The evolution of endocrine disruptor chemical assessments worldwide in the last three decades.

Endocrine Disrupting Chemicals (EDCs) encompass a wide variety of substances capable of interfering with the endocrine system, including but not limited to bisphenol A, organochlorines, polybrominated flame retardants, alkylphenols and phthalates. These compounds are widely produced and used in everyday modern life and have increasingly been detected in aquatic matrices worldwide. In this context, this study aimed to carry out a literature review to assess the evolution of EDCs detected in different matrices in the last thirty years. A bibliometric analysis was conducted at the Scopus, Web of Science, and Google Scholar databases. Data were evaluated using the Vosviewer 1.6.17 software. A total of 3951 articles in English were retrieved following filtering. The results demonstrate a gradual and significant growth in the number of published documents, strongly associated with the increasing knowledge on the real environmental impacts of these compounds. Studied were mostly conducted by developed countries in the first two decades, 1993 to 2012, but in the last decade (2013 to 2022), an exponential leap in the number of publications by countries such as China and an advance in research by developing countries, such as Brazil, was verified.

Probucol neuroprotection against manganese-induced damage in adult Wistar rat brain slices.

Manganese (Mn) is an abundant element used for commercial purposes and is essential for the proper function of biological systems. Chronic exposure to high Mn concentrations causes Manganism, a Parkinson's-like neurological disorder. The pathophysiological mechanism of Manganism remains unknown; however, it involves mitochondrial dysfunction and oxidative stress. This study assessed the neuroprotective effect of probucol, a hypolipidemic agent with anti-inflammatory and antioxidant properties, on cell viability and oxidative stress in slices of the cerebral cortex and striatum from adult male Wistar rats. Brain structure slices were kept separately and incubated with manganese chloride (MnCl2) and probucol to evaluate the cell viability and oxidative parameters. Probucol prevented Mn toxicity in the cerebral cortex and striatum, as evidenced by the preservation of cell viability observed with probucol (10 and 30 µM) pre-treatment, as well as the prevention of mitochondrial complex I inhibition in the striatum (30 µM). These findings support the protective antioxidant action of probucol, attributed to its ability to prevent cell death and mitigate Mn-induced mitochondrial dysfunction.

Persistence of SARS-CoV-2 Antigens in the Nasal Mucosa of Eight Patients with Inflammatory Rhinopathy for over 80 Days following Mild COVID-19 Diagnosis.

The nasal mucosa is the main gateway for entry, replication and elimination of the SARS-CoV-2 virus, the pathogen that causes severe acute respiratory syndrome (COVID-19). The presence of the virus in the epithelium causes damage to the nasal mucosa and compromises mucociliary clearance. The aim of this study was to investigate the presence of SARS-CoV-2 viral antigens in the nasal mucociliary mucosa of patients with a history of mild COVID-19 and persistent inflammatory rhinopathy. We evaluated eight adults without previous nasal diseases and with a history of COVID-19 and persistent olfactory dysfunction for more than 80 days after diagnosis of SARS-CoV-2 infection. Samples of the nasal mucosa were collected via brushing of the middle nasal concha. The detection of viral antigens was performed using immunofluorescence through confocal microscopy. Viral antigens were detected in the nasal mucosa of all patients. Persistent anosmia was observed in four patients. Our findings suggest that persistent SARS-CoV-2 antigens in the nasal mucosa of mild COVID-19 patients may lead to inflammatory rhinopathy and prolonged or relapsing anosmia. This study sheds light on the potential mechanisms underlying persistent symptoms of COVID-19 and highlights the importance of monitoring patients with persistent anosmia and nasal-related symptoms.

Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 µg/kg or 25 µg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

Whole-genome sequencing of 1,171 elderly admixed individuals from São Paulo, Brazil.

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.

Protective Effects of Probucol on Different Brain Cells Exposed to Manganese.

Manganese (Mn) is an essential metal for many functions in the body. However, in excess, it can be neurotoxic and cause a Parkinson-like syndrome, known as manganism. Here, we aimed to identify a protective effect of probucol, a lipid-lowering agent with anti-inflammatory and antioxidant properties, against Mn-induced toxicity in human neuroblastoma (SH-SY5Y) and glioblastoma (C6) cell lines. The cells were incubated with increasing concentrations of Mn followed by probucol addition 1, 3, 6, and/or 24 h to assess the metal toxic doses and measure the protective effect of probucol against Mn-induced oxidative damage. Longer exposition to Mn showed decreased SH-SY5Y cellular viability in concentrations higher than 100 µM, and probucol was able to prevent this effect. The C6 cells were more sensitive to the Mn deleterious actions, decreasing the cell viability after 6 h of 500 µM Mn exposure. In addition, probucol prevents the complex I and II of the mitochondrial respiratory chain (MRC) inhibition caused by Mn and decreased the intracellular ROS production. Taken together, our results showed that Mn toxicity affects differently both cell lines and probucol has a protective effect against the oxidative imbalance in the central nervous system.

ß-hydroxy-ß-methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue.

The effects of resistance training (RT) associated with calcium ß-hydroxyß-methylbutyrate (CaHMB) supplementation on the body composition and gene expression of cytokines related to skeletal muscle hypertrophy and adipose tissue metabolism were studied in rats. Male Wistar rats were divided into four groups of 12 animals: sedentary control (SC); sedentary supplemented (SS); resistance training control (RTC) and resistance training supplemented (RTS). Rats from RTC and RTS groups were submitted to an RT programme and those from SS and RTS groups received 1 mL of CaHMB (320 mg kg-1 day-1) by gavage, for 8 weeks. We evaluated: body composition; plasma lipid profile; the gene expression of interleukin (IL)-6, IL-10, IL-15 and fibronectin type III domain-containing protein 5 (FNDC-5) in skeletal muscle, and IL-6, mitochondrial uncoupling protein 1 (UCP-1) in white adipose tissue (WAT); and the concentration of irisin in WAT. Compared to RTC alone, the combination of CaHMB with RT (RTS) further reduced abdominal circumference (5.3%), Lee index (2.4%), fat percentage (24.4%), plasma VLDL cholesterol (16.8%) and triglycerides (17%) and increased the gene expression of FNDC-5 (78.9%) and IL-6 (47.4%) in skeletal muscle and irisin concentration (26.9%) in WAT. Neither RT nor CaHMB affected the protein percentage or the gene expression of IL-6 and UCP-1 in WAT and IL-10, IL-15 in skeletal muscle. In conclusion, CaHMB supplementation increased the beneficial effects of RT on body fat reduction and was associated with muscular genic expression of IL-6 and FNDC-5 and irisin concentration in WAT, despite the lack of change in protein mass and maximal strength.

Prediction of extubation outcome in mechanically ventilated patients: Development and validation of the Extubation Predictive Score (ExPreS).

Despite the best efforts of intensive care units (ICUs) professionals, the extubation failure rates in mechanically ventilated patients remain in the range of 5%-30%. Extubation failure is associated with increased risk of death and longer ICU stay. This study aimed to identify respiratory and non-respiratory parameters predictive of extubation outcome, and to use these predictors to develop and validate an "Extubation Predictive Score (ExPreS)" that could be used to predict likelihood of extubation success in patients receiving invasive mechanical ventilation (IMV). Derivation cohort was composed by patients aged ≥18 years admitted to the ICU and receiving IMV through an endotracheal tube for >24 hours. The weaning process followed the established ICU protocol. Clinical signs and ventilator parameters of patients were recorded during IMV, in the end phase of weaning in pressure support ventilation (PSV) mode, with inspiratory pressure of 7 cm H2O over the PEEP (positive end expiratory pressure). Patients who tolerated this ventilation were submitted to spontaneous breathing trial (SBT) with T-tube for 30 minutes. Those who passed the SBT and a subsequent cuff-leak test were extubated. The primary outcome of this study was extubation success at 48 hours. Parameters that showed statistically significant association with extubation outcome were further investigated using the receiver operating characteristics (ROC) analysis to assess their predictive value. The area under the curve (AUC) values were used to select parameters for inclusion in the ExPreS. Univariable logistic regression analysis and ROC analysis were performed to evaluate the performance of ExPreS. Patients' inclusion and statistical analyses for the prospective validation cohort followed the same criteria used for the derivation cohort and the decision to extubate was based on the ExPreS result. In the derivation cohort, a total of 110 patients were extubated: extubation succeeded in 101 (91.8%) patients and failed in 9 (8.2%) patients. Rapid shallow-breathing index (RSBI) in SBT, dynamic lung compliance, duration of IMV, muscle strength, estimated GCS, hematocrit, and serum creatinine were significantly associated with extubation outcome. These parameters, along with another parameter-presence of neurologic comorbidity-were used to create the ExPreS. The AUC value for the ExPreS was 0.875, which was higher than the AUCs of the individual parameters. The total ExPreS can range from 0 to 100. ExPreS ≥59 points indicated high probability of success (OR = 23.07), while ExPreS ≤44 points indicated low probability of success (OR = 0.82). In the prospective validation cohort, 83 patients were extubated: extubation succeeded in 81 (97.6%) patients and failed in 2 (2.4%) patients. The AUC value for the ExPreS in this cohort was 0.971. The multiparameter score that we propose, ExPreS, shows good accuracy to predict extubation outcome in patients receiving IMV in the ICU. In the prospective validation, the use of ExPreS decreased the extubation failure rate from 8.2% to 2.4%, even in a cohort of more severe patients.

The impact of sediment dumping sites on the concentrations of microplastic in the inner continental shelf of Rio de Janeiro/Brazil.

The marine environment is constantly being impacted by anthropogenic activities. Nowadays, microplastics (MPs) representing one of the most deleterious material among of all substances and material from anthropogenic origin. The Microplastics (MPs) are particles smaller than 5 mm. This study presents information on abundance, distribution, type and colour of microplastics in the bottom sediments of the continental Shelf of Rio de Janeiro State. This area is strongly impacted due to its location in front of one of the most polluted coastal bays in the Brazilian Coastline. It receives untreated sewage from an Ipanema Beach submarine emissary and also a great amount of sediments dredged from Rio de Janeiro Harbour, which strongly influences the distribution of MPs in the area. The analyses detected the presence of MP in 100% of the samples, composed mainly by secondary microplastics, and almost 50% were fibers, followed by plastic films, plastic fragments and pellets. Based on the nature of the sources of the MP, a great variety of colours was shown, dominated by four main colours: blue, white, transparent, and black, this pattern could potentially increase their bioavailability due to resemblance to prey items, especially to visual raptorial species.

Sex differences in subacute manganese intoxication: Oxidative parameters and metal deposition in peripheral organs of adult Wistar rats.

INTRODUCTION: Manganese (Mn) is an essential element required for several biological systems. However, it is toxic in excessive accumulation. The toxic effects following Mn overexposure is well known in the CNS but other studies evaluating other target tissues remain scarce. OBJECTIVE: This study aimed to investigate sex-related differences in oxidative stress, metabolic parameters and Mn deposition in peripheral organs of Wistar rats exposed to subacute model of intoxication. METHODS: Male and female adult Wistar rats received 6 or 15 mg/kg of MnCl2, intraperitoneally, 5 days a week, for 4 consecutive weeks to mimic subacute intoxication. Control group received sterile saline 0,9% following the same protocol. After this period, the metal accumulation, oxidative stress, mitochondrial activity and histological parameters in cardiac muscle, kidney, lungs and liver were analysed. RESULTS: Increased Mn concentrations were found in all organs, especially kidneys. The cardiac muscle analysis revealed increased lipid peroxidation and decreasing of GSH levels in both doses of Mn in male and female rats. The increase of lipid peroxidation in liver was more evident in the male group, and there was a significant decrease of antioxidant capacity in males' kidney. Nevertheless, there was an increase of mitochondrial complex I activity in kidney of females and increase of mitochondrial complex II activity in male group. Histological analysis revealed morphological changes in hepatic and pulmonary tissue. CONCLUSION: Taken together, our results showed that subacute Mn exposure lead to significant metabolic, biochemical alterations especially in kidney and liver. Nevertheless, despite Mn deposition was virtually the same in the peripheral organs of male and female rats, it promotes different toxic effects between sexes.

[Anatomic and surgical study of the recurrent laryngeal nerve and its involvement with the ligament of Berry]. / Estudo das relações anatomocirúrgicas entre os nervos laríngeos recorrentes e o ligamento de Berry.

OBJECTIVE: To study the anatomical relations of the recurrent laryngeal nerve (RLN) with the ligament of Berry (LB), and point out the different ways of presenting the relationship between these two structures. METHODS: We conducted a study with anterior cervical dissection of 22 corpses, in the years 2009 and 2010, with attention towards the frequency of presentation of anatomical relations between the NLR and Berry ligament, with the following classification: Type I or intraligamentary: the nerve and / or its branches were visualized in the ligament substance conjunctiva; Type IIA or lateral: nerve and / or its branches lateral to the ligament; Type IIB or lateral paraligamentary: nerve and / or its side branches and in contact with the ligament without penetrating it; Type III or medial: nerve and / or its branches visualized after complete dissection of the ligament, in lateral-medial position. RESULTS: The study analyzed 41 RLNs, which comprised eight (19.5%) of type I, 20 (48.8%) Type II, five (12.2%) Type IIB and eight (19.5%) type III. Of the 19 (86.3%) RLNs dissected bilaterally in the same cadaver, 11 (57.8%) displayed a classification in one side of the neck different from the one of the other side. CONCLUSION: Due to its proximity to the RLN and the anatomical variability, the Berry ligament should not be considered a reliable parameter for repair and preservation of the recurrent laryngeal nerve. Hence, the indiscriminate latero-medial dissection of the ligament is not recommended without direct visualization of the nerve.

Relation between the external branch of the superior laryngeal nerve and the superior thyroid artery: a study in 101 nerves.

OBJECTIVE: This paper aims to propose a protocol with the topographical relations of the ESLN and the superior thyroid artery in order to minimize the number of flaws in the proposals found in the literature. METHODS: the cervical regions of 57 human cadavers from the Forensic Medicine Institute were dissected bilaterally, with photographic identification of the ESLNs and their relation to the superior thyroid artery. These data were used to propose the following classification: Type 1: unidentified ESLN; Type 2: the ESLN crosses the superior thyroid artery 1.5 cm above the upper pole of the thyroid gland; Type 3: the ESLN crosses the superior thyroid artery between 1 and 1.5 cm above the upper pole of the thyroid gland; Type 4: the ESLN crosses the superior thyroid artery less than 1cm above the upper pole of the thyroid gland; Type 5: the ESLN crosses lateral-medially below the upper pole of the thyroid gland. As a supplement, types 2, 3 and 4 received the subclassification: A - the ESLN was partially or totally enclosed in the perimuscular or intramuscular areolar connective tissue, in the inferior pharyngeal constrictor muscle, in more than half of its path after crossing the superior thyroid artery; B - the ESLN was not enclosed in either of these tissues. RESULTS: Type 1, 11.88%; Type 2, 13.86%; Type 3, 34.65%; Type 4, 38.61%; Type 5, 0.99%. CONCLUSION: the majority of the ESLN nearest to the upper pole of the gland (types 3 and 4) followed the perimuscular or intramuscular superficial connective tissue in the upper pole of the thyroid gland, which, in this study, disobliges the systematic identification of the nerve in thyroidectomies (p=0.075).