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Competing Interests: DISCLOSURE: There are no conflicts of interest. Ethical Approval: The study was approved with registration: CARMS-18769.

Background : Chronic obstructive pulmonary disease (COPD) is a frequent but underdiagnosed disease, primarily due to the lack of access to forced spirometry (FS) in primary care. Portable, easy-to-use expiratory flow meters like Piko-6 ® and COPD-6 ® that measure FEV 1 , FEV 6 , and FEV 1 /FEV 6 ratio provide an alternative. Given that Piko-6 ® and COPD-6 ® devices measure FEV 6 but not FVC, the aim of the study is to determine the optimal cutoff value for the FEV 1 /FEV 6 ratio of each device to avoid false negatives when these devices are used for COPD screening in primary care (PC). Methods : A total of 664 patients of 35 years of age or older with a cumulative tobacco consumption of 10 or more packs/year were recruited at two university hospitals. FS (gold standard) was performed and FEV 1 , FVC, and FEV 1 /FVC measurements were compared with FEV 1 , FEV 6 , and FEV 1 /FEV 6 measurements acquired using Piko-6 ® and COPD-6 ® devices. The devices were compared using statistical methods including Pearson correlation coefficients, the Youden index (YI), kappa coefficient, Bland-Altman plots, and ROC curves analysis. Results : Correlations between FEV 1 /FEV 6 using Piko-6 ® and COPD-6 ® and FEV 1 /FVC with FS were 0.79 and 0.73, respectively. Piko-6 ® achieved the best YI in FEV 1 /FEV 6 (0.73), whereas for COPD-6 ® , it was 0.80. Concordance between Piko-6 ® and FS was 83.9% (kappa 0.67 ± 0.028) and for COPD-6 ® , it was 68.7% (kappa 0.42 ± 0.02). Conclusions : This is the first study that compares two hand-held expiratory flow meters with FS. Piko-6 ® and COPD-6 ® devices are effective tools for COPD detection, as their measurements provide a good correlation with FS. In order to avoid false negative results, the FEV 1 /FEV 6 cutoff point needs to be increased to 0.73 and 0.80 with Piko-6 ® and COPD-6 ® , respectively.

Objective: This study examines how age at death, sex, and socio-historical context relate to the frequency, location, and severity of Schmorl's nodes., Materials: The sample comprised thoracic and lumbar vertebrae of 192 skeletons from two contemporary documented osteological collections from Spain, in Valladolid and Granada, both of which contain individuals who died during the second half of the 20th century., Methods: Schmorl's nodes were recorded on the superior and inferior surfaces of vertebral bodies and their location was categorized in one of three areas: center, canal, and periphery., Results: The prevalence of Schmorl's nodes was 57.42 % for the Valladolid collection and 67.39 % for Granada, with no significant differences between collections. Statistically significant differences were found between the sexes, but age at death did not correlate with the presence of the lesion., Conclusions: This analysis supports the absence of a direct relationship between the pathology and the aging process, but shows a greater predisposition in male individuals, suggesting that vertebral morphology and/or physical activity might be key etiological factors., Significance: This research enhances our understanding of the etiology of Schmorl's nodes by highlighting sex as a key variable and suggesting a lack of association with age., Limitations: The absence of data on occupational activity prevents correlating this variable with the presence of Schmorl's nodes., Suggestions for Further Research: Conduct studies on geometric morphometric data to corroborate the evolutionary hypothesis proposed by other authors., Competing Interests: Declaration of Competing Interest None, (Copyright © 2025 Elsevier Inc. All rights reserved.)

Treatment of non-small-cell lung cancers (NSCLC) has evolved over the last decade. According to studies, the use of targeted therapies has significantly increased the life expectancy of patients. Moreover, ALK-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes. In Lebanon, translating recommendations into clinical practice remains challenging. A Lebanese expert panel of oncologists was convened to describe the management paradigm and the clinical evidence supporting the optimal use of next-generation TKIs in patients with ALK -rearranged NSCLC and to provide an expert overview of local challenges and recommendations for optimizing the management of advanced NSCLC in Lebanese patients. The experts agreed that these recommendations should be part of a healthcare strategy to be implemented at the national level.

Introduction and Objectives: This article presents the 2023 activity report of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC)., Methods: All interventional cardiology laboratories in Spain were invited to participate in an online survey. Data analysis was carried out by an external company and subsequently reviewed and presented by the members of the ACI-SEC board., Results: A total of 119 hospitals participated. The number of diagnostic studies decreased by 1.8%, while the number of percutaneous coronary interventions (PCI) showed a slight increase. There was a reduction in the number of stents used and an increase in the use of drug-coated balloons. The use of intracoronary diagnostic techniques remained stable. For the first time, data on PCI guided by intracoronary imaging was reported, showing a 10% usage rate in Spain. Techniques for plaque modification continued to grow. Primary PCI increased, becoming the predominant treatment for myocardial infarction (97%). Noncoronary structural procedures continued their upward trend. Notably, the number of left atrial appendage closures, patent foramen ovale closures, and tricuspid valve interventions grew in 2023. There was also a significant increase in interventions for acute pulmonary embolism., Conclusions: The 2023 Spanish cardiac catheterization and coronary intervention registry indicates a stabilization in coronary interventions, together with an increase in complexity. There was consistent growth in procedures for both valvular and nonvalvular structural heart diseases., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Anxiety and depression are highly prevalent disorders among individuals undergoing chronic haemodialysis. For patients with kidney disease, the haemodialysis process often exacerbates these conditions. This study aims to investigate the effects of listening to live classical music on anxiety and depression scales during haemodialysis sessions., Methods: A randomised clinical trial was conducted with a group of patients who listened to live classical music during haemodialysis sessions, while the control group received treatment as usual. Anxiety and depression levels were assessed at baseline and after 4 weeks of listening to live music. The study comprised 90 patients., Results: The results demonstrated a significant decrease in anxiety and depression among the intervention group, who listened to music, compared to the control group, who did not receive this intervention. Specifically, the intervention group, presented a decrease in score on the anxiety scale of -5.35 (p < 0.001) points on average and a decrease in score on the depression scale of -5.88 (p < 0.001) points on average, while in the control group the levels worsened with the progression of time., Conclusion: It is concluded that listening to live classical music during haemodialysis sessions reduces anxiety and depression levels in HD patients. This conclusion adds value to listening to live music in the hospital context, specifically in this case, in haemodialysis rooms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Soliva 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.)

Various exogenous factors, such as microbiological and chemical contamination condition food security. Salmonella Typhimurium ( S. Typhimurium ) is the cause of salmonellosis. This bacterium utilizes phagocytosis to create bacterial reservoirs. On the other hand, exposure to chemical contaminants, such as pesticides, increases susceptibility to numerous infections. Therefore, this research aims to evaluate the effect of co-exposure to diazoxon and S. Typhimurium on the in vitro infection dynamics. For this purpose, human mononuclear cells were pre-exposed in vitro to diazoxon and then challenged with S. Typhimurium at 1, 8, and 24 h. Bacterial internalization, actin polymerization, and reactive oxygen species (ROS) were analyzed. Obtained data show that mononuclear cells previously exposed to diazoxon exhibit greater internalization of S. Typhimurium . Likewise, greater ROS production and an increase in actin polymerization were observed. Therefore, in the proposed scenario, obtained data suggest that co-exposure to diazoxon and S. Typhimurium increases susceptibility to acquiring an illness.

Objective: The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA)., Design: This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment., Methods: Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality., Results: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline., Conclusion: In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. 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.)

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden. Considering that CVDs are one of the top mortality causes worldwide, the concept of residual cardiovascular risk is an important emerging area of study. Different factors have been proposed as sources of residual risk markers, including non-HDL particles characterization, as well as inflammation measured by serum and imaging technics. Among these, metabolic-associated steatotic liver disease (MASLD) remains controversial. Two opposing viewpoints contend: one positing that fatty liver disease merely reflects classical risk factors and thus adds no additional risk and another asserting that fatty liver disease independently impacts cardiovascular disease incidence. To address this dilemma, one hypothetical approach is to identify specific hepatic energy-yielding mechanisms and assess their impact on the cardiovascular system. Ketogenesis, a metabolic intermediate process particularly linked to energy homeostasis during fasting, might help to link these concepts. Ketogenic metabolism has been shown to vary through MASLD progression. Additionally, newer evidence supports the significance of circulating ketone bodies in cardiovascular risk prediction. Furthermore, ketogenic metabolism modification seems to have a therapeutic impact on cardiovascular and endothelial damage. Describing the relationship, if any, between steatotic liver disease and cardiovascular disease development through ketogenesis impairment might help to clarify MASLD's role in cardiovascular risk. Furthermore, this evidence might help to solve the controversy surrounding liver steatosis impact in CVD and might lead to a more accurate risk assessment and therapeutic targets in the pursuit of precision medicine.

In this paper, we outline the development of stoichiometric chalcostibite, CuSbS 2 thin films, from a single bath by pulse electrodeposition for its application as a photocathode in photoelectrochemical cells (PEC). The Cu/Sb precursor molar ratio of the deposition bath was varied to obtain stoichiometric CuSbS 2 thin films. The optimized deposition and dissolution potentials were -0.72 V and -0.1 V vs saturated calomel electrode, respectively. The formation of CuSbS 2 was analyzed using different characterization tools. X-ray diffraction and Raman results showed the formation of the pure chalcostibite phase from a precursor bath with molar ratio Cu/Sb = 0.41. The heterostructure CuSbS 2 /CdS/Pt was tested as a photocathode in the PEC. The energy positions of the conduction and valence bands were estimated from the Mott Schottky plots. The conduction band and valence band offset of CuSbS 2 /CdS heterojunction were 0.1 eV and 1.04 eV, respectively. The electric field created in the junction reduced the recombination of the electron/hole pairs and improved charge transfer in the interface. The heterostructure CuSbS 2 /CdS/Pt demonstrated an improved photocurrent density of 3.4 mA cm -2 at 0 V vs reversible hydrogen electrode. The PEC efficiency obtained from the CuSbS 2 /CdS heterojunction was 0.56 %. Therefore, we demonstrated the feasibility of an inexpensive technique like electrodeposition for the development of an efficient earth-abundant photocathode., Competing Interests: 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., (© 2024 The Author(s).)

Introduction and Importance: Pemphigus Vulgaris (PV) is a low incidence autoimmune mucocutaneous bullous disease, in which pathogenic antibodies are directed against the keratinocyte cell surface. Although anal involvement is unusual, correlations between its appearance and disease severity have been recently reported., Case Presentation: A 42-year-old male presented with an anal fissure and a year of recurrent oral and pharyngeal aphtha. A chemical sphincterotomy with botulinum toxin plus fissurectomy was performed. 3 years later an upper eyelid injury raised suspicion of pemphigus vulgaris (PV), tested negative for specific antibodies. A couple years later, an anal fissure, and suspected Crohn's disease, led to a second intervention. Surgical analysis unveiled characteristics indicative of a vegetating variant of PV., Clinical Discussion: Anal involvement in PV varies in prevalence, with studies reporting rates between 2 % and 27.98 %. This manifestation often accompanies late disease stages and may indicate severity, notably in association with oral lesions. Patients might not readily discuss anal symptoms, leading to potential underreporting. Anal PV is linked to other lesions (ocular, nasal, genital) and the severity of oral PV. Even when other sites are in remission, anal recurrence can occur. Early recognition and follow-up are crucial, highlighting the need for routine anal examination and confirmatory diagnostics., Conclusion: PV lesions can present on the skin or mucosa, although oral lesions are the most common site of initial presentation. Anal PV is a diagnostic challenge, and this case illustrates the importance of a careful evaluation., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this study was to investigate the efficacy of physical exercise in chronic kidney disease, describing its impact on the Klotho-FGF23 axis. PubMed, Web of Science and Scopus databases, updated to January 2023, were searched. The present study employed mean difference and a 95% confidence interval (CI) to examine the efficacy of the intervention. Heterogeneity was assessed through inconsistency statistics (I2). Out of the 299 studies identified, a total of 4 randomized controlled trials (RCTs), comprising 272 participants, met the eligibility criteria. Compared with the control group, physical exercise significantly decreased the concentrations of FGF23 (MD: -102.07 Pg/mL, 95% CI: -176.23.47, -27.91 I2= 97%, p = 0.001), and a significantly increased the concentrations of Klotho protein: (MD: 158.82 Pg/mL, 95% CI: 123.33, -194.31, I2 = 0%, p = 0.001). The results of our study indicated that the exercise has a direct relationship with Klotho-FGF23 axis. We can conclude that physical exercise in patients with CKD produces beneficial effects on the pathophysiological components related to this disease, including cardiorespiratory fitness and vascular functions. As observed, both endurance and aerobic physical exercise increase Klotho production and decrease FGF23 levels. Evidence indicates that exercise attenuates the progression of CKD, improves uremic parameters and down-regulates inflammation-related markers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Early stress can increase vulnerability to psychopathological disorders, including substance use disorders. The effects of stress in the juvenile period of the rat, that extends between weaning and the onset of adolescence (equivalent to late human childhood), have received little attention. This study assessed short and long-term behavioral effects of juvenile stress, with a focus on effects on ethanol intake. Male and female Wistar rats were exposed to variable stress (restraint, elevated platform, forced swimming, and social instability) or to restraint stress only, between postnatal days 26 to 29 (PDs 26-29). During adolescence, patterns of anxiety (PD 31) and depression (PD 33), ethanol intake (PDs 36-45) and behavioral sensitivity to the effects of acute stress (PD 47) were evaluated. In adulthood, alcohol ingestion was assessed through two-bottle ethanol intake tests (PDs 75-85). An additional experiment measured blood ethanol levels after a limited access intake session in adolescence. Exposure to juvenile variable stress exerted very mild effects in adolescence, but reduced ethanol ingestion in adulthood, in females only. Ethanol intake during the limited access session was significantly correlated to blood alcohol levels. The results indicate that a schedule of juvenile variable stress that did not significantly alter anxiety-related behaviors induced, nonetheless, sexually dimorphic effects on ethanol intake in adulthood. Early stress exposure that reduced alcohol intake in Wistar rats has been associated with changes on brain opioid and dopamine receptors. These results highlight the impact of early stress exposure on adult female ethanol consumption and its possible underlying neurobiological changes, involving opioid and dopamine receptors., Competing Interests: Declaration of Competing Interest We declare having no competing interest nor conflict of interest related to our MS or its results., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Anxiety and stress are common mental health conditions reported by university workers. Practices of mindfulness represent one promising approach as an effective and feasible means to reduce stress, improve mental health and promote well-being; however, there are no clinical trials that have combined long-term stress biomarkers (hair cortisol) and psychometric assessments in a sample of university workers., Objective: This study investigated the effectiveness of a mindfulness-based program on long-term stress, by measuring hair cortisol concentration and perceived stress and anxiety among workers who were undergoing high levels of stress., Method: We conducted a randomized clinical trial at work among the employees of a public university. We compared a group that received the eight-week mindfulness intervention with the wait list group who received no intervention., Results: A total of 30 participants were included in the study, with n = 15 subjects in the intervention group and n = 15 in the control group. Hair cortisol, perceived stress and anxiety significantly reduced after the intervention compared to the control group, which had no appreciable decline in the measured variables., Conclusion: This clinical trial showed the effectiveness of a mindfulness program on mental health psychometric measures (perceived stress and anxiety) and on a long-term stress biomarker (hair cortisol). It can be concluded that an eight-week mindfulness program could be implemented as an effective strategy to reduce stress biomarkers (hair cortisol) as well as perceived stress and anxiety, improving the mental health of university workers.

Purpose: On the 14th of March 2020, the Spanish government decreed a state of alarm due to the coronavirus disease 2019 (COVID-19) pandemic, directly affecting healthcare. This situation led to delayed diagnosis of several serious diseases, and its impact on many diseases such as the onset of type 1 diabetes mellitus (T1DM) remains unknown. The aim of this study is to determine the impact of the COVID-19 pandemic on the onset of T1DM in children., Methods: A descriptive-observational study was performed using data from children younger than 18 years (n=115) admitted with diagnosis of T1DM. We compared the 8 months from May-December 2020 to the same timeframe in 2019., Results: Our data show an increase of newly attended cases of T1DM in 2020, due to referral of Catalan children with onset of diabetes to our centre. Moreover, fewer patients presented with simple hyperglycaemia at the onset of the COVID-19 period. Delay in consulting the hospital, decreased access to the healthcare system, and avoidance of hospitals to minimize exposure to COVID-19 could have contributed to this finding. There were no differences in the number of days of hospitalization (including days in the paediatric intensive care uniy) between the years., Conclusion: The effects of the lockdown during the COVID-19 pandemic not only delayed the diagnosis of diabetes, but also its allowed time for its severity to increase. Future studies should focus on the influence of new variants of COVID-19 on the onset of T1DM during the postvaccination period.

Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14-19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48-120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation., 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 © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: Melanoma differentiation-associated gene 5 antibody (anti-MDA5) in dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease and poor prognosis. Early diagnosis is key to improving the prognosis of these patients. The aim was to confirm cutaneous characteristics in patients with anti-MDA5 dermatomyositis and to explore new diagnostic markers for the presence of anti-MDA5 (anti-MDA5 + )., Patients and Methods: A multicenter cross-sectional retrospective cohort study of 124 patients diagnosed with DM, of which 37 were anti-MDA5 + . Demographic data, laboratory data, and clinical manifestations were collected., Results: Anti-MDA5 + DM is characterized by a distinct mucocutaneous phenotype that includes oral lesions, alopecia, mechanic's hands, palmar and dorsal papules, palmar erythema, vasculopathy, and skin ulceration. We found vasculopathy and digit tip involvement very frequently in anti-MDA5 + patients (p <0.001), being a diagnostic marker of anti-MDA5 + (OR, 12.355; 95% CI 2.850-79.263; p  =  0.012 and OR, 7.447; 95% CI 2.103-46.718; p  =  0.004, respectively). The presence of ulcers deserves special mention, especially in anti-MDA5 + patients, because in our cohort, up to 97% of the anti-MDA5 + patients had ulcers., Conclusions: In patients with suspected DM with digit tip involvement or vasculopathy, the presence of anti-MDA5 antibodies must be ruled out, as it may be a clinical predictor., (© 2023 Deutsche Dermatologische Gesellschaft (DDG).)

Background: Vaccines reduce the risk of contracting and developing complications from coronavirus disease 2019 (COVID-19). Pregnant people are at increased risk of disease-related complications but have a higher prevalence of vaccine hesitancy (VH) than their nonpregnant counterparts., Objective: This study aimed to describe risk factors and COVID-19- and vaccine-related perspectives that lead to VH among pregnant people in Mexico to target strategies to increase vaccine acceptance in this population., Methods: A cross-sectional survey-based study to evaluate risk factors and COVID-19- and vaccine-related perspectives associated with VH among pregnant people was conducted. Respondents were pregnant people of all ages attending a regular follow-up visit or admitted to labor and delivery in a third-level maternity hospital in Mexico. VH was defined as not having received a COVID-19 vaccine and either declining or being undecided to accept a vaccine during their pregnancy. We used bivariate and multivariable logistic regression models to estimate assess the relationship among demographic factors, COVID-19- and vaccine-related perspectives, and VH., Results: A total of 1475 respondents completed the questionnaire; 216 (18%) were under the age of 18 years, and 860 (58%) had received at least one dose of a COVID-19 vaccine. In this sample, 264 (18%) were classified as vaccine hesitant. Key factors associated with VH were adolescence, having family as a primary source of information, first pregnancy, and history of vaccines in previous pregnancies. COVID-19 perspectives were also strongly associated with VH., Conclusions: Among pregnant people in Mexico, VH is associated with demographic factors, vaccination history, sources of information, and perceived risks to the fetus. This information is relevant to policy makers and health care professionals to identify those more likely to be hesitant and to inform strategies to increase vaccine uptake among pregnant people., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Patients with arthralgias who could be at risk of progressing to rheumatoid arthritis (RA) represent a clinical challenge. Recommendations for their management and treatment are lacking. The purpose of the present study was to determine how Argentinean rheumatologists deal with these patients. We developed an anonymous ad hoc survey which was sent to 522 Argentinean rheumatologists. The RA study group of our Argentinean Rheumatology National Society assisted in forwarding the surveys to its members via the internet (e-mail or WhatsApp). The findings of the collected data are presented as descriptive statistics. The questionnaires were completed by 255 rheumatologists (overall response rate of 48.9%), and 97.6% confirmed that their practices had received medical consultations to rule out RA in patients with arthralgias. Ultrasound (US) was the method of first choice (93.7%) as part of the evaluation of these patients. For those in whom US power Doppler signal was present in at least one joint, 93.7% of the participants would start treatment and methotrexate was the first choice (58.1%). In patients with tenosynovitis but no synovitis on US, most rheumatologists would start treatment (89.4%), being NSAIDs the drug of first choice (52.3%). Argentinean rheumatologists evaluate patients with imminent RA and treat them based on their clinical judgment and findings from the US evaluation of affected joints; the drug of first choice for these patients among these rheumatologists was methotrexate. Despite published data of recent clinical trials, recommendations for the management and treatment of these patients are necessary., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a lupus-like syndrome and patients with cutaneous lupus have reduced P-selectin expression in skin vessels. Using flow cytometry we analyzed in healthy donors and patients the expression of P-selectin Glycoprotein Ligand-1 (PSGL-1) in circulating neutrophils and the implication of PSGL-1/P-selectin interaction in neutrophil extracellular traps (NETs) generation. We found a statistical significance that neutrophils from active SLE patients have a reduced expression of PSGL-1 and low levels of PSGL-1 in neutrophils from SLE patients associated with the presence of anti-dsDNA antibodies, clinical lung involvement, Raynaud's phenomenon, and positive lupus anticoagulant. PSGL-1 is present along the DNA in the NET. In healthy donors, neutrophil interaction with immobilized P-selectin triggers Syk activation, increases the NETs percentage and reduces the amount of DNA extruded in the NETs. In active SLE patients, neutrophil interaction with P-selectin does not activate Syk or reduce the amount of DNA extruded in the NETs, that might contribute to increase the extracellular level of DNA and hence, to disease pathogenesis.

Malignant tumors can evade destruction by the immune system by attracting immune-suppressive regulatory T cells (Treg) cells. The IKZF2 (Helios) transcription factor plays a crucial role in maintaining function and stability of Treg cells, and IKZF2 deficiency reduces tumor growth in mice. Here we report the discovery of NVP-DKY709, a selective molecular glue degrader of IKZF2 that spares IKZF1/3. We describe the recruitment-guided medicinal chemistry campaign leading to NVP-DKY709 that redirected the degradation selectivity of cereblon (CRBN) binders from IKZF1 toward IKZF2. Selectivity of NVP-DKY709 for IKZF2 was rationalized by analyzing the DDB1:CRBN:NVP-DKY709:IKZF2(ZF2 or ZF2-3) ternary complex X-ray structures. Exposure to NVP-DKY709 reduced the suppressive activity of human Treg cells and rescued cytokine production in exhausted T-effector cells. In vivo, treatment with NVP-DKY709 delayed tumor growth in mice with a humanized immune system and enhanced immunization responses in cynomolgus monkeys. NVP-DKY709 is being investigated in the clinic as an immune-enhancing agent for cancer immunotherapy., Competing Interests: Declaration of interests All authors are past or current employees of Novartis Institutes for Biomedical Research. Some of the authors have patents related to this work: WO2019038717, 3-(1-oxoisoindolin-2-YL)Piperidine-2-6-Dione derivatives and uses thereof (R.E.J.B., S.B., A.C., A.F., and M.V.); and WO2020128972, Dosing regimen and pharmaceutical combinations comprising 3-(1-oxoisoindolin-2-YL)Piperidine-2-6-Dione derivatives (S.B., E.d’H., G.D., R.R.F., D.H., and J.K.-A.)., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Organophosphate pesticides (OPs) have greatly facilitated food production worldwide, and their use is not limited to agriculture and the control of pests and disease vectors. However, these substances can directly affect the immune response of non-target organisms. In this sense, exposure to OPs can have negative effects on innate and adaptive immunity, promoting deregulation in humoral and cellular processes such as phagocytosis, cytokine expression, antibody production, cell proliferation, and differentiation, which are crucial mechanisms for host defense against external agents. This review focuses on the scientific evidence of exposure to OPs and their toxic effects on the immune system of non-target organisms (invertebrates and vertebrates) from a descriptive perspective of the immuno-toxic mechanisms associated with susceptibility to the development of bacterial, viral, and fungal infectious diseases. During the exhaustive review, we found that there is an important gap in the study of non-target organisms, examples of which are echinoderms and chondrichthyans. It is therefore important to increase the number of studies on other species directly or indirectly affected by Ops, to assess the degree of impact at the individual level and how this affects higher levels, such as populations and ecosystems.

Purpose: The aim of this study was to assess the cost-effectiveness of using next-generation sequencing (NGS) versus single-gene testing (SgT) for the detection of genetic molecular subtypes and oncogenic markers in patients with advanced non-small-cell lung cancer (NSCLC) in the setting of Spanish reference centers., Methods: A joint model combining decision tree with partitioned survival models was developed. A two-round consensus panel was performed to describe clinical practice of Spanish reference centers, providing data on testing rate, prevalence of alterations, turnaround times, and treatment pathways. Treatment efficacy data and utility values were obtained from the literature. Only direct costs (euros, 2022), obtained from Spanish databases, were included. A lifetime horizon was considered, so a 3% discount rate for future costs and outcomes was considered. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainty., Results: A target population of 9,734 patients with advanced NSCLC was estimated. If NGS was used instead of SgT, 1,873 more alterations would be detected and 82 more patients could potentially be enrolled in clinical trials. In the long term, using NGS would provide 1,188 additional quality-adjusted life-years (QALYs) in the target population compared with SgT. On the other hand, the incremental cost of NGS versus SgT in the target population was €21,048,580 euros for a lifetime horizon (€1,333,288 for diagnosis phase only). The obtained incremental cost-utility ratios were €25,895 per QALY gained, below the standard cost-effectiveness thresholds., Conclusion: Using NGS in Spanish reference centers for the molecular diagnosis of patients with metastatic NSCLC would be a cost-effective strategy over SgT.

Purpose: Molibresib is a selective, small molecule inhibitor of the bromodomain and extra-terminal (BET) protein family. This was an open-label, two-part, Phase I/II study investigating molibresib monotherapy for the treatment of hematological malignancies (NCT01943851)., Patients and Methods: Part 1 (dose escalation) determined the recommended Phase 2 dose (RP2D) of molibresib in patients with acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), or multiple myeloma. Part 2 (dose expansion) investigated the safety and efficacy of molibresib at the RP2D in patients with relapsed/refractory myelodysplastic syndrome (MDS; as well as AML evolved from antecedent MDS) or cutaneous T-cell lymphoma (CTCL). The primary endpoint in Part 1 was safety and the primary endpoint in Part 2 was objective response rate (ORR)., Results: There were 111 patients enrolled (87 in Part 1, 24 in Part 2). Molibresib RP2Ds of 75 mg daily (for MDS) and 60 mg daily (for CTCL) were selected. Most common Grade 3+ adverse events included thrombocytopenia (37%), anemia (15%), and febrile neutropenia (15%). Six patients achieved complete responses [3 in Part 1 (2 AML, 1 NHL), 3 in Part 2 (MDS)], and 7 patients achieved partial responses [6 in Part 1 (4 AML, 2 NHL), 1 in Part 2 (MDS)]. The ORRs for Part 1, Part 2, and the total study population were 10% [95% confidence interval (CI), 4.8-18.7], 25% (95% CI, 7.3-52.4), and 13% (95% CI, 6.9-20.6), respectively., Conclusions: While antitumor activity was observed with molibresib, use was limited by gastrointestinal and thrombocytopenia toxicities. Investigations of molibresib as part of combination regimens may be warranted., (©2022 The Authors; Published by the American Association for Cancer Research.)

The "epithelial barrier hypothesis" states that a barrier dysfunction can result in allergy development due to tolerance breakdown. This barrier alteration may come from the direct contact of epithelial and immune cells with the allergens, and indirectly, through deleterious effects caused by environmental changes triggered by industrialization, pollution, and changes in the lifestyle. Apart from their protective role, epithelial cells can respond to external factors secreting IL-25 IL-33, and TSLP, provoking the activation of ILC2 cells and a Th2-biased response. Several environmental agents that influence epithelial barrier function, such as allergenic proteases, food additives or certain xenobiotics are reviewed in this paper. In addition, dietary factors that influence the allergenic response in a positive or negative way will be also described here. Finally, we discuss how the gut microbiota, its composition, and microbe-derived metabolites, such as short-chain fatty acids, alter not only the gut but also the integrity of distant epithelial barriers, focusing this review on the gut-lung axis., 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., (© 2023 Parrón-Ballesteros, Gordo, López-Rodríguez, Olmo, Villalba, Batanero and Turnay.)

Objectives: This study aims to increase the awareness of the association between lateralized overgrowth (LO) and abdominal tumor among the pediatric orthopedic community and to evaluate its incidence in our center., Patients and Methods: Between January 1997 and December 2021, a total of 166 patients with Wilms tumors and hepatoblastomas were retrospectively analyzed. Data including age, sex, initial clinical signs (hematuria, abdominal mass with or without general discomfort), type of asymmetric regional body overgrowth (isolated or in relation with any syndrome), and tumor stage at diagnosis were recorded. In addition, age at which asymmetric regional body overgrowth was described and age at the time of tumor diagnosis were noted., Results: Of a total of 166 patients, 133 were diagnosed with Wilms tumors (nephroblastomas) and 33 were diagnosed with hepatoblastomas. In 94% of the cases, the initial clinical signs were an abdominal mass and/or hematuria. Overall, five (3%) patients presented with LO. Four patients with Wilms tumor presented it at the initial clinical examinations. In three of these cases (2.3%), we found it isolated and, in the remaining patient (0.75%), it was associated with Beckwith-Wiedemann spectrum. Only one patient affected from hepatoblastoma (3%) presented with an isolated LO at the time of tumor diagnosis., Conclusion: Our study results show an incidence of LO in relation to intra-abdominal tumors of 3%. The latest updates recommend genetic testing to identify subgroups with a higher risk for tumor development that are more likely to benefit from tumor protocol surveillance.

Saffron ( Crocus sativus L.) is a spice used worldwide as a colouring and flavouring agent. Saffron is also a source of multiple bioactive constituents with potential health benefits. Notably, saffron displays consistent beneficial effects against a range of human neurological disorders (depression, anxiety, sleeping alterations). However, the specific compounds and biological mechanisms by which this protection may be achieved have not yet been elucidated. In this review, we have gathered the most updated evidence of the neurological benefits of saffron, as well as the current knowledge on the main saffron constituents, their bioavailability and the potential biological routes and postulated mechanisms by which the beneficial protective effect may occur. Our aim was to provide an overview of the neuroprotective effects attributed to this product and its main bioactive compounds and to highlight the main research gaps that need to be further pursued to achieve full evidence and understanding of the benefits of saffron. Overall, improved clinical trials and adequately designed pre-clinical studies are needed to support the evidence of saffron and of its main bioactive components (e.g., crocin, crocetin) as a therapeutic product to combat neurological disorders.

Gelatin methacryloyl (GelMA)-based composites are evolving three-dimensional (3D) networking hydrophilic protein composite scaffolds with high water content. These protein composites have been devoted to biomedical applications due to their unique abilities, such as flexibility, soft structure, versatility, stimuli-responsiveness, biocompatibility, biodegradability, and others. They resemble the native extracellular matrix (ECM) thanks to their remarkable cell-adhesion and matrix-metalloproteinase (MMP)-responsive amino acid motifs. These favorable properties promote cells to proliferate and inflate within GelMA-protein scaffolds. The performance of GelMA composites has been enriched using cell-amenable components, including peptides and proteins with a high affinity to harmonize cellular activities and tissue morphologies. Due to their inimitable merits, GelMA systems have been used in various fields such as drug delivery, biosensor, the food industry, biomedical, and other health sectors. The current knowledge and the role of GelMA scaffolds in bone tissue engineering are limited. The rational design and development of novel nanomaterials-incorporated GelMA-based composites with unique physicochemical and biological advantages would be used to regulate cellular functionality and bone regeneration. Substantial challenges remain. This review focuses on recent progress in mitigating those disputes. The study opens with a brief introduction to bone tissue engineering and GelMA-based composites, followed by their potential applications in bone tissue engineering. The future perspectives and current challenges of GelMA composites are demonstrated. This review would guide the researchers to design and fabricate more efficient multifunctional GelMA-based composites with improved characteristics for their practical applications in bone tissue engineering and biomedical segments.

Evaluation of right ventricular (RV) function after tricuspid valve surgery is complex. The objective was to identify the most appropriate RV function parameters for this purpose. This prospective study included 70 patients undergoing cardiac and tricuspid valve (TV) surgery. RV size and function parameters were determined at 3 months and 1-year post-surgery. Categorical variables were analyzed with the McNemar test and numerical variables with the Student's t-test for related samples or, when non-normally distributed, the Wilcoxon test. Spearman's rho was used to determine correlations between variables at 3 months and 1 year. RV diameters were reduced at 3 months post-surgery and were then unchanged at 1 year. Tricuspid annular plane systolic excursion (TAPSE) and S' wave values were worse at 3 months and then improved at 1 year (t-score-2.35, p 0.023; t-score-2.68; p 0.010). There was no significant reduction in free wall longitudinal strain (LS) or shortening fraction (SF) at 3 months (t-score 1.421 and - 1.251; p 0.218 and 0.172), and they were only slightly below pre-surgical values at 1 year. No relationship was found between RV function parameters and mortality or major complications. During the first few months after TV surgery, LS may be a more appropriate parameter to evaluate global ventricular function in comparison to TAPSE. At 1 year, good correlations are observed between TAPSE, S' wave, and LS values., (© 2022. The Author(s).)

Persistent COVID is a symptomatic disease involving multiple organs which affects patients who have had COVID-19 and who continue to have symptoms (asthenia, arthralgia, myalgia, headache, dyspnea, cough, chest pain, dysphonia) for more than 4-12 weeks after infection. Its presentation is independent of the severity of the acute COVID-19 phase. It is predominant in middle-aged women. Symptoms frequently fluctuate. It can progress in the form of flare-ups and cannot be explained by an alternative underlying pathology. The incidence of persistent COVID is estimated to be about 10% of those infected. In addition to this symptomatic disease, it is possible that survivors of COVID-19 pneumonia may present with lung sequelae. It is probable that a high number of patients who have had COVID-19 pneumonia will require specialized follow-up by the pulmonology department after overcoming the acute phase. Different algorithms are being established to ensure proper follow-up for these patients., (.)

Background and Aim: The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT) requires accurate target delineation. Magnetic resonance imaging (MRI) and/or 18 fludesoxyglucose positron emission tomography (18FDG-PET) allow for better visualization of the extent of bone metastases and optimizes the accuracy of tumor delineation for stereotactic radiotherapy compared to computed tomography (CT) alone. We evaluated the interobserver agreement in GTV of non-spine bone metastases in a single center and compared MRI and/or 18FDG-PET and CT in GTV delineation., Methods: Anonymous CT and MRI and/or 18FDG-PET obtained from 10 non-spine bone metastases were analyzed by six radiation oncologists at our center. Images acquired by CT and MRI and/or 18FDG-PET were used to delineate 10 GTVs of non-spine bone metastases in the pelvis, extremities, and skull. The cases showed different characteristics: blastic and lytic metastases, and different primary cancers (lung, breast, prostate, rectum, urothelial, and biliary). In both CT and MRI and/or 18FDG-PET, the GTV volumes were compared. The index of agreement was evaluated according to Landis and Koch protocol., Results: The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT ( P =0.25). The median GTV volume on MRI was 3.15 cc (0.027-70.64 cc) compared to 2.8 cc on CT (0.075-77.95 cc). Interobserver variance and standard deviation were lower in CT than MRI (576.3 vs. 722.2 and 24.0 vs. 26.9, respectively). The level of agreement was fair (kappa=0.36) between CT and MRI. The median GTV volume on 18FDG-PET in five patients was 5.8 cc (0.46-64.17 cc), compared to 4.1 cc on CT (0.99-54.2 cc) ( P =0.236). Interobserver variance and standard deviation in CT, MRI, and 18FDG-PET were 576.3 versus 722.2 versus 730.5 and 24 versus 26.9 versus 27.0, respectively. The level of agreement was slight (kappa=0.08) between CT and 18FDG-PET., Conclusions: Interobserver variance in non-spine bone metastases was equal when MRI and PET were compared to CT. CT was associated with the lowest variance and standard deviation. Compared to CT GTVs, the GTVs rendered from MRI images had fair agreement, while the GTVs rendered from 18FDG-PET had only slight agreement., Relevance for Patients: The delimitation of the treatment volume in non-spine bone metastases with SBRT is important for the results determining its efficacy. It is therefore essential to know the variability and to manage it to achieve the highest quality of treatment., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Author(s).)

Unique properties and potential applications of nanofibers have emerged as innovative approaches and opportunities in the biomedical, healthcare, environmental, and biosensor fields. Electrospinning and centrifugal spinning strategies have gained considerable attention among all kinds of strategies to produce nanofibers. These techniques produce nanofibers with high porosity and surface area, adequate pore architecture, and diverse chemical compositions. The extraordinary characteristics of nanofibers have unveiled new gates in nanomedicine to establish innovative fiber-based formulations for biomedical use, healthcare, and a wide range of other applications. The present review aims to provide a comprehensive overview of nanofibers and their broad range of applications, including drug delivery, biomedical scaffolds, tissue/bone-tissue engineering, dental applications, and environmental remediation in a single place. The review begins with a brief introduction followed by potential applications of nanofibers. Finally, the future perspectives and current challenges of nanofibers are demonstrated. This review will help researchers to engineer more efficient multifunctional nanofibers with improved characteristics for their effective use in broad areas. We strongly believe this review is a reader's delight and will help in dealing with the fundamental principles and applications of nanofiber-based scaffolds. This review will assist students and a broad range of scientific communities to understand the significance of nanofibers in several domains of nanotechnology, nanomedicine, biotechnology, and environmental remediation, which will set a benchmark for further research.

Background: Haemoptysis is a rare symptom associated with endocarditis. We describe the unusual clinical manifestation of endocarditis on regurgitant bicuspid aortic valve and (probably) secondarily on a perimembranous ventricular septal defect (VSD) as massive haemoptysis., Case Summary: A 24-year-old male with aortic coarctation, bicuspid aortic valve, and VSD since birth. Previously asymptomatic, he came after an episode of haemoptysis. A computed tomography (CT) scan showed a cavitated lesion in lung. Streptococo viridans was identified in serial blood cultures. Transthoracic echocardiography showed a bicuspid aortic valve with vegetations, suggesting infectious involvement, and severe aortic insufficiency. Transoesophageal echocardiography (TEE) study showed a bicuspid aortic valve with complete fusion of coronary valves. An elongated oscillating tumour, 9.5 mm in length, was observed in the centre of the ventricular side of the non-coronary valve. Another vegetation was seen on the VSD. During his hospital stay and under antibiotic treatment, he reported abdominal pain. Computed tomography examination showed splenic infarction. In the echocardiogram no vegetation masses were observed on the aortic valve or on the VSD closure aneurysm., Discussion: The main debate about this patient's treatment concerned the indication of surgery, especially after the onset of fever with splenic septic embolism while under appropriate antibiotic treatment. He was stable, with no signs of heart failure and the echocardiogram repeated after the septic splenic embolism showed no residual vegetations on the aortic valve or VSD, and the TEE study ruled out a local complication. Finally, the multidisciplinary team decided against surgical management., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction and Objective: Music has been closely linked to medicine since ancient times, and has brought numerous benefits to the health of patients. Patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) generally have a health-related quality of life (HRQL) lower than the reference values ​​of the general population. The objective of the present study is to verify if the intervention of classical music live and "in situ" during the treatment of HD has effects on the HRQoL of the patients., Materials and Methods: A prospective, group-randomized intervention study of 4 weeks' duration was carried out in patients with chronic kidney disease undergoing hemodialysis. Descriptive variables are included for data analysis: age, sex, months in treatment, Kt/V, hemoglobinand albumin. Result variable: HRQL, measured with the Kidney Diseasse health questionnaire Quality of life (KDQOL-SF) before and after the musical intervention., Results: Patients participated in 2 groups, the intervention group and the control group. The analysis of the results shows that the intervention group improved their quality of life compared to the initial measurement. The difference between the pre and post time of the intervention group with respect to the control group increased the mean score (pm) in all the scales significantly, except in the Work situation, Sexual function and Social support scales. The most important results were given on the Symptoms/problems scale with an increase of 15.78 (p < 0.001) pm; in scale Effects of kidney disease with an increase of 14.96 (p < 0.001) pm; in scale Burden of kidney disease with an increase of 16.36 (p < 0.001) pm; on the Dream scale with an increase of 14.78 (p < 0.001) pm; on the Vitality scale with an increase of 25.46 (p < 0.001) pm; on the Emotional well-being scale with an increase of 29.57 (p < 0.001) pm; on the Pain scale with an increase of 41.92 (p < 0.001) pm and on the General Health scale with an increase of 23.39 (p < 0.001) pm., Conclusion: Intervention with live music and on-site while receiving hemodialysis treatment improves self-perceived HRQL in patients with chronic kidney disease., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

To improve the monitoring of the electrical power grid, it is necessary to evaluate the influence of contamination in relation to leakage current and its progression to a disruptive discharge. In this paper, insulators were tested in a saline chamber to simulate the increase of salt contamination on their surface. From the time series forecasting of the leakage current, it is possible to evaluate the development of the fault before a flashover occurs. In this paper, for a complete evaluation, the long short-term memory (LSTM), group method of data handling (GMDH), adaptive neuro-fuzzy inference system (ANFIS), bootstrap aggregation (bagging), sequential learning (boosting), random subspace, and stacked generalization (stacking) ensemble learning models are analyzed. From the results of the best structure of the models, the hyperparameters are evaluated and the wavelet transform is used to obtain an enhanced model. The contribution of this paper is related to the improvement of well-established models using the wavelet transform, thus obtaining hybrid models that can be used for several applications. The results showed that using the wavelet transform leads to an improvement in all the used models, especially the wavelet ANFIS model, which had a mean RMSE of 1.58 ×10-3, being the model that had the best result. Furthermore, the results for the standard deviation were 2.18 ×10-19, showing that the model is stable and robust for the application under study. Future work can be performed using other components of the distribution power grid susceptible to contamination because they are installed outdoors.

The study described sought further understanding of the synergies in a mix of CDW pozzolans, containing (calcareous and siliceous) concrete and glass waste, used to prepare ternary eco-cement paste bearing 7% of the binary blend at concrete/glass ratios of 2:1 and 1:2. The mineralogical phases in the 2-day, 28-day, and 90-day cement matrices were identified and monitored using XRF, XRD-Rietveld, SEM-EDX, FT-IR, and NMR. The findings showed that changes in the reaction kinetics in the ternary blended pastes relative to OPC pastes depended on the nature of the recycled concrete and the glass content. Adding the binary mix bearing calcareous concrete (at a ratio of 2:1) favoured ettringite, portlandite, and amorphous phase formation, whilst the blends with siliceous concrete favoured C-S-H gel formation. Monocarboaluminate was detected in the 90-day siliceous concrete and glass pastes in amounts similar to those found in the reference OPC paste.

The mitochondrial membrane potential (ΔΨ m ) is a parameter often used to determine mitochondrial function; therefore, it can be used to determine the integrity and functionality of cells. A decrement of ΔΨ m is implicated in several inflammatory-related pathologies, such phenomena can be related to COVID-19 infection. The present work aimed to compare the ΔΨ m in leucocytes (human PBMCs; HPBMC) isolated from healthy control (HC) subjects, patients with COVID-19 (C-19), recovered subjects at 40 ± 13 (R1) and 335 ± 20 (R2) days after infection (dai). Obtained data showed that ΔΨ m decreased in HPBMC of subjects with C-19, R1, and R2 compared with HC. When analyzing the ΔΨ m data by sex, in females, a significant decrease was observed in R1 and R2 groups versus HC. Regarding men, a significant decrease of ΔΨ m was observed in R1, with respect to HC, contrary to R2 group, who reestablished this parameter. Obtained results suggest that the loss of ΔΨ m could be related to the long-COVID., (©2022 Society for Leukocyte Biology.)

Ochratoxin A (OTA) and fumonisin B 1 (FB 1 ) are mycotoxins distributed in a wide variety of foods for human or animal consumption and are classified as possible carcinogens for humans. This study aimed to evaluate the cytotoxic, cytostatic and genotoxic effects of OTA and its main metabolite, ochratoxin α (OTα), FB 1 and three combinations of OTA and FB 1 at moderate and environmental doses. Cell viability was evaluated through MTT assay and the trypan blue exclusion method. The cytostatic and genotoxic effects were evaluated through the cytokinesis-block micronucleus assay. The results showed synergistic time- and concentration-dependent cytotoxic effects of one of the combinations of OTA and FB 1 . In contrast, significant differences were observed in the micronuclei (MN) frequency from OTA, OTα and coexposure of OTA + FB 1 . Some of these combinations increased the frequency of nuclear buds, nucleoplasmic bridges, donut-shaped nuclei, necrotic and apoptotic cells and MN in mononucleated cells. In conclusion, OTA and its main metabolite OTα, as well as the co-exposure of OTA and FB 1 , cause stable DNA damage at environmentally relevant concentrations, which was greater in metabolically competent cells. More studies are needed to understand the chemical interactions that occur due to the joint presence of mycotoxins, which occurs commonly., (Copyright © 2022 Elsevier B.V. All rights reserved.)