Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

Comparison of OSCE performance between 6- and 7-year medical school curricula in Taiwan.

BACKGROUND: The year 2013 marks a watershed in the history of medical education in Taiwan. Following Taiwan's Taskforce of Medical School Curriculum Reform recommendations, the medical school curriculum was reduced from 7 to 6 years. This study aimed to analyze the impact of medical school curriculum reform on medical students' performance in objective structured clinical examinations (OSCEs). METHODS: We retrospectively analyzed the OSCE records at Taipei Veterans General Hospital (Taipei VGH), one of Taiwan's largest tertiary medical centers, between November 2016 and July 2020. The eligibility criteria were medical students receiving a full one-year clinical sub-internship training at Taipei VGH and in their last year of medical school. All medical students received a mock OSCE-1 at the beginning of their sub-internship, a mock OSCE-2 after six months of training, and a national OSCE at the end of their sub-internship. The parameters for performance in OSCEs included "percentage of scores above the qualification standard" and "percentage of qualified stations." RESULTS: Between November 2016 and July 2020, 361 undergraduates underwent clinical sub-internship training at Taipei VGH. Among them, 218 were taught under the 7-year curriculum, and 143 were instructed under the 6-year curriculum. Based on baseline-adjusted ANCOVA results, medical students under the 7-year curriculum had a higher percentage of scores above the qualification standard than those under the 6-year curriculum at the mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 33.8% [95% CI 32.0-35.7] vs. 28.2% [95% CI 25.9-30.4], p < 0.001), and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001). Moreover, medical students in the 7-year curriculum had a higher percentage of qualified stations in mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001) and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 91.9% [95% CI 90.1-93.8] vs. 86.1% [95% CI 83.8-88.3], p = 0.001). After clinical sub-internship training, there were no differences in the percentage of scores above the qualification standard (7-year curriculum vs. 6-year curriculum: 33.5% [95% CI 32.2-34.9] vs. 34.6 [95% CI 32.9-36.3], p = 0.328) and percentage of qualified stations (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 88.1-90.7] vs. 90.2% [95% CI 88.6-91.8], p = 0.492). CONCLUSIONS: At the beginning of the sub-internship, medical students under the 7-year curriculum had better OSCE performance than those under the 6-year curriculum. After the clinical sub-internship training in Taipei VGH, there was no difference in the national OSCE score between the 6- and 7-year curricula. Our study suggests that clinical sub-internship is crucial for the development of clinical skills and performance in the national OSCE.

Genome-Wide Identification and Characterization of the NF-YA Gene Family and Its Expression in Response to Different Nitrogen Forms in Populus × canescens.

The NF-YA gene family is a class of conserved transcription factors that play important roles in plant growth and development and the response to abiotic stress. Poplar is a model organism for studying the rapid growth of woody plants that need to consume many nutrients. However, studies on the response of the NF-YA gene family to nitrogen in woody plants are limited. In this study, we conducted a systematic and comprehensive bioinformatic analysis of the NF-YA gene family based on Populus × canescens genomic data. A total of 13 PcNF-YA genes were identified and mapped to 6 chromosomes. According to the amino acid sequence characteristics and genetic structure of the NF-YA domains, the PcNF-YAs were divided into five clades. Gene duplication analysis revealed five pairs of replicated fragments and one pair of tandem duplicates in 13 PcNF-YA genes. The PcNF-YA gene promoter region is rich in different cis-acting regulatory elements, among which MYB and MYC elements are the most abundant. Among the 13 PcNF-YA genes, 9 contained binding sites for P. × canescens miR169s. In addition, RT-qPCR data from the roots, wood, leaves and bark of P. × canescens showed different spatial expression profiles of PcNF-YA genes. Transcriptome data and RT-qPCR analysis showed that the expression of PcNF-YA genes was altered by treatment with different nitrogen forms. Furthermore, the functions of PcNF-YA genes in transgenic poplar were analyzed, and the potential roles of PcNF-YA genes in the response of poplar roots to different nitrogen forms were revealed, indicating that these genes regulate root growth and development.

Transcranial electrostimulation with special waveforms enhances upper-limb motor function in patients with chronic stroke: a pilot randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) and intermittent theta burst stimulation (iTBS) were both demonstrated to have therapeutic potentials to rapidly induce neuroplastic effects in various rehabilitation training regimens. Recently, we developed a novel transcranial electrostimulation device that can flexibly output an electrical current with combined tDCS and iTBS waveforms. However, limited studies have determined the therapeutic effects of this special waveform combination on clinical rehabilitation. Herein, we investigated brain stimulation effects of tDCS-iTBS on upper-limb motor function in chronic stroke patients. METHODS: Twenty-four subjects with a chronic stroke were randomly assigned to a real non-invasive brain stimulation (NIBS; who received the real tDCS + iTBS output) group or a sham NIBS (who received sham tDCS + iTBS output) group. All subjects underwent 18 treatment sessions of 1 h of a conventional rehabilitation program (3 days a week for 6 weeks), where a 20-min NIBS intervention was simultaneously applied during conventional rehabilitation. Outcome measures were assessed before and immediately after the intervention period: Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Jebsen-Taylor Hand Function Test (JTT), and Finger-to-Nose Test (FNT). RESULTS: Both groups showed improvements in FMA-UE, JTT, and FNT scores after the 6-week rehabilitation program. Notably, the real NIBS group had greater improvements in the JTT (p = 0. 016) and FNT (p = 0. 037) scores than the sham NIBS group, as determined by the Mann-Whitney rank-sum test. CONCLUSIONS: Patients who underwent the combined ipsilesional tDCS-iTBS stimulation with conventional rehabilitation exhibited greater impacts than did patients who underwent sham stimulation-conventional rehabilitation in statistically significant clinical responses of the total JTT time and FNT after the stroke. Preliminary results of upper-limb functional recovery suggest that tDCS-iTBS combined with a conventional rehabilitation intervention may be a promising strategy to enhance therapeutic benefits in future clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04369235. Registered on 30 April 2020.

3,6'-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6'-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

Sustained effects of faculty leadership development modules for clinical instructors of core competences education in Taiwan: a four-year explanatory case study.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) core competencies (CC) in general medicine-based primary care are essential for junior medical trainees. In this country, a regular faculty development (FD) program aimed at training faculty in instructing (teaching and assessing) these CC had operated. However, leadership was not emphasized. In a new intervention module, the roles and associated responsibilities of clinical instructors to conduct, design, and lead CC-based education were emphasis. AIMS: This follow-up explanatory case study compares the effectiveness of intervention module with that of the previous regular module. METHODS: The regular group (n = 28) comprised clinical instructors who participated in the FD module during the 2013-2014 year while the intervention group (n = 28) was composed of 2015-2016 participants. Prior to the formal (hands-on) training, participants in the intervention group were asked to study the online materials of the regular module. These participants then received a 30-h hands-on training in conducting, designing, and leading skills. Finally, they prepared a 10-h reflective end-of-module presentation of their real-world practices. RESULTS: Following the training, a higher degree improvement in participants self-reported familiarity with CC education, self-confidence in their ability to deliver CC education and sustained involve CC education were noted among the intervention FD group, compared with the regular FD group. In the intervention group, senior academicians (associate and full professor) are more substantially involved in designing and leading CC-based courses than junior academicians (lecturers and assistant professors). Among non-teaching award winners of in the intervention FD group, the follow-up degree of sustained involvement in delivering, designing and leading CC-based courses was significantly higher than that of the regular group. CONCLUSIONS: Our study demonstrated that leadership training in the intervention FD modules substantially motivated clinical instructors to become leaders in CC education.

Standard setting made easy: validating the Equal Z-score (EZ) method for setting cut-score for clinical examinations.

BACKGROUND: This study aims to assess the feasibility, reliability and validity of the panel-based Equal Z-score (EZ) method applied to objective structural clinical examination (OSCE) of Chinese medical students and undertaking a comparison with the statistical techniques-based Borderline Regression Method (BRM). METHODS: Data received from two cohorts of 6th and 7th year medical students in Taiwan who set the mock OSCE as a formative assessment. Traditionally this medical school uses BRM to set the pass/fail cut-score. For the current study, 31 OSCE panellists volunteered to participate in the EZ method in parallel to the BRM. RESULTS: In the conduct of this study, each panel completed this task for an OSCE exam comprising 12 stations within less than 60 min. Moreover, none of the 31 panellists, whose are busy clinicians, had indicated that the task was too difficult or too time-consuming. Although EZ method yielded higher cut-scores than the BRM it was found reliable. Intraclass correlation (ICC) measuring absolute agreement, across the three groups of panellists was .893 and .937 for the first and second rounds respectively, demonstrating high level of agreement across groups with the EZ method and the alignment between the BRM and the EZ method was visually observed. The paired t-test results identified smaller differences between the cut-scores within methods than across methods. CONCLUSIONS: Overall this study suggests that the EZ method is a feasible, reliable and valid standard setting method. The EZ method requires relatively little resources (takes about an hour to assess a 12 station OSCE); the calculation of the cut-score is simple and requires basic statistical skills; it is highly reliable even when only 10 panellists participate in the process; and its validity is supported by comparison to BRM. This study suggests that the EZ method is a feasible, reliable and valid standard setting method.

Designing and Implementing an Implantable Wireless Micromanometer System for Real-Time Bladder Pressure Monitoring: A Preliminary Study.

Many mini-implantable devices have been developed and fabricated for diagnostic and treatment purposes. Wireless implantable biomicrosystems provide a desirable approach for long-term physiological signal monitoring. In this study, we implemented a wireless implantable biomicrosystem for bladder-cavity pressure measurements in a freely moving rabbit. To manage the power more effectively, a magnetic reed switch was applied to turn on/off the implantable module using a neodymium-iron-boron (NdFeB) magnet. The measured bladder pressure signal was wirelessly transmitted from the implantable module to a host unit. Our results indicated that the implantable biomicrosystem exhibited satisfactory performance and safety, as evidenced by an error percentage of less than ±1% for pressure measurements and less than 2 °C of a temperature rise under normal operation. The wireless biomicrosystem was implanted into the bladder cavity of a rabbit. Bladder pressure was simultaneously measured by both the biomicrosystem and conventional cystometry in the animal. The two signals were similar during the voiding phase, with a correlation coefficient of 0.885. Additionally, the biomicrosystem coated with polydimethylsiloxane in this study showed no cytotoxicity, which confirmed its biocompatibility. In conclusion, we demonstrated a good biocompatible wireless biomicrosystem which showed good reproducibility with respect to pressure monitoring by conventional cystometry. Further studies are needed to confirm the results of this preliminary feasibility study for actual clinical applications.

Multi-Ray Modeling of Ultrasonic Sensors and Application for Micro-UAV Localization in Indoor Environments.

Due to its payload, size and computational limits, localizing a micro air vehicle (MAV) using only its onboard sensors in an indoor environment is a challenging problem in practice. This paper introduces an indoor localization approach that relies on only the inertial measurement unit (IMU) and four ultrasonic sensors. Specifically, a novel multi-ray ultrasonic sensor model is proposed to provide a rapid and accurate approximation of the complex beam pattern of the ultrasonic sensors. A fast algorithm for calculating the Jacobian matrix of the measurement function is presented, and then an extended Kalman filter (EKF) is used to fuse the information from the ultrasonic sensors and the IMU. A test based on a MaxSonar MB1222 sensor demonstrates the accuracy of the model, and a simulation and experiment based on the T h a l e s I I MAV platform are conducted. The results indicate good localization performance and robustness against measurement noises.

Impaired Autophagy in Intestinal Epithelial Cells Alters Gut Microbiota and Host Immune Responses.

Establishing and maintaining beneficial interactions between the host and associated gut microbiota are pivotal requirements for host health. Autophagy is an important catabolic recycling pathway that degrades long-lived proteins and some organelles by lysosome to maintain cellular homeostasis. Although impaired autophagy is thought to be closely correlated with Crohn's disease (CD), the functional role of autophagy in the maintenance of gut microbiota is poorly understood. As autophagy-related 5 (Atg5) is a key gene associated with the extension of the phagophoric membrane in autophagic vesicles, we established a gut-specific Atg5 knockout mouse model, and we found that the disruption of autophagic flux in the intenstinal epithelium cells dramatically altered the composition of the gut microbiota and reduced alpha diversity. Microbial function prediction indicated that the pathway allocated for infectious diseases was enriched in Atg5-/- mice. "Candidatus Arthromitus" and the Pasteurellaceae family were increased in Atg5-/- mice, whereas Akkermansia muciniphila and the Lachnospiraceae family were reduced. Transcriptome analysis revealed that two key inflammatory bowel disease (IBD)-related transcription factors, RORC and TBX21, of host cells were upregulated in Atg5-/- mice, thus elevating the Muc2-related immunological response. The findings suggest that intestinal autophagy plays a vital role in modulating the diversity and composition of gut microbiota.IMPORTANCE The homeostasis of host-microbiota interactions is of great importance to host health. Previous studies demonstrated that disruption of autophagy was linked to inflammatory bowel disease. However, the interaction mechanism of gut microbiota regulated by autophagy was obscure. In an intestinal epithelium-specific autophagy-related 5 (Atg5) knockout mouse model, we observed a significant alteration and decreased diversity in the gut microbiota of Atg5-deficient mice compared with that of wild-type mice. Although the numbers of some organisms (e.g., Akkermansia muciniphila and members of the Lachnospiraceae family) associated with the control of inflammation decreased, those of proinflammationory bacteria (e.g., "Candidatus Arthromitus") and potential pathogens (the Pasteurellaceae family) increased in Atg5-/- mice. Differential gene expression analysis revealed that two key genes, RORC and TBX21, involved in inflammatory bowel disease were upregulated in Atg5-/- mice. Our study suggests that Atg5 deficiency results in an imbalance of the host-microbe interaction and deterioration of the gut microenvironment.

Mechanisms of the prevention and inhibition of the progression and development of non-alcoholic steatohepatitis by genetic and pharmacological decoy receptor 3 supplementation.

AIMS: Treatment of non-alcoholic steatohepatitis (NASH) is difficult due to the absence of a proven treatment and its comprehensive mechanisms. In the NASH animal model, upregulated hepatic inflammation and oxidative stress, with the resultant M1 polarization of macrophages as well as imbalanced adipocytokines, all accelerate NASH progression. As a member of the tumor necrosis factor receptor superfamily, decoy receptor 3 (DcR3) not only neutralizes the death ligands, but also performs immune modulations. In this study, we aimed to investigate the possible non-decoy effects of DcR3 on diet-induced NASH mice. METHODS: Methionine- and choline-deficient (MCD) diet feeding for 9 weeks was applied to induce NASH in BALB/c mice. Decoy receptor 3 heterozygous transgenesis or pharmacological pretreatment with DcR3a for 1 month were designed as interventions. Intrahepatic inflammatory status as well as macrophage polarization, oxidative stress, and steatosis as well as lipogenic gene expression and fibrotic status were analyzed. Additionally, acute effects of DcR3a on HepG2 cells, Hep3B cells, and primary mouse hepatocytes in various MCD medium-stimulated changes were also evaluated. RESULTS: Both DcR3 genetic and pharmacologic supplement significantly reduced MCD diet-induced hepatic M1 polarization. In addition, DcR3 supplement attenuated MCD diet-increased hepatic inflammation, oxidative stress, adipocytokine imbalance, steatosis, and fibrogenesis. Moreover, acute DcR3a incubation in HepG2 cells, Hep3B cells, and mouse hepatocytes could normalize the expression of genes related to lipid oxidation along with inflammation and oxidative stress. CONCLUSION: The ability of DcR3 to attenuate hepatic steatosis and inflammation through its non-decoy effects of immune modulation and oxidative stress attenuation makes it a potential treatment for NASH.

Voluntary attendance of small-group brainstorming tutoring courses intensify new clerk's "excellence in clinical care": a pilot study.

BACKGROUND: Clerkship provides a unique way of transferring the knowledge and skills gathered during medical school's curriculum into real-ward clinical care environment. The annual program evaluation has indicated that the training of clerks in diagnostic and clinical reasoning skills needed to be enhanced. Recently, "clinical excellence" program have been promoted in our institution to augment the excellence in clinical care of new clerks. Current study aims to evaluate whether this pilot program improve the "clinical excellence" of new clerks. METHODS: In a pilot study, groups of new clerks in years 2013 and 2014 voluntarily attended either a small-group brainstorming course or a didactic classroom tutoring courses as part of their 3-month internal medicine clinical rotation block. A third group of new clerks did not join either of the above courses and this group served as the control group. Pre-block/post-block self-assessment and post-block 5-station mini-Objective Subjective Clinical Examinations (OSCEs) were used to evaluate the effectiveness of these two additional courses that trained diagnostic and clinical reasoning skills. RESULTS: Overtime, the percentages of new clerks that attended voluntarily either the small-group brainstorming or classroom tutoring courses were increased. Higher post-block self-assessed diagnostic and clinical reasoning skill scores were found among individuals who attended the small-group brainstorming courses compared to either the didactic group or the control group. In a corresponding manner, the small-group brainstorming group obtained higher summary OSCEdiag and OSCEreason scores than either the didactic group or control group. For all basic images/laboratory OSCE stations, the individual diagnostic skill (OSCEdiag) scores of the small-group brainstorming group were higher than those of the didactic group. By way of contrast, only the clinical reasoning skill (OSCEreason) scores of the basic electrocardiogram and complete blood count + biochemistry OSCE station of thesmall-group brainstorming group were higher than those of the didactic group. Among the small-group brainstorming group, clerks with higher cumulative learning hours (>30-h) had significant higher OSCEdiag and OSCEreason scores (>400) than those with less cumulative learning hours. CONCLUSION: Our pilot study provides a successful example of the use of a small-group tutoring courses for augmenting the diagnostic and clinical reasoning skills of new clerks. The positive results obtained during the initial 2-year long pilot "clinical excellence" program have encouraged the formal implementation of this course as part of the clerkship curriculum.

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Neuronal apoptosis in the hippocampus has been detected after TBI. The hippocampal dysfunction may result in cognitive deficits in learning, memory, and spatial information processing. Our previous studies demonstrated that a p53 inhibitor, pifithrin-α oxygen analogue (PFT-α (O)), significantly reduced cortical cell death, which is substantial following controlled cortical impact (CCI) TBI, and improved neurological functional outcomes via anti-apoptotic mechanisms. In the present study, we examined the effect of PFT-α (O) on CCI TBI-induced hippocampal cellular pathophysiology in light of this brain region's role in memory. To investigate whether p53-dependent apoptosis plays a role in hippocampal neuronal loss and associated cognitive deficits and to define underlying mechanisms, SD rats were subjected to experimental CCI TBI followed by the administration of PFT-α or PFT-α (O) (2mg/kg, i.v.) or vehicle at 5h after TBI. Magnetic resonance imaging (MRI) scans were acquired at 24h and 7days post-injury to assess evolving structural hippocampal damage. Fluoro-Jade C was used to stain hippocampal sub-regions, including CA1 and dentate gyrus (DG), for cellular degeneration. Neurological functions, including motor and recognition memory, were assessed by behavioral tests at 7days post injury. p53, p53 upregulated modulator of apoptosis (PUMA), 4-hydroxynonenal (4-HNE), cyclooxygenase-IV (COX IV), annexin V and NeuN were visualized by double immunofluorescence staining with cell-specific markers. Levels of mRNA encoding for caspase-3, p53, PUMA, Bcl-2, Bcl-2-associated X protein (BAX) and superoxide dismutase (SOD) were measured by RT-qPCR. Our results showed that post-injury administration of PFT-α and, particularly, PFT-α (O) at 5h dramatically reduced injury volumes in the ipsilateral hippocampus, improved motor outcomes, and ameliorated cognitive deficits at 7days after TBI, as evaluated by novel object recognition and open-field test. PFT-α and especially PFT-α (O) significantly reduced the number of FJC-positive cells in hippocampus CA1 and DG subregions, versus vehicle treatment, and significantly decreased caspase-3 and PUMA mRNA expression. PFT-α (O), but not PFT-α, treatment significantly lowered p53 and elevated SOD2 mRNA expression. Double immunofluorescence staining demonstrated that PFT-α (O) treatment decreased p53, annexin V and 4-HNE positive neurons in the hippocampal CA1 region. Furthermore, PUMA co-localization with the mitochondrial maker COX IV, and the upregulation of PUMA were inhibited by PFT-α (O) after TBI. Our data suggest that PFT-α and especially PFT-α (O) significantly reduce hippocampal neuronal degeneration, and ameliorate neurological and cognitive deficits in vivo via antiapoptotic and antioxidative properties.

Reparixin attenuates neuronal injury in experimental Klebsiella pneumoniae meningoencephalitis through dual effects on neuroprotection and neuroinflammation.

AIMS: Bacterial meningitis causes high mortality and brain damage. The host immune response is associated with brain injury. Chemokine (C-X-C motif) (CXC) chemokines are neutrophil chemoattractants. This study focused on the beneficial effects of intracerebroventricular administration of reparixin, an inhibitor of chemokine (C-X-C motif) receptor (CXCR)1/2, to rats at 2 h following experimental Klebsiella pneumoniae meningoencephalitis. METHODS: We used a previously established meningoencephalitis animal model in which Sprague-Dawley rats were infected by K. pneumoniae. Sham and infected animals were treated with vehicle or reparixin and sacrificed at various time points. Leukocyte infiltration into cerebrospinal fluid (CSF) and brain as well as gene and protein expression of chemokines and receptors, and neuronal apoptosis were examined. Primary cultures of neuron/glia were infected with K. pneumoniae as an in vitro model of meningoencephalitis. RESULTS: Levels of chemokine (C-X-C motif) ligand (CXCL)2 in CSF time-dependently increased markedly as early as 2 h, and peaked at 8 h following infection and were much higher than those in serum collected simultaneously. Reparixin significantly reduced leukocyte infiltration into CSF and brain tissues, clinical illness, and brain cell apoptosis at 24 h. Reparixin reduced the elevated CSF concentrations of chemokines [CXCL1, CXCL2, chemokine (C-C motif) ligand (CCL)2 and CCL5] and proinflammatory cytokines. Reparixin also reduced the expression of mRNA of various chemokines, chemokine receptors and proinflammatory cytokines in infected brain tissues. Using primary cultures that are devoid of leukocytes, we further observed that reparixin attenuated the neuronal, but not microglial cell death after infection. CONCLUSIONS: Reparixin not only reduces amplified inflammation, but also provides direct neuroprotective effects in K. pneumoniae meningoencephalitis.

Association of traumatic brain injury in childhood and attention-deficit/hyperactivity disorder: a population-based study.

BACKGROUND: We evaluated the risk of attention-deficit hyperactivity disorder (ADHD) following childhood traumatic brain injury (TBI). METHODS: Using Taiwan's National Health Insurance Research Database, we included 10,416 newly diagnosed TBI children (aged ≤12 y) between 2001 and 2002 and 41,664 children without TBI, who were frequency matched by sex, age, and year of the index medical service with each TBI child, as controls. Children who had been diagnosed with ADHD prior to their medical service index were excluded. Each individual was followed for 9 y to identify ADHD diagnosis. We also compared the ADHD risk in children who were treated for fractures but not TBI as sensitivity analysis. RESULTS: During the 9-y follow-up period, children with TBI had a higher ADHD risk (adjusted hazard ratio (AHR) = 1.32, 95% confidence interval (CI) = 1.19, 1.45) than did those without TBI. Furthermore, children with mild and severe TBI had higher AHRs for ADHD than did those without TBI (AHR = 1.30; 95% CI = 1.10, 1.53; and AHR = 1.37; 95% CI = 1.22, 1.55). However, no significant association was observed between fractures and ADHD. CONCLUSION: TBI in childhood is associated with a greater likelihood of developing ADHD.

Identification of alleles and genotypes of beta-casein with DNA sequencing analysis in Chinese Holstein cow.

The study reported in this Regional Research Communication aimed to analyse the genetic polymorphisms of ß-casein in Chinese Holstein cows. ß-casein has received considerable research interest in the dairy industry and animal breeding in recent years as a source not only of high quality protein, but also of bioactive peptides that may be linked to health effects. Morever, the polymorphic nature of ß-casein and its association with milk production traits, composition, and quality also attracted several efforts in evaluating the allelic distribution of ß-casein locus as a potential dairy trait marker. However, few data on beta-casein variants are available for the Chinese Holstein cow. In the present paper, one hundred and thirty three Holstein cows were included in the analysis. Results revealed the presence of 5 variants (A1, A2, A3, B and I), preponderance of the genotype A1A2 (0·353) and superiorities of A1/A2 alleles (0·432 and 0·459, respectively) in the population. Sequence analysis of ß-casein gene in the cows showed four nucleotide changes in exon 7. Our study can provide reference and guidance for selection for superior milk for industrial applications and crossbreeding and genetic improvement programmes.

The epidemiology and prognostic factors of mortality in critically ill children with acute kidney injury in Taiwan.

The incidence of acute kidney injury (AKI) in critically ill children varies among countries. Here we used claims data from the Taiwanese National Health Insurance program from 2006 to 2010 to investigate the epidemiological features and identify factors that predispose individuals to developing AKI and mortality in critically ill children with AKI. Of 60,338 children in this nationwide cohort, AKI was identified in 850, yielding an average incidence rate of 1.4%. Significant independent risk factors for AKI were the use of extracorporeal membrane oxygenation, mechanical ventilation or vasopressors, intrinsic renal diseases, sepsis, and age more than 1 year. Overall, of the AKI cases, 46.5% were due to sepsis, 36.1% underwent renal replacement therapy, and the mortality rate was 44.2%. Multivariate analysis showed that the use of vasopressors, mechanical ventilation, and hemato-oncological disorders were independent predictors of mortality in AKI patients. Thirty-two of the 474 patients who survived had progression to chronic kidney disease or end-stage renal disease. Thus, although not common, AKI in critically ill children still has a high mortality rate associated with a variety of factors. Long-term close follow-up to prevent progressive chronic kidney disease in survivors of critical illnesses with AKI is mandatory.

MRAC Control with Prior Model Knowledge for Asymmetric Damaged Aircraft.

This paper develops a novel state-tracking multivariable model reference adaptive control (MRAC) technique utilizing prior knowledge of plant models to recover control performance of an asymmetric structural damaged aircraft. A modification of linear model representation is given. With prior knowledge on structural damage, a polytope linear parameter varying (LPV) model is derived to cover all concerned damage conditions. An MRAC method is developed for the polytope model, of which the stability and asymptotic error convergence are theoretically proved. The proposed technique reduces the number of parameters to be adapted and thus decreases computational cost and requires less input information. The method is validated by simulations on NASA generic transport model (GTM) with damage.

Streptomyces zhaozhouensis sp. nov., an actinomycete isolated from candelabra aloe (Aloe arborescens Mill).

A novel endophytic actinomycete, designated strain NEAU-LZS-5(T), was isolated from the leaf of candelabra aloe (Aloe arborescens Mill) and characterized using a polyphasic approach. Analysis of the 16S rRNA gene sequence showed that strain NEAU-LZS-5(T) belongs to the genus Streptomyces and exhibited 99.51 and 97.37 % similarity to Streptomyces sedi YIM 65188(T) and Streptomyces specialis GW41-1564(T), respectively, whereas low similarity values (<97 %) distinguished strain NEAU-LZS-5(T) from all other species of the genus Streptomyces with validly published names. Two tree-making algorithms also supported the position that strain NEAU-LZS-5(T) formed a distinct clade with Streptomyces sedi YIM 65188(T) and Streptomyces specialis GW41-1564(T). However, levels of DNA-DNA relatedness between strain NEAU-LZS-5(T) and Streptomyces sedi YIM 65188(T) and Streptomyces specialis GW41-1564(T) were 45.59 and 31.90 %, respectively. A comparative study between strain NEAU-LZS-5(T) and the type strains of closest related species of the genus Streptomyces revealed that it differed from them in morphological, physiological and biochemical characteristics. Therefore, strain NEAU-LZS-5(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces zhaozhouensis sp. nov. is proposed. The type strain is NEAU-LZS-5(T) ( = CGMCC 4.7095(T) = DSM 42101(T)).

Micromonospora polyrhachis sp. nov., an actinomycete isolated from edible Chinese black ant (Polyrhachis vicina Roger).

A novel actinomycete, designated strain NEAU-ycm2(T), was isolated from edible Chinese black ants (Polyrhachis vicina Roger) and characterized using a polyphasic approach. The organism was found to have morphological and chemotaxonomic characteristics typical of the genus Micromonospora. The 16S rRNA gene sequence of strain NEAU-ycm2(T) showed highest similarity to those of Micromonospora sonneratiae 274745(T) (99.12%), Micromonospora pattaloongensis TJ2-2(T) (98.85%), Micromonospora pisi GUI 15(T) (98.76%), Polymorphospora rubra TT 97-42(T) (98.42%) and Micromonospora eburnea LK2-10(T) (98.21%). Phylogenetic analysis based on the 16S rRNA gene and gyrB gene demonstrated that strain NEAU-ycm2(T) is a member of the genus Micromonospora and supported the close phylogenetic relationship to M. sonneratiae 274745(T), M. pattaloongensis JCM 12833(T) and M. pisi GUI 15(T). Furthermore, a combination of DNA-DNA hybridization and some physiological and biochemical properties indicated that the novel strain could be readily distinguished from its closest phylogenetic relatives. Therefore, it is proposed that NEAU-ycm2(T) represents a novel species of the genus of Micromonospora, for which the name Micromonospora polyrhachis sp. nov. is proposed. The type strain is NEAU-ycm2(T) ( = CGMCC 4.7100(T) = DSM 45886(T)).