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Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease that mainly affects the joints, on reducing functional capacity and impacting quality of life. Cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are crucial in the pathogenesis and treatment of this disease. Some patients using TNF inhibitors (TNFi) do not respond or lose their response to these medications. Clinical, sociodemographic, and genetic data were used to evaluate the associations of single nucleotide polymorphisms (SNP) in TNF, TNFRSF1A, and TNFRSF1B genes with the diagnosis of RA, standardized score results, laboratory tests, and response to TNFi. In one subsample, TNF and IL-6 serum levels cytokines were performed. A total of 654 subjects (360 healthy controls and 294 diagnosed with RA) were included in the analysis. Higher levels of TNF have been found in individuals diagnosed with RA. IL-6 levels were higher in individuals who did not respond to TNFi treatment, while responders had levels comparable to those without the disease. No associations were found between the SNPs studied and the diagnosis of RA; however, rs767455-C seems to play a role in the response to golimumab treatment, being related to better therapeutic response and lower mean serum leukocyte levels. In addition, rs1061622-G was associated with poorer functional capacity and rs1800629-A was associated with higher leukocyte values and serum transaminase levels. The rs1061622-G and rs767455-C may play a role in the response to TNFi treatment, especially for patients using golimumab, although they do not seem to be associated with the diagnosis of RA. Polymosphisms in the TNF pathway may impact baseline levels of immune cells and markers of renal and hepatic function in RA patients. Our results highlight the importance of evaluating the impact of these polymorphisms on TNFi response and safety, particularly in larger-scale studies., 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.)

Introduction: Donor human milk is increasingly being utilized for both preterm and term infants when mother's milk is unavailable. With the rising prevalence of maternal overweight and obesity, it is crucial to evaluate the relationship between maternal body mass index and the fat and energy content of donor human milk. Objectives: To assess the impact of maternal body mass index on human milk fat content. Methods: A cross-sectional study was carried out using retrospective data from women who made their first human milk donation at ≥15 days postpartum at a human milk bank in São Paulo, Brazil, from January 2018 to December 2020. Data of sociodemographic, obstetric, health, and anthropometric measures were collected by the human milk bank staff. Milk fat and energy content were determined using the crematocrit test. Analysis of variance and multiple linear regression were used to compare means of crematocrit and fat. We determined the p -values using a test of heterogeneity and linear trend and presented the one with the lower p -value. Results: Most donors were between 25 and 35 years old, had higher education, were employed, and lived with a partner. At the time of milk donation, 40.9% of women were overweight or obese. The fat (1.09 g/dL) and energy (9.83 kcal/dL) content of human milk were higher in obese donor compared with eutrophic donors. Conclusions: The fat and energy content of human milk were associated with maternal body mass index, suggesting the potential value for selective use of high fat and high calorie donor milk for very low birthweight or premature infants.

Background: The COVID-19 pandemic has seriously affected older adults' social lives, physical activity, and cognitive functions. Additionally, the lockdowns have disrupted regular healthcare for patients with chronic illnesses or needing acute care. Furthermore, the pandemic has negatively affected different psychosocial influences in each country due to the various cultural characteristics, technology, health system, and financial opportunities. This study aimed to investigate the effects of COVID-19 on mood, social participation, and healthcare use in older adults living in Turkey., Methods: A cross-sectional study was conducted during the third wave of the COVID-19 pandemic (March-December 2021) in three medical centers in Turkey. Patients aged 60 + years without significant cognitive impairment were recruited by mail or at hospital admissions. Information on demographics, pandemic-related distancing measures, healthcare use, lifestyle, symptoms of anxiety, depression, and social participation were assessed., Results: A total of 343 participants were included in the study. Women had a higher rate of hypertension, symptoms of anxiety, depression, and fatigue compared to men (p < 0.05). Since the start of the pandemic, only 22.4% of non-acute healthcare appointments were conducted face-to-face. Time spent with family and friends, hope for the future, and physical activity decreased. At the same time, the experience of loneliness, the number of meals and unhealthy snacks, and the use of digital services increased. Women were also more concerned about getting coronavirus infection, transmitting the virus to others, and being discriminated against because of the infection (p < 0.05)., Conclusions: These pandemic days have had a significant psychosocial impact on Turkish older adults, especially women. As a strategy of the health care policy, easy access and follow-up to the health system should be provided, and the necessary support should be procured to minimize the detrimental effects of the pandemic on older people., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Dokuz Eylul University of Non-Interventional Clinical Researches Ethics Board as a multicenter study and conformed to the Declaration of Helsinki. Permission was also obtained from the Turkish Ministry of Health for research on COVID-19. All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/Objectives: Among US breastfeeding women, those with obesity have significantly increased breast milk fat and caloric content from foremilk to hindmilk, with a 4-fold increase in fat content from the first to last milk sample. In view of different dietary norms and nutritional standards, we sought to evaluate the relationship between maternal BMI with breast milk fat and calorie content in women from Brazil, a low-middle-income country. Methods: Women who delivered singleton-term neonates were recruited from the Ana Abrao Breastfeeding Center (AABC) and Human Milk Bank at the Federal University of Sao Paulo, Brazil. These women were then studied at 7-8 weeks postpartum. Women were grouped by BMI categories of nonobese (NonOB; BMI 18.5-29.9) and obese (OB; BMI ≥ 30). A breast pump was applied, and milk samples were obtained continuously in 10 mL aliquots from foremilk to hindmilk; samples were analyzed for macronutrients and lipids, and maternal blood was analyzed for serum lipids and glucose. Results: As compared to NonOB women, those with OB had significantly higher milk fat in the mid (4.9 ± 0.3 vs. 3.9 ± 0.2) and last hindmilk (6.6 ± 0.4 vs. 5.5 ± 0.3) samples, though not in the first foremilk sample, as compared to NonOB women. In both NonOB and OB subjects, milk caloric and fat content increased 1.5 to 2-fold from foremilk to hindmilk, with the average milk caloric value being 11% greater in OB women. Protein content was significantly increased in all three milk samples (first, middle, and last) in women with OB. Conclusions : Although the value of breastfeeding remains clear, these findings may have significant implications for infant nutrition and excessive infant weight gain in women with OB.

Background: Investigate the utility of cardiovascular responses such as heart rate (HR), blood pressure (BP), and heart rate variability (HRV) in the prognosis of children with acute acquired brain injury (ABI)., Methods: Children under 18 years with severe acute acquired brain injury (ABI) who survived at least 12 h after PICU admission were included in a prospective observational cohort in a tertiary academic PICU. Physiological variables, neurological data, laboratory tests (chemistry and hematology), and medications were recorded within 12 h of admission. Linear and nonlinear HRV indices, CT scans, PICU scores, and survival rates were evaluated., Results: Seventy-two children, median age 10.7 years (IQR 4.1-13.6), were eligible for the study; 28 (38.9%) were diagnosed with brain death (BD). Tachycardia, SBP and MBP < 5th percentile, and MBP and DBP> 99th percentile were significantly associated with mortality. Poincaré SD1/SD2 was significantly associated with mortality after adjusting for age, sex and ongoing medication., Conclusion: Tachycardia, systolic hypotension and median hypo and hypertension were associated to mortality in children with severe ABI. While further validation through larger, multicenter studies is necessary, the Poincaré SD1/SD2 ratio has shown promise as a prognostic tool for predicting mortality in children with severe ABI., Impact Statement: This study explores cardiovascular changes, including heart rate and blood pressure, and linear/nonlinear HRV measures using ECG at 1000 Hz, and compare them with other prognostic factors like brain tomography and PICU scores. Tachycardia, hypo/hypertension in the early hours after admission are linked to early mortality in children with severe traumatic and non-traumatic brain injury. Linear/non-linear measures of HRV were also related to survival. Higher HRV values indicating better survival chances. We identified Poincaré SD1/SD2 ratio as a promising tool for predicting mortality in children with severe ABI., Competing Interests: Competing interests The authors whose names are listed immediately above certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

This study investigated the effects of fermenting plum pulp with Bifidobacterium animalis ssp. lactis (BAL) on its physicochemical and bioactive properties, as well as the optimization of the freeze-drying (FD) process to develop a fruit-based probiotic delivery system. Fermentation significantly reduced the pH and total acidity of the pulp, achieving a cell viability of 11 log CFU/mL. The FD process was optimized using a factorial design, with maltodextrin concentration (3, 5, and 7%) and freezing temperature (-150, -100, and -50 °C) as variables. The P2 experiment, which used 7% maltodextrin and freezing at -150 °C, showed the best results in terms of yield (25.67%), cell viability (8 log CFU/g), and probiotic survival rate (97.66%). Samples P5, P6, and P7, prepared with 5% maltodextrin and freezing at -100 °C, exhibited the highest levels of bioactive compounds and antioxidant activity ( p < 0.05). During 28 days of storage, all samples maintained cell viability without significant logarithmic reduction. In summary, probiotic plum powders offer an excellent plant-based alternative for probiotic consumption, providing safe levels of beneficial bacteria and bioactive compounds with antioxidant action, meeting health and nutrition needs.

Background and Aims: Stricturing [B2] and penetrating [B3] ileal Crohn's disease have been reported to present similar levels of histopathological transmural fibrosis. This study aimed to compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal Crohn's disease., Methods: Using Nanostring technology and comparative bioinformatics, we analysed the expression of 787 fibrosis-related genes in 36 ileal surgical specimens, 12 B2 and 24 B3, the latter including 12 cases with associated stricture[s] [B3s] and 12 without [B3o]. Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis for the distribution analysis. For the selection of the differentially expressed genes, a p-adjusted <0.05 and fold change ≤-1.5 or ≥1.5 were adopted. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses were used to validate selected differentially expressed genes., Results: We included 34 patients with B2 and B3 phenotypes, balanced for age at diagnosis, age at surgery, gender, Crohn's disease localisation, perianal disease, and therapy. Inflammation and fibrosis histopathological scoring were similar in all cases. B2 and B3 groups showed a very good clustering regarding 30 significantly differentially expressed genes, all being remarkably upregulated in B3. More than half of these genes were involved in Crohn's disease fibrogenesis, and eight differentially expressed genes were so in other organs. The most significantly active biological processes and pathways in penetrating disease were response to TGFβ and matrix organisation and degradation, as validated by immunohistochemistry., Conclusions: Despite the histopathological similarities in fibrosis between stricturing and penetrating ileal Crohn's disease, their fibrosis-related transcriptomic profiles are distinct. Penetrating disease exhibits a distinctive transcriptomic landscape related to enhanced matrix remodelling., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We present here a user-friendly calculator for the setting of a pediatric split-bolus polytrauma computed tomography (CT) protocol with a mixed arterial and venous phase, aiming to both reduce radiation dose and improve workflow while assuring optimal image quality. All the different parameters are calculated based on patient's weight with rapid computation of the injected contrast media and saline volumes, injection's flow rate, injection's timing, and optimal acquisition time. The designed calculator is built in a widely available Google Sheets file, accessible by a quick response (QR) code. Although polytrauma imaging represents the main goal of the technique, it can be used in a wide variety of contexts, including oncological, infectious, and vascular pathologies., Competing Interests: Declarations. Conflicts of interest: None Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/aim: This study aimed to investigate the influence of Western diet on mammary cancer in Wistar female rats, focusing on systemic responses and tumor development., Materials and Methods: Twenty-eight Wistar female rats were acclimatized and divided into four experimental groups (n=7 each): Western diet (WD), Western diet with N-methyl-N-nitrosourea (MNU) administration (WD+MNU), standard diet (CTR), and standard diet with MNU administration (CTR+MNU). MNU was administered intraperitoneally at 50 mg/kg at seven weeks of age to induce mammary cancer. The 20-week experiment involved monitoring animal weight, food and water intake. At the end of the study, rats were euthanized, and blood samples and organs were collected for hematological and plasma biochemical analysis, oxidative stress, and histo-pathological and immunobiological evaluations of the tumors., Results: No significant differences were found in body weight, composition, or organ weights, but the WD group showed reduced food and water intake and lower cholesterol levels. Leptin and adiponectin levels were higher in the WD+MNU group, suggestive of changes in appetite regulation. Histopathological analysis showed malignant tumors in both MNU-induced groups. However, WD groups had fewer tumors compared to the CTR+MNU group., Conclusion: WD led to higher feed efficiency and increased visceral adipose tissue but decreased systemic cholesterol and triglyceride levels. While this diet resulted in lower tumor incidence, the volume and weight of the tumors were higher. Additionally, the WD decreased ERα and progesterone receptor immunoexpression, while Ki-67 immunoexpression was elevated., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To analyze risk factors (maternal, obstetric and demographic) associated with congenital syphilis and the clinical characteristics of the newborns., Method: A cross-sectional study carried out in ten public maternity hospitals in Fortaleza, Ceará, Brazil that included cases of live births reported with congenital syphilis in 2015., Results: 469 cases were analyzed; 199 (42.4 %) showed some sign or symptom suggestive of congenital syphilis; of these, 65 (32.7 %) were preterm, 87 (43.7 %) had low birth weight, 116 (58.3 %) had jaundice that required phototherapy, 13 (6.5 %) had hepatomegaly, 10 (5 %) had skin lesions, eight (4.0 %) had splenomegaly and one (0.5 %) had limb pseudoparalysis. Records of other clinical changes were identified in 36 (7.7 %) children. Children whose mothers were not treated or who received a drug other than penicillin and those whose mothers had a VDRL titer ≥ 1:16 at birth were 3.7 and 3.2 times more likely to be born with signs of congenital syphilis (p < 0.001- 95 % CI 2.41-5.58; p < 0.001 - 95 % CI 2.41-5.58) respectively., Conclusions: The findings of this study draw attention to the importance of improving the quality of prenatal care and the development of studies aimed at finding alternative drugs for the treatment of syphilis in pregnant women and the prevention of congenital syphilis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Low medication literacy is prevalent among older adults and is associated with adverse drug events. The Medication Literacy Test for Older Adults (TELUMI) was developed and content validated in a previously published study., Aim: To evaluate the psychometric properties and provide norms for TELUMI scores., Method: This was a cross-sectional methodological study with older adults selected from the community and from two outpatient services. Descriptive item-analysis, exploratory factor analysis (EFA), item response theory (IRT), reliability, and validity analysis with schooling and health literacy were performed to test the psychometric properties of the TELUMI. The classification of the TELUMI scores was performed using percentile norms., Results: A total of 344 participants, with a mean age of 68.7 years (standard deviation = 6.7), were included; most were female (66.6%), black/brown (61.8%), had low schooling level (60.2%) and low income (55.2%). The EFA pointed to the one-dimensional structure of TELUMI. A three-parameter logistic model was adopted for IRT. All items had an adequate difficulty index. One item had discrimination < 0.65, and three items had an unacceptable guessing index (< 0.35) and were excluded. The 29-item version of TELUMI had excellent internal consistency (KR20 = 0.89). There was a positive and strong association between TELUMI scores and health literacy and education level. The scores were classified as inadequate medication literacy (≤ 10.0 points), medium medication literacy (11-20 points), and adequate medication literacy (≥ 21 points)., Conclusion: The results suggest that the 29-item version of TELUMI is psychometrically adequate for measuring medication literacy in older adults., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: To evaluate the impact of levonorgestrel-releasing intrauterine device (LNG-IUD) use on the incidence of acne in adolescents and young women., Methods: A narrative review was conducted in PubMed, Embase, Cochrane, and SciELO assessing the incidence of acne in adolescents and young women using LNG-IUD (13.5, or 19.5 mg, or 52 mg). Cohort, cross-sectional studies, clinical trials, and meta-analyses were included, without a date limit. Studies that didn't evaluate women in the age of interest were excluded. Only articles in English were selected., Results: Nine articles were included in this narrative review. Only clinical trials, cohort studies, and cross-sectional studies were evaluated. Two cross-sectional studies evaluated the incidence of acne in women using any contraceptive methods, with the incidence of acne being 36% in women aged 17 to 47 using LNG-IUD in one study. In another study, acne incidence ranged from 2 to 8% in women using any contraceptive methods, with higher rates in younger women and LNG-IUD users. The incidence of acne varies and participants between 16 to 35 years were more likely to report new acne or worsening of pre-existing acne. In a prospective cohort study of women between 16 and 24 years, acne was a common adverse effect, with 44% in the first year., Conclusion: The data indicate variability in the incidence of acne among LNG-IUD users, with a higher prevalence observed in younger women. Further research should focus on the effects of LNG-IUD on acne in young populations, with rigorous study designs and consideration of previous contraceptive use.

Echocardiography is a reliable and non-invasive method for assessing cardiac structure and function in both clinical and experimental settings, offering valuable insights into disease progression and treatment efficacy. The successful application of echocardiography in murine models of disease has enabled the evaluation of disease severity, drug testing, and continuous monitoring of cardiac function in these animals. However, there is insufficient standardization of echocardiographic measurements for smaller animals. This article aims to address this gap by providing a guide and practical tips for the appropriate acquisition and analysis of echocardiographic parameters in adult rats, which may also be applicable in other small rodents used for scientific purposes, like mice. With advancements in technology, such as ultrahigh-frequency ultrasonic transducers, echocardiography has become a highly sophisticated imaging modality, offering high temporal and spatial resolution imaging, thereby allowing for real-time monitoring of cardiac function throughout the lifespan of small animals. Moreover, it allows the assessment of cardiac complications associated with aging, cancer, diabetes, and obesity, as well as the monitoring of cardiotoxicity induced by therapeutic interventions in preclinical models, providing important information for translational research. Finally, this paper discusses the future directions of cardiac preclinical ultrasound, highlighting the need for continued standardization to advance research and improve clinical outcomes to facilitate early disease detection and the translation of findings into clinical practice.

Background: To analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system., Methods: A cross-sectional analysis of retinal images of patients with type 2 diabetes (n = 160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC-50DX ® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques., Results: Images of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10-20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k > 0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions., Conclusions: UWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images., Trial Registration: Approved by the AIBILI - Association for Innovation and Biomedical Research on Light and Image Ethics Committee for Health with number CEC/009/17- EYEMARKER., (© 2024. The Author(s).)

Overexpression of the agouti-signaling protein ( asip1 ), an endogenous melanocortin antagonist, under the control of a constitutive promoter in zebrafish [Tg(Xla.Eef1a1:Cau.Asip1]iim4] ( asip1 -Tg) increases food intake by reducing sensitivity of the central satiety systems and abolish circadian activity rhythms. The phenotype also shows increased linear growth and body weight, yet no enhanced aggressiveness in dyadic fights is observed. In fact, asip1 -Tg animals choose to flee to safer areas rather than face a potential threat, thus suggesting a potential anxiety-like behavior (ALB). Standard behavioral tests, i.e., the open field test (OFT), the novel object test (NOT), and the novel tank dive test (NTDT), were used to investigate thigmotaxis and ALB in male and female zebrafish. Results showed that the asip1 -Tg strain exhibited severe ALB in every test, mainly characterized by pronounced freezing behavior and increased linear and angular swimming velocities. asip1 -Tg animals exhibited low central serotonin (5-HT) and dopamine (DA) levels and high turnover rates, thus suggesting that central monoaminergic pathways might mediate melanocortin antagonist-induced ALB. Accordingly, the treatment of asip1 -Tg animals with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversed the ALB phenotype in NTDT as well as 5-HT turnover. Genomic and anatomical data further supported neuronal interaction between melanocortinergic and serotonergic systems. These results suggest that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonist has an anxiogenic effect mediated by serotonergic transmission., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Verbal communication has key information for mental health evaluation. Researchers have linked psychopathology phenomena to some of their counterparts in natural-language-processing (NLP). We study the characterization of subtle impairments presented in early stages of psychosis, developing new analysis techniques and a comprehensive map associating NLP features with the full range of clinical presentation., Methods: We used NLP to assess elicited and free-speech of 60 individuals in at-risk-mental-states (ARMS) and 73 controls, screened from 4,500 quota-sampled Portuguese speaking citizens in Sao Paulo, Brazil. Psychotic symptoms were independently assessed with Structured-Interview-for-Psychosis-Risk-Syndromes (SIPS). Speech features (e.g.sentiments, semantic coherence), including novel ones, were correlated with psychotic traits (Spearman's-ρ) and ARMS status (general linear models and machine-learning ensembles)., Results: NLP features were informative inputs for classification, which presented 86% balanced accuracy. The NLP features brought forth (e.g. Semantic laminarity as 'perseveration', Semantic recurrence time as 'circumstantiality', average centrality in word repetition graphs) carried most information and also presented direct correlations with psychotic symptoms. Out of the standard measures, grammatical tagging (e.g. use of adjectives) was the most relevant., Conclusion: Subtle speech impairments can be grasped by sensitive methods and used for ARMS screening. We sketch a blueprint for speech-based evaluation, pairing features to standard thought disorder psychometric items., Competing Interests: FA has provided consulting services and developed technology for private companies. NBM works at Mobile Brain, an Education and Health Tech startup, and has been a consultant to Boehringer Ingelheim. JMG works at mobile Brain and has provided consulting for developing machine learning models for private companies. The other authors report no conflicts of interest.

Currently, the market for wearable devices is expanding, with a growing trend towards the use of these devices for continuous-monitoring applications. Among these, real-time posture monitoring and assessment stands out as a crucial application given the rising prevalence of conditions like forward head posture (FHP). This paper proposes a wearable device that combines the acquisition of electromyographic signals from the cervical region with inertial data from inertial measurement units (IMUs) to assess the occurrence of FHP. To improve electronics integration and wearability, e-textiles are explored for the development of surface electrodes and conductive tracks that connect the different electronic modules. Tensile strength and abrasion tests of 22 samples consisting of textile electrodes and conductive tracks produced with three fiber types (two from Shieldex and one from Imbut) were conducted. Imbut's Elitex fiber outperformed Shieldex's fibers in both tests. The developed surface electromyography (sEMG) acquisition hardware and textile electrodes were also tested and benchmarked against an electromyography (EMG) gold standard in dynamic and isometric conditions, with results showing slightly better root mean square error (RMSE) values (for 4 × 2 textile electrodes (10.02%) in comparison to commercial Ag/AgCl electrodes (11.11%). The posture monitoring module was also validated in terms of joint angle estimation and presented an overall error of 4.77° for a controlled angular velocity of 40°/s as benchmarked against a UR10 robotic arm.

Etonorgestrel implant is inserted on the inner surface of the non-dominant medial upper arm in women, over the triceps area. However, this case report aims to describe an alternative insertion site for etonorgestrel implant - the medial side of the thigh - in nephropathic patients with arteriovenous fistulas undergoing hemodialysis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Inherited bleeding disorders may cause heavy menstrual bleeding in women, impacting quality of life and impairing daily and social activities. The levonorgestrel-releasing intrauterine system is a potential treatment for these women, which might reduce menstrual blood loss., Study Design: We performed a systematic review and single-arm meta-analysis to examine the levonorgestrel-releasing intrauterine system in women with inherited bleeding disorders and heavy menstrual bleeding., Results: A systematic search on PubMed, Embase and Cochrane yielded 583 results, of which six observational studies (n = 156) met inclusion criteria. Levonorgestrel-releasing intrauterine system use in patients with inherited bleeding disorders and heavy menstrual bleeding was associated with amenorrhea in 60% of patients and a significant increase of 1.40 g/dL in hemoglobin and of 19.75 ng/mL in ferritin levels when comparing post- and pre-treatment levels. The post-treatment mean hemoglobin was 13.32 g/dL and the mean ferritin was 43.22 ng/dL. The rate of intrauterine device expulsion or removal due to mal position was low (13%), as was the need for intrauterine device removal due to lack of efficacy (14%)., Conclusion: The levonorgestrel-releasing intrauterine system may improve bleeding patterns and quality of life in patients with inherited bleeding disorders and heavy menstrual bleeding., Implications: Women with inherited bleeding disorders could benefit from levonorgestrel-releasing intrauterine system, so its use should be an option for this women., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the efficacy of a self-assessment questionnaire for hirsutism using the latest cutoff values recommended by the Endocrine Society (ES) for Latin-American women and by the European Society for Human Reproduction and Embryology (ESHRE)., Subject and Methods: Female premenopausal outpatients (n = 188) completed a self-assessment questionnaire, scoring hair presence across the nine areas evaluated by the modified Ferriman-Gallwey (mFG) scale. The results were compared with clinician-assessed scores rated independently by two trained physicians. Scores in the Hirsuta questionnaire, derived from self-assessment of five areas of the mFG scale, were also evaluated., Results: The ethnic composition of the sample was as follows: 23.1% white, 25.8% black, 48.9% mixed, and 2.1% other backgrounds (Indigenous, Asian). The participants had age and BMI of (mean ± standard deviation) 33.7 ± 9.9 years and 29.8 ± 7.21 kg/m 2 , respectively. The most common areas of excessive hair growth were the chin, upper and lower abdomen, and thighs. Relative to clinician-assessed mFG scores, self-assessed mFG scores had an accuracy of 80% using ES criteria for hirsutism diagnosis, with a sensitivity of 95.45%, specificity of 56.25%, positive predictive value of 30.10%, and negative predictive value of 98.40%. Self-assessed mFG had lower accuracy (71%) for diagnosing hirsutism when the ESHRE criteria were applied., Conclusions: Self-assessed mFG had low specificity, limiting its application. The results of this study do not support the use of the self-assessed mFG or Hirsuta scores for diagnosing hirsutism in a clinical setting, although both scoring systems may be useful for screening hirsutism in epidemiological studies., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

The dangers and stresses of a police officer's career cause physical and psychological distress which in turn cause considerable challenges for the integration of professional, family, and personal life. This study focuses on the conditions that influence this articulation between the personal, family, and professional lives of Portuguese Police (PSP) officers. A questionnaire survey was applied to 414 police officers from 11 divisions of COMETLIS. At the empirical level, several models were tested to assess the articulation between the professional, family, and personal lives of police officers. The results highlight the influence of having young children, elderly people or other dependents living in the family home, as well as the employee's age, on the job's interaction with professional life. At a professional level, the variables shift work, professional category, years of service and working away from home were identified by the officers as conditioning factors in the work-family-personal life balance. Sex differences in the articulation of professional, family, and personal life were also observed., 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., (Copyright © 2024 Rocha, Espírito Santo and Ferreira.)

Introduction: Antibody-mediated rejection (AMR) is the most common cause of immune-mediated allograft failure after kidney transplant and impacts allograft survival. Previous sensitization is a major risk factor for development of donor specific antibodies (DSA). AMR can have a wide range of clinical features such as impaired kidney function, proteinuria/hypertension or can be subclinical. HLA molecules have specific regions of antigens binding antibodies called epitopes and eplets are considered essential components responsible for immune recognition. We present a patient with subclinical AMR 1 week post transplantation., Case Report: A 48-year-old, caucasian woman with end-stage kidney disease (ESKD) secondary to autosomal dominant polycystic kidney disease (ADPKD) on peritoneal dialysis was registered in deceased donor waitlist. She was a hypersensitized patient from 3 prior pregnancies with a calculated panel reactive antibody of 93,48%. She was transplanted through kidney paired exchange donation with no evidence of DSA pre transplantation. Surgery and post-op were unremarkable with excellent and immediate graft function. Per protocol DSA levels on the 5th day was DR1 of 3300 MFI, with an increase in MFI by day 13 with 7820 MFI and a new B41 1979MFI. Allograft kidney biopsy findings were diagnostic of AMR and she was treated with immunoglobulin and plasmapheresis. As early onset AMR post transplantation was observed an anamnestic response was hypothesized from a previous exposure to allo-HLA. We decided to type her husband, her son's father, which was presented with DSA. Mismatch eplet analysis revealed a shared 41 T and 67LQ eplets between the donor and husband, responsible for the reactivity and new HLA class I B41 and HLA class II DR1 DSA, respectively., Discussion: Shared eplets between the patient husband and donor was responsible for the alloimmune response and early development of DSAs. This case highlights the importance of early monitoring DSA levels in highly sensitized patients after transplant in order to promptly address and lower inflammatory damage. Mismatch eplet analysis can provide a thorough and precise evaluation of immune compatibility providing a useful technique to immune risk stratification, donor selection and post-transplant immunosuppressive therapy and monitoring., (Copyright © 2023. Published by Elsevier B.V.)

Background: Diabetes mellitus is a chronic and multifactorial condition, including environmental risk factors such as lifestyle habits and genetic conditions., Objective: We aimed to evaluate the association of VDR gene polymorphism (rs2228570) FokI and vitamin D levels with diabetes in adults., Methods: Cross-sectional population-based study in adults, conducted from October to December 2020 in two Brazilian cities. The outcome variable was diabetes, defined as glycated hemoglobin ≥ 6.5% or self-report medical diagnosis or use of oral hypoglycemic drugs. Vitamin D (25-hydroxyvitamin D) was measured by indirect electrochemiluminescence, and classified as deficiency when 25(OH)D < 20 ng/mL. All participants were genotyped for VDR FokI polymorphism by qPCR and classified as homozygous mutant (ff or GG), heterozygous (Ff or AG), or homozygous wild (FF or AA). A combined analysis between the FokI polymorphism and vitamin D levels with diabetes was also examined. A directed acyclic graph (DAG) was used to select minimal and sufficient adjustment for confounding variables by the backdoor criterion., Results: The prevalence of DM was 9.4% and vitamin D deficiency (VDD) was 19.9%. The genotype distribution of FokI polymorphism was 9.9% FF, 44.8% Ff, and 45.3% ff. It was possible to verify a positive association between vitamin D deficiency and DM (OR = 2.19; 95% CI: 1.06-4.50). Individuals with the altered allele (ff) had a 1.78 higher prevalence of DM (OR: 1.78; 95% CI; 1.10-2.87). Combined analyses, individuals with vitamin D deficiency and one or two copies of the altered FokI allele had a higher prevalence of DM (Ff + ff: OR: 1.67; 95% CI; 1.07-2.61; ff: OR: 3.60; 95% CI; 1.40-9.25)., Conclusion: Our data suggest that vitamin D deficiency and FokI polymorphism are associated with DM., (© 2024. The Author(s).)

The increasing availability of time series data depicting the evolution of physical system properties has prompted the development of methods focused on extracting insights into the system behavior over time, discerning whether it stems from deterministic or stochastic dynamical systems. Surrogate data testing plays a crucial role in this process by facilitating robust statistical assessments. This ensures that the observed results are not mere occurrences by chance, but genuinely reflect the inherent characteristics of the underlying system. The initial process involves formulating a null hypothesis, which is tested using surrogate data in cases where assumptions about the underlying distributions are absent. A discriminating statistic is then computed for both the original data and each surrogate data set. Significantly deviating values between the original data and the surrogate data ensemble lead to the rejection of the null hypothesis. In this work, we present various surrogate methods designed to assess specific statistical properties in random processes. Specifically, we introduce methods for evaluating the presence of autodependencies and nonlinear dynamics within individual processes, using Information Storage as a discriminating statistic. Additionally, methods are introduced for detecting coupling and nonlinearities in bivariate processes, employing the Mutual Information Rate for this purpose. The surrogate methods introduced are first tested through simulations involving univariate and bivariate processes exhibiting both linear and nonlinear dynamics. Then, they are applied to physiological time series of Heart Period (RR intervals) and respiratory flow (RESP) variability measured during spontaneous and paced breathing. Simulations demonstrated that the proposed methods effectively identify essential dynamical features of stochastic systems. The real data application showed that paced breathing, at low breathing rate, increases the predictability of the individual dynamics of RR and RESP and dampens nonlinearity in their coupled dynamics., 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. The author(s) LF, RP, AR and YA declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pinto, Lazic, Antonacci, Pernice, Gu, Barà, Faes and Rocha.)

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ferreira, et al.)

Introduction: Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center., Methods: We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments)., Results: Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2)., Conclusions: Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.

This study explores a nanoemulsion formulated with açaí seed oil, known for its rich fatty acid composition and diverse biological activities. This study aimed to characterise a nanoemulsion formulated with açaí seed oil and explore its cytotoxic effects on HeLa and SiHa cervical cancer cell lines, alongside assessing its antioxidant and toxicity properties both in vitro and in vivo. Extracted from fruits sourced in Brazil, the oil underwent thorough chemical characterization using gas chromatography-mass spectrometry. The resulting nanoemulsion was prepared and evaluated for stability, particle size, and antioxidant properties. The nanoemulsion exhibited translucency, fluidity, and stability post centrifugation and temperature tests, with a droplet size of 238.37, PDI -9.59, pH 7, and turbidity 0.267. In vitro assessments on cervical cancer cell lines revealed antitumour effects, including inhibition of cell proliferation, migration, and colony formation. Toxicity tests conducted in cell cultures and female Swiss mice demonstrated no adverse effects of both açaí seed oil and nanoemulsion. Overall, açaí seed oil, particularly when formulated into a nanoemulsion, presents potential for cancer treatment due to its bioactive properties and safety profile.

The aim of this study was to evaluate the influence of different stunning methods on the meat quality of Arapaima gigas fillets from fish farming. A total of 48 specimens of A. gigas in the weight class 11.1 to 14.0 kg were investigated; these fish were subjected to different stunning methods for slaughter: ice asphyxia (IA), air asphyxia (AA), electronarcosis (EE) and hypothermia followed by bleeding (HB). Then, data were obtained from the analysis of pH, rigor mortis index (RI), water activity (Aw), instrumental texture (compression strength, firmness and adhesiveness) and blood glucose and via instrumental colourimetry. During the study, for up to 15 days of refrigerated storage, the methods provided pH values below 6.0. A. gigas submitted to EE and HB remained longer in the pre-rigor status. In addition, they expressed lower percentages of Aw. The EE method resulted in better texture assignments in the fillets. The blood glucose values indicated that the fish subjected to EE were less stressed. Concerning instrumental colourimetry, the fillets submitted to EE and HB showed greater luminosity; the fillets subjected to AA showed greater red-green colour intensity, while the fillets subjected to EE showed greater yellow-blue colour intensity. Therefore, the fish did not suffer stress with electronarcosis, and the fillets showed better preservation, juiciness, and tenderness.

Malnutrition is considered one of the major public health problems worldwide and negatively affects the growth, development and learning of schoolchildren. This study developed and evaluated a fermented milk drink with added Umbu (Spondias tuberosa) pulp in the weight gain and renutrition of mice submitted to malnutrition by calorie restriction, and in malnourished children. The supplementation with this fermented milk drink contributed to an increase of 7.2 % in body weight, and 64.3 % in albumin, and a reduction of 35 % in cholesterol in malnourished mice. In humans, a group of nine malnourished children consumed a daily 200 mL serving of the milk drink (for 60 days). For humans, the fermented milk drink allowed an increase of 16.5 % in body weight, and 20.9 % in body mass index in malnourished children. In conclusion, fermented milk drink has a positive effect on the re-nutrition of malnourished mice and helps to improve the nutritional status of malnourished children., 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.)

Purpose: To determine the degree of central microvascular closure using optical coherence tomography angiography in eyes of patients with type 2 diabetes with visible lesions only in the central retina or only in the periphery., Methods: Cross-sectional study. All 127 eyes underwent ultra-widefield fundus photography 200° examinations with OPTOS California (Optos, Dunfermline, United Kingdom) and Cirrus Angioplex optical coherence tomography angiography 3 × 3 mm acquisitions (ZEISS, Dublin, CA)., Results: Twenty-five eyes showed visible lesions only in the central retina, 57 only in the peripheral retina, and 45 presented visible lesions in entire retina. The group with visible lesions only in the periphery showed definite closure in the superficial capillary plexus in 49% of the eyes, whereas the group with visible lesions only in the central seven-early treatment diabetic retinopathy study fields area showed a definite closure in 64%., Conclusion: Central capillary closure is already present in the initial stages of diabetic retinopathy even when lesions are only visible in the peripheral retina. Capillary closure in the superficial capillary plexus is three times more frequent than in the deep capillary plexus, demonstrating earlier closure of the superficial capillary plexus. Eyes with visible lesions only in the periphery show a milder form of retinopathy., Competing Interests: A.R. Santos, A.C. Almeida, A.C. Rocha, D. Reste-Ferreira, I.P. Marques, A. Cunha-Vaz Martinho, L. Mendes and T. Santos declare no conflicts of interest. W. Lewis is a consultant/contractor for Carl Zeiss Meditec. J. Cunha-Vaz reports grants from Bayer, Boehringer Ingelheim, and Carl Zeiss Meditec and is a consultant for Alimera Sciences, Bayer, Boehringer Ingelheim, Carl Zeiss Meditec, and Roche., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often linked to metabolic syndrome (MS), raising the risk of cardiovascular disease and type II diabetes. Certain indicators, such as the lipid accumulation product (LAP) and homeostatic model assessment for insulin resistance (HOMA-IR), can predict MS in PCOS patients. This study aimed to assess the predictive power of the visceral adiposity index (VAI) in comparison to LAP and HOMA-IR as predictors of MS in PCOS patients., Methods: In this cross-sectional observational study, data from 317 diagnosed PCOS women were analyzed. VAI, LAP, and HOMA-IR were computed as indexes. Participants were categorized into two groups for index accuracy comparison: PCOS patients with and without MS. The data were assessed using a ROC curve., Results: Among PCOS women with MS, 92.3% had abnormal VAI results, 94.5% had abnormal LAP results, and only 50.5% had abnormal HOMA-IR results. Conversely, the majority of PCOS women without MS had normal HOMA-IR (64.6%). When comparing these indexes using the ROC curve, VAI displayed the highest accuracy, followed by LAP and HOMA-IR., Conclusion: The VAI index proved to be a superior predictor of metabolic MS in PCOS women when compared to other indexes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Novelty influences hippocampal-dependent memory through metaplasticity. Mismatch novelty detection activates the human hippocampal CA1 area and enhances rat hippocampal-dependent learning and exploration. Remarkably, mismatch novelty training (NT) also enhances rodent hippocampal synaptic plasticity while inhibition of VIP interneurons promotes rodent exploration. Since VIP, acting on VPAC 1 receptors (Rs), restrains hippocampal LTP and depotentiation by modulating disinhibition, we now investigated the impact of NT on VPAC 1 modulation of hippocampal synaptic plasticity in male Wistar rats. NT enhanced both CA1 hippocampal LTP and depotentiation unlike exploring an empty holeboard (HT) or a fixed configuration of objects (FT). Blocking VIP VPAC 1 Rs with PG 97269 (100 nM) enhanced both LTP and depotentiation in naïve animals, but this effect was less effective in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). HT and FT animals showed mildly enhanced synaptic VPAC 1 R levels, but neither VIP nor VPAC 1 R levels were altered in NT animals. Conversely, NT enhanced the GluA1/GluA2 AMPAR ratio and gephyrin synaptic content but not PSD-95 excitatory synaptic marker. In conclusion, NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons while upregulation of VIP VPAC 1 Rs is associated with the maintenance of VIP control of LTP in FT and HT animals. This suggests VIP receptor ligands may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs., (© 2024 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous vasoactive intestinal peptide (VIP) acting on its VPAC 1 receptor strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC 1 receptor levels are developmentally regulated during embryogenesis, their variation along postweaning development is unknown, as is the VPAC 1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC 1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by mild TBS (5 bursts, 4 pulses delivered at 100 Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC 1 receptor antagonist PG 97-269 (100 nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young adult (6-7-week-old) or adult (12-week-old) rats. This effect was not associated with a developmental decrease in synaptic VPAC 1 receptor levels. However, an increase in pre and post-synaptic GABAergic synaptic markers suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC 2 receptor activation did not significantly influence TBS-induced LTP. VPAC 2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis.

Novelty detection, crucial to episodic memory formation, is impaired in epileptic patients with mesial temporal lobe resection. Mismatch novelty detection, that activates the hippocampal CA1 area in humans and is vital for memory reformulation and reconsolidation, is also impaired in patients with hippocampal lesions. In this work, we investigated the response to mismatch novelty, as occurs with the new location of known objects in a familiar environment, in the Li 2+ -pilocarpine rat model of TLE and its correlation with hippocampal monoaminergic markers. Animals showing spontaneous recurrent seizures ( SRSs ) for at least 4 weeks at the time of behavioural testing showed impaired spatial learning in the radial arm maze, as described. Concurrently, SRS rats displayed impaired exploratory responses to mismatch novelty, yet novel object recognition was not significantly affected in SRS rats. While the levels of serotonin and dopamine transporters were mildly decreased in hippocampal membranes from SRS rats, the levels on the norepinephrine transporter, tyrosine hydroxylase and dopamine-β-hydroxylase were enhanced, hinting for an augmentation, rather than an impairment in noradrenergic function in SRS animals. Altogether, this reveals that mismatch novelty detection is particularly affected by hippocampal damage associated to the Li 2+ -pilocarpine model of epilepsy 4-8 weeks after the onset of SRSs and suggests that deficits in mismatch novelty detection may substantially contribute to cognitive impairment in MTLE. As such, behavioural tasks based on these aspects of mismatch novelty may prove useful in the development of cognitive therapy strategies aiming to rescue cognitive deficits observed in epilepsy.

Background: We aimed to describe the event rates and risk-factors for symptomatic venous thromboembolism (VTE) and major bleeding in a population of hospitalized acutely ill medical patients., Methods: Patients ≥40 years old and hospitalized for acute medical illness who initiated enoxaparin prophylaxis were selected from the US Optum research database. Rates of symptomatic VTE and major bleeding at 90-days were estimated via the Kaplan-Meier (KM) method. Risk factors were identified via the Cox proportional hazards model., Results: A total of 123,022 patients met the selection criteria. The KM rates of VTE and major bleeding at 90-days were 3.5 % and 2.2 %, respectively. Among subgroups, the risk of VTE varied from 3.0 % in patients with ischemic stroke to 6.9 % in patients with a cancer-related hospitalization, and the risk of major bleeding varied from 1.9 % in patients with inflammatory conditions to 3.6 % in patients with ischemic stroke. Key risk factors for VTE were prior VTE (HR=4.15, 95 % confidence interval [CI] 3.80-4.53), cancer-related hospitalization (HR=2.35, 95 % CI 2.10-2.64), and thrombophilia (HR=1.64, 95 % CI 1.29-2.08). Key risk factors for major bleeding were history of major bleeding (HR=2.17, 95 % CI 1.72-2.74), history of non-major bleeding (HR=2.46, 95 % CI 2.24-2.70), and hospitalization for ischemic stroke (2.42, 95 % CI 2.11-2.78)., Conclusion: There is substantial heterogeneity in the event rates for VTE and major bleeding in acute medically ill patients. History of VTE and cancer related hospitalization represent profiles with a high risk of VTE, where continued VTE prophylaxis may be warranted., Competing Interests: Declaration of Competing Interest Dr. Le Gal reports financial support, article publishing charges, statistical analysis, and writing assistance were provided by Sanofi, honoraria for lectures and advisory boards from BMS, Inari, Leo Pharma, Pfizer, Sanofi and Stago. Dr. Agnelli reports financial support, statistical analysis, and writing assistance were provided by Sanofi, honoraria for lecture and advisory board contribution from BMS, Pfizer, Daiichi Sankyo and Anthos Therapeutics; reports a relationship with European Journal of Internal Medicine that includes: board membership. Dr. Darius reports financial support, statistical analysis, and writing assistance were provided by Sanofi. Dr. Kahn reports financial support was provided by Sanofi, and reports research grants from the Canadian Institutes of Health Research and consulting honoraria from Alexion for unrelated educational activities. Dr. Owaidah reports honoraria from Sanofi and financial support, statistical analysis, and writing assistance were provided by Sanofi. Dr. Rocha reports financial support, statistical analysis, and writing assistance were provided by Sanofi, and honoraria from the pharmaceutical industry for lectures on anticoagulation; is on speaker’s bureau for Bayer, Boehringer and Pfizer, and is a consultant/advisor for Pfizer and Sanofi. Dr. Zhai reports financial support, statistical analysis, and writing assistance were provided by Sanofi. Dr. Khan is an employee and stockholder of Sanofi and reports financial support was provided by Sanofi. Dr. Djoudi is an employee and stockholder of Sanofi and reports financial support was provided by Sanofi. Dr. Ponomareva is a consultant to Sanofi and reports financial support, statistical analysis, and writing assistance were provided by Sanofi. Dr. Cohen reports financial support, statistical analysis, and writing assistance were provided by Sanofi and fees for serving on adjudication committees for Boehringer Ingelheim and AbbVie; grant support and fees for serving on committees from Bristol Myers Squibb, Daiichi Sankyo, and Pfizer; consulting fees from Janssen, Portola Pharmaceuticals, and Ono Pharmaceuticals; and fees for serving on a steering committee and consulting fees from Bayer., (Copyright © 2023. Published by Elsevier B.V.)

Bryconops Kner, 1858, includes two well defined subgenera based on morphological evidence, with each containing at least one species (B. (Bryconops) caudomaculatus and B. (Creatochanes) melanurus) with a very wide distribution, within which regional populations present color variations. To test if phenotypic variation is related to cladogenetic events, we performed tests for phylogenetic independence and determined the strength of convergence for color characters in relation to water type, as the variation between clear, black and white waters is considered to be one of the major driving forces in the evolution of Amazonian fishes. Color characters for fins above the median line of the body were generally found to be independent from phylogeny and the Wheatsheaf test strongly supports convergence of the dorsal fin color between populations of species in the same type of water, with a similar trend suggested for the color of the dorsal lobe of the caudal fin. This means that simple color characters cannot necessarily be relied upon for taxonomic revisions of the genus as local phenotypic variants may represent environmentally determined plasticity or convergent evolution. Further studies are required to determine the validity of these characters., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gonçalves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, p = 0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined., Competing Interests: Declaration of competing interest Dr. Leucker has received grants from American Heart Association Career Development Award, National Institutes of Health, Merck, and Amgen. The remaining authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.

Introduction: Animal models play a crucial role in breast cancer research, in particular mice and rats, who develop mammary tumors that closely resemble their human counterparts. These models allow the study of mechanisms behind breast carcinogenesis, as well as the efficacy and safety of new, and potentially more effective and advantageous therapeutic approaches. Understanding the advantages and disadvantages of each model is crucial to select the most appropriate one for the research purpose., Area Covered: This review provides a concise overview of the animal models available for breast cancer research, discussing the advantages and disadvantages of each one for searching new and more effective approaches to treatments for this type of cancer., Expert Opinion: Rodent models provide valuable information on the genetic alterations of the disease, the tumor microenvironment, and allow the evaluation of the efficacy of chemotherapeutic agents. However, in vivo models have limitations, and one of them is the fact that they do not fully mimic human diseases. Choosing the most suitable model for the study purpose is crucial for the development of new therapeutic agents that provide better care for breast cancer patients.

This work aimed to understand how lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of PCa. Fifty-five male Wistar rats were divided into four groups: control sedentary, control exercised, induced PCa sedentary and induced PCa exercised. Exercised animals were trained in a treadmill for 53 weeks. Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants. Serum concentrations of C-reactive protein (CRP) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) were not different among groups. Peripheral levels of γδ T cells were higher in Pca exercised group than in the PCa sedentary group (p < 0.05). Exercise training also induced Oestrogen Receptor (ESR1) upregulation and Mitogen-activated Protein Kinase 13 (MAPK13) downregulation, changed the content of the phosphorylated (at Ser-104) form of this receptor (coded by the gene ESR1) and seemed to increase Erα phosphorylation and activity in exercised PCa rats when compared with sedentary PCa rats. Our data highlight the exercise-induced remodelling of peripheral lymphocyte subpopulations and lymphocyte infiltration in prostate tissue. Moreover, exercise training promotes the remodelling prostate signalome in this rat model of prostate carcinogenesis., (© 2023. The Author(s).)

Subjective cognitive complaints (SCC) is a self-reported experience of persistently impaired cognitive functions which could be the earliest red flag of neurocognitive disorders. The COVID-19 pandemic and related restriction measures changed the lifestyle and behaviour of older adults. The aim of this study was to assess the relation of these changes and SCC status in Hungary. This cross-sectional study analysed the data of 359 elderly Hungarians who filled out the WW-FINGERS-SARS-CoV2 survey. A quarter of the respondents (n:88) reported SCC in connection with the pandemic. We compared sociodemographic features, health status, lifestyle, and social life parameters between subjects with reported SCC and without. To eliminate the potential interrelation across group differences, stepwise logistic regression was applied. Participants with SCC showed the following characteristics, compared to individuals without: (1) they were older; (2) they were more likely to be women; (3) they had a higher number of chronic disorders; (4) showed more prominent impairment in physical mobility; (5) had worse sleep quality; (6) spent less time with family; and (7) used internet more frequently during the pandemic (all p's < 0.001). Logistic regression highlighted that only two parameters were related to SCC status independently, the physical mobility (ability to walk 500 m without difficulties; OR = 1.186; p < 0.001; 95%CI = 1.101, 1.270) and changes in time spent with grandchildren (OR = 1.04; p = 0.015; 95%CI = 1.008, 1.073). Our study draws attention to the importance of physical mobility and quality time with family as key factors in the cognitive well-being of elderly people., (© 2024. The Author(s).)

The COVID-19 pandemic imposed changes upon the capacity of healthcare systems, with significant repercussions on healthcare provision, particularly at end-of-life. This study aims to analyze the concept map of death unpreparedness due to the COVID-19 pandemic, capturing the relationships among the attributes, antecedents, consequences, and empirical indicators. Walker and Avant's method was used to guide an analysis of this concept. A literature search was performed systematically, between May 2022 and August 2023, using the following electronic databases on the Elton Bryson Stephens Company (EBSCO) host platform: Medical Literature Analysis and Retrieval System Online (Medline), Psychological Information Database (PsycINFO), Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, Cochrane Library, and Nursing and Allied Health Collection. Thirty-four articles were retrieved. The unexpected and unpredictable impositions associated with inexperience and unskillfulness in dealing with COVID-19 configured challenges for healthcare professionals, family/caregivers, and even the dying person. Nine key attributes emerged in three main domains: (1) Individual: (a) disease-related conditions, (b) separation distress, and (c) scarcity of death and grief literacy; (2) Relational: (a) Dying alone, (b) poor communication, and (c) existential issues; and (3) Contextual: (a) disrupted collective mourning and grieving, (b) disrupted compassionate care and, (c) pandemic social stigma. This study contributed a full definition of death unpreparedness in a global pandemic scenario such as COVID-19. In this sense, feeling unprepared or unready for death brought new challenges to the bioecological resources of those affected. It is essential to embrace strategies capable of providing emotional and spiritual support in the dying process and to respect patient wishes. The lessons learned from COVID-19 should be applied to events with a comparable impact to minimize their consequences.

Prostate cancer is a very common cancer in men, affecting approximately 1.40 million men worldwide in 2020. To improve the quality of life and survival of both animals and humans, effective therapeutic approaches have been developed and evaluated using animal models. The rat model of prostate cancer induced by a multi-step protocol that consists of a sequential administration of flutamide, followed by testosterone propionate, then the administration of N-methyl-N-nitrosourea, and finally subcutaneous implantation of tubes filled with crystalline testosterone, is one of the most frequently used for prostate cancer research. However, the lack of standardization in procedures for prostate cancer induction, sample collection, and analysis represents a challenge for researchers. To address this issue, we aim to provide investigators with a detailed, step-by-step guide to implementing a rat model of prostate cancer, based on our extensive experience in this field. First, we briefly review the prostate cancer-induced protocols found in the literature, then we provide a detailed description of the prostate cancer rat model implemented by our team. After, we explore the rats' prostate monitoring during the experiment protocol through imaging modalities, such as ultrasonography, computed tomography, and magnetic resonance imaging. We also describe animal welfare monitoring based on a table of humane endpoints, as well as data collection, such as biological variables and prostate samples. In sum, this article will ensure the quality of results and enable their comparison among different researchers using this rat model. Guidelines, Male, Murinic, Rodent, Tumor., Competing Interests: There are no conflicts of interest to declare for any of the authors., (© 2024 Urmia University. All rights reserved.)

Parasitism is one of the most important diseases in nonhuman primates (NHP). Parasitism by Prosthenorchis elegans can be a threat to health and conservation of NHP in Costa Rica. Surgical management of intestinal acanthocephalan infection in two squirrel monkeys ( Saimiri oerstedii ) and one white-faced monkey ( Cebus imitator ) is described as an alternative to the lack of pharmacologic control options when there is a high burden of parasites present. A complete physical evaluation, including medical ultrasound techniques, allow for diagnosis of the parasite and its lesions. When animals present with a high burden of parasites, surgical management has shown to promote good health outcomes and increase the probability of survival.

The salivary glands play a central role in the secretion of saliva, whose composition and volume affect oral and overall health. A lesser-explored dimension encompasses the possible changes in salivary gland proteomes in response to fluctuations in sex hormone levels. This study aimed to examine the effects of chronic exposure to testosterone on salivary gland remodeling, particularly focusing on proteomic adaptations. Therefore, male Wistar rats were implanted with subcutaneous testosterone-releasing devices at 14 weeks of age. Their submandibular glands were histologically and molecularly analyzed 47 weeks later. The results underscored a significant increase in gland mass after testosterone exposure, further supported by histologic evidence of granular duct enlargement. Despite increased circulating sex hormones, there was no detectable shift in the tissue levels of estrogen alpha and androgen receptors. GeLC-MS/MS and subsequent bioinformatics identified 308 proteins in the submandibular glands, 12 of which were modulated by testosterone. Of note was the pronounced upregulation of Klk3 and the downregulation of Klk6 and Klk7 after testosterone exposure. Protein-protein interaction analysis with the androgen receptor suggests that Klk3 is a potential target of androgenic signaling, paralleling previous findings in the prostate. This exploratory analysis sheds light on the response of salivary glands to testosterone exposure, providing proteome-level insights into the associated weight and histological changes.

Aims: Endovascular therapy (EVT) is a highly effective stroke treatment, but it requires the administration of contrast media which puts patients at risk of acute kidney injury (AKI). AKI is associated with increased morbidity and mortality in cardiovascular patients., Methods: PubMed, Scopus, ISI and the Cochrane Library were systematically searched for observational and experimental studies assessing the occurrence of AKI in adult acute stroke patients submitted to EVT. Two independent reviewers collected study data regarding study setting, period, source of data, and AKI definition and predictors, the outcomes of interest being AKI incidence and 90-day death or dependency (modified Rankin Scale score ≥3). These outcomes were pooled using random effect models, and heterogeneity was measured using the I 2 statistic., Results: 22 studies were identified and included in the analysis, involving 32 034 patients. Pooled incidence of AKI was 7% (95% CI 5% to 10%), but heterogeneity was high across studies (I 2 =98%), and not accounted for by the definition of AKI used. The most frequently reported AKI predictors were impaired baseline renal function (5 studies) and diabetes (3 studies); 3 studies (2103 patients) reported data on death and 4 studies (2424 patients) reported data on dependency. Overall, AKI was associated with both outcomes, with ORs of 6.21 (95% CI 3.52 to 10.96) and 2.86 (95% CI 1.88 to 4.37), respectively. Heterogeneity was low for both analyses (I 2 =0%)., Conclusions: AKI affects 7% of acute stroke patients submitted to EVT and identifies a subgroup of patients for which treatment outcomes are suboptimal, with an increased risk of death and dependency., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)