Ammonia Detection by Electronic Noses for a Safer Work Environment.

Providing employees with proper work conditions should be one of the main concerns of any employer. Even so, in many cases, work shifts chronically expose the workers to a wide range of potentially harmful compounds, such as ammonia. Ammonia has been present in the composition of products commonly used in a wide range of industries, namely production in lines, and also laboratories, schools, hospitals, and others. Chronic exposure to ammonia can yield several diseases, such as irritation and pruritus, as well as inflammation of ocular, cutaneous, and respiratory tissues. In more extreme cases, exposure to ammonia is also related to dyspnea, progressive cyanosis, and pulmonary edema. As such, the use of ammonia needs to be properly regulated and monitored to ensure safer work environments. The Occupational Safety and Health Administration and the European Agency for Safety and Health at Work have already commissioned regulations on the acceptable limits of exposure to ammonia. Nevertheless, the monitoring of ammonia gas is still not normalized because appropriate sensors can be difficult to find as commercially available products. To help promote promising methods of developing ammonia sensors, this work will compile and compare the results published so far.

Cerebrospinal Fluid Biomarkers of Symptomatic Neurosyphilis in People With HIV Compared with Uninfected Individuals.

We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n = 42), presumptive NS (n = 74), systemic syphilis (SS) (n = 38), serological diagnosis of syphilis (n = 18), PWH without SS and NS (n = 10), and negative control (n = 72). In PWoH, for presumptive NS, the combination of CSF TP > 45 mg/dL and/or WBC > 5.0 cells/mm3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS, however the DCPC were better in the suppressed group. In PWoH, the value of CSF TP > 45 mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count > 20 cell/mm3, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of > 10 or > 20 cells/mm3, was moderately applicable for screening.As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, better in the former. These biomarkers could be included for presumptive NS diagnosis. DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection.

Distinct engrams control fear and extinction memory.

Memories are stored in engram cells, which are necessary and sufficient for memory recall. Recalling a memory might undergo reconsolidation or extinction. It has been suggested that the original memory engram is reactivated during reconsolidation so that memory can be updated. Conversely, during extinction training, a new memory is formed that suppresses the original engram. Nonetheless, it is unknown whether extinction creates a new engram or modifies the original fear engram. In this study, we utilized the Daun02 procedure, which uses c-Fos-lacZ rats to induce apoptosis of strongly activated neurons and examine whether a new memory trace emerges as a result of a short or long reactivation, or if these processes rely on modifications within the original engram located in the basolateral amygdala (BLA) and infralimbic (IL) cortex. By eliminating neurons activated during consolidation and reactivation, we observed significant impacts on fear memory, highlighting the importance of the BLA engram in these processes. Although we were unable to show any impact when removing the neurons activated after the test of a previously extinguished memory in the BLA, disrupting the IL extinction engram reactivated the aversive memory that was suppressed by the extinction memory. Thus, we demonstrated that the IL cortex plays a crucial role in the network involved in extinction, and disrupting this specific node alone is sufficient to impair extinction behavior. Additionally, our findings indicate that extinction memories rely on the formation of a new memory, supporting the theory that extinction memories rely on the formation of a new memory, whereas the reconsolidation process reactivates the same original memory trace.

Overall survival and associated factors in women with metastatic breast cancer treated with trastuzumab at a public referral institution.

OBJECTIVE: To characterize associated factors and overall survival of women with metastatic breast cancer treated with trastuzumab after its incorporation into the SUS, and additionally to present the direct costs of this technology. METHODS: This is a retrospective cohort, based on data from computerized medical records from one of the units of the National Cancer Institute (INCA), in Rio de Janeiro-RJ, Brazil. Women with HER-2 positive metastatic breast cancer undergoing trastuzumab treatment from September 2017 to August 2018 were included. Overall survival was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. RESULTS: 136 women were selected, whose median age at diagnosis was 51 years (range: 21-81 years). The median OS was 43.63 months (95%CI 33.92-53.34). It is observed that the median OS for the population already diagnosed with metastatic disease (stage IV) was significantly lower than for patients diagnosed in stages I-III (37.43 months vs. 48.6 months, p<0, 01). Women without previous use of trastuzumab had a higher median OS than patients pretreated with trastuzumab (45.16 months vs. 40.73 months, p<0.01). CONCLUSION: Trastuzumab improves survival in HER-2 positive metastatic breast cancer. Brain and multiple metastases are associated with a worse prognosis. It is essential to avoid advanced staging and perform surgical treatment, with emphasis on radical mastectomy. The SUS must adopt policies and strategies for early diagnosis and guarantee access to trastuzumab, considering its high cost.

ß-Carboline-α-aminophosphonate Derivative: A Promising Antitumor Agent for Breast Cancer Treatment.

Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments available, we analyzed the in vitro cytotoxic potential of ((4-Fluoro-phenyl)-{2-[(1-phenyl-9H-ß-carboline-3-carbonyl)-amino]-ethylamino}-methyl)-phosphonic acid dibutyl ester (BCP-1) in breast cancer cells (MCF-7 and MDA-MB-231) and in a non-tumor breast cell line (MCF-10A). BCP-1 has an α-aminophosphonate unit linked to the ß-carboline nucleus, and the literature indicates that compounds of these classes have high biological potential. In the present study, the mechanism of action of BCP-1 was investigated through methods of spectrofluorimetry, flow cytometry, and protein expression analysis. It was found that BCP-1 inhibited the proliferation of both cancer cell lines. Furthermore, it induced oxidative stress and cell cycle arrest in G2/M. Upregulation of apoptosis-related proteins such as Bax, cytochrome C, and caspases, as well as a decrease in the anti-apoptotic protein Bcl-2, indicated potential induction of apoptosis in the MDA-MB-231 cells. While in MCF-7 cells, BCP-1 activated the autophagic death pathway, which was demonstrated by an increase in autophagic vacuoles and acidic organelles, in addition to increased expression of LC3I/LC3II and reduced SQSTM1/p62 expression. Further, BCP-1 demonstrated antimetastatic potential by reducing MMP-9 expression and cell migration in both breast cancer cell lines. In conclusion, BCP-1 is a promising candidate for breast cancer chemotherapy.

Effectiveness of non-operative approaches in active enamel carious lesions: a retrospective longitudinal study.

The aim of the study was to investigate the effectiveness of non-invasive and micro-invasive treatments in active enamel carious lesions in high-caries-risk children. Clinical records of children treated in a dental school setting were retrospectively screened for active enamel carious lesions treated non-invasively (topical fluoride applications, oral hygiene instruction, or dietary guidance) or micro-invasively (sealant). The control of active carious lesions was set as the main outcome established by the combination of inactivation and non-progression of the lesions based on Nyvad and ICDAS criteria, respectively. Individual and clinical factors associated with the outcome were analyzed by Poisson regression. The sample consisted of 105 high-caries-risk children with a mean age of 8.3 (± 2.4) years. From a total of 365 active enamel carious lesions, most lesions (84.1%) were active non-cavitated carious lesions (ICDAS scores 1 and 2) and only 15.9% presented localized enamel breakdown (ICDAS score 3). Of these, 72.6% were inactivated and 92.1% did not progress (mean time of 6.5 ± 4.1 months). The prevalence of controlled carious lesions was higher among children older than 6 years (PR:1.43; 95%CI:1.00-2.03; p = 0.04) and in those with better biofilm control (PR:0.99; 95%CI: 0.98-0.99; p = 0.03). Non-operative approaches are effective for controlling active enamel carious lesions. The majority of active enamel carious lesions became inactive and did not progress after treatment. Caries control was associated with older children and better biofilm control.

Toxicological evaluation of zidovudine and novel chalcogen derivatives in Drosophila melanogaster.

Zidovudine (AZT) is the most commonly prescribed antiviral drug for the treatment of human immunodeficiency virus (HIV) infection. However, its chronic administration causes toxic side effects limiting its use. This study aimed to evaluate the toxicity of different concentrations of AZT and novel chalcogen derivatives (7A, 7D, 7G, 7K, 7M) on locomotion, mitochondrial dysfunction, acetylcholinesterase (AChE) activity, and production of reactive oxygen species (ROS) in adult Drosophila melanogaster. Our results show that AZT and its derivative 7K at a concentration of 10 µM impaired flies' locomotor behavior. Furthermore, AZT and the derivatives 7K, 7A, and 7M induced mitochondrial dysfunction observed by a decrease in oxygen flux through mitochondrial complexes I and II. Neither of the compounds tested affected AChE activity or ROS production in flies. According to these data, AZT derivatives presented the following decreasing order of toxicity: 7K > AZT > 7G > 7A > 7M > 7D. Based on the chemical structure, it is possible to infer that the presence of the seleno-phenyl group in 7A and 7G increases their toxicity compared to compounds 7D and 7M. In addition, compounds 7G, 7M, and 7K with three carbon atoms as spacer were more toxic than analogs containing one carbon atom (7A and 7D). Finally, the insertion of a p-methoxyl group enhances toxicity (7K). Based on these results, excepting 7K, all other chalcogen derivatives presented lower toxicity than AZT and are potential drug candidates.

Caffeine improves mitochondrial function in PINK1B9-null mutant Drosophila melanogaster.

Mitochondrial dysfunction plays a central role in Parkinson's disease (PD) and can be triggered by xenobiotics and mutations in mitochondrial quality control genes, such as the PINK1 gene. Caffeine has been proposed as a secondary treatment to relieve PD symptoms mainly by its antagonistic effects on adenosine receptors (ARs). Nonetheless, the potential protective effects of caffeine on mitochondrial dysfunction could be a strategy in PD treatment but need further investigation. In this study, we used high-resolution respirometry (HRR) to test caffeine's effects on mitochondrial dysfunction in PINK1B9-null mutants of Drosophila melanogaster. PINK1 loss-of-function induced mitochondrial dysfunction in PINK1B9-null flies observed by a decrease in O2 flux related to oxidative phosphorylation (OXPHOS) and electron transfer system (ETS), respiratory control ratio (RCR) and ATP synthesis compared to control flies. Caffeine treatment improved OXPHOS and ETS in PINKB9-null mutant flies, increasing the mitochondrial O2 flux compared to untreated PINKB9-null mutant flies. Moreover, caffeine treatment increased O2 flux coupled to ATP synthesis and mitochondrial respiratory control ratio (RCR) in PINK 1B9-null mutant flies. The effects of caffeine on respiratory parameters were abolished by rotenone co-treatment, suggesting that caffeine exerts its beneficial effects mainly by stimulating the mitochondrial complex I (CI). In conclusion, we demonstrate that caffeine may improve mitochondrial function by increasing mitochondrial OXPHOS and ETS respiration in the PD model using PINK1 loss-of-function mutant flies.

Effectiveness of non-operative approaches in active enamel carious lesions: a retrospective longitudinal study

Abstract The aim of the study was to investigate the effectiveness of non-invasive and micro-invasive treatments in active enamel carious lesions in high-caries-risk children. Clinical records of children treated in a dental school setting were retrospectively screened for active enamel carious lesions treated non-invasively (topical fluoride applications, oral hygiene instruction, or dietary guidance) or micro-invasively (sealant). The control of active carious lesions was set as the main outcome established by the combination of inactivation and non-progression of the lesions based on Nyvad and ICDAS criteria, respectively. Individual and clinical factors associated with the outcome were analyzed by Poisson regression. The sample consisted of 105 high-caries-risk children with a mean age of 8.3 (± 2.4) years. From a total of 365 active enamel carious lesions, most lesions (84.1%) were active non-cavitated carious lesions (ICDAS scores 1 and 2) and only 15.9% presented localized enamel breakdown (ICDAS score 3). Of these, 72.6% were inactivated and 92.1% did not progress (mean time of 6.5 ± 4.1 months). The prevalence of controlled carious lesions was higher among children older than 6 years (PR:1.43; 95%CI:1.00-2.03; p = 0.04) and in those with better biofilm control (PR:0.99; 95%CI: 0.98-0.99; p = 0.03). Non-operative approaches are effective for controlling active enamel carious lesions. The majority of active enamel carious lesions became inactive and did not progress after treatment. Caries control was associated with older children and better biofilm control.

Overall survival and associated factors in women with metastatic breast cancer treated with trastuzumab at a public referral institution / Sobrevida global e fatores associados em mulheres com câncer de mama metastático tratadas com trastuzumabe em uma instituição pública de referência

ABSTRACT Objective: To characterize associated factors and overall survival of women with metastatic breast cancer treated with trastuzumab after its incorporation into the SUS, and additionally to present the direct costs of this technology. Methods: This is a retrospective cohort, based on data from computerized medical records from one of the units of the National Cancer Institute (INCA), in Rio de Janeiro-RJ, Brazil. Women with HER-2 positive metastatic breast cancer undergoing trastuzumab treatment from September 2017 to August 2018 were included. Overall survival was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Results: 136 women were selected, whose median age at diagnosis was 51 years (range: 21-81 years). The median OS was 43.63 months (95%CI 33.92-53.34). It is observed that the median OS for the population already diagnosed with metastatic disease (stage IV) was significantly lower than for patients diagnosed in stages I-III (37.43 months vs. 48.6 months, p<0, 01). Women without previous use of trastuzumab had a higher median OS than patients pretreated with trastuzumab (45.16 months vs. 40.73 months, p<0.01). Conclusion: Trastuzumab improves survival in HER-2 positive metastatic breast cancer. Brain and multiple metastases are associated with a worse prognosis. It is essential to avoid advanced staging and perform surgical treatment, with emphasis on radical mastectomy. The SUS must adopt policies and strategies for early diagnosis and guarantee access to trastuzumab, considering its high cost.

RESUMO Objetivo: Caracterizar fatores associados e sobrevida global de mulheres com câncer de mama metastático tratadas com trastuzumabe, após sua incorporação ao Sistema Único de Saúde, e apresentar os custos diretos dessa tecnologia. Métodos: Trata-se de uma coorte retrospectiva, baseada em dados de prontuários do Instituto Nacional do Câncer, no Rio de Janeiro (RJ). Foram incluídas mulheres com câncer de mama metastático HER-2 positivo em tratamento com trastuzumabe no período de setembro de 2017 a agosto de 2018. A sobrevida global foi estimada pelo método Kaplan-Meier e comparada entre grupos pelo teste de log-rank. Resultados: Foram selecionadas 136 mulheres, cuja mediana da idade do diagnóstico foi de 51 anos (amplitude: 21-81 anos). A mediana da sobrevida global foi de 43,63 meses (IC95% 33,92-53,34). Observa-se que a mediana da sobrevida global para a população já diagnosticada com doença metastática (estádio IV) foi significativamente menor do que para as pacientes diagnosticadas nos estádios I-III (37,43 meses vs. 48,6 meses, p<0,01). Já mulheres sem uso prévio de trastuzumabe apresentaram uma mediana de sobrevida global maior do que as pacientes pré-tratadas com trastuzumabe (45,16 meses vs. 40,73 meses, p<0,01). Conclusão: O trastuzumabe aumentou a sobrevida no câncer de mama metastático HER-2 positivo. Metástases cerebrais e múltiplas mostraram-se associadas a um pior prognóstico. É fundamental evitar o estadiamento avançado e realizar tratamento cirúrgico, destacando-se a mastectomia radical. O Sistema Único de Saúde deve adotar políticas e estratégias para o diagnóstico precoce e garantir acesso ao trastuzumabe, considerando seu alto custo.

Colorimetric Detection of SARS-CoV-2 Using Plasmonic Biosensors and Smartphones.

Low-cost, instrument-free colorimetric tests were developed to detect SARS-CoV-2 using plasmonic biosensors with Au nanoparticles functionalized with polyclonal antibodies (f-AuNPs). Intense color changes were noted with the naked eye owing to plasmon coupling when f-AuNPs form clusters on the virus, with high sensitivity and a detection limit of 0.28 PFU mL-1 (PFU stands for plaque-forming units) in human saliva. Plasmon coupling was corroborated with computer simulations using the finite-difference time-domain (FDTD) method. The strategies based on preparing plasmonic biosensors with f-AuNPs are robust to permit SARS-CoV-2 detection via dynamic light scattering and UV-vis spectroscopy without interference from other viruses, such as influenza and dengue viruses. The diagnosis was made with a smartphone app after processing the images collected from the smartphone camera, measuring the concentration of SARS-CoV-2. Both image processing and machine learning algorithms were found to provide COVID-19 diagnosis with 100% accuracy for saliva samples. In subsidiary experiments, we observed that the biosensor could be used to detect the virus in river waters without pretreatment. With fast responses and requiring small sample amounts (only 20 µL), these colorimetric tests can be deployed in any location within the point-of-care diagnosis paradigm for epidemiological control.

Mitochondrial function and cellular energy maintenance during aging in a Drosophila melanogaster model of Parkinson disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by movement disorders as well as loss of dopaminergic neurons. Moreover, genes affecting mitochondrial function, such as SNCA, Parkin, PINK1, DJ-1 and LRRK2, were demonstrated to be associated with PD and other neurodegenerative disease. Additionally, mitochondrial dysfunction and cellular energy imbalance are common markers found in PD. In this study, we used the pink1 null mutants of Drosophila melanogaster as a Parkinson's disease model to investigate how the energetic pathways and mitochondrial functions change during aging in a PD model. In our study, the loss of the pink1 gene decreased the survival percent and the decreased climbing index during aging in pink1-/- flies. Furthermore, there was an impairment in mitochondrial function demonstrated by a decrease in OXPHOS CI&CII-Linked and ETS CI&CII-Linked in pink1-/- flies at 3, 15 and 30 days of life. Interestingly, OXPHOS CII-Linked and ETS CII-Linked presented decreases only at 15 days of life in pink1-/- flies. Moreover, there was an increase in peroxide (H2O2) levels in pink1-/- flies at 15 and 30 days of life. Loss of the pink1 gene also decreased the activity of citrate synthase (CS) and increased the activity of lactate dehydrogenase (LDH) in pink1-/- flies head. Our results demonstrate a metabolic shift in ATP production in pink1-/- flies, which changed from oxidative to glycolytic pathways from 15 days of age, and is apparently more pronounced in the central nervous system.

Detection of SARS-CoV-2 virus via dynamic light scattering using antibody-gold nanoparticle bioconjugates against viral spike protein.

Mass testing for the diagnosis of COVID-19 has been hampered in many countries owing to the high cost of genetic material detection. This study reports on a low-cost immunoassay for detecting SARS-CoV-2 within 30 min using dynamic light scattering (DLS). The immunosensor comprises 50-nm gold nanoparticles (AuNPs) functionalized with antibodies against SARS-CoV-2 spike glycoprotein, whose bioconjugation was confirmed using transmission electron microscopy (TEM), UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and surface-enhanced Raman scattering spectroscopy (SERS). The specific binding of the bioconjugates to the spike protein led to an increase in bioconjugate size, with a limit of detection (LOD) 5.29 × 103 TCID50/mL (Tissue Culture Infectious Dose). The immunosensor was also proven to be selective upon interaction with influenza viruses once no increase in size was observed after DLS measurement. The strategy proposed here aimed to use antibodies conjugated to AuNPs as a generic platform that can be extended to other detection principles, enabling technologies for low-cost mass testing for COVID-19.

Neurotoxicity induced by toluene: In silico and in vivo evidences of mitochondrial dysfunction and dopaminergic neurodegeneration.

Toluene is an air pollutant widely used as an organic solvent in industrial production and emitted by fossil fuel combustion, in addition to being used as a drug of abuse. Its toxic effects in the central nervous system have not been well established, and how and which neurons are affected remains unknown. Hence, this study aimed to fill this gap by investigating three central questions: 1) How does toluene induce neurotoxicity? 2) Which neurons are affected? And 3) What are the long-term effects induced by airborne exposure to toluene? To this end, a Caenorhabditis elegans model was employed, in which worms at the fourth larval stage were exposed to toluene in the air for 24 h in a vapor chamber to simulate four exposure scenarios. After the concentration-response curve analysis, we chose scenarios 3 (E3: 792 ppm) and 4 (E4: 1094 ppm) for the following experiments. The assays were performed 1, 48, or 96 h after removal from the exposure environments, and an irreversible reduction in neuron fluorescence and morphologic alterations were observed in different neurons of exposed worms, particularly in the dopaminergic neurons. Moreover, a significant impairment in a dopaminergic-dependent behavior was also associated with negative effects in healthspan endpoints, and we also noted that mitochondria may be involved in toluene-induced neurotoxicity since lower adenosine 5'-triphosphate (ATP) levels and mitochondrial viability were observed. In addition, a reduction of electron transport chain activity was evidenced using ex vivo protocols, which were reinforced by in silico and in vitro analysis, demonstrating toluene action in the mitochondrial complexes. Based on these findings model, it is plausible that toluene neurotoxicity can be initiated by complex I inhibition, triggering a mitochondrial dysfunction that may lead to irreversible dopaminergic neuronal death, thus impairing neurobehavioral signaling.

Frontal Sinus Cholesteatoma Presenting with Intracranial and Orbital Complications: Diagnosis and Treatment.

Frontal sinus keratoma or cholesteatoma is a rare disease of paranasal sinuses and presents as a slow-growing mass that becomes symptomatic as it grows to the surrounding structures. Intracranial complications are not a common presentation and are potentially life-threatening. Frequently the final diagnosis is only made intraoperatively because several other frontal sinus tumors behave likewise. Definitive treatment requires complete removal of the keratoma, and a combined endoscopic and external frontal sinus approach is a good treatment option. In this report, we presented a 68-year-old female with frontal sinus cholesteatoma with diagnostic and therapeutic features of this pathology with the review of the literature.

Recent advances and future perspective of essential oils in control Colletotrichum spp.: A sustainable alternative in postharvest treatment of fruits.

The world population growth has raised concerns about food security. Agricultural systems are asked to satisfy a growing demand for food with increasingly limited resources, and simultaneously still must reduce the impacts on the environment. This scenario encourages the search for safe and sustainable production strategies. Reducing losses in the production process can be one of the main ways to guarantee food safety. In fruticulture, it is estimated that more than 50% of the production can be lost between harvest and the final consumer due to postharvest diseases caused by phytopathogenic fungi. The fungi of the genus Colletotrichum are opportunistic and are associated with several diseases, being the anthracnose the most relevant in terms of the quality and yield losses in fruit species around worldwide. To control these diseases, the use of synthetic fungicides has been the main instrument utilized, however, because of their phytotoxicity to human health, the environment, and strong selection pressure imposed by continuous applications, the fungicides have caused resistance in the pathogen populations. So reducing the excessive application of these products is indispensable for human health and for sustainable Agriculture. Towards this purpose, research has been carried out to identify the phytopathological potentiality of essential oils (EOs) extracted from plants. Therefore, this review aims to contribute to the formation of knowledge bases, about the discoveries, recent advances, and the use of EOs as a strategy to alternatively control fungal disease caused by Colletotrichum spp. in postharvest fruits. Here, we provide valuable information exploring the application potential of essential oils as commercially useful biorational pesticides for food preservation, contributing to sustainable production and global food security.

Caenorhabditis elegans as a model for studies on quinolinic acid-induced NMDAR-dependent glutamatergic disorders.

Quinolinic acid (QUIN) is an agonist of the neurotransmitter glutamate (Glu) capable of binding to N-methyl-D-aspartate receptors (NMDAR) increasing glutamatergic signaling. QUIN is known for being an endogenous neurotoxin, able to induce neurodegeneration. In Caenorhabditis elegans, the mechanism by which QUIN induces behavioral and metabolic toxicity has not been fully elucidated. The effects of QUIN on behavioral and metabolic parameters in nmr-1 and nmr-2 NMDA receptors in transgenic and wild-type (WT) worms were performed to decipher the pathway by which QUIN exerts its toxicity. QUIN increased locomotion parameters such as wavelength and movement amplitude medium, as well as speed and displacement, without modifying the number of body bends in an NMDAR-dependent-manner. QUIN increased the response time to the chemical stimulant 1-octanol, which is modulated by glutamatergic neurotransmission in the ASH neuron. Brood size increased after exposure to QUIN, dependent upon nmr-2/NMDA-receptor, with no change in lifespan. Oxygen consumption, mitochondrial membrane potential, and the flow of coupled and unbound electrons to ATP production were reduced by QUIN in wild-type animals, but did not alter citrate synthase activity, altering the functionality but the mitochondrial viability. Notably, QUIN modified fine locomotor and chemosensory behavioral parameters, as well as metabolic parameters, analogous to previously reported effects in mammals. Our results indicate that QUIN can be used as a neurotoxin to elicit glutamatergic dysfunction in C. elegans in a way analogous to other animal models.

JM-20 Treatment After Mild Traumatic Brain Injury Reduces Glial Cell Pro-inflammatory Signaling and Behavioral and Cognitive Deficits by Increasing Neurotrophin Expression.

Traumatic brain injury (TBI) is considered a public health problem and is often related to motor and cognitive disabilities, besides behavioral and emotional changes that may remain for the rest of the subject's life. Resident astrocytes and microglia are the first cell types to start the inflammatory cascades following TBI. It is widely known that continuous or excessive neuroinflammation may trigger many neuropathologies. Despite the large numbers of TBI cases, there is no effective pharmacological treatment available. This study aimed to investigate the effects of the new hybrid molecule 3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro1H-pyrido[2,3-b][1,5]benzodiazepine (JM-20) on TBI outcomes. Male Wistar rats were submitted to a weight drop model of mild TBI and treated with a single dose of JM-20 (8 mg/kg). Twenty-four hours after TBI, JM-20-treated animals showed improvements on locomotor and exploratory activities, and short-term memory deficits induced by TBI improved as well. Brain edema was present in TBI animals and the JM-20 treatment was able to prevent this change. JM-20 was also able to attenuate neuroinflammation cascades by preventing glial cells-microglia and astrocytes-from exacerbated activation, consequently reducing pro-inflammatory cytokine levels (TNF-α and IL-1ß). BDNF mRNA level was decreased 24 h after TBI because of neuroinflammation cascades; however, JM-20 restored the levels. JM-20 also increased GDNF and NGF levels. These results support the JM-20 neuroprotective role to treat mild TBI by reducing the initial damage and limiting long-term secondary degeneration after TBI.

Is lentulospiral the best option for root canal filling of endodontically treated primary teeth? A systematic review and meta-analysis.

PURPOSE: To evaluate the quality of root canal filling of primary teeth using lentulospiral in comparison with other instruments. METHODS: Electronic databases (PubMed/MEDLINE, Scopus, TRIP, LILACS, and CENTRAL Cochrane) were searched up to Jan 2021. Clinical trials that compared the quality of root canal filling of endodontically treated primary teeth using lentulospiral with other instruments were included. Two reviewers independently selected the studies, extracted data, and assessed the risk of bias. Two outcomes were considered: inadequate root canal filling (under or overfilling) and presence of voids. Conventional meta-analyses were performed using a fixed-effects model. Statistical analyses were performed using RevMan5.3 at a significance level of 5%. RESULTS: Of the 68 potentially relevant studies, eight were selected for full-text analysis, and three were included in the systematic review. The use of syringes resulted in a lower risk of presence of voids in the root canal filling compared to the use of lentulospiral (RR: 0.62 95% CI 0.45; 0.85). However, there was no difference between lentulospiral and bi-directional spiral (RR:1.17 95% CI: 0.90; 1.51). There was no significant difference between lentulospiral and syringes (RR: 1.37 95% CI 1.00; 1.87) considering the length of the root canal filling. The use of bi-directional spiral had a higher risk of inadequate root canal filling compared to the use of lentulospiral (RR: 1.75 95% CI: 1.12; 2.74). Two studies were at "high", and one study at "unclear" risk of bias in the key domains. CONCLUSIONS: There is insufficient scientific evidence showing the superiority of using lentulospiral for the root canal filling in endodontically treated primary teeth. Due to the limited level of evidence, professionals may opt to choose the instrument based on their preferences.

Cellular uptake of polymeric nanoparticles by bovine cumulus-oocyte complexes and their effect on in vitro developmental competence.

Polymeric nanoparticles (NPs) are produced using bio-compatible and bio-degradable materials such as PLGA (Poly(lactic-co-glycolic acid)). This technology provides a valuable tool to deliver molecules to the subcellular level with a relatively low risk of cytotoxicity. However their use in the field of reproductive biotechnology is not yet scientifically substantiated. The aim of the present study was to test if PLGA NPs can be taken-up by cumulus-enclosed oocytes as a first step towards potential oocyte-targeted applications to enhance oocyte quality and fertility. We conducted a series of experiments using bovine in vitro oocyte maturation as a model to study FITC-conjugated PLGA internalization (using laser-scanning confocal microscopy) and the effect of some important physical (particle size) and chemical (conjugation with PEG) modifications. We show evidence that PLGA NPs can be taken-up by cumulus cells and to a less extent by the enclosed oocytes regardless of the NP size. The NP transfer to the oocyte appear to be transcellular (via cumulus cells and transzonal projections) and paracellular (via zona pellucida). The PLGA NPs were detected in the vicinity of the oocyte as quick as 2 h post-exposure in a protein-free medium and did not compromise cumulus cell viability nor subsequent early embryo development or embryo quality. These results suggest that PLGA NPs may have promising applications as carriers for drug or molecule delivery targeting cumulus cells and oocytes.