Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease

RATIONALE: We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction. OBJECTIVES: Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. METHODS: In a FEV(1 )% matched population of 100 men and women with COPD we measured: age, MMRC, FEV(1), FVC, TLC, IC/TLC, PaO(2), PaCO(2), D(LCO), P(imax), P(0.1), Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations. RESULTS: MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:-0.39, p = 0.01), FEV(1 )% (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO(2 )(men:-0.59, p < 0.001), PaCO(2 )(men:0.27, p = 0.05), D(LCO )(men:-0.54, p < 0.001), P(0.1)/P(imax )(men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P(0.1)/P(imax )in women (r(2 )= 0.30) and BMI, DL(CO), PaO(2 )and P(0.1)/P(imax )in men (r(2 )= 0.81) were the strongest predictors of MMRC scores. CONCLUSION: In mild to severe COPD patients attending a pulmonary clinic, P(0.1)/P(imax )was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD

Comorbidity and Sex-Related Differences in Mortality in Oxygen-Dependent Chronic Obstructive Pulmonary Disease

Background: It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD). The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD. Methods: National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008. Comorbidities were obtained from the Swedish Hospital Discharge Register. Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion. The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, Pa O2 breathing air, FEV 1, smoking history and year of inclusion. Results: In total, 8,712 patients (55 % women) were included and 6,729 patients died during the study period. No patient was lost to follow-up. Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P,0.05 for all odds ratios). Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes. Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95 % confidence interval, 0.68–0.77; P,0.001)

Antibodies from rabbits immunized with HIV-1 clade B SOSIP trimers can neutralize multiple clade B viruses by destabilizing the envelope glycoprotein

The high HIV-1 viral diversity is a formidable hurdle for the development of an HIV-1 vaccine. Elicitation of broadly neutralizing antibodies (bNAbs) would offer a solution, but so far immunization strategies have failed to elicit bNAbs efficiently. To overcome the obstacles, it is important to understand the immune responses elicited by current HIV-1 envelope glycoprotein (Env) immunogens. To gain more insight, we characterized monoclonal antibodies (mAbs) isolated from rabbits immunized with Env SOSIP trimers based on the clade B isolate AMC008. Four rabbits that were immunized three times with AMC008 trimer developed robust autologous and sporadic low-titer heterologous neutralizing responses. Seventeen AMC008 trimer-reactive mAbs were isolated using antigen-specific single B cell sorting. Four of these mAbs neutralized the autologous AMC008 virus and several other clade B viruses. When visualized by electron microscopy, the complex of the neutralizing mAbs with the AMC008 trimer showed binding to the gp41 subunit with unusual approach angles and we observed that their neutralization ability depended on their capacity to induce Env trimer dissociation. Thus, AMC008 SOSIP trimer immunization induced clade B neutralizing mAbs with unusual approach angles with neutralizing effects that involve trimer destabilization. Optimizing these responses might provide an avenue to the induction of trimer dissociating bNAbs. IMPORTANCE Roughly 32 million people have died as a consequence of HIV-1 infection since the start of the epidemic and still 1.7 million people get infected with HIV-1 annually. Therefore, a vaccine to prevent HIV-1 infection is urgently needed. Current HIV-1 immunogens are not able to elicit the broad immune responses needed to provide protection against the large variation of HIV-1 strains circulating globally. A better understanding of the humoral immune responses elicited by immunization with state-of-the-art HIV-1 immunogens should facilitate the design of improved HIV-1 vaccine candidates. We identified antibodies with the ability to neutralize multiple HIV-1 viruses by destabilization of the envelope glycoprotein. Their weak but consistent cross-neutralization ability indicates the potential of this epitope to elicit broad responses. The trimer-destabilizing effect of the neutralizing mAbs combined with detailed characterization of the neutralization epitope can be used to shape the next generation of HIV-1 immunogens to elicit improved humoral responses after vaccination

Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted

Toxoplasma gondii infection and liver disease: a case-control study in a Northern Mexican population

<p>Abstract</p> <p>Background</p> <p>Infection with the protozoan parasite <it>Toxoplasma gondii </it>may cause liver disease. However, the impact of the infection in patients suffering from liver disease is unknown. Therefore, through a case-control study design, 75 adult liver disease patients attending a public hospital in Durango City, Mexico, and 150 controls from the general population of the same region matched by gender, age, and residence were examined with enzyme-linked immunoassays for the presence of anti-<it>Toxoplasma </it>IgG and anti-<it>Toxoplasma </it>IgM antibodies. Socio-demographic, clinical and behavioral characteristics from the study subjects were obtained.</p> <p>Results</p> <p>Seroprevalence of anti-<it>Toxoplasma </it>IgG antibodies and IgG titers did not differ significantly in patients (10/75; 13.3%) and controls (16/150; 10.7%). Two (2.7%) patients and 5 (3.3%) controls had anti-<it>Toxoplasma </it>IgM antibodies (<it>P </it>= 0.57). Seropositivity to <it>Toxoplasma </it>did not show any association with the diagnosis of liver disease. In contrast, seropositivity to <it>Toxoplasma </it>in patients was associated with consumption of venison and quail meat. <it>Toxoplasma </it>seropositivity was more frequent in patients with reflex impairment (27.8%) than in patients without this impairment (8.8%) (<it>P </it>= 0.05). Multivariate analysis showed that <it>Toxoplasma </it>seropositivity in patients was associated with consumption of sheep meat (OR = 8.69; 95% CI: 1.02-73.71; <it>P </it>= 0.04) and rabbit meat (OR = 4.61; 95% CI: 1.06-19.98; <it>P </it>= 0.04).</p> <p>Conclusions</p> <p>Seropositivity to <it>Toxoplasma </it>was comparable among liver disease patients and controls. Further studies with larger sample sizes are needed to elucidate the association of <it>Toxoplasma </it>with liver disease. Consumption of venison, and rabbit, sheep, and quail meats may warrant further investigation.</p

Asteroseismology

Asteroseismology is the determination of the interior structures of stars by using their oscillations as seismic waves. Simple explanations of the astrophysical background and some basic theoretical considerations needed in this rapidly evolving field are followed by introductions to the most important concepts and methods on the basis of example. Previous and potential applications of asteroseismology are reviewed and future trends are attempted to be foreseen.Comment: 38 pages, 13 figures, to appear in: "Planets, Stars and Stellar Systems", eds. T. D. Oswalt et al., Springer Verla

The ρ(1S,2S)\rho(1S,2S), ψ(1S,2S)\psi(1S,2S), Υ(1S,2S)\Upsilon(1S,2S) and ψt(1S,2S)\psi_t(1S,2S) mesons in a double pole QCD Sum Rule

We use the method of double pole QCD sum rule which is basically a fit with two exponentials of the correlation function, where we can extract the masses and decay constants of mesons as a function of the Borel mass. We apply this method to study the mesons: $\rho(1S,2S)$, $\psi(1S,2S)$, $\Upsilon(1S,2S)$ and $\psi_t(1S,2S)$. We also present predictions for the toponiuns masses $\psi_t(1S,2S)$ of m(1S)=357 GeV and m(2S)=374 GeV.Comment: 14 pages, 11 figures in Braz J Phys (2016

The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis

Background Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes. Methods Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1. Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use. Results With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes. Conclusions These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes

Health-related quality of life and long-term prognosis in chronic hypercapnic respiratory failure: a prospective survival analysis

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life (HRQL) is considered as an important outcome parameter in patients with chronic diseases. This study aimed to assess the role of disease-specific HRQL for long-term survival in patients of different diagnoses with chronic hypercapnic respiratory failure (CHRF).</p> <p>Methods</p> <p>In a cohort of 231 stable patients (chronic obstructive pulmonary disease (COPD), n = 98; non-COPD (obesity-hypoventilation syndrome, restrictive disorders, neuromuscular disorders), n = 133) with CHRF and current home mechanical ventilation (HMV), HRQL was assessed by the disease-specific Severe Respiratory Insufficiency (SRI) questionnaire and its prognostic value was prospectively evaluated during a follow-up of 2–4 years, using univariate and multivariate regression analysis.</p> <p>Results</p> <p>HRQL was more impaired in COPD (mean ± SD SRI-summary score (SRI-SS) 52.5 ± 15.6) than non-COPD patients (67.6 ± 16.4; p < 0.001). Overall mortality during 28.9 ± 8.8 months of follow-up was 19.1% (31.6% in COPD, 9.8% in non-COPD). To identify the overall role of SRI, we first evaluated the total study population. SRI-SS and its subdomains (except attendance symptoms and sleep), as well as body mass index (BMI), leukocyte number and spirometric indices were associated with long-term survival (p < 0.01 each). Of these, SRI-SS, leukocytes and forced expiratory volume in 1 s (FEV₁) turned out to be independent predictors (p < 0.05 each). More specifically, in non-COPD patients SRI-SS and most of its subdomains, as well as leukocyte number, were related to survival (p < 0.05), whereas in patients with COPD only BMI and lung function but not SRI were predictive.</p> <p>Conclusion</p> <p>In patients with CHRF and HMV, the disease-specific SRI was an overall predictor of long-term survival in addition to established risk factors. However, the SRI predominantly beared information regarding long-term survival in non-COPD patients, while in COPD patients objective measures of the disease state were superior. This on one hand highlights the significance of HRQL in the long-term course of patients with CHRF, on the other hand it suggests that the predictive value of HRQL depends on the underlying disease.</p