Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes.

Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.

IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques.

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.

Computational Mechanisms Underlying Motivation to Earn Symbolic Reinforcers.

Reinforcement learning is a theoretical framework that describes how agents learn to select options that maximize rewards and minimize punishments over time. We often make choices, however, to obtain symbolic reinforcers (e.g., money, points) that are later exchanged for primary reinforcers (e.g., food, drink). Although symbolic reinforcers are ubiquitous in our daily lives, widely used in laboratory tasks because they can be motivating, mechanisms by which they become motivating are less understood. In the present study, we examined how monkeys learn to make choices that maximize fluid rewards through reinforcement with tokens. The question addressed here is how the value of a state, which is a function of multiple task features (e.g., the current number of accumulated tokens, choice options, task epoch, trials since the last delivery of primary reinforcer, etc.), drives value and affects motivation. We constructed a Markov decision process model that computes the value of task states given task features to then correlate with the motivational state of the animal. Fixation times, choice reaction times, and abort frequency were all significantly related to values of task states during the tokens task (n = 5 monkeys, three males and two females). Furthermore, the model makes predictions for how neural responses could change on a moment-by-moment basis relative to changes in the state value. Together, this task and model allow us to capture learning and behavior related to symbolic reinforcement.

Motor System-Dependent Effects of Amygdala and Ventral Striatum Lesions on Explore-Exploit Behaviors.

Deciding whether to forego immediate rewards or explore new opportunities is a key component of flexible behavior and is critical for the survival of the species. Although previous studies have shown that different cortical and subcortical areas, including the amygdala and ventral striatum (VS), are implicated in representing the immediate (exploitative) and future (explorative) value of choices, the effect of the motor system used to make choices has not been examined. Here, we tested male rhesus macaques with amygdala or VS lesions on two versions of a three-arm bandit task where choices were registered with either a saccade or an arm movement. In both tasks we presented the monkeys with explore-exploit tradeoffs by periodically replacing familiar options with novel options that had unknown reward probabilities. We found that monkeys explored more with saccades but showed better learning with arm movements. VS lesions caused the monkeys to be more explorative with arm movements and less explorative with saccades, although this may have been due to an overall decrease in performance. VS lesions affected the monkeys' ability to learn novel stimulus-reward associations in both tasks, while after amygdala lesions this effect was stronger when choices were made with saccades. Further, on average, VS and amygdala lesions reduced the monkeys' ability to choose better options only when choices were made with a saccade. These results show that learning reward value associations to manage explore-exploit behaviors is motor system dependent and they further define the contributions of amygdala and VS to reinforcement learning.

Pruning recurrent neural networks replicates adolescent changes in working memory and reinforcement learning.

Adolescent development is characterized by an improvement in multiple cognitive processes. While performance on cognitive operations improves during this period, the ability to learn new skills quickly, for example, a new language, decreases. During this time, there is substantial pruning of excitatory synapses in cortex and specifically in prefrontal cortex. We have trained a series of recurrent neural networks to solve a working memory task and a reinforcement learning (RL) task. Performance on both of these tasks is known to improve during adolescence. After training, we pruned the networks by removing weak synapses. Pruning was done incrementally, and the networks were retrained during pruning. We found that pruned networks trained on the working memory task were more resistant to distraction. The pruned RL networks were able to produce more accurate value estimates and also make optimal choices more consistently. Both results are consistent with developmental improvements on these tasks. Pruned networks, however, learned some, but not all, new problems more slowly. Thus, improvements in task performance can come at the cost of flexibility. Our results show that overproduction and subsequent pruning of synapses is a computationally advantageous approach to building a competent brain.

Effect of Smoking on Longitudinal Interferon-ϒ Release Assay Results among Close Contacts of People with Pulmonary Tuberculosis.

Diagnosis of M. tuberculosis (Mtb) infection in close contacts is critical for TB control. Smoking is a risk factor for Mtb infection and TB disease but its effect on longitudinal interferon-gamma release assay (IGRA) results remains unknown. We conducted a multi-site prospective study in Brazil between 2015-2019, among close contacts of adults with culture-confirmed pulmonary TB. IGRA was performed at baseline, month 6 if negative at baseline, and month 24-30 after enrollment. IGRA results were categorized as IGRA-positive (maintained from baseline to last visit), IGRA-conversion (from negative to positive at any time), IGRA-reversion (from positive to negative at any time), and IGRA-negative (maintained from baseline to last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models. Estimated propensity score was used as a covariate in models, which regressed the outcome (IGRA-positive, IGRA-conversion, IGRA-reversion) on smoking status. Of 430 close contacts, 89 (21%) were IGRA-positive, 30 (7%) were converters, 30 (7%) were reverters and 22 were indeterminate. Smoking frequency was 26 (29%) among IGRA-positive contacts, 7 (23%) in converters, and 3 (10%) in reverters. Smoking in contacts was associated with lower odds of IGRA-reversion (adjusted odds ratio = 0.16; 95% confidence interval = [0.03-0.70]). We did not detect associations between smoking and IGRA-positive or IGRA-conversion. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome.

Prediction Models for Adverse Drug Reactions During Tuberculosis Treatment in Brazil.

BACKGROUND: Tuberculosis (TB) treatment-related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates. METHODS: We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk. RESULTS: There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74-.83) and fit (optimism-corrected slope and intercept of -0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75-4.09]) and CM use (HR, 5.26 [95% CI, 2.63-10.52]) increased TB-ADR risk. CONCLUSIONS: The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs.

Transcriptomic signatures of progression to TB disease among close contacts in Brazil.

BACKGROUND: Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB, so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. METHODS: Close contacts (≥4 hours exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically-confirmed or clinically-diagnosed pulmonary or extra-pulmonary TB disease through 24 months of follow-up was symptom-triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative PCR. Prognostic performance for incident TB was tested using receiver operating characteristic curve (ROC) analysis at 6, 9, 12, and 24 months of follow-up. RESULTS: Between June 2015 and June 2019, 1,854 close contacts were enrolled; Twenty-five progressed to incident TB, of whom 13 had microbiologically-confirmed disease. Baseline transcriptomic signature scores were measured in 1,789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile (TPP) for a prognostic test through 6 months; three (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the TPP threshold through 12 or more months of follow-up. CONCLUSIONS: Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts, to target preventive therapy administration.

Changes in Behavior and Neural Dynamics across Adolescent Development.

Adolescence is an important developmental period, during which substantial changes occur in brain function and behavior. Several aspects of executive function, including response inhibition, improve during this period. Correspondingly, structural imaging studies have documented consistent decreases in cortical and subcortical gray matter volume, and postmortem histologic studies have found substantial (∼40%) decreases in excitatory synapses in prefrontal cortex. Recent computational modeling work suggests that the change in synaptic density underlie improvements in task performance. These models also predict changes in neural dynamics related to the depth of attractor basins, where deeper basins can underlie better task performance. In this study, we analyzed task-related neural dynamics in a large cohort of longitudinally followed subjects (male and female) spanning early to late adolescence. We found that age correlated positively with behavioral performance in the Eriksen Flanker task. Older subjects were also characterized by deeper attractor basins around task related evoked EEG potentials during specific cognitive operations. Thus, consistent with computational models examining the effects of excitatory synaptic pruning, older adolescents showed stronger attractor dynamics during task performance.SIGNIFICANCE STATEMENT There are well-documented changes in brain and behavior during adolescent development. However, there are few mechanistic theories that link changes in the brain to changes in behavior. Here, we tested a hypothesis, put forward on the basis of computational modeling, that pruning of excitatory synapses in cortex during adolescence changes neural dynamics. We found, consistent with the hypothesis, that variability around event-related potentials shows faster decay dynamics in older adolescent subjects. The faster decay dynamics are consistent with the hypothesis that synaptic pruning during adolescent development leads to stronger attractor basins in task-related neural activity.

The Xpert® MTB/RIF cycle threshold value predicts M. tuberculosis transmission to close contacts in a Brazilian prospective multicenter cohort.

BACKGROUND: The Xpert® MTB/RIF rapid molecular test provides a quantitative measure of Mycobacterium tuberculosis (Mtb) DNA in the form of cycle threshold (Ct) values. This information can be translated into mycobacterial load and used as a potential risk measure of bacterial spread for tuberculosis cases, which can impact infection control. However, the role of Ct values in assessing Mtb transmission to close contacts has not yet been demonstrated. METHODS: A prospective study was performed to investigate the association between Xpert® MTB/RIF Ct values and Mtb transmission to close contacts of patients with culture-confirmed pulmonary TB in a multi-center Brazilian cohort. We evaluated clinical and laboratory data, such as age, sex, race, smoking habits, drug use, alcohol use, chest radiograph, Xpert® MTB/RIF results among pulmonary tuberculosis cases, and QuantiFERON(QFT)-Plus results at baseline and after six months for close contacts who had a negative result at baseline. RESULTS: A total of 1,055 close contacts of 382 pulmonary tuberculosis cases were included in the study. The median Ct values from pulmonary tuberculosis cases of QFT-Plus positive (at baseline or six months) close contacts were lower compared with those who were QFT-Plus negative. An adjusted logistic regression demonstrated that reduced Ct values from the index cases were independently associated with QFT-Plus conversion from negative to positive (OR: 1.61, 95% CI: 1.12-2.32) after adjusting for clinical characteristics. CONCLUSION: Close contacts of pulmonary TB index cases exhibiting low Xpert MTB/RIF Ct values displayed higher rates of TB infection, reflecting Mtb transmission.

Environmental uncertainty and the advantage of impulsive choice strategies.

Choice impulsivity is characterized by the choice of immediate, smaller reward options over future, larger reward options, and is often thought to be associated with negative life outcomes. However, some environments make future rewards more uncertain, and in these environments impulsive choices can be beneficial. Here we examined the conditions under which impulsive vs. non-impulsive decision strategies would be advantageous. We used Markov Decision Processes (MDPs) to model three common decision-making tasks: Temporal Discounting, Information Sampling, and an Explore-Exploit task. We manipulated environmental variables to create circumstances where future outcomes were relatively uncertain. We then manipulated the discount factor of an MDP agent, which affects the value of immediate versus future rewards, to model impulsive and non-impulsive behavior. This allowed us to examine the performance of impulsive and non-impulsive agents in more or less predictable environments. In Temporal Discounting, we manipulated the transition probability to delayed rewards and found that the agent with the lower discount factor (i.e. the impulsive agent) collected more average reward than the agent with a higher discount factor (the non-impulsive agent) by selecting immediate reward options when the probability of receiving the future reward was low. In the Information Sampling task, we manipulated the amount of information obtained with each sample. When sampling led to small information gains, the impulsive MDP agent collected more average reward than the non-impulsive agent. Third, in the Explore-Exploit task, we manipulated the substitution rate for novel options. When the substitution rate was high, the impulsive agent again performed better than the non-impulsive agent, as it explored the novel options less and instead exploited options with known reward values. The results of these analyses show that impulsivity can be advantageous in environments that are unexpectedly uncertain.

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease.

BACKGROUND: Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction. METHODS: In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure. Reactive hyperemia index and flow-mediated dilation were used to measure microvascular and endothelial function, respectively, before and 30 minutes after a public-speaking mental stress task. Survival models for recurrent events were used to examine the association between vascular response to stress (difference between poststress and resting values) and MACE. Reactive hyperemia index and flow-mediated dilation were standardized in analyses. RESULTS: Of 263 patients (the mean age was 51 years; range, 25-61), 48% were women, and 65% were Black. During a median follow-up of 4.3 years, 64 patients had 141 adverse cardiovascular events (first and repeated). Worse microvascular response to stress (for each SD decrease in the reactive hyperemia index) was associated with 50% greater risk of MACE (hazard ratio, 1.50 [95% CI, 1.05-2.13]; P=0.03) among women only (sex interaction: P=0.03). Worse transient endothelial dysfunction in response to stress (for each SD decrease in flow-mediated dilation) was associated with a 35% greater risk of MACE (hazard ratio, 1.35 [95% CI, 1.07-1.71]; P=0.01), and the association was similar in women and men. CONCLUSIONS: Peripheral microvascular dysfunction with mental stress was associated with adverse events among women but not men. In contrast, endothelial dysfunction was similarly related to MACE among both men and women. These results suggest a female-specific mechanism linking psychological stress to adverse outcomes.

Wall Thickness Ratio-A New Magnetic Resonance Parameter-Is Associated With the Outcome of Biological Therapy in Patients With Ileal and Ileocolonic Crohn's Disease.

GOALS: The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD). BACKGROUND: Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH. MATERIALS AND METHODS: Ileal/ileocolonic CD patients scheduled for biological therapy were prospectively evaluated, at baseline (T0) and after 1 year of treatment (T1), with Harvey Bradshaw Index score, blood tests, ileocolonscopy, and MRE. Clinical activity was assessed after 2 years of treatment (T2). Wall thickness ratio (WTR) was calculated in the same affected ileal segment, as the ratio between the ileum wall thickness value at T1 and the ileum wall thickness value at T0. RESULTS: A total of 103 patients were included. Mean WTR at T1 in nonresponders was significantly higher than in responders. At receiver operating characteristic analysis, WTR values were significantly associated to biological therapy responsiveness. A WTR cutoff value of 0.77 mm was identified to discriminate responders from nonresponders (sensitivity: 79%; specificity: 67%). In responders, the proportion of patients with a WTR<0.77 was significantly higher than the proportion of patients achieving TH at T1. Among patients achieving endoscopic remission, 11/29 (37.9%) presented TH, while 20/29 (68.9%) presented WTR<0.77 ( P : 0.035). At multivariate logistic regression analysis, WTR<0.77 was significantly associated to biological therapy response. CONCLUSION: WTR index represents an easy-to-calculate MRE parameter and seems to be a promising tool for monitoring therapeutic response in CD patients during biological therapy.

Novel yeast-based biosensor for environmental monitoring of tebuconazole.

Due to increasing demand for high and stable crop production, human populations are highly dependent on pesticide use for growing and storing food. Environmental monitoring of these agrochemicals is therefore of utmost importance, because of their collateral effects on ecosystem and human health. Even though most current-use analytical methods achieve low detection limits, they require procedures that are too complex and costly for routine monitoring. As such, there has been an increased interest in biosensors as alternative or complementary tools to streamline detection and quantification of environmental contaminants. In this work, we developed a biosensor for environmental monitoring of tebuconazole (TEB), a common agrochemical fungicide. For that purpose, we engineered S. cerevisiae cells with a reporter gene downstream of specific promoters that are expressed after exposure to TEB and characterized the sensitivity and specificity of this model system. After optimization, we found that this easy-to-use biosensor consistently detects TEB at concentrations above 5 µg L-1 and does not respond to realistic environmental concentrations of other tested azoles, suggesting it is specific. We propose the use of this system as a complementary tool in environmental monitoring programs, namely, in high throughput scenarios requiring screening of numerous samples. KEY POINTS: • A yeast-based biosensor was developed for environmental monitoring of tebuconazole. •The biosensor offers a rapid and easy method for tebuconazole detection ≥ 5 µg L-1. •The biosensor is specific to tebuconazole at environmentally relevant concentrations.

Machine learning algorithms using national registry data to predict loss to follow-up during tuberculosis treatment.

BACKGROUND: Identifying patients at increased risk of loss to follow-up (LTFU) is key to developing strategies to optimize the clinical management of tuberculosis (TB). The use of national registry data in prediction models may be a useful tool to inform healthcare workers about risk of LTFU. Here we developed a score to predict the risk of LTFU during anti-TB treatment (ATT) in a nationwide cohort of cases using clinical data reported to the Brazilian Notifiable Disease Information System (SINAN). METHODS: We performed a retrospective study of all TB cases reported to SINAN between 2015 and 2022; excluding children (< 18 years-old), vulnerable groups or drug-resistant TB. For the score, data before treatment initiation were used. We trained and internally validated three different prediction scoring systems, based on Logistic Regression, Random Forest, and Light Gradient Boosting. Before applying our models we splitted our data into training (~ 80% data) and test (~ 20%) sets, and then compared the model metrics using the test data set. RESULTS: Of the 243,726 cases included, 41,373 experienced LTFU whereas 202,353 were successfully treated. The groups were different with regards to several clinical and sociodemographic characteristics. The directly observed treatment (DOT) was unbalanced between the groups with lower prevalence in those who were LTFU. Three models were developed to predict LTFU using 8 features (prior TB, drug use, age, sex, HIV infection and schooling level) with different score composition approaches. Those prediction scoring systems exhibited an area under the curve (AUC) ranging between 0.71 and 0.72. The Light Gradient Boosting technique resulted in the best prediction performance, weighting specificity and sensitivity. A user-friendly web calculator app was developed ( https://tbprediction.herokuapp.com/ ) to facilitate implementation. CONCLUSIONS: Our nationwide risk score predicts the risk of LTFU during ATT in Brazilian adults prior to treatment commencement utilizing schooling level, sex, age, prior TB status, and substance use (drug, alcohol, and/or tobacco). This is a potential tool to assist in decision-making strategies to guide resource allocation, DOT indications, and improve TB treatment adherence.

Editorial Commentary: Complications After Meniscal Surgery Are Rare and Generally Associated With Medical Comorbidity.

Meniscal tears are prevalent and frequently require surgical intervention. This injury affects younger, active patients after acute trauma. Meniscal repair is often indicated. Degenerative tears are more common in elderly patients and are generally treated with partial meniscectomy. Other factors such as chronicity, stability, tear type, and associated injuries may also play a role in the treatment algorithm. In terms of complications, both procedures are generally safe, with a complication rate approximating 1%, but adverse effects such as deep venous thrombosis, pulmonary embolism, surgical-site infection, readmission, and reoperation can occur. Complications are more common in elderly patients. Moreover, recent research shows that complications are associated with medical comorbidities, with smoking, and with longer operating times.

Efficiency of protein combinations in diets for Rhamdia quelen: growth, digestive and metabolic biochemistry and nutrient deposition.

This study was conducted to determine the best combination of protein sources in diets for jundiá, based on growth, metabolism, and nutrient deposition. Five protein combinations were tested: casein + fish meal (control), casein + gelatin, casein + albumin, casein + albumin + fish meal, and albumin + fish meal, in diets containing 370 g Kg-1 of crude protein and 13.4 MJ Kg-1 of digestible energy. The fish (9.38 ± 0.12 g) were allocated in a water recirculation system at a density of 3.35 g L-1 per experimental unit and fed until apparent satiety for 40 days with the diets. The fish fed with the control diet had the highest final weight, specific growth rate, protein and feed efficiency ratio, protein retention, and best apparent feed conversion. On the other hand, fish that received casein + albumin and albumin + fish meal diets showed worse results in growth and body protein retention, low trypsin and chymotrypsin activity, and high intestinal amylase activity. Therefore, the combination referred to as control (casein + fish meal) conclusively provides the best rhythm for nutrient digestion and metabolism processes, enabling fish to reach greater growth and retention of body protein with low whole-fish fat content.

Growth performance, plasma and hepatic biochemistry of jundiá Rhamdia quelen fed dephytinized rice bran protein concentrate.

A 45-day feeding assay was carried out to evaluate the effects of crescent levels of dephytinized rice bran protein concentrate (DRBPC) on growth performance, nutrient deposition, plasma and liver parameters of jundiá Rhamdia quelen. Five experimental diets were formulated with inclusion of 0 (control), 10, 15, 20, and 30% of DRBPC. In total 500 jundiás (initial body weight 6.28 ± 0.12 g) were allocated in 20 tanks (230 L) to give four groups for each treatment. Fish were fed to apparent satiation for 45 days. Weight gain and specific growth rate were evaluated by cubic regression analysis (P < 0.05) and displayed maximal growth on the inclusion level of 25% of DRBPC. The results indicated that fish fed DRBPC15 and DRBPC30 had lower body protein deposition and hepatosomatic index compared to CONTROL diet, respectively. No significant differences (P > 0.05) were assessed in plasma parameters. The alanine aminotransferase activity was higher in fish fed DRBPC30 compared to CONTROL group. The present study has demonstrated that DRBPC displayed significant nutritional quality for the jundiá. Thus, this new ingredient could be included as a protein source in fish for minimizing the use of fish meal.

Comparative life-history strategies in three Lebiasinidae (Characiformes) in a Rio Negro tributary, Brazilian Amazon.

Reproductive traits co-evolve and form successful life-history strategies adapted to the biology and environment of a particular taxon, maximizing offspring and species survival chances, therefore studies investigating differences in adaptive traits across different environments can enhance our understanding of the natural selection process and evolution. Herein, we address whether the reproductive strategies of phylogenetically closely related fishes are influenced by habitat predictability, using three species of the Lebiasinidae family as models. The predominance of larger and mature individuals during the flood season, with high waters characterized by smaller immature individuals, suggests a seasonal reproductive strategy for Nannostomus trifasciatus. Copella callolepis, which inhabits both habitats, also showed a single reproductive peak. However, compared to N. trifasciatus, this species displayed late spawning, restricted to the flood season, as indicated by the higher abundance of larger and mature individuals during this period and the presence of smaller (juveniles) and spawned individuals in the following season. The reproductive tactics observed in N. marginatus differed significantly from the single reproductive peak of the other species, as two reproductive peaks were observed: one during the flood season and another during the low water season. In conclusion, our study demonstrates that the environment strongly influences reproductive strategies for lebiasinids. N. marginatus, restricted to small water bodies, exhibited an opportunistic reproductive strategy, whereas the species inhabiting main rivers, N. trifasciatus and C. callolepis, exhibited a more seasonal strategy.

Celiac trunk stenosis by median arcuate ligament in orthotopic liver transplantation: a potential hidden foe to the biliary tree.

BACKGROUND: Celiac trunk compression by the median arcuate ligament (MAL) increases the risk of ischemic complications following gastrointestinal surgical procedures. Previous studies suggest increased risk of hepatic artery thrombosis (HAT) in orthotopic liver transplant (OLT) recipients. The aim of this study is to investigate the impact of untreated MAL compression (MAL-C) on biliary complications in OLT. METHODS: Contrast-enhanced imaging was used to classify celiac trunk stenosis by MAL-C. Medical records were reviewed to extract pre-transplant, transplant and post-transplant data. Patients were divided into two groups: no MAL compression (nMAL-C) and MAL-C. The primary endpoint was biliary complications. Secondary endpoints were HAT and graft survival. RESULTS: 305 OLT were performed from 2010 to 2021, of which 219 were included for analysis: 185 (84.5%) patients without and 34 (15.5%) with MAL-C. The incidence of HAT was 5.9% in both groups. Biliary complications were more common in the MAL-C group (35.3% vs. 17.8%, p = 0.035). Graft survival was decreased in patients with MAL-C (p = 0.035). CONCLUSIONS: MAL-C of the celiac trunk was associated with increased risk of biliary complications and inferior graft survival in OLT patients. These findings highlight the importance of preoperative screening and treatment of MAL in this population.