Fusarium species,Scedosporium species, and Lomentospora prolificans: A systematic review to inform the World Health Organization priority list of fungal pathogens

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required

Fusarium species,Scedosporium species, and Lomentospora prolificans: A systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required

Effect of Muscle Length on Cross-Bridge Kinetics in Intact Cardiac Trabeculae at Body Temperature

Dynamic force generation in cardiac muscle, which determines cardiac pumping activity, depends on both the number of sarcomeric cross-bridges and on their cycling kinetics. The Frank–Starling mechanism dictates that cardiac force development increases with increasing cardiac muscle length (corresponding to increased ventricular volume). It is, however, unclear to what extent this increase in cardiac muscle length affects the rate of cross-bridge cycling. Previous studies using permeabilized cardiac preparations, sub-physiological temperatures, or both have obtained conflicting results. Here, we developed a protocol that allowed us to reliably and reproducibly measure the rate of tension redevelopment (ktr; which depends on the rate of cross-bridge cycling) in intact trabeculae at body temperature. Using K+ contractures to induce a tonic level of force, we showed the ktr was slower in rabbit muscle (which contains predominantly β myosin) than in rat muscle (which contains predominantly α myosin). Analyses of ktr in rat muscle at optimal length (Lopt) and 90% of optimal length (L90) revealed that ktr was significantly slower at Lopt (27.7 ± 3.3 and 27.8 ± 3.0 s−1 in duplicate analyses) than at L90 (45.1 ± 7.6 and 47.5 ± 9.2 s−1). We therefore show that ktr can be measured in intact rat and rabbit cardiac trabeculae, and that the ktr decreases when muscles are stretched to their optimal length under near-physiological conditions, indicating that the Frank–Starling mechanism not only increases force but also affects cross-bridge cycling kinetics

Efficacy of Early Oral Switch with β-Lactams for Low-Risk <i>Staphylococcus aureus</i> Bacteremia

The aim of this study was to assess the safety of early oral switch (EOS) prior to 14 days for low-risk Staphylococcus aureus bacteremia (LR-SAB), which is the primary treatment strategy used at our institution. The usual recommended therapy is 14 days of intravenous (i.v.) antibiotics. All patients with SAB at our hospital were identified between 1 January 2014 and 31 December 2018. Those meeting low-risk criteria (health care-associated, no evidence of deep infection or demonstrated involvement of prosthetic material, and no further positive blood cultures after 72 h) were included in the study. </jats:p

Moderate intensity of regular exercise improves cardiac SR Ca²⁺ uptake activity in ovariectomized rats

The impact of regular exercise in protecting cardiac deteriorating results of female sex hormone deprivation was evaluated by measuring changes in intracellular Ca2+ removal activity of sarcoplasmic reticulum (SR) in ovariectomized rats following 9-wk treadmill running exercise at moderate intensity. Despite induction of cardiac hypertrophy in exercised groups of both sham-operated and ovariectomized rats, exercise training had no effect on SR Ca2+ uptake and SR Ca2+-ATPase (SERCA) in hormone intact rat heart. However, exercise training normalized the suppressed maximum SR Ca2+ uptake and SERCA activity in ovariectomized rat heart. While exercise training normalized the leftward shift in pCa (−log[Ca2+])-SR Ca2+ uptake relation in ovariectomized rats, no effect was detected in exercised sham-operated rats. Similar phenomena were also observed on SERCA and on phospholamban (PLB) phosphorylation levels; exercise training in ovariectomized rats enhanced SERCA expression to reach the level as that in sham-operated rats, in which there were no differences in SERCA and phospho-PLB levels between sedentary and exercised groups. In addition, the reduction in phospho-Thr17 PLB in myocardium of ovariectomized rats was abolished by exercise training. These results showed that regular exercise maintains the molecular activation of cardiac SR Ca2+ uptake under normal physiological conditions and is able to induce a protective impact on cardiac SR Ca2+ uptake in ovarian sex hormone-deprived status. </jats:p

Increased myocardial stiffness with maintenance of length-dependent calcium activation by female sex hormones in diabetic rats

A decrease in peak early diastolic filling velocity in postmenopausal women implies a sex hormone-related diastolic dysfunction. The regulatory effect of female sex hormones on cardiac distensibility therefore was evaluated in ovariectomized rats by determining the sarcomere length-passive tension relationship of ventricular skinned fiber preparations. Diabetes also was induced in the rat to assess the protective significance of female sex hormones on diastolic function. While ovariectomy had no effect on myocardial stiffness, collagen content, or titin ratio, a significant increase in myocardial stiffness was observed in diabetic rat only when female sex hormones were intact. The increased stiffness in diabetic-sham rats was accompanied by an elevated collagen content resulting from increases in the levels of procollagen and Smad2. Surprisingly, the increased myocardial stiffness in diabetic-sham rats was accompanied by a shift toward a more compliant N2BA of cardiac titin isoforms. The pCa-active tension relationship was analyzed at fixed sarcomere lengths of 2.0 and 2.3 μm to determine the magnitude of changes in myofilament Ca2+ sensitivity between the two sarcomere lengths. Interestingly, high expression of N2BA titin was associated with a suppressed magnitude of changes in myofilament Ca2+ sensitivity only in the diabetic-ovariectomized condition. Estrogen supplementation in diabetic-ovariectomized rats partially increased myocardial stiffness but completely reversed the change in myofilament Ca2+ sensitivity. These results indicate a restrictive adaptation of myocardium governed by female sex hormones to maintain myofilament activity in compensation to the pathophysiological induction of cardiac dilatation by the diabetic condition. </jats:p