Thrombomodulin Improves Cognitive Deficits in Heat-Stressed Mice.

BACKGROUND: Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed (HS) mice. METHODS: Adult male mice were exposed to HS (33°C for 2 hours daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble TM (1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide (LPS), high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were biochemically measured. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined. RESULTS: Compared with controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice. CONCLUSIONS: The findings suggest that HS can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. TM, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.

Evaluation of the reliability of the upper lip bite test and the modified mallampati test in predicting difficult intubation under direct laryngoscopy in apparently normal patients: a prospective observational clinical study.

BACKGROUND AND AIMS: Difficult endotracheal intubation is one of the most challenging operations in anesthesia. How to better predict difficult airway and make corresponding preparations to reduce the occurrence of accidents is a difficult task faced by anesthesiologists every day. This study decide to evaluate the value of the Upper Lip Bite Test (ULBT) and the Modified Mallampati Test (MMT) in predicting difficult intubation under direct laryngoscopy and find out the most intuitive and simple method to predict difficult intubation under direct laryngoscopy in apparently normal patients. PATIENTS AND METHODS: This descriptive-analytical study was performed on 450 patients for elective surgery under general anesthesia requiring endotracheal intubation. The ULBT and MMT grading were evaluated preoperatively and Cormack and Lehane's (CL) classification was recorded on the day of surgery during intubation under direct laryngoscopy. The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR), Youden index and area under ROC curve of ULBT and MMT respectively and in combination were calculated and compared. And the consistency between the total scores of ULBT and MMT combined in different ways and CL grading was counted. RESULTS: Of the 450 patients, 69 (15.3%) were classified as difficult cases of direct laryngoscopy. The accuracy, sensitivity, specificity, PPV and NPV of ULBT were 81.33, 11.59, 93.96, 25.81, 85.44%; and those the corresponding values for MMT were 66.22, 62.32, 69.29, 26.88 and 91.03%. A combination of ULBT and MMT did not improve the sensitivity in the sample tested. The combined total scores of ULBT and MMT in both ways were less consistent with CL grading in predicting difficult intubation under direct laryngoscopy. CONCLUSION: Based on findings of current study, we conclude that ULBT and MMT for difficult intubation have only poor to moderate discriminative power when used alone. The combination of the two tests in fractional form is also not a good predictor of difficult intubation under direct laryngoscopy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100052987, Registered 07 November 2021, http://www.chictr.org.cn.

Quantitative Real-Time Assessment for Feeding Skill of Preterm Infants.

Nutritive sucking is the approach of obtaining primary food for newborns within six months. However, completing the precise coordination of sucking-swallowing-respiratory actions under oral feeding is usually difficult for preterm infants and may affect the body and neural development of the premature infant. For this reason, how to obtain the quantitatively physiological information related to oral feeding is useful for physicians making more accurate clinical diagnoses for oral feeding disorders. However, there is still lack of monitoring systems for evaluating the feeding skill of infants quantitatively and objectively. The assessment of the feeding skill or the diagnosis of oral-feeding disorders still depends on the clinical experience of medical staffs. In this study, a novel wireless monitoring system is proposed to evaluate the feeding behavior of infants quantitatively and objectively and analyze the characteristics of these actions under oral feeding. Here, a specific feeding bottle and an optical probe are also designed and successfully applied to non-invasively monitor the sucking and respiratory actions, and a microphone is also applied to monitor the swallowing action. From the experimental results, the sucking and swallowing rate increases and the respiratory rate decreases with the increase of the infant age. Moreover, the duration increases and the interval of sucking-action sequence decreases with the increase of the infant age respectively. The proposed system successfully assesses the feeding behavior of preterm infants and may provide an objective evaluation tool for oral feeding ability and identifying the risk of infant developmental delay in the future.

CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain.

BACKGROUND: In very preterm infants, white matter injury is a prominent brain injury, and hypoxic ischemia (HI) and infection are the two primary pathogenic factors of this injury. Microglia and microvascular endothelial cells closely interact; therefore, a common signaling pathway may cause neuroinflammation and blood-brain barrier (BBB) damage after injury to the immature brain. CXC chemokine ligand 5 (CXCL5) is produced in inflammatory and endothelial cells by various organs in response to insults. CXCL5 levels markedly increased in the amniotic cavity in response to intrauterine infection and preterm birth in clinical studies. The objective of this study is to determine whether CXCL5 signaling is a shared pathway of neuroinflammation and BBB injury that contributes to white matter injury in the immature brain. METHODS: Postpartum day 2 (P2) rat pups received lipopolysaccharide (LPS) followed by 90-min HI. Immunohistochemical analyses were performed to determine microglial activation, neutrophil infiltration, BBB damage, and myelin basic protein and glial fibrillary acidic protein expression. Immunofluorescence experiments were performed to determine the cellular distribution of CXCL5. Pharmacological tests were performed to inhibit or enhance CXCL5 activity. RESULTS: On P2, predominant increases in microglial activation and BBB damage were observed 24 h after LPS-sensitized HI induction, and white matter injury (decreased myelination and increased astrogliosis) was observed on P12 compared with controls. Immunohistochemical analyses revealed increased CXCL5 expression in the white matter 6 and 24 h after insult. Immunofluorescence experiments revealed upregulated CXCL5 expression in the activated microglia and endothelial cells 24 h after insult. CXCL5 inhibition by SB225002, a selective nonpeptide inhibitor of CXCR2, significantly attenuated microglial activation and BBB damage, increased myelination, and reduced astrogliosis in the white matter after LPS-sensitized HI. In addition, CXCL5-sensitized HI or CXCL5 alone significantly induced BBB damage and white matter injury in association with different neuroinflammation mechanisms. CXCL5-sensitized HI-induced microglial activation and neutrophil infiltration, whereas CXCL5 alone predominately caused neutrophil infiltration. CONCLUSIONS: CXCL5 is a potential biomarker for white matter injury in preterm infants. Pharmacological blockade of CXCL5 signaling that attenuates dysregulated neuroinflammation can be used a therapeutic strategy against white matter injury in the immature brain.

Analysis of drug-induced posterior reversible encephalopathy syndrome using the food and drug administration adverse drug events reporting system database.

OBJECTIVE: In this retrospective pharmacovigilance study, we gathered data on drug-induced posterior reversible encephalopathy syndrome (PRES). Our goal was to identify the primary suspect drugs in PRES by analyzing the Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHODS: We identified and analyzed reports of PRES listed in the FAERS database between 2004 and 2021. Using the reporting odds ratio and 95% confidence interval, we evaluated the safety signals for each of the drugs associated with PRES. RESULTS: We reviewed 11,077 reports of adverse events corresponding to PRES. The primary suspect drug categories were antineoplastics, immunosuppressants, and glucocorticoids. PRES was 24.77% more likely to occur in females than in males. Drug-induced PRES usually occurs in individuals with cancer, those who have undergone an organ/stem cell transplant, and those with autoimmune conditions. CONCLUSION: Our results show that the drugs most commonly suspected to cause PRES were antineoplastics, immunosuppressants, and glucocorticoids. Future studies are needed to illuminate the pathophysiological alterations that underlie PRES. In the meantime, prescribers and patients should be made aware of the potential risks of PRES associated with pharmaceutical therapy, and the summaries of product characteristics for individual drugs should be updated to include this information.

Implementing Explainable Machine Learning Models for Practical Prediction of Early Neonatal Hypoglycemia.

Hypoglycemia is a common metabolic disorder that occurs in the neonatal period. Early identification of neonates at risk of developing hypoglycemia can optimize therapeutic strategies in neonatal care. This study aims to develop a machine learning model and implement a predictive application to assist clinicians in accurately predicting the risk of neonatal hypoglycemia within four hours after birth. Our retrospective study analyzed data from neonates born ≥35 weeks gestational age and admitted to the well-baby nursery between 1 January 2011 and 31 August 2021. We collected electronic medical records of 2687 neonates from a tertiary medical center in Southern Taiwan. Using 12 clinically relevant features, we evaluated nine machine learning approaches to build the predictive models. We selected the models with the highest area under the receiver operating characteristic curve (AUC) for integration into our hospital information system (HIS). The top three AUC values for the early neonatal hypoglycemia prediction models were 0.739 for Stacking, 0.732 for Random Forest and 0.732 for Voting. Random Forest is considered the best model because it has a relatively high AUC and shows no significant overfitting (accuracy of 0.658, sensitivity of 0.682, specificity of 0.649, F1 score of 0.517 and precision of 0.417). The best model was incorporated in the web-based application integrated into the hospital information system. Shapley Additive Explanation (SHAP) values indicated mode of delivery, gestational age, multiparity, respiratory distress, and birth weight < 2500 gm as the top five predictors of neonatal hypoglycemia. The implementation of our machine learning model provides an effective tool that assists clinicians in accurately identifying at-risk neonates for early neonatal hypoglycemia, thereby allowing timely interventions and treatments.

Early neonatal hypoglycemia in term and late preterm small for gestational age newborns.

BACKGROUND: Neonatal hypoglycemia is a common metabolic occurrence among small for gestational age (SGA) neonates. This study aims to determine the incidence of early neonatal hypoglycemia and confirms the potential risk factors among term and late preterm SGA neonates in a well-baby newborn nursery of a tertiary medical center in Southern Taiwan. METHODS: We performed a retrospective medical record review of term and late preterm SGA (birth weight <10 percentile) neonates, born between January 1, 2012 and December 31, 2020, in the well-baby newborn nursery, of a tertiary medical center in Southern Taiwan. Blood glucose monitoring was routinely performed at 0.5, 1, 2, and 4 h of life. Antenatal and postnatal risk factors were recorded. Mean blood glucose level, age of occurrence, symptomatic hypoglycemia, and need for intravenous glucose treatment of early hypoglycemia in SGA neonates were documented. RESULTS: 690 SGA neonates in the nursery met the criteria and were retrospectively enrolled in the study, 358 of whom (51.80%) were male and 332 (48.10%) female. Of 690 enrolled SGA neonates, 134(19.42%) SGA neonates developed hypoglycemia during a well-baby nursery stay. Among these neonates, 97% of early hypoglycemic episodes occur during the first 2 h of life. The lowest blood glucose level was 46.78 ± 11.13 mg/dL, recorded in the first hour of life. Among the hypoglycemic 134 neonates, 26 (19.40%) neonates had to be transferred from the nursery to the neonatal ward and they required intravenous glucose treatment to achieve euglycemia. 14 (10.40%) neonates had symptomatic hypoglycemia. A multivariate logistic regression analysis revealed that cesarean delivery, small head circumference, small chest circumference, and low 1-min Apgar score were significant risk factors for early hypoglycemia in these neonates. CONCLUSION: Periodic routine blood glucose level monitoring within the first 4 h of life in term and late preterm SGA neonates is required, especially those with cesarean delivery and low Apgar score.

Data mining for signal detection of adverse events for taxanes based on the food and drug administration adverse drug events reporting system database.

BACKGROUND: This study aimed to mine and compare the positive signals of adverse drug events (ADE) in paclitaxel, docetaxel, and nab-paclitaxel to evaluate the accuracy of current drug package information inserts and enable clinicians to select the appropriate treatment. RESEARCH DESIGN AND METHODS: ADE data reported from January 2006 to December 2020 were extracted from the Food and Drug Adverse Drug Events Reporting System (FAERS) database, and the reporting odds ratio (ROR) was used to detect the risk signals of the 3 taxanes. The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). RESULTS: A total of 39,163 case reports on paclitaxel, docetaxel and nab-paclitaxel involving 25 different system organ classes (SOCs) were retrieved from the database. The ADE paclitaxel and nab-paclitaxel reports mainly focused on 'general disorders and administration site conditions' and the docetaxel ADE reports focused on 'skin and subcutaneous tissue diseases.' Among the three taxanes, nab-paclitaxel had the highest positive signal for serious adverse events. CONCLUSIONS: Overall, the most common ADE signals and ADE mapping systems obtained in this study were consistent with the package inserts. However, some inconsistencies were noted. Further research is recommended to confirm some of the strong risk signals for ADEs for taxanes before updating the drug package information inserts.

Myocardial structure and functional alterations in a preclinical model of exertional heat stroke.

AIM: Relatively little information is available about the effect of an acute exertional heat stroke (EHS) on myocardium structure and function. Herein, we used a survival male rat model of EHS to answer the question. MAIN METHODS: Adult male Wistar rats underwent forced treadmill running at a 36 °C room temperature and 50 % relative humidity until EHS onset, characterized by hyperthermia and collapse. All rats that were followed for 14 days survived. Injury severity scores of both gastrocnemius and myocardium were determined histologically. Following an EHS event, pathological echocardiography, skeletal muscle and myocardial damage scores and indicators, myocardial fibrosis, hypertrophy, and autophagy were elucidated. KEY FINDINGS: Rats with EHS onset displayed skeletal muscle damage, elevated serum levels of skeletal muscle damage indicators (e.g., creatinine kinase, myoglobin, and potassium), and myocardial injury indicators (e.g., cardiac troponin I, creatinine kinase, and lactate dehydrogenase) returning to homeostasis within 3 days post-EHS. However, EHS-induced myocardial damage, pathological echocardiography, myocardial fibrosis, hypertrophy, and deposited misfolded proteins lasted up to 14 days post-EHS at least. SIGNIFICANCE: First, we provide evidence to confirm that despite the apparent return to homeostasis, underlying processes may still be ongoing after EHS onset. Second, we provide several key findings emphasizing the pathophysiology and risk factors of EHS, highlighting gaps in knowledge with the aim of stimulating future studies.

Evaluation of feeding difficulties using videofluoroscopic swallow study and swallowing therapy in infants and children.

BACKGROUND: Infants and children with feeding difficulties have swallowing dysfunction and high risk of aspiration, which could be silent without choking, resulting in recurrent pneumonia and long-term respiratory morbidity. Videofluoroscopic swallow study (VFSS) is a useful tool for real-time visualization of the swallowing process and airway aspiration. This study reported a single-institutional 10-year experience of VFSS in pediatric patients with feeding difficulties and the efficacy of swallowing therapy. METHODS: From 2011 to 2020, 30 infants and children with feeding difficulties received VFSS examinations in a medical center at a median age of 19 months (range 7 days-8 years). The images of the swallowing process (oral phase, triggering of pharyngeal swallowing, and pharyngeal phase) under videofluoroscopy were analyzed by a radiologist and a speech-language pathologist. Aspiration severity was assessed from VFSS observations and rated by an eight-point Penetration-Aspiration-Scale (PAS), with higher scores indicating increased severity. Swallowing therapy was performed by experienced speech-language therapists, and follow-up of oral feeding tolerance and risk of aspiration pneumonia was done. RESULTS: Of the 30 patients, 24 (80%) had neurological deficits. High PAS scores (6-8) were observed in 25 (83.4%) patients, and 22 had a PAS score of 8, indicating silent aspiration. Of the 25 patients with high PAS scores, 19 (76%) had neurological deficits, and 18 (72%) depended on tube feeding at a median age of 20 months. Swallowing problems occurred most frequently during the pharyngeal phase in the patients with high PAS scores. VFSS-based swallowing therapy improved oral feeding ability and reduced aspiration episodes. CONCLUSION: Infants and children with swallowing dysfunction and neurological deficits had high risk of severe aspiration. Swallowing problems in the pharyngeal phase were the most common VFSS findings in patients with severe aspiration. VFSS may help guide problem-oriented swallowing therapy to reduce the risk of recurrent aspiration.

Cisplatin disrupts the latency of human herpesvirus 8 and induces apoptosis in primary effusion lymphoma cells.

Human herpesvirus 8 (HHV8) is the etiologic agent for primary effusion lymphoma (PEL). The aim of this study is to investigate the effects of cisplatin on the PEL cells. Cisplatin treatment induced apoptosis and inhibited the growth of PEL cells, and the effect was more profound in the HHV8-positive lymphoma cells compared with the EBV-positive lymphoma cells. Cisplatin treatment decreased the expression of HHV8 latent genes and activated p53 at serine 15 in PEL cells. Our results indicate that cisplatin can disrupt HHV8 latency and induce reactivation of p53 and highly selective treatment modality for this virally induced lymphoma.

Genetic polymorphisms influence the steroid treatment of children with idiopathic nephrotic syndrome.

BACKGROUND: Idiopathic nephrotic syndrome (INS) is the most frequent type of nephrotic syndrome that occurs in children. Its response to treatment with steroids varies. The aim of this study was to analyze the correlation between steroid metabolism-related genes and the response to steroid treatment. METHODS: The patient cohort comprised 74 children with INS, of whom were 58 steroid-sensitive (SS) cases and 16 steroid-resistant (SR) cases. The genetic polymorphisms analyzed were those of the CYP3A5 gene (A6986G) and ABCB1 gene (C1236T, G2677T/A, and C3435T), and the polymorphisms between SS and SR children were compared. RESULTS: C1236T in ABCB1 was associated with steroid resistance in INS children [odds ratio (OR) 2.65, 95 % confidence interval (CI) 1.01-6.94; p = 0.042] The frequency of the T allele was significantly higher in SR subjects than in SS subjects (0.81 vs. 0.62, respectively). A6986G in CYP3A5 showed a trend of association, but this association did not reach statistical significance (OR 2.63, 95 % CI 0.94-7.37; p = 0.059). No significant correlation was found between treatment response and G2677T/A or C3435T in ABCB1. CONCLUSIONS: Our results indicate that among our pediatric patients with INS the C1236T polymorphism in the ABCB1 gene was associated with steroid resistance, while the A6986G polymorphism in the CYP3A5 gene showed a trend of association, but did not reach statistical significance, requiring further analysis.

Comparison of the Effectiveness of Various Drug Interventions to Prevent Etomidate-Induced Myoclonus: A Bayesian Network Meta-Analysis.

Background: Myoclonic movement is a very common but undesirable phenomenon during the induction of general anesthesia using etomidate. Such movement may cause unnecessary problems. Currently, there is an increasing number of drugs for preventing etomidate-induced myoclonus (EM). However, direct comparisons of various drugs are lacking, and this interferes with clinical decision-making. Our network meta-analysis (NMA) aimed to compare the efficacy of different drugs for the prevention of moderate-to-severe general myoclonus. Methods: Using several biomedical databases, randomized controlled trials (RCTs) published in English from inception to August 22, 2021 were searched. Among the various interventions, we selected nine types of intervention drugs (dexmedetomidine, etomidate, lidocaine, NMDA receptor antagonist, κ opioid receptor agonist, µ opioid receptor agonist, muscle relaxant, gabapentin, and midazolam) for comparison, according to the number of studies. Bayesian NMA was performed using STATA16 and R softwares. The relative risk of EM was assessed using risk ratios (RRs) and the corresponding 95% confidence intervals (CI). Results: A total of 31 RCTs (3209 patients) were included. NMA results showed that, compared with a placebo, etomidate (RR 4.0, 95%CI 2.1-7.8), κ opioid receptor agonist (RR 2.9, 95%CI 1.9-4.6), µ opioid receptor agonist (RR 3.1, 95%CI 2.3-4.3), NMDA receptor antagonist (RR 1.7, 95%CI 1.0-2.8), dexmedetomidine (RR 2.4, 95%CI 1.5-3.9), lidocaine (RR 2.1, 95%CI 1.2-3.9), and midazolam (RR 2.2, 95%CI 1.5-3.2) can significantly reduce the risk of EM. In contrast, the effects of muscle relaxants (RR 2.1, 95%CI 0.81-5.3) and gabapentin (RR 2.8, 95%CI 0.92-9.3) were inconclusive. Further subgroup analyses showed that preoperative low-dose etomidate, µ-opioid receptor agonist, and κ-opioid receptor agonist were significantly better than other interventions in the prevention of moderate to severe EM. Conclusion: Preoperative use of small doses of etomidate or opioids may be the most effective way to avoid EM, especially moderate and severe EM, which makes anesthesia induction safer, more stable, and aligns better with the requirements of comfortable medicine. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], [CRD4202127706].

Glabridin from Glycyrrhiza glabra Possesses a Therapeutic Role against Keloid via Attenuating PI3K/Akt and Transforming Growth Factor-ß1/SMAD Signaling Pathways.

Glabridin (Gla) is a typical flavonoid isolated from the Glycyrrhiza glabra with various bioactivities and is a common additive in many cosmetics. In our study, we evaluated the antiscarring effect of Gla from G. glabra in a rabbit ear hyperplastic scar model. Hematoxylin and eosin staining and Masson staining were applied to determine the pathological changes and collagen fibers of scar tissue in rabbits. The results suggested that Gla could reduce rabbit ear scar hyperplasia, inhibit inflammation, and decrease collagen production. Furthermore, the in vitro cell experiments were applied to determine the effects of Gla on human keloid fibroblasts (HKFs), and we observed that Gla suppressed the HKF cells' proliferation via inducing apoptosis. Subsequently, we found that Gla reduced collagen production in HKF cells. The further molecular mechanisms investigations suggested that Gla played a therapeutic role against keloid by attenuating PI3K/Akt and TGFß1/SMAD pathways. Our study would be beneficial for extending the applications of the known sweet plant of G. glabra.

Effect of Exercise Interventions on Health-Related Quality of Life in Patients with Fibromyalgia Syndrome: A Systematic Review and Network Meta-Analysis.

Objective: Several guidelines highlight the beneficial impact of exercise on the management of symptoms and health-related quality of life (HRQOL) in patients with fibromyalgia syndrome (FMS). However, few analyses have compared different types of exercise. We, therefore, intent to compare the effects of different exercise types on improving the overall HRQOL and typical symptoms in patients with FMS. Methods: Medline, Embase, the Cochrane Register of Clinical Trials, and NIH ClinicalTrials.gov were searched from inception to April 21, 2022. Randomized clinical trials (RCTs) were included to assess the impact of exercise intervention on health parameters in adult FMS patients. Data were extracted independently and a frequentist network meta-analyses (NMA) was performed to rank the effects of interventions according to P-scores. The NMA evidence certainty was assessed using the method recommended by Grading of Recommendations Assessment, Development, and Evaluation Working Group. Results: A total of 57 RCTs were identified, including 3319 participants, involving 9 interventions (7 types of exercise, 2 controls). Of all treatments compared with usual care in efficacy outcomes, Mind-body exercise was associated with the best HRQOL (SMD, -12.12; 95% CI, -15.79 to -8.45). On the other characteristic symptom dimensions, based on moderate quality evidence, sensorimotor training was associated with minimal pain scores compared with usual care (SMD, -1.81; 95% CI, -2.81 to -0.82), whole body vibration therapy was most promising for improving sleep quality (SMD, -6.95; 95% CI, -10.03 to -3.87), pool-based aerobic exercise was most likely to ease anxiety (SMD, -4.83; 95% CI, -7.47 to -2.19), and whole body vibration was most likely to improve depression (SMD, -10.44; 95% CI, -22.00 to 1.12). Conclusion: Mind-body exercise seems to be the most effective exercise to improve the overall HRQOL of patients with FMS. But at the same time, clinicians still need to develop individualized exercise plans for patients according to their symptoms and accessibility.

The interrelationships between neuronal viability, synaptic integrity, microglial responses, and amyloid-beta formation in an in vitro neurotrauma model.

The interrelationships between neuronal viability, synaptic integrity, and microglial responses remain in infancy. In dealing with the question, we induced a stretch injury to evaluate the mechanical effects of trauma on rat primary cortical neurons and BV2 microglial cells in a transwell culture system. The viability of primary neurons and BV2 cells was determined by MTT. Synaptic integrity was evaluated by determining the expression of beta-secretase 1 (BACE1), amyloid-beta (Aß), microtubule-associated protein 2 (MAP2), and synaptophysin (vehicle protein). Both CD16/32-positive (CD16/32+) and CD206-positive (CD206+) microglia cells were detected by immunofluorescence staining. The phagocytic ability of the BV2 cells was determined using pHrodo E. coli BioParticles conjugates and flow cytometry. We found that stretch injury BV2 cells caused reduced viability and synaptic abnormalities characterized by Aß accumulation and reductions of BACE1, MAP2, and synaptophysin in primary neurons. Intact BV2 cells exhibited normal phagocytic ability and were predominantly CD206+ microglia cells, whereas the injured BV2 cells exhibited reduced phagocytic ability and were predominantly CD16/32+ microglial cells. Like a stretch injury, the injured BV2 cells can cause both reduced viability and synaptic abnormalities in primary neurons; intact BV2 cells, when cocultured with primary neurons, can protect against the stretch-injured-induced reduced viability and synaptic abnormalities in primary neurons. We conclude that CD206+ and CD16/32+ BV-2 cells can produce neuroprotective and cytotoxic effects on primary cortical neurons.

The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and ovarian cancer, etc. The related molecular mechanisms corresponding to the anticancer activities of emodin are involved in the induction of apoptosis, inhibition of cell proliferation, enhanced reactive oxygen species (ROS) accumulation, and induction of autophagy, etc. In the present review, we summarized the sources, anticancer properties in vitro and in vivo, molecular mechanisms, metabolic transformation and toxicities of emodin. In addition, we also discussed the limitations of the present investigations of emodin against cancers and gave some perspectives for them, which would be beneficial for the further exploration and development of this natural compound as a clinical cancer drug.

Atypical Sensory Processing and Its Correlation with Behavioral Problems in Late Preterm Children at Age Two.

This study aimed to compare the prevalence rate of atypical sensory processing in late preterm (LP) and term children at two years of age and to further investigate the co-occurrence of atypical sensory processing and behavioral problems (internalizing/externalizing) in both groups of children. A total of 104 children (52 LP and 52 sex- and birth order-matched term children) were included. The primary caregivers were asked to complete the Infant/Toddler Sensory Profile-Chinese version and the Child Behavior Checklist 1.5-5Y-Chinese version (CBCL-C/1.5-5). We found that the LP group had a similar prevalence rate of atypical sensory processing to the term group. However, neonatal intensive care unit experience (r = -0.356, p = 0.013, with visual processing) and days of ventilation and supplementary oxygen (r = -0.392, p = 0.004, with low registration) after birth were significantly correlated with the atypical sensory processing of LP children. Both LP and term children with behavioral problems seemed to have a higher prevalence rate of atypical sensory processing than their peers without behavioral problems. However, when Bonferroni correction was used to control for the statistical errors of multiple comparisons, only in the LP group did the co-occurrence of atypical sensory processing (auditory and oral sensory processing and sensation avoiding) and behavioral problems reach significance. In conclusion, the influence of late preterm birth on sensory processing may become subtle at age two, with the exception of those LP children experiencing complicated medical management after birth. A high level of co-occurrence of atypical sensory processing and behavioral problems suggests that the administration of a sensory processing assessment may be helpful to clarify the cause of problematic behavior and to recommend an appropriate intervention for LP children with behavioral problems.

Human herpesvirus 8 viral FLICE-inhibitory protein retards cell proliferation via downregulation of Id2 and Id3 expression.

Death receptor-mediated apoptosis is potently inhibited by viral FLIP (FLICE/caspase 8 inhibitory protein) through reduced activation of procaspase 8. In this study, we show that the human herpesvirus 8-encoded vFLIP retards cell proliferation. Overexpression of vFLIP caused cell cycle arrest, with an apparent decrease of cells in the S phase. The Id (inhibitor of DNA binding) proteins are considered as dominant negative regulators of differentiation pathways, but positive regulators of cellular proliferation. The mechanisms by which Id proteins promote the cell cycle are diverse, but appear to involve affecting the expression of cell cycle regulators. RT-PCR results demonstrated that the expression of vFLIP decreased the expression levels of Id2 and Id3 as well as cyclin E and cyclin A compared with the vFLIP-null cells. These indicate that vFLIP affects cell proliferation by decreasing the expression levels of cell cycle regulatory proteins.

Near-future levels of ocean temperature weaken the byssus production and performance of the mussel Mytilus coruscus.

Marine mussels are key ecological engineers that form dense aggregations to maintain the vital habitat in benthic systems. It is essential to understand the consequences of mussel byssus attachment in elevated temperatures associated with ocean warming. We evaluated byssus production and the mechanical performance of threads in the mussel Mytilus coruscus at 21° (control), 27 °C (average temperature in the M. coruscus habitat during the summer season) and 31 °C (4 °C raised) for 72 h. We quantified byssus secretion and shedding number, measured byssal breaking force, byssal polyphenol oxidase (PPO) activity, byssal thread length and diameter. Expression of byssus foot protein genes was analyzed by quantitative real-time PCR in foot tissue. High seawater temperature decreased the number of newly secreted byssus and the diameter of byssal threads, leading to the reduction of byssal breaking force and the alteration of the weakest part of the thread. Increased breakpoints in the upper part of the thread (proximal region) were higher at 27 °C than at 21 °C. High-temperature stress significantly reduced the PPO activity in byssus at 31 °C in comparison to 21 °C. The expression of mussel foot protein genes was affected by elevated temperature. The increased gene expression of byssus collagen-like protein 2 (Mccol2) at 31 °C conflicted with the number of byssuses produced. Suggesting the reduction of mussel foot protein abundance is not the cause of decreased byssus production at 31 °C. These results show that byssus, as an extracellular structure of mussels, may be highly susceptible to the adverse effects of ocean warming.