Analysis of the interaction of antimalarial agents with Plasmodium falciparum glutathione reductase through molecular mechanical calculations.

CONTEXT: Malaria remains a significant global health challenge with emerging resistance to current treatments. Plasmodium falciparum glutathione reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarials and dual drugs combining aminoquinoline derivatives with GR inhibitors, which reveal promising interactions between PfGR and studied drugs. The naphthoquinone Atovaquone demonstrated particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity, suggesting their efficacy in inhibiting PfGR, where the aliphatic ester bond (linker) is essential for effective binding with the enzyme's active site. Overall, this research provides important insights into the interactions between antimalarial agents and PfGR and encourages further exploration of its role in the mechanisms of action of antimalarials, including dual drugs, to enhance antiparasitic efficacy. METHODS: The drugs were tested as PfGR potential inhibitors via molecular docking on AutoDock 4, which was performed based on the preoptimized structures in HF/3-21G-PCM level of theory on ORCA 5. Drug-receptor systems with the most promising binding affinities were then studied with a molecular dynamic's simulation on AMBER 16. The molecular dynamics simulations were performed with a 100 ns NPT ensemble employing GAFF2 forcefield in the temperature of 310 K, integration time step of 2 fs, and non-bond cutoff distance of 6.0 Å.

Chemical constituents and antifungal potential of Attalea geraensis Barb. Rodr. (Arecaceae) palm leaves, a species native to the Cerrado of Brazil.

Fungal diseases, especially those that affect the root systems of plants, caused by Rhizoctonia and Macrophomina are limiting factors for achieving high crop yields. Alternatives to controlling fungi with chemical products drive the search for new options for bioactive compounds from plants. Attalea geraensis, a palm tree from the Brazilian Cerrado, is rich in flavonoids with antifungal actions. The objective of this work is to identify the chemical classes present in the ethanolic extract of green leaves of A. geraensis and determine the antifungal potential of the extract against isolates of Macrophomina phaseolina (Tassi) Goid. and Rhizoctonia solani JG Kühn. Phytochemical prospection, flavonoid dereplication, and antifungal activity were carried out of the ethanolic extract of the green leaves of A. geraensis harvested in the Cerrado area of Brazil. Steroids, triterpenes, saponins, and anthraquinones are described here for the first time for the leaves of A. geraensis. The flavonoids quercetin, isorhamnetin, 3,7-dimethylquercetin, quercetin 3-galactoside, 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-{[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4H-chromen-4-one, rhamnazin 3-galactoside, keioside, and rhamnazin 3-rutinoside were identified. Of these, only quercetin and isorhamnetin had already been identified in the leaves of A. geraensis. The results show a fungistatic potential for the species. The diversity of flavonoids present in the leaves of A. geraensis may be the result of a synergistic action between fungus and plant or there could be an antagonistic effect between flavonoids and the other identified chemical classes.

Study of the senescence of rice leaves through stationary and time-resolved photoluminescence.

This work describes the relationship between the complex of photosystem I and photosystem II in the senescence process of rice leaves observed through changes in the optical response. We studied three varieties of rice plants at different aging times using time-resolved photoluminescence to measure the time decay of the emission, and stationary photoluminescence, to measure the emission wavelength. The spectra obtained with the former technique were fitted with decreasing exponential functions. Two relaxation times were obtained, one ranging between 1.0 and 1.7 ns, and the other, from 5.0 to 10.5 ns. They are associated with the electron's deexcitation of PSI and PSII, respectively, and these decay times increase as the leaf senescence process takes place. The spectra obtained with stationary photoluminescence were fitted with Voigt functions. These spectra exhibit two main peaks around 683 and 730 nm, which could be associated mainly with PSII and PSI emissions, respectively. The PSI de-excitation exhibits higher dispersive processes because chlorophyll-a molecules in it move away from each other, decreasing their concentration. Therefore, it takes longer for electrons to recombine during photosynthesis, as seen in the time-resolve response. Articulating the results of both photoluminescence techniques, the changes in the response of the photosystems of the living rice leaves during senescence are evidenced.

Chemical constituents and antifungal potential of Attalea geraensis Barb. Rodr. (Arecaceae) palm leaves, a species native to the Cerrado of Brazil / Constituintes químicos e potencial antifúngico de folhas da Attalea geraensis Barb. Rodr. (Arecaceae), uma espécie nativa do Cerrado do Brasil

Fungal diseases, especially those that affect the root systems of plants, caused by Rhizoctonia and Macrophomina are limiting factors for achieving high crop yields. Alternatives to controlling fungi with chemical products drive the search for new options for bioactive compounds from plants. Attalea geraensis, a palm tree from the Brazilian Cerrado, is rich in flavonoids with antifungal actions. The objective of this work is to identify the chemical classes present in the ethanolic extract of green leaves of A. geraensis and determine the antifungal potential of the extract against isolates of Macrophomina phaseolina (Tassi) Goid. and Rhizoctonia solani JG Kühn. Phytochemical prospection, flavonoid dereplication, and antifungal activity were carried out of the ethanolic extract of the green leaves of A. geraensis harvested in the Cerrado area of Brazil. Steroids, triterpenes, saponins, and anthraquinones are described here for the first time for the leaves of A. geraensis. The flavonoids quercetin, isorhamnetin, 3,7-dimethylquercetin, quercetin 3-galactoside, 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-{[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4H-chromen-4-one, rhamnazin 3-galactoside, keioside, and rhamnazin 3-rutinoside were identified. Of these, only quercetin and isorhamnetin had already been identified in the leaves of A. geraensis. The results show a fungistatic potential for the species. The diversity of flavonoids present in the leaves of A. geraensis may be the result of a synergistic action between fungus and plant or there could be an antagonistic effect between flavonoids and the other identified chemical classes.

Doenças fúngicas, especialmente as que afetam os sistemas radiculares das plantas, causadas por Rhizoctonia e Macrophomina, são fatores limitantes para obtenção de grande produtividade das culturas. Alternativas ao controle dos fungos com produtos químicos impulsionam a pesquisa de novas opções de compostos bioativos oriundos de plantas. A Attalea geraensis, uma palmeira do Cerrado brasileiro, é rica em flavonoides com ações antifúngicas. O objetivo do trabalho foi identificar as classes químicas presentes no extrato etanólico das folhas verdes de A. geraensis e determinar o potencial antifúngico do extrato frente a isolados de Macrophomina phaseolina (Tassi) Goid. e Rhizoctonia solani J.G. Kühn. Realizou-se a prospecção fitoquímica, desreplicação de flavonoides e atividade antifúngica a partir do extrato etanólico das folhas verdes da A. geraensis, colhida em área de Cerrado do Brasil. Os esteroides, triterpenos, saponinas e antraquinonas estão sendo descritos pela primeira vez para as folhas de A. geraensis. Foram identificados os flavonoides quercetina, isoramnetina, 3,7-dimetilquercetina, quercetina 3-galactosídeo, 5,7-dihidroxi-2-(4-hidroxi-3-metoxifenil)-3-{[3,4,5-trihidroxi-6-(hidroximetil)oxan-2-il]oxi}-4H-cromen-4-ona, ramnazina 3-galactosídeo, keiosídeo e ramnazina 3-rutinosídeo. Destes, somente a quercetina e isorhamnetin já haviam sido identificadas nas folhas da A. geraensis. Os resultados indicam potencial fungistático para a espécie. Infere-se que a diversidade de flavonoides presentes nas folhas de A. geraensis pode ser resultado da ação sinérgica entre fungo e planta ou que haja um efeito antagonista entre os flavonoides e as demais classes químicas identificadas.

The potential of mRNA expression evaluation in predicting HER2 positivity in gastroesophageal cancer.

Gastroesophageal cancer (GEC) is an aggressive disease characterized by a high frequency of metastasis and poor overall survival rates. GEC presents HER2 overexpression in 5 to 25% of tumors eligible for HER2-targeted therapy. HER2 evaluation requires protein levels and copy number alteration analyses by immunohistochemistry (IHC) and in situ hybridization (FISH or SISH), respectively. These are semiquantitative methodologies that need an expert and well-trained pathologist. Therefore, the use of new surrogate methods for HER2 evaluation in cancer, such as gene expression analysis, might improve GEC HER2 classification. We evaluated HER2 positivity in GEC through conventional IHC and SISH analyses and investigated the potential application of HER2 mRNA expression by quantitative PCR to categorize GEC samples as HER2-positive or HER2-negative. Among 270 GEC samples, 10.9% were HER2-positive by IHC and SISH analyses. HER2 mRNA was overexpressed in HER2-positive GEC samples and presented high accuracy in distinguishing those tumors from HER2-negative GEC. Nevertheless, HER2 mRNA analysis was not capable of classifying HER2-equivocal GEC samples into HER2-positive or -negative according to SISH data. Quantitative PCR analysis showed HER2 overexpression in HER2-positive GEC samples. Nevertheless, HER2 mRNA analysis failed to classify HER2-equivocal GEC according to SISH data.

Convalescent plasma therapy in COVID-19 patients: a non-randomized case-control study with concurrent control.

Convalescent plasma therapy has shown controversial results in coronavirus disease-19 (COVID-19) patients. We performed a non-randomized case-control study with contemporaneous controls in a hospital in southern Brazil. Patients were selected for treatment with convalescent plasma by medical decision and compared with patients who did not receive plasma and were hospitalized due to COVID-19 at the same time. The outcomes of interest were intensive care unit (ICU) admission and in-hospital death. Patients that received convalescent plasma had lower in-hospital mortality than patients that did not receive plasma (relative risk (RR) 0.48; 95% confidence interval (CI) 0.29 to 0.79) and these results were consistent after changing the subset of control patients. There were no differences regarding ICU admission between groups (RR=0.80; 95%CI: 0.47 to 1.35). In this study, patients that received convalescent plasma for COVID-19 had lower in-hospital mortality, but this finding requires further confirmation given the retrospective nature of the study.

Why do men have worse COVID-19-related outcomes? A systematic review and meta-analysis with sex adjusted for age.

We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the meta-regression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.

Immunoexpression of REGγ and apoptosis-related proteins in oral tongue squamous cell carcinoma.

The aim of this study was to investigate the immunohistochemical expression of REGγ, p53, MDM-2, Bcl-2, and Bax in oral tongue squamous cell carcinoma (OTSCC), and to correlate the findings with clinicopathological parameters. Fifty-eight OTSCC cases were selected for the study. The percentages of nuclear (REGγ, p53, and MDM-2) and cytoplasmic (Bcl-2 and Bax) staining in epithelial cells were determined and correlated with clinicopathological parameters (regional lymph node metastasis, clinical stage, clinical outcome, and histopathological grade of malignancy). Expression of REGγ was observed in all cases studied. Significantly lower percentages were observed in tumours with lymph node metastasis (P = 0.036) and in high-grade tumours (P = 0.013). No significant differences in p53, MDM-2, or Bax expression were observed according to the clinicopathological parameters. Lower percentages of Bcl-2 staining were found in high-grade OTSCC (P = 0.040) and in cases of disease-related death (P = 0.032). The expression of REGγ showed a weak positive correlation with the expression of MDM-2 (P = 0.001) and Bcl-2 (P = 0.014). The results of this study suggest that lower expression of REGγ may contribute to the progression of OTSCC. The role of REGγ in the development of OTSCC does not appear to be primarily related to the modulation of apoptosis in neoplastic cells.

Molar-incisor hypomineralisation: an updated view for aetiology 20 years later.

BACKGROUND: The term Molar-Incisor Hypomineralisation (MIH) was introduced in 2001 by Weerheijm, Jälevik and Alaluusua, and describes a defect of systemic origin that affects one to four first permanent molars, often associated with permanent incisors. In the past 20 years, this definition dictated the work regarding MIH prevalence, associated risk factors, association with dental caries, impact on quality of life, and therapeutic options. PURPOSE: In this report, we offer an updated and comprehensive view of MIH centred on the patient and the tooth. CONCLUSION: MIH today is globally recognized as a potential public health problem and it is not a defect of purely systemic origin but rather a condition with complex aetiology that in some instances may be the result of gene-environmental interactions.

Convalescent plasma therapy in COVID-19 patients: a non-randomized case-control study with concurrent control

Convalescent plasma therapy has shown controversial results in coronavirus disease-19 (COVID-19) patients. We performed a non-randomized case-control study with contemporaneous controls in a hospital in southern Brazil. Patients were selected for treatment with convalescent plasma by medical decision and compared with patients who did not receive plasma and were hospitalized due to COVID-19 at the same time. The outcomes of interest were intensive care unit (ICU) admission and in-hospital death. Patients that received convalescent plasma had lower in-hospital mortality than patients that did not receive plasma (relative risk (RR) 0.48; 95% confidence interval (CI) 0.29 to 0.79) and these results were consistent after changing the subset of control patients. There were no differences regarding ICU admission between groups (RR=0.80; 95%CI: 0.47 to 1.35). In this study, patients that received convalescent plasma for COVID-19 had lower in-hospital mortality, but this finding requires further confirmation given the retrospective nature of the study.

The potential of mRNA expression evaluation in predicting HER2 positivity in gastroesophageal cancer

Gastroesophageal cancer (GEC) is an aggressive disease characterized by a high frequency of metastasis and poor overall survival rates. GEC presents HER2 overexpression in 5 to 25% of tumors eligible for HER2-targeted therapy. HER2 evaluation requires protein levels and copy number alteration analyses by immunohistochemistry (IHC) and in situ hybridization (FISH or SISH), respectively. These are semiquantitative methodologies that need an expert and well-trained pathologist. Therefore, the use of new surrogate methods for HER2 evaluation in cancer, such as gene expression analysis, might improve GEC HER2 classification. We evaluated HER2 positivity in GEC through conventional IHC and SISH analyses and investigated the potential application of HER2 mRNA expression by quantitative PCR to categorize GEC samples as HER2-positive or HER2-negative. Among 270 GEC samples, 10.9% were HER2-positive by IHC and SISH analyses. HER2 mRNA was overexpressed in HER2-positive GEC samples and presented high accuracy in distinguishing those tumors from HER2-negative GEC. Nevertheless, HER2 mRNA analysis was not capable of classifying HER2-equivocal GEC samples into HER2-positive or -negative according to SISH data. Quantitative PCR analysis showed HER2 overexpression in HER2-positive GEC samples. Nevertheless, HER2 mRNA analysis failed to classify HER2-equivocal GEC according to SISH data.

Why do men have worse COVID-19-related outcomes? A systematic review and meta-analysis with sex adjusted for age

We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the meta-regression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.

Genome-wide association study and pathway analysis for carcass fatness in Nellore cattle measured by ultrasound.

Identifying genes or genomic regions influencing carcass-quality traits such as fatness (FTN) is essential to optimize the genetic selection processes in beef cattle. The aim of this study was to identify genomic regions associated with FTN in Nellore cattle as well as to elucidate the metabolic pathways related to the phenotypic expression. Ultrasound-based measurements of FTN were collected in 11 750 animals, with 39 903 animals in the pedigree file. Additionally, 1440 animals were genotyped using the GGP-indicus 35K SNP panel, which contained 33 623 SNPs after quality control. Twenty genes related to FTN were found on 11 chromosomes, explaining 12.96% of the total additive genetic variance. Gene ontology revealed seven genes: NR1L2, PKD2, GSK3ß, EXT1, RAD51B, SORCS1 and DPH6, associated with important processes related to FTN. In addition, novel candidate genes (MAATS1, LYPD1, CDK5RAP2, RAD51B, c13H2Oorf96 and TRAPPC11) were detected and could provide further knowledge to uncover genetic regions associated to carcass fatness in beef cattle.

MET overexpression and intratumor heterogeneity in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the ten most frequent and deadly cancers, without effective therapies for most patients. More recently, drugs targeting deregulated growth factor signaling receptors have been developed, such as HGF-MET targeted therapy. We assessed MET and HGF genetic alterations and gene and protein expression profiles in ESCC patients from the Brazilian National Cancer Institute and publicly available datasets, as well as the intratumor heterogeneity of the alterations found. Our analyses showed that HGF and MET genetic alterations, both copy number and mutations, are not common in ESCC, affecting 5 and 6% of the cases, respectively. HGF showed a variable mRNA expression profile between datasets, with no alterations (GSE20347), downregulation (GSE45670), and upregulation in ESCC (our dataset and GSE75241). On the other hand, MET was found consistently upregulated in ESCC compared to non-tumor surrounding tissue, with median fold-changes of 5.96 (GSE20347), 3.83 (GSE45670), 6.02 (GSE75241), and 5.0 (our dataset). Among our patients, 84% of the tumors showed at least a two-fold increase in MET expression. This observation was corroborated by protein levels, with 55% of cases exhibiting positivity in 100% of the tumor cells. Intratumor heterogeneity was evaluated in at least four tumor biopsies from five patients and two cases showed a consistent increase in MET expression (at least two-fold) in all tumor samples. Our data suggested that HGF-MET signaling pathway was likely to be overactivated in ESCC, representing a potential therapeutic target, but eligibility for this therapy should consider intratumor heterogeneity.

Multicenter Validation of the Neonatal Sequential Organ Failure Assessment Score for Prognosis in the Neonatal Intensive Care Unit.

Infants in the neonatal intensive care unit are at risk of life-threatening organ dysfunction, but few objective tools with utility exist. In a multicenter cohort of 20 152 infants, we show the neonatal sequential organ failure assessment score had good-to-excellent discrimination of mortality across centers, birth weights, and time points after admission.

Aesthetic perception in children with molar incisor hypomineralization.

PURPOSE: To investigate the relationship between aesthetic perception and molar incisor hypomineralization (MIH) in schoolchildren aged 8-12 years. METHODS: The study included 467 pupils enrolled in elementary schools. Once authorization was received, the students were examined for DMFT and dmft indexes (WHO criteria), and for MIH (EAPD criteria). The aesthetic perceptions were verified by the Child Perceptions Questionnaire About Tooth Appearance (CQATA), a questionnaire divided into several items, including physical, psychological and social domains; perception about tooth pleasantness, tooth alignment, tooth discoloration and tooth health; and reported pleasant colour. Data analysis was carried out using descriptive statistics, the Chi-square, the Mann-Whitney and the Kruskal-Wallis tests, and linear regression at a significance level of 0.05. RESULTS: The tooth health perception was worse when the child had MIH, and the tooth alignment and tooth discoloration perceptions, when MIH affected the incisors. The number of teeth affected by MIH was associated with higher averages in the tooth discoloration perception. CONCLUSIONS: Children with MIH showed more negative perceptions toward tooth health, tooth alignment and tooth discoloration. However, none of the clinically investigated variables negatively impacted the reported pleasant colour question.

MET overexpression and intratumor heterogeneity in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is among the ten most frequent and deadly cancers, without effective therapies for most patients. More recently, drugs targeting deregulated growth factor signaling receptors have been developed, such as HGF-MET targeted therapy. We assessed MET and HGF genetic alterations and gene and protein expression profiles in ESCC patients from the Brazilian National Cancer Institute and publicly available datasets, as well as the intratumor heterogeneity of the alterations found. Our analyses showed that HGF and MET genetic alterations, both copy number and mutations, are not common in ESCC, affecting 5 and 6% of the cases, respectively. HGF showed a variable mRNA expression profile between datasets, with no alterations (GSE20347), downregulation (GSE45670), and upregulation in ESCC (our dataset and GSE75241). On the other hand, MET was found consistently upregulated in ESCC compared to non-tumor surrounding tissue, with median fold-changes of 5.96 (GSE20347), 3.83 (GSE45670), 6.02 (GSE75241), and 5.0 (our dataset). Among our patients, 84% of the tumors showed at least a two-fold increase in MET expression. This observation was corroborated by protein levels, with 55% of cases exhibiting positivity in 100% of the tumor cells. Intratumor heterogeneity was evaluated in at least four tumor biopsies from five patients and two cases showed a consistent increase in MET expression (at least two-fold) in all tumor samples. Our data suggested that HGF-MET signaling pathway was likely to be overactivated in ESCC, representing a potential therapeutic target, but eligibility for this therapy should consider intratumor heterogeneity.

HbA1c variability and long-term glycemic control are linked to peripheral neuropathy in patients with type 1 diabetes.

BACKGROUND: HbA1c variability has been linked to retinopathy, renal disease and autonomic neuropathy in patients with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D). Although the same relationship has been demonstrated for diabetic peripheral neuropathy (DPN) in patients with T2D, data for T1D are still lacking. METHODS: Patients older than 17 years of age with ≥ 10 years of T1D duration and follow-up were included. All patients underwent nerve conduction studies and neurological examination. Laboratorial data was retrospectively extracted from chart review. Mean HbA1c (mHbA1c) over 10 years was calculated, as well as HbA1c variability estimated by standard deviation (HbA1c-SD) and coefficient of variation (HbA1c-CV). RESULTS: Fifty patients with T1D were included (30 females and 21 non-caucasians), with mean age and T1D duration of 25.6 ± 5.0 and 17.9 ± 6.1 years, respectively. The frequency of DPN was 24%. Higher mHbA1c (10.4 ± % vs 8.1 ± %; p < 0.001), HbA1c-SD (1.8 ± 0.8 vs 0.9 ± 0.4; p < 0.001), and HbA1c-CV (1.7 ± 0.8 vs 1.2 ± 1.1; p = 0.006) were observed in patients with DPN compared to others. SD-HbA1c and HbA1c-CV were associated with DPN, diagnosed by either clinical or NCS criteria, independent of mHbA1c, age and gender. CONCLUSIONS: Not only long-term glycemic control, but also its variability is associated with DPN in patients with T1D. Larger studies are required to confirm this finding.

A Simulation-Optimisation approach for hospital beds allocation.

The planning of hospital beds is among the most debated problems in healthcare. Despite being an important issue, many initiatives have failed to sustain services improvements, resulting in high costs and also high refusal rates. The stochastic problem involves conflicting criteria, therefore, we propose a Simulation-Optimisation approach to solve it. The Evolutionary Algorithm NSGA-II drives the process, and the solutions are validated and evaluated via Discrete Event Simulation. An application is performed in one of the health regions of the state of Minas Gerais, Brazil, where the public health system assists nearly 80% of the patients. The results pointed out that the proposed approach could find efficient and feasible solutions for the problem. Therefore, it is a good alternative to empirical methods currently used in Brazil to set hospital beds allocation.