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Gastric cancer (GC) is a leading cause of cancer-related deaths globally. It is a multifactorial, molecularly heterogeneous disease whose carcinogenic patterns are not yet well established, requiring the development of new tools for better understanding and identifying gastric carcinogenesis. From this point of view, this study aims to compare transcriptome profiles from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) and a human-merged dataset to identify potential biomarkers and therapeutic targets. Principal component analysis (PCA) revealed shared and distinct gene expression patterns between datasets. Differential expression analysis identified key genes with altered expression across non-malignant and malignant samples. Six genes, including SERPINE1 and CLDN9, were significantly associated with patient survival. The findings underscore the molecular diversity of GC and highlight novel biomarkers for early diagnosis and therapeutic strategies. Further validation in clinical specimens is necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Gastric cancer (GC) is a common cancer worldwide. Therefore, searching for effective treatments is essential, and drug repositioning can be a promising strategy to find new potential drugs for GC therapy. For the first time, we sought to identify molecular alterations and validate new mechanisms related to Mebendazole (MBZ) treatment in GC cells through transcriptome analysis using microarray technology. Data revealed 1066 differentially expressed genes (DEGs), of which 345 (2.41 %) genes were upregulated, 721 (5.04 %) genes were downregulated, and 13,231 (92.54 %) genes remained unaltered after MBZ exposure. The overexpressed genes identified were CCL2, IL1A, and CDKN1A. In contrast, the H3C7, H3C11, and H1-5 were the top 3 underexpressed genes. Gene set enrichment analysis (GSEA) identified 8 pathways significantly overexpressed in the treated group (p < 0.05 and FDR<0.25). The validation of the expression of top desregulated genes by RT-qPCR confirmed the transcriptome results, where MBZ increased the CCL2, IL1A, and CDKN1A and reduced the H3C7, H3C11, and H1-5 transcript levels. Expression analysis in samples from TCGA databases correlated that the lower ILI1A and higher H3C11 and H1-5 gene expression are associated with decreased overall survival rates in patients with GC, indicating that MBZ treatment can improve the prognosis of patients. Thus, the data demonstrated that the drug MBZ alters the transcriptome of the AGP-01 lineage, mainly modulating the expression of histone proteins and inflammatory cytokines, indicating a possible epigenetic and immunological effect on tumor cells, these findings highlight new mechanisms of action related to MBZ treatment. Additional studies are still needed to better clarify the epigenetic and immune mechanism of MBZ in the therapy of GC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Antihypertensives (AHD) can influence cerebral autoregulation (CA) and attenuate hypertrophic concentric remodelling of arterioles. The aim of this study was to examine the associations between AHD, CA and structural and functional properties of cerebral arteries., Methods: In this observational, cross-sectional study 115 volunteers were divided in group 1 (non-hypertensive) [n = 30]; group 2 (hypertensive with systolic blood pressure [SBP] < 140 and diastolic blood pressure [DBP] < 90 mmHg) [n = 54]; group 3 (hypertensive with SBP ≥ 140 or DBP ≥ 90 mmHg) [n = 31] and simultaneous measurements of systemic blood pressure (BP) and middle cerebral artery blood flow velocity (CBFV) were obtained from digital plethysmography and transcranial Doppler. Beat-to-beat, critical closing pressure (CrCP), resistance-area product (RAP) and autoregulation index (ARI) values were extracted by linear regression analysis of instantaneous BP and CBFV waveforms using computerised analysis. Pulsatility index (PI) was calculated and CO 2 reactivity was assessed by the breath-holding test., Results: Despite their higher RAP (1.7 [±0.7], p < 0.001) compared to groups 1 and 2, uncontrolled hypertensive using diuretics (p = 0.047) and α2-agonists (p = 0.009) had significantly lower PI. Impaired CO 2 reactivity was common between the two hypertensive groups (p = 0.008), however ARI, CrCP and CBFV did not differ between them and non-hypertensive individuals and also did not correlate with any AHD used., Conclusions: Unlike the RAP, PI does not seem to reflect the real cerebrovascular resistence resulting from chronic arterial remodelling. Despite impaired CO 2 reactivity, hypertensive have arterial tonus and CA comparable to non-hypertensive. Experimental studies involving an untreated hypertensive control group are required to robustly make definitive conclusions about these questions., (© 2024 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Background: It has been established that concurrent ST-T alterations in limb leads can assist in identifying the location of left anterior descending (LAD) artery occlusion. The de Winter pattern is an atypical electrocardiographic manifestation characterized by ST-segment depression associated with LAD artery occlusion. We hypothesized that this atypical pattern could potentially interfere with the accurate localization of the LAD occlusion site on the electrocardiogram. We aimed to describe the distinctive characteristics of the de Winter pattern and to compare electrocardiographic variables in proximal and distal occlusions of the LAD artery., Methods: A systematic review was conducted using the PRISMA guidelines. PubMed, Scopus, and Web of Science were searched from their inception to June 2024. Continuous variables were compared using the Kruskal-Wallis test., Results: Sixty-six cases with LAD related lesions were included. The majority of cases involved young males with a low proportion of prior coronary artery disease. Most patients had sinus rhythm and normal QRS duration. ST-T changes in limb leads were common in the patients studied (91%), but our analysis showed that differentiating between proximal and distal occlusions based on these changes was challenging., Conclusion: The de Winter pattern is primarily observed in young males with a low proportion of prior coronary artery disease. While ST-T changes in limb leads are frequent, localizing the LAD occlusion site based on these changes can be difficult. Further research is needed to understand the underlying mechanisms, prevalence, and improve diagnostic accuracy for this atypical pattern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To evaluate whether the presence of proteinuria, although no longer mandatory in the revised diagnostic criteria, results in worse maternal and fetal outcomes in preeclampsia (PE). A retrospective cohort study was conducted, analyzing data from pregnant patients diagnosed with PE between January 2015 and December 2019 at a tertiary care center in Brazil. Ethical approval was obtained, and the patient records were reviewed to assess maternal and perinatal outcomes based on the revised diagnostic criteria by the College of Obstetricians and Gynecologists, focusing on the presence or absence of proteinuria. The study included 816 pregnant patients with PE, of whom 685 (83.9%) were diagnosed based on proteinuria. The revised criteria, which include indicators of organ damage, identified an additional 131 cases (16.4%). Analysis showed no significant differences in maternal outcomes between proteinuria and non-proteinuria groups, including intensive care unit (ICU) admission, acute pulmonary edema (APE), HELLP syndrome, eclampsia, or C-section rates. However, babies born to mothers with proteinuria PE experienced worse outcomes, including fetal growth restriction, low birth weight, ICU admission, and higher rates of preterm birth. Relative risk analysis demonstrated a high risk of babies being born with low birth weight, ICU admission, and being born preterm and very preterm in cases where proteinuria was present in mothers with PE. The presence of proteinuria is associated with significantly worse outcomes in babies born to mothers with preeclampsia, while no significant differences were observed in maternal outcomes., (© 2024 International Federation of Gynecology and Obstetrics.)

Background/aim: SARS-CoV-2 infection presents different severity levels that suggest the influence of genetic factors on the clinical outcome of the disease. In cases of severe COVID-19, the presence of elevated coagulation markers, increased platelet activation and aggregation and the risk of thrombotic complications are described. Given the participation of these cells in several serious viral infections and their negative role when associated with a prothrombotic response, it is important to understand the mechanistic role of SARS-CoV-2 in platelet physiology. This study evaluated the hyperexpression of platelet-activating factor receptor (PTAFR) and platelet factor 4 (PF4) in unvaccinated and hospitalized patients with COVID-19., Patients and Methods: The study included 43 COVID-19 patients stratified according to WHO guidelines. Subsequently, the expression of the PTAFR and PF4 genes were evaluated using the real-time quantitative PCR and their possible correlation with the severity of the disease and clinical variables including hospitalization, outcome, sex, age and laboratory parameters (platelet count, INR and D-dimer)., Results: The analysis demonstrated a significant (p<0.05) hyperexpression of these genes COVID-19 patients (n=43) compared to healthy controls. Expression of these genes in patients was not statistically significant (p>0.05) different between patients stratified according to clinical variables., Conclusion: The expression of PTAFR and PF4 suggests an important molecular pathway in the pathophysiology of the disease and may be valuable platelet biomarkers to indicate increased risk in patients with COVID-19 who require hospital care, contributing to personalized intervention strategies and improving their clinical management., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded protein response (UPR), which can either restore cellular homeostasis or induce cell death. Melatonin, a safe and multifunctional compound, shows promise in controlling ER stress and could be a valuable therapeutic agent for managing the UPR. By regulating ER and mitochondrial functions, melatonin helps maintain cellular homeostasis via reduction of oxidative stress, inflammation, and apoptosis. Melatonin can directly or indirectly interfere with ER-associated sensors and downstream targets of the UPR, impacting cell death, autophagy, inflammation, molecular repair, among others. Crucially, this review explores the mechanistic role of melatonin on ER stress in various diseases including liver damage, neurodegeneration, reproductive disorders, pulmonary disease, cardiomyopathy, insulin resistance, renal dysfunction, and cancer. Interestingly, while it alleviates the burden of ER stress in most pathological contexts, it can paradoxically stimulate ER stress in cancer cells, highlighting its intricate involvement in cellular homeostasis. With numerous successful studies using in vivo and in vitro models, the continuation of clinical trials is imperative to fully explore melatonin's therapeutic potential in these conditions., (© 2024 Wiley Periodicals LLC.)

Background: Talented athletes exhibit remarkable skills and performance in their respective sports, setting them apart from their peers. It has been observed that genetic polymorphisms can influence variations in sports performance, leading to numerous studies aimed at validating genetic markers for identifying sports talents. This study aims to evaluate the potential contribution of genetic factors associated with athletic performance predisposition in identifying sports talents., Methods: A systematic review was conducted following the PRISMA framework, utilizing the PICO methodology to develop the research question. The search was limited to case-control studies published between 2003 and June 2024, and databases such as Medline, LILACS, WPRIM, IBECS, CUMED, VETINDEX, Web of Science, Science Direct, Scopus and Scielo were utilized. The STREGA tool was employed to assess the quality of the selected studies., Results: A total of 1,132 articles were initially identified, of which 119 studies were included in the review. Within these studies, 50 genes and 94 polymorphisms were identified, showing associations with sports talent characteristics such as endurance, strength, power, and speed. The most frequently mentioned genes were ACTN3 (27.0%) and ACE (11.3%)., Conclusion: The ACE I/D and ACTN3 R577X polymorphisms are frequently discussed in the literature. Although athletic performance may be influenced by different genetic polymorphisms, limitations exist in associating them with athletic performance across certain genotypes and phenotypes. Future research is suggested to investigate the influence of polymorphisms in elite athletes from diverse backgrounds and sports disciplines., (© 2024. The Author(s).)

In honey bees, appetitive motivation is primarily driven by the needs of the colony rather than individual needs. The regulation of appetitive behavior is achieved through the coordinated action of neuropeptides, hormones and biogenic amines, which integrate multiple signals to ensure appropriate appetitive responses. Dopamine signalling underpins a food-related wanting system that is sensitive to aversive experiences. The short neuropeptide F (sNPF) enhances appetitive responsiveness, food intake and behavioral and neural responsiveness to food-related odorants. Additionally, it facilitates appetitive learning and memory. On the contrary, tachykinin-related peptides (TRPs) inhibit appetitive responses. Physiological changes during the transition to the foraging state lead to distinct patterns of insulin and adipokinetic hormone (AKH) signaling, different from those seen in solitary insects, indicating that social life had significant consequences on the systems controlling appetitive motivation. Overall, studying the neural bases of appetitive behavior in bees reveals unique aspects that arise from their social lifestyle., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors have no conflicts of interest to declare.

Rationale: Despite the existing anatomical and physiological evidence pointing to the involvement of orexinergic projections from the lateral hypothalamus (LH) in regulating fear-related responses, little is known regarding the contribution of the orexin system in the prelimbic cortex (PL) on contextual fear., Objectives: We investigated the role of orexin-A (Orx A ) and orexin type 1 receptors (Orx 1 R) in the PL during the expression of contextual conditioned fear in mice., Methods: Neural tract tracing of the LH-PL pathway and Orx 1 R immunoreactivity in the PL of C57BL/6 male mice were performed. In a pharmacological approach, the animals were treated with either the Orx 1 R selective antagonist SB 334,867 (3, 30, and 300 nM/0.1 µL) or Orx A (28, 70, and 140 pmol/0.1 µL) in the PL before the test session of contextual fear conditioning., Results: Neural tract tracing deposits in the LH showed some perikarya, mainly axons and terminal buttons in the PL, suggesting LH-PL reciprocate pathways. Furthermore, we showed a profuse network comprised of Orx 1 R-labeled thin varicose fibers widely distributed in the same field of LH-PL pathways projection. The selective blockade of Orx 1 R with SB 334,867 at 30 and 300 nM in the PL caused a decrease in freezing response, whereas the treatment with Orx A at 140 pmol promoted an increase in freezing response., Conclusion: In summary, these data confirmed an anatomical link between LH and PL, established the presence of Orx 1 R in the PL, and a modulatory role of the orexin system in such structure, possibly mainly via Orx 1 R, during contextual fear conditioning., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The dorsal midbrain comprises dorsal columns of the periaqueductal grey matter and corpora quadrigemina. These structures are rich in beta-endorphinergic and leu-enkephalinergic neurons and receive GABAergic inputs from substantia nigra pars reticulata. Although the inferior colliculus (IC) is mainly involved in the acoustic pathways, the electrical and chemical stimulation of central and pericentral nuclei of the IC elicits a vigorous defensive behaviour. The defensive immobility and escape elicited by IC activation is commonly related to panic-like emotional states. To investigate the role of κ-opioid receptor of the IC in the antiaversive effects of endogenous opioid receptor blockade in a dangerous situation, male Wistar rats were pretreated in the IC with the κ-opioid receptor-selective antagonist nor-binaltorphimine at different concentrations and submitted to the non-enriched polygonal arena for a snake panic test in the presence of a rattlesnake and, after 24 h, prey were resubmitted to the experimental context. The snakes elicited in prey a set of antipredatory behaviours, such as the anxiety-like responses of defensive attention and risk assessment, and the panic-like reactions of defensive immobility and either escape or active avoidance during the elaboration of unconditioned and conditioned fear-related responses. Pretreatment of the IC with microinjections of nor-binaltorphimine at higher concentrations significantly decreased the frequency and duration of both anxiety- and panic-attack-like behaviours. These findings suggest that κ-opioid receptor blockade in the IC causes anxiolytic- and panicolytic-like responses in threatening conditions, and that kappa-opioid receptor-selective antagonists can be a putative coadjutant treatment for panic syndrome treatment.

The mixture of pesticides is widely employed in cattle farming to combat ectoparasite resistance, such as ticks. The commercial formulation COLOSSO FC30, which contains three active ingredients (Cypermethrin, Chlorpyrifos, and Fenthion), stands out due to its efficiency. However, animals exposed to this product may become vectors of potentially toxic molecules, possibly causing contamination in aquatic and terrestrial ecosystems. In light of this, this study evaluated the eco(geno)toxic potential of the commercial formulation COLOSSO FC30, using plants (Allium cepa L., Lactuca sativa L., Raphanus sativus L., Pennisetum glaucum L., and Triticum aestivum L.) and Artemia salina L. as model organisms. In the phytotoxicity test, the species were ranked in order of sensitivity to the commercial formulation as follows: P. glaucum > L. sativa > T. aestivum > R. sativus. The most sensitive parameters were root length (RL) and shoot length (SL) of seedlings. In the cytogenotoxicity test with A. cepa, cell division was decreased at concentrations from 0.351 mL L -1 in the meristematic region and root F1. Chromosomal aberrations and micronucleus were observed at all concentrations. In the test with A. salina, the IC 50 after 24 h of exposure was 0.01207 mL L -1 of the commercial formulation. The results highlight the need for further research and regulations to understand and minimize the potential environmental impacts of COLOSSO FC30., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2-9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO 2 (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively. Neonatal exposure to LBN increased panic-like jumping during the CO 2 challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic-inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg -1 i.p.) whilst tolerance to the close proximity of the aversive robo-beetle increased. The anxiolytic diazepam (1 mg.kg -1  i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro-panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex-specific increase in susceptibility to panic-like behaviour in adulthood. Whilst non-respiratory-related panic-like behaviour was enhanced in both sexes, females were resilient to respiratory-related challenges., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Introduction: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes., Patients and Methods: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics., Results: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049)., Conclusions: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort., Competing Interests: Disclosure Dr. Gustavo Werutsky reports personal fees from AstraZeneca, Bayer, Beigene, Daiichi Sankyo, Genentech/Roche, GSK, Lilly, MSD, Novartis, Pfizer, Sanofi, and Seattle Genetics outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ovarian cancer (OC) adjusts energy metabolism in favor of its progression and dissemination. Because melatonin (Mel) has antitumor actions, we investigated its impact on energy metabolism and kinase signaling in OC cells (SKOV-3 and CAISMOV-24). Cells were divided into control and Mel-treated groups, in the presence or absence of the antagonist luzindole. There was a decrease in the levels of HIF-1α, G6PDH, GAPDH, PDH, and CS after Mel treatment even in the presence of luzindole in both OC cells. Mel treatment also reduced the activity of OC-related enzymes including PFK-1, G6PDH, LDH, CS, and GS whereas PDH activity was increased. Lactate and glutamine levels dropped after Mel treatment. Mel further promoted a reduction in the concentrations of CREB, JNK, NF-kB, p-38, ERK1/2, AKT, P70S6K, and STAT in both cell lines. Mel reverses Warburg-type metabolism and possibly reduces glutaminolysis, thereby attenuating various oncogenic molecules associated with OC progression and invasion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In Brazil, the prevalence of mental disorders is heterogeneous, with most studies conducted in large cities with high population density. This study aimed to assess the prevalence of mental disorders and psychiatric comorbidities among young adults (22-23 years old) and adults (37-38 years old) from Ribeirão Preto, a city located in the Northeast of the São Paulo state, with approximately 700,000 inhabitants, and to explore associations with sociodemographic variables, suicide risk, and health service usage. Second, we aimed to evaluate the performance of the Self-Report Questionnaire (SRQ-20) as a screening tool for mental disorders to be applied to the local population., Methods: Participants from the 1978/1979 and 1994 Ribeirão Preto birth cohorts were evaluated using the Mini International Neuropsychiatric Interview (MINI) and the SRQ-20 at mean ages of 22-23, and 37-38 years, respectively., Results: Our sample comprised 1,769 individuals from the 1978/1979 cohort and 1,037 from the 1994 cohort. The prevalence of mental disorders ranged from 28.6% (1978/79) to 31% (1994), with frequent comorbid diagnoses (42.7% and 43.3%, respectively). Men and women had a similar prevalence of mental disorders in the younger cohort, while women had a higher prevalence in the older cohort. Low educational attainment was associated with higher rates of diagnosis. In both cohorts, alcohol and other psychoactive substance use was higher among those with a psychiatric diagnosis. Although those with a psychiatric diagnosis were less satisfied with their own health, only one-fifth had seen a mental health professional in the previous year. A psychiatric diagnosis increased the suicide risk by 5.6 to 9.1 times. Regarding the SRQ-20, the best cutoff points were 5/6 for men and 7/8 for women, with satisfactory performance., Conclusions: The prevalence and comorbidity of mental disorders were high in both cohorts and comparable to those in larger Brazilian cities. However, few individuals with a diagnosis had sought specialized care. These data suggest that the mental health gap is still significant in Brazil., (© 2024. The Author(s).)

Objective: This study aims to create a new screening for preterm birth < 34 weeks after gestation with a cervical length (CL) ≤ 30 mm, based on clinical, demographic, and sonographic characteristics., Methods: This is a post hoc analysis of a randomized clinical trial (RCT), which included pregnancies, in middle-gestation, screened with transvaginal ultrasound. After observing inclusion criteria, the patient was invited to compare pessary plus progesterone (PP) versus progesterone only (P) (1:1). The objective was to determine which variables were associated with severe preterm birth using logistic regression (LR). The area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were calculated for both groups after applying LR, with a false positive rate (FPR) set at 10%., Results: The RCT included 936 patients, 475 in PP and 461 in P. The LR selected: ethnics white, absence of previous curettage, previous preterm birth, singleton gestation, precocious identification of short cervix, CL < 14.7 mm, CL in curve > 21.0 mm. The AUC (CI95%), sensitivity, specificity, PPV, and PNV, with 10% of FPR, were respectively 0.978 (0.961-0.995), 83.4%, 98.1%, 83.4% and 98.1% for PP < 34 weeks; and 0.765 (0.665-0.864), 38.7%, 92.1%, 26.1% and 95.4%, for P < 28 weeks., Conclusion: Logistic regression can be effective to screen preterm birth < 34 weeks in patients in the PP Group and all pregnancies with CL ≤ 30 mm., Competing Interests: Conflicts to interest: none to declare.

Background:  Olfactory dysfunction (OD) represents a frequent manifestation of the coronavirus disease 2019 (COVID-19). Apolipoprotein E (APOE) is a protein that interacts with the angiotensin-converting enzyme receptor, essential for viral entry into the cell. Previous publications have suggested a possible role of APOE in COVID-19 severity. As far as we know, no publications found significant associations between this disease's severity, OD, and APOE polymorphisms (E2, E3, and E4)., Objective:  To analyze the epidemiology of OD and its relationship with APOE polymorphisms in a cohort of Long-COVID patients., Methods:  We conducted a prospective cohort study with patients followed in a post-COVID neurological outpatient clinic, with OD being defined as a subjective reduction of olfactory function after infection, and persistent OD being defined when the complaint lasted more than 3 months after the COVID-19 infection resolution. This cross-sectional study is part of a large research with previously reported data focusing on the cognitive performance of our sample., Results:  The final sample comprised 221 patients, among whom 186 collected blood samples for APOE genotyping. The persistent OD group was younger and had a lower hospitalization rate during the acute phase of the disease ( p  < 0.001). Furthermore, the APOE variant E4 allele frequency was lower in this group ( p  = 0.035). This study evaluated OD in an outpatient population with COVID-19. In the current literature on this disease, anosmia is associated with better clinical outcomes and the E4 allele is associated with worse outcomes., Conclusion:  Our study provides new information to these correlations, suggesting APOE E4 as a protective factor for OD., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

This study investigates the influence of pregnancy on the in vivo activity of the intestinal P-glycoprotein (P-gp) and hepatic organic anion transporters polypeptide (OATP/BCRP) using, respectively, fexofenadine and rosuvastatin as probe drugs. Eleven healthy participants were investigated during the third trimester of pregnancy (Phase 1, 28 to 38 weeks of gestation) and in the postpartum period (Phase 2, 8 to 12 weeks postpartum). In both phases, after administration of a single oral dose of fexofenadine (60 mg) and rosuvastatin (5 mg), serial blood samples were collected for up to 24 h. Rosuvastatin and fexofenadine in plasma were analyzed by LC-MS/MS using previously validated methods. The pharmacokinetic parameters of fexofenadine and rosuvastatin (Phoenix WinNonLin software) with normal distribution (Shapiro-Wilk test) are presented as geometric mean and 90% confidence interval. Phases 1 and 2 were compared using the t test (P < .05). Fexofexadine AUC 0-24 values do not differ (P-value: .0715) between Phase 1 (641.9 ng h/mL [500.6-823.1]) and Phase 2 (823.8 ng h/mL [641.5-1057.6]) showing that pregnancy (third trimester) does not alter intestinal P-gp activity. However, rosuvastatin AUC 0-24 values are higher (P-value: .00005) in Phase 1 (18.7 ng h/mL [13.3-26.4]) when compared to Phase 2 (9.5 ng h/mL [6.7-13.4]), suggesting inhibition of OATP1B1/OATP1B3 transporters. In conclusion, pregnancy assessed during the third trimester does not alter the intestinal P-gp activity but reduces the activity of hepatic OATP1B1/OATP1B3 transporters. Therefore, adjustments in dosage regimens may be necessary for drugs with low therapeutic index, substrates of the OATP1B1/OATP1B3 transporters, administered during the third trimester of pregnancy., (© 2024, The American College of Clinical Pharmacology.)

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

Silver nanoparticles (AgNPs) hold promise for cancer therapy. This study aimed to evaluate their impact on tumor and non-tumor cell number, viability, and morphology. Antitumor activity was tested on U-87MG (glioblastoma) and DU-145 (prostate cancer) cell lines. Treatment with AgNPs notably reached a reduction of U-87MG and DU-145 cell growth by 89.30% and 79.74%, respectively, resulting in slower growth rates. AgNPs induced DNA damage, evidenced by reduced nuclear area and DNA content via fluorescent image-based analyses. Conversely, HFF-1 non-tumor cells displayed no significant changes post-AgNPs exposure. Viability assays revealed substantial reductions in U-87MG and DU-145 cells (79% and 63% in MTT assays, 30% and 52.2% in high-content analyses), while HFF-1 cells exhibited lower sensitivity. Tumor cells had notably lower IC 50 values than non-tumor cells, indicating selective susceptibility. Transmission electron microscopy (TEM) showed morphological changes post-AgNPs administration, including increased vacuoles, myelin figures, membrane ghosts, cellular extravasation, and membrane projections. The findings suggest the potential of AgNPs against glioblastoma and prostate cancer, necessitating further exploration across other cancer cell lines., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Melanoma is a type of tumor skin with high metastatic potential. Reconstructed human skin, development for pre-clinic assay, are make using primary human cells, but with same limitations. The aim this study was to characterize a cell culture model, with structure similar to human skin containing melanoma cells entirely from cell lines. Reconstructed skin with melanoma were development using human fibroblasts (MRC5), human epidermal keratinocytes (HaCat), and human melanoma (SK-MEL-28) embedded in collagen type I. The structure was characterized by hematoxylin-eosin stained, as well as points of melanoma cell invasion, which was associated with activity of MMPs (MMP-2 and MMP-9) by zymographic method. Then, the gene expression of the target molecular mechanisms involved in melanoma progression were evaluated. Here, the model development showed a region epidermis organized and separated from the dermis, with fibroblast cells confined and melanoma cells form delimited area invasion. MMP-2 and MMP-9 were identified during of cell culture and gene expression of BRAF, NRAS, and Vimentin was confirmed. The proposed model provides one more opportunity to study in vitro tumor biology of melanoma and also to allows the study of new drugs with more reliable results then whats we would find in vivo., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marne Carvalho de Vasconcellos has patent #BR 102019 017285 1 pending to Licensse. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Fatigue is a common symptom in patients with multiple sclerosis and it can lead to activity limitations. Thus, it is important to analyze the relationship between fatigue and activity outcomes, such as walking speed and mobility., Objectives: To investigate the relationship between fatigue and walking speed and mobility in individuals with multiple sclerosis., Methods: A cross-sectional study was performed. Adults with multiple sclerosis, without cognitive impairments and who were able to walk were recruited. Fatigue was assessed with the Modified Fatigue Impact Scale (MFIS). Walking speed, usual and fast, was assessed with the 10-meter Walk Test (10MWT), and mobility with the Timed Up and Go Test (TUG). Pearson correlation analysis was performed. A significance level of 5 % was used., Results: Thirty participants were included, most of the relapsing-remitting multiple sclerosis (n = 24, 80 %). A mean age of 41 (11) years and the median Expanded Disability Status Scale (EDSS) score was 2.65 (2.18) points. Mean MFIS score was 41.87 ± 19.42 points, mean usual walking speed was 1.02 ± 0.28 m/s, mean fast walking speed was 1.55 ± 0.48 m/s, and the mean total time in the TUG was 10.07 ± 3.05 s. A significant negative correlation of moderate magnitude was found between fatigue and usual walking speed (r=₋0.51, p < 0.05). A significant negative correlation of moderate magnitude was found between fatigue and fast walking speed (r=₋0.54, p < 0.05). A significant, positive correlation of moderate magnitude was found between fatigue and mobility (r = 0.54, p < 0.05)., Conclusion: There was a correlation between fatigue and walking speed and mobility in individuals with multiple sclerosis. These results highlight the need to assess fatigue in individuals with multiple sclerosis, since the presence of fatigue is associated with reduced walking speed and mobility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: 3D biomodels represent a cutting-edge advancement in medical imaging technology. The incorporation of 3D technologies in dermatology through the acquisition of onychological images, 3D reconstruction, and development of customized equipment to assist in surgeries demonstrated reduction in operating times and improved surgical outcomes. Additionally, the use of 3D printing in surgical simulation provided a safe environment for training and education. This article explores the application of 3D biomodels in dermatology, focusing on three clinical cases involving nail tumors., Case Presentation: In case 1, a glomus tumor was visualized in 3D, guiding the creation of a personalized surgical device. The minimally invasive surgery, facilitated by the biomodel, resulted in successful tumor removal. Case 2, featuring a subungual keratoacanthoma, utilized 3D biomodels for conservative surgery planning, anatomical comprehension, and patient communication. Case 3 involved a longitudinal groove, where biomodels aided in precise lesion localization and surgical planning., Conclusion: The integration of virtual and physical anatomical biomodels proves valuable in surgical dermatology, contributing to enhanced treatment quality, patient safety, and medical education., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 S. Karger AG, Basel.)

Unconventional food plants, popularized in Brazil as PANC, remain underutilized globally. In that sense, this study aims to explore the nutritional and functional properties of taioba ( Xanthosoma sagittifolium ), a plant with edible leaves and tubers, and to investigate its potential for industrial-scale application as a source of starch. A systematic review was carried out and meta-analysis following the PRISMA guidelines was conducted based on a random effects synthesis of multivariable-adjusted relative risks (RRs). The searches were carried out in seven search sources, among which were Web of Science, Elsevier's Science Direct, Wiley Online Library, Springer Nature, Taylor & Francis, Hindawi, Scielo, ACS-American Chemical Society, and Google Scholar. The systematic review was guided by a systematic review protocol based on the POT strategy (Population, Outcome, and Types of studies), adapted for use in this research. Mendeley was a resource used for organization, to manage references, and to exclude duplicates of studies selected for review. The findings revealed that taioba leaves are abundant in essential nutrients, proteins, vitamins, and minerals. Additionally, the tubers offer rich starch content along with vitamins and minerals like iron, potassium, and calcium, making them an ideal substitute for conventional sources on an industrial scale. This research highlights the significance of studying the functionalities, applicability, and integration of this PANC in our diets, while also emphasizing its capability as a substitute for traditional starch varieties. Moreover, exploiting this plant's potential adds value to Amazonian resources, reduces import costs, and diversifies resource utilization across multiple industrial sectors.

Objective: To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD)., Methods: Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20 +0 to 25 +6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve., Results: Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1β, TNFβ, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%., Conclusion: IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response., Competing Interests: Conflicts to interest: none to declare.

Background: Continuous investment and systematic evaluation of program accomplishments are required to achieve excellence in ST-segment elevation myocardial infarction (STEMI) care, especially in resource-limited settings. Therefore, this study evaluates the impact of problem-driven interventions on reperfusion use rate in a long-term operating STEMI network from a low- to middle-income country., Methods: This is a healthcare improvement evaluation study of Salvador's public STEMI network in a quasi-experimental design, comparing data from 2009 to 2010 (pre-intervention) and 2019-2020 (post-intervention). There were evaluated all confirmed STEMI cases assisted in both periods. The interventions, implemented since 2017, included: expanding the support team, defining criteria to be a spoke, and initiating continuous education activities. The primary outcome was the rate of patients undergoing reperfusion, with secondary outcomes being time from door-to-ECG (D2E) and ECG-to-STEMI-team trigger (E2T)., Results: Over ten years, the network's coverage increased by 300,000 individuals, and expanded by 1,800 km 2 . A total of 885 records were analyzed, 287 in the pre-intervention group (182 men [63·4%]; mean [SD] age 62·1 [12·5] years) and 598 in the post-intervention group (356 men [59·5%]; mean [SD] age 61.9 [11·8] years). It was noticed a substantial increase in reperfusion delivery rate (90 [31%] vs. 431 [73%]; P  = 001) and reductions in time from D2E (159 [83-340] vs. 29 [15-63], P  = 001), and E2T (31 [21-44] vs. 16 [6-40], P  = 001)., Conclusion: The strategies adopted by Salvador's STEMI network were associated with significant improvements in the rate of patients undergoing reperfusion and in D2E and E2T. However, the mortality rate remains high., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Roriz, Ferreira, Pontes, Machado, Aguiar, Matos, Paiva Filho, Menezes and Andrade.)

Purpose: The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity., Methods and Materials: We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint., Results: From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003)., Conclusions: HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although the existing framework for classifying acute myocardial infarction (AMI) into STEMI and NSTEMI has been beneficial, it is now considered to be falling short in addressing the complexity of acute coronary syndromes. The study aims to scrutinize the current STEMI-NSTEMI paradigm and advocate for a more nuanced framework, termed as occlusion myocardial infarction (OMI) and non-occlusion myocardial infarction (NOMI), for a more accurate diagnosis and management of AMI. A comprehensive analysis of existing medical literature was conducted, with a focus on the limitations of the STEMI-NSTEMI model. The study also outlines a new diagnostic approach for patients presenting with chest pain in emergency settings. The traditional STEMI-NSTEMI model falls short in diagnostic precision and effective treatment, especially in identifying acute coronary artery occlusions. The OMI-NOMI framework offers a more anatomically and physiologically accurate model, backed by a wealth of clinical research and expert opinion. It underscores the need for quick ECG assessments and immediate reperfusion therapies for suspected OMI cases, aiming to improve patient outcomes. The OMI-NOMI framework offers a new avenue for future research and clinical application. It advocates for a more comprehensive understanding of the underlying mechanisms of acute coronary syndromes, leading to individualized treatment plans. This novel approach is expected to ignite further scholarly debate and research, particularly in the Brazilian cardiology sector, with the goal of enhancing diagnostic accuracy and treatment effectiveness in AMI patients.

To investigate the effects of 8-weeks of full versus split body resistance training (RT) on appetite and energy intake in non-obese untrained men. The participants were pair-matched based on their initial fat mass and then randomly allocated into one of two treatment groups: Full body (FB, n = 20), in which all muscle groups were trained in every session, or Split body (SB, n = 15), in which upper and lower muscle groups were trained alternated per session; both groups trained in non-consecutive days, three times per week with total number of sets performed equated between groups. Energy intake, body composition, and strength performance were evaluated at pre-training, and after 8-weeks of RT, as well as self-reported hunger, fullness, and desire to eat, that were assessed at fasted and feed states pre- and post-intervention. FB and SB resistance training increased fat-free mass (FFM) (p < 0.001); and FB induced greater maximal strength improvement (p = 0.027). At fasted state self-reported hunger increased, and fullness decreased, while in feed state desire to eat something fatty increased in both groups. Carbohydrate intake (p = 0.011) decreased in both groups. In conclusion, FB and SB training increased orexigenic drive (increasing hunger and decreasing fullness), however, total energy intake and fat mass did not change after 8-weeks of RT in non-obese untrained men.Registered under Brazilian Registry of Clinical Trials no. RBR-3wkcvyw., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The transition from the second to the third millennium happened to be a turning point in the history of myocardial revascularization on a beating heart, which moved from technical development to critical evaluation. This article describes how the initial acceptance and spread of off-pump coronary artery bypass grafting (OPCABG) was followed by the general perception that the technique could not fulfill the expectations placed in it and provides some insight on what should we do with the know-how of OPCABG in the present and the future of coronary surgical revascularization., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose: Varicocele is a condition known to cause damage to seminal parameters and sperm function. Furthermore, it has been hypothesized that the varicocele effect on fertility is time-dependent; however, little is known about the consequences of its establishment time on reproductive organs and/or sperm function. This study aimed to evaluate the effect of the duration of experimental varicocele on reproductive organs, sperm parameters, and sperm function., Materials and Methods: Varicocele induction surgeries were performed in Wistar rats aged 40 or 100 days old. At 160-day-old, analyses were performed, including biometry of reproductive organs (prostate, seminal vesicles, epididymis, and testis), sperm parameters (vitality, morphology, and motility), and sperm function tests (nuclear DNA integrity, acrosome integrity, and mitochondrial activity)., Results: The analysis of the biometry of reproductive organs showed no differences between distinct ages in which varicocele was induced. The total abnormal sperm morphology was bigger in animals with varicocele induced to 100 days old than in animals with varicocele induced to 40 days old. Regarding nuclear DNA integrity, animals of varicocele induced to 100 days old showed worse results compared to animals of varicocele induced to 40 days old. Other parameters analyzed showed no differences between varicocele groups., Conclusion: In this study conducted on rats, we conclude that varicocele adversely affects sperm, particularly its function. However, we did not observe a negative progressive effect on sperm., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Athletes with tetraplegia may experience marked hyperthermia while exercising under environmental heat stress due to their limited ability to dissipate heat through evaporative means. This study investigated the effectiveness of two external cooling strategies (i.e., spraying water onto the body surface or using a cooling vest) on physiological and perceptual variables in tetraplegic athletes during and after an aerobic exercise session in a hot environment. Nine male wheelchair rugby players performed an incremental test to determine their maximum aerobic power output. After that, they were subjected to three experimental trials in a counter-balanced order: control (CON, no body cooling), cooling vest (CV), and water spraying (WS). During these trials, they performed 30 min of a submaximal exercise (at 65% of their maximum aerobic power) inside an environmental chamber set to maintain the dry-bulb temperature at 32 °C. The following variables were recorded at regular intervals during the exercise and for an additional 30 min following the exertion (i.e., post-exercise recovery) with the participants also exposed to 32 °C: body core temperature (T CORE ), skin temperature (T SKIN ), heart rate (HR), rating of perceived exertion (RPE), thermal comfort (TC), and thermal sensation (TS). While exercising in CON conditions, the tetraplegic athletes had the expected increases in T CORE , T SKIN , HR, RPE, and TC and TS scores. HR, TC, and TS decreased gradually toward pre-exercise values after the exercise, whereas T CORE and T SKIN remained stable at higher values. Using a cooling vest decreased the temperature measured only on the chest and reduced the scores of RPE, TC, and TS during and after exercise but did not influence the other physiological responses of the tetraplegic athletes. In contrast, spraying water onto the athletes' body surface attenuated the exercise-induced increase in T SKIN , led to lower HR values during recovery, and was also associated with better perception during and after exercise. We conclude that water spraying is more effective than the cooling vest in attenuating physiological strain induced by exercise-heat stress. However, although both external cooling strategies do not influence exercise hyperthermia, they improve the athletes' thermal perception and reduce perceived exertion., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Fatigue is one of the most common symptoms reported by individuals with multiple sclerosis and it contributes to the reduction of the functionality. Therefore, it is important to assess the impact of fatigue on daily living of individuals with multiple sclerosis. The Modified Fatigue Impact Scale (MFIS) is an instrument to assess the perception of the impact of fatigue. However, there have been no investigations about the measurement properties of this instrument administered over the telephone for individuals with multiple sclerosis., Objectives: To verify the concurrent validity, the test-retest reliability, the standard error of measurement (SEM) and the minimal detectable change (MDC) of the MFIS applied over the telephone to assess the perception of the impact of fatigue of individuals with multiple sclerosis., Methods: The MFIS, composed of 21 items covering three domains: physical, cognitive and psychosocial, was applied at three different moments with an interval of 5-7 days. To establish the concurrent criterion validity, the face-to-face application and the first evaluation by telephone were used. The two telephone assessments were used to assess the test-retest reliability The intraclass correlation coefficient (ICC) with 95 % confidence interval (CI) and the Bland-Altman method were used. The standard error of measurement (SEM) and the MDC was calculated according to reliability results., Results: Thirty individuals (40.83 ± 10.61, 60 % female) were included. The median score on the Expanded Disability Status Scale was 2.00 (±4.00). The majority of participants experienced fatigue (n = 17; 56.67 %). A significant and high magnitude correlation (0.70 ≤ ICC ≤ 0.87, p < 0.001) was found in the investigation of concurrent criterion validity. The Bland-Altman method showed a mean difference between 0.70 to 2.17 points between face-to-face and telephone-based application of the MFIS. For test-retest reliability, a significant and very high magnitude correlation (0.91 ≤ ICC ≤ 0.97, p < 0.001) was found. The Bland-Altman method showed a mean difference between -0.03 and -0.77 points between two telephone-based applications. The SEM and the MDC were 0.71 and 1.97 points., Conclusion: The telephone-based application of the MFIS to assess the perceived impact of fatigue in individuals with multiple sclerosis demonstrated adequate measurement properties, and may be a valuable tool to assess patients in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Monoclonal antibodies (MAbs) have clinical benefits for treating several atopic diseases. However, consensus on its use for eosinophilic esophagitis (EoE) is lacking. The present meta-analysis aimed to compare the efficacy and safety of MAbs versus placebo for treating EoE., Methods: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcomes were changes in peak esophageal eosinophils count/high power field (HPF) and mean esophageal eosinophils count/HPF. The secondary outcomes were changes in the EoE-Histology Scoring System (EoE-HSS), Endoscopic Reference Score (EREFS), dysphagia score, and adverse events (AEs). We compared binary outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD) or standardized mean difference (SMD), with 95% confidence interval (CI). Considering the diversity of mechanistic properties of MAbs, a pre-specified subgroup analysis by MAb mechanism of action was performed for all outcomes, provided that at least two studies were in each subgroup. Heterogeneity was assessed using Cochran's Q test and I 2 statistics., Results: 6 RCTs were included (533 patients). Compared to placebo, MAbs led to a significant reduction in peak esophageal eosinophils count/HPF (MD -0.78; CI 95% -0.87, -0.6801) and mean esophageal eosinophils count/HPF (SMD -0.79; CI 95% -1.5, -0.08). Moreover, MAbs significantly reduced EoE-HSS scores (grade score: SMD -9.31; 95% CI -13.95, -4.6701; stage score: SMD -10.18; 95% CI -15.06, -5.31), EREFS (SMD -5.95; CI 95% -9.19, -2.71) and dysphagia score (SMD -1.79; CI 95% -3.36, -0.23) without increasing AEs compared to placebo. Among those MAbs whose mechanism of action includes the blockage of the receptor for IL-13 (Dupilumab, QAX576, and RPC4046), the scores of EoE-HSS grade, EoE-HSS stage, EREFS, and dysphagia were significantly reduced, and they presented a similar risk of overall and serious AEs compared to placebo., Conclusion: MAbs seem effective and safe in reducing esophageal eosinophil infiltrate, EoE-HSS score, EREFS score, and dysphagia symptoms in patients with EoE. However, further evidence is needed to establish its place in EoE management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)