Comparison of the Effects of Ice and 3.5% Menthol Gel on Blood Flow and Muscle Strength of the Lower Arm

Context: Soft-tissue injuries are commonly treated with ice or menthol gels. Few studies have compared the effects of these treatments on blood flow and muscle strength. Objective: To compare blood flow and muscle strength in the forearm after an application of ice or menthol gel or no treatment. Design: Repeated measures design in which blood-flow and muscle-strength data were collected from subjects under 3 treatment conditions. Setting: Exercise physiology laboratory. Participants: 17 healthy adults with no impediment to the blood flow or strength in their right arm, recruited through word of mouth. Intervention: Three separate treatment conditions were randomly applied topically to the right forearm: no treatment, 0.5 kg of ice, or 3.5 mL of 3.5% menthol gel. To avoid injury ice was only applied for 20 min. Main Outcome Measures: At each data-collection session blood flow (mL/min) of the right radial artery was determined at baseline before any treatment and then at 5, 10, 15, and 20 min after treatment using Doppler ultrasound. Muscle strength was assessed as maximum isokinetic flexion and extension of the wrist at 30°/s 20, 25, and 30 min after treatment. Results: The menthol gel reduced (–42%, P \u3c .05) blood flow in the radial artery 5 min after application but not at 10, 15, or 20 min after application. Ice reduced (–48%, P \u3c .05) blood flow in the radial artery only after 20 min of application. After 15 min of the control condition blood flow increased (83%, P \u3c .05) from baseline measures. After the removal of ice, wrist-extension strength did not increase per repeated strength assessment as it did during the control condition (9–11%, P \u3c .05) and menthol-gel intervention (8%, P \u3c .05). Conclusions: Menthol has a fast-acting, short-lived effect of reducing blood flow. Ice reduces blood flow after a prolonged duration. Muscle strength appears to be inhibited after ice application

Implications of the diversity of class I HLA associations in psoriatic arthritis

We sought to validate and extend the findings of a 282 psoriatic arthritis patient cohort from Dublin using a 219 patient cohort from Bath. The central finding of this study was that several structurally unrelated HLA alleles, including B*08:01:01, B*18:01:01, B*27:05:02, B*55:01:01 and C*06:02:01, were found to be significantly associated with particular phenotypic features of psoriatic arthritis, implying that the clinical diagnosis of psoriatic arthritis designates a genetically heterogeneous subset of individuals. Radiographic sacroiliitis was associated with either B*08:01:01, or B*27:05:02 with implications about the role of MHC molecules in an adaptive immune response. There are implications for psoriatic arthritis diagnostic criteria since some disease features used in the criteria are under genetic control. These findings have important implications for understanding the role of MHC alleles in directing the adaptive immune response to mediate the inflammation responsible for psoriatic arthritis

Predictors of ADL Disability in Culturally Diverse Older Adults

The purpose of this study was to utilize the disablement pathway model to examine the contribution of physical function, dyspnea, and pain to disability in activities-of-daily-living (ADL) in culturally diverse older adults. Participants were 51 older adults (age = 69.0 years ± 9.7; 76.5% African-American, 51.0% \u3c high school education, 52.9% \u3c $20,000 annual income) from an urban community center and an independent living housing facility for seniors. Participants completed the Functional Status Index (FSI), which provides ratings of need for assistance (FSIA) and pain (FSIP) with ADL, the Continuous Scale Physical Functional Performance 10-item Test (CS-PFP10), and an analog dyspnea scale. Hierarchical multiple regression analyses revealed that facility, physical function, pain, and dyspnea accounted for 50.5% of the variance in disability and that pain (β = .43, p \u3c .01) and physical function (β = -.39, p \u3c .01) were the only significant predictors. In the second model, facility, dyspnea, and pain explained 27.6% of the variance in physical function, and facility (β = .39, p \u3c .01) and dyspnea (β = -.26, p = .05) were the only significant predictors. Based on the disablement pathway model, physical functional improvement and pain prevention and management should be targeted when designing culturally appropriate strategies for delaying disability and maintaining independent life

Accelerating causal inference based RCA using prior knowledge from functional connectivity inference

A crucial step in remedying faults within network infrastructures is to determine their root cause. However, the large-scale, complex and dynamic nature of modern networks makes causal inference-based root cause analysis challenging in terms of scalability and knowledge drift over time. In this paper, we propose a framework that utilises the neuroscientific concept of functional connectivity– a graph representation of statistical dependencies between events– as a scalable approach to acquire and maintain prior knowledge for causal inferencebased RCA approaches in dynamic networks. We demonstrate on both synthetic and real-world data that our proposed approach can provide significant speedups to existing causal inference approaches without significant loss of accuracy. We show that, in some cases, such prior knowledge can even improve the accuracy of causal inference. Finally, we discuss the impact of the choice of user-defined parameters on causal inference accuracy and conclude that the framework can safely be deployed in the real world

Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype

This review focuses on the genetic features of psoriatic arthritis (PsA) and their relationship to phenotypic heterogeneity in the disease, and addresses three questions: what do the recent studies on human leukocyte antigen (HLA) tell us about the genetic relationship between cutaneous psoriasis (PsO) and PsA – that is, is PsO a unitary phenotype; is PsA a genetically heterogeneous or homogeneous entity; and do the genetic factors implicated in determining susceptibility to PsA predict clinical phenotype? We first discuss the results from comparing the HLA typing of two PsO cohorts: one cohort providing the dermatologic perspective, consisting of patients with PsO without evidence of arthritic disease; and the second cohort providing the rheumatologic perspective, consisting of patients with PsA. We show that these two cohorts differ considerably in their predominant HLA alleles, indicating the heterogeneity of the overall PsO phenotype. Moreover, the genotype of patients in the PsA cohort was shown to be heterogeneous with significant elevations in the frequency of haplotypes containing HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39. Because different genetic susceptibility genes imply different disease mechanisms, and possibly different clinical courses and therapeutic responses, we then review the evidence for a phenotypic difference among patients with PsA who have inherited different HLA alleles. We provide evidence that different alleles and, more importantly, different haplotypes implicated in determining PsA susceptibility are associated with different phenotypic characteristics that appear to be subphenotypes. The implication of these findings for the overall pathophysiologic mechanisms involved in PsA is discussed with specific reference to their bearing on the discussion of whether PsA is conceptualised as an autoimmune process or one that is based on entheseal responses

Interleukin 15 Primes Natural Killer Cells to Kill via NKG2D and cPLA2 and This Pathway Is Active in Psoriatic Arthritis

NK cells are large granular lymphocytes that form a critical component of the innate immune system, whose functions include the killing of cells expressing stress-induced molecules. It is increasingly accepted that despite being considered prototypical effector cells, NK cells require signals to reach their full cytotoxic potential. We previously showed that IL-15 is capable of arming CD8 effector T cells to kill independently of their TCR via NKG2D in a cPLA2-dependent process. As NK cells also express NKG2D, we wanted to investigate whether this pathway functioned in an analogous manner and if resting NK cells could be primed to the effector phase by IL-15. Furthermore, to establish relevance to human disease we studied a possible role for this pathway in the pathogenesis of psoriatic arthritis, since there are aspects of this disease that suggest a potential effector role for the innate immune system. We found that PsA patients had upregulated IL-15 and MIC in their affected synovial tissues, and that this unique inflammatory environment enabled NK cell activation and killing via NKG2D and cPLA2. Moreover, we were able to reproduce the phenotype of joint NK cells from blood NK cells by incubating them with IL-15. Altogether, these findings suggest a destructive role for NK cells when activated by environmental stress signals during the pathogenesis of PsA and demonstrate that IL-15 is capable of priming resting NK cells in tissues to the effector phase.</p