GWAS and genetic and phenotypic correlations of plasma metabolites with complete blood count traits in healthy young pigs reveal implications for pig immune response.

Introduction: In this study estimated genetic and phenotypic correlations between fifteen complete blood count (CBC) traits and thirty-three heritable plasma metabolites in young healthy nursery pigs. In addition, it provided an opportunity to identify candidate genes associated with variation in metabolite concentration and their potential association with immune response, disease resilience, and production traits. Methods: The blood samples were collected from healthy young pigs and Nuclear Magnetic Resonance (NMR) was used to quantify plasma metabolites. CBC was determined using the ADVIA® 2120i Hematology System. Genetic correlations of metabolite with CBC traits and single step genome-wide association study (ssGWAS) were estimated using the BLUPF90 programs. Results: Results showed low phenotypic correlation estimates between plasma metabolites and CBC traits. The highest phenotypic correlation was observed between lactic acid and plasma basophil concentration (0.36 ± 0.04; p < 0.05). Several significant genetic correlations were found between metabolites and CBC traits. The plasma concentration of proline was genetically positively correlated with hemoglobin concentration (0.94 ± 0.03; p < 0.05) and L-tyrosine was negatively correlated with mean corpuscular hemoglobin (MCH; -0.92 ± 0.74; p < 0.05). The genomic regions identified in this study only explained a small percentage of the genetic variance of metabolites levels that were genetically correlated with CBC, resilience, and production traits. Discussion: The results of this systems approach suggest that several plasma metabolite phenotypes are phenotypically and genetically correlated with CBC traits, suggesting that they may be potential genetic indicators of immune response following disease challenge. Genomic analysis revealed genes and pathways that might interact to modulate CBC, resilience, and production traits.

Heritability and genetic correlations of plasma metabolites of pigs with production, resilience and carcass traits under natural polymicrobial disease challenge.

Metabolites in plasma of healthy nursery pigs were quantified using nuclear magnetic resonance. Heritabilities of metabolite concentration were estimated along with their phenotypic and genetic correlations with performance, resilience, and carcass traits in growing pigs exposed to a natural polymicrobial disease challenge. Variance components were estimated by GBLUP. Heritability estimates were low to moderate (0.11 ± 0.08 to 0.19 ± 0.08) for 14 metabolites, moderate to high (0.22 ± 0.09 to 0.39 ± 0.08) for 17 metabolites, and highest for L-glutamic acid (0.41 ± 0.09) and hypoxanthine (0.42 ± 0.08). Phenotypic correlation estimates of plasma metabolites with performance and carcass traits were generally very low. Significant genetic correlation estimates with performance and carcass traits were found for several measures of growth and feed intake. Interestingly the plasma concentration of oxoglutarate was genetically negatively correlated with treatments received across the challenge nursery and finisher (- 0.49 ± 0.28; P < 0.05) and creatinine was positively correlated with mortality in the challenge nursery (0.85 ± 0.76; P < 0.05). These results suggest that some plasma metabolite phenotypes collected from healthy nursery pigs are moderately heritable and genetic correlations with measures of performance and resilience after disease challenge suggest they may be potential genetic indicators of disease resilience.

Novel Resilience Phenotypes Using Feed Intake Data From a Natural Disease Challenge Model in Wean-to-Finish Pigs.

The objective of this study was to extract novel phenotypes related to disease resilience using daily feed intake data from growing pigs under a multifactorial natural disease challenge that was designed to mimic a commercial environment with high disease pressure to maximize expression of resilience. Data used were the first 1,341 crossbred wean-to-finish pigs from a research facility in Québec, Canada. The natural challenge was established under careful veterinary oversight by seeding the facility with diseased pigs from local health-challenged farms, targeting various viral and bacterial diseases, and maintaining disease pressure by entering batches of 60-75 pigs in a continuous flow system. Feed intake (FI) is sensitive to disease, as pigs tend to eat less when they become ill. Four phenotypes were extracted from the individual daily FI data during finishing as novel measures of resilience. The first two were daily variability in FI or FI duration, quantified by the root mean square error (RMSE) from the within individual regressions of FI or duration at the feeder (DUR) on age (RMSEFI and RMSEDUR). The other two were the proportion of off-feed days, classified based on negative residuals from a 5% quantile regression (QR) of daily feed intake or duration data on age across all pigs (QRFI and QRDUR). Mortality and treatment rate had a heritability of 0.13 (±0.05) and 0.29 (±0.07), respectively. Heritability estimates for RMSEFI, RMSEDUR, QRFI, and QRDUR were 0.21 (±0.07) 0.26 (±0.07), 0.15 (±0.06), and 0.23 (±0.07), respectively. Genetic correlations of RMSE and QR measures with mortality and treatment rate ranged from 0.37 to 0.85, with QR measures having stronger correlations with both. Estimates of genetic correlations of RMSE measures with production traits were typically low, but often favorable (e.g., -0.31 between RMSEFI and finishing ADG). Although disease resilience was our target, fluctuations in FI and duration can be caused by many factors other than disease and should be viewed as overall indicators of general resilience to a variety of stressors. In conclusion, daily variation in FI or duration at the feeder can be used as heritable measures of resilience.

Optimizing urothelial cell preparation for the human urinary micronucleus assay.

Biological monitoring of early genotoxic effects in urothelial cells using the urinary micronucleus (MNu) assay is promising for early detection of cancer, such as bladder carcinoma. But many problems are encountered, the major being the poorly differential staining of cells, particularly in women having an important amount of squamous cells. We have optimized the protocol and obtained a differential staining of the cell types present in urine on 10 subjects. Following Carnoy I fixation and Papanicolaou staining, urothelial cells were blue while most squamous cells were pink. This differential staining allowed for optimization of the MNu assay on a single urine void, for both females and males. Even if our MNu means were comparable to the literature, the great variation in reported MNu results could reside in the ability of scorers to distinguish correctly between urothelial and squamous cells. When monitoring exposed populations, this erroneous distinction could largely influence the results, even more in women's urine samples. Given a situation where exposure would not increase micronuclei frequency in vaginal squamous cells, their erroneous analysis in the MNu assay could mask an early genotoxic effect. Therefore, as transitional cell carcinoma of the bladder originates from transformed urothelial cells, restricting micronuclei analysis to urothelial cells could yield a more precise estimate of cancer risk in exposed populations. Moreover, it is hoped that the improvements proposed in this paper will allow for an easier implementation of the MNu assay in various set-ups and enhance its specificity, since MNu are considered a suitable biomarker.

Frequency of chromosome healing and interstitial telomeres in 40 cases of constitutional abnormalities.

Human telomeres play a major role in stabilizing chromosome ends and preventing fusions. Chromosomes bearing a broken end are rescued by the acquisition of a new telomeric cap without any subtelomeric sequences being present at the breakpoint, a process referred to as chromosome healing. Conversely, a loss of telomeric function or integrity can lead to the presence of interstitial telomeres at the junction site in translocations or ring chromosomes. In order to determine the frequency at which interstitial telomeres or chromosome healing events are observed in target chromosome abnormalities, we conducted a retrospective FISH study using pan-telomeric and chromosome-specific subtelomeric probes on archival material from 40 cases of terminal deletions, translocations or ring chromosomes. Of the 19 terminal deletions investigated, 17 were negative for the subtelomeric probe specific to the deleted arm despite being positive for the pan-telomeric probe. These 17 cases were thus considered as having been rescued through chromosome healing, suggesting that this process is frequent in terminal deletions. In addition, as 2 of these cases were inherited from a parent bearing the same deletion, chromosomes healed by this process are thus stable through mitosis and meiosis. Regarding the 13 cases of translocations and 8 ring chromosomes, 4 and 2 cases respectively demonstrated pan-telomeric sequences at the interstitial junction point. Furthermore, 2 cases of translocations and 1 ring chromosome had both interstitial pan-telomeres and subtelomeres, whereas 2 other cases of ring chromosomes and 1 case of translocation only showed interstitial subtelomeres. Therefore, interstitial (sub)telomeric sequences in translocations and ring chromosomes are more common than previously thought, as we found a frequency of 43% in this study. Moreover, our results illustrate the necessity of performing FISH with both subtelomeric and pan-telomeric probes when investigating these rearrangements, as the breakpoints can be either in the distal part of the pan-telomeres, or in between the 2 types of sequences.

Dynamic increase of a 45,X cell line in a patient with multicentric ring Y chromosomes.

Because ring Y chromosomes are unstable during cell division most reported patients are mosaics, usually including a 45,X cell line. The phenotype varies from normal males or females with streak gonads to sexual ambiguities. We present here the case of a 23-year-old man who was referred at 11 years for growth delay. The GTG-banded karyotypes of lymphocytes revealed two cell lines: 46,X,dic r(Y) seen in 76% of the metaphases analyzed and 45,X (24%). Karyotypes and FISH were performed eight years later with the following probes: DYZ3 (Y centromere), SRY (sex-region of the Y), DYZ1 (Yq heterochromatin), CEPX/Y (X centromere and Yq heterochromatin), TelVysion Xp/Yp, Xq/Yq (X and Y subtelomeres), pan-telomeric, cosmid clones LLycos130G04 and LLycos37C09 (PARII), and BAC clone RP11-5C5 (Yq11.223). The results showed an increase in the 45,X cell line (60%) and a reduction in the 46,X,dic r(Y) cell line (36.4%). The use of Yq probes showed that the ring Y chromosome was dicentric. In addition, other ring Y structures were observed. The breakpoints occurred in proximal Yp11.32 or in Yp11.31 distal to SRY and in Yq12 distal to the PARII region. Therefore, most of the Y remained intact and all genes, with the exception of those in PARI, are present in double dosage in the dic r(Y). The level of mosaicism was important in defining the phenotype.

The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation. OBJECTIVE AND METHODS: To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 mug once daily or placebo for 12 weeks. RESULTS: Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 +/- 0.08 liters) and 84 (0.20 +/- 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 +/- 0.07 liters) and 84 (0.15 +/- 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 +/- 12 (day 42) and 36 +/- 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George's Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living. CONCLUSION: Tiotropium 18 mug once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.

Complex mosaicism in sex reversed SRY+ male twins.

Sex reversal is characterized by discordance between genetic and phenotypic sex. Most XX males result from an unequal interchange between X and Y chromosomes during paternal meiosis, therefore transferring SRY to the X chromosome, which explains the male development in the presence of an otherwise normal female karyotype. We present here the case of sex reversed SRY+ male twins with several cell lines. They consulted for infertility. The presence of SRY on an X chromosome was demonstrated by FISH. Their respective karyotypes were: 46,X,der(X)t(X;Y)(p22.3;p11.2)[249]/45,X [12]/45,der(X)t(X;Y)(p22.3;p11.2)[11]/47,XX,der(X)t(X;Y) (p22.3;p11.2)[1]/47,X,der(X)t(X;Y)(p22.3;p11.2)x2[1]/50, XX,der(X)t(X;Y)(p22.3;p11.2)x4[1]/46,XX[1] for the first twin (SH-1) and 46,X,der(X)t(X;Y)(p22.3;p11.2)[108]/45,X [3]/47,XX,der(X)t(X;Y)(p22.3;p11.2)[2]/45,der(X)t(X;Y) (p22.3;p11.2)[1]/47,X,der(X)t(X;Y)(p22.3;p11.2)x2[1] for the second twin (SH-2). There are three different types of XX males: 1) with normal genitalia, 2) with genital ambiguity, and 3) XX true hermaphrodites. The phenotype of the twins presented in this report is consistent with what is generally seen in XX SRY+ males: they have normal genitalia.

A randomized, controlled trial of vicarious experience through peer support for male first-time cardiac surgery patients: impact on anxiety, self-efficacy expectation, and self-reported activity.

OBJECTIVES: The purpose of this study was to determine whether vicarious experience, in which former patients exemplify the active lives they are leading, reduces anxiety and increases self-efficacy expectation and self-reported activity in patients after cardiac surgery. DESIGN: A randomized, controlled trial was used to evaluate an intervention that linked volunteers who had recovered from cardiac surgery in dyadic support with patients about to undergo similar surgery. The linking was achieved by means of visits during the hospitalization and recovery period. SUBJECTS: Fifty-six first-time male patients undergoing coronary artery bypass graft (CABG) surgery, with a mean age of 56.5 years, were randomly assigned to an experimental (n = 27) or control group (n = 29). OUTCOME MEASURES: Anxiety was measured at 48 hours and 24 hours before surgery, and again at 5 days and 4 weeks after surgery. Self-efficacy expectation and self-reported activity were both evaluated at 5 days and 4 weeks after surgery. RESULTS: Only the experimental group showed a significant decrease in anxiety during hospitalization. At all measurement times after the first intervention, the experimental group reported significantly lower levels of anxiety compared with the control group. The experimental group reported significantly higher levels of self-efficacy expectation and self-reported activity for general activities, walking, and climbing stairs evaluated at 5 days, and for general activities at 4 weeks after surgery. CONCLUSIONS: Vicarious experience provided through dyadic support is effective in helping patients undergoing cardiac surgery cope with surgical anxiety and in improving self-efficacy expectations and self-reported activity after surgery. Dyadic support is a valuable tool for recovery from cardiac surgery that needs to be maintained and explored through nursing practice and research.

Long-term benefits of exercise maintenance after outpatient rehabilitation program in patients with chronic obstructive pulmonary disease.

BACKGROUND: Optimal strategies to maintain short-term benefits of an initial rehabilitation program (RP) are not known. To assess the long-term effects of exercise maintenance (EM) after an initial outpatient RP, the authors conducted a prospective study. PATIENTS AND METHODS: Fifty-eight patients with moderate to moderately severe chronic obstructive pulmonary disease who completed an initial 7-week outpatient RP were included. They were allocated into four groups according to the conditions of EM they self-selected: 15 patients received a structured EM session supervised by a physiotherapist twice a week (group A); 14 patients received a structured EM session supervised by a physiotherapist once a week (group B); 15 patients continued self EM daily at home (group C); and 14 patients did not continue EM (group D). Patients were evaluated before, immediately after, and 18 months after the initial outpatient RP. Measurements included exercise testing on a cycle ergometer and a visual analog scale to evaluate chronic dyspnea. RESULTS: After RP, all patients exhibited improvements in maximal workload (P < 0.05) and in dyspnea (P < 0.05). Improvements in maximal workload were maintained at 18 months in patients in groups A, B, and C but these only reached significance in groups B and C (P < 0.05). On the other hand, maximal workload returned to baseline values in group D (P = 0.01) at 18 months. CONCLUSION: Our results indicate definite benefits of EM after an initial outpatient RP compared with no EM. Daily EM at home appears to be as efficient as structured EM sessions supervised by a physiotherapist, once or twice a week, in moderate to moderately severe chronic obstructive pulmonary disease.

[Use of research in clinical practice: support program for cardiac patients]. / L'utilisation de la recherche dans la pratique clinique: programme de parrainage à l'intention de patients cardiaques.

The research aims at the acquisition of knowledge and its application in the practice. The knowledge which most interests the nurses is the one pertaining to the improvement of nursing practice. Before initiating a change in the clinical practice on the basis of the research results, it is important to consider some rigorous criteria which will provide guidance to an enlightened decision as to whether such results should be adopted or not. With the help of an example of nursing care concerning a support programme for the benefit of heart patients, this article presents the application of a model of use of research results. The model consists of six phases in support of a critical judgement on the value of a scientific work: preparation, validation, comparative evaluation, decision making, adoption/application and evaluation. Each of these phases states the application of the model criteria, not only to the results, but to the whole research processes followed by the author. This model of research use can provide the nurse with means of proposing changes in the practice, based on the knowledge issuing from research.

The role of the Health Belief Model in amputees' self-evaluation of adherence to diabetes self-care behaviors.

This study involving 76 amputated patients with non-insulin-dependent diabetes mellitus examined the relationship between their beliefs regarding diabetes and its treatment and their self-evaluation of adherence to diabetes self-care behaviors. Descriptive results showed a high level of adherence to medication, foot care, and blood glucose testing, and a low level of adherence to diet and exercise. The correlative analysis revealed significant relationships between perceived social support and adherence to diet, and between perceived social support, barriers, and adherence to the practice of exercise. The regression analysis showed a significant influence of perceived social support on adherence to diet. The same relationship was observed for the influence of perceived social support and barriers on adherence to exercise. Findings support the importance of giving more attention to patients' needs regarding adherence to diet and exercise, improving social support, and removing barriers to patients' treatment. After an amputation it is important to provide patients with an appropriate diabetes teaching and follow-up program.

[Effects of ambulatory respiratory rehabilitation on exercise tolerance and quality of life in chronic obstructive lung disease patients]. / Effets de la réhabilitation respiratoire en ambulatoire sur la tolérance à l'effort et la qualité de vie des patients atteints de bronchopneumopathie chronique obstructive.

Respiratory rehabilitation is a multidisciplinary medical approach which allows a total care of patients suffering from COPD. Optimisation of bronchodilator treatment, health education, cessation of smoking, dietetic, relaxation and re-entrainment to effort. We report out experience concerning 88 BPCO (mean age 62.1, FEV1 of 1.4 litres; or 48% of predicted normal); these 88 patients were cared for on an ambulatory basis at our centre for two hours per session, three times per week for seven weeks. The objective results were analysed on exercise tests before and after treatment. For ventilation, there was a significant improvement in the power developed (from 45.5+/-17.1 to 53.4+/-23 watts; p<0.001) without any change in the oxygen consumption (VO2), ventilation (VE) or heart rate (FC) and of oxygen pulse (VO2/FC). For the same level of power (80% of maximum power for the initial exercise test) there was a significant lowering of ventilation (V=33.5+/-9.4 to 30.7+/-7.4 litres per minute, p<0.001), cardiac frequency (FC: from 116.9+/-16 to 111.1+/-13.1 beats per minute, p<0.001) as well as the oxygen pulse (VO2/FC: from 7.9+/-2.7 to 8.3+/-3.7). At the maximum on the exercise test all the parameters studied were significantly better: watts, VO2, VE, cardiac frequency and VO2/FC. A study of the visual analogue scale (EVA), analysing sleep, anxiety, dyspnoea and the physical aspects showed a significant improvement in the four subjective parameters. Respiratory rehabilitation of BPCO practiced as an out patient has shown an improvement in exercise tolerance in every day activities and improvement in dyspnoea and in the quality of life.

[The significance of maximal expiratory concentrations of CO2 (MEC CO2) in the negative diagnosis of acute pulmonary embolism in chronic obstructive bronchopneumopathies]. / Intérêt de la concentration expiratoire maximale de CO2 (CEM CO2) pour le diagnostic négatif de l'embolie pulmonaire aiguë au cours des bronchopneumopathies chroniques obstructives.

The aim of this prospective study was to analyse the contribution of the measurement of alveolar arterial gradients of CO2 during forced expiration in the diagnosis of pulmonary emboli occurring in chronic airflow obstruction (COPD) as a result of smoking. The study was carried out on 178 patients: Group 1: 54 subjects without emboli (14 controls, 33 COPD and 7 patients with chest pain); Group 2: 72 patients with proved emboli (49 non COPD, 23 COPD); Group 3: 52 patients COPD presenting with varied non-embolic broncho-pulmonary pathology (pneumonia, bronchospasm, pulmonary oedema, bronchial neoplasm). The diagnosis of pulmonary emboli was confirmed by scintigraphy in patients with non COPD or angiography (in patients with COPD). The maximal fraction of CO2 was measured using a capnologue during a forced expiration which was long and prolonged until residual volume was achieved. The PaCO2 was measured simultaneously by an analysis of arterial blood gases. The D index was calculated according to the formula [(PaCO2-PEM CO2)/PaCO2] x 100. The D index was significantly lower in Group 1 (3.42 +/- 3.8% p < 0.0001) than in Group 2 (20.8 +/- 10%) and Group 3 (17.6 +/- 11.7%) (not significant between Groups 2 and 3). In patients with COPD the specificity and sensitivity and the predicted positive and negative value were 100% for a D limit of 7%. In COPD patients these values were respectively 82, 95, 75 and 96% for a D limit of 7%; on the other hand for a D below 5% the values were 60, 100, 64 and 100% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A phase-ii study testing weekly platinum derivative combination chemotherapy as 2nd-line treatment in patients with advanced small-cell lung-cancer.

A phase II trial was conducted to determine the effectiveness of weekly administration of cisplatin (25 mg/m(2) on day 1) and carboplatin (100 mg/m(2) on day 1) as salvage chemotherapy for patients with small cell lung cancer after first-line chemotherapy without platinum derivatives. Of 40 eligible patients, 38 were evaluable for response. Interval between last course of first-line chemotherapy and first course of salvage therapy was less than 3 months in 34 and greater in 4. Five partial responses (13%; confidence interval at 95%:0.01-0.25) were documented (including 4 in patients with a treatment-free interval <3 months) as well as 8 no change, 21 progressions and 4 early deaths due to malignant disease. Toxicity consisted mainly of moderate thrombopenia and leucopenia. Grade I nephrotoxicity was observed in 6 patients. In conclusion, weekly administration of moderate doses of cisplatin and carboplatin as salvage chemotherapy for small cell lung cancer appeared feasible and was associated with a moderate but definitive anticancer activity.