Spirooxadiazoline-oxindoles derived from imatinib show antimyeloproliferative potential in K562 cells.

Imatinib mesylate was the first representative BCR-ABL1 tyrosine kinase inhibitor (TKI) class for the treatment of chronic myeloid leukemia. Despite the revolution promoted by TKIs in the treatment of this pathology, a resistance mechanism occurs against all BCR-ABL1 inhibitors, necessitating a constant search for new therapeutic options. To develop new antimyeloproliferative substances, we applied a medicinal chemistry tool known as molecular hybridization to design 25 new substances. These compounds were synthesized and biologically evaluated against K562 cells, which express BCR-ABL1, a constitutively active tyrosine kinase enzyme, as well as in WSS-1 cells (healthy cells). The new compounds are conjugated hybrids that contain phenylamino-pyrimidine-pyridine (PAPP) and an isatin backbone, which are the main pharmacophoric fragments of imatinib and sunitinib, respectively. A spiro-oxindole nucleus was used as a linker because it occurs in many compounds with antimyeloproliferative activity. Compounds 2a, 2b, 3c, 4c, and 4e showed promise, as they inhibited cell viability by between 45% and 61% at a concentration of 10 µM. The CC50 of the most active substances was determined to be within 0.8-9.8 µM.

New azaaurone derivatives as potential multitarget agents in HIV-TB coinfection.

Tuberculosis (TB) disease, caused by Mycobacterium tuberculosis (Mtb) is the leading cause of death among people with human immunodeficiency virus (HIV) infection. No dual-target drug is currently being used to simultaneously treat both infections. This work aimed to obtain new multitarget HIV-TB agents, with the goal of optimizing treatments and preventing this coinfection. These compounds incorporate the structural features of azaaurones as anti-Mtb and zidovudine (AZT) as the antiretroviral moiety. The azaaurone scaffold displayed submicromolar activities against Mtb, and AZT is a potent antiretroviral drug. Six derivatives were synthetically generated, and five were evaluated against both infective agents. Evaluations of anti-HIV activity were carried out in HIV-1-infected MT-4 cells and on endogenous HIV-1 reverse transcriptase (RT) activity. The H37Rv strain was used for anti-Mtb assessments. Most compounds displayed potent antitubercular and moderate anti-HIV activity. (E)-12 exhibited a promising multitarget profile with an MIC90 of 2.82 µM and an IC50 of 1.98 µM in HIV-1-infected T lymphocyte cells, with an 84% inhibition of RT activity. Therefore, (E)-12 could be the first promising compound from a family of multitarget agents used to treat HIV-TB coinfection. In addition, the compound could offer a prototype for the development of new strategies in scientific research to treat this global health issue.

Impact of the Koala Project on clinical outcomes of preterm infants in two maternity hospitals.

OBJECTIVE: To describe the impact of the Koala project (Actively Controlling Target Oxygen) on clinical outcomes in patients born with less than 36 weeks of gestation, in two maternity hospitals, comparing before and after the strategy implementation. METHODS: This is an intervention study with 100 preterm infants with gestational age ≤36 weeks, who used oxygen in two maternity hospitals between January 2020 and August 2021. One of the hospitals was a private institution and the other was philanthropic. The goal for the target oxygen saturation with this project was 91-95%. Comparisons between the two stages (before and after the implementation of the project) were made evaluating the outcomes of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and deaths. The continuous variables were described using mean, median, standard deviation and interquartile interval. The significance level adopted was 5% and the software used was R Core Team 2021 (version 4.1.0). RESULTS: After oxygen control use according to the Koala protocol, there was a significant reduction in the cases of retinopathy of prematurity (p<0.001) and bronchopulmonary dysplasia (p<0.001). There were no deaths in the second stage, and there was a non-significant increase in the absolute number of necrotizing enterocolitis cases. CONCLUSIONS: The Koala project seems to be an effective and feasible strategy to reduce adverse situations in the management of premature children, but research with a greater sample is needed.

Antiplasmodial, Trypanocidal, and Genotoxicity In Vitro Assessment of New Hybrid α,α-Difluorophenylacetamide-statin Derivatives.

BACKGROUND: Statins present a plethora of pleiotropic effects including anti-inflammatory and antimicrobial responses. A,α-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. METHODS: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of α,α-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. RESULTS: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. CONCLUSIONS: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments.

Measuring resilience and stress during pregnancy and its relation to vulnerability and pregnancy outcomes in a nulliparous cohort study.

BACKGROUND: Resilience reflects coping with pregnancy-specific stress, including physiological adaptations of the maternal organism or factors arising from the socioeconomic context, such as low income, domestic violence, drug and alcohol use, lack of a support network and other vulnerability characteristics. Resilience is a dynamic characteristic that should be comparatively evaluated within a specific context; its association with perceived stress and social vulnerability during pregnancy is still not fully understood. This study aimed at exploring maternal resilience, perceived stress and social vulnerability during pregnancy and its associated factors and outcomes. METHODS: Prospective multicenter cohort study of nulliparous women in Brazil determining resilience (Resilience Scale; RS) and stress (Perceived Stress Scale; PSS) at 28 weeks of gestation (± 1 week). Resilience and stress scores were compared according to sociodemographic characteristics related to maternal/perinatal outcomes and social vulnerability, defined as having low level of education, being adolescent, without a partner or ethnicity other than white. RESULTS: We included 383 women who completed the RS and PSS instruments. Most women showed low resilience scores (median: 124.0; IQR 98-143). Women with a low resilience score (RS < 125) were more likely from the Northeast region, adolescents, other than whites, did not study or work, had a low level of education, low family income and received public antenatal care. Higher scores of perceived stress were shown in the Northeast, other than whites, at low levels of education, low annual family income and public antenatal care. Pregnant women with low resilience scores (n = 198) had higher perceived stress scores (median = 28) and at least one vulnerability criterion (n = 181; 91.4%). CONCLUSION: Our results reinforce the role of resilience in protecting women from vulnerability and perceived stress. It may prevent complications and build a positive experience during pregnancy.

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens.

The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient's immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and Mycobacterium tuberculosis (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.

Influence of methanolic extracts from seeds and pulp of Annona squamosa L. on osmotic and morphological fragility in human erythrocytes.

Medicinal plants have been used for many years by communities to treat illnesses. The need for scientific proof of these vegetable's curative effects is as necessary as the proof of the inexistence of toxicity related to the use of extracts with therapeutic potential. Annona squamosa L. (Annonaceae), popularly known as "pinha", "ata" or "fruta do conde", has been used in traditional medicine for its analgesic and antitumor activities. The toxic effects attributed to this plant have also been explored as a pesticide and an insecticide. The aim of the present study was to investigate the toxicity of the methanolic extract of A. squamosa seeds and pulp against human erythrocytes. Blood samples were treated with methanolic extract at different concentrations, osmotic fragility was determined using saline tension assays and morphological analyzes were performed using optical microscopy. The extracts were analyzed using high performance liquid chromatography with diode array detection (HPLC-DAD) for phenolic quantification. The seed's methanolic extract showed toxicity above 50% from a concentration of 100 µg/mL, while also presenting echinocytes in the morphological analysis. The pulp's methanolic extract did not show toxicity to red blood cells or morphological changes at the concentrations tested. HPLC-DAD analysis revealed the presence of caffeic acid in the seed extract and gallic acid in the pulp extract. The seed's methanolic extract is toxic and the pulp's methanolic extract showed no toxicity against human erythrocytes.

Clinical outcomes in patients undergoing invasive mechanical ventilation using NAVA and other ventilation modes - A systematic review and meta-analysis.

PURPOSE: Neurally adjusted ventilatory assist mode (NAVA) benefit in mechanical ventilation (MV) patients with regard to clinically outcomes is still uncertain. Recent randomized clinical trials (RCTs) have addressed this issue, making it important to assess the real impact of NAVA in relation to these outcomes. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of RCTs comparing NAVA ventilation mode versus the standard ventilation mode in critically ill adult patients admitted to the ICU with invasive MV. The main outcome was 28-days ventilatory free-days (VFD). Secondary outcomes were weaning failure, mortality, ICU and hospital length of stay and need for tracheostomy. RESULTS: We included 5 RCTs (643 patients). The patients in the NAVA group had increased VFDs compared to the control group: mean difference (MD) 3.42 (95% CI 1.21 to 5.62, I2 = 0%). NAVA and control groups did not differ in ICU mortality [OR 0.58 (95% CI 0.33 to 1.03), I2 = 41%]. NAVA mode was associated with a reduced incidence of weaning failure [OR 0.51 (95% CI 0.29 to 0.88), I2 = 0%]. NAVA and control groups did not differ in the number of MV days: MD -1.9 days (95% CI -4.2 to 0.3, I2 = 0%). CONCLUSIONS: NAVA mode has a modest impact on MV-free days and weaning success, with no association with improvements in other relevant clinical outcomes.

Antimicrobial profile of non-typhoidal Salmonella isolated from raw sewage in the Metropolitan Region of São Paulo, Brazil.

INTRODUCTION: Non-typhoidal Salmonella (NTS), are frequently found in sewage and are one of the main causes of diarrhea in developed and developing countries due to poor sanitation conditions. In addition, NTS can potentially act as reservoirs and vehicles for the transmission of antimicrobial resistance (AMR), which can be facilitated by the discharge of sewage effluents into environmental matrices. This study aimed to analyze a NTS Brazilian collection, focusing on their antimicrobial susceptibility profile and the presence of clinically relevant AMR-encoding genes. METHODOLOGY: Forty-five non-clonal NTS strains from serotypes Salmonella enteritidis (n = 6), Salmonella enterica serovar 1,4,[5],12:i:- (S. 1,4,[5],12:i:-) (n = 25), Salmonella cerro (n = 7), Salmonella typhimurium (n = 3) and Salmonella braenderup (n = 4) were studied. Antimicrobial susceptibility testing was done using the Clinical and Laboratory Standards Institute guidelines (2017) and genes encoding resistance to beta-lactams, fluoroquinolones and aminoglycosides were identified by polymerase chain reaction and sequencing. RESULTS: Resistance to ß-lactams, fluoroquinolones, tetracyclines and aminoglycosides was frequent. The highest rates were observed for nalidixic acid (89.0%), followed by tetracycline (67.0%), ampicillin (67.0%), amoxicillin + clavulanic acid (64.0%); ciprofloxacin (47.0%) and streptomycin (42.0%). The AMR-encoding genes detected were qnrB, oqxAB, blaCTX-M and rmtA. CONCLUSIONS: Raw sewage has been considered a valuable tool to evaluate epidemiological population patterns and this study supports the view that NTS with pathogenic potential and resistance to antimicrobials are circulating in the studied region. This is worrisome due to the dissemination of these microorganisms throughout the environment.

Impact of the Koala Project on clinical outcomes of preterm infants in two maternity hospitals / Impacto do Projeto Coala nos resultados clínicos de pacientes prematuros em duas maternidades

ABSTRACT Objective: To describe the impact of the Koala project (Actively Controlling Target Oxygen) on clinical outcomes in patients born with less than 36 weeks of gestation, in two maternity hospitals, comparing before and after the strategy implementation. Methods: This is an intervention study with 100 preterm infants with gestational age ≤36 weeks, who used oxygen in two maternity hospitals between January 2020 and August 2021. One of the hospitals was a private institution and the other was philanthropic. The goal for the target oxygen saturation with this project was 91-95%. Comparisons between the two stages (before and after the implementation of the project) were made evaluating the outcomes of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and deaths. The continuous variables were described using mean, median, standard deviation and interquartile interval. The significance level adopted was 5% and the software used was R Core Team 2021 (version 4.1.0). Results: After oxygen control use according to the Koala protocol, there was a significant reduction in the cases of retinopathy of prematurity (p<0.001) and bronchopulmonary dysplasia (p<0.001). There were no deaths in the second stage, and there was a non-significant increase in the absolute number of necrotizing enterocolitis cases. Conclusions: The Koala project seems to be an effective and feasible strategy to reduce adverse situations in the management of premature children, but research with a greater sample is needed.

RESUMO Objetivo: Descrever o impacto do projeto Coala (Controle Ativo de Oxigênio Alvo) nos desfechos clínicos em pacientes nascidos com menos de 36 semanas de gestação, em duas maternidades, comparando antes e depois da implementação da estratégia. Métodos: Trata-se de um estudo de intervenção com cem prematuros vivos, com idade gestacional ≤36 semanas, que utilizaram oxigênio em duas maternidades entre janeiro de 2020 e agosto de 2021. A meta para a saturação de oxigênio alvo com este projeto foi de 91-95%. Comparações entre as duas etapas (antes e depois da implantação do projeto) foram feitas avaliando os desfechos de retinopatia da prematuridade, displasia broncopulmonar, enterocolite necrosante e óbitos. As variáveis contínuas foram descritas por meio de média, mediana, desvio padrão e intervalo interquartil. O nível de significância adotado foi de 5% e o software empregado foi o R Core Team 2021 (versão 4.1.0). Resultados: Observou-se que, após o uso de controle de oxigênio segundo o protocolo Coala, houve redução significativa nos casos de retinopatia da prematuridade (p<0,001) e displasia broncopulmonar (p<0,001). Não houve óbitos na segunda etapa e houve aumento não significativo no número absoluto de casos de enterocolite necrosante. Conclusões: O projeto Coala parece ser uma estratégia eficaz e viável para reduzir situações adversas no manejo de crianças prematuras, mas pesquisas com amostras maiores são necessárias.

The Use of Zidovudine Pharmacophore in Multi-Target-Directed Ligands for AIDS Therapy.

The concept of polypharmacology embraces multiple drugs combined in a therapeutic regimen (drug combination or cocktail), fixed dose combinations (FDCs), and a single drug that binds to different targets (multi-target drug). A polypharmacology approach is widely applied in the treatment of acquired immunodeficiency syndrome (AIDS), providing life-saving therapies for millions of people living with HIV. Despite the success in viral load suppression and patient survival of combined antiretroviral therapy (cART), the development of new drugs has become imperative, owing to the emergence of resistant strains and poor adherence to cART. 3'-azido-2',3'-dideoxythymidine, also known as azidothymidine or zidovudine (AZT), is a widely applied starting scaffold in the search for new compounds, due to its good antiretroviral activity. Through the medicinal chemistry tool of molecular hybridization, AZT has been included in the structure of several compounds allowing for the development of multi-target-directed ligands (MTDLs) as antiretrovirals. This review aims to systematically explore and critically discuss AZT-based compounds as potential MTDLs for the treatment of AIDS. The review findings allowed us to conclude that: (i) AZT hybrids are still worth exploring, as they may provide highly active compounds targeting different steps of the HIV-1 replication cycle; (ii) AZT is a good starting point for the preparation of co-drugs with enhanced cell permeability.

Analysis toxicity by different methods and anxiolytic effect of the aqueous extract Lippia sidoides Cham.

Lippia sidoides Cham. (Verbenaceae) is a species often mentioned in traditional medicine due to the medicinal properties attributed to its leaves, which include antibacterial, antifungal, acaricidal and antioxidant. Several of these actions have been scientifically proven, according to reports in the literature; however, little is known about toxicological aspects of this plant. This work included studies to determine the chemical composition and toxicity tests, using several methods aiming to evaluate the safety for use of the aqueous extract of L. sidoides leaves, in addition, the anxiolytic effect on adult zebrafish was investigated, thus contributing to the pharmacological knowledge and traditional medicine concerning the specie under study. The chemical profile was determined by liquid chromatography coupled to mass spectrometry-HPLC/MS with electrospray ionization. Toxicity was evaluated by zebrafish, Drosophila melanogaster, blood cells, and Artemia salina models. 12 compounds belonging to the flavonoid class were identified. In the toxicity assays, the observed results showed low toxicity of the aqueous extract in all tests performed. In the analysis with zebrafish, the highest doses of the extract were anxiolytic, neuromodulating the GABAa receptor. The obtained results support the safe use of the aqueous extract of L. sidoides leaves for the development of new drugs and for the use by populations in traditional medicine.

Chemical Composition and Antimicrobial Potential of Essential Oil of Acritopappus confertus (Gardner) R.M.King & H.Rob. (Asteraceae).

Microbial resistance has become a worrying problem in recent decades after the abusive use of antibiotics causing the selection of resistant microorganisms. In order to circumvent such resistance, researchers have invested efforts in the search for promising natural substances, such as essential oils. Thus, the objective of this work was to determine the chemical composition of the essential oil of Acritopappus confertus leaves, to evaluate its intrinsic effect and its effects in combination with drugs against pathogenic fungi and bacteria, in addition to verifying the inhibition of virulence in Candida strains. To this end, the oil was verified by gas chromatography coupled with mass spectrometry (GC/MS). Candida strains were used for antifungal assays by means of the serial microdilution technique, in order to determine the average inhibitory concentration (IC50), and for the modification assays, sub-inhibitory concentrations (MIC/8) were used. Finally, the natural product's ability to inhibit the formation of filamentous structures was evaluated. In antibacterial tests, the MIC of the oil against strains of Staphylococcus aureus and Escherichia coli and its modifying effects in association with gentamicin, erythromycin, and norfloxacin were determined. The major constituent of the essential oil was the monoterpene myrcene (54.71%). The results show that the essential oil has an antifungal effect, with C. albicans strains being the most susceptible. Furthermore, the oil can potentiate the effect of fluconazole against strains of C. tropicalis and C. albicans. Regarding its effect on micromorphology, the oil was also able to inhibit the filaments in all strains. In combination with antibiotics, the oil potentiated the drug's action by reducing the MIC against E. coli and S. aureus. It can be concluded that the essential oil of A. confertus has potential against pathogenic fungi and bacteria, making it a target for the development of an antimicrobial drug.

Head circumference as an epigenetic risk factor for maternal nutrition.

Nutrition indicators for malnutrition can be screened by many signs such as stunting, underweight or obesity, muscle wasting, and low caloric and nutrients intake. Those deficiencies are also associated with low socioeconomic status. Anthropometry can assess nutritional status by maternal weight measurements during pregnancy. However, most studies have focused primarily on identifying changes in weight or Body Mass Index (BMI), and their effects on neonatal measures at present time. Whereas head circumference (HC) has been associated with nutrition in the past. When the mother was exposed to poor nutrition and unfavorable social conditions during fetal life, it was hypothesized that the intergenerational cycle was potentially mediated by epigenetic mechanisms. To investigate this theory, maternal head circumference (MHC) was associated with neonatal head circumference (NHC) in pregnant women without preexisting chronic conditions, differentiated by sociodemographic characteristics. A multiple linear regression model showed that each 1 cm-increase in MHC correlated with a 0.11 cm increase in NHC (ß95% CI 0.07 to 0.15). Notwithstanding, associations between maternal and neonatal anthropometrics according to gestational age at birth have been extensively explained. Path analysis showed the influence of social status and the latent variable was socioeconomic status. A model of maternal height and head circumference was tested with effects on neonatal HC. The social variable lacked significance to predict neonatal HC in the total sample (p = 0.212) and in the South/Southeast (p = 0.095), in contrast to the Northeast (p = 0.047). This study highlights the potential intergenerational influence of maternal nutrition on HC, suggesting that maternal nutrition may be more relevant in families with major social vulnerability.

Performances of birthweight charts to predict adverse perinatal outcomes related to SGA in a cohort of nulliparas.

BACKGROUND: Small-for-gestational-age neonates (SGA) are at increased risk of neonatal morbidity. Nulliparity represents a risk factor for SGA; birthweight charts may perform differently for the detection of SGA among nulliparas. This study aimed at describing the prevalence of SGA in nulliparas according to different birthweight charts and evaluating the diagnostic performance of these charts to maternal and perinatal outcomes. METHODS: This is a secondary analysis of a Brazilian cohort of nulliparas named Preterm SAMBA study. Birthweight centiles were calculated using the Intergrowth-21st, WHO-Fetal Growth Charts, Birth in Brazil population chart and GROW-customised chart. The risks of outcomes among SGA neonates and their mothers in comparison to neonates with birthweights between the 40th-60th centiles were calculated, according to each chart. ROC curves were used to detect neonatal morbidity in neonates with birth weights below different cutoff centiles for each chart. RESULTS: A sample of 997 nulliparas was assessed. The rate of SGA infants varied between 7.0-11.6%. All charts showed a significantly lower risk of caesarean sections in women delivering SGA neonates compared to those delivering adequate-for-gestational-age neonates (OR 0.55-0.64, p < .05). The charts had poor performance (AUC 0.492 - 0.522) for the detection of neonatal morbidity related to SGA born at term. CONCLUSION: The populational and customised birthweight charts detected different prevalence of small-for-gestational-age neonates and showed similar and poor performance to identify related neonatal adverse outcomes in this population.

Deep endometriosis: clinical and epidemiological findings of diagnosed women according to the criteria of the international deep endometriosis analysis group (IDEA) / Endometriose profunda: achados clínicos e epidemiológicos de mulheres diagnosticadas segundo critérios do International Deep Endometriosis Analysis Group (IDEA)

Introdução: endometriose ocorre quando o tecido semelhante ao endométrio acomete o peritônio, podendo infiltrar estruturas e órgãos como o intestino, o ureter, a bexiga ou a vagina e geralmente está acompanhado de processo inflamatório. Estima-se que a doença acometa 6 a 10% das mulheres em idade reprodutiva e mais de 50% das mulheres inférteis. Os dados clínicos e epidemiológicos das pacientes com EP disponíveis na literatura são provenientes de estudos cujas amostras foram selecionadas por cirurgia, portanto passíveis de vieses de seleção. A ultrassonografia pélvica endovaginal com preparo intestinal (USGTVP) tem valores de especificidade e sensibilidade elevados.Objetivo: analisar o perfil clínico e epidemiológico das pacientes portadoras de EP diagnosticadas através da USGTVP.Método: estudo transversal, que analisou 227 pacientes com diagnóstico ultrassonográfico de endometriose profunda. Resultados: infertilidade acometeu 43,8% das mulheres. Sintomas álgicos considerados como moderado ou grave (escala visual analógica, EVA, >3) apresentaram respectivamente a seguinte prevalência e valores médios na escala de EVA: dismenorreia em 84,7% (6,9), dispareunia em 69,1%, (4,5) disquezia menstrual em 60,7% (4,3) e disúria menstrual em 35,7% das pacientes. Antecedente de múltiplas cirurgias ocorreu em 10,4 % e apenas 6,8 % das portadoras haviam realizado fisioterapia para assoalho pélvico.Conclusão: a população portadora de EP apresentou alta prevalência de infertilidade e sintomas álgicos, achados que refletem o impacto social na qualidade de vida e no planejamento familiar dessas mulheres. A alta frequência de antecedentes de múltiplas abordagens cirúrgicas e a baixa incidência de antecedente de realização de fisioterapia pélvica na população com EP, contrariando as recomendações de tratamento ideal atualmente já estabelecidas, sinalizam a dificuldade de acesso das portadoras a centros especializados.

Introduction: endometriosis occurs when tissue similar to the endometrium affects the peritoneum, which can infiltrate structures and organs such as the bowel, ureter, bladder or vagina and is usually accompanied by an inflammatory process. It is estimated that the disease affects 6 to 10% of women of reproductive age and more than 50% of infertile women. The clinical and epidemiological data of patients with deep endometriosis (DE) available in the literature come from studies whose samples were selected by surgery, therefore subject to selection bias. Transvaginal pelvic ultrasound with bowel preparation (TVUBP) has high specificity and sensitivity values. Objective: to analyze the clinical and epidemiological profile of patients with DE diagnosed through the TVUBP.Methods: it is a cross-sectional study of 227 patients with an ultrasound diagnosis of deep endometriosis. Results: infertility affected 43.8% of women. Painful symptoms considered as moderate or severe (visual analogue scale, VAS, >3) had the following prevalence and mean values on the VAS scale, respectively: dysmenorrhea in 84.7% (6.9), dyspareunia in 69.1%, (4.5), menstrual dyschezia in 60.7% (4.3) and menstrual dysuria in 35.7% of patients. A history of multiple surgeries occurred in 10.4% and only 6.8% of patients had undergone physiotherapy for the pelvic floor. Conclusion: the DE population had a high prevalence of infertility and pain symptoms, which reflect the social impact on these women's quality of life and family planning. The high frequency of history of multiple surgical approaches and the low incidence of history of pelvic physiotherapy in the population with DE, contrary to the currently established ideal treatment recommendations, indicate the difficulty of access for patients to specialized centers

Prediction of pregnancy-related hypertensive disorders using metabolomics: a systematic review.

OBJECTIVE: To determine the accuracy of metabolomics in predicting hypertensive disorders in pregnancy. DESIGN: Systematic review of observational studies. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: An electronic literature search was performed in June 2019 and February 2022. Two researchers independently selected studies published between 1998 and 2022 on metabolomic techniques applied to predict the condition; subsequently, they extracted data and performed quality assessment. Discrepancies were dealt with a third reviewer. The primary outcome was pre-eclampsia. Cohort or case-control studies were eligible when maternal samples were taken before diagnosis of the hypertensive disorder. STUDY APPRAISAL AND SYNTHESIS METHODS: Data on study design, maternal characteristics, how hypertension was diagnosed, metabolomics details and metabolites, and accuracy were independently extracted by two authors. RESULTS: Among 4613 initially identified studies on metabolomics, 68 were read in full text and 32 articles were included. Studies were excluded due to duplicated data, study design or lack of identification of metabolites. Metabolomics was applied mainly in the second trimester; the most common technique was liquid-chromatography coupled to mass spectrometry. Among the 122 different metabolites found, there were 23 amino acids and 21 fatty acids. Most of the metabolites were involved with ammonia recycling; amino acid metabolism; arachidonic acid metabolism; lipid transport, metabolism and peroxidation; fatty acid metabolism; cell signalling; galactose metabolism; nucleotide sugars metabolism; lactose degradation; and glycerolipid metabolism. Only citrate was a common metabolite for prediction of early-onset and late-onset pre-eclampsia. Vitamin D was the only metabolite in common for pre-eclampsia and gestational hypertension prediction. Meta-analysis was not performed due to lack of appropriate standardised data. CONCLUSIONS AND IMPLICATIONS: Metabolite signatures may contribute to further insights into the pathogenesis of pre-eclampsia and support screening tests. Nevertheless, it is mandatory to validate such methods in larger studies with a heterogeneous population to ascertain the potential for their use in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42018097409.

Comparative analysis of chemical profiles and antioxidant activities of essential oils obtained from species of Lippia L. by chemometrics.

Due to the importance of diseases associated with oxidative stress, the search for natural antioxidants proves to be essential. This work aimed to compare the chemical composition and antioxidant potential of essential oils from the genus Lippia L. through chemometric analysis. The essential oils were characterized by gas chromatography coupled with mass spectrometry. Antioxidant potentials were determined by DPPH, ABTS, Deoxyribose and ß-carotene protection, Iron chelation and reduction methods. All data were related by multivariate analyzes. Essential oils showed low similar chemical compositions and no statistically significant relationship. These showed relevant antioxidant activity, especially for L. sidoides that obtained IC50 of 5.22 ± 0.08 µg/mL in ABTS capture. Multivariate analyzes showed the effectiveness of L. alba compounds to DPPH scavenging, Fe3+ reduction and ß-carotene protection, and L. gracilis components to deoxyribose protect. Thus, studies proving the antioxidant potential of Lippia compounds against oxidative stress and their use in food conservation are fundamental.

Agreement between the short and long versions of the Resilience Scale: A validation among the obstetric population according to vulnerability status.

OBJECTIVE: To compare the 14-item Resilience Scale (RS-14) and the original 25-item scale (RS-25) in the obstetric population, including vulnerable and non-vulnerable women. METHODS: A Brazilian prospective cohort study was conducted of nulliparous singleton pregnant women from March 2018 to March 2020. Women who completed the RS-25 at 27-29 weeks of pregnancy were included in the analysis. RS-25 and RS-14 scores were converted to comparable scales of 0-100. Medians, standard deviations, and centiles between versions were compared for the general, vulnerable, and non-vulnerable populations. Correlation, concordance, and internal consistency and reliability analyses were performed. P < 0.05 was considered statistically significant. RESULTS: In total, 381 women who completed the RS-25 were included. Medians of RS-14 and RS-25 scores were significantly different (73.4 and 70.8, respectively; P < 0.001), regardless of the vulnerability status. The RS-14 showed a high correlation (Pearson´s correlation coefficient of -0.379 (P-value < 0.001)), but no agreement (Pitman's test of difference in variance: r = 0.422; P < 0.001) with the RS-25 version. RS-14 showed high internal consistency and reliability with only one component (Variance of 59.82%, Cronbach's Alpha 0.947). CONCLUSION: The RS-14 may overestimate the RS-25 score and different domains may not be assessed by the short version. The psychometric properties of the RS-14 and the clinical relevance of the variation between versions require further evaluation.