Long term outcomes of pituitary adenomas in Multiple Endocrine Neoplasia type 1: a nationwide study.

Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs.

Hemorrhagic Cholecystitis in a Patient Under Anticoagulant and Antiplatelet Therapy: A Case Report.

Hemorrhagic cholecystitis is an uncommon presentation of acute cholecystitis. Due to its etiology and unspecific clinical data, it is an entity that represents a diagnostic challenge. We present a case of a 70-year-old male with diabetes type 2, hypertension, and chronic kidney disease with hemodialysis, who attended the emergency department with sudden-onset abdominal pain in the epigastrium. The patient presented no additional symptoms, a normal electrocardiogram, but due to the characteristics of the pain and elevated troponin I, emergency medicine specialists considered an acute coronary syndrome and initiated antiplatelet and anticoagulant therapy. Due to persistent abdominal pain, a decrease in hemoglobin, and the onset of arterial hypotension, a computed tomography (CT) scan was performed, which revealed perforation of the gallbladder, apparent hemorrhagic cholecystitis, and hemoperitoneum. The patient underwent emergent surgery, where CT findings were confirmed. In our case, the suspicion of hemorrhagic cholecystitis arose until the clinical case was advanced, after receiving anticoagulant and antiplatelet therapy, and it was confirmed during surgery and with histopathology. This concludes that hemorrhagic cholecystitis is a rare disease and difficult to diagnose. Therefore, studies should focus on clinical presentation and risk factors (e.g., trauma, malignancy, renal failure, cirrhosis, and anticoagulation therapy) to promote early diagnosis and avoid complications.

Venous valve hypoxia as a possible mechanism of deep vein thrombosis: a scoping review.

INTRODUCTION: The pathogenesis of deep vein thrombosis (DVT) has been explained by an interplay between a changed blood composition, vein wall alteration, and blood flow abnormalities. A comprehensive investigation of these components of DVT pathogenesis has substantially promoted our understanding of thrombogenesis in the venous system. Meanwhile, the process of DVT initiation remains obscure. This systematic review aims to collect, analyze, and synthesize the published evidence to propose hypoxia as a possible trigger of DVT. EVIDENCE ACQUISITION: An exhaustive literature search was conducted across multiple electronic databased including PubMed, EMBASE, Scopus, and Web of Science to identify studies pertinent to the research hypothesis. The search was aimed at exploring the connection between hypoxia, reoxygenation, and the initiation of deep vein thrombosis (DVT). The following key words were used: "deep vein thrombosis," "venous thrombosis," "venous thromboembolism," "hypoxia," "reoxygenation," "venous valve," and "venous endothelium." Reviews, case reports, editorials, and letters were excluded. EVIDENCE SYNTHESIS: Based on the systematic search outcome, 156 original papers relevant to the issue were selected for detailed review. These studies encompassed a range of experimental and observational clinical research, focusing on various aspects of DVT, including the anatomical, physiological, and cellular bases of the disease. A number of studies suggested limitations in the traditional understanding of Virchow's triad as an acceptable explanation for DVT initiation. Emerging evidence points to more complex interactions and additional factors that may be critical in the early stages of thrombogenesis. The role of venous valves has been recognized but remains underappreciated, with several studies indicating that these sites may act as primary loci for thrombus formation. A collection of studies describes the effects of hypoxia on venous endothelial cells at the cellular and molecular levels. Hypoxia influences several pathways that regulate endothelial cell permeability, inflammatory response, and procoagulation activity, underpinning the endothelial dysfunction noted in DVT. CONCLUSIONS: Hypoxia of the venous valve may serve as an independent hypothesis to outline the DVT triggering process. Further research projects in this field may discover new molecular pathways responsible for the disease and suggest new therapeutic targets.

Venous thromboembolism swine model with reflux-induced venous hypertension.

Objective: This study describes a novel swine model of venous thromboembolism (VTE) with reflux-induced venous hypertension. Methods: Six pigs underwent disruption of the tricuspid chordae tendineae to create reflux and venous hypertension in the femoral vein. The vein was traumatized 2 to 3 weeks later by repeated withdrawal of a slightly overinflated occlusion balloon across the lumen, followed by balloon occlusion of the outflow. A small amount of thrombin was injected into the traumatized vein segment immediately after outflow occlusion. Thrombosis of the traumatized vein evolved into an organized thrombus seven weeks later. The histological features of the harvested post-thrombotic femoral vein were studied with hematoxylin and eosin and Trichrome stains. Results: In all six pigs, initial disruption of the chordae tendineae was successfully performed to create tricuspid reflux and venous hypertension. After two-stage sequential procedures, a thrombus formed in the target femoral vein segment. Histology of the harvested thrombotic vein showed features of an organizing thrombus with collagen formation and fibrosis. Conclusions: The novel swine VTE model may serve as a platform for developing and testing human-sized therapeutic procedures and devices in translational venous research. Clinical Relevance: This study describes a swine model of VTE created by incorporating all three elements of Virchow's triad. The model uniquely incorporates reflux-induced venous hypertension, which may be used in studying venous insufficiency and VTE in those with systemic venous hypertension. Likewise, this model may serve as a platform for development and evaluation of diagnostic imaging or therapeutic procedures and devices in subjects with systemic venous hypertension.

Exposure to neighborhood violence, and laboratory-based and ambulatory cognitive task performance in adulthood.

OBJECTIVE: Exposure to neighborhood violence may have negative implications for adults' cognitive functioning, but the ecological sensitivity of these effects has yet to be determined. We first evaluated the link between exposure to neighborhood violence and two latent constructs of cognitive function that incorporated laboratory-based and ambulatory, smartphone-based, cognitive assessments. Second, we examined whether the effect of exposure to violence was stronger for ambulatory assessments compared to in-lab assessments. METHODS: We used data from 256 urban-dwelling adults between 25 and 65 years old (M = 46.26, SD = 11.07); 63.18% non-Hispanic Black, 9.21% non-Hispanic White, 18.41% Hispanic White, 5.02% Hispanic Black, and 4.18% other. Participants completed baseline surveys on neighborhood exposures, cognitive assessments in a laboratory/research office, and ambulatory smartphone-based cognitive assessments five-times a day for 14 days. RESULTS: Exposure to neighborhood violence was associated with poorer performance in a latent working memory construct that incorporated in-lab and ambulatory assessments, but was not associated with the perceptual speed construct. The effect of exposure to neighborhood violence on the working memory construct was explained by its effect on the ambulatory working memory task and not by the in-lab cognitive assessments. CONCLUSION: This study shows the negative effect that exposure to neighborhood violence may have on everyday working memory performance in urban-dwelling adults in midlife. Results highlight the need for more research to determine the sensitivity of ambulatory assessments to quantify the effects of neighborhood violence on cognitive function.

Higher order aberrations according to spherical, and astigmatic refractive errors in children.

CLINICAL RELEVANCE: The results of this study present novel insights into the impact of spherical and astigmatic refractive errors on overall, corneal and internal aberrations and may provide a clear understanding of the emmetropisation process and the development of visual function. BACKGROUND: This study aimed to assess the association between overall, corneal and internal higher-order aberrations and the spherical and astigmatic components (magnitude and angle) of refractive error in a large sample of children. METHODS: A total of 311 children aged 7 - 8 years old were classified based on spherical equivalent refraction (myopic, emmetropic and hyperopic); magnitude of astigmatism (none, low and moderate); and angle of astigmatism (with-the-rule, against-the-rule and oblique). Refractive error and overall, corneal and internal higher-order aberrations were measured using the OPD-Scan III workstation. RESULTS: Regarding spherical equivalent refraction, myopic eyes had greater root mean square (RMS) overall higher-order values, total spherical, tetrafoil and secondary astigmatism aberrations, and internal higher-order, total spherical and tetrafoil aberrations in comparison to emmetropic eyes. The magnitude of astigmatism was positively associated with all overall RMS aberrations and with internal higher order, coma, total coma, total spherical and tetrafoil aberrations. Eyes with with-the-rule astigmatism showed higher RMS values of coma and total coma compared to eyes with against-the-rule and oblique astigmatism. CONCLUSIONS: Higher-order aberrations are dependent on the spherical as well as astigmatic components of refractive error. These findings enhance the current understanding of the emmetropisation process and visual function development.

Modifiable Risk Factors and Trends in Changes in Glucose Regulation during the First Three Years Postdelivery: The St Carlos Gestational Diabetes Mellitus Prevention Cohort.

OBJECTIVE: Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum. METHODS: The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed. RESULTS: 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y. CONCLUSIONS: 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

Back To Basics: Theory of Thrombus Formation and Potential Implications for Therapies?

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially fatal condition. Despite existing treatments, recurrence rates and complications remain high. Understanding the pathophysiology of thrombus formation is crucial for developing effective therapies. This narrative review provides an overview of the critical elements of acute and chronic DVT, presents a theoretical framework for understanding thrombus formation, and discusses potential implications for therapeutic interventions. In addition, a hypothesis of thrombus formation is formulated, encompassing all elements described in this work.

Myocardial revascularization failure among patients requiring cardiac catheterization and secondary revascularization in contemporary clinical practice: Results of the REVASEC multicenter registry.

BACKGROUND: Myocardial revascularization failure (MRF) and Secondary revascularization (SR) are contemporary interventional cardiology challenges. AIM: To investigate the characteristics, management, and prognosis of patients with myocardial revascularization failure (MRF) and need for secondary revascularization (SR) in contemporary practice. METHODS: The REVASEC study is a prospective registry (NCT03349385), which recruited patients with prior revascularization referred for coronary angiography at 19 centers. The primary endpoint is a patient-oriented composite (POCE) at 1 year, including death, myocardial infarction, or repeat revascularization. RESULTS: A total of 869 patients previously revascularized by percutaneous intervention (83%) or surgery (17%) were recruited. MRF was found in 83.7% (41.1% stent/graft failure, 32.1% progression of coronary disease, and 10.5% residual disease). SR was performed in 70.1%, preferably by percutaneous intervention (95%). The POCE rate at 1 year was 14% in the overall cohort, with 6.4% all-cause death. In the multivariate analysis, lower POCE rates were found in the groups without MRF (9.4%) and with disease progression (11%) compared with graft/stent failure (17%) and residual disease (18%), hazard ratio 0.67 (95% confidence interval: 0.45-0.99), p = 0.043. At 1 year, the SR group had less chronic persistent angina (19% vs. 34%, p < 0.001), but a higher rate of repeat revascularization (9% vs. 2.9%, p < 0.001). CONCLUSION: MRF was found in 84% of patients with prior revascularization referred for coronary angiography. Stent/graft failure and residual coronary disease were associated with a worse prognosis. SR provided better symptom control at the expense of a higher rate of new revascularization.

Selenium nanoparticles based on Amphipterygium glaucum extract with antibacterial, antioxidant, and plant biostimulant properties.

BACKGROUND: In recent years, crop production has expanded due to the variety of commercially available species. This increase in production has led to global competition and the search for biostimulant products that improve crop quality and yield. At the same time, agricultural products that protect against diseases caused by phytopathogenic microorganisms are needed. Thus, the green synthesis of selenium nanoparticles (SeNPs) is a proposal for achieving these needs. In this research, SeNPs were synthesized from methanolic extract of Amphipterygium glaucum leaves, and chemically and biologically characterized. RESULTS: The characterization of SeNPs was conducted by ultraviolet-visible spectrophotometry (UV-Vis), scanning electron microscopy (SEM), electron microscopy transmission (TEM), Dynamic Light Scattering (DLS), energy dispersion X-ray spectroscopy (EDX), and infrared spectrophotometry (FTIR) techniques. SeNPs with an average size of 40-60 nm and spherical and needle-shaped morphologies were obtained. The antibacterial activity of SeNPs against Serratia marcescens, Enterobacter cloacae, and Alcaligenes faecalis was evaluated. The results indicate that the methanolic extracts of A. glaucum and SeNPs presented a high antioxidant activity. The biostimulant effect of SeNPs (10, 20, 50, and 100 µM) was evaluated in vinca (Catharanthus roseus), and calendula (Calendula officinalis) plants under greenhouse conditions, and they improved growth parameters such as the height, the fresh and dry weight of roots, stems, and leaves; and the number of flowers of vinca and calendula. CONCLUSIONS: The antibacterial, antioxidant, and biostimulant properties of SeNPs synthesized from A. glaucum extract demonstrated in this study support their use as a promising tool in crop production.

Negative effects of the spatial clumping of thermal resources on lizard thermoregulation in a fragmented habitat.

In ecosystems threatened by the expansion of croplands, habitat fragmentation and climate change, two of the main extinction drivers, may have thermoregulation-mediated interacting effects on demographic trends of terrestrial ectotherms. We studied the thermal biology of a metapopulation of the widespread Mediterranean lacertid Psammodromus algirus in ten fragments of evergreen or deciduous oak forests interspersed among cereal fields. We obtained thermoregulation statistics (selected temperature range, body and operative temperatures, thermal quality of the habitat, and precision, accuracy, and effectiveness of thermoregulation) that could be compared among fragments and with conspecific populations living in unfragmented habitat. We also measured the selection (use vs. availability) and spatial distribution of sunlit and shaded patches used for behavioral thermoregulation in fragments, and we estimated operative temperatures and thermal habitat quality in the agricultural matrix surrounding the fragments. Variation of the thermal environment was much larger within fragments than among them, and thermoregulation was accurate, precise, and efficient throughout the fragmented landscape; its effectiveness was similar to that of previously studied unfragmented populations. The average distance between sunlit and shaded patches was shorter in deciduous than in evergreen fragments, producing a more clumped distribution of the mosaic of thermal resources. Consequently, in evergreen habitat the cost of thermoregulation was higher, because lizards were more selective in their choice of sunlit sites (i.e. they used sunlit patches closer to shade and refuge than expected at random, and the extent of such selection was larger than at deciduous habitat). Temperatures available in croplands were too high to allow lizard dispersal, at least in the post-breeding season. This result confirms the role of croplands as a thermal barrier that promotes inbreeding and associated fitness losses in isolated fragments, and it forecasts a dark future for populations of forest lizards in agricultural landscapes under the combined effects of habitat fragmentation and global warming.

Neuroendocrine Tumor Metastases to the Breast: A Case Report and Review of the Literature.

Breast metastases from neuroendocrine neoplasms (NENs) are considered infrequent. We report a case of a patient with ileocecal neuroendocrine tumor (NET) metastases to both breasts, for whom the initial clinical presentation was chronic diarrhea. Breast metastasis was initially suspected by a 68-Gallium DOTANOC positron emission tomography (PET)/CT and was confirmed by histopathology. We also performed a literature review in which we identified 116 cases of NENs metastatic to the breast reported so far. Most cases occurred in older women, were caused by NETs, and had the gastrointestinal tract as the primary site.

Phytochemical Analysis and Biological Activities of Ripe Fruits of Mistletoe (Psittacanthus calyculatus).

Psittacanthus calyculatus is a hemiparasitic plant of an arboreal species (e.g., forest, fruit trees). Its foliage has therapeutic potential; however, little is known about its fruits. In this study, the phytochemical profile and biological activities of P. calyculatus fruits hosted by Prosopis laevigata and Quercus deserticola were evaluated. The fruits of P. calyculatus from P. laevigata showed the highest content of total phenols (71.396 ± 0.676 mg GAE/g DW). The highest content of flavonoids and anthocyanins was presented in those from Q. deserticola (14.232 ± 0.772 mg QE/g DW; 2.431 ± 0.020 mg C3GE/g DW). The anthocyanin cyanidin-3-glucoside was detected and quantified via high-performance thin-layer chromatography (HPTLC) (306.682 ± 11.804 mg C3GE/g DW). Acidified extracts from host P. laevigata showed the highest antioxidant activity via ABTS•+ (2,2'azinobis-(3-ethylbenzothiazdin-6-sulfonic acid) (214.810 ± 0.0802 mg TE/g DW). Fruit extracts with absolute ethanol from the P. laevigata host showed the highest antihypertensive activity (92 ± 3.054% inhibition of an angiotensin converting enzyme (ACE)). Fruit extracts from both hosts showed a minimum inhibitory concentration (MIC) of 6.25 mg/mL and a minimum bactericidal concentration (MBC) of 12.5 mg/mL against Escherichia coli, Salmonella choleraesuis and Shigella flexneri. Interestingly, a significant host effect was found. P. calyculatus fruits extract could be used therapeutically. However, further confirmation experiments should be carried out.

Parthenolide inhibits proliferation and invasion, promotes apoptosis, and reverts the cell-cell adhesion loss through downregulation of NF-κB pathway TNF-α-activated in colorectal cancer cells.

The activation of the nuclear factor-κB (NF-κB) pathway has been associated with the development and progression of colorectal cancer (CRC). Parthenolide (PTL), a well-known inhibitor of the NF-κB pathway, has emerged as an alternative treatment. However, whether PTL activity is tumor cell-specific and dependent on the mutational background has not been defined. This study investigated the antitumor role of PTL after tumor necrosis factor-α (TNF-α) stimulation in various CRC cell lines with different mutational statuses of TP53. We observed that CRC cells displayed different patterns of basal p-IκBα levels; PTL reduced cell viability according to p-IκBα levels and p-IκBα levels varied among the cell lines according to the time of TNF-α stimulation. High concentrations of PTL reduced more effectively p-IκBα levels than low doses of PTL. However, PTL increased total IκBα levels in Caco-2 and HT-29 cells. In addition, PTL treatment downregulated p-p65 levels in HT-29 and HCT-116 cells stimulated by TNF-α in a dose-dependent manner. Moreover, PTL induced cell death via apoptosis and reduced the proliferation rate of TNF-α-treated HT-29 cells. Finally, PTL downregulated the messenger RNA levels of interleukin-1ß, a downstream cytokine of NF-κB, reverted the E-cadherin-mediated disorganization of cell-cell contacts, and decreased the invasion of HT-29 cells. Together, these results suggest a differential antitumoral activity of PTL on CRC cells with different mutational statuses of TP53, modulating cell death, survival, and proliferation underlying the NF-κB pathway TNF-α-induced. Therefore, PTL has emerged as a potential treatment for CRC in an inflammatory NF-κB-dependent manner.

Antifungal Activity of Selenium Nanoparticles Obtained by Plant-Mediated Synthesis.

The continuous need to satisfy world food demand has led to the search for new alternatives to combat economic losses in agriculture caused by phytopathogenic fungi. These organisms cause plant diseases, reducing their productivity and decreasing fruit quality. Among the new tools being explored is nanotechnology. Nanoparticles with antimicrobial properties could be an excellent alternative to address this problem. In this work, selenium nanoparticles (SeNPs) were obtained using plant extracts of Amphipterygium glaucum leaves (SeNPs-AGL) and Calendula officinalis flowers (SeNPs-COF). Characterization of the SeNPs was performed and their ability as antifungal agents against two commercially relevant plant pathogenic fungi, Fusarium oxysporum and Colletotrichum gloeosporioides, was evaluated. Assays were performed with different concentrations of SeNPs (0, 0.25, 0.5, 1.0, and 1.7 mg/mL). It was observed that both SeNPs had antifungal activity against both plant pathogens at concentrations of 0.25 mg/mL and above. SeNPs-AGL demonstrated better antifungal activity and smaller size (around 8.0 nm) than SeNPs-COF (134.0 nm). FTIR analysis evidenced the existence of different functional groups that constitute both types of SeNPs. There are factors that have to be considered in the antimicrobial activity of SeNPs such as nanoparticle size and phytochemical composition of the plant extracts used, as these may affect their bioavailability.

Revisiting the high-fat diet/low streptozotocin prediabetic rat model: A bioanalytical adjustment.

Insulin resistance (IR) is the main feature of prediabetes (PD), which ultimately leads to diabetes. High-dose streptozotocin-treated rodents often show irreversible ß-cell mass loss and function, leaving the premorbid diabetic state (PD/IR) unnoticed. This study aimed to re-evaluate the synergistic/independent effect of a sub-chronic consumption (1-5 weeks) of a high-fat diet (60% gross energy from fat, 3.8 kcal.g-1) with [PD/IR-2 (week 2) to PD/IR-5 week five)] or without [HFD-5 (week five)] a single intraperitoneal dose (35 mg.kg-1) of streptozotocin in Wistar rats. Bioassay performance and clinical/histological features suggesting PD/IR or diabetes, were documented weekly and compared to standard chow-fed (3.5 kcal.g-1) rats (healthy controls, HC). PD/IR1-5 (fed with HFD for 1 to 5 weeks plus a single dose of streptozotocin) and HFD-5 (just fed with HFD for 5 weeks) groups reduced their food intake yet gained more body weight than HC. Groups exhibited hyperglycemia, dyslipidemia, and impaired glucose tolerance in decreasing order as follows: PD/IR-5, PD/IR-4, HFD-5, PD/IR-2-3, and HC. Histological disturbances in the pancreas, Soleus muscle, and liver were mostly observed in HFD-5 and PD/IR4-5 groups. HFD administration for 4 weeks white a single moderate dose of streptozotocin four days before sacrifice, leads to a convenient PD/IR rat model.

Mechanisms of radioresistance and the underlying signaling pathways in colorectal cancer cells.

Radiotherapy is one of the most common modalities for the treatment of a wide range of tumors, including colorectal cancer (CRC); however, radioresistance of cancer cells remains a major limitation for this treatment. Following radiotherapy, the activities of various cellular mechanisms and cell signaling pathways are altered, resulting in the development of radioresistance, which leads to therapeutic failure and poor prognosis in patients with cancer. Furthermore, even though several inhibitors have been developed to target tumor resistance, these molecules can induce side effects in nontumor cells due to low specificity and efficiency. However, the role of these mechanisms in CRC has not been extensively studied. This review discusses recent studies regarding the relationship between radioresistance and the alterations in a series of cellular mechanisms and cell signaling pathways that lead to therapeutic failure and tumor recurrence. Our review also presents recent advances in the in vitro/in vivo study models aimed at investigating the radioresistance mechanism in CRC. Furthermore, it provides a relevant biochemical basis in theory, which can be useful to improve radiotherapy sensitivity and prolong patient survival.

Overlapping versus single long stents in long chronic total occlusions: insights of the Iberian CTO Registry.

BACKGROUND: It is unknown whether the availability of long drug-eluting stents modify the PCI strategy of long CTO. To describe the contemporary PCI strategy of long chronic total occlusions (CTO) using overlapping (OS) or single long stents (SS) and to analyze its results. METHODS: 2842 consecutive CTO PCIs were included. Those with an occlusion length ≥20 mm in which ≥1 drug eluting stent (DES) was implanted were analyzed. We compared procedural characteristics and clinical outcomes of CTO treated with OS or SS. RESULTS: 1088 CTO PCIs were analyzed (79.9% males; 64.7±10.6 years). Mean J-score was 2.8±0.9. A SS was used in 38.5% of cases and OS in 61.5%. Total stent length was 64.1±29.9 mm; it was higher in the OS group (OS: 79.9±25.5 mm vs. SS: 38.3±14.7 mm; P<0.0001). Mean number of stents in the OS group was 2.3±1. Very long stents (≥40 mm) were used in 27.4% of cases, more frequently in the OS group (OS:32.4% vs. SS:19.3%; P<0.0001). After a mean follow-up of 19±15.9 months, the rate of adverse events (MACE) was 2% (cardiac death: 1.6%, myocardial infarction: 1.6%, target lesion revascularization: 1.9% and stent thrombosis: 0.18%) with no significant differences between both groups. Overlapping was not an independent predictor of MACE. CONCLUSIONS: In long CTO PCIs, OS is more frequently used than single stenting, especially in more complex procedures. Clinical outcomes at a mid-term follow-up are favorable. Using newer generation DES, overlapping was not an independent predictor of MACE; however, a trend toward a higher event rate was observed in the OS group.

Videoconferencias para residentes de Histología en la Universidad de Ciencias Médicas de Sancti Spíritus / Videoconferences to Histology residents at the Sancti Spíritus University of Medical Sciences

Fundamento: No se conoce cómo aceptan los residentes de Histología la inclusión de un sistema de videoconferencias sobre la estructura microscópica del cuerpo humano en su estrategia de autoaprendizaje. Objetivo: Explorar en profundidad la experiencia de los residentes de Histología de la Universidad de Ciencias Médicas de Sancti Spíritus que utilizaron un sistema de videoconferencias para su formación profesional. Metodología: Estudio cualitativo en el que se realizó una entrevista a profundidad con los especialistas y residentes de Histología que han utilizado el sistema de videoconferencias en la Universidad de Ciencias Médicas de Sancti Spíritus. Se transcribieron las entrevistas, se codificaron y se seleccionaron los principales temas abordados. Resultados: Se entrevistaron 5 usuarios del sistema de videoconferencias; de la entrevista surgieron 5 temas: 1) Como los residentes insertan las videoconferencias en su estrategia de autoaprendizaje, 2) Preferencia de las videoconferencias sobre los libros de texto, 3) Aciertos y desaciertos de las videoconferencias, 4) ¿Qué aportan las videoconferencias a la formación del residente, ventajas y desventajas? y 5) Sugerencias para mejorar las videoconferencias. Conclusiones: Un sistema de videoconferencias sobre la estructura microscópica del cuerpo humano puede ocupar un papel protagónico en la estrategia de aprendizaje de residentes de Histología. La preferencia que muestran los residentes por las videoconferencias sobre otros medios didácticos puede estar asociada a la capacidad de la multimedia para disminuir la carga cognitiva y facilitar el aprendizaje cuando se siguen los principios de Mayer al elaborar estos medios. La presencia de imágenes digitales en estas videoconferencias fue clave para su aceptación.

Background: It is not known how Histology residents accept the inclusion of a videoconferencing system on the microscopic structure of the human body in their self-learning strategy. Objective: To explore to depth the experience of Histology residents at the Sancti Spíritus University of Medical Sciences who used a videoconferencing system for their professional training. Methodology: Qualitative study with in-depth interview was conducted with Histology specialists and residents who have used the videoconferencing system at the Sancti Spíritus University of Medical Sciences. The interviews were transcribed, coded and the main topics addressed were selected. Results: 5 users of the videoconferencing system were interviewed; 5 themes emerged from the interview: 1) How residents insert videoconferences into their self-learning strategy, 2) Preference for videoconferences over textbooks, 3) Successes and failures of videoconferences, 4) What do videoconferences contribute to the training of the resident, advantages and disadvantages?, 5) Suggestions to improve videoconferences. Conclusions: A videoconferencing system on the microscopic structure of the human body can play a leading role in the learning strategy of Histology residents. The preference shown by residents for videoconferencing over other teaching media may be associated with the ability of multimedia to reduce cognitive load and facilitate learning when Mayer's principles are followed to developing these media. The presence of digital images in these videoconferences was essential to their acceptance.