MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines.

The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional mode of hypoxia-inducible factor (HIF)-dependent transcriptional regulation, involving modulation of a specific set of micro RNAs (miRNAs), including miR-210, has emerged. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. Therefore, we hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed a non-small cell lung carcinoma (NSCLC)-derived cell line (A549) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). The miR-210-expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. Cells were subjected to radiation levels ranging from 0 to 10 Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of radioresistance as control cells in hypoxia. Under hypoxia, pmiR-210 cells showed a low mortality rate owing to a decrease in apoptosis, with an ability to grow even at 10 Gy. This miR-210 phenotype was reproduced in another NSCLC cell line (H1975) and in HeLa cells. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we have shown that genomic double-strand breaks (DSBs) foci disappear faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells removed the radioresistant phenotype, showing that this mechanism is dependent on HIF-1. In conclusion, miR-210 appears to be a component of the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could be used by tumor cells in conditions where reoxygenation has occurred and suggests that strategies targeting miR-210 could enhance tumor radiosensitization.

Toll-like receptor 2 is critical for induction of Reg3 beta expression and intestinal clearance of Yersinia pseudotuberculosis.

OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches that are positioned in the terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting Peyer's patches against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y pseudotuberculosis via the oral or systemic route. The role of microbiota in conditioning Peyer's patches against Yersinia through TLR2 was assessed by delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free and streptomycin-treated animals. Bacterial eradication from Peyer's patches was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3 beta was quantified by quantitative reverse transcriptase polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer's patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3 beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3 beta expression in Peyer's patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial load in Peyer's patches. CONCLUSIONS: TLR2/REG3 beta is thus an essential component in conditioning epithelial defence signalling pathways against bacterial invasion.

Candidate genes for quantitative resistance to Mycosphaerella pinodes in pea (Pisum sativum L.).

Partial resistance to Mycosphaerella pinodes in pea is quantitatively inherited. Genomic regions involved in resistance (QTLs) have been previously identified in the pea genome, but the molecular basis of the resistance is still unknown. The objective of this study was to map resistance gene analogs (RGA) and defense-related (DR) genes in the JI296 x DP RIL population that has been used for mapping QTLs for resistance to M. pinodes, and identify co-localizations between candidate genes and QTLs. Using degenerate oligonucleotide primers designed on the conserved motifs P-loop and GLPL of cloned resistance genes, we isolated and cloned 16 NBS-LRR sequences, corresponding to five distinct classes of RGAs. Specific second-generation primers were designed for each class. RGAs from two classes were located on the linkage group (LG) VII. Another set of PCR-based markers was designed for four RGA sequences previously isolated in pea and 12 previously cloned DR gene sequences available in databases. Out of the 16 sequences studied, the two RGAs RGA-G3A and RGA2.97 were located on LG VII, PsPRP4A was located on LG II, Peachi21, PsMnSOD, DRR230-b and PsDof1 were mapped on LG III and peabetaglu and DRR49a were located on LG VI. Two co-localizations between candidate genes and QTLs for resistance to M. pinodes were observed on LG III, between the putative transcription factor PsDof1 and the QTL mpIII-1 and between the pea defensin DRR230-b gene and the QTL mpIII-4. Another co-localization was observed on LG VII between a cluster of RGAs and the QTL mpVII-1. The three co-localizations appear to be located in chromosomal regions containing other disease resistance or DR genes, suggesting an important role of these genomic regions in defense responses against pathogens in pea.

Measurement properties of a new quality of life measure for patients with work disability associated with musculoskeletal pain.

INTRODUCTION: The Quality of Life Systemic Inventory (QLSI) measures patients' goal attainment based on the system control theory. It quantifies the perceived impact of the disorder and the gap between the present and aspired states. PURPOSE: To evaluate concurrent validity and responsiveness of the QLSI among workers on sick leave due to musculoskeletal disorders (MSDs). METHODS: Participants (10 women; 29 men) were recruited at a work rehabilitation centre and had more than 4 weeks of absence from work due to MSDs compensated by the Workers' Compensation Board. Concurrent validity and external responsiveness were based on baseline and post-treatment measures of external criteria. Criteria and related instruments were the following: perception of disability (Roland-Morris Disability Questionnaire); health-related quality of life (SF-12); stress (Psychological Stress Measure) and distress (Psychological Distress Index). RESULTS: Regression analyses revealed significant correlations between QLSI scores and the Psychological Distress Index (r2 = .11 to .19 and .66; p < .001), with either the SF-12 mental component scale (r2 = .18 and .11; p < .01) or the Roland-Morris Disability Questionnaire (r2 = .04 and .10; p < .05). All measures showed highly significant change over time. CONCLUSION: Results support the concurrent validity and responsiveness of the QLSI, with an MSD population. SIGNIFICANCE: This instrument could serve in future research as an outcome measurement instrument in the evaluation of more long-term effects of rehabilitation programs.

Vasopressin and galanin expression in the hypothalamus of two African rodents, Taterillus gracilis and Steatomys caurinus, subjected to water-restriction.

The expression of arginine-vasopressin (AVP) and galanin (GAL) was studied by immunohistochemistry and in situ hybridization in the hypothalamus of two species of African rodents. In the wild, these animals experience successive arid and wet seasons that alternately stimulate their antidiuretic and diuretic systems. In this study, animals were subjected to both standardized laboratory conditions and to eight days of water-restriction. Under both sets of conditions, AVP and GAL were detected in the supraoptic nucleus (SON), paraventricular nucleus (PVN), and median eminence (ME). AVP and GAL responses to water-restriction differed in the two species, as did behavioral adaptations to the hot-dry season. In Taterillus gracilis, AVP- and GAL-LI (like immunoreactivity) peptide and mRNA levels increased in the SON. AVP-LI peptide and mRNA levels increased in the PVN, whereas only AVP-LI peptide levels increased in the ME. Pituitary gland AVP pools were unchanged by water deprivation, whereas urinary AVP levels and osmolality increased. The AVP response is typical of that of desert rodents, favoring survival under conditions of water-restriction. In Steatomys caurinus, which estivates, AVP and GAL-LI peptide levels decreased in the hypothalamus, as they did in the laboratory rat. In the SON, AVP, and GAL mRNA levels increased, whereas, in the PVN, only AVP mRNA levels increased. Pituitary gland AVP levels decreased, whereas urinary AVP levels and osmolality increased. In both species, the changes in the amount of GAL-LI peptide appeared to be closely linked to changes in AVP levels, suggesting that this peptide is involved in the osmoregulatory response to water-restriction.

Descriptive study to compare patient recall of information: nurse-taught versus video supplement.

An important goal in oncology nursing is to provide outpatients receiving chemotherapy with adequate information about their treatment so they will be able to cope with treatment reactions and make appropriate decisions about seeking early medical attention when potentially serious side-effects occur. The purpose of the present study was to evaluate patient teaching strategies at one cancer centre. A comparative descriptive study design was employed. A group of patients receiving one-to-one nurse/patient teaching was compared to a group of patients receiving one-to-one nurse/patient teaching plus a take-home instructional chemotherapy video. The patient groups were compared with respect to: a) level of recall of chemotherapy information; b) the sources of information used; and c) preferred information sources. When the mean scores achieved on the chemotherapy knowledge questionnaire were compared, no statistically significant differences were found between the two groups. In fact, both groups showed a "high" level of information recall. Both patient groups reported using a variety of information sources to learn about their chemotherapy, however, for both groups the preferred sources of information were their direct health care providers. The results of the study raise interesting issues about the feasibility of developing "high-tech" patient education strategies.

Changes in the electromyographic spectrum power distribution caused by a progressive increase in the force level.

The purpose of the present study was to determine the specific changes occurring in the power spectrum with an increasing force level during isometric contractions. Surface electromyographic signals of the triceps brachii (TB) and the anconeus (AN) of 29 normal subjects were recorded during isometric ramp contractions performed from 0 to 100% of the maximum voluntary contraction (MVC) in a 5-s period. Power spectra were obtained at 10, 20, 30, 40, 50, 60, 70, 80 and 90% MVC. Changes in the shape of these spectra were evaluated visually and with the calculation of several statistical parameters related to the distribution of power along the frequency axis, such as median frequency and mean power frequency, standard deviation, skewness, first and third quartiles and half-power range. For the AN, the behaviour of the spectrum was relatively similar across subjects, presenting a shift toward higher frequencies without any major change in the shape of the spectrum. For the TB, subjects with a thin skinfold thickness presented similar behaviours. In subjects with a thicker skinfold, however, a loss of power in the high frequency region paralleled the increase in the force level. Significant correlations were obtained between the extent of the change in the value of higher order statistical parameters across force and the thickness of the skin. This points out the importance of the skinfold layer when recording with surface electrodes. Furthermore, the use of a combination of several parameters appears to provide a better appreciation of the changes occurring in the spectrum than any single parameter taken alone.

[Social reintegration: a dynamic program to help psychiatric patients acquire functional and interpersonal skills]. / Réinsertion sociale: programme d'action pour permettre aux patients psychiatriques d'acquérir des habiletés fonctionnelles et relationnelles.

Since new mental health policies have been developed, government and community-based organizations appear to be working closer toward facilitating the social reintegration process regarding persons experiencing psychiatric problems. This article describes a project which fosters the development of a patient's functional and interpersonal skills in a para-hospital environment: supervised apartments. The program's objective is to encourage awareness of an individual's situation and especially to allow him or her to acquire and experiment a certain number of skills for the ultimate purpose of reintegrating the community. This project is carried out by the psychiatry department of Notre-Dame Hospital in collaboration with the Maison l'Echelon Inc., a non-profit organization that manages a group of supervised apartments for psychiatric patients.

Predictive model to determine cost/benefit of early detection and intervention in occupational low back pain.

Low back pain related to work injury has major socioeconomic implications. Theoretically, the early detection of patients at risk for continued work disability after 6 months of work absence, and of those with a recurrence of pain (RP) and leave work once again, should be cost-effective if combined with effective intervention. The objective of this prospective research was to analyze the cost-effectiveness of a detection-intervention system (DIS) developed from a logistic predictive model of work status. A sample of newly injured workers (N=135 males) were assessed following a first episode of compensated low back pain. A predictive biopsychosocial profile was obtained from a series of univariate and multivariate regression analyses. Structural diagnosis, pain rating, length of inactivity before treatment, negative life changes, and self-efficacy expectancies were found to be best predictors. With a correct classification rate of 72% the predictive model parameters (sensitivity and specificity) were chosen in order to reduce the number of false negatives (recurrence of pain or chronic patients not detected). The calculation of the cost/benefit proportions reveals that the detection-intervention system generates savings of up to $39,595 Can./100 patients a year. By combining low treatment expenses ($250 Can to $1,000 Can.) and increasing the success rates (40-75% return to work), the detection-intervention system is potentially more cost effective than the current approach without detection-intervention.

A comparison between manual and semiautomatic white cell differentiation.

Manual and semiautomatic white cell differentiations have been found to produce comparable results. Semiautomatic counting can be accomplished with a smaller number of cells than required in manual counting without significant loss of accuracy. Cell types have been compared one by one to detect systematic deviations between the counting procedures. Complete differentials have been compared by means of a multivariate method called canonical correlation. The result of the canonical correlation is displayed graphically. Highly significant correlations have been found between 100-cell manual and 100-, 50-cell semiautomatic differentials.