Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

Single-fraction radiation retreatment for bone metastases: role of a rapid access clinic.

OBJECTIVES: This study investigates retreatment rates in single-fraction radiation therapy (SFRT) for painful bone metastasis in patients with limited life expectancy. We compared retreatment-free survival (RFS) in patients from a rapid access bone metastases clinic (RABC) and non-RABC patients, identifying factors associated with retreatment. METHODS: In this observational study, we analysed RABC patients who received SFRT between April 2018 and November 2019, using non-RABC SFRT patients as a comparison group. Patients with prior or perioperative radiation therapy (RT) were excluded. The primary endpoint was same-site and any-site retreatment with RT or surgery. Patient characteristics were compared using χ2 and Student's t-tests, with RFS estimates based on a multistate model considering death as a competing risk using Aalen-Johansen estimates. RESULTS: We identified 151 patients (79 RABC, 72 non-RABC) with 225 treatments (102 RABC, 123 non-RABC) meeting eligibility criteria. Of the 22 (10.8%) same-site retreatments, 5 (22.7%) received surgery, 14 (63.6%) received RT and 3 (13.6%) received both RT and surgery. We found no significant differences in any-site RFS (p=0.97) or same-site RFS (p=0.11). CONCLUSIONS: RFS is high and similar comparable in the RABC and non-RABC cohorts. Retreatment rates are low, even in patients with low Eastern Cooperative Oncology Group scores.

Vaginal peritoneum fistula through pouch of Douglas during peritoneal dialysis: Case report and literature review.

INTRODUCTION: Peritoneal dialysis is the preferred approach for kidney replacement therapy. A peritoneal-vaginal fistula is a rare complication associated with peritoneal dialysis. CASE PRESENTATION: A 69-year-old woman with a history of type two diabetes and systemic arterial hypertension for twenty years is scheduled to undergo the surgical placement of a Tenckoff catheter to begin renal replacement therapy. After having thirty dialysis sessions, she was discharged to continue therapy at home. Five days later, she observed a notable rise in vaginal discharge after peritoneal dialysis. This case report investigates the etiology, diagnosis, and management of peritoneal vaginal fistula and analyzes current medical literature. DISCUSSION: Factors associated with the formation of peritoneum-vaginal fistula include increased intra-abdominal pressure due to dialysis, anatomical predisposition, peritonitis, and malnutrition. CONCLUSIONS: Peritoneal vaginal fistula is an uncommon consequence of peritoneal dialysis. Diagnosis entails demonstrating the movement of dialysis fluid from the peritoneum to the vagina. Treatment should be customized according to the etiology of the fistula and the individual needs of each patient.

VirtualPain. Preliminary findings from a group-based digital therapeutics intervention for fibromyalgia.

Introduction: Fibromyalgia (FM) is a disorder characterized by chronic pain, with significant medical, psychological, and socio-economic implications. Although there is limited evidence, cognitive-behavioral therapy (CBT) has shown to be effective in improving FM symptoms. An alternative to enhance CBT effectiveness is to incorporate digital therapeutics (DTx). Aim: We conducted a pilot study to investigate whether the addition of a DTx intervention (VirtualPain) to cognitive-behavioral group therapy (CBGT) can reduce pain perception and associated symptoms in patients with FM. Method: Ten patients with FM were initially recruited from a public hospital in Barcelona. The treatment consisted of 6 weeks of VirtualPain group sessions and 16 weeks of CBGT. Measures of catastrophizing, self-efficacy, and coping were recorded before, during, and after the protocol. In the DTx sessions, pain intensity was recorded before and after each session. Results: The program (DTx and CBGT) showed a significant improvement in pain-related self-efficacy and relaxation measures. Improvement in pain perception was observed only after the DTx intervention. Conclusions: This study provides preliminary results regarding the added value of DTx (VirtualPain) as part of a CBGT for FM. The use of the program has facilitated a significant reduction in pain perception in each of the VirtualPain sessions, which provides further evidence of how this technology can be beneficial for improving FM treatments.

Neurovascular Complications of Iatrogenic Fusarium solani Meningitis.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

Patentes, acesso e produção local de medicamentos: reflexões a partir de experiências no SUS / Patents, access, and local production of medicines: reflections from experiences in the SUS

Resumo Este artigo procurou contribuir para a literatura e para o debate nacional e global sobre a superação de uma polarização relacionada ao aspecto jurídico e administrativo do processo de inovação, procurando se concentrar nas patentes como um fator condicionante das trajetórias tecnológicas que viabilizam o aprendizado em âmbito produtivo. Baseou-se em um arcabouço teórico e político relacionado à inovação e ao acesso a medicamentos, especialmente quanto aos direitos de Propriedade Intelectual, e na análise crítico-reflexiva de instrumentos de Propriedade Intelectual utilizados em Parcerias para o Desenvolvimento Produtivo (PDP), desenvolvidas por um instituto de tecnologia em fármacos sintéticos, público e nacional. Os resultados demonstram a relevância da compatibilização dos direitos de patentes com a construção de uma capacidade tecnológica e de inovação no país, vinculada ao acesso universal, especialmente quando envolverem produtos que se destinam ao tratamento de doenças graves, de alta complexidade tecnológica e de alto custo. Conclui-se que, para superação da dependência tecnológica e ampliação do acesso a medicamentos no Brasil, o Estado deve buscar o equilíbrio entre os interesses públicos e privados na área da saúde, a articulação entre os instrumentos jurídicos legais existentes e o alinhamento entre suas políticas de saúde, industriais, de CT&I e Propriedade intelectual.

Abstract This article aims to contribute to the literature and to the national and global debate on overcoming the polarization related to the legal and administrative aspect of the innovation process, seeking to focus on patents as a conditioning factor of the technological trajectories that enable learning in the productive scope. It was based on a theoretical and political framework related to innovation and access to medicines, especially regarding Intellectual Property rights, and on a critical-reflexive analysis of Intellectual Property instruments used in Productive Development Partnerships (PDP), developed by a public national institute for synthetic drug technology. The results demonstrate the importance of making patent rights compatible with the construction of technological and innovation capacities in the country, which are linked to universal access, especially when they involve products that are intended to treat serious, technologically complex and high-cost diseases. In conclusion, to overcome technological dependence and expand access to medicines in Brazil, the State must seek a balance between public and private interests in the healthcare area, articulate the existing legal instruments and align its health, industry, ST&I and intellectual property policies.

Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study.

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .

Fatal iatrogenic cerebral ß-amyloid-related arteritis in a woman treated with lecanemab for Alzheimer's disease.

We report the case of a 79-year-old woman with Alzheimer's disease who participated in a Phase III randomized controlled trial called CLARITY-AD testing the experimental drug lecanemab. She was randomized to the placebo group and subsequently enrolled in an open-label extension which guaranteed she received the active drug. After the third biweekly infusion, she suffered a seizure characterized by speech arrest and a generalized convulsion. Magnetic resonance imaging revealed she had multifocal swelling and a marked increase in the number of cerebral microhemorrhages. She was treated with an antiepileptic regimen and high-dose intravenous corticosteroids but continued to worsen and died after 5 days. Post-mortem MRI confirmed extensive microhemorrhages in the temporal, parietal and occipital lobes. The autopsy confirmed the presence of two copies of APOE4, a gene associated with a higher risk of Alzheimer's disease, and neuropathological features of moderate severity Alzheimer's disease and severe cerebral amyloid angiopathy with perivascular lymphocytic infiltrates, reactive macrophages and fibrinoid degeneration of vessel walls. There were deposits of ß-amyloid in meningeal vessels and penetrating arterioles with numerous microaneurysms. We conclude that the patient likely died as a result of severe cerebral amyloid-related inflammation.

Estratégias de inovação em medicamentos e vacinas no âmbito do Ceis - modelos, mecanismos e expectativas / Innovation strategies in medicines and vaccines within the scope of CEIS - models, mechanisms, and expectations

RESUMO O artigo objetivou apresentar informações relevantes e originais sobre as estratégias de inovação utilizadas por Laboratórios Farmacêuticos Oficiais (LFO) para redução das vulnerabilidades do Sistema Único de Saúde (SUS) e capacitação produtiva e tecnológica do Complexo Econômico-Industrial da Saúde. Como métodos, foram utilizadas a revisão da literatura e a análise de dados primários oriundos de entrevistas realizadas em dois dos maiores LFO do País. Foram identificados e analisados os seus esforços e resultados em Pesquisa e Desenvolvimento (P&D) assim como a incorporação de tecnologias de medicamentos e vacinas, com destaque para as Parcerias para Desenvolvimento Produtivo (PDP). Conclui-se que, apesar de as atividades de P&D ainda precisarem avançar, benefícios foram trazidos pelos acordos de transferência de tecnologia, especialmente pelas PDP. No entanto, a capacidade industrial e tecnológica dos Institutos ainda é limitada e carente de investimentos, dificultando a acumulação e a difusão tecnológica. Dessa forma, melhorias são necessárias para que as estratégias de inovação para o SUS apresentem resultados mais efetivos e possam ser revertidos para o bem-estar da sociedade.

ABSTRACT The article aimed to present relevant and original information about the innovation strategies used by Official Pharmaceutical Laboratories (LFO) to reduce the vulnerabilities of the Brazilian Unified Health System (SUS) and the productive and technological capacity of the Health Economic-Industrial Complex. The methods used included a literature review and the analysis of primary data from interviews conducted in two of the largest LFOs in the country. Their efforts and results in Research and Development (R&D) and incorporation of medicines and vaccine technologies were identified and analyzed, with emphasis on Productive Development Partnerships (PDP). Although R&D activities still need to advance, benefits were brought about by technology transfer agreements, especially by PDPs. However, the industrial and technological capacity of the Institutes is still limited and lacks investments, which hinders technological accumulation and diffusion. Thus, improvements are necessary so that the innovation strategies for the SUS present more effective results and can be reversed to the welfare of society.

Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.

Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients.

GWAS-Identified Variants for Obesity Do Not Influence the Risk of Developing Multiple Myeloma: A Population-Based Study and Meta-Analysis.

Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls). Results were then validated through meta-analysis with data from the UKBiobank (554 MM cases and 402,714 controls) and FinnGen cohorts (914 MM cases and 248,695 controls). Finally, we evaluated the correlation of these single nucleotide polymorphisms (SNPs) with cQTL data, serum inflammatory proteins, steroid hormones, and absolute numbers of blood-derived cell populations (n = 520). The meta-analysis of the four European cohorts showed no effect of obesity-related variants on the risk of developing MM. We only found a very modest association of the POC5rs2112347G and ADCY3rs11676272G alleles with MM risk that did not remain significant after correction for multiple testing (per-allele OR = 1.08, p = 0.0083 and per-allele OR = 1.06, p = 0.046). No correlation between these SNPs and functional data was found, which confirms that obesity-related variants do not influence MM risk.

Caracterización de la identidad digital en estudiantes chilenos de ciencias de la salud. Un estudio de caso según género / Self-discrepancy and compulsive buying in Chilean university students

Resumen El consumo se ha instaurado en las sociedades posmodernas como un medio regulador de las relaciones sociales. En este contexto, la compra compulsiva se establece como patológica y genera un malestar psicológico significativo en las personas, al punto de deteriorar el funcionamiento social y profesional. A esto se suman graves problemas económicos como producto del endeudamiento. Bajo este escenario, los jóvenes son particularmente sensibles, ya que con el consumo acceden a objetos simbólicos que forman parte de su construcción de identidad. Una dimensión relacionada con la compra compulsiva y el acceso al consumo bajo elementos simbólicos es la discrepancia del yo, la cual establece la distancia entre quién soy y quién me gustaría ser de acuerdo a patrones sociales que motivan el consumo como extensión del sujeto y materialización de la propia identidad. En base a lo anterior, la presente investigación tiene por objetivo determinar el efecto de la discrepancia del yo sobre las actitudes hacia la compra compulsiva en estudiantes universitarios chilenos. A través de una regresión lineal múltiple se aprecia que la discrepancia del yo físico (belleza), económico y el sexo son predictores significativos de la compra compulsiva. De igual manera, se observa que las mujeres son un grupo con mayores puntuaciones en cuanto a las compras compulsivas que los hombres, las cuales pueden verse mayormente afectadas por el contexto, y las campañas de marketing pueden influir en una mayor brecha entre el yo real y el yo ideal.

Abstract Consumption has been established in postmodern societies as a means of regulating social relations. In this context, compulsive buying could be established as pathological, creating significant psychological discomfort in people, to the point of impairing social and professional functioning, coupled with serious economic problems resulting from indebtedness. Along the same lines, in the construction of a social identity and a socially shared reality, consumption patterns arise that are linked to what the public should be and what they want to be. Therefore, while compulsive buying has been conceptualized for decades, it is a substantial threat to psychological and financial well-being. Few studies have explored the link between self-discrepancy and compulsive buying within an identity construction context. In this scenario, it is young people who become particularly sensitive, since with consumption they access symbolic objects that are part of their identity construction and a dimension related to compulsive buying. Therefore, it can be hypothesized that access to the consumption of symbolic elements is self-discrepancy. That is why this research aims at determining the effect of the self-discrepancy on attitudes towards compulsive buying in Chilean university students. The study uses a quantitative, correlational, and non-experimental cross-sectional design. Study sample was comprised of 1 229 Chilean university students, who responded to the scale of attitudes towards consumption, the self-discrepancy scale, and answered questions for sociodemographic characterization including: gender (male/female), age, geographical area of residence (rural/urban), people with whom they live, and whether they have any bank credit cards. Prior to data collection, a letter was sent to Faculty Deans and Program Directors of all the universities associated with the Council of Rectors of Chile; these letters described the aims of the study, and requested information and authorization for the distribution of the instrument previously described. It is important to indicate that, after this, a random sampling process was initiated, after which each participant was contacted, so that they could sign an informed consent form, thus ensuring the anonymity ethical guidelines of the study. The data was processed through SPSS version 22 software, looking for the presence of univariate and multivariate outliers through Z-scores and Mahalanobis distance. A descriptive analysis of the variables was then carried out based on the dispersion, central trend and shape measurements. Subsequently, the data was analysed through bivariate statistics through Pearson correlations, to indicate into empirical relationships between compulsive purchase as a dependent variable and sociodemographic variables (sex and bank credit card holding) and the dimensions associated with the self-discrepancy (intellectual, physical, physical beauty, personal, social, emotional and economic) as independent variables. Once the behaviour of the variables was observed, a hierarchical multiple linear regression was performed. Regarding the results of this research, multiple linear regression shows that physical self-discrepancy (beauty), economic self-discrepancy and gender are significant predictors of compulsive buying. Similarly, it is noted that women are a group with higher scores in terms of compulsive purchases than men, which may be mostly affected by the context, where marketing campaigns can influence a greater gap between the real self and the ideal self.

Neurotrophic factors and brain health in children with overweight and obesity: The role of cardiorespiratory fitness.

ABSTRACTNeurotrophic factors and cardiorespiratory fitness are both considered important in developmental trajectories but their link to brain health remains poorly understood. The aims of the study were to examine whether levels of plasma-derived neurotrophic factors were associated with brain health indicators in children with overweight or obesity; and to test whether these associations were moderated by cardiorespiratory fitness. 100 children (41% girls) were included in this analysis. Plasma levels of brain-derived neurotrophic factor, insulin-like growth factor-1, vascular endothelial growth factor A, and epidermal growth factor were determined by XMap technology. Academic performance and executive function were assessed using validated neuropsychological tests. Hippocampal volume was measured using magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20-m Shuttle Run Test. Insulin-like growth factor-1 was positively associated with cognitive flexibility. Stratified analyses by fitness categories (i.e. unfit vs. fit) showed that brain-derived neurotrophic factor was positively associated with right posterior hippocampal volume in fit children, and epidermal growth factor was negatively associated with right hippocampal, and right anterior hippocampal volumes in their unfit peers, with a moderating role of cardiorespiratory fitness in these associations. However, all these significant associations disappeared after correction for multiple comparisons. The association between neurotrophic factors and brain health indicators in children with overweight/obesity was neither strong nor consistent. These results could help enhance our understanding of determinants of brain health in children with overweight/obesity.HighlightsThis study provides novel findings on the associations between neurotrophic factors and a wide range of brain health indicators in children.This study additionally explored the role of cardiorespiratory fitness in these associations.The association between neurotrophic factors and brain health in children with overweight/obesity was neither strong nor consistent.Cardiorespiratory fitness moderated the associations of brain-derived neurotrophic factor and epidermal growth factor with right hippocampal volume.

Efecto del Endeudamiento Estudiantil en Salud Mental y Bienestar Subjetivo de Estudiantes de Educación Superior de Chile / Effect of Student Debt on Mental Health and Subjective Well-being on Chilean University Students

Resumen Objetivo: Identificar en qué medida la salud mental y bienestar subjetivo son predichas por el endeudamiento por motivos de estudio en estudiantes universitarios de la ciudad de Temuco, Chile. Método: Una muestra no probabilística de 151 estudiantes universitarios de quinto año o superior de su respectiva carrera universitaria respondió a medidas de salud mental (DASS-21), de bienestar subjetivo (satisfacción con la vida y felicidad subjetiva), y del nivel de endeudamiento asumido para financiar sus estudios universitarios. Los análisis incluyeron regresiones lineales múltiples jerárquicas donde se incluyeron como variables independientes la variable género en un primer paso y el endeudamiento por créditos universitarios en el segundo paso. En cada regresión se incluyó un factor de salud mental y de bienestar subjetivo como variable dependiente. Resultados: Resultados indican que el endeudamiento por motivos de estudio predice significativa- mente satisfacción con la vida (F(2, 148) = 5,95, p = 0,003, R2Adjusted = 0,06; β =-0,16, p = 0,049), pero no predice felicidad subjetiva (p = n.s.) (factores de bienestar subjetivo), sintomatología depresiva (p = n.s.), ansiosa (p = n.s.), ni estrés (p = n.s.) (factores de salud mental). Conclusión: Resultados del estudio sugieren que los estudiantes universitarios pudieran percibir el endeudamiento estudiantil como una inversión hacia el futuro lo que pudiera operar como un factor protector de su salud mental y bienestar subjetivo.

Abstract Objective: To evaluate if debt due to university loans predicts mental health and subjective well-being in university students of Temuco, Chile. Method: A non-probabilistic sample of 151 last-year university students completed measures of mental health (DASS-21), of subjective well-being (satisfaction with life, and subjective happiness), and debt levels due to student loans. Analyses included hierarchical multiple linear regressions where gender was entered in a first step and debt due to university loans on a second step as independent variables. Each regression considered a factor of mental health or a factor of subjective well-being as the dependent variable. Results: Results show that debt due to university loans predict predicts satisfaction with life (F(2, 148) = 5,95, p = 0,003, R2Adjusted = 0,06; β =-0,16, p = 0,049), but not subjective happiness (p = n.s.) (factors of subjective well-being), nor symptoms of depression (p = n.s.), anxiety (p = n.s.), or stress (p = n.s.) (factors of mental health). Conclusion: Results of this study suggest that university students may perceive student debt as an investment which may act as a protective factor of their mental health and subjective well-being.

A single-session Mindfulness-Based Swinging Technique vs. cognitive disputation intervention among women with breast cancer: A pilot randomised controlled study examining the efficacy at 8-week follow-up.

Objective: Previously Mindfulness-Based Swinging Technique (MBST)'s immediate efficacy for overcoming psychological concerns has recently received empirical support, yet its longer-term efficacy needed to be evaluated among women with breast cancer. The objective of this study was to assess and report the efficacy of MBST intervention among breast cancer patients for hopelessness, anxiety, depression, self-efficacy, oxygen (SpO2) intensity, and heart rate-beats per minute (HR-bpm) at an 8-week period. Method: The State-Trait Anxiety Inventory, The Emotion Thermometer, Hospital Anxiety and Depression Scale, Self-Efficacy for Managing Chronic Disease, and Beck's Hopelessness Scale were used for assessing the intervention's outcome; 149 BC patients were randomly assigned into two groups (equal-mean-age, p = 0.262). The participants in the control group (CG, n = 73) received Cognitive Behavioural Therapy (CBT)-Cognitive-Disputation (CBT-CD) for 20 min, and intervention group (IG, n = 76) received MBST intervention. No additional psychological interventions were given between week-1 and week-8. Result: Outcomes of the 8-week post-treatment follow-up exhibited significantly higher improvements in all evaluated-measurements for CG, and some for IG with large effect size in the following: anxiety (CG p < 0.05, r = 0.57; IG p < 0.05, r = 0.44) and depression levels (CG p < 0.05, r = 0.43). It increased self-efficacy for managing disease (CG p < 0.05, r = 0.49; IG p < 0.05, r = 0.41) and hopefulness (CG p < 0.05, r = 0.59; IG p < 0.05, r = 0.46), and saturation levels measured by pulse-meter/oximeter (CG p < 0.05, r = 0.49; IG p < 0.05, r = 0.32). Conclusions: Both CBT-CD and MBST have been found to be efficacious interventions to shorten the psychotherapy duration for reducing clinical anxiety and hopelessness as well as increase self-efficacy for BC women. This may have a distinct clinical importance for supporting BC patient's adherence-to-treatment since CBT-CD could be an alternative technique to MBST as a brief intervention. In future studies, the effectiveness of MBST through adapting to virtual reality and other online delivery methods should be examined.

Autophagy in Hematological Malignancies.

Autophagy is a highly conserved metabolic pathway via which unwanted intracellular materials, such as unfolded proteins or damaged organelles, are digested. It is activated in response to conditions of oxidative stress or starvation, and is essential for the maintenance of cellular homeostasis and other vital functions, such as differentiation, cell death, and the cell cycle. Therefore, autophagy plays an important role in the initiation and progression of tumors, including hematological malignancies, where damaged autophagy during hematopoiesis can cause malignant transformation and increase cell proliferation. Over the last decade, the importance of autophagy in response to standard pharmacological treatment of hematological tumors has been observed, revealing completely opposite roles depending on the tumor type and stage. Thus, autophagy can promote tumor survival by attenuating the cellular damage caused by drugs and/or stabilizing oncogenic proteins, but can also have an antitumoral effect due to autophagic cell death. Therefore, autophagy-based strategies must depend on the context to create specific and safe combination therapies that could contribute to improved clinical outcomes. In this review, we describe the process of autophagy and its role on hematopoiesis, and we highlight recent research investigating its role as a potential therapeutic target in hematological malignancies. The findings suggest that genetic variants within autophagy-related genes modulate the risk of developing hemopathies, as well as patient survival.

Impacto en la morbilidad de la técnica quirúrgica abierta vs cerrada en cáncer de colon. Un reporte de 6 años de un centro único / Impact on morbidity of the open vs closed surgical technique in colon cancer.A 6-Year single-center study

Introducción: La cirugía laparoscópica es una alternativa segura para el tratamiento en el cáncer de colon y además permite todas las ventajas de un procedimiento de mínima invasión. El objetivo de la presente investigación fue medir el impacto en la morbilidad de la técnica quirúrgica abierta vs cerrada en cáncer de colon. Metodología: El estudio se realizó en el Hospital Solón Espinosa Ayala, en Quito-Ecuador, período marzo del 2012 hasta marzo del 2017, con una muestra no probabilística, se incluyeron pacientes mayores de edad, con cáncer de colon. Se incluyen variables socio-demográficas, histología, días de hospitalización, sangrado quirúrgico, tiempo quirúrgico, estancia hospitalaria, márgenes quirúrgicos, ganglios reseca-dos, inicio de dieta, % de conversión quirúrgica, complicación quirúrgica, recidiva, morbilidad quirúrgica, mortalidad quirúrgica. Se utiliza estadística descriptiva univariada y bivariada.Resultados: Se analizan 85casos, 52 casos se realizaron cirugía abierta y 33 casos se realizaron cirugía laparoscópica.La conversión quirúrgica fue 75% por adherencias y 25% por infiltración a duodeno. El tiempo quirúrgico similar 121 a 180 minutos 61%. Complicaciones laparoscópicas 2,3% y 9,4% abierta (colecciones pélvicas y fistulas intestinales 2.4% vs 1.7%). La desnutrición no presentó relación. Inicio de dieta 2 a4 días 83% laparoscópica y 67% abierta. Hospitalización de 4 a 8 días fue laparoscópica 87% y abierta 78%. Pérdida sanguínea menor a 100cc fue laparoscópicas 82%, y abiertas 60%. La resección de ganglios (+13) en laparoscopía 69.6% y abierta 68.1%. El margen proximal de pieza quirúrgica por laparoscopía 5.1 a 10cm (43.5%), por abierta (55.3%), la recaída tumoral del 56.2%y 52.3%. El estado vital por laparoscopía fue fallecido 12.5%, y abierta 28.8%, en relación a su enfermedad tumoral Conclusión: Las comorbilidades quirúrgicas y recuperación fueron menores por laparoscopía, pero la cirugía abierta mostro mejores resultados anatomopatológicos post quirúrgicos

Introduction:Laparoscopic surgery is a safe alternative for colon cancer treatment and allows all the advantages of a minimally invasive procedure. The objective of the present investigation was to measure the impact on morbidity of the open vs. closed surgical technique in colon cancer.Methodology: The study was carried out at the Solón Espinosa Ayala Hospital, in Quito-Ecuador, from March 2012 to March 2017, with a non-probabilistic sample, including elderly patients with colon cancer. Socio-demographic variables, histology, days of hospitalization, surgical bleeding, surgical time, hospital stay, surgical margins, resected lymph nodes, the start of the diet, % surgical conversion, surgical com-plication, recurrence, surgical morbidity, and surgical mortality are included. Univariate and bivariate de-scriptive statistics are used.Results: 85 cases are analyzed; 52 underwent open surgery, and 33 underwent laparoscopic surgery. The surgical conversion was 75% due to adhesions and 25% due to duodenal infiltration. The similar surgical time is 121 to 180 minutes 61%. Laparoscopic complications 2.3% and 9.4% open (pelvic col-lections and intestinal fistulas 2.4% vs 1.7%). Malnutrition was not related. Start of diet 2 to 4 days 83% laparoscopic and 67% open. Hospitalization from 4 to 8 days was laparoscopic 87% and open 78%. Blood loss less than 100cc was laparoscopic in 82% and opened in 60%. Lymph node resection (+13) in lapa-roscopy 69.6% and open 68.1%. The proximal margin of the surgical piece by laparoscopy is 5.1 to 10cm (43.5%), by open (55.3%), the tumor recurrenceof 56.2% and 52.3%. The mortality in laparoscopy surgery was 12.5%, and in open surgery was 28.8%.Conclusion: Laparoscopy's surgical comorbidities and recovery were lower, but open surgery showed better post-surgical pathological results

Efficacy of New Mindfulness-Based Swinging Technique Intervention: A Pilot Randomised Controlled Trial Among Women With Breast Cancer.

Objective: Combining 3rd-wave-therapies with Cognitive-Behavioural-Therapy (CBT) has increased in recent years. Usually these therapies require longer sessions which therefore increases the psychotherapy drop-out rate for cancer patients for multiple medical reasons. This inspired intervention of a shorter 20 min-long mindfulness-therapy (MBST) to be developed for Breast-Cancer-patients (BC). Method: This pilot randomised controlled trial was to assess the immediate-outcome of the MBST-intervention for its efficacy for BC-patients by using the Pearson Chi-square test, Fisher-Freeman-Halton exact test, and McNemar test for categorical variables; Mann-Whitney U and Wilcoxon test for the continuous variables. The Emotion Thermometer, State Trait Anxiety Inventory, Hospital Anxiety and Depression Scale, Self-Efficacy for Managing Chronic Disease, and Beck's Hopelessness Scale were used for measuring the intervention outcomes. One hundred seventy-three BC patients were randomly assigned in two-groups (equal-mean-age, p = 0.417). Control-Group (CG, n = 82) received cognitive-disputation-technique a form-of-CBT, and Intervention-Group (IG, n = 74) received MBST. The directives are given to IG: psychoeducation about Mindfulness, and to imagine themselves swinging-in a peaceful environment. When the patients imagine their swing going up, they physically take a deep-breath, and when going down they physically release their breath, and this process is repeated. Result: Outcomes post-treatment showed significant higher-improvement in IG in all the assessed-measurements, with large-effect-size: anxiety (p < 0,05, r = 0,67) and depression-levels (p < 0,05, r = 0,71); anxiety-trait (p < 0,05; r = 0,79) reduced, it increases self-efficacy for managing-disease (p < 0,05, r = 0,82) as-well-as hopefulness (p < 0,05, r = 0,61) and saturation-level measured by pulse-meter/oximeter (p < 0,05, r = 0,51). Conclusion: MBST is an efficacious intervention to reduce psychotherapy session time for immediate relief from clinical anxiety and hopelessness as well as increase self-efficacy and improve tranquillity for BC-women. It may have a particular clinical significance for supporting patient's adherence to treatment. Although in this pilot sample MBST was found to be effective for short-term-outcome, its efficacy for longer-term-outcome should be examined in future trials. Additionally, breathing laps can be increased possibly for a greater result on rise of saturation levels of patients.