Melaleuca alternifolia essential oil in a natural product-based formulation: Antimicrobial and healing effects in Staphylococcus aureus-infected wounds.

Owing to its exposed nature, the skin can be injured by various factors, including by Staphylococcus aureus, which inhabits its innate microbiota. Treatment of infected wounds presents an important challenge, making it imperative to develop new treatment options. Plant-derived formulations, such as those containing Melaleuca alternifolia essential oil (MaEO), are used for wound treatment because of their healing, anti-inflammatory, and antimicrobial properties. This study presents a cream containing 2% MaEO (2% CMa) and evaluates its effects in an S. aureus-infected wound murine model. The 2% CMa was subjected to quality control testing and pH and analysis of density, organoleptic characteristics, and microbiological effects. The quality control parameters all revealed the good stability of the 2% CMa. The formulation strongly reduced the S. aureus ATCC 6538 colony-forming unit (CFU) count in an ex vivo porcine skin model. In the murine model, daily topical application of 2% CMa reduced the severity and size of S. aureus-infected wounds and the bacterial load. These effects may be due to the presence of terpinen-4-ol, which exhibits anti-inflammatory activity. Based on these findings, the formulation exhibits good quality and safety. We suggest the topical application of this formulation, which exhibited an antimicrobial effect, as an interesting treatment strategy for wound healing.

Galactose-1-phosphate inhibits cytochrome c oxidase and causes mitochondrial dysfunction in classic galactosemia.

Classic galactosemia is an inborn error of metabolism caused by mutations in the GALT gene resulting in the diminished activity of the galactose-1-phosphate uridyltransferase enzyme. This reduced GALT activity leads to the buildup of the toxic intermediate galactose-1-phosphate and a decrease in ATP levels upon exposure to galactose. In this work, we focused our attention on mitochondrial oxidative phosphorylation in the context of this metabolic disorder. We observed that galactose-1-phosphate accumulation reduced respiratory rates in vivo and changed mitochondrial function and morphology in yeast models of galactosemia. These alterations are harmful to yeast cells since the mitochondrial retrograde response is activated as part of the cellular adaptation to galactose toxicity. In addition, we found that galactose-1-phosphate directly impairs cytochrome c oxidase activity of mitochondrial preparations derived from yeast, rat liver, and human cell lines. These results highlight the evolutionary conservation of this biochemical effect. Finally, we discovered that two compounds - oleic acid and dihydrolipoic acid - that can improve the growth of cell models of mitochondrial diseases, were also able to improve galactose tolerance in this model of galactosemia. These results reveal a new molecular mechanism relevant to the pathophysiology of classic galactosemia - galactose-1-phosphate-dependent mitochondrial dysfunction - and suggest that therapies designed to treat mitochondrial diseases may be repurposed to treat galactosemia.

Identification of SNP Markers and Candidate Genes Associated with Major Agronomic Traits in Coffea arabica.

Genome-wide association studies (GWASs) allow for inferences about the relationships between genomic variants and phenotypic traits in natural or breeding populations. However, few have used this methodology in Coffea arabica. We aimed to identify chromosomal regions with significant associations between SNP markers and agronomic traits in C. arabica. We used a coffee panel consisting of 195 plants derived from 13 families in F2 generations and backcrosses of crosses between leaf rust-susceptible and -resistant genotypes. The plants were phenotyped for 18 agronomic markers and genotyped for 21,211 SNP markers. A GWAS enabled the identification of 110 SNPs with significant associations (p < 0.05) for several agronomic traits in C. arabica: plant height, plagiotropic branch length, number of vegetative nodes, canopy diameter, fruit size, cercosporiosis incidence, and rust incidence. The effects of each SNP marker associated with the traits were analyzed, such that they can be used for molecular marker-assisted selection. For the first time, a GWAS was used for these important agronomic traits in C. arabica, enabling applications in accelerated coffee breeding through marker-assisted selection and ensuring greater efficiency and time reduction. Furthermore, our findings provide preliminary knowledge to further confirm the genomic loci and potential candidate genes contributing to various structural and disease-related traits of C. arabica.

Comparison of speech changes caused by four different orthodontic retainers: a crossover randomized clinical trial.

OBJECTIVE: This study aimed to compare the influence of four different maxillary removable orthodontic retainers on speech. MATERIAL AND METHODS: Eligibility criteria for sample selection were: 20-40-year subjects with acceptable occlusion, native speakers of Portuguese. The volunteers (n=21) were divided in four groups randomized with a 1:1:1:1 allocation ratio. The four groups used, in random order, the four types of retainers full-time for 21 days each, with a washout period of 7-days. The removable maxillary retainers were: conventional wraparound, wraparound with an anterior hole, U-shaped wraparound, and thermoplastic retainer. Three volunteers were excluded. The final sample comprised 18 subjects (11 male; 7 female) with mean age of 27.08 years (SD=4.65). The speech evaluation was performed in vocal excerpts recordings made before, immediately after, and 21 days after the installation of each retainer, with auditory-perceptual and acoustic analysis of formant frequencies F1 and F2 of the vowels. Repeated measures ANOVA and Friedman with Tukey tests were used for statistical comparison. RESULTS: Speech changes increased immediately after conventional wraparound and thermoplastic retainer installation, and reduced after 21 days, but not to normal levels. However, this increase was statistically significant only for the wraparound with anterior hole and the thermoplastic retainer. Formant frequencies of vowels were altered at initial time, and the changes remained in conventional, U-shaped and thermoplastic appliances after three weeks. CONCLUSIONS: The thermoplastic retainer was more harmful to the speech than wraparound appliances. The conventional and U-shaped retainers interfered less in speech. The three-week period was not sufficient for speech adaptation.

Evaluation of in vivo and in vitro efficacy of solasonine/solamargine-loaded lipid-polymer hybrid nanoparticles against bladder cancer.

Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in nanoparticles. This led to a study on the potential therapeutic benefits of SS and SM against bladder cancer when encapsulated in lipid-polymer hybrid nanoparticles (LPHNP). The LPHNP loaded with SS/SM were prepared using the emulsion and sonication method and their physical-chemical properties characterized. The biological effects of these nanoparticles were then tested in both 2D and 3D bladder cancer cell culture models, as well as in a syngeneic orthotopic mouse model based on the MB49 cell line and ethanol epithelial injury. The LPHNP-SS/SM had an average size of 130 nm, a polydispersity index of 0.22 and a positive zeta potential, indicating the presence of chitosan coating on the nanoparticle surface. The dispersion of LPHNP-SS/SM was found to be monodispersed with a span index of 0.539, as measured by nanoparticle tracking analysis (NTA). The recrystallization index, calculated from DSC data, was higher for the LPHNP-SS/SM compared to LPHNPs alone, confirming the presence of alkaloids within the lipid matrix. The encapsulation efficiency (EE%) was also high, with 91.08 % for SS and 88.35 % for SM. Morphological analysis by AFM and Cryo-TEM revealed that the nanoparticles had a spherical shape and core-shell structure. The study showed that the LPHNP-SS/SM exhibited mucoadhesive properties by physically interacting with mucin, suggesting a potential improvement in interaction with mucous membrane. Both the free and nanoencapsulated SS/SM demonstrated dose-dependent cytotoxicity against bladder cancer cell lines after 24 and 72 h of treatment. In 3D bladder cell culture, the nanoencapsulated SS/SM showed an IC50 two-fold lower than free SS/SM. In vivo studies, the LPHNP-SS/SM displayed an antitumoral effect at high doses, leading to a significant reduction in bladder volume compared to the positive control. However, there were observed instances of systemic toxicity and liver damage, indicated by elevated levels of transaminases (TGO and TGP). Overall, these results indicate that the LPHNPs effectively encapsulated SS/SM, showing high encapsulation efficiency and stability, along with promising in vitro and in vivo antitumoral effects against bladder cancer. Further evaluation of its systemic toxicity effects is necessary to ensure its safety and efficacy for potential clinical application.

Partnerships for the Productive Development of the Health Economic-Industrial Complex: the health question / Parcerias para o Desenvolvimento Produtivo do Complexo Econômico-Industrial da Saúde: a questão da saúde

This paper discusses some of the main criteria used to define priorities for technological and industrial development by the Brazilian Ministry of Health regarding the Partnerships for Productive Development (PDP) Program. In order to focus on the question of how to define priorities for technological development, the methodologies developed by the WHO and the EMA for that purpose are presented. WHO's and Brazilian findings on main causes of burden of disease are briefly compared. WHO's selected findings on major therapeutical gaps and technological development priorities are also compared to priorities selected and supported by the PDP program since its inception. A divorce between medicines prioritized and supported by the PDP program and the main causes of the Brazilian burden of disease was observed. Also, the incremental cost-effectiveness ratios of several medications supported by the program were preliminarily estimated. The resulting ratios were about thirty times higher than the opportunity cost estimated for Brazil. Findings of the above comparisons and cost-effectiveness exercise indicate that inadequate choices were made by the PDP program in the way to a progressive and equanimous universal health access in Brazil, anticipating a low impact on the Brazilian total burden of disease as well as a low effectiveness, efficiency and equity of the program regarding the health of the Brazilian population as a whole.

Estudos brasileiros que analisaram as Parcerias para o Desenvolvimento Produtivo (PDP) apontam limitações do desenho e da implementação das PDPs de medicamentos vis à vis os objetivos de saúde do SUS. Este artigo discute a definição de prioridades para o desenvolvimento tecnológico e industrial do complexo da saúde (CEIS), com foco na universalidade e na equidade em saúde, tendo por objeto o programa de Parcerias para o Desenvolvimento Produtivo (PDP) do Ministério da Saúde, programa de gastos anuais multibilionários, iniciado em 2009. Para aprofundar a questão do processo utilizado para definir prioridades de desenvolvimento tecnológico, o presente trabalho revê as metodologias utilizadas pela OMSepela European Medicines Agency (EMA) para esse propósito. As prioridades de saúde definidas pela OMS, partindo principalmente do critério carga de doença, e as correspondentes lacunas terapêuticas selecionadas para desenvolvimento tecnológico, com base sobretudo em evidências de monitoramento do horizonte e de avaliação tecnológica, são resumidamente apresentadas. A seguir, foram comparados os achados do relatório da OMS_ as prioridades de saúde selecionadas e as prioridades tecnológicas resultantes_ com os achados sobre carga de doença no Brasil e as prioridades selecionadas e apoiadas pelas PDPs. Observou-se um divórcio entre as prioridades medicamentosas apoiadas pelas PDPs e as principais causas de carga de doença no país. Abordamos ainda, nesse artigo, o papel da análise de custo-efetividade e do custo de oportunidade na discussão das escolhas do programa PDP. O exemplo trabalhado indica que o custo de oportunidade de várias tecnologias apoiadas pelas PDPs vigentes é dezenas de vezes superior ao limiar de custo-efetividade estimado para o Brasil. O divórcio entre as prioridades apoiadas pelas PDPs e as principais causas de carga de doença no país e o limiar de custo-efetividade assumido pelo programa PDP indicam escolhas insatisfatórias na busca para alcançar, de forma progressiva e equânime, o acesso universal à atenção de saúde em nosso país, no SUS. Essas escolhas devem resultar em uma baixa efetividade, baixa eficiência e baixa equidade do programa do ponto de vista da saúde da população brasileira como um todo.

Evaluation of the testicular artery Doppler velocimetry and its correlation with sperm defects in domestic cats.

Several studies have demonstrated the correlation between Doppler velocimetric parameters of testicular artery and semen quality in domestic species, but in felines data are scarce. This study aimed to correlate the Doppler velocimetry of the testicular artery with sperm kinetics and sperm defects, in sedated and non-sedated cats. Forty tomcats were divided into two groups: sedated (SG; n=20) with dexmedetomidine (10 µm/kg) and ketamine (12 mg/kg), and non-sedated (NSG; n=20). The animals were subjected to ultrasound Doppler velocimetry of the distal supratesticular and marginal region of the testicular artery and subsequently orchiectomized. Epididymal tail spermatozoa were recovered and analyzed using a CASA system for motility, and morphology took place. Animals of SG presented a significantly higher velocity in the marginal region of the cat's testicular artery [peak systolic velocity (PSV) 11.51 cm/s; end-diastolic velocity (EDV) 7.72 cm/s] compared to NSG (PSV 7.72 cm/s, P < 0.001; EDV 4.93 cm/s, P < 0.001). Sedated cats presented higher pulsatility and resistivity indexes than non-sedated cats. The supratesticular PSV of NSG was moderately correlated with major (rs = 0621; P < 0.001) and total sperm defects (rs = 0614; P < 0001). Doppler velocimetry was fairly correlated with minor, major, and total sperm defects. In conclusion, Doppler velocimetric evaluation emerges as an important possibility in the reproductive evaluation of tomcats, once the testicular artery hemodynamics were associated with sperm defects. However, it is advisable to carry out this evaluation in non-sedated animals. If sedation is necessary, peripheral vasoconstriction should be considered.

Remediation of soils contaminated with methomyl using electrochemically produced gaseous oxidants.

This prospective work focuses on the use of two different gaseous oxidants (chlorine dioxide and ozone) to remediate soil polluted with methomyl in two different applications: ex-situ and in-situ. In the first, the soil washing is integrated with the bubbling of the oxidant, while in the second, the gas was introduced by a perforated pipe located sub-superficially. Regarding the soil washing treatment, results demonstrate that direct use of ozone is not very efficient, although an important improvement is obtained following activation with hydrogen peroxide or UV light. In contrast, chlorine dioxide exhibited complete methomyl depletion from the soil, although with higher energy consumption and technical complexity compared to ozone. The direct dosing of the gaseous oxidants in perforated pipes is effective, achieving methomyl removals of 7.8 % and 9.2 % using ozone and chlorine dioxide, respectively. In these cases, soil conditions are not significantly modified, which becomes an important advantage of the technology as compared with other electrochemically assisted soil remediation process, in which large regions of the treated soil are affected by important changes in the pH or by depletion of ions. This lower impact makes these novel technologies more promising for further evaluations.

Bioisosteric analogs of MDMA: Improving the pharmacological profile?

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is re-emerging in clinical settings as a candidate for the treatment of specific neuropsychiatric disorders (e.g. post-traumatic stress disorder) in combination with psychotherapy. MDMA is a psychoactive drug, typically regarded as an empathogen or entactogen, which leads to transporter-mediated monoamine release. Despite its therapeutic potential, MDMA can induce dose-, individual-, and context-dependent untoward effects outside safe settings. In this study, we investigated whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. In vitro methods included radiotracer assays, transporter electrophysiology, bioluminescence resonance energy transfer and fluorescence-based assays, pooled human liver microsome/S9 fraction incubations, metabolic stability studies, isozyme mapping, and liquid chromatography coupled to high-resolution mass spectrometry. In silico methods included molecular docking. Compared with MDMA, all three MDMA bioisosteres (ODMA, TDMA, and SeDMA) showed similar pharmacological activity at human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) but decreased agonist activity at 5-HT2A/2B/2C receptors. Regarding their hepatic metabolism, they differed from MDMA, with N-demethylation being the only metabolic route shared, and without forming phase II metabolites. In addition, TDMA showed an enhanced intrinsic clearance in comparison to its congeners. Additional screening for their interaction with human organic cation transporters (hOCTs) and plasma membrane monoamine transporter (hPMAT) revealed a weaker interaction of the MDMA analogs with hOCT1, hOCT2, and hPMAT. Our findings suggest that these new MDMA bioisosteres might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT, hDAT, and hNET, but displaying a reduced activity at 5-HT2A/2B/2C receptors and alternative hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies.

Luteoma da gravidez: um pseudotumor ovariano / Luteoma of pregnancy: an ovarian pseudotumor

Contexto: Luteoma é neoplasia rara e benigna do ovário, específica da gravidez. Considera-se que seja causada por efeitos hormonais, principalmente da gonadotrofina coriônica. Objetivo: Analisar artigos selecionados sobre luteoma da gravidez e realizar revisão bibliográfica a partir dessas publicações. Desenho: A busca dos artigos foi realizada por meio da plataforma PubMed. Procedeu-se uma busca aos descritores da doença e seu correspondente em inglês (luteoma) no portal da BVSalud. Métodos: Consistiu em revisão bibliográfica, onde foram utilizados artigos publicados de 1972 até 2022. Resultados: A origem celular dos luteomas ainda é desconhecida, mas considera-se que tal processo ocorra devido a uma reação hiperplásica à gravidez, visto que o efeito de virilização regride após o parto. Discussão: Sendo pouco diagnosticado, tendo menos de 200 casos reportados, são geralmente achados durante parto cesáreo ou durante ligadura tubária no pós-parto. Seu aparecimento está relacionado a fatores hormonais da gravidez e hiperplasia ocasionada pela luteinização das células estromais. Os efeitos do luteoma gravídico no organismo estão relacionados, além da virilização da paciente e do feto, com o surgimento da síndrome do ovário policístico e diabetes. Conclusões: Tendo baixa incidência, o luteoma gravídico pode se apresentar como desafio para seu diagnóstico adequado. O diagnóstico precoce permitirá o tratamento adequado, evitando-se efeitos indesejáveis, virilizantes, para a gestante e para o nascituro. É fundamental o preparo dos profissionais de saúde para o diagnóstico e tratamento do luteoma gravídico.

Oral Delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats.

Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide's low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management.

Antibacterial Activity of Epigallocatechin-3-gallate (EGCG) Loaded Lipid-chitosan Hybrid Nanoparticle against Planktonic Microorganisms.

Epigallocatechin-3-gallate (EGCG), a polyphenol derived from Green Tea, is one of the sources of natural bioactive compounds which are currently being developed as medicinal ingredients. Besides other biological activities, this natural compound exhibits anti-cariogenic effects. However, EGCG has low physical-chemical stability and poor bioavailability. Thus, the purpose of this study was to develop and characterize lipid-chitosan hybrid nanoparticle with EGCG and to evaluate its in vitro activity against cariogenic planktonic microorganisms. Lipid-chitosan hybrid nanoparticle (LCHNP-EGCG) were prepared by emulsion and sonication method in one step and characterized according to diameter, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (EE), mucoadhesion capacity and morphology. Strains of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus casei were treated with LCHNP- EGCG, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated. LCHNP-EGCG exhibited a size of 217.3 ± 5.1 nm with a low polydispersity index (0.17) and positive zeta potential indicating the presence of chitosan on the lipid nanoparticle surface (+33.7 mV). The LCHNP-EGCG showed a spherical morphology, high stability and a mucoadhesive property due to the presence of chitosan coating. In addition, the EGCG encapsulation efficiency was 96%. A reduction of almost 15-fold in the MIC and MBC against the strains was observed when EGCG was encapsulated in LCHNP, indicating the potential of EGCG encapsulation in lipid-polymer hybrid nanoparticles. Taking the results together, the LCHNP-EGCG could be an interesting system to use in dental care due to their nanometric size, mucoadhesive properties high antibacterial activity against relevant planktonic microorganisms.

Microplastics and 17α Ethinylestradiol: How Do Different Aquatic Invertebrates Respond to This Combination of Contaminants?

The synthetic hormone 17α ethinyl estradiol (EE2) is a molecule widely used in female contraceptives and recognized as a contaminant of attention (Watch List) in the European Union due to its high consumption, endocrine effects and occurrence in aquatic environments. Its main source of introduction is domestic sewage where it can be associated with other contaminants such as microplastics (MPs). Due to their characteristics, they can combine with each other and exacerbate their isolated effects on biota. This study evaluated the combined effects of microplastics (MPs) and 17α ethinylestradiol (EE2) on two tropical estuarine invertebrate species: Crassostrea gasar and Ucides cordatus. Polyethylene particles were spiked with EE2 and organisms were exposed to three treatments, categorized into three groups: control group (C), virgin microplastics (MPs), and spiked microplastics with EE2 (MPEs). All treatments were evaluated after 3 and 7 days of exposure. Oysters exhibited changes in phase 2 enzymes and the antioxidant system, oxidative stress in the gills, and reduced lysosomal membrane stability after exposure to MPs and MPEs. Crabs exposed to MPs and MPEs after seven days showed changes in phase 1 enzymes in the gills and changes in phases 1 and 2 enzymes in the hepatopancreas, such as disturbed cellular health. The combined effects of microplastics and EE2 increased the toxicity experienced by organisms, which may trigger effects at higher levels of biological organization, leading to ecological disturbances in tropical coastal ecosystems.

Effect of Prenatal Care on Perinatal Outcomes of Pregnant Women with Diabetes Mellitus: A Systematic Review.

Objective: to evaluate the effect of prenatal care (PC) on perinatal outcomes of pregnant women with diabetes mellitus (DM). Methods: systematic review developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines and conducted through the population, intervention, control, and outcomes (PICO) strategy. Clinical trials and observational studies were selected, with adult pregnant women, single-fetus pregnancy, diagnosis of DM, or gestational DM and who had received PC and/or nutritional therapy (NT). The search was carried out in PubMed, Scopus, and BIREME databases. The quality of the studies was evaluated using the tools of the National Heart, Lung and Blood Institute-National Institutes of Health (NHLBI-NIH). Results: We identified 5972 records, of which 15 (n=47 420 pregnant women) met the eligibility criteria. The most recurrent outcomes were glycemic control (14 studies; n=9096 participants), hypertensive disorders of pregnancy (2; n=39 282), prematurity (6; n=40 163), large for gestational age newborns (4; n=1556), fetal macrosomia (birth weight >4kg) (6; n=2980) and intensive care unit admission (4; n=2022). Conclusions: The findings suggest that PC interferes with the perinatal outcome, being able to reduce the risks of complications associated with this comorbidity through early intervention, especially when the NT is an integral part of this assistance.

Bioisosteric analogs of MDMA with improved pharmacological profile.

3,4-Methylenedioxymethamphetamine (MDMA, ' ecstasy' ) is re-emerging in clinical settings as a candidate for the treatment of specific psychiatric disorders (e.g. post-traumatic stress disorder) in combination with psychotherapy. MDMA is a psychoactive drug, typically regarded as an empathogen or entactogen, which leads to transporter-mediated monoamine release. Despite its therapeutic potential, MDMA can induce dose-, individual-, and context-dependent untoward effects outside safe settings. In this study, we investigated whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. In vitro methods included radiotracer assays, transporter electrophysiology, bioluminescence resonance energy transfer and fluorescence-based assays, pooled human liver microsome/S9 fraction incubation with isozyme mapping, and liquid chromatography coupled to high-resolution mass spectrometry. In silico methods included molecular docking. Compared with MDMA, all three MDMA bioisosteres (ODMA, TDMA, and SeDMA) showed similar pharmacological activity at human serotonin and dopamine transporters (hSERT and hDAT, respectively) but decreased activity at 5-HT 2A/2B/2C receptors. Regarding their hepatic metabolism, they differed from MDMA, with N -demethylation being the only metabolic route shared, and without forming phase II metabolites. Additional screening for their interaction with human organic cation transporters (hOCTs) and plasma membrane transporter (hPMAT) revealed a weaker interaction of the MDMA analogs with hOCT1, hOCT2, and hPMAT. Our findings suggest that these new MDMA analogs might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT and hDAT, but displaying a reduced activity at 5-HT 2A/2B/2C receptors and reduced hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies.

Mapa de evidências - Estratégias para o cuidado de pessoas com diabetes mellitus tipo 2, hipertensão arterial sistêmica ou obesidade / Evidence map - Strategies for the care of people with type 2 diabetes mellitus, systemic arterial hypertension or obesity

DESTAQUES ● Este mapa de evidências tem como objetivo apresentar estratégias que podem ser efetivas para o cuidado de pessoas com diabetes, hipertensão ou obesidade. ● Foram incluídas 93 revisões sistemáticas, cujos estudos primários foram realizados em sua maioria (65,1%) na América do Norte, Ásia e Europa. ● As intervenções foram classificadas em 5 categorias e 26 subcategorias. Observouse maior frequência da categoria "Teleconsulta/eHealth" e da subcategoria "cuidado assistencial". ● Os desfechos analisados foram classificados em clínicos e não clínicos. Desfechos clínicos foram relatados em 53 revisões sistemáticas, com destaque para a pressão arterial. Desfechos não clínicos foram relatados em 51 revisões sistemáticas, com destaque para a adesão ao tratamento farmacológico. ● As cinco categorias de intervenções - Teleconsulta/eHealth, Educação, Automonitoramento/autogerenciamento, Tratamento farmacológico, Serviço de saúde - apresentaram efeito positivo ou potencialmente positivo acima de 50% para os desfechos avaliados.

HIGHLIGHTS ● This evidence map aims to present strategies that may be effective for the care of people with diabetes, hypertension or obesity. ● 93 systematic reviews were included, the majority of whose primary studies were carried out (65.1%) in North America, Asia and Europe. ● Interventions were classified into 5 categories and 26 subcategories. There was a greater frequency of the "Teleconsultation/eHealth" category and the "assistance care" subcategory. ● The analyzed outcomes were classified as clinical and non-clinical. Clinical outcomes were reported in 53 systematic reviews, with emphasis on blood pressure. Non-clinical outcomes were reported in 51 systematic reviews, with emphasis on adherence to pharmacological treatment. ● The five categories of interventions - Teleconsultation/eHealth, Education, Self-monitoring/self-management, Pharmacological treatment, Health service - showed a positive or potentially positive effect above 50% for the evaluated outcomes.

Treatment of Organics in Wastewater Using Electrogenerated Gaseous Oxidants.

This work focuses on the comparison of the performance of direct electrochemical oxidation with indirect electrolysis mediated by gaseous oxidants in the treatment of diluted wastewater. To do this, energy consumptions of the electrolysis using mixed metal oxide (MMO) electrodes are compared with those required for the production and use of chlorine dioxide in the degradation of methomyl contained in aqueous solutions. Results demonstrate the feasibility of the mediated oxidation process and that this process is competitive with direct oxidation. The oxidants are produced under optimized conditions using the same anodic material applied for the direct degradation of organics, thus avoiding efficiency losses associated with mass transfer limitations in the degradation of dilute organic solutions. Thus, using the ClO2 gaseous oxidant, a concentration of 0.1 mM of methomyl from a solution containing 500 mL is completely removed with an energy consumption as low as 50 Wh. The application of the same energy to a direct electrolytic process for treating the same wastewater can only reach less than half of this removal. These findings may have a very important application in the use of electrochemical technology to achieve the remediation of persistent pollutants in wastewater, where their low concentrations typically make direct processes very inefficient.

Individualized positive end-expiratory pressure reduces driving pressure in obese patients during laparoscopic surgery under pneumoperitoneum: a randomized clinical trial.

Introduction: During pneumoperitoneum (PNP), airway driving pressure (ΔPRS) increases due to the stiffness of the chest wall and cephalic shift of the diaphragm, which favors atelectasis. In addition, depending on the mechanical power (MP) formulas, they may lead to different interpretations. Methods: Patients >18 years of age with body mass index >35 kg/m2 were included in a single-center randomized controlled trial during their admission for bariatric surgery by abdominal laparoscopy. Intra-abdominal pressure was set at 15 mmHg at the pneumoperitoneum time point (PNP). After the recruitment maneuver, the lowest respiratory system elastance (ERS) was detected during the positive end-expiratory pressure (PEEP) step-wise decrement. Patients were randomized to the 1) CTRL group: ventilated with PEEP of 5 cmH2O and 2) PEEPIND group: ventilated with PEEP value associated with ERS that is 5% higher than its lowest level. Respiratory system mechanics and mean arterial pressure (MAP) were assessed at the PNP, 5 min after randomization (T1), and at the end of the ventilation protocol (T2); arterial blood gas was assessed at PNP and T2. ΔPRS was the primary outcome. Three MP formulas were used: MPA, which computes static PEEP × volume, elastic, and resistive components; MPB, which computes only the elastic component; and MPC, which computes static PEEP × volume, elastic, and resistive components without inspiratory holds. Results: Twenty-eight patients were assessed for eligibility: eight were not included and 20 patients were randomized and allocated to CTRL and PEEPIND groups (n = 10/group). The PEEPIND ventilator strategy reduced ΔPRS when compared with the CTRL group (PEEPIND, 13 ± 2 cmH2O; CTRL, 22 ± 4 cmH2O; p < 0.001). Oxygenation improved in the PEEPIND group when compared with the CTRL group (p = 0.029), whereas MAP was comparable between the PEEPIND and CTRL groups. At the end of surgery, MPA and MPB were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). At the end of the surgery, MPA and MPC were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). Conclusion: Individualized PEEP was associated with a reduction in ΔPRS and an improvement in oxygenation with comparable MAP. The MP, which solely computes the elastic component, better reflected the improvement in ΔPRS observed in the individualized PEEP group. Clinical Trial Registration: The protocol was registered at the Brazilian Registry of Clinical Trials (U1111-1220-7296).

The Impact of Motherhood on Women's Career Progression: A Scoping Review of Evidence-Based Interventions.

(1) Background: Despite the progress made by women in the workplace, mothers still face systemic barriers that prevent them from advancing professionally. This "motherhood penalty" involves a variety of discriminatory practices and experiences that mothers can face at work, including being held to stricter standards regarding salary and recruitment. Despite ongoing research on the association between motherhood and career outcomes, few studies specifically explore how motherhood impacts career advancement and, consequently, access to leadership. This scoping review seeks to gain an understanding of how motherhood impacts women's career progression, and how interventions can address the underrepresentation of mothers in leadership. (2) Methods: Following the PRISMA-ScR framework, we analyzed 52 articles from 2010 to 2022, drawn from 10 databases. (3) Results: The results showed both negative and positive impacts of motherhood on career progression, affecting mothers' attitudes, feelings, and behaviors and yielding changes in interpersonal relationships and work conditions. Intersectionality is highlighted, urging a nuanced examination of challenges faced by mothers from a diversity of backgrounds. Recommendations for interventions include individual and institutional efforts, comprising societal support structures, organizational policy changes, and cultural shifts. (4) Conclusions: This scoping review offers an updated perspective on a classic challenge, providing practical insights for a more inclusive and structural understanding of the career trajectories of working mothers.

Motion Analysis of the Mug Transportation Task Through Upper Limb Kinematics.

The task of transporting objects is a fundamental part of daily living activities. Previous kinematic studies focusing on tasks such as pointing, reach-to-grasp, and drinking have not fully captured the motor behaviors involved in object transportation, including placing a cup on a table or storing items in specific places. Hence, this study aimed to analyze the motor behavior associated with transporting a mug using upper limb kinematic variables. Fifteen healthy adults were instructed to transport an open-handle mug across a table. The kinematic metrics evaluated included object end-error for accuracy, frontal and lateral end-range for precision, movement time, peak velocity, time to peak velocity for control strategy, object path ratio for efficiency, and interjoint coordination. The stability of motor behavior was assessed through a test-retest analysis. The mug transporting task achieved accuracy with a radius <10 mm around the target, a peak velocity of ∼0.4 m/s, a control strategy where acceleration time constituted about 30% of the movement time, and a slightly curved trajectory. The test-retest analysis confirmed stable motor behavior across all kinematic metrics (ICCs > 0.75). Thus, the mug transporting task exhibited unique and stable kinematic characteristics, distinguishing it from non-transport activities and effectively mirroring transporting activities of daily living.