Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study

OBJECTIVES: This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. METHODS: Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. RESULTS: The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. CONCLUSION: The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting) in thoracic surgery patients requiring one-lung ventilation

Prognostic value of vitamin D in patients with pneumonia: A systematic review and meta-analysis

Purpose: To investigate the prognostic role of vitamin D in pneumonia patients  through meta-analysis.Methods: PubMed and Embase were systematically searched for relevant studies that assessed the impact of vitamin D on the risk of adverse outcomes among patients with pneumonia. Risk ratios (RR) with 95 % confidence intervals (95 % CI) were pooled using meta-analysis. Q-test and I2 statistics were used to evaluate between-study heterogeneity.Results: Six studies were finally included in the meta-analysis. The results of meta-analysis of these studies indicated that low vitamin D status was associated with higher risk of mortality among pneumonia patients (RR = 2.59, 95 % CI = 1.32-5.08; p = 0.005). Results from meta-analysis of studies with adjusted estimates suggest that low vitamin D status was independently associated with higher risk of mortality among pneumonia patients (RR = 3.15, 95 % CI 1.54-6.44, p = 0.002). There was no significant risk of bias in the meta-analysis.Conclusion: This study demonstrates that low vitamin D level is associated with a higher risk of adverse outcomes in patients with pneumonia.Keywords: Pneumonia, Vitamin D, Prognosis, Meta-analysis, Systematic revie

Intrathecal Delivery of Ketorolac Loaded In Situ Gels for Prolonged Analgesic and Anti-Inflammatory Activity in Vertebral Fracture

Purpose: To develop biodegradable, polymeric in situ gels based on sodium alginate and hydroxypropyl methylcellulose for intrathecal delivery of ketorolac tromethamine (KT) for effective management of pain and inflammation in vertebral fracture.Method: Ion activated in situ gels were used as implants and were prepared from sodium alginate and hydroxypropyl methylcellulose. The fabricated gels were evaluated for visual appearance, clarity, pH, gelling capacity, drug content, viscosity (using Brookfield viscometer), in vitro drug release (using a fabricated KC cell) and in vivo analgesic and anti-inflammatory activity (by intrathecal administration of in situ gel near the fractured vertebra in a rat model).Results: The physicochemical properties (visual appearance, clarity, pH, gelling capacity, drug content and viscosity) of in situ gels were acceptable for therapeutic use. KT-loaded gels demonstrated high drug encapsulation efficiency (98.3 - 103.3 %). Further, KT-loaded gels exhibited viscosity in the range of 1.11 to 6 cps at 50 rpm and shear thinning property (rheology testing). Additionally, the gels demonstrated 84.43 to 96.98 % drug release at the end of 12 h. In particular, in situ gels prepared from 1.2 % alginate/0.4 % HPMC (G7) exhibited excellent analgesic (54.28 %) and anti-inflammatory activity (51.6 % inhibition of rat paw edema) in the animal model of vertebral fracture.Conclusion: The formulated in situ gels can potentially be used as implants for the treatment of patients with vertebral fracture.Keywords: Ketorolac, Orthopaedic implant, Extended release, Analgesic, Anti inflammation, Vertebral fractur

Mechanistic Insights into Dimethylsulfoniopropionate Lyase DddY, a New Member of the Cupin Superfamily

The marine osmolyte dimethylsulfoniopropionate (DMSP) is one of Earth's most abundant organosulfur molecules. Bacterial DMSP lyases cleave DMSP, producing acrylate and dimethyl sulfide (DMS), a climate-active gas with roles in global sulfur cycling and atmospheric chemistry. DddY is the only known periplasmic DMSP lyase and is present in β-, γ-, δ- and ε-proteobacteria. Unlike other known DMSP lyases, DddY has not been classified into a protein superfamily, and its structure and catalytic mechanism are unknown. Here, we determined the crystal structure of DddY from the γ-proteobacterium Acinetobacter bereziniae originally isolated from human clinical specimens. This structure revealed that DddY contains a cap domain and a catalytic domain with a Zn2 + bound at its active site. We also observed that the DddY catalytic domain adopts a typical β-barrel fold and contains two conserved cupin motifs. Therefore, we concluded that DddY should belong to the cupin superfamily. Using structural and mutational analyses, we identified key residues involved in Zn2 + coordination, DMSP binding and the catalysis of DMSP cleavage, enabling elucidation of the catalytic mechanism, in which the residue Tyr271 of DddY acts as a general base to attack DMSP. Moreover, sequence analysis suggested that this proposed mechanism is common to DddY proteins from β-, γ-, δ- and ε-proteobacteria. The DddY structure and proposed catalytic mechanism provide a better understanding of how DMSP is catabolized to generate the important climate-active gas DMS

A Stem Cell-Based Tool for Small Molecule Screening in Adipogenesis

Techniques for small molecule screening are widely used in biological mechanism study and drug discovery. Here, we reported a novel adipocyte differentiation assay for small molecule selection, based on human mesenchymal stem cells (hMSCs) transduced with fluorescence reporter gene driven by adipogenic specific promoter - adipocyte Protein 2 (aP2; also namely Fatty Acid Binding Protein 4, FABP4). During normal adipogenic induction as well as adipogenic inhibition by Ly294002, we confirmed that the intensity of green fluorescence protein corresponded well to the expression level of aP2 gene. Furthermore, this variation of green fluorescence protein intensity can be read simply through fluorescence spectrophotometer. By testing another two small molecules in adipogenesis –Troglitazone and CHIR99021, we proved that this is a simple and sensitive method, which could be applied in adipocyte biology, drug discovery and toxicological study in the future

The complete genome of Zunongwangia profunda SM-A87 reveals its adaptation to the deep-sea environment and ecological role in sedimentary organic nitrogen degradation

<p>Abstract</p> <p>Background</p> <p><it>Zunongwangia profunda </it>SM-A87, which was isolated from deep-sea sediment, is an aerobic, gram-negative bacterium that represents a new genus of <it>Flavobacteriaceae</it>. This is the first sequenced genome of a deep-sea bacterium from the phylum <it>Bacteroidetes</it>.</p> <p>Results</p> <p>The <it>Z. profunda </it>SM-A87 genome has a single 5 128 187-bp circular chromosome with no extrachromosomal elements and harbors 4 653 predicted protein-coding genes. SM-A87 produces a large amount of capsular polysaccharides and possesses two polysaccharide biosynthesis gene clusters. It has a total of 130 peptidases, 61 of which have signal peptides. In addition to extracellular peptidases, SM-A87 also has various extracellular enzymes for carbohydrate, lipid and DNA degradation. These extracellular enzymes suggest that the bacterium is able to hydrolyze organic materials in the sediment, especially carbohydrates and proteinaceous organic nitrogen. There are two clustered regularly interspaced short palindromic repeats in the genome, but their spacers do not match any sequences in the public sequence databases. SM-A87 is a moderate halophile. Our protein isoelectric point analysis indicates that extracellular proteins have lower predicted isoelectric points than intracellular proteins. SM-A87 accumulates organic osmolytes in the cell, so its extracelluar proteins are more halophilic than its intracellular proteins.</p> <p>Conclusion</p> <p>Here, we present the first complete genome of a deep-sea sedimentary bacterium from the phylum <it>Bacteroidetes</it>. The genome analysis shows that SM-A87 has some common features of deep-sea bacteria, as well as an important capacity to hydrolyze sedimentary organic nitrogen.</p

Cross-sectional study of the relationship of peripheral blood cell profiles with severity of infection by adenovirus type 55

BACKGROUND: The immunologic profiles of patients with human adenovirus serotype 55 (HAdV-55) infections were characterized in subjects diagnosed with silent infections (n = 30), minor infections (n = 27), severe infections (n = 34), and healthy controls (n = 30) during a recent outbreak among Chinese military trainees. METHODS: Blood was sampled at the disease peak and four weeks later, and samples were analyzed to measure changes in leukocyte and platelet profiles in patients with different severities of disease. Differential lymphocyte subsets and cytokine profiles were measured by flow cytometry and Luminex xMAP®, and serum antibodies were analyzed by ELISA and immunofluorescence staining. RESULTS: Patients with severe HAdV infections had higher proportions of neutrophils and reduced levels of lymphocytes (p < 0.005 for both). Patients with minor and severe infections had significantly lower platelet counts (p < 0.005 for both) than those with silent infections. The silent and minor infection groups had higher levels of dendritic cells than the severe infection group. Relative to patients with silent infections, patients with severe infections had significantly higher levels of IL-17(+)CD4(+) cells, decreased levels of IL-17(+)CD8(+) cells, and higher levels of IFN-γ, IL-4, IL-10, and IFN-α2 (p < 0.001 for all comparisons). CONCLUSIONS: Patients with different severities of disease due to HAdV-55 infection had significantly different immune responses. These data provide an initial step toward the identification of patients at risk for more severe disease and the development of treatments against HAdV-55 infection