STING signaling modulates CD8 T cell memory fitness via differential TCR signaling

STING functions as a critical mediator of DNA sensing to direct both innate immune responses as well as functioning to maintain cellular homeostasis. While STING has been extensively investigated in innate cells, autoimmune disorders, and cancer, little is known about STING's role in CD8 T cell processes. We show here that high levels of STING signaling induce potent reductions in CD8 T cell memory formation. STING functions in both a T cell intrinsic and T cell extrinsic manner to regulate the survival of T cells as they progress to a memory phenotype. Moreover, TCR signal strength regulates the sensitivity of T cells to STING-induced cellular apoptosis and the ability of T cells to join the pool of memory cells. Our data suggests that STING signaling pushes ER stress and death through the UPR to regulate T cell memory. Together, these provide insight into how enhanced STING signals and TCR signaling coalesce to regulate the T cell memory pool and the efficacy of the immune response.Includes bibliographical references

A Pilot Study to Measure Upper Extremity H-reflexes Following Neuromuscular Electrical Stimulation Therapy after Stroke

Upper extremity (UE) hemiparesis persists after stroke, limiting hand function. Neuromuscular electrical stimulation (NMES) is an effective intervention to improve UE recovery, although the underlying mechanisms are not fully understood. Our objective was to establish a reliable protocol to measure UE agonist–antagonist forearm monosynaptic reflexes in a pilot study to determine if NMES improves wrist function after stroke. We established the between-day reliability of the H-reflex in the extensor carpi radialis longus (ECRL) and flexor carpi radialis (FCR) musculature for individuals with prior stroke (n = 18). The same-day generation of ECRL/FCR H-reflex recruitment curves was well tolerated, regardless of age or UE spasticity. The between-day reliability of the ECRL H-reflex was enhanced above FCR, similar to healthy subjects [20], with the Hmax the most reliable parameter quantified in both muscles. H-reflex and functional measures following NMES show the potential for NMES-induced increases in ECRL Hmax, but confirmation requires a larger clinical study. Our initial results support the safe, easy, and efficacious use of in-home NMES, and establish a potential method to measure UE monosynaptic reflexes after stroke

Cardiopulmonary Response to Exercise Testing in People with Chronic Stroke: A Retrospective Study

Background and Purpose. This study investigated the cardiopulmonary response and safety of exercise testing at peak effort in people during the chronic stage of stroke recovery. Methods. This retrospective study examined data from 62 individuals with chronic stroke (males: 32; mean (SD); age: (12.0) yr) participating in an exercise test. Results. Both males and females had low cardiorespiratory fitness levels. No significant differences were found between gender for peak HR (P = 0.27), or VO2 peak (P = 0.29). Males demonstrated higher values for minute ventilation, tidal volume, and respiratory exchange ratio. No major adverse events were observed in the exercise tests conducted. Discussion and Conclusion. There are differences between gender that may play a role in exercise testing performance and should be considered when developing exercise programs. The low VO2 peak of this cohort of chronic stroke survivors suggests the need for participation in exercise interventions

A novel device to measure power grip forces in squirrel monkeys

Understanding the neural bases for grip force behaviors in both normal and neurologically impaired animals is imperative prior to improving treatments and therapeutic approaches. The present paper describes a novel device for the assessment of power grip forces in squirrel monkeys. The control of grasping and object manipulation represents a vital aspect of daily living by allowing the performance of a wide variety of complex hand movements. However, following neurological injury such as stroke, these grasping behaviors are often severely affected, resulting in persistent impairments in strength, grip force modulation and kinematic hand control. While there is a significant clinical focus on rehabilitative strategies to address these issues, there exists the need for translational animal models. In the study presented here, we describe a simple grip force device designed for use in nonhuman primates, which provides detailed quantitative information regarding distal grip force dynamics. Adult squirrel monkeys were trained to exceed a specific grip force threshold, which was rewarded with a food pellet. One of these subjects then received an infarct of the M1 hand representation area. Results suggest that the device provides detailed and reliable information on grip behaviors in healthy monkeys and can detect deficits in grip dynamics in monkeys with cortical lesions (significantly longer release times). Understanding the physiological and neuroanatomical aspects of grasping function following neurological injury may lead to more effective rehabilitative interventions

Incremental Exact Min-Cut in Poly-logarithmic Amortized Update Time

We present a deterministic incremental algorithm for exactly maintaining the size of a minimum cut with ~O(1) amortized time per edge insertion and O(1) query time. This result partially answers an open question posed by Thorup [Combinatorica 2007]. It also stays in sharp contrast to a polynomial conditional lower-bound for the fully-dynamic weighted minimum cut problem. Our algorithm is obtained by combining a recent sparsification technique of Kawarabayashi and Thorup [STOC 2015] and an exact incremental algorithm of Henzinger [J. of Algorithm 1997]. We also study space-efficient incremental algorithms for the minimum cut problem. Concretely, we show that there exists an O(n log n/epsilon^2) space Monte-Carlo algorithm that can process a stream of edge insertions starting from an empty graph, and with high probability, the algorithm maintains a (1+epsilon)-approximation to the minimum cut. The algorithm has ~O(1) amortized update-time and constant query-time

Plantar forefoot pressures in psoriatic arthritis-related dactylitis: an exploratory study

Dactylitis is a common feature of psoriatic arthritis (PsA); local physical trauma has been identified as a possible contributing factor. The aim of this study was to explore differences in forefoot plantar pressures in patients with PsA with and without dactylitis and compare to healthy controls. Thirty-six participants were recruited into three groups: group A PsA plus a history of dactylitis; group B PsA, no dactylitis; group C control participants. Forefoot plantar pressures were measured barefoot and in-shoe at the left second and fourth toes and corresponding metatarsophalangeal joints. Temporal and spatial parameters were measured and data from the foot impact scale for rheumatoid arthritis (FIS-RA), EQ5D and health assessment questionnaire (HAQ) were collected. Pressure time integral peak plantar pressure, and contact time barefoot and in-shoe were not significantly different between groups. Temporal and spatial parameters reported no significant differences between groups. ANOVA analysis and subsequent post hoc testing using Games-Howell test yielded significance in FIS-RA scores between both PsA groups versus controls, A p ≤ 0.0001 and PsA group B p < 0.0001 in the FIS-RA impairment and footwear domain, PsA group A p < 0.03 and PsA group B p ≤ 0.05 in the FIS-RA activity and participation domain compared to controls. This is the first exploratory study to investigate forefoot plantar pressures in patients with and without historical dactylitis in PsA. FIS-RA scores indicate PsA patients have significant limitations compared to controls, although a history of dactylitis does not appear to worsen patient reported outcomes

Testing the proficiency to distinguish locations with elevated plantar pressure within and between professional groups of foot therapists

BACKGROUND: Identification of locations with elevated plantar pressures is important in daily foot care for patients with rheumatoid arthritis, metatarsalgia and diabetes. The purpose of the present study was to evaluate the proficiency of podiatrists, pedorthists and orthotists, to distinguish locations with elevated plantar pressure in patients with metatarsalgia. METHODS: Ten podiatrists, ten pedorthists and ten orthotists working in The Netherlands were asked to identify locations with excessively high plantar pressure in three patients with forefoot complaints. Therapists were instructed to examine the patients according to the methods used in their everyday clinical practice. Regions could be marked through hatching an illustration of a plantar aspect. A pressure sensitive platform was used to quantify the dynamic bare foot plantar pressures and was considered as 'Gold Standard' (GS). A pressure higher than 700 kPa was used as cut-off criterion for categorizing peak pressure into elevated or non-elevated pressure. This was done for both patient's feet and six separate forefoot regions: big toe and metatarsal one to five. Data were analysed by a mixed-model ANOVA and Generalizability Theory. RESULTS: The proportions elevated/non-elevated pressure regions, based on clinical ratings of the therapists, show important discrepancies with the criterion values obtained through quantitative plantar pressure measurement. In general, plantar pressures in the big toe region were underrated and those in the metatarsal regions were overrated. The estimated method agreement on clinical judgement of plantar pressures with the GS was below an acceptable level: i.e. all intraclass correlation coefficient's equal or smaller than .60. The inter-observer agreement for each discipline demonstrated worrisome results: all below .18. The estimated mutual agreements showed that there was virtually no mutual agreement between the professional groups studied. CONCLUSION: Identification of elevated plantar pressure through clinical evaluation is difficult, insufficient and may be potentially harmful. The process of clinical plantar pressure screening has to be re-evaluated. The results of this study point towards the merit of quantitative plantar pressure measurement for clinical practice

High-intensity interval training vs. moderate-intensity continuous training in the prevention/management of cardiovascular disease

Moderate-intensity continuous training (MICT) has long been considered the most effective exercise treatment modality for the prevention and management of cardiovascular disease, but more recently high-intensity interval training (HIIT) has emerged into the clinical environment has been viewed as a potential alternative to MICT in accruing such benefits. HIIT was initially found to induce significant improvements in numerous physiological and health-related indices, to a similar if not superior extent to MICT. Since then, many studies have attempted to explore the potential clinical utility of HIIT, relative to MICT, with respect to treating numerous cardiovascular conditions such as coronary artery disease, heart failure, stroke, and hypertension. Despite this, however, the efficacy of HIIT compared to MICT with respect to in reversing the specific symptoms and risk factors of these cardiovascular pathologies for improved health and wellbeing as well as reduced morbidity and mortality is not well understood. In addition, HIIT is often perceived as very strenuous, which could potentially render it unsafe for those at risk of or afflicted with cardiovascular disease, but these issues are also yet to be reviewed. Furthermore, the optimal HIIT protocol for each of the cardiovascular disease cohorts has not been established. Thus, the purpose of this review article is to (i) evaluate the efficacy of HIIT relative to MICT in the prevention and management of cardiovascular conditions, and (ii) explore any potential safety issues surrounding the suitability and/or tolerability of HIIT for patients with cardiovascular disease, as well as the potential optimal prescriptive variables of HIIT for application in the clinical environment

The cognitive neuroscience of prehension: recent developments

Prehension, the capacity to reach and grasp, is the key behavior that allows humans to change their environment. It continues to serve as a remarkable experimental test case for probing the cognitive architecture of goal-oriented action. This review focuses on recent experimental evidence that enhances or modifies how we might conceptualize the neural substrates of prehension. Emphasis is placed on studies that consider how precision grasps are selected and transformed into motor commands. Then, the mechanisms that extract action relevant information from vision and touch are considered. These include consideration of how parallel perceptual networks within parietal cortex, along with the ventral stream, are connected and share information to achieve common motor goals. On-line control of grasping action is discussed within a state estimation framework. The review ends with a consideration about how prehension fits within larger action repertoires that solve more complex goals and the possible cortical architectures needed to organize these actions