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Background The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs). Methods All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5–11 days) or PC (12–24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. Results A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7–11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14–16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P =.02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P =.03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31–1.47; P =.20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20–5.80; P =.94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35–1.50; P =.38) did not differ between groups. Conclusions Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia. [ABSTRACT FROM AUTHOR]

Background. Glucose infusion test (GIT) is a new method to measure vascular access recirculation (R) based on basal glucose increase in the arterial blood line after a 20% glucose bolus (5 ml) into the venous chamber. [ABSTRACT FROM PUBLISHER]

Background. Blood flow (Qa) measurements are an important step in the surveillance protocol of haemodialysis vascular access (VA). The glucose pump test (GPT) is a new test for Qa measurement based on the dilution of a constant glucose infusion. The aim of this study is to verify the clinical accuracy of GPT in a graft surveillance protocol with sequential Qa measurements.Methods. In 30 chronic haemodialysis patients with graft, we compared monthly sequential Qa measurements performed with GPT in pre-dialysis and the ultrasound dilution technique (HD01 device Transonic Systems Inc., USA) during dialysis. The colour Doppler ultrasonography study (CDU) was our reference standard for the diagnosis of stenosis. The endpoints were the graft thrombosis or PTA treatment.Results. According to the K/DOQI guidelines we could identify the thrombosis high-risk grafts when Qa was <600 ml/min or <1000 ml/min with a decrease >25% in serial Qa measurements. HD01 yielded 27 of 112 high-risk Qa measurements (21 Qa <600 ml/min; mean 406±145 ml/min; 6 ΔQa >25%; mean 43±7%). In 12 of 27 cases the CDU control did not show haemodynamically significant stenoses (false positive); 15 of 27 cases were confirmed high-risk accesses by CDU and did PTAs (HD01 specificity 86%). GPT yielded 14 of 112 high-risk Qa measurements (8 Qa <600 ml/min; mean 404±135 ml/min; 6 ΔQa >25%; mean 38±8%) and all had severe stenoses and underwent PTA treatments showing a GPT specificity of 100%. The CDU study allowed us to correctly assess the Qa negative cases. HD01 method had 10 false negative cases (treated or clotted grafts with a Qa >600 ml/min and ΔQa <25%) with a sensitivity of 60%, while GPT had 11 false negative cases with a sensitivity of 56%. The diagnostic accuracy tested with the ROC curves was similar with both tests (area under the curve was 0.762 and 0.752 with GPT and ultrasound dilution, respectively; P = 0.985). The diagnostic efficiency (percentage of grafts with agreement between test result and factual situation) was 90 and 80% (P = 0.056) for GPT and HD01, respectively.Conclusion. Compared with HD01, the GPT had a lower false positive rate and similar diagnostic accuracy and efficiency. The clinical implication is a smaller number of unnecessary, invasive procedures (angiographies or PTAs), without increasing the thrombosis risk. This study has shown that GPT is an accurate, quick and economic test for Qa monitoring. [ABSTRACT FROM AUTHOR]

Background. A good test for monitoring blood flow (Qa) must be accurate, rapid and economical in order to allow frequent easy measurements. The glucose pump test (GPT) is based on a constant glucose infusion as a dilutional indicator of Qa. [ABSTRACT FROM PUBLISHER]

The mechanism responsible for proteinuria in non-genetic idiopathic nephrotic syndrome (iNS) is unknown. Animal models suggest an effect of free radicals on podocytes, and indirect evidence in humans confirm this implication. We determined the oxidative burst by blood CD15+ polymorphonucleates (PMN) utilizing the 5-(and-6)-carboxy-2′,7′-dichlorofluorescin diacetate (DCF-DA) fluorescence assay in 38 children with iNS. Results were compared with PMN from normal subjects and patients with renal pathologies considered traditionally to be models of oxidative stress [six anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis, seven post-infectious glomerulonephritis]. Radicals of oxygen (ROS) production was finally determined in a patient with immunodeficiency, polyendocrinopathy, enteropathy X-linked (IPEX) and in seven iNS children after treatment with Rituximab. Results demonstrated a 10-fold increase of ROS production by resting PMN in iNS compared to normal PMN. When PMN were separated from other cells, ROS increased significantly in all conditions while a near-normal production was restored by adding autologous cells and/or supernatants in controls, vasculitis and post-infectious glomerulonephritis but not in iNS. Results indicated that the oxidative burst was regulated by soluble factors and that this regulatory circuit was altered in iNS. PMN obtained from a child with IPEX produced 100 times more ROS during exacerbation of clinical symptoms and restored to a near normal-level in remission. Rituximab decreased ROS production by 60%. In conclusion, our study shows that oxidant production is increased in iNS for an imbalance between PMN and other blood cells. Regulatory T cells (Tregs) and CD20 are probably involved in this regulation. Overall, our observations reinforce the concept that oxidants deriving from PMN are implicated in iNS. [ABSTRACT FROM AUTHOR]

Background. The problem of pure red cell aplasia (PRCA) prompted nephrologists to revert to a wider intravenous (i.v.) utilization of erythropoeitin (Epo). Once weekly i.v. Epo administration has been suggested to be as effective as the twice/thrice weekly i.v. dose. The aim of the present study was to test whether once weekly i.v. Epo administration is equally as cost-effective as once weekly subcutaneous (s.c.) and 2–3 times weekly i.v. administration.Methods. We prospectively studied 41 patients (23 males, aged 28–82 years), on renal replacement therapy for 18–286 months, stabilized on twice or thrice weekly s.c. Epo-α (basal). The patients were treated for three consecutive 6 month periods with once weekly s.c. (OWSC), once weekly i.v. (OWIV) and twice/thrice weekly i.v. (TWIV) Epo-α. The initial dose for each period was equal to the final dose of the previous one; when necessary, the dose was adjusted according to DOQY guidelines. Iron, folic acid and vitamin B12 supplementations were given throughout all the study periods. At the end of each of the four study periods, the following parameters were evaluated: haemoglobin, haematocrit, hypochromic red blood cells (RBCs), iron, serum ferritin, transferrin, folate, vitamin B12, C-reactive protein (CRP), Kt/V, parathyroid hormone (PTH) and weekly dose of Epo-α.Results. Thirty-three out of 41 enrolled patients completed the study (there were five deaths, two renal transplants and one transfer). No significant changes were observed as regards iron, serum ferritin, transferrin, folate, vitamin B12, CRP, Kt/V or PTH level. Haemoglobin levels were not different at the end of the basal (11.7±1.21), OWSC (11.8±0.86) and TWIV (12.1±1.04) periods, while significantly lower levels were observed after the OWIV period (11.0±0.97, P<0.01). Weekly Epo consumption (Epo U/week/kg body weight/g haemoglobin) was: basal 11.57±5.96; OWSC 10.22±4.53; OWIV 15.99±7.7*a; and TWIV 11.89±6.3*a (*P<0.01 vs basal; aP<0.01 vs OWSC).Conclusions. From our results, the OWIV schedule seems to have less efficacy in the control of anaemia of chronic renal failure patients on dialysis treatment than either OWSC or TWIV schedules. [ABSTRACT FROM AUTHOR]

Background The consequences of low-level viremia in people with HIV are unclear. We used data from the US Military HIV Natural History Study to examine the association of low-level viremia (LLV) and serious non-AIDS events (SNAEs). Methods Included participants initiated antiretroviral therapy after 1996 and had ≥3 viral loads (VLs) measured, using an assay with a lower limit of detection of <50 copies/mL, ≥6 months after antiretroviral therapy initiation. VLs were categorized as lower levels of LLV (51–199 copies/mL), higher level of low-level viremia (HLLV; 200–999 copies/mL), and (VF; ≥200 copies/mL on 2 or more successive determinations or a single VL ≥1000 copies/mL), and virologic suppression (VS; ie, VL <50 copies/mL). Viral blips (ie, VLs between 50 and 999 copies/mL that are preceded and succeeded by VL <50 copies/mL) were analyzed in the VS category. Cox proportional hazards models were used to examine the association of LLV and SNAEs, adjusted hazard ratios and 95% confidence intervals are presented. Results A total of 439 (17.4%) SNAEs were recorded among the 2528 participants (93% male, 40% Caucasian, 43% African American) followed for a median of 11 years. In 8.5% and 4.6% of the participants, respectively, LLV and HLLV were the highest recorded viremia strata. Compared with VS, SNAEs were associated with LLV (1.3 [1.2–1.4]), HLLV (1.6 [1.5–1.7]), and virologic failure (1.7 [1.7–1.8]). Conclusions The results of this study suggest that LLV is associated with the occurrence of SNAEs and needs further study. [ABSTRACT FROM AUTHOR]

Background An association between coronavirus disease 2019 (COVID-19)–associated invasive fungal infections (CAIFIs) and high mortality among intubated patients has been suggested in previous research. However, some of the current evidence was derived from small case series and multicenter studies conducted during different waves of the COVID-19 pandemic. We examined the incidence of CAIFIs and their associated mortality using a large, multicenter COVID-19 database built throughout the pandemic. Methods We conducted a retrospective analysis of the National COVID Cohort Collaborative (N3C) database collected from 76 medical centers in the United States between January 2020 and August 2022. Patients were 18 years or older and intubated after severe acute respiratory syndrome coronavirus 2 infection. The primary outcomes were incidence and all-cause mortality at 90 days. To assess all-cause mortality, we fitted Cox proportional hazard models after adjusting for confounders via inverse probability weighting. Results Out of the 4 916 229 patients with COVID-19 diagnosed during the study period, 68 383 (1.4%) met our cohort definition. The overall incidence of CAIFI was 2.80% (n = 1934/68 383). Aspergillus (48.2%; n = 933/1934) and Candida (41.0%; n = 793/1934) were the most common causative organisms. The incidence of CAIFIs associated with Aspergillus among patients who underwent BAL was 6.2% (n = 83/1328). Following inverse probability weighting, CAIFIs caused by Aspergillus (hazard ratio [HR], 2.0; 95% CI, 1.8–2.2) and Candida (HR, 1.7; 95% CI, 1.5–1.9) were associated with increased all-cause mortality. Systemic antifungals reduced mortality in 17% of patients with CAIFI with Aspergillus and 24% of patients with CAIFI with Candida. Conclusions The incidence of CAIFI was modest but associated with higher 90-day all-cause mortality among intubated patients. Systemic antifungals modified mortality. [ABSTRACT FROM AUTHOR]

Veins are a critical component of the plant growth and development system, playing an integral role in supporting and protecting leaves, as well as transporting water, nutrients, and photosynthetic products. A comprehensive understanding of the form and function of veins requires a dual approach that combines plant physiology with cutting-edge image recognition technology. The latest advancements in computer vision and machine learning have facilitated the creation of algorithms that can identify vein networks and explore their developmental progression. Here, we review the functional, environmental, and genetic factors associated with vein networks, along with the current status of research on image analysis. In addition, we discuss the methods of venous phenotype extraction and multi-omics association analysis using machine learning technology, which could provide a theoretical basis for improving crop productivity by optimizing the vein network architecture. [ABSTRACT FROM AUTHOR]

Cleavage and polyadenylation of pre-mRNAs is a necessary step for gene expression and function. Majority of human genes exhibit multiple polyadenylation sites, which can be alternatively used to generate different mRNA isoforms from a single gene. Alternative polyadenylation (APA) of pre-mRNAs is important for the proteome and transcriptome landscape. APA is tightly regulated during development and contributes to tissue-specific gene regulation. Mis-regulation of APA is linked to a wide range of pathological conditions. APA-mediated gene regulation in the heart is emerging as a new area of research. Here, we will discuss the impact of APA on gene regulation during heart development and in cardiovascular diseases. First, we will briefly review how APA impacts gene regulation and discuss molecular mechanisms that control APA. Then, we will address APA regulation during heart development and its dysregulation in cardiovascular diseases. Finally, we will discuss pre-mRNA targeting strategies to correct aberrant APA patterns of essential genes for the treatment or prevention of cardiovascular diseases. The RNA field is blooming due to advancements in RNA-based technologies. RNA-based vaccines and therapies are becoming the new line of effective and safe approaches for the treatment and prevention of human diseases. Overall, this review will be influential for understanding gene regulation at the RNA level via APA in the heart and will help design RNA-based tools for the treatment of cardiovascular diseases in the future. [ABSTRACT FROM AUTHOR]

Herbivory can impact gas exchange, but the causes of interspecific variation in response remain poorly understood. We aimed to determine (1) what effects does experimental herbivory damage to leaf midveins have on leaf gas exchange and, (2) whether changes in leaf gas exchange after damage was predicted by leaf mechanical or venation traits. We hypothesized that herbivory-driven impacts on leaf gas exchange would be mediated by (1a/1b) venation networks, either by more vein resistance, or possibly trading off with other structural defenses; (2a/2b) or more reticulation (resilience, providing more alternate flow pathways after damage) or less reticulation (sectoriality, preventing spread of reduced functionality after damage). We simulated herbivory by damaging the midveins of four leaves from each of nine Sonoran Desert species. We then measured the percent change in photosynthesis (ΔAn%), transpiration (ΔEt%) and stomatal conductance (Δgsw%) between treated and control leaves. We assessed the relationship of each with leaf venation traits and other mechanical traits. ΔAn% varied between +10 % and −55%, similar to ΔEt% (+27%, −54%) and Δgsw% (+36%, −53%). There was no tradeoff between venation and other structural defenses. Increased damage resilience (reduced ΔAn% , ΔEt% , Δgsw%) was marginally associated with lower force-to-tear (P < 0.05), and higher minor vein density (P < 0.10) but not major vein density or reticulation. Leaf venation networks may thus partially mitigate the response of gas exchange to herbivory and other types of vein damage through either resistance or resilience. [ABSTRACT FROM AUTHOR]

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020–2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%–40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Language is often thought as being poorly adapted to precisely describe or quantify smell and olfactory attributes. In this work, we show that semantic descriptors of odors can be implemented in a model to successfully predict odor mixture discriminability, an olfactory attribute. We achieved this by taking advantage of the structure-to-percept model we previously developed for monomolecular odorants, using chemical descriptors to predict pleasantness, intensity and 19 semantic descriptors such as "fish," "cold," "burnt," "garlic," "grass," and "sweet" for odor mixtures, followed by a metric learning to obtain odor mixture discriminability. Through this expansion of the representation of olfactory mixtures, our Semantic model outperforms state of the art methods by taking advantage of the intermediary semantic representations learned from human perception data to enhance and generalize the odor discriminability/similarity predictions. As 10 of the semantic descriptors were selected to predict discriminability/similarity, our approach meets the need of rapidly obtaining interpretable attributes of odor mixtures as illustrated by the difficulty of finding olfactory metamers. More fundamentally, it also shows that language can be used to establish a metric of discriminability in the everyday olfactory space. [ABSTRACT FROM AUTHOR]

Background We evaluated the epidemiology of candidemia among coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs). Methods We conducted a retrospective multicenter study in Turkey between April and December 2020. Results Twenty-eight of 148 enrolled patients developed candidemia, yielding an incidence of 19% and incidence rate of 14/1000 patient-days. The probability of acquiring candidemia at 10, 20, and 30 days of ICU admission was 6%, 26%, and 50%, respectively. More than 80% of patients received antibiotics, corticosteroid, and mechanical ventilation. Receipt of a carbapenem (odds ratio [OR] = 6.0, 95% confidence interval [CI] = 1.6–22.3, P  = .008), central venous catheter (OR = 4.3, 95% CI = 1.3–14.2, P  = .02), and bacteremia preceding candidemia (OR = 6.6, 95% CI = 2.1–20.1, P  = .001) were independent risk factors for candidemia. The mortality rate did not differ between patients with and without candidemia. Age (OR = 1.05, 95% CI = 1.01–1.09, P  = .02) and mechanical ventilation (OR = 61, 95% CI = 15.8–234.9, P  < .0001) were independent risk factors for death. Candida albicans was the most prevalent species overall. In Izmir, Candida parapsilosis accounted for 50% (2 of 4) of candidemia. Both C parapsilosis isolates were fluconazole nonsusceptible, harbored Erg11-Y132F mutation, and were clonal based on whole-genome sequencing. The 2 infected patients resided in ICUs with ongoing outbreaks due to fluconazole-resistant C parapsilosis. Conclusions Physicians should be aware of the elevated risk for candidemia among patients with COVID-19 who require ICU care. Prolonged ICU exposure and ICU practices rendered to COVID-19 patients are important contributing factors to candidemia. Emphasis should be placed on (1) heightened infection control in the ICU and (2) developing antibiotic stewardship strategies to reduce irrational antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020–2021, with 241 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% confidence interval: 35.34%–43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, P = 0.45). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Large body sizes have evolved structures to facilitate resource transport. Like unitary organisms, social insect colonies must transport information and resources. Colonies with more individuals may experience transport challenges similar to large‐bodied organisms. In ant colonies, transport occurs in the nest, which may consist of structures that facilitate movement. We examine three attributes of nests that might have evolved to mitigate transport challenges related to colony size: (1) subdivision—nests of species with large colonies are more subdivided to reduce crowd viscosity; (2) branching—nest tunnels increase branching in species with large colonies to reduce travel distances; and (3) shortcuts—nests of species with large colonies have cross‐linking tunnels to connect distant parts of the nest and create alternative routes. We test these hypotheses by comparing nest structures of species with different colony sizes in phylogenetically controlled meta‐analyses. Our findings support the hypothesis that nest subdivision and branching evolved to mitigate transport challenges related to colony size. Nests of species with large colonies contain more chambers and branching tunnels. The similarity in how ant nests and bodies of unitary organisms have evolved in response to increasing size suggests common solutions across taxa and levels of biological organization. [ABSTRACT FROM AUTHOR]

Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, over 100 million people have been infected by COVID-19, millions of whom have died. In the latest year, a large number of omics data have sprung up and helped researchers broadly study the sequence, chemical structure and function of SARS-CoV-2, as well as molecular abnormal mechanisms of COVID-19 patients. Though some successes have been achieved in these areas, it is necessary to analyze and mine omics data for comprehensively understanding SARS-CoV-2 and COVID-19. Hence, we reviewed the current advantages and limitations of the integration of omics data herein. Firstly, we sorted out the sequence resources and database resources of SARS-CoV-2, including protein chemical structure, potential drug information and research literature resources. Next, we collected omics data of the COVID-19 hosts, including genomics, transcriptomics, microbiology and potential drug information data. And subsequently, based on the integration of omics data, we summarized the existing data analysis methods and the related research results of COVID-19 multi-omics data in recent years. Finally, we put forward SARS-CoV-2 (COVID-19) multi-omics data integration research direction and gave a case study to mine deeper for the disease mechanisms of COVID-19. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19–associated fungal infections. [ABSTRACT FROM AUTHOR]

Background The ongoing pandemic of coronavirus disease 2019 (COVID-19) has overwhelmed healthcare facilities and raises an important novel concern of nosocomial transmission of Candida species in the intensive care units (ICUs). Methods We evaluated the incidence and risk factors for development of candidemia in 2384 COVID-19 patients admitted during August 2020–January 2021 in ICUs of 2 hospitals (Delhi and Jaipur) in India. A 1:2 case-control matching was used to identify COVID-19 patients who did not develop candidemia as controls. Results A total of 33 patients developed candidemia and accounted for an overall incidence of 1.4% over a median ICU stay of 24 days. A 2-fold increase in the incidence of candidemia in COVID-19 versus non-COVID-19 patients was observed with an incidence rate of 14 and 15/1000 admissions in 2 ICUs. Candida auris was the predominant species (42%) followed by Candida tropicalis. Multivariable regression analysis revealed the use of tocilizumab, duration of ICU stay (24 vs 14 days), and raised ferritin level as an independent predictor for the development of candidemia. Azole resistance was observed in C auris and C tropicalis harboring mutations in the azole target ERG11 gene. Multilocus sequence typing (MLST) identified identical genotypes of C tropicalis in COVID-19 patients, raising concern for nosocomial transmission of resistant strains. Conclusions Secondary bacterial infections have been a concern with the use of tocilizumab. In this cohort of critically ill COVID-19 patients, tocilizumab was associated with the development of candidemia. Surveillance of antifungal resistance is warranted to prevent transmission of multidrug-resistant strains of nosocomial yeasts in COVID-19 hospitalized patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVD-19) emerged as a pandemic in December 2019. Infection has spread quickly and renal transplant recipients receiving chronic immunosuppression have been considered a population at high risk of infection, complications and infection-related death. During this year a large amount of information from nationwide registries, multicentre and single-centre studies have been reported. The number of renal transplant patients diagnosed with COVID-19 was higher than in the general population, but the lower threshold for testing may have contributed to its better identification. Major complications such as acute kidney injury and acute respiratory distress syndrome were very frequent in renal transplant patients, with a high comorbidity burden, but further studies are needed to support that organ transplant recipients receiving chronic immunosuppression are more prone to develop these complications than the general population. Kidney transplant recipients experience a high mortality rate compared with the general population, especially during the very early post-transplant period. Despite the fact that some studies report more favourable outcomes in patients with a kidney transplant than in patients on the kidney waiting list, the higher mortality described in the very early post-transplant period would advise against performing a kidney transplant in areas where the spread of infection is high, especially in recipients >60 years of age. Management of transplant recipients has been challenging for clinicians and strategies such as less use of lymphocyte-depleting agents for new transplants or anti-metabolite withdrawal and calcineurin inhibitor reduction for transplant patients with COVID-19 are not based on high-quality evidence. [ABSTRACT FROM AUTHOR]

Color and pitch perception are largely understandable from characteristics of physical stimuli: the wavelengths of light and sound waves, respectively. By contrast, understanding olfactory percepts from odorous stimuli (volatile molecules) is much more challenging. No intuitive set of molecular features is up to the task. Here in Chemical Senses , the Ray lab reports using a predictive modeling framework—first breaking molecular structure into thousands of features and then using this to train a predictive statistical model on a wide range of perceptual descriptors—to create a tool for predicting the odor character of hundreds of thousands of available but previously uncharacterized molecules (Kowalewski et al. 2021). This will allow future investigators to representatively sample the space of odorous molecules as well as identify previously unknown odorants with a target odor character. Here, I put this work into the context of other modeling efforts and highlight the urgent need for large new datasets and transparent benchmarks for the field to make and evaluate modeling breakthroughs, respectively. [ABSTRACT FROM AUTHOR]

Background In patients with adrenal incidentalomas (AIs), there is uncertainty on how to rule out hypercortisolism. The occurrence of postsurgical (unilateral adrenalectomy) hypocortisolism (PSH) has been proposed as a proof of the presence of presurgical hypercortisolism in AI patients. The aim of this study was to define the thresholds of cortisol level after the 1 mg overnight dexamethasone suppression test (F-1mgDST), urinary free cortisol (UFC), midnight serum cortisol (MSC), and adrenocorticotropin (ACTH) to predict the absence of PSH in AI patients undergoing surgery. Methods In 60 patients who underwent AI excision, cortisol secretion was assessed by a low-dose corticotropin stimulation test or insulin tolerance test when needed. We searched for the lowest presurgical value of F-1mgDST, UFC, and MSC and the highest value for ACTH in AI patients with PSH as indexes of normal cortisol secretion. Results The lowest values of F-1mgDST, UFC, and MSC and the highest value for ACTH in PSH patients were 1.2 µg/dL (33 nmol/L), 10.4 µg/24 hours (29 nmol/24 hours), 1.2 µg/dL (33 nmol/L), and 26.9 pg/mL (6 pmol/L), respectively, but only F-1mgDST <1.2 µg/dL (33 nmol/L) was able to predict the absence of PSH. Among AI patients with F-1mgDST <1.2 µg/dL (33 nmol/L) no subjects had diabetes mellitus and/or metabolic syndrome, and these subjects tended to have a better metabolic profile than those with F-1mgDST ≥1.2 µg/dL (33 nmol/L) Conclusion In AI patients a F-1mgDST <1.2 µg/dL (33 nmol/L) rules out PSH and could be used to exclude hypercortisolism in AI patients. [ABSTRACT FROM AUTHOR]

All behaviors of an organism are rooted in sensory processing of signals from its environment, and natural selection shapes sensory adaptations to ensure successful detection of cues that maximize fitness. Sensory drive, or divergent selection for efficient signal transmission among heterogeneous environments, has been a useful hypothesis for describing sensory adaptations, but its current scope has primarily focused on visual and acoustic sensory modalities. Chemosensation, the most widespread sensory modality in animals that includes the senses of smell and taste, is characterized by rapid evolution and has been linked to sensory adaptations to new environments in numerous lineages. Yet, olfaction and gustation have been largely underappreciated in light of the sensory drive hypothesis. Here, we examine why chemosensory systems have been overlooked and discuss the potential of chemosensation to shed new insight on the sensory drive hypothesis and vice versa. We provide suggestions for developing a framework to better incorporate studies of chemosensory adaptation that have the potential to shape a more complete, coherent, and holistic interpretation of the sensory drive. [ABSTRACT FROM AUTHOR]

The objective of the study was to investigate the relationships between vaginal temperature during the dry-period and health, milk production, and reproduction in the subsequent lactation of cows during the warm season. A total of 105 nonlactating Holstein cows from 2 dairies were enrolled in the study during summer. At enrollment, cows were between 250 and 260 d of gestation. Vaginal temperature (VT) and corral ambient temperature and humidity were recorded every 5 min for 4 consecutive days starting at enrollment. Cows were categorized as presenting high (HT) or low temperature (LT) based on the median values of average VT and were followed until 300 d in milk (DIM) of the subsequent lactation to evaluate health disorders, culling rate, milk yield, and reproductive efficiency. Cows that became pregnant were followed until subsequent calving. Cows were monitored for uterine diseases (UTD) and mastitis (MAST) by farm personnel. Individual milk yield was recorded monthly until 300 DIM. Cows classified as HT had shorter (P < 0.01) gestation length (273.9 ± 0.9 vs. 278.7 ± 1.0 d) and spent fewer (P < 0.01) days in the closeup pen (14.3 ± 0.8 vs. 19.4 ± 1.0 d) than LT cows. Hazard to UTD or MAST in the first 60 DIM was greater for HT than LT cows (adjusted hazard ratio [AHR] = 5.15, 95% CI = 1.91 to 13.86). Cows classified as HT had greater hazard to MAST in the first 300 DIM compared with LT cows (AHR = 2.39; 1.03 to 5.56). Vaginal temperature was not associated with milk yield. In contrast, the interaction between VT category and month of lactation tended to influence milk yield. This interaction was observed because cows categorized as LT had greater (P < 0.01) milk yield in the first month of lactation compared with HT cows (39.2 ± 1.6 vs. 33.7 ± 1.5 kg), whereas milk yield tended (P = 0.07) and was greater (P = 0.05) for HT cows in the ninth (32.7 ± 1.6 vs. 28.5 ± 1.9 kg) and tenth (29.9 ± 1.7 vs. 25.0 ± 2.0 kg) month of lactation, respectively. Pregnancy per AI at first service, interval from calving to pregnancy, and percentage of cows calving in the subsequent lactation did not differ between HT and LT cows. In conclusion, VT assessed between 20 and 30 d before expected calving is associated with health outcomes and milk production in the subsequent lactation. In addition, cows susceptible to be affected by postpartum disorders after calving may be identified during the summer by evaluating VT temperature at 250 to 260 d of gestation. [ABSTRACT FROM AUTHOR]

Obesity is a major health concern in modern societies. Although decreased physical activity and enhanced intake of high-caloric foods are important risk factors for developing obesity, human behavior during eating also plays a role. Previous studies have shown that distraction while eating increases food intake and leads to impaired processing of food stimuli. As olfaction is the most important sense involved in flavor perception, we used functional magnetic resonance imaging techniques to investigate the influence of cognitive memory load on olfactory perception and processing. Low and high-caloric food odors were presented in combination with either low or high cognitive loads utilizing a memory task. The efficacy of the memory task was verified by a decrease in participant recall accuracy and an increase in skin conductance response during high cognitive load. Our behavioral data reveal a diminished perceived intensity for low- but not highcaloric food odors during high cognitive load. For low-caloric food odors, bilateral orbitofrontal (OFC) and piriform cortices (pirC) showed significantly lower activity during high compared with low cognitive load. For high-caloric food odors, a similar effect was established in pirC, but not in OFC. Insula activity correlates with higher intensity ratings found during the low cognitive load condition. We conclude lower activity in pirC and OFC to be responsible for diminished intensity perception, comparable to results in olfactory impaired patients and elderly. Further studies should investigate the influence of olfactory/gustatory intensities on food choices under distraction with special regards to low-caloric food. [ABSTRACT FROM AUTHOR]

A sexual signal can indicate not only the signaler's attractiveness as a potential mate but also the signaler's competitiveness relative to rivals. As the attractiveness or competitiveness of the prevailing signaling environment increases, individuals prospecting for mates should change their choice threshold, whereas competing individuals should shift resources toward elevating their own competitiveness. Previous studies show that experimental elevations of song competition increase male competitive behavior in Lincoln's sparrows (Melospiza lincolnii) and European starlings (Sturnus vulgaris). Through a series of experimental manipulations using laboratory-housed Lincoln's sparrows, we have also discovered that females change the strength of their song preferences depending on the attractiveness of the song environment to which they have recently been exposed; compared to a less-attractive environment, a highlyattractive environment elevates the threshold for releasing phonotaxis behavior toward male song. These behavioral adjustments are associated with changes in forebrain monoaminergic activity that are triggered by experimental manipulations of the quality of the song environment. Findings from these studies suggest possible neural mechanisms for the regulation of adaptive behavioral plasticity associated with dynamic sexual signaling environments. [ABSTRACT FROM AUTHOR]

Unlike vision or audition, human olfaction is generally considered evolutionarily ancient and well-functioning at birth, yet there have been few empirical data on the development of olfactory acuity. The current study has assessed olfactory discriminability in children aged 3 to 6 years with 16 pairs of single-compound odorants that differ in various degrees in structure and smell. We report a significant improvement over age in young children's overall olfactory discriminability. Critically, such improvement is modulated by the degree of structural similarity between odorants independent of odor familiarity. Our findings indicate that odor representations in the olfactory system are fine-tuned during early childhood (3-6 years of age) to allow refined discrimination. Moreover, they suggest the need to take molecular similarity into consideration in the evaluation of olfactory discrimination in pediatric populations. [ABSTRACT FROM AUTHOR]