The metabolic baton: conducting the dance of N6-methyladenosine writing and erasing.

The modification N6-methyladenosine (m6A) plays an important role in determining the functional output of gene expression programs. Throughout the transcriptome, the levels of m6A are tightly regulated by the opposing activities of methyltransferases and demethylases, as well as the interaction of modified transcripts with m6A-dependent RNA-binding proteins that modulate transcript stability, often referred to as writers, erasers, and readers. The enzymatic activities of both writers and erasers are tightly linked to the cellular metabolic environment, as these enzymatic reactions rely on metabolism intermediaries as cofactors. In this review, we highlight the examples of intersection between metabolism and m6A-dependent gene regulation and discuss the different contexts where this interaction plays important roles.

The modification landscape of P. aeruginosa tRNAs.

RNA modifications have a substantial impact on tRNA function, with modifications in the anticodon loop contributing to translational fidelity and modifications in the tRNA core impacting structural stability. In bacteria, tRNA modifications are crucial for responding to stress and regulating the expression of virulence factors. Although tRNA modifications are well-characterized in a few model organisms, our knowledge of tRNA modifications in human pathogens, such as Pseudomonas aeruginosa, remains limited. Here we leveraged two orthogonal approaches to build a reference landscape of tRNA modifications in E. coli, which enabled us to identify similar modifications in P. aeruginosa. Our analysis revealed a substantial degree of conservation between the two organisms, while also uncovering potential sites of tRNA modification in P. aeruginosa tRNAs that are not present in E. coli. The mutational signature at one of these sites, position 46 of tRNAGln1(UUG) is dependent on the P. aeruginosa homolog of TapT, the enzyme responsible for the 3-(3-amino-3-carboxypropyl) uridine (acp3U) modification. Identifying which modifications are present on different tRNAs will uncover the pathways impacted by the different tRNA modifying enzymes, some of which play roles in determining virulence and pathogenicity.

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species.

Although few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability of these methyltransferases to methylate thiol-based HDACis is conserved across different species. We found that TMT1A was conserved across rats, mice, chickens, and zebrafish, displaying 85.7%, 84.8%, 60.7%, and 51.0% amino acid sequence identity, respectively, with human TMT1A. Because TMT1B was not found in the chicken or zebrafish, we focused our studies on the TMT1A homologs. HEK-293 cells were transfected to express mouse, rat, chicken, or zebrafish homologs of TMT1A and all conferred resistance to the thiol-based HDACIs NCH-51, KD-5170, and romidepsin compared to empty vector-transfected cells. Additionally, all homologs blunted the downstream effects of HDACi treatment such as increased p21 expression, increased acetylated histone H3, and cell cycle arrest. Increased levels of dimethylated romidepsin were also found in the culture medium of cells transfected to express any of the TMT1A homologs after a 24 h incubation with romidepsin compared to empty-vector transfected cells. Our results indicate that the ability of TMT1A to methylate molecules is conserved across species. Animal models may therefore be useful in elucidating the role of these enzymes in humans.

The modification landscape of P. aeruginosa tRNAs.

RNA modifications have a substantial impact on tRNA function, with modifications in the anticodon loop contributing to translational fidelity and modifications in the tRNA core impacting structural stability. In bacteria, tRNA modifications are crucial for responding to stress and regulating the expression of virulence factors. Although tRNA modifications are well-characterized in a few model organisms, our knowledge of tRNA modifications in human pathogens, such as Pseudomonas aeruginosa, remains limited. Here we leveraged two orthogonal approaches to build a reference landscape of tRNA modifications in E. coli, which enabled us to identify similar modifications in P. aeruginosa. Our analysis revealed a substantial degree of conservation between the two organisms, while also uncovering potential sites of tRNA modification in P. aeruginosa tRNAs that are not present in E. coli. The mutational signature at one of these sites, position 46 of tRNAGln1(UUG) is dependent on the P. aeruginosa homolog of TapT, the enzyme responsible for the 3-(3-amino-3-carboxypropyl) uridine (acp3U) modification. Identifying which modifications are present on different tRNAs will uncover the pathways impacted by the different tRNA modifying enzymes, some of which play roles in determining virulence and pathogenicity.

Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma.

Metabolic reprogramming is a hallmark of cancer that facilitates changes in many adaptive biological processes. Mutations in the tricarboxylic acid cycle enzyme fumarate hydratase (FH) lead to fumarate accumulation and cause hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is a rare, inherited disease characterized by the development of non-cancerous smooth muscle tumors of the uterus and skin, and an increased risk of an aggressive form of kidney cancer. Fumarate has been shown to inhibit 2-oxoglutarate-dependent dioxygenases (2OGDDs) involved in the hydroxylation of HIF1α, as well as in DNA and histone demethylation. However, the link between fumarate accumulation and changes in RNA post-transcriptional modifications has not been defined. Here, we determine the consequences of fumarate accumulation on the activity of different members of the 2OGDD family targeting RNA modifications. By evaluating multiple RNA modifications in patient-derived HLRCC cell lines, we show that mutation of FH selectively affects the levels of N6-methyladenosine (m6A), while the levels of 5-formylcytosine (f5C) in mitochondrial tRNA are unaffected. This supports the hypothesis of a differential impact of fumarate accumulation on distinct RNA demethylases. The observation that metabolites modulate specific subsets of RNA-modifying enzymes offers new insights into the intersection between metabolism and the epitranscriptome.

Chemical and Pharmacological Prospection of the Ascidian Cystodytes dellechiajei.

Marine invertebrates are a traditional source of natural products with relevant biological properties. Tunicates are soft-bodied, solitary or colonial, sessile organisms that provide compounds unique in their structure and activity. The aim of this work was to investigate the chemical composition of the ascidian Cystodytes dellechiajei, selected on the basis of a positive result in biological screening for ligands of relevant receptors of the innate immune system, including TLR2, TLR4, dectin-1b, and TREM2. Bioassay-guided screening of this tunicate extract yielded two known pyridoacridine alkaloids, shermilamine B (1) and N-deacetylshermilamine B (2), and a family of methyl-branched cerebrosides (3). Compounds 2 and 3 showed selective binding to TREM2 in a dose-dependent manner. N-deacetylshermilamine B (2), together with its acetylated analogue, shermilamine B (1), was also strongly cytotoxic against multiple myeloma cell lines. TREM2 is involved in immunomodulatory processes and neurodegenerative diseases. N-deacetylshermilamine B (2) is the first example of a polycyclic alkaloid to show an affinity for this receptor.

Prognosis of programmed ventricular stimulation in adult patients with syncope of unexplained origin: A historical cohort.

Background: Programmed ventricular stimulation (PVS) during electrophysiological study (EPS), is a globally accepted tool for risk stratification of sudden cardiac death (SCD) in some specific clinical situations. The aim of this study was to evaluate the prognosis of ventricular arrhythmia induction in a cohort of patients with syncope of undetermined origin (SUO). Methods: This is a historical cohort study in a population of patients with SUO referred for EPS between the years 2008-2021. In this interval, 575 patients underwent the procedure. Results: Patients with induced ventricular arrhythmias had a higher occurrence of structural heart disease (36.7% vs. 76.5%), ischemic heart disease (28.2 vs. 57.1%), heart failure (15.5% vs. 34.4%), and lower left ventricular ejection fraction (59.16% vs. 47.51%), when compared to the outcome with a negative study. PVS triggered ventricular arrhythmias in 98 patients, 62 monomorphic and 36 polymorphic. During a median follow-up of 37.6 months, 100 deaths occurred. Only the induction of sustained ventricular arrhythmias showed a significant association with the primary outcome (all-cause mortality) with a p value <.001. After the performance of EPS, 142 patients underwent cardioverter-defibrillator (ICD) implantation. At study follow-up, 30 patients had therapies by the device. Only the induction of sustained monomorphic ventricular arrhythmia showed statistically significant association with appropriate therapies by the device (p = .012). Conclusion: In patients with SUO, the induction of sustained monomorphic ventricular arrhythmia after programmed ventricular pacing is related to a worse prognosis, with a higher incidence of mortality and appropriate therapies by the ICD.

The Methyltransferases METTL7A and METTL7B Confer Resistance to Thiol-Based Histone Deacetylase Inhibitors.

Histone deacetylase inhibitors (HDACi) are part of a growing class of epigenetic therapies used for the treatment of cancer. Although HDACis are effective in the treatment of T-cell lymphomas, treatment of solid tumors with this class of drugs has not been successful. Overexpression of the multidrug resistance protein P-glycoprotein (P-gp), encoded by ABCB1, is known to confer resistance to the HDACi romidepsin in vitro, yet increased ABCB1 expression has not been associated with resistance in patients, suggesting that other mechanisms of resistance arise in the clinic. To identify alternative mechanisms of resistance to romidepsin, we selected MCF-7 breast cancer cells with romidepsin in the presence of the P-gp inhibitor verapamil to reduce the likelihood of P-gp-mediated resistance. The resulting cell line, MCF-7 DpVp300, does not express P-gp and was found to be selectively resistant to romidepsin but not to other HDACis such as belinostat, panobinostat, or vorinostat. RNA-sequencing analysis revealed upregulation of the mRNA coding for the putative methyltransferase, METTL7A, whose paralog, METTL7B, was previously shown to methylate thiol groups on hydrogen sulfide and captopril. As romidepsin has a thiol as the zinc-binding moiety, we hypothesized that METTL7A could inactivate romidepsin and other thiol-based HDACis via methylation of the thiol group. We demonstrate that expression of METTL7A or METTL7B confers resistance to thiol-based HDACis and that both enzymes are capable of methylating thiol-containing HDACis. We thus propose that METTL7A and METTL7B confer resistance to thiol-based HDACis by methylating and inactivating the zinc-binding thiol.

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species.

Although few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability of these methyltransferases to methylate thiol-based HDACis is conserved across different species. We found that TMT1A was conserved across rats, mice, chickens, and zebrafish, displaying 85.7%, 84.8%, 60.7% and 51.0% amino acid sequence identity, respectively, with human TMT1A. Because TMT1B was not found in the chicken or zebrafish, we focused our studies on the TMT1A homologs. HEK-293 cells were transfected to express mouse, rat, chicken, or zebrafish homologs of TMT1A and all conferred resistance to the thiol-based HDACIs NCH-51, KD-5170 and romidepsin compared to empty vector-transfected cells. Additionally, all homologs blunted the downstream effects of HDACi treatment such as increased p21 expression, increased acetylated histone H3, and cell cycle arrest. Increased levels of dimethylated romidepsin were also found in the culture medium of cells transfected to express any of the TMT1A homologs after a 24 h incubation with romidepsin compared to empty-vector transfected cells. Our results indicate that the ability of TMT1A to methylate molecules is conserved across species. Animal models may therefore be useful in elucidating the role of these enzymes in humans.

Wide-Awake Local Anesthesia No Tourniquet for Rhizarthrosis Surgery: Technique and Experience for 16 Consecutive Cases.

Since it was described, wide-awake local anaesthesia no tourniquet (WALANT) has gained popularity. Our department has started using WALANT for hand surgery with increasing complexity. We present our results with WALANT rhizarthrosis surgery, including prosthetic replacement, trapeziectomy with suture button suspensionplasty and revision surgery. A retrospective review of all rhizarthrosis procedures under WALANT was performed from April 2021 to July 2022. We included patients who fulfilled inclusion criteria and had adequate imaging and clinical follow-up. A satisfaction survey was performed by telephone. Surgical time, complications, conversion to conventional anesthesia, pain, anxiety and global satisfaction were recorded. Tumescent anesthesia is performed 20-25 minutes before surgery, and is performed in four or five strategic locations that allow adequate anesthesia and vasoconstriction for the procedure to be comfortably carried out. We observed a series of 16 sequential surgeries involving 14 patients. All were female with a mean age of 65 years. Fourteen cases were performed due to primary rhizarthrosis, eight trapeziectomies with suture button suspensionplasty, six prosthetic replacements, and two revision surgeries. One patient needed to be converted to conventional anaesthesia due to anxiety during the procedure. Mean procedure time was 73 minutes. There were no WALANT-related complications. Mean patient-reported satisfaction with the anesthetic technique was a 9 (on a scale from 1 to 10) and 100% of patients would choose to undergo surgery with WALANT anesthesia for a future procedure. We find it useful to actively engage the patients during surgery to keep them comfortable and also help the surgeons assess stability and functional results. After wound closure, the hand is shown to the patient and he performs various tasks. There is somewhat of a learning curve for rhizarthrosis surgery under WALANT; patient comfort can be achieved through an adequate anesthetic technique and reassurance before and during surgery. We recommend that the first few cases be done in the presence of an anesthesiologist and a fasting patient in case there is a need to convert to conventional anesthesia. Wide awake rhizarthrosis surgery, even revision surgery, is safe and pain-free. Patient-reported satisfaction is also high. The authors find that including patient participation in their own surgery might be promising for post-op rehabilitation. There are limitations in this study such as the absence of a control conventional anesthesia group, the satisfaction questionnaire was not done immediately post-operatively, as such, a memory bias cannot be excluded, and it is not yet validated for the Portuguese population.

Cryptic splice mutation in the fumarate hydratase gene in patients with clinical manifestations of Hereditary Leiomyomatosis and Renal Cell Cancer.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant condition characterized by the development of cutaneous and uterine leiomyomas and risk for development of an aggressive form of papillary renal cell cancer. HLRCC is caused by germline inactivating pathogenic variants in the fumarate hydratase (FH) gene, which encodes the enzyme that catalyzes the interconversion of fumarate and L-malate. We utilized enzyme and protein mobility assays to evaluate the FH enzyme in a cohort of patients who showed clinical manifestations of HLRCC but were negative for known pathogenic FH gene variants. FH enzyme activity and protein levels were decreased by 50% or greater in three family members, despite normal FH mRNA expression levels as measured by quantitative PCR. Direct Nanopore RNA sequencing demonstrated 57 base pairs of retained intron sequence between exons 9 and 10 of polyadenylated FH mRNA in these patients, resulting in a truncated FH protein. Genomic sequencing revealed a heterozygous intronic alteration of the FH gene (chr1: 241498239 T/C) resulting in formation of a splice acceptor site near a polypyrimidine tract, and a uterine fibroid obtained from a patient showed loss of heterozygosity at this site. The same intronic FH variant was identified in an unrelated patient who also showed a clinical phenotype of HLRCC. These data demonstrate that careful clinical assessment as well as biochemical characterization of FH enzyme activity, protein expression, direct RNA sequencing, and genomic DNA sequencing of patient-derived cells can identify pathogenic variants outside of the protein coding regions of the FH gene.

First evidence of widespread, severe soil erosion underneath centre-pivot irrigation systems.

Centre-pivot systems are widely used for irrigation in agriculture. However, excessive water application rates under low pressure centre-pivot systems can lead to soil erosion, which degrades soil structure and increases crop vulnerability to droughts. Although efforts have been deployed to measure soil erosion underneath individual centre pivots, a large-scale systematic assessment of extent and severity of soil erosion in centre-pivot irrigated fields is currently lacking. Here we used Google Earth™ satellite images to provide first evidence of widespread, severe soil erosion in centre-pivot irrigated agricultural land. We focused on the municipality of Cristalina (6154 km2), in the Brazilian Central Highlands, where centre pivots irrigate approximately 60,000 ha of cropland. The study area is in the Cerrado biome, which is one of the most important grain-producing regions in the world and Brazil's main centre-pivot irrigation area. By mapping erosion features under centre pivots, we found that 29 % of centre-pivot fields displayed signs of rill erosion, with individual rills up to a length of 1200 m. Most erosion features were identified during the dry season of the Brazilian Cerrado, which coincided with the period of greater satellite-image availability. Moreover, we found that compacted centre-pivot-wheel tracks often triggered rill incision and that eroding centre-pivot fields displayed higher slope gradients and were better connected to surface waters than the non-eroding fields. Ultimately, the frequent identification of severe erosion features in the centre-pivot fields during the dry season indicates that irrigation causes and/or aggravates soil erosion in Cristalina and likely in other parts of the Brazilian Cerrado. This first systematic evidence of widespread soil erosion underneath centre-pivot systems highlights that irrigation erosion is an important but neglected driver of land degradation, and that urgent action is required to protect affected soils for future generations.

Phenotypic plasticity and behavioral responses of dairy cattle on rotational grazing.

Heat stress is one of the most important environmental challenges faced by dairy cattle, with a deleterious effect on animal production and welfare. This research was conducted to evaluate the effects of the thermal environment on the physiological and behavioral responses of dairy cattle in a rotational picket. The research was conducted on an experimental farm, located in the Agreste region of the state of Pernambuco, Brazil. The animals were managed in a rotational picket system of signal grass, with an occupation and a rest period of 7 and 28 days, respectively, for a stocking rate of 3.2 AU ha-1. The determination of the effect of stressors on the animals was performed by recording the dry bulb temperature (°C), and the relative humidity, which allowed the characterization of the thermal environment by the temperature and humidity index and by the specific enthalpy (kJ kg-1). The physiological variables monitored were respiratory rate (mov. min-1), rectal temperature (°C), and skin temperature (°C). The behavioral responses quantified were activities, walking, ruminating, idling and ingestive behaviors, eating, and drinking, with the percentage of time spent on each activity being recorded. According to the canonical multivariate analysis, the chi-square test, and the variation of physiological patterns, the animals, even in a situation of greater thermal challenge, presented physiological responses within conditions considered normal; however, they reduced grazing activity (eating) during the hottest hours and increased the activities of rumination and idling.

The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1.

The chromodomain helicase DNA-binding protein CHD8 is the most frequently mutated gene in autism spectrum disorder. Despite its prominent disease involvement, little is known about its molecular function in the human brain. CHD8 is a chromatin regulator which binds to the promoters of actively transcribed genes through genomic targeting mechanisms which have yet to be fully defined. By generating a conditional loss-of-function and an endogenously tagged allele in human pluripotent stem cells, we investigated the molecular function and the interaction of CHD8 with chromatin in human neurons. Chromatin accessibility analysis and transcriptional profiling revealed that CHD8 functions as a transcriptional activator at its target genes in human neurons. Furthermore, we found that CHD8 chromatin targeting is cell context-dependent. In human neurons, CHD8 preferentially binds at ETS motif-enriched promoters. This enrichment is particularly prominent on the promoters of genes whose expression significantly changes upon the loss of CHD8. Indeed, among the ETS transcription factors, we identified ELK1 as being most highly correlated with CHD8 expression in primary human fetal and adult cortical neurons and most highly expressed in our stem cell-derived neurons. Remarkably, ELK1 was necessary to recruit CHD8 specifically to ETS motif-containing sites. These findings imply that ELK1 and CHD8 functionally cooperate to regulate gene expression and chromatin states at MAPK/ERK target genes in human neurons. Our results suggest that the MAPK/ERK/ELK1 axis potentially contributes to the pathogenesis caused by CHD8 mutations in human neurodevelopmental disorders.

Atuação do enfermeiro na prevenção das toxemias gravídicas / Nurse's role in the prevention of pregnancy toxemia / Papel de la enfermera en la prevención de la toxemia del embarazo

Objetivo: Analisar as publicações científicas relacionadas à atuação do Enfermeiro na prevenção das toxemias gravídicas.Método: Revisão integrativa da literatura. As buscas das evidências científicas foram realizadas nas bases de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde, Base de Dados de Enfermagem e Medical Literature Analysis and Retrieval System Online via Biblioteca Virtual da Saúde e Scientific Electronic Library Online, utilizando-se dos termos de busca: Assistência de Enfermagem, Cuidados de Enfermagem, Enfermagem, Pré-eclâmpsia e Eclâmpsia, com auxílio dos operadores booleanos "AND" e "OR". Resultado: Após a seleção, leitura e filtragem, identificaram-se 10 estudos para análise, que foram agrupados porsimilaridade semântica e discutidos em categorias temáticas, sendo elas: Atuação do Enfermeiro na prevenção das toxemias gravídicas e Dificuldades encontradas na atuação do Enfermeiro na prevenção das toxemias gravídicas. Conclusão: É notável que com a realização de um acompanhamento pré-natal de qualidade durante toda a gestação é possível detectar de forma precoce as alterações nos sinais clínicos causadas pela toxemias gravídicas e iniciar um tratamento adequado.

Objective: To analyze scientific publications related to the role of nurses in the prevention of pregnancy toxemia. Method: Integrative literature review. Searches for scientific evidence were carried out in the following databases: Latin American and Caribbean Literature on Health Sciences, Nursing Database and Medical Literature Analysis and Retrieval System Online via the Virtual Health Library and Scientific Electronic Library Online, using-search terms: Nursing Care, Nursing Care, Nursing, Preeclampsia and Eclampsia, with the help of the Boolean operators "AND" and "OR". Result: After selection, reading and filtering, 10 studies were identified for analysis, which were grouped by semantic similarity and discussed in thematic categories, namely: Nurse's role in the prevention of pregnancy toxemia and Difficulties encountered in the nurse's role in prevention of pregnancy toxemia. Conclusion: It is notable that with quality prenatal care throughout pregnancy, it is possible to detect early changes in clinical signs caused by pregnancy toxemia and initiate appropriate treatment.

Objetivo: Analizar las publicaciones científicas relacionadas con el papel de las enfermeras en la prevención de la toxemia del embarazo.Método: Revisión integrativa de la literatura. Se realizaron búsquedas de evidencia científica en las siguientes bases de datos: Literatura Latinoamericana y del Caribe en Ciencias de la Salud, Base de Datos de Enfermería y Sistema de Análisis y Recuperación de Literatura Médica en Línea a través de la Biblioteca Virtual en Salud y Biblioteca Electrónica Científica en Línea, utilizando los términos de búsqueda: Cuidados de Enfermería, Cuidados de Enfermería, Enfermería, Preeclampsia y Eclampsia, con la ayuda de los operadores booleanos "AND" y "OR". Resultado: después de la selección, lectura y filtrado, fueron identificados 10 estudios para análisis, que fueron agrupados por similitud semántica y discutidos en categorías temáticas, a saber: Rol del enfermero en la prevención de la toxemia del embarazo y Dificultades encontradas en el rol del enfermero en la prevención de la toxemia del embarazo. Conclusión: Es de destacar que con un control prenatal de calidad durante todo el embarazo, es posible detectar cambios tempranos en los signos clínicos causados por la toxemia del embarazo e iniciar el tratamiento adecuado.

Impacto da pandemia na saúde mental dos discentes de enfermagem no contexto da COVID-19 / Impact of the pandemic on the mental health of nursing students in the context of COVID-19 / Impacto de la pandemia en la salud mental de los estudiantes de enfermería en el contexto del COVID-19

Objetivo: Investigar os impactos da pandemia da COVID-19 na saúde mental dos discentes de enfermagem e avaliar a relação entre o evento e os indicadores para transtorno de estresse pós-traumático (TEPT). Método: estudo exploratório, analítico, transversal, com abordagem quantitativa. A amostra estudada foi constituída por 164 estudantes de uma instituição de ensino superior privada, matriculado no curso de Enfermagem, convidado por meio eletrônico, que responderam ao questionário on-line sobre dados sociodemográficos, percepção de risco pela pandemia COVID-19 e sintomas de estresse pós-traumático avaliados pela Impact of Event Scale (IES-R) em sua versão brasileira validada. Resultados: A maioria dos participantes eram da faixa etária de 18 a 23 anos (70,8%), do sexo feminino (91,5%), sem filhos (86%), residem com 2 a 4 pessoa (75%). 51,2% apresentam indicação alta para TEPT, 14,0% apresentam preocupação clínica para TEPT. Houve associação do escore da IES-R com a idade, quantidade de filhos e quantidade de pessoas com quem reside. Conclusão: O evento da pandemia da Covid-19 provocou um impacto na saúde mental dos discentes de Enfermagem, com uma elevada classificação de participantes com indicação alta para TEPT. Esses dados são importantes para futuras intervenções psicológicas e pedagógicas entre estudantes.

Objective: To investigate the impacts of the COVID-19 pandemic on the mental health of nursing students and to assess the relationship between the event and the indicators for post-traumatic stress disorder (PTSD). Method: exploratory, analytical, cross-sectional study with a quantitative approach. The sample studied consisted of 164 students from a private higher education institution, enrolled in the Nursing course, invited by electronic means, who answered the online questionnaire on sociodemographic data, risk perception by the COVID-19 pandemic and symptoms of stress. trauma assessed by the Impact of Event Scale (IES-R) in its validated Brazilian version. Results: Most participants were aged between 18 and23 years (70.8%), female (91.5%), without children (86%), living with 2 to 4 people (75%). 51.2% have a high indication for PTSD, 14.0% have clinical concern for PTSD. There was an association of the IES-R score with age, number of children and number of people with whom they live. Conclusion: The Covid-19 pandemic event had an impact on the mental health of Nursing students, with a high rating of participants with a high indication for PTSD. These data are important for future psychological and pedagogical interventions among students.

Objetivo: Investigar los impactos de la pandemia de COVID-19 en la salud mental de estudiantes de enfermería y evaluar la relación entre el evento y los indicadores de trastorno de estrés postraumático (TEPT). Método: estudio exploratorio, analítico, transversal con enfoque cuantitativo. La muestra estudiada estuvo conformada por 164 estudiantes de una institución de educación superior privada, matriculados en la carrera de Enfermería, invitados por medios electrónicos, quienes respondieron el cuestionario en línea sobre datos sociodemográficos, percepción de riesgo por la pandemia del COVID-19 y síntomas de estrés y trauma evaluados por la Escala de Impacto de Evento (IES-R) en su versión brasileña validada. Resultados: La mayoría de los participantes tenían entre 18 y 23 años (70,8%), sexo femenino (91,5%), sin hijos (86%), viviendo con 2 a 4 personas (75%). El 51,2% tiene una alta indicación de TEPT, el 14,0% tiene preocupación clínica por TEPT. Hubo asociación del puntaje IES-R con la edad, número de hijos y número de personas con las que conviven. Conclusión: El evento pandémico de la Covid-19 tuvo impacto en la saludmental de los estudiantes de Enfermería, con alta calificación de participantes con alta indicación para TEPT. Estos datos son importantes para futuras intervenciones psicológicas y pedagógicas entre los estudiantes.

Improving the design and implementation of sediment fingerprinting studies: summary and outcomes of the TRACING 2021 Scientific School.

Purpose: Identifying best practices for sediment fingerprinting or tracing is important to allow the quantification of sediment contributions from catchment sources. Although sediment fingerprinting has been applied with reasonable success, the deployment of this method remains associated with many issues and limitations. Methods: Seminars and debates were organised during a 4-day Thematic School in October 2021 to come up with concrete suggestions to improve the design and implementation of tracing methods. Results: First, we suggest a better use of geomorphological information to improve study design. Researchers are invited to scrutinise all the knowledge available on the catchment of interest, and to obtain multiple lines of evidence regarding sediment source contributions. Second, we think that scientific knowledge could be improved with local knowledge and we propose a scale of participation describing different levels of involvement of locals in research. Third, we recommend the use of state-of-the-art sediment tracing protocols to conduct sampling, deal with particle size, and examine data before modelling and accounting for the hydro-meteorological context under investigation. Fourth, we promote best practices in modelling, including the importance of running multiple models, selecting appropriate tracers, and reporting on model errors and uncertainty. Fifth, we suggest best practices to share tracing data and samples, which will increase the visibility of the fingerprinting technique in geoscience. Sixth, we suggest that a better formulation of hypotheses could improve our knowledge about erosion and sediment transport processes in a more unified way. Conclusion: With the suggested improvements, sediment fingerprinting, which is interdisciplinary in nature, could play a major role to meet the current and future challenges associated with global change. Supplementary information: The online version contains supplementary material available at 10.1007/s11368-022-03203-1.

Attitude Uncertainty Analysis of a Three-Vehicle Constrained Formation.

The uncertainty analysis of attitude estimates enables the comparison between different methods, and, thus, it is important for practical applications. This work studies the uncertainty for the attitude determination of a three-vehicle constrained formation. Moreover, the existing solution is improved by including the uncertainty results in a weighted orthogonal Procrustes problem. In the formation considered herein, the vehicles measure inertial references and relative line-of-sight vectors. Nonetheless, the line of sight between two elements of the formation is restricted. The uncertainty analysis uses perturbation theory and, consequently, considers a small first-order perturbation in the measurements. The covariance matrices are obtained for all relative and inertial attitude candidates from the linearization of the solution using a first-order Taylor expansion. Then, the uncertainty is completed by considering the covariance for the weighted orthogonal Procrustes problem, from the literature, and the definition of covariance for the remaining attitudes. The uncertainty characterization is valid for configurations with a unique solution. Finally, the theoretical results are validated by applying Monte Carlo simulations, which show that the predicted errors are statistically consistent with the numerical implementation of the solution with noise. Furthermore, the theoretical uncertainty predicts the accuracy changes near special configurations where there is loss of information.

Identification of Protein-RNA Interactions in Mouse Testis Tissue Using fRIP.

During development, cells must quickly switch from one cell state to the next to execute precise and timely differentiation. One method to ensure fast transitions in cell states is by controlling gene expression at the post-transcriptional level through action of RNA-binding proteins on mRNAs. The ability to accurately identify the RNA targets of RNA-binding proteins at specific stages is key to understanding the functional role of RNA-binding proteins during development. Here we describe an adapted formaldehyde RNA immunoprecipitation (fRIP) protocol to identify the in vivo RNA targets of a cytoplasmic RNA-binding protein, YTHDC2, from testis, during the first wave of spermatogenesis, at the stage when germ cells are shutting off the proliferative program and initiating terminal differentiation ( Bailey et al., 2017 ). This protocol enables quick and efficient identification of endogenous RNAs bound to an RNA-binding protein, and facilitates the monitoring of stage-specific changes during development.