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  • As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing of ECM remodeling pathways, we conducted a systematic review in which we describe protein and mRNA markers for ECM remodeling that are differentially expressed in the hearts of animals with anthracycline-induced cardiomyopathy. We included 68 studies in ****, rats, rabbits, and pigs with follow-up of 0.1-8.2 human equivalent years after anthracycline administration. Using meta-analysis, we found 29 proteins and 11 mRNAs that were differentially expressed in anthracycline-induced cardiomyopathy compared to controls. Collagens, matrix metalloproteinases (MMPs), inflammation markers, transforming growth factor ß signaling markers, and markers for cardiac hypertrophy were upregulated, whereas the protein kinase B (AKT) pro-survival pathway was downregulated. Their expression patterns over time from single time point studies were studied with meta-regression using human equivalent years as the time scale. Connective tissue growth factor showed an early peak in expression but remained upregulated at all studied time points. Brain natriuretic peptide (BNP) and MMP9 protein levels increased in studies with longer follow-up. Significant associations were found for higher atrial natriuretic peptide with interstitial fibrosis and for higher BNP and MMP2 protein levels with left ventricular systolic function.
    The purpose of this study was to investigate the relationship between recreational marijuana use and patient-reported outcomes two years after orthopaedic surgery. We hypothesized that pre-operative recreational marijuana use would be associated with less pain, better function, and better mental health measures two years after orthopaedic surgery.

    Patients were retrospectively analyzed from a prospective orthopaedic registry at a single urban institution. A total of 1710 patients completed the pre-operative assessment and 1103 patients (64.5%) completed the two-year follow-up questionnaires. The cohort was then divided into two groups based on reported preoperative recreational marijuana usage, and statistical analysis was performed to determine if marijuana use was associated with two-year outcomes. Multivariable analysis was used to control for confounding variables.

    Marijuana use was reported by 47 (4.3%) patients. Significantly worse scores for two-year PROMIS Anxiety (53.2 vs. 49.2, p = 0.005), PROMIS Depression (51.1 vs. 46.5, p = 0.001), Met Expectations (63.1 vs. 74.4, p = 0.024), Surgical Satisfaction Questionnaire-8 (71.7 vs. 80.4, p = 0.005), and Numeric Satisfaction Scale (75.6 vs. 83.1, p = 0.041) were associated with marijuana use. Marijuana users also had less improvement of Numeric Pain Scores at the operative site (- 1.8 vs. - 2.7, p = 0.037) and greater decrease in Marx activity scores for lower extremities (- 12.3 vs. - 3.9, p = 0.024). Marijuana use was not an independent predictor of any outcome measure in the multivariable analysis.

    Marijuana use was associated with worse mental health scores, lower activity level, less pain relief, and worse satisfaction two years after orthopaedic surgery. However, after controlling for confounding variables, marijuana use was not predictive of any two-year outcome measure.

    Cross-sectional study.
    Cross-sectional study.
    Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. https://www.selleckchem.com/products/tak-981.html However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH.

    We created **** with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO **** fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control ****.

    MffLiKO ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO **** were more susceptible to HFD-induced NASH phenotype than control ****, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH.Objectives Poor psychosocial work environments in hospitals are associated with higher employee turnover. In this prospective cohort study, we aimed to identify and quantify which aspects of the psychosocial work environment have the greatest impact on one-year employee turnover rates within a hospital setting, both overall and within occupational groups. Methods The study population included 24 385 public hospital employees enrolled in the Danish Well-being in Hospital Employees cohort in 2014. We followed the participants for one year and registered if they permanently left their workplace. Using baseline sociodemographic, workplace, and psychosocial work environment characteristics, we applied the parametric g-formula to simulate hypothetical improvements in the psychosocial work environment and estimated turnover rate differences (RD) per 10 000 employees per year and 95% confidence intervals (95% CI). Results Of the 24 385 participants, 2552 (10.5%) left the workplace during the one-year follow-up. Up to 44% of this turnover was potentially preventable through hypothetical improvements in the psychosocial work environment. The specific hypothetical improvements with the largest effects were in satisfaction with work prospects (RD -522 turnovers per 10 000 person-years, 95% CI -536- -508), general job satisfaction (RD -339, 95% CI -353- -325) and bullying (RD -200, 95% CI -214- -186). The potential for preventing turnover was larger for nurses than for physicians and other healthcare employees. Conclusions Improvements in the psychosocial work environment may have great potential for reducing turnover among hospital staff, particularly among nurses.
    As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing of ECM remodeling pathways, we conducted a systematic review in which we describe protein and mRNA markers for ECM remodeling that are differentially expressed in the hearts of animals with anthracycline-induced cardiomyopathy. We included 68 studies in mice, rats, rabbits, and pigs with follow-up of 0.1-8.2 human equivalent years after anthracycline administration. Using meta-analysis, we found 29 proteins and 11 mRNAs that were differentially expressed in anthracycline-induced cardiomyopathy compared to controls. Collagens, matrix metalloproteinases (MMPs), inflammation markers, transforming growth factor ß signaling markers, and markers for cardiac hypertrophy were upregulated, whereas the protein kinase B (AKT) pro-survival pathway was downregulated. Their expression patterns over time from single time point studies were studied with meta-regression using human equivalent years as the time scale. Connective tissue growth factor showed an early peak in expression but remained upregulated at all studied time points. Brain natriuretic peptide (BNP) and MMP9 protein levels increased in studies with longer follow-up. Significant associations were found for higher atrial natriuretic peptide with interstitial fibrosis and for higher BNP and MMP2 protein levels with left ventricular systolic function. The purpose of this study was to investigate the relationship between recreational marijuana use and patient-reported outcomes two years after orthopaedic surgery. We hypothesized that pre-operative recreational marijuana use would be associated with less pain, better function, and better mental health measures two years after orthopaedic surgery. Patients were retrospectively analyzed from a prospective orthopaedic registry at a single urban institution. A total of 1710 patients completed the pre-operative assessment and 1103 patients (64.5%) completed the two-year follow-up questionnaires. The cohort was then divided into two groups based on reported preoperative recreational marijuana usage, and statistical analysis was performed to determine if marijuana use was associated with two-year outcomes. Multivariable analysis was used to control for confounding variables. Marijuana use was reported by 47 (4.3%) patients. Significantly worse scores for two-year PROMIS Anxiety (53.2 vs. 49.2, p = 0.005), PROMIS Depression (51.1 vs. 46.5, p = 0.001), Met Expectations (63.1 vs. 74.4, p = 0.024), Surgical Satisfaction Questionnaire-8 (71.7 vs. 80.4, p = 0.005), and Numeric Satisfaction Scale (75.6 vs. 83.1, p = 0.041) were associated with marijuana use. Marijuana users also had less improvement of Numeric Pain Scores at the operative site (- 1.8 vs. - 2.7, p = 0.037) and greater decrease in Marx activity scores for lower extremities (- 12.3 vs. - 3.9, p = 0.024). Marijuana use was not an independent predictor of any outcome measure in the multivariable analysis. Marijuana use was associated with worse mental health scores, lower activity level, less pain relief, and worse satisfaction two years after orthopaedic surgery. However, after controlling for confounding variables, marijuana use was not predictive of any two-year outcome measure. Cross-sectional study. Cross-sectional study. Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. https://www.selleckchem.com/products/tak-981.html However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. MffLiKO ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH.Objectives Poor psychosocial work environments in hospitals are associated with higher employee turnover. In this prospective cohort study, we aimed to identify and quantify which aspects of the psychosocial work environment have the greatest impact on one-year employee turnover rates within a hospital setting, both overall and within occupational groups. Methods The study population included 24 385 public hospital employees enrolled in the Danish Well-being in Hospital Employees cohort in 2014. We followed the participants for one year and registered if they permanently left their workplace. Using baseline sociodemographic, workplace, and psychosocial work environment characteristics, we applied the parametric g-formula to simulate hypothetical improvements in the psychosocial work environment and estimated turnover rate differences (RD) per 10 000 employees per year and 95% confidence intervals (95% CI). Results Of the 24 385 participants, 2552 (10.5%) left the workplace during the one-year follow-up. Up to 44% of this turnover was potentially preventable through hypothetical improvements in the psychosocial work environment. The specific hypothetical improvements with the largest effects were in satisfaction with work prospects (RD -522 turnovers per 10 000 person-years, 95% CI -536- -508), general job satisfaction (RD -339, 95% CI -353- -325) and bullying (RD -200, 95% CI -214- -186). The potential for preventing turnover was larger for nurses than for physicians and other healthcare employees. Conclusions Improvements in the psychosocial work environment may have great potential for reducing turnover among hospital staff, particularly among nurses.
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  • Recently, non-canonical DNA structures, such as G-quadruplexes (GQs), were found to be highly pressure sensitive, suggesting that pressure modulation studies can provide additional mechanistic details of such biomolecular systems. Using FRET and CD spectroscopy as well as binding equilibrium measurements, we investigated the effect of pressure on the binding reaction of the ligand ThT to the quadruplex 22AG in solutions containing different ionic species and a crowding agent mimicking the intracellular milieu. Pressure modulation helped us to identify the different conformational substates adopted by the quadruplex at the different solution conditions and to determine the volumetric changes during complex formation and the conformational transitions involved. The magnitudes of the binding volumes are a hallmark of packing defects and hydrational changes upon ligand binding. The conformational substates of the GQ as well as the binding strength and the stoichiometry of complex formation depend strongly on the solution conditions as well as on pressure. High hydrostatic pressure can also impact GQs inside living cells and thus affect expression of genetic information in deep sea organisms. We show that sub-kbar pressures do not only affect the conformational dynamics and structures of GQs, but also their ligand binding reactions.Long non-coding RNAs (lncRNAs) play important roles in a range of different human cancers. However, the role of lncRNA solute carrier organic anion transporter family member 4A1-AS1 (SLCO4A1-AS1) in colon cancer remains enigmatic. Hence, we aimed to explore the specific role of SLCO4A1-AS1 in colon cancer stem cells. Colon cancer-related differentially expressed lncRNA and mRNA were screened using microarray-based analysis, and the expression of SLCO4A1-AS1 and SLCO4A1 in colon cancer tissues was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. The interaction among SLCO4A1-AS1, microRNA-150-3p (miR-150-3p) and SLCO4A1 was verified using dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Moreover, SLCO4A1-AS1, miR-150-3p and/or SLCO4A1 were overexpressed or depleted in colon cancer cells to detect their effects on migration, invasion, sphere formation, apoptosis and tumorigenesis abilities of colon cancer stem CD133+CD44+ cells using both in vitro and in vivo assays. SLCO4A1-AS1 and SLCO4A1 were screened as the differentially expressed lncRNA and mRNA in colon cancer tissues. SLCO4A1-AS1 was confirmed to competitively bind to miR-150-3p to elevate SLCO4A1 expression. Moreover, knockdown of SLCO4A1-AS1 decreased SLCO4A1 expression, thus inhibiting cell migration, invasion, sphere formation, and tumorigenesis abilities and enhancing the apoptosis of CD133+CD44+ cells. Collectively, these findings provide evidence demonstrating that depleting SLCO4A1-AS1 competitively binds to miR-150-3p, which downregulates SLCO4A1 expression, thus hindering colon cancer progression.Recent studies indicate that yawning evolved as a brain cooling mechanism. Given that larger brains have greater thermolytic needs and brain temperature is determined in part by heat production from neuronal activity, it was hypothesized that animals with larger brains and more neurons would yawn longer to produce comparable cooling effects. To test this, we performed the largest study on yawning ever conducted, analyzing 1291 yawns from 101 species (55 mammals; 46 birds). Phylogenetically controlled analyses revealed robust positive correlations between yawn duration and (1) brain mass, (2) total neuron number, and (3) cortical/pallial neuron number in both mammals and birds, which cannot be attributed solely to allometric scaling rules. These relationships were similar across clades, though mammals exhibited considerably longer yawns than birds of comparable brain and body mass. These findings provide further evidence suggesting that yawning is a thermoregulatory adaptation that has been conserved across amniote evolution.Aberrant DNA methylation plays a pivotal role in tumor development and progression. DNA hypomethylating agents (HMA) constitute a class of drugs which are able to reverse DNA methylation, thereby triggering the re-programming of tumor cells. The first-generation HMA azacitidine and decitabine have now been in standard clinical use for some time, offering a valuable alternative to previous treatments in acute myeloid leukemia and myelodysplastic syndromes, so far particularly in older, medically non-fit patients. However, the longer we use these drugs, the more we are confronted with the (almost inevitable) development of resistance. This review provides insights into the mode of action of HMA, mechanisms of resistance to this treatment, and strategies to overcome HMA resistance including next-generation HMA and HMA-based combination therapies.The aim was to establish and evaluate a new clustering method for visual field (VF) test points to predict future VF in retinitis pigmentosa. A Humphrey Field Analyzer 10-2 test was clustered using total deviation values from 858 VFs. We stratified 68 test points into 24 sectors. Then, mean absolute error (MAE) of the sector-wise regression with them (S1) was evaluated using 196 eyes with 10 VF sequences and compared to pointwise linear regression (PLR), mean sensitivity of total area (MS) and also another sector-wise regression basing on VF mapping for glaucoma (29 sectors; S2). MAE with S1 were smaller than with PLR when between the first-third and first-seventh VFs were used. MAE with the method were significantly smaller than those of S2 when between the first-sixth and first-ninth VFs were used. The MAE of MS was smaller than those with S1 only when first to 3rd and first to 4th VFs were used; however, the prediction accuracy became far larger than any other methods when larger number of VFs were used. More accurate prediction was achieved using this new sector-wise regression than with PLR. In addition, the obtained cluster was more useful than that for glaucoma to predict progression.For natural selection to operate there must exist heritable variation among individuals that affects their survival and reproduction. Among free-living microbes, where differences in growth rates largely define selection intensities, competitive exclusion is common. However, among surface attached communities, these dynamics become less predictable. If extreme circumstances were to dictate that a surface population is immortal and all offspring must emigrate, the offspring would be unable to contribute to the composition of the population. Meanwhile, the immortals, regardless of reproductive capacity, would remain unchanged in relative abundance. The normal cycle of birth, death, and competitive exclusion would be broken. https://www.selleckchem.com/products/pf-06826647.html We tested whether conditions required to set up this idealized scenario can be approximated in a microbial biofilm. Using two differentially-reproducing strains of Shewanella oneidensis grown on an anode as the sole terminal electron acceptor - a system in which metabolism is obligately tied to surface attachment - we found that selection against a slow-growing competitor is drastically reduced.
    Recently, non-canonical DNA structures, such as G-quadruplexes (GQs), were found to be highly pressure sensitive, suggesting that pressure modulation studies can provide additional mechanistic details of such biomolecular systems. Using FRET and CD spectroscopy as well as binding equilibrium measurements, we investigated the effect of pressure on the binding reaction of the ligand ThT to the quadruplex 22AG in solutions containing different ionic species and a crowding agent mimicking the intracellular milieu. Pressure modulation helped us to identify the different conformational substates adopted by the quadruplex at the different solution conditions and to determine the volumetric changes during complex formation and the conformational transitions involved. The magnitudes of the binding volumes are a hallmark of packing defects and hydrational changes upon ligand binding. The conformational substates of the GQ as well as the binding strength and the stoichiometry of complex formation depend strongly on the solution conditions as well as on pressure. High hydrostatic pressure can also impact GQs inside living cells and thus affect expression of genetic information in deep sea organisms. We show that sub-kbar pressures do not only affect the conformational dynamics and structures of GQs, but also their ligand binding reactions.Long non-coding RNAs (lncRNAs) play important roles in a range of different human cancers. However, the role of lncRNA solute carrier organic anion transporter family member 4A1-AS1 (SLCO4A1-AS1) in colon cancer remains enigmatic. Hence, we aimed to explore the specific role of SLCO4A1-AS1 in colon cancer stem cells. Colon cancer-related differentially expressed lncRNA and mRNA were screened using microarray-based analysis, and the expression of SLCO4A1-AS1 and SLCO4A1 in colon cancer tissues was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. The interaction among SLCO4A1-AS1, microRNA-150-3p (miR-150-3p) and SLCO4A1 was verified using dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Moreover, SLCO4A1-AS1, miR-150-3p and/or SLCO4A1 were overexpressed or depleted in colon cancer cells to detect their effects on migration, invasion, sphere formation, apoptosis and tumorigenesis abilities of colon cancer stem CD133+CD44+ cells using both in vitro and in vivo assays. SLCO4A1-AS1 and SLCO4A1 were screened as the differentially expressed lncRNA and mRNA in colon cancer tissues. SLCO4A1-AS1 was confirmed to competitively bind to miR-150-3p to elevate SLCO4A1 expression. Moreover, knockdown of SLCO4A1-AS1 decreased SLCO4A1 expression, thus inhibiting cell migration, invasion, sphere formation, and tumorigenesis abilities and enhancing the apoptosis of CD133+CD44+ cells. Collectively, these findings provide evidence demonstrating that depleting SLCO4A1-AS1 competitively binds to miR-150-3p, which downregulates SLCO4A1 expression, thus hindering colon cancer progression.Recent studies indicate that yawning evolved as a brain cooling mechanism. Given that larger brains have greater thermolytic needs and brain temperature is determined in part by heat production from neuronal activity, it was hypothesized that animals with larger brains and more neurons would yawn longer to produce comparable cooling effects. To test this, we performed the largest study on yawning ever conducted, analyzing 1291 yawns from 101 species (55 mammals; 46 birds). Phylogenetically controlled analyses revealed robust positive correlations between yawn duration and (1) brain mass, (2) total neuron number, and (3) cortical/pallial neuron number in both mammals and birds, which cannot be attributed solely to allometric scaling rules. These relationships were similar across clades, though mammals exhibited considerably longer yawns than birds of comparable brain and body mass. These findings provide further evidence suggesting that yawning is a thermoregulatory adaptation that has been conserved across amniote evolution.Aberrant DNA methylation plays a pivotal role in tumor development and progression. DNA hypomethylating agents (HMA) constitute a class of drugs which are able to reverse DNA methylation, thereby triggering the re-programming of tumor cells. The first-generation HMA azacitidine and decitabine have now been in standard clinical use for some time, offering a valuable alternative to previous treatments in acute myeloid leukemia and myelodysplastic syndromes, so far particularly in older, medically non-fit patients. However, the longer we use these drugs, the more we are confronted with the (almost inevitable) development of resistance. This review provides insights into the mode of action of HMA, mechanisms of resistance to this treatment, and strategies to overcome HMA resistance including next-generation HMA and HMA-based combination therapies.The aim was to establish and evaluate a new clustering method for visual field (VF) test points to predict future VF in retinitis pigmentosa. A Humphrey Field Analyzer 10-2 test was clustered using total deviation values from 858 VFs. We stratified 68 test points into 24 sectors. Then, mean absolute error (MAE) of the sector-wise regression with them (S1) was evaluated using 196 eyes with 10 VF sequences and compared to pointwise linear regression (PLR), mean sensitivity of total area (MS) and also another sector-wise regression basing on VF mapping for glaucoma (29 sectors; S2). MAE with S1 were smaller than with PLR when between the first-third and first-seventh VFs were used. MAE with the method were significantly smaller than those of S2 when between the first-sixth and first-ninth VFs were used. The MAE of MS was smaller than those with S1 only when first to 3rd and first to 4th VFs were used; however, the prediction accuracy became far larger than any other methods when larger number of VFs were used. More accurate prediction was achieved using this new sector-wise regression than with PLR. In addition, the obtained cluster was more useful than that for glaucoma to predict progression.For natural selection to operate there must exist heritable variation among individuals that affects their survival and reproduction. Among free-living microbes, where differences in growth rates largely define selection intensities, competitive exclusion is common. However, among surface attached communities, these dynamics become less predictable. If extreme circumstances were to dictate that a surface population is immortal and all offspring must emigrate, the offspring would be unable to contribute to the composition of the population. Meanwhile, the immortals, regardless of reproductive capacity, would remain unchanged in relative abundance. The normal cycle of birth, death, and competitive exclusion would be broken. https://www.selleckchem.com/products/pf-06826647.html We tested whether conditions required to set up this idealized scenario can be approximated in a microbial biofilm. Using two differentially-reproducing strains of Shewanella oneidensis grown on an anode as the sole terminal electron acceptor - a system in which metabolism is obligately tied to surface attachment - we found that selection against a slow-growing competitor is drastically reduced.
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  • Our analysis of the pharmacokinetic profile of dipraglurant revealed a relatively short half-life, which led us to uncover a peculiar time-course of recovery based on the timing from last dipraglurant injection. Indeed, striatal spiny projection neurons (SPNs) recorded within 2 h from last administration showed full expression of synaptic plasticity, whilst the extent of recovery progressively diminished when SPNs were recorded 4-6 h after treatment. Our findings suggest that distinct dystonia genes may share common signaling pathway dysfunction. More importantly, they indicate that dipraglurant might be a potential novel therapeutic agent for this disabling disorder.Glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system. https://www.selleckchem.com/products/LDE225(NVP-LDE225).html Once released, it binds to specific membrane receptors and transporters activating a wide variety of signal transduction cascades, as well as its removal from the synaptic cleft in order to avoid its extracellular accumulation and the overstimulation of extra-synaptic receptors that might result in neuronal death through a process known as excitotoxicity. Although neurodegenerative diseases are heterogenous in clinical phenotypes and genetic etiologies, a fundamental mechanism involved in neuronal degeneration is excitotoxicity. Glutamate homeostasis is critical for brain physiology and Glutamate transporters are key players in maintaining low extracellular Glutamate levels. Therefore, the characterization of Glutamate transporters has been an active area of glutamatergic research for the last 40 years. Transporter activity its regulated at different levels transcriptional and translational control, transporter protein trafficking and membrane mobility, and through extensive post-translational modifications. The elucidation of these mechanisms has emerged as an important piece to shape our current understanding of glutamate actions in the nervous system.Freeze resistance is critical to successful dormant bud (DB) cryopreservation, and is affected by genotype, environmental conditions, dormancy phase and processing techniques. Pretreatment induced freeze resistance may contribute to more successful and efficient protocols for cryopreserving DB. Differential thermal analysis (DTA) was used to quantify the effects of cryopreservation pretreatments on freeze resistance of dormant budwood. Low temperature exotherm (LTE) profiles created by DTA could rapidly identify pretreatments that are contributing to increased freeze resistance in tree fruit species. In this study, DTA was used to help elucidate the effects of varying pretreatments (sucrose, desiccation and their combination) on peach, a model crop in tree fruit physiology that has shown little cryosurvival using the DB method in the past. Post cryopreservation recovery trials using an antimicrobial forced bud development (AFBD) protocol evaluated the ability of selected pretreatments, that improved freeze remperate woody crops which could be recovered as complete plants by coupling AFBD and plant tissue culture.A prevailing conception of cross-linguistic transfer is that first language experience poses perceptual interference, or at best null effect, on second language speech perception. Surprisingly, a recent study found that Cantonese listeners outperformed English listeners on English stress perception. The present study further evaluated whether segmental variations would constrain the Cantonese advantage on English stress perception. Cantonese and English listeners were tested with both active and passive oddball paradigms in which ERP responses to English stress deviations were elicited. Behaviorally, the Cantonese listeners exhibited a perceptual advantage relative to the English listeners, but this advantage disappeared upon the introduction of segmental variations. Neurophysiologically, segmental variations diminished the P3b amplitudes of the Cantonese but not the English listeners. Collectively, results suggest that segmental variations constrain the Cantonese advantage on English stress perception.Statistical learning, or the ability to extract statistical regularities from the sensory environment, plays a critical role in language acquisition and reading development. Here we employed electroencephalography (EEG) with frequency-tagging measures to track the temporal evolution of speech-structure learning in individuals with reading difficulties due to developmental dyslexia and in typical readers. We measured EEG while participants listened to (a) a structured stream of repeated tri-syllabic pseudowords, (b) a random stream of the same isochronous syllables, and (c) a series of tri-syllabic real Dutch words. Participants' behavioral learning outcome (pseudoword recognition) was measured after training. We found that syllable-rate tracking was comparable between the two groups and stable across both the random and structured streams of syllables. More importantly, we observed a gradual emergence of the tracking of tri-syllabic pseudoword structures in both groups. Compared to the typical readers, however, in the dyslexic readers this implicit speech structure learning seemed to build up at a slower pace. A brain-behavioral correlation analysis showed that slower learners (i.e., participants who were slower in establishing the neural tracking of pseudowords) were less skilled in phonological awareness. Moreover, those who showed stronger neural tracking of real words tended to be less fluent in the visual-verbal conversion of linguistic symbols. Taken together, our study provides an online neurophysiological approach to track the progression of implicit learning processes and gives insights into the learning difficulties associated with dyslexia from a dynamic perspective.Neurological and neuropsychiatric disorders, including addiction, schizophrenia, and Parkinson's disease (PD), involve dysfunction in midbrain dopamine (DA) neurotransmission with severity of disease symptoms and progression associated with disrupted circadian rhythms. The nuclear transcription factor Nurr1, essential for DA neuron (DAN) development, survival, and maintenance, is also known to interact with circadian rhythm regulating clock proteins. In the Nurr1-null heterozygous (+/-) ****, a Nurr1 deficient model which reproduces some of the alterations in DA function found in schizophrenia and PD, we measured, using wheel-running activity, the free running period (tau) and photoperiod entrainment. Because Nurr1 has a role in regulating the DA phenotype, we also measured the circadian fluctuations in the number of DANs using tyrosine hydroxylase (TH) immunofluorescence. In Nurr1 +/- ****, tau was significantly shorter and entrainment to a 6 h earlier shift in the dark cycle was accelerated. The Nurr1 wild-type (+/+) **** cycled DAN numbers across time, with a significantly greater number (∼2-fold increase) of DANs at zeitgeber time (ZT) 0 than ZT12.
    Our analysis of the pharmacokinetic profile of dipraglurant revealed a relatively short half-life, which led us to uncover a peculiar time-course of recovery based on the timing from last dipraglurant injection. Indeed, striatal spiny projection neurons (SPNs) recorded within 2 h from last administration showed full expression of synaptic plasticity, whilst the extent of recovery progressively diminished when SPNs were recorded 4-6 h after treatment. Our findings suggest that distinct dystonia genes may share common signaling pathway dysfunction. More importantly, they indicate that dipraglurant might be a potential novel therapeutic agent for this disabling disorder.Glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system. https://www.selleckchem.com/products/LDE225(NVP-LDE225).html Once released, it binds to specific membrane receptors and transporters activating a wide variety of signal transduction cascades, as well as its removal from the synaptic cleft in order to avoid its extracellular accumulation and the overstimulation of extra-synaptic receptors that might result in neuronal death through a process known as excitotoxicity. Although neurodegenerative diseases are heterogenous in clinical phenotypes and genetic etiologies, a fundamental mechanism involved in neuronal degeneration is excitotoxicity. Glutamate homeostasis is critical for brain physiology and Glutamate transporters are key players in maintaining low extracellular Glutamate levels. Therefore, the characterization of Glutamate transporters has been an active area of glutamatergic research for the last 40 years. Transporter activity its regulated at different levels transcriptional and translational control, transporter protein trafficking and membrane mobility, and through extensive post-translational modifications. The elucidation of these mechanisms has emerged as an important piece to shape our current understanding of glutamate actions in the nervous system.Freeze resistance is critical to successful dormant bud (DB) cryopreservation, and is affected by genotype, environmental conditions, dormancy phase and processing techniques. Pretreatment induced freeze resistance may contribute to more successful and efficient protocols for cryopreserving DB. Differential thermal analysis (DTA) was used to quantify the effects of cryopreservation pretreatments on freeze resistance of dormant budwood. Low temperature exotherm (LTE) profiles created by DTA could rapidly identify pretreatments that are contributing to increased freeze resistance in tree fruit species. In this study, DTA was used to help elucidate the effects of varying pretreatments (sucrose, desiccation and their combination) on peach, a model crop in tree fruit physiology that has shown little cryosurvival using the DB method in the past. Post cryopreservation recovery trials using an antimicrobial forced bud development (AFBD) protocol evaluated the ability of selected pretreatments, that improved freeze remperate woody crops which could be recovered as complete plants by coupling AFBD and plant tissue culture.A prevailing conception of cross-linguistic transfer is that first language experience poses perceptual interference, or at best null effect, on second language speech perception. Surprisingly, a recent study found that Cantonese listeners outperformed English listeners on English stress perception. The present study further evaluated whether segmental variations would constrain the Cantonese advantage on English stress perception. Cantonese and English listeners were tested with both active and passive oddball paradigms in which ERP responses to English stress deviations were elicited. Behaviorally, the Cantonese listeners exhibited a perceptual advantage relative to the English listeners, but this advantage disappeared upon the introduction of segmental variations. Neurophysiologically, segmental variations diminished the P3b amplitudes of the Cantonese but not the English listeners. Collectively, results suggest that segmental variations constrain the Cantonese advantage on English stress perception.Statistical learning, or the ability to extract statistical regularities from the sensory environment, plays a critical role in language acquisition and reading development. Here we employed electroencephalography (EEG) with frequency-tagging measures to track the temporal evolution of speech-structure learning in individuals with reading difficulties due to developmental dyslexia and in typical readers. We measured EEG while participants listened to (a) a structured stream of repeated tri-syllabic pseudowords, (b) a random stream of the same isochronous syllables, and (c) a series of tri-syllabic real Dutch words. Participants' behavioral learning outcome (pseudoword recognition) was measured after training. We found that syllable-rate tracking was comparable between the two groups and stable across both the random and structured streams of syllables. More importantly, we observed a gradual emergence of the tracking of tri-syllabic pseudoword structures in both groups. Compared to the typical readers, however, in the dyslexic readers this implicit speech structure learning seemed to build up at a slower pace. A brain-behavioral correlation analysis showed that slower learners (i.e., participants who were slower in establishing the neural tracking of pseudowords) were less skilled in phonological awareness. Moreover, those who showed stronger neural tracking of real words tended to be less fluent in the visual-verbal conversion of linguistic symbols. Taken together, our study provides an online neurophysiological approach to track the progression of implicit learning processes and gives insights into the learning difficulties associated with dyslexia from a dynamic perspective.Neurological and neuropsychiatric disorders, including addiction, schizophrenia, and Parkinson's disease (PD), involve dysfunction in midbrain dopamine (DA) neurotransmission with severity of disease symptoms and progression associated with disrupted circadian rhythms. The nuclear transcription factor Nurr1, essential for DA neuron (DAN) development, survival, and maintenance, is also known to interact with circadian rhythm regulating clock proteins. In the Nurr1-null heterozygous (+/-) mice, a Nurr1 deficient model which reproduces some of the alterations in DA function found in schizophrenia and PD, we measured, using wheel-running activity, the free running period (tau) and photoperiod entrainment. Because Nurr1 has a role in regulating the DA phenotype, we also measured the circadian fluctuations in the number of DANs using tyrosine hydroxylase (TH) immunofluorescence. In Nurr1 +/- mice, tau was significantly shorter and entrainment to a 6 h earlier shift in the dark cycle was accelerated. The Nurr1 wild-type (+/+) mice cycled DAN numbers across time, with a significantly greater number (∼2-fold increase) of DANs at zeitgeber time (ZT) 0 than ZT12.
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  • nutrition or a vulnerability for developing or maintaining AN.Brain stimulation by electroconvulsive therapy is effective in neuropsychiatric disorders by unknown mechanisms. Microglial toxicity plays key role in neuropsychiatric, neuroinflammatory and degenerative diseases. We examined the mechanism by which electroconvulsive seizures (ECS) regulates microglial phenotype and response to stimuli. Microglial responses were examined by morphological analysis, Iba1 and cytokine expression. ECS did not affect resting microglial phenotype or morphology but regulated their activation by Lipopolysaccharide stimulation. Microglia were isolated after ECS or sham sessions in naïve **** for transcriptome analysis. RNA sequencing identified 141 differentially expressed genes. ECS modulated multiple immune-associated gene families and attenuated neurotoxicity-associated gene expression. Blood brain barrier was examined by injecting Biocytin-TMR tracer. There was no breakdown of the BBB, nor increase in gene-signature of peripheral monocytes, suggesting that ECS effect is mainly on resident microglia. Unbiased analysis of regulatory sequences identified the induction of microglial retinoic acid receptor α (RARα) gene expression and a putative common RARα-binding motif in multiple ECS-upregulated genes. The effects of AM580, a selective RARα agonist on microglial response to LPS was examined in vitro. https://www.selleckchem.com/products/gsk1016790a.html AM580 prevented LPS-induced cytokine expression and reactive oxygen species production. Chronic murine experimental autoimmune encephalomyelitis (EAE) was utilized to confirm the role RARα signaling as mediator of ECS-induced transcriptional pathway in regulating microglial toxicity. Continuous intracerebroventricular delivery of AM580 attenuated effectively EAE severity. In conclusion, ECS regulates CNS innate immune system responses by activating microglial retinoic acid receptor α pathway, signifying a novel therapeutic approach for chronic neuroinflammatory, neuropsychiatric and neurodegenerative diseases.Physical and social environments influence immune homeostasis within adipose tissue, yet the mechanisms remain poorly defined. We report that an enriched environment (EE) housing modulates the immune cell population in white adipose tissue of **** including an increase in the abundance of natural killer (NK) cells. EE upregulates the expression of IL-15 and its receptor IL-15Rα specifically within mature adipocytes. Mechanistically, we show that hypothalamic brain-derived neurotrophic factor (BDNF) upregulates IL-15 production in adipocytes via sympathetic β-adrenergic signaling. Overexpressing BDNF mediated by recombinant adeno-associated virus (rAAV) vector in the hypothalamus expands adipose NK cells. Conversely, inhibition of hypothalamic BDNF signaling via gene transfer of a dominant negative TrkB receptor suppresses adipose NK cells. In white adipose tissue, overexpression of IL-15 using an adipocyte-specific rAAV vector stimulates adipose NK cells and inhibits the progression of subcutaneous melanoma, whereas local IL-15 knockdown blocks the EE effect. These results suggest that bio-behavioral factors regulate adipose NK cells via a hypothalamic BDNF-sympathoneural-adipocyte IL-15 axis. Targeting this pathway may have therapeutic significance for cancer.Stroke is an acute neurological disease with a strong inflammatory component that can be regulated by the intestinal microbiota and intestinal immune cells. Although stroke has been shown to alter immune cell populations in the gut, the dynamics of cell trafficking have not been elucidated. To study the trafficking of gut-derived immune cells after stroke, we used **** expressing the photoconvertible protein Kikume Green-Red, which turns form green to red when exposed to violet light. **** underwent laparotomy and the small intestine was exposed to violet laser light. Immune cells were isolated from the small intestine immediately after photoconversion and 2 days later. Percentage of immune cells (CD45+KikR+) that expressed the red variant of the protein (KikR) was higher immediately after photoconversion than 2 days later, indicating cell egress from the small intestine. To investigate whether intestinal immune cells traffic to the periphery and/or the central nervous system (CNS) after stroke, we analyzed KikR+ immune cells (2 days after photoconversion) in peripheral lymphoid organs, meninges and brain, 3 and 14 days after transient occlusion of the middle cerebral artery (tMCAo) or sham-surgery. Although migration was observed in naïve and sham animals, stroke induced a higher mobilization of gut KikR+ immune cells, especially at 3 days after stroke, to all the organs analyzed. Notably, we detected a significant migration of CD45hi immune cells from the gut to the brain and meninges at 3 days after stroke. Comparison of cell trafficking between organs revealed a significant preference of intestinal CD11c+ cells to migrate from the small intestine to brain and meninges after stroke. We conclude that stroke increases immune cell trafficking from the small intestine to peripheral lymphoid organs and the CNS where they might contribute to post-stroke inflammation.Maternal infection during pregnancy is a known risk factor for offspring mental health disorders. Animal models of maternal immune activation (MIA) have implicated specific cellular and molecular etiologies of psychiatric illness, but most rely on pathogen mimetics. Here, we developed a mouse model of live H3N2 influenza A virus (IAV) infection during pregnancy that induces a robust inflammatory response but is sublethal to both dams and offspring. We observed classic indicators of lung inflammation and severely diminished weight gain in IAV-infected dams. This was accompanied by immune cell infiltration in the placenta and partial breakdown of placental integrity. However, indications of fetal neuroinflammation were absent. Further hallmarks of mimetic-induced MIA, including enhanced circulating maternal IL-17A, were also absent. Respiratory IAV infection did result in an upregulation in intestinal expression of transcription factor RORγt, master regulator of a subset of T lymphocytes, TH17 cells, which are heavily implicated in MIA-induced etiologies.
    nutrition or a vulnerability for developing or maintaining AN.Brain stimulation by electroconvulsive therapy is effective in neuropsychiatric disorders by unknown mechanisms. Microglial toxicity plays key role in neuropsychiatric, neuroinflammatory and degenerative diseases. We examined the mechanism by which electroconvulsive seizures (ECS) regulates microglial phenotype and response to stimuli. Microglial responses were examined by morphological analysis, Iba1 and cytokine expression. ECS did not affect resting microglial phenotype or morphology but regulated their activation by Lipopolysaccharide stimulation. Microglia were isolated after ECS or sham sessions in naïve mice for transcriptome analysis. RNA sequencing identified 141 differentially expressed genes. ECS modulated multiple immune-associated gene families and attenuated neurotoxicity-associated gene expression. Blood brain barrier was examined by injecting Biocytin-TMR tracer. There was no breakdown of the BBB, nor increase in gene-signature of peripheral monocytes, suggesting that ECS effect is mainly on resident microglia. Unbiased analysis of regulatory sequences identified the induction of microglial retinoic acid receptor α (RARα) gene expression and a putative common RARα-binding motif in multiple ECS-upregulated genes. The effects of AM580, a selective RARα agonist on microglial response to LPS was examined in vitro. https://www.selleckchem.com/products/gsk1016790a.html AM580 prevented LPS-induced cytokine expression and reactive oxygen species production. Chronic murine experimental autoimmune encephalomyelitis (EAE) was utilized to confirm the role RARα signaling as mediator of ECS-induced transcriptional pathway in regulating microglial toxicity. Continuous intracerebroventricular delivery of AM580 attenuated effectively EAE severity. In conclusion, ECS regulates CNS innate immune system responses by activating microglial retinoic acid receptor α pathway, signifying a novel therapeutic approach for chronic neuroinflammatory, neuropsychiatric and neurodegenerative diseases.Physical and social environments influence immune homeostasis within adipose tissue, yet the mechanisms remain poorly defined. We report that an enriched environment (EE) housing modulates the immune cell population in white adipose tissue of mice including an increase in the abundance of natural killer (NK) cells. EE upregulates the expression of IL-15 and its receptor IL-15Rα specifically within mature adipocytes. Mechanistically, we show that hypothalamic brain-derived neurotrophic factor (BDNF) upregulates IL-15 production in adipocytes via sympathetic β-adrenergic signaling. Overexpressing BDNF mediated by recombinant adeno-associated virus (rAAV) vector in the hypothalamus expands adipose NK cells. Conversely, inhibition of hypothalamic BDNF signaling via gene transfer of a dominant negative TrkB receptor suppresses adipose NK cells. In white adipose tissue, overexpression of IL-15 using an adipocyte-specific rAAV vector stimulates adipose NK cells and inhibits the progression of subcutaneous melanoma, whereas local IL-15 knockdown blocks the EE effect. These results suggest that bio-behavioral factors regulate adipose NK cells via a hypothalamic BDNF-sympathoneural-adipocyte IL-15 axis. Targeting this pathway may have therapeutic significance for cancer.Stroke is an acute neurological disease with a strong inflammatory component that can be regulated by the intestinal microbiota and intestinal immune cells. Although stroke has been shown to alter immune cell populations in the gut, the dynamics of cell trafficking have not been elucidated. To study the trafficking of gut-derived immune cells after stroke, we used mice expressing the photoconvertible protein Kikume Green-Red, which turns form green to red when exposed to violet light. Mice underwent laparotomy and the small intestine was exposed to violet laser light. Immune cells were isolated from the small intestine immediately after photoconversion and 2 days later. Percentage of immune cells (CD45+KikR+) that expressed the red variant of the protein (KikR) was higher immediately after photoconversion than 2 days later, indicating cell egress from the small intestine. To investigate whether intestinal immune cells traffic to the periphery and/or the central nervous system (CNS) after stroke, we analyzed KikR+ immune cells (2 days after photoconversion) in peripheral lymphoid organs, meninges and brain, 3 and 14 days after transient occlusion of the middle cerebral artery (tMCAo) or sham-surgery. Although migration was observed in naïve and sham animals, stroke induced a higher mobilization of gut KikR+ immune cells, especially at 3 days after stroke, to all the organs analyzed. Notably, we detected a significant migration of CD45hi immune cells from the gut to the brain and meninges at 3 days after stroke. Comparison of cell trafficking between organs revealed a significant preference of intestinal CD11c+ cells to migrate from the small intestine to brain and meninges after stroke. We conclude that stroke increases immune cell trafficking from the small intestine to peripheral lymphoid organs and the CNS where they might contribute to post-stroke inflammation.Maternal infection during pregnancy is a known risk factor for offspring mental health disorders. Animal models of maternal immune activation (MIA) have implicated specific cellular and molecular etiologies of psychiatric illness, but most rely on pathogen mimetics. Here, we developed a mouse model of live H3N2 influenza A virus (IAV) infection during pregnancy that induces a robust inflammatory response but is sublethal to both dams and offspring. We observed classic indicators of lung inflammation and severely diminished weight gain in IAV-infected dams. This was accompanied by immune cell infiltration in the placenta and partial breakdown of placental integrity. However, indications of fetal neuroinflammation were absent. Further hallmarks of mimetic-induced MIA, including enhanced circulating maternal IL-17A, were also absent. Respiratory IAV infection did result in an upregulation in intestinal expression of transcription factor RORγt, master regulator of a subset of T lymphocytes, TH17 cells, which are heavily implicated in MIA-induced etiologies.
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  • Melicope pteleifolia, an important medicinal and horticultural plant, has antipyretic, anti-inflammatory, and analgesic effects. Here, the complete chloroplast genome of M. pteleifolia was sequenced and its phylogenetic relationship was investigated. The complete chloroplast genome of M. pteleifolia was 159,014 bp in size, including a pair of inverted repeat regions (IR, 27,640 bp), a large single copy region (LSC, 85,124 bp), and a small single copy region (SSC, 18,610 bp). The GC content of the chloroplast genome was 38.3%. A total of 133 genes were annotated, including 88 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Phylogenetic analysis revealed that M. pteleifolia clusters together with species of Toddalia, Zanthoxylum, Tetradium, Phellodendron, and Casimiroa.The mudskipper, Boleophthalmus pectinirostris (B. pectinirostris), is an amphibious fish that lives in the intertidal mudflats. It is a cultured economic fish with nutritional and pharmacological value. Here, we report the complete mitochondrial genome sequence of B. pectinirostris, which is 17,111 base pairs (55.3% A + T content) in length and consists of 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and a 1453 bp D-loop region. The complete mitochondrial genome of B. pectinirostris will provide useful genetic information for future phylogenetic and taxonomic classification of B. pectinirostris.Bupleurum euphorbioides is a rare native plant attributed with analgesic, gallbladder-supportive, and other functions in China and the Republic of Korea. However, the complete chloroplast genome sequence of the native plant B. euphorbioides has not been determined. In this study, we sequenced the complete chloroplast genome sequence, and examined the molecular phylogeny and genetic information of B. euphorbioides. The total chloroplast genome of B. euphorbioides was 154,871 bp in length with a large single-copy region (85,089 bp), small single-copy region (17,714 bp), and pair of inverted repeats regions (26,034 bp). The chloroplast genome encoded a total of 176 genes, including 131 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic tree indicated that B. euphorbioides was the most closely related to B. latissimum.Stemona tuberosa Lour is a perennial herb in the family of Stemonaceae. It is commonly used as traditional medicine in China. Here, we assembled and annotated the complete chloroplast genome of S. tuberosa. The chloroplast genome was 154,374 bp in length, containing a typical quadripartite structure with a large single copy (LSC) of 82,305 bp, a small single copy (SSC) of 17,929 bp, and two inverted repeats (IRa and IRb) regions of 27,070 bp each. The overall GC content of the genome was 37.88%. A total of 134 genes were annotated in the chloroplast genome, including 88 protein-coding genes, 38 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis suggested that S. tuberosa was closely related to S. japonica and S. mairei.The complete chloroplast genome sequence of Haplopteris flexuosa, a member of Vittarioideae (family Pteridaceae), was determined. The chloroplast genome of H. flexuosa was 165,664 bp in length with two inverted repeats (32,556 bp) between a large single copy (79,996 bp) and a small single copy (20,556 bp). The GC content was higher than that of related taxa H. elongate, and it was caused by high GC content of expanded regions by insertion of mobile open reading frames in fern organelles (MORFFO) found in the family Pteridaceae. And also, we found that rrn5-rps12 enlarged region of H. flexuosa was similar to MORFFOs of other Pteridaceae.The complete mitochondrial genome of Didesmococcus koreanus is described in this study. The complete mitogenome is a 15,162 bp circular DNA molecule with a high A + T content of 82.5%, containing the typical 37 genes. A novel gene rearrangement is detected in the mitogenome. The phylogenetic result supports the monophyly of Coccoidea and the closer relationship between the Ceroplastinae and Coccinae.Acanthus ilicifolius is an excellent mangrove plant. In this study, the complete chloroplast genome of A. ilicifolius, a salt tolerant plant of Acanthaceae, was generated. The length of chloroplast genome is 150,758 bp, in which the large-single copy region (LSC) is 82,963 bp, the small-single copy (SSC) region is 17,191 bp, and a pair of inverted repeat (IRa and IRb) regions is 25,302 bp. The chloroplast genome contains 128 genes, including 84 protein-coding genes, eight rRNA genes, and 36 tRNAs genes, with a total GC content of 38%. Phylogenetic analysis showed that A. ilicifolius was closely related to A. ebracteatus, both species belonged to Acanthus genus.
    To conduct a clinical study of a family with neurologic symptoms and findings carrying a novel
    mutation and to analyze the molecular consequences of the mutation.

    We analyzed a family with complex neurologic symptoms by MRI and neurologic examinations. Exome sequencing of the
    locus was conducted, and whole-genome sequencing was performed to identify
    ,
    , and
    mutations. Cell lines expressing the normal or NOTCH3
    receptors were analyzed to assess proteolytic processing, cell morphology, receptor routing, and receptor signaling.

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary form of cerebral small vessel disease (SVD) and caused by mutations in the
    gene. Most CADASIL mutations alter the number of cysteine residues in the extracellular domain of the NOTCH3 receptor, but in this article, we describe a family in which some members carry a novel cysteine-sparing NOTCH3 mutation (c.4810 G>A, p.Ala1604Thr). https://www.selleckchem.com/products/Roscovitine.html Two of 3 siblings heterozygous for the NOTCH3
    mutation presented with migraine and white matter lesions (WMLs), the latter of a type related to but distinct from what is normally observed in CADASIL. Two other members instead carried a novel COL4A1 missense mutation (c.4795 G>A; p.(Ala1599Thr)). The NOTCH3
    receptor was aberrantly processed, showed reduced presence at the cell surface, and less efficiently activated Notch downstream target genes.

    We identify a family with migraine and WML in which some members carry a cysteine-sparing hypomorphic
    mutation. Although a causal relationship is not established, we believe that the observations contribute to the discussion on dysregulated Notch signaling in cerebral SVDs.
    We identify a family with migraine and WML in which some members carry a cysteine-sparing hypomorphic NOTCH3 mutation. Although a causal relationship is not established, we believe that the observations contribute to the discussion on dysregulated Notch signaling in cerebral SVDs.
    Melicope pteleifolia, an important medicinal and horticultural plant, has antipyretic, anti-inflammatory, and analgesic effects. Here, the complete chloroplast genome of M. pteleifolia was sequenced and its phylogenetic relationship was investigated. The complete chloroplast genome of M. pteleifolia was 159,014 bp in size, including a pair of inverted repeat regions (IR, 27,640 bp), a large single copy region (LSC, 85,124 bp), and a small single copy region (SSC, 18,610 bp). The GC content of the chloroplast genome was 38.3%. A total of 133 genes were annotated, including 88 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Phylogenetic analysis revealed that M. pteleifolia clusters together with species of Toddalia, Zanthoxylum, Tetradium, Phellodendron, and Casimiroa.The mudskipper, Boleophthalmus pectinirostris (B. pectinirostris), is an amphibious fish that lives in the intertidal mudflats. It is a cultured economic fish with nutritional and pharmacological value. Here, we report the complete mitochondrial genome sequence of B. pectinirostris, which is 17,111 base pairs (55.3% A + T content) in length and consists of 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and a 1453 bp D-loop region. The complete mitochondrial genome of B. pectinirostris will provide useful genetic information for future phylogenetic and taxonomic classification of B. pectinirostris.Bupleurum euphorbioides is a rare native plant attributed with analgesic, gallbladder-supportive, and other functions in China and the Republic of Korea. However, the complete chloroplast genome sequence of the native plant B. euphorbioides has not been determined. In this study, we sequenced the complete chloroplast genome sequence, and examined the molecular phylogeny and genetic information of B. euphorbioides. The total chloroplast genome of B. euphorbioides was 154,871 bp in length with a large single-copy region (85,089 bp), small single-copy region (17,714 bp), and pair of inverted repeats regions (26,034 bp). The chloroplast genome encoded a total of 176 genes, including 131 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic tree indicated that B. euphorbioides was the most closely related to B. latissimum.Stemona tuberosa Lour is a perennial herb in the family of Stemonaceae. It is commonly used as traditional medicine in China. Here, we assembled and annotated the complete chloroplast genome of S. tuberosa. The chloroplast genome was 154,374 bp in length, containing a typical quadripartite structure with a large single copy (LSC) of 82,305 bp, a small single copy (SSC) of 17,929 bp, and two inverted repeats (IRa and IRb) regions of 27,070 bp each. The overall GC content of the genome was 37.88%. A total of 134 genes were annotated in the chloroplast genome, including 88 protein-coding genes, 38 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis suggested that S. tuberosa was closely related to S. japonica and S. mairei.The complete chloroplast genome sequence of Haplopteris flexuosa, a member of Vittarioideae (family Pteridaceae), was determined. The chloroplast genome of H. flexuosa was 165,664 bp in length with two inverted repeats (32,556 bp) between a large single copy (79,996 bp) and a small single copy (20,556 bp). The GC content was higher than that of related taxa H. elongate, and it was caused by high GC content of expanded regions by insertion of mobile open reading frames in fern organelles (MORFFO) found in the family Pteridaceae. And also, we found that rrn5-rps12 enlarged region of H. flexuosa was similar to MORFFOs of other Pteridaceae.The complete mitochondrial genome of Didesmococcus koreanus is described in this study. The complete mitogenome is a 15,162 bp circular DNA molecule with a high A + T content of 82.5%, containing the typical 37 genes. A novel gene rearrangement is detected in the mitogenome. The phylogenetic result supports the monophyly of Coccoidea and the closer relationship between the Ceroplastinae and Coccinae.Acanthus ilicifolius is an excellent mangrove plant. In this study, the complete chloroplast genome of A. ilicifolius, a salt tolerant plant of Acanthaceae, was generated. The length of chloroplast genome is 150,758 bp, in which the large-single copy region (LSC) is 82,963 bp, the small-single copy (SSC) region is 17,191 bp, and a pair of inverted repeat (IRa and IRb) regions is 25,302 bp. The chloroplast genome contains 128 genes, including 84 protein-coding genes, eight rRNA genes, and 36 tRNAs genes, with a total GC content of 38%. Phylogenetic analysis showed that A. ilicifolius was closely related to A. ebracteatus, both species belonged to Acanthus genus. To conduct a clinical study of a family with neurologic symptoms and findings carrying a novel mutation and to analyze the molecular consequences of the mutation. We analyzed a family with complex neurologic symptoms by MRI and neurologic examinations. Exome sequencing of the locus was conducted, and whole-genome sequencing was performed to identify , , and mutations. Cell lines expressing the normal or NOTCH3 receptors were analyzed to assess proteolytic processing, cell morphology, receptor routing, and receptor signaling. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary form of cerebral small vessel disease (SVD) and caused by mutations in the gene. Most CADASIL mutations alter the number of cysteine residues in the extracellular domain of the NOTCH3 receptor, but in this article, we describe a family in which some members carry a novel cysteine-sparing NOTCH3 mutation (c.4810 G>A, p.Ala1604Thr). https://www.selleckchem.com/products/Roscovitine.html Two of 3 siblings heterozygous for the NOTCH3 mutation presented with migraine and white matter lesions (WMLs), the latter of a type related to but distinct from what is normally observed in CADASIL. Two other members instead carried a novel COL4A1 missense mutation (c.4795 G>A; p.(Ala1599Thr)). The NOTCH3 receptor was aberrantly processed, showed reduced presence at the cell surface, and less efficiently activated Notch downstream target genes. We identify a family with migraine and WML in which some members carry a cysteine-sparing hypomorphic mutation. Although a causal relationship is not established, we believe that the observations contribute to the discussion on dysregulated Notch signaling in cerebral SVDs. We identify a family with migraine and WML in which some members carry a cysteine-sparing hypomorphic NOTCH3 mutation. Although a causal relationship is not established, we believe that the observations contribute to the discussion on dysregulated Notch signaling in cerebral SVDs.
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  • Atriofacicular pathways of Mahaim type are typically decrementally conducting accessory pathways without retrograde conduction properties, located on the right ventricular free wall at the tricuspid annulus. We report a patient with an atriofascicular pathway with minimal anterograde decremental conduction. Both long and short V-H antidromic atriofascicular reentrant tachycardias were induced and mechanism confirmed with electrophysiologic testing. Additionally, orthodromic atriofascicular reentrant tachycardia with narrow and right bundle branch block morphologies were inducible. https://www.selleckchem.com/products/hsp990-nvp-hsp990.html Mahaim pathway was successfully ablated with elimination of both antidromic and orthodromic tachycardias.
    Pressure ulcers (PUs) are a serious health problem. They can be considered as an indicator of the quality of health care and are associated with considerable cost increases for the health care system. The prevention of PUs is a major concern in hospital care. The aim of the study was to reveal the current PU prevention-related processes and structures with a specific focus on the Accident and Emergency (A&E) Department.

    In late 2018/early 2019, all German hospitals were invited to participate in a nationwide cross-sectional survey. One standardized questionnaire was assigned to a representative of each hospital. The representative was asked to state what PU-related structures and processes are implemented in their hospital, in general and specific to the A&E department. Besides mostly descriptive analysis, PU-related processes were analysed on PU incidence in a multivariate linear regression model.

    Two hundred seventy-six hospitals participated in the survey. 63.4% (n = 175) of the participating new scientific findings such as the use of local skin protection dressings into clinical practice. Prevention guidelines should be established in all areas of care even for A&E as well as when patients are transferred inside or out of the hospital, where the risk of PU development was considered low.Aging is accompanied by chronic, low-grade systemic inflammation, termed inflammaging, a main driver of age-associated diseases. Such sterile inflammation is typically characterized by elevated levels of pro-inflammatory mediators, such as cytokines, chemokines and reactive oxygen species causing organ damage. Lipid mediators play important roles in the fine-tuning of both the promotion and the resolution of inflammation. Yet, it remains unclear how lipid mediators fit within the concept of inflammaging and how their biosynthesis and function is affected by aging. Here, we provide comprehensive signature profiles of inflammatory markers in organs afflicted with inflammation of young and old C57BL/6 ****. We reveal an organ-specific footprint of inflammation-related cytokines, chemokines and lipid mediators, which are distinctively affected by aging. While some organs are characterized by a pronounced pro-inflammatory microenvironment and impaired resolution during aging, others display elevated levels of pro-resolving mediators or an overall decrease in inflammatory signaling. Our results demonstrate that it proves difficult to establish a unifying concept for alterations of immunomodulatory mediators as consequence of aging and that organ specificity needs to be considered. Moreover, our data imply that inclusion of lipid mediators into the concept of inflammaging provides a comprehensive tool to characterize the inflammatory microenvironment during aging on a broader and yet, more detailed scope.This study assesses and compares the productive efficiency of the national healthcare system of the ASEAN region which includes Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam amidst rising mortality rate from noncommunicable diseases (NCDs) in the Sustainable Development Goals (SDGs) era. Nonparametric data envelopment analysis technique based on the Malmquist Productivity Index is performed and its components, total factor productivity change, technical change and technological change are compared across the region. Two different models are considered in assessing and comparing the technical efficiency of the national healthcare system across the region with life expectancy at birth and mortality rate from NCDs as parallel health care output for both the models. The mean value of total factor productivity is 0.983 and 0.974 which suggests that national healthcare system productivity efficiency decays by 1.7% for Model I and 2.6% for Model II, respectively. This suggests that the health care system inefficiencies across the ASEAN region have not made life expectancy to improve as **** as it should be and curtailed the mortality rate from growing chronic NCDs within a decade. The region is likely to lag behind in achieving SDGs 3 target 4 on reducing by one-third premature mortality from chronic NCDs unless the health care system's technical efficiency is improved across the region. The finding suggests a microlevel study on each country to identify major sources of healthcare system inefficiency in a bid to ameliorate it.Cognitive impairment affects patients suffering from various neuropsychiatric diseases, which are often accompanied by changes in the glutamatergic system. Epidemiological studies indicate that predispositions to the development of neuropsychiatric diseases may be programmed prenatally. Mother's improper diet during pregnancy and lactation may cause fetal abnormalities and, consequently, predispose to diseases in childhood and even adulthood. Considering the prevalence of obesity in developed countries, it seems important to examine the effects of diet on the behavior and physiology of future generations. We hypothesized that exposure to sugar excess in a maternal diet during pregnancy and lactation would affect memory as the NMDA receptor-related processes. Through the manipulation of the sugar amount in the maternal diet in rats, we assessed its effect on offspring's memory. Then, we evaluated if memory alterations were paralleled by molecular changes in NMDA receptors and related modulatory pathways in the prefrontal cortex and the hippocampus of adolescent and young adult female and male offspring.
    Atriofacicular pathways of Mahaim type are typically decrementally conducting accessory pathways without retrograde conduction properties, located on the right ventricular free wall at the tricuspid annulus. We report a patient with an atriofascicular pathway with minimal anterograde decremental conduction. Both long and short V-H antidromic atriofascicular reentrant tachycardias were induced and mechanism confirmed with electrophysiologic testing. Additionally, orthodromic atriofascicular reentrant tachycardia with narrow and right bundle branch block morphologies were inducible. https://www.selleckchem.com/products/hsp990-nvp-hsp990.html Mahaim pathway was successfully ablated with elimination of both antidromic and orthodromic tachycardias. Pressure ulcers (PUs) are a serious health problem. They can be considered as an indicator of the quality of health care and are associated with considerable cost increases for the health care system. The prevention of PUs is a major concern in hospital care. The aim of the study was to reveal the current PU prevention-related processes and structures with a specific focus on the Accident and Emergency (A&E) Department. In late 2018/early 2019, all German hospitals were invited to participate in a nationwide cross-sectional survey. One standardized questionnaire was assigned to a representative of each hospital. The representative was asked to state what PU-related structures and processes are implemented in their hospital, in general and specific to the A&E department. Besides mostly descriptive analysis, PU-related processes were analysed on PU incidence in a multivariate linear regression model. Two hundred seventy-six hospitals participated in the survey. 63.4% (n = 175) of the participating new scientific findings such as the use of local skin protection dressings into clinical practice. Prevention guidelines should be established in all areas of care even for A&E as well as when patients are transferred inside or out of the hospital, where the risk of PU development was considered low.Aging is accompanied by chronic, low-grade systemic inflammation, termed inflammaging, a main driver of age-associated diseases. Such sterile inflammation is typically characterized by elevated levels of pro-inflammatory mediators, such as cytokines, chemokines and reactive oxygen species causing organ damage. Lipid mediators play important roles in the fine-tuning of both the promotion and the resolution of inflammation. Yet, it remains unclear how lipid mediators fit within the concept of inflammaging and how their biosynthesis and function is affected by aging. Here, we provide comprehensive signature profiles of inflammatory markers in organs afflicted with inflammation of young and old C57BL/6 mice. We reveal an organ-specific footprint of inflammation-related cytokines, chemokines and lipid mediators, which are distinctively affected by aging. While some organs are characterized by a pronounced pro-inflammatory microenvironment and impaired resolution during aging, others display elevated levels of pro-resolving mediators or an overall decrease in inflammatory signaling. Our results demonstrate that it proves difficult to establish a unifying concept for alterations of immunomodulatory mediators as consequence of aging and that organ specificity needs to be considered. Moreover, our data imply that inclusion of lipid mediators into the concept of inflammaging provides a comprehensive tool to characterize the inflammatory microenvironment during aging on a broader and yet, more detailed scope.This study assesses and compares the productive efficiency of the national healthcare system of the ASEAN region which includes Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam amidst rising mortality rate from noncommunicable diseases (NCDs) in the Sustainable Development Goals (SDGs) era. Nonparametric data envelopment analysis technique based on the Malmquist Productivity Index is performed and its components, total factor productivity change, technical change and technological change are compared across the region. Two different models are considered in assessing and comparing the technical efficiency of the national healthcare system across the region with life expectancy at birth and mortality rate from NCDs as parallel health care output for both the models. The mean value of total factor productivity is 0.983 and 0.974 which suggests that national healthcare system productivity efficiency decays by 1.7% for Model I and 2.6% for Model II, respectively. This suggests that the health care system inefficiencies across the ASEAN region have not made life expectancy to improve as much as it should be and curtailed the mortality rate from growing chronic NCDs within a decade. The region is likely to lag behind in achieving SDGs 3 target 4 on reducing by one-third premature mortality from chronic NCDs unless the health care system's technical efficiency is improved across the region. The finding suggests a microlevel study on each country to identify major sources of healthcare system inefficiency in a bid to ameliorate it.Cognitive impairment affects patients suffering from various neuropsychiatric diseases, which are often accompanied by changes in the glutamatergic system. Epidemiological studies indicate that predispositions to the development of neuropsychiatric diseases may be programmed prenatally. Mother's improper diet during pregnancy and lactation may cause fetal abnormalities and, consequently, predispose to diseases in childhood and even adulthood. Considering the prevalence of obesity in developed countries, it seems important to examine the effects of diet on the behavior and physiology of future generations. We hypothesized that exposure to sugar excess in a maternal diet during pregnancy and lactation would affect memory as the NMDA receptor-related processes. Through the manipulation of the sugar amount in the maternal diet in rats, we assessed its effect on offspring's memory. Then, we evaluated if memory alterations were paralleled by molecular changes in NMDA receptors and related modulatory pathways in the prefrontal cortex and the hippocampus of adolescent and young adult female and male offspring.
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  • The birth of neuroendocrinology as a scientific discipline is traced **** to 1900-1901, when Joseph Babinski, Alfred Fröhlich, and Harvey Cushing independently identified adiposogenital dystrophy (Fröhlich syndrome), and related gonadal underdevelopment and obesity to a tumor near the pituitary gland. This discovery prompted decades of research into the brain mechanisms responsible for the control of peripheral metabolism and endocrine functions. On the occasion of the 150th anniversary of Fröhlich's birth, this study traces the origins of his intellectual formation and his association with renowned contemporaries in Austria, England, Italy, and finally Cincinnati, Ohio, where he sought refuge after Austria's annexation by **** Germany. Fröhlich interacted with seminal figures in biomedicine, including Lothar von Frankl-Hochwart, Hans Horst Meyer, Ernst Peter Pick, Harvey Cushing, John Newport Langley, and the Nobel laureates Charles Scott Sherrington and Otto Loewi. Alfred Fröhlich, one of the 20th century's most emblematic physicians, left his mark on neurophysiology and neuropharmacology with important works, and published authoritative manuals of drug dispensing and clinical therapy. He confronted the calamities of two World Wars with remarkable resilience like many of his Viennese colleagues who, overcoming the constraints of National Socialism, settled overseas to fulfil their calling as physicians, researchers, and teachers.African Americans (AAs) are 20% more likely to develop serious psychological distress compared to Whites but are less likely to use mental health services. The study objective was to evaluate the effectiveness of recruitment strategies to engage AA fathers in a mental health intervention.Using the community-based participatory research (CBPR) approach, a community-academic partnership (CAP) developed and implemented direct and indirect referral strategies to engage AA fathers in a mental health intervention. Direct referral strategies focused on community partner identification of potentially eligible participants, providing information about the study (i.e., study flyer), and referring potential participants to the study. Indirect referrals included posting flyers in local businesses frequented by AA men, radio advertisements, and social media posts from community organizations.From January to October 2019, 50 direct and 1388 indirect referrals were documented, yielding 24 participants screened and 15 enrolled. Of all participants screened, 58% were referred through indirect referral, 38% were referred directly by community partners, and 4% of the participants were referred through both direct and indirect referrals. Twenty percent of those exposed to the direct referral methods and 1% of those exposed to the indirect referral methods were enrolled. The indirect referrals accounted for 60% of enrollment, whereas the direct referrals accounted for 33.3% of enrollment.Collaborating with the community partners to engage hard-to-reach populations in mental health studies allowed for broad dissemination of recruitment methods, but still resulted in low participant accrual. Additional focus on increasing direct referral methods appears to be a fruitful area of CBPR.
    This article evaluates the evidence for the inclusion of patient narratives in patient decision aids (PtDAs). We define patient narratives as stories, testimonials, or anecdotes that provide illustrative examples of the experiences of others that are relevant to the decision at hand.

    To evaluate the evidence for the effectiveness of narratives in PtDAs, we conducted a narrative scoping review of the literature from January 2013 through June 2019 to identify relevant literature published since the last International Patient Decision Aid Standards (IPDAS) update in 2013. We considered research articles that examined the impact of narratives on relevant outcomes or described relevant theoretical mechanisms.

    The majority of the empirical work on narratives did not measure concepts that are typically found in the PtDA literature (e.g., decisional conflict). https://www.selleckchem.com/products/kt-474.html Yet, a few themes emerged from our review that can be applied to the PtDA context, including the impact of narratives on relevant outcomes (knowledge, benarratives to be a necessary component of PtDAs.
    Personalizing medical treatment decisions based on patient-specific risks and/or preferences can improve health outcomes. Decision makers frequently select treatments based on partial personalization (e.g., personalization based on risks but not preferences or vice versa) due to a lack of data about patient-specific risks and preferences. However, partially personalizing treatment decisions based on a subset of patient risks and/or preferences can result in worse population-level health outcomes than no personalization and can increase the variance of population-level health outcomes.

    We develop a new method for partially personalizing treatment decisions that avoids these problems. Using a case study of antipsychotic treatment for schizophrenia, as well as 4 additional illustrative examples, we demonstrate the adverse effects and our method for avoiding them.

    For the schizophrenia treatment case study, using a previously proposed modeling approach for personalizing treatment decisions and using only a ments for patients should be done in a way that does not decrease expected population-level health outcomes and does not increase their variance, thereby resulting in worse risk-adjusted, population-level health outcomes compared with treatment selection with no personalization. Our method can be used to ensure this, thereby helping patients realize the benefits of treatment personalization without the potential harms.These global consensus recommendations on caries and cavities, as well as evidence that caries is the most prevalent noncommunicable disease (NCD) globally, should be shared throughout institutional, health care professional, industrial, civil society, and patient communities so that the recommendations can be incorporated into policies for achieving a dental cavity-free future. Appropriate inclusion within strategies and action plans globally and locally will accelerate progress toward Making Cavities History, as well as improving NCDs and wider health.
    The birth of neuroendocrinology as a scientific discipline is traced back to 1900-1901, when Joseph Babinski, Alfred Fröhlich, and Harvey Cushing independently identified adiposogenital dystrophy (Fröhlich syndrome), and related gonadal underdevelopment and obesity to a tumor near the pituitary gland. This discovery prompted decades of research into the brain mechanisms responsible for the control of peripheral metabolism and endocrine functions. On the occasion of the 150th anniversary of Fröhlich's birth, this study traces the origins of his intellectual formation and his association with renowned contemporaries in Austria, England, Italy, and finally Cincinnati, Ohio, where he sought refuge after Austria's annexation by Nazi Germany. Fröhlich interacted with seminal figures in biomedicine, including Lothar von Frankl-Hochwart, Hans Horst Meyer, Ernst Peter Pick, Harvey Cushing, John Newport Langley, and the Nobel laureates Charles Scott Sherrington and Otto Loewi. Alfred Fröhlich, one of the 20th century's most emblematic physicians, left his mark on neurophysiology and neuropharmacology with important works, and published authoritative manuals of drug dispensing and clinical therapy. He confronted the calamities of two World Wars with remarkable resilience like many of his Viennese colleagues who, overcoming the constraints of National Socialism, settled overseas to fulfil their calling as physicians, researchers, and teachers.African Americans (AAs) are 20% more likely to develop serious psychological distress compared to Whites but are less likely to use mental health services. The study objective was to evaluate the effectiveness of recruitment strategies to engage AA fathers in a mental health intervention.Using the community-based participatory research (CBPR) approach, a community-academic partnership (CAP) developed and implemented direct and indirect referral strategies to engage AA fathers in a mental health intervention. Direct referral strategies focused on community partner identification of potentially eligible participants, providing information about the study (i.e., study flyer), and referring potential participants to the study. Indirect referrals included posting flyers in local businesses frequented by AA men, radio advertisements, and social media posts from community organizations.From January to October 2019, 50 direct and 1388 indirect referrals were documented, yielding 24 participants screened and 15 enrolled. Of all participants screened, 58% were referred through indirect referral, 38% were referred directly by community partners, and 4% of the participants were referred through both direct and indirect referrals. Twenty percent of those exposed to the direct referral methods and 1% of those exposed to the indirect referral methods were enrolled. The indirect referrals accounted for 60% of enrollment, whereas the direct referrals accounted for 33.3% of enrollment.Collaborating with the community partners to engage hard-to-reach populations in mental health studies allowed for broad dissemination of recruitment methods, but still resulted in low participant accrual. Additional focus on increasing direct referral methods appears to be a fruitful area of CBPR. This article evaluates the evidence for the inclusion of patient narratives in patient decision aids (PtDAs). We define patient narratives as stories, testimonials, or anecdotes that provide illustrative examples of the experiences of others that are relevant to the decision at hand. To evaluate the evidence for the effectiveness of narratives in PtDAs, we conducted a narrative scoping review of the literature from January 2013 through June 2019 to identify relevant literature published since the last International Patient Decision Aid Standards (IPDAS) update in 2013. We considered research articles that examined the impact of narratives on relevant outcomes or described relevant theoretical mechanisms. The majority of the empirical work on narratives did not measure concepts that are typically found in the PtDA literature (e.g., decisional conflict). https://www.selleckchem.com/products/kt-474.html Yet, a few themes emerged from our review that can be applied to the PtDA context, including the impact of narratives on relevant outcomes (knowledge, benarratives to be a necessary component of PtDAs. Personalizing medical treatment decisions based on patient-specific risks and/or preferences can improve health outcomes. Decision makers frequently select treatments based on partial personalization (e.g., personalization based on risks but not preferences or vice versa) due to a lack of data about patient-specific risks and preferences. However, partially personalizing treatment decisions based on a subset of patient risks and/or preferences can result in worse population-level health outcomes than no personalization and can increase the variance of population-level health outcomes. We develop a new method for partially personalizing treatment decisions that avoids these problems. Using a case study of antipsychotic treatment for schizophrenia, as well as 4 additional illustrative examples, we demonstrate the adverse effects and our method for avoiding them. For the schizophrenia treatment case study, using a previously proposed modeling approach for personalizing treatment decisions and using only a ments for patients should be done in a way that does not decrease expected population-level health outcomes and does not increase their variance, thereby resulting in worse risk-adjusted, population-level health outcomes compared with treatment selection with no personalization. Our method can be used to ensure this, thereby helping patients realize the benefits of treatment personalization without the potential harms.These global consensus recommendations on caries and cavities, as well as evidence that caries is the most prevalent noncommunicable disease (NCD) globally, should be shared throughout institutional, health care professional, industrial, civil society, and patient communities so that the recommendations can be incorporated into policies for achieving a dental cavity-free future. Appropriate inclusion within strategies and action plans globally and locally will accelerate progress toward Making Cavities History, as well as improving NCDs and wider health.
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  • The field of genetic counseling in India has enormously transformed over the past few years. Genetic counseling is a communication process which deals with the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. Genetic counseling is not merely having a conversation based on genomic data. It addresses the "information needs" of a particular patient, and customizes a session according to each patient's individual circumstances, thereby aiding in decision-making. In 2012, AIIMS (New *****) became the first tertiary care center in North India to provide genetic counseling for cancer. https://www.selleckchem.com/products/as1842856.html Among 200 cases that were referred for genetic counseling to the AIIMS clinic at the Department of Surgical Disciplines, about 30% of patients chose to undergo testing. Five cases of BRCA1/2 mutation were found conforming to the hereditary breast and ovarian cancer syndrome. There was one case of TP53 mutation conforming to Li-Fraumeni syndrome. One case each of Xeroderma Pigmentosum (XP) and Cowden's syndrome was also detected. All these cases were offered risk-reducing measures and put under life-long surveillance as per protocol. Their family members were also offered genetic counseling and subsequent testing if they agreed. Cancer genetic counseling service was a new exercise, and hence, several challenges were faced. The clinical utility of genetic testing, coupled with counseling, should be established by trials. Documenting the achievements of counseling by surrogate parameters like "improved recruitment rate of patients for genetic tests" and "improved patient satisfaction levels" will go a long way in garnering the **** needed institutional support.CanAssist Breast (CAB) has thus far been validated on a retrospective cohort of 1123 patients who are mostly Indians. Distant metastasis-free survival (DMFS) of more than 95% was observed with significant separation (P  less then  0.0001) between low-risk and high-risk groups. In this study, we demonstrate the usefulness of CAB in guiding physicians to assess risk of cancer recurrence and to make informed treatment decisions for patients. Of more than 500 patients who have undergone CAB test, detailed analysis of 455 patients who were treated based on CAB-based risk predictions by more than 140 doctors across India is presented here. Majority of patients tested had node negative, T2, and grade 2 disease. Age and luminal subtypes did not affect the performance of CAB. On comparison with Adjuvant! Online (AOL), CAB categorized twice the number of patients into low risk indicating potential of overtreatment by AOL-based risk categorization. We assessed the impact of CAB testing on treatment decisions for 254 patients and observed that 92% low-risk patients were not given chemotherapy. Overall, we observed that 88% patients were either given or not given chemotherapy based on whether they were stratified as high risk or low risk for distant recurrence respectively. Based on these results, we conclude that CAB has been accepted by physicians to make treatment planning and provides a cost-effective alternative to other similar multigene prognostic tests currently available.Breast cancer is no longer considered a single disease, and with better understanding of cancer biology, its management has evolved over the years, into a complex individualized use of therapeutics based on variable expressions of predictive and prognostic factors. With the advent of molecular and genetic research, the complexity and diversity of breast cancer cells and their ability to survive and develop resistance to treatment strategies became more evident. At the same time, targeted therapies evolved, as specific targets were discovered such as HER2 receptor, and androgen receptor. More recent is the development of immunotherapy which aims at strengthening the host immune system to identify and kill the tumor cells. In breast cancer treatment, use of molecular tests has been a target of controversies, due to their high costs and inaccessibility in limited resource situations. Research in breast cancer is also proceeding at a rapid pace, but it is important to remember that breast cancer continues to be a complex interplay of alterations at molecular and genetic level, with the variability in expressions at protein level leading to difference in behavior and responses to treatment and overall outcome. In the succeeding paragraphs, we will try to review the available evidence in literature and attempt to understand the molecular complexity of breast cancer in order to simplify the art of treating the disease and improving outcomes.The current COVID-19 pandemic has led to severe disruptions in health care delivery for cancer patients. These interruptions in cancer care delivery may have an unknown effect on cancer outcomes at the individual and population level. These yet to be known variations in individual and population-level cancer outcomes resulting from COVID-19 related interruptions in care can be labeled as COVID-19 Stage Migration (CSM).Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.Hepatic encephalopathy due to portosystemic shunts is a well-defined entity in patients with cirrhosis. Rarely, liver transplant recipients develop hepatic encephalopathy owing to persistence or surgically created portosystemic shunts. We present a case of post-transplant recurrent hepatic encephalopathy due to a surgically created portocaval shunt. The patient was managed by a covered metal stent placement in the inferior vena cava, thus causing functional closure of the shunt.
    The field of genetic counseling in India has enormously transformed over the past few years. Genetic counseling is a communication process which deals with the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. Genetic counseling is not merely having a conversation based on genomic data. It addresses the "information needs" of a particular patient, and customizes a session according to each patient's individual circumstances, thereby aiding in decision-making. In 2012, AIIMS (New Delhi) became the first tertiary care center in North India to provide genetic counseling for cancer. https://www.selleckchem.com/products/as1842856.html Among 200 cases that were referred for genetic counseling to the AIIMS clinic at the Department of Surgical Disciplines, about 30% of patients chose to undergo testing. Five cases of BRCA1/2 mutation were found conforming to the hereditary breast and ovarian cancer syndrome. There was one case of TP53 mutation conforming to Li-Fraumeni syndrome. One case each of Xeroderma Pigmentosum (XP) and Cowden's syndrome was also detected. All these cases were offered risk-reducing measures and put under life-long surveillance as per protocol. Their family members were also offered genetic counseling and subsequent testing if they agreed. Cancer genetic counseling service was a new exercise, and hence, several challenges were faced. The clinical utility of genetic testing, coupled with counseling, should be established by trials. Documenting the achievements of counseling by surrogate parameters like "improved recruitment rate of patients for genetic tests" and "improved patient satisfaction levels" will go a long way in garnering the much needed institutional support.CanAssist Breast (CAB) has thus far been validated on a retrospective cohort of 1123 patients who are mostly Indians. Distant metastasis-free survival (DMFS) of more than 95% was observed with significant separation (P  less then  0.0001) between low-risk and high-risk groups. In this study, we demonstrate the usefulness of CAB in guiding physicians to assess risk of cancer recurrence and to make informed treatment decisions for patients. Of more than 500 patients who have undergone CAB test, detailed analysis of 455 patients who were treated based on CAB-based risk predictions by more than 140 doctors across India is presented here. Majority of patients tested had node negative, T2, and grade 2 disease. Age and luminal subtypes did not affect the performance of CAB. On comparison with Adjuvant! Online (AOL), CAB categorized twice the number of patients into low risk indicating potential of overtreatment by AOL-based risk categorization. We assessed the impact of CAB testing on treatment decisions for 254 patients and observed that 92% low-risk patients were not given chemotherapy. Overall, we observed that 88% patients were either given or not given chemotherapy based on whether they were stratified as high risk or low risk for distant recurrence respectively. Based on these results, we conclude that CAB has been accepted by physicians to make treatment planning and provides a cost-effective alternative to other similar multigene prognostic tests currently available.Breast cancer is no longer considered a single disease, and with better understanding of cancer biology, its management has evolved over the years, into a complex individualized use of therapeutics based on variable expressions of predictive and prognostic factors. With the advent of molecular and genetic research, the complexity and diversity of breast cancer cells and their ability to survive and develop resistance to treatment strategies became more evident. At the same time, targeted therapies evolved, as specific targets were discovered such as HER2 receptor, and androgen receptor. More recent is the development of immunotherapy which aims at strengthening the host immune system to identify and kill the tumor cells. In breast cancer treatment, use of molecular tests has been a target of controversies, due to their high costs and inaccessibility in limited resource situations. Research in breast cancer is also proceeding at a rapid pace, but it is important to remember that breast cancer continues to be a complex interplay of alterations at molecular and genetic level, with the variability in expressions at protein level leading to difference in behavior and responses to treatment and overall outcome. In the succeeding paragraphs, we will try to review the available evidence in literature and attempt to understand the molecular complexity of breast cancer in order to simplify the art of treating the disease and improving outcomes.The current COVID-19 pandemic has led to severe disruptions in health care delivery for cancer patients. These interruptions in cancer care delivery may have an unknown effect on cancer outcomes at the individual and population level. These yet to be known variations in individual and population-level cancer outcomes resulting from COVID-19 related interruptions in care can be labeled as COVID-19 Stage Migration (CSM).Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.Hepatic encephalopathy due to portosystemic shunts is a well-defined entity in patients with cirrhosis. Rarely, liver transplant recipients develop hepatic encephalopathy owing to persistence or surgically created portosystemic shunts. We present a case of post-transplant recurrent hepatic encephalopathy due to a surgically created portocaval shunt. The patient was managed by a covered metal stent placement in the inferior vena cava, thus causing functional closure of the shunt.
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  • EDTA showed the most significant stabilizing effect. Synergism among antioxidants was not observed. Our findings on vitamin D3 instability in aqueous media also correlated with its instability in commercial products. Vitamin D3 aqueous products require proper stabilization, thereby signifying the importance and contribution of the obtained results to the formulation of stable and quality products.Clear cell renal cell carcinoma (ccRCC) is curable when diagnosed at an early stage, but when disease is non-confined it is the urologic cancer with worst prognosis. Antiangiogenic treatment and immune checkpoint inhibition therapy constitute a very promising combined therapy for advanced and metastatic disease. Many exploratory studies have identified epigenetic markers based on DNA methylation, histone modification, and ncRNA expression that epigenetically regulate gene expression in ccRCC. Additionally, epigenetic modifiers genes have been proposed as promising biomarkers for ccRCC. We review and discuss the current understanding of how epigenetic changes determine the main molecular pathways of ccRCC initiation and progression, and also its clinical implications. Despite the extensive research performed, candidate epigenetic biomarkers are not used in clinical practice for several reasons. However, the accumulated body of evidence of developing epigenetically-based biomarkers will likely allow the identification of ccRCC at a higher risk of progression. That will facilitate the establishment of firmer therapeutic decisions in a changing landscape and also monitor active surveillance in the aging population. What is more, a better knowledge of the activities of chromatin modifiers may serve to develop new therapeutic opportunities. Interesting clinical trials on epigenetic treatments for ccRCC associated with well established antiangiogenic treatments and immune checkpoint inhibitors are revisited.MUC16, a sialomucin that contains the ovarian cancer biomarker CA125, binds at low abundance to leucocytes via the immune receptor, Siglec-9. Conventional fluorescence-based imaging techniques lack the sensitivity to assess this low-abundance event, prompting us to develop a novel "digital" optical cytometry technique for qualitative and quantitative assessment of CA125 binding to peripheral blood mononuclear cells (PBMC). Plasmonic nanoparticle labeled detection antibody allows assessment of CA125 at the near-single molecule level when bound to specific immune cell lineages that are simultaneously identified using multiparameter fluorescence imaging. Image analysis and deep learning were used to quantify CA125 per each cell lineage. PBMC from treatment naïve ovarian cancer patients (N = 14) showed higher cell surface abundance of CA125 on the aggregate PBMC population as well as on NK (p = 0.013), T (p less then 0.001) and B cells (p = 0.024) compared to circulating lymphocytes of healthy donors (N = 7). Differences in CA125 binding to monocytes or NK-T cells between the two cohorts were not significant. There was no correlation between the PBMC-bound and serum levels of CA125, suggesting that these two compartments are not in stoichiometric equilibrium. Understanding where and how subset-specific cell-bound surface CA125 takes place may provide guidance towards a new diagnostic biomarker in ovarian cancer.Cholangiocarcinomas (CCAs) are a heterogeneous group of tumors that arise from the biliary tract. Jaundice is a common clinical presentation; however, the prognostic impact of this symptom is poorly understood, and current management recommendations lack solid evidence. https://www.selleckchem.com/products/R406.html We aim to assess the clinical outcomes and predictive factors of CCA patients presenting with jaundice in the Emergency Room (ER). We retrospectively analyzed all consecutive ER cases presenting with jaundice between January 2010 and December 2017. During the study period, 403,766 patients were admitted to the ER, 1217 (0.3%) presented with jaundice, and in 200 (0.049%), the diagnosis was CCA. CCA cases increased during the study period (p for trend 0.026). Most of them presented with advance disease (stage III 46.5%, stage IV 43.5%) and median survival was 4.5 months (95% CI 3.4-6.0). Factors associated with better survival were age, stage of disease, presence of jaundice at the moment of diagnosis, and lack of concomitant viral hepatitis. A nomogram was constructed that significantly predicts 1-month, 6-month, and 1-year survival after patients' admission. In conclusion, the majority of CCA patients presenting with jaundice to the ER have advanced disease and poor prognosis. Risk stratification of these patients can allow tailored management.The RAV family is part of the B3 superfamily and is one of the most abundant transcription factor families in plants. Members have highly conserved B3 or AP2 DNA binding domains. Although the RAV family genes of several species have been systematically identified from genome-wide studies, there has been no comprehensive study to identify rice RAV family genes. Here, we identified 15 genes of the RAV family in the rice genome and analyzed their phylogenetic relationships, gene structure, conserved domains, and chromosomal distribution. Based on domain similarity and phylogenetic topology, rice RAV transcription factors were phylogenetically clustered into four groups. qRT-PCR analyses showed that expression of these RAV genes was significantly up-regulated or down-regulated by plant hormone treatments, including BL, NAA, IAA, MeJA, and SA. Most of the rice RAV genes were dramatically down-regulated in response to rice stripe virus (RSV) and mostly up-regulated in response to Southern rice black-streaked dwarf virus (SRBSDV). These results suggest that the rice RAV genes are involved in diverse signaling pathways and in varied responses to virus infection.Studies have explored how vitamin B12 status affects sleep among elders and children, but this remains to be investigated among young adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess the association between serum vitamin B12 and sleep among female college students in Saudi Arabia. In this cross-sectional study, we enrolled 355 participants (age (years), 20.7 ± 1.5; body mass index, 23.6 kg/m2 ± 5.2) at King Saud University, Riyadh, Saudi Arabia. Fasting blood samples were analyzed regarding the serum vitamin B12 and blood lipids. Anthropometric, socio-demographic, clinical history, stress, physical activity, and dietary data were collected. We assessed the sleep statuses of the participants using the PSQI. Around 72% of the participants were "poor" sleepers (PSQI > 5). Subgroup analysis within the tertiles showed that participants with higher vitamin B12 in the second and third tertiles reported better scores for sleep quality (B ± SE = -12.7 ± 5.6, p = 0.03; B ± SE = -32.7 ± 16.4, p = 0.05, respectively) and also reported a lower use of sleep medication (B ± SE = -21.
    EDTA showed the most significant stabilizing effect. Synergism among antioxidants was not observed. Our findings on vitamin D3 instability in aqueous media also correlated with its instability in commercial products. Vitamin D3 aqueous products require proper stabilization, thereby signifying the importance and contribution of the obtained results to the formulation of stable and quality products.Clear cell renal cell carcinoma (ccRCC) is curable when diagnosed at an early stage, but when disease is non-confined it is the urologic cancer with worst prognosis. Antiangiogenic treatment and immune checkpoint inhibition therapy constitute a very promising combined therapy for advanced and metastatic disease. Many exploratory studies have identified epigenetic markers based on DNA methylation, histone modification, and ncRNA expression that epigenetically regulate gene expression in ccRCC. Additionally, epigenetic modifiers genes have been proposed as promising biomarkers for ccRCC. We review and discuss the current understanding of how epigenetic changes determine the main molecular pathways of ccRCC initiation and progression, and also its clinical implications. Despite the extensive research performed, candidate epigenetic biomarkers are not used in clinical practice for several reasons. However, the accumulated body of evidence of developing epigenetically-based biomarkers will likely allow the identification of ccRCC at a higher risk of progression. That will facilitate the establishment of firmer therapeutic decisions in a changing landscape and also monitor active surveillance in the aging population. What is more, a better knowledge of the activities of chromatin modifiers may serve to develop new therapeutic opportunities. Interesting clinical trials on epigenetic treatments for ccRCC associated with well established antiangiogenic treatments and immune checkpoint inhibitors are revisited.MUC16, a sialomucin that contains the ovarian cancer biomarker CA125, binds at low abundance to leucocytes via the immune receptor, Siglec-9. Conventional fluorescence-based imaging techniques lack the sensitivity to assess this low-abundance event, prompting us to develop a novel "digital" optical cytometry technique for qualitative and quantitative assessment of CA125 binding to peripheral blood mononuclear cells (PBMC). Plasmonic nanoparticle labeled detection antibody allows assessment of CA125 at the near-single molecule level when bound to specific immune cell lineages that are simultaneously identified using multiparameter fluorescence imaging. Image analysis and deep learning were used to quantify CA125 per each cell lineage. PBMC from treatment naïve ovarian cancer patients (N = 14) showed higher cell surface abundance of CA125 on the aggregate PBMC population as well as on NK (p = 0.013), T (p less then 0.001) and B cells (p = 0.024) compared to circulating lymphocytes of healthy donors (N = 7). Differences in CA125 binding to monocytes or NK-T cells between the two cohorts were not significant. There was no correlation between the PBMC-bound and serum levels of CA125, suggesting that these two compartments are not in stoichiometric equilibrium. Understanding where and how subset-specific cell-bound surface CA125 takes place may provide guidance towards a new diagnostic biomarker in ovarian cancer.Cholangiocarcinomas (CCAs) are a heterogeneous group of tumors that arise from the biliary tract. Jaundice is a common clinical presentation; however, the prognostic impact of this symptom is poorly understood, and current management recommendations lack solid evidence. https://www.selleckchem.com/products/R406.html We aim to assess the clinical outcomes and predictive factors of CCA patients presenting with jaundice in the Emergency Room (ER). We retrospectively analyzed all consecutive ER cases presenting with jaundice between January 2010 and December 2017. During the study period, 403,766 patients were admitted to the ER, 1217 (0.3%) presented with jaundice, and in 200 (0.049%), the diagnosis was CCA. CCA cases increased during the study period (p for trend 0.026). Most of them presented with advance disease (stage III 46.5%, stage IV 43.5%) and median survival was 4.5 months (95% CI 3.4-6.0). Factors associated with better survival were age, stage of disease, presence of jaundice at the moment of diagnosis, and lack of concomitant viral hepatitis. A nomogram was constructed that significantly predicts 1-month, 6-month, and 1-year survival after patients' admission. In conclusion, the majority of CCA patients presenting with jaundice to the ER have advanced disease and poor prognosis. Risk stratification of these patients can allow tailored management.The RAV family is part of the B3 superfamily and is one of the most abundant transcription factor families in plants. Members have highly conserved B3 or AP2 DNA binding domains. Although the RAV family genes of several species have been systematically identified from genome-wide studies, there has been no comprehensive study to identify rice RAV family genes. Here, we identified 15 genes of the RAV family in the rice genome and analyzed their phylogenetic relationships, gene structure, conserved domains, and chromosomal distribution. Based on domain similarity and phylogenetic topology, rice RAV transcription factors were phylogenetically clustered into four groups. qRT-PCR analyses showed that expression of these RAV genes was significantly up-regulated or down-regulated by plant hormone treatments, including BL, NAA, IAA, MeJA, and SA. Most of the rice RAV genes were dramatically down-regulated in response to rice stripe virus (RSV) and mostly up-regulated in response to Southern rice black-streaked dwarf virus (SRBSDV). These results suggest that the rice RAV genes are involved in diverse signaling pathways and in varied responses to virus infection.Studies have explored how vitamin B12 status affects sleep among elders and children, but this remains to be investigated among young adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess the association between serum vitamin B12 and sleep among female college students in Saudi Arabia. In this cross-sectional study, we enrolled 355 participants (age (years), 20.7 ± 1.5; body mass index, 23.6 kg/m2 ± 5.2) at King Saud University, Riyadh, Saudi Arabia. Fasting blood samples were analyzed regarding the serum vitamin B12 and blood lipids. Anthropometric, socio-demographic, clinical history, stress, physical activity, and dietary data were collected. We assessed the sleep statuses of the participants using the PSQI. Around 72% of the participants were "poor" sleepers (PSQI > 5). Subgroup analysis within the tertiles showed that participants with higher vitamin B12 in the second and third tertiles reported better scores for sleep quality (B ± SE = -12.7 ± 5.6, p = 0.03; B ± SE = -32.7 ± 16.4, p = 0.05, respectively) and also reported a lower use of sleep medication (B ± SE = -21.
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  • Duohua huangjing (Polygonatum cyrtonema Hua) seedling basal stem rot caused by Fusarium redolens in China Tao Tang1, Fanfan Wang1, Jie Guo1, Xiaoliang Guo1, Yuanyuan Duan1,Jingmao You1* 1 Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi, 445000, China. Duohua huangjing (Polygonatum cyrtonema Hua), a herbal medicine, that is mostly planted in several provinces in China. In April 2020, severe diseases with about 40% seedling losse was found in the Huangjing seedling base in Shiyan city, Hubei province. The symptoms included softening and decay of the roots and stem bases, a progressive yellowing and wilting of leaves, and finally being completely rotted. Small pieces of symptomatic stems (0.5 cm in length) and leaves (0.5 × 0.5 cm in size) were surface sterilized with 75% ethanol for 30 s, followed by 0.1% HgCl2 for 1 min, rinsed three times with sterile water, and then dried with sterilized absorbent paper. The sections were placed on potato dextrose agar (PDA) medium contai China, Ministry of Agriculture, P. R. China / Hubei Key Laboratory of Crop Disease, Insect Pests and Weeds Control (grant no.2020ZTSJJ6).Plumeria alba L. is a flowering plant in the family Apocynaceae and widely cultivated in Malaysia as a cosmopolitan ornamental plant. In January 2020, anthracnose lesions were observed on leaves of Plumeria alba planted in Agricultural Farm, Universiti Putra Malaysia, in Selangor state, Malaysia. The disease mainly affected the leaves with symptoms occurring with approximately a 60% disease incidence. Ten symptomatic leaves were sampled from 3 different trees in the farm. Symptoms initiated as small circular necrotic spots that rapidly enlarged into black lesions with pale brown borders. Diseased tissues (5×5 mm) were surface-sterilized with 70% ethanol for 1 min, rinsed three times with sterile distilled water, dried on sterile filter papers, plated on PDA and, incubated at 25 °C with a 12-h photoperiod. A total of seven single-spore isolates with similar colony morphologies were obtained from tissue samples. After 7 days, the colonies raised the entire margin and showed white-to-gray aerial mycelium, orangenthracnose symptoms were observed on all inoculated leaves after 3 days, whereas controls showed no symptoms. Fungal isolates from the diseased leaves showed the same morphological characteristics as isolates PL3 and PL4, confirming Koch's postulates. C. siamense has been reported causing anthracnose on rose (Rosa chinensis) in China (Feng et al. 2019), Coffea arabica in Thailand (Prihastuti et al. 2009) and mango leaf anthracnose in Vietnam (Li et al. 2020). To our knowledge, this is the first report of Colletrotrichum siamense causing leaf anthracnose on Plumeria alba in Malaysia. Accurate identification of this pathogen provides a foundation in controlling anthracnose disease on Plumeria alba.Plum pox or Sharka disease, caused by infection with plum pox virus (PPV), results in enormous economic losses to the stone fruit industry. However, the frequency and distribution of PPV remains unclear in China, the world's largest stone fruit producer. Systemic visual surveys were performed on stone fruit trees in China from 2008 to 2018, and the results suggest that plum pox disease is widely distributed on common apricots (Prunus armeniaca) and Japanese apricots (P. mume), with an average symptoms incidence rate >30% in the latter. In samples collected from Beijing, Nanjing, Shanghai, Wuhan, Wuxi, and Yuncheng, PPV was detected in 77% (85 out of 110) of collected samples by immunochromatographic (IC) strip tests and RT-PCR, and 96% (67 out of 70) of samples showing Sharka symptoms were PPV-positive. Transmission electron microscopy revealed filamentous particles of ~640 × 12.5 nm (n = 19) in size, and pinwheel inclusions in symptomatic plants, but not in the asymptomatic and PPV negative plant. Full-length genomes were determined for four isolates (three from Japanese apricot and one from common apricot), and phylogenetic analyses indicated that all four isolates belong to a clade PPV-D, despite slight differences in genome size. These findings not only highlight the widespread occurrence and distribution of PPV in China, but also provide detailed information about the genomic characteristics and evolutionary position of PPV isolates in China.Walnut bacterial blight caused by Xanthomonas arboricola pv. juglandis (Xaj) has serious repercussions for walnut production around the world. Between 2015 and 2017, disease samples were collected from six counties (Danjiangkou, Baokang, Suizhou, Shennongjia, Zigui, and Xingshan) in Hubei province, China. Fifty-nine Xaj strains were identified by morphology and specific PCR primers from 206 isolates. The genetic diversity of 60 Xaj strains (59 from Hubei plus one from Beijing) was evaluated by Multilocus Sequence Analysis (MLST), and their resistance to copper ion (Cu2+) treatment was determined. A Neighbor Joining phylogenetic dendrogram was constructed based on four sequences of housekeeping genes (atpD-dnaK-glnA-gyrB). Two groups of strains were identified whose clustering was consistent with that of glnA. The minimal inhibitory concentration of copper ion on representative Xaj strain DW3F3 (the first genome sequenced Xaj from China) was 115 μg/ml. Setting the copper resistant threshold value to 125 μg/ml, 47 and 13 strains were considered sensitive and resistant to Cu2+, respectively. Furthermore, five strains showed Cu2+ resistance at 270 μg/ml. Compared to the copB from sensitive strains, the copB gene in resistant strains had a 15-bp insertion and eight scattered single nucleotide polymorphisms. https://www.selleckchem.com/products/glesatinib.html Interestingly, the clustering based on MLSA was distinct between Xaj copper ion resistant and sensitive strains.In 2020, severely infected fruit of pecan, Carya illinoiensis, showing distinct anthracnose symptoms were observed from pecan orchards in Uiseong (36°21'31.5"N 128°27'15.9"E) and Miryang (35°22'54.9"N 128°48'06.5"E) in South Korea. Visible symptoms occurred on fruit of the tree between June and July, which included dark, depressed and covered with irregularly shaped lesions. As the disease progressed, the lesions expanded and merged over time, leading to abscission of the fruit, which resulted in severe yield loss of pecan fruit. Of pecan varieties including Caddo, Giles and Peruque that were cultivated in each pecan orchard, Caddo appeared to be most susceptible to the disease. Estimated losses were approximately 30% and 70% for the Uiseong and Miryang pecan orchard, respectively. For pathogen isolation, ten symptomatic fruits of pecan were randomly collected and brought to the laboratory. The fruits were surface disinfested for 30 s with 70% ethanol and 1% sodium hypochlorite. These were then rinsed with sterile distilled water twice, placed in a humid chamber, and incubated at 25 ± 1°C with a photoperiod of 12 h.
    Duohua huangjing (Polygonatum cyrtonema Hua) seedling basal stem rot caused by Fusarium redolens in China Tao Tang1, Fanfan Wang1, Jie Guo1, Xiaoliang Guo1, Yuanyuan Duan1,Jingmao You1* 1 Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi, 445000, China. Duohua huangjing (Polygonatum cyrtonema Hua), a herbal medicine, that is mostly planted in several provinces in China. In April 2020, severe diseases with about 40% seedling losse was found in the Huangjing seedling base in Shiyan city, Hubei province. The symptoms included softening and decay of the roots and stem bases, a progressive yellowing and wilting of leaves, and finally being completely rotted. Small pieces of symptomatic stems (0.5 cm in length) and leaves (0.5 × 0.5 cm in size) were surface sterilized with 75% ethanol for 30 s, followed by 0.1% HgCl2 for 1 min, rinsed three times with sterile water, and then dried with sterilized absorbent paper. The sections were placed on potato dextrose agar (PDA) medium contai China, Ministry of Agriculture, P. R. China / Hubei Key Laboratory of Crop Disease, Insect Pests and Weeds Control (grant no.2020ZTSJJ6).Plumeria alba L. is a flowering plant in the family Apocynaceae and widely cultivated in Malaysia as a cosmopolitan ornamental plant. In January 2020, anthracnose lesions were observed on leaves of Plumeria alba planted in Agricultural Farm, Universiti Putra Malaysia, in Selangor state, Malaysia. The disease mainly affected the leaves with symptoms occurring with approximately a 60% disease incidence. Ten symptomatic leaves were sampled from 3 different trees in the farm. Symptoms initiated as small circular necrotic spots that rapidly enlarged into black lesions with pale brown borders. Diseased tissues (5×5 mm) were surface-sterilized with 70% ethanol for 1 min, rinsed three times with sterile distilled water, dried on sterile filter papers, plated on PDA and, incubated at 25 °C with a 12-h photoperiod. A total of seven single-spore isolates with similar colony morphologies were obtained from tissue samples. After 7 days, the colonies raised the entire margin and showed white-to-gray aerial mycelium, orangenthracnose symptoms were observed on all inoculated leaves after 3 days, whereas controls showed no symptoms. Fungal isolates from the diseased leaves showed the same morphological characteristics as isolates PL3 and PL4, confirming Koch's postulates. C. siamense has been reported causing anthracnose on rose (Rosa chinensis) in China (Feng et al. 2019), Coffea arabica in Thailand (Prihastuti et al. 2009) and mango leaf anthracnose in Vietnam (Li et al. 2020). To our knowledge, this is the first report of Colletrotrichum siamense causing leaf anthracnose on Plumeria alba in Malaysia. Accurate identification of this pathogen provides a foundation in controlling anthracnose disease on Plumeria alba.Plum pox or Sharka disease, caused by infection with plum pox virus (PPV), results in enormous economic losses to the stone fruit industry. However, the frequency and distribution of PPV remains unclear in China, the world's largest stone fruit producer. Systemic visual surveys were performed on stone fruit trees in China from 2008 to 2018, and the results suggest that plum pox disease is widely distributed on common apricots (Prunus armeniaca) and Japanese apricots (P. mume), with an average symptoms incidence rate >30% in the latter. In samples collected from Beijing, Nanjing, Shanghai, Wuhan, Wuxi, and Yuncheng, PPV was detected in 77% (85 out of 110) of collected samples by immunochromatographic (IC) strip tests and RT-PCR, and 96% (67 out of 70) of samples showing Sharka symptoms were PPV-positive. Transmission electron microscopy revealed filamentous particles of ~640 × 12.5 nm (n = 19) in size, and pinwheel inclusions in symptomatic plants, but not in the asymptomatic and PPV negative plant. Full-length genomes were determined for four isolates (three from Japanese apricot and one from common apricot), and phylogenetic analyses indicated that all four isolates belong to a clade PPV-D, despite slight differences in genome size. These findings not only highlight the widespread occurrence and distribution of PPV in China, but also provide detailed information about the genomic characteristics and evolutionary position of PPV isolates in China.Walnut bacterial blight caused by Xanthomonas arboricola pv. juglandis (Xaj) has serious repercussions for walnut production around the world. Between 2015 and 2017, disease samples were collected from six counties (Danjiangkou, Baokang, Suizhou, Shennongjia, Zigui, and Xingshan) in Hubei province, China. Fifty-nine Xaj strains were identified by morphology and specific PCR primers from 206 isolates. The genetic diversity of 60 Xaj strains (59 from Hubei plus one from Beijing) was evaluated by Multilocus Sequence Analysis (MLST), and their resistance to copper ion (Cu2+) treatment was determined. A Neighbor Joining phylogenetic dendrogram was constructed based on four sequences of housekeeping genes (atpD-dnaK-glnA-gyrB). Two groups of strains were identified whose clustering was consistent with that of glnA. The minimal inhibitory concentration of copper ion on representative Xaj strain DW3F3 (the first genome sequenced Xaj from China) was 115 μg/ml. Setting the copper resistant threshold value to 125 μg/ml, 47 and 13 strains were considered sensitive and resistant to Cu2+, respectively. Furthermore, five strains showed Cu2+ resistance at 270 μg/ml. Compared to the copB from sensitive strains, the copB gene in resistant strains had a 15-bp insertion and eight scattered single nucleotide polymorphisms. https://www.selleckchem.com/products/glesatinib.html Interestingly, the clustering based on MLSA was distinct between Xaj copper ion resistant and sensitive strains.In 2020, severely infected fruit of pecan, Carya illinoiensis, showing distinct anthracnose symptoms were observed from pecan orchards in Uiseong (36°21'31.5"N 128°27'15.9"E) and Miryang (35°22'54.9"N 128°48'06.5"E) in South Korea. Visible symptoms occurred on fruit of the tree between June and July, which included dark, depressed and covered with irregularly shaped lesions. As the disease progressed, the lesions expanded and merged over time, leading to abscission of the fruit, which resulted in severe yield loss of pecan fruit. Of pecan varieties including Caddo, Giles and Peruque that were cultivated in each pecan orchard, Caddo appeared to be most susceptible to the disease. Estimated losses were approximately 30% and 70% for the Uiseong and Miryang pecan orchard, respectively. For pathogen isolation, ten symptomatic fruits of pecan were randomly collected and brought to the laboratory. The fruits were surface disinfested for 30 s with 70% ethanol and 1% sodium hypochlorite. These were then rinsed with sterile distilled water twice, placed in a humid chamber, and incubated at 25 ± 1°C with a photoperiod of 12 h.
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  • Point shear-wave elastography (pSWE) is a new method to assess the degree of liver fibrosis. It has been shown to be effective in detecting stiffness in viral hepatitis.

    To determine the feasibility of pSWE for assessing liver stiffness and fibrosis in liver diseases of different etiologies.

    This prospective single-center study included a population of adult patients with chronic liver diseases from different etiologies, who were scheduled for liver biopsy, and a control group of healthy adults who prospectively underwent pSWE. Ten consecutive pSWE measurements of the liver were performed using a Philips iU22 ultrasound system. Stiffness degree was compared to liver biopsy results. Fibrosis degree was staged according to METAVIR scoring system.

    The study group was comprised of 202 patients who underwent liver biopsy and pSWE test and a control group consisting of 14 healthy adults who underwent pSWE for validation. In the study group, the median stiffness was 5.35 ± 3.37 kilopascal (kPa). The median stiffness for F0-1, F2, F3, and F4 as determined by liver biopsy results were 4.9 kPa, 5.4 kPa, 5.7 kPa, and 8 kPa, respectively. The median stiffness in the control group was 3.7 ± 0.6 kPa. Subgroup analyses were conducted for viral hepatitis vs. non-viral hepatitis and steatohepatitis vs. non-steatohepatitis groups.

    pSWE is a reproducible method for assessing liver stiffness and is in a linear relationship with fibrosis degree as seen in pathology. Compared with patients with non-significant fibrosis, healthy controls showed significantly lower values.
    pSWE is a reproducible method for assessing liver stiffness and is in a linear relationship with fibrosis degree as seen in pathology. Compared with patients with non-significant fibrosis, healthy controls showed significantly lower values.
    The coronavirus disease-2019 (COVID-19) social-distancing strategy, including 7 weeks of strict lockdown, enabled an extraordinary test of stay-at-home regulations, which forced a sedentary lifestyle on all children and adolescents.

    To assess the lockdown effect on pediatric weight.

    A retrospective-prospective cohort study at our hospital's pediatric outpatient clinics following the COVID-19 lockdown. Patients aged 0-18 years visiting the clinic were weighed and previous weight and other clinical data were collected from the medical charts. Weight-percentile-for-age standardization was calculated according to the U.S. Centers for Disease Control and Prevention and the World Health Organization growth tables. Pre- and post-lockdown weight-percentiles-for-age were compared using paired t-test. Multivariate analysis was conducted using linear regression model.

    The study was comprised of 229 patients; 117/229 (51.1%) were boys, 60/229 (26.2%) aged under 6 years. Total mean weight-percentile was significantly higher following the lockdown (40.44 vs. 38.82, respectively, P = 0.029). Boys had a significant post-lockdown weight-percentile rise (37.66 vs. 34.42, P = 0.014), whereas girls had higher baseline pre-quarantine weight-percentile of 43.42, which did not change. Patients younger than 6 years had a significant increase in weight-percentiles (39.18 vs. 33.58, P = 0.021). In multivariate analysis these correlations were preserved.
    The study was comprised of 229 patients; 117/229 (51.1%) were boys, 60/229 (26.2%) aged under 6 years. https://www.selleckchem.com/products/pfk158.html Total mean weight-percentile was significantly higher following the lockdown (40.44 vs. 38.82, respectively, P = 0.029). Boys had a significant post-lockdown weight-percentile rise (37.66 vs. 34.42, P = 0.014), whereas girls had higher baseline pre-quarantine weight-percentile of 43.42, which did not change. Patients younger than 6 years had a significant increase in weight-percentiles (39.18 vs. 33.58, P = 0.021). In multivariate analysis these correlations were preserved.
    The effect of extended shift length on pediatric residency is controversial. Israeli residents perform shifts extending up to 26 hours, a practice leading to general dissatisfaction. In early 2020, during the coronavirus disease-2019 (COVID-19) pandemic, many Israeli hospitals transitioned from 26-hour shifts to 13-hour shifts in fixed teams (capsules) followed by a 24-hour rest period at home. The regulation changes enacted by the Israeli government during the COVID-19 pandemic provided a rare opportunity to assess perception by residents regarding length of shifts before and after the change.

    To assess perception of pediatric residency in three aspects resident wellness, ability to deliver quality healthcare, and acquisition of medical education following the change to the shorter shifts model.

    We performed a prospective observational study among pediatric residents. Residents completed an online self-assessment questionnaire before and after the COVID-19 emergency regulations changed toward shorter shifts.

    Sixty-seven residents answered the questionnaires before (37) and after (30) the shift changes. The average score was significantly better for the 13-hour shifts versus the 26-hour shifts, except for questions regarding available time for research. There was a positive perception regarding the shorter night shifts model among pediatric residents, with an increase in general satisfaction and improvement in perception of general wellness, ability to deliver quality healthcare, and medical education acquisition.

    Following the change to shorter shift length, perception of pediatric residents included improvement in wellness, ability to deliver quality healthcare, and availability of medical education.
    Following the change to shorter shift length, perception of pediatric residents included improvement in wellness, ability to deliver quality healthcare, and availability of medical education.
    Coronavirus disease-2019 (COVID-19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series.
    Coronavirus disease-2019 (COVID-19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic.
    Point shear-wave elastography (pSWE) is a new method to assess the degree of liver fibrosis. It has been shown to be effective in detecting stiffness in viral hepatitis. To determine the feasibility of pSWE for assessing liver stiffness and fibrosis in liver diseases of different etiologies. This prospective single-center study included a population of adult patients with chronic liver diseases from different etiologies, who were scheduled for liver biopsy, and a control group of healthy adults who prospectively underwent pSWE. Ten consecutive pSWE measurements of the liver were performed using a Philips iU22 ultrasound system. Stiffness degree was compared to liver biopsy results. Fibrosis degree was staged according to METAVIR scoring system. The study group was comprised of 202 patients who underwent liver biopsy and pSWE test and a control group consisting of 14 healthy adults who underwent pSWE for validation. In the study group, the median stiffness was 5.35 ± 3.37 kilopascal (kPa). The median stiffness for F0-1, F2, F3, and F4 as determined by liver biopsy results were 4.9 kPa, 5.4 kPa, 5.7 kPa, and 8 kPa, respectively. The median stiffness in the control group was 3.7 ± 0.6 kPa. Subgroup analyses were conducted for viral hepatitis vs. non-viral hepatitis and steatohepatitis vs. non-steatohepatitis groups. pSWE is a reproducible method for assessing liver stiffness and is in a linear relationship with fibrosis degree as seen in pathology. Compared with patients with non-significant fibrosis, healthy controls showed significantly lower values. pSWE is a reproducible method for assessing liver stiffness and is in a linear relationship with fibrosis degree as seen in pathology. Compared with patients with non-significant fibrosis, healthy controls showed significantly lower values. The coronavirus disease-2019 (COVID-19) social-distancing strategy, including 7 weeks of strict lockdown, enabled an extraordinary test of stay-at-home regulations, which forced a sedentary lifestyle on all children and adolescents. To assess the lockdown effect on pediatric weight. A retrospective-prospective cohort study at our hospital's pediatric outpatient clinics following the COVID-19 lockdown. Patients aged 0-18 years visiting the clinic were weighed and previous weight and other clinical data were collected from the medical charts. Weight-percentile-for-age standardization was calculated according to the U.S. Centers for Disease Control and Prevention and the World Health Organization growth tables. Pre- and post-lockdown weight-percentiles-for-age were compared using paired t-test. Multivariate analysis was conducted using linear regression model. The study was comprised of 229 patients; 117/229 (51.1%) were boys, 60/229 (26.2%) aged under 6 years. Total mean weight-percentile was significantly higher following the lockdown (40.44 vs. 38.82, respectively, P = 0.029). Boys had a significant post-lockdown weight-percentile rise (37.66 vs. 34.42, P = 0.014), whereas girls had higher baseline pre-quarantine weight-percentile of 43.42, which did not change. Patients younger than 6 years had a significant increase in weight-percentiles (39.18 vs. 33.58, P = 0.021). In multivariate analysis these correlations were preserved. The study was comprised of 229 patients; 117/229 (51.1%) were boys, 60/229 (26.2%) aged under 6 years. https://www.selleckchem.com/products/pfk158.html Total mean weight-percentile was significantly higher following the lockdown (40.44 vs. 38.82, respectively, P = 0.029). Boys had a significant post-lockdown weight-percentile rise (37.66 vs. 34.42, P = 0.014), whereas girls had higher baseline pre-quarantine weight-percentile of 43.42, which did not change. Patients younger than 6 years had a significant increase in weight-percentiles (39.18 vs. 33.58, P = 0.021). In multivariate analysis these correlations were preserved. The effect of extended shift length on pediatric residency is controversial. Israeli residents perform shifts extending up to 26 hours, a practice leading to general dissatisfaction. In early 2020, during the coronavirus disease-2019 (COVID-19) pandemic, many Israeli hospitals transitioned from 26-hour shifts to 13-hour shifts in fixed teams (capsules) followed by a 24-hour rest period at home. The regulation changes enacted by the Israeli government during the COVID-19 pandemic provided a rare opportunity to assess perception by residents regarding length of shifts before and after the change. To assess perception of pediatric residency in three aspects resident wellness, ability to deliver quality healthcare, and acquisition of medical education following the change to the shorter shifts model. We performed a prospective observational study among pediatric residents. Residents completed an online self-assessment questionnaire before and after the COVID-19 emergency regulations changed toward shorter shifts. Sixty-seven residents answered the questionnaires before (37) and after (30) the shift changes. The average score was significantly better for the 13-hour shifts versus the 26-hour shifts, except for questions regarding available time for research. There was a positive perception regarding the shorter night shifts model among pediatric residents, with an increase in general satisfaction and improvement in perception of general wellness, ability to deliver quality healthcare, and medical education acquisition. Following the change to shorter shift length, perception of pediatric residents included improvement in wellness, ability to deliver quality healthcare, and availability of medical education. Following the change to shorter shift length, perception of pediatric residents included improvement in wellness, ability to deliver quality healthcare, and availability of medical education. Coronavirus disease-2019 (COVID-19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series. Coronavirus disease-2019 (COVID-19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic.
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