The Role and Applications of Artificial Intelligence in the Treatment of Chronic Pain.

PURPOSE OF REVIEW: This review aims to explore the interface between artificial intelligence (AI) and chronic pain, seeking to identify areas of focus for enhancing current treatments and yielding novel therapies. RECENT FINDINGS: In the United States, the prevalence of chronic pain is estimated to be upwards of 40%. Its impact extends to increased healthcare costs, reduced economic productivity, and strain on healthcare resources. Addressing this condition is particularly challenging due to its complexity and the significant variability in how patients respond to treatment. Current options often struggle to provide long-term relief, with their benefits rarely outweighing the risks, such as dependency or other side effects. Currently, AI has impacted four key areas of chronic pain treatment and research: (1) predicting outcomes based on clinical information; (2) extracting features from text, specifically clinical notes; (3) modeling 'omic data to identify meaningful patient subgroups with potential for personalized treatments and improved understanding of disease processes; and (4) disentangling complex neuronal signals responsible for pain, which current therapies attempt to modulate. As AI advances, leveraging state-of-the-art architectures will be essential for improving chronic pain treatment. Current efforts aim to extract meaningful representations from complex data, paving the way for personalized medicine. The identification of unique patient subgroups should reveal targets for tailored chronic pain treatments. Moreover, enhancing current treatment approaches is achievable by gaining a more profound understanding of patient physiology and responses. This can be realized by leveraging AI on the increasing volume of data linked to chronic pain.

Safety evaluation of 8 drug degradants present in over-the-counter cough and cold medications.

Although the United States Food & Drug Administration (FDA) has provided guidance on the control of drug degradants for prescription drugs, there is less guidance on how to set degradant specifications for FDA OTC monograph drugs. Given that extensive impurity testing was not part of the safety paradigm in original OTC monographs, a weight of evidence (WOE) approach to qualify OTC degradants is proposed. This approach relies on in silico tools and read-across approaches alongside standard toxicity testing to determine safety. Using several drugs marketed under 21 CFR 341 as case studies, this research demonstrates the utility of a WOE approach across data-rich and data-poor degradants. Based on degradant levels ranging from 1 to 4% of the maximum daily doses of each case study drug and 10th percentile body weight data for each patient group, children were recognized as having the highest potential exposure relative to adults per body mass. Depending on data availability and relationship to the parent API, margins of safety (MOS) or exposure margins were calculated for each degradant. The findings supported safe use, and indicated that this contemporary WOE approach could be utilized to assess OTC degradants. This approach is valuable to establish specifications for degradants in OTCs.

The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls.

In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive "Best-Estimate" TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The "Best-Estimate" TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Methodological and ethical challenges in the use of focused ultrasound for blood-brain barrier disruption in neuro-oncology.

BACKGROUND: Focused ultrasound (FUS) shows promise for enhancing drug delivery to the brain by temporarily opening the blood-brain barrier (BBB), and it is increasingly used in the clinical setting to treat brain tumours. It remains however unclear whether FUS is being introduced in an ethically and methodologically sound manner. The IDEAL-D framework for the introduction of surgical innovations and the SYRCLE and ROBINS-I tools for assessing the risk of bias in animal studies and non-randomized trials, respectively, provide a comprehensive evaluation for this. OBJECTIVES AND METHODS: A comprehensive literature review on FUS in neuro-oncology was conducted. Subsequently, the included studies were evaluated using the IDEAL-D framework, SYRCLE, and ROBINS-I tools. RESULTS: In total, 19 published studies and 12 registered trials were identified. FUS demonstrated successful BBB disruption, increased drug delivery, and improved survival rates. However, the SYRCLE analysis revealed a high risk of bias in animal studies, while the ROBINS-I analysis found that most human studies had a high risk of bias due to a lack of blinding and heterogeneous samples. Of the 15 pre-clinical stage 0 studies, only six had formal ethical approval, and only five followed animal care policies. Both stage 1 studies and stage 1/2a studies failed to provide information on patient data confidentiality. Overall, no animal or human study reached the IDEAL-D stage endpoint. CONCLUSION: FUS holds promise for enhancing drug delivery to the brain, but its development and implementation must adhere to rigorous safety standards using the established ethical and methodological frameworks. The complementary use of IDEAL-D, SYRCLE, and ROBINS-I tools indicates a high risk of bias and ethical limitations in both animal and human studies, highlighting the need for further improvements in study design for a safe implementation of FUS in neuro-oncology.

Passive In-Line Chlorination for Drinking Water Disinfection: A Critical Review.

The world is not on track to meet Sustainable Development Goal 6.1 to provide universal access to safely managed drinking water by 2030. Removal of priority microbial contaminants by disinfection is one aspect of ensuring water is safely managed. Passive chlorination (also called in-line chlorination) represents one approach to disinfecting drinking water before or at the point of collection (POC), without requiring daily user input or electricity. In contrast to manual household chlorination methods typically implemented at the point of use (POU), passive chlorinators can reduce the user burden for chlorine dosing and enable treatment at scales ranging from communities to small municipalities. In this review, we synthesized evidence from 27 evaluations of passive chlorinators (in 19 articles, 3 NGO reports, and 5 theses) conducted across 16 countries in communities, schools, health care facilities, and refugee camps. Of the 27 passive chlorinators we identified, the majority (22/27) were solid tablet or granular chlorine dosers, and the remaining devices were liquid chlorine dosers. We identified the following research priorities to address existing barriers to scaled deployment of passive chlorinators: (i) strengthening local chlorine supply chains through decentralized liquid chlorine production, (ii) validating context-specific business models and financial sustainability, (iii) leveraging remote monitoring and sensing tools to monitor real-time chlorine levels and potential system failures, and (iv) designing handpump-compatible passive chlorinators to serve the many communities reliant on handpumps as a primary drinking water source. We also propose a set of reporting indicators for future studies to facilitate standardized evaluations of the technical performance and financial sustainability of passive chlorinators. In addition, we discuss the limitations of chlorine-based disinfection and recognize the importance of addressing chemical contamination in drinking water supplies. Passive chlorinators deployed and managed at-scale have the potential to elevate the quality of existing accessible and available water services to meet "safely managed" requirements.

7-Hydroxycoumarin Induces Vasorelaxation in Animals with Essential Hypertension: Focus on Potassium Channels and Intracellular Ca2+ Mobilization.

Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. Additionally, natural products remain crucial to the design of new drugs. The natural product 7-hydroxycoumarin (7-HC) exhibits pharmacological properties linked to antihypertensive mechanisms of action. This study aimed to evaluate the vascular effects of 7-HC in an experimental model of essential hypertension. The isometric tension measurements assessed the relaxant effect induced by 7-HC (0.001 µM-300 µM) in superior mesenteric arteries isolated from hypertensive rats (SHR, 200-300 g). Our results suggest that the relaxant effect induced by 7-HC rely on K+-channels (KATP, BKCa, and, to a lesser extent, Kv) activation and also on Ca2+ influx from sarcolemma and sarcoplasmic reticulum mobilization (inositol 1,4,5-triphosphate (IP3) and ryanodine receptors). Moreover, 7-HC diminishes the mesenteric artery's responsiveness to α1-adrenergic agonist challenge and improves the actions of the muscarinic agonist and NO donor. The present work demonstrated that the relaxant mechanism of 7-HC in SHR involves endothelium-independent vasorelaxant factors. Additionally, 7-HC reduced vasoconstriction of the sympathetic agonist while improving vascular endothelium-dependent and independent relaxation.

Risk factors for non-specific low back pain in older people: a systematic review with meta-analysis.

PURPOSE: To conduct a systematic review about risk factors associated with non-specific low back pain (LBP) in older people. METHODS: The study protocol was prospectively registered with Prospero (CRD42020191619). This systematic review with meta-analysis included cohort studies that investigated risk factors for LBP in older people. The following databases were searched up to 12 December 2020: MEDLINE (Ovid), Embase, CINAHL, SCOPUS and Web of Science. Two independent reviewers appraised methodological quality using the Critical Appraisal Checklist for Cohort Studies instrument. RESULTS: We identified 3939 potentially relevant publications. After removing duplicates, screening title, and abstracts, we assessed 86 publications in full text. We included the remaining 11 publications for analysis. There is strong evidence that depressive symptoms are a risk of reporting future back pain onset (I2 = 52,7%, Odds ratio 1.4, CI 1.28-1.53). CONCLUSION: Depressive symptoms are a risk factor for LBP in older people. Due to the limitations of the literature, the role of some risk factors remains unclear. An additional high-quality prospective cohort is needed to better elucidate these relationships.

Chlorine efficacy against bacteriophage Phi6, a surrogate for enveloped human viruses, on porous and non-porous surfaces at varying temperatures and humidity.

While efficacy of chlorine against Phi6, a widely-used surrogate for pathogenic enveloped viruses, is well-documented, surfaces common to low-resource contexts are under-researched. We evaluated seven surfaces (stainless steel, plastic, nitrile, tarp, cloth, concrete, wood) and three environmental conditions-temperature (4, 25, 40 °C), relative humidity (RH) (23, 85%), and soiling-to determine Phi6 recoverability and the efficacy of disinfection with 0.5% NaOCl. Overall, Phi6 recovery was >4 log10 PFU/mL on most surfaces after drying 1 hour at all temperature/humidity conditions. After disinfection, all non-porous test conditions (48/48) achieved ≥4 LRV at 1 and 5 minutes of exposure; significantly more non-porous surfaces met ≥4 LRV than porous (p < 0.001). Comparing porous surfaces, significantly fewer wood samples met ≥4 LRV than cloth (p < 0.001); no differences were observed between concrete and either wood (p = 0.083) or cloth (p = 0.087). Lastly, no differences were observed between soil and no-soil conditions for all surfaces (p = 0.712). This study highlights infectious Phi6 is recoverable across a range of surfaces and environmental conditions, and confirms the efficacy of chlorine disinfection. We recommend treating all surfaces with suspect contamination as potentially infectious, and disinfecting with 0.5% NaOCl for the minimum contact time required for the target enveloped virus (e.g. Ebola, SARS-CoV-2).

Stereological analysis of the New Zealand rabbits (Oryctolagus cuniculus) placenta.

The onset of gestation is characterized by growth, morphological and functional changes of the placenta. We aim to evaluate the placental compartments in New Zealand rabbits by means of stereological methods. The fetal and maternal portion of placenta (12, 14, 18 and 20 gestational days) was randomly sampled for the stereological analysis. Histological sections were scanned to estimate fetal (labyrinth and junctional) and maternal (decidua) compartment volumes. The total volume of the placenta for the ages of 12, 14, 18 and 20 days was, respectively, 320 mm3, 340 mm3, 940 mm3 and 1300 mm3. The volume of the labyrinth was 56 mm3, 119 mm3, 231 mm3 and 481 mm3, respectively. The volume of junctional zone was 75 mm3, 76 cm3, 238 mm3 and 314 mm3, respectively. The volume of decidua was 174 mm3, 143 mm3, 469 mm3 and 504 mm3, respectively. We concluded that the rabbit´s placenta compartments varied according to the gestational period, increasing continuously over the 20 gestational days. However, on the onset of the development of the placenta the decidua presented faster growth, whereas after the 20 days of development, the labyrinth developed more quickly. This study represents an aid to the understanding of placentation in humans.

In Vivo and in Silico Trypanocidal Activity Evaluation of (-)-Cubebin Encapsulated in PLGA Microspheres as Potential Treatment in Acute Phase.

In this study, the trypomastigotes of a Y strain of Trypanosoma cruzi were inoculated intraperitoneally into male BALB/c mice weighing approximately 25 g each, which were divided into groups for evaluation of the trypanocidal activity. For the treatment of experimental groups, encapsulated and unencapsulated (-)-cubebin, Benznidazole, and two groups as negative controls were used. The encapsulated (-)-cubebin showed a 68.1 % encapsulation efficiency. The parasitemia peak of substances remained around the 9th day after the observed reduction in the number of circulating trypomastigotes. The encapsulated (-)-cubebin and (-)-cubebin unloaded showed a decrease of 61.3 % and 58.5 % in the number of parasites as compared to the negative control, respectively. Moreover, animals treated with encapsulated (-)-cubebin had a higher survival time as compared to the other groups. In conclusion, the results obtained were more promising for encapsulated (-)-cubebin as compared to unloaded particles.

Trypanocidal Activity of Dysphania ambrosioides, Lippia alba, and Tetradenia riparia Essential Oils against Trypanosoma cruzi.

Despite the current treatments against Chagas Disease (CD), this vector-borne parasitic disease remains a serious public health concern. In this study, we have explored the in vitro and/or in vivo trypanocidal and cytotoxic activities of the essential oils (EOs) obtained from Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) (DA-EO), Lippia alba (Mill.) N.E. Brown (Verbenaceae) (LA-EO), and Tetradenia riparia (Hochst.) Codd (Lamiaceae) (TR-EO) grown in Brazil Southeast. DA-EO was the most active against the trypomastigote and amastigote forms in vitro; the IC50 values were 8.7 and 12.2 µg mL-1 , respectively. The EOs displayed moderate toxicity against LLCMK2 cells, but the DA-EO showed high selectivity index (SI) for trypomastigote (SI=33.2) and amastigote (SI=11.7) forms. Treatment with 20 mg/kg DA-EO, LA-EO, or TR-EO for 20 days by intraperitoneal administration reduced parasitemia by 6.36 %, 4.74 %, and 32.68 % on day 7 and by 12.04 %, 27.96 %, and 65.5 % on day 9. These results indicated that DA-EO, LA-EO, and TR-EO have promising trypanocidal potential in vitro, whereas TR-EO has also potential trypanocidal effects in vivo.

Yeast Mycocins: a great potential for application in health.

Mycocins have demonstrated inhibition of fungi, bacteria, parasites and viruses, in addition to being studied as epidemiological markers and in the development of vaccines. They are defined as extracellular proteins or glycoproteins with different activities, the main mechanism of action being the inhibition of ß-glucan synthesis in the cell wall of sensitive strains. Given the resistance problems created by several microorganisms to agents commonly used in clinical practice, the discovery of new substances with this purpose becomes essential. Mycocins have potential as anti-microbials because they show minimal toxicity and do not present resistance.

Oxidative stress, inflammation and disease activity biomarkers in lupus nephropathy.

Lupus nephropathy is a severe and frequent complication of systemic lupus erythematosus. Here, we assessed the biomarkers of oxidative stress, inflammation and disease activity in patients with lupus nephritis. Thirty-four patients with active lupus nephritis, 31 patients with inactive lupus nephritis and 20 lupus patients without renal damage (non-lupus nephritis) were studied. Oxidative stress biomarkers malonyldialdehyde, oxidized-to-total glutathione, catalase, superoxide dismutase and total antioxidant status were assessed, as well as inflammation biomarkers CRP, interleukin 6 and monocyte chemoattractant protein 1. Renal tubular disease biomarkers neutrophil gelatinase-associated lipocalin and ß2-microglobulin were assessed, together with the classic disease activity biomarkers urinary protein/creatinine ratio, anti-dsDNA, anti-C1q antibody and complement proteins C3 and C4. Significant differences were found between active lupus nephritis and inactive lupus nephritis patients and between active lupus nephritis and non-lupus nephritis patients for all the assessed biomarkers (P < 0.05), except for catalase, superoxide dismutase and interleukin 6. There is an imbalance in the redox status in active lupus nephritis patients that would be involved in lipid peroxidation of the glomerular basal membrane that would alter its integrity and could also affect renal tubular function in these patients.

Antibiotic Activity of Wickerhamomyces anomalus Mycocins on Multidrug-Resistant Acinetobacter baumannii.

To evaluate the susceptibility of multidrug-resistant Acinetobacter baumannii to mycocins produced by Wickerhamomyces anomalus and to verify the cytotoxicity of these compounds. Three culture supernatants of W. anomalus (WA40, WA45, and WA92), containing mycocins (WA40M1, WA45M2, and WA92M3), were tested on A. baumannii using broth microdilution methods, solid medium tests, and cytotoxicity tests in human erythrocytes and in Artemia saline Leach. W. anomalus was able to produce high antimicrobial mycocins, as even at high dilutions, they inhibited A. baumannii. In a solid medium, it was possible to observe the inhibition of A. baumannii, caused by the diffusion of mycocins between agar. Finally, the three supernatants were not cytotoxic when tested on human erythrocytes and Artemia salina. According to the evidence in this study, the mycocins of W. anomalus have been effective and could be used in the development of new antimicrobial substances.

Current and potential biotechnological applications of odorant-binding proteins.

Odorant-binding proteins (OBPs) are small soluble proteins whose biological function is believed to be facilitating olfaction by assisting the transport of volatile chemicals in both vertebrate and insect sensory organs, where they are secreted. Their capability to interact with a broad range of hydrophobic compounds combined with interesting features such as being small, stable, and easy to produce and modify, makes them suitable targets for applied research in various industrial segments, including textile, cosmetic, pesticide, and pharmaceutical, as well as for military, environmental, health, and security field applications. In addition to reviewing already established biotechnological applications of OBPs, this paper also discusses their potential use in prospecting of new technologies. The development of new products for insect population management is currently the most prevailing use for OBPs, followed by biosensor technology, an area that has recently seen a significant increase in studies evaluating their incorporation into sensing devices. Finally, less typical approaches include applications in anchorage systems and analytical tools. KEY POINTS: • Odorant-binding proteins (OBPs) present desired characteristics for applied research. • OBPs are mainly used for developing new products for insect population control. • Incorporation of OBPs into chemosensory devices is a growing area of study. • Less conventional uses for OBPs include anchorage systems and analytical purposes. Graphical Abstract.

Laboratory efficacy of surface disinfection using chlorine against Vibrio cholerae.

Disinfecting surfaces with chlorine is commonly conducted in cholera outbreaks to prevent ongoing fomite-based transmission, yet evidence gaps have led to contradictory guidance. In this study, we tested the efficacy of spraying and wiping chlorine on five representatives non-porous and five porous surfaces to remove Vibrio cholerae. In total, 120 disinfection tests were run in replicate on carriers inoculated with 1.02 × 107-1.73 × 108 V. cholerae CFU/cm2. Surfaces disinfected by spraying 0.2% chlorine had >3 log reduction value (LRV) on 7/10 and 9/10 surfaces at 1 and 10 min, respectively; and 2.0% chlorine on 9/10 and 10/10 surfaces at 1 and 10 min, respectively. Surfaces disinfected by wiping 0.2% chlorine had >3 LRV on 3/10 and 7/10 surfaces at 1 and 10 min, respectively; and 2.0% chlorine on 8/10 surfaces at 1 and 10 min. We found no significant differences between chlorine types (p < 0.05), higher reductions with spraying compared to wiping (p = 0.001), and lower reductions on porous compared to non-porous surfaces (p = 0.006 spraying and p < 0.001 wiping). Our results support using 0.2% chlorine sprayed on all surfaces, or wiped on most non-heavily soiled surfaces, and a 2.0% concentration on contaminated porous surfaces; and emphasize surfaces must be visibly wetted to achieve disinfection.

Misoprostol administered sublingually at a dose of 12.5 µg versus vaginally at a dose of 25 µg for the induction of full-term labor: a randomized controlled trial.

BACKGROUND: Labor induction is defined as any procedure that stimulates uterine contractions before labor begins spontaneously. The vaginal and oral routes of administration of misoprostol are those most used for the induction of labor in routine practice, with the recommended dose being 25 µg. Nevertheless, the sublingual route may reduce the number of vaginal examinations required, increasing patient comfort and lowering the risk of maternal and fetal infection. Based on a previous systematic review, the objective of this study was to compare the frequency of tachysystole as the main outcome measure when misoprostol is administered sublingually at the dose of 12.5 µg versus vaginally at a dose of 25 µg to induce labor in a full-term pregnancy with a live fetus. METHODS: A randomized, placebo-controlled, triple-blind clinical trial was conducted at two maternity hospitals in northeastern Brazil. Two hundred patients with a full-term pregnancy, a live fetus, Bishop score ≤ 6 and an indication for induction of labor were included. Following randomization, one group received 12.5 µg misoprostol sublingually and a vaginal placebo, while the other group received a sublingual placebo and 25 µg misoprostol vaginally. The primary outcome was the frequency of tachysystole. Student's t-test, the chi-square test of association and Fisher's exact test were used, as appropriate. Risk ratios and their 95% confidence intervals were calculated. RESULTS: The frequency of tachysystole was lower in the group using 12.5 µg misoprostol sublingually compared to the group using 25 µg misoprostol vaginally (RR = 0.15; 95%CI: 0.02-0.97; p = 0.002). Failure to achieve vaginal delivery within 12 and 24 h was similar in both groups. Sublingual administration was preferred to vaginal administration by women in both groups; however, the difference was not statistically significant. CONCLUSION: The effectiveness of labor induction with low-dose sublingual misoprostol was similar to that achieved with vaginal administration of the recommended dose; however, the rate of tachysystole was lower in the sublingual group, and this route of administration may prove a safe alternative. TRIAL REGISTRATION: Registration number: NCT01406392, ClinicalTrials.gov. Date of registration: August 1, 2011.

The timeline development of female canine germ cells.

During the sex differentiation, the primordial germ cells (PGCs) pass through a differentiation, becoming spermatogonial cells in males and oocytes in females. In this phase, there is difference in gene expression and differentiation potency between males and females. Specific cell markers have been essential in the PGC meiosis beginning and become oocyte cells. However, there are few studies about germline in domestic animals. The domestic dog (Canis lupus familiaris) is an interesting animal model to be used in the investigation about the mammal development because it has several biochemical and physiological similarities to humans. In addition, some additional investigations about dogs may contribute to a better understanding of the biology and genetic components, improving clinical veterinary and zoological sciences. Here, we elucidated by immunofluorescence and quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR), the dynamics of the expression of pluripotent (POU5F1 and NANOG) and germline (DDX4, DAZL and DPPA3) markers that are very important in the development of female canine germ cells during 35-50 days post-fertilization (dpf). The female canine germ cells were positive for pluripotent markers during middle developmental period. The number of DDX4, DAZL and DPPA3 cells increased along the germ cell maturation from 45 to 50 dpf. We provided an expression analysis of the pluripotent and germline markers in paraffin sections using the middle and later periods in female canine germ cells. The results can contribute the understanding about the timeline of each marker along the maturation of female canine germ cells. These results have a great significance to demonstrate the germ cell profile changes because it may allow the development of protocols about in vitro germ cell derivation.

Intake, digestibility, and growth performance of Girolando bulls supplemented on pasture in Bahia, Brazil.

The objective of this trial was to evaluate intake, digestibility, and growth performance of Girolando bulls submitted to two nutritional planes while grazing on Brachiaria brizantha cv. Marandu pasture. Twenty-two animals, with average initial body weight = 209.1 ± 8.2 kg, were used in this trial. The experimental design was repeated measurements, in a 2 × 3 factorial arrangement, with two nutritional planes (NP1 and NP2) and three seasons of the year, with 11 replicates per treatment. The animals of the NP1 received mineral mixture ad libitum during rainy season 1 (15 February through 5 July 2014), energy protein supplement in the amount of 1 g d kg BW-1 during the dry season (from 6 July through 22 November 2014), and again mineral mixture ad libitum during rainy season 2 (from 23 November 2014 through 9 March 2015). The NP2 animals received 2 g d kg BW-1, 2 g d kg BW-1, and 1 g d kg BW-1 of energy-protein supplement in the respective seasons of the year. Forage intakes were similar between nutritional planes, 6.8 and 7.6 kg DM day-1 and 2.1 and 2.22% BW for NP1 and NP2, respectively. There was no statistical difference (level) between the intakes of neutral detergent fiber corrected for ash and protein (4.1 and 4.3 kg day-1 and 1.2 and 1.3% BW, respectively for nutritional planes 1 and 2). For the other nutrients, NP2 showed greater values. The highest intakes and digestibilities of dry matter, organic matter, and non-fiber carbohydrate were in rainy season 2. Performance and feed conversion were similar among NPs. This study showed that lower levels of supplementation could be done in order to reduce feeding costs with no impact on performance.