Measuring disease activity and response to treatment in rheumatoid arthritis

Introduction: Effective treatment of rheumatoid arthritis (RA) requires suppression of the underlying inflammation. Measurement of such inflammation, the disease activity, is mandatory to target treatment and maximize outcomes. However, this is not as straightforward as it may seem.

Areas covered: The many tools developed to measure disease activity in RA, from composite scores and patient-reported outcomes, to laboratory markers and imaging are discussed, with a focus on their utility in guiding therapy and assessing response. The complex issues in measuring disease activity in RA, whether in clinical trials or normal clinical practice, and in the context of national guidelines and recommendations, available time, and resources are considered.

Expert commentary: The key to effective management of RA is the rapid suppression of inflammation, ideally to remission, with maintenance of such remission. The aim is to prevent disability and maximize quality of life. Central to this is the ability to determine disease activity (potentially open to suppression) as opposed to damage (irreversible). A variety of measures are currently available, allowing better assessment of response to treatment. In the future, the development of predictive biomarkers allowing targeting of drugs may revolutionize this field and render the tools of today redundant.     

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin and LEAP2, in a 4‐day binge eating model

The growth hormone secretagogue receptor (GHSR) is a G protein‐coupled receptor that is highly expressed in the central nervous system. GHSR acts as a receptor for ghrelin and for liver‐expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin‐evoked activity. GHSR also displays ligand‐independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced by LEAP2. GHSR activity modulates a variety of food intake‐related behaviours, including binge eating. Previously, we reported that GHSR‐deficient mice daily and time‐limited exposed to a high‐fat (HF) diet display an attenuated binge‐like HF intake compared to wild‐type mice. In the present study, we aimed to determine whether ligand‐independent GHSR activity affects binge‐like HF intake in a 4‐day binge‐like eating protocol. We found that plasma levels of ghrelin and LEAP2 were not modified in mice exposed to this binge‐like eating protocol. Moreover, systemic administration of ghrelin or LEAP2 did not alter HF intake in our experimental conditions. Interestingly, we found that central administration of LEAP2 or K‐(D‐1‐Nal)‐FwLL‐NH₂, which are both blockers of constitutive GHSR activity, reduced binge‐like HF intake, whereas central administration of ghrelin or the ghrelin‐evoked GHSR activity blockers [D‐Lys3]‐GHRP‐6 and JMV2959 did not modify binge‐like HF intake. Taken together, current data indicate that GHSR activity in the brain affects binge‐like HF intake in mice independently of plasma levels of ghrelin and LEAP2.     

Factors determining phage stability/activity: challenges in practical phage application

Introduction: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer. Significant factors are the manner of phage application, the patient’s immune system status, the type of medication being taken, and diet.

Areas covered: We discuss factors determining phage activity and stability, which is relevant for the preparation and application of phage formulations with the highest therapeutic efficacy. Our article should be helpful for more insightful implementation of clinical trials, which could pave the way for successful phage therapy.

Expert opinion: The number of naturally occurring phages is practically unlimited and phages vary in their susceptibility to external factors. Modern methods offer engineering techniques which should lead to enhanced precision in phage delivery and anti-bacterial activity. Recent data suggesting that phages may also be used in treating nonbacterial infections as well as anti-inflammatory and immunomodulatory agents add further weight to such studies. It may be anticipated that different phage activities could have varying susceptibility to factors determining their actions.     

基于网络药理学的气滞胃痛颗粒抗炎镇痛活性作用分析

目的通过网络药理学的方法预测气滞胃痛颗粒抗炎镇痛主要活性成分的作用靶点,结合中医方解配伍理论对其多成分-多靶点-多通路的作用进行分析。方法基于TCMSP中药系统生物学分析数据库收集气滞胃痛颗粒中6味中药的主要化学成分,并借助LC-MS技术对所筛成分进行分析,通过TCMSP检索和Pharmmapper软件预测获取各成分主要的作用靶标,并通过DIP数据库,利用蛋白质相互作用信息建立药物靶标与炎症疼痛靶标的关联,构建药物-靶标-疾病网络,通过网络特征分析气滞胃痛颗粒抗炎镇痛的作用靶标,阐释其抗炎镇痛的主要作用机制。结果根据网络分析,共有44个炎症疼痛靶点与气滞胃痛颗粒密切相关,其中直接作用靶点有20个,主要是对环加氧酶-2(COX-2)和诱导型一氧化氮合酶(i NOS)等蛋白酶的作用,作用机制可能与调节肿瘤坏死因子(TNF)信号通路、NOD样受体(NLR)信号通路、血管内皮生长因子(VEGF)信号通路等与炎症疼痛密切相关的信号通路有关。结论气滞胃痛颗粒抗炎镇痛作用体现了中药多成分、多靶点、多途径的作用特点,该研究为深入阐释气滞胃痛颗粒抗炎镇痛作用机制提供科学依据,并且进一步说明了中医药古方配伍理论的科学性。     

Cross‐sectional and longitudinal association of sports participation,media consumption and motor competence in youth

The beneficial associations of physical activity (PA) and sports with motor competence have been well documented. Similarly, high media time has been associated with poor motor competence. Limited information, however, is available on the combined effects of sport participation and media consumption on motor competence. The present study followed 213 Austrian middle‐school students (57% male; age at baseline: 10.4 ± 0.6 years) over a 4‐year period. Annual assessments included the German Motor Test 6‐18, along with self‐reported participation in club sports, time spent watching TV and using the computer. There were no interaction effects between sports participation and media time on motor competence. Club sports participation, however, was associated with higher motor competence, while there was an inverse association between media time and motor competence. Further, motor competence affected future participation in club sports while club sports had limited effects on subsequent motor development. High media time, on the other hand, impaired subsequent motor development, while effects of motor competence on media time were limited. Taken together, these results emphasize the importance of motor competence in the facilitation of sports participation during adolescence. Accordingly, a wide variety of movement experiences should be provided at young ages to promote motor development. In addition, the detrimental effects of media time on motor competence warrant that sedentary behaviors are targeted separately, particularly in youth not participating in sports.     

A standing posture support device that reduces laparoscopic surgeons’ occupational lower limb stress

Background: We developed a surgical knee rest (SKR) that can be used to decrease the stress placed on the lower half of the body when surgeons work in the standing position. We tested the effectiveness of this device in the context of laparoscopic surgery.

Material and methods: Five healthy, right-handed male surgeons participated, and we recorded surface electromyography (sEMG) signals from the two heads of the left and right gastrocnemius (Gc) muscles during laparoscopic resections of colorectal cancer. The outcome variable was the percentage of maximum Gc muscle effort generated, reported as percent maximal isometric voluntary contraction (%MVC), and this variable was compared between surgeries performed with and without use of the SKR. Assessment covered the first 100?min of surgery, subdivided into two 50-min periods.

Results: Mean %MVC of the left Gc muscle for the full 100-min test period was significantly decreased when the SKR was used (p?=?.027, vs. SKR not used). Notably, mean %MVC of both Gc muscles was significantly decreased during the first 50?min of surgery (p?=?.008 and p?=?.0046).

Conclusion: The SKR is useful for decreasing physical stress incurred by laparoscopic surgeons when working in the standing position.     

Long-term neighborhood ethnic composition and weight-related outcomes among immigrants: The Multi-Ethnic Study of Atherosclerosis

Weight among immigrants in the United States (US) is lower than among the US-born on average, but higher among long-term immigrants than the newly arrived. Neighborhood coethnic concentration—the proportion of neighborhood residents of the same ethnic background—may influence weight among immigrants via behavioral norms and market-driven community resources. However, the relevant exposure timeframe may be far longer than is captured by existing cross-sectional and short-term studies. Using detailed historical residential address information on 1449 older Latino and Chinese long-term immigrants, we investigated associations of 10–20-year neighborhood coethnic concentration trajectories with current waist circumference and weight-related behaviors (diet, physical activity, and sedentary time). Among Chinese participants, compared to persistent low coethnic concentration, increasing coethnic concentration was associated with higher waist circumference (difference = 1.45 cm [0.51, 2.39]). In contrast, both increasing coethnic concentration and persistent high coethnic concentration were associated with a healthier diet. Among Latino participants, trajectories characterized by higher coethnic concentration were associated with higher waist circumference (e.g., difference = 2.11 cm [0.31, 3.91] for persistent high vs. persistent low) and low physical activity. Long-term patterns of neighborhood coethnic concentration may affect weight-related outcomes among immigrants in complex ways that differ by ethnicity and outcome.