Oncogenic and telomeric G-quadruplexes: Targets for porphyrin-triphenylphosphonium conjugates.

DNA chains with sequential guanine (G) repeats can lead to the formation of G-quadruplexes (G4), which are found in functional DNA and RNA regions like telomeres and oncogene promoters. The development of molecules with adequate structural features to selectively stabilize G4 structures can counteract cell immortality, highly described for cancer cells, and also downregulate transcription events underlying cell apoptosis and/or senescence processes. We describe here, the efficiency of four highly charged porphyrins-phosphonium conjugates to act as G4 stabilizing agents. The spectrophotometric results allowed to select the conjugates P2-PPh3 and P3-PPh3 as the most promising ones to stabilize selectively G4 structures. Molecular dynamics simulation experiments were performed and support the preferential binding of P2-PPh3 namely to MYC and of P3-PPh3 to KRAS. The ability of both ligands to block the activity of Taq polymerase was confirmed and also their higher cytotoxicity against the two melanoma cell lines A375 and SK-MEL-28 than to immortalized skin keratinocytes. Both ligands present efficient cellular uptake, nuclear co-localization and high ability to generate 1O2 namely when interacting with G4 structure. The obtained data points the synthesized porphyrins as promising ligands to be used in a dual approach that can combine G4 stabilization and Photodynamic therapy (PDT).

Apomixis beyond trees in the Brazilian savanna: new insights from the orchid Zygopetalum mackayi.

n the Neotropics, the focus of apomictic studies predominantly centres on trees within the Brazilian savanna, characterized, mostly as sporophytic and facultative, associated with polyploidy and polyembryony. To enhance our understanding of the mechanisms governing apomixis and sexual reproduction in tropical herbaceous plants, we clarify the relationship between apomixis, chromosome counts, and polyembryony in the epiphytic orchid Zygopetalum mackayi, which forms a polyploid complex within rocky outcrops in both the Brazilian savanna and the Atlantic forest. To define embryo origins and describe megasporogenesis and megagametogenesis, we performed manual self-pollinations in first-day flowers of cultivated plants, considering all three cytotypes (2x, 3x, 4x) of this species. Flowers and fruits at different stages were collected to describe the development and morphology of ovules and seeds considering sexual and apomictic processes. As self-pollination treatments resulted in high fruit abortion in diploids, we also examined pollen tube development in aborted flowers and fruits to search for putative anomalies. Megasporogenesis and megagametogenesis occur regularly in all cytotypes. Apomixis is facultative and sporophytic, and associated with polyploid cytotypes, while diploid individuals exclusively engage in sexual reproduction. Polyembryony is caused mainly by the production of adventitious embryos from nucellar cells of triploids and tetraploids, but also by the development of multiple archesporia in all cytotypes. Like other apomictic angiosperms within the Brazilian savanna, our findings demonstrate that apomixis in Z. mackayi relies on pollinators for seed production. We also consider the ecological implications of these apomictic patterns in Z. mackayi within the context of habitat loss and its dependence on pollinators.

Intricate interplay between cell metabolism and necroptosis regulation in metabolic dysfunction-associated steatotic liver disease: A narrative review.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), encompasses a progressive spectrum of liver conditions, ranging from steatosis to metabolic dysfunction-associated steatohepatitis, characterised by hepatocellular death and inflammation, potentially progressing to cirrhosis and/or liver cancer. In both experimental and human MASLD, necroptosis-a regulated immunogenic necrotic cell death pathway-is triggered, yet its exact role in disease pathogenesis remains unclear. Noteworthy, necroptosis-related signalling pathways are emerging as key players in metabolic reprogramming, including lipid and mitochondrial metabolism. Additionally, metabolic dysregulation is a well-established contributor to MASLD development and progression. This review explores the intricate interplay between cell metabolism and necroptosis regulation and its impact on MASLD pathogenesis. Understanding these cellular events may offer new insights into the complexity of MASLD pathophysiology, potentially uncovering therapeutic opportunities and unforeseen metabolic consequences of targeting necroptosis.

Opposing effects of the purinergic P2X7 receptor on seizures in neurons and microglia in male mice.

BACKGROUND: The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood. METHODS: Effects of P2X7R signaling on seizures and epilepsy were analyzed in induced seizure models using male mice including the kainic acid model of status epilepticus and pentylenetetrazole model and in male and female mice in a genetic model of Dravet syndrome. RNA sequencing was used to analyze P2X7R downstream signaling during seizures. To investigate the cell type-specific role of the P2X7R during seizures and epilepsy, we generated mice lacking exon 2 of the P2rx7 gene in either microglia (P2rx7:Cx3cr1-Cre) or neurons (P2rx7:Thy-1-Cre). To investigate the protective potential of overexpressing P2X7R in GABAergic interneurons, P2X7Rs were overexpressed using adeno-associated virus transduction under the mDlx promoter. RESULTS: RNA sequencing of hippocampal tissue from wild-type and P2X7R knock-out mice identified both glial and neuronal genes, in particular genes involved in GABAergic signaling, under the control of the P2X7R following seizures. Mice with deleted P2rx7 in microglia displayed less severe acute seizures and developed a milder form of epilepsy, and microglia displayed an anti-inflammatory molecular profile. In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice. Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. Functional studies determined that GABAergic interneurons display increased responses to P2X7R activation in experimental epilepsy. Finally, we show that viral transduction of P2X7R in GABAergic interneurons protects against evoked and spontaneous seizures in experimental temporal lobe epilepsy and in mice lacking Scn1a, a model of Dravet syndrome. CONCLUSIONS: Our results suggest a dual and opposing action of P2X7R in epilepsy and suggest P2X7R overexpression in GABAergic interneurons as a novel therapeutic strategy for acquired and, possibly, genetic forms of epilepsy.

Artificial cornea transplantation and visual rehabilitation: an integrative review / Transplante de córnea artificial e reabilitação visual: uma revisão integrativa

ABSTRACT Due to the development of complications and the biocompatibility and scarcity of transplant donor tissues, artificial corneas, which can be used for the rehabilitation of optical functions, have been developed. The current study aimed to analyze the visual rehabilitation effects of the Boston type I keratoprosthesis, Boston type II keratoprosthesis, Aurolab keratoprosthesis, osteo-odonto-keratoprosthesis, and tibial bone keratoprosthesis. Results showed that the Boston type I keratoprosthesis was the most effective for visual rehabilitation in patients with moist ocular surfaces. The Aurolab keratoprosthesis had a lower efficacy for visual rehabilitation. Nevertheless, it is still a viable option for individuals in economically restricted countries. In patients with dry eyes, the Boston type II keratoprosthesis was associated with the best visual rehabilitation. However, the final visual acuity of patients who received osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis implantation was not evaluated as the necessary information was not available.

RESUMO Em decorrência de complicações, da biocompatibilidade e da escassez de tecido doador para transplantes de córnea natural, foram elaboradas córneas artificiais que são potenciais para reabilitar funções ópticas. Nessa perspectiva, objetivou-se a análise da eficácia da reabilitação visual entre os implantes: Boston tipo I, Boston tipo II, Aurolab, osteo-odonto-ceratoprótese e ceratoprótese de Osso Tibial. De modo geral, a princípio observou-se uma tendência de melhoria da Best-corrected visual acuity em todos os tipos de lentes, mas considerável queda durante acompanhamento a longo prazo. O dispositivo com melhor reabilitação visual em pacientes com superfícies oculares úmidas é a Boston tipo I, seguida pela Aurolab, que é economicamente viável em países emergentes. Ao considerar pacientes com olhos secos, o implante de Boston tipo II apresenta maior reabilitação visual. Por fim, em virtude de não apresentarem dados equiparáveis, as lentes osteo-odonto-ceratoprótese e de osso tibial não puderam ser analisadas.

Validação biológica de grânulos de vidro bioativas (compostos por biovidro 45S5): estudo in vitro e in vivo / Biological validation of bioactive glass granules (composed of 45S5 bioglass): in vitro and in vivo study

O tecido ósseo, embora tenha a capacidade de regeneração, é limitado em sua eficácia diante de defeitos críticos que impedem a regeneração natural. Dessa forma, materiais como a hidroxiapatita (HA) têm sido considerados promissores na engenharia de tecido ósseo. Contudo, apesar de sua ampla utilização, a hidroxiapatita apresenta desvantagens, como a taxa de reabsorção e remodelação lenta. Em contraste, o biovidro 45S5 se destaca por sua biocompatibilidade, propriedades bioativas e degradabilidade. Este estudo objetivou avaliar o comportamento biológico in vitro e in vivo de grânulos de vidro bioativas de biovidro 45S5 fabricadas pelo método de fusão. Os biovidros foram caracterizados por meio da difração de raios X (DRX), espectroscopia de infravermelho por transformação de Fourier (FTIR), calorimetria diferencial de varredura (DSC) e espectrometria de emissão óptica com plasmas indutivamente acoplados (ICP OES). Em seguida, foi realizado o estudo in vitro, utilizando células osteoblásticas isoladas de fêmures de ratos, que foram submetidas a análise da morfologia celular (MEV), viabilidade celular (MTT), conteúdo de proteína total (PT), atividade de fosfatase alcalina (ALP) e formação de nódulos de mineralização. No estudo in vivo, foram realizados defeitos ósseos críticos de 7 mm na tíbia de coelhos da raça New Zealand, que foram divididos em dois grupos (n=6) de acordo com o material de preenchimento: hidroxiapatita comercial (HA) e biovidro 45S5 (BG45S5). Após 2, 8 e 12 semanas, os animais foram eutanasiados e as peças ósseas foram submetidas as análises histológicas e histomorfométricas. Os dados foram submetidos ao teste de normalidade Shapiro-Wilk (p=0,05) e quando normais realizamos o teste t de student e quando não normais realizamos o teste de Mann-Whitney. Os resultados dos testes físico-químicos mostraram sucesso na produção do novo biomaterial. Nos testes in vitro, observou-se que o grupo BG45S5 não apresentou citotoxicidade e mostrou-se promissor com diferença estatisticamente significante em relação ao grupo hidroxiapatita comercial (p=0.0263). Nos testes de PT, ALP e nódulos de mineralização, os grupos não apresentaram diferença estatística entre eles (p<0,05). Contudo, o grupo BG45S5 mostrou-se promissor em relação aos outros grupos. Na análise histológica, ambos os grupos apresentaram neoformação óssea nos defeitos após 2, 8 e 12 semanas. Na histomorfometria, observou-se que os grupos BG45S5 e HA apresentaram maior área de neoformação óssea em 12 semanas. Houve diferença estatisticamente significante entre os grupos no tempo de 2 semanas, com maior neoformação para o grupo BG45S5. Apesar dos resultados promissores do grupo BG45S5, não houve diferença estatisticamente significativa entre os grupos (p<0,05) nos tempos de 8 e 12 semanas. Em resumo, os resultados evidenciaram o sucesso na produção do biomaterial sintético e o potencial do biomaterial BG45S5 como um material promissor para tratamento de defeitos ósseos críticos. (AU)

Bone tissue, despite its capacity of regeneration, is limited in its effectiveness when faced with critical defects that prevent natural regeneration. Therefore, materials such as hydroxyapatite (HA) have been considered promising in bone tissue engineering. However, despite its wide use, hydroxyapatite has disadvantages, such as slow resorption and remodeling rates. In contrast, 45S5 bioglass stands out for its biocompatibility, bioactive properties and degradability. This study aimed to evaluate the in vitro and in vivo biological behavior of bioactive 45S5 bioglass beads manufactured by the melt quenched method. The bioglasses were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and inductively coupled plasma optical emission spectrometry (ICP OES). Following this, an in vitro study was conducted using osteoblastic cells isolated from rat femurs, which were subjected to analysis of cell morphology (SEM), cell viability (MTT), total protein content (TP), alkaline phosphatase activity (ALP) and mineralization nodule formation. In the in vivo study, critical bone defects of 7 mm were created in the tibia of New Zealand rabbits, which were divided into two groups (n=6) according to the filling material: commercial hydroxyapatite (HA) and bioactive glass 45S5 (BG45S5). After 2, 8, and 12 weeks, the animals were euthanized and the bone pieces were subjected to histological and histomorphometric analyses. Data were subjected to the Shapiro-Wilk normality test (p=0.05), and when normal, we performed the Student's t-test, and when non-normal, we performed the Mann-Whitney test. The results of the physicochemical tests showed success in the production of the new biomaterial. In the in vitro tests, it was observed that the BG45S5 group did not present cytotoxicity and showed promise with a statistically significant difference compared to the commercial hydroxyapatite group (p=0.0263). In the TP, ALP and mineralization nodule tests, the groups showed no statistical difference between them (p<0.05). However, the BG45S5 group showed promise compared to the other groups. In the histological analysis, both groups showed new bone formation in the defects after 2, 8, and 12 weeks. In the histomorphometric analysis, it was observed that the BG45S5 and HA groups presented a larger area of new bone formation at 12 weeks. There was a statistically significant difference between the groups at 2 weeks, with greater new formation for the BG45S5 group. Despite the promising results of the BG45S5 group, there was no statistically significant difference between the groups (p<0.05) at 8 and 12 weeks. In summary, the results evidenced the successful production of the synthetic biomaterial and the potential of the BG45S5 bioglass as a promising material for treating critical bone defect.(AU)

Endoparasites in domestic cats (Felis catus) in the semi-arid region of Northeast Brazil.

The aim of this study was to evaluate the prevalence of endoparasites in domestic cats (Felis catus) in the city of Sousa, state of Paraíba, Northeast Brazil. A total of 207 samples of fresh feces were randomly collected from domestic and semi-domiciled cats. The samples were analyzed by simple centrifugation and centrifuge-flotation in sucrose solution for the diagnosis of helminth eggs and enteric protozoan oocysts and cysts. Epidemiological information was obtained to determine risk factors related to infections. Among the samples collected, 81.6% (169/207; 95% CI: 77.4-83.8) were positive for at least one parasite genus. Ancylostoma spp. was the most prevalent, at 67.1% (139/207), followed by Taenia spp. at 28.5% (59/207), and Spirometra spp. and Platynosomum sp., both at 17.3% (36/207). The variables associated with helminth infection were a historic lack of deworming (Odds ratio = 12.25) and the presence of dry fur (Odds ratio = 2.15). No risk factors were observed for enteric protozoa infection. This study demonstrated a high prevalence of endoparasites in domestic cats in the city of Sousa, state of Paraíba, and associated risk factors, thus establishing an overview of the main helminths and protozoa that affect cats in this region.

Preliminary Findings on the Salivary Metabolome of Hookah and Cigarette Smokers.

The aim of the study was to evaluate the salivary metabolomic profile of patients who habitually smoke hookah and cigarettes. The groups consisted of 33 regular and exclusive hookah smokers, 26 regular and exclusive cigarette smokers, and 30 nonsmokers. Unstimulated whole saliva was collected for the measurement of salivary metabolites by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The MetaboAnalyst software was used for statistical analysis and evaluation of biomarkers. 11 smoking salivary biomarkers were identified using the area under receiving-operator curver criterion and threshold of 0.9. Xylitol and octadecanol were higher in cigarette smokers compared to controls; arabitol and maltose were higher in controls compared to cigarette smokers; octadecanol and tyramine were higher in hookah smokers compared to controls; phenylalanine was higher in controls compared to hookah smokers; and fructose, isocitric acid, glucuronic acid, tryptamine, maltose, tyramine, and 3-hydroxyisolvaleric acid were higher in hookah smokers compared to cigarettes smokers. Conclusions: The evaluation of the salivary metabolome of hookah smokers, showing separation between the groups, especially between the control versus hookah groups and cigarette versus hookah groups, and it seems to demonstrate that the use of hookah tobacco is more damaging to health.

Inhibiting SETD7 methyl-transferase activity impairs differentiation, lipid metabolism and lactogenesis in mammary epithelial cells.

SETD7 (SET7/9, KMT7) is a lysine methyltransferase that targets master regulators of cell proliferation and differentiation. Here, the impact of inhibiting SETD7 catalytic activity on mammary epithelial cell differentiation was studied by focusing on genes associated with epithelial differentiation, lactogenesis, and lipid metabolism in HC11 and EpH4 cell lines. Setd7 mRNA and protein levels were induced upon lactogenic differentiation in both cell lines. Inhibition of SETD7 activity by the compound (R)-PFI-2 increased cell proliferation and downregulated E-cadherin, beta-catenin, lactoferrin, insulin-like growth factor binding protein 5, and beta-casein levels. In addition, inhibition of SETD7 activity affected the lipid profile and altered the mRNA expression of the phospholipid biosynthesis-related genes choline phosphotransferase 1, and ethanolamine-phosphate cytidylyltransferase. Altogether, the results suggest that inhibiting SETD7 catalytic activity impairs mammary epithelial and lactogenic differentiation.

Functional expression of the ATP-gated P2X7 receptor in human iPSC-derived astrocytes.

Activation of the ATP-gated P2X7 receptor (P2X7R), implicated in numerous diseases of the brain, can trigger diverse responses such as the release of pro-inflammatory cytokines, modulation of neurotransmission, cell proliferation or cell death. However, despite the known species-specific differences in its pharmacological properties, to date, most functional studies on P2X7R responses have been analyzed in cells from rodents or immortalised cell lines. To assess the endogenous and functional expression of P2X7Rs in human astrocytes, we differentiated human-induced pluripotent stem cells (hiPSCs) into GFAP and S100 ß-expressing astrocytes. Immunostaining revealed prominent punctate P2X7R staining. P2X7R protein expression was also confirmed by Western blot. Importantly, stimulation with the potent non-selective P2X7R agonist 2',3'-O-(benzoyl-4-benzoyl)-adenosine 5'- triphosphate (BzATP) or endogenous agonist ATP induced robust calcium rises in hiPSC-derived astrocytes which were blocked by the selective P2X7R antagonists AFC-5128 or JNJ-47965567. Our findings provide evidence for the functional expression of P2X7Rs in hiPSC-derived astrocytes and support their in vitro utility in investigating the role of the P2X7R and drug screening in disorders of the central nervous system (CNS).

Astrocyte-neuron circuits in epilepsy.

The epilepsies are a diverse spectrum of disease states characterized by spontaneous seizures and associated comorbidities. Neuron-focused perspectives have yielded an array of widely used anti-seizure medications and are able to explain some, but not all, of the imbalance of excitation and inhibition which manifests itself as spontaneous seizures. Furthermore, the rate of pharmacoresistant epilepsy remains high despite the regular approval of novel anti-seizure medications. Gaining a more complete understanding of the processes that turn a healthy brain into an epileptic brain (epileptogenesis) as well as the processes which generate individual seizures (ictogenesis) may necessitate broadening our focus to other cell types. As will be detailed in this review, astrocytes augment neuronal activity at the level of individual neurons in the form of gliotransmission and the tripartite synapse. Under normal conditions, astrocytes are essential to the maintenance of blood-brain barrier integrity and remediation of inflammation and oxidative stress, but in epilepsy these functions are impaired. Epilepsy results in disruptions in the way astrocytes relate to each other by gap junctions which has important implications for ion and water homeostasis. In their activated state, astrocytes contribute to imbalances in neuronal excitability due to their decreased capacity to take up and metabolize glutamate and an increased capacity to metabolize adenosine. Furthermore, due to their increased adenosine metabolism, activated astrocytes may contribute to DNA hypermethylation and other epigenetic changes that underly epileptogenesis. Lastly, we will explore the potential explanatory power of these changes in astrocyte function in detail in the specific context of the comorbid occurrence of epilepsy and Alzheimer's disease and the disruption in sleep-wake regulation associated with both conditions.

Increased uptake of the P2X7 receptor radiotracer 18 F-JNJ-64413739 in the brain and peripheral organs according to the severity of status epilepticus in male mice.

OBJECTIVE: The P2X7 receptor (P2X7R) is an important contributor to neuroinflammation, responding to extracellularly released adenosine triphosphate. Expression of the P2X7R is increased in the brain in experimental and human epilepsy, and genetic or pharmacologic targeting of the receptor can reduce seizure frequency and severity in preclinical models. Experimentally induced seizures also increase levels of the P2X7R in blood. Here, we tested 18 F-JNJ-64413739, a positron emission tomography (PET) P2X7R antagonist, as a potential noninvasive biomarker of seizure-damage and epileptogenesis. METHODS: Status epilepticus was induced via an intra-amygdala microinjection of kainic acid. Static PET studies (30 min duration, initiated 30 min after tracer administration) were conducted 48 h after status epilepticus via an intravenous injection of 18 F-JNJ-64413739. PET images were coregistered with a brain magnetic resonance imaging atlas, tracer uptake was determined in the different brain regions and peripheral organs, and values were correlated to seizure severity during status epilepticus. 18 F-JNJ-64413739 was also applied to ex vivo human brain slices obtained following surgical resection for intractable temporal lobe epilepsy. RESULTS: P2X7R radiotracer uptake correlated strongly with seizure severity during status epilepticus in brain structures including the cerebellum and ipsi- and contralateral cortex, hippocampus, striatum, and thalamus. In addition, a correlation between radiotracer uptake and seizure severity was also evident in peripheral organs such as the heart and the liver. Finally, P2X7R radiotracer uptake was found elevated in brain sections from patients with temporal lobe epilepsy when compared to control. SIGNIFICANCE: Taken together, our data suggest that P2X7R-based PET imaging may help to identify seizure-induced neuropathology and temporal lobe epilepsy patients with increased P2X7R levels possibly benefitting from P2X7R-based treatments.

Antiproliferative effects and main molecular mechanisms of Brazilian native fruits and their by-products on lung cancer.

Lung Cancer (LC) is an emergent disease widespread globally. Compared to other types of cancer, LC has one of the lowest survival rates (18%). As some risk factors associated with the development of lung carcinogenesis are still unavoidable, researchers have been trying to find efficient and safe alternatives that can help prevent LC or even attenuate its rapid evolution after diagnosis. Studies with natural products promise to offer biological effects against several types of cancers, including LC. The uncountable types of plant matrices dispersed in nature, or even their extracts, contain a powerful composition of bioactive compounds with promising biological effects on LC. The biomes in Brazil are examples of regions with a great biodiversity of bioactive compounds-rich fruits. Therefore, this review aimed to present the potential anticancer effect of Brazilian native fruits, their fractions, and by-products on LC through the elucidation of the main molecular mechanisms involved. The Brazilian plant matrices discussed here (açaí, achiote, araticum, camu camu, cocoa, jaboticaba, genipap, guarana, and pequi) showed promising evidence by inducing cellular apoptosis, reducing cancer cell viability and tumor growth, and regulating cell cycle.

Applicability, Safety, and Efficiency of Salpingectomy versus Electrocoagulation and Laparoscopic Tubal Section in Ambulatory / Aplicabilidade, segurança e eficiência da salpingectomia versus eletrocoagulação e secção tubar laparoscópica em regime de ambulatório

Abstract Objective Female sterilization is a surgical procedure that aims women to permanently stop the use of conception. The benefits, risks and cost-effectiveness are important issues. The purpose of this study was comparing the applicability, complications and efficacy of salpingectomy versus electrocoagulation and tubal occlusion by laparoscopy in the Ambulatory Surgery Unit. Methods We performed a retrospective and observational study that included women undergoing laparoscopic sterilization procedures at our Ambulatory Surgery Unit, during three years. Statistical analysis was performed using SPSS, applying the Fisher exact test, the Mann-Whitney test, and Linear Regression. Results Two hundred and twenty-one laparoscopic surgical procedures were performed, including 79 (35.7%) bilateral total salpingectomies and 142 (64.3%) electrocoagulation and bilateral tubal occlusion procedures. The majority of the procedures were performed by a resident (n = 162; 73.3%), with 40% (n = 33) of salpingectomies. The surgical time, independently the type of surgeon, was significantly shorter in the tubal occlusion (42.2 vs. 52.7 min, p < 0.001). Safety and efficacy endpoints were not significantly different between the two groups, with a case of pregnancy in tubal occlusion group. Conclusion Salpingectomy is a safe and effective alternative comparing with electrocoagulation and tubal occlusion.

Resumo Objetivo A esterilização feminina é um procedimento cirúrgico que auxilia as mulheres na paragem permanente de utilização de métodos contraceptivos. Os objetivos desde estudo foram comparar a aplicabilidade, complicações e eficácia da salpingectomia vs. eletrocoagulação e secção tubar na esterilização feminina em regime de ambulatório. Métodos Realizou-se um estudo retrospectivo e observacional que incluiu mulheres submetidas a procedimentos de esterilização por laparoscopia no Serviço de Cirurgia de Ambulatório da ULSAM, durante três anos. A análise estatística foi realizada com recurso ao SPSS, aplicando o teste exato de Fisher, o teste de Mann-Whitney e Regressão Linear. Resultados Foram realizados 221 procedimentos cirúrgicos por laparoscopia, incluindo 79 (35,7%) salpingectomias totais bilaterais e 142 (64,3%) procedimentos por eletrocoagulação e secção tubar bilateral. A maioria dos procedimentos foram realizados por um interno de formação específica (n = 162; 73,3%), com 40% (n = 33) de salpingectomias. O tempo operatório foi significativamente inferior no grupo da eletrocoagulação (42,2 vs. 52,7 min, p < 0,001). Em relação à segurança e à eficácia não se observaram diferenças estatisticamente significativas entre os dois grupos, com um caso de gravidez após eletrocoagulação e secção tubar. Conclusão A salpingectomia é uma alternativa segura e com alta taxa de eficácia quando comparada com eletrocoagulação e secção tubar.

Applicability, Safety, and Efficiency of Salpingectomy versus Electrocoagulation and Laparoscopic Tubal Section in Ambulatory.

OBJECTIVE: Female sterilization is a surgical procedure that aims women to permanently stop the use of conception. The benefits, risks and cost-effectiveness are important issues. The purpose of this study was comparing the applicability, complications and efficacy of salpingectomy versus electrocoagulation and tubal occlusion by laparoscopy in the Ambulatory Surgery Unit. METHODS: We performed a retrospective and observational study that included women undergoing laparoscopic sterilization procedures at our Ambulatory Surgery Unit, during three years. Statistical analysis was performed using SPSS, applying the Fisher exact test, the Mann-Whitney test, and Linear Regression. RESULTS: Two hundred and twenty-one laparoscopic surgical procedures were performed, including 79 (35.7%) bilateral total salpingectomies and 142 (64.3%) electrocoagulation and bilateral tubal occlusion procedures. The majority of the procedures were performed by a resident (n = 162; 73.3%), with 40% (n = 33) of salpingectomies. The surgical time, independently the type of surgeon, was significantly shorter in the tubal occlusion (42.2 vs. 52.7 min, p < 0.001). Safety and efficacy endpoints were not significantly different between the two groups, with a case of pregnancy in tubal occlusion group. CONCLUSION: Salpingectomy is a safe and effective alternative comparing with electrocoagulation and tubal occlusion.

OBJETIVO: A esterilização feminina é um procedimento cirúrgico que auxilia as mulheres na paragem permanente de utilização de métodos contraceptivos. Os objetivos desde estudo foram comparar a aplicabilidade, complicações e eficácia da salpingectomia vs. eletrocoagulação e secção tubar na esterilização feminina em regime de ambulatório. MéTODOS: Realizou-se um estudo retrospectivo e observacional que incluiu mulheres submetidas a procedimentos de esterilização por laparoscopia no Serviço de Cirurgia de Ambulatório da ULSAM, durante três anos. A análise estatística foi realizada com recurso ao SPSS, aplicando o teste exato de Fisher, o teste de Mann-Whitney e Regressão Linear. RESULTADOS: Foram realizados 221 procedimentos cirúrgicos por laparoscopia, incluindo 79 (35,7%) salpingectomias totais bilaterais e 142 (64,3%) procedimentos por eletrocoagulação e secção tubar bilateral. A maioria dos procedimentos foram realizados por um interno de formação específica (n = 162; 73,3%), com 40% (n = 33) de salpingectomias. O tempo operatório foi significativamente inferior no grupo da eletrocoagulação (42,2 vs. 52,7 min, p < 0,001). Em relação à segurança e à eficácia não se observaram diferenças estatisticamente significativas entre os dois grupos, com um caso de gravidez após eletrocoagulação e secção tubar. CONCLUSãO: A salpingectomia é uma alternativa segura e com alta taxa de eficácia quando comparada com eletrocoagulação e secção tubar.

Occurrence and removal of drugs and endocrine disruptors in water supply systems in the metropolitan region of Belo Horizonte (Minas Gerais State, Brazil).

This study evaluates both the occurrence and removal of 24 compounds, including drugs and endocrine disruptors, in 8 water treatment plants (WTP) located in the metropolitan region of Belo Horizonte (Minas Gerais State, Brazil). The compounds 4-nonylphenol, 4-octylphenol, 17α-ethinylestradiol, 17ß-estradiol, acyclovir, bisphenol A, bezafibrate, caffeine, dexamethasone, diclofenac sodium, diltiazem, estrone, estriol, gemfibrozil, ibuprofen, linezolid, loratadine, losartan, metformin, naproxen, paracetamol, promethazine, propranolol and sulfamethoxazole were monitored at 3 sampling points (raw water, filtered water, treated water) over 10 or 12 collection campaigns for each WTP. The results showed that bisphenol A occurred at higher concentrations during the dry period with a maximum concentration of 3257.1 ng L-1, while the compounds 4-nonylphenol and losartan exhibited higher concentrations in the rainy period with maximum concentrations of 8577.2 ng L-1 and 705.8 ng L-1, respectively. Regarding the removal of compounds in the monitored WTPs, the clarification step demonstrated better removals for 4-nonylphenol, bisphenol-A, paracetamol, and sulfamethoxazole, whereas the disinfection step mainly removed the compounds 4-octylphenol and estrone. Margin of exposure (ME) assessment results indicated that only dexamethasone, ethinyl estradiol, diclofenac, estradiol, and estrone were classified as imminent risk or alert considering the 95th percentile concentration found in the samples of treated water.

Biological Synthesis of Low Cytotoxicity Silver Nanoparticles (AgNPs) by the Fungus Chaetomium thermophilum-Sustainable Nanotechnology.

Fungal biotechnology research has rapidly increased as a result of the growing awareness of sustainable development and the pressing need to explore eco-friendly options. In the nanotechnology field, silver nanoparticles (AgNPs) are currently being studied for application in cancer therapy, tumour detection, drug delivery, and elsewhere. Therefore, synthesising nanoparticles (NPs) with low toxicity has become essential in the biomedical area. The fungus Chaetomium thermophilum (C. thermophilum) was here investigated-to the best of our knowledge, for the first time-for application in the production of AgNPs. Transmission electronic microscopy (TEM) images demonstrated a spherical AgNP shape, with an average size of 8.93 nm. Energy-dispersive X-ray spectrometry (EDX) confirmed the presence of elemental silver. A neutral red uptake (NRU) test evaluated the cytotoxicity of the AgNPs at different inhibitory concentrations (ICs). A half-maximal concentration (IC50 = 119.69 µg/mL) was used to predict a half-maximal lethal dose (LD50 = 624.31 mg/kg), indicating a Global Harmonized System of Classification and Labelling of Chemicals (GHS) acute toxicity estimate (ATE) classification category of 4. The fungus extract showed a non-toxic profile at the IC tested. Additionally, the interaction between the AgNPs and the Balb/c 3T3 NIH cells at an ultrastructural level resulted in preserved cells structures at non-toxic concentrations (IC20 = 91.77 µg/mL), demonstrating their potential as sustainable substitutes for physical and chemically made AgNPs. Nonetheless, at the IC50, the cytoplasm of the cells was damaged and mitochondrial morphological alteration was evident. This fact highlights the fact that dose-dependent phenomena are involved, as well as emphasising the importance of investigating NPs' effects on mitochondria, as disruption to this organelle can impact health.