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Due to their extensive use, the release of zinc oxide nanoparticles (ZnO NP) into the environment is increasing and may lead to unintended risk to both human health and ecosystems. Access of ZnO NP to the brain has been demonstrated, so their potential toxicity on the nervous system is a matter of particular concern. Although evaluation of ZnO NP toxicity has been reported in several previous studies, the specific effects on the nervous system are not completely understood and, particularly, effects on genetic material and on organism behaviour are poorly addressed. We evaluated the potential toxic effects of ZnO NP in vitro and in vivo, and the role of zinc ions (Zn 2+ ) in these effects. In vitro, the ability of ZnO NP to be internalized by A172 glial cells was verified, and the cytotoxic and genotoxic effects of ZnO NP or the released Zn 2+ ions were addressed by means of vital dye exclusion and comet assay, respectively. In vivo, behavioural alterations were evaluated in zebrafish embryos using a total locomotion assay. ZnO NP induced decreases in viability of A172 cells after 24 h of exposure and genetic damage after 3 and 24 h. The involvement of the Zn 2+ ions released from the NP in genotoxicity was confirmed. ZnO NP exposure also resulted in decreased locomotor activity of zebrafish embryos, with a clear role of released Zn 2+ ions in this effect. These findings support the toxic potential of ZnO NP showing, for the first time, genetic effects on glial cells and proving the intervention of Zn 2+ ions., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Epigenetic modifications are closely related to certain disorders of the organism, including the development of tumors. One of the main epigenetic modifications is the methylation of DNA cytosines, 5-methyl-2'-deoxycycytidine. Furthermore, 5-mdC can be oxidized to form three new modifications, 5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine, and 5-carboxy-2'-deoxycytidine. The coupling of liquid chromatography with tandem mass spectrometry has been widely used for the total determination of methylated DNA cytosines in samples of biological and clinical interest. These methods are based on the measurement of the free compounds (e.g., urine) or after complete hydrolysis of the DNA (e.g., tissues) followed by a preconcentration, derivatization, and/or clean-up step. This review highlights the main advances in the quantification of modified nucleotides and nucleosides by isotope dilution using isotopically labeled analogs combined with liquid or gas chromatography coupled to mass spectrometry reported in the last 20 years. The different possible sources of labeled compounds are indicated. Special emphasis has been placed on the different types of chromatography commonly used (reverse phase and hydrophilic interaction liquid chromatography) and the derivatization methods developed to enhance chromatographic resolution and ionization efficiency. We have also revised the application of bidimensional chromatography and indicated significant biological and clinical applications of these determinations., (© 2023 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.)

Objective: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies., Design: We used the KPC mouse model ( LSL-Kras G12D/+ ; LSL-Trp53 R172H/+ ; Pdx-1-Cre ) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed., Results: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC., Conclusions: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Body temperature must be monitored in patients receiving Hospital-at-Home (HaH) care for COVID-19 and other infectious diseases. Continuous temperature telemonitoring (CTT) detects fever and patient deterioration early, facilitating decision-making. We performed a validation clinical study assessing the safety, comfort, and impact on healthcare practice of Viture ® , a CTT system, compared with a standard digital axillary thermometer in 208 patients with COVID-19 and other infectious diseases treated in HaH at the Navarra University Hospital (HUN). Overall, 3258 pairs of measurements showed a clinical bias of -0.02 °C with limits of agreement of -0.96/+0.92 °C, a 95% acceptance rate, and a mean absolute deviation of 0.36 (SD 0.30) °C. Viture ® detected 3 times more febrile episodes and revealed fever in 50% more patients compared with spot measurements. Febrile episodes were detected 7.23 h (mean) earlier and modified the diagnostic and/or therapeutic approach in 43.2% of patients. Viture ® was validated for use in a clinical setting and was more effective in detecting febrile episodes than conventional methods.

Among the causes of chest pain, slipping rib has a low prevalence, usually with a history of trauma, and its management is controversial. Slipping rib syndrome should be included in the differential diagnosis of causes of chest pain in children. When not associated with previous trauma and cartilage deformity, it is necessary to consider an alteration in rib development, regardless of the typical traumatic etiology in adults. Here we describe a series of pediatric patients with slipping rib seen at a referral hospital between 2001 and 2022. Nine patients aged 11 to 16 years were included. Only 2 had a history of trauma. All patients described a sudden onset of severe thoracic abdominal pain. The patients underwent open resection of the affected costal cartilages, with resolution of pain., (Sociedad Argentina de Pediatría.)

Multimodal analgesia is defined as using several drugs or techniques simultaneously to target different pain pathways or receptors to avoid pain propagation. This study evaluated the pharmacokinetic profile and comparative bioavailability of etoricoxib 90 mg and tramadol 50 mg dosing alone (reference drugs) or in a novel fixed-dose combination (test drug) under fasting conditions in Mexican healthy volunteers. This was a randomized, open-label, 3-way, crossover, single-dose, prospective, and longitudinal study with a 14-day washout period. Eligible subjects were healthy Mexican adult volunteers. The drugs were dosing orally, according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast with 250 mL of water at room temperature. Serial blood samples were collected before and after dosing, both drugs were quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Forty-two subjects were enrolled and 38 completed the study (28 men and 14 women, mean age 25.2 years, mean weight 66.6 kg). Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed for (maximum plasma drug concentration (C max ), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC 0-t ), and (area under the plasma drug concentration-time curve from 0 up to infinity (AUC 0-∞ ) data were within the range of 80%-125%. Non-serious adverse events were observed. The results demonstrate that the pharmacokinetic profile and bioavailability of the etoricoxib/tramadol fixed-dose combination are comparable to those of the reference products., (© 2024 Laboratorios Silanes. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

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.

Estuarine sediments intercept and temporarily retain microplastics before they reach the marine seafloor, impacting various organisms, including key commercial species. This highlights the critical need for research on microplastic exposure in these transitional environments. This study provides a detailed assessment of microplastic pollution in the sediment compartment of the Limfjord, a 1500 km 2 large Danish fjord, and introduces the Polymer Hazard Index (PHI) as a tool for evaluating polymer-specific risks. Thirteen sediment samples were collected, covering an anthropogenic gradient along the fjord. State-of-the-art methods were applied for extracting and identifying (FPA-μFT-IR imaging) microplastics (10-5000 μm). Our results indicate that microplastic contamination is pervasive across all sampled locations with concentrations ranging from 273 to 4288 particles kg -1 , with a predominance of small microplastics (<100 μm). The estimated mass-based concentrations ranged between 2.60 × 10 4 -1.11 × 10 6 ng kg -1 . Overall, we estimated a microplastic stock of 3.8 × 10 3 -1.65 × 10 5 kg in the surface sediments of the Limfjord, i.e., some 2.5-110 kg km -2 . The application of the PHI revealed significant risks associated with specific polymers, such as polyacrylonitrile (PAN) and acrylonitrile butadiene styrene (ABS), underscoring the importance of considering polymer-specific hazards in environmental assessments., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Several species of ectoparasites, including chewing lice and mites are closely associated with their hosts. The Andean condor (Vultur gryphus) is globally listed as vulnerable by the IUCN and its population has been steadily declining in recent decades suggesting a potential extinction of associated entomofauna. The purpose of this study was to record the species of ectoparasites infesting three individuals of Andean condor found dead in the 'Páramo del Almorzadero' Santander Department, Northeastern Colombia. One juvenile (male) and two adults (male and female) Andean condors received for necropsy were carefully examined for ectoparasite infestation. Specimens were collected and preserved in ethanol (70%) for taxonomic studies. Morphologic identification and morphometric records were made under light microscopy. Some specimens were also prepared for scanning electron microscopy and others were subjected to DNA extraction to amplify and obtain sequences of the cytochrome-C oxidase subunit I (COI) gene for phylogenetic analyses. Lice were collected from the juvenile condor and the adult female and identified as Falcolipeurus assesor (Phthiraptera: Ischnocera) in the juvenile condor (8 females, 19 males and 8 nymphs) and the adult (1 female); Colpocephalum trichosum (Phthiraptera: Amblycera) in the juvenile (19 females, 24 males and 1 nymph) and the adult (2 females, 2 males and 3 nymphs); and Cuculiphilus zonatus (Phthiraptera: Amblycera) in the juvenile (40 females, 43 males and 15 nymphs) and the adult (1 male and 2 nymphs). Moreover, one mite collected from the juvenile condor was identified as Ancyralges cathartinus (Acari: Astigmata) (1 female). Morphometric data was obtained for the adult stages of F. assesor (6 females and 13 males), C. trichosum (9 females and 9 males) and C. zonatus (10 females and 10 males). We obtained the first DNA sequences of COI for F. assessor, and C. trichosum, where phylogenetic tree analysis showed that F. assessor is more closely related to Falcolipeurus marginalis, and C. trichosum to Colpocephalum kelloggi. This represents the first record of parasites in Andean condor from Colombia and contributes to the knowledge of chewing lice and mites associated with an endemic and endangered bird species. Further studies on Andean condor ectoparasites should be focused on documenting host-parasite interactions and potential health impacts in these wild birds., (© 2024 Royal Entomological Society.)

Global concerns about food security, driven by rising demand, have prompted the exploration of nanotechnology as a solution to enhance food supply. This shift comes in response to the limitations of conventional technologies in meeting the ever-increasing demand for food products. Consequently, nanoparticles play a crucial role in enhancing food production, preservation, and extending shelf life by imparting exceptional properties to materials. Nanoparticles and nanostructures with attributes like expansive surface area and antimicrobial efficacy, are versatile in both traditional packaging and integration into biopolymer matrices. These distinctive qualities contribute to their extensive use in various food sector applications. Hence, this review explores the physicochemical properties, functions, and biological aspects of nanoparticles in the context of food packaging. Furthermore, the synergistic effect of nanoparticles with different biopolymers, alongside its different potential applications such as food shelf-life extenders, antimicrobial agents and as nanomaterials for developing smart packaging systems were summarily explored. While the ongoing exploration of this research area is evident, our review highlights the substantial potential of nanomaterials to emerge as a viable choice for food packaging if the challenges regarding toxicity are carefully and effectively modulated., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Objectives: This study assessed the transparency and replicability of exercise-based interventions following bariatric surgery by evaluating the content reporting of exercise-based clinical trials., Design: The study design of the present article is a systematic review., Data Sources: PubMed, Scopus, Web of Sciences, PsycINFO, and Cochrane were searched from their inception to May 2023., Eligibility Criteria: Eligible studies were clinical trials including exercise interventions in participants following bariatric surgery. There were 28 unique exercise interventions. Two independent reviewers applied the exercise prescription components of Frequency, Intensity, Time, and Type (FITT; four items) and the Consensus on Exercise Reporting Template (CERT; 19 items). Exercise interventions were organized into four major exercise components: aerobic training, resistance training, concurrent training, and "others.", Results: The FITT assessment revealed that 53% of the trials did not report the training intensity, whereas 25% did not indicate the duration of the major exercise component within the training session. The mean CERT score was 5 out of a possible score of 19. No studies reached CERT score >10, while 13 out of the total 19 CERT items were not adequately reported by ≥75% of the studies., Conclusion: This study highlights that the exercise interventions following bariatric surgery are poorly reported, non-transparent, and generally not replicable. This precludes understanding the dose-response association of exercise and health-related effects and requires action to improve this scientific field., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as β-resorcylic acid (β-RA). Here, we show that oral supplementation with β-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of β-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of β-RA. Consequently, β-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of β-RA supports its translational potential. Thus, β-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luis C. Lopez reports article publishing charges was provided by University of Granada. Luis C. Lopez has patent #WO2022123103 issued to No. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hyperparasitism is defined as the interaction where one parasite is infected by another parasite. In bat flies (Streblidae and Nycteribiidae), both hyperparasites and microparasites (bacteria, viruses, fungi, and arthropods such as mites) have been documented. Fungi belonging to the order Laboulbeniales are microscopic parasites of a wide diversity of arthropod hosts. Three genera exclusively target bat flies: Arthrorhynchus, which parasitizes species within Nycteribiidae in the Eastern Hemisphere, while genus Gloeandromyces and Nycteromyces parasitize Streblidae in the Western Hemisphere. Among the hyperparasitic arthropods, mites of family Neothrombidiidae, particularly the monospecific genus Monunguis, are known to parasitize bat flies. Here we present the first records of the hyperparasites Monunguis streblida and Gloeandromyces pageanus f. polymorphus parasitizing Streblidae bat flies in Colombia and a summary of these hyperparasitic interactions in the Neotropics. We detected fungi and mites parasitizing bat flies that were collected in the Magdalena River Basin, Colombia, in field expeditions in 2018, 2022, and 2023. We identified 17 bat flies and two species of hyperparasites, specifically M. streblida and the fungi Gloeandromyces. Our search for reports of these interactions in the Neotropics revealed that seven species of Trichobius (Streblidae) are parasitized by M. streblida, whereas Paratrichobius longicrus (Streblidae) is parasitized by Gloeandromyces pageanus f. polymorphus. These interactions have been reported in 11 countries, but our records are the first of M. streblida and Laboulbeniales fungi parasitizing bat flies in Colombia. So far, a total of 14 species of fungi and one species of mite have been associated with 19 species of bat flies, which in turn, are linked to 15 species of Neotropical bats., (© 2024. The Author(s).)

Background: Data on antifungal prescribing in neonatal patients are limited to either single-center or single-country studies or to 1-day recording. Therefore, we assessed antifungal longitudinal usage in neonatal units (NUs) within Europe., Methods: CALYPSO, a prospective weekly point prevalence study on antifungal drug usage in NUs in 18 hospitals (8 European countries), was conducted in 2020 during a 12-week period. All patients receiving systemic antifungals were included. Ward demographics were collected at the beginning; ward and patient data including indication, risk factors and antifungal regimen were weekly collected prospectively., Results: Among 27 participating NUs, 15 (56%) practiced antifungal prophylaxis for neonates with birth weight <1000 g or <1500 g and additional risk factors. In total, 174 patients received antifungals with a median frequency per week of 10.5% ranging from 6.9% to 12.6%. Indication for antifungal prescribing was prophylaxis in 135/174 (78%) courses and treatment in 22% [39 courses (69% empirical, 10% preemptive, 21% targeted)]. Fluconazole was the most frequent systemic agent used both for prophylaxis (133/135) and treatment (15/39, 39%). Among neonates receiving prophylaxis, the most common risk factors were prematurity (119/135, 88%), mechanical ventilation (109/135, 81%) and central vascular catheters (89/135, 66%). However, gestational age <28 weeks was only recorded in 55/135 (41%) courses and birth weight <1000 g in 48/135 (35%). Most common reason for empirical treatment was late-onset sepsis; all 8 targeted courses were prescribed for invasive candidiasis., Conclusion: Antifungal usage in European NUs is driven by prophylaxis and empirical treatment with fluconazole being the most prescribed agent for both indications., Competing Interests: E.C.: Speaker at sponsored symposia for Pfizer and F2G. C.G. is funded by the Spanish Ministry of Science and Innovation—Instituto de Salud Carlos III and Fondos FEDER (Contrato Juan Rodés JR22/00044). A.H.G. has received grants from Gilead, Merck, Sharp & Dohme and Pfizer and has served as a consultant to Amplyx, Astellas, Basilea, F2G, Gilead. Merck, Sharp & Dohme, Pfizer, Scynexis and Mundipharma. T.L. has received a grant from Gilead Sciences, has served as a consultant to Gilead Sciences, Merck/MSD, Pfizer, Astellas, AstraZeneca, Recordati and Roche and served at the speaker´s bureau of Gilead Sciences, Merck/MSD, Astellas, Pfizer and GSK and Recordati. E.R. has received research grants from Merck, Abvie, Shionogi, Cidara and Pfizer Inc. to his institution and is a scientific advisor and member of the speaker bureaux for Gilead, Merck, Shionogi, Mundipharma and Pfizer Inc. For the remaining authors, there are no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The evaluation of the university experience of students is an increasingly frequent field of analysis among the academic community, as they represent one of the most important groups in universities and it is essential to know their opinion and satisfaction with the different services and resources that the university institution makes available to them. In this sense, the two objectives of the study were the following: 1) To analyse the undergraduate university experience of the different groups of students (graduates, students, drop-outs). 2) To identify which aspects of the academic training received predict each of the student groups. To this end, a study was carried out specifically aimed at undergraduate education students at the University of Granada (Spain), distinguishing between graduates, students, and those who had dropped out of their studies. A total of 292 students participated (82 female and 210 male), of whom 123 were graduates, 98 were still students and 71 were drop-outs. After the application of three questionnaires, it was found that the three aforementioned groups of participants coincided in particularly valuing characteristic dimensions of the formal teaching-learning scenario in the university experience. In addition, the linear regression analysis carried out identified the personalised attention factor as having the highest predictive value as regards student type. Thus, the results of the study point to an assessment of academic training focused on the need on the part of all three groups of participants for teacher support and individualised guidance. The study may be useful in providing universities with new data to help improve the teaching performance of Education degree teaching staff concerning students; for example, by encouraging their participation in tutorial action programmes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Oswaldo Lorenzo Quiles reports financial support was provided by European Union. Oswaldo Lorenzo Quiles reports financial support was provided by Government of Andalusia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Allergic rhinoconjunctivitis (AR) is an IgE-mediated inflammation of nasal and ocular mucosa after environmental allergen exposure, mainly by house dust mites (HDM). AR affects more than one third of the population worldwide and it is associated with loss of quality of life (QoL)., Aim: To analyse the improvement in the QoL in 50 patients with moderate-persistent AR due to house HDM before and after receiving 1 year of subcutaneous specific aeroallergen immunotherapy treatment (SAIT)., Material and Methods: A prospective observational study was performed based on clinical practice in 50 patients with moderate-severe persistent AR due to HDM and candidates to SAIT. Forty-one patients completed the study. Patients were evaluated with the ESPRINT short-version QoL questionnaire, a score of medication use and visual analogue scale (VAS) symptom score, prior to and 12 months after SAIT., Results: Forty-one patients (25 women, mean age 26.9 years). Mean ESPRINT values prior to the start SAIT was 3.06 (moderate-severe) and 1 year after starting subcutaneous SAIT the mean value dropped in all patients to 0.88 (mild). The VAS score symptom dropped from 8.26 to 3.68. 97.56% of patients used 3 or more drugs (oral antihistamine, ophthalmic/intranasal antihistamine, intranasal corticosteroid and/or oral antileukotrienes) prior to starting SAIT, and 1 year after it, 58.53% used one on-demand medication to control symptoms, oral antihistamine or nasal spray, and not daily use., Conclusions: Subcutaneous SAIT seems to be a valid treatment in our patients with moderate-persistent AR due to HDM, since it reduces the ESPRINT score, VAS score and the use of medication. An improvement in the quality of life and satisfaction was observed by the patients themselves., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia Sp. z o. o.)

Background: Mediastinal lymph node staging is a key element in the diagnosis of lung cancer. The combination of computed tomography (CT) and positron emission tomography (PET) has improved staging but some circumstances are known to influence their negative predictive value. The objective of this study was to assess the impact on survival of avoiding invasive mediastinal staging in surgical lung cancer patients with negative mediastinum in CT and PET and intermediate risk of unexpected pN2., Methods: Data were collected from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS), from December 2016 to March 2018. For this study, patients were selected if they had negative mediastinum in CT and PET findings but tumours >3 cm or located centrally, or with cN1 disease. Patients who did and did not undergo invasive staging [invasive group (IG) and non-invasive group (NIG)] were compared, analysing unexpected pN2 and survival with Kaplan-Meier curves and Cox regression., Results: A total of 2,826 patients underwent surgery for primary lung cancer. We selected 1,247 patients who had tumours >3 cm, central tumours or cN1. Invasive staging was performed in 275 (22.1%) cases. The unexpected pN2 rate was 9.6% in the NIG and 13.8% in the IG, but half of them were discovered prior to surgery in the IG. Five-year overall survival (OS) was poorer in the IG (52.4% vs . 64%; P<0.001). In the Cox regression model, male sex, older age, diabetes, synchronous tumour, lower diffusing capacity for carbon monoxide, larger tumour size, higher pathological N-stage, and IG status were significant independent risk factors., Conclusions: Invasive staging recommended by guidelines could be reduced with an appropriate selection in mediastinal CT- and PET-negative patients with risk factors for unexpected pN2, because rates of pN2 and survival did not worsen without invasive staging., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1900/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous CoQ 10 . Poor outcomes result from low absorption and bioavailability of CoQ 10 and the clinical heterogenicity of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues of Coq2 mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema, and neurodevelopmental delay. In contrast, exogenous CoQ 10 supplementation falls short in fully restoring the phenotype. The treatment is translatable to human use, as proven by in vitro studies in skin fibroblasts from patients with pathogenic variants in COQ2. The therapeutic approach extends to other disorders characterized by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary CoQ deficiency., Competing Interests: Declaration of interests J.C.-S., J.M.M.-G., P.G.-G., L.J.-S., M.E.D.-C., S.L.-H., and L.C.L. are inventors listed on the patent “Compound to stimulate mitochondrial metabolism in gametes and embryos” filed in Spain on February 28, 2024 (application number P202430145)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Raphanus sativus L. cv. Sango, commonly known as red radish , is widely consumed around the world as a vegetable, but its benefit in pain relief is not sufficiently investigated. This study aimed to evaluate the antinociceptive effects of R. sativus and a possible mechanism of action. An aqueous extract of R. sativus sprouts (AERSS) was investigated by parenteral (10, 30, and 100 mg kg -1 , i.p.) and enteral (500 mg kg -1 , p.o.) administration in the neurogenic and inflammatory phases of the formalin test, where gastric damage was also evaluated as a possible adverse effect. Ketorolac (5 mg kg -1 , i.p.) was used as the reference drug. Endogenous opioid and 5-HT1A serotonin receptors, as well as the cAMP/NO-cGMP pathways, were explored in the study of a possible mechanism of action by using their corresponding antagonists: naloxone, 1 mg kg -1 , i.p., WAY100635, 1 mg kg -1 , i.p., and enzymatic activators or inhibitors, respectively. Sulforaphane (SFN), a known bioactive metabolite, was analyzed using electroencephalography (EEG) to evidence its central involvement. A significant and dose-dependent antinociceptive activity was observed with the AERSS resembling the antinociceptive effect of the reference drug, with an equivalent significant response with a dose of 500 mg kg -1 , p.o. without causing gastric damage. The participation of the endogenous opioid and 5-HT 1A serotonin receptors at central and peripheral levels was also observed, with a differential participation of cAMP/NO-cGMP. SFN as one metabolite produced significant changes in the EEG analysis, reinforcing its effects on the CNS. Our preclinical evidence supports the benefits of consuming Raphanus sativus cv. Sango sprouts for pain relief.

Purpose: The main purpose of this study was to perform an immunohistochemical, functional, and anatomical evaluation of patients with idiopathic epiretinal membrane (ERM)., Methods: Twenty-four specimens of idiopathic ERM from 24 consecutive patients who underwent 23 G pars plana vitrectomy for ERM and internal limiting membrane (ILM) peeling at the San Juan University Hospital in Alicante (Spain) in 2019 were analyzed. All patients underwent a complete ophthalmological examination including measurement of best corrected visual acuity (BCVA) and macular analysis by spectral-domain optical coherence tomography (SD-OCT) at the time of diagnosis and 3 months after surgery. Specific glial fibrillar acid protein antibodies (GFAP) and S100 calcium-binding protein β (S100β) immunostaining markers were used to identify the macroglial component of the ERM, Müller cells, and astrocytes. Ionized calcium-binding adapter molecule 1 protein (Iba1) antibodies were used as specific markers for inflammatory cells, such as microglia and macrophages., Results: Mean preoperative BCVA measured with Snellen chart was 0.3 and 0.6 preoperatively and at 3 months after surgery, respectively. SD-OCT identified 15 patients (62.5%) with a disruption of the outer retinal hyperreflective bands. The immunohistochemical study showed the presence of Müller cells in almost all cases (91.6%), as well of abundant microglia and macrophages. Microglia and macrophages were more frequently present in earlier stages of ERM. Microglia were present in ERM independently of the outer retinal hyperreflective bands integrity as measured by SD-OCT. A greater presence of macrophages was found in those ERMs with no outer retinal hyperreflective band disruption., Conclusions: Müller cells seem to be the most frequent cell group in ERMs, with also presence of microglia cells and macrophages. Astrocytes were more frequently found in early stages of ERMs. Microglia and macrophages were most frequent in ERMs with early stage (1, 2, or 3) than in advanced stages (4)., (© 2024. The Author(s).)

The study of neurogenesis is essential to understanding fundamental developmental processes and for the development of cell replacement therapies for central nervous system disorders. Here, we designed an in vivo drug screening protocol in developing zebrafish to find new molecules and signalling pathways regulating neurogenesis in the ventral spinal cord. This unbiased drug screen revealed that 4 cyclooxygenase (COX) inhibitors reduced the generation of serotonergic interneurons in the developing spinal cord. These results fitted very nicely with available single-cell RNAseq data revealing that floor plate cells show differential expression of 1 of the 2 COX2 zebrafish genes (ptgs2a). Indeed, several selective COX2 inhibitors and two different morpholinos against ptgs2a reduced the number of serotonergic neurons in the ventral spinal cord and led to locomotor deficits. Single-cell RNAseq data and different pharmacological manipulations further revealed that COX2-floor plate-derived prostaglandin D 2 promotes neurogenesis in the developing spinal cord by promoting mitotic activity in progenitor cells. Rescue experiments using a phosphodiesterase-4 inhibitor suggest that intracellular changes in cAMP levels underlie the effects of COX inhibitors on neurogenesis and locomotion. Our study provides compelling in vivo evidence showing that prostaglandin signalling promotes neurogenesis in the ventral spinal cord., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Background: Acute kidney injury (AKI) is a significant postoperative complication associated with increased mortality and hospital costs. Hemodynamic strategies, such as goal-directed therapy, might reduce AKI risk. Predicting and proactively managing intraoperative hypotension may be helpful. This trial aims to investigate if a preemptive hemodynamic strategy guided by the hypotension prediction index (HPI) can decrease the incidence of moderate-to-severe AKI within 30 days following major elective abdominal surgery., Methods: This is an open-label, controlled, multicenter, randomized clinical trial that involves daily patient follow-up until hospital discharge. Inclusion criteria are patients aged over 65 and/or categorized as ASA III or IV physical status, undergoing major elective abdominal surgery (general, urological, or gynecological procedures) via laparoscopic or open approach under general or combined anesthesia., Intervention: In the intervention group, hemodynamic management will be based on the HPI and the advanced functional hemodynamic variables provided by the Hemosphere platform and the AcumenIQ® sensor (Edwards Lifesciences). The primary outcome is the incidence of moderate-to-severe AKI within 7 days post-surgery. Secondary outcomes include postoperative complications and 30-day mortality., Discussion: This study explores the potential of HPI-guided hemodynamic management in reducing AKI after major elective abdominal surgery, with implications for postoperative outcomes and patient care., Trial Registration: ClinicalTrials.gov NCT05569265. Registered on October 6, 2022., (© 2024. The Author(s).)

The mammal retina does not have the capacity to regenerate throughout life, although some stem and progenitor cells persist in the adult retina and might retain multipotentiality, as previously described in many tissues. In this work we demonstrate the presence of a small lineage - Sca-1 + cell population in the adult mouse retina which expresses functional TLR2 receptors as in vitro challenge with the pure TLR2 agonist Pam 3 CSK 4 increases cell number and upregulates TLR2. Therefore, this population could be of interest in neuroregeneration studies to elucidate its role in these processes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study examined the roles of anxiety, experiential avoidance and meaning in life in the abusive use of social networks. Participants in the study (N = 235: 172 women, 62 men, 1 non-binary) volunteered to complete a brief online survey measuring experiential avoidance, anxiety and meaning in life. Correlational and linear regression analyses were performed controlling for age in both the total sample and the subsamples of men and women. The partial correlation analyses showed that, once age was controlled for experiential avoidance, anxiety and meaning in life were related to the abusive use of social networks in women, while for men, only anxiety was significant. For women the linear regression equation which best predicted abusive use of social networks included little meaning in life and high experiential avoidance. For men, only anxiety was a possible predictive factor of abusive use of social networks. These results are discussed with regard to existing research on abusive use of social networks, noting the possible protective effect of meaning in life and calling greater attention to gender differences in behaviors related to online social networks.

Major Depressive Disorder (MDD) is one of the most disabling diseases in the world. MDD is traditionally diagnosed based on a patient's symptoms, which can lead to misdiagnosis. Although the pathogenic mechanisms of MDD are unknown, several studies have identified mitochondrial dysfunction as a central factor in the onset and progression of MDD. In the context of MDD, alterations in mitochondrial metabolism can lead to imbalances in energy production and oxidative stress, contributing to the disorder´s underlying pathophysiological mechanisms. Consequently, the identification of mitochondrial dysfunction as a key biomarker for early and accurate diagnosis of MDD represents a significant challenge. Faced with the limits of traditional treatments with antidepressants, new pharmacological therapeutic targets are being investigated such as ketamine/esketamine, psychedelics, or anti-inflammatories. All of these drugs show potential antidepressant effects due to their speed of action and ability to modulate neuroplasticity and/or motor processing. In parallel, non-pharmacological therapeutic targets are studied, like Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS), recognized for their ability to modulate neuronal activity and offer treatment alternatives. As cellular activity is directly related to mitochondrial respiration, the aim of this review is examining the link between mitochondrial dysfunction and MDD, assessing how mitochondrial biomarkers could provide a more objective and precise diagnostic tool, and exploring other treatments in addition to traditional antidepressants, with a specific focus on emerging therapeutic targets. Finally, a detailed analysis of the strengths, weaknesses, opportunities, and threats of these approaches was carried out, highlighting the key challenges that must be addressed.

Objective: Our primary objective is to evaluate the local control of optic nerve sheath meningiomas (ONSMs) treated with ionizing radiation and related visual changes after treatment. Our secondary objective is to describe the clinical characteristics and perform an analysis of the treatment impact on the functional status of this group of patients., Methods: We present our series of 19 patients treated with ionizing radiation therapy at our radio-neurosurgery unit between 2016 and 2022. The setting, ophthalmological follow-up, morbidity, and survival are analyzed and discussed., Results: Patients were followed up, and the impact of treatment on local disease control, visual alterations of the affected eye, and functional status of the patient were analyzed. The progression-free survival (PFS) median was 60 months (95% CI 50.3-69.6 months). The estimated PFS rates at 48 and 66 months were 100% and 66%, respectively. At diagnosis, nine (47.3%) eyes were in amaurosis and ten (52.6%) with vision. Of the ten patients without amaurosis at the time of diagnosis, three (30%) maintained unchanged visual acuity, and seven (70%) had decreased visual acuity; three of them developed amaurosis during the first year after treatment ( p  = 0.018)., Conclusions: Using ionizing radiation therapy is a successful treatment for the local control of ONSMs. This therapeutic modality can compromise the visual acuity of the affected eye and improve dyschromatopsia and campimetry defects. The life prognosis is good for these patients, with a zero mortality rate, but their vision prognosis is poor., 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 Authors.)

Bipolar plates (BPs) are one of the most important components of polymer electrolyte membrane fuel cells (PEMFCs) because of their important role in gas and water management, electrical performance, and mechanical stability. Therefore, promising materials for use as BPs should meet several technical targets established by the United States Department of Energy (DOE). Thus far, in the literature, many materials have been reported for possible applications in BPs. Of these, polymer composites reinforced with carbon allotropes are one of the most prominent. Therefore, in this review article, we present the progress and critical analysis on the use of carbon material-reinforced polymer composites as BPs materials in PEMFCs. Based on this review, it is observed that numerous polymer composites reinforced with carbon allotropes have been produced in the literature, and most of the composites synthesized and characterized for their possible application in BPs meet the DOE requirements. However, these composites can still be improved before their use for BPs in PEMFCs.

Background: To inform the development of an online tool to be potentially used in shared decision-making about breast cancer screening, French women were questioned about participation in breast cancer screening, the health professional's role, and their perceptions of the proposed tool., Methods: We organised focus group discussions with 55 French women. Two different strategies were used to recruit women from high and low socioeconomic backgrounds. We applied both inductive and deductive approaches to conduct a thematic analysis of the discussions. We analysed the responses by using the main determinants from different health behaviour models and compared the two groups., Results: Independently of socioeconomic status, the most important determinant for a woman's participation in breast cancer screening was the perceived severity of breast cancer and the perceived benefits of its early detection by screening. Cues to action reported by both groups were invitation letters; recommendations by health professionals, or group/community activities and public events were reported by women from high and low socioeconomic backgrounds, respectively. Among other positive determinants, women from high socioeconomic backgrounds reported making informed decisions and receiving peer support whereas women from low socioeconomic backgrounds reported community empowerment through group/community events. Fear of cancer was reported as a barrier in both groups. Among other barriers, language issues were reported only by women from low socioeconomic backgrounds; women from high socioeconomic backgrounds reported breast cancer screening-related risks other than overdiagnosis and/or overtreatment. Barriers to accessing the online tool to be developed were mainly reported by women from high socioeconomic backgrounds., Conclusion: Limitations in implementing shared decision-making for women from low socioeconomic backgrounds were highlighted. An online tool that is suitable for all women, regardless of socioeconomic status, would provide "on-demand" reliable and tailored information about breast cancer screening and improve access to health professionals and social exchanges., (© 2024. The Author(s).)

Background: Studies addressing second hematologic malignancies (SHMs) in patients with primary mediastinal germ cell tumors (PMGCTs) are scarce. To better describe this phenomenon, we analyzed a large case series from a population-based registry., Methods: The Surveillance, Epidemiology, and End Results database was used to report the clinical characteristics and incidence of SHMs in patients with PMGCT., Results: Among 1297 PMGCTs, 27 cases (2.08%) of SHM were found, with a median latency period of 12 months (95% CI: 5-41). All SHM occurred in males, 20 of whom (74.1%) had a previous nonseminomatous tumor. Acute myeloid leukemia was the most frequent SHM, accounting for 13 cases, 4 of which were acute megakaryoblastic leukemia that occurred within 5 months of diagnosis. The median survival after the diagnosis of SHM was 6 months (95% CI: 2-41). The risk of SHM was significantly higher than expected for the reference population, with a standardized incidence ratio of 6.21 (95% CI: 3.31-10.62) and an absolute excess risk of 19.19 per 10,000 person-years., Conclusions: Patients with PMGCT are at a higher risk of developing SHMs than the general population, particularly acute myeloid leukemia. This risk ranges from synchronous diagnosis of acute megakaryoblastic leukemia to the later onset of other hematological disorders that might be related to PMGCT therapies. Our findings may help create follow-up schedules for patients with PMGCT and raise the level of suspicion surrounding this association., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille's heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking., Methods: The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action., Results: We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration., Conclusions: Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS., (© 2024. The Author(s).)

Significance: The study of sublingual microcirculation offers valuable insights into vascular changes and overcomes some limitations of peripheral microcirculation assessment. Videomicroscopy and pulse oximetry have been used to assess microcirculation, providing insights into organ perfusion beyond macrohemodynamics parameters. However, both techniques have important limitations that preclude their use in clinical practice., Aim: To address this, we propose a non-invasive approach using photoplethysmography (PPG) to assess microcirculation., Approach: Two experiments were performed on different samples of 31 subjects. First, multi-wavelength, finger PPG signals were compared before and while applying pressure on the sensor to determine if PPG signals could detect changes in peripheral microcirculation. For the second experiment, PPG signals were acquired from the ventral region of the tongue, aiming to assess the microcirculation through features calculated from the PPG signal and its first derivative., Results: In experiment 1, 13 out of 15 features extracted from green PPG signals showed significant differences ( p < 0.05 ) before and while pressure was applied to the sensor, suggesting that green light could detect flow distortion in superficial capillaries. In experiment 2, 15 features showed potential application of PPG signal for sublingual microcirculation assessment., Conclusions: The PPG signal and its first derivative have the potential to effectively assess microcirculation when measured from the fingertip and the tongue. The assessment of sublingual microcirculation was done through the extraction of 15 features from the green PPG signal and its first derivative. Future studies are needed to standardize and gain a deeper understanding of the evaluated features., (© 2024 The Authors.)

Ischemia is the main cause of cell death in retinal diseases such as vascular occlusions, diabetic retinopathy, glaucoma, or retinopathy of prematurity. Although excitotoxicity is considered the primary mechanism of cell death during an ischemic event, antagonists of glutamatergic receptors have been unsuccessful in clinical trials with patients suffering ischemia or stroke. Our main purpose was to analyze if the transient receptor potential channel 7 (TRPM7) could contribute to retinal dysfunction in retinal pathologies associated with ischemia. By using an experimental model of acute retinal ischemia, we analyzed the changes in retinal function by electroretinography and the changes in retinal morphology by optical coherence tomography (OCT) and OCT-angiography (OCTA). Immunohistochemistry was performed to assess the pattern of TRPM7 and its expression level in the retina. Our results show that ischemia elicited a decrease in retinal responsiveness to light stimuli along with reactive gliosis and a significant increase in the expression of TRPM7 in Müller cells. TRPM7 could emerge as a new drug target to be explored in retinal pathologies associated with ischemia.

Background: Obstructive Sleep Apnea (OSA) is a significant health issue due to noncompliance with continuous positive airway pressure treatment. Therefore, evaluating alternative treatments is crucial., Purpose: Analyze the impact of maxillomandibular advancement using bilateral internal ramus distraction (BIRD) on quality of life (QOL) in OSA patients., Study Design, Setting, and Sample: A prospective cohort study was conducted at the Oral and Maxillofacial Surgery Department of the University Hospital "La Princesa." The study included patients with moderate to severe OSA who were treated with the BIRD approach., Predictor Variable: Changes in measured variables were analyzed at three time points: before surgery (T1), after mandibular advancement (T2), and after maxillary advancement (T3)., Main Outcome Variable(s): QOL changes measured by Quebec Sleep Questionnaire and the Epworth Sleepiness Scale. Secondary outcomes included: apnea-hypopnea index (AHI), oxygen desaturation index, and percentage of time with saturation below 90%., Covariates: Age, sex, continuous positive airway pressure treatment, cephalometric variables and cardiovascular risk parameters were considered., Analyses: Statistical analysis employed the Friedman test and χ 2 test, with a significance level of P ≤ .05., Results: The study included 32 patients (22% with moderate OSA, 78% with severe OSA). Epworth Sleepiness Scale scores significantly decreased between T1 (13.4 ± 4.4) and T2 (5.8 ± 3.6) and T3 (1.9 ± 1.8) (P < .001). QOL improvements were observed in all domains: daytime sleepiness T1 (3.0 ± 1.3) T2 (5.4 ± 1.4) T3 (6.3 ± 1.0); diurnal symptoms T1 (2.5 ± 1.4) T2 (5.2 ± 1.3) T3 (6.2 ± 1.1); nocturnal symptoms T1 (2.5 ± 1.1) T2 (5.6 ± 1.1) T3 (6.5 ± 0.8); emotions T1 (2.6 ± 1.6) T2 (5.3 ± 1.4) T3 (6.5 ± 0.9); and social interaction T1 (2.5 ± 1.6) T2 (5.4 ± 1.6) T3 (6.3 ± 1.2) (P < .001). AHI decreased between T1 (47.9 ± 23.1) and T2 (14.4 ± 14.3) and T3 (4.7 ± 5.6) h -1 (P < .001), with a final cure rate of 81.2% (defined as final AHI<5 h -1 ). Oxygen desaturation index and percentage of time with saturation below 90% also showed significant reductions (P < .001)., Conclusions and Relevance: BIRD approach for OSA demonstrated a high cure rate and significant QOL improvements. It shows promise as an effective surgical option. Further research and long-term follow-up are needed., (Copyright © 2023 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Rickettsiae are obligate intracellular Gram-negative bacteria that are the causative agent of rickettsioses and are spread to vertebrate hosts by arthropods. There are no previous reports of isolation of Rickettsia amblyommatis for Colombia., Methods: A convenience sampling was executed in three departments in Colombia for direct collection of adult ticks on domestic animals or over vegetation. Ticks were screened for the presence of Rickettsia spp. by real-time polymerase chain reaction (qPCR) amplifying the citrate synthase gene (gltA), and the positive sample was processed for isolation and further molecular characterization by conventional PCR. The absolute and relative frequencies were calculated for several tick species variables. All products from conventional PCR were further purified and sequenced by the Sanger technique. Representative sequences of 18 Rickettsia species were downloaded from GenBank. Consensus phylogenetic trees were constructed for the gltA, ompB, ompA, and htrA genes with 1000 replicates, calculating bootstrap values through the maximum likelihood method and the generalized time reversible substitution model in the MEGA 7.0 software program., Results: One female Amblyomma mixtum collected on vegetation was amplified by qPCR (gltA), indicating a frequency of 1.6% (1/61) for Rickettsia spp., Infection: Sequence analysis of a rickettsial isolate from this tick in BLASTn showed 100% identity with gltA (340 base pairs [bp]), 99.87% for ompB (782 bp), 98.99% for htrA (497 bp), and 100% for ompA (488 bp) to R. amblyommatis. Concatenated phylogenetic analysis confirmed these findings indicating that the isolate is grouped with other sequences of Amblyomma cajennense complex from Panama and Brazil within the R. amblyommatis clade., Conclusions: This paper describes the isolation and early molecular identification of a R. amblyommatis strain from A. mixtum in Colombia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Raphanus sativus L. (Brassicaceae), commonly known as radish, is consumed worldwide as a vegetable. However, its benefits on mental health are unknown. The aim of this study was to evaluate its anxiolytic-like effects and safety using different experimental models. An aqueous extract of R. sativus sprouts (AERSS) was pharmacologically evaluated by intraperitoneal route (i.p.) at 10, 30, and 100 mg/kg and orally (p.o.) at 500 mg/kg on behavior by using open-field and plus-maze tests. In addition, its acute toxicity (LD 50 ) was determined by the Lorke's method. Diazepam (1 mg/kg, i.p.) and buspirone (4 mg/kg, i.p.) were the reference drugs. A significant and anxiolytic-like dosage of AERSS (30 mg/kg, i.p.) resembling the effects of reference drugs was chosen to explore the involvement of GABA A /BDZs site (flumazenil, 5 mg/kg, i.p.) and serotonin 5-HT 1A receptors (WAY100635, 1 mg/kg, i.p.) as a possible mechanism of action. A 500 mg/kg, p.o. dosage of AERSS produced an anxiolytic-like response equivalent to 100 mg/kg, i.p. No acute toxicity was observed since a LD 50 > 2000 mg/kg, i.p. The phytochemical analysis allowed the identification and quantification of major presence of sulforaphene (2500 µM), sulforaphane (15 µM), iberin (0.75 µM), and indol-3-carbinol (0.75 µM), as major constituents. Both the GABA A /BDZs site and serotonin 5-HT 1A receptors were involved in the anxiolytic-like activity of AERSS, depending on the pharmacological parameter or the experimental assay tested. Our results demonstrate that the anxiolytic activity of R. sativus sprouts involves GABA A /BDZs site and serotonin 5-HT 1A receptors supporting its health benefits in the treatment of anxiety beyond the satisfaction of basic nutritional needs., Competing Interests: Conflicts of interest statement The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide., Methods: This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients., Results: 66% are women and 34% are men with a median age of 59 years (range 17-86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0-39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo-Clavien grade III-IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0-259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients., Conclusions: large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM.

Background: Skin and soft tissue infections are one of the main causes of consultations worldwide. The objective was to determine the treatment of a group of patients with uncomplicated skin and soft tissue infections in Colombia. Methods: Follow-up study of a cohort of patients with skin infections who were treated in the Colombian Health System. Sociodemographic, clinical and pharmacological variables were identified. Treatments were evaluated using clinical practice guidelines for skin infections. Results: A total of 400 patients were analyzed. They had a median age of 38.0 years and 52.3% were men. The most commonly used antibiotics were cephalexin (39.0%), dicloxacillin (28.0%) and clindamycin (18.0%). A total of 49.8% of the subjects received inappropriate antibiotics, especially those with purulent infections (82.0%). Being cared for in an outpatient clinic (OR: 2.09; 95% CI: 1.06-4.12), presenting pain (OR: 3.72; 95% CI: 1.41-9.78) and having a purulent infection (OR: 25.71; 95% CI: 14.52-45.52) were associated with a higher probability of receiving inappropriate antibiotics. Conclusions: Half of patients with uncomplicated skin and soft tissue infections were treated with antibiotics that were not recommended by clinical practice guidelines. This inappropriate use of antibiotics occurred in the vast majority of patients with purulent infections because the antimicrobials used had no effect on methicillin-resistant Staphylococcus aureus .

Objective: Incidental gallbladder lesions are common in imaging studies, although it is not always easy to discriminate benign lesions from gallbladder cancer with conventional imaging procedures. The present study aims to assess the capacity of positron emission tomography/computed tomography (PET/CT) with 2-[ 18 F]FDG to distinguish between benign and malignant pathology of the gallbladder, compared with conventional imaging techniques (contrast-enhanced CT or magnetic resonance imaging)., Methods: Positron emission tomography/CT and conventional imaging studies of 53 patients with gallbladder lesions were evaluated and visually classified as benign, malignant, or inconclusive. Agreement between PET/CT and conventional imaging was determined, and imaging findings were correlated with histology or follow-up. Positron emission tomography/CT images were also analyzed semiquantitatively (SUV max and maximum tumor-to-liver ratio [TLR max ]). The presence of adenopathies and distant metastases was assessed and compared between both imaging procedures., Results: According to histology or follow-up, 33 patients (62%) had a malignant process and 20 (38%) had benign lesions. Positron emission tomography/CT and conventional imaging showed a moderate agreement ( κ = 0.59). Conventional imaging classified more studies as inconclusive compared with PET/CT (17.0% and 7.5%, respectively), although both procedures showed a similar accuracy. Malignant lesions had significantly higher SUV max and, especially, TLR max (0.89 and 2.38 [ P = 0.00028] for benign and malignant lesions, respectively). Positron emission tomography/CT identified more pathologic adenopathies and distant metastases, and patients with regional or distant spread had higher SUV max and TLR max in the gallbladder., Conclusions: Positron emission tomography/CT is accurate to distinguish between benign and malignant pathology of the gallbladder, with a similar performance to conventional imaging procedures but with less inconclusive results. Malignant lesions present higher SUV max and TLR max values., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality., Methods: In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality., Results: A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84-1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36-0.86)., Conclusions: We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this work was to develop niosomes for the ocular delivery of epalrestat, a drug that inhibits the polyol pathway and protects diabetic eyes from damage linked to sorbitol production and accumulation. Cationic niosomes were made using polysorbate 60, cholesterol, and 1,2-di-O-octadecenyl-3-trimethylammonium propane. The niosomes were characterized using dynamic light scattering, zeta-potential, and transmission electron microscopy to determine their size (80 nm; polydispersity index 0.3 to 0.5), charge (-23 to +40 mV), and shape (spherical). The encapsulation efficiency (99.76%) and the release (75% drug release over 20 days) were measured with dialysis. The ocular irritability potential (non-irritating) was measured using the Hen's Egg Test on the Chorioallantoic Membrane model, and the blood glucose levels (on par with positive control) were measured using the gluc-HET model. The toxicity of the niosomes (non-toxic) was monitored using a zebrafish embryo model. Finally, corneal and scleral permeation was assessed with the help of Franz diffusion cells and confirmed with Raman spectroscopy. Niosomal permeation was higher than an unencapsulated drug in the sclera, and accumulation in tissues was confirmed with Raman. The prepared niosomes show promise to encapsulate and carry epalrestat through the eye to meet the need for controlled drug systems to treat the diabetic eye.

There is a widely recognized need to reduce human activity's impact on the environment. Many industries of the leather and textile sector (LTI), being aware of producing a significant amount of residues (Keßler et al. 2021; Liu et al. 2021), are adopting measures to reduce the impact of their processes on the environment, starting with a more comprehensive characterization of the chemical risk associated with the substances commonly used in LTI. The present work contributes to these efforts by compiling and toxicologically annotating the substances used in LTI, supporting a continuous learning strategy for characterizing their chemical safety. This strategy combines data collection from public sources, experimental methods and in silico predictions for characterizing four different endpoints: CMR, ED, PBT, and vPvB. We present the results of a prospective validation exercise in which we confirm that in silico methods can produce reasonably good hazard estimations and fill knowledge gaps in the LTI chemical space. The proposed protocol can speed the process and optimize the use of resources including the lives of experimental animals, contributing to identifying potentially harmful substances and their possible replacement by safer alternatives, thus reducing the environmental footprint and impact on human health., (© 2023. The Author(s).)

Training in emotional regulation skills is one of the most important resources for the adaptation of athletes to contexts of sports pressure, especially during competitions. This study explored the effects of a mindfulness programme (Flow Meditation) on levels of impulsivity, mood and pre-competition anxiety-state in a sample of athletes (N = 41, 22.83 ± 5.62 years). Participants were randomly assigned to an intervention group (N = 21; 14 males and 7 females) which received the intervention over 10 weeks (a weekly session) and a control group (wait-list; N = 20; 13 males and 7 females). The variables under study were assessed through different questionnaires at pre- and post-test (T1-T2) in both groups. The mindfulness intervention was effective in reducing impulsivity (cognitive (t = -4.48, p ≤ 0.001, Cohen's d = 1.40), both motor ( t = -4.03, p ≤ 0.001, Cohen's d = 1.20) and unplanned ( t = -5.32, p ≤ 0.001, Cohen's d = 1.66)), mood (tension ( t = -4.40, p ≤ 0.001, Cohen's d = 1.37), depression ( t = -4.56, p ≤ 0.001, Cohen's d = 1.42), anger ( t = -7.80, p ≤ 0.001, Cohen's d = 2.47), somatic anxiety ( t = -5.28, p ≤ 0.001, Cohen's d = 1.65), and cognitive anxiety ( t = -6.62, p ≤ 0.001, Cohen's d = 2.07) in the intervention group compared to the control group and with large to very large effect sizes. Mindfulness is a factor that enhances athletes' ability to cope with high sport pressure and the healthy management of competition (e.g., fear of failure), or with their daily life.

Niemann Pick disease type C (NPC) is an autosomal recessive neurodegenerative lysosomal disorder characterized by an accumulation of lipids in different organs. Clinical manifestations can start at any age and include hepatosplenomegaly, intellectual impairment, and cerebellar ataxia. NPC1 is the most common causal gene, with over 460 different mutations with heterogeneous pathological consequences. We generated a zebrafish NPC1 model by CRISPR/Cas9 carrying a homozygous mutation in exon 22, which encodes the end of the cysteine-rich luminal loop of the protein. This is the first zebrafish model with a mutation in this gene region, which is frequently involved in the human disease. We observed a high lethality in npc1 mutants, with all larvae dying before reaching the adult stage. Npc1 mutant larvae were smaller than wild type (wt) and their motor function was impaired. We observed vacuolar aggregations positive to cholesterol and sphingomyelin staining in the liver, intestine, renal tubules and cerebral gray matter of mutant larvae. RNAseq comparison between npc1 mutants and controls showed 284 differentially expressed genes, including genes with functions in neurodevelopment, lipid exchange and metabolism, muscle contraction, cytoskeleton, angiogenesis, and hematopoiesis. Lipidomic analysis revealed significant reduction of cholesteryl esters and increase of sphingomyelin in the mutants. Compared to previously available zebrafish models, our model seems to recapitulate better the early onset forms of the NPC disease. Thus, this new model of NPC will allow future research in the cellular and molecular causes/consequences of the disease and on the search for new treatments., 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 © 2023 Quelle-Regaldie, Gandoy-Fieiras, Rodríguez-Villamayor, Maceiras, Losada, Folgueira, Cabezas-Sáinz, Barreiro-Iglesias, Villar-López, Quiroga-Berdeal, Sánchez and Sobrido.)

The dynamic intercommunication between tumour cells and cells from the microenvironment, such as cancer-associated fibroblast (CAFs), is a key factor driving breast cancer (BC) metastasis. Clusters of circulating tumour cells (CTCs), known to bare a higher efficiency at establishing metastases, are found in the blood of BC patients, often accompanied by CAFs in heterotypic CTC-clusters. Previously we have shown the utility of CTC-clusters models and the zebrafish embryo as a model of metastasis to understand the biology of breast cancer CTC-clusters. In this work, we use the zebrafish embryo to study the interactions between CTCs in homotypic clusters and CTC-CAFs in heterotypic CTC-clusters to identify potential pro-metastatic traits derived from CTC-CAF communication. We found that upon dissemination CAFs seem to exert a pro-survival and pro-proliferative effect on the CTCs, but only when CTCs and CAFs remain joined as cell clusters. Our data indicate that the clustering of CTC and CAF allows the establishment of physical interactions that when maintained over time favour the selection of CTCs with a higher capacity to survive and proliferate upon dissemination. Importantly, this effect seems to be dependent on the survival of disseminated CAFs and was not observed in the presence of normal fibroblasts. Moreover, we show that CAFs can exert regulatory effects on the CTCs without being involved in promoting tumour cell invasion. Lastly, we show that the physical communication between BC cells and CAFs leads to the production of soluble factors involved in BC cell survival and proliferation. These findings suggest the existence of a CAF-regulatory effect on CTC survival and proliferation sustained by cell-to-cell contacts and highlight the need to understand the molecular mechanisms that mediate the interaction between the CTCs and CAFs in clusters enhancing the metastatic capacity of CTCs., Competing Interests: RL-L reports grants and personal fees from Roche, Merck, AstraZeneca, Bayer, Pharmamar, Leo, and personal fees and non-financial support from Bristol-Myers Squibb and Novartis, outside of the submitted work. The other authors declare no conflict of interest., (Copyright © 2023 Hurtado, Martínez-Pena, Yepes-Rodríguez, Bascoy-Otero, Abuín, Fernández-Santiago, Sánchez, López-López and Piñeiro.)

Purpose: Lymph node density (LND) has been reported to be a significant predictor of survival in oral squamous cell carcinoma (OSCC). The aim of this study was to analyze LND as a prognostic factor in OSCC and create a predictive model that determines the probability of death in these patients., Methods: A retrospective cohort study was carried out with a cohort of patients who underwent cervical dissection and primary resection of OSCC between 1980 and 2020. The primary predictor variable in this study was LND, which is defined as the number of positive lymph nodes divided by the total number of lymph nodes removed. The cutoff values for prediction of disease-specific survival (DSS) were calculated by receiver operating characteristic curve analysis, which determined the best cutoff value was 0.07. Patients were divided into binary subgroups (low and high risk) using the best cutoff value of LND. The outcome variable was DSS, defined as the duration from the date of diagnosis to death due to OSCC and not due to other causes or secondary tumors. Other variables were type of neck dissection, postsurgical treatment, surgical margin, pathological T category stage, pathological N category (pN) stage, extranodal extension, perineural invasion, bone invasion, and presence of recurrence. A predictive model (score) was generated by selecting variables using a log-rank test and by using the Cox proportional-hazards regression (multivariate analysis)., Results: The sample consisted of 368 patients, 252 (68.5%) male and 116 (31.5%) female patients, with a mean age of 60.3 years. According to the LND cutoff value, there were 289 patients with a low LND (≤0.07) and 79 with a high LND (>0.07). The univariate analysis showed LND as a significant predictor of DSS at 5 years (67.1% in LND ≤ 0.07 vs 32.9% in LND > 0.07; P < .001). The Cox multivariate analysis identified LND (hazard ratio [HR] = 27.2; 95% confidence interval [CI], 3.18-231; P = .002), recurrence (HR = 4.45; 95% CI, 2.3-8.4; P < .001), and type of treatment (HR = 0.52; 95% CI, 0.34-0.81; P < .001) as independent predictive factors for DSS. In the predictive model, the presence of recurrence was the most important factor with 8 points, whereas LND >0.07 contributed only 1 point; however, the 2 categories resulting from this limit were statistically significant., Conclusions: Our study demonstrates that LND is an additional prognostic factor in patients with a pN+ disease. In addition, our predictive model could be useful in the therapeutic algorithm of OSCC patients, as it can predict the probability of death in these patients., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

The accumulation of microplastics (MPs) in the sediments of a stormwater treatment pond was studied to gain knowledge on how these facilities protect the natural environment against this emerging pollutant. Thirteen sediment samples were analyzed for MPs down to 10 μm, mapping the pattern of accumulation in the pond. The average abundance in terms of MP-number and mass was 11.8 μg kg -1 and 44,383 item kg -1 , respectively. They were rather unevenly distributed, with concentrations varying up to two orders of magnitude within the pond, showing that a trustworthy quantification of MPs retained by such units must rely on many and well-distributed subsamples. Buoyant MPs made up 95.4 % of the MP-mass and 83.5 % of the MP-number and in most of the sampled locations, polypropylene dominated the polymer fingerprint, followed by polyethylene. No spatial pattern in the distribution of MPs in the pond was identified. Instead, the MP content correlated to the organic matter and silt content, indicating that the processes leading to deposition could be similar. A computational fluid dynamics model was set up and used to simulate the transport mechanisms governing the conveyance of MPs in the pond from water to sediments. The results showed that the combination of advection and dispersion were likely the driving mechanism for buoyant (and non-buoyant) MPs to get in contact with the sediment bed and spread over the pond. Once in contact with the sediments, the MPs would have some probability of being permanently incorporated and hereby preventing them from entering the downstream aquatic environment., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Mindfulness practice and mindfulness-based interventions are widely known, especially for women's sexuality. However, it is currently unknown how this practice affects the experience of male sexuality, possibly due to the existence of pharmacological treatments that are usually the first choice of treatment for men. The objectives of this study are to explore the influence of mindfulness on different components of men's sexuality from a scoping review of relevant scientific articles existing in the literature. A literature search from 2010 to 2022 was carried out in the electronic databases MEDLINE, Embase, PsycINFO, Web of Science, Scopus, PubMed, Dialnet, SciELO Citation Index, and Redalyc. Out of the 238 studies, 12 that met the defined selection criteria were selected. The analysis of these studies seems to indicate that the practice of mindfulness favours different variables of male sexuality, such as satisfaction and sexual functioning or genital self-image. Mindfulness-based interventions represent a valuable and promising contribution. No adverse effects were detected from the review of scientific articles considered in this work. Nevertheless, more randomized studies with active control groups are necessary to establish the benefits of mindfulness-based interventions in sex therapy for men.