Nutritional and productive performance of purebred Nellore heifers and crossed with Brangus and Braford finished in a feedlot system.

This study evaluated the nutritional and productive performance of Nellore purebred heifers and crossbred Brangus x Nellore (BGNE) and Braford x Nellore (BFNE) in a feedlot system. Thirty heifers (10 of each genetic group) with an average age of 18 months and an initial body weight of 261 kg were used. The experiment was structured and conducted according to a completely randomized design, with three treatments. Heifers received two diets (60 days each) during the experimental period. The experiment lasted 120 days with four experimental periods. Nellore heifers had a lower intake than crossbred heifers (P <0.05). There were no differences between BGNE and BFNE heifers, which had higher final body weight, average daily gain, feed efficiency, hot carcass weight and carcass length than NE heifers. Crossed heifers presented better fat cover than NE heifers. However, NE heifers had higher carcass dressing Despite presenting lower carcass yields than Nellore heifers, crossed heifers are more efficient and have higher performance and better fat cover on the carcass than purebred Nellore heifers. Crossbreeding synthetic breeds, such as Brangus and Braford breeds, with the Nellore breed is an effective way to increase the productivity and efficiency of feedlot heifers in tropical regions.

PCSK9 inhibition attenuates alcohol-associated neuronal oxidative stress and cellular injury.

Alcohol Use Disorder (AUD) is a persistent condition linked to neuroinflammation, neuronal oxidative stress, and neurodegenerative processes. While the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has demonstrated effectiveness in reducing liver inflammation associated with alcohol, its impact on the brain remains largely unexplored. This study aimed to assess the effects of alirocumab, a monoclonal antibody targeting PCSK9 to lower systemic low-density lipoprotein cholesterol (LDL-C), on central nervous system (CNS) pathology in a rat model of chronic alcohol exposure. Alirocumab (50 mg/kg) or vehicle was administered weekly for six weeks in 32 male rats subjected to a 35 % ethanol liquid diet or a control liquid diet (n = 8 per group). The study evaluated PCSK9 expression, LDL receptor (LDLR) expression, oxidative stress, and neuroinflammatory markers in brain tissues. Chronic ethanol exposure increased PCSK9 expression in the brain, while alirocumab treatment significantly upregulated neuronal LDLR and reduced oxidative stress in neurons and brain vasculature (3-NT, p22phox). Alirocumab also mitigated ethanol-induced microglia recruitment in the cortex and hippocampus (Iba1). Additionally, alirocumab decreased the expression of pro-inflammatory cytokines and chemokines (TNF, CCL2, CXCL3) in whole brain tissue and attenuated the upregulation of adhesion molecules in brain vasculature (ICAM1, VCAM1, eSelectin). This study presents novel evidence that alirocumab diminishes oxidative stress and modifies neuroimmune interactions in the brain elicited by chronic ethanol exposure. Further investigation is needed to elucidate the mechanisms by which PCSK9 signaling influences the brain in the context of chronic ethanol exposure.

Even worse for Black girls: the longitudinal association of racial bullying with the initiation of alcohol and tobacco use.

We used Poisson's linear regression to examine the association between racial bullying (RB) and the initiation of alcohol and tobacco uses after nine months. Two cluster randomized controlled trials were conducted in 2019 with fifth (girls: 50.0%; 10 years old: 82.0%; White: 36.8%; Black: 58.7%; Others: 4.5%) and seventh graders (girls: 49.5%; 12 years old: 78.1%; White: 33.2%; Black: 60.4%; Others: 6.4%) from 30 public schools in the municipality of São Paulo, Brazil. We restricted our analyzes on two subsets of students in each grade: those who reported no lifetime alcohol use at baseline and those who reported no lifetime baseline tobacco use. At baseline, 16.2% of fifth and 10.7% of seventh graders reported suffering from RB in the 30 days before data collection. After nine months, 14.9% of fifth graders started using alcohol and 2.5%, tobacco. Among seventh graders, the figures were 31.2% and 7.7%, respectively. RB predicted the initiation of use of alcohol (risk ratio - RR=1.36, 95%CI=1.07-1.70) and tobacco (RR=1.81, 95%CI=1.14-2.76) among seventh graders, with race-gender differences, particularly in Black girls (alcohol: RR=1.45, 95%CI=1.07-1.93; tobacco: RR=2.34, 95%CI=1.31-3.99). School-based programs and policies must explicitly address issues related to racism and gender in alcohol and tobacco prevention strategies.

Social support and suicidality during the COVID-19 pandemic among Brazilian healthcare workers: a longitudinal assessment of an online repeated cross-sectional survey.

INTRODUCTION: Healthcare workers (HCWs) are at an increased risk of suicide compared to non-healthcare workers. This study aims to investigate the association between social support and suicidal ideation and behavior (SIB) during the COVID-19 pandemic among Brazilian HCWs. METHODS: This study utilizes data from 10,885 participants who answered the first (time point 1 - between May and June of 2020) and second (time point 2 - between December 2020 and February 2021) assessments of an online repeated cross-sectional survey for evaluating mental health and quality of life of HCWs during the COVID-19 pandemic in Brazil. Logistic regression analysis was conducted to investigate the relationship between social support as the independent variable (time point 1) and SIB as the outcomes (time point 2). RESULTS: Higher social support was associated with a significantly lower chance of reporting SIB in the month prior to follow-up assessment (adjusted odds ratio [AOR]: 0.71, CI 95% 0.66 - 0.76 and AOR 0.61, CI 95% 0.54 - 0.68, respectively). These associations were independent of sex, age, feelings of loneliness, and self-reported psychiatric disorders. CONCLUSION: Social support is associated with a lower chance of suicidality among HCWs, a protective role that is probably more evident for suicidal behavior.

Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels? A device-based cohort study.

OBJECTIVES: This study aims to examine the associations of daily step count with all-cause mortality and incident cardiovascular disease (CVD) by sedentary time levels and to determine if the minimal and optimal number of daily steps is modified by high sedentary time. METHODS: Using data from the UK Biobank, this was a prospective dose-response analysis of total daily steps across low (<10.5 hours/day) and high (≥10.5 hours/day) sedentary time (as defined by the inflection point of the adjusted absolute risk of sedentary time with the two outcomes). Mortality and incident CVD was ascertained through 31 October 2021. RESULTS: Among 72 174 participants (age=61.1±7.8 years), 1633 deaths and 6190 CVD events occurred over 6.9 (±0.8) years of follow-up. Compared with the referent 2200 steps/day (5th percentile), the optimal dose (nadir of the curve) for all-cause mortality ranged between 9000 and 10 500 steps/day for high (HR (95% CI)=0.61 (0.51 to 0.73)) and low (0.69 (0.52 to 0.92)) sedentary time. For incident CVD, there was a subtle gradient of association by sedentary time level with the lowest risk observed at approximately 9700 steps/day for high (0.79 (0.72 to 0.86)) and low (0.71 (0.61 to 0.83)) sedentary time. The minimal dose (steps/day associated with 50% of the optimal dose) of daily steps was between 4000 and 4500 steps/day across sedentary time groups for all-cause mortality and incident CVD. CONCLUSIONS: Any amount of daily steps above the referent 2200 steps/day was associated with lower mortality and incident CVD risk, for low and high sedentary time. Accruing 9000-10 500 steps/day was associated with the lowest mortality risk independent of sedentary time. For a roughly equivalent number of steps/day, the risk of incident CVD was lower for low sedentary time compared with high sedentary time.

Joint Associations of Diet and Device-measured Physical Activity with Mortality and Incident CVD and Cancer: a prospective analysis of the UK Biobank Study.

BACKGROUND: We examined the joint associations of diet and device-measured intensity-specific PA with all-cause mortality (ACM), cardiovascular disease (CVD) and cancer incidence. METHODS: We used data from 79,988 participants from the UK Biobank, a population-based prospective cohort study. Light PA (LPA), moderate-to-vigorous PA (MVPA), vigorous PA (VPA) and total PA (TPA) were measured using a wrist-worn accelerometer. Diet Quality Score (DQS) was based on 10 foods and ranged from 0 (unhealthiest) to 100 (healthiest) points. We derived joint PA and diet variables. Outcomes were all-cause mortality, CVD and cancer incidence including PA, diet and adiposity-related (PDAR) cancer. RESULTS: During a median follow-up of 8 years, 2,863 deaths occurred, 11,053 participants developed CVD, 7,005 developed cancer and 3,400 developed PDAR cancer. Compared with the least favourable referent group (bottom PA tertile/low DQS), participants with middle and high (total and intensity specific) PA, except for LPA, had lower all-cause mortality risk and incident CVD risk, regardless of DQS. For example, among middle and high VPA and high DQS groups, CVD HR were 0.79 (95%CI 0.74-0.86) and 0.75 (95%CI 0.69-0.82), respectively. The pattern of cancer results was less pronounced but in agreement with the ACM and CVD incidence findings (e.g. HR 0.90, 95%CI 0.81-0.99; 0.88,0.79-0.98 and 0.82,0.74-0.92 among high VPA for low, moderate and high DQS group, respectively). CONCLUSIONS: Device-measured PA reveals novel joint associations with diet on health outcomes. IMPACT: Our results emphasize the crucial role of PA in addition to a healthy diet for reducing chronic diseases and mortality risk.

Ketone Supplementation Dampens Subjective and Objective Responses to Alcohol: Evidence From a Preclinical Rat Study and a Randomized, Cross-Over Trial in Healthy Volunteers.

BACKGROUND: Previous preclinical and human studies have shown that a high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal. However, the effects of KS on alcohol sensitivity are unknown. METHODS: In this single-blind, cross-over study, 10 healthy participants (3 females) were administered a single, oral dose of a KS (25 g of ketones from D-ß-hydroxybutyric acid and R-1,3-butanediol) or placebo 30 minutes before an oral alcohol dose (0.25 g/kg for women; 0.31 g/kg for men). Assessments of breath alcohol concentration and blood alcohol levels (BAL) and responses on the Drug Effect Questionnaire were repeatedly obtained over 180 minutes after alcohol consumption. In a parallel preclinical study, 8 Wistar rats (4 females) received an oral gavage of KS (0.42 g ketones/kg), water, or the sweetener allulose (0.58 g/kg) followed 15 minutes later by an oral alcohol dose (0.8 g/kg). BAL was monitored for 240 minutes after alcohol exposure. RESULTS: In humans, the intake of KS before alcohol significantly blunted breath alcohol concentration and BAL, reduced ratings of alcohol liking and wanting more, and increased disliking for alcohol. In rats, KS reduced BAL more than either allulose or water. CONCLUSION: KS altered physiological and subjective responses to alcohol in both humans and rats, and the effects were likely not mediated by the sweetener allulose present in the KS drink. Therefore, KS could potentially reduce the intoxicating effects of alcohol.

µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice.

Mood and anxiety disorders are leading causes of disability worldwide and are major contributors to the global burden of diseases. Neuropeptides, such as oxytocin and opioid peptides, are important for emotion regulation. Previous studies have demonstrated that oxytocin reduced depression- and anxiety-like behavior in male and female mice, and opioid receptor activation reduced depression-like behavior. However, it remains unclear whether the endogenous opioid system interacts with the oxytocin system to facilitate emotion regulation in male and female mice. We hypothesized that opioid receptor blockade would inhibit the anxiolytic- and antidepressant-like effects of oxytocin. In this study, we systemically administered naloxone, a preferential µ-opioid receptor antagonist, and then intracerebroventricularly administered oxytocin. We then tested mice on the elevated zero maze and the tail suspension tests, respective tests of anxiety- and depression-like behavior. Contrary to our initial hypothesis, naloxone potentiated the anxiolytic-like, but not the antidepressant-like, effect of oxytocin. Using a selective µ-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, and a selective κ-opioid receptor antagonist, norbinaltorphimine, we demonstrate that µ-opioid receptor blockade potentiated the anxiolytic-like effect of oxytocin, whereas κ-opioid receptor blockade inhibited the oxytocin-induced anxiolytic-like effects. The present results suggest that endogenous opioids can regulate the oxytocin system to modulate anxiety-like behavior. Potential clinical implications of these findings are discussed.

An Integrated Framework for Image Acquisition, Processing, and Analysis Procedures for Automated Damage Evaluation of Concrete Surfaces.

Concrete surface cracks serve as early indicators of potential structural threats. Visual inspection, a commonly used and versatile concrete condition assessment technique, is employed to assess concrete degradation by observing signs of damage on the surface level. However, the method tends to be qualitative and needs to be more comprehensive in providing accurate information regarding the extent of damage and its evolution, notwithstanding its time-consuming and environment-sensitive nature. As such, the integration of image analysis techniques with artificial intelligence (AI) has been increasingly proven efficient as a tool to capture damage signs on concrete surfaces. However, to improve the performance of automated crack detection, it is imperative to intensively train a machine learning model, and questions remain regarding the required image quality and image collection methodology needed to ensure the model's accuracy and reliability in damage quantitative analysis. This study aims to establish a procedure for image acquisition and processing through the application of an image-based measurement approach to explore the capabilities of concrete surface damage diagnosis. Digitizing crack intensity measurements were found to be feasible; however, larger datasets are required. Due to the anisotropic behavior of the damage, the model's ability to capture crack directionality was developed, presenting no statistically significant differences between the observed and predicted values used in this study with correlation coefficients of 0.79 and 0.82.

Lifestyle risk factors and all-cause and cause-specific mortality in the Mexico City prospective study: Assessing the influence of reverse causation.

BACKGROUND: We examined the association between individual lifestyle risk factors with all-cause and cause-specific mortality. METHODS: Prospective cohort study including 155,002 participants from the Mexico City Prospective Study. Cox regression models were used to estimate the association between individual lifestyle risk factors and all-cause and cause-specific mortality. Participants with prevalent diseases at baseline and participants who died during the first 2, 5, 10, and 15 years of follow-up were excluded to account for reverse causation. RESULTS: 27,469 people died during 18.3 years of follow-up years. Overweight and moderate alcohol consumption were inversely associated with all-cause mortality, while low physical activity and smoking were positively associated when all participants were included, regardless of prevalent disease or duration of follow-up. The direction of the association of overweight with all-cause mortality changed from inverse to positive after excluding the first 10 years of follow-up. Compared with normal weight, the hazard ratio (95 % confidence interval) was 1.17 (1.13,1.22) for obesity after excluding those who died in the first 5 years of follow-up and 1.71 (1.59,1.84) after excluding the first 15 years of follow-up. The magnitude of the association of alcohol intake, low physical activity, and smoking with mortality attenuated, whereas for fruits and vegetables increased, after excluding longer periods of follow-up. LIMITATIONS: The data were collected exclusively in Mexico City; lifestyle risk factors were self-reported and thus prone to misclassification bias. CONCLUSIONS: Reverse causation may influence both the magnitude and the direction of the associations between lifestyle risk factors and mortality.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

Invited for the cover of this issue are the groups of Holger Braunschweig at the Julius-Maximilians-Universität Würzburg, Germany and Eufrânio N. da Silva Júnior at the Universidade Federal de Minas Gerais, UFMG, Brazil. The image depicts the electrochemical synthesis of selenium-containing BODIPY molecules with lightning symbolizing the electrifying synthetic process, while the surrounding elemental chaos hints at the red-shifted absorption and emission and the transformative photophysical properties of these new compounds. Read the full text of the article at 10.1002/chem.202303883.

Cancer Diagnoses After Recent Weight Loss.

Importance: Weight loss is common in primary care. Among individuals with recent weight loss, the rates of cancer during the subsequent 12 months are unclear compared with those without recent weight loss. Objective: To determine the rates of subsequent cancer diagnoses over 12 months among health professionals with weight loss during the prior 2 years compared with those without recent weight loss. Design, Setting, and Participants: Prospective cohort analysis of females aged 40 years or older from the Nurses' Health Study who were followed up from June 1978 until June 30, 2016, and males aged 40 years or older from the Health Professionals Follow-Up Study who were followed up from January 1988 until January 31, 2016. Exposure: Recent weight change was calculated from the participant weights that were reported biennially. The intentionality of weight loss was categorized as high if both physical activity and diet quality increased, medium if only 1 increased, and low if neither increased. Main Outcome and Measures: Rates of cancer diagnosis during the 12 months after weight loss. Results: Among 157 474 participants (median age, 62 years [IQR, 54-70 years]; 111 912 were female [71.1%]; there were 2631 participants [1.7%] who self-identified as Asian, Native American, or Native Hawaiian; 2678 Black participants [1.7%]; and 149 903 White participants [95.2%]) and during 1.64 million person-years of follow-up, 15 809 incident cancer cases were identified (incident rate, 964 cases/100 000 person-years). During the 12 months after reported weight change, there were 1362 cancer cases/100 000 person-years among all participants with recent weight loss of greater than 10.0% of body weight compared with 869 cancer cases/100 000 person-years among those without recent weight loss (between-group difference, 493 cases/100 000 person-years [95% CI, 391-594 cases/100 000 person-years]; P < .001). Among participants categorized with low intentionality for weight loss, there were 2687 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 1220 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 1467 cases/100 000 person-years [95% CI, 799-2135 cases/100 000 person-years]; P < .001). Cancer of the upper gastrointestinal tract (cancer of the esophagus, stomach, liver, biliary tract, or pancreas) was particularly common among participants with recent weight loss; there were 173 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 36 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 137 cases/100 000 person-years [95% CI, 101-172 cases/100 000 person-years]; P < .001). Conclusions and Relevance: Health professionals with weight loss within the prior 2 years had a significantly higher risk of cancer during the subsequent 12 months compared with those without recent weight loss. Cancer of the upper gastrointestinal tract was particularly common among participants with recent weight loss compared with those without recent weight loss.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.

Cold nociception as a measure of hyperalgesia during spontaneous heroin withdrawal in mice.

Opioids are powerful analgesic drugs that are used clinically to treat pain. However, chronic opioid use causes compensatory neuroadaptations that result in greater pain sensitivity during withdrawal, known as opioid withdrawal-induced hyperalgesia (OWIH). Cold nociception tests are commonly used in humans, but preclinical studies often use mechanical and heat stimuli to measure OWIH. Thus, further characterization of cold nociception stimuli is needed in preclinical models. We assessed three cold nociception tests-thermal gradient ring (5-30 °C, 5-50 °C, 15-40 °C, and 25-50 °C), dynamic cold plate (4 °C to -1 °C at -1 °C/min, -1 °C to 4 °C at +1 °C/min), and stable cold plate (10 °C, 6 °C, and 2 °C)-to measure hyperalgesia in a mouse protocol of heroin dependence. On the thermal gradient ring, mice in the heroin withdrawal group preferred warmer temperatures, and the results depended on the ring's temperature range. On the dynamic cold plate, heroin withdrawal increased the number of nociceptive responses, with a temperature ramp from 4 °C to -1 °C yielding the largest response. On the stable cold plate, heroin withdrawal increased the number of nociceptive responses, and a plate temperature of 2 °C yielded the most significant increase in responses. Among the three tests, the stable cold plate elicited the most robust change in behavior between heroin-dependent and nondependent mice and had the highest throughput. To pharmacologically characterize the stable cold plate test, we used µ-opioid and non-opioid receptor-targeting drugs that have been previously shown to reverse OWIH in mechanical and heat nociception assays. The full µ-opioid receptor agonist methadone and µ-opioid receptor partial agonist buprenorphine decreased OWIH, whereas the preferential µ-opioid receptor antagonist naltrexone increased OWIH. Two N-methyl-d-aspartate receptor antagonists (ketamine, MK-801), a corticotropin-releasing factor 1 receptor antagonist (R121919), a ß2-adrenergic receptor antagonist (butoxamine), an α2-adrenergic receptor agonist (lofexidine), and a 5-hydroxytryptamine-3 receptor antagonist (ondansetron) had no effect on OWIH. These data demonstrate that the stable cold plate at 2 °C yields a robust, reliable, and concise measure of OWIH that is sensitive to opioid agonists.

Cryo-EM structure of influenza helical nucleocapsid reveals NP-NP and NP-RNA interactions as a model for the genome encapsidation.

Influenza virus genome encapsidation is essential for the formation of a helical viral ribonucleoprotein (vRNP) complex composed of nucleoproteins (NP), the trimeric polymerase, and the viral genome. Although low-resolution vRNP structures are available, it remains unclear how the viral RNA is encapsidated and how NPs assemble into the helical filament specific of influenza vRNPs. In this study, we established a biological tool, the RNP-like particles assembled from recombinant influenza A virus NP and synthetic RNA, and we present the first subnanometric cryo-electron microscopy structure of the helical NP-RNA complex (8.7 to 5.3 Å). The helical RNP-like structure reveals a parallel double-stranded conformation, allowing the visualization of NP-NP and NP-RNA interactions. The RNA, located at the interface of neighboring NP protomers, interacts with conserved residues previously described as essential for the NP-RNA interaction. The NP undergoes conformational changes to enable RNA binding and helix formation. Together, our findings provide relevant insights for understanding the mechanism for influenza genome encapsidation.

Excess mortality in adults from Sao Paulo during the COVID-19 pandemic in 2020: analyses of all-cause and noncommunicable diseases mortality.

In this study, we estimated the excess mortality from all-causes of death and noncommunicable diseases (NCDs) in adults living in the state of São Paulo during the COVID-19 pandemic in 2020. Number of deaths were retrieved from the Mortality Information System before (2017-2019) and during (2020) the COVID-19 pandemic, considering the following underlying causes of death: Neoplasms; Diabetes Mellitus; Circulatory System Diseases, and Respiratory System Diseases. Standardized Mortality Ratio (SMR) were calculated by dividing the mortality rates in 2020 by average mortality rates in 2017-2019, according to sex, age group, geographic location (state, capital, and Regional Health Departments). In 2020, occurred 341,704 deaths in the state of São Paulo vs 290,679 deaths in 2017-2019, representing an 18% increase in all-cause mortality (SMR 1.18) or 51,025 excess deaths during the first year of COVID-19 pandemic. The excess mortality was higher in men (186,741 deaths in 2020 vs 156,371 deaths in 2017-2019; SMR 1.18; 30,370 excess deaths) compared to women (154,963 deaths in 2020 vs 134,308 deaths in 2017-2019; SMR 1.15; 20,655 excess deaths). Regarding NCDs mortality, we observed a reduction in cancer mortality (SMR 0.98; -1,354 deaths), diseases of the circulatory system (SMR 0.95; -4,277 deaths), and respiratory system (SMR 0.88; -1,945). We found a 26% increase in Diabetes Mellitus mortality (SMR 1.26; 2885 deaths) during the pandemic year. Our findings corroborate the need to create and strengthen policies aimed at the prevention and control of NCDs, in order to mitigate the impact of future infectious disease pandemics.

Ketone supplementation dampens subjective and objective responses to alcohol in rats and humans.

Previous preclinical and human studies have shown that high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal. However, the effects of KS on alcohol sensitivity are unknown. In this single-blind, cross-over study, 10 healthy participants (3 females) were administered a single, oral dose of a KS (25 g of ketones from D-ß-hydroxybutyric acid and R-1,3-butanediol) or placebo 30 min prior to an oral alcohol dose (0.25 g/kg for women; 0.31 g/kg for men). Assessments of breath alcohol concentration (BrAC) and blood alcohol levels (BAL) and responses on the Drug Effect Questionnaire were repeatedly obtained over 180 min after alcohol consumption. In a parallel preclinical study, 8 Wistar rats (4 females) received an oral gavage of KS (0.42 g ketones/kg), water, or the sweetener allulose (0.58 g/kg) followed 15 min later by an oral alcohol dose (0.8 g/kg). BAL were monitored for 240 min after alcohol exposure. In humans, the intake of KS prior to alcohol significantly blunted BrAC and BAL, reduced ratings of alcohol liking and wanting, and increased disliking for alcohol. In rats, KS reduced BAL more than either allulose or water. In conclusion, KS altered physiological and subjective responses to alcohol in both humans and rats and the effects were likely not mediated by the sweetener allulose present in the KS drink. Therefore, KS could potentially reduce the intoxicating and rewarding effects of alcohol and thus be a novel intervention for treating alcohol use disorder.

Sugarcane: an unexpected habitat for black yeasts in Chaetothyriales.

Sugarcane (Saccharum officinarum, Poaceae) is cultivated on a large scale in (sub)tropical regions such as Brazil and has considerable economic value for sugar and biofuel production. The plant is a rich substrate for endo- and epiphytic fungi. Black yeasts in the family Herpotrichiellaceae (Chaetothyriales) are colonizers of human-dominated habitats, particularly those rich in toxins and hydrocarbon pollutants, and may cause severe infections in susceptible human hosts. The present study assessed the diversity of Herpotrichiellaceae associated with sugarcane, using in silico identification and selective isolation. Using metagenomics, we identified 5833 fungal sequences, while 639 black yeast-like isolates were recovered in vitro. In both strategies, the latter fungi were identified as members of the genera Cladophialophora, Exophiala, and Rhinocladiella (Herpotrichiellaceae), Cyphellophora (Cyphellophoraceae), and Knufia (Trichomeriaceae). In addition, we discovered new species of Cladophialophora and Exophiala from sugarcane and its rhizosphere. The first environmental isolation of Cladophialophora bantiana is particularly noteworthy, because this species up to now is exclusively known from the human host where it mostly causes fatal brain disease in otherwise healthy patients.

The current and future costs of colorectal cancer attributable to red and processed meat consumption in Brazil.

BACKGROUND: Compelling evidence supports the association between red and processed meat consumption and increased risk of colorectal cancer. Herein, we estimated the current (2018) and future (2030) federal direct healthcare costs of colorectal cancer in the Brazilian Unified Health System attributable to red and processed meat consumption. Considering reduced red and processed meat consumption, we also projected attributable costs of colorectal cancer in 2040. METHODS: We retrieved information on red and processed meat consumption from two nationally representative dietary surveys, the Household Budget Survey 2008-2009 and 2017-2018; relative risks for colorectal cancer from a meta-analysis; direct healthcare costs of inpatient and outpatient procedures in adults ≥ 30 years with colorectal cancer (C18-C20) from 2008-2019 by sex. RESULTS: Attributable costs of colorectal cancer were calculated via comparative risk assessment, assuming a 10-year lag. In 2018, US$ 20.6 million (8.4%) of direct healthcare costs of colorectal cancer were attributable to red and processed meat consumption. In 2030, attributable costs will increase to US$ 86.6 million (19.3%). Counterfactual scenarios of reducing red and processed meat consumption in 2030 suggested that US$ 2.2 to 11.9 million and US$ 13 to 74 million could be saved in 2040, respectively. CONCLUSION: Red and processed meat consumption has an escalating economic impact on the Brazilian Unified Health System. Our findings support interventions and policies focused on primary prevention and cancer.