The role of CD44 in the pathophysiology of chronic lymphocytic leukemia

CD44 interactions with hyaluronan (HA) play a key role in various malignancies, supporting tumor cell migration, adhesion, and survival. In contrast to solid tumors, the expression of CD44 standard and variant forms and their functional interplay with HA is less understood in hematological malignancies. Chronic lymphocytic leukemia (CLL) is a highly abundant Bcell malignancy with a well coordinated balance between cell cycle-arrest and proliferation of tumor subpopulations.The long-term survival and proliferation of CLL cells requires their dynamic interactions with stromal and immune cells in lymphoid organs. Interactions of HA with CD44 and HA-mediated motility receptor (RHAMM) contribute to CLL cell localization, and hence CLL pathophysiology, by shaping homing, interstitial migration, and adhesion of the tumor cells. CD44 can complex with key prognostic factors of CLL, particularly CD38 and CD49d, bridging the gap between prognosis and cellular function. Here, we review the current evidence for the individual and associated contributions of CD44 to CLL pathophysiology, the dynamic functional regulation of CD44 upon CLL cell activation, and possible therapeutic strategies targeting CD44 in CLL

A Novel Non-invasive Method to Detect RELM Beta Transcript in Gut Barrier Related Changes During a Gastrointestinal Nematode Infection

Currently, methods for monitoring changes of gut barrier integrity and the associated immune response via non-invasive means are limited. Therefore, we aimed to develop a novel non-invasive technique to investigate immunological host responses representing gut barrier changes in response to infection. We identified the mucous layer on feces from mice to be mainly composed of exfoliated intestinal epithelial cells. Expression of RELM-β, a gene prominently expressed in intestinal nematode infections, was used as an indicator of intestinal cellular barrier changes to infection. RELM-β was detected as early as 6 days post-infection (dpi) in exfoliated epithelial cells. Interestingly, RELM-β expression also mirrored the quality of the immune response, with higher amounts being detectable in a secondary infection and in high dose nematode infection in laboratory mice. This technique was also applicable to captured worm-infected wild house mice. We have therefore developed a novel non-invasive method reflecting gut barrier changes associated with alterations in cellular responses to a gastrointestinal nematode infection

Changes in plasma membrane fluidity of Bryonia dioica internodes during thigmomorphogenesis

AbstractFluidity changes in plasma membrane (PM) lipid extracts or native membranes isolated from Bryonia dioica internodes after a mechanical stimulation were monitored by steady-state fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene as a probe. The signal was shown to rapidly induce an increase in the bulk lipid fluidity. This event was closely related to a relative enrichment in some phospholipid species (PC, PG and PS) as well as a significant increase in the unsaturation index of total fatty acyl chains. Free sterols and protein content did not appear to be involved into this process. After 48 h, lipids from rubbed internodes became less fluid than PM lipids from control internodes

Drawings or 3D models: Do illustration methods matter when assessing perceived body size and body dissatisfaction?

Research has reported that both men and women experience body dissatisfaction. Among other instruments, a widely used method to assess perceived body size and body dissatisfaction are figure rating scales. Although a variety of illustration methods (e.g., three-dimensional, or 3D, models and line-drawing models) have been used to create these figure rating scales, to date, they have not been directly compared to one another. Thus, in the first study, which includes 511 participants at a mean age of 46 years old (range: 20–70), the present research work aims to assess how the line-drawing and 3D model scales, representing different body illustration methods, relate to each other. Furthermore, the first study assesses the validity of the indication of body dissatisfaction measured using these figure rating scales by comparing them to body checking or scrutinizing behavior and body appreciation levels. The project’s second study examines the two figure rating scales using objectively measured anthropometric data. In total, 239 participants at a mean age of 54 years (range: 18–94) were included. The results show that figure rating scales can be considered tools that measure perceptual body image due to their positive correlations with body checking behavior (for women) and their negative correlations with body appreciation. The 3D model and line-drawing scales show good to excellent inter-scale reliability, and both scales agree equally well with body mass index (BMI) measurements. Thus, the 3D model and line-drawing scales both seem well suited for assessing perceived body size and perceptual body dissatisfaction, suggesting that neither illustration method is superior to the other

Age-dependent rise in IFN-γ competence undermines effective type 2 responses to nematode infection

The efficient induction of type 2 immune responses is central to the control of helminth infections. Previous studies demonstrated that strong Th1 responses driven by intracellular pathogens as well as a bias for type 1 activity in senescent mice impedes the generation of Th2 responses and the control of intestinal nematode infections. Here, we show that the spontaneous differentiation of Th1 cells and their expansion with age restrains type 2 immunity to infection with the small intestinal nematode H. polygyrus much earlier in life than previously anticipated. This includes the more extensive induction of IFN-γ competent, nematode-specific Th2/1 hybrid cells in BALB/c mice older than three months compared to younger animals. In C57BL/6 mice, Th1 cells accumulate more rapidly at steady state, translating to elevated Th2/1 differentiation and poor control of parasite fitness in primary infections experienced at a young age. Blocking of early IFN-γ and IL-12 signals during the first week of nematode infection leads to sharply decreased Th2/1 differentiation and promotes resistance in both mouse lines. Together, these data suggest that IFN-γ competent, type 1 like effector cells spontaneously accumulating in the vertebrate host progressively curtail the effectiveness of anti-nematode type 2 responses with rising host age

A quantitative synthesis study on body mass index and associated factors among adult men and women in Switzerland

Excess weight is caused by multiple factors and has increased sharply in Switzerland since the 1990s. Its consequences represent a major challenge for Switzerland, both in terms of health and the economy. Until now, there has been no cross-dataset overview study on excess weight in adults in Switzerland. Therefore, our aim was to conduct the first synthesis on excess weight in Switzerland. We included all existing nationwide Swiss studies (eight total), which included information on body mass index (BMI). Mixed multinomial logistic regression analyses were performed to assess the associations between different socio-demographic, lifestyle cofactors and the World Health Organization (WHO) categories for BMI. Along with lifestyle factors, socio-demographic factors were among the strongest determinants of BMI. In addition, self-rated health status was significantly lower for underweight, pre-obese and obese men and women than for normal weight persons. The present study is the first to synthesise all nationwide evidence on the importance of several socio-demographic and lifestyle factors as risk factors for excess weight. In particular, the highlighted importance of lifestyle factors for excess weight opens up the opportunity for further public health interventions

A quantitative synthesis study on body mass index and associated factors among adult men and women in Switzerland.

Excess weight is caused by multiple factors and has increased sharply in Switzerland since the 1990s. Its consequences represent a major challenge for Switzerland, both in terms of health and the economy. Until now, there has been no cross-dataset overview study on excess weight in adults in Switzerland. Therefore, our aim was to conduct the first synthesis on excess weight in Switzerland. We included all existing nationwide Swiss studies (eight total), which included information on body mass index (BMI). Mixed multinomial logistic regression analyses were performed to assess the associations between different socio-demographic, lifestyle cofactors and the World Health Organization (WHO) categories for BMI. Along with lifestyle factors, socio-demographic factors were among the strongest determinants of BMI. In addition, self-rated health status was significantly lower for underweight, pre-obese and obese men and women than for normal weight persons. The present study is the first to synthesise all nationwide evidence on the importance of several socio-demographic and lifestyle factors as risk factors for excess weight. In particular, the highlighted importance of lifestyle factors for excess weight opens up the opportunity for further public health interventions

Asthma management programs in managed care organizations

The aim of this work was to investigate how managed care organizations (MCOs) currently approach asthma treatment and management and to determine factors affecting asthma outcomes. A Web-based survey was administered to a national sample of 351 medical directors of MCOs to investigate the asthma management program components in their organizations as well as gaps and barriers in the management of patients with asthma. All 134 (38.2%) responding medical directors reported that their organizations monitor asthma patients. Plans use a variety of asthma management activities, including general member education (90%), member education by mail (87%), self-management education (85%), and provider education (82%). Educational resources (89%) and telephone advice nurse (77%) were the most common self-management strategies offered. Among factors impeding the provision of effective asthma care, noncompliance with asthma treatment, the inappropriate use of medications, and the need for multiple medications were cited by virtually all respondents. Health plans rely on an array of strategies to manage asthma patients. Education encouraging patient self-management is a key component of asthma management programs. However, a considerable number of treatment approach barriers are impeding the achievement of proper asthma care. Without innovative approaches to care, it appears that current MCOs’ asthma management efforts may not result in substantial improvements in asthma outcomes

A minimal model of peptide binding predicts ensemble properties of serum antibodies

<p/> <p>Background</p> <p>The importance of peptide microarrays as a tool for serological diagnostics has strongly increased over the last decade. However, interpretation of the binding signals is still hampered by our limited understanding of the technology. This is in particular true for arrays probed with antibody mixtures of unknown complexity, such as sera. To gain insight into how signals depend on peptide amino acid sequences, we probed random-sequence peptide microarrays with sera of healthy and infected mice. We analyzed the resulting antibody binding profiles with regression methods and formulated a minimal model to explain our findings.</p> <p>Results</p> <p>Multivariate regression analysis relating peptide sequence to measured signals led to the definition of amino acid-associated weights. Although these weights do not contain information on amino acid position, they predict up to 40-50% of the binding profiles' variation. Mathematical modeling shows that this position-independent ansatz is only adequate for highly diverse random antibody mixtures which are not dominated by a few antibodies. Experimental results suggest that sera from healthy individuals correspond to that case, in contrast to sera of infected ones.</p> <p>Conclusions</p> <p>Our results indicate that position-independent amino acid-associated weights predict linear epitope binding of antibody mixtures only if the mixture is random, highly diverse, and contains no dominant antibodies. The discovered ensemble property is an important step towards an understanding of peptide-array serum-antibody binding profiles. It has implications for both serological diagnostics and B cell epitope mapping.</p