The impact of diabetes on the pathogenesis of sepsis Koh, G. C. K. W.; Peacock, S. J.; van der Poll, T. ...
European journal of clinical microbiology & infectious diseases,
04/2012, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, ...fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones.
Purpose
This study aimed to assess the factors associated with pain and evaluate the impact of dual-task exercise on pain improvement, quality of life (QOL), cognition and function in older adults.
...Patients and Methods
This study is a secondary data analysis of the HAPPY (Healthy Ageing Promotion Program for You) study. At risk older adults ≥ 60 years old were enrolled in a community dual-task exercise program. Assessments for frailty, sarcopenia, falls, quality of life (QOL) and perceived health, depression, cognition and physical function were performed at baseline and 3 months. Pain intensity was derived from EQ-5D and stratified into no pain, slight pain and moderate to extreme pain.
Results
Out of 296 participants, 37.2% had slight pain and 11.1% had moderate to severe pain. Both slight and moderate to extreme pain compared with no pain group were significantly associated with lower perceived health (68.2,63.6 vs 76.0) and QOL index (0.70,0.59 vs 0.93); moderate to extreme pain was also significantly associated with depression, low mental vitality, frailty, sarcopenia and poorer physical performance. After 3 months of dual-task exercise, pain improved in 70.8% of the moderate to extreme pain group and 50.8% of slight pain group. Significant improvement in perceived health, QOL, physical function and cognition were also observed.
Conclusion
Proactive efforts are required to screen for pain and manage frailty, sarcopenia and depression. Dual-task exercise proved safe and possibly effective in reducing pain and improving QOL, physical and cognitive function in older adults. Prospective randomized studies are needed to validate the effectiveness of dual-task vs single-task exercise, including impact of reversal of frailty and sarcopenia in pain management.
Myofascial pain syndrome is a chronic pain disorder characterized by myofascial trigger points (MTrPs). Quantitative ultrasound (US) techniques can be used to discriminate MTrPs from healthy muscle. ...In this study, 90 B-mode US images of upper trapezius muscles were collected from 63 participants (left and/or right side(s)). Four texture feature approaches (individually and a combination of them) were employed that focused on identifying spots, and edges were used to explore the discrimination between the three groups: active MTrPs (
= 30), latent MTrPs (
= 30), and healthy muscle (
= 30). Machine learning (ML) and one-way analysis of variance were used to investigate the discrimination ability of the different approaches. Statistically significant results were seen in almost all examined features for each texture feature approach, but, in contrast, ML techniques struggled to produce robust discrimination. The ML techniques showed that two texture features (i.e., correlation and mean) within the combination of texture features were most important in classifying the three groups. This discrepancy between traditional statistical analysis and ML techniques prompts the need for further investigation of texture-based approaches in US for the discrimination of MTrPs.
Escalating costs have made the accessibility of drugs one of the biggest challenges faced by the Malaysian government. The government agreed to regulate drug prices by means of external reference ...pricing, but its proposed policy had a setback owing to much opposition from the pharmaceutical industry. The policy did gain support from the public and from non-governmental organisations because it ensured easy access to affordable medicines. Comments from public consultations with key stakeholders were used to explore stakeholders' perceptions of the external reference pricing policy. A total of 140 comments were analysed for this study. Stakeholders' views were classified as being from the Socioeconomic, industrial, and government sectors. To summarise, the government must carefully manage and consider stakeholders' views to ensure a sound policy. Using Mendelow's stakeholder mapping, this study mapped out stakeholders' views in a systematic approach. The classification of different stakeholders' views and recommendations led to suggestions for reviewing current practices in pharmaceutical pricing regulations in the Malaysian healthcare system. The analyses can be extended to other countries that face similar concerns.
Summary
All-cause mortality risk persisted for 5 years after hip fractures in both men and women. There may be gender-specific differences in effect and duration of excess risk for cause-specific ...mortality after hip fracture.
Introduction
To determine all-cause and cause-specific mortality risk in the first 5 years after hip fracture in an Asian Chinese population.
Methods
The Singapore Chinese Health Study is a population-based cohort of 63,257 middle-aged and elderly Chinese men and women in Singapore recruited between 1993 and 1998. This cohort was followed up for hip fracture and death via linkage with nationwide hospital discharge database and death registry. As of 31 December 2008, we identified 1,166 hip fracture cases and matched five non-fracture cohort subjects by age and gender for each fracture case. Cox proportional hazards and competing risks regression models with hip fracture as a time-dependent covariate were used to determine all-cause and cause-specific mortality risk, respectively.
Results
Increase in all-cause mortality risk persisted till 5 years after hip fracture (adjusted hazard ratio, aHR = 1.58 95 % CI, 1.35–1.86 for females and aHR = 1.64 95 % CI, 1.30–2.06 for males). Men had higher mortality risk after hip fracture than women for deaths from stroke and cancer up to 1 year post-fracture but women with hip fracture had higher coronary artery mortality risk than men for 5 years post-fracture. Men had higher risk of death from pneumonia while women had increased risk of death from urinary tract infections. There was no difference in mortality risk by types of hip fracture surgery.
Conclusions
All-cause mortality risk persisted for 5 years after hip fractures in men and women. There are gender-specific differences in effect size and duration of excess mortality risk from hip fractures between specific causes of death.
It is difficult to create intuitive methods of controlling prosthetic limbs, often resulting in abandonment. Peripheral nerve interfaces can be used to convert motor intent into commands to a ...prosthesis. The Extraneural Spatiotemporal Compound Action Potentials Extraction Network (ESCAPE-NET) is a convolutional neural network (CNN) that has previously been demonstrated to be effective at discriminating neural sources in rat sciatic nerves. ESCAPE-NET was designed to operate using data from multi-channel nerve cuff arrays, and use the resulting spatiotemporal signatures to classify individual naturally evoked compound action potentials (nCAPs) based on differing source fascicles. The applicability of this approach to larger and more complex nerves is not well understood. To support future translation to humans, the objective of this study was to characterize the performance of this approach in a computational model of the human median nerve.
Using a cross-sectional immunohistochemistry image of a human median nerve, a finite-element model was generated and used to simulate extraneural recordings. ESCAPE-NET was used to classify nCAPs based on source location, for varying numbers of sources and noise levels. The performance of ESCAPE-NET was also compared to ResNet-50 and MobileNet-V2 in the context of classifying human nerve cuff data.
Classification accuracy was found to be inversely related to the number of nCAP sources in ESCAPE-NET (3-class: 97.8% ± 0.1%; 10-class: 89.3% ± 5.4% in low-noise conditions, 3-class: 70.3% ± 0.1%; 10-class: 52.5% ± 0.3% in high-noise conditions). ESCAPE-NET overall outperformed both MobileNet-V2 (3-class: 96.5% ± 1.1%; 10-class: 84.9% ± 1.7% in low-noise conditions, 3-class: 86.0% ± 0.6%; 10-class: 41.4% ± 0.9% in high-noise conditions) and ResNet-50 (3-class: 71.2% ± 18.6%; 10-class: 40.1% ± 22.5% in low-noise conditions, 3-class: 81.3% ± 4.4%; 10-class: 31.9% ± 4.4% in high-noise conditions).
All three networks were found to learn to differentiate nCAPs from different sources, as evidenced by performance levels well above chance in all cases. ESCAPE-NET was found to have the most robust performance, despite decreasing performance as the number of classes increased, and as noise was varied. These results provide valuable translational guidelines for designing neural interfaces for human use.
Abstract
Central sensitization is a condition that represents a cascade of neurological adaptations, resulting in an amplification of nociceptive responses from noxious and non-noxious stimuli. ...However, whether this abnormality translates into motor output and more specifically, ventral horn abnormalities, needs to be further explored. Twenty healthy participants aged 20–70 were randomly allocated to topical capsaicin or a placebo topical cream which was applied onto their left upper back to induce a transient state of sensitization. Visual analogue scale (VAS) ratings of pain intensity and brush allodynia score (BAS) were used to determine the presence of pain and secondary allodynia. Surface electromyography (sEMG) and intramuscular electromyography (iEMG) were used to record motor unit activity from the upper trapezius and infraspinatus muscles before and twenty minutes after application of capsaicin/placebo. Motor unit recruitment and variability were analyzed in the sEMG and iEMG, respectively. An independent t-test and Kruskal–Wallis H test were performed on the data. The sEMG results demonstrated a shift in the motor unit recruitment pattern in the upper trapezius muscle, while the iEMG showed a change in motor unit variability after application of capsaicin. These results suggest that capsaicin-induced central sensitization may cause changes in ventral horn excitability outside of the targeted spinal cord segment, affecting efferent pathway outputs. This preclinical evidence may provide some explanation for the influence of central sensitization on changes in movement patterns that occur in patients who have pain encouraging of further clinical investigation.
Clinical Trials registration number: NCT04361149; date of registration: 24-Apr-2020.
Vascular endothelial growth factor (VEGF) induces adhesion molecules on endothelial cells during inflammation. Here we examined the mechanisms underlying VEGF-stimulated expression of intercellular ...adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin in human umbilical vein endothelial cells. VEGF (20 ng/ml) increased expression of ICAM-1, VCAM-1, and E-selectin mRNAs in a time-dependent manner. These effects were significantly suppressed by Flk-1/kinase-insert domain containing receptor (KDR) antagonist and by inhibitors of phospholipase C, nuclear factor (NF)-κB, sphingosine kinase, and protein kinase C, but they were not affected by inhibitors of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1/2 or nitric-oxide synthase. Unexpectedly, the phosphatidylinositol (PI) 3′-kinase inhibitor wortmannin enhanced both basal and VEGF-stimulated adhesion molecule expression, whereas insulin, a PI 3′-kinase activator, suppressed both basal and VEGF-stimulated expression. Gel shift analysis revealed that VEGF stimulated NF-κB activity. This effect was inhibited by phospholipase C, NF-κB, or protein kinase C inhibitor. VEGF increased VCAM-1 and ICAM-1 protein levels and increased leukocyte adhesiveness in a NF-κB-dependent manner. These results suggest that VEGF-stimulated expression of ICAM-1, VCAM-1, and E-selectin mRNAs was mainly through NF-κB activation with PI 3′-kinase-mediated suppression, but was independent of nitric oxide and MEK. Thus, VEGF simultaneously activates two signal transduction pathways that have opposite functions in the induction of adhesion molecule expression. The existence of parallel inverse signaling implies that the induction of adhesion molecule expression by VEGF is very finely regulated.
Abstract There is an unmet clinical need for wound dressings to treat partial thickness burns that damage the epidermis and dermis. An ideal dressing needs to prevent infection, maintain skin ...hydration to facilitate debridement of the necrotic tissue, and provide cues to enhance tissue regeneration. We developed a class of ‘smart’ peptide hydrogels, which fulfill these criteria. Our ultrashort aliphatic peptides have an innate tendency to self-assemble into helical fibers, forming biomimetic hydrogel scaffolds which are non-immunogenic and non-cytotoxic. These nanofibrous hydrogels accelerated wound closure in a rat model for partial thickness burns. Two peptide hydrogel candidates demonstrate earlier onset and completion of autolytic debridement, compared to Mepitel® , a silicone-coated polyamide net used as standard-of-care. They also promote epithelial and dermal regeneration in the absence of exogenous growth factors, achieving 86.2% and 92.9% wound closure respectively, after 14 days. In comparison, only 62.8% of the burnt area is healed for wounds dressed with Mepitel® . Since the rate of wound closure is inversely correlated with hypertrophic scar formation and infection risks, our peptide hydrogel technology fills a niche neglected by current treatment options. The regenerative properties can be further enhanced by incorporation of bioactive moieties such as growth factors and cytokines.
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