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In a recent study, our research group demonstrated that the essential oil of Ocotea odorifera (EOOO) and its major compound safrole potentiated the action fluoroquinolones, modulating bacterial resistance possibly due to direct inhibition of efflux pumps. Thus, in the present study, we investigated whether these treatments could enhance the activity of gentamicin and erythromycin against multidrug-resistant (MDR) bacteria. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC–MS). The antibiotic-enhancing effect of the EOOO and safrole against MDR strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was analyzed by the broth microdilution method. The chemical analysis confirmed the presence of safrole as a major component among the 16 compounds identified in the EOOO. Both the essential oil and the isolated compound showed clinically relevant antibacterial activities against S. aureus. Regarding the modulation of antibiotic resistance, the EOOO was found to enhance the activity of erythromycin against the strains of P. aeruginosa and S. aureus, as well as improving the action of gentamicin against S. aureus. On the other hand, safrole potentiated the activity of gentamicin against the S. aureus strain alone. It is concluded, therefore, that the EOOO and safrole can enhance the activity of macrolides and aminoglycosides, and as such are useful in the development of therapeutic tools to combat bacterial resistance against these classes of antibiotics.

Abstract The evaluation of competence of Alzheimer's disease (AD) patients to assume personal or collective responsibilities and the resulting legal implications is a relevant issue. Objectives: The aim of this study was to evaluate the attitudes of different medical specialists towards the disability of patients with Alzheimer's disease and practitioners' competence to interfere with decision-making autonomy. Methods: Professionals from different areas (Neurology, Psychiatry, Geriatrics, and General Practice) were interviewed by one of the authors, after being presented a fictitious clinical case which raised several topics, namely: [1] Critical judgment and capacity of the patient to take decisions related to daily activities; [2] The role of family physicians in nominating trustees and caregivers. Results: Answers to the first question did not differ regarding degree of preservation of awareness but at least 25% stressed that the patient must be carefully listened to, independent of caregiver or legal representative opinion. There were significant knowledge gaps in responses to the second question. Half of the physicians interviewed did not have adequate information about the legal aspects of caring for patients with Alzheimer's disease. Conclusions: Legal aspects is a topic that must be incorporated into professional training in order to improve attitudes toward the long-term management of patients with dementia.

Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are the primary bacteria that cause clinical infections, such as urinary and intestinal infections, pneumonia, endocarditis, and sepsis. Bacterial resistance is an innate natural occurrence in microorganisms, resulting from mutations or the lateral exchange of genetic material. This serves as evidence for the association between drug consumption and pathogen resistance. Evidence has demonstrated that the association between conventional antibiotics and natural products is a promising pharmacological strategy to overcome resistance mechanisms. Considering the large body of research demonstrating the significant antimicrobial activities of Schinus terebinthifolius Raddi, the present study aimed to evaluate the chemical composition and antibiotic-enhancing effects of Schinus terebinthifolius Raddi essential oil (STEO) against the standard and multidrug-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The STEO was extracted by hydrodistillation using a Clevenger-type vacuum rotary evaporator. The Minimum Inhibitory Concentration (MIC) of the STEO was assessed by the microdilution method to evaluate the antibacterial activity. The antibiotic-enhancing activity of the essential oil was assessed by determining the MIC of antibiotics in the presence of a sub-inhibitory concentration (MIC/8) of the natural product. The GC-MS analysis revealed alpha-pinene (24.3%), gamma-muurolene (16.6%), and myrcene (13.7%) as major constituents of the STEO. The STEO potentiated the enhanced antibacterial activity of norfloxacin and gentamicin against all the strains and increased the action of penicillin against the Gram-negative strains. Therefore, it is concluded that although the STEO does not exhibit clinically effective antibacterial activity, its association with conventional antibiotics results in enhanced antibiotic activity.

Objective: Efflux pumps are transmembrane proteins associated with bacterial resistance mechanisms. Bacteria use these proteins to actively transport antibiotics to the extracellular medium, preventing the pharmacological action of these drugs. This study aimed to evaluate in vitro the antibacterial activity of 1,8-naphthyridines sulfonamides, as well as their ability to inhibit efflux systems of Staphylococcus aureus strains expressing different levels of the NorA efflux pump. Methods: The broth microdilution test was performed to assess antibacterial activity. Efflux pump inhibition was evaluated in silico by molecular docking and in vitro by fluorometric tests, and the minimum inhibitory concentration (MIC) was determined. The MIC was determined in the association between 1,8-naphthyridine and norfloxacin or ethidium bromide. Results: The 1,8-naphthyridines did not show direct antibacterial activity. However, they effectively reduced the MIC of multidrug-resistant bacteria by associating with norfloxacin and ethidium bromide, in addition to increasing the fluorescence emission. In silico analysis addressing the binding between NorA and 1,8-naphthyridines suggests that hydrogen bonds and hydrophilic interactions represent the interactions with the most favourable binding energy, corroborating the experimental data. Conclusion: Our data suggest that 1,8-naphthyridines sulfonamides inhibit bacterial resistance through molecular mechanisms associated with inhibition of the NorA efflux pump in S. aureus strains.

Objective: to analyze the spatial distribution of microcephaly cases by Zika virus in a Brazilian municipality. Methods: ecological study that analyzed 53 confirmed cases of microcephaly by Zika virus, reported between 2015 and 2016, extracted from the Registry of Public Health Events - Microcephaly. Incidence rates of the disease in neighborhoods of the municipality, Global and Local Moran Index and Kernel dispersion method were calculated. Results: common areas with high Zika microcephaly incidence rates were identified. The value of Moran’s I demonstrated the presence of clusters, with p=0.001, I=0.3159 in 2015 and I=0.2158 in 2016. According to the Kernel map, there was concentration of cases in Regional Executive Secretariats IV and VI. Most of the cases are within or near precarious settlements. Conclusion: the cases did not occur randomly and reinforce their relationship with the living conditions of the population. Contributions to practice: it is expected that this study can contribute to reflect on public policies and surveillance actions to reduce Zika transmission, recognizing the territories of higher risk for the disease. In addition, to expand discussions between managers and health professionals to qualify notification, care, and monitoring of children with microcephaly by Zika.

The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of β-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of β-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of S. aureus. All substances were prepared at an initial concentration of 1024 μg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on β-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and β-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of S. aureus. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and β-lactam antibiotics, suggesting that they may act by inhibiting β-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.

Abstract The Atlantic Forest is regarded a rich source of aromatic plants with a broad spectrum of biological properties. The leaves of seven Piper species were collected from the Atlantic Forest domain in the coastal region of Paraná state in winter (W) and spring (S). The volatile oils were extracted from the leaves through hydrodistillation method. The volatile oils were characterized by means of GC-FID and GC-MS. Sesquiterpenes were among the major compounds in all species studied, with many dozens of representatives. However, very low concentrations of monoterpenes were observed; α-pinene in Piper mosenii and P. cernuum, δ-3-carene in P. rivinoides, camphene and β-pinene in P. cernuum are exceptions. The arylpropanoides myristicine and elemicin were found in considerable amount in P. diospyrifolium (26.2%/S) and P. mosenii (16.4%/W), respectively. These oils were also screened for inhibitory activities against acetylcholinesterase (AChE) and α-glucosidase (AG). For AChE the most active samples were P. diospyrifolium, P. aduncum and P. cernuum, with inhibiting level > 93%. For the less sensitive AG, the most promising candidates were P. diospyrifolium and P. mosenii, with inhibiting level > 65%. These results highlight the importance of native plants as renewable source of new inhibitors for AChE and AG. Further investigation is required to identify the most active constituents or fractions from the selected volatile oils.

O presente ensaio aborda as categorias acumulação capitalista e trabalho a partir da perspectiva marxista, evidenciando a atualidade e o vigor das discussões dessa matriz teórica para compreensão da conjuntura atual. Buscou-se, na produção de Mészáros, os elementos para caracterizar o sociometabolismo do capital e o processo de acumulação capitalista com vistas a compreender as expressões do acirramento do processo de acumulação capitalista no mundo do trabalho. Para clarificar o debate, recorreu-se aos estudos de Ruy Mauro Marini que, ancorado na perspectiva marxista, analisa o desenvolvimento do Brasil e da América Latina. Nesta perspectiva, evidenciou-se a categoria “superexploração do trabalho” como um dos vetores do desenvolvimento das regiões periféricas no sistema capitalista mundializado. Essa discussão nos conduziu à centralidade da categoria trabalho, como a atividade que garante a sobrevivência da maioria da população, e que lhes dá identidade e reconhecimento. Por fim, concluímos com a importância e premência da construção teórica marxista tanto para desvelar a conjuntura atual quanto para tecer e subsidiar a luta social na construção de outra sociabilidade. Palavras-chave: Acumulação capitalista. Trabalho. Superexploração do Trabalho. Capitalist Accumulation And Labor: The Actuality And Vigor Of Marxist Theoretical Production ABSTRACT The presente article delas with the categories capitalista accumulation and work from the Marxist perspective, evidencing the actuality and the vigor of the discussions of this theoretical matrix for understanding the current conjuncture. The elements for characterizing the sociometabolismofthe capital werestudied in the production of Mészáros and the process of capitalist accumulation with a viewtounderstandingtheexpressionsoftheintensificationoftheprocessofcapitalistaccumulation in the world of work. To clarify the debate, were sort to the studies of Ruy Mauro Marini, anchored in the Marxist perspective, analyzing the development of Brazil and Latin America. In this perspective, the category "superexploitation of labor" was shown as one of the vectors of the development of peripheral regions in the globalized capitalist system. This discussion le dust othe centrality of the category of labor, as theactivitythatguaranteesthesurvivalofthemajorityofthepopulation, and which gives them identity and recognition. Concludes with the aimandurgency of the theoretical Marxist construction both tounveil the current conjuncture and toweave and subsidize the social struggle in the construction of the sociability. Keywords: Capitalistaccumulation. Labor. Superexploration of Labor.

Commercialized mouthwashes are generally expensive for the most financially vulnerable populations. Thus, several studies evaluate the antimicrobial potential of herbal products, such as essential oils, to reduce the activity of microorganisms in the mouth. The objective of this research was to carry out the chemical characterization and antibacterial activity of the essential oil of Piper mosenii (EOPm), providing data that enable the development of a low-cost mouthwash formulation aimed at vulnerable communities. The analysis of the antibacterial potential and modulator of bacterial resistance was verified by the microdilution method to determine the minimum inhibitory concentration-MIC. The chemical components were characterized by gas chromatography coupled to mass spectrometry, where 23 chemical constituents were detected, with α-pinene, being the major compound. The EOPm showed a MIC ≥ 1024 µg/mL for all bacterial strains used in the tests. When the EOPm modulating activity was evaluated together with chlorhexidine, mouthwash and antibiotics against bacterial resistance, the oil showed a significant synergistic effect, reducing the MIC of the products tested in combination, in percentages between 20.6% to 96.3%. Therefore, it is recommended to expand the tests with greater variation of EOPm concentration and the products used in this research, in addition to the evaluation of toxicity and in vivo tests, seeking the development of a possible formulation of mouthwash accessible to the vulnerable population.

Studies show that more consumers are using natural health products in the modern world. We have noticed a growing demand in markets and the professional community for mouthwashes that contain natural compounds. The objective of this study was to assess the chemical characterization and microbiological potential of the essential oil Piper arboreum (EOPa) to provide data to enable the development of a low-cost mouthwash. The evaluation of the antibacterial and bacterial resistance modulating activity was performed by the microdilution method to determine the minimum inhibitory concentration. The chemical components were characterized by gas chromatography coupled with mass spectrometry, which identified 20 chemical constituents, with caryophyllene oxide being one of the major compounds. The EOPa showed an MIC ≥ 1024 µg/mL for all bacterial strains used in the tests. When evaluating the modulating activity of EOPa combined with chlorhexidine, mouthwash and antibiotics against the bacterial resistance, the oil limited synergistic activity between the MIC of the products tested in combination (37% to 87.5%). Therefore, we recommend expanding the tests with greater variation in the EOPa concentration and the products used, as well as toxicity assessments and in vivo testing, with the purpose of the development of a possible low-cost mouthwash base that is accessible to the most vulnerable populations.

Efflux pumps are proteins capable of expelling antibiotics from bacterial cells, have emerged as a major mechanism of bacterial resistance. In the ongoing pursuit to overcome and reduce bacterial resistance, novel substances are being explored as potential efflux pump inhibitors. Meldrum's acid, a synthetic molecule widely studied for its role in synthesizing bioactive compounds, holds promise in this regard. Therefore, the objective of this study is to evaluate the antibacterial activity of three derivatives of Meldrum's acid and assess their ability to inhibit efflux mechanisms, employing both in silico and in vitro approaches. The antibacterial activity of the derivatives was assessed using a broth microdilution testing method. Surprisingly, the derivatives did not exhibit direct antibacterial activity on their own. However, they displayed a significant effect in enhancing the efficacy of antibiotics, suggesting a potential role in potentiating their effects. Furthermore, fluorescence emission assays using ethidium bromide indicated that the derivatives could potentially block efflux pumps, as they exhibited fluorescence levels comparable to the positive control. To further investigate their inhibitory capacity, molecular docking studies were conducted in silico, revealing binding interactions similar to ciprofloxacin and carbonyl cyanide 3‐chlorophenylhydrazone, known efflux pump inhibitors. These findings highlight the potential of Meldrum's acid derivatives as effective inhibitors of efflux pumps. By targeting these mechanisms, the derivatives offer a promising avenue to enhance the effectiveness of antibiotics and combat bacterial resistance. This study underscores the importance of exploring novel strategies in the fight against bacterial resistance and provides valuable insights into the potential of Meldrum's acid derivatives as efflux pump inhibitors. Further research and exploration in this field are warranted to fully exploit their therapeutic potential. [ABSTRACT FROM AUTHOR]