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Colleges and universities increasingly employ temporary instructors. Researchers in higher education have voiced strong concerns about this trend because of its impact on educational outcomes, operations of academic institutions, and the composition of academic workforce. To enhance our understanding of this employment practice, this article makes three contributions to the research on the growing non-tenured employment in academia. First, we advance the theory by arguing that the "value co-creation framework," also referred to as "service science," is an appropriate theoretical lens for studying higher education, including faculty employment. Second, we use this framework to analyze operations of a selective undergraduate program in Finland that has been functioning for over 30 years without permanent teaching faculty. Housed at a premier business school, the program relies on an expansive international network of instructors who travel to teach on short-term contracts. Third, we demonstrate that the staffing model used by this Finnish program is distinct from other forms of temporary academic employment, and therefore we label it "a networked faculty staffing model." To the best of our knowledge, this is the first time the "value co-creation framework" is used as a theoretical lens to study employment in higher education. Moreover, this is the first time "a networked faculty staffing model" is explicitly identified and described. Besides researchers, this article might be of interest to the diverse international audience who are involved in management and policy setting in higher education.

BACKGROUND: Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence. METHODS: We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate. RESULTS: 724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/μL; IQR: 9-76) and lower CSF white blood cell (WBC; 4 cells/μL; IQR: 4-85) counts than paradoxical IRIS (CD4: 78 cells/μL; IQR: 47-142; WBC: 45 cells/μL; IQR: 8-128). Among those with CSF WBC

Background: The phenomena of emerging infectious diseases accelerating once they reach healthcare facilities have been well documented. Outbreaks of MERS-CoV, SARS-CoV, and COVID-19 have led to in-hospital transmission where the initial patient infects healthcare workers, patients, visitors, etc., with infection control policies unable to curtail the spread early on. We refer to this phenomenon as nosocomial amplification. Nosocomial amplification causes an undue burden on a hospital that’s already strained from the pandemic. We aimed to understand which hospital-level parameters impact the community most and vice versa. Methods: We adapted an SEIR compartmental model to have two interconnected units, a community unit and a hospital special care unit, to determine the number of COVID-19 acquisitions in each of them over a hypothetical year. The model was stochastically simulated using Gillespie’s Direct Method for 1000 iterations. A parameter sensitivity analysis assessed the effects each parameter had on the model. The original values of all parameters were allowed to vary +/- 50%. The number of simulation acquisitions was normalized as a percent change from the original model’s mean acquisition. Results: Our analysis found that parameters impacting the community had a disproportionate impact on COVID-19 acquisitions in the hospital as compared to the special care unit, as did the parameters governing the level of asymptomatic transmission. Transmission between healthcare workers facilitated within-hospital transmission even when strict patient-based cohorting and testing were in place. Extensive community-level transmission was also found to readily overwhelm hospital-level infection control at realistic levels of effectiveness and compliance. Conclusion: These findings illustrate that hospitals and the community are tightly linked systems. Hospitals may reintroduce infection into the community that might have contained or mitigated ongoing outbreaks or introduce the disease into a disease-free population; community transmission puts tremendous pressure on infection control. In the future, we can model policies to curb an existing COVID-19 outbreak or subsequent outbreaks to avoid or minimize nosocomial amplification, thus improving the disproportionate burdens on the healthcare system.

Understanding the impact of mpox-related hospitalizations for medical versus infection control indications in New York City Background: New York City (NYC) accounted for 15-20% of new mpox infections at the peak of the 2022-2023 United States outbreak. Globally, 8% of mpox patients required hospitalization. We investigated the proportion of mpox hospitalizations for medical versus infection control indications at two large healthcare systems in the New York metropolitan area. Methods: We included all patients admitted to NYU Langone Health or NYC Health + Hospitals for laboratory-confirmed mpox between May 1, 2022, and April 28, 2023. We analyzed demographic information, reasons for hospitalization, length of stay, number and type of co-infections, healthcare encounters, complications, and treatments received. Results: Sixty-five patients were hospitalized for mpox, with 8 (12%) admitted primarily for infection control isolation (Table 1). Median age was 35 years (IQR=31-40), 69% were cisgender men, and 38% were Black. Those hospitalized primarily for isolation were more likely to reside in a homeless shelter (50% vs. 9%, p < 0 .01) and less likely to have a private residence (25% vs. 81%, p < 0 .01) than those hospitalized for medical indications. Those hospitalized for medical indications were more likely to have HIV (63% vs. 25%, p=0.04), secondary bacterial infections (67% vs. 25%, p=0.02), and to receive antibiotics (82% vs. 25%, p < 0 .01) (Tables 2 and 3). There was no significant difference in median cumulative length of stay per patient (p=0.69) between those hospitalized for medical versus isolation purposes. Most admissions for medical indications were for soft tissue superinfection (40%), severe pharyngitis and/or proctitis (28%) and pain management (20%). There was no significant difference in the proportion of tecovirimat receipt (65% vs. 38%, p=0.14) between those hospitalized for medical versus isolation purposes. Conclusion: Infection control isolation accounted for a significant proportion (12%) of mpox hospitalizations and was associated with a similar median length of stay per patient as hospitalization for medical indications. Our small cohort limits statistical power for comparison between groups. However, our findings argue for increased community-based isolation capacity. This may reduce unnecessary hospitalizations during future outbreaks, particularly amongst unsheltered individuals or those living in congregate settings.

Objectives Perinatal substance use is a growing concern across the United States. Universal screening, brief intervention, and referral to treatment (SBIRT) is one systems-level approach to addressing perinatal substance use. The objective of this study is to assess early efforts to implement SBIRT in an outpatient obstetric clinic. Methods The research team implemented universal screening with the 5 P&apos;s screening tool. Providers then engaged patients in a brief intervention and referred to a care manager who then worked with patients via tele-health to connect patients with needed services. Feasibility was measured through the collection of aggregate data describing frequency of universal screening and referral to treatment. The implementation team met bi-weekly to reflect on implementation barriers and facilitators. Results In the first year of implementation, 48.5% of patients receiving care in the clinic completed the 5 P&apos;s screener at least once during the perinatal period. Screening occurred in a little over a quarter (26.5%) of eligible visits. Of the 463 patients that completed the 5 P&apos;s at least once during the perinatal period, 195 (42%) unique patients screened positive (answered yes to at least one question). Conclusions for Practice Early implementation efforts suggest this approach is feasible in this obstetric setting. Similar implementation studies should consider implementing universal screening for substance use and perinatal mood and anxiety disorders simultaneously; guide efforts using an implementation framework; invest resources in more intensive training and ongoing coaching for providers; and adopt strategies to track frequency and fidelity of brief intervention., Author(s): Sarah E. Reese [sup.1] [sup.2] [sup.4] , Annie Glover [sup.1] , Stephanie Fitch [sup.3] , Joe Salyer [sup.3] , Valerie Lofgren [sup.3] , Clayton "Tersh" McCracken III [sup.3] Author [...]

Abstract Acute kidney injury is a common complication of trauma and hemorrhagic shock. In a porcine model of hemorrhagic shock, resuscitative endovascular balloon aortic occlusion (REBOA) and hemodilution, we hypothesized that invasive kidney oxygen concentration measurements would correlate more strongly with noninvasive near infra-red spectroscopy (NIRS) oxygen saturation measurements when cutaneous sensors were placed over the kidney under ultrasound guidance compared to placement over the thigh muscle and subcutaneous tissue. Eight anesthetized swine underwent hemorrhagic shock 4 of which were resuscitated with intravenous fluids prior to the return of shed blood (Hemodilution protocol) and 4 of which underwent REBOA prior to resuscitation and return of shed blood (REBOA protocol). There was a moderate correlation between the NIRS and kidney tissue oxygen measurements (r = 0.61 p

Purpose: Finance is a male-dominated field of work. This study aims to understand if learning in finance follows the same pattern. Furthermore, the authors want to understand if foreign female students are subject to the same cultural norms and sorting mechanisms as their counterparts from the USA or Finland. Design/methodology/approach: In the context of a capstone course, students of two well-known international business programs (one in the USA, the other in Finland) participate in a business simulation. The authors surveyed the students on their learning experience across different business functions. The authors collected 440 responses over five years. Findings: A gender gap exists in learning finance. Females surveyed reported learning less (9%-15%) than males. However, foreign females reported learning more (11%-17%). Additionally, the authors find no gender gap in learning of other business functions (i.e. marketing and strategy). Foreign females seem to bypass traditional roles and sorting mechanisms. Originality/value: To the best of the authors' knowledge, this study is the first to document the moderating effect of foreignness on the gender gap in learning.

Background Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterising recent RVF disease events in East Africa.Methods Data on 100 disease events (2008–2022) from Kenya, Uganda and Tanzania were obtained from public databases and institutions, and modelled against possible geoecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalised difference vegetation index (NDVI), livestock production system, land-use change and long-term climatic variations. Decadal climatic variations between 1980 and 2022 were evaluated for association with the changing disease pattern.Results Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1–3) and three livestock cases (IQR, 2–7). These clusters exhibited minimal human mortality (IQR, 0–1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geoecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1°C increase in temperature and a 1-unit increase in NDVI, one months prior were associated with increased RVF incidence rate ratios of 1.20 (95% CI 1.1, 1.2) and 1.93 (95% CI 1.01, 3.71), respectively. Long-term climatic trends showed a significant decadal increase in annual mean temperature (0.12–0.3°C/decade, p

Abstract Fungal conservation is gaining momentum globally, but many challenges remain. To advance further, more data are needed on fungal diversity across space and time. Fundamental information regarding population sizes, trends, and geographic ranges is also critical to accurately assess the extinction risk of individual species. However, obtaining these data is particularly difficult for fungi due to their immense diversity, complex and problematic taxonomy, and cryptic nature. This paper explores how citizen science (CS) projects can be leveraged to advance fungal conservation efforts. We present several examples of past and ongoing CS‐based projects to record and monitor fungal diversity. These include projects that are part of broad collecting schemes, those that provide participants with targeted sampling methods, and those whereby participants collect environmental samples from which fungi can be obtained. We also examine challenges and solutions for how such projects can capture fungal diversity, estimate species absences, broaden participation, improve data curation, and translate resulting data into actionable conservation measures. Finally, we close the paper with a call for professional mycologists to engage with amateurs and local communities, presenting a framework to determine whether a given project would likely benefit from participation by citizen scientists.

ABSTRACTEctomycorrhizal fungi establish mutually beneficial relationships with trees, trading nutrients for carbon. Suillus are ectomycorrhizal fungi that are critical to the health of boreal and temperate forest ecosystems. Comparative genomics has identified a high number of non-ribosomal peptide synthetase and terpene biosynthetic gene clusters (BGC) potentially involved in fungal competition and communication. However, the functionality of these BGCs is not known. This study employed co-culture techniques to activate BGC expression and then used metabolomics to investigate the diversity of metabolic products produced by three Suillus species (Suillus hirtellus EM16, Suillus decipiens EM49, and Suillus cothurnatus VC1858), core members of the pine microbiome. After 28 days of growth on solid media, liquid chromatography–tandem mass spectrometry identified a diverse range of extracellular metabolites (exometabolites) along the interaction zone between Suillus co-cultures. Prenol lipids were among the most abundant chemical classes. Out of the 62 unique terpene BGCs predicted by genome mining, 41 putative prenol lipids (includes 37 putative terpenes) were identified across the three Suillus species using metabolomics. Notably, some terpenes were significantly more abundant in co-culture conditions. For example, we identified a metabolite matching to isomers isopimaric acid, sandaracopimaric acid, and abietic acid, which can be found in pine resin and play important roles in host defense mechanisms and Suillus spore germination. This research highlights the importance of combining genomics and metabolomics to advance our understanding of the chemical diversity underpinning fungal signaling and communication.IMPORTANCEUsing a combination of genomics and metabolomics, this study’s findings offer new insights into the chemical diversity of Suillus fungi, which serve a critical role in forest ecosystems.

Birds are highly susceptible to aspergillosis, which can manifest as a primary infection in both domestic and wild birds. Aspergillosis in wild birds causes mortalities ranging in scale from single animals to large-scale epizootic events. However, pathogenicity factors associated with aspergillosis in wild birds have not been examined. Specifically, it is unknown whether wild bird-infecting strains are host-adapted (i.e. phylogenetically related). Similarly, it is unknown whether epizootics are driven by contact with clonal strains that possess unique pathogenic or virulence properties, or by distinct and equally pathogenic strains. Here, we use a diverse collection of Aspergillus fumigatus isolates taken from aspergillosis-associated avian carcasses, representing 24 bird species from a wide geographic range, and representing individual bird mortalities as well as epizootic events. These isolates were sequenced and analyzed along with 130 phylogenetically diverse human clinical isolates to investigate the genetic diversity and phylogenetic placement of avian-associated A. fumigatus, the geographic and host distribution of avian isolates, evidence for clonal outbreaks among wild birds, and the frequency of azole resistance in avian isolates. We found that avian isolates were phylogenetically diverse, with no clear distinction from human clinical isolates, and no sign of host or geographic specificity. Avian isolates from the same epizootic events were diverse and phylogenetically distant, suggesting that avian aspergillosis is not contagious among wild birds and that outbreaks are likely driven by environmental spore loads or host comorbidities. Finally, all avian isolates were susceptible to Voriconazole and none contained the canonical azole resistance gene variants.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

Aspergillus fumigatus is a deadly agent of human fungal disease where virulence heterogeneity is thought to be at least partially structured by genetic variation between strains. While population genomic analyses based on reference genome alignments offer valuable insights into how gene variants are distributed across populations, these approaches fail to capture intraspecific variation in genes absent from the reference genome. Pan-genomic analyses based on de novo assemblies offer a promising alternative to reference-based genomics with the potential to address the full genetic repertoire of a species. Here, we evaluate 260 genome sequences of A. fumigatus including 62 newly sequenced strains, using a combination of population genomics, phylogenomics, and pan-genomics. Our results offer a high-resolution assessment of population structure and recombination frequency, phylogenetically structured gene presence-absence variation, evidence for metabolic specificity, and the distribution of putative antifungal resistance genes. Although A. fumigatus disperses primarily via asexual conidia, we identified extraordinarily high levels of recombination with the lowest linkage disequilibrium decay value reported for any fungal species to date. We provide evidence for 3 primary populations of A. fumigatus, with recombination occurring only rarely between populations and often within them. These 3 populations are structured by both gene variation and distinct patterns of gene presence-absence with unique suites of accessory genes present exclusively in each clade. Accessory genes displayed functional enrichment for nitrogen and carbohydrate metabolism suggesting that populations may be stratified by environmental niche specialization. Similarly, the distribution of antifungal resistance genes and resistance alleles were often structured by phylogeny. Altogether, the pan-genome of A. fumigatus represents one of the largest fungal pan-genomes reported to date including many genes unrepresented in the Af293 reference genome. These results highlight the inadequacy of relying on a single-reference genome-based approach for evaluating intraspecific variation and the power of combined genomic approaches to elucidate population structure, genetic diversity, and putative ecological drivers of clinically relevant fungi.

NATSUKO IMAMURA This Is Amiko, Do You Copy? Trans. Hitomi Yoshio. London. Pushkin Press. 2023. 128 pages. WHEN NATSUKO IMAMURA (b. 1980) initially published the novella This Is Amiko, Do [...]

Aspergillus fumigatus isolates display significant heterogeneity in growth, virulence, pathology, and inflammatory potential in multiple murine models of invasive aspergillosis. Previous studies have linked the initial germination of a fungal isolate in the airways to the inflammatory and pathological potential, but the mechanism(s) regulating A. fumigatus germination in the airways is unresolved. To explore the genetic basis for divergent germination phenotypes, we utilized a serial passaging strategy in which we cultured a slow germinating strain (AF293) in a murine-lung-based medium for multiple generations. Through this serial passaging approach, a strain emerged with an increased germination rate that induces more inflammation than the parental strain (herein named LH-EVOL for lung homogenate evolved). We identified a potential loss-of-function allele of Afu5g08390 (sskA) in the LH-EVOL strain. The LH-EVOL strain had a decreased ability to induce the SakA-dependent stress pathway, similar to AF293 ΔsskA and CEA10. In support of the whole-genome variant analyses, sskA, sakA, or mpkC loss-of-function strains in the AF293 parental strain increased germination both in vitro and in vivo. Since the airway surface liquid of the lungs contains low glucose levels, the relationship of low glucose concentration on germination of these mutant AF293 strains was examined; interestingly, in low glucose conditions, the sakA pathway mutants exhibited an enhanced germination rate. In conclusion, A. fumigatus germination in the airways is regulated by SskA through the SakA mitogen-activated protein kinase (MAPK) pathway and drives enhanced disease initiation and inflammation in the lungs. IMPORTANCE Aspergillus fumigatus is an important human fungal pathogen particularly in immunocompromised individuals. Initiation of growth by A. fumigatus in the lung is important for its pathogenicity in murine models. However, our understanding of what regulates fungal germination in the lung environment is lacking. Through a serial passage experiment using lung-based medium, we identified a new strain of A. fumigatus that has increased germination potential and inflammation in the lungs. Using this serially passaged strain, we found it had a decreased ability to mediate signaling through the osmotic stress response pathway. This finding was confirmed using genetic null mutants demonstrating that the osmotic stress response pathway is critical for regulating growth in the murine lungs. Our results contribute to the understanding of A. fumigatus adaptation and growth in the host lung environment.

Fungi have successfully established themselves across seemingly every possible niche, substrate, and biome. They are fundamental to biogeochemical cycling, interspecies interactions, food production, and drug bioprocessing, as well as playing less heroic roles as difficult to treat human infections and devastating plant pathogens. Despite community efforts to estimate and catalog fungal diversity, we have only named and described a minute fraction of the fungal world. The identification, characterization, and conservation of fungal diversity is paramount to preserving fungal bioresources, and to understanding and predicting ecosystem cycling and the evolution and epidemiology of fungal disease. Although species and ecosystem conservation are necessarily the foundation of preserving this diversity, there is value in expanding our definition of conservation to include the protection of biological collections, ecological metadata, genetic and genomic data, and the methods and code used for our analyses. These definitions of conservation are interdependent. For example, we need metadata on host specificity and biogeography to understand rarity and set priorities for conservation. To aid in these efforts, we need to draw expertise from diverse fields to tie traditional taxonomic knowledge to data obtained from modern -omics-based approaches, and support the advancement of diverse research perspectives. We also need new tools, including an updated framework for describing and tracking species known only from DNA, and the continued integration of functional predictions to link genetic diversity to functional and ecological diversity. Here, we review the state of fungal diversity research as shaped by recent technological advancements, and how changing viewpoints in taxonomy, -omics, and systematics can be integrated to advance mycological research and preserve fungal biodiversity.

Uterine carcinosarcoma (UCS) is a rare but aggressive endometrial cancer. Survival outcomes for women diagnosed with UCS remain poor with lower survival than those of endometrioid or high-grade serous uterine cancers. The histopathological hallmark of carcinosarcoma is the presence of both sarcomatous and carcinomatous elements. The survival rates for UCS have not improved for over 40 years; therefore, there is a profound need to identify new treatments. To investigate novel chemotherapy treatment combinations for UCS, we generated a UCS patient-derived organoid (PDO) cell line from a patient that received neoadjuvant treatment with paclitaxel and carboplatin. The PDO cell line (UCS1) was grown in three-dimensional domes. The PDO domes were treated with six individual chemotherapies or nine combinations of those six drugs. Cell death in response to chemotherapy was assessed. We found that the six monotherapies had minimal effectiveness at inducing cell death after 48 h of treatment. The combination of paclitaxel and carboplatin (which is the standard-of-care chemotherapy treatment for UCS) led to a small increase in apoptosis compared with the monotherapies. Importantly, when either carboplatin or paclitaxel was combined with gemcitabine, there was an appreciable increase in cell death. In conclusion, for the UCS1 patient-derived tumor cells, gemcitabine combinations were more effective than carboplatin/paclitaxel. Our data support the use of PDOs to predict responses to second-line chemotherapy.

IntroductionThis study examined the relationship between fat distribution and diabetes by sex-specific racial/ethnic groups.MethodsA secondary data analysis of National Health and Nutrition Examination Survey 2011–2018 data (n = 11,972) was completed. Key variables examined were visceral adipose tissue area (VATA), subcutaneous fat area (SFA), diabetes prevalence, and race/ethnicity. The association of VATA and SFA and diabetes prevalence was examined separately and simultaneously using multiple logistic regression. Bonferroni corrections were applied to all multiple comparisons between racial/ethnic groups. All analyses were adjusted for demographics and muscle mass.ResultsVATA was positively associated with diabetes in both sexes (p

Objective: Create a longitudinal, multi-modal and multi-level surveillance cohort that targets early detection of symptomatic and asymptomatic COVID-19 cases among Native Hawaiian and Pacific Islander adults in the Continental US and identify effective modalities for participatory disease surveillance and sustainably integrate them into ongoing COVID-19 and other public health surveillance efforts. Materials and methods: We recruited cohorts from three sites: Federal Way, WA; Springdale, AR; and remotely. Participants received a survey that included demographic characteristics and questions regarding COVID-19. Participants completed symptom checks via text message every month and recorded their temperature daily using a Kinsa smart thermometer. Results: Recruitment and data collection is ongoing. Presently, 441 adults have consented to participate. One-third of participants were classified as essential workers during the pandemic. Discussion: Over the past 18 months, we have improved our strategies to elicit better data from participants and have learned from some of the weaknesses in our initial deployment of this type of surveillance system. Other limitations stem from historic inequities and barriers which limited Native Hawaiian and Pacific Island representation in academic and clinical environments. One manifestation of this was the limited ability to provide study materials and support in multiple languages. We hope that continued partnership with the community will allow further opportunities to help restore trust in academic and medical institutions, thus generating knowledge to advance health equity. Conclusion: This participatory disease surveillance mechanism complements traditional surveillance systems by engaging underserved communities. We may also gain insights generalizable to other pathogens of concern.

The prevalence of Aspergillus fumigatus colonization in individuals with cystic fibrosis (CF) and subsequent fungal persistence in the lung is increasingly recognized. However, there is no consensus for clinical management of A. fumigatus in CF individuals, due largely to uncertainty surrounding A. fumigatus CF pathogenesis and virulence mechanisms. To address this gap in knowledge, a longitudinal series of A. fumigatus isolates from an individual with CF were collected over 4.5 years. Isolate genotypes were defined with whole-genome sequencing that revealed both transitory and persistent A. fumigatus in the lung. Persistent lineage isolates grew most readily in a low-oxygen culture environment, and conidia were more sensitive to oxidative stress-inducing conditions than those from nonpersistent isolates. Closely related persistent isolates harbored a unique allele of the high-osmolarity glycerol (HOG) pathway mitogen-activated protein kinase kinase, Pbs2 (pbs2C2). Data suggest this novel pbs2C2 allele arose in vivo and is necessary for the fungal response to osmotic stress in a low-oxygen environment through hyperactivation of the HOG (SakA) signaling pathway. Hyperactivation of the HOG pathway through pbs2C2 comes at the cost of decreased conidial stress resistance in the presence of atmospheric oxygen levels. These novel findings shed light on pathoadaptive mechanisms of A. fumigatus in CF, lay the foundation for identifying persistent A. fumigatus isolates that may require antifungal therapy, and highlight considerations for successful culture of persistent Aspergillus CF isolates. IMPORTANCE Aspergillus fumigatus infection causes a spectrum of clinical manifestations. For individuals with cystic fibrosis (CF), allergic bronchopulmonary aspergillosis (ABPA) is an established complication, but there is a growing appreciation for A. fumigatus airway persistence in CF disease progression. There currently is little consensus for clinical management of A. fumigatus long-term culture positivity in CF. A better understanding of A. fumigatus pathogenesis mechanisms in CF is expected to yield insights into when antifungal therapies are warranted. Here, a 4.5-year longitudinal collection of A. fumigatus isolates from a patient with CF identified a persistent lineage that harbors a unique allele of the Pbs2 mitogen-activated protein kinase kinase (MAPKK) necessary for unique CF-relevant stress phenotypes. Importantly for A. fumigatus CF patient diagnostics, this allele provides increased fitness under CF lung-like conditions at a cost of reduced in vitro growth under standard laboratory conditions. These data illustrate a molecular mechanism for A. fumigatus CF lung persistence with implications for diagnostics and antifungal therapy.

BackgroundIt is unknown whether prenatal lipid-based nutrient supplements (LNSs) affect blood pressure (BP). Associations between hypertension and birth outcomes using recently updated BP cutoffs are undetermined.ObjectivesWe aimed to assess the impact of LNSs on maternal hypertension and associations between hypertension and birth outcomes.MethodsPregnant Ghanaian women at ≤20 weeks of gestation (n = 1320) were randomly assigned to receive daily 1) iron and folic acid (IFA), 2) multiple micronutrients (MMN), or 3) LNSs until delivery. BP was measured at enrollment and 36 weeks of gestation. We analyzed the effect of LNSs on BP using ANOVA and associations between hypertension [systolic BP (SBP) ≥130 mm Hg or diastolic BP (DBP) ≥80 mm Hg] and birth outcomes by linear and logistic regressions.ResultsMean ± SD SBP and DBP were 110 ± 11 and 63 ± 8 mm Hg at 36 weeks of gestation and did not differ by supplementation group (SBP, P > 0.05; DBP, P > 0.05). At enrollment, higher DBP was associated with lower birth weight and shorter gestation; women with high DBP had greater risk of low birth weight (LBW) [risk ratio (RR): 2.58; 95% CI: 1.09, 6.08] and preterm birth (PTB) (RR: 3.30; 95% CI: 1.47, 7.40). At 36 weeks of gestation, higher SBP was associated with lower birth weight, length, and head circumference and shorter gestation; higher DBP was associated with lower birth weight and length; and women with high DBP had greater risk of LBW (RR: 3.39; 95% CI: 1.32, 8.69). Neither high SBP nor hypertension were associated with birth outcomes at either time point.ConclusionsDaily provision of LNSs does not affect maternal hypertension, compared with IFA and MMN. Higher SBP and DBP are associated with a shorter gestation and smaller birth size; however, only high DBP is associated with LBW and PTB. The new BP cutoffs may help identify pregnancies at risk of adverse birth outcomes.This trial was registered at clinicaltrials.gov as NCT00970866.

While there has been significant progress characterizing the 'symbiotic toolkit' of ectomycorrhizal (ECM) fungi, how host specificity may be encoded into ECM fungal genomes remains poorly understood. We conducted a comparative genomic analysis of ECM fungal host specialists and generalists, focusing on the specialist genus Suillus. Global analyses of genome dynamics across 46 species were assessed, along with targeted analyses of three classes of molecules previously identified as important determinants of host specificity: small secreted proteins (SSPs), secondary metabolites (SMs) and G-protein coupled receptors (GPCRs). Relative to other ECM fungi, including other host specialists, Suillus had highly dynamic genomes including numerous rapidly evolving gene families and many domain expansions and contractions. Targeted analyses supported a role for SMs but not SSPs or GPCRs in Suillus host specificity. Phylogenomic-based ancestral state reconstruction identified Larix as the ancestral host of Suillus, with multiple independent switches between white and red pine hosts. These results suggest that like other defining characteristics of the ECM lifestyle, host specificity is a dynamic process at the genome level. In the case of Suillus, both SMs and pathways involved in the deactivation of reactive oxygen species appear to be strongly associated with enhanced host specificity.