New Insights into the Reparative Angiogenesis after Myocardial Infarction.

Myocardial infarction (MI) causes massive loss of cardiac myocytes and injury to the coronary microcirculation, overwhelming the limited capacity of cardiac regeneration. Cardiac repair after MI is finely organized by complex series of procedures involving a robust angiogenic response that begins in the peri-infarcted border area of the infarcted heart, concluding with fibroblast proliferation and scar formation. Efficient neovascularization after MI limits hypertrophied myocytes and scar extent by the reduction in collagen deposition and sustains the improvement in cardiac function. Compelling evidence from animal models and classical in vitro angiogenic approaches demonstrate that a plethora of well-orchestrated signaling pathways involving Notch, Wnt, PI3K, and the modulation of intracellular Ca2+ concentration through ion channels, regulate angiogenesis from existing endothelial cells (ECs) and endothelial progenitor cells (EPCs) in the infarcted heart. Moreover, cardiac repair after MI involves cell-to-cell communication by paracrine/autocrine signals, mainly through the delivery of extracellular vesicles hosting pro-angiogenic proteins and non-coding RNAs, as microRNAs (miRNAs). This review highlights some general insights into signaling pathways activated under MI, focusing on the role of Ca2+ influx, Notch activated pathway, and miRNAs in EC activation and angiogenesis after MI.

Digestive pseuodpolyposis as a form of presentation of digestive metastases of primary gastric leiomyosarcoma.

A 71-year-old male was diagnosed with gastric leiomyosarcoma in 2020 after biopsies of an ulcerated gastric lesion. Despite oncological treatment, he presented bone, liver and lung progression. Fourth line treatment with Pazopanib was started in 2022 with no evidence of intestinal or peritoneal metastases. He was attended in the Emergency Department in February 2023 due to symptoms of gastrointestinal bleeding with clinical and analytical repercussion with hemoglobin 5.8g/dl. Initially he presented hematemesis and subsequently hematochezia. An upper and lower endoscopic study was performed, revealing multiple sessile polypoid lesions with an irregular mucosal pattern of between 5-30 mm distributed throughout all explored sections at the gastric, duodenal and colic mucosal; some of them ulcerated with fibrin deposits on the surface and signs of recent hemostasis. The histological study demonstrated infiltration by spindle-shaped mesenchymal cells with atypical nuclei, a Ki-67 proliferation index >80%, and an immunohistochemical profile consistent with digestive metastases of primary gastric leiomyosarcoma. CT scan was performed confirming tumor progression with pulmonary, digestive, hepatic, bone, muscle and peritoneal dissemination of gastric leiomyosarcoma.

Retrospective cohort study of laparoscopic ICG-Guided Lymphadenectomy in gastric cancer from a Western country center.

BACKGROUND: Indocyanine green (ICG) guided lymphadenectomy has been proposed has a technique to improve the lymphadenectomy of patients with gastric cancer. Nevertheless, experience with this procedure is scarce in Western countries. METHODS: A retrospective analytic study in a tertiary hospital in Spain was performed, comparing patients who underwent laparoscopic gastrectomy with (ICG cohort) and without (historic cohort) ICG guided lymphadenectomy. RESULTS: Thirty four patients were included (17 in each group). Although the number of positive nodes was similar in both groups (0.0 in the ICG cohort vs. 2 in the historic cohort, p = 0.119), the number of lymph nodes removed was higher in the ICG cohort (42.0 vs 28.0, p = 0.040). In the ICG cohort, more lymph nodes were positive for adenocarcinoma in the group of nodes that were positive for IGC (10.6% of the IGC + nodes vs. 1.9% in the ICG - nodes, p < 0.001). CONCLUSIONS: ICG lymphadenectomy is a promising procedure that could improve the lymphadenectomy of patients with gastric cancer. ICG lymphadenectomy could be used to increase the number of lymph nodes removed in patients with a high-risk of nodal invasion or it could be used to reduce the surgical aggressiveness in fragile patients with a low-risk of nodal invasion.

Esophageal fish bone impaction: the importance of early diagnosis and treatment to avoid severe complications.

Esophageal fish bone impaction (EFBI) is a common reason for presentation in the emergency department and a frequent indication for urgent esophagogastroduodenoscopy (EGD). Although it is usually effectively diagnosed and treated by EGD, a confirmed diagnosis prior to the endoscopy is rare as blood tests, radiography and direct laryngoscopy are usually normal. We herein report three cases of EFBI. Two patients had been previously discharged without a correct diagnosis. In one case, the patient had a severe complication that required urgent surgery which could have probably been averted with an early diagnosis. Remarkably, a cervical CT scan was key to diagnose the EFBI in one case and a large retroesophageal abscess in another cases, thus guiding their management. Both patients that underwent an urgent EGD had a favorable outcome without the need for hospitalization. Therefore, meticulous anamnesis, adequate imaging and urgent EGD are key to treat patients with EFBI.

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Non-coding RNAs and Ischemic Cardiovascular Diseases.

The Ischemic Heart Disease (IHD) is considered a clinical condition characterized by myocardial ischemia causing an imbalance between myocardial blood supply and demand, leading to morbidity and mortality across the worldwide. Prompt diagnostic and prognostic represents key factors for the treatment and reduction of the mortality rate. Therefore, one of the newest frontiers in cardiovascular research is related to non-coding RNAs (ncRNAs), which prompted a huge interest in exploring ncRNAs candidates for utilization as potential therapeutic targets for diagnostic and prognostic and/or biomarkers in IHD. However, there are undoubtedly many more functional ncRNAs yet to be discovered and characterized. Here we will discuss our current knowledge and we will provide insight on the roles and effects elicited by some ncRNAs related to IHD.

Pathophysiological Significance of Store-Operated Calcium Entry in Cardiovascular and Skeletal Muscle Disorders and Angiogenesis.

Store-Operated Ca2+ Entry (SOCE) is an important Ca2+ influx pathway expressed by several excitable and non-excitable cell types. SOCE is recognized as relevant signaling pathway not only for physiological process, but also for its involvement in different pathologies. In fact, independent studies demonstrated the implication of essential protein regulating SOCE, such as STIM, Orai and TRPCs, in different pathogenesis and cell disorders, including cardiovascular disease, muscular dystrophies and angiogenesis. Compelling evidence showed that dysregulation in the function and/or expression of isoforms of STIM, Orai or TRPC play pivotal roles in cardiac hypertrophy and heart failure, vascular remodeling and hypertension, skeletal myopathies, and angiogenesis. In this chapter, we summarized the current knowledge concerning the mechanisms underlying abnormal SOCE and its involvement in some diseases, as well as, we discussed the significance of STIM, Orai and TRPC isoforms as possible therapeutic targets for the treatment of angiogenesis, cardiovascular and skeletal muscle diseases.

TRPC and TRPV Channels' Role in Vascular Remodeling and Disease.

Transient receptor potentials (TRPs) are non-selective cation channels that are widely expressed in vascular beds. They contribute to the Ca2+ influx evoked by a wide spectrum of chemical and physical stimuli, both in endothelial and vascular smooth muscle cells. Within the superfamily of TRP channels, different isoforms of TRPC (canonical) and TRPV (vanilloid) have emerged as important regulators of vascular tone and blood flow pressure. Additionally, several lines of evidence derived from animal models, and even from human subjects, highlighted the role of TRPC and TRPV in vascular remodeling and disease. Dysregulation in the function and/or expression of TRPC and TRPV isoforms likely regulates vascular smooth muscle cells switching from a contractile to a synthetic phenotype. This process contributes to the development and progression of vascular disorders, such as systemic and pulmonary arterial hypertension, atherosclerosis and restenosis. In this review, we provide an overview of the current knowledge on the implication of TRPC and TRPV in the physiological and pathological processes of some frequent vascular diseases.

Overview on radiation and tissue banking in Latin America.

The International Atomic Energy Agency (IAEA) played an important role in the establishment of new tissue banks and the improvement of already existing ones in Latin America. The Agency strongly supported, through regional, interregional and national technical cooperation projects, providing equipment, expert missions and training for the production and application of human tissues for transplantation. From 1999 to 2005 five regional courses were given in Buenos Aires under the modality of 1-year distance learning training courses and 1-week face to face courses. The courses were organized by the IAEA, through the National Atomic Energy Commission (CNEA) and the Faculty of Medicine of Buenos Aires University as Post Graduate Specialization Course. In 2005 the Latin American countries joined with Spain and Portugal, and created the Ibero American Network Council of Donation and Transplant (Red Consejo Iberoamericano de Donación y Trasplantes-RCIDT). The objective of this network is to cooperate among twenty-one Ibero American countries in organizational and legislative aspects, training of professionals, and ethical and social issues related to the donation and transplantation of organs, tissues and cells. The members of this Network work actively to harmonize the regulations and the control of donation and transplantation of human organs, tissues and cells. At present, in Latin America, more than 220 facilities of tissues banks are operating and tissue allografts are being produced by single and multi-tissue banks. The efforts made by the governments and professionals from the region allow the tissue banks to operate under quality systems and introduce new technologies.

Adherence to follow-up in high-risk adenoma patients diagnosed by, and excluded from the Barcelona colorectal cancer screening programme. / Adherencia al seguimiento de las personas con adenoma de alto riesgo diagnosticadas y excluidas del Programa de detección precoz de cáncer de colon y recto de Barcelona.

INTRODUCTION: Colorectal cancer screening programmes have been shown to reduce incidence and mortality. High-risk adenomas (HRA) are the most frequently diagnosed lesions in these programmes, and these patients are referred to a specialist. However, few studies have evaluated the adherence of HRA patients to the recommended endoscopic follow-up. OBJECTIVES: To analyse follow-up adherence and duration in patients diagnosed with HRA in a screening programme. METHODS: Retrospective cohort study of patients diagnosed with HRA within one of the participating hospitals of the colorectal cancer screening programme of Barcelona, during the first round of the programme (2010-2011). The follow-up period was 75.5 months. Descriptive analyses, logistic regression and survival models were performed. RESULTS: 602 patients were included in the study, 66.6% of which were men. The adherence rate was 83.7% (n=504). Follow-up colonoscopy was performed within the recommended time (36±6months) in 57.7%, with a mean follow-up of 34 months. The Cox regression only showed differences at the socioeconomic level, with a lower adherence rate in the most deprived quintile (HR 0.70; 95% CI, 0.53-0.93). CONCLUSIONS: Compared to previous studies, the follow-up adherence rate is considered to be acceptable. However, follow-up was not performed within the recommended time frame in a high proportion of cases. There is a need to further explore the reasons leading to lower follow-up adherence in the most deprived socioeconomic group and to increase the equity of the programme beyond participation.

Digital imaging information technology for biospeckle activity assessment relative to bacteria and parasites.

This paper reports on the biospeckle processing of biological activity using a visualization scheme based upon the digital imaging information technology. Activity relative to bacterial growth in agar plates and to parasites affected by a drug is monitored via the speckle patterns generated by a coherent source incident on the microorganisms. We present experimental results to demonstrate the potential application of this methodology for following the activity in time. The digital imaging information technology is an alternative visualization enabling the study of speckle dynamics, which is correlated to the activity of bacteria and parasites. In this method, the changes in Red-Green-Blue (RGB) color component density are considered as markers of the growth of bacteria and parasites motility in presence of a drug. The RGB data was used to generate a two-dimensional surface plot allowing an analysis of color distribution on the speckle images. The proposed visualization is compared to the outcomes of the generalized differences and the temporal difference. A quantification of the activity is performed using a parameterization of the temporal difference method. The adopted digital image processing technique has been found suitable to monitor motility and morphological changes in the bacterial population over time and to detect and distinguish a short term drug action on parasites.

Landscape character assessment with GIS using map-based indicators and photographs in the relationship between landscape and roads.

Planning and monitoring of landscapes cannot be reduced to its outstanding features, but must take into account all its characteristics. In this context, the relationship of landscape with roads is of particular importance, because roads alter the territory's environmental resources but also constitute a resource through which the individual comes into contact with the landscape. The aim of this work is to design a methodology to evaluate both the character and the scenic quality of the landscape as viewed from motorways and to provide measures to assess whether the motorway conveys the character of the landscape of which it forms part. The main contribution of this research consists of assessing landscape character through a novel series of map-based indicators and combining the findings with a photo-based method of assessing visual landscape quality. The method has been applied to a case study around a motorway in Madrid Region (Spain). Landscape character values regarding coherence, complexity, naturalness, visual scale, disturbance, historicity, and ephemera are obtained using Geographic Information Systems. Additionally, the landscape quality results derived using photographs allow the incorporation of the user's perception at a local scale.

Stress levels experienced by parents of children with and without attention-deficit/hyperactivity disorder during the back-to-school period: results of a European and Canadian survey.

OBJECTIVE: The back-to-school stress survey was designed to compare stress in parents of children/ adolescents with/without attention-deficit/hyperactivity disorder (ADHD) in six European countries and Canada when children prepare to return to school. METHODS: Parents of children/adolescents (6-17 years) with/without ADHD were recruited and interviewed by a consumer research organization. Parents rated potentially stress-causing situations (both standard and specifically related to the return to school) on a scale from 1 (low stress) to 10 (high stress). Mean scores were compared using Student's t-test. RESULTS: In Europe, 613/693 (mean [SD] age: 40.7 [7.0]/40.1 [6.9] years) and in Canada, 102/150 (mean [SD] age: 44.4 [8.1]/44.1 [7.2] years) parents of children with/without ADHD, respectively, participated in the survey. Children with ADHD (mean [SD] age: 11.2 [3.2]/12.6 [3.2] years in Europe/Canada) had generally similar characteristics in both samples. Parents in the ADHD group showed higher stress levels than parents in the non-ADHD group in all situations (p < 0.001 for Europe). The return to school was considered one of the most stressful events during the year. CONCLUSIONS: In Europe and Canada, ADHD has a significant impact on parental stress, particularly during the back-to-school period. This can have important implications as parental stress can affect presentation of ADHD symptoms.

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized, controlled trial.

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6-17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners' Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment - placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).

Expert recommendation: contributions to clinical practice of the new prodrug lisdexamfetamine dimesylate (LDX) in the treatment of attention deficit hyperactivity disorder (ADHD).

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobiological disorders in childhood, and is characterized by inappropriate levels of inattention, hyperactivity and/or impulsiveness, with an estimated prevalence of 5.29%. ADHD can have a negative impact upon all areas of the life of the patient. The main clinical guides accept multimodal treatment, involving both pharmacological and psychological measures, as the best management approach in ADHD (psychoeducational, behavioural and academic). Lisdexamfetamine dimesylate (LDX) is a new drug for the treatment of ADHD. A multidiscipline expert document has been developed, compiling the scientific evidence referred to this new molecule. The study also addresses the existing shortcomings in current drug therapy for ADHD and the contributions of LDX to routine clinical practice, in an attempt to help and guide physicians in the use of this new treatment. This document is endorsed by the ADHD and Psychoeducational Development task Group of the Spanish Society of Primary Care Pediatrics (Grupo de TDAH y Desarrollo Psicoeducativo de la Asociación Española de Pediatría de Atención Primaria, AEPap), the Spanish Society of Pediatric Neurology (Sociedad Española de Neurología Pediátrica, SENEP) and the Spanish Society of Out-hospital Pediatrics and Primary Care (Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria, SEPEAP).

Evaluation of the impact of NCI's Summer Curriculum on Cancer Prevention on participants from low- and middle-income countries.

The National Cancer Institute (NCI) Summer Curriculum on Cancer Prevention provides scientists and health care professionals training in principles and practices of cancer prevention and control, and molecular biology and genetics of cancer. Originally intended for US scientists, the curriculum's enrollment of international scientists has increased steadily. The objective of the current study was to evaluate the curriculum's impact on knowledge, skills, and career accomplishments of the international participants from low- and middle-income countries. International participants from 1998 to 2009 completed questionnaires regarding knowledge, overall experience, and accomplishments directly associated with the curriculum. Almost all respondents agreed that the curriculum enhanced their knowledge and skills, prepared them to contribute to cancer control activities in their home countries, and addressed specific needs and achieve research goals. The NCI Summer Curriculum on Cancer Prevention gives international participants a unique opportunity to enhance their knowledge and effectively contribute to cancer control activities in their home country.

Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-κB and calcium activity repression.

The overexpression of the immunoinhibitory receptor programmed death-1 (PD1) on T-cells is involved in immune evasion in cancer. The use of anti-PD-1/PDL-1 strategy has deeply changed the therapies of cancers and patient survival. However, their efficacy diverges greatly along with tumor type and patient populations. Thereby, novel treatments are needed to interfere with the anti-tumoral immune responses and propose an adjunct therapy. In the current study, we found that the antifungal drug Sulconazole (SCZ) inhibits PD-1 expression on activated PBMCs and T cells at the RNA and protein levels. SCZ repressed NF-κB and calcium signaling, both, involved in the induction of PD-1. Further analysis revealed cancer cells treatment with SCZ inhibited their proliferation, and migration and ability to mediate tumor growth in zebrafish embryos. SCZ found also to inhibit calcium mobilization in cancer cells. These results suggest the SCZ therapeutic potential used alone or as adjunct strategy to prevent T-cell exhaustion and promotes cancer cell malignant phenotype repression in order to improve tumor eradication.

Approaches for the Evaluation of the National Cancer Institute's Summer Curriculum in Cancer Prevention: lessons from the all-Ireland NCI cancer consortium.

The NCI Summer Curriculum in Cancer Prevention (SCCP) has provided interdisciplinary training in cancer prevention and control to cancer health-care professionals, including nurses, physicians, and scientists, since 1986. It has trained over 1,200 participants, 256 of them from Ireland and Northern Ireland through two summer courses: a 4-week course on Principles and Practice of Cancer Prevention and Control (PP) and 1-week on Molecular Prevention (MP). This report is our attempt to measure achievements and level of satisfaction among alumni from the island of Ireland upon return to their home institution. A questionnaire was developed to assess this. Our analysis found statistically significant differences in the types of accomplishments reported among respondents of the MP and PP courses as well as statistically significant differences in their level of satisfaction. More data are needed to better explain the differences observed as well as level of resources available to alumni upon their return home.

Optimisation of breast cancer management in low-resource and middle-resource countries: executive summary of the Breast Health Global Initiative consensus, 2010.

The purpose of the Breast Health Global Initiative (BHGI) 2010 summit was to provide a consensus analysis of breast cancer control issues and implementation strategies for low-income and middle-income countries (LMCs), where advanced stages at presentation and poor diagnostic and treatment capacities contribute to lower breast cancer survival rates than in high-income countries. Health system and patient-related barriers were identified that create common clinical scenarios in which women do not present for diagnosis until their cancer has progressed to locally advanced or metastatic stages. As countries progress to higher economic status, the rate of late presentation is expected to decrease, and diagnostic and treatment resources are expected to improve. Health-care systems in LMCs share many challenges including national or regional data collection, programme infrastructure and capacity (including appropriate equipment and drug acquisitions, and professional training and accreditation), the need for qualitative and quantitative research to support decision making, and strategies to improve patient access and compliance as well as public, health-care professional, and policy-maker awareness that breast cancer is a cost-effective, treatable disease. The biggest challenges identified for low-income countries were little community awareness that breast cancer is treatable, inadequate advanced pathology services for diagnosis and staging, and fragmented treatment options, especially for the administration of radiotherapy and the full range of systemic treatments. The biggest challenges identified for middle-resource countries were the establishment and maintenance of data registries, the coordination of multidisciplinary centres of excellence with broad outreach programmes to provide community access to cancer diagnosis and treatment, and the resource-appropriate prioritisation of breast cancer control programmes within the framework of existing, functional health-care systems.

Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation.

Urocortin-2 (Ucn-2) has demonstrated cardioprotective actions against myocardial ischemia-reperfusion (I/R) injuries. Herein, we explored the protective role of Ucn-2 through microRNAs (miRNAs) post-transcriptional regulation of apoptotic and pro-fibrotic genes. We determined that the intravenous administration of Ucn-2 before heart reperfusion in a Wistar rat model of I/R recovered cardiac contractility and decreased fibrosis, lactate dehydrogenase release, and apoptosis. The infusion of Ucn-2 also inhibited the upregulation of 6 miRNAs in revascularized heart. The in silico analysis indicated that miR-29a and miR-451_1∗ are predicted to target many apoptotic and fibrotic genes. Accordingly, the transfection of neonatal rat ventricular myocytes with mimics overexpressing miR-29a, but not miR-451_1∗, prevented I/R-induced expression of pro- and anti-apoptotic genes such as Apaf-1, Hmox-1, and Cycs, as well as pro-fibrotic genes Col-I and Col-III. We also confirmed that Hmox-1, target of miR-29a, is highly expressed at the mRNA and protein levels in adult rat heart under I/R, whereas, Ucn-2 abolished I/R-induced mRNA and protein upregulation of HMOX-1. Interestingly, a significant upregulation of Hmox-1 was observed in the ventricle of ischemic patients with heart failure, correlating negatively with the left ventricle ejection fraction. Altogether, these data indicate that Ucn-2, through miR-29a regulation, provides long-lasting cardioprotection, involving the post-transcriptional regulation of apoptotic and fibrotic genes.