Search

Candida auris is an emerging fungal pathogen that exhibits resistance to multiple drugs, including the most commonly prescribed antifungal, fluconazole. Here, we use a combinatorial screening approach to identify a bis-benzodioxolylindolinone (azoffluxin) that synergizes with fluconazole against C. auris. Azoffluxin enhances fluconazole activity through the inhibition of efflux pump Cdr1, thus increasing intracellular fluconazole levels. This activity is conserved across most C. auris clades, with the exception of clade III. Azoffluxin also inhibits efflux in highly azole-resistant strains of Candida albicans, another human fungal pathogen, increasing their susceptibility to fluconazole. Furthermore, azoffluxin enhances fluconazole activity in mice infected with C. auris, reducing fungal burden. Our findings suggest that pharmacologically targeting Cdr1 in combination with azoles may be an effective strategy to control infection caused by azole-resistant isolates of C. auris.

Abstract Objectives We aimed to operationalize a head and neck microvascular free tissue transfer (MVFTT) program at a Veterans Affairs (VA) hospital with the emphasis on initiating radiotherapy within 6 weeks of surgery for cancer patients and minimizing readmissions. Study Design Case series. Setting Tertiary care VA hospital. Methods A retrospective analysis was performed on consecutive head and neck MVFTT patients from May 1, 2017 and April 30, 2022. Demographics, patient and disease characteristics, per‐operative data and postoperative outcomes were recorded from the electronic medical record. We sought to compare our rate of 30‐day readmissions with those published in the literature. Results One hundred and forty‐one procedures were performed in the queried timeframe. Eighty‐four percent (119) were performed after oncologic resections and 16% (22) were for nononcologic procedures. The rate of total flap loss was

Abstract The niche variation hypothesis (NVH) predicts that populations with wider niches exhibit greater morphological variation through increased interindividual differences in both niche and morphology. In this study, we examined niche–trait relationships in three passerine species (Cyanoderma ruficeps, Sinosuthora webbiana, and Zosterops simplex). A total of 289 C. ruficeps from 7 sites, 259 S. webbiana from 8 sites, and 144 Z. simplex from 6 sites were sampled along an elevation gradient (0–2,700 m) in Taiwan from 2009 to 2017. We measured bill traits (length, width, and depth of bill) and body size traits (length of head, tarsus, and wing) of the birds, which were reduced to four principal components (bill PC1, bill PC2, body size PC1, and body size PC2). We collected feather tissues for stable carbon and nitrogen isotope analyses to quantify their isotope niche. We quantified interindividual differences in isotope space and trait space with four diversity metrics (divergence, dispersion, evenness, and uniqueness) and tested whether interindividual differences in isotope space and trait space are positively associated. We quantified population isotope niche width by Bayesian ellipse area and population morphological variation by variances of the PCs. The results showed that individual uniqueness in isotope niche and bill morphology (average closeness of individuals within the population isotope/trait space) were positively associated across three species. Furthermore, isotope niche width and bill PC1 (reflecting the size of bill) variation at population level were also positively associated across the three species, supporting the NVH. Of the three species, C. ruficeps and S. webbiana showed stronger support for the NVH than Z. simplex, possibly due to the latter having narrower elevational distribution and a more specialized, plant‐based diet. The diversity metrics represented different aspects of interindividual differences in niche/trait space, and for the passerines, individual uniqueness appeared to play an important role in their niche–trait dynamics.

The fungal pathogen Candida auris is resistant to multiple drugs including the common antifungal fluconazole. Here, Iyer et al. identify a compound that potentiates fluconazole activity against C. auris in vitro and in vivo by inhibiting a major efflux pump and thus increasing intracellular fluconazole accumulation.

Abstract Based on 20,000 records representing c. 11,000 individuals from an 8-year capture-mark-recapture (CMR) study, we tested and confirmed a new case of invariant clutch size (ICS) in a sexually dichromatic lacertid lizard, Takydromus viridipunctatus. In the grassland habitat of the early succession stage, females showed strictly low and invariant clutch size, multiple clutches in a breeding season, high reproductive potential, and annual breeding cycles that correspond to the emergence of male courtship coloration. The hatchlings mature quickly, and join the adult cohort for breeding within a few months, whereas adults show low survival rates and a short lifespan, such that most die within one year. Mortality increased in both sexes during the breeding season, especially in females, indicating an unequal cost of reproduction in survival. These life history characters may be explained by two non-exclusive hypotheses of ICS—arboreal hypothesis and predation hypothesis—within the ecological context of their habitat. Our study highlights a confirmed case of ICS, which adapts well to this r-selected grassland habitat that experiences seasonal fluctuation and frequent disturbance.

Women remain underrepresented in physical science, engineering, and computer science college majors and careers. Prior research has suggested that motivational beliefs and experiences in high school play a critical role in girls' persistence in science fields. We hypothesized that compared to male students, female high school students may experience less daily autonomy support from teachers and lower psychological need satisfaction in physics, chemistry, and engineering courses. In turn, we expected that these differences would explain girls' lower daily engagement in these courses compared to boys. In line with current trends indicating gender parity in biology and biomedical fields, we did not expect to find gender differences in biology courses. Results from a six-week intensive longitudinal study in which high school students reported their daily experiences of teacher autonomy support, need satisfaction, and engagement during science class supported our hypotheses. The implications of the results for theory and practice are discussed.

This diary study provided the first classroom-based empirical test of the relations between student perceptions of high school science teachers' various autonomy supporting and thwarting practices and students' motivation and engagement on a daily basis over the course of an instructional unit. Perceived autonomy supporting practices were hypothesized to predict autonomous motivation and engagement outcomes, while perceived autonomy thwarting practices were hypothesized to predict controlled motivation and disaffection outcomes. In line with this prediction, multilevel modeling results based on regular reports of 208 high school students in 41 science classes across 6 weeks suggested that 4 perceived daily supports (choice provision, consideration for student preferences and interests, rationales for importance, and question opportunities) and 1 daily thwart (use of uninteresting activities) predicted changes in daily autonomous motivation and engagement. In contrast, changes in students' daily controlled motivation and disaffection were predicted primarily by 3 perceived daily thwarts (controlling messages, suppression of student perspectives, and use of uninteresting activities). Results also suggested that practices interacted such that the perception of thwarts generally bolstered desirable daily relationships between perceived supports and students' motivation and the perception of supports generally mitigated undesirable daily relationships between thwarts and motivation. Supplemental exploratory results suggested that the effects of choice and suppression of student perspectives may be heterogeneous and depend on the outcome and/or the presence of other practices. Implications of the findings are discussed.

EEG is a convenient method to study the functional state of the brain and brainbody-mind connection. This study investigates the EEG signal during meditation; a mental activity described as being in a state of calmness and focused attention. The objective is to study and extract features present in the EEG signal during meditation. The approach taken to extract EEG features associated with meditation is done through time series analysis, using the normalised signal amplitude mean as the primary feature. EEG signal is recorded at point F3 and F4, during meditation and post-meditation. A significant difference in signal amplitude means between these two states of the mind was observed. A 82.4% classification accuracy was achieved when using a BLR model to automatically classify the signal amplitude mean.

BackgroundSerum amyloid A (SAA), a potent inflammatory mediator, and Janus kinase 2 (JAK2), an intracellular signaling kinase, are increased by diabetes. The aims were to elucidate: 1) a JAK2-mediated pathway for increased SAA in the kidneys of diabetic mice; 2) a JAK2-SAA pathway for inflammation in podocytes.MethodsAkita diabetic mice (129S6) with podocyte JAK2 overexpression and angiotensin II infusion (4 weeks) were given a JAK1,2 inhibitor (LY03103801, 3 mg/kg/day orally for the last two weeks). Kidneys were immunostained for SAA isoform 3 (SAA3). SAA3 knockout and control mouse podocytes were exposed to advanced glycation end products (AGE) or exogenous SAA with JAK2 inhibition (Tyrphostin AG 490, 50μM). JAK2 activity (phosphorylation, Western blot, 1 hour) and mRNA for SAA3 and associated inflammatory genes (Cxcl5, Ccl2, and Ccl5) were measured by RT-PCR (20 hours).ResultsSAA3 protein was present throughout the diabetic kidney, and podocyte JAK2 overexpression increased tubulointerstitial SAA3 compared to wild type diabetic controls, 43% versus 14% (p = 0.007); JAK1,2 inhibition attenuated the increase in SAA3 to 15% (p = 0.003). Urine albumin-to-creatinine ratio (r = 0.49, p = 0.03), mesangial index (r = 0.64, p = 0.001), and glomerulosclerosis score (r = 0.51, p = 0.02) were associated with SAA3 immunostaining scores across mouse groups. Exposing podocytes to AGE or exogenous SAA increased JAK2 activity within one hour and mRNA for associated inflammatory genes after 20 hours. JAK2 inhibition reduced SAA3 mRNA expression in podocytes exposed to AGE or SAA. SAA3 knockout podocytes had >85% lower AGE-induced inflammatory genes.ConclusionJAK1,2 inhibition reduced SAA and histological features of DKD in podocyte JAK2-overexpressing mice. In podocytes exposed to a diabetes-like condition, JAK2 inhibition reduced expression of SAA, while SAA knockout blocked expression of associated pro-inflammatory mediators. SAA may promote JAK2-dependent inflammation in the diabetic kidney.

Values are freely chosen life directions and/or qualities of being that can motivate behavior change. There is nascent support for the utility of values work as a part of the therapeutic process across treatments, particularly in third wave therapy approaches (e.g., acceptance and commitment therapy). However, therapeutic values work is underresearched in clinical samples of youth. The aim of the present study is to examine the role of the two distinct values processes (engagement and obstruction), body image inflexibility, alongside other common comorbid symptoms of eating disorders (anxiety, depression) in a sample of female adolescents with eating disorders attending a residential eating disorder treatment program. Participants (N = 75) were patients at a residential eating disorder treatment facility and completed a battery of measures at time of admission. Correlational analyses and multiple regression were performed. Results found correlations between eating disorder severity, values engagement, values obstruction, body image flexibility, anxiety, and depression in the expected directions. Regression results found body image inflexibility, progression towards values, and anxiety as significant predictors of eating disorder severity (adjusted R2 =.54). This study points to the importance of emphasizing values engagement in youth with eating disorders, highlighting a potential treatment target for future research. [ABSTRACT FROM AUTHOR]