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This paper reports on the development of a collection of dynamical models of one-dimensional peak profile functions used to fit dynamic structure factors S (Q, ħω) of Quasi Elastic Neutron Scattering (QENS) data. The objective of this development is to create a maintainable and interoperable Python library with models reusable in other projects related to the analysis of data from Quasi Elastic Neutron Scattering experiments. The ambition is that the library also will serve as a platform where scientists can make their models available for others. We illustrate how the library can be used by newcomers to the field as well as by experts via different examples. These examples, provided as Jupyter notebooks, show how the QENS models can be integrated in the whole QENS data processing pipeline.

Julio C Sánchez, Jenny P Ospina, Martha I GonzálezCell and Applied Physiology Group, Department of Basic Sciences, Faculty of Health, Universidad Tecnológica de Pereira, Pereira, ColombiaAbstract: Leptin is a hormone with significant effects on the brain, both at the cellular level and cognitive level. This study aimed to establish the association between leptin levels and delirium in a Colombian elderly population. 115 patients older than 60 years were included. Leptin was measured by enzyme-linked immunosorbent assay after overnight fasting and Mini-Mental State Examination and Confusion Assessment Method (CAM) tests were employed. Delirium was diagnosed using CAM in 23.48% of patients, being most frequent in men. There were no significant differences in hematology and renal test values between patients with delirium and those without delirium, but cerebrovascular diagnoses were more frequent in patients with delirium. No correlation with any specific medication was found, but patients with delirium had a higher number of comorbidities and medications. Leptin levels were significantly lower in patients with delirium and correlated negatively with the number of diagnoses and medications, but not with age, gender, body mass index, or hematology and renal test results. Leptin levels may have a role in the pathophysiological process of delirium and low leptin could be a useful clinical biomarker to establish risk in elderly patients given the association with delirium.Keywords: delirium, elderly, hospitalization, leptin

Este trabajo propone comparar dos métodos de evaluación de fósforo extractable, Bray & Kurtz I, de uso habitual en la zona pampeana y Mehlich III, de uso internacional en suelos que han recibido fertilizaciones fosfatadas continuas. Los suelos estudiados recibieron dosis crecientes de fertilizante fosfatado, aplicadas al inicio de una rotación de maíz, trigo y soja. Sobre parcelas de campo, se tomaron muestras de suelo, se analizaron y se compararon los datos de fósforo extractable (P) por Mehlich III y Bray & Kurtz I. Para determinar la bondad de ambos métodos, se ajustaron los datos con la prueba de Peto-Wilcoxon de determinación de curvas de concordancia y análisis de regresión para evaluar la sensibilidad de ambos métodos. Los resultados mostraron que a valores bajos, ambos métodos no se diferencian sustancialmente, pero a partir de los 15 (mg kg-1) de P en el suelo, el método de Mehlich III sobreestima el valor con respecto a Bray & Kurtz I.También fue Bray & Kurtz I el que detectó la mejor variación de las dosis agregadas de P, mostrando mayor sensibilidad entre los tratamientos efectuados. Se concluye que de los estudios realizados el método de Bray & Kurtz I es el que mejor se adapta a las prácticas de diagnóstico y recomendaciones regionales de uso de fertilizante.In this work, we compared two methods of available phosphorus evaluation, Bray & Kurtz I, (the most common in the pampean zone), and Mehlich III, (commonly used in other countries in soils with contionuous P applications). The studied soils received increasing doses of phosphate fertilizer, applied to the beginning of a maize, wheat and soybean rotation. Soil samples were taken in the field, and extractable phosphorus (P) by Mehlich III and Bray & Kurtz I methods were compared. The data were adjusted with the Peto-Wilcoxon test of determination and regression analysis to evaluate the sensitivity of both methods. The results indicated that to low values, these are not different substantially, but from the 15 (mg kg-1) of P in soil, the Mehlich III method overestimates the value with respect to Bray & Kurtz I. This method was the one that showed greater variation to the added doses of P, showing greater sensitivity between treatments. It was concluded that the Bray & Kurtz I method is the one that better adapts to the practices of diagnosis and recommendations of fertilizer use.

Fundamento: Conocer las percepciones de los consumidores acerca del riesgo asociado al uso de medicamentos genéricos y los factores que más influyen en la intención de solicitar un genérico al médico (prescriptor) y/o al farmacéutico, a fin de determinar posibles barreras o frenos a la aceptación de los mismos y obtener información que apoye la toma de decisiones de los gestores sanitarios. Métodos: Estudio sobre utilización de medicamentos centrado en la disposición de los pacientes a solicitar una EFG. En esta investigación transversal cuantitativa se entrevistó personalmente a 542 individuos, a la salida de un centro de salud o de un establecimiento de farmacia en Asturias. En el cuestionario se incluía una escala de medición del riesgo percibido en la compra de un medicamento con 15 atributos agrupados en cinco dimensiones. Asimismo se recogió información sobre la intención de consumir medicamentos genéricos y sobre las características demográficas y socioeconómicas de los entrevistados. Para el análisis de los resultados se aplicaron un análisis factorial confirmatorio, regresión múltiple y análisis univariable. El tratamiento de los datos se efectuó con los programas estadísticos EQS y SPSS. Resultados: Percepción media del riesgo (escalas de 1 a 7): funcional: 2,75; físico: 2,68; financiero: 2,19; psicológico: 1,99; social: 1,42. Factores influyentes sobre la intención de solicitar genéricos al médico: riesgo psicológico (p=0,000). Sobre la solicitud al farmacéutico: riesgo psicológico (p=0,000) y riesgo social (p=0,020). Conclusiones: Los agentes interesados en el desarrollo en el mercado de las EFG deben mantener sus esfuerzos de comunicación hacia la equiparación de los aspectos funcionales y financieros entre especialidades del fabricante y especialidades genéricas, pero no deben dejar de lado aspectos psicológicos y sociales del comportamiento de compra del consumidor.

El análisis palinológico de los 6 m superiores de un perfil turboso de la sección V delValle de Tenjo, permitió evidenciar periodos fríos dominados por vegetación depáramo (pajonales y matorrales) con especies de Poaceae, Asteraceae, Ericaceae eHypericum, y periodos cálidos dominados por bosques de la región andina y de lafranja altoandina con especies de Weinmannia y Melastomataceae que fueron sustituidosdurante algunos periodos por bosques con especies de Myrica. En la basede las laderas se establecieron bosques con especies de Podocarpus que paulatinamentefueron sustituidos por bosques dominados por especies de Ilex, Panopsis,Miconia y Xylosma. En las partes planas se encontraban los bosques de Alnusacuminata (vegetación local), que en algunos periodos climáticos muy húmedosdisminuyeron su área de distribución con lo cual se favoreció el avance de otroselementos de la vegetación de pantano. En la sección analizada están representadoslos eventos acaecidos entre 40.000 y 21.000 años A.P., correspondientes a la partemedia y superior del Pleniglacial, con los estadiales de Faca (36.000 - 33.500 añosA.P.) y Güicán (28.000 - 24.000 años A.P.) y los interestadiales de Tenjo (39.000 -36.000 años A.P.), Santuario (33.500 - 28.000 años A.P.) y Saravita (24.000 - 21.000años A.P.).

Objetivo. Determinar las concentraciones de plomo, cadmio y cromo, y establecer su posible asociación con diferentes factores sociodemográficos. Material y métodos. Se seleccionó una muestra representativa de 100 estudiantes de posgrado de la Facultad de Odontología de la Universidad Nacional Autónoma de México (UNAM), a los cuales se les colectó saliva total no estimulada. Dichas muestras fueron analizadas por espectrofotometría de absorción atómica con horno de grafito. Resultados. Metales pesados como el plomo, el cadmio y el cromo se encuentran en concentraciones mucho más altas que las informadas en la literatura: Pb, = 3.10 m g/dL-1, máxima: 16.8 my g/dL-1, y mínima: 0.04 my g/dL-1; Cd, = 0.25 my g/dL-1, máxima: 2.04 my g/dL-1, y mínima: 0.004 my g/dL-1; y Cr, = 1.43 my g/dL-1, máxima: 4.82 my g/dL-1, y mínima: 0.05 my g/dL-1. Asimismo, variables como la zona de residencia, el sexo, la edad y la ingesta de comida enlatada no influyen en los niveles de plomo y cromo. Sin embargo, en el caso del cadmio y la edad existe una asociación inversa (ji²= 5.9012, p

Abstract Background The aim of the study was to determine the most common pharmacological strategies used in the management of major depressive disorder (MDD) after an inadequate response to first-line antidepressant treatment in clinical practice. Methods Multicenter, non-interventional study in adult outpatients with a DSM-IV-TR diagnosis of MDD and inadequate response to first-line antidepressant medication. Multiple logistic regression analyses were performed to identify independent factors associated with the adoption of a specific second-line strategy. Results A total of 273 patients were analyzed (mean age: 46.8 years, 67.8% female). Baseline mean Montgomery-Asberg Depression Rating Scale total score was 32.1 (95%CI 31.2-32.9). The most common strategies were: switching antidepressant medication (39.6%), augmentation (18.8%), and combination therapy (17.9%). Atypical antipsychotic drugs were the most commonly used agent for augmenting antidepressant effect. The presence of psychotic symptoms and the number of previous major depressive episodes were associated with the adoption of augmenting strategy (OR = 3.2 and 1.2, respectively). Conclusion The switch to another antidepressant agent was the most common second-line therapeutic approach. Psychiatrists chose augmentation based on a worse patients’ clinical profile (number of previous episodes and presence of psychotic symptoms).

Abstract Background The availability of genetic and genomic resources for melon has increased significantly, but functional genomics resources are still limited for this crop. TILLING is a powerful reverse genetics approach that can be utilized to generate novel mutations in candidate genes. A TILLING resource is available for cantalupensis melons, but not for inodorus melons, the other main commercial group. Results A new ethyl methanesulfonate-mutagenized (EMS) melon population was generated for the first time in an andromonoecious non-climacteric inodorus Piel de Sapo genetic background. Diverse mutant phenotypes in seedlings, vines and fruits were observed, some of which were of possible commercial interest. The population was first screened for mutations in three target genes involved in disease resistance and fruit quality (Cm-PDS, Cm-eIF4E and Cm-eIFI(iso)4E). The same genes were also tilled in the available monoecious and climacteric cantalupensis EMS melon population. The overall mutation density in this first Piel de Sapo TILLING platform was estimated to be 1 mutation/1.5 Mb by screening four additional genes (Cm-ACO1, Cm-NOR, Cm-DET1 and Cm-DHS). Thirty-three point mutations were found for the seven gene targets, six of which were predicted to have an impact on the function of the protein. The genotype/phenotype correlation was demonstrated for a loss-of-function mutation in the Phytoene desaturase gene, which is involved in carotenoid biosynthesis. Conclusions The TILLING approach was successful at providing new mutations in the genetic background of Piel de Sapo in most of the analyzed genes, even in genes for which natural variation is extremely low. This new resource will facilitate reverse genetics studies in non-climacteric melons, contributing materially to future genomic and breeding studies.

Abstract Although the importance of wild ruminants as potential reservoirs of bluetongue virus (BTV) has been suggested, the role played by these species in the epidemiology of BT in Europe is still unclear. We carried out a serologic and virologic survey to assess the role of wild ruminants in the transmission and maintenance of BTV in Andalusia (southern Spain) between 2006 and 2010. A total of 473 out of 1339 (35.3%) wild ruminants analyzed showed antibodies against BTV by both ELISA and serum neutralization test (SNT). The presence of neutralizing antibodies to BTV-1 and BTV-4 were detected in the four species analyzed (red deer, roe deer, fallow deer and mouflon), while seropositivity against BTV-8 was found in red deer, fallow deer and mouflon but not in roe deer. Statistically significant differences were found among species, ages and sampling regions. BTV RNA was detected in twenty-one out of 1013 wild ruminants (2.1%) tested. BTV-1 and BTV-4 RNA were confirmed in red deer and mouflon by specific rRT-PCR. BTV-1 and BTV-4 seropositive and RNA positive wild ruminants, including juveniles and sub-adults, were detected years after the last outbreak was reported in livestock. In addition, between the 2008/2009 and the 2010/2011 hunting seasons, the seroprevalence against BTV-1, BTV-4 and BTV-8 increased in the majority of provinces, and these serotypes were detected in many areas where BTV outbreaks were not reported in domestic ruminants. The results indicate that wild ruminants seem to be implicated in the dissemination and persistence of BTV in Spain.

Abstract The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

Abstract Retroviruses, hepadnaviruses, and some other retroelements are vulnerable to editing by single stranded DNA cytidine deaminases. Of the eleven human genes encoding such enzymes, eight have demonstrable enzymatic activity. Six of seven human APOBEC3 are able to hyperedit HBV DNA, frequently on both strands. Although human APOBEC1 (hA1) is not generally expressed in normal liver, hA1 can edit single stranded DNA in a variety of experimental assays. The possibility of ectopic expression of hA1 in vivo cannot be ruled out and interestingly, transgenic mice with A1 expressed under a liver specific promoter develop hepatocellular carcinoma. The impact of hA1 on HBV in tissue culture is varied with reports noting either reduced DNA synthesis or not, with cytidine deamination taking a low profile. We sought to examine the hA1 editing activity on replicating HBV. Using highly sensitive 3DPCR it was possible to show that hA1 edits the HBV minus DNA strand as efficiently as hA3G, considered the reference deaminase for HIV and HBV. The dinucleotide specificity of editing was unique among human cytidine deaminases providing a hallmark of use in a posteriori analyses of in vivo edited genomes. Analysis of sequences derived from the serum of two chronic carriers, indicated that hA1 explained only a small fraction of edited HBV genomes. By contrast, several human APOBEC3 deaminases were active including hA3G.

Objetivos: Conocer, mediante la monitorización ambulatoria de la presión arterial (MAPA) en farmacia comunitaria (FC), el grado de control de la presión arterial (PA) del paciente hipertenso anciano. Identificación del perfil circadiano. Identificación de hipertensión clínica aislada (HCA) e hipertensión enmascarada no controlada (HENC). Métodos: Muestreo consecutivo de los pacientes hipertensos ancianos con tratamiento farmacológico antihipertensivo atendidos en dos FC. Se realizó medida aislada de presión arterial en farmacia comunitaria (MAFC) y MAPA durante un mínimo de 29h a cada paciente. Se envió informe al médico para su valoración. Resultados: 219 pacientes (47,9% mujeres, edad media 71,5±5,4 años). El grado de control con medida con MAFC (74 pacientes) es del 34% y con MAPA (99 pacientes) es del 45%. La prevalencia de patrón circadiano dipper fue del 29,7%. 21 pacientes hipertensos controlados con MAFC (

The taxonomic study of the Chilean Ennomini genera is still in its early stages. Within this group, the maculation patterns of Chilean species are uniform and often inadequate for distinguishing between many species, compounded by a lack of taxonomic revisions focused on the genera within the tribe. In this study, the genus Digonis Butler, 1882, is reviewed and redefined based on characteristics of wing patterns and genitalia. Digonis comprises the following five species: D.aspersa Butler, 1882, D.cervinaria (Blanchard, 1852), D.punctifera Butler, 1882, D.gungnir Ramos-González & Parra, sp. nov ., and D.apocrypha Ramos-González & Parra, sp. nov. Additionally, D.cuprea Butler, 1882 is synonymized with D.cervinaria (Blanchard, 1852), and all varieties of D.punctifera Butler, 1882, and D.cuprea are synonymized with their respective species. Furthermore, two new genera are introduced: Phasmadigonis Ramos-González & Parra, gen. nov. , erected for P.alba (Butler, 1882), comb. nov. , and Gugnelve Ramos-González & Parra, gen. nov. , established for G.butleri Ramos-González & Parra, sp. nov. With the species and genus descriptions, a comparative diagnosis, genitalia illustrations for all species, and wing venation for each genus are provided., Competing Interests: The authors have declared that no competing interests exist., (Mario I. Ramos-González, María Francisca Venegas-González, Carlos Zamora-Manzur, Luis E. Parra.)

Background: Granulosa cell ovarian tumors (GCT) are orphan disease with limited treatments. Hormone therapy is a potential treatment, due to the overexpression of hormone receptors in most tumors. This study explores the activity of the antiandrogen, enzalutamide, in metastatic cases., Methods: We designed a phase II clinical trial under the Spanish Collaborative Group for Transversal Oncology and Rare and Orphan Tumors (GETTHI). Eligible participants were adult women with advanced GCT. Primary endpoint was objective response rate. Secondary endpoints included clinical benefit rate, progression-free survival, overall survival, and safety profile. Patients received enzalutamide 160 mg once daily., Results: From April 2018 to March 2020, eighteen patients were screened, and sixteen were included across nine institutions. Median age was 56.4 years (range 45-71), and most were Caucasian (14 cases), one Arabian and one Latin. ECOG performance status was zero in 13 cases (81 %) and one in three (19 %). Six patients (38 %) had previously received hormone therapy as adjuvant treatment or for advanced disease, and 15 (94 %) chemotherapy. Median time from metastasis to study entry was 96 months (range 4.5-198). No objective response was observed, but the clinical benefit rate reached 68.8 % (95 % CI [46 %-91.5 %]). Median progression-free survival was 3.8 months (95 % CI [1.36-6.14]). Median overall survival was not reached, with a median follow-up of 6 months (range 2.2-19). At the time of database closure, 14 patients had discontinued treatment, 13 due to disease progression and one by personal choice. Two deaths attributed to disease progression were recorded. Five grade 3 adverse events were reported, with only one (asthenia) deemed related to the therapy., Conclusions: Although enzalutamide demonstrated modest activity in GCT, durable stabilization was observed in some cases., Trial Registration: ClinicalTrials.gov Identifier: NCT03464201., Competing Interests: Declaration of competing interest Jesus Garcia-Donas, corresponding author, has received research funding from Gilead Inc., Pfizer Inc., Merck Inc., Bristol-Myers Squibb, AstraZeneca, Novartis, MSD Inc., Roche Inc., Astellas Inc., Novartis Inc., and Exelixis Inc. He has acted as a speaker for Gilead Inc., Pfizer Inc., Merck Inc., Bristol-Myers Squibb, AstraZeneca, Novartis, Glaxo Smithkline Inc. and MSD Inc. He has served as a scientific advisor for Pfizer Inc., Merck Inc., Bristol-Myers Squibb, AstraZeneca, Novartis, and MSD Inc. Enrique Grande has received honoraria for speaker engagements, advisory roles or funding of continuous medical education from Adacap, AMGEN, Angelini, Astellas, Astra Zeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, Clovis-Oncology, Eisai, Eusa Pharma, Genetracer, Guardant Health, HRA-Pharma, IPSEN, ITM-Radiopharma, Janssen, Lexicon, Lilly, Merck KGaA, MSD, Nanostring Technologies, Natera, Novartis, ONCODNA (Biosequence), Palex, Pharmamar, Pierre Fabre, Pfizer, Roche, Sanofi-Genzyme, Servier, Taiho, and Thermo Fisher Scientific. EG has received research grants from Pfizer, Astra Zeneca, Astellas, and Lexicon Pharmaceuticals. AR has received honoraria for speaker engagements, advisory roles or funding of continuous medical education from Astellas, Bristol Myers Squibb, IPSEN, Pfizer, and MSD., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The NLRP3 receptor can assemble inflammasome platforms to trigger inflammatory responses; however, accumulating evidence suggests that it can also display anti-inflammatory properties. Here, we explored the role of nucleotide-binding oligomerization domain pyrin-containing protein 3 (NLRP3) in Taenia crassiceps experimental infection, which requires immune polarization into a Th2-type profile and peritoneal influx of suppressive macrophages for successful colonization. NLRP3 deficient mice (NLRP3 -/- ) were highly resistant against T. crassiceps, relative to wild-type (WT) mice. Resistance in NLRP3 -/- mice was associated with a diminished IL-4 output, high levels of IL-15, growth factor for both innate and adaptive lymphocytes, and a dramatic decrease in peritoneum-infiltrating suppressive macrophages. Also, a transcriptional analysis on bone marrow-derived macrophages exposed to Taenia-secreted antigens and IL-4 revealed that NLRP3 -/- macrophages express reduced transcripts of relm-α and PD-1 ligands, markers of alternative activation and suppressive ability, respectively. Finally, we found that the resistance displayed by NLRP3 -/- mice is transferred through intestinal microbiota exchange, since WT mice co-housed with NLRP3 -/- mice were significantly more resistant than WT animals preserving their native microbiota. Altogether, these data demonstrate that NLRP3 is a component of innate immunity required for T. crassiceps to establish, most likely contributing to macrophage recruitment, and controlling lymphocyte-stimulating cytokines such as IL-15., Competing Interests: Declarations Conflicts of interest The authors declare no competing interests. Institutional review board statement The study was approved by the FES-Iztacala Bioethics Committee (CE/FESI/042022/1513) and met the recommended guidelines issued by government for experimental animal care (NOM-062-ZOO-1999). Informed consent Not applicable., (© 2024. The Author(s).)

Purpose: To explore the role of the proinflammatory cytokine, macrophage migration inhibitory factor (MIF), in a murine model of dry eye disease (DED)., Methods: The role of MIF on DED was determined using genetically MIF deficient mice and pharmacological inhibition of MIF. DED was induced with 0.5 mg of scopolamine via subcutaneous injection in wild type (WT) and mice lacking MIF (Mif -/- ), three times a day for 21 days. DED signs, tear volume, ferning pattern and cytology impression were evaluated. Also, eye tissues were collected to determine transcripts of key inflammatory mediators and histopathological damage. In a second set of experiments, we neutralized MIF with ISO-1, an isozaxiline-derivative MIF tautomerase activity-inhibiting small molecule in WT mice, following an acute DED model for 10 days. ISO-1 was given starting on day 3 after DED induction and signs were evaluated, including a recovery phase in both experimental approaches., Results: When compared to WT, Mif -/- mice showed attenuated signs of DED like preserved mucin pattern and increased tear volume. Also, Mif -/- mice maintained conjunctival epithelial cells and less corneal damage, associated with lower levels of TNFα and IL-1β. At recovery phase, Mif -/- mice presented improved signs. Interestingly, in cornea and conjunctiva the absence of MIF selectively downregulated the transcription of inflammatory enzymes like inos and nox4 whereas displayed enhanced transcripts of il-4, il-13, tgfβ and cox2. Finally, pharmacological inhibition of MIF using ISO-1, replicated the above findings in the mouse model., Conclusion: MIF is a central positive mediator of the inflammatory process in experimental DED, thus, targeting MIF could be used as a novel therapy in ocular surface inflammatory pathologies.

Introduction: Three-dimensional (3D)-printing technology can provide customizable simulations, but its effects on patient care quality have not been well studied. This study aimed to assess the impact of practicing with patient-specific 3D-printed teeth models on the quality of patients' dental preparations performed by students transitioning to clinical training. Accordingly, the quality of posterior crown preparations was evaluated by objectively analyzing digital scans and grades in two groups: the study group, which practiced beforehand with patient-specific 3D-printed teeth models, and the control group, which did not practice with these models., Methods: All 78 fourth-year dental students who had just finished their fixed prosthodontics course at the simulation laboratory with training on phantom heads and without previous clinical experience in crown preparations were invited to participate in the study. Sixty-eight agreed to take part and were randomly divided into a study group that practiced crown preparations on 3D-printed models of their own patient's teeth and a control group that did not practice with 3D-printed models and started their clinical work straightforwardly after simulation training. Students completed validated perception questionnaires on self-confidence and clinical skills before and after the protocol, which were compared using a chi-squared test. Crown preparations performed on 3D-printed models and then on patients were digitally scanned and objectively graded by prepCheck software for critical parameters, such as undercuts, taper, and occlusion reduction. Non-parametric tests were used to compare preparations on 3D-printed models and on patients performed by the study group and those on patients made by the control group., Results: Initially, both groups reported similar perceptions of self-confidence and clinical skills levels. The study group significantly improved both aspects after the protocol. Analysis of the scanned preparations demonstrated that the study group removed less tooth structure from actual patients than from the initial 3D-printed models. In contrast, the control group showed excess occlusal clearance in their patients compared to the study group., Conclusions: Practicing patient-specific 3D-printed teeth before performing procedures clinically appears to enhance preparation quality and minimize unnecessary tooth reduction in early clinical experiences., (© 2024 American Dental Education Association.)

Background: Previous studies have indicated the association between poor oral health and depression in adults. This study evaluated oral and social functions contribution to the association between tooth loss and depressive symptoms in Chilean individuals., Methods: We used data from the Chilean National Health Survey. The number of remaining teeth (≤19 versus ≥20 teeth) and anterior tooth losses were the exposure variables. Outcome was depression, measured through a self-report question and with the Composite International Diagnostic Interview - Short Form (CIDI SF). Mediating variables were determined by five questions, including problems regarding "speaking", "pain and suffering", "eating", "daily activities", and "social relationships". We performed logistic regression models adjusted by multiple confounders variables. Finally, we calculated indirect, direct effect, total effect, and the proportion mediated (PM)., Results: We included 5383 participants. The self-reported depression and suspected depression prevalence were 22,1 % and 14,0 % respectively. The total effect of fewer remaining teeth (≤19) on self-reported depression was 1.21 (95 % CI 1.02-1.44), and 1.09 (95 % CI 0.90-1.33) for suspected depression. All five variables of oral and social functions significantly mediated the association between tooth loss and depression. Feeling uncomfortable when speaking or eating discomfort were the most significant mediators., Limitations: The mediation analysis should be interpreted with caution due to the cross-sectional design., Conclusions: Deterioration of oral and social functions was a significant mediator in the association between tooth loss and depression, in particular feeling uncomfortable when speaking or eating. This mechanism should be considered in interventions to improve mental health., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Our aim is to review and perform a meta-analysis on the role of impulsivity in fatal suicide behaviour. We included papers who used psychological autopsy methodology, assessed adult death by suicide, and included assessment of impulsivity. We excluded papers about assisted suicide, terrorist suicide, or other cause of death other than suicide or postmortem diagnosis made only from medical records or database. 97 articles were identified. 33 were included in the systematic review and nine in the meta-analysis. We found that people who die by suicide with high impulsivity are associated with younger age, substance abuse, and low intention to die, whereas those with low impulsivity were associated with older age, depression, schizophrenia, high intention to die and low social support. In the meta-analysis, suicide cases had higher impulsivity scores than living controls (Hedges' g = 0.59, 95 % CI [0.28, 0.89], p=.002). However, studies showed heterogeneity (Q = 90.86, p<.001, I2=89.0 %). Impulsivity-aggressiveness interaction was assessed through meta-regression (β=0.447, p=.045). Individuals with high impulsivity would be exposed to a higher risk of fatal suicide behaviour, aggressiveness would play a mediating role. People who die by suicide with high and low impulsivity display distinct characteristics, which may reflect different endophenotypes leading to suicide by different pathways., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This article reports a case of maxillary rehabilitation with implant-supported fixed dental prostheses on six zirconia implants. A woman with impacted maxillary canines attended our dental clinic seeking a metal-free maxillary restoration. After the extraction of both impacted maxillary canines and the placement of autogenous bone graft, six two-piece zirconia implants with straight abutments were placed in the anterior maxilla. Two zirconia fixed dental prostheses with porcelain veneering, separated at the midline, were placed on these zirconia implants. The 10-year follow-up monitored the adequate evolution of both implants and restorations with no signs of peri-implant disease.

Colorectal cancer (CRC) is one of the most prevalent fatal neoplasias worldwide. Despite efforts to improve the early diagnosis of CRC, the mortality rate of patients is still nearly 50%. The primary treatment strategy for CRC is surgery, which may be accompanied by chemotherapy and radiotherapy. The conventional and first-line chemotherapeutic agent utilized is 5-fluorouracil (5FU). However, it has low efficiency. Combination treatment with leucovorin and oxaliplatin or irinotecan improves the effectiveness of 5FU therapy. Unfortunately, most patients develop drug resistance, leading to disease progression. Here, we evaluated the effect of a potential alternative adjuvant treatment for 5FU, helminth-derived Taenia crassiceps (TcES) molecules, on treating advanced colitis-associated colon cancer. The use of TcES enhanced the effects of 5FU on established colonic tumors by downregulating the expression of the immunoregulatory cytokines, Il-10 and Tgf-β, and proinflammatory cytokines, Tnf-α and Il-17a, and reducing the levels of molecular markers associated with malignancy, cyclin D1, and Ki67, both involved in apoptosis inhibition and the signaling pathway of β-catenin. TcES+5FU therapy promoted NK cell recruitment and the release of Granzyme B1 at the tumor site, consequently inducing tumor cell death. Additionally, it restored P53 activity which relates to decreased Mdm2 expression. In vitro assays with human colon cancer cell lines showed that therapy with TcES+5FU significantly reduced cell proliferation and migration by modulating the P53 and P21 signaling pathways. Our findings demonstrate, for the first time in vivo, that helminth-derived excreted/secreted products may potentiate the effect of 5FU on established colon tumors., Competing Interests: Declaration of Competing Interest All the authors declare no conflict of interest for the current study., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Objective: to assess the effectiveness of immunonutrition (IN) compared to standard nutritional formulas in patients undergoing gastric cancer surgery. Material and methods: this is a real-life, observational retrospective cohort study. It included 134 patients, all of whom underwent gastrectomy at Montecelo Hospital between December 2019 and December 2022. Group A (N = 79 patients) received standard nutrition, and Group B (N = 55 patients) received formulas containing arginine, nucleotides, omega-3 fatty acids, and extra virgin olive oil. This protocol was carried out both pre and postoperatively for an average period of 10 days. The study evaluated hospital stay, the need for parenteral nutrition (PN), postoperative complications, as well as anthropometric and laboratory variables. Statistical analyses were performed using Stata 16.1.® Results: in the IN group compared to the standard nutrition group, the hospital stay was reduced by 34 % (p < 0.001). The number of patients requiring PN decreased by 21.1 % (p = 0.022), and its duration also decreased by 33.2 % (p < 0.001). The risk of infectious complications was lower with IN, specifically 70.1 % less (p < 0.001). As for other postoperative complications, IN reduced the risk of intestinal obstruction by 84 % (p < 0.002), suture dehiscence by 90.9 % (p < 0.001), blood transfusion by 99.8 % (p < 0.001), pleural effusion by 90.9 % (p = 0.021), acute renal failure by 84.02 % (p = 0.047), and surgical re-intervention by 69.93 % (p < 0.011). In the IN group, there was less weight loss (p = 0.048) and a smaller decrease in postoperative albumin (p = 0.005) and cholesterol (p < 0.001). Conclusion: immunonutrition reduces postoperative complications, decreases hospital stay, and optimizes nutritional outcomes.

Purpose: The Gram-positive Staphylococcus aureus bacterium is one of the leading causes of infection in humans. The lack of specific noninvasive techniques for diagnosis of staphylococcal infection together with the severity of its associated complications support the need for new specific and selective diagnostic tools. This work presents the successful synthesis of an immunotracer that targets the α -toxin released by S. aureus ., Methods: [ 89 Zr]Zr-DFO-ToxAb was synthesized based on radiolabeling an anti- α -toxin antibody with zirconium-89. The physicochemical characterization of the immunotracer was performed by high-performance liquid chromatography (HPLC), radio-thin layer chromatography (radio-TLC), and electrophoretic analysis. Its diagnostic ability was evaluated in vivo by positron emission tomography/computed tomography (PET/CT) imaging in an animal model of local infection-inflammation (active S. aureus vs. heat-killed S. aureus ) and infective osteoarthritis., Results: Chemical characterization of the tracer established the high radiochemical yield and purity of the tracer while maintaining antibody integrity. In vivo PET/CT image confirmed the ability of the tracer to detect active foci of S. aureus . Those results were supported by ex vivo biodistribution studies, autoradiography, and histology, which confirmed the ability of [ 89 Zr]Zr-DFO-ToxAb to detect staphylococcal infectious foci, avoiding false-positives derived from inflammatory processes., Conclusions: We have developed an immuno-PET tracer capable of detecting S. aureus infections based on a radiolabeled antibody specific for the staphylococcal alpha toxins. The in vivo assessment of [ 89 Zr]Zr-DFO-ToxAb confirmed its ability to selectively detect staphylococcal infectious foci, allowing us to discern between infectious and inflammatory processes., Competing Interests: The authors declare that there are no conflicts of interest regarding financial interests or personal beliefs, although this project has been funded by various public and private institutions, as indicated in the funding statement section., (Copyright © 2024 María Isabel González et al.)

Curcumin is a natural molecule widely tested in preclinical and clinical studies due to its antioxidant and anti-inflammatory activity. Nevertheless, its high hydrophobicity and low bioavailability limit in vivo applications. To overcome curcumin´s drawbacks, small extracellular vesicles (sEVs) have emerged as potential drug delivery systems due to their non-immunogenicity, nanometric size and amphiphilic composition. This work presents curcumin cargo into milk sEV structure and further in vitro and in vivo evaluation as a therapeutic nanoplatform. The encapsulation of curcumin into sEV was performed by two methodologies under physiological conditions: a passive incorporation and active cargo employing saponin. Loaded sEVs (sEVCurPas and sEVCurAc) were fully characterized by physicochemical techniques, confirming that neither methodology affects the morphology or size of the nanoparticles (sEV: 113.3±5.1 nm, sEVCurPas: 127.0±4.5 nm and sEVCurAc: 98.5±3.6 nm). Through the active approach with saponin (sEVCurAc), a three-fold higher cargo was obtained (433.5 µg/mL) in comparison with the passive approach (129.1 µg/mL). These sEVCurAc were further evaluated in vitro by metabolic activity assay (MTT), confocal microscopy, and flow cytometry, showing a higher cytotoxic effect in the tumoral cells RAW264.7 and HepG2 than in primary hepatocytes, specially at high doses of sEVCurAc (4%, 15% and 30% of viability). In vivo evaluation in an experimental model of liver fibrosis confirmed sEVCurAc therapeutic effects, leading to a significant decrease of serum markers of liver damage (ALT) (557 U/L to 338 U/L with sEVCurAc therapy) and a tendency towards decreased liver fibrogenesis and extracellular matrix (ECM) deposition., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Manuel Desco & Beatriz Salinas reports financial support was provided by Community of Madrid. Beatriz Salinas reports financial support was provided by Spain Ministry of Science and Innovation. Beatriz Salinas reports financial support was provided by Carlos III Health Institute. Virgina Albaladejo & Ana Santos reports financial support was provided by Consejería de Educación e Investigación. Virginia Albaladejo & Ana Santos reports financial support was provided by European Social Fund. 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. Published by Elsevier Masson SAS.)

Fluoroquinolones (FQs) are one of the most commonly prescribed classes of antibiotics. Although they were initially well tolerated in randomized clinical trials, subsequent epidemiological studies have reported an increased risk of threatening, severe, long-lasting, disabling and irreversible adverse effects (AEs), related to neurotoxicity and collagen degradation, such as tendonitis, Achilles tendon rupture, aortic aneurysm, and retinal detachment. This article reviews the main potentially threatening AEs, the alarms issued by regulatory agencies and therapeutic alternatives., (©The Author 2023. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Purpose: The aim of the study is to describe the genotype and phenotype of a Mexican cohort with PCARE -related retinal disease., Methods: The study included 14 patients from 11 unrelated pedigrees with retinal dystrophies who were demonstrated to carry biallelic pathogenic variants in PCARE . Visual assessment methods included best corrected visual acuity, color fundus photography, Goldmann visual field test, kinetic perimetry, dark/light adapted chromatic perimetry, full-field electroretinography, autofluorescence imaging, and spectral domain-optical coherence tomography imaging. Genetic screening was performed either by gene panel sequencing or by exome sequencing., Results: According to the results of multimodal imaging and functional tests, all 14 patients were diagnosed with cone-rod dystrophy. Six different PCARE pathogenic alleles were identified in our cohort, including three novel mutations: c.3048&#95;3049del (p.Tyr1016 ∗ ), c.3314&#95;3315del (p.Ser1105 ∗ ), and c.551A > G (p.His184Arg). Notably, alleles p.His184Arg, p.Arg613 ∗ , and p.Arg984 ∗ were present in 18 of the 22 (82%) PCARE alleles from probands in our cohort., Conclusion: Our work expands the PCARE mutational profile by identifying three novel pathogenic variants causing retinal dystrophy. While phenotypic variations occurred among patients, a cone-rod dystrophy pattern was observed in all affected individuals., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Víctor R. López-Rodríguez et al.)