Conditioned Pain Modulation Predicts Exercise-Induced Hypoalgesia in Healthy Adults

Introduction: Conditioned pain modulation (CPM) is the concept that pain inhibits pain and has potential rehabilitation implications for exercise prescription. The purpose of this study was to determine whether changes in pressure pain perception after a thermal conditioning stimulus (i.e., CPM) was attenuated with aging and whether CPM predicted pain relief after exercise (exercise-induced hypoalgesia (EIH)) in healthy young and older adults. Methods: Twenty young (21.9 ± 3.3 yr, 10 men) and 19 older (72.0 ± 4.5 yr, 10 men) adults participated in three sessions: one familiarization and two experimental (EIH and CPM) sessions. Pressure pain perception was assessed using a weighted Lucite edge placed on the right index finger for 1 min. EIH was determined by measuring pressure pain perception before and after prolonged submaximal isometric contraction of the elbow flexors. CPM was assessed by measuring pressure pain perception at the finger while the foot was immersed in neutral water versus painful ice water. Results: Young, but not older, adults reported a decrease in pressure pain at the finger while their foot was immersed in the ice water bath compared with the neutral bath (i.e., CPM, trial–age: P = 0.001). Pressure pain ratings decreased after exercise (P = 0.03) that was perceived as painful (peak arm pain, 7.0 ± 3.3) for both young and older adults. Regression analysis showed that after controlling for age and baseline pain, CPM predicted EIH (model adjusted R2 = 0.23, P = 0.007). Conclusions: CPM was attenuated in older adults, as measured with a noxious pressure stimulus after a thermal conditioning stimulus, and adults with greater CPM were more likely to report greater EIH

Pain Relief in Older Adults Following Static Contractions is not Task-Dependent

Pain complaints increase with age. Exercise is frequently utilized for pain relief but the optimal exercise prescription to relieve pain is not clear. Following static contractions, young adults experience the greatest pain relief with low intensity, long duration contractions. The pain response to static contractions in older adults however is unknown. PURPOSE : To compare pain reports in healthy older adults before and after static contractions of varying intensity and duration. METHODS: Pain perception was assessed in 23 healthy older adults (11 men, 12 women; 72.0 ± 6.3 yrs) using a pressure pain device consisting of a 10 N force applied to the right index finger through a Lucite edge (8 x 1.5mm) for two minutes. Subjects pushed a timing device when they first felt pain (i.e., pain threshold) and rated their pain intensity every 20 seconds using a 0-10 numerical rating scale. Pain threshold and pain ratings were measured before and immediately after static contractions of the left elbow flexors at the following three doses: 1) three brief maximal voluntary contractions (MVC); 2) 25% MVC sustained for 2 minutes; and 3) 25% MVC sustained until task failure. Experimental sessions were randomized and separated by one week. RESULTS : Time to task failure for the 25% MVC contraction was 11.8 ± 5.1 minutes. A reduction in pain was found following all three tasks with no difference between tasks (trial x task effect: p \u3e 0.05), despite the duration of the 2 minute low-intensity contraction being ~17% of the contraction held to task failure. Pain thresholds for all doses increased 20% from 51 ± 33 to 61 ± 37 seconds and pain ratings averaged over the six time points decreased 20% from 3.3 ± 2.8 to 2.6 ± 2.5 following static contractions (trial effect: p \u3c 0.001 and p \u3c 0.001, respectively). CONCLUSION : Low and high intensity static contractions of both long and short duration produce similar levels of pain reduction in older adults. These preliminary data suggest that several different types of static contractions can induce significant pain relief in older adults. Age-related changes in the pain response to static contractions must be taken into account when prescribing static exercise for the management of pain

Pain Relief in Older Adults Following Static Contractions is not Task-Dependent

Pain complaints increase with age. Exercise is frequently utilized for pain relief but the optimal exercise prescription to relieve pain is not clear. Following static contractions, young adults experience the greatest pain relief with low intensity, long duration contractions. The pain response to static contractions in older adults however is unknown. PURPOSE : To compare pain reports in healthy older adults before and after static contractions of varying intensity and duration. METHODS: Pain perception was assessed in 23 healthy older adults (11 men, 12 women; 72.0 ± 6.3 yrs) using a pressure pain device consisting of a 10 N force applied to the right index finger through a Lucite edge (8 x 1.5mm) for two minutes. Subjects pushed a timing device when they first felt pain (i.e., pain threshold) and rated their pain intensity every 20 seconds using a 0-10 numerical rating scale. Pain threshold and pain ratings were measured before and immediately after static contractions of the left elbow flexors at the following three doses: 1) three brief maximal voluntary contractions (MVC); 2) 25% MVC sustained for 2 minutes; and 3) 25% MVC sustained until task failure. Experimental sessions were randomized and separated by one week. RESULTS : Time to task failure for the 25% MVC contraction was 11.8 ± 5.1 minutes. A reduction in pain was found following all three tasks with no difference between tasks (trial x task effect: p \u3e 0.05), despite the duration of the 2 minute low-intensity contraction being ~17% of the contraction held to task failure. Pain thresholds for all doses increased 20% from 51 ± 33 to 61 ± 37 seconds and pain ratings averaged over the six time points decreased 20% from 3.3 ± 2.8 to 2.6 ± 2.5 following static contractions (trial effect: p \u3c 0.001 and p \u3c 0.001, respectively). CONCLUSION : Low and high intensity static contractions of both long and short duration produce similar levels of pain reduction in older adults. These preliminary data suggest that several different types of static contractions can induce significant pain relief in older adults. Age-related changes in the pain response to static contractions must be taken into account when prescribing static exercise for the management of pain

Only Women Report Increase in Pain Threshold Following Fatiguing Contractions of the Upper Extremity

Purpose The perception of pain in response to a noxious stimulus can be markedly reduced following an acute bout of exercise [exercise-induced hypoalgesia (EIH)]. Sex differences in EIH frequently occur after exercise but may be confounded by the sex differences in muscle fatigue. The purpose was to determine if sex differences in pain relief occur after an exercise protocol when muscle fatigue is similar for both young and older men and women. Methods Pain perception of 33 men (15 young) and 31 women (19 young) was measured using a pressure pain stimulus on the left index finger before and after maximal velocity concentric contractions of knee extensors or elbow flexors (separate days). During the 2-min pressure pain test, participants verbally indicated the onset of pain (pain threshold) and reported pain intensity (0–10) every 20 s. Results Only women experienced an increase in pain threshold (30 ± 27 to 41 ± 32 s) following elbow flexor exercise (trial × sex: p = 0.03). Neither men nor women experienced an increase in pain threshold following knee extensor exercise, and pain ratings were unchanged after exercise with either limb (p \u3e 0.05). The pain response to exercise was similar in young and older adults (trial × age: p \u3e 0.05), despite older adults demonstrating greater fatigability than young adults for the elbow flexor and knee extensor exercise tasks. Conclusions Under controlled conditions where muscle fatigue is similar, sex differences in EIH occur in young and older adults that is site specific (upper extremity). Only women experience EIH following acute single limb high-velocity contractions

Plasma zonulin levels in childhood nephrotic syndrome

© 2019 Trachtman, Gipson, Lemley, Troost, Faul, Morrison, Vento, Ahn and Goldberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Objective: We conducted this study to test the hypothesis that plasma zonulin levels are elevated in pediatric patients with nephrotic syndrome compared to healthy controls. Study Design: Plasma zonulin levels were measured by ELISA in 114 children enrolled in the NEPTUNE study. Clinical and laboratory data were retrieved from the NEPTUNE database. Results: The median age of the patients was 10 (IQR = 5 to 14) years, 59 were male, 64 had minimal change disease, 47 focal segmental glomerulosclerosis, median eGFR was 96 (IQR = 80 to 114) ml/min/1.73 m2, and median urine protein:creatinine ratio was 0.5 (IQR = 0.1 to 3.4) (g:g). The plasma zonulin level was 14.2 ± 5.0 vs. 10.2 ± 2.5 ng/ml in healthy adults in a report using the same assay kit, P = 0.0025. These findings were confirmed in an independent cohort of children with nephrotic syndrome compared to healthy age-matched controls, P = 0.01. Zonulin concentrations did not differ in children with minimal change disease vs. focal segmental glomerulosclerosis, frequently relapsing vs. steroid-dependent vs. steroid-resistant clinical course, and were not influenced by the immunosuppressive treatment regimen. There was no relationship between plasma zonulin levels and the absolute or percentage change in proteinuria from enrollment until the time of the zonulin assay. Conclusion: Plasma zonulin levels are elevated in childhood nephrotic syndrome regardless of level of proteinuria or specific treatment. The cause of the high plasma zonulin levels and whether zonulin contributes to glomerular injury requires further study

A study of patent thickets

Report analysing whether entry of UK enterprises into patenting in a technology area is affected by patent thickets in the technology area

Text Messaging for Disease Monitoring in Childhood Nephrotic Syndrome

Introduction: There is limited information on effective disease monitoring for prompt interventions in childhood nephrotic syndrome. We examined the feasibility and effectiveness of a novel text messaging system (SMS) for disease monitoring in a multicenter, prospective study. Methods: A total of 127 patients <19 years with incident nephrotic syndrome were enrolled in the ongoing Nephrotic Syndrome Study Network between June 2015 and March 2018. Text messages soliciting home urine protein results, symptoms, and medication adherence were sent to a designated caregiver (n = 116) or adolescent patient (n = 3). Participants responded by texting. Feasibility of SMS was assessed by SMS adoption, retention, and engagement, and concordance between participant-reported results and laboratory/clinician assessments. The number of disease relapses and time-to-remission data captured by SMS were compared with data collected by conventional visits. Results: A total of 119 of 127 (94%) patients agreed to SMS monitoring. Retention rate was 94%, with a median follow-up of 360 days (interquartile range [IQR] 353–362). Overall engagement was high, with a median response rate of 87% (IQR, 68–97). Concordance between SMS-captured home urine protein results and edema status with same-day in-person study visit was excellent (kappa values 0.88 and 0.92, respectively). SMS detected a total of 108 relapse events compared with 41 events captured by scheduled visits. Median time to remission after enrollment was 22 days as captured by SMS versus 50 days as captured by scheduled visits. Conclusion: SMS was well accepted by caregivers and adolescent patients and reliably captured nephrotic syndrome disease activity between clinic visits. Additional studies are needed to explore the impact of SMS on disease outcomes

To be financed or not : the role of patents for venture capital financing

This paper investigates how patent applications and grants held by new ventures improve their ability to attract venture capital (VC) financing. We argue that investors are faced with considerable uncertainty and therefore rely on patents as signals when trying to assess the prospects of potential portfolio companies. For a sample of VC-seeking German and British biotechnology companies we have identified all patents filed at the European Patent Office (EPO). Applying hazard rate analysis, we find that in the presence of patent applications, VC financing occurs earlier. Our results also show that VCs pay attention to patent quality, financing those ventures faster which later turn out to have high-quality patents. Patent oppositions increase the likelihood of receiving VC, but ultimate grant decisions do not spur VC financing, presumably because they are anticipated. Our empirical results and interviews with VCs suggest that the process of patenting generates signals which help to overcome the liabilities of newness faced by new ventures

International patent families: from application strategies to statistical indicators

This paper provides an in-depth analysis of the characteristics of international patent families, including their domestic component. We exploit a relatively under-studied feature of patent families, namely the number of patents covering the same invention within a given jurisdiction. Using this information, we highlight common patterns in the structure of international patent families, which reflect both the patenting strategies of innovators and the peculiarities of the different patent systems. While the literature has extensively used family size, i.e. the number of countries in which a given invention is protected, as a measure of patent value, our results suggest that the number of patent filings in the priority country within a patent family as well as the timespan between the first and last fillings within a family are other insightful indicators of the value of patented innovations