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1.
Forensic Sci Res ; 9(2): owad046, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38903907

ABSTRACT

Several studies have evaluated the parameters of normality of the sella turcica (ST), which is important to face different craniofacial syndromes that may affect this structure. Therefore, this research summarized the scientific evidence on the role of ST in the sex estimation of non-syndromic individuals. The research protocol was registered (Prospective International Registry of Systematic Reviews # CRD42021256469), followed by an electronic search in six databases (PubMed, LILACS, Web of Science, Scopus, EMBASE, and LIVIVO) and gray literature (Google Scholar and OpenGrey). Meta-analysis of linear (width, length, height, and diameter) and volumetric measurements, in addition to an assessment of risk of bias (RoB) and certainty of evidence, were performed. After the screening of 986 articles, 13 were evaluated by meta-analysis (1 307 males and 1 231 females). In subgroup analysis, females had lower values for width (lateral radiograph; -0.67 mm; P = 0.040), length (computed tomography; -0.23 mm; P = 0.020), and diameter (computed tomography; -0.27 mm; P < 0.001) compared to males. There was no statistically significant difference regarding height (P = 0.95), area (P = 0.72), and volume (P = 0.21). Most studies exhibited moderate RoB, and the certainty of evidence of the outcomes was very low. In this review, significant differences were observed between the sexes for the length and diameter of the ST; however, the heterogeneity of the studies must be considered. Key points: Studies from different geographic regions evaluated the morphology of ST according to sex and showed this anatomical structure as an important indicator of dimorphism.Meta-analysis showed shorter ST length and diameter in women.Subgroup analysis found lower ST width in women based on lateral skull radiographs.Subgroup analysis found smaller lengths and diameters in women based on CT scans.

2.
iScience ; 27(5): 109782, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38711449

ABSTRACT

Ten-eleven translocation (TET) proteins are DNA dioxygenases that mediate active DNA demethylation. TET3 is the most highly expressed TET protein in thymic developing T cells. TET3, either independently or in cooperation with TET1 or TET2, has been implicated in T cell lineage specification by regulating DNA demethylation. However, TET-deficient mice exhibit complex phenotypes, suggesting that TET3 exerts multifaceted roles, potentially by interacting with other proteins. We performed liquid chromatography with tandem mass spectrometry in primary developing T cells to identify TET3 interacting partners in endogenous, in vivo conditions. We discover TET3 interacting partners. Our data establish that TET3 participates in a plethora of fundamental biological processes, such as transcriptional regulation, RNA polymerase elongation, splicing, DNA repair, and DNA replication. This resource brings in the spotlight emerging functions of TET3 and sets the stage for systematic studies to dissect the precise mechanistic contributions of TET3 in shaping T cell biology.

3.
Article in English | MEDLINE | ID: mdl-38771167

ABSTRACT

BACKGROUND: The aim of this paper was to evaluate the predictive role of the uterocervical angle (UCA) in spontaneous preterm birth (sPTB). METHODS: A systematic review of the literature was performed including all studies reporting the association between UCA and sPTB. Searches were performed with the use of a combination of keywords: "cervical length," "uterocervical angle," and "preterm birth" from inception of each database to March 2022. The statistical evaluations were carried out using the Comprehensive Meta-Analysis version 3 (Biostat Inc. USA). RESULTS: Sixteen studies all conducted on the second trimester UCA as well as its association with sPTB were included in this study. In all studies the measurements of cervical length (CL) and UCA were performer in the second trimester, except in one that in the third trimester. In most studies the CL is greater than 30 mm and the UCA is greater than 110 °. In seven studies women with symptoms were considered while in 8 studies the women were asymptomatic. CONCLUSIONS: It is too early for it to reach a firm conclusion on UCA utilization in clinical settings. A higher UCA measurement (greater than 150°) is an important risk factor for deliveries before 37 weeks' gestation. It provides a higher diagnostic performance in high risk patients than the CL measurement. However, the most relevant ultrasound parameter for the prediction of delivery within the next few data in women with preterm delivery remains the cervical length. There is a need to consider both markers and create protocols so that the values obtained with UCA and those with CL can make a real contribution to decisions to be made rather than using only CL.

4.
Rev Sci Instrum ; 94(4)2023 Apr 01.
Article in English | MEDLINE | ID: mdl-38081256

ABSTRACT

The characterization of the mechanical behavior of shape memory thin film alloys is essential for their application as microactuators. Depending on the particular application, different elements have been considered for the fabrication of ternary NiTi-based alloys in order to shift the martensitic transformation toward a lower or a higher temperature range. This work presents the design and implementation of a specific device to perform thermal cycles at constant stress on film-like samples over a wide temperature range, between -130 and 300 °C. The uniaxial stress application, the elongations and contractions measurements associated with the martensitic transformations, and the cooling and heating methods are detailed in the present work. The fabrication and operation features of this relatively low cost device facilitate and promote the study of shape memory thin films.

5.
Sci Total Environ ; 904: 167320, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37748613

ABSTRACT

The increased use of agrochemicals raises concerns about environmental, animal, and mainly human toxicology. The development of New Approach Methodologies (NAMs) for toxicological risk assessment including new in vitro tests and in silico protocols is encouraged. Although agrochemical mutagenicity testing is well established, a complementary alternative approach may contribute to increasing reliability, with the consequent reduction of false-positive results that lead to unnecessary use of animals in follow-up in vivo testing. Additionally, it is unreasonable to underestimate the phototoxic effects of an accidental dermal exposure to agrochemicals during agricultural work or domestic application in the absence of adequate personal protection equipment, especially in terms of photomutagenicity. In this scenario, we addressed the integration of in vitro and in silico techniques as NAMs to assess the mutagenic and phototoxic potential of agrochemicals. In the present study we used the yno1 S. cerevisiae strain as a biomodel for in vitro assessment of agrochemical mutagenicity, both in the absence and in the presence of simulated sunlight. In parallel, in silico predictions were performed using a combination of expert rule-based and statistical-based models to assess gene mutations and phototoxicity. None of the tested agrochemicals showed mutagenic potential in the two proposed approaches. The Gly and 2,4D herbicides were photomutagenic in the in vitro yeast test despite the negative in silico prediction of phototoxicity. Herein, we demonstrated a novel experimental approach combining both in silico and in vitro experiments to address the complementary investigation of the phototoxicity and (photo)mutagenicity of agrochemicals. These findings shed light on the importance of investigating and reconsidering the photosafety assessment of these products, using not only photocytotoxicity assays but also photomutagenicity assays, which should be encouraged.


Subject(s)
Mutagens , Saccharomyces cerevisiae , Humans , Animals , Agrochemicals/toxicity , Reproducibility of Results , Risk Assessment , In Vitro Techniques
6.
Rev. enferm. neurol ; 22(1): 31-46, 04-09-2023. tab
Article in Spanish | LILACS, BDENF - Nursing | ID: biblio-1509757

ABSTRACT

Introducción: El cuidado a pacientes oncológicos consiste, más allá de satisfacer necesidades físicas, en una atención holística, pues el cuidado humanizado favorece una interrelación esencial entre ciencia y valores para establecer una asistencia de calidad, que dé solución a las demandas humanas del usuario. Objetivo: Identificar el nivel de cuidado humanizado que proporciona el profesional enfermero a pacientes hospitalizados en un centro de oncología. Material y métodos: Estudio descriptivo, observacional-transversal. Muestreo no probabilístico de oportunidad y secuencial con cuota de 35 pacientes. Medición realizada con el instrumento "Percepción del cuidado humanizado en pacientes hospitalizados". Análisis de resultados mediante estadística descriptiva. Resultados: El cuidado proporcionado a pacientes oncológicos hospitalizados es humanizado, pues afirman recibir trato amable con efecto positivo en ellos derivado de la actitud de la enfermera en su labor, en la que impera el conocimiento y la experiencia para proveer cuidados individualizados y empáticos a partir de comunicación, expresión de sentimientos y escucha, atendiendo no sólo necesidades físicas, sino también sociales, culturales y espirituales. Discusión: Los pacientes oncológicos mencionan que el profesional de enfermería actúa comprendiendo al usuario integralmente, lo que les permite enfrentar positivamente su proceso de enfermedad. Conclusiones: El cuidado humanizado de calidad es una relación entre el profesional de enfermería y el paciente a cuidar, en la que impera la comunicación, el debido uso de la palabra y la escucha para generar confianza, lo cual se suma a la base científica y las habilidades técnicas, a fin de intervenir de forma humana, eficiente y segura.


Introduction: Caring for cancer patients is an interaction that goes beyond satisfying physical needs, it is caring for the person in a holistic way, where the humanization of care favors the essential link of the profession, it is an interaction between science and values to establish quality care. quality, giving solution to the human responses of the patient. Objective: To identify the level of humanized care provided by the nursing professional to patients hospitalized in an oncology center. Material and methods: Descriptive, observational cross-sectional study. Non-probabilistic opportunity and sequential sampling with a quota of 35 patients. Measurement carried out with the: "Instrument Perception of Humanized Care in Hospitalized Patients". Analysis of results through descriptive statistics. Results: The level of care provided to hospitalized cancer patients is very humanized, patients report receiving friendly treatment with a positive effect on them, derived from the attitude of the nurse in her being and doing care, they perceive a relationship of trust where knowledge and Experience in favor of your health since the nursing professional provides individualized and empathetic care, favoring communication, expression of feelings and emotions; listening to them beyond their illness satisfying their physical, social, cultural and spiritual needs. Discussion: People with oncological disease perceive receiving humanized care when mentioning that the nursing professional acts understanding the patient from knowing, knowing how to do and knowing how to be, which allows them to positively face their disease process. Conclusions: The level of quality humanized care is a relationship that occurs between the nursing professional and the person they care for, in this human quality of care, communication prevails, the power that the word and hearing have in the field of attention, transcendental to generate confidence; coupled with the scientific foundation, empathetic attitude, technical and professional skills given by experience, allowing intervention in a humane, effective, efficient and safe way.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Patient Care , Humanism , Nursing Care , Patients , Medical Oncology
7.
An Acad Bras Cienc ; 94(suppl 3): e20211321, 2022.
Article in English | MEDLINE | ID: mdl-36417607

ABSTRACT

The concern about the risks of viral infections transmission through blood transfusion has led into a search for improvements on screening tests used for the selection of blood donors. Molecular biology techniques applied in researches of viral genomes, known as Nucleic Acid-amplification-Test (NAT), represent a technology capable of increasing transfusion safety by shortening the diagnostic window period. In Brazil, the implementation of this technology for the detection of HIV, HCV and HBV occurred due to the implantation of the NAT Kit - produced by Immunobiological Technology Institute (Biomanguinhos-FIOCRUZ), in the Brazilian blood centers. The National Health Surveillance Agency attaches great importance to validation, since it standardizes, disciplines and regulates criteria for the registration of health products. This work aims to establish a protocol of performance validation by real-time PCR method, taking as the object of study the Bio-Manguinhos NAT Kit, in order to update the product registration or to meet any future needs to ensure all regulatory requirements for the performance validation of the real-time PCR diagnostic kit. The protocol developed followed the ICH recommendations. The results revealed that the adopted methodology contemplates the necessary requirements for compliance with the Brazilian legislation, as well as the established validation parameters.


Subject(s)
HIV Infections , Hepatitis C , Nucleic Acids , Humans , Hepacivirus/genetics , Hepatitis B virus/genetics , Hepatitis C/diagnosis , Hepatitis C/epidemiology , HIV Infections/diagnosis , HIV
8.
Front Immunol ; 13: 1011772, 2022.
Article in English | MEDLINE | ID: mdl-36426368

ABSTRACT

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.


Subject(s)
Cyclooxygenase 2 , Interleukin-1alpha , Monocytes , Oropharyngeal Neoplasms , Humans , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Monocytes/enzymology , Oropharyngeal Neoplasms/metabolism , Prostaglandins E , Tumor Microenvironment , Interleukin-1alpha/metabolism
9.
J Neurosci ; 42(42): 7900-7920, 2022 10 19.
Article in English | MEDLINE | ID: mdl-36261270

ABSTRACT

Neuronal activity initiates signaling cascades that culminate in diverse outcomes including structural and functional neuronal plasticity, and metabolic changes. While studies have revealed activity-dependent neuronal cell type-specific transcriptional changes, unbiased quantitative analysis of cell-specific activity-induced dynamics in newly synthesized proteins (NSPs) synthesis in vivo has been complicated by cellular heterogeneity and a relatively low abundance of NSPs within the proteome in the brain. Here we combined targeted expression of mutant MetRS (methionine tRNA synthetase) in genetically defined cortical glutamatergic neurons with tight temporal control of treatment with the noncanonical amino acid, azidonorleucine, to biotinylate NSPs within a short period after pharmacologically induced seizure in male and female mice. By purifying peptides tagged with heavy or light biotin-alkynes and using direct tandem mass spectrometry detection of biotinylated peptides, we quantified activity-induced changes in cortical glutamatergic neuron NSPs. Seizure triggered significant changes in ∼300 NSPs, 33% of which were decreased by seizure. Proteins mediating excitatory and inhibitory synaptic plasticity, including SynGAP1, Pak3, GEPH1, Copine-6, and collybistin, and DNA and chromatin remodeling proteins, including Rad21, Smarca2, and Ddb1, are differentially synthesized in response to activity. Proteins likely to play homeostatic roles in response to activity, such as regulators of proteastasis, intracellular ion control, and cytoskeleton remodeling proteins, are activity induced. Conversely, seizure decreased newly synthetized NCAM, among others, suggesting that seizure induced degradation. Overall, we identified quantitative changes in the activity-induced nascent proteome from genetically defined cortical glutamatergic neurons as a strategy to discover downstream mediators of neuronal plasticity and generate hypotheses regarding their function.SIGNIFICANCE STATEMENT Activity-induced neuronal and synaptic plasticity are mediated by changes in the protein landscape, including changes in the activity-induced newly synthesized proteins; however, identifying neuronal cell type-specific nascent proteome dynamics in the intact brain has been technically challenging. We conducted an unbiased proteomic screen from which we identified significant activity-induced changes in ∼300 newly synthesized proteins in genetically defined cortical glutamatergic neurons within 20 h after pharmacologically induced seizure. Bioinformatic analysis of the dynamic nascent proteome indicates that the newly synthesized proteins play diverse roles in excitatory and inhibitory synaptic plasticity, chromatin remodeling, homeostatic mechanisms, and proteasomal and metabolic functions, extending our understanding of the diversity of plasticity mechanisms.


Subject(s)
Amino Acyl-tRNA Synthetases , Proteome , Male , Female , Mice , Animals , Proteome/metabolism , Proteomics/methods , Biotin/metabolism , Neurons/metabolism , Neuronal Plasticity/physiology , Amino Acids/metabolism , Methionine/metabolism , Alkynes/metabolism , Seizures/metabolism , Amino Acyl-tRNA Synthetases/genetics , Amino Acyl-tRNA Synthetases/metabolism , Neural Cell Adhesion Molecules/metabolism , ras GTPase-Activating Proteins/metabolism
10.
An Acad Bras Cienc ; 94(suppl 3): e20211287, 2022.
Article in English | MEDLINE | ID: mdl-36197362

ABSTRACT

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the latest class of drugs approved to treat type 2 DM (T2DM). Although adverse effects are often caused by a metabolite rather than the drug itself, only the safety assessment of disproportionate drug metabolites is usually performed, which is of particular concern for drugs of chronic use, such as SGLT2i. Bearing this in mind, in silico tools are efficient strategies to reveal the risk assessment of metabolites, being endorsed by many regulatory agencies. Thereby, the goal of this study was to apply in silico methods to provide the metabolites toxicity assessment of the SGLT2i. Toxicological assessment from SGLT2i metabolites retrieved from the literature was estimated using the structure and/or statistical-based alert implemented in DataWarrior and ADMET predictorTM softwares. The drugs and their metabolites displayed no mutagenic, tumorigenic or cardiotoxic risks. Still, M1-2 and M3-1 were recognized as potential hepatotoxic compounds and M1-2, M1-3, M3-1, M3-2, M3-3 and M4-3, were estimated to have very toxic LD50 values in rats. All SGLT2i and the metabolites M3-4, M4-1 and M4-2, were predicted to have reproductive toxicity. These results support the awareness that metabolites may be potential mediators of drug-induced toxicities of the therapeutic agents.


Subject(s)
Sodium-Glucose Transporter 2 Inhibitors , Animals , Rats , Risk Assessment , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/toxicity
11.
Transbound Emerg Dis ; 69(6): 3153-3159, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36057790

ABSTRACT

Schistosomiasis is a tropical neglected disease commonly associated with rural areas; however, urban schistosomiasis has been reported worldwide, and increasing urbanization is one of the most important demographic shifts of the 20th and now 21st centuries. The pattern of urbanization is not uniform so that within the same city the rates and sources of population increase vary. Here, we report on the parasite composition in one neighbourhood in the metropolitan area of Salvador, Bahia, Brazil. Using epidemiological data and population genetics, we find evidence for local transmission and maintenance of Schistosoma mansoni infection within an urban population and little contribution from rural-urban migration. Our findings provide direction for local mitigation strategies and to assist the public living in this neighbourhood to interrupt the local transmission cycle.


Subject(s)
Schistosomiasis mansoni , Schistosomiasis , Animals , Schistosoma mansoni/genetics , Brazil/epidemiology , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Schistosomiasis/veterinary , Schistosomiasis mansoni/epidemiology , Schistosomiasis mansoni/prevention & control , Schistosomiasis mansoni/veterinary , Urban Population
12.
Pharmaceuticals (Basel) ; 15(9)2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36145320

ABSTRACT

In this study, we report the synthesis of twenty new acridine-thiosemicarbazone derivatives and their antiproliferative activities. Mechanisms of action such as the inhibition of topoisomerase IIα and the interaction with DNA have been studied for some of the most active derivatives by means of both in silico and in vitro methods, and evaluations of the non-clinical toxicities (in vivo) in mice. In general, the compounds showed greater cytotoxicity against B16-F10 cells, with the highest potency for DL-08 (IC50 = 14.79 µM). Derivatives DL-01 (77%), DL-07 (74%) and DL-08 (79%) showed interesting inhibition of topoisomerase IIα when compared to amsacrine, at 100 µM. In silico studies proposed the way of bonding of these compounds and a possible stereoelectronic reason for the absence of enzymatic activity for CL-07 and DL-06. Interactions with DNA presented different spectroscopic effects and indicate that the compound CL-07 has higher affinity for DNA (Kb = 4.75 × 104 M-1; Ksv = 2.6 × 103 M-1). In addition, compounds selected for non-clinical toxicity testing did not show serious signs of toxicity at the dose of 2000 mg/kg in mice; cytotoxic tests performed on leukemic cells (K-562) and its resistant form (K-562 Lucena 1) identified moderate potency for DL-01 and DL-08, with IC50 between 11.45 and 17.32 µM.

13.
J Forensic Sci ; 67(6): 2151-2164, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35906754

ABSTRACT

This systematic review aimed to answer the question, "Are paranasal measurements obtained with multislice computed tomography able to accurately estimate sex?" This PROSPERO-registered systematic review included six databases and gray literature. Meta-analysis of linear and volumetric data was performed using a random-effects model, mean differences (MDs), and inverse variance. The QUADAS-2 tool-related risk of bias (RoB) and certainty evidence (GRADE approach) were assessed. A total of 1651 articles were initially selected from the main electronic databases for title and abstract screening. After removing duplicates and studies that did not meet the inclusion criteria, 18 studies were eligible for the meta-analysis. The screened studies included 2507 computed tomography of non-pathologic paranasal sinuses of adults aged between 18 and 40 years. Frontal sinus (FS) width (-4.89 mm; p < 0.00001) and maxillary sinus (MS) height (-3.73 mm; p < 0.00001) showed the greatest MD between females and males. Regarding volume, the MD was significant (p < 0.00001) in both paranasal sinuses (-3.01 and -1.04 cm3 , respectively). The best sensitivity (ability to identify males) and specificity (ability to identify females) were found for the anteroposterior (72.3%) and intermaxillary (69%) MS distances, respectively. In general, all studies exhibited low RoB and applicability concerns. The certainty of the evidence was categorized as very low to moderate. Both paranasal sinuses were shown to be dimorphic structures, which could be valuable tools for forensic identification using the FS width and MS anteroposterior distance measurements. However, heterogeneity among studies must be considered.


Subject(s)
Frontal Sinus , Multidetector Computed Tomography , Adult , Male , Female , Humans , Adolescent , Young Adult , Maxillary Sinus/diagnostic imaging , Forensic Medicine , Databases, Factual
14.
Eur J Pharm Sci ; 175: 106222, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35649471

ABSTRACT

The drug delivery systems are an important strategy of pharmaceutical technology to modulate undesirable properties, increasing efficacy, and reducing the side effects of active pharmaceutical ingredients (API). The sustained release is a type of controlled-release system that provides a suitable drug level in the blood through a slow release rate. An interesting alternative to achieve a controlled release is the application of carrier materials such as polymers, cyclodextrins, and clays. Sodium montmorillonite (Na-MMT) is a biocompatible natural clay that allows the insertion of organic compounds in interlamellar space, owing to its high cation exchange capacity and large internal surface area. Bromopride (BPD) is an aminated compound with antiemetic properties classified as class II (low solubility, high permeability) of the Biopharmaceutical Classification System (BCS). Herein, the aim of the study was the development and investigation of a drug delivery system formed by intercalation of BPD with Na-MMT. The results indicate the successful intercalation of this API with the lamellar silicate, meanwhile, there was no evidence of BPD intercalation in organic montmorillonite. The Na-MMT/BPD molecular complex exhibits a sustained release in performed assays. Molecular dynamics simulations suggested that BPD molecules interact with the montmorillonite layer through ion-dipole interactions and also between BPD molecules, forming hydrogen bonds web into montmorillonite interlayer space. The new drug delivery system showed an alternative to achieve the BPD sustained release, which may improve its pharmacological performance in therapeutic applications.


Subject(s)
Bentonite , Metoclopramide , Bentonite/chemistry , Clay , Delayed-Action Preparations , Metoclopramide/analogs & derivatives
15.
J Neurosci ; 42(19): 4042-4052, 2022 05 11.
Article in English | MEDLINE | ID: mdl-35396330

ABSTRACT

Retinal ganglion cells (RGCs) die after optic nerve trauma or in degenerative disease. However, acute changes in protein expression that may regulate RGC response to injury are not fully understood, and detailed methods to quantify new protein synthesis have not been tested. Here, we develop and apply a new in vivo quantitative measure of newly synthesized proteins to examine changes occurring in the retina after optic nerve injury. Azidohomoalanine, a noncanonical amino acid, was injected intravitreally into the eyes of rodents of either sex with or without optic nerve injury. Isotope variants of biotin-alkyne were used for quantitative BONCAT (QBONCAT) mass spectrometry, allowing identification of protein synthesis and transport rate changes in more than 1000 proteins at 1 or 5 d after optic nerve injury. In vitro screening showed several newly synthesized proteins regulate axon outgrowth in primary neurons in vitro This novel approach to targeted quantification of newly synthesized proteins after injury uncovers a dynamic translational response within broader proteostasis regulation and enhances our understanding of the cellular response to injury.SIGNIFICANCE STATEMENT Optic nerve injury results in death and degeneration of retinal ganglion cells and their axons. The specific cellular response to injury, including changes in new protein synthesis, is obscured by existing proteins and protein degradation. In this study, we introduce QBONCAT to isolate and quantify acute protein synthesis and subsequent transport between cellular compartments. We identify novel candidate protein effectors of the regenerative response and uncover their regulation of axon growth in vitro, validating the utility of QBONCAT for the discovery of novel regulatory and therapeutic candidates after optic nerve injury.


Subject(s)
Optic Nerve Injuries , Axons/metabolism , Humans , Nerve Regeneration/physiology , Optic Nerve Injuries/metabolism , Retina/metabolism , Retinal Ganglion Cells/metabolism
16.
Elife ; 112022 03 08.
Article in English | MEDLINE | ID: mdl-35259089

ABSTRACT

Many neurons in the adult central nervous system, including retinal ganglion cells (RGCs), degenerate and die after injury. Early axon protein and organelle trafficking failure is a key component in many neurodegenerative disorders yet changes to axoplasmic transport in disease models have not been quantified. We analyzed early changes in the protein 'transportome' from RGC somas to their axons after optic nerve injury and identified transport failure of an anterograde motor protein Kif5a early in RGC degeneration. We demonstrated that manipulating Kif5a expression affects anterograde mitochondrial trafficking in RGCs and characterized axon transport in Kif5a knockout mice to identify proteins whose axon localization was Kif5a-dependent. Finally, we found that knockout of Kif5a in RGCs resulted in progressive RGC degeneration in the absence of injury. Together with expression data localizing Kif5a to human RGCs, these data identify Kif5a transport failure as a cause of RGC neurodegeneration and point to a mechanism for future therapeutics.


Subject(s)
Optic Nerve Injuries , Animals , Axonal Transport , Axons/metabolism , Kinesins/genetics , Mice , Mice, Inbred C57BL , Nerve Regeneration , Retinal Ganglion Cells/metabolism
17.
Sci Rep ; 12(1): 1059, 2022 01 20.
Article in English | MEDLINE | ID: mdl-35058485

ABSTRACT

Patterns of diversity in pathogen genomes provide a window into the spatiotemporal spread of disease. In this study, we tested the hypothesis that Schistosoma mansoni parasites form genetic clusters that coincide with the communities of their human hosts. We also looked for genetic clustering of parasites at the sub-community level. Our data consists of 14 microsatellite DNA markers, typed from pooled DNA samples from [Formula: see text] infected individuals living in three Brazilian communities. We found a one-to-one correspondence between genetic clusters found by K-means cluster analysis and communities when [Formula: see text]. These clusters are also easily identified in a neighbor-joining tree and principal coordinates plots. K-means analysis with [Formula: see text] also reveals genetic clusters of parasites at the sub-community level. These sub-clusters also appear on the neighbor-joining tree and principal coordinates plots. A surprising finding is a genetic relationship between subgroups in widely separated human communities. This connection suggests the existence of common transmission sites that have wide influence. In summary, the genetic structure of S. mansoni in Brazil juxtaposes local isolation that is occasionally broken by long-range migration. Permanent eradication of schistosomes will require both local efforts and the identification of regional infection reservoirs.


Subject(s)
Genetics, Population , Schistosoma mansoni/genetics , Schistosomiasis mansoni/parasitology , Animals , Brazil , Cluster Analysis , Host-Parasite Interactions/genetics , Humans , Microsatellite Repeats , Schistosoma mansoni/isolation & purification , Schistosomiasis mansoni/transmission
18.
Cell Rep ; 38(4): 110287, 2022 01 25.
Article in English | MEDLINE | ID: mdl-35081342

ABSTRACT

Intercellular transfer of toxic proteins between neurons is thought to contribute to neurodegenerative disease, but whether direct interneuronal protein transfer occurs in the healthy brain is not clear. To assess the prevalence and identity of transferred proteins and the cellular specificity of transfer, we biotinylated retinal ganglion cell proteins in vivo and examined biotinylated proteins transported through the rodent visual circuit using microscopy, biochemistry, and mass spectrometry. Electron microscopy demonstrated preferential transfer of biotinylated proteins from retinogeniculate inputs to excitatory lateral geniculate nucleus (LGN) neurons compared with GABAergic neurons. An unbiased mass spectrometry-based screen identified ∼200 transneuronally transported proteins (TNTPs) isolated from the visual cortex. The majority of TNTPs are present in neuronal exosomes, and virally expressed TNTPs, including tau and ß-synuclein, were detected in isolated exosomes and postsynaptic neurons. Our data demonstrate transfer of diverse endogenous proteins between neurons in the healthy intact brain and suggest that TNTP transport may be mediated by exosomes.


Subject(s)
Cell Communication/physiology , Exosomes/metabolism , Neurons/metabolism , Visual Cortex/metabolism , Animals , Neuroanatomical Tract-Tracing Techniques , Proteomics , Rats , Rats, Wistar , Visual Pathways/metabolism , Xenopus
19.
Rev. enferm. neurol ; 21(2): 142-156, may.-ago. 2022.
Article in Spanish | LILACS, BDENF - Nursing | ID: biblio-1411073

ABSTRACT

Introducción: La pandemia por COVID-19 requirió que los profesionales de enfermería enfocaran su atención en salvaguardar la integridad, seguridad y salud tanto del paciente como la propia. Objetivo: Analizar la percepción de la seguridad del cuidado profesional enfermero al paciente oncológico durante la contingencia por COVID-19. Material y métodos: Estudio descriptivo, observacional-transversal. Muestra de 50 profesionales de enfermería. Medición realizada con el instrumento Hospital Survey on Patient Safety adaptado al contexto de contingencia por COVID-19. Análisis de resultados mediante estadística descriptiva. Resultados: El grado de seguridad del cuidado profesional enfermero al paciente oncológico en contingencia por COVID-19 es aceptable en 11 de 16 dimensiones, según los rangos de medición: muy pobre, pobre, aceptable, muy bueno y excelente. Se identificaron las siguientes áreas de oportunidad para mejorar la seguridad del cuidado profesional enfermero: se pone en riesgo la seguridad de paciente con mayor presión de trabajo, la dotación del personal de enfermería es insuficiente para afrontar la carga de trabajo por pandemia, pues no se puede proporcionar la mejor atención si la jornada laboral es agotadora. Conclusiones: Los profesionales de enfermería ofrecen un cuidado aceptable a los pacientes oncológicos durante a la pandemia, pues afirman que tienen un protocolo de actuación adecuado y funcional que les brinda seguridad; sin embargo, existen factores como vulnerabilidad, equipo de protección y falta de personal que influyen en dicho grado de seguridad.


Introduction: The COVID-19 pandemic required nursing professionals to focus their attention on safeguarding the integrity, safety and health of cancer patients as well as their own. Objective: To analyze safety perception of professional nursing care for cancer patients during the COVID-19 contingency. Material and methods: Descriptive, cross-sectional observational study. Sample of 50 nursing professionals. Measurement was made according to the Hospital Survey on Patient Safety instrument adapted to the COVID-19 contingency context. The results were analyzed through descriptive statistics. Results: The safety level of professional nursing care for cancer patients during COVID-19 contingency was acceptable in 11 of 16 dimensions, according to the following scale: very poor, poor, acceptable, very good and excellent. Opportunity areas to improve safety of professional nursing care were identified: patient safety is put at risk when work pressure increases, staffing is not sufficient enough to deal with workload due to the pandemic, optimal patient care cannot be provided because of exhausting work schedules. Conclusions: Nursing professionals provide acceptable care for cancer patients during the pandemic, since they declare they have an adequate and functional action protocol that makes them feel secure; however, there are factors such as vulnerability, protective equipment and lack of personnel that influence this degree of safety.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Patient Care , Safety , Attention , Nursing
20.
Laryngoscope ; 132(5): 989-998, 2022 05.
Article in English | MEDLINE | ID: mdl-34637145

ABSTRACT

OBJECTIVE: To compare overall survival (OS) and disease-free survival (DFS) between sentinel lymph node biopsy (SNB) and elective neck dissection (END) in the surgical management of cT1-2N0 oral cavity squamous cell carcinoma (OCSCC). METHODS: English full-text articles were searched in PubMed and Embase on May 9, 2021. Articles had to compare SNB with END in cT1-T2N0 OCSCC patients; report hazard ratios (HRs), Kaplan-Meier curves, or P-values with total number of events for survival outcomes; be from a clinical trial, cohort, or case-control study. Two reviewers reviewed articles and a third settled disagreements. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Risk of Bias in Non-randomized Studies of Interventions tool and revised Cochrane risk-of-bias tool for randomized trials were used. The generic inverse variance method with a random-effect model was used for meta-analysis. RESULTS: Ten studies, five retrospective, three prospective, and two randomized controlled trials, were included (total number of patients [n] = 10,498, END n = 9102, SNB n = 1396). No significant differences were found in OS (HR = 0.92; 95% confidence interval [CI]: 0.65-1.31) or DFS (HR = 0.70; 95% CI: 0.41-1.20). Heterogeneity was not detected in pooled OS analysis (P = .18; I2  = 30%), but was in pooled DFS analysis (P = .003; I2  = 66%). CONCLUSIONS: No statistically significant differences in OS or DFS were observed between SNB and END in cT1-2N0 OCSCC, suggesting that SNB might be an alternative to END in the management of early-stage, clinically node-negative OCSCC. Laryngoscope, 132:989-998, 2022.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Head and Neck Neoplasms/surgery , Humans , Mouth Neoplasms/pathology , Mouth Neoplasms/surgery , Neck Dissection , Neoplasm Staging , Prospective Studies , Retrospective Studies , Sentinel Lymph Node Biopsy/methods , Squamous Cell Carcinoma of Head and Neck/pathology
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