Metabolic Requirements of Farmers/Ranchers Performing Simulated Occupational Tasks: Recommendations for Cardiovascular Rehabilitation

Current ACSM guidelines for cardiac rehabilitation (rehab) return to work state that exercise training should mimic the muscle groups, movements, and energy systems utilized in a patient’s occupational tasks. The aims of this study were to evaluate the metabolic costs of typical farming/ranching tasks, determine the pattern of movement and muscle groups involved in these tasks, and determine the approximate duration of these tasks. Methods: Participants (n=29) were employed in the farming/ranching field and ranged in aged from 18-57 years. The participants performed four tasks: loading 10 hay bales, digging a fence post hole, filling eight seed hoppers, and shoveling grain. Results: Ranges for mean metabolic equivalent (MET) levels of the tasks were 5.9-7.6 while respiratory exchange ratio (RER) values ranged from .85-.93. Mean times (min:sec) for task duration were 1:42-3:34. Conclusion: MET levels recorded in this study are in agreement with the Compendium of Physical Activities for farming tasks and meet the standard requirements for cardiovascular training in cardiac rehab (~ 8 METS). However, these tasks are of high intensity and require an exercise prescription based on specificity of training for the muscle groups and energy systems involved. In accordance to ACSM guidelines, this study includes recommendations for exercise prescription specific to supervised resistance training appropriate for a farmer/rancher population in cardiac rehab settings

Casein Kinase II Phosphorylation of Spt6 Enforces Transcriptional Fidelity by Maintaining Spn1-Spt6 Interaction

Spt6 is a histone chaperone that associates with RNA polymerase II and deposits nucleosomes in the wake of transcription. Although Spt6 has an essential function in nucleosome deposition, it is not known whether this function is influenced by post-translational modification. Here, we report that casein kinase II (CKII) phosphorylation of Spt6 is required for nucleosome occupancy at the 5' ends of genes to prevent aberrant antisense transcription and enforce transcriptional directionality. Mechanistically, we show that CKII phosphorylation of Spt6 promotes the interaction of Spt6 with Spn1, a binding partner required for chromatin reassembly and full recruitment of Spt6 to genes. Our study defines a function for CKII phosphorylation in transcription and highlights the importance of post-translational modification in histone chaperone function

Protocol for a multi-centre, parallel-arm, 12-month, randomised controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN)

INTRODUCTION: Femoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome. METHODS: We will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02). ETHICS AND DISSEMINATION: Ethical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, including Health Technology Assessment, and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN64081839; Pre-results

Comparison of embedded and added motor imagery training in patients after stroke: Results of a randomised controlled pilot trial

Copyright @ 2012 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Motor imagery (MI) when combined with physiotherapy can offer functional benefits after stroke. Two MI integration strategies exist: added and embedded MI. Both approaches were compared when learning a complex motor task (MT): ‘Going down, laying on the floor, and getting up again’. Methods: Outpatients after first stroke participated in a single-blinded, randomised controlled trial with MI embedded into physiotherapy (EG1), MI added to physiotherapy (EG2), and a control group (CG). All groups participated in six physiotherapy sessions. Primary study outcome was time (sec) to perform the motor task at pre and post-intervention. Secondary outcomes: level of help needed, stages of MT-completion, independence, balance, fear of falling (FOF), MI ability. Data were collected four times: twice during one week baseline phase (BL, T0), following the two week intervention (T1), after a two week follow-up (FU). Analysis of variance was performed. Results: Thirty nine outpatients were included (12 females, age: 63.4 ± 10 years; time since stroke: 3.5 ± 2 years; 29 with an ischemic event). All were able to complete the motor task using the standardised 7-step procedure and reduced FOF at T0, T1, and FU. Times to perform the MT at baseline were 44.2 ± 22s, 64.6 ± 50s, and 118.3 ± 93s for EG1 (N = 13), EG2 (N = 12), and CG (N = 14). All groups showed significant improvement in time to complete the MT (p < 0.001) and degree of help needed to perform the task: minimal assistance to supervision (CG) and independent performance (EG1+2). No between group differences were found. Only EG1 demonstrated changes in MI ability over time with the visual indicator increasing from T0 to T1 and decreasing from T1 to FU. The kinaesthetic indicator increased from T1 to FU. Patients indicated to value the MI training and continued using MI for other difficult-to-perform tasks. Conclusions: Embedded or added MI training combined with physiotherapy seem to be feasible and benefi-cial to learn the MT with emphasis on getting up independently. Based on their baseline level CG had the highest potential to improve outcomes. A patient study with 35 patients per group could give a conclusive answer of a superior MI integration strategy.The research project was partially funded by the Gottfried und Julia Bangerter-Rhyner Foundation

Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies

The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PD-L1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment. Targeting the prominent myeloid compartment within the tumor microenvironment, and in particular the ever-abundant tumor-associated macrophages (TAMs), may be a promising strategy to complement existing therapies and enhance treatment success. TAMs are a highly diverse and plastic subset of cells whose pro-tumor properties can support melanoma growth, angiogenesis and invasion. Understanding of their diversity, plasticity and multifaceted roles in cancer forms the basis for new promising TAM-centered treatment strategies. There are multiple mechanisms by which macrophages can be targeted with antibodies in a therapeutic setting, including by depletion, inhibition of specific pro-tumor properties, differential polarization to pro-inflammatory states and enhancement of antitumor immune functions. Here, we discuss TAMs in melanoma, their interactions with checkpoint inhibitor antibodies and emerging mAbs targeting different aspects of TAM biology and their potential to be translated to the clinic

Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes

Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.</p

Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study

INTRODUCTION: Given the emerging evidence that osteoarthritis (OA) may have a vascular basis, the aim of this study was to determine whether serum lipids were associated with change in knee cartilage, presence of bone marrow lesions (BMLs) at baseline and the development of new BMLs over a 2-year period in a population of pain-free women in mid-life. METHODS: One hundred forty-eight women 40 to 67 years old underwent magnetic resonance imaging (MRI) of their dominant knee at baseline and 2.2 (standard deviation 0.12) years later. Cartilage volume and BMLs were determined for both time points. Serum lipids were measured from a single-morning fasting blood test approximately 1.5 years prior to the MRI. RESULTS: The incidence of BML at follow-up was associated with higher levels of total cholesterol (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.01, 3.36; P = 0.048) and triglycerides (OR 8.4, 95% CI 1.63, 43.43; P = 0.01), but not high-density lipoprotein (HDL) (P = 0.93), low-density lipoprotein (LDL) (P = 0.20) or total cholesterol/HDL ratio (P = 0.17). No association between total cholesterol, triglycerides, HDL, LDL or total cholesterol/HDL ratio and presence of BMLs at baseline or annual change in total tibial cartilage volume was observed. CONCLUSIONS: In this study of asymptomatic middle-aged women with no clinical knee OA, serum cholesterol and triglyceride levels were associated with the incidence of BMLs over 2 years. This provides support for the hypothesis that vascular pathology may have a role in the pathogenesis of knee OA. Further work is warranted to clarify this and whether treatments aimed at reducing serum lipids may have a role in reducing the burden of knee OA

The Impact of Occupational Therapy on the Self‐Management of Rheumatoid Arthritis: A Mixed Methods Systematic Review

Objective: To determine the impact of occupational therapy (OT) on the self‐management of function, pain, fatigue, and lived experience for people living with rheumatoid arthritis (RA). Methods: Five databases and gray literature were searched up to June 30, 2022. Three reviewers screened titles and abstracts, with two independently extracting and assessing full texts using the Cochrane risk of bias (quantitative) and Critical Appraisal Skills Programme (qualitative) tools to assess study quality. Studies were categorized into four intervention types. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (quantitative) and GRADE‐ Confidence in Evidence from Reviews of Qualitative research (qualitative) were used to assess the quality of evidence for each intervention type. Results: Of 39 eligible papers, 29 were quantitative (n = 2,029), 4 qualitative (n = 50), and 6 mixed methods (n = 896). Good evidence supports patient education and behavior change programs for improving pain and function, particularly group sessions of joint protection education, but these do not translate to long‐term improvements for RA (>24 months). Comprehensive OT had mixed evidence (limited to home OT and an arthritis gloves program), whereas limited evidence was available for qualitative insights, splints and assistive devices, and self‐management for fatigue. Conclusion: Although patient education is promising for self‐managing RA, no strong evidence was found to support OT programs for self‐managing fatigue or patient experience and long‐term effectiveness. More research is required on lived experience, and the long‐term efficacy of self‐management approaches incorporating OT, particularly timing programs to meet the individual's conditional needs (i.e., early or established RA) to build on the few studies to date

Public and professional involvement in a systematic review investigating the impact of occupational therapy on the self-management of rheumatoid arthritis

Introduction: Public and health professional involvement (PHPI) is essential in healthcare research yet uncommonly integrated into systematic reviews. We incorporated and evaluated PHPI in a mixed methods review of occupational therapy for self-management of rheumatoid arthritis (RA). Methods: Public partners were living with or caring for someone with RA. Our steering group comprised two public, two professionals (one occupational therapist, one rheumatologist), and one reviewer who planned the review’s PHPI (August 2021). Involvement was evaluated from public and health professional (PHP) perspectives using a survey and workshops (August–October 2022) exploring reasons for involvement, challenges and learning opportunities. Results: Alongside the steering group, 16 public and 6 professionals were involved throughout the review. Five public refined the search strategy, with three assisting in subsequent review activities. PHPs helped interpret findings during three public ( n = 12) and one professional workshop ( n = 4). Three occupational therapists and one public co-authored (ED) publications. In evaluation, PHPs felt valued and that their involvement was well-integrated. The researchers underestimated the time required for communicating and conducting PHPI in the review. Conclusions: PHPI is worthwhile, feasible and can be integrated within a systematic review. PHP partners considered participation valuable; researchers must prioritise time to prepare and communicate PHPI activities

Cross-site comparison of ribosomal depletion kits for Illumina RNAseq library construction

Background Ribosomal RNA (rRNA) comprises at least 90% of total RNA extracted from mammalian tissue or cell line samples. Informative transcriptional profiling using massively parallel sequencing technologies requires either enrichment of mature poly-adenylated transcripts or targeted depletion of the rRNA fraction. The latter method is of particular interest because it is compatible with degraded samples such as those extracted from FFPE and also captures transcripts that are not poly-adenylated such as some non-coding RNAs. Here we provide a cross-site study that evaluates the performance of ribosomal RNA removal kits from Illumina, Takara/Clontech, Kapa Biosystems, Lexogen, New England Biolabs and Qiagen on intact and degraded RNA samples. Results We find that all of the kits are capable of performing significant ribosomal depletion, though there are differences in their ease of use. All kits were able to remove ribosomal RNA to below 20% with intact RNA and identify ~ 14,000 protein coding genes from the Universal Human Reference RNA sample at >1FPKM. Analysis of differentially detected genes between kits suggests that transcript length may be a key factor in library production efficiency. Conclusions These results provide a roadmap for labs on the strengths of each of these methods and how best to utilize them. Keywords: RNAseqr; RNA depletion; Illumina; NGS; ABRF; TranscriptomicsNational Cancer Institute (U.S.) (Grant P30-CA14051)National Institute of Environmental Health Sciences (Grant P30-ES002109