Evolutionary trends of respiratory syncytial viruses: Insights from large-scale surveillance and molecular dynamics of G glycoprotein.

Human respiratory syncytial virus (RSV) is an underlying cause of lower respiratory illnesses in children, elderly and immunocompromised adults. RSV contains multiple structural and non-structural proteins with two major glycoproteins that control the initial phase of infection, fusion glycoprotein and the attachment (G) glycoprotein. G protein attaches to the ciliated cells of airways initiating the infection. The hypervariable G protein plays a vital role in evolution of RSV strains. We employed multiple bioinformatics tools on systematically accessed large-scale data to evaluate mutations, evolutionary history, and phylodynamics of RSV. Mutational analysis of central conserved region (CCR) on G protein-coding sequences between 163 and 189 positions revealed frequent mutations at site 178 in human RSV (hRSV) A while arginine to glutamine substitutions at site 180 positions in hRSV B, remained prevalent from 2009 to 2014. Phylogenetic analysis indicates multiple signature mutations within G protein responsible for diversification of clades. The USA and China have highest number of surveillance records, followed by Kenya. Markov Chain Monte Carlo Bayesian skyline plot revealed that RSV A evolved steadily from 1990 to 2000, and rapidly between 2003 and 2005. Evolution of RSV B continued from 2003 to 2022, with a high evolution stage from 2016 to 2020. Throughout evolution, cysteine residues maintained their strict conserved states while CCR has an entropy value of 0.0039(±0.0005). This study concludes the notion that RSV G glycoprotein is continuously evolving while the CCR region of G protein maintains its conserved state providing an opportunity for CCR-specific monoclonal antibodys (mAbs) and inhibitors as potential candidates for immunoprophylaxis.

Unveiling the nexus of postoperative fever and delirium in cardiac surgery: identifying predictors for enhanced patient care.

Background: Postoperative delirium (POD) is a significant complication observed in cardiac surgery patients, characterized by acute cognitive decline, fluctuating mental status, consciousness impairment, and confusion. Despite its impact, POD often goes undiagnosed. Postoperative fever, a common occurrence after cardiac surgery, has not been comprehensively studied in relation to delirium. This study aims to identify perioperative period factors associated with POD in patients undergoing cardiopulmonary bypass, with the potential for implementing preventive interventions. Methods: In a prospective observational study conducted between February 2023 and April 2023 at the Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, a total of 232 patients who underwent cardiac surgery were enrolled. POD assessment utilized the Confusion Assessment Method for the ICU (CAM-ICU), while high fever was defined as a bladder temperature exceeding 39°C. Statistical analysis included univariate and multivariate analyses, logistic regression, nomogram development, and internal validation. Result: The overall incidence of postoperative delirium was found to be 12.1%. Multivariate analysis revealed that postoperative lactate levels [odds ratio (OR) = 1.787], maximum temperature (OR = 11.290), and cardiopulmonary bypass time (OR = 1.015) were independent predictors of POD. A predictive nomogram for POD was developed based on these three factors, demonstrating good discrimination and calibration. The prediction model exhibited a C-statistic value of 0.852 (95% CI, 0.763-0.941), demonstrating excellent discriminatory power. Sensitivity and specificity, based on the area under the receiver operating characteristic (AUROC) curve, were 91.2% and 67.9%, respectively. Conclusion: This study underscores the high prevalence of POD in cardiac surgery patients and identifies postoperative lactate levels, cardiopulmonary bypass duration, and postoperative fever as independent predictors of delirium. The association between postoperative fever and POD warrants further investigation. These findings have implications for implementing preventive strategies in high-risk patients, aiming to mitigate postoperative complications and improve patient outcomes.

A randomized double-blinded study assessing the dose-response of ropivacaine with dexmedetomidine for maintenance of labor with epidural analgesia in nulliparous parturients.

Background: The combination of ropivacaine and dexmedetomidine has been used as an epidural analgesic for inducing labor. However, there is limited data regarding the administration of epidural analgesia for labor maintenance, hence, this study aimed to determine the optimum concentration through dose-response curves of ropivacaine plus dexmedetomidine, which could be used along with the Programmed Intermittent Epidural Bolus (PIEB) technique. Methods: One hundred parturients were randomized into 4 groups who were administered four different doses of ropivacaine (dexmedetomidine at 0.4 µg mL-1): 0.04%, 0.06%, 0.08%, and 0.1%. The primary outcome that was determined included the proportion of patients experiencing breakthrough pain during their 1st stage of labor. Breakthrough pain was described as a visual analog scale [VAS] score of >30 mm, requiring supplemental epidural analgesia after the administration of at least one patient-controlled bolus. The effective concentration of analgesia that was used for labor maintenance in 50% (EC50) and 90% (EC90) of patients were calculated with the help of probit regression. Secondary outcomes included epidural block characteristics, side effects, neonatal outcomes, and patient satisfaction. Results: The results indicated that the proportion of patients without breakthrough pain was 45% (10/22), 55% (12/22), 67% (16/24), and 87% (20/23) for 0.04%, 0.06%, 0.08%, and 0.10% doses of the analgesic that were administered, respectively. The EC50 value was 0.051% (95% confidence interval [CI], 0.011%-0.065%) while the EC90 value was recorded to be 0.117% (95% CI, 0.094%-0.212%). Side effects were similar among groups. Conclusion: A ropivacaine dose of 0.117% can be used as epidural analgesia for maintaining the 1st stage of labor when it was combined with dexmedetomidine (0.4 µg mL-1) and the PIEB technique. Clinical Trial Register: https://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059557.

Enhancement Effects and Mechanism Studies of Two Bismuth-Based Materials Assisted by DMSO and Glycerol in GC-Rich PCR.

Polymerase chain reaction (PCR) has extensive bioanalytical applications in molecular diagnostics and genomic research studies for rapid detection and precise genomic amplification. Routine integrations for analytical workflow indicate certain limitations, including low specificity, efficiency, and sensitivity in conventional PCR, particularly towards amplifying high guanine-cytosine (GC) content. Further, there are many ways to enhance the reaction, for example, using different PCR strategies such as hot-start/touchdown PCR or adding some special modifications or additives such as organic solvents or compatible solutes, which can improve PCR yield. Due to the widespread use of bismuth-based materials in biomedicine, which have not yet been used for PCR optimization, this attracts our attention. In this study, two bismuth-based materials that are inexpensive and readily available were used to optimize GC-rich PCR. The results demonstrated that ammonium bismuth citrate and bismuth subcarbonate effectively enhanced PCR amplification of the GNAS1 promoter region (∼84% GC) and APOE (75.5% GC) gene of Homo sapiens mediated by Ex Taq DNA polymerase within the appropriate concentration range. Combining DMSO and glycerol additives was critical in obtaining the target amplicons. Thus, the solvents mixed with 3% DMSO and 5% glycerol were used in bismuth-based materials. That allowed for better dispersion of bismuth subcarbonate. As for the enhanced mechanisms, the surface interaction of PCR components, including Taq polymerase, primer, and products with bismuth-based materials, was maybe the main reason. The addition of materials can reduce the melting temperature (Tm), adsorb polymerase and modulate the amount of active polymerase in PCR, facilize the dissociation of DNA products, and enhance the specificity and efficiency of PCR. This work provided a class of candidate enhancers for PCR, deepened our understanding of the enhancement mechanisms of PCR, and also explored a new application field for bismuth-based materials.

Exploring the Inhibitory Effect of AgBiS2 Nanoparticles on Influenza Viruses.

Influenza viruses are respiratory pathogens that are major threats to human health. Due to the emergence of drug-resistant strains, the use of traditional anti-influenza drugs has been hindered. Therefore, the development of new antiviral drugs is critical. In this article, AgBiS2 nanoparticles were synthesized at room temperature, using the bimetallic properties of the material itself to explore its inhibitory effect on the influenza virus. By comparing the synthesized Bi2S3 and Ag2S nanoparticles, it is found that after adding the silver element, the synthesized AgBiS2 nanoparticles have a significantly better inhibitory effect on influenza virus infection than Bi2S3 and Ag2S nanoparticles. Recent studies have shown that the inhibitory effect of AgBiS2 nanoparticles on the influenza virus mainly occurs in the stages of influenza virus-cell internalization and intracellular replication. In addition, it is found that AgBiS2 nanoparticles also have prominent antiviral properties against α and ß coronaviruses, indicating that AgBiS2 nanoparticles have significant potential in inhibiting viral activity.

Application of Nanomaterials to Enhance Polymerase Chain Reaction.

Polymerase Chain Reaction (PCR) is one of the most common technologies used to produce millions of copies of targeted nucleic acid in vitro and has become an indispensable technique in molecular biology. However, it suffers from low efficiency and specificity problems, false positive results, and so on. Although many conditions can be optimized to increase PCR yield, such as the magnesium ion concentration, the DNA polymerases, the number of cycles, and so on, they are not all-purpose and the optimization can be case dependent. Nano-sized materials offer a possible solution to improve both the quality and productivity of PCR. In the last two decades, nanoparticles (NPs) have attracted significant attention and gradually penetrated the field of life sciences because of their unique chemical and physical properties, such as their large surface area and small size effect, which have greatly promoted developments in life science and technology. Additionally, PCR technology assisted by NPs (NanoPCR) such as gold NPs (Au NPs), quantum dots (QDs), and carbon nanotubes (CNTs), etc., have been developed to significantly improve the specificity, efficiency, and sensitivity of PCR and to accelerate the PCR reaction process. This review discusses the roles of different types of NPs used to enhance PCR and summarizes their possible mechanisms.

Determination of the Relative Potency of Norepinephrine and Phenylephrine Given as Infusions for Preventing Hypotension During Combined Spinal-Epidural Anesthesia for Cesarean Delivery: A Randomized Up-And-Down Sequential Allocation Study.

Purpose: The relative potency of norepinephrine and phenylephrine given as boluses to treat hypotension during spinal anesthesia for cesarean delivery has been reported but few data are available for infusions. This study aimed to determine the relative potency of norepinephrine and phenylephrine when given by infusion for preventing hypotension during combined spinal-epidural anesthesia for cesarean delivery. Methods: This was a prospective, randomized, double-blind, up-and-down sequential allocation study. Patients were randomly allocated to receive a prophylactic infusion of norepinephrine or phenylephrine started immediately after induction of anesthesia. The first patients received either norepinephrine 0.1 µg/kg/min or phenylephrine 0.5 µg/kg/min. An effective infusion rate was defined when no hypotension occurred before delivery. For each subsequent patient, the norepinephrine infusion rate was decreased or increased by 0.01 µg/kg/min or the phenylephrine infusion rate was decreased or increased by 0.05 µg/kg/min according to whether the infusion was effective or ineffective respectively in the previous patient. Values for the infusion rate that was effective in preventing hypotension in 50% of patients (ED50) for norepinephrine and phenylephrine were estimated using up-and-down sequential analysis and relative potency was estimated. Probit regression was used as a backup and sensitivity analysis. Results: The ED50 values for norepinephrine and phenylephrine calculated by the up-and-down method were 0.061 (95% CI 0.054-0.068) µg/kg/min and 0.368 (95% CI 0.343-0.393) µg/kg/min respectively. The estimated relative potency ratio for ED50 for norepinephrine to phenylephrine was 6.03:1 (95% CI 5.26:1 to 6.98:1). Conclusion: Under the conditions of this study, norepinephrine given by infusion was about 6 times more potent than phenylephrine. This information is useful for clinical practice and further comparative studies of norepinephrine versus phenylephrine. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx, identifier [ChiCTR2200056237].

[Diagnosis and treatment of orbital complications of acute sinusitis in 51 children].

Objective:To analyze the clinical features, diagnosis and treatment of acute sinusitis related orbital cellulitis in children. Methods:The data of 51 cases with acute sinusitis comorbid with orbital cellulitis in Tianjin Children's Hospital from April 2016 to March 2021 were retrospectively analyzed. According to the extent of infection, the patients were divided into two groups:pre-septal orbital cellulitis（7 cases） and post-septal orbital cellulitis（44 cases）. The general clinical characteristics, clinical manifestations, laboratory examination and treatment were compared between the two groups. Among them, 23 cases（6 in pre-septal orbital cellulitis group and 17 in post-septal orbital cellulitis group） were cured by medicine treatment; 28 cases were cured by surgical treatment after failure of medicine treatment. Results:There was no significant difference in age, gender and medical history between the two groups. Redness, swelling, heat and pain in eyelid was the most common clinical manifestations of orbital cellulitis in children, followed by fever, headache, runny nose, eye fixation, and vision loss. WBC count and neutrophils percentage were significantly higher in post-septal orbital cellulitis group. All children were followed up for 3 months to 3 years， 1 case was lost to follow-up， 50 cases had no recurrence and recovered well. Conclusion:Orbital cellulitis is a common and rapid developing complication of sinusitis in children. Early diagnosis and effective anti-infection treatment are very important for prognosis. Orbital CT plays an important role in the determination and evaluation of this complication. When conservative treatment is ineffective, surgical drainage in time can reduce the occurrence of serious ocular sequelae.

Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.

The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.

Impact of Different Proportions of 2D and 3D Scaffolds on the Proliferation and Differentiation of Human Adipose-Derived Stem Cells.

PURPOSE: To observe the proliferation and differentiation of human adipose-derived stem cells (hADSCs) on 2D and 3D scaffolds, the sodium alginate and collagen interpenetrating network hydrogel were developed to determine optimal properties for bone tissue engineering. METHODS: Three groups of scaffold materials were prepared according to the ratio of sodium alginate to collagen: A (4:1), B (2:1), and C (1:1), respectively. For each group, gel beads (3D surfaces) and freeze-dried films (2D surfaces) were respectively prepared. For gel beads, hADSCs were mixed during the preparation of the beads, and then stem cells were applied to the surface of each film after freeze-drying and sterilization during the preparation of the freeze-dried films. Cell proliferation and osteogenic differentiation potential were detected by cell counting kit, viable/dead cell staining kit, quantitative reverse transcription polymerase chain reaction, and immunofluorescent staining, respectively. RESULTS: Results showed that cell proliferation rate progressively increased with the increase of collagen ratio, with group C of 3D surfaces of gel beads achieving the highest rate. In particular, highest cell viability on the 2D surfaces was achieved in group B. Differences in BGLAP and RUNX2 expression in hADSCs on 2D or 3D surfaces of the 3 groups were statistically significant. Particularly, BGLAP and RUNX2 gene expression levels were highest in group C of freeze-dried films and were highest in group B of gel beads. Furthermore, the trend of immunofluorescence expression of RUNX2 and osteocalcin expression were consistent with the genetic testing results. CONCLUSIONS: All data indicated that sodium alginate-collagen scaffolding materials had no adverse impact on the proliferation and osteogenic differentiation of hADSCs. Cell differentiation and proliferation of bone tissue engineering can be promoted with the use of sodium alginate and collagen interpenetrating network hydrogel, and the appropriate ratio of sodium alginate and collagen is 2:1.

IL-32 exacerbates adenoid hypertrophy via activating NLRP3-mediated cell pyroptosis, which promotes inflammation.

Adenoid hypertrophy (AH) is a common pediatric disease caused by inflammatory stimulation. The pro-inflammatory cytokine IL-32 has been reported to promote airway inflammation and also be involved in the pyroptosis pathway. However, whether IL-32 can contribute to AH by mediating pyroptosis remains to be elucidated. The present study aimed to investigate the role of IL-32 in AH and determine the potential underlying mechanisms. Adenoid tissues were collected from healthy children and children with AH, and the expression of IL-32, NACHT LRR and PYD domains-containing protein 3 (NLRP3) and IL-1ß in normal and hypertrophic tissues were measured. Human nasal epithelial cells (HNEpCs) were exposed to a series of IL-32 concentrations. HNEpCs with or without IL-32 silencing were stimulated with lipopolysaccharide (LPS), and cell proliferation, cell apoptosis, gasdermin D (GSDMD) activation, production of inflammatory cytokines and the expression levels of proteins related to the potential mechanisms were evaluated by Cell Counting Kit-8, flow cytometry, immunofluorescence staining, ELISA and western blot assays, respectively. The results showed that IL-32, NLRP3 and IL-1ß exhibited higher expression in adenoid tissues with AH compared with normal tissues. In HNEpC cells, treatment with IL-32 (2 and 10 ng/ml) promoted cell proliferation, while 50 ng/ml IL-32 inhibited cell proliferation at 12, 24 and 48 h post-treatment. IL-32 (2, 10 and 50 ng/ml) also resulted in differing degrees of apoptosis, GSDMD activation, release of IL-1ß, IL-6 and TNF-α, and increased protein expression levels of NLRP3, cleaved-caspase-1, activated GSDMD, nucleotide-binding oligomerization domain-containing protein (NOD) 1/2 and Toll-like receptor (TLR)4 in a concentration-dependent manner. In addition, compared with the LPS group, IL-32 knockdown significantly inhibited LPS-induced enhancement of cell proliferation, cell apoptosis, GSDMD activation and production of inflammatory cytokines, and reversed the increased protein expression of NLRP3, cleaved-caspase-1, activated GSDMD, NOD1/2 and TLR4. In conclusion, IL-32 may play a role in the progression of AH via promoting inflammation, and the potential mechanism may involve the activation of NLRP3-mediated pyroptosis.

Clinical Application of a New Assessment Tool for Myelopathy Hand Using Virtual Reality.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To assess the effectiveness of a new assessment tool, myelopathy-hand functional evaluation system (MFES), in evaluating the hand dysfunction of patients with cervical myelopathy in the 10-second grip-and-release test (10 second G-R test). SUMMARY OF BACKGROUND DATA: Clumsy fingers movement is a common symptom of myelopathy patients. Evaluating the impaired hand function can provide a strong basis in assessing the severity of myelopathy. Currently, no objective and effective evaluation method is widely accepted in clinical practice. METHODS: MFES mainly consists of a pair of wise-gloves and a computer with software. One hundred and ninety-eight consecutive participants were asked to wear the wise-gloves and then perform 10 seconds G-R test. The movements of each finger were recorded by MFES and converted into waveforms. Relevant waveform parameters were measured and analyzed. The Japanese Orthopedics Association (JOA) scores of each patient were marked and the maximum spinal cord compression (MSCC) was measured on midsagittal T2-weighted magnetic resonance imaging (MRI). RESULTS: Myelopathy patients had a lower number of G-R cycles and a longer time per cycle than healthy subjects. There were significant differences in adduction and abduction time in patients with JOA scores greater than 6, but not in healthy subjects and patients with JOA scores less than 6. The waveforms of ulnar three fingers in myelopathy patients were lower and wider than those in healthy individuals. The average ratio value of wave height to wave width (a/b) could quantitatively reflect such differences of waveforms. According to receiver operating characteristic (ROC) curve analysis, the optimal threshold value of the normal average ratio was more than 1.92. The average a/b value was correlated with the JOA scores of the motor function in the upper extremities (r = 0.842). CONCLUSION: MFES appears to be an objective and quantitative assessment tool for patients with cervical myelopathy. LEVEL OF EVIDENCE: 3.

[The role of rigid bronchoscope combined with high frequency ventilation in the diagnosis and treatment of infantile acute fibrinous laryngotracheobronchitis].

Objective:To explore the role of rigid bronchoscope combined with high frequency ventilation in the diagnosis and treatment of infantile acute fibrinous laryngotracheobronchitis. Method:The clinical data of 7 children with acute fibrinous laryngotracheobronchitis were analyzed retrospectively. Laryngology and bronchoscopy were conducted by hard tube bronchoscopy combined with high frequency ventilation in all cases. During the operation, a large quantity of membranous scabs was removed from subglottic area, trachea and bronchus. Result:Six cases were treated by emergency operation and cured. One patient was treated with mechanical ventilation for 48 hours because of respiratory failure. Then the operation was performed to remove the endogenous foreign body since no improvement was observed after prolonged ventilation. This patient died of multiple organ failure. The histopathological examination of these 7 cases of endogenous foreign bodies showed fibrinous exudation and necrosis, accompanied by a large quantity of inflammatory cells infiltration. Conclusion:Removal of the plastic endogenous foreign bodies which block the respiratory tract by rigid bronchoscope and high frequency ventilation under general anesthesia facilitates the diagnosis and treatment of acute fibrinous laryngotracheobronchitis in pediatric patients. Prompt surgical intervention could relieve the obstruction of respiratory tract, which is crucial to reduce mortality.

Increased number of intratumoral IL-17+ cells, a harbinger of the adverse prognosis of triple-negative breast cancer.

INTRODUCTION: Triple negative breast cancer (TNBC) is an aggressive cancer subtype and lack of effective targeted therapies. It has been recently reported that Interleukin 17 (IL-17), a family of cytokines secreted in tumor microenvironment, affects tumor progression through a variety of molecular pathways. Its role in TNBC is so far still poorly explored. MATERIALS AND METHODS: We employed immunohistochemistry to evaluate the distribution of IL-17+ cells in TNBC with no special type features (TNBC-NST), their association with tumor microangiogenesis, as well as their impact on prognosis of the patients. RESULTS: In comparison to medullary carcinoma with triple-negative molecular features (TNBC-MC), we found a significant increase in IL-17+ cell infiltrates in intratumoral stroma and extratumoral stroma of TNBC-NST. Similarly, stromal cells with co-expression of CD4 and IL-17 were noted in intratumoral and extratumoral stroma in both TNBC-NST and TNBC-MC. In addition, intratumoral IL-17+ cells were positively associated with tumor cell expression of vascular endothelial growth factor A (VEGFA) and with intratumoral tumor microvascular density (MVD). Multivariate analysis identified that intratumoral IL-17+ cells (P = 0.018), MVD (P = 0.039), and TNM stage (P = 0.002) were independent prognostic factors for predicting poor PFS. CONCLUSION: The study indicates that IL-17 is overexpressed in intratumoral stromal cells of TNBC-NST. The overexpression of IL-17 might engage in active tumor microangiogenesis through its signal transduction pathways resulting in increased tumor secretion of VEGFA, and then promote tumor progression. IL-17 might serve as a potential new target for individualized therapy to TNBC-NST patients by development of specific antibodies. Additional study is deemed to further explore the role of IL-17+ stromal cells in breast cancer.

Dose-Response Study of 4 Weight-Based Phenylephrine Infusion Regimens for Preventing Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia.

BACKGROUND: Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight. METHODS: Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal-epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to <90 mm Hg) during the interval from the initiation of spinal anesthesia to delivery of the infant. Values for ED50 and ED90 of prophylactic phenylephrine were calculated using probit analysis. RESULTS: Hypotension occurred in 13/20, 8/20, 2/20, and 1/20 patients in the groups that received phenylephrine infusion at 0.25, 0.375, 0.5, or 0.625 µg/kg/min, respectively. The calculated values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively. No difference was found in the incidence of adverse effects and neonatal outcomes among groups. CONCLUSIONS: Under the conditions of this study, when phenylephrine was given as a fixed-rate prophylactic infusion during spinal anesthesia for cesarean delivery to prevent hypotension, the values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively.

[Hydrochemical and Isotopic Characteristics of the Lake Balkhash Catchment, Kazakhstan].

Lake Balkhash is one of the largest lakes in the world. It is located in arid Central Asia and receives major water from the Ili River, which is an international river flowing across China and Kazakhstan. Hydrochemical and isotopic measurements of waters can provide an improved understanding of hydrogeochemical processes and environmental characteristics, which is useful for water resource management in arid regions. In this study, δD, δ18 O, and major ions in water samples from the Lake Balkhash catchment were analyzed using an integration of mathematical statistics, Piper diagrams, Gibbs model, and principal component analysis (PCA). Water types and main mechanisms controlling the hydrochemistry presented a clear spatial heterogeneity. The chemical composition of lake waters was dominated by SO4-Na and Cl-Na type, whereas river waters were classified as a HCO3-Ca type. The chemical composition downstream of the Ili River evolved from HCO3-Ca to SO4-Na-Cl type. Gibbs model suggested that the main mechanisms controlling the lake water chemistry were evaporation-crystallization processes, and that major ions in the river water were affected by rock-weathering and evaporation processes. The main controlling factors of the water chemistry changed from the upstream to the downstream, and may have related to spatial differences whereby the upstream area experienced higher rainfall and snow melt, and the downstream area experienced relatively higher evaporation. PCA analysis showed that human activities also played an important role in the chemical composition of water sampled from the lake, middle and lower reaches of the Ili River, and other rivers. The isotopic compositions of the lake and river waters varied spatially. In the lake waters, positive isotopic ratios and negative deuterium-excess values indicated that evaporitic enrichment dominated the changes in the isotopic signature of the lake water. In river waters, isotope values located near the global meteoric water line (GMWL) and lower slopes of the regression lines (r=0.91, P<0.001 for Ili River, and r=0.63, P<0.001 for other rivers), were associated with a stronger influence of rainfall and weaker evaporation. Correlation analysis showed that there were significant relationships between isotope values and chemical parameters in the lake water, especially in the eastern area, thus suggesting that extensive evaporation led to simultaneous enrichment of isotopes and ions in the lake water.

Intrathecal dexmedetomidine can decrease the 95% effective dose of bupivacaine in spinal anesthesia for cesarean section: A prospective, double-blinded, randomized study.

BACKGROUND: Dexmedetomidine (Dex), as an adjuvant, has been reported to prolong the duration of spinal analgesia when adding to local anesthetic. We hypothesized that Dex could enhance the efficiency of intrathecal bupivacaine for spinal anesthesia in cesarean section. The aim of his study is to test our hypothesis that 5 µg Dex could enhance the efficiency of intrathecal bupivacaine and reduce the dose requirement of spinal bupivacaine for patients undergoing cesarean section. METHODS: Ninety patients with ASA I or II, who underwent cesarean section, were randomized into 2 groups: group D (bupivacaine + 5 µg Dex) and group C (bupivacaine + the same volume of saline). The subsequent dose of spinal bupivacaine was determined by the improved up-down allocation method. The initial dose of bupivacaine in the 2 groups was 4 mg, and the subsequent dose for the following patient was depended on the probability of the current dose. ED95 of spinal bupivacaine was calculated using logistic regression model. RESULTS: The ED95 and 95% confidence intervals (95% CI) of spinal hyperbaric bupivacaine in group D and group C were 7.4 mg (95% CI, 5.6-12.4 mg) and 11.0 mg (95% CI, 4.4-56.8 mg), respectively. The duration of sensory block was 120.5 ±â€Š37.0 minutes in Dex group and 70.5 ±â€Š34.5 minutes in Control group, respectively (P < .05). The duration of analgesia was 230.5 ±â€Š40.5 minutes in Dex group and 145.1 ±â€Š28.5 minutes in Control group, respectively (P < .001). The consumption of postoperative rescued sufentanil was significantly lower in Dex group than in the Control group (56.3 ±â€Š9.4 vs 65.9 ±â€Š10.7 µg). There was not significantly different in the patient satisfaction of analgesia, incidence of side effects, neonatal outcomes and neurological deficit between the 2 groups. CONCLUSION: Intrathecal 5 µg Dex enhances the efficacy of spinal bupivacaine by 24% in patients undergoing cesarean section with spinal anesthesia. No additional side effect was observed by adding spinal Dex.

The extracellular domain of Staphylococcus aureus LtaS binds insulin and induces insulin resistance during infection.

Insulin resistance is a risk factor for obesity and diabetes and predisposes individuals to Staphylococcus aureus colonization; however, the contribution of S. aureus to insulin resistance remains unclear. Here, we show that S. aureus infection causes impaired glucose tolerance via secretion of an insulin-binding protein extracellular domain of LtaS, eLtaS, which blocks insulin-mediated glucose uptake. Notably, eLtaS transgenic mice (eLtaS trans ) exhibited a metabolic syndrome similar to that observed in patients, including increased food and water consumption, impaired glucose tolerance and decreased hepatic glycogen synthesis. Furthermore, transgenic mice showed significant metabolic differences compared to their wild-type counterparts, particularly for the early insulin resistance marker α-hydroxybutyrate. We subsequently developed a full human monoclonal antibody against eLtaS that blocked the interaction between eLtaS and insulin, which effectively restored glucose tolerance in eLtaS trans and S. aureus-challenged mice. Thus, our results reveal a mechanism for S. aureus-induced insulin resistance.

[Distribution of n-alkanes from Lake Wanghu Sediments in Relation to Environmental Changes].

Concentrations and distribution of n-alkanes (n-C14 to n-C33) in Lake Wanghu sediment core were analyzed to investigate the environmental changes in the lake during the past~100 years. Relatively higher concentrations of mid-and long-chain n-alkanes with a strong odd-over-even carbon number predominance indicated organic matter contributions dominated by aquatic macrophytes and terrestrial plants. The lower values of 2n-C31/(n-C27+n-C29) highlighted a type of landscape dominated by woody plants. The environmental changes that have been happening over the past 100 years in Lake Wanghu can be divided into three stages, based on the organic matter sources inferred from the changes in n-alkane parameters in the sediments. Before the 1950s, higher values of terrigenous/aquatic ratio (TAR) and high-/low-molecular weight n-alkanes (H/L) indicated vascular, plant-derived sediments deposited during a low-nutrient, clear-water phase with frequent water exchange between the lake and the Yangtze River. Between the 1950s and 1980s, decrease in values of H/L and TAR, and increase in the proportion of mid-and short-chain n-alkanes indicated a shift towards mid-and shorter-chain components likely associated with the increasing contribution of macrophytes and algae. Lower 2n-C17/(n-C23+n-C25) values indicated a relatively low algal abundance. In that stage, the lake trophic state increased slightly with the decreasing influence of the Yangtze River flow. After the 1980s,H/L and TAR values increased and then decreased, total n-alkane concentrations and 2n-C17/(n-C23+n-C25) increased significantly, especially after 2000s, suggesting the main contributor to high organic matter input most likely shifted to algae because of the eutrophication caused by anthropogenic activities.