIV (PLHIV) and 233 health workers. Quantitative data were analyzed using SAS v9.4; qualitative data was analyzed using QRS NVIVO version 11.0 Pro. Internalized stigma ranged between 20.8% and 31.8% of PLHIV; more among females than males. About one third (31%, n=104)) of the 337 participants reported that they were aware of being gossiped once, a few times, or often; more among females than males. 62.3%, 63.1%, and 55.1% of the 233 health workers said it was somewhat true or certainly true that in their catchment areas, PLHIV struggle to have an HIV test because of stigma, were hesitant to start ART due to stigma; told them that they had challenges taking their ARVs because of stigma respectively. ©Copyright the Author(s), 2019.Background Multiple sclerosis is an immune mediated disease targeting the central nervous system. Association of non-human leukocyte antigen gene, CD58, with multiple sclerosis has been reported in several populations but is unclear among Southeast Asians. This pilot study was conducted to explore the association between CD58 polymorphism and multiple sclerosis among the Malay population in Malaysia. Methods Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals. All patients were tested negative for anti-aquaporin 4. DNA was extracted from the blood and genotyped for 3 single nucleotide polymorphisms rs12044852, rs2300747 and rs1335532 of gene CD58 by real-time PCR. Results The majority of multiple sclerosis patients were female (85.2%). https://www.selleckchem.com/products/opn-expression-inhibitor-1.html The general mean age of onset was 30.5 years. Genotyping results showed that frequencies of the alleles were between 40 and 50% for MS patients and healthy individuals. Association (allelic model) between multiple sclerosis and CD58 gene polymorphism alleles rs12044852 (p = 0.410), rs2300747 (p = 0.881) and rs1335532 (p = 0.407) were indistinct. Conclusions The impact of the CD58 gene polymorphism was not prominent in this pilot study, implying that genetic composition contributing to multiple sclerosis may be different between different populations, thus results in a heterogeneity of disease manifestation and distribution. © The Author(s) 2019.Background Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Methods Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients through real time PCR. Results HERV-K was overexpressed only in moderately affected individuals but HERV-W showed no difference. Conclusions This is the first report about HERV-K differential expression in moderate ME/CFS. Although the relationship between HERVs and ME/CFS has yet to be proven, the observation of this phenomenon deserves further attention. © The Author(s) 2019.Background The human monoclonal autoantibody K1-70™ binds to the TSH receptor (TSHR) with high affinity and blocks TSHR cyclic AMP stimulation by TSH and thyroid stimulating autoantibodies. Methods The preclinical toxicology assessment following weekly intravenous (IV) or intramuscular (IM) administration of K1-70™ in rats and cynomolgus monkeys for 29 days was carried out. An assessment of delayed onset toxicity and/or reversibility of toxicity was made during a further 4 week treatment free period. The pharmacokinetic parameters of K1-70™ and the effects of different doses of K1-70™ on serum thyroid hormone levels in the study animals were determined in rats and primates after IV and IM administration. Results Low serum levels of T3 and T4 associated with markedly elevated levels of TSH were observed in the study animals following IV and IM administration of K1-70™. The toxicological findings were attributed to the pharmacology of K1-70™ and were consistent with the hypothyroid state. The no observable adverse effect level (NOAEL) could not be established in the rat study while in the primate study it was 100 mg/kg/dose for both males and females. Conclusions The toxicology, pharmacodynamic and pharmacokinetic data in this preclinical study were helpful in designing the first in human study with K1-70™ administered to subjects with Graves' disease. © The Author(s) 2019.Background Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years. Methods 327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50-7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (É£GT) and ELF score were measured by automated methods. Results Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.
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  • Background and purpose Whiplash-associated disorders frequently develop following motor vehicle collisions and often involve a range of cognitive and affective symptoms, though the neural correlates of the disorder are largely unknown. In this study, a sample of participants with chronic whiplash injuries were scanned by using resting-state fMRI to assess brain network changes associated with long-term outcome metrics. Materials and methods Resting-state fMRI was collected for 23 participants and used to calculate network modularity, a quantitative measure of the functional segregation of brain region communities. This was analyzed for associations with whiplash-associated disorder outcome metrics, including scales of neck disability, traumatic distress, depression, and pain. In addition to these clinical scales, cervical muscle fat infiltration was quantified by using Dixon fat-water imaging, which has shown promise as a biomarker for assessing disorder severity and predicting recovery in chronic whiplash. Results An association was found between brain network structure and muscle fat infiltration, wherein lower network modularity was associated with larger amounts of cervical muscle fat infiltration after controlling for age, sex, body mass index, and scan motion (t = -4.02, partial R 2 = 0.49, P less then .001). Conclusions This work contributes to the existing whiplash literature by examining a sample of participants with whiplash-associated disorder by using resting-state fMRI. Less modular brain networks were found to be associated with greater amounts of cervical muscle fat infiltration suggesting a connection between disorder severity and neurologic changes, and a potential role for neuroimaging in understanding the pathophysiology of chronic whiplash-associated disorders.Background and purpose Focal cortical dysplasias are the most common resected epileptogenic lesions in children and the third most common lesion in adults, but they are often subtle and frequently overlooked on MR imaging. The purpose of this study was to evaluate whether MP2RAGE-based morphometric MR imaging analysis is superior to MPRAGE-based analysis in the detection of focal cortical dysplasia. Materials and methods MPRAGE and MP2RAGE datasets were acquired in a consecutive series of 640 patients with epilepsy. Datasets were postprocessed using the Morphometric Analysis Program to generate morphometric z score maps such as junction, extension, and thickness images based on both MPRAGE and MP2RAGE images. Focal cortical dysplasia lesions were manually segmented in the junction images, and volumes and mean z scores of the lesions were measured. https://www.selleckchem.com/products/imp-1088.html Results Of 21 focal cortical dysplasias discovered, all were clearly visible on MP2RAGE junction images, whereas 2 were not visible on MPRAGE junction images. In all except 4 patients, the volume of the focal cortical dysplasia was larger and mean lesion z scores were higher on MP2RAGE junction images compared with the MPRAGE-based images (P = .005, P = .013). Conclusions In this study, MP2RAGE-based morphometric analysis created clearer output maps with larger lesion volumes and higher z scores than the MPRAGE-based analysis. This new approach may improve the detection of subtle, otherwise overlooked focal cortical dysplasia.Background and purpose Carotid near-occlusion has been subclassified into near-occlusion with and without collapse. We aimed to compare the technical success and perioperative complication rates of carotid artery stent placement with special attention to these subtypes to see whether there is a clinical relevance of this subclassification. Materials and methods From January 2014 to January 2018, we retrospectively evaluated all patients with atherosclerotic extracranial carotid stenosis treated by carotid artery stent placement. Patients with near-occlusion were identified based on DSA findings. Patient characteristics, the presence of criteria for near-occlusion and collapse, arterial diameters, technical success rate, and perioperative (≤30 days) complications were analyzed. Results We identified 59 near-occlusions in 58 (46 men, 11 with collapse) patients. Forty-one patients (70.7%) were symptomatic. Technical success rate was 98.3% (58 of 59 procedures). In 1 case of near-occlusion with collapse, we were near-occlusion undergoing CAS, especially in the subgroup of patients with collapse and in patients with both symptomatic and asymptomatic carotid stenosis.Background and purpose Cortical amyloid quantification on PET by using the standardized uptake value ratio is valuable for research studies and clinical trials in Alzheimer disease. However, it is resource intensive, requiring co-registered MR imaging data and specialized segmentation software. We investigated the use of deep learning to automatically quantify standardized uptake value ratio and used this for classification. Materials and methods Using the Alzheimer's Disease Neuroimaging Initiative dataset, we identified 2582 18F-florbetapir PET scans, which were separated into positive and negative cases by using a standardized uptake value ratio threshold of 1.1. We trained convolutional neural networks (ResNet-50 and ResNet-152) to predict standardized uptake value ratio and classify amyloid status. We assessed performance based on network depth, number of PET input slices, and use of ImageNet pretraining. We also assessed human performance with 3 readers in a subset of 100 randomly selected cases. Results We have found that 48% of cases were amyloid positive. The best performance was seen for ResNet-50 by using regression before classification, 3 input PET slices, and pretraining, with a standardized uptake value ratio root-mean-square error of 0.054, corresponding to 95.1% correct amyloid status prediction. Using more than 3 slices did not improve performance, but ImageNet initialization did. The best trained network was more accurate than humans (96% versus a mean of 88%, respectively). Conclusions Deep learning algorithms can estimate standardized uptake value ratio and use this to classify 18F-florbetapir PET scans. Such methods have promise to automate this laborious calculation, enabling quantitative measurements rapidly and in settings without extensive image processing manpower and expertise.
    Background and purpose Whiplash-associated disorders frequently develop following motor vehicle collisions and often involve a range of cognitive and affective symptoms, though the neural correlates of the disorder are largely unknown. In this study, a sample of participants with chronic whiplash injuries were scanned by using resting-state fMRI to assess brain network changes associated with long-term outcome metrics. Materials and methods Resting-state fMRI was collected for 23 participants and used to calculate network modularity, a quantitative measure of the functional segregation of brain region communities. This was analyzed for associations with whiplash-associated disorder outcome metrics, including scales of neck disability, traumatic distress, depression, and pain. In addition to these clinical scales, cervical muscle fat infiltration was quantified by using Dixon fat-water imaging, which has shown promise as a biomarker for assessing disorder severity and predicting recovery in chronic whiplash. Results An association was found between brain network structure and muscle fat infiltration, wherein lower network modularity was associated with larger amounts of cervical muscle fat infiltration after controlling for age, sex, body mass index, and scan motion (t = -4.02, partial R 2 = 0.49, P less then .001). Conclusions This work contributes to the existing whiplash literature by examining a sample of participants with whiplash-associated disorder by using resting-state fMRI. Less modular brain networks were found to be associated with greater amounts of cervical muscle fat infiltration suggesting a connection between disorder severity and neurologic changes, and a potential role for neuroimaging in understanding the pathophysiology of chronic whiplash-associated disorders.Background and purpose Focal cortical dysplasias are the most common resected epileptogenic lesions in children and the third most common lesion in adults, but they are often subtle and frequently overlooked on MR imaging. The purpose of this study was to evaluate whether MP2RAGE-based morphometric MR imaging analysis is superior to MPRAGE-based analysis in the detection of focal cortical dysplasia. Materials and methods MPRAGE and MP2RAGE datasets were acquired in a consecutive series of 640 patients with epilepsy. Datasets were postprocessed using the Morphometric Analysis Program to generate morphometric z score maps such as junction, extension, and thickness images based on both MPRAGE and MP2RAGE images. Focal cortical dysplasia lesions were manually segmented in the junction images, and volumes and mean z scores of the lesions were measured. https://www.selleckchem.com/products/imp-1088.html Results Of 21 focal cortical dysplasias discovered, all were clearly visible on MP2RAGE junction images, whereas 2 were not visible on MPRAGE junction images. In all except 4 patients, the volume of the focal cortical dysplasia was larger and mean lesion z scores were higher on MP2RAGE junction images compared with the MPRAGE-based images (P = .005, P = .013). Conclusions In this study, MP2RAGE-based morphometric analysis created clearer output maps with larger lesion volumes and higher z scores than the MPRAGE-based analysis. This new approach may improve the detection of subtle, otherwise overlooked focal cortical dysplasia.Background and purpose Carotid near-occlusion has been subclassified into near-occlusion with and without collapse. We aimed to compare the technical success and perioperative complication rates of carotid artery stent placement with special attention to these subtypes to see whether there is a clinical relevance of this subclassification. Materials and methods From January 2014 to January 2018, we retrospectively evaluated all patients with atherosclerotic extracranial carotid stenosis treated by carotid artery stent placement. Patients with near-occlusion were identified based on DSA findings. Patient characteristics, the presence of criteria for near-occlusion and collapse, arterial diameters, technical success rate, and perioperative (≤30 days) complications were analyzed. Results We identified 59 near-occlusions in 58 (46 men, 11 with collapse) patients. Forty-one patients (70.7%) were symptomatic. Technical success rate was 98.3% (58 of 59 procedures). In 1 case of near-occlusion with collapse, we were near-occlusion undergoing CAS, especially in the subgroup of patients with collapse and in patients with both symptomatic and asymptomatic carotid stenosis.Background and purpose Cortical amyloid quantification on PET by using the standardized uptake value ratio is valuable for research studies and clinical trials in Alzheimer disease. However, it is resource intensive, requiring co-registered MR imaging data and specialized segmentation software. We investigated the use of deep learning to automatically quantify standardized uptake value ratio and used this for classification. Materials and methods Using the Alzheimer's Disease Neuroimaging Initiative dataset, we identified 2582 18F-florbetapir PET scans, which were separated into positive and negative cases by using a standardized uptake value ratio threshold of 1.1. We trained convolutional neural networks (ResNet-50 and ResNet-152) to predict standardized uptake value ratio and classify amyloid status. We assessed performance based on network depth, number of PET input slices, and use of ImageNet pretraining. We also assessed human performance with 3 readers in a subset of 100 randomly selected cases. Results We have found that 48% of cases were amyloid positive. The best performance was seen for ResNet-50 by using regression before classification, 3 input PET slices, and pretraining, with a standardized uptake value ratio root-mean-square error of 0.054, corresponding to 95.1% correct amyloid status prediction. Using more than 3 slices did not improve performance, but ImageNet initialization did. The best trained network was more accurate than humans (96% versus a mean of 88%, respectively). Conclusions Deep learning algorithms can estimate standardized uptake value ratio and use this to classify 18F-florbetapir PET scans. Such methods have promise to automate this laborious calculation, enabling quantitative measurements rapidly and in settings without extensive image processing manpower and expertise.
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  • Acupuncture at LR3 + KI3 specifically affected brain areas involved in BP regulation, as well as those involved in auditory sense, speech, vision, movement and sensation. Conclusion Acupuncture at LR3 + KI3 showed positive immediate and long-term effects on BP, particularly systolic blood pressure (SBP). After ALFF analysis, we concluded that LR3 + KI3 activates brain areas related to BP regulation. In addition, after acupuncture at LR3 + KI3, a highly targeted effect was observed in brain areas associated with BP. In addition, extracerebral areas involving vision, motion control, cognition and hearing were activated, which could potentially contribute to the mitigation of hypertensive complications in patients in an advanced stage of the disease.Background The aim of this study was to investigate the central mechanism underlying the putative beneficial effects of electroacupuncture (EA) on learning and memory ability of rats with ischemic stroke-induced cognitive deficits by resting-state functional magnetic resonance imaging (fMRI). Methods A rat model of middle cerebral artery occlusion (MCAO)-induced cognitive deficit (****) was established. Rats were randomly assigned into a sham-operated control group (SC group, n = 12), untreated **** model group (**** group, n = 12), and **** group receiving EA treatment at GV20 and GV24 (**** + EA group, n = 12). Results Compared to the **** group, rats in the **** + EA group receiving EA at GV20 and GV24 exhibited significantly shortened escape latency times and crossed the position of the platform a significantly increased number of times during the Morris water maze test on the 14th day after EA, which suggested EA could significantly improve spatial learning and memory ability. Furthermore, compared to the **** group, functional connectivity of the left retrosplenial cortex (RSC) with the left hippocampus, left RSC, right RSC, left cingulate gyrus, right cingulate gyrus, right tegmentum of midbrain, and right visual cortex was increased in the **** + EA group; the **** group showed decreased functional connectivity of the left RSC with the left hippocampus, right hippocampus, left RSC, right RSC, right amygdaloid body, left visual cortex, and right visual cortex. Conclusion These findings suggest that EA at GV20 and GV24 might improve the learning and memory ability of **** rats by increasing the functional connectivity between the RSC and hippocampus, cingulate gyrus and midbrain, which is encouraging for the potential treatment for cognitive impairment secondary to ischemia stroke.Objective Postoperative delirium (POD) has rarely been investigated in breast cancer patients. Herein, we assessed the association between serum levels of the inflammatory biomarker translocator protein (TP) and the occurrence of POD in breast cancer patients. Methods In this prospective, observational study, TP levels were detected in preoperative and postoperative serum samples from 152 elderly breast cancer patients, samples from 152 healthy elderly women, and samples from 152 elderly women with benign breast diseases. The relationship between serum TP levels and POD was investigated using multivariate analysis. Results TP levels in postoperative patient serum samples were significantly higher than in preoperative patient serum samples and serum from women in the two control groups. Postoperative serum TP levels were independently correlated with serum C-reactive protein levels and the occurrence of POD. Postoperative serum TP levels had a high discriminatory ability for POD under the receiver operating characteristic curve. Conclusions Increased postoperative serum TP levels are independently associated with the degree of inflammatory response and the risk of POD in elderly breast cancer patients, substantializing TP as an inflammatory biomarker that can efficiently discriminate POD after breast cancer surgery.Objective This study investigated the effects of leptin on intestinal flora and inflammation in **** with high-fat diet (HFD)-induced obesity. Methods **** were fed an HFD for 8 weeks; some were concurrently administered oral leptin for 4 weeks. Pathological changes in adipose tissue were detected using hematoxylin-eosin staining; endotoxin content in adipose tissue was measured by enzyme-linked immunosorbent assay. Intestinal flora were characterized by 16S bacterial rDNA sequencing. Levels of Toll-like receptor 4 (TLR4), nuclear factor-κB inhibitor α (IκB-α), and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by western blotting. Results **** in the HFD group exhibited weight gain, elevated endotoxin content, and adipocyte hypertrophy, compared with the non-obese control group. Moreover, abundance of bacteria in the Bacteroides genus and community diversity were both reduced in the HFD group; reductions also were observed at corresponding phylum, class, and order levels. Levels of TLR4, IκB-α, and p-JNK were also elevated in the HFD group. Compared with the model group, leptin administration reduced the weight gain and endotoxin content, while increasing Bacteroides abundance and community diversity; it also reduced the levels of TLR4, IκB-α, and p-JNK. Conclusion Leptin administration improved intestinal flora dysfunction and inflammation in **** with HFD-induced obesity.Gestational gigantomastia (GGM) is a rare complication of pregnancy. The etiology of GGM is yet to be fully established. Treatment methods for GGM include medical therapy and surgery. If medical treatment is unsuccessful, surgery may be required. Currently available surgical interventions are either breast reduction or mastectomy with delayed reconstruction. We report a case of a 25-year-old woman (G1P1) who presented with massive enlargement of both breasts during puerperium. Because of the limited effect of medical therapy, surgical intervention was considered to be the first choice. https://www.selleckchem.com/products/azd8797.html Bilateral mastectomies with grafting of the nipple-areola complex and immediate bilateral tissue expander implantation were performed. Reconstruction was fully completed 8 months after the initial procedure by replacing tissue expanders with definitive implants. Despite being a benign condition, GGM can turn into a serious problem. GGM can be successfully reconstructed by mastectomy with delayed reconstruction and grafting of the nipple-areola complex.
    Acupuncture at LR3 + KI3 specifically affected brain areas involved in BP regulation, as well as those involved in auditory sense, speech, vision, movement and sensation. Conclusion Acupuncture at LR3 + KI3 showed positive immediate and long-term effects on BP, particularly systolic blood pressure (SBP). After ALFF analysis, we concluded that LR3 + KI3 activates brain areas related to BP regulation. In addition, after acupuncture at LR3 + KI3, a highly targeted effect was observed in brain areas associated with BP. In addition, extracerebral areas involving vision, motion control, cognition and hearing were activated, which could potentially contribute to the mitigation of hypertensive complications in patients in an advanced stage of the disease.Background The aim of this study was to investigate the central mechanism underlying the putative beneficial effects of electroacupuncture (EA) on learning and memory ability of rats with ischemic stroke-induced cognitive deficits by resting-state functional magnetic resonance imaging (fMRI). Methods A rat model of middle cerebral artery occlusion (MCAO)-induced cognitive deficit (MICD) was established. Rats were randomly assigned into a sham-operated control group (SC group, n = 12), untreated MICD model group (MICD group, n = 12), and MICD group receiving EA treatment at GV20 and GV24 (MICD + EA group, n = 12). Results Compared to the MICD group, rats in the MICD + EA group receiving EA at GV20 and GV24 exhibited significantly shortened escape latency times and crossed the position of the platform a significantly increased number of times during the Morris water maze test on the 14th day after EA, which suggested EA could significantly improve spatial learning and memory ability. Furthermore, compared to the MICD group, functional connectivity of the left retrosplenial cortex (RSC) with the left hippocampus, left RSC, right RSC, left cingulate gyrus, right cingulate gyrus, right tegmentum of midbrain, and right visual cortex was increased in the MICD + EA group; the MICD group showed decreased functional connectivity of the left RSC with the left hippocampus, right hippocampus, left RSC, right RSC, right amygdaloid body, left visual cortex, and right visual cortex. Conclusion These findings suggest that EA at GV20 and GV24 might improve the learning and memory ability of MICD rats by increasing the functional connectivity between the RSC and hippocampus, cingulate gyrus and midbrain, which is encouraging for the potential treatment for cognitive impairment secondary to ischemia stroke.Objective Postoperative delirium (POD) has rarely been investigated in breast cancer patients. Herein, we assessed the association between serum levels of the inflammatory biomarker translocator protein (TP) and the occurrence of POD in breast cancer patients. Methods In this prospective, observational study, TP levels were detected in preoperative and postoperative serum samples from 152 elderly breast cancer patients, samples from 152 healthy elderly women, and samples from 152 elderly women with benign breast diseases. The relationship between serum TP levels and POD was investigated using multivariate analysis. Results TP levels in postoperative patient serum samples were significantly higher than in preoperative patient serum samples and serum from women in the two control groups. Postoperative serum TP levels were independently correlated with serum C-reactive protein levels and the occurrence of POD. Postoperative serum TP levels had a high discriminatory ability for POD under the receiver operating characteristic curve. Conclusions Increased postoperative serum TP levels are independently associated with the degree of inflammatory response and the risk of POD in elderly breast cancer patients, substantializing TP as an inflammatory biomarker that can efficiently discriminate POD after breast cancer surgery.Objective This study investigated the effects of leptin on intestinal flora and inflammation in mice with high-fat diet (HFD)-induced obesity. Methods Mice were fed an HFD for 8 weeks; some were concurrently administered oral leptin for 4 weeks. Pathological changes in adipose tissue were detected using hematoxylin-eosin staining; endotoxin content in adipose tissue was measured by enzyme-linked immunosorbent assay. Intestinal flora were characterized by 16S bacterial rDNA sequencing. Levels of Toll-like receptor 4 (TLR4), nuclear factor-κB inhibitor α (IκB-α), and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by western blotting. Results Mice in the HFD group exhibited weight gain, elevated endotoxin content, and adipocyte hypertrophy, compared with the non-obese control group. Moreover, abundance of bacteria in the Bacteroides genus and community diversity were both reduced in the HFD group; reductions also were observed at corresponding phylum, class, and order levels. Levels of TLR4, IκB-α, and p-JNK were also elevated in the HFD group. Compared with the model group, leptin administration reduced the weight gain and endotoxin content, while increasing Bacteroides abundance and community diversity; it also reduced the levels of TLR4, IκB-α, and p-JNK. Conclusion Leptin administration improved intestinal flora dysfunction and inflammation in mice with HFD-induced obesity.Gestational gigantomastia (GGM) is a rare complication of pregnancy. The etiology of GGM is yet to be fully established. Treatment methods for GGM include medical therapy and surgery. If medical treatment is unsuccessful, surgery may be required. Currently available surgical interventions are either breast reduction or mastectomy with delayed reconstruction. We report a case of a 25-year-old woman (G1P1) who presented with massive enlargement of both breasts during puerperium. Because of the limited effect of medical therapy, surgical intervention was considered to be the first choice. https://www.selleckchem.com/products/azd8797.html Bilateral mastectomies with grafting of the nipple-areola complex and immediate bilateral tissue expander implantation were performed. Reconstruction was fully completed 8 months after the initial procedure by replacing tissue expanders with definitive implants. Despite being a benign condition, GGM can turn into a serious problem. GGM can be successfully reconstructed by mastectomy with delayed reconstruction and grafting of the nipple-areola complex.
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  • Background Elderly population's health is a major concern for most industrial nations. National health surveys provide a measure of the state of elderly health. One such survey is the Chinese Longitudinal Healthy Longevity Survey. It collects data on risk factors and outcomes on the elderly. We examine these longitudinal survey data to determine the changes in health and to identify risk factors as they impact health outcomes including the elderly's ability to do a physical check. Methods We use a Partitioned GMM logistic regression model to identify risk factors. The model also accounts for the correlation between lagged time-dependent covariates and the outcomes. It addresses present and past measures of time-dependent covariates on simultaneous outcomes. The relation produces additional regression coefficients as byproduct of the Partitioned model, identifying the immediate, delayed effects (lag - 1), further delayed (lag-2), etc. Therefore, the model presents the opportunity for decision makers to monitor the covariate over time. This technique is particularly useful in healthcare and health related research. We use the Chinese Longitudinal Health Longevity Survey data to identify those risk factors and to display the utility of the model. Results We found that one's ability to make own decisions, frequently consuming vegetables, exercise frequently, one's ability to transfer without assistance, having visual difficulties and being able to pick book from floor while standing had varying effects of significance on one's health and ability to complete physical checks as they get older. Conclusions The partitioning of the covariates as immediate effect, delayed effect or further delayed effect are important measures in a declining population.Background Osteoblastoma (OB) is an intermediate lesion, which makes the accurate preoperative diagnosis very important. 99mTc-methylene diphosphonate (99mTc-MDP) bone scan and SPECT/CT imaging were evaluated for their diagnostic value in spinal OB. Methods This study was a retrospective analysis of patients with spinal OB lesions confirmed by pathology and diagnosed with bone scan and SPECT/CT for preoperative diagnosis from January 2008 to December 2018. The uptake levels of OB on planar bone scan were divided into low, medium, and high groups by visual assessment referring to the uptake of the normal rib, spine, and bladder. X-ray, CT, MRI, bone scan, and SPECT/CT imaging of the patients were analyzed for characteristics summary. Results Twenty-five patients were diagnosed for spinal OB (17 males and 8 females with a proportion of 2.11), and the average age was 26.8 ± 10.8 years (range 5~59). There were 8 lesions located in the cervical, 6 in the thoracic, and 11 in the lumbar vertebrae. Twenty-four lesions involved posterior elements, especially the pedicles (14/25). Symptoms were predominantly painful with a duration of 18.3 ± 13.9 months (range 0.5~60 months). The lesion size ranged from 9 to 35 mm. All the lesions were low to high uptake in the planar bone scan, and the percentages of low to high levels were 1 (4%), 8 (32%), and 16 (64%) cases. Conclusions Spinal OB mainly involved the posterior area, and elderly patients should be considered as well. SPECT/CT combined the characteristics of bone uptake and anatomical features of bone tumors, proving its one-in-all diagnostic value for spinal OB and other osteogenic tumors.Background Long-lasting insecticidal nets (LLINs) are the most favoured vector control tools worldwide. Timely monitoring and evaluation of LLINs is important to sustain the impact of this promising vector control method and for replacement of worn-out and those rendered ineffective. During the mid-2017, LLINs were distributed by the National Vector Borne Disease Control Programme (NVBDCP) in high malaria endemic districts of the eastern coastal state of Odisha. The study was carried out to assess the field performance of the LLINs post 30 months of distribution in Koraput district of Odisha state. Methods A total of 130 households were randomly selected from three villages of Laxmipur CHC in Koraput district, Odisha, India; one each from hilltop, foothill and plain terrain. The net users were interviewed to elicit information on usage, washing practices, physical integrity, bio-efficacy and survivorship of LLINs to confirm the claimed three-year life of the LLINs. Results 74.8% of the LLINs were physically present after 30 months of distribution. The numbers (%) of LLINs used previous night varied from 30 to 61% between study villages. 74% respondents were using the LLINs throughout the year and 26% only seasonally. Of the total, 85% of the nets were reported to be washed and 95% nets were dried under shade as recommended. Altogether, 58% of the surveyed nets were found torn with holes. Of these, 74 (57%) nets were in good condition, 10 (8%) nets were in serviceable and 45 (35%) nets were badly torn and needed replacement. A total of 45 (93.75%), 68 (80%) and 71 (63.8%) LLINs were physically present in hilltop, foothill and plain villages, respectively. The LLINs did meet the efficacy criteria, given the 100% mortality to the exposed Anopheles jeyporiensis mosquitoes post 30 months distribution. Conclusions The findings of this study were communicated to the programme officials of the state and LLINs were replenished soon after 31st month post-distribution of LLINs.Background Short-segment internal fixation with intermediate straight-forward monoaxial screws (SSIF-SFM) and long-segment internal fixation (LSIF) are the two major surgical options for thoracolumbar (TL) fracture. However, SSIF-SFM might not provide adequate support to the spine, and LSIF is unnecessarily extensive. SSIF with intermediate inclined-angle polyxial screw (SSIF-IAP) might offer an alternative solution for the treatment of TL fracture. Methods A retrospective study was conducted. Sixty-nine patients (47 males and 22 females; average 34.5 years) with Denis type B TL fracture who met the criteria for inclusion were enrolled. Sagittal Cobb's angle (SCA), anterior vertebral body height (AVBH), vertebral body index (VBI), and spinal canal encroachment (SCE) were measured and assessed. https://www.selleckchem.com/products/heptadecanoic-acid.html Visual analogue scale (VAS) and Oswestry disability index (ODI) were also evaluated. Results The average values of incision length, blood loss, duration of operation, and hospital stay in the SSIF-IAP group and SSIF-SFM group were significantly decreased compared with those in the LSIF group.
    Background Elderly population's health is a major concern for most industrial nations. National health surveys provide a measure of the state of elderly health. One such survey is the Chinese Longitudinal Healthy Longevity Survey. It collects data on risk factors and outcomes on the elderly. We examine these longitudinal survey data to determine the changes in health and to identify risk factors as they impact health outcomes including the elderly's ability to do a physical check. Methods We use a Partitioned GMM logistic regression model to identify risk factors. The model also accounts for the correlation between lagged time-dependent covariates and the outcomes. It addresses present and past measures of time-dependent covariates on simultaneous outcomes. The relation produces additional regression coefficients as byproduct of the Partitioned model, identifying the immediate, delayed effects (lag - 1), further delayed (lag-2), etc. Therefore, the model presents the opportunity for decision makers to monitor the covariate over time. This technique is particularly useful in healthcare and health related research. We use the Chinese Longitudinal Health Longevity Survey data to identify those risk factors and to display the utility of the model. Results We found that one's ability to make own decisions, frequently consuming vegetables, exercise frequently, one's ability to transfer without assistance, having visual difficulties and being able to pick book from floor while standing had varying effects of significance on one's health and ability to complete physical checks as they get older. Conclusions The partitioning of the covariates as immediate effect, delayed effect or further delayed effect are important measures in a declining population.Background Osteoblastoma (OB) is an intermediate lesion, which makes the accurate preoperative diagnosis very important. 99mTc-methylene diphosphonate (99mTc-MDP) bone scan and SPECT/CT imaging were evaluated for their diagnostic value in spinal OB. Methods This study was a retrospective analysis of patients with spinal OB lesions confirmed by pathology and diagnosed with bone scan and SPECT/CT for preoperative diagnosis from January 2008 to December 2018. The uptake levels of OB on planar bone scan were divided into low, medium, and high groups by visual assessment referring to the uptake of the normal rib, spine, and bladder. X-ray, CT, MRI, bone scan, and SPECT/CT imaging of the patients were analyzed for characteristics summary. Results Twenty-five patients were diagnosed for spinal OB (17 males and 8 females with a proportion of 2.11), and the average age was 26.8 ± 10.8 years (range 5~59). There were 8 lesions located in the cervical, 6 in the thoracic, and 11 in the lumbar vertebrae. Twenty-four lesions involved posterior elements, especially the pedicles (14/25). Symptoms were predominantly painful with a duration of 18.3 ± 13.9 months (range 0.5~60 months). The lesion size ranged from 9 to 35 mm. All the lesions were low to high uptake in the planar bone scan, and the percentages of low to high levels were 1 (4%), 8 (32%), and 16 (64%) cases. Conclusions Spinal OB mainly involved the posterior area, and elderly patients should be considered as well. SPECT/CT combined the characteristics of bone uptake and anatomical features of bone tumors, proving its one-in-all diagnostic value for spinal OB and other osteogenic tumors.Background Long-lasting insecticidal nets (LLINs) are the most favoured vector control tools worldwide. Timely monitoring and evaluation of LLINs is important to sustain the impact of this promising vector control method and for replacement of worn-out and those rendered ineffective. During the mid-2017, LLINs were distributed by the National Vector Borne Disease Control Programme (NVBDCP) in high malaria endemic districts of the eastern coastal state of Odisha. The study was carried out to assess the field performance of the LLINs post 30 months of distribution in Koraput district of Odisha state. Methods A total of 130 households were randomly selected from three villages of Laxmipur CHC in Koraput district, Odisha, India; one each from hilltop, foothill and plain terrain. The net users were interviewed to elicit information on usage, washing practices, physical integrity, bio-efficacy and survivorship of LLINs to confirm the claimed three-year life of the LLINs. Results 74.8% of the LLINs were physically present after 30 months of distribution. The numbers (%) of LLINs used previous night varied from 30 to 61% between study villages. 74% respondents were using the LLINs throughout the year and 26% only seasonally. Of the total, 85% of the nets were reported to be washed and 95% nets were dried under shade as recommended. Altogether, 58% of the surveyed nets were found torn with holes. Of these, 74 (57%) nets were in good condition, 10 (8%) nets were in serviceable and 45 (35%) nets were badly torn and needed replacement. A total of 45 (93.75%), 68 (80%) and 71 (63.8%) LLINs were physically present in hilltop, foothill and plain villages, respectively. The LLINs did meet the efficacy criteria, given the 100% mortality to the exposed Anopheles jeyporiensis mosquitoes post 30 months distribution. Conclusions The findings of this study were communicated to the programme officials of the state and LLINs were replenished soon after 31st month post-distribution of LLINs.Background Short-segment internal fixation with intermediate straight-forward monoaxial screws (SSIF-SFM) and long-segment internal fixation (LSIF) are the two major surgical options for thoracolumbar (TL) fracture. However, SSIF-SFM might not provide adequate support to the spine, and LSIF is unnecessarily extensive. SSIF with intermediate inclined-angle polyxial screw (SSIF-IAP) might offer an alternative solution for the treatment of TL fracture. Methods A retrospective study was conducted. Sixty-nine patients (47 males and 22 females; average 34.5 years) with Denis type B TL fracture who met the criteria for inclusion were enrolled. Sagittal Cobb's angle (SCA), anterior vertebral body height (AVBH), vertebral body index (VBI), and spinal canal encroachment (SCE) were measured and assessed. https://www.selleckchem.com/products/heptadecanoic-acid.html Visual analogue scale (VAS) and Oswestry disability index (ODI) were also evaluated. Results The average values of incision length, blood loss, duration of operation, and hospital stay in the SSIF-IAP group and SSIF-SFM group were significantly decreased compared with those in the LSIF group.
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