Aspergillus fumigatus is a clinically important fungus with the ability to cause invasive aspergillosis with high mortality rates in immunocompromised patients and chronic pulmonary aspergillosis in immunocompetent individuals. Virulence of mutants has traditionally been assessed using mammalian hosts such as mice and rats and more recently the fruit fly, Drosophila melanogaster, demonstrated the potential to act as an in vivo host suitable for screening Aspergillus mutants. In this study using a larger thermotolerant invertebrate, Galleria mellonella, the virulence of individual gene deletants of Aspergillus fumigatus (cpcA, sidA, sidC, sidD, sidF and paba,) were compared to the parental and gene-replacement strains, if available. A range of infectious challenges consisting of from 3 × 10(3)-3 × 10(6) spores/larva was followed by observation of larval survival with mean survival time used as a surrogate of microbial pathogenicity. Mutants cpcA, sidA, sidF and paba were avirulent and sidC and sidD showed attenuated virulence. Virulence assessment in G. mellonella correlated closely with the historic data generated using mice and Drosophila. Pre-screening Aspergillus mutants using G. mellonella could significantly reduce the number of mammals required to assess changes in virulence.

These results provide the experimental foundation for the selection of candidate posaconazole regimens for the primary treatment of invasive pulmonary aspergillosis in profoundly neutropenic hosts.

Low energy availability (LEA) describes the disruption in normal physiological function existent when insufficient energy intake is combined with exercise. To conserve energy a range of endocrine adaptations occur, impairing health and athletic performance. The prevalence of LEA has not been fully established especially among recreational exercisers. Determining recreational exercisers at risk of LEA may help to maximize prevention, early diagnosis and treatment. The design of this study was a cross-sectional online survey. One-hundred and nine female recreational exercisers, with a mean age of 23.8 (SD 6.9) years were recruited via gyms and fitness centers throughout NZ. Participants completed an online questionnaire including questions from the LEAF-Q (Low Energy Availability in Females Questionnaire). A total of 45.0% (CI, 35.4%, 54.8%) of participants were classified as "at risk" of LEA. For every extra hour of exercise per week the odds of being at risk of LEA were 1.13 times greater (CI 1.02, 1.25, p = .016). All participants reporting previous stress fracture injuries (n = 4) were classified as at risk for LEA. Significantly more subjects participating in an individual sport were classified as at risk for LEA (69.6%, CI 24.3%, 54.8%) compared with team sports (34.8%, CI 18.7%, 40.5%) (p = .006). The high prevalence of female recreational exercisers at risk of LEA is of concern, emphasizing the importance of increasing awareness of the issue, and promoting prevention and early detection strategies, so treatment can be implemented before health is severely compromised.

The clinical utility of the echinocandins is potentially compromised by the emergence of drug resistance. We investigated whether Candida albicans with amino acid substitutions at position Ser645 in Fks1 can be treated with either a conventional or an elevated dosage of micafungin. We studied Candida albicans (wild-type SC5314; MIC, 0.06 mg/liter) and four fks1 mutants (one FKS1/fks1 heterozygote mutant [MIC, 0.5 mg/liter] and three fks1/fks1 homozygous mutants [MICs for all, 2 mg/liter]) with a variety of amino acid substitutions at Ser645. The pharmacokinetic and pharmacodynamic relationships were characterized in a persistently neutropenic murine model of disseminated candidiasis. A mathematical model was fitted to all pharmacokinetic and pharmacodynamic data. This mathematical model was then used to "humanize" the murine pharmacokinetics, and the predicted antifungal effect was determined. The estimated maximal rate of growth and ultimate fungal densities in the kidney for each of the strains were similar. The administration of micafungin at 1 mg/kg of body weight to the wild type resulted in moderate antifungal activity, whereas the administration of 5 and 20 mg/kg resulted in rapid fungicidal activity. In contrast, the FKS1/fks heterozygote was killed only with 20 mg/kg, and the homozygous fks1 mutants failed to respond to any dosage. The bridging study revealed that human dosages of 100 and 400 mg/day were active only against the wild type, with no activity against either the heterozygote or the homozygote mutants. Ser645 Fks1 Candida albicans mutants cannot be treated with either conventional or elevated dosages of micafungin and should be deemed resistant.

Research on the health of female athletes has developed substantially over the past 50 years. This review aims to provide an overview of this research and identify directions for future work. While early cross-sectional studies focused primarily on menstruation, research has progressed to now encompass hormonal changes, bone health and lipid profiles. The seminal work of Loucks and colleagues distinguished that these health concerns were due to low energy availability (LEA) rather than exercise alone. LEA occurs when the body has insufficient energy available to meet the needs of training and normal physiological functioning. While there appears to be agreement that LEA is the underlying cause of this syndrome, controversy regarding terminology has emerged. Originally coined the female athlete triad (Triad), some researchers are now advocating the use of the term relative energy deficiency in sport (RED-S). This group argues that the term Triad excludes male athletes who also have the potential to experience LEA and its associated negative impact on health and performance. At present, implications of LEA among male athletes are poorly understood and should form the basis of future research. Other directions for future research include determination of the prevalence and long-term risks of LEA in junior and developmental athletes, and the development of standardised tools to diagnose LEA. These tools are required to aid comparisons between studies and to develop treatment strategies to attenuate the long-term health consequences of LEA. Continued advances in knowledge on LEA and its associated health consequences will aid development of more effective prevention, early detection and treatment strategies.

Objective: To assess associations between physical activity (PA), body composition, and biomarkers of metabolic health in Pacific and New Zealand European (NZE) women who are known to have different metabolic disease risks.Methods: Pacific (n = 142) or NZE (n = 162) women aged 18–45 years with a self-reported body mass index (BMI) of either 18.5–25.0 kg⋅m–2 or ≥30.0 kg⋅m–2 were recruited and subsequently stratified as either low (<35%) or high (≥35%) BF%, with approximately half of each group in either category. Seven-day accelerometery was used to assess PA levels. Fasting blood was analysed for biomarkers of metabolic health, and whole body dual-energy X-ray absorptiometry (DXA) was used to estimate body composition.Results: Mean moderate-to-vigorous physical activity (MVPA; min⋅day–1) levels differed between BF% (p < 0.05) and ethnic (p < 0.05) groups: Pacific high- 19.1 (SD 15.2) and low-BF% 26.3 (SD 15.6) and NZE high- 30.5 (SD 19.1) and low-BF% 39.1 (SD 18.4). On average Pacific women in the low-BF% group engaged in significantly less total PA when compared to NZE women in the low-BF% group (133 cpm); no ethnic difference in mean total PA (cpm) between high-BF% groups were observed: Pacific high- 607 (SD 185) and low-BF% 598 (SD 168) and NZE high- 674 (SD 210) and low-BF% 731 (SD 179). Multiple linear regression analysis controlling for age and deprivation showed a significant inverse association between increasing total PA and fasting plasma insulin among Pacific women; every 100 cpm increase in total PA was associated with a 6% lower fasting plasma insulin; no significant association was observed in NZE women. For both Pacific and NZE women, there was an 8% reduction in fasting plasma insulin for every 10-min increase in MVPA (p ≤ 0.05).Conclusion: Increases in total PA and MVPA are associated with lower fasting plasma insulin, thus indicating a reduction in metabolic disease risk. Importantly, compared to NZE, the impact of increased total PA on fasting insulin may be greater in Pacific women. Considering Pacific women are a high metabolic disease risk population, these pre-clinical responses to PA may be important in this population; indicating promotion of PA in Pacific women should remain a priority.

Black, K, Slater, J, Brown, RC, and Cooke, R. Low energy availability, plasma lipids, and hormonal profiles of recreational athletes. J Strength Cond Res 32(10): 2816-2824, 2018-It has been postulated that low energy availability (LEA) impacts bone health, hormonal concentrations, and cardiovascular function. This study describes the lipid levels, hormonal profiles, and nutrient intakes of recreationally active adults at risk of LEA compared with those not at risk. Thirty-eight women who meet or exceed the New Zealand guidelines for physical activity participated. Each participant completed an online questionnaire including the Low Energy Availability in Females questionnaire (LEAF-Q), demographic questions, and daily exercise to determine energy expenditure. Participants also provided a weighed 3-day diet record, a blood sample analyzed for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and cortisol, and a saliva sample analyzed for testosterone. Body composition was assessed using bioelectrical impedance. Those classed as at risk of LEA according to the LEAF-Q showed very likely lower energy availability (at risk: mean, 36.3 [95% confidence interval, 30.8-41.7] kcal·kg·FFMd vs. not at risk: mean, 47.5 [95% CI, 39.5-55.4] kcal·kg·FFMd) and lower calcium intakes (mean, 847 [95% CI, 695-998] mg, vs. mean, 1488 [95% CI, 690-2,286] mg). Those at risk also had a likely small lower T3 concentration of 1.78 (SD: 0.36) nmol·L compared with 2.01 (SD: 0.53) nmol·L for those not at risk. These data suggest that recreationally active female subjects classed as at risk of LEA according to the LEAF-Q also have lower energy availability as determined by diet records and exercise diaries. The results also suggests that those at risk of LEA have reductions in T3, and their low energy intake, in addition to a low calcium intake, could put them at an increased risk of poor bone health.

Reducing obesity positively impacts diabetes and cardiovascular risk; however, evidence-based lifestyle programs, such as the Diabetes Prevention Program (DPP), show reduced effectiveness in African American (AA) women. In addition to an attenuated response to lifestyle programs, AA women also demonstrate high rates of obesity, diabetes, and cardiovascular disease. To address these disparities, enhancements to evidence-based lifestyle programs for AA women need to be developed and evaluated with culturally relevant and rigorous study designs. This study describes a community-based participatory research (CBPR) approach to design a novel faith-enhancement to the DPP for AA women. A long-standing CBPR partnership designed the faith-enhancement from focus group data (N=64 AA adults) integrating five components: a brief pastor led sermon, memory verse, in class or take-home faith activity, promises to remember, and scripture and prayer integrated into participant curriculum and facilitator materials. The faith components were specifically linked to weekly DPP learning objectives to strategically emphasize behavioral skills with religious principles. Using a CBPR approach, the Better Me Within trial was able to enroll 12 churches, screen 333 AA women, and randomize 221 (Mage=48.8±11.2; MBMI=36.7±8.4; 52% technical or high school) after collection of objective eligibility measures. A prospective, randomized, nested by church, design will be used to evaluate the faith-enhanced DPP as compared to a standard DPP on weight, diabetes and cardiovascular risk, over a 16-week intervention and 10-month follow up. This study will provide essential data to guide enhancements to evidence-based lifestyle programs for AA women who are at high risk for chronic disease.