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  • At a minimum power consumption of 87 μW, the LDC still achieves 95 dB DR. The LDC is also validated with on-body PPG and NIRS measurement by using a photodiode (PD) and a silicon photomultiplier (SIPM), respectively.In the past few years it has been demonstrated that electroencephalography (EEG) can be recorded from inside the ear (in-ear EEG). To open the door to low-profile earpieces as wearable brain-computer interfaces (BCIs), this work presents a practical in-ear EEG device based on multiple dry electrodes, a user-generic design, and a lightweight wireless interface for streaming data and device programming. The earpiece is designed for improved ear canal contact across a wide population of users and is fabricated in a low-cost and scalable manufacturing process based on standard techniques such as vacuum forming, plasma-treatment, and spray coating. A 2.5 × 2.5 cm2 wireless recording module is designed to record and stream data wirelessly to a host computer. Performance was evaluated on three human subjects over three months and compared with clinical-grade wet scalp EEG recordings. Recordings of spontaneous and evoked physiological signals, eye-blinks, alpha rhythm, and the auditory steady-state response (ASSR), are presented. This is the first wireless in-ear EEG to our knowledge to incorporate a dry multielectrode, user-generic design. The user-generic ear EEG recorded a mean alpha modulation of 2.17, outperforming the state-of-the-art in dry electrode in-ear EEG systems.In this work, a dual-mode stimulus chip with a built-in high voltage generator was proposed to offer a broad-range current or voltage stimulus patterns for biomedical applications. With an on-chip and built-in high voltage generator, this stimulus chip could generate the required high voltage supply without additional supply voltage. With a nearly 20 V operating voltage, the overstress and reliability issues of the stimulus circuits were thoroughly considered and carefully addressed in this work. This stimulus system only requires an area of 0.22 mm2 per single channel and is fully on-chip implemented without any additional external components. The dual-mode stimulus chip was fabricated in a 0.25-μm 2.5V/5V/12V CMOS (complementary metal-oxide-semiconductor) process, which can generate the biphasic current or voltage stimulus pulses. The current level of stimulus is up to 5 mA, and the voltage level of stimulus can be up to 10 V. Moreover, this chip has been successfully applied to stimulate a guinea pig in an animal experiment. The proposed dual-mode stimulus system has been verified in electrical tests and also demonstrated its stimulation function in animal experiments.Magnetomyography (MMG) with superconducting quantum interference devices (SQUIDs) enabled the measurement of very weak magnetic fields (femto to pico Tesla) generated from the human skeletal muscles during contraction. However, SQUIDs are bulky, costly, and require working in a temperature-controlled environment, limiting wide-spread clinical use. We introduce a low-profile magnetoelectric (ME) sensor with analog frontend circuitry that has sensitivity to measure pico-Tesla MMG signals at room temperature. It comprises magnetostrictive and piezoelectric materials, FeCoSiB/AlN. Accurate device modelling and simulation are presented to predict device fabrication process comprehensively using the finite element method (FEM) in COMSOL Multiphysics. The fabricated ME chip with its readout circuit was characterized under a dynamic geomagnetic field cancellation technique. The ME sensor experiment validate a very linear response with high sensitivities of up to 378 V/T driven at a resonance frequency of fres = 7.76 kHz. Measurements show the sensor limit of detections of down to 175 pT/√Hz at resonance, which is in the range of MMG signals. Such a small-scale sensor has the potential to monitor chronic movement disorders and improve the end-user acceptance of human-machine interfaces.In this article, we present a real-time electroencephalogram (EEG) based depth of anesthesia (DoA) monitoring system in conjunction with a deep learning framework, AnesNET. An EEG analog front-end (AFE) that can compensate ±380-mV electrode DC offset using a coarse digital DC servo loop is implemented in the proposed system. The EEG-based MAC, EEGMAC, is introduced as a novel index to accurately predict the DoA, which is designed for applying to patients anesthetized by both volatile and intravenous agents. The proposed deep learning protocol consists of four layers of convolutional neural network and two dense layers. In addition, we optimize the complexity of the deep neural network (DNN) to operate on a microcomputer such as the Raspberry Pi 3, realizing a cost-effective small-size DoA monitoring system. Fabricated in 110-nm CMOS, the prototype AFE consumes 4.33 μW per channel and has the input-referred noise of 0.29 μVrms from 0.5 to 100 Hz with the noise efficiency factor of 2.2. https://www.selleckchem.com/products/pterostilbene.html The proposed DNN was evaluated with pre-recorded EEG data from 374 subjects administrated by inhalational anesthetics under surgery, achieving an average squared and absolute errors of 0.048 and 0.05, respectively. The EEGMAC with subjects anesthetized by an intravenous agent also showed a good agreement with the bispectral index value, confirming the proposed DoA index is applicable to both anesthetics. The implemented monitoring system with the Raspberry Pi 3 estimates the EEGMAC within 20 ms, which is about thousand-fold faster than the BIS estimation in literature.Neurons are the primary building block of the nervous system. Exploring the mysteries of the brain in science or building a novel brain-inspired hardware substrate in engineering are inseparable from constructing an efficient biological neuron. Balancing the functional capability and the implementation cost of a neuron is a grand challenge in neuromorphic field. In this paper, we present a low-cost adaptive exponential integrate-and-fire neuron, called SC-AdEx, for large-scale neuromorphic systems using stochastic computing. In the proposed model, arithmetic operations are performed on stochastic bit-streams with small and low-power circuitry. To evaluate the proposed neuron, we perform biological behavior analysis, including various firing patterns. Furthermore, the model is synthesized and implemented physically on FPGA as a proof of concept. Experimental results show that our model can precisely reproduce wide range biological behaviors as the original model, with higher computational performance and lower hardware cost against state-of-the-art AdEx hardware neurons.
    At a minimum power consumption of 87 μW, the LDC still achieves 95 dB DR. The LDC is also validated with on-body PPG and NIRS measurement by using a photodiode (PD) and a silicon photomultiplier (SIPM), respectively.In the past few years it has been demonstrated that electroencephalography (EEG) can be recorded from inside the ear (in-ear EEG). To open the door to low-profile earpieces as wearable brain-computer interfaces (BCIs), this work presents a practical in-ear EEG device based on multiple dry electrodes, a user-generic design, and a lightweight wireless interface for streaming data and device programming. The earpiece is designed for improved ear canal contact across a wide population of users and is fabricated in a low-cost and scalable manufacturing process based on standard techniques such as vacuum forming, plasma-treatment, and spray coating. A 2.5 × 2.5 cm2 wireless recording module is designed to record and stream data wirelessly to a host computer. Performance was evaluated on three human subjects over three months and compared with clinical-grade wet scalp EEG recordings. Recordings of spontaneous and evoked physiological signals, eye-blinks, alpha rhythm, and the auditory steady-state response (ASSR), are presented. This is the first wireless in-ear EEG to our knowledge to incorporate a dry multielectrode, user-generic design. The user-generic ear EEG recorded a mean alpha modulation of 2.17, outperforming the state-of-the-art in dry electrode in-ear EEG systems.In this work, a dual-mode stimulus chip with a built-in high voltage generator was proposed to offer a broad-range current or voltage stimulus patterns for biomedical applications. With an on-chip and built-in high voltage generator, this stimulus chip could generate the required high voltage supply without additional supply voltage. With a nearly 20 V operating voltage, the overstress and reliability issues of the stimulus circuits were thoroughly considered and carefully addressed in this work. This stimulus system only requires an area of 0.22 mm2 per single channel and is fully on-chip implemented without any additional external components. The dual-mode stimulus chip was fabricated in a 0.25-μm 2.5V/5V/12V CMOS (complementary metal-oxide-semiconductor) process, which can generate the biphasic current or voltage stimulus pulses. The current level of stimulus is up to 5 mA, and the voltage level of stimulus can be up to 10 V. Moreover, this chip has been successfully applied to stimulate a guinea pig in an animal experiment. The proposed dual-mode stimulus system has been verified in electrical tests and also demonstrated its stimulation function in animal experiments.Magnetomyography (MMG) with superconducting quantum interference devices (SQUIDs) enabled the measurement of very weak magnetic fields (femto to pico Tesla) generated from the human skeletal muscles during contraction. However, SQUIDs are bulky, costly, and require working in a temperature-controlled environment, limiting wide-spread clinical use. We introduce a low-profile magnetoelectric (ME) sensor with analog frontend circuitry that has sensitivity to measure pico-Tesla MMG signals at room temperature. It comprises magnetostrictive and piezoelectric materials, FeCoSiB/AlN. Accurate device modelling and simulation are presented to predict device fabrication process comprehensively using the finite element method (FEM) in COMSOL Multiphysics. The fabricated ME chip with its readout circuit was characterized under a dynamic geomagnetic field cancellation technique. The ME sensor experiment validate a very linear response with high sensitivities of up to 378 V/T driven at a resonance frequency of fres = 7.76 kHz. Measurements show the sensor limit of detections of down to 175 pT/√Hz at resonance, which is in the range of MMG signals. Such a small-scale sensor has the potential to monitor chronic movement disorders and improve the end-user acceptance of human-machine interfaces.In this article, we present a real-time electroencephalogram (EEG) based depth of anesthesia (DoA) monitoring system in conjunction with a deep learning framework, AnesNET. An EEG analog front-end (AFE) that can compensate ±380-mV electrode DC offset using a coarse digital DC servo loop is implemented in the proposed system. The EEG-based MAC, EEGMAC, is introduced as a novel index to accurately predict the DoA, which is designed for applying to patients anesthetized by both volatile and intravenous agents. The proposed deep learning protocol consists of four layers of convolutional neural network and two dense layers. In addition, we optimize the complexity of the deep neural network (DNN) to operate on a microcomputer such as the Raspberry Pi 3, realizing a cost-effective small-size DoA monitoring system. Fabricated in 110-nm CMOS, the prototype AFE consumes 4.33 μW per channel and has the input-referred noise of 0.29 μVrms from 0.5 to 100 Hz with the noise efficiency factor of 2.2. https://www.selleckchem.com/products/pterostilbene.html The proposed DNN was evaluated with pre-recorded EEG data from 374 subjects administrated by inhalational anesthetics under surgery, achieving an average squared and absolute errors of 0.048 and 0.05, respectively. The EEGMAC with subjects anesthetized by an intravenous agent also showed a good agreement with the bispectral index value, confirming the proposed DoA index is applicable to both anesthetics. The implemented monitoring system with the Raspberry Pi 3 estimates the EEGMAC within 20 ms, which is about thousand-fold faster than the BIS estimation in literature.Neurons are the primary building block of the nervous system. Exploring the mysteries of the brain in science or building a novel brain-inspired hardware substrate in engineering are inseparable from constructing an efficient biological neuron. Balancing the functional capability and the implementation cost of a neuron is a grand challenge in neuromorphic field. In this paper, we present a low-cost adaptive exponential integrate-and-fire neuron, called SC-AdEx, for large-scale neuromorphic systems using stochastic computing. In the proposed model, arithmetic operations are performed on stochastic bit-streams with small and low-power circuitry. To evaluate the proposed neuron, we perform biological behavior analysis, including various firing patterns. Furthermore, the model is synthesized and implemented physically on FPGA as a proof of concept. Experimental results show that our model can precisely reproduce wide range biological behaviors as the original model, with higher computational performance and lower hardware cost against state-of-the-art AdEx hardware neurons.
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  • An important unanswered question in chromatin biology is the extent to which long-range looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Computational tools for rigorous assessment of cell type-specific loops across multiple biological conditions are needed. We present 3DeFDR, a simple and effective statistical tool for classifying dynamic loops across biological conditions from Chromosome-Conformation-Capture-Carbon-Copy (5C) and Hi-C data. Our work provides a statistical framework and open-source coding libraries for sensitive detection of cell type-specific loops in high-resolution 5C and Hi-C data from multiple cellular conditions.
    Although a relationship between Helicobacter pylori and oral malodor has been suggested, it remains to be confirmed. One reason for this is that many studies assess oral malodor subjectively. Another reason for the uncertainty is that the reduction in oral malodor may be due to the effect of antibiotics on the oral microbiota. In this study, changes in oral malodor along with the eradication treatment of H. pylori were investigated by organoleptic test and gas chromatography. In addition, the salivary bacterial composition and clinical parameters were analyzed.

    The organoleptic test score, hydrogen sulfide and dimethyl sulfide concentrations, and all clinical parameters except for tongue-coating score were significantly decreased at 1week compared with baseline. Although antibiotic treatment also altered the overall composition of the salivary bacterial population, it had recovered at 7weeks. On the date that H. pylori was determined to have been eradicated from all of the subjects (7weeks after treatment), only the organoleptic test score was significantly lower compared with baseline. The hydrogen sulfide and dimethyl sulfide concentrations were non-significantly lower than those at baseline.
    The organoleptic test score, hydrogen sulfide and dimethyl sulfide concentrations, and all clinical parameters except for tongue-coating score were significantly decreased at 1 week compared with baseline. Although antibiotic treatment also altered the overall composition of the salivary bacterial population, it had recovered at 7 weeks. On the date that H. pylori was determined to have been eradicated from all of the subjects (7 weeks after treatment), only the organoleptic test score was significantly lower compared with baseline. The hydrogen sulfide and dimethyl sulfide concentrations were non-significantly lower than those at baseline.
    Lysine succinylation is an emerging posttranslational modification that has garnered increased attention recently, but its role in gastric cancer (GC) remains underexplored.

    Proteomic quantification of lysine succinylation was performed in human GC tissues and adjacent normal tissues by mass spectrometry. The mRNA and protein levels of lactate dehydrogenase A (LDHA) in GC and adjacent normal tissues were analyzed by qRT-PCR and western blot, respectively. The expression of K222-succinylated LDHA was measured in GC tissue microarray by the K222 succinylation-specific antibody. The interaction between LDHA and sequestosome 1 (SQSTM1) was measured by co-immunoprecipitation (co-IP) and proximity ligation assay (PLA). The binding of carnitine palmitoyltransferase 1A (CPT1A) to LDHA was determined by co-IP. The effect of K222-succinylated LDHA on tumor growth and metastasis was evaluated by in vitro and in vivo experiments.

    Altogether, 503 lysine succinylation sites in 303 proteins were identified. Lactate deata revealed a novel lysosomal pathway of LDHA degradation, which is mediated by the binding of K63-ubiquitinated LDHA to SQSTM1. Strikingly, CPT1A succinylates LDHA on K222, which thereby reduces the binding and inhibits the degradation of LDHA, as well as promotes GC invasion and proliferation. This study thus uncovers a new role of lysine succinylation and the mechanism underlying LDHA upregulation in GC.
    The hemodialysis setting is suitable for trials that use cluster randomization, where intact groups of individuals are randomized. However, cluster randomized trials (CRTs) are complicated in their design, analysis, and reporting and can pose ethical challenges. We reviewed CRTs in the hemodialysis setting with respect to reporting of key methodological and ethical issues.

    We conducted a systematic review of CRTs in the hemodialysis setting, published in English, between 2000 and 2019, and indexed in MEDLINE or Embase. Two reviewers extracted data, and study results were summarized using descriptive statistics.

    We identified 26 completed CRTs and five study protocols of CRTs. These studies randomized hemodialysis centers (n= 17, 55%), hemodialysis shifts (n= 12, 39%), healthcare providers (n= 1, 3%), and nephrology units (n= 1, 3%). https://www.selleckchem.com/products/phycocyanobilin.html Trials included a median of 28 clusters with a median cluster size of 20 patients. Justification for using a clustered design was provided by 15 trials (48%). Methods that accounted for clustering were used during sample size calculation in 14 (45%), during analyses in 22 (71%), and during both sample size calculation and analyses in 13 trials (42%). Among all CRTs, 26 (84%) reported receiving research ethics committee approval; patient consent was reported in 22 trials 10 (32%) reported the method of consent for trial participation and 12 (39%) reported no details about how consent was obtained or its purpose. Four trials (13%) reported receiving waivers of consent, and the remaining 5 (16%) provided no or unclear information about the consent process.

    There is an opportunity to improve the conduct and reporting of essential methodological and ethical issues in future CRTs in hemodialysis.

    We conducted this systematic review using a pre-specified protocol that was not registered.
    We conducted this systematic review using a pre-specified protocol that was not registered.We present a base editing system, in which base editors are attached to different sites of sgRNA scaffold (sgBE). Each independent sgBE has its own specific editing pattern for a given target site. Among tested sgBEs, sgBE-SL4, in which deaminase is attached to the last stem-loop of sgRNA, yields the highest editing efficiency in the window several nucleotides next to the one edited by BE3. sgBE enables the simultaneous editing of adenine and cytosine. Finally, in order to facilitate in vivo base editing, we extend our sgBE system to an AAV-compatible Cas9, SaCas9 (Staphylococcus aureus), and observe robust base editing.
    An important unanswered question in chromatin biology is the extent to which long-range looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Computational tools for rigorous assessment of cell type-specific loops across multiple biological conditions are needed. We present 3DeFDR, a simple and effective statistical tool for classifying dynamic loops across biological conditions from Chromosome-Conformation-Capture-Carbon-Copy (5C) and Hi-C data. Our work provides a statistical framework and open-source coding libraries for sensitive detection of cell type-specific loops in high-resolution 5C and Hi-C data from multiple cellular conditions. Although a relationship between Helicobacter pylori and oral malodor has been suggested, it remains to be confirmed. One reason for this is that many studies assess oral malodor subjectively. Another reason for the uncertainty is that the reduction in oral malodor may be due to the effect of antibiotics on the oral microbiota. In this study, changes in oral malodor along with the eradication treatment of H. pylori were investigated by organoleptic test and gas chromatography. In addition, the salivary bacterial composition and clinical parameters were analyzed. The organoleptic test score, hydrogen sulfide and dimethyl sulfide concentrations, and all clinical parameters except for tongue-coating score were significantly decreased at 1week compared with baseline. Although antibiotic treatment also altered the overall composition of the salivary bacterial population, it had recovered at 7weeks. On the date that H. pylori was determined to have been eradicated from all of the subjects (7weeks after treatment), only the organoleptic test score was significantly lower compared with baseline. The hydrogen sulfide and dimethyl sulfide concentrations were non-significantly lower than those at baseline. The organoleptic test score, hydrogen sulfide and dimethyl sulfide concentrations, and all clinical parameters except for tongue-coating score were significantly decreased at 1 week compared with baseline. Although antibiotic treatment also altered the overall composition of the salivary bacterial population, it had recovered at 7 weeks. On the date that H. pylori was determined to have been eradicated from all of the subjects (7 weeks after treatment), only the organoleptic test score was significantly lower compared with baseline. The hydrogen sulfide and dimethyl sulfide concentrations were non-significantly lower than those at baseline. Lysine succinylation is an emerging posttranslational modification that has garnered increased attention recently, but its role in gastric cancer (GC) remains underexplored. Proteomic quantification of lysine succinylation was performed in human GC tissues and adjacent normal tissues by mass spectrometry. The mRNA and protein levels of lactate dehydrogenase A (LDHA) in GC and adjacent normal tissues were analyzed by qRT-PCR and western blot, respectively. The expression of K222-succinylated LDHA was measured in GC tissue microarray by the K222 succinylation-specific antibody. The interaction between LDHA and sequestosome 1 (SQSTM1) was measured by co-immunoprecipitation (co-IP) and proximity ligation assay (PLA). The binding of carnitine palmitoyltransferase 1A (CPT1A) to LDHA was determined by co-IP. The effect of K222-succinylated LDHA on tumor growth and metastasis was evaluated by in vitro and in vivo experiments. Altogether, 503 lysine succinylation sites in 303 proteins were identified. Lactate deata revealed a novel lysosomal pathway of LDHA degradation, which is mediated by the binding of K63-ubiquitinated LDHA to SQSTM1. Strikingly, CPT1A succinylates LDHA on K222, which thereby reduces the binding and inhibits the degradation of LDHA, as well as promotes GC invasion and proliferation. This study thus uncovers a new role of lysine succinylation and the mechanism underlying LDHA upregulation in GC. The hemodialysis setting is suitable for trials that use cluster randomization, where intact groups of individuals are randomized. However, cluster randomized trials (CRTs) are complicated in their design, analysis, and reporting and can pose ethical challenges. We reviewed CRTs in the hemodialysis setting with respect to reporting of key methodological and ethical issues. We conducted a systematic review of CRTs in the hemodialysis setting, published in English, between 2000 and 2019, and indexed in MEDLINE or Embase. Two reviewers extracted data, and study results were summarized using descriptive statistics. We identified 26 completed CRTs and five study protocols of CRTs. These studies randomized hemodialysis centers (n= 17, 55%), hemodialysis shifts (n= 12, 39%), healthcare providers (n= 1, 3%), and nephrology units (n= 1, 3%). https://www.selleckchem.com/products/phycocyanobilin.html Trials included a median of 28 clusters with a median cluster size of 20 patients. Justification for using a clustered design was provided by 15 trials (48%). Methods that accounted for clustering were used during sample size calculation in 14 (45%), during analyses in 22 (71%), and during both sample size calculation and analyses in 13 trials (42%). Among all CRTs, 26 (84%) reported receiving research ethics committee approval; patient consent was reported in 22 trials 10 (32%) reported the method of consent for trial participation and 12 (39%) reported no details about how consent was obtained or its purpose. Four trials (13%) reported receiving waivers of consent, and the remaining 5 (16%) provided no or unclear information about the consent process. There is an opportunity to improve the conduct and reporting of essential methodological and ethical issues in future CRTs in hemodialysis. We conducted this systematic review using a pre-specified protocol that was not registered. We conducted this systematic review using a pre-specified protocol that was not registered.We present a base editing system, in which base editors are attached to different sites of sgRNA scaffold (sgBE). Each independent sgBE has its own specific editing pattern for a given target site. Among tested sgBEs, sgBE-SL4, in which deaminase is attached to the last stem-loop of sgRNA, yields the highest editing efficiency in the window several nucleotides next to the one edited by BE3. sgBE enables the simultaneous editing of adenine and cytosine. Finally, in order to facilitate in vivo base editing, we extend our sgBE system to an AAV-compatible Cas9, SaCas9 (Staphylococcus aureus), and observe robust base editing.
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  • Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. We aimed to identify a robust lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients.

    We analyzed the gene expression profiles of lipid metabolism from Molecular Signatures Database and information of patients from The Cancer Genome Atlas. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and principal component analysis (PCA) were employed for functional annotation. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to verify the expression of model genes in HCC and adjacent tissues.

    As a result, a lipid metabolism-related signature consisting of acyl-CoA synthetase long-chain family member 6 (ACSL6), lysophosphatidylcholine acyltransferase 1, phospholipase A2 group 1B, lecithin-cholesterol acyltransferase (LCAT), and sphingomyelin phosphodiesterase 4 (SMPD4) was identified among HCC patients. Lysophosphatidylcholiner HCC.
    Retinoids are widely used in different cosmetic products because of general improvement of skin appearance. However, retinoid concentration in cosmetics is restricted, and one particular form-retinoic acid, is banned in cosmetics due to safety reasons.

    Within this study, we aimed to examine the quality of a considerable number of commercial retinoid cosmetic products in terms of their content and labeling, including also screening for the presence of retinoic acid.

    An appropriate analytical methodology, based on HPLC-UV for the simultaneous determination of common retinoids, along with a screening method for retinoic acid, was developed and validated. Structural identity confirmation of the newer retinoid-hydroxypinacolone retinoate, was performed by LC-MS.

    Retinol and retinyl palmitate were most often found, in concentrations mostly below 0.3%, and up to 1.3% retinol equivalents. Determined contents deviated significantly from the quantitatively declared ones in seven products (0%-130%). In more thanore strict regulation and quality control to ensure their efficacy and safety.
    Fragment reattachment is a procedure that can immediately restore form and function in crown-root fracture cases and is considered a minimally invasive and cost-effective treatment option. The aim of this systematic review was to analyze the methods used and the outcome of fragment reattachment for complicated crown-root fractures of anterior teeth.

    Five electronic databases (PubMed, Web of Science, Embase, Scopus, and Google Scholar) were searched for English language articles regarding fragment reattachment after complicated crown-root fractures of anterior teeth.

    Twelve case reports and two case series were selected for this review after applying the inclusion and exclusion criteria. In eleven articles, the fracture line was exposed prior to reattachment. Root canal treatment was performed in all cases except one, where conservative pulp treatment was done prior to reattachment. A post was used as part of the restoration in 85% of the cases. Additional fragment preparation was done in 42% of the cases in the form of beveling and groove formation. Adhesive strategies used to reattach the coronal fragments were total-etch, self-etch, or self-cure adhesive. Intermediate materials used for reattachment were resin cement, glass-ionomer cement, composite and self-adhesive cement. Treatment outcomes were favorable in all the included articles and the follow-up period ranged from three months to seven years.

    Fragment reattachment after complicated crown-root fractures of anterior teeth can be considered as a viable treatment option if the clinical conditions are favorable.
    Fragment reattachment after complicated crown-root fractures of anterior teeth can be considered as a viable treatment option if the clinical conditions are favorable.
    The major aims of this study are to determine the capability of sulphur oxidizing bacterium (SOB-1) to desulphurize dibenzothiophene (DBT) and crude oil, detection of the reaction kinetics and identify the proposed pathway of DBT desulphurization.

    The isolate was genetically identified based on 16S rRNA gene sequencing as Klebsiella oxytoca and deposited in the Genebank database under the accession number MT355440. The HPLC analysis of the remaining DBT concentration revealed that, SOB-1 could desulphurize 90% of DBT (0·25mmoll
    ) within 96h. https://www.selleckchem.com/products/AS703026.html The maximum production of sulphate ions from the desulphurization of DBT (0·36mmoll
    ) and crude oil (0·4mmoll
    ) could be quantitatively detected after 48h of incubation at 30°C. The high values of correlation coefficient (R
    ) obtained at all studied concentrations; suggested that biodesulfurization kinetics of DBT follows the first-order reaction model. The kinetics studies showed that, DBT may have an inhibitory effect on SOB-1 when the initial concentration exceeded 0·75mmoll
    . The GC-MS analysis exhibited four main metabolites rather than DBT. The most important ones are 2-hydroxybiphenyl (2-HBP) and methoxybiphenyl n(2-MBP).

    Klebsiella oxytoca SOB-1 catalyzes the desulphurization of DBT through 4S pathway and forms four main metabolic products. The release of sulphate ion and formation of 2-HBP indicating the elimination of sulphur group without altering the carbon skeleton of DBT. The bacterial strain could also catalyzes desulphurization of crude oil. The desulphurization kinetics follows the first-order reaction model.

    Klebsiella oxytoca SOB-1 could be used as a promising industrial and environmental biodesulfurizing agent as it is not affecting carbon skeleton of thiophenic compounds and forming less toxic metabolic product (2-MBP).
    Klebsiella oxytoca SOB-1 could be used as a promising industrial and environmental biodesulfurizing agent as it is not affecting carbon skeleton of thiophenic compounds and forming less toxic metabolic product (2-MBP).
    To verify which one improves better stress urinary incontinence (SUI) symptoms abdominal hypopressive technique (AHT) or pelvic floor muscle training (PFMT).

    Randomized controlled trial. Women with SUI who had not participated of physiotherapy program before were invited. The outcome measures were 7-day bladder diary, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and pelvic floor muscles (PFM) function measured by Modified Oxford grading System with vaginal palpation and manometry with Peritron. Intervention consisted by 12 weeks of exercises program including PFMT or AHT program, in groups of maximum three women, twice a week, with physiotherapist supervision.

    AHT and PFMT groups reduced urinary leakage episodes in 7 days, -0.64 and -1.91, respectively, but PFMT was superior, whit mean difference -1.27 (95% confidence interval [CI] -1.92 to -0,62) and effect size was 0.94 in favor to PFMT. Regarding to total score of ICIQ-SF, both groups improved, with mean difference between groups -4.
    Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. We aimed to identify a robust lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients. We analyzed the gene expression profiles of lipid metabolism from Molecular Signatures Database and information of patients from The Cancer Genome Atlas. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and principal component analysis (PCA) were employed for functional annotation. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to verify the expression of model genes in HCC and adjacent tissues. As a result, a lipid metabolism-related signature consisting of acyl-CoA synthetase long-chain family member 6 (ACSL6), lysophosphatidylcholine acyltransferase 1, phospholipase A2 group 1B, lecithin-cholesterol acyltransferase (LCAT), and sphingomyelin phosphodiesterase 4 (SMPD4) was identified among HCC patients. Lysophosphatidylcholiner HCC. Retinoids are widely used in different cosmetic products because of general improvement of skin appearance. However, retinoid concentration in cosmetics is restricted, and one particular form-retinoic acid, is banned in cosmetics due to safety reasons. Within this study, we aimed to examine the quality of a considerable number of commercial retinoid cosmetic products in terms of their content and labeling, including also screening for the presence of retinoic acid. An appropriate analytical methodology, based on HPLC-UV for the simultaneous determination of common retinoids, along with a screening method for retinoic acid, was developed and validated. Structural identity confirmation of the newer retinoid-hydroxypinacolone retinoate, was performed by LC-MS. Retinol and retinyl palmitate were most often found, in concentrations mostly below 0.3%, and up to 1.3% retinol equivalents. Determined contents deviated significantly from the quantitatively declared ones in seven products (0%-130%). In more thanore strict regulation and quality control to ensure their efficacy and safety. Fragment reattachment is a procedure that can immediately restore form and function in crown-root fracture cases and is considered a minimally invasive and cost-effective treatment option. The aim of this systematic review was to analyze the methods used and the outcome of fragment reattachment for complicated crown-root fractures of anterior teeth. Five electronic databases (PubMed, Web of Science, Embase, Scopus, and Google Scholar) were searched for English language articles regarding fragment reattachment after complicated crown-root fractures of anterior teeth. Twelve case reports and two case series were selected for this review after applying the inclusion and exclusion criteria. In eleven articles, the fracture line was exposed prior to reattachment. Root canal treatment was performed in all cases except one, where conservative pulp treatment was done prior to reattachment. A post was used as part of the restoration in 85% of the cases. Additional fragment preparation was done in 42% of the cases in the form of beveling and groove formation. Adhesive strategies used to reattach the coronal fragments were total-etch, self-etch, or self-cure adhesive. Intermediate materials used for reattachment were resin cement, glass-ionomer cement, composite and self-adhesive cement. Treatment outcomes were favorable in all the included articles and the follow-up period ranged from three months to seven years. Fragment reattachment after complicated crown-root fractures of anterior teeth can be considered as a viable treatment option if the clinical conditions are favorable. Fragment reattachment after complicated crown-root fractures of anterior teeth can be considered as a viable treatment option if the clinical conditions are favorable. The major aims of this study are to determine the capability of sulphur oxidizing bacterium (SOB-1) to desulphurize dibenzothiophene (DBT) and crude oil, detection of the reaction kinetics and identify the proposed pathway of DBT desulphurization. The isolate was genetically identified based on 16S rRNA gene sequencing as Klebsiella oxytoca and deposited in the Genebank database under the accession number MT355440. The HPLC analysis of the remaining DBT concentration revealed that, SOB-1 could desulphurize 90% of DBT (0·25mmoll ) within 96h. https://www.selleckchem.com/products/AS703026.html The maximum production of sulphate ions from the desulphurization of DBT (0·36mmoll ) and crude oil (0·4mmoll ) could be quantitatively detected after 48h of incubation at 30°C. The high values of correlation coefficient (R ) obtained at all studied concentrations; suggested that biodesulfurization kinetics of DBT follows the first-order reaction model. The kinetics studies showed that, DBT may have an inhibitory effect on SOB-1 when the initial concentration exceeded 0·75mmoll . The GC-MS analysis exhibited four main metabolites rather than DBT. The most important ones are 2-hydroxybiphenyl (2-HBP) and methoxybiphenyl n(2-MBP). Klebsiella oxytoca SOB-1 catalyzes the desulphurization of DBT through 4S pathway and forms four main metabolic products. The release of sulphate ion and formation of 2-HBP indicating the elimination of sulphur group without altering the carbon skeleton of DBT. The bacterial strain could also catalyzes desulphurization of crude oil. The desulphurization kinetics follows the first-order reaction model. Klebsiella oxytoca SOB-1 could be used as a promising industrial and environmental biodesulfurizing agent as it is not affecting carbon skeleton of thiophenic compounds and forming less toxic metabolic product (2-MBP). Klebsiella oxytoca SOB-1 could be used as a promising industrial and environmental biodesulfurizing agent as it is not affecting carbon skeleton of thiophenic compounds and forming less toxic metabolic product (2-MBP). To verify which one improves better stress urinary incontinence (SUI) symptoms abdominal hypopressive technique (AHT) or pelvic floor muscle training (PFMT). Randomized controlled trial. Women with SUI who had not participated of physiotherapy program before were invited. The outcome measures were 7-day bladder diary, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and pelvic floor muscles (PFM) function measured by Modified Oxford grading System with vaginal palpation and manometry with Peritron. Intervention consisted by 12 weeks of exercises program including PFMT or AHT program, in groups of maximum three women, twice a week, with physiotherapist supervision. AHT and PFMT groups reduced urinary leakage episodes in 7 days, -0.64 and -1.91, respectively, but PFMT was superior, whit mean difference -1.27 (95% confidence interval [CI] -1.92 to -0,62) and effect size was 0.94 in favor to PFMT. Regarding to total score of ICIQ-SF, both groups improved, with mean difference between groups -4.
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  • These findings confirm that KIR-SOCS1-based drugs could be excellent antioxidant agents to contrast atherosclerosis.Enterococcus faecalis is one of the major causes of urinary tract infection, showing acquired resistance to various classes of antimicrobials. The objective of this study was to determine the prevalence of drug resistance and its genetic determinants for E. faecalis clinical isolates in north-central Bangladesh. Among a total of 210 E. faecalis isolates, isolated from urine, the resistance rates to erythromycin, levofloxacin, and gentamicin (high level) were 85.2, 45.7, and 11.4%, respectively, while no isolates were resistant to ampicillin, vancomycin and teicoplanin. The most prevalent resistance gene was erm(B) (97%), and any of the four genes encoding aminoglycoside modifying enzyme (AME) were detected in 99 isolates (47%). The AME gene aac(6')-Ie-aph(2")-Ia was detected in 46 isolates (21.9%) and was diverse in terms of IS256-flanking patterns, which were associated with resistance level to gentamicin. Tetracycline resistance was ascribable to tet(M) (61%) and tet(L) (38%), and mutations in the quinolone resistance-determining region of both GyrA and ParC were identified in 44% of isolates. Five isolates (2.4%) exhibited non-susceptibility to linezolide (MIC, 4 μg/mL), and harbored the oxazolidinone resistance gene optrA, which was located in a novel genetic cluster containing the phenicol exporter gene fexA. The optrA-positive isolates belonged to ST59, ST902, and ST917 (CC59), while common lineages of other multiple drug-resistant isolates were ST6, ST28, CC16, and CC116. The present study first revealed the prevalence of drug resistance determinants of E. faecalis and their genetic profiles in Bangladesh.Free air ball (FAB) and bonded strength were performed on an Ag-10Au-3.6Pd alloy bonding wire (diameter of 0.025 mm) for different electronic flame-off (EFO) currents, times and bonding parameters. The effects of the EFO and bonding parameters on the characteristics of the FAB as well as the bonded strength were investigated using scanning electron microscopy. The results showed that, for a constant EFO time, the FAB of the Ag-10Au-3.6Pd alloy bonding wire transitioned from a pointed defined ball to an oval one, then to a perfectly shaped one, and finally to a golf ball with an increase in the EFO current. On the other hand, when the EFO current was constant and the EFO time was increased, the FAB changed from a small ball to a perfect one, then to a large one, and finally to a golf ball. The FAB exhibited the optimal geometry at an EFO current of 0.030 A and EFO time of 0.8 ms. Further, in the case of the Ag-10Au-3.6Pd alloy bonding wire, for an EFO current of 0.030 A, the FAB diameter exhibited a nonlinear relationship with the EFO time, which could be expressed by a quadratic function. Finally, the bonded strength decreased when the bonding power and force were excessively high, causing the ball bond to overflow. This led to the formation of neck cracks and decrease in the bonded strength. On the other hand, the bonded strength was insufficiently when the bonding power and force were small. The bonded strength was of the desired level when the bonding power and force were 70 mW and 0.60 N (for the ball bonded) and 95 mW and 0.85 N (for the wedge bonded), respectively.Renal disorders are associated with Hepatitis E virus (HEV) infection. Progression to end-stage renal disease and acute kidney injury are complications associated with HEV infection. The mechanisms by which HEV mediates the glomerular diseases remain unclear. CD10+/CD13+ primary proximal tubular (PT) epithelial cells, isolated from healthy donors, were infected with HEV. Inflammatory markers and kidney injury markers were assessed in the presence or absence of peripheral blood mononuclear cells (PBMCs) isolated from the same donors. HEV replicated efficiently in the PT cells as shown by the increase in HEV load over time and the expression of capsid Ag. In the absence of PBMCs, HEV was not nephrotoxic, with no direct effect on the transcription of chemokines (Cxcl-9, Cxcl-10, and Cxcl-11) nor the kidney injury markers (kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin 18 (lL-18)). While higher inflammatory responses, upregulation of chemokines and kidney injury markers expression, and signs of nephrotoxicity were recorded in HEV-infected PT cells cocultured with PBMCs. Interestingly, a significantly higher level of IFN-γ was released in the PBMCs-PT coculture compared to PT alone during HEV infection. In conclusion The crosstalk between immune cells and renal epithelium and the signal axes IFN-γ/chemokines and IL-18 could be the immune-mediated mechanisms of HEV-induced renal disorder.Axillary osmidrosis (AO) is a common chronic skin condition characterized by unpleasant body odors emanating from the armpits, and its aetiology is not fully understood. AO can seriously impair the psychosocial well-being of the affected individuals; however, no causal therapy has been established for it other than surgical treatment. Recent studies have revealed that human ATP-binding cassette transporter C11 (ABCC11) is an AO risk factor when it is expressed in the axillary apocrine glands-the sources of the offensive odors. Hence, identifying safe ways to inhibit ABCC11 may offer a breakthrough in treating AO. We herein screened for ABCC11-inhibitory activities in 34 natural products derived from plants cultivated for human consumption using an in vitro assay system to measure the ABCC11-mediated transport of radiolabeled dehydroepiandrosterone sulfate (DHEA-S-an ABCC11 substrate). The water extract of soybean (Glycine max) was found to exhibit the strongest transport inhibition. From this extract, via a fractionation approach, we successfully isolated and identified genistein, a soy isoflavone, as a novel ABCC11 inhibitor with a half-maximal inhibitory concentration value of 61.5 μM. https://www.selleckchem.com/products/omaveloxolone-rta-408.html Furthermore, we examined the effects of other dietary flavonoids on the ABCC11-mediated DHEA-S transport to uncover the effects of these phytochemicals on ABCC11 function. While further human studies are needed, our findings here about the natural compounds will help develop a non-surgical therapy for AO.
    These findings confirm that KIR-SOCS1-based drugs could be excellent antioxidant agents to contrast atherosclerosis.Enterococcus faecalis is one of the major causes of urinary tract infection, showing acquired resistance to various classes of antimicrobials. The objective of this study was to determine the prevalence of drug resistance and its genetic determinants for E. faecalis clinical isolates in north-central Bangladesh. Among a total of 210 E. faecalis isolates, isolated from urine, the resistance rates to erythromycin, levofloxacin, and gentamicin (high level) were 85.2, 45.7, and 11.4%, respectively, while no isolates were resistant to ampicillin, vancomycin and teicoplanin. The most prevalent resistance gene was erm(B) (97%), and any of the four genes encoding aminoglycoside modifying enzyme (AME) were detected in 99 isolates (47%). The AME gene aac(6')-Ie-aph(2")-Ia was detected in 46 isolates (21.9%) and was diverse in terms of IS256-flanking patterns, which were associated with resistance level to gentamicin. Tetracycline resistance was ascribable to tet(M) (61%) and tet(L) (38%), and mutations in the quinolone resistance-determining region of both GyrA and ParC were identified in 44% of isolates. Five isolates (2.4%) exhibited non-susceptibility to linezolide (MIC, 4 μg/mL), and harbored the oxazolidinone resistance gene optrA, which was located in a novel genetic cluster containing the phenicol exporter gene fexA. The optrA-positive isolates belonged to ST59, ST902, and ST917 (CC59), while common lineages of other multiple drug-resistant isolates were ST6, ST28, CC16, and CC116. The present study first revealed the prevalence of drug resistance determinants of E. faecalis and their genetic profiles in Bangladesh.Free air ball (FAB) and bonded strength were performed on an Ag-10Au-3.6Pd alloy bonding wire (diameter of 0.025 mm) for different electronic flame-off (EFO) currents, times and bonding parameters. The effects of the EFO and bonding parameters on the characteristics of the FAB as well as the bonded strength were investigated using scanning electron microscopy. The results showed that, for a constant EFO time, the FAB of the Ag-10Au-3.6Pd alloy bonding wire transitioned from a pointed defined ball to an oval one, then to a perfectly shaped one, and finally to a golf ball with an increase in the EFO current. On the other hand, when the EFO current was constant and the EFO time was increased, the FAB changed from a small ball to a perfect one, then to a large one, and finally to a golf ball. The FAB exhibited the optimal geometry at an EFO current of 0.030 A and EFO time of 0.8 ms. Further, in the case of the Ag-10Au-3.6Pd alloy bonding wire, for an EFO current of 0.030 A, the FAB diameter exhibited a nonlinear relationship with the EFO time, which could be expressed by a quadratic function. Finally, the bonded strength decreased when the bonding power and force were excessively high, causing the ball bond to overflow. This led to the formation of neck cracks and decrease in the bonded strength. On the other hand, the bonded strength was insufficiently when the bonding power and force were small. The bonded strength was of the desired level when the bonding power and force were 70 mW and 0.60 N (for the ball bonded) and 95 mW and 0.85 N (for the wedge bonded), respectively.Renal disorders are associated with Hepatitis E virus (HEV) infection. Progression to end-stage renal disease and acute kidney injury are complications associated with HEV infection. The mechanisms by which HEV mediates the glomerular diseases remain unclear. CD10+/CD13+ primary proximal tubular (PT) epithelial cells, isolated from healthy donors, were infected with HEV. Inflammatory markers and kidney injury markers were assessed in the presence or absence of peripheral blood mononuclear cells (PBMCs) isolated from the same donors. HEV replicated efficiently in the PT cells as shown by the increase in HEV load over time and the expression of capsid Ag. In the absence of PBMCs, HEV was not nephrotoxic, with no direct effect on the transcription of chemokines (Cxcl-9, Cxcl-10, and Cxcl-11) nor the kidney injury markers (kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin 18 (lL-18)). While higher inflammatory responses, upregulation of chemokines and kidney injury markers expression, and signs of nephrotoxicity were recorded in HEV-infected PT cells cocultured with PBMCs. Interestingly, a significantly higher level of IFN-γ was released in the PBMCs-PT coculture compared to PT alone during HEV infection. In conclusion The crosstalk between immune cells and renal epithelium and the signal axes IFN-γ/chemokines and IL-18 could be the immune-mediated mechanisms of HEV-induced renal disorder.Axillary osmidrosis (AO) is a common chronic skin condition characterized by unpleasant body odors emanating from the armpits, and its aetiology is not fully understood. AO can seriously impair the psychosocial well-being of the affected individuals; however, no causal therapy has been established for it other than surgical treatment. Recent studies have revealed that human ATP-binding cassette transporter C11 (ABCC11) is an AO risk factor when it is expressed in the axillary apocrine glands-the sources of the offensive odors. Hence, identifying safe ways to inhibit ABCC11 may offer a breakthrough in treating AO. We herein screened for ABCC11-inhibitory activities in 34 natural products derived from plants cultivated for human consumption using an in vitro assay system to measure the ABCC11-mediated transport of radiolabeled dehydroepiandrosterone sulfate (DHEA-S-an ABCC11 substrate). The water extract of soybean (Glycine max) was found to exhibit the strongest transport inhibition. From this extract, via a fractionation approach, we successfully isolated and identified genistein, a soy isoflavone, as a novel ABCC11 inhibitor with a half-maximal inhibitory concentration value of 61.5 μM. https://www.selleckchem.com/products/omaveloxolone-rta-408.html Furthermore, we examined the effects of other dietary flavonoids on the ABCC11-mediated DHEA-S transport to uncover the effects of these phytochemicals on ABCC11 function. While further human studies are needed, our findings here about the natural compounds will help develop a non-surgical therapy for AO.
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  • © 2020 Wiley Periodicals, Inc.Air-stable 2D materials are relatively inert, which makes their chemical modification difficult. In the case of MoS2, the semiconducting 2H-MoS2 is **** less reactive than its metallic counterpart, 1T-MoS2. As a consequence, there are very few methods for the covalent modification of 2H-MoS2. An ideal method for the functionalization of 2H-MoS2 should be mild, without introduction of a large number of defects, and versatile, allowing for the decoration with as many different functional groups as possible. Herein, a comprehensive study on the covalent functionalization of 2H-MoS2 with maleimides is presented. The use of a base leads to the in situ formation of a succinimide polymer layer covalently connected to MoS2. In the absence of base, functionalization stops at the molecular monolayer. The protocol is mild (room temperature), fast (nearly complete in 1h), and very flexible (10 different maleimides tested). In practical terms, the procedures described here allow for the decoration of 2H-MoS2 with polymers or molecules, and with a wide range of functional groups for subsequent modification. Conceptually, the spurious formation of an organic polymer might be general to other methods of functionalization of 2D materials, where a large excess of molecular reagents is typically used. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Double perovskite structure (A 2 BB'O 6 ) oxides exhibit a breadth of multifunctional properties with a huge potential range of applications in fields as diverse as spintronics, magneto-optic devices or catalysis, and most of these applications require the use of thin films and heterostructures. Chemical solution deposition techniques are appearing as a very promising methodology to achieve epitaxial oxide thin films combining high performance with high throughput and low cost. In addition, physical properties of these materials are strongly dependent on the ordered arrangement of cations in the double perovskite structure. Thus, promoting spontaneous cationic ordering has become a very relevant issue. In this work, our recent achievements using polymer assisted deposition (PAD) of environmentally friendly, water-based solutions for the growth of epitaxial ferromagnetic insulating double perovskite La 2 CoMnO 6 and La 2 NiMnO 6 thin films on SrTiO 3 and LaAlO 3 single-crystal substrates are presented. We show that the particular crystallization and growth process conditions of PAD (very slow rate, close to thermodynamic equilibrium conditions) promote high crystallinity and quality of the films, as well as favors spontaneous B-site cationic ordering. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The potential for coordination and H-transfer from Cp2MH2 (M=Zr, W) to gold(I) and gold(III) complexes was explored in a combined experimental and computational study. [(L)Au]+ cations react with Cp2WH2 giving [(L)Au(κ2-H2WCp2)]+ (L = IPr (1), cyclic (alkyl)-(amino)-carbene (2), or phosphines PPh3 (3) and Dalphos-Me (4; IPr=1,3-bis(di iso propylphenyl)imidazolylidene; Dalphos-Me = di(1-adamantyl)-2-(dimethylamino)phenyl-phosphine), while [Au(DMAP)2]+ (DMAP= p -dimethyl-amino-pyridine) affords the  C2-symmetric [Au(κ-H2WCp2)2]+ (5). The Dalphos complex 4 can be protonated to give the bicationic adduct 4H, showing Au(I)…H+ -N hydrogen bonding. The gold(III) Lewis acid [(C^N-CH)Au(C6F5)(OEt2)]+ binds Cp2WH2 to give a Au-H-W σ-complex. By contrast, the pincer species [(C^N^C)Au]+ adds Cp2WH2 by a purely dative W→Au bond, without Au···H interaction. The biphenyl-based chelate [(C^C)Au]+ forms [(C^C)Au(μ-H)2WCp2 ]+ , with two 2-electron-3-centre W-H…Au interactions and practically no Au-W donor acceptor contribution. In all these complexes strong but polarised W-H bonds are maintained, without H-transfer to gold. On the other hand, the reactions of Cp2ZrH2 with gold complexes led in all cases to rapid H-transfer and formation of gold hydrides. Relativistic DFT calculations were used to rationalize the striking reactivity and bonding differences in these heterobimetallic hydride complexes along with an analysis of their characteristic NMR parameters and UV-vis absorption properties. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment-resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis by the mushroom kinase PsiK. This enzyme was biochemically characterized and used to produce one gram of psilocybin from psilocin within 20 minutes. We also describe a pilot-scale protocol for recombinant PsiK that yielded 150 mg enzyme in active and soluble form. Our work consolidates the simplicity of tryptamine chemistry with the specificity and selectivity of enzymatic catalysis and helps provide access to an important drug at potentially reasonable cost. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Mesenchymal stem cells (****) are used in various clinical and preclinical models for immunomodulation. However, it remains unclear how the immunomodulatory effect of ****is communicated. ****induced immunomodulation is known to be mediated through both ****secreted cytokines and direct cell-cell interactions. Recently, it has been demonstrated that metabolically inactive, heat-inactivated **** (HI-****) have similar anti-inflammatory capacities in LPS-induced sepsis compared with viable MSC. To further investigate the immunomodulatory effects of MSC, we introduced ****and HI-****in two animal models with different immunological causes. In the first model, allogeneic hearts were transplanted from C57BL/6 **** to BALB/c recipients. https://www.selleckchem.com/products/abr-238901.html ****in combination with mycophenolate mofetil (MMF) significantly improved graft survival compared with MMF alone, whereas the application of HI-****had no effect on graft survival. We revealed that control ****dose-dependently inhibited CD3+ and CD8+ T-cell proliferation in vitro, whereas HI-****had no effect.
    © 2020 Wiley Periodicals, Inc.Air-stable 2D materials are relatively inert, which makes their chemical modification difficult. In the case of MoS2, the semiconducting 2H-MoS2 is much less reactive than its metallic counterpart, 1T-MoS2. As a consequence, there are very few methods for the covalent modification of 2H-MoS2. An ideal method for the functionalization of 2H-MoS2 should be mild, without introduction of a large number of defects, and versatile, allowing for the decoration with as many different functional groups as possible. Herein, a comprehensive study on the covalent functionalization of 2H-MoS2 with maleimides is presented. The use of a base leads to the in situ formation of a succinimide polymer layer covalently connected to MoS2. In the absence of base, functionalization stops at the molecular monolayer. The protocol is mild (room temperature), fast (nearly complete in 1h), and very flexible (10 different maleimides tested). In practical terms, the procedures described here allow for the decoration of 2H-MoS2 with polymers or molecules, and with a wide range of functional groups for subsequent modification. Conceptually, the spurious formation of an organic polymer might be general to other methods of functionalization of 2D materials, where a large excess of molecular reagents is typically used. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Double perovskite structure (A 2 BB'O 6 ) oxides exhibit a breadth of multifunctional properties with a huge potential range of applications in fields as diverse as spintronics, magneto-optic devices or catalysis, and most of these applications require the use of thin films and heterostructures. Chemical solution deposition techniques are appearing as a very promising methodology to achieve epitaxial oxide thin films combining high performance with high throughput and low cost. In addition, physical properties of these materials are strongly dependent on the ordered arrangement of cations in the double perovskite structure. Thus, promoting spontaneous cationic ordering has become a very relevant issue. In this work, our recent achievements using polymer assisted deposition (PAD) of environmentally friendly, water-based solutions for the growth of epitaxial ferromagnetic insulating double perovskite La 2 CoMnO 6 and La 2 NiMnO 6 thin films on SrTiO 3 and LaAlO 3 single-crystal substrates are presented. We show that the particular crystallization and growth process conditions of PAD (very slow rate, close to thermodynamic equilibrium conditions) promote high crystallinity and quality of the films, as well as favors spontaneous B-site cationic ordering. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The potential for coordination and H-transfer from Cp2MH2 (M=Zr, W) to gold(I) and gold(III) complexes was explored in a combined experimental and computational study. [(L)Au]+ cations react with Cp2WH2 giving [(L)Au(κ2-H2WCp2)]+ (L = IPr (1), cyclic (alkyl)-(amino)-carbene (2), or phosphines PPh3 (3) and Dalphos-Me (4; IPr=1,3-bis(di iso propylphenyl)imidazolylidene; Dalphos-Me = di(1-adamantyl)-2-(dimethylamino)phenyl-phosphine), while [Au(DMAP)2]+ (DMAP= p -dimethyl-amino-pyridine) affords the  C2-symmetric [Au(κ-H2WCp2)2]+ (5). The Dalphos complex 4 can be protonated to give the bicationic adduct 4H, showing Au(I)…H+ -N hydrogen bonding. The gold(III) Lewis acid [(C^N-CH)Au(C6F5)(OEt2)]+ binds Cp2WH2 to give a Au-H-W σ-complex. By contrast, the pincer species [(C^N^C)Au]+ adds Cp2WH2 by a purely dative W→Au bond, without Au···H interaction. The biphenyl-based chelate [(C^C)Au]+ forms [(C^C)Au(μ-H)2WCp2 ]+ , with two 2-electron-3-centre W-H…Au interactions and practically no Au-W donor acceptor contribution. In all these complexes strong but polarised W-H bonds are maintained, without H-transfer to gold. On the other hand, the reactions of Cp2ZrH2 with gold complexes led in all cases to rapid H-transfer and formation of gold hydrides. Relativistic DFT calculations were used to rationalize the striking reactivity and bonding differences in these heterobimetallic hydride complexes along with an analysis of their characteristic NMR parameters and UV-vis absorption properties. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment-resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis by the mushroom kinase PsiK. This enzyme was biochemically characterized and used to produce one gram of psilocybin from psilocin within 20 minutes. We also describe a pilot-scale protocol for recombinant PsiK that yielded 150 mg enzyme in active and soluble form. Our work consolidates the simplicity of tryptamine chemistry with the specificity and selectivity of enzymatic catalysis and helps provide access to an important drug at potentially reasonable cost. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Mesenchymal stem cells (MSCs) are used in various clinical and preclinical models for immunomodulation. However, it remains unclear how the immunomodulatory effect of MSC is communicated. MSC-induced immunomodulation is known to be mediated through both MSC-secreted cytokines and direct cell-cell interactions. Recently, it has been demonstrated that metabolically inactive, heat-inactivated MSCs (HI-MSCs) have similar anti-inflammatory capacities in LPS-induced sepsis compared with viable MSC. To further investigate the immunomodulatory effects of MSC, we introduced MSC and HI-MSC in two animal models with different immunological causes. In the first model, allogeneic hearts were transplanted from C57BL/6 mice to BALB/c recipients. https://www.selleckchem.com/products/abr-238901.html MSC in combination with mycophenolate mofetil (MMF) significantly improved graft survival compared with MMF alone, whereas the application of HI-MSC had no effect on graft survival. We revealed that control MSC dose-dependently inhibited CD3+ and CD8+ T-cell proliferation in vitro, whereas HI-MSC had no effect.
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  • Thus, CD57- NKG2C+ NK cells may represent a less differentiated, but readily expanding stage of the adaptive-like CD57+ NKG2C+ NK cells. Moreover, it is shown that NK cells have certain phenotypic plasticity and may both lose NKG2C expression and acquire it de novo during proliferation, induced by IL-2 and K562-mbIL21 feeder cells.
    Mediator is a conserved transcriptional co-activator that links transcription factors bound at enhancer elements to RNA Polymerase II. Mediator-RNA Polymerase II interactions can be sterically hindered by the Cyclin Dependent Kinase 8 (CDK8) module, a submodule of Mediator that acts to repress transcription in response to discrete cellular and environmental cues. The CDK8 module is conserved in all eukaryotes and consists of 4 proteins CDK8, CYCLIN C (CYCC), MED12, and MED13.

    In this study, we have characterized the CDK8 module of Mediator in maize using genomic, molecular and functional resources.

    The maize genome contains single copy genes for Cdk8, CycC, and Med13, and two genes for Med12. Analysis of expression data for the CDK8 module demonstrated that all five genes are broadly expressed in maize tissues, and change their expression in response to phosphate and nitrogen limitation. We performed Dissociation (Ds) insertional mutagenesis, recovering two independent insertions in the ZmMed12a gene, one of which produces a truncated transcript.

    Our molecular identification of the maize CDK8 module, assays of CDK8 module expression under nutrient limitation, and characterization of transposon insertions in ZmMed12a establish the basis for molecular and functional studies of the role of these important transcriptional regulators in development and nutrient homeostasis in Zea mays.
    Our molecular identification of the maize CDK8 module, assays of CDK8 module expression under nutrient limitation, and characterization of transposon insertions in ZmMed12a establish the basis for molecular and functional studies of the role of these important transcriptional regulators in development and nutrient homeostasis in Zea mays.The olfactory epithelia arise from morphologically identifiable structures called olfactory placodes. Sensory placodes are generally described as being induced from the ectoderm suggesting that their development is separate from the coordinated cell movements generating the central nervous system. Previously, we have shown that the olfactory placodes arise from a large field of cells bordering the telencephalic precursors in the neural plate, and that cell movements, not cell division, underlie olfactory placode morphogenesis. https://www.selleckchem.com/products/azd9291.html Subsequently by image analysis, cells were tracked as they moved in the continuous sheet of neurectoderm giving rise to the peripheral (olfactory organs) and central (olfactory bulbs) nervous system (Torres-Paz and Whitlock, 2014). These studies lead to a model whereby the olfactory epithelia develop from within the border of the neural late and are a neural tube derivative, similar to the retina of the eye (Torres-Paz and Whitlock, 2014; Whitlock, 2008). Here we show that randomly generated clones of cells extend across the morphologically differentiated olfactory placodes/olfactory bulbs, and test the hypothesis that these structures are patterned by a different level of distal-less (dlx) gene expression subdividing the anterior neurectoderm into OP precursors (high Dlx expression) and OB precursors (lower Dlx expression). Manipulation of DLX protein and RNA levels resulted in morphological changes in the size of the olfactory epithelia and olfactory bulb. Thus, the olfactory epithelia and bulbs arise from a common neurectodermal region and develop in concert through coordinated morphological movements.Rax (Rx) genes encode paired-type homeodomain-containing transcription factors pre-sent in virtually all metazoan groups. In vertebrates, studies in fish, amphibian, chick and mouse models have revealed that these genes play important roles in the development of structures **-cated at the anterior portion of the central nervous system, in particular the eyes, the hypothala-mus and the pituitary gland. In addition, human patients with eye and brain defects carry muta-tions in the two human Rax paralogues, RAX and RAX2. Here, we review work done in the last years on Rax genes, focusing especially on the function that mouse Rax and its zebrafish homo-logue, rx3, play in hypothalamic and pituitary development. Work on both of these model organ-isms indicate that Rax genes are necessary for the patterning, growth and differentiation of the hypothalamus, in particular the dorso-anterior hypothalamus, where they effect their action by controlling expression of the secreted signalling protein, Sonic hedgehog (Shh). In addition, Rax/rx3 mutations disturb the development of the pituitary gland, mimicking phenotypes ob-served in human subjects carrying mutations in the RAX gene. Thus, along with their crucial role in eye morphogenesis, Rax genes play a conserved role in the development of the hypothalamus and adjacent structures in the vertebrate clade.
    The mechanisms controlling evolutionary shifts between dry and fleshy fruits in angiosperms are poorly understood. In Solanaceae, Cestrum and Brugmansia represent cases of convergent evolution of fleshy and dry fruits, respectively. Here we study the anatomical and genetic bases of the independent origin of fleshy fruits in Cestrum and the reversion to dry dehiscent fruits in Brugmansia. We also characterize the expression of candidate fruit development genes, including ALCATRAZ/SPATULA, FRUITFULL, HECATE1/2/3, REPLUMLESS and SHATTERPROOF.

    We identify anatomical changes to establish developmental stages in the ovary-to-fruit transition in Cestrum nocturnum and Brugmansia suaveolens. We generate reference transcriptomes for both species, isolate homologs for all genes in the fruit genetic regulatory network (GRN) and perform gene expression analyses for ALC/SPT, FUL, HEC1/2/3, RPL and SHP throughout fruit development. Finally, we compare our results to expression patterns found in typical capsules of Nicotion of FUL2 and RPL1 is lacking.
    Thus, CD57- NKG2C+ NK cells may represent a less differentiated, but readily expanding stage of the adaptive-like CD57+ NKG2C+ NK cells. Moreover, it is shown that NK cells have certain phenotypic plasticity and may both lose NKG2C expression and acquire it de novo during proliferation, induced by IL-2 and K562-mbIL21 feeder cells. Mediator is a conserved transcriptional co-activator that links transcription factors bound at enhancer elements to RNA Polymerase II. Mediator-RNA Polymerase II interactions can be sterically hindered by the Cyclin Dependent Kinase 8 (CDK8) module, a submodule of Mediator that acts to repress transcription in response to discrete cellular and environmental cues. The CDK8 module is conserved in all eukaryotes and consists of 4 proteins CDK8, CYCLIN C (CYCC), MED12, and MED13. In this study, we have characterized the CDK8 module of Mediator in maize using genomic, molecular and functional resources. The maize genome contains single copy genes for Cdk8, CycC, and Med13, and two genes for Med12. Analysis of expression data for the CDK8 module demonstrated that all five genes are broadly expressed in maize tissues, and change their expression in response to phosphate and nitrogen limitation. We performed Dissociation (Ds) insertional mutagenesis, recovering two independent insertions in the ZmMed12a gene, one of which produces a truncated transcript. Our molecular identification of the maize CDK8 module, assays of CDK8 module expression under nutrient limitation, and characterization of transposon insertions in ZmMed12a establish the basis for molecular and functional studies of the role of these important transcriptional regulators in development and nutrient homeostasis in Zea mays. Our molecular identification of the maize CDK8 module, assays of CDK8 module expression under nutrient limitation, and characterization of transposon insertions in ZmMed12a establish the basis for molecular and functional studies of the role of these important transcriptional regulators in development and nutrient homeostasis in Zea mays.The olfactory epithelia arise from morphologically identifiable structures called olfactory placodes. Sensory placodes are generally described as being induced from the ectoderm suggesting that their development is separate from the coordinated cell movements generating the central nervous system. Previously, we have shown that the olfactory placodes arise from a large field of cells bordering the telencephalic precursors in the neural plate, and that cell movements, not cell division, underlie olfactory placode morphogenesis. https://www.selleckchem.com/products/azd9291.html Subsequently by image analysis, cells were tracked as they moved in the continuous sheet of neurectoderm giving rise to the peripheral (olfactory organs) and central (olfactory bulbs) nervous system (Torres-Paz and Whitlock, 2014). These studies lead to a model whereby the olfactory epithelia develop from within the border of the neural late and are a neural tube derivative, similar to the retina of the eye (Torres-Paz and Whitlock, 2014; Whitlock, 2008). Here we show that randomly generated clones of cells extend across the morphologically differentiated olfactory placodes/olfactory bulbs, and test the hypothesis that these structures are patterned by a different level of distal-less (dlx) gene expression subdividing the anterior neurectoderm into OP precursors (high Dlx expression) and OB precursors (lower Dlx expression). Manipulation of DLX protein and RNA levels resulted in morphological changes in the size of the olfactory epithelia and olfactory bulb. Thus, the olfactory epithelia and bulbs arise from a common neurectodermal region and develop in concert through coordinated morphological movements.Rax (Rx) genes encode paired-type homeodomain-containing transcription factors pre-sent in virtually all metazoan groups. In vertebrates, studies in fish, amphibian, chick and mouse models have revealed that these genes play important roles in the development of structures lo-cated at the anterior portion of the central nervous system, in particular the eyes, the hypothala-mus and the pituitary gland. In addition, human patients with eye and brain defects carry muta-tions in the two human Rax paralogues, RAX and RAX2. Here, we review work done in the last years on Rax genes, focusing especially on the function that mouse Rax and its zebrafish homo-logue, rx3, play in hypothalamic and pituitary development. Work on both of these model organ-isms indicate that Rax genes are necessary for the patterning, growth and differentiation of the hypothalamus, in particular the dorso-anterior hypothalamus, where they effect their action by controlling expression of the secreted signalling protein, Sonic hedgehog (Shh). In addition, Rax/rx3 mutations disturb the development of the pituitary gland, mimicking phenotypes ob-served in human subjects carrying mutations in the RAX gene. Thus, along with their crucial role in eye morphogenesis, Rax genes play a conserved role in the development of the hypothalamus and adjacent structures in the vertebrate clade. The mechanisms controlling evolutionary shifts between dry and fleshy fruits in angiosperms are poorly understood. In Solanaceae, Cestrum and Brugmansia represent cases of convergent evolution of fleshy and dry fruits, respectively. Here we study the anatomical and genetic bases of the independent origin of fleshy fruits in Cestrum and the reversion to dry dehiscent fruits in Brugmansia. We also characterize the expression of candidate fruit development genes, including ALCATRAZ/SPATULA, FRUITFULL, HECATE1/2/3, REPLUMLESS and SHATTERPROOF. We identify anatomical changes to establish developmental stages in the ovary-to-fruit transition in Cestrum nocturnum and Brugmansia suaveolens. We generate reference transcriptomes for both species, isolate homologs for all genes in the fruit genetic regulatory network (GRN) and perform gene expression analyses for ALC/SPT, FUL, HEC1/2/3, RPL and SHP throughout fruit development. Finally, we compare our results to expression patterns found in typical capsules of Nicotion of FUL2 and RPL1 is lacking.
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  • esponses. ClinicalTrials.gov no NCT03270085. Tracking variation in hosts' responses to parasitism across space in a metapopulation is critical to assess the current status of parasitism/anti-parasitism in a host-parasite system, which is also helpful to infer its coevolutionary history. The barn swallow Hirundo rustica is a tractable bird species to understand potential fine-tuned adaptations to avian brood parasitism across small geographic scales, both in the context of variation in its foreign-egg rejection pattern, and its widespread distribution in cuckoo-free urban areas and in cuckoo-present rural habitats, including reedbeds. Here we tested whether variation in co-occurrence between the host and its rare brood parasite, the common cuckoo Cuculus canorus (i.e., high level of co-occurrence in reed habitats, low in town habitats) at the metapopulation level predicts patterns of antiparasitic egg rejection behaviors in barn swallows in response to different types of model and natural eggs. Contrary to our predictions, higher parasite detectability in the reed habitat did not translate into higher parasitism rate and, in turn, we also found similarly low egg rejection rates across both sampled habitat types. These patterns implied a lack of fine-tuned increase of egg rejection rate in the reed-breeding population of barn swallows as a response to the increased perceived cuckoo encounter rate, perhaps because higher potential parasitism threat did not transfer into greater actual parasitism rate. It remains to be assessed whether the lack of small-scale geographic variation in barn swallows' egg rejection rates persists because this species responds to selection by parasitism as a spatially contiguous evolutionary unit. The UBE3A gene is part of the chromosome 15q11-q13 region that is frequently deleted or duplicated, leading to several neurodevelopmental disorders (NDD). Angelman syndrome (AS) is caused by the absence of functional maternally derived UBE3A protein, while the paternal UBE3A gene is present but silenced specifically in neurons. Patients with AS present with severe neurodevelopmental delay, with pronounced motor deficits, absence of speech, intellectual disability, epilepsy, and sleep problems. The pathophysiology of AS is still unclear and a treatment is lacking. Animal models of AS recapitulate the genotypic and phenotypic features observed in AS patients, and have been invaluable for understanding the disease process as well as identifying apropriate drug targets. Using these AS mouse models we have learned that loss of UBE3A probably affects many areas of the brain, leading to increased neuronal excitability and a loss of synaptic spines, along with changes in a number of distinct behaviours. Inducible AS mouse models have helped to identify the critical treatment windows for the behavioral and physiological phenotypes. Additionally, AS mouse models indicate an important role for the predominantly nuclear UBE3A isoform in generating the characteristic AS pathology. Last, but not least, the AS **** have been crucial in guiding Ube3a gene reactivation treatments, which present a very promising therapy to treat AS. Two major processes tightly regulate protein synthesis, the initiation of mRNA translation and elongation phase that mediates the movement of ribosomes along the mRNA. The elongation phase is a high energy-consuming process, and is mainly regulated by the eukaryotic elongation factor 2 kinase (eEF2K) activity that phosphorylates and inhibits eEF2, the only known substrate of the kinase. eEF2K activity is closely regulated by several signaling pathways because the translation elongation phase strongly influences the cellular energy demand and can change the expression of specific proteins in different tissues. An increasing number of recent findings link eEF2k over activation to an array of human diseases, such as atherosclerosis, pulmonary arterial hypertension, progression of solid tumors, and some major neurological disorders. Several neurological studies suggest that eEF2K is a valuable target in treating epilepsy, depression and major neurodegenerative diseases. Despite eEF2k is an ubiquitous and conserved protein, it has been proved that its deletion does not affect development in animal models and in general cell viability. Therefore, it is possible to postulate that inhibiting its function may not cause serious side effects. In addition, eEF2K is a peculiar kinase molecularly different from most of other mammalian kinases and new compounds that inhibit eEF2K should not necessarily interfere with other important protein kinases. In this review we will critically summarize the evidence supporting the role of the altered eEF2K/eEF2 pathway in defined neurological diseases and its implications in curing these diseases in animal models, and possibly in humans, by targeting eEF2K activity. https://www.selleckchem.com/products/AS703026.html PURPOSE Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly collimated synchrotron beam into arrays of parallel microbeams depositing several hundred grays. It appears relevant to combine MRT with a conventional treatment course, preparing a treatment scheme for future patients in clinical trials. The efficiency of MRT delivered after several broad beam (BB) fractions to palliate of F98 brain tumors in rats in comparison with BB fractions alone was evaluated in this study. MATERIALS/METHODS Rats bearing 106 F98 cells implanted in the caudate nucleus were irradiated by 5 fractions in broad beam (BB) mode (3x6Gy + 2x8Gy BB) or by 2 boost fractions in MRT mode, of a total of 5 fractions (3x6Gy BB + MRT 2x8Gy valley dose; peak dose 181Gy (50/200μm)). Tumor growth was evaluated in vivo by MRI follow up at T-1, T7, T12 T15, T20, T25 days, after radiotherapy, and by histology and FACS studies. RESULTS MRT-boosted tumors displayed lower cell density and cell proliferation compared with BB-irradiated tumors. The MRT boost completely stopped tumor growth during ∼4 weeks and led to a significant increase in MST, while tumors treated with BB alone recurred within few days after the last radiation fraction. CONCLUSIONS The first evidence is presented that MRT, delivered as a boost of a conventional fractionated irradiation by orthovoltage broad X-ray beams, is feasible and more efficient than a conventional radiotherapy alone.
    esponses. ClinicalTrials.gov no NCT03270085. Tracking variation in hosts' responses to parasitism across space in a metapopulation is critical to assess the current status of parasitism/anti-parasitism in a host-parasite system, which is also helpful to infer its coevolutionary history. The barn swallow Hirundo rustica is a tractable bird species to understand potential fine-tuned adaptations to avian brood parasitism across small geographic scales, both in the context of variation in its foreign-egg rejection pattern, and its widespread distribution in cuckoo-free urban areas and in cuckoo-present rural habitats, including reedbeds. Here we tested whether variation in co-occurrence between the host and its rare brood parasite, the common cuckoo Cuculus canorus (i.e., high level of co-occurrence in reed habitats, low in town habitats) at the metapopulation level predicts patterns of antiparasitic egg rejection behaviors in barn swallows in response to different types of model and natural eggs. Contrary to our predictions, higher parasite detectability in the reed habitat did not translate into higher parasitism rate and, in turn, we also found similarly low egg rejection rates across both sampled habitat types. These patterns implied a lack of fine-tuned increase of egg rejection rate in the reed-breeding population of barn swallows as a response to the increased perceived cuckoo encounter rate, perhaps because higher potential parasitism threat did not transfer into greater actual parasitism rate. It remains to be assessed whether the lack of small-scale geographic variation in barn swallows' egg rejection rates persists because this species responds to selection by parasitism as a spatially contiguous evolutionary unit. The UBE3A gene is part of the chromosome 15q11-q13 region that is frequently deleted or duplicated, leading to several neurodevelopmental disorders (NDD). Angelman syndrome (AS) is caused by the absence of functional maternally derived UBE3A protein, while the paternal UBE3A gene is present but silenced specifically in neurons. Patients with AS present with severe neurodevelopmental delay, with pronounced motor deficits, absence of speech, intellectual disability, epilepsy, and sleep problems. The pathophysiology of AS is still unclear and a treatment is lacking. Animal models of AS recapitulate the genotypic and phenotypic features observed in AS patients, and have been invaluable for understanding the disease process as well as identifying apropriate drug targets. Using these AS mouse models we have learned that loss of UBE3A probably affects many areas of the brain, leading to increased neuronal excitability and a loss of synaptic spines, along with changes in a number of distinct behaviours. Inducible AS mouse models have helped to identify the critical treatment windows for the behavioral and physiological phenotypes. Additionally, AS mouse models indicate an important role for the predominantly nuclear UBE3A isoform in generating the characteristic AS pathology. Last, but not least, the AS mice have been crucial in guiding Ube3a gene reactivation treatments, which present a very promising therapy to treat AS. Two major processes tightly regulate protein synthesis, the initiation of mRNA translation and elongation phase that mediates the movement of ribosomes along the mRNA. The elongation phase is a high energy-consuming process, and is mainly regulated by the eukaryotic elongation factor 2 kinase (eEF2K) activity that phosphorylates and inhibits eEF2, the only known substrate of the kinase. eEF2K activity is closely regulated by several signaling pathways because the translation elongation phase strongly influences the cellular energy demand and can change the expression of specific proteins in different tissues. An increasing number of recent findings link eEF2k over activation to an array of human diseases, such as atherosclerosis, pulmonary arterial hypertension, progression of solid tumors, and some major neurological disorders. Several neurological studies suggest that eEF2K is a valuable target in treating epilepsy, depression and major neurodegenerative diseases. Despite eEF2k is an ubiquitous and conserved protein, it has been proved that its deletion does not affect development in animal models and in general cell viability. Therefore, it is possible to postulate that inhibiting its function may not cause serious side effects. In addition, eEF2K is a peculiar kinase molecularly different from most of other mammalian kinases and new compounds that inhibit eEF2K should not necessarily interfere with other important protein kinases. In this review we will critically summarize the evidence supporting the role of the altered eEF2K/eEF2 pathway in defined neurological diseases and its implications in curing these diseases in animal models, and possibly in humans, by targeting eEF2K activity. https://www.selleckchem.com/products/AS703026.html PURPOSE Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly collimated synchrotron beam into arrays of parallel microbeams depositing several hundred grays. It appears relevant to combine MRT with a conventional treatment course, preparing a treatment scheme for future patients in clinical trials. The efficiency of MRT delivered after several broad beam (BB) fractions to palliate of F98 brain tumors in rats in comparison with BB fractions alone was evaluated in this study. MATERIALS/METHODS Rats bearing 106 F98 cells implanted in the caudate nucleus were irradiated by 5 fractions in broad beam (BB) mode (3x6Gy + 2x8Gy BB) or by 2 boost fractions in MRT mode, of a total of 5 fractions (3x6Gy BB + MRT 2x8Gy valley dose; peak dose 181Gy (50/200μm)). Tumor growth was evaluated in vivo by MRI follow up at T-1, T7, T12 T15, T20, T25 days, after radiotherapy, and by histology and FACS studies. RESULTS MRT-boosted tumors displayed lower cell density and cell proliferation compared with BB-irradiated tumors. The MRT boost completely stopped tumor growth during ∼4 weeks and led to a significant increase in MST, while tumors treated with BB alone recurred within few days after the last radiation fraction. CONCLUSIONS The first evidence is presented that MRT, delivered as a boost of a conventional fractionated irradiation by orthovoltage broad X-ray beams, is feasible and more efficient than a conventional radiotherapy alone.
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  • Finally, sdAb production was scaled up to shake-flask fermentation where the product yield was improved 2.6-fold compared to the control strain with no sgRNA target sequence. An sdAb content of 14.6% was reached in the best-performing pyrG growth decoupling strain.
    Screening tests are a key step in the diagnosis of dementia and should therefore be highly sensitive to the detection of mild neurocognitive disorders (NCD). The Mini Mental State Examination (MMSE) is the most commonly used screening method. The Montreal Cognitive Assessment (****) is a newer and less well-known screening tool, which has none of the limitations of the MMSE.

    The aim of this study was to analyse the reliability of the Polish versions of **** 7.2 vs MMSE in the detection of mild NCD among people aged over 60.

    The study was carried out at the Department and Clinic of Geriatrics from September 2014 to March 2017. The study included 281 participants, 91 of whom were assigned to the group without NCD. The other 190 had been diagnosed with mild NCD.

    In the analysis of the ROC curve of the **** 7.2 results, the AUC was 0.925 (p < 0.001). The optimal cut-off point for mild NCD was 23/24 points, with sensitivity and specificity of 83.2% and 79.1%. In the ROC curve of MMSE results, the AUC was 0.847 (p < 0.001). The optimal cut-off point for mild NCD was 27/28 points, with sensitivity and specificity of 75.8% and 66.7%. The difference between AUC **** 7.2 and MMSE was 0.078 (p = 0.036).

    **** 7.2 detects mild NCD with more sensitivity than MMSE. We recommend using the cut-off point for **** of 23/24 points, because this is characterised by a higher sensitivity than the previously recommended cut-off point of 25/26 points. For the MMSE, the recommended cut-off point should be 27/28, which gives greater diagnostic accuracy than the previously recommended 25/26 points.
    **** 7.2 detects mild NCD with more sensitivity than MMSE. We recommend using the cut-off point for **** of 23/24 points, because this is characterised by a higher sensitivity than the previously recommended cut-off point of 25/26 points. https://www.selleckchem.com/products/relacorilant.html For the MMSE, the recommended cut-off point should be 27/28, which gives greater diagnostic accuracy than the previously recommended 25/26 points.Alterations in messenger RNAs (mRNAs) of protein-coding genes can influence the malignant behaviors of acute lymphoblastic leukemia (ALL) cells. According to the prediction from The Cancer Genome Atlas (TCGA) database, we discovered that glutathione peroxidase 1 (GPX1) was up-regulated in acute myeloid leukemia (LAML) tissues, which pushed us to explore the feasible role and its related modulatory mechanism of GPX1 in ALL. In this research, we first proved the high expression of GPX1 in ALL cells compared with normal cells. Functional assays further revealed that the proliferation was obstructed and the apoptosis was facilitated in ALL cells with silenced GPX1. Then, both miR-491-5p and miR-214-3p that were down-regulated in ALL cells were affirmed to target GPX1. Subsequently, VPS9D1 antisense RNA 1 (VPS9D1-AS1) was recognized as the upstream regulator of miR-491-5p-miR-214-3p/GPX1 axis in a competing endogenous RNA (ceRNA) model. Importantly, we proved that VPS9D1-AS1 served as a tumor promoter in ALL through elevating GPX1. In conclusion, VPS9D1-AS1 contributed to ALL cell proliferation through miR-491-5p-miR-214-3p/GPX1 axis, hinting an optional choice for the treatment of ALL.Malaria, dengue, yellow fever, and the Zika and West Nile Viruses are major vector-borne diseases of humans transmitted by mosquitoes. According to the World Health Organization, over 80% of the world's population is at risk of contacting these diseases. Insecticides are critical for mosquito control and disease prevention, and insect insecticide resistance is on the increase; new alternatives with potentially different modes of action from current chemistry are needed. During laboratory screening of industrial minerals for insecticide activity against Anopheles gambiae (Giles) (Diptera Culicidae) we discovered a novel mechanical insecticide derived from volcanic rock (MIVR) with potential use as a residual spray. In modified WHO cone tests, the time to 50% mortality was 5 h under high-humidity conditions. MIVR treated surfaces demonstrated no mosquito repellency. In field studies where the mechanical insecticide was applied to wood using standard spray equipment and then placed under stilt homes in New Orleans, LA, the residual activity was >80% after 9 wk against Aedes aegypti (L.) (Diptera Culicidae), Aedes albopictus (Skuse) (Diptera Culicidae) and Culex quinquefasciatus (Say) (Diptera Culicidae) (with similar efficacy to a positive chemical insecticide control). In scanning electron microcopy studies, the MIVR was transferred as particles mostly to the legs of the mosquito. This wettable powder made from volcanic rock is a mechanical insecticide representing a potential new mode of action different from current chemistry for mosquito control and is in commercial development under the trade name Imergard™WP as an indoor and outdoor residual spray.
    Evidence of daily fluctuations in subjective age and their association with older adults' well-being was recently obtained. Yet, neither the simultaneous tracking of two daily views on aging (i.e., daily subjective age and daily ageist attitudes) nor their interactive effect on mental health (i.e., depressive symptoms) has been explored. We hypothesized that (1) Days on which older adults feel older or report high ageist attitudes they would report higher depressive symptoms, (2) Combined older subjective age and high ageist attitudes will be associated with the highest daily depressive symptoms.

    Community-dwelling older adults (N=134, mean age=69.66) completedmeasures of subjective age, ageist attitudes, and depressive symptoms for 10 consecutive days.

    Daily older subjective age and higher ageist attitudes were related to higher depressive symptoms, but there was no combined effect of both on depressive symptoms. There was a significant three-way interaction between subjective age, ageist attitudes, and chronological age, demonstrating the interactive effect of subjective age and ageist attitudes on depressive symptoms only among the old-old respondents.
    Finally, sdAb production was scaled up to shake-flask fermentation where the product yield was improved 2.6-fold compared to the control strain with no sgRNA target sequence. An sdAb content of 14.6% was reached in the best-performing pyrG growth decoupling strain. Screening tests are a key step in the diagnosis of dementia and should therefore be highly sensitive to the detection of mild neurocognitive disorders (NCD). The Mini Mental State Examination (MMSE) is the most commonly used screening method. The Montreal Cognitive Assessment (MoCA) is a newer and less well-known screening tool, which has none of the limitations of the MMSE. The aim of this study was to analyse the reliability of the Polish versions of MoCA 7.2 vs MMSE in the detection of mild NCD among people aged over 60. The study was carried out at the Department and Clinic of Geriatrics from September 2014 to March 2017. The study included 281 participants, 91 of whom were assigned to the group without NCD. The other 190 had been diagnosed with mild NCD. In the analysis of the ROC curve of the MoCA 7.2 results, the AUC was 0.925 (p < 0.001). The optimal cut-off point for mild NCD was 23/24 points, with sensitivity and specificity of 83.2% and 79.1%. In the ROC curve of MMSE results, the AUC was 0.847 (p < 0.001). The optimal cut-off point for mild NCD was 27/28 points, with sensitivity and specificity of 75.8% and 66.7%. The difference between AUC MoCA 7.2 and MMSE was 0.078 (p = 0.036). MoCA 7.2 detects mild NCD with more sensitivity than MMSE. We recommend using the cut-off point for MoCA of 23/24 points, because this is characterised by a higher sensitivity than the previously recommended cut-off point of 25/26 points. For the MMSE, the recommended cut-off point should be 27/28, which gives greater diagnostic accuracy than the previously recommended 25/26 points. MoCA 7.2 detects mild NCD with more sensitivity than MMSE. We recommend using the cut-off point for MoCA of 23/24 points, because this is characterised by a higher sensitivity than the previously recommended cut-off point of 25/26 points. https://www.selleckchem.com/products/relacorilant.html For the MMSE, the recommended cut-off point should be 27/28, which gives greater diagnostic accuracy than the previously recommended 25/26 points.Alterations in messenger RNAs (mRNAs) of protein-coding genes can influence the malignant behaviors of acute lymphoblastic leukemia (ALL) cells. According to the prediction from The Cancer Genome Atlas (TCGA) database, we discovered that glutathione peroxidase 1 (GPX1) was up-regulated in acute myeloid leukemia (LAML) tissues, which pushed us to explore the feasible role and its related modulatory mechanism of GPX1 in ALL. In this research, we first proved the high expression of GPX1 in ALL cells compared with normal cells. Functional assays further revealed that the proliferation was obstructed and the apoptosis was facilitated in ALL cells with silenced GPX1. Then, both miR-491-5p and miR-214-3p that were down-regulated in ALL cells were affirmed to target GPX1. Subsequently, VPS9D1 antisense RNA 1 (VPS9D1-AS1) was recognized as the upstream regulator of miR-491-5p-miR-214-3p/GPX1 axis in a competing endogenous RNA (ceRNA) model. Importantly, we proved that VPS9D1-AS1 served as a tumor promoter in ALL through elevating GPX1. In conclusion, VPS9D1-AS1 contributed to ALL cell proliferation through miR-491-5p-miR-214-3p/GPX1 axis, hinting an optional choice for the treatment of ALL.Malaria, dengue, yellow fever, and the Zika and West Nile Viruses are major vector-borne diseases of humans transmitted by mosquitoes. According to the World Health Organization, over 80% of the world's population is at risk of contacting these diseases. Insecticides are critical for mosquito control and disease prevention, and insect insecticide resistance is on the increase; new alternatives with potentially different modes of action from current chemistry are needed. During laboratory screening of industrial minerals for insecticide activity against Anopheles gambiae (Giles) (Diptera Culicidae) we discovered a novel mechanical insecticide derived from volcanic rock (MIVR) with potential use as a residual spray. In modified WHO cone tests, the time to 50% mortality was 5 h under high-humidity conditions. MIVR treated surfaces demonstrated no mosquito repellency. In field studies where the mechanical insecticide was applied to wood using standard spray equipment and then placed under stilt homes in New Orleans, LA, the residual activity was >80% after 9 wk against Aedes aegypti (L.) (Diptera Culicidae), Aedes albopictus (Skuse) (Diptera Culicidae) and Culex quinquefasciatus (Say) (Diptera Culicidae) (with similar efficacy to a positive chemical insecticide control). In scanning electron microcopy studies, the MIVR was transferred as particles mostly to the legs of the mosquito. This wettable powder made from volcanic rock is a mechanical insecticide representing a potential new mode of action different from current chemistry for mosquito control and is in commercial development under the trade name Imergard™WP as an indoor and outdoor residual spray. Evidence of daily fluctuations in subjective age and their association with older adults' well-being was recently obtained. Yet, neither the simultaneous tracking of two daily views on aging (i.e., daily subjective age and daily ageist attitudes) nor their interactive effect on mental health (i.e., depressive symptoms) has been explored. We hypothesized that (1) Days on which older adults feel older or report high ageist attitudes they would report higher depressive symptoms, (2) Combined older subjective age and high ageist attitudes will be associated with the highest daily depressive symptoms. Community-dwelling older adults (N=134, mean age=69.66) completedmeasures of subjective age, ageist attitudes, and depressive symptoms for 10 consecutive days. Daily older subjective age and higher ageist attitudes were related to higher depressive symptoms, but there was no combined effect of both on depressive symptoms. There was a significant three-way interaction between subjective age, ageist attitudes, and chronological age, demonstrating the interactive effect of subjective age and ageist attitudes on depressive symptoms only among the old-old respondents.
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  • Applications of additive manufacturing (commonly referred to as 3D printing) in direct fabrication of models for pre-surgical planning, functional testing, and medical training are on the rise. However, one current limitation to the accuracy of models for cardiovascular procedural training is a lack of printable materials that accurately mimic human tissue. Most of the available elastomeric materials lack mechanical properties representative of human tissues. To address the gap, the authors explore the multi-material capability of material jetting additive manufacturing to combine non-curing and photo-curing inks to achieve material properties that more closely replicate human tissues. The authors explore the impact of relative material concentration on tissue-relevant properties from puncture and tensile testing under submerged conditions. Further, the authors demonstrate the ability to mimic the mechanical properties of the fossa ovalis, which proves beneficial for accurately simulating transseptal punctures. A fossa ovalis mimic was printed and assembled within a full patient-specific heart model for validation, where it exhibited accuracy in both mechanical properties and geometry. https://www.selleckchem.com/products/hydroxyfasudil-ha-1100.html The explored material combination provides the opportunity to fabricate future medical models that are more realistic and better suited for pre-surgical planning and medical student training. This will ultimately guide safer, more efficient practices.Podcasting is used in higher education so various digital resources can be shared with students. This review aims to synthesise evidence on podcasting in nursing and midwifery education. PubMed, MEDLINE, CINAHL, Scopus and ERIC databases were searched using key terms. 242 articles were found and screened. Data extraction, quality assessment and data analysis, underpinned by a Social Media Learning Model, were conducted on relevant studies. Twenty-six studies were included in the review. Three themes emerged; 1) learning and other outcomes, 2) antecedents to learning, and 3) learning process. Students seemed to acquire new knowledge and skills by using podcasts and it also appeared to improve clinical confidence. The organisation of podcasting, digital literacy and e-Professionalism, the personal motivation of learners, and flexible access to the technology seemed to impact the delivery of this educational intervention. Mechanisms that appeared to affect the learning process were the speed of exchange, the type of social media user, the timeframe, quality of information, the functionality of podcasts and other learning activities. This review synthesised evidence on podcasting in nursing and midwifery education. The technology was seen as a positive learning tool but more robust research examining its efficacy in improving learning outcomes is needed.
    To systematically review the efficacy of five-element music interventions in perinatal mental health and labor pain. To provide evidence for future research on Chinese Traditional Music Interventions.

    An electronically search was conducted in Web of Science, PubMed, EMbase, The Cochrane Library, CNKI databases, WanFang Data and VIP Database for Chinese Technical Periodicals from inception to January 07, 2020 to collect randomized controlled trials (RCTs) on five-element music interventions for prenatal, perinatal and postpartum women. Literature screening, data extraction, and the risk of bias assessment of all eligible studies were conducted by two reviewers independently. Then, meta-analysis was performed by RevMan 5.3 software.

    A total of 13 RCTs involving 2387 patients were included. The results of meta-analysis showed that five-element music could significantly improve the depression levels (SMD=-2.03, 95%CI -2.88 to -1.19, P<0.00001), anxiety levels (SMD=-3.49, 95%CI -4.47 to -2.24, P<0.0000 high-quality studies were needed to confirm the above conclusion.Individuals affected with two genetic syndromes identified in Ecuador have severe short stature and diminished insulin secretion, along with essentially different GH counterregulatory effects on insulin action, which leads to the appearance of opposing metabolic phenotypes. In the case of Laron syndrome, subjects have enhanced insulin sensitivity and diminished incidence of type 2 diabetes mellitus. In the other clinical entity, individuals have innate insulin resistance, a varying degree of carbohydrate metabolism disturbances, glucose intolerance, and eventually insulin-resistant diabetes mellitus. Since both groups have diminished insulin secretion, the standard homeostatic minimal models for assessment of insulin sensitivity and resistance were used to see if they could properly identify the metabolic status, especially considering that these methodologies are simple and non-invasive procedures.
    Fasting insulin concentrations, fasting glucose/fasting insulin ratio and various minimal models were determincal situations where reduced secretion of the metabolic peptide is found or suspected.Migraine with aura is a highly prevalent disorder involving transient neurological disturbances associated with migraine headache. While the pathophysiology is incompletely understood, findings from clinical and basic science studies indicate a potential key role of the thalamus in the mechanisms underlying migraine with and without aura. Two recent, clinic-based MRI studies investigated the volumes of individual thalamic nuclei in migraine patients with and without aura using two different data analysis methods. Both studies found differences of thalamic nuclei volumes between patients and healthy controls, but the results of the studies were not consistent. Here, we investigated whether migraine with aura is associated with changes in thalamic volume by analysing MRI data obtained from a large, cross-sectional population-based study which specifically included women with migraine with aura (N = 156), unrelated migraine-free matched controls (N = 126), and migraine aura-free co-twins (N = 29) identified frome alteration of thalamic volume.
    Self-efficacy has been shown to influence initiating and maintaining physical activity. Pregnancy often leads to a decline in physical activity and exercise self-efficacy assessments could be a tool to help women stay active during pregnancy. The Pregnancy Exercise Self-Efficacy Scale (P-ESES) is an English questionnaire assessing the self-efficacy in pregnant women to perform physical activity. The aim of this study was to translate the P-ESES questionnaire into a valid and reliable Danish version, P-ESES-DK.

    The study included a qualitative design for the validation of the questionnaire and a prospective longitudinal observational study for the reliability testing.

    The questionnaire was translated into Danish in a four-stage process with translation, ****-translation and synthesis. The pre-final version was tested by eight women and changes were made to complete the final version of P-ESES-DK. The reliability testing was performed using a test-retest analysis of P-ESES-DK with 75 Danish pregnant women.
    Applications of additive manufacturing (commonly referred to as 3D printing) in direct fabrication of models for pre-surgical planning, functional testing, and medical training are on the rise. However, one current limitation to the accuracy of models for cardiovascular procedural training is a lack of printable materials that accurately mimic human tissue. Most of the available elastomeric materials lack mechanical properties representative of human tissues. To address the gap, the authors explore the multi-material capability of material jetting additive manufacturing to combine non-curing and photo-curing inks to achieve material properties that more closely replicate human tissues. The authors explore the impact of relative material concentration on tissue-relevant properties from puncture and tensile testing under submerged conditions. Further, the authors demonstrate the ability to mimic the mechanical properties of the fossa ovalis, which proves beneficial for accurately simulating transseptal punctures. A fossa ovalis mimic was printed and assembled within a full patient-specific heart model for validation, where it exhibited accuracy in both mechanical properties and geometry. https://www.selleckchem.com/products/hydroxyfasudil-ha-1100.html The explored material combination provides the opportunity to fabricate future medical models that are more realistic and better suited for pre-surgical planning and medical student training. This will ultimately guide safer, more efficient practices.Podcasting is used in higher education so various digital resources can be shared with students. This review aims to synthesise evidence on podcasting in nursing and midwifery education. PubMed, MEDLINE, CINAHL, Scopus and ERIC databases were searched using key terms. 242 articles were found and screened. Data extraction, quality assessment and data analysis, underpinned by a Social Media Learning Model, were conducted on relevant studies. Twenty-six studies were included in the review. Three themes emerged; 1) learning and other outcomes, 2) antecedents to learning, and 3) learning process. Students seemed to acquire new knowledge and skills by using podcasts and it also appeared to improve clinical confidence. The organisation of podcasting, digital literacy and e-Professionalism, the personal motivation of learners, and flexible access to the technology seemed to impact the delivery of this educational intervention. Mechanisms that appeared to affect the learning process were the speed of exchange, the type of social media user, the timeframe, quality of information, the functionality of podcasts and other learning activities. This review synthesised evidence on podcasting in nursing and midwifery education. The technology was seen as a positive learning tool but more robust research examining its efficacy in improving learning outcomes is needed. To systematically review the efficacy of five-element music interventions in perinatal mental health and labor pain. To provide evidence for future research on Chinese Traditional Music Interventions. An electronically search was conducted in Web of Science, PubMed, EMbase, The Cochrane Library, CNKI databases, WanFang Data and VIP Database for Chinese Technical Periodicals from inception to January 07, 2020 to collect randomized controlled trials (RCTs) on five-element music interventions for prenatal, perinatal and postpartum women. Literature screening, data extraction, and the risk of bias assessment of all eligible studies were conducted by two reviewers independently. Then, meta-analysis was performed by RevMan 5.3 software. A total of 13 RCTs involving 2387 patients were included. The results of meta-analysis showed that five-element music could significantly improve the depression levels (SMD=-2.03, 95%CI -2.88 to -1.19, P<0.00001), anxiety levels (SMD=-3.49, 95%CI -4.47 to -2.24, P<0.0000 high-quality studies were needed to confirm the above conclusion.Individuals affected with two genetic syndromes identified in Ecuador have severe short stature and diminished insulin secretion, along with essentially different GH counterregulatory effects on insulin action, which leads to the appearance of opposing metabolic phenotypes. In the case of Laron syndrome, subjects have enhanced insulin sensitivity and diminished incidence of type 2 diabetes mellitus. In the other clinical entity, individuals have innate insulin resistance, a varying degree of carbohydrate metabolism disturbances, glucose intolerance, and eventually insulin-resistant diabetes mellitus. Since both groups have diminished insulin secretion, the standard homeostatic minimal models for assessment of insulin sensitivity and resistance were used to see if they could properly identify the metabolic status, especially considering that these methodologies are simple and non-invasive procedures. Fasting insulin concentrations, fasting glucose/fasting insulin ratio and various minimal models were determincal situations where reduced secretion of the metabolic peptide is found or suspected.Migraine with aura is a highly prevalent disorder involving transient neurological disturbances associated with migraine headache. While the pathophysiology is incompletely understood, findings from clinical and basic science studies indicate a potential key role of the thalamus in the mechanisms underlying migraine with and without aura. Two recent, clinic-based MRI studies investigated the volumes of individual thalamic nuclei in migraine patients with and without aura using two different data analysis methods. Both studies found differences of thalamic nuclei volumes between patients and healthy controls, but the results of the studies were not consistent. Here, we investigated whether migraine with aura is associated with changes in thalamic volume by analysing MRI data obtained from a large, cross-sectional population-based study which specifically included women with migraine with aura (N = 156), unrelated migraine-free matched controls (N = 126), and migraine aura-free co-twins (N = 29) identified frome alteration of thalamic volume. Self-efficacy has been shown to influence initiating and maintaining physical activity. Pregnancy often leads to a decline in physical activity and exercise self-efficacy assessments could be a tool to help women stay active during pregnancy. The Pregnancy Exercise Self-Efficacy Scale (P-ESES) is an English questionnaire assessing the self-efficacy in pregnant women to perform physical activity. The aim of this study was to translate the P-ESES questionnaire into a valid and reliable Danish version, P-ESES-DK. The study included a qualitative design for the validation of the questionnaire and a prospective longitudinal observational study for the reliability testing. The questionnaire was translated into Danish in a four-stage process with translation, back-translation and synthesis. The pre-final version was tested by eight women and changes were made to complete the final version of P-ESES-DK. The reliability testing was performed using a test-retest analysis of P-ESES-DK with 75 Danish pregnant women.
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  • To date, few programs that integrate traditional practices with evidence-based practices have been developed, implemented, and evaluated with urban American Indians/Alaska Natives (AI/ANs) using a strong research design. The current study recruited urban AI/AN teens across northern, central, and southern California during 2014-2017 to participate in a randomized controlled trial testing two cultural interventions that addressed alcohol and other drug (AOD) use. Adolescents were 14-18 years old (inclusive), and either verbally self-identified as AI/AN or were identified as AI/AN by a parent or community member. We tested the added benefit of MICUNAY (Motivational Interviewing and Culture for Urban Native American Youth) to a CWG (Community Wellness Gathering). MICUNAY was a group intervention with three workshops that integrated traditional practices with motivational interviewing. CWGs were cultural events held monthly in each city. AI/AN urban adolescents (N = 185) completed a baseline survey, were randomized to MICUNAY + CWG or CWG only, and then completed a three- and six-month follow-up. We compared outcomes on AOD use, spirituality, and cultural identification. Overall, AOD use remained stable over the course of the study, and we did not find significant differences between these two groups over time. It may be that connecting urban AI/AN adolescents to culturally centered activities and resources is protective, which has been shown in other work with this population. Given that little work has been conducted in this area, longer term studies of AOD interventions with urban AI/AN youth throughout the U.S. are suggested to test the potential benefits of culturally centered interventions. Screening and brief intervention (SBI) for unhealthy alcohol use is recommended as a routine clinical procedure for adults in primary care settings. However, implementation of SBI remains suboptimal, in part reflecting time constraints in clinical settings. Single Item Screening Questions (SISQ) have increasingly been studied as a means of minimizing assessment burden. Although the ability of SISQ to accurately detect unhealthy alcohol use (i.e., at-risk drinking or alcohol use disorder) has been studied in various clinical and population settings, results have not been summarized in aggregate. This descriptive summarizes SISQ performance metrics across various clinical settings and populations. Based on results from 40 identified studies, there is consistent support that SISQ have good sensitivity as screeners for unhealthy drinking, with performance generally being comparable to longer validated instruments. Collectively, these results justify further efforts to evaluate SISQ as a means of maximizing SBI uptake and efficiency in various clinical settings. BACKGROUND Drug, alcohol, and tobacco use among adolescents pose significant short- and long-term health consequences and are associated with more severe use as adults. Screening, brief intervention, and referral to treatment in primary care settings has the potential to deliver preventive interventions to a diverse range of adolescents, but optimal implementation of these services needs to be determined. The purpose of this study was to compare implementation of two different SBIRT service delivery models in primary care settings. METHODS This cluster-randomized trial assigned 7 primary care clinics of a federally qualified health center to implement brief interventions (BI) using a Generalist model (4 sites), in which BIs were delivered by the primary care provider (PCP), or a Specialist model (3 sites), in which BIs were delivered by a behavioral health counselor (BHC) for adolescent patients ages 12-17 years. Implementation was tracked through the clinic's electronic health record, spanning 9639 clinic viith adolescent primary care patients whose substance use might have otherwise gone undetected. The organizational context in which substance use disorder treatment (SUDT) evidence-based practices (EBPs) are implemented plays a critical role in successful implementation. Employee behaviors that go above and beyond typical job requirements to support EBP implementation have been suggested to facilitate the likelihood of overall implementation success. The current study explored the psychometric properties of the Implementation Citizenship Behavior Scale (ICBS) within SUDT settings. Utilizing a sample of 322 direct service providers and 60 of their respective supervisors from three SUDT agencies, results from a confirmatory factor analysis and construct validity analysis support the use of the ICBS in the SUDT context. Validation of the ICBS provides a useful, pragmatic tool for both researchers and practitioners to assess employee citizenship behavior to support EBP implementation. The ICBS can provide critical insights into how providers respond to organizational context that may facilitate EBP implementation. BACKGROUND Internet-based intervention could help drug users recover from drug dependence. This study evaluated the effectiveness of a newly developed web-based relapse prevention program (e-SMARPP) for people with a drug problem, including the use of methamphetamine, in Japan. METHODS The study was a pilot randomized controlled trial comprised of 48 psychiatric outpatients diagnosed with drug use disorder. The participants were randomly assigned to an eight-week, six-session web-based relapse prevention program (an intervention group) or only web-based self-monitoring (a control group). The primary outcome was the duration of abstinence from a primary drug during the intervention and relapse risk. Secondary outcomes included motivation to change, self-efficacy, and money spent on drugs. The outcomes, except for the duration of abstinence during the intervention, were assessed at baseline, 2-, 5-, and 8-months. Program completion rate was also assessed. RESULTS No significant difference was observed between the intervention and the control groups for the primary and the secondary outcomes. The effect size of the duration of abstinence during the intervention was d = 0.42, which was comparable to previous studies. https://www.selleckchem.com/products/relacorilant.html In the intervention group, about 26% did not complete the entire intervention. CONCLUSIONS e-SMARPP failed to demonstrate efficacy, however, is potentially helpful for enhancing abstinence. The low attrition rate may suggest the acceptance and feasibility of the program. Further improvement of the program and evaluation in a full-scale trial are needed.
    To date, few programs that integrate traditional practices with evidence-based practices have been developed, implemented, and evaluated with urban American Indians/Alaska Natives (AI/ANs) using a strong research design. The current study recruited urban AI/AN teens across northern, central, and southern California during 2014-2017 to participate in a randomized controlled trial testing two cultural interventions that addressed alcohol and other drug (AOD) use. Adolescents were 14-18 years old (inclusive), and either verbally self-identified as AI/AN or were identified as AI/AN by a parent or community member. We tested the added benefit of MICUNAY (Motivational Interviewing and Culture for Urban Native American Youth) to a CWG (Community Wellness Gathering). MICUNAY was a group intervention with three workshops that integrated traditional practices with motivational interviewing. CWGs were cultural events held monthly in each city. AI/AN urban adolescents (N = 185) completed a baseline survey, were randomized to MICUNAY + CWG or CWG only, and then completed a three- and six-month follow-up. We compared outcomes on AOD use, spirituality, and cultural identification. Overall, AOD use remained stable over the course of the study, and we did not find significant differences between these two groups over time. It may be that connecting urban AI/AN adolescents to culturally centered activities and resources is protective, which has been shown in other work with this population. Given that little work has been conducted in this area, longer term studies of AOD interventions with urban AI/AN youth throughout the U.S. are suggested to test the potential benefits of culturally centered interventions. Screening and brief intervention (SBI) for unhealthy alcohol use is recommended as a routine clinical procedure for adults in primary care settings. However, implementation of SBI remains suboptimal, in part reflecting time constraints in clinical settings. Single Item Screening Questions (SISQ) have increasingly been studied as a means of minimizing assessment burden. Although the ability of SISQ to accurately detect unhealthy alcohol use (i.e., at-risk drinking or alcohol use disorder) has been studied in various clinical and population settings, results have not been summarized in aggregate. This descriptive summarizes SISQ performance metrics across various clinical settings and populations. Based on results from 40 identified studies, there is consistent support that SISQ have good sensitivity as screeners for unhealthy drinking, with performance generally being comparable to longer validated instruments. Collectively, these results justify further efforts to evaluate SISQ as a means of maximizing SBI uptake and efficiency in various clinical settings. BACKGROUND Drug, alcohol, and tobacco use among adolescents pose significant short- and long-term health consequences and are associated with more severe use as adults. Screening, brief intervention, and referral to treatment in primary care settings has the potential to deliver preventive interventions to a diverse range of adolescents, but optimal implementation of these services needs to be determined. The purpose of this study was to compare implementation of two different SBIRT service delivery models in primary care settings. METHODS This cluster-randomized trial assigned 7 primary care clinics of a federally qualified health center to implement brief interventions (BI) using a Generalist model (4 sites), in which BIs were delivered by the primary care provider (PCP), or a Specialist model (3 sites), in which BIs were delivered by a behavioral health counselor (BHC) for adolescent patients ages 12-17 years. Implementation was tracked through the clinic's electronic health record, spanning 9639 clinic viith adolescent primary care patients whose substance use might have otherwise gone undetected. The organizational context in which substance use disorder treatment (SUDT) evidence-based practices (EBPs) are implemented plays a critical role in successful implementation. Employee behaviors that go above and beyond typical job requirements to support EBP implementation have been suggested to facilitate the likelihood of overall implementation success. The current study explored the psychometric properties of the Implementation Citizenship Behavior Scale (ICBS) within SUDT settings. Utilizing a sample of 322 direct service providers and 60 of their respective supervisors from three SUDT agencies, results from a confirmatory factor analysis and construct validity analysis support the use of the ICBS in the SUDT context. Validation of the ICBS provides a useful, pragmatic tool for both researchers and practitioners to assess employee citizenship behavior to support EBP implementation. The ICBS can provide critical insights into how providers respond to organizational context that may facilitate EBP implementation. BACKGROUND Internet-based intervention could help drug users recover from drug dependence. This study evaluated the effectiveness of a newly developed web-based relapse prevention program (e-SMARPP) for people with a drug problem, including the use of methamphetamine, in Japan. METHODS The study was a pilot randomized controlled trial comprised of 48 psychiatric outpatients diagnosed with drug use disorder. The participants were randomly assigned to an eight-week, six-session web-based relapse prevention program (an intervention group) or only web-based self-monitoring (a control group). The primary outcome was the duration of abstinence from a primary drug during the intervention and relapse risk. Secondary outcomes included motivation to change, self-efficacy, and money spent on drugs. The outcomes, except for the duration of abstinence during the intervention, were assessed at baseline, 2-, 5-, and 8-months. Program completion rate was also assessed. RESULTS No significant difference was observed between the intervention and the control groups for the primary and the secondary outcomes. The effect size of the duration of abstinence during the intervention was d = 0.42, which was comparable to previous studies. https://www.selleckchem.com/products/relacorilant.html In the intervention group, about 26% did not complete the entire intervention. CONCLUSIONS e-SMARPP failed to demonstrate efficacy, however, is potentially helpful for enhancing abstinence. The low attrition rate may suggest the acceptance and feasibility of the program. Further improvement of the program and evaluation in a full-scale trial are needed.
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  • Increased knowledge about the fate and behaviour of weathered oil in different sea ice conditions is essential for our ability to model oil spill trajectories in ice more precisely and for oil spill response decision making in northern and Arctic areas. As part of the 3-year project "Fate, Behaviour and Response to Oil Drifting into Scattered Ice and Ice Edge in the Marginal Ice Zone", a novel wave and current flume was built to simulate these processes in the laboratory. This paper discusses some of the findings from this project, which included Marine Gas Oil and four Norwegian crude oils. All crude oils were weathered prior to testing, simulating having drifted on the sea surface for a period (tentatively 1-3 days) before encountering ice. The build-up of oil drifting against an ice barrier and horizontal and vertical migration of oil droplets under solid ice and in frazil ice was studied.Plastic pollution is a concern in many nearshore ecosystems, and it is critical to understand how microplastics (plastics less then 5 mm in length) affect nearshore marine biota. Here, we report the presence of microplastics in the benthic, upside-down jellyfish (Cassiopea xamachana) across three estuaries in south Florida. Microplastics were recovered from Cassiopea using an acid digestion, then enumerated via microscopy, and identified using micro Fourier-transform interferometer (μFTIR) analysis. Out of 115 specimens analyzed, 77% contained microplastics. **** diameter and number of plastics per individual varied significantly across locations with the highest plastic densities and **** diameter observed in individuals from Big Pine Key, followed by Jupiter, and Sarasota. μFTIR analysis confirmed that synthetic microfibers were the dominant microplastic measured at all three locations and may indicate Cassiopea as potential sinks of microplastic. Cassiopea may be used as bioindicators of microplastic contamination in the future, allowing for potential plastic pollution mitigation.Previous studies have identified the brain correlates of social pain processing during ostracism. However, the affective response to ostracism may vary according to individual differences in interpersonal needs and subsequent social actions. Despite this relationship, how the neural processes underlying ostracism may be modulated by interpersonal needs to regulate prosocial behaviors remains unknown. Here, in an fMRI study of 64 adults performing the Cyberball task, we quantified ball catching and tossing response time (RT) as a behavioral measure of participants' willingness to seek and reciprocate social interactions. Neural activations to social exclusion were identified and characterized in relation to individual differences in behavioral performance and perceived burdensomeness (PB), a measure of interpersonal needs. The results showed that social exclusion elicited activity in the anterior insula, middle frontal gyrus, postcentral gyrus, and dorsomedial prefrontal cortex, replicating previous studies on ostracism. Importantly, those with higher PB also exhibited greater brain activations to exclusion as well as reduced prosocial behaviors, as reflected by slower ball catching and tossing RT in the Cyberball task. Taken together, these findings suggest that emotional distress in ostracism may increase with PB, resulting in stronger neural responses to social pain and behavioral avoidance of social interactions.Multimodal in-patient treatment incorporating intensive cognitive-behaviour therapy (CBT) and medication management is a promising alternative for obsessive-compulsive disorder (OCD) patients who do not respond to standard out-patient treatment. We prospectively examined the short-term outcome and predictors of outcome of intensive in-patient treatment in a largely pharmacotherapy-resistant OCD sample. Fifty eight consecutive patients, admitted for treatment of OCD were evaluated at admission, at discharge and 2 months post-discharge for psychiatric diagnosis, personality disorders, obsessive beliefs, insight into obsessions and severity of obsessive-compulsive, depressive and anxiety symptoms. All patients received comprehensive treatment consisting of a combination of pharmacotherapy and intensive CBT. The mean Y-**** score was 29.38(±5.72) at admission, which reduced to 16.62(±7.91) at discharge and 16.75(±8.85) at follow-up. Thirty five participants (60.3%) met the prespecified criteria for response and 19 (32.8%) for remission. There was a significant reduction in Y-**** scores at discharge [43.67 (23.81)%] and post-discharge follow-up [2.18 (29.32)%] as compared to baseline (p less then 0.01). Baseline Browns Assessment of Beleifs Scale score (insight) was the only variable that statistically differentiated responders and non-responders. In-patient treatment is an effective treatment for medication resistant, severe and chronic OCD. Poor insight is a potential predictor of non-response to in-patient treatment.In everyday clinical work, psychiatrists encounter patients who present with symptoms spanning several diagnostic categories, e.g., showing signs of a psychosis, depression, and anxiety. This raises the critical question of which symptoms hold precedence over other and, by extension, which diagnosis is the right diagnosis. ICD-10 and DSM-5 do not provide unambiguous answers to this question and therefore psychiatry remains exposed to diagnostic disagreement with consequences for treatment and research. We explored symptom distribution in a sample of 98 first-admission psychiatric patients. We extracted and categorized singular symptoms into symptom domains anxiety, mania, delusions, hallucinations, first-rank symptoms, and negative symptoms. https://www.selleckchem.com/products/AS703026.html Most symptoms were seen in most disorders. We found symptoms of depression and anxiety in almost all patients. Thus, just counting symptoms do not seem to be a valid way to make diagnoses. We elaborately discuss these issues in the context of the differential-diagnosis between schizophrenia and depression. Finally, we suggest that a combination of a criteria- and Gestalt-based approach to diagnosing mental disorders may contribute to counteract some of the current differential-diagnostic confusion.
    Increased knowledge about the fate and behaviour of weathered oil in different sea ice conditions is essential for our ability to model oil spill trajectories in ice more precisely and for oil spill response decision making in northern and Arctic areas. As part of the 3-year project "Fate, Behaviour and Response to Oil Drifting into Scattered Ice and Ice Edge in the Marginal Ice Zone", a novel wave and current flume was built to simulate these processes in the laboratory. This paper discusses some of the findings from this project, which included Marine Gas Oil and four Norwegian crude oils. All crude oils were weathered prior to testing, simulating having drifted on the sea surface for a period (tentatively 1-3 days) before encountering ice. The build-up of oil drifting against an ice barrier and horizontal and vertical migration of oil droplets under solid ice and in frazil ice was studied.Plastic pollution is a concern in many nearshore ecosystems, and it is critical to understand how microplastics (plastics less then 5 mm in length) affect nearshore marine biota. Here, we report the presence of microplastics in the benthic, upside-down jellyfish (Cassiopea xamachana) across three estuaries in south Florida. Microplastics were recovered from Cassiopea using an acid digestion, then enumerated via microscopy, and identified using micro Fourier-transform interferometer (μFTIR) analysis. Out of 115 specimens analyzed, 77% contained microplastics. Bell diameter and number of plastics per individual varied significantly across locations with the highest plastic densities and bell diameter observed in individuals from Big Pine Key, followed by Jupiter, and Sarasota. μFTIR analysis confirmed that synthetic microfibers were the dominant microplastic measured at all three locations and may indicate Cassiopea as potential sinks of microplastic. Cassiopea may be used as bioindicators of microplastic contamination in the future, allowing for potential plastic pollution mitigation.Previous studies have identified the brain correlates of social pain processing during ostracism. However, the affective response to ostracism may vary according to individual differences in interpersonal needs and subsequent social actions. Despite this relationship, how the neural processes underlying ostracism may be modulated by interpersonal needs to regulate prosocial behaviors remains unknown. Here, in an fMRI study of 64 adults performing the Cyberball task, we quantified ball catching and tossing response time (RT) as a behavioral measure of participants' willingness to seek and reciprocate social interactions. Neural activations to social exclusion were identified and characterized in relation to individual differences in behavioral performance and perceived burdensomeness (PB), a measure of interpersonal needs. The results showed that social exclusion elicited activity in the anterior insula, middle frontal gyrus, postcentral gyrus, and dorsomedial prefrontal cortex, replicating previous studies on ostracism. Importantly, those with higher PB also exhibited greater brain activations to exclusion as well as reduced prosocial behaviors, as reflected by slower ball catching and tossing RT in the Cyberball task. Taken together, these findings suggest that emotional distress in ostracism may increase with PB, resulting in stronger neural responses to social pain and behavioral avoidance of social interactions.Multimodal in-patient treatment incorporating intensive cognitive-behaviour therapy (CBT) and medication management is a promising alternative for obsessive-compulsive disorder (OCD) patients who do not respond to standard out-patient treatment. We prospectively examined the short-term outcome and predictors of outcome of intensive in-patient treatment in a largely pharmacotherapy-resistant OCD sample. Fifty eight consecutive patients, admitted for treatment of OCD were evaluated at admission, at discharge and 2 months post-discharge for psychiatric diagnosis, personality disorders, obsessive beliefs, insight into obsessions and severity of obsessive-compulsive, depressive and anxiety symptoms. All patients received comprehensive treatment consisting of a combination of pharmacotherapy and intensive CBT. The mean Y-BOCS score was 29.38(±5.72) at admission, which reduced to 16.62(±7.91) at discharge and 16.75(±8.85) at follow-up. Thirty five participants (60.3%) met the prespecified criteria for response and 19 (32.8%) for remission. There was a significant reduction in Y-BOCS scores at discharge [43.67 (23.81)%] and post-discharge follow-up [2.18 (29.32)%] as compared to baseline (p less then 0.01). Baseline Browns Assessment of Beleifs Scale score (insight) was the only variable that statistically differentiated responders and non-responders. In-patient treatment is an effective treatment for medication resistant, severe and chronic OCD. Poor insight is a potential predictor of non-response to in-patient treatment.In everyday clinical work, psychiatrists encounter patients who present with symptoms spanning several diagnostic categories, e.g., showing signs of a psychosis, depression, and anxiety. This raises the critical question of which symptoms hold precedence over other and, by extension, which diagnosis is the right diagnosis. ICD-10 and DSM-5 do not provide unambiguous answers to this question and therefore psychiatry remains exposed to diagnostic disagreement with consequences for treatment and research. We explored symptom distribution in a sample of 98 first-admission psychiatric patients. We extracted and categorized singular symptoms into symptom domains anxiety, mania, delusions, hallucinations, first-rank symptoms, and negative symptoms. https://www.selleckchem.com/products/AS703026.html Most symptoms were seen in most disorders. We found symptoms of depression and anxiety in almost all patients. Thus, just counting symptoms do not seem to be a valid way to make diagnoses. We elaborately discuss these issues in the context of the differential-diagnosis between schizophrenia and depression. Finally, we suggest that a combination of a criteria- and Gestalt-based approach to diagnosing mental disorders may contribute to counteract some of the current differential-diagnostic confusion.
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