Oxidation-sensitive cysteines drive IL-38 amyloid formation.

Interleukin (IL)-1 family cytokines are essential for host defense at epithelial barriers. The IL-1 family member IL-33 was recently linked to stress granules (SGs). Formation of SGs and other biomolecular condensates is promoted by proteins containing low-complexity regions (LCRs). Computational analysis predicts LCRs in six of the 11 IL-1 family members. Among these, IL-38 contains a long LCR including two amyloid cores. IL-38 localizes to intracellular granules in keratinocytes under oxidative stress (OS) and forms OS-induced amyloid aggregates in cells and in vitro. Interestingly, soluble and aggregated IL-38 are released from keratinocytes in an exosome-enriched extracellular vesicle fraction. Disulfide-bond mapping, in silico modeling, and mutational analysis suggest that oxidation-sensitive cysteines act as redox switches to alter IL-38 conformation and promote its aggregation. Finally, the presence of IL-38 granules in human epidermis facing environmental OS suggests that oxidation-induced amyloidogenesis, as an intrinsic property of IL-38, supports barrier function.

Accuracy of mitral annular plane systolic excursion in diagnosing anthracycline-induced subclinical cardiotoxicity in patients with breast cancer - a retrospective cohort study.

BACKGROUND: The mitral annular plane systolic excursion (MAPSE) is used to analyze the left ventricle longitudinal function. However, the accuracy of MAPSE in diagnosing oncological populations is unclear. In this study, we aimed to assess the accuracy of MAPSE in diagnosing subclinical cardiotoxicity in women with breast cancer undergoing anthracycline treatment. METHODS: This retrospective cohort study included echocardiographic assessments of patients with breast cancer who underwent anthracycline treatment as part of their therapeutic regimen. Assessments were performed before treatment, after administering the first dose of anthracycline, after completing anthracycline treatment, and 6 and 12 months after treatment. Left ventricular ejection fraction was calculated using the modified biplane Simpson method. The performances of MAPSE and global longitudinal strain (GLS) were analyzed using receiver operating characteristic (ROC) curves. Their accuracies were measured using the area under the ROC curves. RESULTS: Sixty-one patients were included in this study. Of them, 8.2% presented cardiotoxicity 6 months after treatment completion. Patients with cardiotoxicity had lower LVEF (47% vs. 63%; p < 0.001), MAPSE (10.23 mm vs. 12.25 mm; p = 0.012), and LV GLS (16.13% vs. 19.05%; p = 0.005) values than those without. A 12% reduction in the GLS exhibited sensitivity, specificity, and overall accuracy of 80%, 70%, and 78%, respectively. A relative reduction of 15% in MAPSE exhibited a sensitivity, specificity, and accuracy of 80%, 77%, and 81.2%, respectively. An absolute MAPSE reduction of 2 mm exhibited a sensitivity, specificity, and accuracy of 80%, 73.21%, and 81.2%, respectively. No differences were observed between the ROC curves. CONCLUSION: MAPSE showed similar accuracy to GLS in diagnosing subclinical cardiotoxicity in women with breast cancer undergoing anthracycline treatment.

Corrigendum: Increased neutrophil counts are associated with poor overall survival in patients with colorectal cancer: a five-year retrospective analysis.

[This corrects the article DOI: 10.3389/fimmu.2024.1415804.].

Molecular Markers for Analyses of Genetic Diversity within the Anastrepha fraterculus Complex with Emphasis on Argentine Populations.

The South American fruit fly Anastrepha fraterculus (Wiedmann) has a vast range extending from northern Mexico, through Central America, to South America where it is an extremely polyphagous pest of wild and cultivated fruits. It is a complex of cryptic species currently composed of eight recognised morphotypes: "Mexican", "Venezuelan", "Andean", "Peruvian", "Ecuadorian", and the three Brazilian morphotypes "Brazilian-1", "Brazilian-2", and "Brazilian-3". Molecular markers that can identify the member species of the complex are crucial for the implementation of effective pest control measures, such as the sterile insect technique. The object of this study was to evaluate the use of the internal transcribed spacer 2 (ITS2) sequence for discriminating several members of the A. fraterculus cryptic species complex (Mexican, Peruvian, and Brazilian-1) and a related species, Anastrepha schultzi Blanchard. The analysis highlighted significant genetic differentiation between the evaluated morphotypes, allowed their discrimination within the A. fraterculus cryptic species complex, and provided new insights into their genetic relationships. The ITS2 marker provides a basis for the development of taxonomic keys for the discrimination of the cryptic taxa within the A. fraterculus cryptic species complex. ITS2 also represents an important marker for the poorly studied species A. schultzi.

Alcohol Abuse and Physical Violence towards a Partner: How Can We Attenuate the Relationship? A Study on Emotional Dysregulation in Adolescents.

BACKGROUND: The previous literature has revealed the relationship between alcohol abuse and violent behaviours; however, the results are not always conclusive, highlighting the need to explore other variables that allow us to establish risk profiles. AIM: The goal is to examine whether the relation between alcohol abuse and physical violence towards a partner can be influenced (moderate) by difficulties in emotional regulation. SETTING: A public high school in Manabí (Ecuador). PARTICIPANTS: A total of 1519 high school students with ages between 14 and 18 years (mean = 15.77, SD = 1.22), with 54% (n = 820) being male. MAIN OUTCOME MEASURES: The measures we observed were alcohol abuse (i.e., frequency of alcohol abuse in the past 30 days), physical violence exercised towards a partner (Violence Received, Exercised and Perceived in Dating Relationships of Young People and Adolescents) and emotional dysregulation (Difficulties in Emotional Regulation Scale; DERS). RESULTS: It is observed that there exists significantly higher alcohol abuse in males, regardless of their age, as well as more physical violence by adolescent males towards their partners. Direct effects of alcohol abuse on physical intimate partner violence are observed in males from the age of 16 and in females from the age of 14. Moreover, the direct effects of different emotional dysregulation strategies on physical violence depend on gender. CONCLUSION: The moderating effects of emotional dysregulation strategies between alcohol abuse and physical intimate partner violence are observed only in the case of adolescent females (16-17 years). In particular, emotional dysregulation variables such as non-awareness, impulse, nonacceptance, or lack of strategies interfere as moderators in the relationship between excessive alcohol abuse and physical violence towards a partner. In the case of non-awareness, contrary to the other three, when scores are low or moderate, a statistically significant relationship between alcohol abuse and violence is observed.

MARRTA: Risk matrix in advanced radiotherapy.

PURPOSE: Proactive risk analyses identify potential risks before they occur, enabling us to pinpoint the most vulnerable aspects of our treatment process, thus promoting safer treatments. The proactive risk matrix methodology assesses the risk from potential errors and failures (initiating events) by evaluating and integrating their frequency, the severity of their potential consequences and the probability of failure of the barriers designed to prevent these consequences. Based on this methodology, the MARRTA project derived a theoretical risk model of advanced radiotherapy treatments and developed software to implement the model and facilitate the risk analysis. METHODS: A multidisciplinary team built the risk model by identifying initiating events in a generic advanced radiotherapy process, along with their preventive and mitigating barriers, categorized by nature and effectiveness. Each initiating event was assigned a frequency, a consequence, and the corresponding failure probability of the barriers in place. By integrating these three parameters, a calculated risk was associated to each given initiating event. This initial risk model was then incorporated into the developed software and distributed to 18 Spanish hospitals for testing. Feedback from these hospitals was used to refine and update the model and software. RESULTS: The final risk model (reference risk model) identifies 110 potential initiating events, 60 barriers, 54 frequency reducers and 13 consequence reducers. CONCLUSIONS: The MARRTA model and software provide a novel means to easily apply the risk matrix methodology for comprehensive and straightforward risk analysis, as it allows the reference model to be customized to the specific features of each radiotherapy department.

Increased neutrophil counts are associated with poor overall survival in patients with colorectal cancer: a five-year retrospective analysis.

Background: Colorectal cancer (CRC) continues to be a major health concern in today's world. Despite conflictive findings, evidence supports systemic inflammation's impact on CRC patients' survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC. Method: A total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured. Results: The non-survival group had increased levels of white blood cells, neutrophils (both p<0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (ß=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05]. Conclusion: This study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools.

Comparison of postoperative outcomes between different dissection techniques during laparoscopic cholecystectomy in rabbits: randomized study.

PURPOSE: Laparoscopic cholecystectomy (LC) is the gold standard for the treatment of gallbladder (GB) disease in small animals. The aims of this study were to investigate and compare the effect of different types of dissectors during LC in rabbits; electrothermal bipolar vessel sealing device (EBVS-LigaSure) and standard electrosurgical dissection (bipolar Maryland) for dissection of the GB in LC, correlating liver function tests (LFTs) in pre and postoperative periods (days 0, 3, 7, 15); macroscopic checking 15 days after surgery through necropsy; histopathological, bacteriological through bacterial growth by culture and intraoperative complications. METHODS: Twenty rabbits were used, group (n = 10) using EBVS for GB dissection and cystic duct seal (GLL), and group (n = 10) using bipolar dissecting forceps and EVBS for cystic duct seal (GLE). RESULTS: A higher concentration of alkaline phosphatase was observed on GLL 15 days after surgery when compared to GLE. In addition, GLE resulted in a higher concentration of alanine aminotransferase at three days when compared to GLL. CONCLUSION: In LC no significant statistical differences were found between EBVS and bipolar Maryland; both devices are equally safe and effective in LC. Further studies are required to evaluate the effectiveness of these devices in animals with gallbladder pathologies. Therefore, clinical studies are necessary.

Intraparenchymal low-grade B-cell lymphomas of the central nervous system: Clinicopathologic and molecular analysis of three cases and a review of the literature.

Primary central nervous system (CNS) lymphomas represent 1 % of all non-Hodgkin lymphomas, with diffuse large B-cell lymphomas as the prevailing subtype. Low-grade B-cell lymphomas are exceptional with only 24 marginal zone B-cell lymphomas (EMZL) and 1 follicular lymphoma (FL) previously reported so far. While their molecular profiles are studied elsewhere, data on primary intraparenchymal CNS cases remain limited. The objective of the present study is to contribute new cases of primary intraprenchymal low-grade B-cell lymphomas in the CNS and characterize their mutational profile. We conducted a comprehensive review of cases and a literature review to identify similar instances. Clinical, imaging, histological, immunohistochemical, and molecular characteristics were analyzed. Diagnoses were established according to established criteria. We present three novel cases of intraparenchymal CNS low-grade B-cell lymphomas. One case of intraparenchymal EMZL exhibited plasmacytic differentiation, while another lacked a plasma cell component. The third case was diagnosed as FL. The L265P mutation of MYD88 was absent in all cases. Next generation sequencing revealed pathogenic mutations in SPEN (Glu1970ValfsTer64) and ARID1A (Pro1355LeufsTer118) genes in one EMZL case. In conclusion, intraparenchymal CNS low-grade B-cell lymphomas are rare, with few reported cases. Our findings expand knowledge on their clinical and molecular features. We present the first molecular profile of primary CNS intraparenchymal EMZL, underscoring the need for further research to understand their biology and optimize treatment strategies.

EDC-3 and EDC-4 regulate embryonic mRNA clearance and biomolecular condensate specialization.

Animal development is dictated by the selective and timely decay of mRNAs in developmental transitions, but the impact of mRNA decapping scaffold proteins in development is unclear. This study unveils the roles and interactions of the DCAP-2 decapping scaffolds EDC-3 and EDC-4 in the embryonic development of C. elegans. EDC-3 facilitates the timely removal of specific embryonic mRNAs, including cgh-1, car-1, and ifet-1 by reducing their expression and preventing excessive accumulation of DCAP-2 condensates in somatic cells. We further uncover a role for EDC-3 in defining the boundaries between P bodies, germ granules, and stress granules. Finally, we show that EDC-4 counteracts EDC-3 and engenders the assembly of DCAP-2 with the GID (CTLH) complex, a ubiquitin ligase involved in maternal-to-zygotic transition (MZT). Our findings support a model where multiple RNA decay mechanisms temporally clear maternal and zygotic mRNAs throughout embryonic development.

Blackcurrant (Ribes nigrum L.) improves cholinergic signaling and protects against chronic Scopolamine-induced memory impairment in mice.

BACKGROUND: Blackcurrant (Ribes nigrum L.) is a berry rich in anthocyanins, bioactive compounds known for their antioxidant and neuroprotective properties that benefit human health. AIMS: This study aimed to investigate the effects of blackcurrant and its association with Donepezil on memory impairment, cholinergic neurotransmission, and antioxidant systems in a mouse model of amnesia induced by chronic administration of Scopolamine. METHODS: Adult male Swiss mice were given saline, blackcurrant (50 mg/kg, orally), and/or Donepezil (5 mg/kg, orally) and/or Scopolamine (1 mg/kg, intraperitoneally). RESULTS: Behavioral tests revealed that blackcurrant and/or Donepezil prevented the learning and memory deficits induced by Scopolamine. In the cerebral cortex and hippocampus, blackcurrant and/or Donepezil treatments prevented the increase in acetylcholinesterase and butyrylcholinesterase activities induced by Scopolamine. Scopolamine also disrupted the glutathione redox system and increased levels of reactive species; nevertheless, blackcurrant and/or Donepezil treatments were able to prevent oxidative stress. Furthermore, these treatments prevented the increase in gene expression and protein density of acetylcholinesterase and the decrease in gene expression of the choline acetyltransferase enzyme induced by Scopolamine. CONCLUSIONS: Findings suggest that blackcurrant and Donepezil, either alone or in combination, have anti-amnesic effects by modulating cholinergic system enzymes and improving the redox profile. Therefore, blackcurrant could be used as a natural supplement for the prevention and treatment of memory impairment in neurodegenerative diseases.

Cognitive behavioral therapy for insomnia in people with chronic musculoskeletal pain. A systematic review and dose-response meta-analysis.

The aims were (i) to determine the effects of Cognitive behavioral therapy for insomnia (CBT-I) on sleep disturbances, pain intensity and disability in patients with chronic musculoskeletal pain (CMP), and (ii) to determine the dose-response association between CBT-I dose (total minutes) and improvements in sleep disorders, pain intensity and disability in patients with CMP. A comprehensive search was conducted in PubMed/MEDLINE, Web of Science, CINAHL, and SCOPUS until December 17, 2023. Randomized clinical trials (RCTs) using CBT-I without co-interventions in people with CMP and sleep disorders were eligible. Two reviewers independently extracted data and assessed risk of bias and certainty of the evidence. A random effects meta-analysis was applied to determine the effects on the variables of interest. The dose-response association was assessed using a restricted cubic spline model. Eleven RCTs (n = 1801 participants) were included. We found a significant effect in favor of CBT-I for insomnia (SMD: -1.34; 95%CI: -2.12 to -0.56), with a peak effect size at 450 min of CBT-I (-1.65, 95%CI: -1.89 to -1.40). A non-significant effect was found for pain intensity. A meta-analysis of disability was not possible due to the lack of data. This review found benefits of CBT-I for insomnia compared to control interventions, with a large effect size. In addition, it was estimated that a 250-min dose of CBT-I had a large effect on reducing insomnia and that the peak effect was reached at 450 min. These novel findings may guide clinicians in optimizing the use of CBT-I in people with CMP and insomnia.

Profile and experiences during the incarceration of transgender women and travestis (TGW) in Brazil: a cross-sectional study.

OBJECTIVE: The objective of the present study is to describe the sociodemographic and behavioral characteristics of a group of transgender women and travestis (TGW) with a history of incarceration and the institutional and social context of this experience in Brazil. METHODS: The analyzed data were derived from the TransOdara Study, a cross-sectional study conducted in five Brazilian capitals from December 2019 to July 2021. Participants were recruited using the Respondent-Driven Sampling (RDS) technique, in which, after an initial formative and exploratory stage, the first participants were identified; in turn, these participants recruited up to six other transgender women and travestis for the research. The study's outcome was the experience of incarceration throughout life, captured through the question: "Have you ever been arrested in your life?" RESULTS: A total of 1,245 TGW were interviewed, of which 20.3% (n=253) experienced incarceration. Incarceration was more frequent among those aged 33 to 42 years (35.6%), with lower level of education (45.5%, p<0.001), engaged in informal work (30.3%), without a partner (67.2%), and among those who reported illicit drug use (66.4%). The majority (60.9%) of TGW were incarcerated with cisgender men, and the most common reasons for imprisonment were drug trafficking (30.4%) followed by robbery (29.2%). Over a quarter of the interviewees (26.3%) experienced assault, and 13.8% reported experiencing sexual violence during incarceration. CONCLUSION: The results emphasize the high prevalence of incarceration among TGW. This incarceration takes place in male wards and in a context of high rates of physical and sexual violence.

Substance Use and Its Relationship With Attachment and Early Maladaptive Schemes in Adolescents in Ecuador.

Given the scarcity of studies addressing substance consumption and its relationship with attachment styles and early maladaptive schemas in adolescents, the present study is proposed. Aims of this study are to analyze the relationship among attachment styles, early maladaptive schemas, and substance use; test the predictive role of attachment styles on substance use; and observe the mediating role of early maladaptive schemas in the relationship between attachment and substance use. The sample consisted of 1533 adolescents from Ecuador (53.9% males) aged between 14 and 18 years (M = 15.76; SD = 1.25). The attachment styles of security, value to parental authority, parental permissiveness, parental interference, self-sufficiency and resentment against parents, childhood trauma, and family concern predict substance use (tobacco, alcohol, tranquilizers/sedatives or sleeping pills, hashish or marijuana, cocaine, GHB or liquid ecstasy, ecstasy, amphetamines/speed, hallucinogens, heroin, inhalants/volatiles), and the mediating role of early maladaptive schemas is confirmed (explained variance up to 33.33%). Identifying risk or vulnerability factors, such as attachment and early maladaptive schemas related to substance consumption, is especially relevant for designing and implementing preventive interventions in the adolescent population.

Neuroprotective effect of long-term resistance physical exercise against memory damage elicited by a lipopolysaccharide-induced neuroinflammation model in male rats.

Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.

Impact of Lowering TSH Cut-Off on Neonatal Screening for Congenital Hypothyroidism in Minas Gerais, Brazil.

A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV.

Characterization of Herpesviridae Family Members, BK Virus, and Adenovirus in Children and Adolescents with Nephrotic Syndrome.

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. METHODS: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. RESULTS: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133-595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. CONCLUSION: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children.

CCL2 and Lactate from Chemotherapeutics-Treated Fibroblasts Drive Malignant Traits by Metabolic Rewiring in Low-Migrating Breast Cancer Cell Lines.

While cytostatic chemotherapy targeting DNA is known to induce genotoxicity, leading to cell cycle arrest and cytokine secretion, the impact of these drugs on fibroblast-epithelial cancer cell communication and metabolism remains understudied. Our research focused on human breast fibroblast RMF-621 exposed to nonlethal concentrations of cisplatin and doxorubicin, revealing reduced proliferation, diminished basal and maximal mitochondrial respirations, heightened mitochondrial ROS and lactate production, and elevated MCT4 protein levels. Interestingly, RMF-621 cells enhanced glucose uptake, promoting lactate export. Breast cancer cells MCF-7 exposed to conditioned media (CM) from drug-treated stromal RMF-621 cells increased MCT1 protein levels, lactate-driven mitochondrial respiration, and a significantly high mitochondrial spare capacity for lactate. These changes occurred alongside altered mitochondrial respiration, mitochondrial membrane potential, and superoxide levels. Furthermore, CM with doxorubicin and cisplatin increased migratory capacity in MCF-7 cells, which was inhibited by MCT1 (BAY-8002), glutamate dehydrogenase (EGCG), mitochondrial pyruvate carrier (UK5099), and complex I (rotenone) inhibitors. A similar behavior was observed in T47-D and ZR-75-1 breast cancer cells. This suggests that CM induces metabolic rewiring involving elevated lactate uptake to sustain mitochondrial bioenergetics during migration. Treatment with the mitochondrial-targeting antioxidant mitoTEMPO in RMF-621 and the addition of an anti-CCL2 antibody in the CM prevented the promigratory MCF-7 phenotype. Similar effects were observed in THP1 monocyte cells, where CM increased monocyte recruitment. We propose that nonlethal concentrations of DNA-damaging drugs induce changes in the cellular environment favoring a promalignant state dependent on mitochondrial bioenergetics.

Consumption of antimicrobials during the period of the COVID-19 pandemic in specific macro-regions of Brazil / Consumo de antimicrobianos durante o período de pandemia de COVID-19 em macrorregiões específicas do Brasil / Consumo de antimicrobianos durante el período de la pandemia de COVID-19 en macrorregiones específicas de Brasil

Background and Objectives: The main objective was to analyze the consumption of antimicrobials (ATMs) subjected to prescription retention, and with indication for the treatment of respiratory infections in Brazil, from 2014 to 2021. Methods: This is an ecological study of mixed design. Secondary data was obtained from the National System for the Management of Controlled Products (SNGPC). Data was presented following the equation: number of total consumption of ATMs for each macro-region of Brazil by year or trimester / number of residents for each macro-region per year *1.000 inhabitants. Annual data was analyzed by Prais-Winsten, and quarterly data was analyzed by automatic forward stepwise regression. Results: The Southern region showed the highest mean rates of consumption when compared to the other macro-regions. For annual analysis, the proportion of stability, increase and decrease of consumption of ATMs was similar among macro-regions. The quarterly period registered an increase in the consumption of Amoxicillin, Amoxicillin+Clavulanate, Azithromycin and Cephalexin altogether, in the Southern, Southeastern and Northern regions. Conclusion: Our data reveals an increased consumption of some ATMs during the pandemic period in specific macro-regions of Brazil. The five macro regions have shown different patterns of ATMs consumption.(AU)

Justificativa e Objetivos: O objetivo principal foi analisar o consumo de antimicrobianos (ATMs) sujeito a retenção de receita e com indicações para tratamento de infecções respiratórias no Brasil de 2014 até 2021. Métodos: Trata-se de um estudo ecológico de desenho misto. Dados secundários foram obtidos do Sistema Nacional de Gerenciamento de Produtos Controlados (SNGPC). Dados foram apresentados conforme a seguinte equação: número total de consumo de ATMs por cada macrorregião do Brasil por ano ou trimestre/ número de residentes por cada macrorregião do Brasil por ano *1.000 habitantes. Dados anuais foram por Prais-Winsten, e dados trimestrais por regressão automática passo-a-passo. Resultados: Região Sul apresentou maiores taxas médias de consumo em comparação às demais macrorregiões. Para análise anual, a proporção de estabilidade, aumento e diminuição dos ATMs foi similar entre as macrorregiões. O trimestre registrou aumento no consumo de Amoxicilina, Amoxicilina+Clavulanato, Azitromicina e Cefalexina, juntas, nas regiões Sul, Sudeste e Norte. Conclusão: Nossos dados revelam um aumento no consumo de alguns ATMs durante o período de pandemia em macrorregiões específicas do Brasil, as cinco macrorregiões apresentaram padrões diferentes de consumo de ATMs.(AU)

Justificación y Objetivos: El objetivo principal fue analizar el consumo de antimicrobianos (ATMs) sujetos a retención de ingresos con indicaciones para el tratamiento de infecciones respiratorias en Brasil de 2014 a 2021. Métodos: Se trata de un estudio ecológico de diseño mixto. Datos secundarios obtenidos del Sistema Nacional de Gestión de Productos Controlados (SNGPC). Los datos fueron presentados siguiendo la ecuación: número de consumo total de cajeros automáticos para cada macro región de Brasil por año o trimestre / número de residentes para cada macro región por año *1.000 habitantes. Los datos anuales fueron analizados por Prais-Winsten, y trimestralmente analizados por regresión paso a paso automática hacia adelante. Resultados: La región Sur mostró las mayores tasas medias de consumo en comparación con las demás macrorregiones. Para el análisis anual, la proporción de estabilidad, aumento y disminución de ATMs fue similar entre las macrorregiones. En el trimestre se registró aumento en el consumo de Amoxicilina, Amoxicilina+Clavulanato, Azitromicina y Cefalexina, en conjunto, en las regiones Sur, Sudeste y Norte. Conclusión: Nuestros datos revelan un mayor consumo de algunos ATMs durante el período de la pandemia en macro regiones específicas de Brasil, las cinco macro regiones han mostrado diferentes patrones de consumo de ATMs.(AU)