Association of Disrupted Delta Wave Activity During Sleep With Long-Term Cardiovascular Disease and Mortality.

BACKGROUND: Delta wave activity is a prominent feature of deep sleep, which is significantly associated with sleep quality. OBJECTIVES: The authors hypothesized that delta wave activity disruption during sleep could predict long-term cardiovascular disease (CVD) and CVD mortality risk. METHODS: The authors used a comprehensive power spectral entropy-based method to assess delta wave activity during sleep based on overnight polysomnograms in 4,058 participants in the SHHS (Sleep Heart Health Study) and 2,193 participants in the MrOS (Osteoporotic Fractures in Men Study) Sleep study. RESULTS: During 11.0 ± 2.8 years of follow-up in SHHS, 729 participants had incident CVD and 192 participants died due to CVD. During 15.5 ± 4.4 years of follow-up in MrOS, 547 participants had incident CVD, and 391 died due to CVD. In multivariable Cox regression models, lower delta wave entropy during sleep was associated with higher risk of coronary heart disease (SHHS: HR: 1.46; 95% CI: 1.02-2.06; P = 0.03; MrOS: HR: 1.79; 95% CI: 1.17-2.73; P < 0.01), CVD (SHHS: HR: 1.60; 95% CI: 1.21-2.11; P < 0.01; MrOS: HR: 1.43; 95% CI: 1.00-2.05; P = 0.05), and CVD mortality (SHHS: HR: 1.94; 95% CI: 1.18-3.18; P < 0.01; MrOS: HR: 1.66; 95% CI: 1.12-2.47; P = 0.01) after adjusting for covariates. The Shapley Additive Explanations method indicates that low delta wave entropy was more predictive of coronary heart disease, CVD, and CVD mortality risks than conventional sleep parameters. CONCLUSIONS: The results suggest that delta wave activity disruption during sleep may be a useful metric to identify those at increased risk for CVD and CVD mortality.

Effect of a reused insulin needle remaining in a patient's body.

Diabetes is one of the most common chronic diseases at present, and insulin pen injection therapy plays an important role in the treatment of diabetes. However, the majority of patients might reuse disposable insulin pen needles for various reasons, which leads to related complications. As far as we know, this article is the first to describe a patient whose needle remained in the right upper limb while reusing a disposable insulin injection needle for subcutaneous insulin injection with the non-dominant hand. The patient went to the doctor 1 week later. The needle moved from the lateral area of the proximal upper arm (the injection site) to the posterolateral area of the distal upper arm. The needle was then successfully removed by surgery. The reuse of disposable insulin pen needles might lead to serious complications. It is suggested to strengthen the education of people living with diabetes to help them use insulin pen needles safely.

Discriminative Suprasphere Embedding for Fine-Grained Visual Categorization.

Despite the great success of the existing work in fine-grained visual categorization (FGVC), there are still several unsolved challenges, e.g., poor interpretation and vagueness contribution. To circumvent this drawback, motivated by the hypersphere embedding method, we propose a discriminative suprasphere embedding (DSE) framework, which can provide intuitive geometric interpretation and effectively extract discriminative features. Specifically, DSE consists of three modules. The first module is a suprasphere embedding (SE) block, which learns discriminative information by emphasizing weight and phase. The second module is a phase activation map (PAM) used to analyze the contribution of local descriptors to the suprasphere feature representation, which uniformly highlights the object region and exhibits remarkable object localization capability. The last module is a class contribution map (CCM), which quantitatively analyzes the network classification decision and provides insight into the domain knowledge about classified objects. Comprehensive experiments on three benchmark datasets demonstrate the effectiveness of our proposed method in comparison with state-of-the-art methods.

Integrating pore architectures to evaluate vascularization efficacy in silicate-based bioceramic scaffolds.

Pore architecture in bioceramic scaffolds plays an important role in facilitating vascularization efficiency during bone repair or orbital reconstruction. Many investigations have explored this relationship but lack integrating pore architectural features in a scaffold, hindering optimization of architectural parameters (geometry, size and curvature) to improve vascularization and consequently clinical outcomes. To address this challenge, we have developed an integrating design strategy to fabricate different pore architectures (cube, gyroid and hexagon) with different pore dimensions (∼350, 500 and 650 µm) in the silicate-based bioceramic scaffolds via digital light processing technique. The sintered scaffolds maintained high-fidelity pore architectures similar to the printing model. The hexagon- and gyroid-pore scaffolds exhibited the highest and lowest compressive strength (from 15 to 55 MPa), respectively, but the cube-pore scaffolds showed appreciable elastic modulus. Moreover, the gyroid-pore architecture contributed on a faster ion dissolution and mass decay in vitro. It is interesting that both µCT and histological analyses indicate vascularization efficiency was challenged even in the 650-µm pore region of hexagon-pore scaffolds within 2 weeks in rabbit models, but the gyroid-pore constructs indicated appreciable blood vessel networks even in the 350-µm pore region at 2 weeks and high-density blood vessels were uniformly invaded in the 500- and 650-µm pore at 4 weeks. Angiogenesis was facilitated in the cube-pore scaffolds in comparison with the hexagon-pore ones within 4 weeks. These studies demonstrate that the continuous pore wall curvature feature in gyroid-pore architecture is an important implication for biodegradation, vascular cell migration and vessel ingrowth in porous bioceramic scaffolds.

Component structure and characteristic analysis of cyanobacterial organic matters.

The characteristic analysis of cyanobacterial organic matters is an important premise of cyanobacterial organic pollution control. This paper investigated the component structure characteristics of algal organic matters (AOM) secreted and released by cyanobacteria in laboratory culture and actual Taihu Lake environment by spectroscopic quantitative and qualitative methods. Results showed that the secretion amount of AOM was mainly 4-6 µg COD/106 cells during the growth period of Microcystis aeruginosa, and the content ratio of extracellular organic matters (EOM) to intracellular organic matters (IOM) gradually increased from 0.83 in adaptation and logarithmic period to 3.33 in stable and decay period. The secretion of IOM showed a decrease trend, which indicated the decrease of its synthesis or the gradual infiltration and loss caused by cell membrane damage. From the component characteristics, the EOM had lower SUVA value and higher proportion of small molecular substances with molecular weight <3 kDa, indicating its more difficult to separate from water than IOM. Compared with the laboratory culture environment, the actual Taihu Lake resulted in more obvious characteristic heterogeneity of cyanobacteria EOM and IOM.

Artificial osteochondral interface of bioactive fibrous membranes mediating calcified cartilage reconstruction.

Calcified cartilage is a mineralized osteochondral interface region between the hyaline cartilage and subchondral bone. There are few reported artificial biomaterials that could offer bioactivities for substantial reconstruction of calcified cartilage. Herein we developed new poly(L-lactide-co-caprolactone) (PLCL)-based trilayered fibrous membranes as a functional interface for calcified cartilage reconstruction and superficial cartilage restoration. The trilayered membranes were prepared by the electrospinning technique, and the fibrous morphology was maintained when the chondroitin sulfate (CS) or bioactive glass (BG) particles were introduced in the upper or bottom layer, respectively. Although 30% BG in the bottom layer led to a significant decrease in tensile resistance, the inorganic ion release was remarkably higher than that in the counterpart with 10% BG. The in vivo studies showed that the fibrous membranes as osteochondral interfaces exhibited different biological performances on superficial cartilage restoration and calcified cartilage reconstruction. All of the implanted host hyaline cartilage enabled a self-healing process and an increase in the BG content in the membranes was desirable for promoting the repair of the calcified cartilage with time. The histological staining confirmed the osteochondral interface in the 30% BG bottom membrane maintained appreciable calcified cartilage repair after 12 weeks. These findings demonstrated that such an integrated artificial osteochondral interface containing appropriate bioactive ions are potentially applicable for osteochondral interface tissue engineering.

Modification of pore-wall in direct ink writing wollastonite scaffolds favorable for tuning biodegradation and mechanical stability and enhancing osteogenic capability.

Surface chemistry and mechanical stability determine the osteogenic capability of bone implants. The development of high-strength bioactive scaffolds for in-situ repair of large bone defects is challenging because of the lack of satisfying biomaterials. In this study, highly bioactive Ca-silicate (CSi) bioceramic scaffolds were fabricated by additive manufacturing and then modified for pore-wall reinforcement. Pure CSi scaffolds were fabricated using a direct ink writing technique, and the pore-wall was modified with 0%, 6%, or 10% Mg-doped CSi slurry (CSi, CSi-Mg6, or CSi-Mg10) through electrostatic interaction. Modified CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds with over 60% porosity demonstrated an appreciable compressive strength beyond 20 MPa, which was ~2-fold higher than that of pure CSi scaffolds. CSi-Mg6 and CSi-Mg10 coating layers were specifically favorable for retarding bio-dissolution and mechanical decay of scaffolds in vitro. In-vivo investigation of critical-size femoral bone defects repair revealed that CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds displayed limited biodegradation, accelerated new bone ingrowth (4-12 weeks), and elicited a suitable mechanical response. In contrast, CSi scaffolds exhibited fast biodegradation and retarded new bone regeneration after 8 weeks. Thus, tailoring of the chemical composition of pore-wall struts of CSi scaffolds is beneficial for enhancing the biomechanical properties and bone repair efficacy.

Postoperative Pain Management in Total Knee Arthroplasty.

Total knee arthroplasty (TKA) is one of the most common surgeries performed to relieve joint pain in patients with end-stage osteoarthritis or rheumatic arthritis of the knee. However, TKA is followed by moderate to severe postoperative pain that affects postoperative rehabilitation, patient satisfaction, and overall outcomes. Historically, opioids have been widely used for perioperative pain management of TKA. However, opioids are associated with undesirable adverse effects, such as nausea, respiratory depression, and retention of urine, which limit their application in daily clinical practice. The aim of this review was to discuss the current postoperative pain management regimens for TKA. Our review of the literature demonstrated that multimodal analgesia is considered the optimal regimen for perioperative pain management of TKA and improves clinical outcomes and patient satisfaction, through a combination of several types of medications and delivery routes, including preemptive analgesia, neuraxial anesthesia, peripheral nerve blockade, patient-controlled analgesia and local infiltration analgesia, and oral opioid/nonopioid medications. Multimodal analgesia provides superior pain relief, promotes recovery of the knee, and reduces opioid consumption and related adverse effects in patients undergoing TKA.

l-Homocysteine-induced cathepsin V mediates the vascular endothelial inflammation in hyperhomocysteinaemia.

BACKGROUND AND PURPOSE: Vascular inflammation, including the expression of inflammatory cytokines in endothelial cells, plays a critical role in hyperhomocysteinaemia-associated vascular diseases. Cathepsin V, specifically expressed in humans, is involved in vascular diseases through its elastolytic and collagenolytic activities. The aim of this study was to determine the effects of cathepsin V on l-homocysteine-induced vascular inflammation. EXPERIMENTAL APPROACH: A high methionine diet-induced hyperhomocysteinaemic mouse model was used to assess cathepsin V expression and vascular inflammation. Cultures of HUVECs were challenged with l-homocysteine and the cathepsin L/V inhibitor SID to assess the pro-inflammatory effects of cathepsin V. Transfection and antisense techniques were utilized to investigate the effects of cathepsin V on the dual-specificity protein phosphatases (DUSPs) and MAPK pathways. KEY RESULTS: Cathepsin L (human cathepsin V homologous) was increased in the thoracic aorta endothelial cells of hyperhomocysteinaemic mice; l-homocysteine promoted cathepsin V expression in HUVECs. SID suppressed the activity of cathepsin V and reversed the up-regulation of inflammatory cytokines (IL-6, IL-8 and TNF-α), adhesion and chemotaxis of leukocytes and vascular inflammation induced by l-homocysteine in vivo and in vitro. Increased cathepsin V promoted the degradation of DUSP6 and DUSP7, phosphorylation and subsequent nuclear translocation of ERK1/2, phosphorylation of STAT1 and expression of IL-6, IL-8 and TNF-α. CONCLUSIONS AND IMPLICATIONS: This study has identified a novel mechanism, which shows that l-homocysteine-induced upregulation of cathepsin V mediates vascular endothelial inflammation under high homocysteine condition partly via ERK1/2 /STAT1 pathway. This mechanism could represent a potential therapeutic target in hyperaemia-associated vascular diseases. LINKED ARTICLES: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

High Prevalence and Properties of Enterotoxin-Producing Staphylococcus aureus ST5 Strains of Food Sources in China.

Staphylococcus aureus with the ability of staphylococcal enterotoxins (SEs) production is one of the most common causes of bacterial foodborne outbreaks worldwide. In our study, 336 S. aureus isolates were recovered from 3476 food samples during 2010-2014. A total of 86 S. aureus isolates were proved to be enterotoxin-producing strains with PCR and enzyme-linked immunosorbent assay. In the 86 isolates, 20 STs were identified using multilocus sequence typing (MLST) and 20 isolates were typed as sequence type 5 (ST5), which was the most prevalent ST using MLST. There were six SE profiles and high carrier rates of sec (50%) and sed (75%) genes in the 20 S. aureus ST5 isolates. Additionally, 8 antibiotic resistance patterns were observed, and 10 multidrug-resistant isolates (50%) and 4 methicillin-resistant S. aureus isolates were identified. Our findings illustrate high prevalence of S. aureus ST5 isolates from food sources and diversity in SE profiles and antibiotic resistance patterns. These results indicate that great difference in the ability of obtaining SE production and antimicrobial resistance may exist between different genetic lineages of S. aureus strains.

The E3 ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp1) promotes M2 macrophage polarization by ubiquitinating and activating transcription factor CCAAT/enhancer-binding Protein ß (C/EBPß).

Macrophage activation, including classical (M1) activation and alternative (M2) activation, plays important roles in host immune response and pathogenesis of diseases. Ubiquitination has been shown to be involved in the differentiation of immune cells and in the regulation of immune responses. However, the role of ubiquitination during M1 versus M2 polarization is poorly explored. Here, we showed that arginase 1 (Arg1), a well recognized marker of M2 macrophages, is highly up-regulated in peritoneal macrophages derived from E3 ubiquitin ligase Nrdp1 transgenic (Nrdp1-TG) mice. Furthermore, other M2 feature markers such as MR, Ym1, and Fizz1, as well as Th2 cytokine IL-10, are also up-regulated in Nrdp1-TG macrophages after IL-4 stimulation. Knockdown of Nrdp1 expression effectively inhibits IL-4-induced expression of M2-related genes in macrophages. Moreover, Nrdp1 inhibits LPS-induced production of inducible NOS and pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in macrophages. Immunoprecipitation assays show that Nrdp1 interacts with and ubiquitinates transcriptional factor C/EBPß via Lys-63-linked ubiquitination. Nrdp1 enhances C/EBPß-triggered transcriptional activation of the Arg1 reporter gene in the presence of IL-4 stimulation. Thus, we demonstrate that Nrdp1-mediated ubiquitination and activation of C/EBPß contributes to a ubiquitin-dependent nonproteolytic pathway that up-regulates Arg1 expression and promotes M2 macrophage polarization.