Exploitation of Other Social Amoebae by Dictyostelium caveatum

Dictyostelium amoebae faced with starvation trigger a developmental program during which many cells aggregate and form fruiting bodies that consist of a ball of spores held aloft by a thin stalk. This developmental strategy is open to several forms of exploitation, including the remarkable case of Dictyostelium caveatum, which, even when it constitutes 1/10(3) of the cells in an aggregate, can inhibit the development of the host and eventually devour it. We show that it accomplishes this feat by inhibiting a region of cells, called the tip, which organizes the development of the aggregate into a fruiting body. We use live-cell microscopy to define the D. caveatum developmental cycle and to show that D. caveatum amoebae have the capacity to ingest amoebae of other Dictyostelid species, but do not attack each other. The block in development induced by D. caveatum does not affect the expression of specific markers of prespore cell or prestalk cell differentiation, but does stop the coordinated cell movement leading to tip formation. The inhibition mechanism involves the constitutive secretion of a small molecule by D. caveatum and is reversible. Four Dictyostelid species were inhibited in their development, while D. caveatum is not inhibited by its own compound(s). D. caveatum has evolved a predation strategy to exploit other members of its genus, including mechanisms of developmental inhibition and specific phagocytosis

The role of the exit in the initial screening of investment opportunities: The case of business angel syndicate gatekeepers

The exit process has been largely ignored in business angel research.. The practitioner community identifies the difficulty in achieving exits as the most pressing problem for investors. This has been attributed to the failure of investors to adopt an exit-centric approach to investing. The validity of this claim is examined via a study of the investment approach of 21 ‘gatekeepers’ (managers) of angel groups in Scotland and Northern Ireland. Most gatekeepers say that they do consider the exit when they invest. However, this is contradicted by a verbal protocol analysis which indicates that the exit is not a significant consideration in their initial screening process. The small number of exits achieved by the groups is consistent with the general lack of an exit-centric approach to investing. Only three groups exhibit evidence of a strong exit-centric approach to investing. The lack of exits may have a negative impact on the level of future angel investment activity

Home-based Circuit Training and Community Walking for Intermittent Claudication

Background: Supervised exercise training is recommended for people with peripheral artery disease (PAD), yet it remains underutilized. Home-based exercise programs (HBEPs) are a potential alternative. The aim of this study was to assess the feasibility of conducting a full scale trial of a 12-week HBEP for people living with symptomatic PAD. Methods: In a randomized feasibility trial, patients with intermittent claudication were allocated to either an HBEP or a nonexercise control. The HBEP group was given a Fitbit to use during a 12-week exercise program comprising of personalized step goals and a resistance-based circuit to be undertaken at home twice weekly. The primary outcome was feasibility, assessed via eligibility, recruitment, attrition, tolerability, and adherence. Acceptability was assessed via semistructured interviews. Secondary analysis was undertaken to determine the feasibility of collecting clinical outcome data. Results: 188 people were screened, 133 were eligible (70.7%), 30 were recruited (22.6%) and one withdrew (3.33%). Mean adherence to the daily step goal was 53.5% (range ¼ 29.8e 90.5%), and 58.6% of prescribed circuits were completed of which 56.4% were at the desired intensity. Six adverse events were recorded, 3 of which were related to study involvement. No significant differences were observed in exploratory outcomes. Small clinically important differences were seen in walking speed and pain-free treadmill walking distance which should be confirmed or refuted in a larger trial. Conclusions: The HBEP was feasible and well tolerated, with successful recruitment and minimal attrition. The intervention was acceptable, with walking seen as more enjoyable than circuit exercise. The WALKSTRONG program may be suitable for those who will not, or cannot, take part in supervised exercise outside of the home

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Review for the generalist: evaluation of low back pain in children and adolescents

Back pain is common in children and adolescents. Most cases of back pain are non-specific and self-limiting. In children and adolescents, pain is usually related to the posterior elements of the spine and disc-related problems are rare. Serious pathology, including malignancy and infection needs to be excluded. Evaluation and management is challenging and requires a thorough history and physical exam, and understanding of the immature skeleton. Diagnostic imaging is useful in the evaluation of a child or adolescent with low back pain and can help guide management. This article will review common causes of back pain in the pediatric population

The establishment of a primary spine care practitioner and its benefits to health care reform in the United States

It is widely recognized that the dramatic increase in health care costs in the United States has not led to a corresponding improvement in the health care experience of patients or the clinical outcomes of medical care. In no area of medicine is this more true than in the area of spine related disorders (SRDs). Costs of medical care for SRDs have skyrocketed in recent years. Despite this, there is no evidence of improvement in the quality of this care. In fact, disability related to SRDs is on the rise. We argue that one of the key solutions to this is for the health care system to have a group of practitioners who are trained to function as primary care practitioners for the spine. We explain the reasons we think a primary spine care practitioner would be beneficial to patients, the health care system and society, some of the obstacles that will need to be overcome in establishing a primary spine care specialty and the ways in which these obstacles can be overcome.https://doi.org/10.1186/2045-709X-19-1

Application of a diagnosis-based clinical decision guide in patients with neck pain

<p>Abstract</p> <p>Background</p> <p>Neck pain (NP) is a common cause of disability. Accurate and efficacious methods of diagnosis and treatment have been elusive. A diagnosis-based clinical decision guide (DBCDG; previously referred to as a diagnosis-based clinical decision rule) has been proposed which attempts to provide the clinician with a systematic, evidence-based guide in applying the biopsychosocial model of care. The approach is based on three questions of diagnosis. The purpose of this study is to present the prevalence of findings using the DBCDG in consecutive patients with NP.</p> <p>Methods</p> <p>Demographic, diagnostic and baseline outcome measure data were gathered on a cohort of NP patients examined by one of three examiners trained in the application of the DBCDG.</p> <p>Results</p> <p>Data were gathered on 95 patients. Signs of visceral disease or potentially serious illness were found in 1%. Centralization signs were found in 27%, segmental pain provocation signs were found in 69% and radicular signs were found in 19%. Clinically relevant myofascial signs were found in 22%. Dynamic instability was found in 40%, oculomotor dysfunction in 11.6%, fear beliefs in 31.6%, central pain hypersensitivity in 4%, passive coping in 5% and depression in 2%.</p> <p>Conclusion</p> <p>The DBCDG can be applied in a busy private practice environment. Further studies are needed to investigate clinically relevant means to identify central pain hypersensitivity, oculomotor dysfunction, poor coping and depression, correlations and patterns among the diagnostic components of the DBCDG as well as inter-examiner reliability, validity and efficacy of treatment based on the DBCDG.</p

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Entamoeba Shows Reversible Variation in Ploidy under Different Growth Conditions and between Life Cycle Phases

Under axenic growth conditions, trophozoites of Entamoeba histolytica contain heterogenous amounts of DNA due to the presence of both multiple nuclei and different amounts of DNA in individual nuclei. In order to establish if the DNA content and the observed heterogeneity is maintained during different growth conditions, we have compared E. histolytica cells growing in xenic and axenic cultures. Our results show that the nuclear DNA content of E. histolytica trophozoites growing in axenic cultures is at least 10 fold higher than in xenic cultures. Re-association of axenic cultures with their bacterial flora led to a reduction of DNA content to the original xenic values. Thus switching between xenic and axenic growth conditions was accompanied by significant changes in the nuclear DNA content of this parasite. Changes in DNA content during encystation-excystation were studied in the related reptilian parasite E. invadens. During excystation of E. invadens cysts, it was observed that the nuclear DNA content increased approximately 40 fold following emergence of trophozoites in axenic cultures. Based on the observed large changes in nuclear size and DNA content, and the minor differences in relative abundance of representative protein coding sequences, rDNA and tRNA sequences, it appears that gain or loss of whole genome copies may be occurring during changes in the growth conditions. Our studies demonstrate the inherent plasticity and dynamic nature of the Entamoeba genome in at least two species

Movement control tests of the low back; evaluation of the difference between patients with low back pain and healthy controls

<p>Abstract</p> <p>Background</p> <p>To determine whether there is a difference between patients with low back pain and healthy controls in a test battery score for movement control of the lumbar spine.</p> <p>Methods</p> <p>This was a case control study, carried out in five outpatient physiotherapy practices in the German-speaking part of Switzerland. Twelve physiotherapists tested the ability of 210 subjects (108 patients with non-specific low back pain and 102 control subjects without back pain) to control their movements in the lumbar spine using a set of six tests. We observed the number of positive tests out of six (mean, standard deviation and 95% confidence interval of the mean). The significance of the differences between the groups was calculated with Mann-Whitney U test and <it>p </it>was set on <0.05. The effect size (d) between the groups was calculated and d>0.8 was considered a large difference.</p> <p>Results</p> <p>On average, patients with low back pain had 2.21(95%CI 1.94–2.48) positive tests and the healthy controls 0.75 (95%CI 0.55–0.95). The effect size was d = 1.18 (p < 0.001). There was a significant difference between acute and chronic (p < 0.01), as well as between subacute and chronic patient groups (p < 0.03), but not between acute and subacute patient groups (p > 0.7).</p> <p>Conclusion</p> <p>This is the first study demonstrating a significant difference between patients with low back pain and subjects without back pain regarding their ability to actively control the movements of the low back. The effect size between patients with low back pain and healthy controls in movement control is large.</p