Fungal pathogens are a global threat to human health. For example, fungi from the genus Aspergillus cause a spectrum of diseases collectively known as aspergillosis. Most of the >200,000 life-threatening aspergillosis infections per year worldwide are caused by Aspergillus fumigatus. Recently, molecular typing techniques have revealed that aspergillosis can also be caused by organisms that are phenotypically similar to A. fumigatus but genetically distinct, such as Aspergillus lentulus and Aspergillus fumigatiaffinis. Importantly, some of these so-called cryptic species are thought to exhibit different virulence and drug susceptibility profiles than A. fumigatus, however, our understanding of their biology and pathogenic potential has been stymied by the lack of genome sequences and phenotypic profiling of multiple clinical strains. To fill this gap, we phenotypically characterized the virulence and drug susceptibility of 15 clinical strains of A. fumigatus, A. lentulus, and A. fumigatiaffinis from Spain and sequenced their genomes. We found heterogeneity in drug susceptibility across species and strains. We further found heterogeneity in virulence within each species but no significant differences in the virulence profiles between the three species. Genes known to influence drug susceptibility (cyp51A and fks1) vary in paralog number and sequence among these species and strains and correlate with differences in drug susceptibility. Similarly, genes known to be important for virulence in A. fumigatus showed variability in number of paralogs across strains and across species. Characterization of the genomic similarities and differences of clinical strains of A. lentulus, A. fumigatiaffinis, and A. fumigatus that vary in disease-relevant traits will advance our understanding of the variance in pathogenicity between Aspergillus species and strains that are collectively responsible for the vast majority of aspergillosis infections in humans.

Background Despite clinical practice guideline recommendations that cardiovascular disease patients participate, cardiac rehabilitation (CR) programs are highly unavailable and underutilized. This is particularly true in low-resource settings, where the epidemic is at its’ worst. The reasons are complex, and include health system, program and patient-level barriers. This is the first study to assess barriers at all these levels concurrently, and to do so in a low-resource setting. Methods In this cross-sectional study, data from three cohorts (healthcare administrators, CR coordinators and patients) were triangulated. Healthcare administrators from all institutions offering cardiac services, and providers from all CR programs in public and private institutions of Minas Gerais state, Brazil were invited to complete a questionnaire. Patients from a random subsample of 12 outpatient cardiac clinics and 11 CR programs in these institutions completed the CR Barriers Scale. Results Thirty-two (35.2%) healthcare administrators, 16 (28.6%) CR providers and 805 cardiac patients (305 [37.9%] attending CR) consented to participate. Administrators recognized the importance of CR, but also the lack of resources to deliver it; CR providers noted referral is lacking. Patients who were not enrolled in CR reported significantly greater barriers related to comorbidities/functional status, perceived need, personal/family issues and access than enrollees, and enrollees reported travel/work conflicts as greater barriers than non-enrollees (all p < 0.01). Conclusions The inter-relationship among barriers at each level is evident; without resources to offer more programs, there are no programs to which physicians can refer (and hence inform and encourage patients to attend), and patients will continue to have barriers related to distance, cost and transport. Advocacy for services is needed.

Highlights d Aspergillus latus clinical isolates were previously misidentified as A. nidulans d A. latus is an allodiploid that arose via hybridization of two Aspergillus species d A. latus hybrid isolates exhibit heterogeneity for several infection-relevant traits d A. latus is phenotypically distinct from parental and closely related species

Most studies regarding the impact of exercise intensity on cardiac autonomic regulation were conducted with athletes and used exercise intensities exceeding those recommended by position stands. We evaluated the influence of exercise intensity in a typical ACSM-aerobic session on 24-h cardiac autonomic modulation in sedentary subjects. Ten healthy sedentary subjects participated in the 3-day study. On 2 days, subjects performed a moderate- or high-intensity aerobic exercise session (MI, HI). The post-exercise protocol consisted of a continuous electrocardiographic recording for 1 h at the laboratory plus 23 h under ambulatory conditions. On the third day 24-h electrocardiographic recording was done without prior exercise (NPE). Heart rate (HR) and frequency-domain parameters (LF, HF) of heart rate variability were evaluated during the entire recovery period. Higher values of HR and lower values of HF and LF were observed throughout the first hour after the HI compared with the MI session. This difference was not observed after in ambulatory awake condition, but reappeared during sleep, when HF values after HI were lower compared with the NPE and MI (p<0.05). Even within the submaximal intensity-range of a typical exercise session, the intensity of exercise influences the post-exercise cardiac autonomic modulation in sedentary subjects.