Effects of Dexmedetomidine on Serum Interleukin-6, Hemodynamic Stability, and Postoperative Pain Relief in Elderly Patients under Spinal Anesthesia

The beneficial effects of dexmedetomidine (DEX) have not been extensively investigated in elderly patients receiving spinal anesthesia. This study evaluated the effects of intravenous DEX infusion on stress and hemodynamic response, as well as on postoperative analgesia in elderly patients undergoing total knee arthroplasty (TKA). We randomly allocated 45 adult patients to 3 patient groups (n=15 each): uni-saline group patients underwent unilateral TKA with saline administration, uni-DEX group patients underwent unilateral TKA with DEX administration, and bilateral-DEX group patients underwent bilateral TKA with DEX administration. Serum interleukin-6 (IL-6) levels were significantly lower in the bilateral-DEX group than in the uni-saline group 6 and 24h postoperatively, and were negatively correlated with total DEX dosage 24h postoperatively. Bradycardia occurred more frequently in the uni-DEX and bilateral-DEX groups than in the uni-saline group. The total dose of required supplementary analgesics was significantly higher in the uni-saline group than in the uni-DEX and bilateral-DEX groups 6h postoperatively. The results indicate that perioperative intravenous DEX administration decreases postoperative serum IL-6 levels in patients undergoing bilateral TKA, and has a postoperative analgesic effect in patients undergoing unilateral or bilateral TKA

China

Economic development processes in post-1949 China can be divided into two periods. In the first, 1950-70, the economy was extensively and intensively controlled by the state with a priority for developing heavy industries. In the second, since the 80s and known as the \u27reform period,\u27 the Chinese economy has increasingly been integrated with the world economy and relying on light (rural) industries as the prime motor of economic growth. Yet, in both these periods, Chinese policymakers shared the same \u27developmental\u27 philosophy in which social costs, that is the reproduction costs of human labour and nature, are largely ignored. The following is a critical sketch of government policies and their impact on the domestic population in these two periods

Influence of Long-term Climate on Fatigue Life of Bridge Pier Concrete and a Reinforcement Method

This paper quantitatively evaluated the fatigue life of concrete around the air-water boundary layer of bridge piers located in inland rivers, considering the long-term climate. The paper suggests a method to predict the low-cycle fatigue life by demonstrating a thermal-fluid-structural analysis of bridge pier concrete according to long-term climate such as temperature, velocity and pressure of air and water in the process of freezing and thawing in winter. In addition, it proposes a reinforcing method to increase the life of damaged piers and proves the feasibility of the proposed method with numerical comparison experiment

Evaluation of Respiratory Dynamics in an Asymmetric Lung Compliance Model

Background Unilateral lung hyperinflation develops in lungs with asymmetric compliance, which can lead to vital instability. The aim of this study was to investigate the respiratory dynamics and the effect of airway diameter on the distribution of tidal volume during mechanical ventilation in a lung model with asymmetric compliance. Methods Three groups of lung models were designed to simulate lungs with a symmetric and asymmetric compliance. The lung model was composed of two test lungs, lung1 and lung2. The static compliance of lung1 in C15, C60, and C120 groups was manipulated to be 15, 60, and 120 ml/cmH2O, respectively. Meanwhile, the static compliance of lung2 was fixed at 60 ml/cmH2O. Respiratory variables were measured above (proximal measurement) and below (distal measurement) the model trachea. The lung model was mechanically ventilated, and the airway internal diameter (ID) was changed from 3 to 8 mm in 1-mm increments. Results The mean ± standard deviation ratio of volumes distributed to each lung (VL1/VL2) in airway ID 3, 4, 5, 6, 7, and 8 were in order, 0.10 ± 0.05, 0.11 ± 0.03, 0.12 ± 0.02, 0.12 ± 0.02, 0.12 ± 0.02, and 0.12 ± 0.02 in the C15 group; 1.05 ± 0.16, 1.01 ± 0.09, 1.00 ± 0.07, 0.97 ± 0.09, 0.96 ± 0.06, and 0.97 ± 0.08 in the C60 group; and 1.46 ± 0.18, 3.06 ± 0.41, 3.72 ± 0.37, 3.78 ± 0.47, 3.77 ± 0.45, and 3.78 ± 0.60 in the C120 group. The positive end-expiratory pressure (PEEP) of lung1 was significantly increased at airway ID 3 mm (1.65 cmH2O) in the C15 group; at ID 3, 4, and 5 mm (2.21, 1.06, and 0.95 cmH2O) in the C60 group; and ID 3, 4, and 5 mm (2.92, 1.84, and 1.41 cmH2O) in the C120 group, compared to ID 8 mm (P < 0.05). Conclusions In the C15 and C120 groups, the tidal volume was unevenly distributed to both lungs in a positive relationship with lung compliance. In the C120 group, the uneven distribution of tidal volume was improved when the airway ID was equal to or less than 4 mm, but a significant increase of PEEP was observed

A case of back pain caused by Salmonella spondylitis -A case report-

Salmonella spondylitis is a rare illness, and it generally occurs in patients who have already had sickle cell anemia, and it is even rarer in patients who are without sickle cell anemia. A 61-year-old male patient was hospitalized for the evaluation of his renal function and then treatment was started for his back pain. His back pain had developed about 2 months previously without any specific trauma. Only a bulging disc was detected on the initial lumbar MRI. Regarding his fever, it was diagnosed as possible atypical pneumonia, scrub typhus, etc., and multiple antibiotic therapy was administered. At the time of transfer, the leucocytes and hs-CRP were normal and the ESR was elevated. A diagnostic epidural block was performed for his back pain, but his symptoms were not improved. Lumbar MRI was performed again and it showed findings of infective spondylitis. Salmonella D was identified on the abscess culture and so he was diagnosed as suffering from Salmonella spondylitis. After antibiotic treatment, his back pain was improved and the patient was able to walk

D-galacto-D-mannan-mediated Dectin-2 activation orchestrates potent cellular and humoral immunity as a viral vaccine adjuvant

IntroductionConventional foot-and-mouth disease (FMD) vaccines have been developed to enhance their effectiveness; however, several drawbacks remain, such as slow induction of antibody titers, short-lived immune response, and local side effects at the vaccination site. Therefore, we created a novel FMD vaccine that simultaneously induces cellular and humoral immune responses using the Dectin-2 agonist, D-galacto-D-mannan, as an adjuvant.MethodsWe evaluated the innate and adaptive (cellular and humoral) immune responses elicited by the novel FMD vaccine and elucidated the signaling pathway involved both in vitro and in vivo using mice and pigs, as well as immune cells derived from these animals.ResultsD-galacto-D-mannan elicited early, mid-, and long-term immunity via simultaneous induction of cellular and humoral immune responses by promoting the expression of immunoregulatory molecules. D-galacto-D-mannan also enhanced the immune response and coordinated vaccine-mediated immune response by suppressing genes associated with excessive inflammatory responses, such as nuclear factor kappa B, via Sirtuin 1 expression.ConclusionOur findings elucidated the immunological mechanisms induced by D-galacto-D-mannan, suggesting a background for the robust cellular and humoral immune responses induced by FMD vaccines containing D-galacto-D-mannan. Our study will help to facilitate the improvement of conventional FMD vaccines and the design of next-generation FMD vaccines

Dectin-1 signaling coordinates innate and adaptive immunity for potent host defense against viral infection

BackgroundMost commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety.ObjectivesTo address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection.MethodsWe demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan.Resultsβ-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host’s innate and adaptive immunity.ConclusionOur study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine’s safety and efficacy, it represents a breakthrough among next-generation FMD vaccines

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms