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[Display omitted] A concentration gradient of surfactants in the presence of polymers that non-covalently associate with surfactants will exhibit a continually varying distribution of complexes with different composition, charge, and size. Since diffusiophoresis of colloids suspended in a solute concentration gradient depends on the relaxation of the gradient and on the interactions between solutes and particles, polymer/surfactant complexation will alter the rate of diffusiophoresis driven by surfactant gradients relative to that observed in the same concentration gradient in the absence of polymers. A microfluidic device was used to measure diffusiophoresis of colloids suspended in solutions containing a gradient of sodium dodecylsulfate (SDS) in the presence or absence of a uniform concentration of Pluronic P123 poly(ethylene oxide- b -propylene oxide- b -ethylene oxide) nonionic triblock copolymers. To interpret the effect of P123 on the rate of colloid diffusiophoresis, electrophoretic mobility and dynamic light scattering measurements of the colloid/solute systems were performed, and a numerical model was constructed to account for the effects of complexation on diffusiophoresis. Polymer/surfactant complexation in solute gradients significantly enhanced diffusiophoretic transport of colloids. Large P123/SDS complexes formed at low SDS concentrations yielded low collective solute diffusion coefficients that prolonged the existence of strong concentration gradients relative to those without P123 to drive diffusiophoresis. [ABSTRACT FROM AUTHOR]

Background: Distinguishing benign inverted papilloma (IP) tumors from those that have undergone malignant transformation to squamous cell carcinoma (IP‐SCC) is important but challenging to do preoperatively. Magnetic resonance imaging (MRI) can help differentiate these 2 entities, but no established method exists that can automatically synthesize all potentially relevant MRI image features to distinguish IP and IP‐SCC. We explored a deep learning approach, using 3‐dimensional convolutional neural networks (CNNs), to address this challenge. Methods: Retrospective chart reviews were performed at 2 institutions to create a data set of preoperative MRIs with corresponding surgical pathology reports. The MRI data set included all available MRI sequences in the axial plane, which were used to train, validate, and test 3 CNN models. Saliency maps were generated to visualize areas of MRIs with greatest influence on predictions. Results: A total of 90 patients with IP (n = 64) or IP‐SCC (n = 26) tumors were identified, with a total of 446 images of distinct MRI sequences for IP (n = 329) or IP‐SCC (n = 117). The best CNN model, All‐Net, demonstrated a sensitivity of 66.7%, specificity of 81.5%, overall accuracy of 77.9%, and receiver‐operating characteristic area under the curve of 0.80 (95% confidence interval, 0.682‐0.898) for test classification performance. The other 2 models, Small‐All‐Net and Elastic‐All‐Net, showed similar performance levels. Conclusion: A deep learning approach with 3‐dimensional CNNs can distinguish IP and IP‐SCC with moderate test classification performance. Although CNNs demonstrate promise to enhance the prediction of IP‐SCC using MRIs, more data are needed before they can reach the predictive value already established by human MRI evaluation. [ABSTRACT FROM AUTHOR]

This study was conducted to assess the effects and safety of Chinese herbal medicine (CHM) on blood lipids among adults with overweight or obesity. Fourteen bibliographic databases were comprehensively searched, from their respective inceptions up to April 2021, for randomised placebo-controlled weight-loss trials using CHM formulation on total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol over ≥4 weeks. Data collection, risk of bias assessment, and statistical analyses were guided by the Cochrane Handbook (v6.1). Continuous outcomes were expressed as the mean difference with 95% confidence intervals, and categorical outcomes were expressed as a risk ratio with 95% confidence intervals. All analyses were two-tailed with a statistical significance of p < 0.05. Fifteen eligible studies with 1,533 participants were included in this meta-analysis. Findings from meta-analyses indicated that CHM interventions, compared to placebo, reduced triglyceride (MD −0.21 mmol/L, 95% CI −0.41 to −0.02, I2 = 81%) and increased HDL cholesterol (MD 0.16 mmol/L, 95% CI 0.04 to 0.27, I2 = 94%) over a median of 12 weeks. The reduction in total cholesterol and LDL cholesterol were not statistically significant. Furthermore, the tendency of reduced triglycerides was identified among overweight participants with high baseline triglycerides. Attrition rates and frequency of adverse events were indifferent between the two groups. CHM may provide lipid-modulating benefits on triglycerides and HDL cholesterol among participants with overweight/obesity, with the tendency for significant triglyceride reduction observed among overweight participants with high baseline triglycerides. However, rigorously conducted randomised controlled trials with larger sample sizes are required to validate these findings. [ABSTRACT FROM AUTHOR]

Objective. This review investigated the effects and safety of Chinese herbal medicine (CHM) formulas on weight management. Methods. Eighteen databases in English, Chinese, Korean, and Japanese were searched from their inceptions to September 2019. The treatment groups included CHM formulations, and the control included placebo, Western medication (WM), and lifestyle intervention (LI), with or without cointerventions (WM and/or LI). Quality of studies was assessed using Cochrane Collaboration's risk of bias assessment tool. Body weight and body mass index (BMI) were analysed in RevMan v5.4.1 and expressed as mean differences with 95% confidence intervals (CI), while adverse events were expressed as risk ratio with 95% CI. Results. Thirty-nine RCTs were eligible for qualitative analysis, 34 of which were included in the meta-analyses. The majority of studies had a high or unclear risk of selection, performance, and detection bias. Twenty-five CHM studies involving cointerventions revealed that CHM had significant adjunct effects on body weight and BMI at the end of treatment compared to control. No serious adverse events were reported in the CHM groups. Conclusion. CHM indicates a promising adjunct to facilitate WM or lifestyle change for weight management. However, methodological barriers such as lack of allocation concealment and double-blinding may have led to challenges in data synthesis. More rigorously designed RCTs involving cointerventions are warranted. [ABSTRACT FROM AUTHOR]

Background. COVID-19 caused by SARS-CoV-2 infection has been spreading through many countries since the end of 2019. The 4th edition of the national guidelines for the management of COVID-19 provides an herbal formula with 9 herbs for its management. Aim of Study. We aimed to predict the mechanism of binding of SARS-CoV-2 and SARS-CoV spike glycoproteins with angiotensin-converting enzyme 2 (ACE2) to provide a molecular-level explanation of the higher pathogenicity of SARS-CoV-2 and to identify protein sites which may be targeted by therapeutic agents to disrupt virus-host interactions. Subsequently, we aimed to investigate the formula for the initial-stage management to identify a therapeutic agent with the most likely potential to become pharmaceutical candidate for the management of this disease. Materials and Methods. GenBank and SWISS-MODEL were applied for model creation. ClusPro was used for protein-protein docking. PDBePISA was applied for identification of possible binding sites. TCMSP was employed for identification of the chemical compounds. AutoDock Vina together with PyRx was used for the prediction and evaluation of binding pose and affinity to ACE2. SwissADME and PreADME were applied to screening and prediction of the pharmacokinetic properties of the identified chemical compounds. PyMOL was used to visualise the structural models of SARS-CoV-2 and SARS-CoV spike glycoproteins complexed to ACE2 and to examine their interactions. Results. SARS-CoV-2 had two chains (labelled chains B and C) which were predicted to bind with ACE2. In comparison, the SARS-CoV had only one chain (labelled chain C) predicted to bind with ACE2. The spike glycoproteins of both viruses were predicted to bind with ACE2 via position 487. Molecular docking screening and pharmacokinetic property prediction of the herbal compounds indicated that atractylenolide III (−9.1 kcal/mol) from Atractylodes lancea (Thunb.) Dc. (Cangzhu) may be a candidate therapeutic agent for initial-stage management. Conclusions. Atractylenolide III is predicted to have a strong binding affinity with ACE2 and eligible pharmacokinetic properties, anti-inflammatory effects and antiviral effects in in vitro study, and high distribution on the lungs in in vivo study. [ABSTRACT FROM AUTHOR]

Purpose: To determine the chair stand test protocol that is most suitable for older adults in clinical settings by reviewing the currently available methods. Methods: Five electronic English databases were searched and details of methods used on individuals aged ≥65 years in the included studies were compared, including the instrument used to record time, units of measurement, chair characteristics (seat height, armrests), footwear, permission to use upper extremities and walking aids, pace of performance, total number of chair stands, timing points, total number of recorded and practice tests. Results: A total of 23 eligible studies were identified. The type of instrument to record performance time, characteristics of the chair and footwear were not frequently mentioned. A majority of studies did not permit the use of the upper extremities or walking aids during assessment. The performance of five chair stands at a fast pace recorded in seconds was most common, with the majority of studies recording the initial and end time point in a seated position. The total number of performed tests and practice tests was not specified in a majority of studies. Conclusion: A feasible and safe protocol for the chair stand test is proposed for assessment of older adults. The chair stand test may provide valuable information on declines in mobility in older adults. The use of the chair stand test within clinical settings of older adults may provide a measure to identify frail individuals and to determine their level of frailty. Using the proposed protocol for the chair stand test may allow for the comparability of results. [ABSTRACT FROM AUTHOR]

Insight into the neural basis of hedonic processing has come from studies of food palatability in rodents. Pharmacological manipulations of the nucleus accumbens shell (NAcSh) have repeatedly been demonstrated to increase hedonic taste reactivity, yet the contribution of specific NAcSh circuit components is unknown. Bidirectional optogenetic manipulations were targeted to the principal NAcSh projection neurons and afferent pathways in mice during free feeding assays. Number of licks per bout of consumption was used as a measure of food palatability as it was confirmed to track sucrose concentration and subjective flavor preferences. Photoinhibition of NAcSh neurons, whether general or cell-type specific, was found to alter consumption without affecting its hedonic impact. Among the principal excitatory afferent pathways, we showed that ventral hippocampal (vHipp) input alone enhances palatability upon low-frequency photostimulation time-locked to consumption. This enhancement in palatability was independent of opioid signaling and not recapitulated by NAcSh or dopamine neuron photostimulation. We further demonstrated that vHipp input photostimulation is sufficient to condition a flavor preference, while its inhibition impedes sucrose-driven flavor preference conditioning. These results demonstrate a novel contribution of vHipp–NAcSh pathway activity to palatability that may relate to its innervation of a particular region or neuronal ensemble in the NAcSh. These findings are consistent with the evidence that vHipp–NAcSh activity is relevant to the pathophysiology of anhedonia and depression as well as the increasing appreciation of hippocampal involvement in people's food pleasantness ratings, hunger, and weight. [ABSTRACT FROM AUTHOR]

B Correction: Trials 23, 818 (2022) b B https://doi.org/10.1186/s13063-022-06725-8 b The original publication of this article [[1]] contained 2 errors: 1. The clinical evaluation of electroacupuncture combined with mindfulness meditation for overweight and obesity: study protocol for a randomized sham-controlled clinical trial. [Extracted from the article]

Forced air cooling studies are hindered by the practical difficulties and cost associated with pallet scale investigations. Produce simulators are a potential solution for overcoming some of these difficulties. Despite their common use in precooling research, there are a lack of design guidelines for such simulators in the literature which in some case has led to their inappropriate use. This review examines previous use of produce simulators in produce cooling studies in the context of transport phenomena theory. This allows constraints to be proposed which facilitate the design of produce simulators that can replicate transport phenomena in horticultural produce. These include the requirements of geometric and thermal property matching as well as the practical constraints imposed on produce simulators. It is suggested that future computational modelling work is well suited to the establishment of produce simulator design guidelines which incorporate complex effects such as the impact of variation in produce geometry on flow. The material engineering challenges posed by produce simulators are also discussed. [ABSTRACT FROM AUTHOR]

The saturation magnetization of Y3Fe5O12 (YIG) epitaxial films 4 to 250 nm in thickness has been determined by complementary measurements including the angular and frequency dependencies of the ferromagnetic resonance fields as well as magnetometry measurements. The YIG films exhibit state-of-the-art crystalline quality, proper stoichiometry, and pure Fe3+ valence state. The values of YIG magnetization obtained from all the techniques significantly exceed previously reported values for single crystal YIG and the theoretical maximum. This enhancement of magnetization, not attributable to off-stoichiometry or other defects in YIG, opens opportunities for tuning magnetic properties in epitaxial films of magnetic insulators. [ABSTRACT FROM AUTHOR]

Poria cocos (PC) is a medicinal herb frequently used in weight-loss clinical trials, however the mechanisms by which its compounds target orexigenic receptors including the neuropeptide Y1 receptor (Y1R) remain largely unknown. This study aimed to screen PC compounds for favourable pharmacokinetics profiles and examine their molecular mechanisms targeting Y1R. Forty-three PC compounds were systematically sought from pharmacological databases and docked with Y1R (PDB: 5ZBQ). By comparing the relative binding affinities, pharmacokinetics and toxicity profiles, we hypothesised that compounds designated PC1 3,4-Dihydroxybenzoic acid, PC8 Vanillic acid, PC40 1-(alpha-L-Ribofuranosyl)uracil, could be potential antagonists as they contact major residues Asn283 and Asp287, similar to various potent Y1R antagonists. In addition, PC21 Poricoic acid B, PC22 Poricoic acid G and PC43 16alpha,25-Dihydroxy-24-methylene-3,4-secolanosta-4(28),7,9(11)-triene-3,21-dioic acid, contacting Asn299, Asp104 and Asp200 proximal to the extracellular surface could also interfere with agonist binding by stabilising the extracellular loop (ECL) 2 of Y1R in a closed position. Owing to their selective interaction with Phe302, an important residue in binding of selective Y1R antagonists, PC12 beta-Amyrin acetate, PC26 3-Epidehydrotumulosic acid and PC27 Cerevisterol were proposed as putative antagonists. Following the consensus approach, PC12 beta-Amyrin acetate, PC26 3-Epidehydrotumulosic acid and PC27 Cerevisterol were identified as candidate compounds due to their high affinities (-12.2, -11.0 and -10.8 kcal, respectively), high drug-likeness and low toxicity profiles. Trajectory analyses and energy contributions of PC12-Y1R complex further confirmed their structural stability and favourable binding free energies, highlighting the feasibility and possible development of PC12 beta-Amyrin acetate as a future Y1R inhibitor. [ABSTRACT FROM AUTHOR]

Traditional continuous training and high-intensity interval training (HIIT) can increase maximal oxygen uptake (V̇O2max). However, there is conflicting evidence regarding which form of training demonstrates the greatest improvements to V̇O2max , and data in women is sparse. We conducted a systematic review and meta-analyses to assess whether moderate to vigorous-intensity continuous training (MVICT) or HIIT was superior at improving V̇O2max in women. Randomised controlled and parallel studies examined the influence of MVICT and/or HIIT on V̇O2max in women. There was no statistical difference in V̇O2max improvements after training between women in the MVICT and HIIT cohorts (mean difference [MD]: −0.42, 95%CI: −1.43 to 0.60, p>0.05). Both MVICT and HIIT increased V̇O2max from baseline (MD: 3.20, 95% CI: 2.73 to 3.67 and MD: 3.16, 95% CI 2.09 to 4.24, respectively, p<0.001). Greater improvements in V̇O2max were observed in women who participated in more training sessions in both training formats. Long-HIIT was superior to short-HIIT protocols at increasing V̇O2max. Although MVICT and long-HIIT sessions elicited greater increases in V̇O2max in younger women compared to short-HIIT protocols, these differences were negligible in older women. Our findings suggest MVICT and HIIT are equally effective strategies for improving V̇O2max and indicate an effect of age on its response to training in women. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity have reached an epidemic level which impacts individual health and creates a financial burden worldwide. Evidence has shown that electroacupuncture is effective for weight loss when combined with lifestyle intervention, while mindfulness meditation can enhance the outcome of weight loss programs. This study aims to evaluate the safety and the add-on effect of electroacupuncture and mindfulness meditation for weight management in overweight and obesity.Methods/design: This is a sham-controlled, three-armed randomized clinical trial. A total of 165 participants with BMI between 25 and 39.99 and aged between 18 and 60 who meet the inclusion and exclusion criteria will be randomized into [1] electroacupuncture plus mindfulness meditation group, [2] sham electroacupuncture plus mindfulness meditation group, and [3] electroacupuncture only group. The total duration of this study will be 22 weeks, which consists of a 2-week run-in period, a 12-week intervention period, and an 8-week follow-up period. Participants will receive 12 weekly treatments during the intervention period. Primary outcomes will include body mass index, waist and hip ratio, and body composition. Secondary outcomes will be measured by the Weight-Related Symptom Measure, Obesity and Weight Loss Quality of Life, the Power of Food Scale, and the Chinese medicine differential diagnosis questionnaire. Outcomes will be assessed at the baseline, and endpoints of the 3rd, 6th, 9th, 12th, 14th, 16th, and 20th week.Discussion: This clinical trial will investigate the add-on effect of two combined interventions for weight loss treatment. The findings of this study may contribute to the development of a cost-effective and multidisciplinary weight management approach.Trial Registration: Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000964213. Registered on 07 June 2018. [ABSTRACT FROM AUTHOR]

Ear-acupuncture/ear-acupressure (EAP) has been used for a range of health conditions with numerous randomized controlled trials (RCTs) investigating its efficacy and safety. However, the design of sham interventions in these RCTs varied significantly. This study systematically reviewed RCTs on EAP for all clinical conditions involving a number of sham EAPs as a control intervention. The review is guided by the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and investigated the types and differences of sham EAP interventions. Four electronic English databases (The Cochrane Library, PubMed, Embase, CINAHL®) and two Chinese databases (CQVIP, CNKI) were searched in December 2012 and 55 published RCTs comparing real and sham EAP for any clinical condition were included. Characteristics of participants, real and sham interventions, and outcomes were extracted. Four types of sham methods were identified. Among the 55 RCTs, 25 studies involved treatment on nonspecific ear acupoints as the sham method; seven studies used nonacupoints on the ear; nine studies selected placebo needles or placebo ear-acupressure on the same ear acupoints for the real treatment; 10 studies employed pseudo-intervention; and five studies combined two of the above methods to be the sham control. Other factors of treatment such as number of points, treatment duration, and frequency also varied greatly. Risk of bias assessment suggests that 32 RCTs were 'high risk' in terms of participants blinding, and 45 RCTs were 'high risk' in terms of personnel blinding. Meta-analysis was not conducted due to the high clinical heterogeneity across included studies. No relationship was found between the sham designs and efficacy outcomes, or between the sham types and dropout rate. No solid conclusion of which design is the most appropriate sham control of EAP could be drawn in this review. [ABSTRACT FROM AUTHOR]

[Display omitted] • A hybrid quantitative method combining a PLS and a Soft Sensor potency estimation. • Implemented and applied on continuous direct compression manufacturing. • Improved overall estimation robustness and facilitates cross-site method transfer. Near Infrared (NIR) spectroscopy is commonly utilized for continuous manufacturing as Process Analytical Technology (PAT) tool. This paper focus on a continuous direct compression manufacturing process, in which an NIR PAT probe is integrated into the tablet press feed frame and into the tablet diversion control system to ensure continuous monitoring of the potency and homogeneity of the blend within the process line. The quantification of NIR spectra is achieved through Partial Least-Squares (PLS) modeling, calibrated with offline analyzed tablet cores at different potency levels. Because the NIR measurements are often sensitive to sample physical properties caused by raw materials or process conditions, etc., adopting a data-driven approach will require a large amount of representative data throughout the method lifecycle. During the early stages of process development, whenever new uncaptured source of variability in the model space are encountered, the chemometric predictions can deviate from the offline reference, requiring frequent model updates. These deviations can be reduced by integrating process and physico-chemical knowledge in the on-line potency estimation. This paper presents a novel hybrid method combining the online NIR PLS and a potency soft sensor estimation, enabling a robust potency prediction whilst minimizing maintenance downtimes and facilitating cross-site method transfer. [ABSTRACT FROM AUTHOR]

[Display omitted] • A material sparing quantitative NIR method was developed for saccharin blend potency. • The method was developed at lab and deployed in continuous mfg. scale at two sites. The method was accurate and robust against material, instrument and process variation. A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to develop a calibration set. The calibration set was designed to create compositional and raw material lots variation using minimum resources. The calibration experiments utilized around 0.5 kg Saccharin (Active Pharmaceutical Ingredient (API) surrogate) and 1.8 kg of excipients. Partial Least Square (PLS) modeling was used to develop a quantitative NIR method from the calibration data. The NIR method was implemented during 5 test batches in two different manufacturing sites across different potency levels at a continuous manufacturing platform for direction compression. Acceptable prediction performance was achieved from the NIR method at both sites. The NIR method was robust against changes in process scale and NIR instruments. The variance information built into the calibration set was found to be critical to successful model performance. This study shows a benchtop feed frame can be used for material sparing calibration method development without operating at a full-scale process line and applied across multiple sites, instruments at different potency levels. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel NIR method was developed for blend potency variation and deviation detection. • NIR method developed at a lab scale was directly applied to full-scale manufacturing. • The method was robust against raw material, instrument, and process variation. • It enables agile NIR development and enhanced performance in continuous manufacturing. Near Infrared (NIR) method for blend potency estimation has been commonly used as an essential tool for process monitoring and control in continuous manufacturing of solid oral dosage forms. Robustness has been the main challenge for successful application of an NIR method, which often results in a long development time with frequent method update. Robustness deficiency often presents as an offset (bias) on the mean potency estimation. In this paper, the purpose of the NIR method has been redefined from estimating potency to potency deviation. This quantitative approach uses the mean centered potency to estimate potency deviations from the process mean, therefore, detects the non-conforming materials for continuous process monitoring and control. An NIR method was developed at the lab benchtop scale and directly deployed to a direct compression continuous manufacturing platform at Pfizer for mean centered potency estimation. The benchtop calibration provided a speedy and efficient NIR method development and the method showed enhanced robustness for estimating potency deviation in presence of wide process and raw material variations. Integrating with the mean centered approach, the NIR model from the lab could be implemented to different sites using different instruments without requiring model update for the established range of process conditions and raw material properties. [ABSTRACT FROM AUTHOR]

The seed of Senna obtusifolia (L.) H. S. Irwin & Barneby (Cassiae semen, CS) also known as Jue ming zi in China, has been traditionally used for weight management by purging the liver and improving the liver functions to support digestion. In the past decades, it has been used for hepatoprotection and treatment of overweight and other metabolic disorders such as hyperlipidaemia and diabetes. This review aimed at providing comprehensive information on the traditional usages, pharmacology, phytochemistry and toxicology of CS and critically exploring its potential usage for clinical weight management from both traditional and modern application perspectives. In order to fully understand the properties, actions and indications of CS, two sets of Chinese classical texts were searched, namely: Zhong Hua Yi Dian (Encyclopedia of Traditional Chinese Medicine) and Zhong Guo Ben Cao Quan Shu (Complete Collection of Traditional Texts on Chinese Materia Medica). The purpose of studying these classical texts was to determine the traditional use of CS in weight management. Comprehensive searches were also performed on seven databases for publications on original randomised clinical trials (RCT), in vivo , in vitro or in silico studies related to pharmacological effects of CS. Detailed information about the phytochemistry of CS was collected from books, encyclopedia, online databases and journal literature. In classical literature review, 89 classic texts provided information of properties, actions and indications of CS. In modern literature review, 44 studies were included for analysis, including 5 RCTs, 7 in vivo studies, 14 in vitro studies, 2 in silico studies and 16 studies of mixed types. Chinese classic literature has provided traditional evidence of the usage of CS for weight management. Contemporary studies have revealed that CS has weight loss effects and possesses some other pharmacological activities supporting weight management. Some chemical compounds of CS have been hypothesised to have a direct or indirect contribution to weight control. The relationships between chemical compounds and the corresponding weight-loss target proteins are not fully understood. Therefore, CS constituents should be further explored for the development of novel therapeutic or preventive agents for the treatment of overweight and obesity. Image 1 [ABSTRACT FROM AUTHOR]

Cnidium monnieri (L.) Cusson (CMC) is a traditional Chinese herbal medicine that has been widely grown and used in Asia. It is also known as "She chuang zi" in China (Chinese: 蛇床子), "Jashoshi" in Japan, "Sasangia" in Korea, and "Xa sang tu" in Vietnam. This study aimed to provide an up-to-date review of its phytochemistry, ethnopharmacology, pharmacokinetics, and toxicology. All available information on CMC was collected from the Encyclopedia of Traditional Chinese Medicines, PubMed, EMBASE, ScienceDirect, Scopus, Web of Science, and China Network Knowledge Infrastructure. The updated chemical structures of the compounds are those ones without chemical ID numbers or references from the previous review. A total of 429 chemical constituents have been elucidated and 56 chemical structures have been firstly identified in CMC with traceable evidence. They can be categorized as coumarins, volatile constituents, liposoluble compounds, chromones, monoterpenoid glucosides, terpenoids, glycosides, glucides, and other compounds. CMC has demonstrated impressive potential for the management of various diseases in extensive preclinical research. Since most of the studies are overly concentrated on osthole, more research is needed to investigate other chemical constituents. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies. [ABSTRACT FROM AUTHOR]

Purpose: To raise awareness of cefotetan-induced hemolytic anemia, a known rare but serious side effect that occurred in 5 patients at our medical center. Summary: Five cases of cefotetan-induced hemolytic anemia, which presented over the period of a single year at our center, are described. In each case, hemolytic anemia was confirmed by testing for the presence of anti-cefotetan antibodies. Each case occurred approximately 1 to 2 weeks following exposure to the drug. All five patients survived. A brief review of drug-induced immune hemolytic anemia (DIIHA) is also discussed. Conclusion: DIIHA may be difficult to distinguish from other causes of hemolytic anemia, but should be included in the differential in patients exposed to medications associated with DIIHA. Once suspected, antibody testing should be performed, and once diagnosed, further exposure should be avoided. [ABSTRACT FROM AUTHOR]

Background. Phellodendri Cortex (PC) or Huang Bai. According to the scientific database of China Plant Species and Chinese pharmacopeia 2015 edition, PC has two main species which are Phellodendron amurense Rupr (PAR) or "Guan Huang bai" in Chinese and Phellodendron chinense Schneid (PCS) or "Chuan Huang bai" in Chinese. The crude drugs of PAR and PCS are also called Phellodendri amurensis cortex (PAC) and Phellodendri chinense cortex (PCC), respectively. The medicinal part of the plant is the dried trunk bark. PC has comprehensive therapeutic effects which include anti-inflammatory, antimicrobial, anticancer, hypotensive, antiarrhythmic, antioxidant, and antipyretic agents. The exact ingredients in PC and its species are not fully summarised. Aim of the Study. This study was designed to review and evaluate the pharmacological actions of compounds and to explore the pharmacokinetic knowledge of PC and its species and to also identify the chemical compound(s) with a potential therapeutic effect on atopic dermatitis. Methods. "Huang Bai" and its English, botanical, and pharmaceutical names were used as keywords to perform database search in Encyclopaedia of traditional Chinese Medicines, PubMed, EMBASE, MEDLINE, Science Direct, Scopus, Web of Science, and China Network Knowledge Infrastructure. The data selection criteria included all the studies that were related to the phytochemical, pharmacological, and pharmacokinetic perspectives of PC and its species or their active constituents. More importantly, the voucher number has been provided to ensure the genuine bark of PC used as the medicinal part in the studies. Results. 140 compounds were summarized from PC and its species: specifically, 18 compounds from PCC, 44 compounds from PCS, 34 compounds from PAC, and 84 compounds from PAR. Obacunone and obaculactone are probably responsible for antiatopic dermatitis effect. PC and its species possess a broad spectrum of pharmacological actions including anti-inflammatory effect, antibacterial effect, antiviral effect, antitumor effect, antigout effect, antiulcer effect, neuroprotective effect, and antiatopic dermatitis effect. PC could widely distribute in plasma, liver, spleen, kidney, and brain. Berberine may be responsible for the toxic effect on the susceptible users with hemolytic disease or in the peripartum and neonatal period. Conclusions. The compounds of the crude bark of PC and its subspecies have showcased a wide range of pharmacological effects. Pharmacological efficacies of PC are supported by its diverse class of alkaloid, limonoid, phenolic acid, quinic acid, lignan, and flavonoid. Obacunone and obaculactone could be the bioactive compounds for atopic dermatitis management. PC and its subspecies are generally safe to use but extra care is required for certain conditions and group of people. [ABSTRACT FROM AUTHOR]

Chronic prostatitis (CP) is a chronic inflammation in the prostate with unsatisfactory management. Danggui Beimu Kushen Wan (DBKW) is a classic formula developed 1800 years ago for patients with difficult urination and it has been widely utilized for CP in modern days. However, scientific understanding of DBKW on CP has not been systematically reviewed. First, we searched the Encyclopedia of Traditional Chinese Medicine for the etiologies and pathogeneses of CP-like symptoms and DBKW and compared their similarities and differences from traditional Chinese medicine and conventional medicine perspectives. Then, we searched 21 electronic databases to identify potential clinical and experimental studies. Characteristics of included studies, ingredients, herb frequency, and possible mechanisms of actions were descriptively summarized. Risk of bias of randomized controlled trials (RCTs) was evaluated using the Cochrane risk of bias assessment tool. A total of 290 studies were identified. Six clinical studies, including four RCTs and two case series, and eight experimental studies were included. Clinical studies indicated that DBKW used alone or as an adjunct therapy significantly reduced the CP symptom scores and decreased the expressed prostatic secretions-pH when compared to antibiotics or α-blocker. Most RCTs have high or unclear risk of bias. Experimental studies revealed that DBKW may have effects on anti-inflammation, antibacteria, antioxidation, sex hormone regulation, and immunoregulation. DBKW demonstrated a great potential in the treatment of CP. High-quality RCTs and network pharmacological studies should be considered for future research. [ABSTRACT FROM AUTHOR]

Introduction: Quality of life (QoL), mental wellbeing, and physical function are often diminished among people with chronic disease. Tai Chi is a moderate form of exercise that may be effective in improving chronic disease management. This protocol paper outlines a trial to determine the therapeutic effects of a Tai Chi program on chronic disease management. Methods and analysis: This study will be a pilot, interventional, single-blind, two-armed, randomised, parallel, and controlled trial involving a 12-week Tai Chi program for Australian adults. Forty people aged 18 years and older, diagnosed with one or more chronic disease from general community will be recruited. All participants will be randomised to either a 12-week Tai Chi program or a waiting list control group. The Tai Chi program will involve 12 weeks of group Tai Chi sessions, with 45 minutes per session, twice a week. The primary outcome will be QoL as measured by mean scores on the 12-item Short Form Health Survey (SF-12v2) and the EuroQoL (EQ-5D). The secondary outcomes will include anxiety as measured by mean score on the generalised anxiety disorder 7 (GAD-7) survey; depression as measured by mean score on the patient health questionnaire (PHQ-9); work productivity and activity assessment (WPAI:SHP); pain (if any) as measured by mean scores on the visual analogue scale (VAS) and the McGill pain questionnaire (MPQ). These primary and secondary outcomes will be self-administered via two online assessments prior to (T0) and post-intervention (T1). Objective measures as additional secondary outcomes, will also be carried out by the research team including flexibility as measured by the finger to floor distance (FFD); obesity as measured by mean scores on body mass index (BMI); vital signs (blood pressure, heart rate, respiratory rate, temperate, and oxygen saturation) as measured by a blood pressure monitor, tympanic, and pulse oximetry device, and these outcomes will be measured at T0 and T1 in the ECU Holistic Health Research Clinic. People diagnosed with pre-diabetes or diabetes, their glycosylated haemoglobin (HbA1C) and fasting (before breakfast) blood glucose level (BGL) will also be measured via test kits at T0 and T1 in the clinic. Linear mixed modelling will be conducted to assess changes in outcomes. Statistical significance will be set at an alpha level of 0.05 with a medium effect size. All analyses will be conducted using R version 4.1. Qualitative data will be analysed using template thematic analysis. Ethics and dissemination: Ethical approval has been obtained from the Edith Cowan University (ECU) Human Research Ethics Committee (2021-03042-WANG). Research findings will be disseminated to the public, health professionals, researchers, and healthcare providers through conference presentations, lay summaries, and peer-reviewed publications. This study will provide an updated evidence on a safe, sustainable, and inexpensive non-pharmacological approach in the management of chronic disease, the number one burden of disease in Australia. Trial registration: Trial registration number:ACTRN12622000042741p. [ABSTRACT FROM AUTHOR]

Abstract: Dendrites and spines undergo dynamic changes in physiological and pathological conditions. Dendritic outgrowth has been observed in surviving neurons months after ischemia, which is associated with the functional compensation. It remains unclear how dendrites in surviving neurons are altered shortly after ischemia, which might reveal the mechanisms underlying neuronal survival. Using primary cortical cultures, we monitored the dendritic changes in individual neurons after oxygen-glucose deprivation (OGD). Two to four hours of OGD induced approximately 30–50% cell death in 24h. However, the total dendritic length in surviving neurons was significantly increased after OGD with a peak at 6h after re-oxygenation. The increase of dendritic length after OGD was mainly due to the sprouting rather than the extension of the dendrites. The dendritic outgrowth after 2h of OGD was greater than that after 4h of OGD. Application of NMDA receptor blocker MK-801 abolished OGD-induced dendritic outgrowth, whereas application of AMPA receptor antagonist CNQX had no significant effects. These results demonstrate a NMDA receptor-dependent dendritic plasticity shortly after OGD, which provides insights into the early response of surviving neurons after ischemia. [Copyright &y& Elsevier]

Background: Empty nose syndrome (ENS) is a controversial upper airway disorder most commonly associated with tissue loss from the inferior turbinates. The inferior meatus augmentation procedure (IMAP) has been shown to effectively reduce ENS symptoms in a durable manner, but the precise mechanisms that may govern this symptomatic improvement remain unknown. Methods: Five patients with ENS who underwent bilateral IMAP via submucosal costal cartilage implant were assessed. Pre‐implant and 6 months post‐implant computed tomography (CT) imaging for each ENS patient was analyzed in a blinded fashion using computational fluid dynamics (CFD) modeling to investigate intrapatient changes in airflow parameters. Results: Following surgery, ENS patients have significantly improved symptoms as indexed by Empty Nose Syndrome 6‐Item Questionnaire (ENS6Q) scoring (pre‐implant: 14.00 ± 4.06 [mean ± standard deviation]; 95% confidence interval [CI], 10.44 to 17.56; post‐implant: 4.8 ± 2.77; 95% CI, 2.37 to 7.23; Cohen's d = 2.64; p = 0.02). Using CFD, a significant shift in nasal airflow patterns was observed, where airflow deviates away from the middle meatus upon hitting the implant (pre‐implant: 67.13% ± 11.14%; 95% CI, 60.22% to 74.04%; post‐implant: 46.18% ± 12.81%; 95% CI, 38.23% to 54.12%; d = 1.74; p < 0.05) toward the inferior meatus (pre‐implant: 30.55% ± 11.29%; 95% CI, 23.55% to 37.55%; post‐implant: 42.59% ± 9.60%; 95% CI, 36.63 to 48.54%; d = 1.14; p < 0.05). No significant changes were found in nasal resistance (pre‐implant: 0.102 ± 0.015; 95% CI, 0.092 to 0.112 Pa*s/mL; post‐implant: 0.105 ± 0.041; 95% CI, 0.081 to 0.130 Pa*s/mL). In addition, the improvement of ENS6Q scoring significantly correlated with percent reduction in aberrant airflow through the middle meatus (R2 = 0.60, p = 0.04). Conclusion: This study supports our prior working hypothesis that disordered vectors of nasal airflow congregate in the middle meatus contribute to ENS symptoms, not nasal resistance. Moreover, these data illuminate a paradoxical, but consistent, restoration of nasal airflow to the inferior meatus following the replacement of turbinate tissue volume in the inferior meatus via IMAP surgery, potentially due to the Coandă effect. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review aimed to evaluate the therapeutic effects and safety of Chinese herbal medicine (CHM) formulae for managing menopausal hot flushes (MHF). Methods: Seven English and Chinese databases were searched for studies from respective inceptions to February 2019. Randomized controlled trials investigating the clinical effects and safety of CHM formulae on MHF were considered for inclusion. The outcomes of subjective feelings (MHF and quality of life), objective changes (hormones and peripheral blood flow) and safety were analyzed. The most frequently prescribed formulae and herbs were summarized. Results: Nineteen randomized clinical trials involving 2469 patients were included. When compared to menopausal hormone therapy, CHM had similar effects to menopausal hormone therapy on total effectiveness rate (OR 1.41, 95% CI 0.84 to 2.35) and total Kupperman index (KI) score (SMD -0.13, 95% CI -0.61 to 0.36), and could significantly reduce vasomotor symptom score (MD -0.43, 95% CI -0.55 to -0.31) and upper-body peripheral blood flow (MD -3.56, 95% CI -5.14 to -1.98 under the jaw, MD -7.10, 95% CI -11.01 to -3.19 in the fingertip). When compared to placebo, CHM could reduce MHF severity (MD -0.70, 95% CI-1.00 to -0.40) and improve total KI score (MD -12.61, 95% CI -15.21 to -10.01). However, no statistically significant changes to hormone levels were detected. Most commonly seen adverse events were mild gastrointestinal tract reactions. The most popularly studied formula was Kun Tai capsule and the most frequently prescribed herb was Bai shao (Paeoniae Radix Alba, Paeonia lactiflora Pall.). More than 50% included studies had low risks of bias in the domains of selection, performance, attrition and reporting. Conclusions: This review indicated that CHM formulae were safe to be applied in MHF females and able to improve MHF-related symptom scores as well as the peripheral blood flow. Further studies should focus on specific formulae. [ABSTRACT FROM AUTHOR]

Overweight and obesity is a growing global health concern. Current management of obesity includes lifestyle intervention, bariatric surgery and medication. The serotonin receptor, 5-HT2C, is known to mediate satiety, appetite and consumption behaviour. Lorcaserin, an appetite control drug, has demonstrated efficacy in appetite control by targeting 5-HT2C but causes undesirable side effects. This study aimed to explore the potential usage of Cassiae semen (CS), a well-known traditional Chinese medicine used to treat obesity. A computational molecular docking study was performed to determine the binding mechanism of CS compounds to the 5-HT2C receptors in both active, agonist-bound and inactive, antagonist-bound conformations. By comparing binding poses and predicted relative binding affinities towards the active or inactive forms of the receptor, we hypothesise that two of the CS compounds studied may be potent agonists which may mimic the appetite suppression effects of lorcaserin: obtusifoliol and cassiaside B2. Furthermore, two ligands, beta-sitosterol and juglanin, were predicted to bind favourably to 5-HT2C outside of the known agonist binding pocket in the active receptor, suggesting that such ligands may serve as positive allosteric modulators of 5-HT2C receptor function. Overall, this study proposed several CS compounds which may be responsible for exerting anti-obesity effects via appetite suppression by 5-HT2C receptor activation. [ABSTRACT FROM AUTHOR]

The therapeutic effects of Guizhi Fuling Wan (GFW) on uterine fibroids have been tested on various animal models, but to date, the findings of these studies have not been comprehensively synthesised. This study aimed to evaluate the preclinical effects of GFW on uterine fibroids in different animal models. Twenty databases were searched from their earliest recorded publications to March 2019 to identify in vivo studies of non-modified GFW compared with no treatment for animal models with uterine fibroids. The methodological quality was assessed using the ARRIVE guidelines. Two groups of outcome measures were evaluated: fibroid characteristics (uterine weight, coefficient or smooth muscle thickness) and sex hormones indexes (oestradiol, progesterone or the gene expression of their receptors). A total of 21 studies (22 experiments) involving 461 female animals met the eligibility criteria. The quality of the included studies scored at 14.24 ± 1.00 out of 20. Four animal species were used and induced by oestrogen or oestrogen combined with progesterone, including guinea pig (n = 20), rats (n = 385, SD and Wister) and mice (n = 56). Overall, the available evidence suggests that GFW has potentially beneficial effects over placebo on both fibroid characteristics and sex hormones in SD rats (except progesterone), Wister rats (except progesterone receptor [PR] gene expression) and ICR mice (except PR gene expression). GFW appears to reduce uterine weight and smooth muscle thickness in the guinea pig, but no data on sex hormone index was available. Noting the unevenly distributed covariates of animal model types, experimental evidence suggested that GFW may be a promising intervention for the management of uterine fibroids in animal models. Future natural product studies should be optimised by reporting the voucher specimen. More studies on composition and providing evidence of the involvement of relevant cell signalling pathways are required. Image 1 [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is an IgE-mediated inflammatory disease. Current conventional therapies for AR are unsatisfactory. Acupuncture has been recommended as an optional treatment for AR patients who are interested in non-pharmacotherapy in the new clinical practice guidelines for AR. Acupressure is a sub-type of acupuncture which is non-invasive with a low risk and can be self-administered. However, the current limited evidence is compromised by the high risk of bias and heterogeneity of methodology. Therefore, rigorously designed randomized controlled trials (RCTs) are needed. This proposed RCT aims to evaluate the efficacy and safety of self-administered acupressure for the management of AR.Methods/design: We have designed a randomized, single-blind, non-specific controlled, two-arm, parallel clinical trial involving a 2-week run-in period, a 4-week intervention period and an 8-week follow-up period. The eligible participants will be randomized into either a specific or a non-specific acupressure group. They will be required to perform self-administered acupressure on either five specific acupressure points or five non-specific acupressure points, 1 min for each point, twice a day for 4 weeks. Participants will be asked to complete self-administered questionnaires for outcome measures including a 7-point scale of symptom severity, the Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities (RQLQs), relief medication scores, adverse events and participants' opinion of this study at the different assessment points throughout the trial period. Data will be analyzed by the chi-square or t test using Statistical Package for Social Science (SPSS) software.Discussion: The findings from this study should provide scientific evidence for the efficacy and safety of self-administered acupressure for the management of AR. This study may assist the development of a non-cost, non-invasive self-management method for AR sufferers.Trial Registration: Australian and New Zealand Clinical Trials Registry (ANZCTR), ID: ACTRN12617001106325 Registered on 28 July 2017. [ABSTRACT FROM AUTHOR]

Fritillariae Thunbergii Bulbus (FTB) has been widely used as an antitussive herb for thousands of years in China. However, FTB's traditional uses, chemical compounds and pharmacological activities have not been systematically reviewed. This study aimed to review its traditional uses, phytochemistry, pharmacodynamics, pharmacokinetics and toxicity. We searched the Encyclopedia of Traditional Chinese Medicine to explore the historical records which indicate that it acts to clear heat, resolve phlegm, relieve cough, remove toxicity and disperse abscesses and nodules. We searched 11 databases to identify potential phytochemical or pharmacological studies. Characteristics of its chemical constituents, pharmacological effects, pharmacokinetic and toxicity were descriptively summarized. A total of 9706 studies were identified and 83 of them were included. As a result, 134 chemical constituents were identified, including 26 alkaloids, 29 compounds found in essential oils, 13 diterpenoids, two carbohydrates, two sterols, 18 amino acids, six nucleosides, four nucleobases, four fatty acids, three lignans, and 27 elements. Thirteen pharmacological effects of FTB were identified, including anti-cancer, tracheobronchial relaxation, antitussive, expectorant, anti-muscarinic, anti-inflammation, anti-thyroid, regulation of blood rheology, antiulcer, anti-diarrhea, pain suppression, antioxidation and neuroprotection. These pharmacological activities may be mainly attributed to the alkaloids in FTB. Further phytochemical, pharmacological and network pharmacological studies are recommended. [ABSTRACT FROM AUTHOR]

• A high-throughput screening strategy is used for natural products in urate-lowering therapy. • NOS3 may be a novel drug target of Simiao Pill for hyperuricemia. • Kihadanin A and limonin are predicted to target NOS3, and chelerythrine and quercetin at XDH. Hyperuricemia (HUA) is a type of purine metabolism disease and Simiao Pill (SMP), a classic herbal prescription, has a long history of treating HUA. Nonetheless, the mechanisms underlying SMP against HUA remain unclear. We employed computational biomedical modeling and screening to explore the potential pharmacodynamic components and the mechanisms of SMP for HUA. We obtained 6,045 docking results between 403 herbal compounds and 15 HUA-related targets (average binding affinity −7.081 kcal/mol). We identified 34 signaling pathways based on the 15 HUA-related proteins. Nitric-oxide synthase 3 (NOS3) was found to be the most promising drug target of SMP against HUA, exhibiting the best average binding affinity of −8.05 kcal/mol. Chelerythrine and quercetin were predicted to be the most bioactive compounds for xanthine dehydrogenase (XDH), a known drug target, along with kihadanin A and limonin for NOS3. Of all SMP compounds, prenol lipids, steroids and alkaloids were predicted to be the three primary classes of compounds with potential for targeting NOS3 and XDH. SMP may treat HUA by mechanisms that involve multi-targets and pathways. Our study presented a novel horizon for exploring the mechanism of SMP against HUA and developing potential drugs. Further experimental research is required to verify our results. [ABSTRACT FROM AUTHOR]

[Display omitted] • Baicalein (HQA004) has the most favorable inhibitory ligand for Mpro of SARS-CoV-2. • Cubebin (CHA008) acted to support the proposed HQA004 inhibitor at the active site. • CHA008 served to enhance HQA004 effects via allosteric effects at two sites. • CHA008 enhanced the stability of HQA004 despite diffusion to a distant site. • Wavelet analysis showed that because of CHA008 binding, the dynamics and structure of Mpro have more subtle changes. Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (Mpro) of SARS-CoV-2 as an example. We first used molecular docking to identify molecular components of the formula which may inhibit Mpro. Baicalein (HQA004) is the most favorable inhibitory ligand. We also identified a ligand from the other component, cubebin (CHA008), which may act to support the proposed HQA004 inhibitor. Molecular dynamics simulations were then performed to further elucidate the possible mechanism of inhibition by HQA004 and synergistic bioactivity conferred by CHA008. HQA004 bound strongly at the active site and that CHA008 enhanced the contacts between HQA004 and Mpro. However, CHA008 also dynamically interacted at multiple sites, and continued to enhance the stability of HQA004 despite diffusion to a distant site. We proposed that HQA004 acted as a possible inhibitor, and CHA008 served to enhance its effects via allosteric effects at two sites. Additionally, our novel wavelet analysis showed that as a result of CHA008 binding, the dynamics and structure of Mpro were observed to have more subtle changes, demonstrating that the inter-residue contacts within Mpro were disrupted by the synergistic ligand. This work highlighted the molecular mechanism of synergistic effects between different herbs as a result of allosteric crosstalk between two ligands at a protein target, as well as revealed that using the multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis to discover novel combination drugs from a Chinese herbal remedy is an innovative pathway. [ABSTRACT FROM AUTHOR]

We measure the spin Hall angle in Au layers of 5-100 nm thicknesses by spin pumping from Y3Fe5O12 epitaxial films grown by ultrahigh vacuum, off-axis sputtering. We observe a striking increase in the spin Hall angle for Au layers thinner than the measured spin diffusion length of 12.6 nm. In particular, the 5 nm Au layer shows a large spin Hall angle of 0.087, compared to those of 0.016 and 0.017 for the 50 and 100 nm Au layers, respectively, suggesting that the top surface plays a dominant role in spin Hall physics when the spin current is able to reach it. Other spin pumping related parameters, including Gilbert damping enhancement, interfacial spin mixing conductance, and spin current are also determined for Au layers of various thicknesses. Given the pervasive role of ultrathin films in electrical and spin transport applications, this result emphasizes the importance of considering the impact of the top surface and reveals the possibility of tuning critical spin parameters by film thickness. [ABSTRACT FROM AUTHOR]

The Global Center is a new partnership between the Indianapolis Zoo and SSC, with the aim of accelerating the global conservation work of the SSC network. As the Global Center is situated within an Association of Zoos and Aquariums accredited zoo and in strong communication with the global conservation community, it is well positioned to enhance communication and align conservation activities between these groups. In August 2021, the Global Center for Species Survival initiated its work plan in support of the IUCN Species Survival Commission (SSC) network. [Extracted from the article]

Introduction: Respiratory Muscle Weakness (RMW) has been defined when the maximum inspiratory pressure (MIP) is lower than 70% of the predictive value. The prevalence of RMW in chronic heart failure patients is 30 to 50%. So far there are no studies on the prevalence of RMW in acute heart failure (AHF) patients. Objectives: Evaluate the prevalence of RMW in patients admitted because of AHF and the condition of respiratory muscle strength on discharge from the hospital. Methods: Sixty-three patients had their MIP measured on two occasions: at the beginning of the hospital stay, after they had reached respiratory, hemodynamic and clinical stability and before discharge from the hospital. The apparatus and technique to measure MIP were adapted because of age-related limitations of the patients. Data on cardiac ejection fraction, ECG, brain natriuretic peptide (BNP) levels and on the use of noninvasive ventilation (NIV) were collected. Results: The mean age of the 63 patients under study was 75 years. On admission the mean ejection fraction was 33% (95% CI: 31–35) and the BNP hormone median value was 726.5 pg/ml (range: 217 to 2283 pg/ml); 65% of the patients used NIV. The median value of MIP measured after clinical stabilization was -52.7 cmH2O (range: -20 to -120 cmH2O); 76% of the patients had MIP values below 70% of the predictive value. On discharge, after a median hospital stay of 11 days, the median MIP was -53.5 cmH2O (range:-20 to -150 cmH2O); 71% of the patients maintained their MIP values below 70% of the predictive value. The differences found were not statistically significant. Conclusion: Elderly patients admitted with AHF may present a high prevalence of RMW on admission; this condition may be maintained at similar levels on discharge in a large percentage of these patients, even after clinical stabilization of the heart condition. [ABSTRACT FROM AUTHOR]

Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot-dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasminogen markedly increased mortality in mice infected with streptococci, and this susceptibility was dependent on bacterial streptokinase expression. Thus, streptokinase is a key pathogenicity factor and the primary determinant of host species specificity for group A Streptococcal infection. In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens. [ABSTRACT FROM AUTHOR]

Shows that deficiency of ADAMTS13, a member of the ADAMTS family of zinc metalloproteinase genes, is the molecular mechanism responsible for thrombotic thrombocytopenic purpura (TTP). Role of the proteolysis of von Willebrande and/or other ADAMTS13 substrates in maintaining the balance between bleeding and clotting; Genetic mutations related to TTP.

Summary Reward-seeking behavior is regulated by a diverse collection of inputs to the nucleus accumbens (NAc). The information encoded in each excitatory afferent to the NAc is unknown, in part because it is unclear when these pathways are active in relation to behavior. Here we compare the activity profiles of amygdala, hippocampal, and thalamic inputs to the NAc shell in mice performing a cued reward-seeking task using GCaMP-based fiber photometry. We find that the rostral and caudal ends of the NAc shell are innervated by distinct but intermingled populations of forebrain neurons that exhibit divergent feeding-related activity. In the rostral NAc shell, a coordinated network-wide reduction in excitatory drive correlates with feeding, and reduced input from individual pathways is sufficient to promote it. Overall, the data suggest that pathway-specific input activity at a population level may vary more across the NAc than between pathways. Highlights • Rostral and caudal NAc have distinct inputs with divergent feeding-related activity • Consumption coincides with a synchronous dip in excitatory input to the rostral NAc • Reduced excitatory input to the NAc shell from multiple sources promotes feeding • Excitatory inputs to the NAc contain heterogeneous activity during reward seeking Reed et al. report that opposing activity is present within each of the excitatory afferents to the nucleus accumbens during reward-seeking behavior. Synchronized reductions in excitatory input to the rostral nucleus accumbens shell correlate with and promote food consumption. [ABSTRACT FROM AUTHOR]

Summary The childhood-onset motor disorder DYT6 dystonia is caused by loss-of-function mutations in the transcription factor THAP1, but the neurodevelopmental processes in which THAP1 participates are unknown. We find that THAP1 is essential for the timing of myelination initiation during CNS maturation. Conditional deletion of THAP1 in the CNS retards maturation of the oligodendrocyte (OL) lineage, delaying myelination and causing persistent motor deficits. The CNS myelination defect results from a cell-autonomous requirement for THAP1 in the OL lineage and is recapitulated in developmental assays performed on OL progenitor cells purified from Thap1 null mice. Loss of THAP1 function disrupts a core set of OL maturation genes and reduces the DNA occupancy of YY1, a transcription factor required for OL maturation. These studies establish a role for THAP1 transcriptional regulation at the inception of myelination and implicate abnormal timing of myelination in the pathogenesis of childhood-onset dystonia. [ABSTRACT FROM AUTHOR]