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Environmental monitoring of protozoa, with the potential to trigger diseases, is essential for decision-making by managing authorities and for the control of water surveillance. This study aimed to detect and quantify Cryptosporidium oocysts and Giardia cysts in surface water for drinking water supply and treated sewage for reuse in the city of São Paulo. Samples collected bimonthly for one year were concentrated using the USEPA 1623.1 and 1693 methods for surface water and treated effluents, respectively. Immunofluorescence and nucleic acid amplification techniques were used to detect and quantify (oo)cysts. The cloning technique followed by sequencing and phylogenetic analyses were performed to characterize species and genotypes. The immunofluorescence detected Cryptosporidium spp. and Giardia spp. in 69.2% (9/13) and 100% (13/13) of the surface water samples (0.1-41 oocysts/L and 7.2-354 cysts/L, respectively). In the reuse samples, 85.7% (12/14) were positive for both protozoa and the concentrations varied from 0.4 to 100.6 oocysts/L and 1.2 and 93.5 cysts/L. qPCR assays showed that 100% of surface water (0.1-14.6 oocysts/L and 0.3-639.8 cysts/L) and reused samples (0.1-26.6 oocysts/L and 0.3-92.5 cysts/L) were positive for both protozoa. Species C. parvum, C. hominis, and C. muris were identified using the 18S rRNA gene, demonstrating anthroponotic and zoonotic species in the samples. Multilocus SSU rRNAanalyses of the SSU rRNA, tpi, and gdh genes from Giardia intestinalis identified the AII, BII, and BIV assemblages, revealing that contamination in the different matrices comes from human isolates. The study showed the circulation of these protozoa in the São Paulo city area and the impairment of surface water supply in metropolitan regions impacted by the discharge of untreated or inadequately treated sewage regarding the removal of protozoa, emphasizing the need to implement policies for water safety, to prevent the spread of these protozoa in the population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Ceroid lipofuscinosis type 11 (CLN11) is a very rare disease, being reported in only 13 unrelated families so far. Further reports are necessary to comprehend the clinical phenotype of this condition. This article aims to report nine additional cases of CLN11 from nine unrelated Latin American families presenting with relatively slow disease progression., Methods: This was a retrospective observational study including patients with CLN11. Patients were identified through an active search for GRN pathogenic variants across the entire database of next-generation sequencing (NGS) of a commercial laboratory and by contacting attending physicians to check for clinical and radiologic findings compatible with a neuronal ceroid lipofuscinosis phenotype., Results: Nine CLN11 patients from unrelated families were evaluated. Age of onset varied between 3 to 17 years. The most common findings were visual impairment, cerebellar ataxia, seizures, myoclonus and cognitive decline. One patient had a previously unreported finding of cervical, perioral and tongue myoclonus. Most of the patients were able to walk unassisted after an average of 14.2 years (SD 4.76y) from disease onset., Conclusion: We describe nine new cases of a very rare type of neuronal ceroid lipofuscinosis (CLN11) from Latin America with a recurrent p.(Gln257ProfsTer27) and a novel p.(Cys83Ter) nonsense variant. Our findings suggest that a slowly progressive NCL might be a clue for the diagnosis of CLN11., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Peripheral nerve injury (PNI) is increasingly prevalent and challenging to treat despite advances in microsurgical techniques. In this context, adipose tissue derivatives, such as adipose-derived stem cells, nanofat, and stromal vascular fraction have been gaining attention as potential allies in peripheral nerve regeneration., Objectives: This study aims to explore the use of adipose tissue derivatives in nerve regeneration following peripheral nerve transection in murine models. Thus, we assess and synthesize the key techniques and methods used for evaluating the obtained nerve regeneration to guide future experimental research and clinical interventions., Methodology: A systematic review was conducted in February 2024, adhering to the Cochrane and PRISMA 2020 guidelines, using the PubMed, SciELO, and LILACS databases. The focus was on experimental studies involving adipose tissue derivatives in nerve regeneration in animal models post-transection. Only experimental trials reporting nerve regeneration outcomes were included; studies lacking a comparator group or evaluation methods were excluded., Results: Out of 273 studies initially identified from MEDLINE, 19 were selected for detailed analysis. The average study included 32.5 subjects, with about 10.2 subjects per intervention subgroup. The predominant model was the sciatic nerve injury with a 10 mm gap. The most common intervention involved unprocessed adipose-derived stem cells, utilized in 14 articles., Conclusions: This review underscores the significant potential of current methodologies in peripheral nerve regeneration, particularly highlighting the use of murine models and thorough evaluation techniques.

The spread of antimicrobial resistance (AMR) through multiple reservoirs is a global concern. Wastewater is a critical AMR dissemination source, so this study aimed to assess the persistence of resistance genetic markers in wastewater using a culture-independent approach. Raw and treated wastewater samples (n = 121) from a wastewater treatment plant (WWTP), a human hospital, a veterinary hospital, and a pig farm were monthly collected and concentrated by filtration. DNA was extracted directly from filter membranes, and PCR was used in the qualitative search of 32 antimicrobial resistance genes (ARGs). Selected genes (bla CTX-M , bla KPC , qnrB, and mcr-1) were enumerated by quantitative real-time PCR (qPCR). Twenty-six ARGs were detected in the qualitative ARGs search, while quantitative data showed a low variation of the ARG's relative abundance (RA) throughout the months, especially at the human hospital and the WWTP. At the WWTP, despite significantly reducing the absolute number of gene copies/L after each treatment stage (p < 0.05), slight increases (p > 0.05) in the RAs of genes bla CTX-M , qnrB, and mcr-1 were observed in reused water (tertiary treatment) when compared with secondary effluent. Although the increase is not statistically significant, it is worth noting that there was some level of ARGs concentration after the disinfection process. No significant absolute or relative after-treatment quantification reductions were observed for any ARGs at the veterinary hospital or the pig farm. The spread of ARGs through sewage needs to be continuously addressed, because their release into natural environments may pose potential risks of exposure to resistant bacteria and impact local ecosystems., (© 2024 John Wiley & Sons Ltd.)

Diverse drugs have been used for the management of inflammation disorders and pain. However, they present many side effects and stimulate the search for new pharmacotherapeutic alternatives. Plant-derived products such as copaiba essential oil (CO) offer beneficial pharmacological effects. On the other hand, essential oil's low water solubility and physical instability hinder its in vivo application. Thus, poly-ɛ-caprolactone (PCL)-based nanocarriers have been used to increase their stability and efficacy. This work aimed to encapsulate CO in PCL nanocapsules and evaluate their effect on inflammation models and pain. The polymeric nanocapsules loading CO (CO-NC) were prepared by nanoprecipitation technique, characterized, and analyzed for their anti-inflammatory effect in vitro and in vivo. The results showed that CO-NC presented a spherical shape, 229.3 ± 1.5 nm diameter, and a negative zeta potential (approximately -23 mV). CO and CO-NC presented anti-inflammatory and antioxidant effects by LPS-activated macrophages (J774 cells). In addition, CO-NC significantly reduced TNF-α secretion (3-fold) compared to CO. In vivo, pre-treatment with CO or CO-NC (50, 100, 200 mg/kg, intraperitoneal; i.p) reduced the mechanical allodynia, paw edema, and pro-inflammatory cytokines induced by intraplantar (i.pl) injection of carrageenan in mice. Specifically, CO-NC (200 mg/kg; i.p.) reduced the production of TNF-α similar to the control group. Our results support using polymeric nanocapsules for CO delivery in inflammatory conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To validate a set of indicators for monitoring the quality of surgical procedures in the Brazilian Unified Health System (SUS)., Methods: Validation study developed in 5 stages: 1) literature review; 2) prioritization of indicators; 3) content validation of indicators by RAND/UCLA consensus method; 4) pilot study for reliability analysis; and 5) development of instruction for tabulation of outcome indicators for monitoring via official information systems., Results: From the literature review, 217 indicators of surgical quality were identified. The excluded indicators were: those based on scientific evidence lower than 1A, similar, specific, which corresponded to sentinel events; and those that did not apply to the SUS context. Twenty-six indicators with a high level of scientific evidence were submitted to expert consensus. Twenty-two indicators were validated, of which 14 process indicators and 8 outcome indicators with content validation index ≥80%. Of the validated process indicators, 6 were considered substantially reliable (Kappa coefficient between 0.6 and 0.8; p < 0.05) and 2 had almost perfect reliability (Kappa coefficient > 0.8, p < 0.05), when the inter-rater agreement was analyzed. One could measure and establish tabulation mechanism for TabWin for 7 outcome indicators., Conclusion: The study contributes to the development of a set of potentially effective surgical indicators for monitoring the quality of care and patient safety in SUS hospital services.

Polymeric nanocapsules (NC) are versatile mixed vesicular nanocarriers, generally containing a lipid core with a polymeric wall. They have been first developed over four decades ago with outstanding applicability in the cosmetic and pharmaceutical fields. Biodegradable polyesters are frequently used in nanocapsule preparation and among them, polylactic acid (PLA) derivatives and copolymers, such as PLGA and amphiphilic block copolymers, are widely used and considered safe for different administration routes. PLA functionalization strategies have been developed to obtain more versatile polymers and to allow the conjugation with bioactive ligands for cell-targeted NC. This review intends to provide steps in the evolution of NC since its first report and the recent literature on PLA-based NC applications. PLA-based polymer synthesis and surface modifications are included, as well as the use of NC as a novel tool for combined treatment, diagnostics, and imaging in one delivery system. Furthermore, the use of NC to carry therapeutic and/or imaging agents for different diseases, mainly cancer, inflammation, and infections is presented and reviewed. Constraints that impair translation to the clinic are discussed to provide safe and reproducible PLA-based nanocapsules on the market. We reviewed the entire period in the literature where the term "nanocapsules" appears for the first time until the present day, selecting original scientific publications and the most relevant patent literature related to PLA-based NC. We presented to readers a historical overview of these Sui generis nanostructures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Vanessa Mosqueira has patents pending numbers WO2015039199A1 and WO2013059898A1, and has a patent-issued number PI 0605102-2 C8., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The aim of this study was to examine the chronic toxicity of imidacloprid (IMI), clothianidin (CLO) and fipronil (FIP) as a single exposure, as well as binary mixtures of IMI with CLO or FIP toward collembolans Folsomia candida , which are fauna present in the soil. Chronic toxicity assays were performed following an ISO guideline in a Tropical Artificial Soil (TAS), and the influence on the number and growth of the juveniles produced were determined. The range of nominal concentrations used in the tests with the individual compounds was 0.08-1.28 mg/kg (IMI), 0.079-1.264 mg/kg (FIP) and 0.007-0.112 mg/kg (CLO), whereas the mixture assays were performed with half the value used in the tests with individual compounds. Based upon single exposures, IMI produced a similar impact of reducing reproduction by 50% (EC 50 ranging from 0.74 to 0.85 mg/kg) compared to FIP (EC 50  = 0.78 mg/kg), whereas CLO was the most toxic to F. candida (EC 50  = 0.08 mg/kg). Their mixtures generally resulted in a diminished effect on reproduction, as evidenced by the higher EC 50 values. In contrast, in the case of the IMI+FIP combination at high concentrations at the EC 50 level, a synergistic effect on toxicity was observed. The single exposure to the three insecticides and the mixture of IMI-FIP also decreased the size of generated juveniles, which was evidenced by the reduction in the proportion of large juveniles and increased proportion of small juveniles. However, both binary mixtures (IMI-FIP and IMI-CLO) presented antagonistic effects as evidenced by less than expected reductions in growth. Data on the toxic effects of IMI in a mixture with other seed dressing insecticides to collembolans provides useful information to environmental risk assessors by diminishing the uncertainties on the ecological risk of exposure to pesticides, enabling soil management degradation by utilizing multiple insecticides.

Infections have emerged as a novel target in managing skin and mucosa diseases. Bacterial resistance to antimicrobials and biofilm elimination from surfaces remains a challenge. Because polymeric nanocapsules (NC) can increase antimicrobial activity, this study aimed to produce and characterize NC into chitosan films (CSF). Copaiba essential oil (CO) presents antimicrobial activity and was chosen to load NC. In addition, the antibacterial activity was evaluated to obtain a new biodegradable polymeric platform system with the potential to treat topical diseases associated with bacterial infections. The CO-NC produced by nanoprecipitation presented particle size lower than 250 nm, negative charge, and encapsulation efficiency higher than 70 %. Direct incorporation of CO into CSF (CO-CSF) by casting method worsened the film's characteristics. However, incorporating CO-NC into CSF (CO-NC-CSF) avoided these drawbacks demonstrating improved physical, mechanical, morphological, and topographical properties. FTIR results demonstrated possible intermolecular interactions among the polymers and CO. The CO-NC-CSF and CO-CSF presented antibacterial properties against Staphylococcus aureus, and Pseudomonas aeruginosa, especially the formulation containing 1 % of CO. These results indicated that CO-NC-CSF is a promising candidate for treating skin disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acute lung injury is an inflammation that triggers acute respiratory distress syndrome with perialveolar neutrophil infiltration, alveolar-capillary barrier damage, and lung edema. Activation of the toll-like receptor 4 complex (TLR4/MD2) and its downstream signaling pathways are responsible for the cytokine storm and cause alveolar damage. Due to the complexity of this pulmonary inflammation, a defined pharmacotherapy has not been established. Thus, this study evaluated the anti-inflammatory potential of milonine, an alkaloid of Cissampelos sympodialis Eichl, in an experimental model of lung inflammation. BALB/c mice were lipopolysaccharide-challenged and treated with milonine at 2.0 mg/kg. Twenty-four hours later, the bronchoalveolar fluid, peripheral blood, and lungs were collected for cellular and molecular analysis. The milonine treatment decreased the cell migration (mainly neutrophils) to the alveoli, the pulmonary edema, and the cytokine levels (IL-1β, IL-6, TNF-α). The systemic IL-6 level was also reduced. The milonine docking analysis demonstrated hydrophobic interaction at TLR4/MD2 groove with Ile124 and Phe126 amino acids. Indeed, the alkaloid downregulated the kinase-Akt and NF-κB through TLR4/MD2. Therefore, milonine is an effective inflammatory modulator being a potential molecule for the treatment of lung inflammation.

Objectives: PHA1 is a rare heterogeneous disorder featured by changes in renal electrolyte transport due to mineralocorticoid resistance. The aim of the current study is to report the case of a child with 5-year follow-up presenting mutation in the ElaC Ribonuclease Z 2 (ELAC2) gene and clinical-laboratory diagnosis of pseudohypoaldosteronism type 1 (PHA1), as well as atypical clinical manifestations such as thrombocytosis, borderline aldosterone levels, and plasma renin activity., Case Presentation: The patient was treated with corticosteroids and salt replenishment. His cardiological condition presented gradual regression and the introduction of new food items in his diet dismissed the need of salt replenishment., Conclusions: This new molecular mechanism should be taken into consideration in differential diagnoses in children with hyperkalemia, hyponatremia, delayed growth, hypertension and hypertrophic cardiomegaly., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Intestinal mucositis (IM) is a frequent adverse effect in anticancer therapy without standard treatment. The oil obtained from sucupira (Pterodon emarginatus) has anti-inflammatory properties, and the soybean lecithin reduces the intestinal toxicity of several xenobiotics. However, their water insolubility impairs the in vivo application. For this reason, we evaluated if the nanoencapsulation of sucupira oil (SO) in lecithin-based nanocapsules (SO-NC) could be a therapeutically effective system for the treatment of IM in murine cisplatin (CDDP)-induced intestinal mucositis model. SO was analyzed by LC-HRMS/MS and HPLC. SO-NC was prepared by nanoprecipitation and characterized using DLS, HPLC, and AFM. Mice body weight and food consumption were assessed daily during experimental mucositis induced by CDDP. The animals were euthanized, and intestinal permeability, inflammatory mediators, and intestinal histology were performed. SO-NC demonstrated adequate characteristics for oral administration as size under 300 nm, IP < 0.3, high EE, and spherical shape. In vitro cytotoxicity performed against RAW 264.7 cell lines resulted in cell viability above 80 % confirming the non-cytotoxic profile of SO (IC 50 268 µg/mL) and SO-NC (IC 50 118.5 µg/mL) up to 117.2 µg/mL. The untreated mice showed intestinal toxicity after i.p. of CDDP, principally weight loss, increased intestinal permeability, and MPO and TNF-α levels. Surprisingly, the administration of SO to CDDP-mucositis animals did not circumvent the CDDP effects and increased intestinal permeability. However, SO-NC proved efficient in mitigating the experimental intestinal mucositis by improving intestinal epithelium architecture, reducing intestinal permeability, and improving the MPO levels. In conclusion, SO-NC can positively impact intestinal mucositis by promoting mucosal recovery. This is a promising strategy for developing a new treatment for intestinal mucositis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Enterocytozoon bieneusi, also known as microsporidia, is an obligate, opportunistic, and neglected intracellular pathogen that causes diarrhea in humans. Although identified in the cat feces by epidemiological studies, no association with diarrhea has been demonstrated. We demonstrated a case of chronic enteritis by E. bieneusi in a 1-year-old male Maine Coon cat, neutered with diarrhea for nine months, by histopathological analysis of gastrointestinal biopsies and PCR of feces. The treatment with albendazole (10 days) followed by fenbendazole (5 days) proved to be effective and safe after diagnosis. This description highlights the need to investigate these pathogens in cases of diarrhea due to their importance in public health since they are zoonotic agents.

Research Background: Commercialization of Mauritia flexuosa (buriti) fruits in Brazil is at an early stage. Herein, we evaluate the nutritional value of pulp, peel and endocarp samples from buriti fruits, perform macroscopic and microscopic evaluations and analyze their physicochemical properties., Experimental Approach: Size and mass, pH, sugar and protein contents, soluble/insoluble fiber, total titratable acidity and energy value of the samples were analyzed. Mineral profiling was performed by energy dispersive X-ray fluorescence spectrometry, and fatty acids and phytosterols were determined by gas chromatography-mass spectrometry. Samples were also submitted to differential scanning calorimetry coupled to a thermal analyzer, and microstructure, morphology, surface and viscosity were evaluated by scanning electron microscopy (SEM) and X-ray diffraction (XRD) with copper radiation. Rheological behavior was also studied., Results and Conclusions: Lyophilized pulp had higher nutritional content of minerals, proteins, carbohydrates and energy than in natura pulp. Lyophilized pulp and its by-products showed suitable yields (>17.31%) and low a w , and potassium, manganese and monounsaturated fatty acid contents. Peels showed elevated amounts of saturated and polyunsaturated fatty acids and phytosterols (β-sitosterol and stigmasterol), and endothermic behavior. The reductions of calcium, magnesium and manganese ranging from 18.5 to 22.7% were observed following the lyophilization. Drying processes generated semi-crystalline powders. Both peels and endocarp contained higher amounts of insoluble fiber and lower contents of sugars. Similar results were obtained by microscopic morphological analysis, differential scanning calorimetry and XRD analysis. Pulp and endocarp exhibited pseudoplastic non-Newtonian behavior, and flow behavior index values were lower than 1, while peels presented dilatant behaviour. Thus, physicochemical and nutritional characterization of pulp and by-products, such as peels and endocarp, are essential to support scientific research and exploration of new sustainable products., Novelty and Scientific Contribution: Processing and conservation techniques, like lyophilization, maintain the good quality of nutritional contents and bioactive compounds of buriti whole fruits, and can be used to extend their shelf life, preserve alimentary characteristics and provide wider purposes and availability. Such parameters may generate income and food security for local and regional communities., Competing Interests: CONFLICT OF INTEREST The authors confirm that they have no conflicts of interest with respect to the work described in this manuscript.

Objectives: To circumvent cisplatin (CDDP) toxic effects and improve the antitumoural effect, our research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). This study aimed to evaluate whether SpHL-CDDP is associated with intestinal protection under in-vitro conditions in the presence of host-microbiota, compared with free CDDP., Methods: The cytotoxicity of CDDP and SpHL-CDDP were evaluated by colorimetric MTT and sulforhodamine B (SRB) assays. Epithelial proliferation was assessed by using an in-vitro wounding model in the presence of host-microbiota with intestinal epithelial cell line 6 (IEC-6) monolayers. Cytokines were determined by ELISA., Key Findings: Reduced cytotoxicity of SpHL-CDDP in IEC-6 cells (minimum of 1.3-fold according to the IC50 values) was observed when compared with CDDP. The presence of microbiota or CDDP reduced the wound healing. The association of microbiota and SpHL-CDDP improved the wound healing and cell number in IEC-6 cells when compared with control. These beneficial results can be associated with increased IL-6 and IL-10 levels induced by SpHL-CDDP which were affected by the presence of microbiota., Conclusions: These results indicate that the presence of microbiota associated with SpHL-CDDP provided less intestinal cellular damages compared with CDDP and constitutes a promising candidate for clinical use., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluated the toxicity and risk (via toxicity exposure ratio approach - TER) of the insecticide fipronil to collembolan's growth and reproduction in three tropical soils, under increasing atmospheric temperatures. Chronic toxicity tests were performed with Folsomia candida in tropical artificial soil (TAS), oxisol, and entisol spiked with increasing concentrations of fipronil, at three room temperature scenarios: a standard (20 ± 2 °C), a tropical condition (25 ± 2 °C) and a global warming simulation (27 ± 2 °C). Temperatures influenced the fipronil effects on the species reproduction differently between soil types. In TAS and oxisol the highest toxicities (EC 50 -based) were found at 27 °C (EC 50 TAS = 0.81, 0.70, 0.31 mg kg -1 ; EC 50 OXISOL = 0.52, 0.54, 0.40 mg kg -1 ; at 20, 25, and 27 °C, respectively). In entisol, the toxicity at 27 °C was lower compared to 25 and 20 °C (EC 50 ENTISOL = 0.33, 0.24, 0.12 mg kg -1 , respectively). Fipronil concentrations also increased the proportion of small juveniles (growth reduction) in all tested soils. However, this effect was greater (EC 10 -based) at higher temperatures (25 and/or 27 °C), regardless of the soil type. TER approach revealed a significant risk of fipronil in entisol, regardless of the tested temperature, while in other soils the risk was found significant only at the higher temperatures (25 and 27 °C for TAS, and 27 °C for oxisol). These results indicate that exposures to fipronil at high temperatures (e.g., those resulting from climate change) can threaten F. candida populations, depending on the soil type., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite the large amounts of freshwater available in Brazil, the deterioration of surface water can represent a risk of waterborne disease for national and international tourists. The main goal of this study was to assess the quality of drinking water in the triple border region of Brazil before and after being treated in water treatment plants (WTPs) and in Municipal Early Childhood Education Centers (MECECs), in terms of parasitological, microbiological, and physical-chemical aspects. Different water samples were monitored: raw water (RW), treated water (TW), and tap water from the MECECs, giving 60 samples in total, to investigate the presence of Giardia and Cryptosporidium, microbiological indicators, Pseudomonas aeruginosa, and antimicrobial resistance profiles using conventional microbiological assays and parasitological, immunological, and molecular techniques. The results obtained were compared with the reference values recommended by the legislation of drinking water in Brazil. For the first time, contamination by Cryptosporidium and Giardia was demonstrated in RW used to supply WTPs, in TW of Foz do Iguaçu, and in water destined for consumption by children. A total of 52 bacterial isolates were obtained, with high percentages of multidrug resistance to antibiotics, including a carbapenem-resistant profile, highlighting the need to improve quality control standards.

The current COVID-19 pandemic has emphasized the vulnerability of communities living in the urban outskirts and informal settlements. The lack of reliable COVID-19 case data highlights the importance and application of wastewater-based epidemiology. This study aimed to monitor the COVID-19 trends in four vulnerable urban communities (slums and low-income neighborhoods) in metropolitan São Paulo by assessing the SARS-CoV-2 RNA viral load in wastewater. We analyzed 160 samples from May 2020 to June 2021 with weekly or fortnightly samplings. The samples were ultracentrifuged with glycine elution and quantified by N1/N2 SARS-CoV-2 RT-qPCR. The results of positivity were 100% (Paraisópolis, Heliópolis and Cidade Tiradentes) and 76.9% (Vila Brasilândia). The new case numbers of COVID-19, counted from the onset of symptoms, positively correlated with SARS-CoV-2 N1 viral loads from the two largest communities (p<0.001). SARS-CoV-2 infectivity was tested in Vero E6 cells after concentration with the two techniques, ultrafiltration (Centricon ® Plus-70 10 kDa) and sucrose cushion ultracentrifugation, but none of the evaluated samples presented positive results. Next-generation sequencing (NGS) analysis from samples collected in March and August 2021 revealed the presence of the clade 20 J (lineage P.1) belonging to the most prevalent circulating variant in the country. Our results showed that wastewater surveillance data can be used as complementary indicators to monitor the dynamics and temporal trends of COVID-19. The infectivity test results strengthened the evidence of low risk of infection associated with SARS-CoV-2 in wastewater.

Hepatitis A virus (HAV) is the major cause of enterically transmitted infectious hepatitis. Between 2016 and 2017, the number of confirmed cases of hepatitis A virus (HAV) increased from 64 to 786 in São Paulo affecting mainly adults aged between 18 and 39 years (80%) and males (88%). To support epidemiological surveillance, the present study monitored the presence of HAV in urban sewage samples collected bimonthly for 1 year (November 2017-November 2018) in the central region of the city, where most of cases were detected. Sewage samples were concentrated by polyethylene glycol precipitation and HAV RNA was quantified by RT-qPCR. Nucleotide sequencing targeting the VP1/2A junction region was carried out to genotype the HAV strains. HAV was detected in 76.9% (40/52) of the samples, with a geometric mean viral load of 5.09 × 10 4 (± SD 4.51 × 10 5 ) genome copies (GC/L) (Mauá Street) and 5.27 × 10 4 (± SD 1.26 × 10 6 ) GC/L (Prestes Maia Avenue). Of the 40 positive samples, 8 were typed as HAV subgenotype IA [100% nucleotide (nt) identity with HAV strain VRD&#95;521&#95;2016]. Highest homology was obtained with sequences from European countries (Italy, Spain) and Israel, all of which had reported recent HAV outbreaks associated with men who have sex with men. Our results highlight that wastewater surveillance is a useful tool to support investigating HAV outbreaks in the community, including circulating genotypes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intravitreal anti-vascular endothelial growth factor agents are the gold standard treatment of ocular neovascular diseases. However, their short-term efficacy implies frequent intravitreal injections. Gene therapy has the ability to provide longer duration of the therapeutic effect. We have previously described the effectiveness of the self-replicating episomal vector, pEPito, in long-term gene expression in mouse retina. In this study, we evaluated different constructs to overexpress pigment epithelium-derived factor (PEDF), an angiogenesis inhibitor, and simultaneously, to silence placental growth factor (PlGF), a key player in neovascularization. We employed the human cytomegalovirus promoter to drive the expression of PEDF and PlGF shRNA, in conjunction with cis-acting ribozymes, using pEPito as expressing vector. Our results demonstrated that the non-viral systems were able to efficiently promote a sustained increase of the PEDF: PlGF ratio in the mice retina, decreased in pathological conditions. This innovative approach could open avenues for the development of new therapeutic strategies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This study aimed to compare the publications authored by plastic surgeons with those from other specialties' surgeons on patient-reported outcomes of oncoplastic surgery., Methods: A review was carried out on the Medline database, emcompassing five years (2015-2020). Studies about partial breast reconstruction after conservative treatment, immediate or delayed, by any technique, which presented patient-reported outcomes, were included., Results: We found 292 articles, from which 142 met the eligibility criteria. Publications were stratified into groups 1 (plastic surgeons) and 2 (other surgical specialties), and also into groups A (only plastic surgeons), B (only other specialties) and C (both), and compared statistically. Most publications (60.6%) were attributed to specialties other than plastic surgery. Nineteen percent had only plastic surgeons as authors, 50% only other specialties' surgeons, and 31% had both. There was no difference between groups regarding the impact factor of the journals in any of the stratifications, and the majority was published in journals with impact factor ≤2. CONCLUSION: In the last years, surgeons from specialties other than plastic surgery published more about the results of the oncoplastic surgery reported by the patients. There was no statistical difference between the groups regarding the impact factor of the journals.

Air pollution has association with chronic obstructive pulmonary disease (COPD) and reduced life expectancy. This study investigated the deleterious effects caused by tobacco smoke and diesel exhaust particles (DEP) from vehicles operating under EURO 3 and EURO 5 standards. Experiments were carried out on C57BL/6 mice divided into six groups: control group, group exposed to cigarette smoke (CS), two groups exposed to DEP (AAE3 and AAE5), and two groups exposed to tobacco smoke and vehicle DEP (CSE3 and CSE5). Results showed that, when compared to AA, groups AAE3 and AAE5 showed changes in respiratory mechanics, and that DEP originating from EURO 5 diesel vehicles was less harmful when compared to DEP originating from EURO 3 diesel vehicles. Analyses of groups CSE3 and CSE5 revealed increased inspiratory capacity and decreased tissue elastance, when compared to their respective controls, suggesting an exacerbation of changes in respiratory system mechanics compatible with COPD development., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Coumarins exhibit a wide variety of biological effects, including activities in the cardiovascular system and the aim of this study was to evaluate the vascular therapeutic potential of 7-Hydroxicoumarin (7-HC). The vascular effects induced by 7-HC (0.001 μM-300 μM), were investigated by in vitro approaches using isometric tension measurements in rat superior mesenteric arteries and by in silico assays using Ligand-based analysis. Our results suggest that the vasorelaxant effect of 7-HC seems to rely on potassium channels, notably through large conductance Ca 2+ -activated K + (BK Ca ) channels activation. In fact, 7-HC (300 μM) significantly reduced CaCl 2 -induced contraction as well as the reduction of intracellular calcium mobilization. However, the relaxation induced by 7-HC was independent of store-operated calcium entry (SOCE). Moreover, in silico analysis suggests that potassium channels have a common binding pocket, where 7-HC may bind and hint that its binding profile is more similar to quinine's than verapamil's. These results are compatible with the inhibition of Ca 2+ release from intracellular stores, which is prompted by phenylephrine and caffeine. Taken together, these results demonstrate a therapeutic potential of 7-HC on the cardiovascular system, making it a promising lead compound for the development of drugs useful in the treatment of cardiovascular diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Intravitreal injections of anti-vascular endothelial growth factor drugs have become the gold standard treatment for diabetic retinopathy (DR). However, several patients are classified as non-responders or poor responders to treatment. Therefore, it is essential to study alternative target molecules. We have previously shown that the progression of DR in the Ins2 Akita mouse reflects the imbalance between pro- and anti-angiogenic molecules found in the human retina. We report, for the first time, the therapeutic potential of a dual-acting antiangiogenic non-viral gene therapy. We have used an expressing vector encoding both the pigment epithelium-derived factor gene and a short hairpin RNA (shRNA) targeted to the placental growth factor to restore the balance between these factors in the retina. Twenty-one days after a single subretinal injection, we observed a marked decrease in the inflammatory response in the neural retina and in the retinal pigment epithelium, together with reduced vascular retinal permeability in the treated diabetic mouse. These results were accompanied by the restoration of the retinal capillary network and regression of neovascularization, with significant improvement of DR hallmarks. Concomitant with the favorable therapeutic effects, this approach did not affect retinal ganglion cells. Hence our results provide evidence toward the use of this approach in DR treatment., (© 2020 The Author(s).)

Selective catalytic reduction of NO with CO (CO-SCR) was investigated based on optimizing the operating conditions by response surface methodology (RSM) and by appropriately choosing the supported SBA-15 catalysts. The effects of the CO-SCR reaction parameters such as NO:CO molar ratios and oxygen concentrations on the catalytic performance were determined by RSM to evaluate the NO conversion using a first-order polynomial model. The CuO/SBA-15 and Fe 2 O 3 /SBA-15 catalysts were synthesized by a hydrothermal method and characterized by X-ray diffraction (XRD), atomic absorption spectroscopy (AAS), N 2 adsorption-desorption (BET), scanning electron microscopy coupled to energy dispersive X-Ray spectroscopy (SEM-EDS), and Fourier transform infrared spectroscopy (FTIR) to investigate the physicochemical properties of the solids. The RSM showed a very good agreement between predicted values and experimental results with the Pareto analysis confirming the accuracy and reliability of the model. The optimized results indicated the maximum NO conversion at 500 °C with using the NO to CO molar ratio of 1:2 (500:1000 ppm) in the absence of oxygen. Under these conditions, CuO/SBA-15 catalyst achieved 99.7% of NO conversion, whereas Fe 2 O 3 /SBA-15 had 98.1% of the catalytic parameter. Catalytic tests in CO-SCR reaction were performed on both catalysts at optimum operating conditions with CuO/SBA-15 exhibiting better performance compared to that of Fe 2 O 3 /SBA-15. The results revealed that CuO/SBA-15 was a promising catalyst for CO-SCR of NO due to the well-dispersed CuO phase on SBA-15 surface that allows the solid being more tolerant to the presence of oxygen.

Objective: To analyze a bibliometric profile of scientific production published in Acta Stomatologica Croatica (ASCRO)., Material and Methods: Scientific papers published from March 2009 to December 2018 were analyzed. Information on the year of publication was collected by four trained examiners. Dentistry area, study type and design, data analysis method, presence of randomization, number of authors and corresponding author affiliation were investigated. Data were analyzed using descriptive statistics., Results: A total of 328 articles were evaluated, with a predominance of research in the field of Dental Materials (16.5%), with original article being the most frequent (74.1%). Observational studies accounted for 52.4%, using inferential statistics (83.2%) and non-randomized experimental studies (66.1%). Cross-sectional studies were more common in areas of Behavioral, Epidemiologic & Health Services Research (86.3%), case reports in Craniofacial Biology (54.0%) and Oral Health Research (53.1%), while in vitro studies were more common in the areas of Dental Materials (90.7%), Microbiology / Immunology (70.0%) and Cariology Research (66.7%). Most articles were written by four authors (24.1%), while foreign affiliation was observed in 53.0% of studies., Conclusion: The profile of ASCRO scientific production shows a predominance of original studies carried out in the areas of Dental Materials and Behavioral, Epidemiologic & Health Services Research, with growing participation of foreign researchers., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest.

Ocular neovascularization is a defining feature of several blinding diseases. We have previously described the effectiveness of long-term pigment epithelium-derived factor (PEDF) expression in the retina of diabetic mice in ameliorating some diabetic retinopathy hallmarks. In this study, we aimed to investigate if the antiangiogenic potential of PEDF overexpression was enhanced in combination with placental growth factor (PlGF) silencing. Human RPE cells were transfected with a self-replicating episomal vector (pEPito) for PEDF overexpression and/or a siRNA targeting PlGF gene. Conditioned media from PEDF overexpression, from PlGF inhibition and from their combination thereof were used to culture human umbilical vein endothelial cells, and their proliferation rate, migration capacity, apoptosis and ability to form tube-like structures were analyzed in vitro. We here demonstrate that pEPito-driven PEDF overexpression in combination with PlGF silencing in RPE cells does not affect their viability and results in an enhanced antiangiogenic activity in vitro. We observed a significant decrease in the migration and proliferation of endothelial cells, and an increase in apoptosis induction as well as a significant inhibitory effect on tube formation. Our findings demonstrate that simultaneous PEDF overexpression and PlGF silencing strongly impairs angiogenesis compared with the single approaches, providing a rationale for combining these therapies as a new treatment for retinal neovascularization.

Background: The nutcracker and May-Thurner syndromes are rare and, although often underdiagnosed, they can cause limiting symptoms. They are frequently considered only after exclusion of other diagnoses and there is no consensus in the literature on prevalence, incidence, or diagnostic criteria., Objectives: To estimate the frequency of compression of the left common iliac vein and left renal vein in CT scans of the abdomen and pelvis., Methods: Descriptive, quantitative, cross-sectional study. The criteria used to define compression of the left renal vein were a hilar/aortomesenteric diameter ratio > 4 and aortomesenteric angle < 39° and the criterion for compression of the left common iliac vein was a diameter < 4mm., Results: CT scans of 95 patients were analyzed; 61% were women and 39% were men. Left renal vein compression was observed in 24.2% of the sample, with a mean age of 48.8 years, occurring in 27.6% of the women and 18.9% of the men (p = 0.3366). Compression of the left common iliac vein was detected in 15.7% of the sample, with a mean age of 45.9 years, occurring in 24.1% of the women and 2.7% of the men (p = 0.0024). Both veins were compressed in 7.4% of the patients., Conclusions: Left renal vein compression was detected in women and men at similar frequencies, whereas left common iliac vein compression was more frequent in women. Both venous compressions were most frequently found in patients aged 41 to 50 years., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article.

Siparuna guianensis (Laurales: Siparunaceae) has a terpene-rich essential oil with great potential for larvicides. The poor water miscibility of their compounds makes nano-emulsions of great interest for novel bioactive systems, including for control of Aedes aegypti (Diptera: Culicidae). This species is adapted to urban environments with important role in the epidemiology of some arboviruses such as dengue, chikungunya fever, zika, and urban yellow fever. The aim of the present study was to evaluate the feasibility of nano-emulsification to affect Ae. aegypti larvae. An optimal system was achieved by using a nonionic single surfactant, highlighted by its satisfactory size distribution profile. Moreover, improved larvicidal activity in comparison to bulk essential oil can be observed for the nano-emulsions. The estimated LC50 and LC90 values after 24 h of treatment of larvae with the essential oil were, respectively, 86.5232 and 134.814 µg/ml, while the estimated LC50 and LC90 value after treatment with the nano-emulsion were 24.7572 and 75.2452 µg/ml, respectively. The utilization of a simple technique to produce a fine nano-emulsion opens perspective for further integrative practices of mosquito control and giving value to this Amazon plant species may encourage its sustainable use and contribute to conservation policies., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diabetic retinopathy (DR) is considered as a diabetes-related complication that can lead to severe visual impairments. By 2030, it is expected that 1 in 5 adults will suffer from the disease. Suitable animal models for chronic DR are essential for a better understanding of the pathophysiology and to further develop new treatments. The Ins2 Akita mouse is a type 1 diabetes model that shows signs of both early and late stages of DR, including pericyte loss, increased vascular permeability, increased acellular capillaries and neovascularization. To further characterize DR in the Ins2 Akita mouse model, we have evaluated the protein levels of the angiogenesis inducers vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and the angiogenesis inhibitor pigment epithelium-derived factor (PEDF). Additionally, we have analyzed the protein expression profile of the glial markers ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) as well as of the chemokine monocyte chemoattractant protein 1 (MCP-1). In this study we demonstrate that, with disease progression, there is the development of an inflammatory response and an unbalanced expression of pro- and antiangiogenic factors in the neural retina and in the retinal pigment epithelium (RPE) of Ins2 Akita mice. Therefore, our data provide support for the diabetic retinopathy features detected in the Ins2 Akita retina, reflecting what is observed in the human pathology., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The presence of synthetic dyes in water causes serious environmental issues owing to the low water quality, toxicity to environment and human carcinogenic effects. Adsorption has emerged as simple and environmental benign processes for wastewater treatment. This work reports the use of porous Fe-based composites as adsorbents for Acid Red 66 dye removal in an aqueous solution. The porous FeC and Fe/FeC solids were prepared by hydrothermal methods using iron sulfates and sucrose as precursors. The physicochemical properties of the solids were evaluated through X-ray diffraction (XRD), Scanning electron microscopy coupled with Energy dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared s (FTIR), Raman and Mössbauer spectroscopies, nitrogen adsorption-desorption isotherms, Electron Paramagnetic Resonance (EPR) and magnetic saturation techniques. Results indicated that the Fe species holds magnetic properties and formed well dispersed Fe 3 O 4 nanoparticles on a carbon layer in FeC nanocomposite. Adding iron to the previous solid resulted in the formation of γ-Fe 2 O 3 coating on the FeC type structure as in Fe/FeC composite. The highest dye adsorption capacity was 15.5 mg·g -1 for FeC nanocomposite at 25 °C with the isotherms fitting well with the Langmuir model. The removal efficiency of 98.4% was obtained with a pristine Fe sample under similar experimental conditions.

The plant species Libidibia ferrea (Mart. ex Tul.) LP Queiroz var. ferrea basionym of Caesalpinia ferrea (Mart. ex Tul.) is used in various regions of Brazil in folk medicine in the treatment of several health problems, especially in acute and chronic inflammatory processes. Most of the preparations employed are alcoholic. Therefore, this study aimed to evaluate the acute toxicity of the hydroethanolic extract of fruits of Libidibia ferrea (EHEFLf) in zebrafish, emphasizing the possible changes in the organic-cellular level of the gills, liver, kidneys, and intestine and on embryos. The result obtained by LC-M/MS from EHEFLf indicated a high concentration of possible polyhydroxylated substances. EHEFLf, at a dose of 2 g/kg orally, produced non-significant alterations of the analyzed organs. However, for embryos, the treatment with different concentrations demonstrated heart toxicity that was concentration-dependent. There is no evidence of a correlation of the observed effects with the phytochemical composition, and considering the species of animal used, it can be suggested that the oral use of L. ferrea hydroethanolic extract has an acceptable degree of safety for use as an oral medicinal product. and embryo results have shown significant affinity to the heart; however, it is perceived to be related to the concentrations used., Competing Interests: The authors declare no conflict of interest.

The present work shows the development and evaluation of the veterinary antibiotic cloxacillin benzathine (CLOXB) loaded into poly-ε-caprolactone (PCL) nanocapsules (NC), as a potential new treatment strategy to manage bovine intramammary infections, such as mastitis. Staphylococcus aureus-induced mastitis is often a recurrent disease due to the persistence of bacteria within infected cells. CLOXB-PCL NC were prepared by interfacial deposition of preformed biodegradable polymer followed by solvent displacement method. The mean diameter of NC varied from 241 to 428 nm and from 326 to 375 nm, when determined by dynamic light scattering and by atomic force microscopy, respectively. The zeta potential of NC was negative and varied from -28 to -51 mV. In vitro release studies from the NC were performed in two media under sink conditions: PBS with 1% polyethylene glycol or milk. A reversed-phase HPLC method was developed to determine the NC entrapment efficiency and kinetics of CLOXB release from the NC. Free CLOXB dissolution occurred very fast in both media, while drug release from the NC was slower and incomplete (below 50%) after 9 h. CLOXB release kinetics from polymeric NC was fitted with the Korsmeyer-Peppas model indicating that CLOXB release is governed by diffusion following Fick's law. The fluorescence confocal microscopy images of macrophage-like J774A.1 cells reveal NC uptake and internalization in vitro. In addition, antimicrobial effect of the intramammary administration of CLOXB-PCL NC in cows with mastitis resulted in no clinical signs of toxicity and allowed complete pathogen elimination after treatment. The in vivo results obtained in this work suggest that CLOXB-PCL NC could be a promising formulation for the treatment of intramammary infections in cattle, considering their physicochemical properties, release profiles and effects on bovine mastitis control., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This study evaluated the factors related to the use of hookah among medical students, the level of knowledge about the involved harms, and their relationship with the use and intention to stop using it., Methods: Students of the 1st and 6th year of medical school were evaluated. A multivariate logistic regression model was used to evaluate the association between the outcome (use of hookah in the last 30 days) and demographic, subjective psychosocial data and level of knowledge about the harms of hookah use., Results: The experimentation rate of hookah and current use was high (59.6% and 27.7%, respectively), with no difference between the 1st and 6th year groups (p=0.70). The 6th grade students were more knowledgeable about the harm of using hookah when compared to the 1st year students (p <0.0001), and there was no association between the use of hookah in the last 30 days and the knowledge about its harms. Cigarette smoking and the use of alcoholic beverages were associated with the use of hookah in the last 30 days, with unadjusted Odds Ratio (OR) of 11.3; 95% CI 4.62-27.7; p <0.0001 and OR 8.74; 95% CI 3.78-20.2; p <0.0001; respectively., Conclusion: There is a high experimentation, current use of hookah and cigarettes among medical students. Sixth year students are more knowledgeable about the harms involved. There was no association between the use of hookah in the last 30 days and the knowledge about its harms. Smoking and the use of alcoholic beverages are independent predictors of use of hookah.

Ninety-seven specimens of spotfin hatchetfish, Thoracocharax stellatus, an ornamental freshwater species from the Amazon basin, were captured in the basin of the Guamá River in the municipality of Belém, in northern Brazil, and analysed for coccidiosis infection. Overall, 26 of the specimens were infected by apicomplexan parasites of the genus Goussia, with unsporulated forms being found in the gastric epithelium and sporulated forms in the intestinal lumen. The spheroid oocysts (mean diameter: 13.2 ± 1.7 μm) have four elliptical sporocysts. A partial sequence of the SSU rDNA of the new species was obtained, which contained 1,121 base pairs, with 43.8% guanine + cytosine (G + C), and the bases distributed as follows: A = 28.1%, C = 18.3%, G = 25.5% and T = 28.1%. The combined analysis of the morphometric and phylogenetic evidence confirmed that the specimens represented the genus Goussia and were allocated to a new species, Goussia guamaensis n. sp., which is described here., (© 2019 John Wiley & Sons Ltd.)

Water is considered an important vehicle for the spread of human toxoplasmosis in several countries. Toxoplasma gondii oocysts can persist in the environment for long periods, being highly resistant to the various chemical inactivation processes commonly used by water supply systems, distinctly from simple filtration and flocculation that are efficient in removing oocysts from drinking water. The existing methodologies for identification and quantification of this parasite in water samples are not standardized and have limitations. This study aimed to evaluate the presence of T. gondii oocysts in surface water samples used as a source for the production of drinking water in the State of São Paulo, through the implementation of a specific methodology using real-time PCR technique (qPCR). Volumes of 20 L of the sample were concentrated by filtration in Envirocheck® HV capsules. For DNA extraction, the PowerSoil DNA isolation® kit (currently DNeasy PowerSoil®) was used. The target sequence selected for qPCR was a 62-base-pair fragment of the B1 gene. In the initial recovery evaluation of the method in four replicates of reverse osmosis water, the mean recovery was 48.5% (SD ± 11.5), while the mean recovery for method performance in matrices was 3.2% (SD ± 3.2) (rainy season) and 62.0% (SD ± 6.2) (dry period), suggesting that the characteristics of the samples and the climatic conditions interfere in the recovery efficiency. Of the 39 samples analyzed (May to December 2015), 7.7% (3/39) were positive for T. gondii, and among the ten sources studied; the occurrence of the oocysts was detected in 30% (3/10).

Secreted trophic factors are key to maintain the structural and functional integrity of the retina, as they regulate cellular pathways responsible for survival, function, and response to injury. Nevertheless, these same factors can also be involved in retinal pathologies, as a consequence of the impairment of the secretory function of cells. The cells considered as major contributors to the retinal secretome are the retinal pigmented epithelium (RPE) and Müller cells. Their role in the pathophysiology of the most common neovascular pathologies in the retina - Age-related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and Retinopathy of Prematurity (ROP) - is highlighted in this short review, together with current trophic factor-based therapies, which are mainly focused on controlling inflammation, cell survival, and angiogenesis., (Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Cryptosporidium and Giardia are associated with cases of water and foodborne outbreaks in the world. This study included 50 samples of surface raw water collected from two watersheds in the state of São Paulo, Brazil. The isolation of (oo)cysts was performed in accordance with the U.S. Environmental Protection Agency's methods 1623 and genotypic characterization and quantification were carried out by Nested PCR and qPCR assays based on 18S rRNA and gdh genes, respectively. U.S. EPA 1623 method showed the presence of (oo)cysts in 40% ([Formula: see text] = 0.10 oocysts/L) and 100% ([Formula: see text] = 7.6 cysts/L) of samples from São Lourenço River, respectively, and 24% ([Formula: see text] = 0.8 oocysts/L) and 60% ([Formula: see text] = 1.64 cysts/L) of Guarapiranga Reservoir, respectively. The qPCR assay detected C. hominis/parvum in 52% (0.06 to 1.85 oocysts/L) of São Lourenço River and 64% (0.09 to 1.4 oocysts/L) of Guarapiranga Reservoir samples. Presence/absence test for Giardia intestinalis was positive in 92% of São Lourenço River and 8% of Guarapiranga Reservoir samples. The assemblage A was detected in 16% (0.58 to 2.67 cysts/L) in São Lourenço River and no positive samples were obtained for assemblage B in both water bodies. The characterization of anthroponotic species C. parvum/hominis, G. intestinalis, and assemblage A was valuable in the investigation of possible sources of contamination in the watersheds studied confirming the need of expanding environmental monitoring measures for protection of these water sources in our country.

Background: Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99m Tc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection., Methods: Fluconazole was radiolabeled with technetium-99 metastable ( 99m Tc) and encapsulated into conventional ( 99m Tc-Fluconazole-PLA-POLOX) and surface-modified ( 99m Tc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated 99m Tc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter., Results: The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free 99m Tc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free 99m Tc-fluconazole, but the results did not show a significant difference between NC formulations., Conclusion: These data indicate that these NCs might represent a therapeutic alternative for the treatment of candidiasis, once they remain more time in the infectious focus, allowing high retention of 99m Tc-fluconazole at this site., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Air pollution is a topic discussed all over the world and the search for alternatives to reduce it is of great interest to many researchers. The use of alternative energy sources and biofuels seems to be the environmentally safer solution. In this work, the deleterious effects on the respiratory system of mice exposed to PM 4.0 or TSP, present in exhaust gases from the combustion of CNS were investigated, through data from respiratory system mechanics, oxidative stress, histopathology and morphometry of the parenchyma pulmonary. The results show changes in all variables of respiratory system mechanics, in oxidative stress, the histopathological analysis and lung morphometry. The results provide experimental support for epidemiological observations of association between effects on the respiratory system and exposure to PM 4.0 or TSP from CNS combustion exhaust gases, even at acute exposure. It can serve as a basis for regulation or adjustment of environmental laws that control the emissions of these gases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Baccharis reticularia DC. is a plant species from the Asteraceae family that is endemic to Brazil. Despite the great importance of Baccharis genus, no study has been carried out regarding either the phytochemical composition of B. reticularia or the evaluation of its larvicidal potential. Considering the intrinsic immiscibility of essential oils, this study shows larvicidal nanoemulsions containing the B. reticularia phytochemically characterized essential oil and its main constituent against Aedes aegypti . The major compound found was d-limonene (25.7%). The essential oil inhibited the acetylcholinesterase, one of the main targets of insecticides. The required hydrophile-lipophile balance of both nanoemulsions was 15.0. The mean droplet sizes were around 90.0 nm, and no major alterations were observed after 24 h of preparation for both formulations. After 48 h of treatment, the estimated LC 50 values were 118.94 μg mL -1 and 81.19 μg mL -1 for B. reticularia essential oil and d-limonene nanoemulsions, respectively. Morphological alterations evidenced by scanning electron micrography were observed on the larvae treated with the d-limonene nanoemulsion. This paper demonstrated a simple and ecofriendly method for obtaining B. reticularia essential oil and d-limonene aqueous nanoemulsions by a non-heating and solvent-free method, as promising alternatives for Aedes aegypti control., Competing Interests: The authors declare no conflict of interest.

Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long-circulating and pH-sensitive liposomes (SpHL-CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24h and 72h after the administration of a single i.p dose of free CDDP or SpHL-CDDP to healthy Swiss mice. Twenty-four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF-κB. These changes persisted after 72h. While signs of intestinal toxicity were also observed 24h after administration of SpHL-CDDP, after 72h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72h after treatment mice in the SpHL-CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL-10 and IgA levels, and less activation of caspase-3, ERK1/2 and NF-κB. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL-CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL-CDDP is a promising candidate for clinical use., (Copyright © 2017. Published by Elsevier B.V.)

Background: The impact of leprosy reduces health-related quality of life of affected patients, interfering with different factors such as nutrition. This study investigated the lipid profile, nutritional status, and risk for cardiovascular disease (CVD) in patients who underwent leprosy treatment in Brazil., Methods: Eighty-four adult patients of both genders ranging in age from 20 to 60 years and diagnosed with paucibacillary (PB) or multibacillary (MB) leprosy were selected after undergoing multidrug treatment. The following data were collected: sociodemographic and clinical data; food intake; anthropometric measures (weight, height, and waist circumference); and lipid profile components (total cholesterol, high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], and triglycerides)., Results: Among the study population, there was a predominance of males (65.48%) aged 50 to 60 years, patients with an income of 248-496 American dollars (63.10%), patients who completed elementary school (65.48%), inactive patients (76.19%), non-smokers (46.43%), and non-drinking patients (69.05%). The levels (mean ± standard deviation) of total cholesterol were 193.8 ± 29.4 mg/dL in the PB form and 203.5 ± 41.7 mg/dL in the MB form. The mean LDL-c was 116.9 ± 22.7 mg/dL in PB patients and 121 ± 31.3 mg/dL in MB patients. Mean triglyceride levels were 123.4 ± 45.2 mg/dL in the PB form and 147.4 ± 88.9 mg/dL in the MB form. The evaluation of nutritional status showed that 41.67% of the patients were eutrophic, while 55.96% had excess weight. Food intake was significantly associated with HDL-c in male patients (P = 0.0264) and with triglycerides in patients above the ideal weight (P = 0.0049)., Conclusions: The risk of acquiring CVDs was observed to be high due to patients' excess weight and increased waist circumference. This study will guide clinicians in the adequate treatment of patients with leprosy in order to avoid adverse cardiovascular events.

Introduction:: The accumulation of visceral fat in obesity is associated with excessive production of proinflammatory adipokines, which contributes to low-grade chronic inflammation state. Moreover, the literature has shown that mineral deficiency, in particular of magnesium, has important role in the pathogenesis of this metabolic disorder with relevant clinical repercussions., Objective:: To bring updated information about the participation of hypomagnesemia in the manifestation of low-grade chronic inflammation in obese individuals., Method:: Articles published in PubMed, SciELO, LILACS and ScienceDirect, using the following keywords: "obesity," "magnesium" and "low grade inflammation.", Results:: Scientific evidence suggests that magnesium deficiency favors the manifestation of low-grade chronic inflammation in obese subjects., Conclusion:: From literature data, it is evident the participation of magnesium through biochemical and metabolic reactions in protecting against this metabolic disorder present in obesity.

The objectives of the study were to detect and genotype Cryptosporidium spp. and Giardia intestinalis in wastewater samples obtained from five cities with high transit of people in the State of São Paulo, Brazil, and at the entrance of a Wastewater Treatment Plant (WWTP) in Lima, Peru. Samples were collected and concentrated by centrifugation. The genomic DNA was extracted for molecular characterization by nested PCR for Cryptosporidium and double nested PCR for Giardia, followed by sequencing and phylogenetic analysis. G. intestinalis was found in 63.6 % of the samples, and the human assemblages A and B were identified. Cryptosporidium sp. was found in 36.4 % of the samples, and the species were corresponding to Cryptosporidium hominis, Cryptosporidium cuniculus, and Cryptosporidium muris. Results revealed the presence of human pathogenic Cryptosporidium species and G. intestinalis human pathogenic assemblages. Molecular tools highlight the importance to map the genetic diversity of these parasites, as well as to detect their epidemiological circulation pathway in the environment.

Introduction: Nutritional intervention in pre-school children using cookies prepared with wheat flour enriched with iron and folic acid (CWFFeFA) and cookies prepared with cowpea (Vigna unguiculata (L.) Walp) flour fortified with iron and zinc and wheat flour enriched with iron and folic acid (CCFFeZn + WFFeFA)., Objective: To assess the impact of the ingestion of CWFFeFA and CCFFeZn + WFFeFA by pre-school children, using the cowpea variety BRS-Xiquexique, to control iron-deficiency anaemia., Methods: Nutritional intervention was conducted in municipal day care centres selected at random (n = 262) involving pre-school children aged 2 to 5 years living in Teresina, state of Piauí, Brazil. To assess the socioeconomic data, BMI-for-age, haemoglobin levels before and after intervention, and dietary intake, the children were divided into group 1 (G1), which received CWFFeFA (30 g), and group 2 (G2), which received CCFFeZn + WFFeFA (30 g). Food acceptance was evaluated daily., Results: The prevalence of anaemia in G1 and G2 before the nutritional intervention was 12.2% (n = 18) and 11.5% (n = 30), respectively. After intervention, the prevalence decreased to 1.4% in G1 (n = 2) and to 4.2% in G2 (n = 11). Food acceptance by pre-school children in G1 and G2 was 97.4% and 94.3%, respectively., Conclusion: The use of both types of cookie formulations decreased the prevalence of anaemia among pre-school children, and CCFFeZn + WFFeFA yielded the greatest decrease.

Purpose: Pancreatic cancer is the fourth most common cause of cancer-related death in the USA. This is mainly because of the chemoresistance of this type of tumor; thus, the development of novel therapeutic modalities is needed., Methods: Long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP) were administered systemically into pancreatic tumor-bearing mice for a period of 14 days. The antitumor efficacy and toxicity of this new treatment method on the basis of cisplatin-loaded liposomes was compared with the classical free-CDDP method. Tc-HYNIC-βAla-bombesin(7-14) tumor uptake and histopathologic findings were used to monitor and compare the two treatment modalities., Results: The antitumor activity of SpHL-CDDP treatment was shown by (a) decrease in tumor volume, (b) development of tumor necrotic areas, and (c) decrease in Tc-HYNIC-βAla-bombesin(7-14) tumor uptake. Toxicity was evaluated by the development of inflammation and necrotic areas in the kidneys, liver, spleen, and intestine: toxic effects were greater with free-CDDP than SpHL-CDDP., Conclusion: SpHL-CDDP showed significant antitumor activity in pancreatic cancer-bearing mice, with lower toxicity in comparison with free-CDDP.