Identification of astrocyte-like cells in an adult ascidian during regeneration of the central nervous system.

The mechanisms underlying regeneration of the central nervous system (CNS) following lesions have been studied extensively in both vertebrate and invertebrate models. To shed light on regeneration, ascidians, a sister group of vertebrates and with remarkable ability to regenerate their brains, constitute an appropriate model system. Glial cells have been implicated in regeneration in vertebrates; however, their role in the adult ascidian CNS regeneration is unknown. A model of degeneration and regeneration using the neurotoxin 3-acetylpyridine (3AP) in the brain of the ascidian Styela plicata was used to identify astrocyte-like cells and investigate their role. We studied the CNS of control ascidians (injected with artificial sea water) and of ascidians whose CNS was regenerating (1 and 10 days after the injection with 3AP). Our results show that the mRNA of the ortholog of glutamine synthetase (GS), a glial-cell marker in vertebrates, is increased during the early stages of regeneration. Confirming the identity of GS, the protein was identified via immunostaining in a cell population during the same regeneration stage. Last, a single ortholog of GS (GSII) is present in ascidian and amphioxus genomes, while two types exist in fungi, some invertebrates, and vertebrates, suggesting that ascidians have lost the GSI type. Taken together, our findings revealed that a cell population expressing glial-cell markers may play a role in regeneration in adult ascidians. This is the first report of astrocyte-like cells in the adult ascidian CNS, and contributes to understanding of the evolution of glial cells among metazoans.

The mlpt smORF gene is essential for digestive physiology and molting during nymphal stages in the kissing bug Rhodnius prolixus.

Chagas disease affects around 8 million people globally, with Latin America bearing approximately 10,000 deaths each year. Combatting the disease relies heavily on vector control methods, necessitating the identification of new targets. Within insect genomes, genes harboring small open reading frames (smORFs - < 100 amino acids) present numerous potential candidates. In our investigation, we elucidate the pivotal role of the archetypal smORF-containing gene, mille-pattes/polished-rice/tarsalless (mlpt/pri/tal), in the post-embryonic development of the kissing bug Rhodnius prolixus. Injection of double-stranded RNA targeting mlpt (dsmlpt) during nymphal stages yields a spectrum of phenotypes hindering post-embryonic growth. Notably, fourth or fifth stage nymphs subjected to dsmlpt do not undergo molting. These dsmlpt nymphs display heightened mRNA levels of JHAMT-like and EPOX-like, enzymes putatively involved in the juvenile hormone (JH) pathway, alongside increased expression of the transcription factor Kr-h1, indicating changes in the hormonal control. Histological examination reveals structural alterations in the hindgut and external cuticle of dsmlpt nymphs compared to control (dsGFP) counterparts. Furthermore, significant changes in the vector's digestive physiology were observed, with elevated hemozoin and glucose levels in the posterior midgut of dsmlpt nymphs. Importantly, dsmlpt nymphs exhibit impaired metacyclogenesis of Trypanosoma cruzi, the causative agent of Chagas disease, underscoring the crucial role of proper gut organization in parasite differentiation. Thus, our findings constitute the first evidence of a smORF-containing gene's regulatory influence on vector physiology, parasitic cycle, and disease transmission.

Assessing outcomes of intravenous insulin therapy in non-intensive care patients.

OBJECTIVES: The aim of this study was to compare outcomes of using intravenous insulin infusion (IVII) therapy for managing hyperglycemia in a non-intensive care unit (ICU) versus an ICU setting. METHODS: We conducted a retrospective analysis on patients who received IVII for hyperglycemia. The analysis compared variables associated with hypoglycemic events while on IVII, and point-of-care blood glucose control and insulin regimens at discharge. Insulin administration errors occurring on IVII were determined. RESULTS: Between November 2020 and August 2022, 881 patients received 1,106 IVIIs (780 in ICU and 326 non-ICU). A cumulative 468 days were spent on IVII in the non-ICU setting and 1564 in the ICU (total 2,032 days). The frequency of hypoglycemia on IVII was higher when provided in the non-ICU vs ICU (1.4% vs 0.7%), p < 0.01). Non-ICU patients had significantly higher average blood glucose during the last 24 h of the hospital stay (185 mg/dL vs 160 mg/dL, non-ICU vs. ICU, Pp < 0.01) and were more likely discharged with basal-bolus insulin therapy (p < 0.01). After adjusting for other variables, the probability of having hypoglycemia (OR 2.35; 95% CI 1.62-3.42; p < 0.001) was higher for the non-ICU cohort. In addition, patients who received IVII in the non-ICU settings had mean glucose levels nearly 26 mg/dL higher (95% CI 19.40-32.9, p < 0.001) at discharge vs. ICU. Seven cases of insulin errors were reported while on IVII in the non-ICU settings, compared to one in the ICU. CONCLUSIONS: A large number (468) of ICU days were avoided by providing IVII in the non-ICU setting. Of the more than 400 days of IVII therapy provided in the non-ICU, only 7 medication errors occurred. Further studies are needed to optimize IVII strategy for non-ICU patients.

Identification of pre-flexion fish larvae from the western South Atlantic using DNA barcoding and morphological characters.

Knowledge on species composition is the first step necessary for the proper conservation and management of biological resources and ecologically relevant species. High species diversity and a lack of diagnostic characters for some groups can impose difficulties for taxonomic identification through traditional methodologies, and ichthyoplankton (fish larvae and eggs) are a good example of such a scenario. With more than 35.000 valid species of fishes worldwide and overall similar anatomies in early developmental stages in closely related groups, fish larvae are often hard to be identified at the species or even more encompassing taxonomic levels. To overcome this situation, molecular techniques have been applied, with different markers tested over the years. Cytochrome c oxidase I (COI) is the most commonly used marker and now has the broadest public reference libraries, providing consistent results for species identification in different metazoan studies. Here we sequenced the mitochondrial COI-5P fragment of 89 fish larvae collected in the Campos Basin, coastal southeastern Brazil, and compared these sequences with references deposited in public databases to obtain taxonomic identifications. Most specimens identified are species of the Blenniiformes, with Parablennius and Labrisomus the most frequently identified genera. Parablennius included two species (P. marmoreus and P. pilicornis), while Labrisomus included three species (L. cricota, L. conditus and L. nuchipinnis). Anatomy of these molecularly identified specimens were then analyzed with the intention of finding anatomical characters that might be diagnostically informative amongst the early development stage (pre-flexion) larvae. Ventral pigmentation patterns are proposed as useful markers to identify Labrisomus species. However, additional specimens are needed to confirm if the character holds stability through the geographic distribution of the species.

Spider's Silk as a Potential Source of Antibiotics: An Integrative Review.

Spiders produce webs, which are still a largely unexplored source of antibacterial compounds, although the reports of its application in the medical field. Therefore, this study aims to present an integrative review of the antibacterial activity of spider webs. The research was conducted using Google Scholar, Scielo, Web of Science, PubMed, ScienceDirect, Medline EBSCO, LILACS, and Embase. The inclusion criteria were original articles written in English that studied the antibiotic properties of the web or isolated compounds tested. The studies were compared according to the spider species studied, the type of web, treatment of the sample, type of antimicrobial test, and the results obtained. Nine hundred and seventy-three publications were found, and after applying the inclusion and exclusion criteria, sixteen articles were selected. Bacterial inhibition was found in seven studies against various species of bacteria such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella Typhi, Bacillus megaterium, Listeria monocytogenes, Acinetobacter baumannii, Streptococcus pneumoniae, Pasteurella multocida, and Bacillus subtilis. Additionally, there was no apparent relationship between the proximity of the spider species evaluated in the studies and the presence or absence of activity. Methodological problems detected may affected the reproducibility and reliability of the results in some studies, such as the lack of description of the web or microorganism strain, as well as the absence of adequate controls and treatments to sterilize the sample. Spider webs can be a valuable source of antibiotics; however, more studies are needed to confirm the real activity of the web or components involved.

The possible impacts of nano and microplastics on human health: lessons from experimental models across multiple organs.

The widespread production and use of plastics have resulted in accumulation of plastic debris in the environment, gradually breaking down into smaller particles over time. Nano-plastics (NPs) and microplastics (MPs), defined as particles smaller than 100 nanometers and 5 millimeters, respectively, raise concerns due to their ability to enter the human body through various pathways including ingestion, inhalation, and skin contact. Various investigators demonstrated that these particles may produce physical and chemical damage to human cells, tissues, and organs, disrupting cellular processes, triggering inflammation and oxidative stress, and impacting hormone and neurotransmitter balance. In addition, micro- and nano-plastics (MNPLs) may carry toxic chemicals and pathogens, exacerbating adverse effects on human health. The magnitude and nature of these effects are not yet fully understood, requiring further research for a comprehensive risk assessment. Nevertheless, evidence available suggests that accumulation of these particles in the environment and potential human uptake are causes for concern. Urgent measures to reduce plastic pollution and limit human exposure to MNPLs are necessary to safeguard human health and the environment. In this review, current knowledge regarding the influence of MNPLs on human health is summarized, including toxicity mechanisms, exposure pathways, and health outcomes across multiple organs. The critical need for additional research is also emphasized to comprehensively assess potential risks posed by degradation of MNPLs on human health and inform strategies for addressing this emerging environmental health challenge. Finally, new research directions are proposed including evaluation of gene regulation associated with MNPLs exposure.

Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma.

DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome DNA damage, we investigate how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting Interleukin enhancer binding factor 2 (ILF2), a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo adaptive metabolic rewiring to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identify the mitochondrial DNA repair protein DNA2, whose loss of function suppresses MM cells' ability to overcome ILF2 ASO-induced DNA damage, as being essential to counteracting oxidative DNA damage. Our study reveals a mechanism of vulnerability of MM cells that have an increased demand for mitochondrial metabolism upon DNA damage activation.

Adrenoreceptor phylogeny and novel functions of nitric oxide in ascidian immune cells.

Nitric oxide (NO) is a simple molecule involved in many biological processes and functions in the cardiovascular, neural, and immune systems. In recent years, NO has also been recognized as a crucial messenger in communication between the nervous and immune systems. Together with NO, catecholamines are the main group of neurotransmitters involved in cross-talk between the nervous and immune systems. Catecholamines such as noradrenaline, can act on immune cells through adrenoreceptors (ARs) present on the cell surface, and NO can cross the cell membrane and interact with secondary messengers, modulating catecholamine production. Here, we analyzed the mutual modulation by noradrenaline and NO in Phallusia nigra immune cells for specific subtypes of ARs. We also investigated the involvement of protein kinases A and C as secondary messengers to these specific subtypes of ARs in the adrenergic signaling pathway that culminates in NO modulation, and the phylogenetic distribution of ARs in deuterostome genomes. This analysis provided evidence for single-copy orthologs of α1, α2 and ß-AR in ascidian genomes, suggesting that NO and NA act on a less diverse set of ARs in urochordates. Pharmacological assays showed that high levels of NO can induce ascidian immune cells to produce catecholamines. We also observed that protein kinases A and C are the secondary messengers involved in downstream modulation of NO production through an ancestral ß-AR. Taken together, these results provide new information on NO as a modulator of immune cells, and reveal the molecules involved in the signaling pathway of ARs. The results also indicate that ARs may participate in NO modulation. Finally, our results suggest that the common ancestor of urochordates possessed a less complex system of ARs required for immune action and diverse pharmacological responses, since the α-ARs are phylogenetically more related to D1-receptors than are the ß-ARs.

Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma.

Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiD). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window. By combining IMiDs with EP300 inhibition, we demonstrate greater downregulation of MYC and IRF4, synergistic killing of myeloma in vitro and in vivo, and an increased therapeutic window. Interestingly, this potent combination failed where MYC and IRF4 expression was maintained by high levels of the AP-1 factor BATF. Our results identify an effective drug combination and a previously unrecognized mechanism of IMiD resistance. SIGNIFICANCE: These results highlight the dependence of MM on IKZF1-bound super-enhancers, which can be effectively targeted by a potent therapeutic combination pairing IMiD-mediated degradation of IKZF1 and IKZF3 with EP300 inhibition. They also identify AP-1 factors as an unrecognized mechanism of IMiD resistance in MM. See related article by Neri, Barwick, et al., p. 56. See related commentary by Yun and Cleveland, p. 5. This article is featured in Selected Articles from This Issue, p. 4.

Efeitos de conteúdos emocionais sobre o raciocínio dedutivo humano: uma revisão sistemática / Effects of emotional content on human reasoning: a systematic review / Efectos de los contenidos emocionales sobre el razonamiento humano: una revisión sistemática / Effets du contenu affectif sur le raisonnement humain: une revue systématique

Resumo: O raciocínio e a emoção apresentam complexas e numerosas relações entre si, podendo prejudicar ou beneficiar o processamento lógico. Visando investigar a influência da tonalidade afetiva sobre o raciocínio, realizou-se uma revisão sistemática advinda da busca de estudos publicados nas bases de dados do Portal de Periódicos da Capes, Scielo, PubMed e Google Acadêmico. Os descritores utilizados foram: (affective content OR evaluative content OR emotion*) AND (reasoning). Após análise e submissão aos critérios de inclusão e exclusão, restaram 17 artigos, duas dissertações de mestrado e uma tese de doutorado. Apenas um dos estudos foi realizado no Brasil. Os participantes das pesquisas selecionadas tiveram pior desempenho nas tarefas de raciocínio formadas por conteúdos valorativos negativos. Entretanto, os conteúdos negativos influenciaram de forma positiva o raciocínio dedutivo quando se mostravam relevantes para a realização da tarefa. Assim, os estudos selecionados parecem apontar para a importância das emoções sobre o raciocínio humano.

Abstract: Reasoning and emotions have many complex relations which can hinder or benefit logical processing. Intending to investigate the influence of affective content on reasoning, we conducted a systematic review on scientific articles published on the Capes Journals Portal, Scielo, PubMed and Academic Google databases, retrieved using the descriptors (affective content OR evaluative content OR emotion*) AND (reasoning). After analysis and application of inclusion and exclusion criteria, 17 papers, two master's dissertations and one doctorate thesis remained. Only one study was conducted in Brazil. Research participants showed a worse performance in reasoning tasks composed by negative emotional content. However, negative emotional content influenced deductive reasoning positively when they proved to be relevant to the task. Hence, the reviewed studies suggest an importance of emotions for human reasoning.

Résumé : Le raisonnement et l'émotion entretiennent de nombreuses relations complexes qui peuvent entraver ou favoriser le procès logique. Dans le but d'étudier l'influence du contenu affectif sur le raisonnement, on a effectué une revue systématique des articles scientifiques publiés sur les base des données Portail des Périodiques du Capes, Scielo, PubMed et Google Académique, retrouvés en utilisant les descripteurs (affective content OR evaluative content OR emotion*) AND (reasoning). Après l'analyse et application des critères d'inclusion et d'exclusion, 17 articles, deux mémoires de maîtrise et une thèse de doctorat ont été retenus. Une seule étude a été menée au Brésil. Les participants aux recherches ont montré une pire perfomance dans les tâches de raisonnement composés d'un contenu affectif négatif. Cependant, ce contenu a influencé positivement le raisonnement déductif lorsqu'il s'est avéré pertinent pour la tâche. Les études examinées suggèrent donc que les émotions jouent un rôle important dans le raisonnement humain.

Resumen: El razonamiento y las emociones tienen relaciones complejas entre sí, que pueden perjudicar o ayudar el procesamiento lógico. Para investigar la influencia del tono afectivo sobre el razonamiento, se realizó una revisión sistemática a partir de la búsqueda de estudios publicados en las bases de datos del Portal de Periódicos Capes, SciELO, PubMed y Google Académico. Los descriptores utilizados fueron los siguientes: (affective content OR evaluative content OR emotion*) AND (reasoning). Después de la aplicación de los criterios de inclusión y exclusión, se seleccionaron 17 artículos, dos disertaciones de maestría y una tesis doctoral. Solo uno de los estudios se llevó a cabo en Brasil. Los participantes de las investigaciones seleccionadas tuvieron un peor desempeño en las tareas de razonamiento formadas por contenidos emocionales negativos. Estos influenciaron de forma positiva el razonamiento deductivo cuando eran relevantes para la realización de la tarea. Los estudios seleccionados parecen evidenciar la importancia de las emociones sobre el razonamiento humano.

Incidence and risk factors of pressure injuries in critically ill patients with COVID-19.

OBJECTIVE: to analyze pressure injury (PI) incidence and risk factors in patients with COVID-19 admitted to an Intensive Care Unit and characterize the identified PIs. METHOD: a retrospective cohort study, consisting of 668 patients, carried out between March 2020 and February 2021. Clinical/demographic and PI variables were collected from medical records and electronic database. Data were analyzed using descriptive and inferential statistics. Logistic regression was performed to analyze risk factors for PI. RESULTS: PI incidence was 30.2% (n=202), with the majority located in the sacral region (52.9%) and in stage 1 (39%). Risk factors were age (p<0.001), Diabetes Mellitus (p=0.005), length of stay (p<0.001), immunosuppression (p=0.034), nutritional risk (p=0.015) and mechanical ventilation (p<0.001). CONCLUSION: PI incidence in critically ill patients with COVID-19 was high.

Physicians' Perspectives on HL7 Information Policy Sensitive Value Set: A Validation Study through Health Concept Categorization.

The Health Level 7 (HL7) organization introduced the Information Sensitivity Policy Value Set with 45 sensitive data categories to facilitate the implementation of granular electronic consent technology. The goal is to allow patients to have control over the sharing of their sensitive medical records. This study represents the first attempt to explore physicians' viewpoints on these categories. Twelve physicians participated in a survey, leading to revisions in 21 HL7 categories. They later classified 600 clinical data items through a second survey using the updated categories. Participants' perspectives were documented, and data analysis included descriptive measures and heat maps. In the first survey, six participants suggested adding 19 new categories (e.g., personality disorder), and modifying 25 category definitions. Two new categories and sixteen revised category definitions were incorporated to support more patient-friendly content and inclusive language. Fifteen new category recommendations were addressed through a revision of category definitions (e.g., personality disorder described as a behavioral health condition). In the second survey, data categorizations led to recommendations for more categories from ten participants. Future revisions of the HL7 categories should incorporate physicians' viewpoints, validate the categories using patient data or/and include patients' perspectives, and develop patient-centric category specifications.

Grupo de orientações em linguagem infantil: experiência com familiares na Atenção Primária à Saúde / Orientation group in child language: experience with family members in Primary Health Care

A família exerce papel crucial no desenvolvimento da linguagem infantil. Entretanto, muitos familiares carecem de conhecimentos voltados a aspectos da linguagem, sendo contundente instruí-los. Este estudo tem como objetivo relatar a experiência da realização de um grupo de orientações em linguagem infantil para familiares de crianças em acompanhamento do Crescimento e Desenvolvimento na Unidade Básica de Saúde Maria das Graças dos Santos, no município de Jucurutu (RN). Trata-se de um relato de experiência constituído pela execução de quatro encontros do grupo operativo intitulado "Crescimento, Desenvolvimento e Fonoaudiologia" (CD e F), a partir da aplicação de estratégias ativas no delineamento de cada etapa. A experiência contou com a participação média de sete familiares, em sua maioria, mães. Os encontros favoreceram a ocorrência de momentos dialógicos satisfatórios, à luz da linguagem infantil e de aspectos correlatos, estimulando a atenção familiar e o acesso a informações substanciais. Os envolvidos consideraram a intervenção grupal positiva, que, por sua vez, deverá ser continuada e expandida no município. A implantação do grupo "CD e F" configura-se como ferramenta potencial de capacitação familiar e alternativa para a prática fonoaudiológica na Atenção Primária à Saúde.

The family presents a crucial paper in the development of child language. However, many family members lack knowledge related to language aspects, making orientation important. This study aims to report the experience of carrying out an orientation group in child language for family members of children that are in monitoring of Growth and Development in the Unidade Básica de Saúde Maria das Graças dos Santos, in Jucurutu (RN) city. This is an experience report consisting of the execution of four meetings of the operative group entitled "Crescimento, Desenvolvimento e Fonoaudiologia" (CD e F), based on the application of active strategies in the design of each stage. The experience had the average participation of seven family members, mostly mothers. The meetings favored the occurrence of satisfactory dialogical moments, in light of child language and related aspects, stimulating family attention and access to substantial information. Those involved considered the group intervention positive, which in turn should be continued and expanded in the city. The implementation of the "CD e F" group is a potential tool for family training and an alternative for speech therapy practice in Primary Health Care.

Inorganic polyphosphate's role in energy production and mitochondrial permeability transition pore opening in tick mitochondria.

Inorganic polyphosphate (polyP) is a biopolymer composed of phosphoanhydride-linked orthophosphate molecules. PolyP is engaged in a variety of cellular functions, including mitochondrial metabolism. Here, we examined the effects of polyP on electron transport chain enzymes and F1 Fo ATP synthase in tick embryos during embryonic development. The study found that polyPs containing medium and long chains (polyP15 and polyP65 ) enhanced the activity of complex I, complex II, complex III, and F1 Fo ATP synthase, while short polyP chains (polyP3 ) had no effect. The study also examined the activity of exopolyphosphatases (PPX) in various energy-demand situations. PPX activity was stimulated when ADP concentrations are high, characterizing a low-energy context. When complexes I-III and F1 Fo ATP synthase inhibitors were added in energized mitochondria, PPX activity decreased, whereas the mitochondrial uncoupler FCCP had no impact on PPX activity. Additionally, the study investigated the effect of polyP on mitochondrial swelling, finding that polyP causes mitochondrial swelling by increasing calcium effects on the mitochondrial permeability transition pore. The findings presented here to increase our understanding of the function of polyP in mitochondrial metabolism and its relationship to mitochondrial permeability transition pore opening in an arthropod model.

Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients.

Minimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS-MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10-6. MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD had poor agreement, with high rates of PET-CT negativity in MRD-positive patients. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the ability to measure deeper and sustainable responses distinguishes patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials.

Targeting DNA2 Overcomes Metabolic Reprogramming in Multiple Myeloma.

DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover novel mechanisms through which MM cells overcome DNA damage, we investigated how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting ILF2, a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo an adaptive metabolic rewiring and rely on oxidative phosphorylation to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identified the mitochondrial DNA repair protein DNA2, whose loss of function suppresses MM cells' ability to overcome ILF2 ASO-induced DNA damage, as being essential to counteracting oxidative DNA damage and maintaining mitochondrial respiration. Our study revealed a novel vulnerability of MM cells that have an increased demand for mitochondrial metabolism upon DNA damage activation. STATEMENT OF SIGNIFICANCE: Metabolic reprogramming is a mechanism through which cancer cells maintain survival and become resistant to DNA-damaging therapy. Here, we show that targeting DNA2 is synthetically lethal in myeloma cells that undergo metabolic adaptation and rely on oxidative phosphorylation to maintain survival after DNA damage activation.

Incidence and risk factors of pressure injuries in critically ill patients with COVID-19 / Incidencia y factores de riesgo de lesiones por presión en pacientes críticos con COVID-19 / Incidência e fatores de risco de lesão por pressão em pacientes críticos com COVID-19

ABSTRACT Objective: to analyze pressure injury (PI) incidence and risk factors in patients with COVID-19 admitted to an Intensive Care Unit and characterize the identified PIs. Method: a retrospective cohort study, consisting of 668 patients, carried out between March 2020 and February 2021. Clinical/demographic and PI variables were collected from medical records and electronic database. Data were analyzed using descriptive and inferential statistics. Logistic regression was performed to analyze risk factors for PI. Results: PI incidence was 30.2% (n=202), with the majority located in the sacral region (52.9%) and in stage 1 (39%). Risk factors were age (p<0.001), Diabetes Mellitus (p=0.005), length of stay (p<0.001), immunosuppression (p=0.034), nutritional risk (p=0.015) and mechanical ventilation (p<0.001). Conclusion: PI incidence in critically ill patients with COVID-19 was high.

RESUMEN Objetivo: analizar la incidencia y factores de riesgo de lesiones por presión (LP) en pacientes con COVID-19 ingresados en Unidad de Cuidados Intensivos y caracterizar las LP identificadas. Método: estudio de cohorte retrospectivo, compuesto por 668 pacientes, realizado entre marzo de 2020 y febrero de 2021. Las variables clínico/demográficas y de LP se recogieron de historias clínicas y bases de datos electrónicas. Los datos fueron analizados mediante estadística descriptiva e inferencial. Se realizó una regresión logística para analizar los factores de riesgo de LP. Resultados: la incidencia de LP fue del 30,2% (n=202), localizándose la mayoría en la región sacra (52,9%) y en estadio 1 (39%). Los factores de riesgo fueron edad (p<0,001), Diabetes Mellitus (p=0,005), tiempo de estancia hospitalaria (p<0,001), inmunosupresión (p=0,034), riesgo nutricional (p=0,015) y ventilación mecánica (p<0,001). Conclusión: la incidencia de LP en pacientes críticos con COVID-19 fue alta.

RESUMO Objetivo: analisar a incidência e os fatores de risco de lesão por pressão (LP) em pacientes com COVID-19 internados em Unidade de Terapia Intensiva e caracterizar as LP identificadas. Método: estudo de coorte retrospectivo, constituído por 668 pacientes, realizado entre março de 2020 e fevereiro de 2021. Variáveis clínicas/demográficas e das LP foram coletadas dos prontuários e banco de dados eletrônico. Os dados foram analisados por meio de estatística descritiva e inferencial. A regressão logística foi realizada para análise dos fatores de risco para LP. Resultados: a incidência de LP foi de 30,2% (n=202), sendo a maioria localizada na região sacral (52,9%) e em estágio 1 (39%). Os fatores de risco foram idade (p<0,001), Diabetes Mellitus (p=0,005), tempo de internação (p<0,001), imunossupressão (p=0,034), risco nutricional (p=0,015) e ventilação mecânica (p<0,001). Conclusão: a incidência de LP em pacientes críticos com COVID-19 foi alta.

Obstetric and neonatal adverse events and association with care models: a cohort study / Eventos adversos obstétricos y neonatales y asociación con modelos de atención: un estudio de cohorte / Eventos adversos obstétricos e neonatais e associação com os modelos de assistência: um estudo coorte

ABSTRACT Objective: to analyze the prevalence of practices in childbirth care, obstetric and neonatal adverse events and their association with care models in three public health services. Method: this is a prospective cohort study carried out with 548 dyads, postpartum women and their newborns, whose pregnancy was of usual risk and vaginal birth, admitted to hospital in three public services, one with an exclusive care model by nurse-midwives (service A), one with a collaborative model involving obstetric doctors and nurses (service B) and one with an exclusive medical care model (service C). Initially, an interview was carried out with participants, and a second contact was carried out 42 days after birth to complement the collection of the adverse event outcome. Results: in service A, no woman underwent the Kristeller maneuver, episiotomy, directed pushing or more than one vaginal examination per hour. Meanwhile, in service C, 19.3%, 39.9%, 77.1% and 26.3% of women underwent these interventions, respectively. Adverse events occurred in 19.2% of the dyads. Occurrence of adverse events was associated with not using partograph (p=0.001; OR: 11.03; CI: 2.64-45.99) and episiotomy (p=0.042; OR: 1.72; CI: 1. 02-2.91). The mean probability of experiencing an adverse event was 5% in service A, 21% in service B and 24% in service C. Conclusion: adverse events had a lower mean probability of occurrence in the service exclusively operated by nurse-midwives, in which greater application of recommendations for labor and birth care was identified.

RESUMEN Objetivo: analizar la prevalencia de prácticas en la atención del childbirth, eventos adversos obstétricos y neonatales y su asociación con los modelos de atención en tres servicios públicos de salud. Método: estudio de cohorte prospectivo realizado con 548 binomios, puérperas y sus recién nacidos, cuyo embarazo fue de riesgo habitual y childbirth vaginal, hospitalizados en tres servicios públicos, uno con modelo de atención exclusiva por enfermeras obstétricas (servicio A), otro con modelo colaborativo. modelo con la labor de médicos y enfermeras obstetras (servicio B) y otro con un modelo de asistencia médica exclusiva (servicio C). Inicialmente se realizó una entrevista a los participantes y se realizó un segundo contacto a los 42 días del nacimiento para complementar la recopilación del resultado del evento adverso. Resultados: en el servicio A ninguna mujer fue sometida a maniobra de Kristeller, episiotomía, pujo dirigido o más de un examen vaginal por hora. Mientras tanto, en el servicio C, el 19,3%, 39,9%, 77,1% y 26,3% de las mujeres se sometieron a estas intervenciones, respectivamente. Los eventos adversos ocurrieron en el 19,2% de los binomios. La aparición de eventos adversos se asoció con la no utilización del partographa (p=0,001; OR: 11,03; IC: 2,64-45,99) y episiotomía (p=0,042; OR: 1,72; IC: 1,02-2,91). La probabilidad promedio de experimentar un evento adverso fue del 5% en el servicio A, del 21% en el servicio B y del 24% en el servicio C. Conclusión: los eventos adversos tuvieron menor probabilidad promedio de ocurrencia en el servicio operado exclusivamente por enfermeras obstétricas, en el que se identificó mayor aplicación de las recomendaciones de asistencia al childbirth y nacimiento.

RESUMO Objetivo: analisar a prevalência de práticas na atenção ao parto, eventos adversos obstétricos e neonatais e sua associação com modelos assistenciais em três serviços de saúde públicos. Método: estudo coorte prospectivo realizado com 548 binômios, puérperas e seus recém-nascidos, cuja gestação foi de risco habitual e o parto vaginal, internados em três serviços públicos, sendo um com modelo de assistência exclusivo por enfermeiras obstetras (serviço A), um com modelo colaborativo com atuação de médicos e enfermeiras obstetras (serviço B) e um com modelo de assistência exclusiva médica (serviço C). Inicialmente, foi realizada uma entrevista com as participantes e um segundo contato foi realizado após 42 dias do parto para complementar a coleta do desfecho evento adverso. Resultados: no serviço A, nenhuma mulher foi submetida à manobra de Kristeller, episiotomia, incentivos a puxos dirigidos ou mais de um toque vaginal por hora. Enquanto, no serviço C, 19,3%, 39,9%, 77,1% e 26,3% das mulheres foram submetidas a essas intervenções, respectivamente. Os eventos adversos ocorreram em 19,2% dos binômios. A ocorrência dos eventos adversos foi associada ao não uso do partograma (p=0,001; OR: 11,03; IC: 2,64-45,99) e episiotomia (p=0,042; OR: 1,72; IC: 1,02-2,91). A probabilidade média de apresentar algum evento adverso foi de 5% no serviço A, 21% no serviço B e 24% no serviço C. Conclusão: os eventos adversos apresentaram menor probabilidade média de ocorrência no serviço com atuação exclusiva de enfermeiras obstetras, no qual se identificou maior aplicação das recomendações para assistência ao parto e nascimento.

Time trend of audiological procedures in the Brazilian Public Health System / Tendência temporal de procedimentos audiológicos no Sistema Único de Saúde

ABSTRACT Purpose: to analyze the time trend of audiological procedures in the Brazilian Public Health System (SUS) between 2008 and 2019 in the geographical regions of Brazil. Methods: a time series ecological study with data on audiological procedures from the SUS Outpatient Information System. The study calculated annual indices of audiological procedures with joinpoint regression for the trend analysis. The progress in the provision of procedures between the initial and final years in the series and the distribution of identified records was calculated. Results: altogether, 38,500,404 records were found in the study period. The South (178.84/10,000 inhabitants) and North of Brazil (130.97/10,000 inhabitants), respectively, had the highest and lowest mean procedure indices. Both were the only regions with a trend towards a significant increase in procedures. In Brazil, they increased by 56.91%, with an emphasis on the increase in "otoacoustic evoked emissions in neonatal hearing screening" and a decrease in "visual reinforcement audiometry (air/bone conduction)." In the distribution, procedures concentrated on basic audiological assessments. Conclusion: audiological procedures have increased at SUS, but there are discrepancies between procedures and geographical regions of Brazil.

RESUMO Objetivo: analisar a tendência temporal de procedimentos audiológicos no Sistema Único de Saúde (SUS), entre 2008 e 2019, nas regiões geográficas brasileiras. Métodos: estudo ecológico de série temporal, com dados de procedimentos audiológicos do Sistema de Informações Ambulatoriais do SUS. Foram calculadas taxas anuais de procedimentos audiológicos, utilizando-se a regressão Joinpoint para análise de tendência. Calculou-se a evolução da oferta destes procedimentos entre os anos inicial e final da série e a distribuição dos registros identificados. Resultados: foram localizados 38.500.404 registros no período investigado. Verificou-se que as regiões Sul (178,84/10.000 habitantes) e Norte (130,97/10.000 habitantes) apresentaram a maior e a menor taxa média de procedimentos, respectivamente. Ambas foram as únicas regiões que exibiram tendências de aumento significativo na realização dos procedimentos. No Brasil, a oferta dos procedimentos demonstrou uma evolução positiva de 56,91%, com destaque para crescimento de "emissões otoacústicas evocadas para triagem auditiva (teste da orelhinha)" e queda de "audiometria de reforço visual (via aérea/óssea)". Na distribuição, houve concentração de procedimentos da avaliação audiológica básica. Conclusão: a realização de procedimentos audiológicos no SUS revela aumento, mas evidencia discrepâncias nas regiões geográficas brasileiras e nos procedimentos executados.