Multi-omic analyses in immune cell development with lessons learned from T cell development

Traditionally, flow cytometry has been the preferred method to characterize immune cells at the single-cell level. Flow cytometry is used in immunology mostly to measure the expression of identifying markers on the cell surface, but—with good antibodies—can also be used to assess the expression of intracellular proteins. The advent of single-cell RNA-sequencing has paved the road to study immune development at an unprecedented resolution. Single-cell RNA-sequencing studies have not only allowed us to efficiently chart the make-up of heterogeneous tissues, including their most rare cell populations, it also increasingly contributes to our understanding how different omics modalities interplay at a single cell resolution. Particularly for investigating the immune system, this means that these single-cell techniques can be integrated to combine and correlate RNA and protein data at the single-cell level. While RNA data usually reveals a large heterogeneity of a given population identified solely by a combination of surface protein markers, the integration of different omics modalities at a single cell resolution is expected to greatly contribute to our understanding of the immune system

Clinimetric evaluation of methods to measure muscle functioning in patients with non-specific neck pain: a systematic review

Contains fulltext : 69123.pdf (publisher's version ) (Open Access)BACKGROUND: Neck pain is a significant health problem in modern society. There is evidence to suggest that neck muscle strength is reduced in patients with neck pain. This article provides a critical analysis of the research literature on the clinimetric properties of tests to measure neck muscle strength or endurance in patients with non-specific neck pain, which can be used in daily practice. METHODS: A computerised literature search was performed in the Medline, CINAHL and Embase databases from 1980 to January 2007. Two reviewers independently assessed the clinimetric properties of identified measurement methods, using a checklist of generally accepted criteria for reproducibility (inter- and intra-observer reliability and agreement), construct validity, responsiveness and feasibility. RESULTS: The search identified a total of 16 studies. The instruments or tests included were: muscle endurance tests for short neck flexors, craniocervical flexion test with an inflatable pressure biofeedback unit, manual muscle testing of neck musculature, dynamometry and functional lifting tests (the cervical progressive iso-inertial lifting evaluation (PILE) test and the timed weighted overhead test). All the articles included report information on the reproducibility of the tests. Acceptable intra- and inter-observer reliability was demonstrated for t enduranctest for short neck flexors and the cervical PILE test. Construct validity and responsiveness have hardly been documented for tests on muscle functioning. CONCLUSION: The endurance test of the short neck flexors and the cervical PILE test can be regarded as appropriate instruments for measuring different aspects of neck muscle function in patients with non-specific neck pain. Common methodological flaws in the studies were their small sample size and an inappropriate description of the study design

Dutch guidelines for physiotherapy in patients with stress urinary incontinence: An update

Introduction and hypothesis: Stress urinary incontinence (SUI) is the most common form of incontinence impacting on quality of life (QOL) and is associated with high financial, social, and emotional costs. The purpose of this study was to provide an update existing Dutch evidence-based clinical practice guidelines (CPGs) for physiotherapy management of patients with stress urinary incontinence (SUI) in order to support physiotherapists in decision making and improving efficacy and uniformity of care. Materials and methods: A computerized literature search of relevant databases was performed to search for information regarding etiology, prognosis, and physiotherapy assessment and management in patients with SUI. Where no evidence was available, recommendations were based on consensus. Clinical application of CPGs and feasibility were reviewed. The diagnostic process consists of systematic history taking and physical examination supported by reliable and valid assessment tools to determine physiological potential for recovery. Therapy is related to different problemcategories. SUI treatment is generally based on pelvic floor muscle exercises combined with patient education and counseling. An important strategy is to reduce prevalent SUI by reducing influencing risk factors. Results: Scientific evidence supporting assessment and management of SUI is strong. Conclusions: The CPGs reflect the current state of knowledge of effective and tailor-made intervention in SUI patients

Plant Stress-Tolerance Traits Predict Salt Marsh Vegetation Patterning

It is increasingly acknowledged that stressors can resonate across the boundaries between ecosystems. Salt marshes, vast areas shaped by ocean-shore interactions, constitute prime examples of ecosystems where multiple stress factors arising from one ecosystem act on the local community of another ecosystem. Although it is generally recognized that zonation of plant communities on salt marshes is strongly affected by marine stress factors associated with frequent flooding (salinity, anoxia), it is largely unknown what the isolated and interacting effect are of these different stressors. This calls for experiments to disentangle the relative effects of these single and interacting multiple stressors. In this study, we determined the single and interacting effects of two main abiotic stress factors on salt marshes: salinity and anoxia (as a result of flooding) and one biotic stress factor: soil compaction (as a result of livestock grazing) on the growth of the twelve dominant salt marsh plant species, using a full-factorial experiment. To link the experimental work to distributions of natural plant communities along a natural stress gradient, we related our experimental results to observed plant species distributions on a salt marsh that is exposed to all these three stressors. Salinity strongly affected ten species with two high-marsh species not surviving the highest salinity levels whereas anoxia only consistently affected growth of four species. Interestingly, we observed no synergistic effect of anoxia and salinity in salt marsh plants. Moreover, we observed a trade-off between the amount of aerenchyma and mechanical strength, indicating that species vary in their resistance to soil compaction. Overall, our results suggest that salinity is a major determinant of plant species composition on the salt marsh, followed by anoxia. The importance of soil compaction depends on salt marsh elevation: on the low marsh, increased oxygen supply by aerenchyma seems to outweigh resistance against mechanical stress whereas on the anaerobe low marsh, the reverse applies. Using the experimental data to predict cover of plant species in the field, our results suggest that the combination of plant responses to the various stressors may be a powerful predictor for explaining the plant composition on the salt marsh

Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multilineage development in the human thymus

T cell development in the mouse thymus has been studied extensively, but less is known regarding T cell development in the human thymus. We used a combination of single-cell techniques and functional assays to perform deep immune profiling of human T cell development, focusing on the initial stages of prelineage commitment. We identified three thymus-seeding progenitor populations that also have counterparts in the bone marrow. In addition, we found that the human thymus physiologically supports the development of monocytes, dendritic cells, and NK cells, as well as limited development of B cells. These results are an important step toward monitoring and guiding regenerative therapies in patients after hematopoietic stem cell transplantation

Subacute and chronic, non-specific back and neck pain: cognitive-behavioural rehabilitation versus primary care. A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>In the industrial world, non-specific back and neck pain (BNP) is the largest diagnostic group underlying sick-listing. For patients with subacute and chronic (= full-time sick-listed for 43 – 84 and 85 – 730 days, respectively) BNP, cognitive-behavioural rehabilitation was compared with primary care. The specific aim was to answer the question: within an 18-month follow-up, will the outcomes differ in respect of sick-listing and number of health-care visits?</p> <p>Methods</p> <p>After stratification by age (≤ 44/≥ 45 years) and subacute/chronic BNP, 125 Swedish primary-care patients were randomly allocated to cognitive-behavioural rehabilitation (rehabilitation group) or continued primary care (primary-care group). Outcome measures were <it>Return-to-work share </it>(percentage) and <it>Return-to-work chance </it>(hazard ratios) over 18 months, <it>Net days </it>(crude sick-listing days × degree), and the number of <it>Visits </it>(to physicians, physiotherapists etc.) over 18 months and the three component six-month periods. Descriptive statistics, Cox regression and mixed-linear models were used.</p> <p>Results</p> <p>All patients: <it>Return-to-work share </it>and <it>Return-to-work chance </it>were equivalent between the groups. <it>Net days </it>and <it>Visits </it>were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods (<it>p </it>< .05). Subacute patients: <it>Return-to-work share </it>was equivalent. <it>Return-to-work chance </it>was significantly greater for the rehabilitation group (hazard ratio 3.5 [95%CI1.001 – 12.2]). <it>Net days </it>were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods and there were 31 days fewer in the third period. <it>Visits </it>showed similar though non-significant differences and there were half as many in the third period. Chronic patients: <it>Return-to-work share, Return-to-work chance </it>and <it>Net days </it>were equivalent. <it>Visits </it>were equivalent over 18 months but tended to decrease more rapidly for the rehabilitation group and there were half as many in the third period (non-significant).</p> <p>Conclusion</p> <p>The results were equivalent over 18 months. However, there were indications that cognitive-behavioural rehabilitation in the longer run might be superior to primary care. For subacute BNP, it might be superior in terms of sick-listing and health-care visits; for chronic BNP, in terms of health-care visits only. More conclusive results concerning this possible long-term effect might require a longer follow-up.</p> <p>Trial registration</p> <p>NCT00488735.</p

Factorial validity and internal consistency of the PRAFAB questionnaire in women with stress urinary incontinence

<p>Abstract</p> <p>Background</p> <p>To investigate the factor structure, dimensionality and construct validity of the (5-item) PRAFAB questionnaire score in women with stress urinary incontinence (stress UI).</p> <p>Methods</p> <p>A cross validation study design was used in a cohort of 279 patients who were randomly divided into Sample A or B. Sample A was used for preliminary exploratory factor analyses with promax rotation. Sample B provided an independent sample for confirming the premeditated and proposed factor structure and item retention. Internal consistency, item-total and subscale correlations were determined to assess the dimensionality. Construct validity was assessed by comparing factor-based scale means by clinical characteristics based on known relationships.</p> <p>Results</p> <p>Factor analyses resulted in a two-factor structure or subscales: items related to 'leakage severity' (protection, amount and frequency) and items related to its 'perceived symptom impact' or consequences of stress UI on the patient's life (adjustment and body (or self) image). The patterns of the factor loadings were fairly identical for both study samples. The two constructed subscales demonstrated adequate internal consistency with Cronbach's alphas in a range of 0.78 and 0.84 respectively. Scale scores differed by clinical characteristics according to the expectations and supported the construct validity of the scales.</p> <p>Conclusion</p> <p>The findings suggest a two-factorial structure of the PRAFAB questionnaire. Furthermore the results confirmed the internal consistency and construct validity as demonstrated in our previous study. The best description of the factorial structure of the PRAFAB questionnaire was given by a two-factor solution, measuring the stress UI leakage severity items and the perceived symptom impact items. Future research will be necessary to replicate these findings in different settings, type of UI and non-white women and men.</p

Predictors of stable return-to-work in non-acute, non-specific spinal pain: low total prior sick-listing, high self prediction and young age. A two-year prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Non-specific spinal pain (NSP), comprising back and/or neck pain, is one of the leading disorders in long-term sick-listing. During 2000-2004, 125 Swedish primary-care patients with non-acute NSP, full-time sick-listed 6 weeks-2 years, were included in a randomized controlled trial to compare a cognitive-behavioural programme with traditional primary care. This prospective cohort study is a re-assessment of the data from the randomized trial with the 2 treatment groups considered as a single cohort. The aim was to investigate which baseline variables predict a stable return-to-work during a 2-year period after baseline: objective variables from function tests, socioeconomic, subjective and/or treatment variables. Stable return-to-work was a return-to-work lasting for at least 1 month from the start of follow-up.</p> <p>Methods</p> <p><it>Stable return-to-work </it>was the outcome variable, the above-mentioned factors were the predictive variables in multiple-logistic regression models, one per follow-up at 6, 12, 18 and 24 months after baseline. The factors from univariate analyzes with a <it>p</it>-value of at most .10 were included. The non-significant variables were excluded stepwise to yield models comprising only significant factors (<it>p </it>< .05). As the comparatively few cases made it risky to associate certain predictors with certain time-points, we finally considered the predictors which were represented in at least 3 follow-ups. They are presented with odds ratios (OR) and 95% confidence intervals.</p> <p>Results</p> <p>Three variables qualified, all of them represented in 3 follow-ups: <it>Low total prior sick-listing </it>(including all diagnoses) was the strongest predictor in 2 follow-ups, 18 and 24 months, OR 4.8 [1.9-12.3] and 3.8 [1.6-8.7] respectively, <it>High self prediction </it>(the patients' own belief in return-to-work) was the strongest at 12 months, OR 5.2 [1.5-17.5] and <it>Young age </it>(max 44 years) the second strongest at 18 months, OR 3.5 [1.3-9.1].</p> <p>Conclusions</p> <p>In primary-care patients with non-acute NSP, the strong predictors of stable return-to-work were 2 socioeconomic variables, <it>Low total prior sick-listing </it>and <it>Young age</it>, and 1 subjective variable, <it>High self-prediction</it>. Objective variables from function tests and treatment variables were non-predictors. Except for <it>Young age</it>, the predictors have previously been insufficiently studied, and so our study should widen knowledge within clinical practice.</p> <p>Trial registration</p> <p>Trial registration number for the original trial NCT00488735.</p

Role of Wnt canonical pathway in hematological malignancies

Wnt canonical signaling pathway plays a diverse role in embryonic development and maintenance of organs and tissues in adults. It has been observed that Wnt/β-catenin signaling pathway is involved in the pathogenesis of many carcinomas. Moreover, Wnt/β-catenin pathway has been revealed to be associated with angiogenesis. Wnt canonical pathway signaling has great potential as a therapeutic target. It has been disclosed that some hematological malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, may occur partly due to the constitutive activation of Wnt canonical signaling pathway. This review will summarize the latest development in Wnt canonical signaling pathway and its roles in tumorigenesis and angiogenesis

Prognostic factors for perceived recovery or functional improvement in non-specific low back pain: secondary analyses of three randomized clinical trials

The objective of this study was to report on secondary analyses of a merged trial dataset aimed at exploring the potential importance of patient factors associated with clinically relevant improvements in non-acute, non-specific low back pain (LBP). From 273 predominantly male army workers (mean age 39 ± 10.5 years, range 20–56 years, 4 women) with LBP who were recruited in three randomized clinical trials, baseline individual patient factors, pain-related factors, work-related psychosocial factors, and psychological factors were evaluated as potential prognostic variables in a short-term (post-treatment) and a long-term logistic regression model (6 months after treatment). We found one dominant prognostic factor for improvement directly after treatment as well as 6 months later: baseline functional disability, expressed in Roland–Morris Disability Questionnaire scores. Baseline fear of movement, expressed in Tampa Scale for Kinesiophobia scores, had also significant prognostic value for long-term improvement. Less strongly associated with the outcome, but also included in our final models, were supervisor social support and duration of complaints (short-term model), and co-worker social support and pain radiation (long-term model). Information about initial levels of functional disability and fear-avoidance behaviour can be of value in the treatment of patient populations with characteristics comparable to the current army study population (e.g., predominantly male, physically active, working, moderate but chronic back problems). Individuals at risk for poor long-term LBP recovery, i.e., individuals with high initial level of disability and prominent fear-avoidance behaviour, can be distinguished that may need additional cognitive-behavioural treatment