Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption.

Purpose: Intestinal ischemia-reperfusion injury (i-IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti-inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i-IRI. Methods: i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 µg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. Results: The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 µg/mL; non-treated, 1.18 ± 0.07 µg/mL; curcumin 1.76 ± 0.3 µg/mL; DEX5, 2.29 ± 0.2 µg/mL; DEX20, 2.25 ± 0.26 µg/mL; and α-tocopherol 1.66 ± 0.21 µg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. Conclusion: All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.

Peripersonal encoding of forelimb proprioception in the mouse somatosensory cortex.

Conscious perception of limb movements depends on proprioceptive neural responses in the somatosensory cortex. In contrast to tactile sensations, proprioceptive cortical coding is barely studied in the mammalian brain and practically non-existent in rodent research. To understand the cortical representation of this important sensory modality we developed a passive forelimb displacement paradigm in behaving mice and also trained them to perceptually discriminate where their limb is moved in space. We delineated the rodent proprioceptive cortex with wide-field calcium imaging and optogenetic silencing experiments during behavior. Our results reveal that proprioception is represented in both sensory and motor cortical areas. In addition, behavioral measurements and responses of layer 2/3 neurons imaged with two-photon microscopy reveal that passive limb movements are both perceived and encoded in the mouse cortex as a spatial direction vector that interfaces the limb with the body's peripersonal space.

The Prevention of Ischemia-Reperfusion Injury in Elderly Rats after Lower Limb Tourniquet Use.

Background: Lower limb ischemia-reperfusion injury (IRI-LL) is a common major complication of orthopedic surgery, especially in elderly patients. It has previously been demonstrated that folinic acid (FA) reduced IRI-LL damage in 3−4-month-old rats. This current work analyses the effect of FA in the prevention of IRI-LL in elderly animals. Methods: Forty-two 18-month-old male WAG/RijHsd rats were subjected to 3 h of ischemia. Eighteen animals received FA (2.5 mg/kg, ip) 20 min before the end of the ischemia period, while the other half received the same volume of saline solution. The animals were sacrificed after 3 h, 24 h, and 14 days of reperfusion for biochemical (tissue damage markers and electrolytes), histopathological studies of the gastrocnemius muscle and the daily assessment of the limb function by the Rota Rod test, respectively. Results: The administration of FA prior to the end of the ischemia period reduced the increase in LDH and CK observed in non-treated animals by 30−40% (p < 0.0001). When the histological sections were analyzed, FA was found to have reduced the number of damaged muscle fibers per field by 20% (60 ± 17.1 vs. 80.7 ± 16.4, p < 0.0001). The functional test revealed that FA also led to an improvement in the muscle function, assessed by the length of time that the animals kept running on the rod, compared to untreated animals. Conclusions: The administration of FA, prior to the end of the ischemic period, decreases the damage induced by IRI-LL, also achieving a faster recovery of mobility.

Conditioned Medium from H2O2-Preconditioned Human Adipose-Derived Stem Cells Ameliorates UVB-Induced Damage to Human Dermal Fibroblasts.

Human skin exposure to ultraviolet B (UVB) radiation can result in acute photodamage through oxidative modifications of cellular components and biomolecules involved in the metabolism of dermal cells. Recently, the therapeutic potential of human adipose-derived stem cells (hASCs) has been investigated as a novel strategy for photoprotection due to their pro-angiogenic properties, protective activity against oxidative stress and paracrine effect on dermal cells. To enhance these therapeutic properties, hASCs can be preconditioned by exposing them to sublethal cellular stressors. In this study, we first analyzed response capacity against UVB-induced oxidative stress in H2O2-preconditioned hASCs (called HC016 cells); and second, we evaluated the photoprotective effect of HC016-conditioned medium (CM) in an in vitro UVB irradiation model in cultured human foreskin fibroblasts (hFFs). The results demonstrated that HC016 cells have a greater capacity to respond efficiently to UVB-induced oxidative stress, evidenced by higher Nrf2 antioxidant system activity and enhanced viability and migration capacity. Further, HC016-CM treatment increased viability, migratory capacity and collagen type I synthesis in hFFs exposed to UVB radiation, as well as reducing their cytotoxicity, apoptosis, senescence and IL-6 secretion. Collectively, these findings support the view that HC016 cells could protect against UVB-induced photodamage via paracrine mechanisms.

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy.

BACKGROUND: Lately, major advances in crucial aspects of magnetic hyperthermia (MH) therapy have been made (nanoparticle synthesis, biosafety, etc.). However, there is one key point still lacking improvement: the magnetic field-frequency product (H × f = 4.85 × 108 Am-1s-1) proposed by Atkinson-Brezovich as a limit for MH therapies. Herein, we analyze both local and systemic physiological effects of overpassing this limit. METHODS: Different combinations of field frequency and intensity exceeding the Atkinson-Brezovich limit (591-920 kHz, and 10.3-18 kA/m) have been applied for 21 min to WAG/RijHsd male rats, randomly distributed to groups of 12 animals; half of them were sacrificed after 12 h, and the others 10 days later. Biochemical serum analyses were performed to assess the general, hepatic, renal and/or pancreatic function. RESULTS: MH raised liver temperature to 42.8 ± 0.4 °C. Although in five of the groups the exposure was relatively well tolerated, in the two of highest frequency (928 kHz) and intensity (18 kA/m), more than 50% of the animals died. A striking elevation in liver and systemic markers was observed after 12 h in the surviving animals, independently of the frequency and intensity used. Ten days later, liver markers were almost recovered in all of the animals. However, in those groups exposed to 591 kHz and 16 kA/m, and 700 kHz and 13.7 kA/m systemic markers remained altered. CONCLUSIONS: Exceeding the Atkinson-Brezovich limit up to 9.59 × 109 Am-1s-1 seems to be safe, though further research is needed to understand the impact of intensity and/or frequency on physiological conditions following MH.

Rendimiento académico en estudiantes de enfermería de una universidad pública / Academic performance in nursing students from a public university

Introducción: la globalización ha impactado el ámbito educativo, por lo que las instituciones de educación superior tienen la responsabilidad de generar en los alumnos destrezas, habilidades y conocimientos que faciliten el proceso de aprendizaje para mejorar y mantener un rendimiento académico eficiente. Objetivo: describir el rendimiento académico desde la perspectiva de los estudiantes de noveno semestre de la Licenciatura en Enfermería de una institución pública del estado de Oaxaca, México. Metodología: el diseño del estudio fue descriptivo transversal. La muestra fue de 159 estudiantes, con un nivel de confianza de 95% y un margen de error del 5%. El muestreo fue probabilístico aleatorio simple. Para la medición del rendimiento académico se aplicó la Escala MEDMAR. La ética del estudio consideró la declaración de Helsinki. El análisis de los datos se procesó a través del programa SPSS, versión 22, y Microsoft Excel Office 10. Para el análisis de los datos se utilizó la estadística descriptiva. La confiabilidad del instrumento reportó un alfa de Cronbach de 0.9. Resultados: los estudiantes percibieron el rendimiento académico como bueno (12.6%) y muy bueno (87.4%). En las variables contextuales se observó en un 74.4% como muy bueno. Para las variables propias del estudiante se percibió un 85.5% en calidad de muy bueno. Conclusión: las evidencias encontradas apuntan a que los estudiantes perciben el rendimiento académico de manera positiva.

Introduction: Globalization has had an impact on the educational field, which is why higher education institutions have the responsibility of generating skills, abilities and knowledge in students that facilitate the learning process to improve and maintain an efficient academic performance. Objective: To describe the academic performance from the perspective of the students of the ninth semester of the Bachelor of Science in Nursing of a public institution of the state of Oaxaca. Methodology: The study design was descriptive, cross-sectional. The sample consisted of 159 students, with a confidence level of 95% and a margin of error of 5%. The sampling was simple random. To measure academic performance, the MEDMAR Scale was applied. The ethics of the study considered the Declaration of Helsinki. The data analysis was processed through the Statistical Package for Social Sciences, version 22, and Microsoft Excel Office 10. Descriptive statistics were used for data analysis. The reliability of the instrument reported a Cronbach's alpha of 0.9 Results: Students perceived the academic performance as good (12.6%) and very good (87.4%). In contextual variables, it was observed in 74.4% as very good. For the student's own variables, 85.5% were perceived as very good. Conclusion: The evidence found indicates that students perceive academic performance in a positive way.

Metástasis cardiacas en paciente con tumor fibroso solitario pleural / Cardiac Metastases in a Patient with a Pleural Solitary Fibrous Tumor

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[Translated article] Cardiac Metastases in a Patient with a Pleural Solitary Fibrous Tumor / Metástasis cardiacas en paciente con tumor fibroso solitario pleural

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Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats.

Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child-Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.

Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats.

Surgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated folinic acid (FA) in a rodent model of lower limb ischemia-reperfusion (IRI-LL). 36 male WAG rats underwent 3 h of lower limb ischemia. In the saline group, rats received intraperitoneal administration of saline (used as vehicle for treatment). In the experimental group, rats were pretreated with FA (2.5 mg/kg) before the end of ischemia. After ischemia, animals were sacrificed at 3 h, 24 h or 14 days (for biochemical determination (Na+, K+, Cl-, urea, creatinine, CK, LDH, ALP, ALT, and AST), pathological assessment, or functional study using the rotarod test; respectively). Another six animals were used to establish the reference values. The prophylactic administration of FA significantly reduced the elevation of biochemical markers, especially those that most directly indicate muscle damage (CK and LDH). In addition, it also improved direct tissue damage, both in terms of edema, weight, PMN infiltrate and percentage of damaged fibers. Finally, the administration of FA allowed the animals to equal baseline values in the rotarod test; what did not occur in the saline group, where pre-ischemia levels were not recovered. Following 3 h of lower limb ischemia, FA minimizes the increase of CK and LDH, as well as local edema and leukocyte infiltration, allowing a faster recovery of limb functionality. Therefore, it could be considered as a prophylactic treatment when tourniquet is used in clinics.

A reproducible method for biochemical, histological and functional assessment of the effects of ischaemia-reperfusion syndrome in the lower limbs.

Current methodology described to mimic lower limb ischaemia-reperfusion injury (LL-IRI) does not accurately define the procedures and pressures exerted to induce and maintain ischaemia. In this piece of work, we propose a well-defined and detailed rat model that simulates the conditions established in clinical practice guidelines for tourniquet application and allows us to test treatments that aim to prevent/reduce LL-IRI. Eighty-six male WAG/RijHsd rats were subjected to hind limb IRI (LL-IRI), using a mechanical system applying a 1 kg tension to induce and maintain ischemia for 2 or 3 h, and assessed the damage caused by reperfusion at biochemical and muscular levels at different time points. At the biochemical level, both 2 and 3 h of ischemia induced changes (except for electrolyte levels); 3 h of ischemia induced greater changes in specific markers of muscular damage: creatine kinase (CK) and lactate dehydrogenase (LDH). At the histopathological level, 3 h of ischemia and 24 h of reperfusion was associated with an increase in hind limb girth, cross-sectional area, and weight and presence of neutrophils, as well as histological damage in more than 60% of muscle fibres. Our model allows to reliably reproduce the damage associated with the use of a pneumatic tourniquet. CK and LDH, as well as measures of tissue damage, allow to define and characterize the response to LL-IRI-related damage. A period of 3 h of ischemia followed by 3 h of reperfusion caused only local damage but showed greater sensitivity to detect differences in future studies on prophylactic treatments against LL-IRI.

Curcumin Reduces Colorectal Cancer Cell Proliferation and Migration and Slows In Vivo Growth of Liver Metastases in Rats.

BACKGROUND: New therapeutic approaches are an essential need for patients suffering from colorectal cancer liver metastases. Curcumin, a well-known plant-derived polyphenol, has been shown to play a role in the modulation of multiple signaling pathways involved in the development and progression of certain cancer cells in vitro. This study aims to assess the anti-tumor effect of curcumin on CC531 colorectal cancer cells, both in vitro and in vivo. METHODS: On CC531 cultures, the cell viability and cell migration capacity were analyzed (wound healing test) 24, 48, and 72 h after treatment with curcumin (15, 20, 25, or 30 µM). Additionally, in WAG/RijHsd tumor-bearing rats, the total and individual liver lobe tumor volume was quantified in untreated and curcumin-treated animals (200 mg/kg/day, oral). Furthermore, serum enzyme measurements (GOT, GPT, glucose, bilirubin, etc.) were carried out to assess the possible effects on the liver function. RESULTS: In vitro studies showed curcumin's greatest effects 48h after application, when all of the tested doses reduced cell proliferation by more than 30%. At 72 h, the highest doses of curcumin (25 and 30 µM) reduced cell viability to less than 50%. The wound healing test also showed that curcumin inhibits migration capacity. In vivo, curcumin slowed down the tumor volume of liver implants by 5.6-fold (7.98 ± 1.45 vs. 1.41 ± 1.33; p > 0.0001). CONCLUSIONS: Curcumin has shown an anti-tumor effect against liver implants from colorectal cancer, both in vitro and in vivo, in this experimental model.

Evolution of Culture on Patient Safety in the Clinical Setting of a Spanish Mutual Insurance Company: Observational Study between 2009 and 2017 Based on AHRQ Survey.

BACKGROUND: Patient safety (PS) is a key factor in reducing or even eradicating adverse incidents and events. Many health organizations promote strategies to improve PS, while also pointing out the importance of measuring it. For more than eight years, our institution has developed strategies focused on improving PS-culture among our personnel. The goal of this paper is to analyze the PS-culture between the years 2009 and 2017. METHODS: A cross-sectional survey focused on PS, and developed by the American Agency for Healthcare Research and Quality (AHRQ), was conducted in 2009 and in 2017 among all healthcare workers at Mutualia, anonymously and voluntarily. RESULTS: The overall response rate was similar in both 2009 and 2017 (37.2% and 38.5%, respectively). The average rating obtained showed a significant improvement over the period (7.7 vs. 8.1; p < 0.05). Itemizing by question, the main strengths were found in management support, organizational learning and continuous improvement, and, especially, in teamwork. Regarding weaknesses, the two lowest scores were those which refer to the balance between clinical safety and workload and the freedom to question the decisions made by superiors. CONCLUSIONS: The results obtained from the PS-surveys show that the overall PS-culture in our institution has increased, suggesting that the strategies focused on the improvement of PS-culture were well adopted among our personnel. The overall score places Mutualia at similar levels to those reached by the AHRQ and Spanish National Health System.

CAPformer: Pedestrian Crossing Action Prediction Using Transformer.

Anticipating pedestrian crossing behavior in urban scenarios is a challenging task for autonomous vehicles. Early this year, a benchmark comprising JAAD and PIE datasets have been released. In the benchmark, several state-of-the-art methods have been ranked. However, most of the ranked temporal models rely on recurrent architectures. In our case, we propose, as far as we are concerned, the first self-attention alternative, based on transformer architecture, which has had enormous success in natural language processing (NLP) and recently in computer vision. Our architecture is composed of various branches which fuse video and kinematic data. The video branch is based on two possible architectures: RubiksNet and TimeSformer. The kinematic branch is based on different configurations of transformer encoder. Several experiments have been performed mainly focusing on pre-processing input data, highlighting problems with two kinematic data sources: pose keypoints and ego-vehicle speed. Our proposed model results are comparable to PCPA, the best performing model in the benchmark reaching an F1 Score of nearly 0.78 against 0.77. Furthermore, by using only bounding box coordinates and image data, our model surpasses PCPA by a larger margin (F1=0.75 vs. F1=0.72). Our model has proven to be a valid alternative to recurrent architectures, providing advantages such as parallelization and whole sequence processing, learning relationships between samples not possible with recurrent architectures.

Urban Intersection Classification: A Comparative Analysis.

Understanding the scene in front of a vehicle is crucial for self-driving vehicles and Advanced Driver Assistance Systems, and in urban scenarios, intersection areas are one of the most critical, concentrating between 20% to 25% of road fatalities. This research presents a thorough investigation on the detection and classification of urban intersections as seen from onboard front-facing cameras. Different methodologies aimed at classifying intersection geometries have been assessed to provide a comprehensive evaluation of state-of-the-art techniques based on Deep Neural Network (DNN) approaches, including single-frame approaches and temporal integration schemes. A detailed analysis of most popular datasets previously used for the application together with a comparison with ad hoc recorded sequences revealed that the performances strongly depend on the field of view of the camera rather than other characteristics or temporal-integrating techniques. Due to the scarcity of training data, a new dataset is created by performing data augmentation from real-world data through a Generative Adversarial Network (GAN) to increase generalizability as well as to test the influence of data quality. Despite being in the relatively early stages, mainly due to the lack of intersection datasets oriented to the problem, an extensive experimental activity has been performed to analyze the individual performance of each proposed systems.

Biochemical and Metabolomic Changes after Electromagnetic Hyperthermia Exposure to Treat Colorectal Cancer Liver Implants in Rats.

BACKGROUND: Hyperthermia (HT) therapy still remains relatively unknown, in terms of both its biological and therapeutic effects. This work aims to analyze the effects of exposure to HT, such as that required in anti-tumor magnetic hyperthermia therapies, using metabolomic and serum parameters routinely analyzed in clinical practice. METHODS: WAG/RigHsd rats were assigned to the different experimental groups needed to emulate all of the procedures involved in the treatment of liver metastases by HT. Twelve hours or ten days after the electromagnetic HT (606 kHz and 14 kA/m during 21 min), blood samples were retrieved and liver samples were obtained. 1H-nuclear-magnetic-resonance spectroscopy (1H-NMR) was used to search for possible diagnostic biomarkers of HT effects on the rat liver tissue. All of the data obtained from the hydrophilic fraction of the tissues were analyzed and modeled using chemometric tools. RESULTS: Hepatic enzyme levels were significantly increased in animals that underwent hyperthermia after 12 h, but 10 d later they could not be detected anymore. The metabolomic profile (main metabolic differences were found in phosphatidylcholine, taurine, glucose, lactate and pyruvate, among others) also showed that the therapy significantly altered metabolism in the liver within 12 h (with two different patterns); however, those changes reverted to a control-profile pattern after 10 days. CONCLUSIONS: Magnetic hyperthermia could be considered as a safe therapy to treat liver metastases, since it does not induce irreversible physiological changes after application.