Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema.

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions.We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients.CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation (V'E)/carbon dioxide output (V'CO2 ) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V'E/V'CO2 ratio in the more dyspnoeic group. V'E/V'CO2 nadir >50 (OR 9.43, 95% CI 5.28-13.6; p=0.0001) and total emphysema extent >15% (2.25, 1.28-3.54; p=0.01) predicted a high dyspnoea burden associated with severely reduced exercise capacity in CPFEContrary to current understanding, hypoxaemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased "wasted" ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.

Carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy humans and in patients with pulmonary arterial hypertension.

KEY POINTS: Dysfunction of post-exercise cardiac autonomic control is associated with increased mortality risk in healthy adults and in patients with cardiorespiratory diseases. The afferent mechanisms that regulate the post-exercise cardiac autonomic control remain unclear. We found that afferent signals from carotid chemoreceptors restrain the post-exercise cardiac autonomic control in healthy adults and patients with pulmonary arterial hypertension (PAH). Patients with PAH had higher carotid chemoreflex sensitivity, and the magnitude of carotid chemoreceptor restraint of autonomic control was greater in patients with PAH as compared to healthy adults. The results demonstrate that the carotid chemoreceptors contribute to the regulation of post-exercise cardiac autonomic control, and suggest that the carotid chemoreceptors may be a potential target to treat post-exercise cardiac autonomic dysfunction in patients with PAH. ABSTRACT: Dysfunction of post-exercise cardiac autonomic control predicts mortality, but its underlying mechanisms remain unclear. We tested whether carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy adults (HA), and whether such restraint is greater in patients with pulmonary arterial hypertension (PAH) who may have both altered carotid chemoreflex and altered post-exercise cardiac autonomic control. Twenty non-hypoxaemic patients with PAH and 13 age- and sex-matched HA pedalled until 90% of peak work rate observed in a symptom-limited ramp-incremental exercise test. Recovery consisted of unloaded pedalling for 5 min followed by seated rest for 6 min. During recovery, subjects randomly inhaled either 100% O2 (hyperoxia) to inhibit the carotid chemoreceptor activity, or 21% O2 (normoxia) as control. Post-exercise cardiac autonomic control was examined via heart rate (HR) recovery (HRR; HR change after 30, 60, 120 and 300 s of recovery, using linear and non-linear regressions of HR decay) and HR variability (HRV; time and spectral domain analyses). As expected, the PAH group had higher carotid chemosensitivity and worse post-exercise HRR and HRV than HA. Hyperoxia increased HRR at 30, 60 and 120 s and absolute spectral power HRV in both groups. Additionally, hyperoxia resulted in an accelerated linear HR decay and increased time domain HRV during active recovery only in the PAH group. In conclusion, the carotid chemoreceptors restrained recovery of cardiac autonomic control from exercise in HA and in patients with PAH, with the restraint greater for some autonomic indexes in patients with PAH.

Interspecific Cross-Attraction between the South American Cerambycid Beetles Cotyclytus curvatus and Megacyllene acuta is Averted by Minor Pheromone Components.

During field screening trials conducted in Brazil in 2015, adults of both sexes of the cerambycid beetles Cotyclytus curvatus (Germar) and Megacyllene acuta (Germar) (subfamily Cerambycinae, tribe Clytini) were significantly attracted to racemic 3-hydroxyhexan-2-one and racemic 2-methylbutan-1-ol, chemicals which previously have been identified as male-produced aggregation-sex pheromones of a number of cerambycid species endemic to other continents. Subsequent analyses of samples of beetle-produced volatiles revealed that males of C. curvatus sex-specifically produce only (R)-3-hydroxyhexan-2-one, whereas males of M. acuta produce the same compound along with lesser amounts of (2S,3S)-2,3-hexanediol and (S)-2-methylbutan-1-ol. Follow-up field trials showed that both sexes of both species were attracted to synthetic reconstructions of their respective pheromones, confirming that males produce aggregation-sex pheromones. The minor pheromone components of M. acuta, (S)-2-methylbutan-1-ol and (2S,3S)-2,3-hexanediol, synergized attraction of that species, but antagonized attraction of C. curvatus to (R)-3-hydroxyhexan-2-one. Beetles of other cerambycine species also were attracted in significant numbers, including Chrysoprasis linearis Bates, Cotyclytus dorsalis (Laporte & Gory), and Megacyllene falsa (Chevrolat). Our results provide further evidence that 3-hydroxyhexan-2-one is a major component of attractant pheromones of numerous cerambycine species world-wide. Our results also highlight our increasing understanding of the crucial role of minor pheromone components in imparting species specificity to cerambycid pheromone blends, as is known to occur in numerous species in other insect families.

Synergic Effect of Brachyspira hyodysenteriae and Lawsonia intracellularis Coinfection: Anatomopathological and Microbiome Evaluation.

Brachyspira hyodysenteriae and Lawsonia intracellularis coinfection has been observed in the diagnostic routine; however, no studies have evaluated their interaction. This study aimed to characterize lesions and possible synergisms in experimentally infected pigs. Four groups of piglets, coinfection (CO), B. hyodysenteriae (BRA), L. intracellularis (LAW), and negative control (NEG), were used. Clinical signals were evaluated, and fecal samples were collected for qPCR. At 21 days post infection (dpi), all animals were euthanized. Gross lesions, bacterial isolation, histopathology, immunohistochemistry, and fecal microbiome analyses were performed. Diarrhea started at 12 dpi, affecting 11/12 pigs in the CO group and 5/11 pigs in the BRA group. Histopathological lesions were significantly more severe in the CO than the other groups. B. hyodysenteriae was isolated from 11/12 pigs in CO and 5/11 BRA groups. Pigs started shedding L. intracellularis at 3 dpi, and all inoculated pigs tested positive on day 21. A total of 10/12 CO and 7/11 BRA animals tested positive for B. hyodysenteriae by qPCR. A relatively low abundance of microbiota was observed in the CO group. Clinical signs and macroscopic and microscopic lesions were significantly more severe in the CO group compared to the other groups. The presence of L. intracellularis in the CO group increased the severity of swine dysentery.

Cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension at rest and during orthostatic stress: role of the peripheral chemoreflex.

The baroreflex integrity in early-stage pulmonary arterial hypertension (PAH) remains uninvestigated. A potential baroreflex impairment could be functionally relevant and possibly mediated by enhanced peripheral chemoreflex activity. Thus, we investigated 1) the cardiac baroreflex in nonhypoxemic PAH; 2) the association between baroreflex indexes and peak aerobic capacity [i.e., peak oxygen consumption (V̇o2peak)]; and 3) the peripheral chemoreflex contribution to the cardiac baroreflex. Nineteen patients and 13 age- and sex-matched healthy adults (HA) randomly inhaled either 100% O2 (peripheral chemoreceptor inhibition) or 21% O2 (control session) while at rest and during a repeated sit-to-stand maneuver. Beat-by-beat analysis of R-R intervals and systolic blood pressure provided indexes of cardiac baroreflex sensitivity (cBRS) and effectiveness (cBEI). The PAH group had lower cBEI for all sequences (cBEIALL) at rest [means ± SD: PAH = 0.5 ± 0.2 vs. HA = 0.7 ± 0.1 arbitrary units (a.u.), P = 0.02] and lower cBRSALL (PAH = 6.8 ± 7.0 vs. HA = 9.7 ± 5.0 ms·mmHg-1, P < 0.01) and cBEIALL (PAH = 0.4 ± 0.2 vs. HA= 0.6 ± 0.1 a.u., P < 0.01) during the sit-to-stand maneuver versus the HA group. The cBEI during the sit-to-stand maneuver was independently correlated to V̇o2peak (partial r = 0.45, P < 0.01). Hyperoxia increased cBRS and cBEI similarly in both groups at rest and during the sit-to-stand maneuver. Therefore, cardiac baroreflex dysfunction was observed under spontaneous and, most notably, provoked blood pressure fluctuations in nonhypoxemic PAH, was not influenced by the peripheral chemoreflex, and was associated with lower V̇o2peak, suggesting that it could be functionally relevant.NEW & NOTEWORTHY Does the peripheral chemoreflex play a role in cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension (PAH)? Here we provide new evidence of cardiac baroreflex dysfunction under spontaneous and, most notably, provoked blood pressure fluctuations in patients with nonhypoxemic PAH. Importantly, impaired cardiac baroreflex effectiveness during provoked blood pressure fluctuations was independently associated with poorer functional capacity. Finally, our results indicated that the peripheral chemoreflex did not mediate cardiac baroreflex dysfunction among those patients.

Oral fluid for detection of exposure to Lawsonia intracellularis in naturally infected pigs.

To demonstrate the utility of oral fluid (OF) for indirect diagnostic detection of Lawsonia intracellularis (Li), 15 pig farms were studied. Serum and fecal samples were collected from 20 animals from five different age groups on each farm. OF samples were collected from animals in two pens of the same age groups. Serum and OF samples were analyzed in an immunoperoxidase in monolayer assay (IPMA) for the detection of anti-Li immunoglobulin G (IgG) and A (IgA). Compatible results were found between PCR and IgG in OF in four of the five ages evaluated. Simultaneous detection of IgG in serum and OF was mainly observed on farms showing clinical signs suggestive of porcine proliferative enteropathy (PPE). These findings demonstrate the potential usefulness of OF in detecting anti-Li antibodies as a diagnostic tool that can be used to monitor PPE in herds with clinical signs compatible with the disease.

2-DE-based proteomic investigation of the saliva of the Amazonian triatomine vectors of Chagas disease: Rhodnius brethesi and Rhodnius robustus.

The triatomine bugs are obligatory haematophagous organisms that act as vectors of Chagas disease by transmitting the protozoan Trypanosoma cruzi. Their feeding success is strongly related to salivary proteins that allow these insects to access blood by counteracting host haemostatic mechanisms. Proteomic studies were performed on saliva from the Amazonian triatomine bugs: Rhodnius brethesi and R. robustus, species epidemiologically relevant in the transmission of T. cruzi. Initially, salivary proteins were separated by two-dimensional gel electrophoresis (2-DE). The average number of spots of the R. brethesi and R. robustus saliva samples were 129 and 135, respectively. The 2-DE profiles were very similar between the two species. Identification of spots by peptide mass fingerprinting afforded limited efficiency, since very few species-specific salivary protein sequences are available in public sequence databases. Therefore, peptide fragmentation and de novo sequencing using a MALDI-TOF/TOF mass spectrometer were applied for similarity-driven identifications which generated very positive results. The data revealed mainly lipocalin-like proteins which promote blood feeding of these insects. The redundancy of saliva sequence identification suggested multiple isoforms caused by gene duplication followed by gene modification and/or post-translational modifications. In the first experimental assay, these proteins were predominantly phosphorylated, suggesting functional phosphoregulation of the lipocalins.