Summary
Smoking increases susceptibility to becoming infected with and developing tuberculosis. Among the components of cigarette smoke, nicotine has been identified as the main immunomodulatory ...molecule; however, its effect on the innate immune system is unknown. In the present study, the effect of nicotine on molecules of the innate immune system was evaluated. Lung epithelial cells and macrophages were infected with Mycobacterium tuberculosis (Mtb) and/or treated with nicotine. The results show that nicotine alone decreases the expression of the Toll‐like receptors (TLR)‐2, TLR‐4 and NOD‐2 in all three cell types, as well as the production of the SP‐D surfactant protein in type II pneumocytes. Moreover, it was observed that nicotine decreases the production of interleukin (IL)‐6 and C‐C chemokine ligand (CCL)5 during Mtb infection in epithelial cells (EpCs), whereas in macrophages derived from human monocytes (MDMs) there is a decrease in IL‐8, IL‐6, tumor necrosis factor (TNF)‐α, IL‐10, CCL2, C‐X‐C chemokine ligand (CXCL)9 and CXCL10 only during infection with Mtb. Although modulation of the expression of cytokines and chemokines appears to be partially mediated by the nicotinic acetylcholine receptor α7, blocking this receptor found no effect on the expression of receptors and SP‐D. In summary, it was found that nicotine modulates the expression of innate immunity molecules necessary for the defense against tuberculosis.
Nicotine modulates the expression of innate immunity molecules necessary for the defense against tuberculosis.
Update
This article was updated on September 4, 2020, because of a previous error. On page 1211, in the author affiliation section, “W.L. Walter, MBBS, PhD
3
” now reads “W.L. Walter, MBBS, PhD
3,4
...,” the affiliation for Dr. Van Onsem that had read “
3
Specialist Orthopedic Group, The Mater Clinic, North Sydney, New South Wales, Australia” now reads “
3
Royal North Shore Hospital, St. Leonards, New South Wales, Australia,” and the affiliation for Dr. Walter that had read “
3
Specialist Orthopedic Group, The Mater Clinic, North Sydney, New South Wales, Australia” now reads “
3
Royal North Shore Hospital, St. Leonards, New South Wales, Australia” and “
4
University of Sydney, Sydney, New South Wales, Australia.”
An erratum has been published: J Bone Joint Surg Am. 2020 Oct 7;102(19):e113
» As we resume elective surgical procedures, it is important to understand what practices and protocols should be altered or implemented in order to minimize the risk of pathogen transfer during the severe acute respiratory syndrome (SARS)-CoV-2 pandemic.
» Each hospital and health system should consider their unique situation in terms of SARS-CoV-2 prevalence, staffing capabilities, personal protection equipment supply, and so on when determining how and when to implement these recommendations.
» All patients should be screened for SARS-CoV-2 by means of a thorough history and physical examination, as well as reverse transcription-polymerase chain reaction (RT-PCR) testing whenever possible, prior to undergoing elective surgery.
» Patients who are currently infected with coronavirus disease 2019 (COVID-19) should not undergo elective surgery.
» These guidelines are based on the available scientific evidence, albeit scant. The recommendations have been reviewed and voted on by the expert delegates who produced this document.
Aim
The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with ...a simulated day shift schedule.
Methods
Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9; day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic clamp respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair samples respectively.
Results
Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L−1; P = .001) and insulin sensitivity decreased (25 ± 7%, P < .05) following the night shift, with no changes following the day shift. Night shift work had no effect on skeletal muscle protein expression (PGC1α, UCP3, TFAM and mitochondria Complex II‐V) or insulin‐stimulated pAkt Ser473, pTBC1D4Ser318 and pTBC1D4Thr642. Importantly, the metabolic changes after simulated night shifts occurred despite no changes in the timing of melatonin rhythmicity or hair follicle cell clock gene expression across the wake period (Per3, Per1, Nr1d1 and Nr1d2).
Conclusion
Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D.
Background. Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens. Methods. Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving ...patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7—21 days. The primary end point was clinical response at follow-up/test-of-cure visit. Results. A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval CI for the difference, −5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, −4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, −0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, −7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%). Conclusions. The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens.
Purpose
To evaluate the effect of immersion in disinfecting solutions on the color stability of denture base resins and artificial teeth obtained by 3D printing.
Materials and methods
Forty discs ...(15 × 3 mm) were obtained for each group: Lucitone 550 and Cosmos Denture 3D (denture base resins), Duralay and Cosmos TEMP 3D (artificial teeth resins). The discs were immersed in disinfectant solutions: Corega Tabs, 2% chlorhexidine digluconate, 0.25% sodium hypochlorite, and distilled water. Color measurements were obtained with a spectrophotometer before immersion in disinfectants and after the simulated periods of 6 and 12 months. Data (ΔE00) were submitted to mixed three‐way ANOVA and Bonferroni post‐test.
Results
For denture base resins, Cosmos Denture 3D showed greater color change regardless of the solution and immersion time. The immersion time of 6 months influenced the color change of the denture base resins regardless of the disinfectant solution. For the artificial teeth resins, the immersion time of 12 months showed a significant color change when compared to 6 months. Cosmos TEMP 3D showed greater color change for all solutions, except for 0.25% sodium hypochlorite. Duralay resin showed greater color change in 2% chlorhexidine, regardless of immersion time.
Conclusions
For denture base resins, the immersion time significantly changed the color regardless of the solution. For artificial teeth resins, Cosmos TEMP 3D showed greater color changes in all solutions when compared to Duralay, except for 0.25% sodium hypochlorite. Chlorhexidine digluconate significantly changed the color of Duralay.
MPNG is an open-source simulation package for solving Optimal Power and Natural Gas Flow (OPNGF) problems. It is coded in Matlab and developed using the widely-used tool for power systems research ...and education, Matpower . MPNG assembles a nonlinear steady state OPNGF formulation for analyzing the integration of electricity and natural gas networks with order-of-priority classes of consumers and gas nodal price-controlled storage facilities. This paper presents the details of the nonlinear optimization model behind MPNG , as well as several features that were designed into it for the purpose of achieving robustness. These include an approximation of the Weymouth equation for handling bi-directional gas flows in pipelines, a per-unit representation for the natural gas network, and penalized slack variables for power and gas balances. Simulation results using a test case and the Colombian power and natural gas networks are presented to highlight MPNG 's capabilities to solve OPNGF problems.
We explored how the odor map in the Drosophila antennal lobe is represented in higher olfactory centers, the mushroom body and lateral horn. Systematic single-cell tracing of projection neurons (PNs) ...that send dendrites to specific glomeruli in the antennal lobe revealed their stereotypical axon branching patterns and terminal fields in the lateral horn. PNs with similar axon terminal fields tend to receive input from neighboring glomeruli. The glomerular classes of individual PNs could be accurately predicted based solely on their axon projection patterns. The sum of these patterns defines an “axon map” in higher olfactory centers reflecting which olfactory receptors provide input. This map is characterized by spatial convergence and divergence of PN axons, allowing integration of olfactory information.
Since the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS) reported a new lung adenocarcinoma (ADC) ...classification, several groups have validated its association with prognosis in early stage disease. To our knowledge, there are no studies in advanced disease. We reviewed 313 patients with invasive lung ADC who were re-classified using the new IASLC/ATS/ERS criteria. Patients received platinum-based chemotherapy. Clinical characteristics, EGFR mutations, response and progression-free survival (PFS) after chemotherapy and overall survival were analysed. ADCs were classified as lepidic 7.4%, acinar 44.7%, papillary 10.1%, micropapillary 3.5% and solid 34.2%. When patterns were lumped into groups, response rates and PFS to platinum-based chemotherapy were better in high-grade ADC (micropapillary, papillary and solid-predominant) versus intermediate-grade ADC (lepidic and acinar-predominant) (36.9% versus 25.4% p=0.034 and 6.4 versus 5.5 months p=0.009, respectively). Overall survival was better in high-grade ADC (25 versus 16.8; p=0.023). Factors associated with better overall survival were Eastern Cooperative Oncology Group (0-1), EGFR mutations and high-grade ADC. Prognostic differences found with the new classification in early disease may not apply to patients with advanced disease. Unlike in early stages, patients with high-grade ADC have longer overall survival compared with intermediate-grade ADC, probably due to a better response to chemotherapy.
In this work, we studied the effect of the triethanolamine (TEA) concentration on the physicochemical properties of copper sulfide (CuS) thin films deposited by the ammonia-free chemical bath ...deposition method (CBD). CuS thin films were characterized in an as-deposited state and annealing at 70 °C/6 h. Raman spectroscopy evidenced the S–S stretching mode associated with the hexagonal structure (covellite) of CuS. The microstructural analysis showed that the TEA concentration and the thermal treatment strongly influence the surface morphology. The surface roughness varied from 6.4 to 14.0 nm. The band gap (
E
g
), thickness (
d
), and optical constants (
n
and
k
) were estimated by simulating the transmission (
T
) and reflection (
R
) spectra. Notably, the thermally treated CuS thin films are thinner when the TEA concentration increases due to the densification phenomenon. The chemical states of elements and the S/Cu ratio on the surface of the CuS films were assessed by X-ray photoelectron spectroscopy (XPS). The electrical properties of the CuS thin films as a function of TEA concentration and thermal treatment were characterized using the Hall effect. These results show the importance of the complexing agent (TEA) and low-temperature thermal treatment on the physicochemical properties of CuS thin films.
Graphical abstract Lipid raft constituents as biomarkers for neurodegenerative diseases. Neuronal and glial lipid rafts may be damaged by different physical, chemical and genetic factors during the ...development of neuropathological processes. Disruption of lipid rafts releases specific subsets of proteins and lipids integrated in these microdomains toward the brain parenchyma. These lipid raft-associated molecules include resident proteins such as caveolin-1 and signalosome interacting proteins including growth factor receptors such as IGF-1R and BDNF, ion channels such as VDAC and NMDA receptor, glycosylphosphatidylinositol-anchored proteins (GPI-APs) such as prionic protein (PrP) and tyrosine kinases of the Src family, among other proteins. Also lipids may be released toward the surrounding parenchyma from lipid rafts. Because of their high concentration in lipid rafts, cholesterol and sphingolipids (including sulfatides and cerebrosides), but also ceramides, which are formed upon catabolism of certain sphingolipids, are particularly accumulated upon disruption of these microdomains. Although less represented in lipid rafts, long-chain polyunsaturated fatty acids (LCPUFA) are important molecules in the progression of oxidative damage given their high susceptibility for oxidation, thus releasing active endoperoxides isoprostanes and neuroprostanes into the brain parenchyma. These raft-derived molecules, proteins and lipids, are poured out for elimination into the cerebrospinal fluid across the ependymal cell layer, or may be released out of the brain through the blood–brain barrier across the endothelial lining to the blood. Accurate measurements of these raft components and by-products in, either CSF or blood, using multivariate approaches such discriminant function analyses may provide a diagnostic tool for the more accurate identification of the type of neurodegenerative disease and its progression.