Purine Nucleotide Alterations in Tumoral Cell Lines Maintained with Physiological Levels of Folic Acid.

Most cancer cells have an increased synthesis of purine nucleotides to fulfil their enhanced division rate. The de novo synthesis of purines requires folic acid in the form of N10-formyltetrahydrofolate (10-formyl-THF). However, regular cell culture media contain very high, non-physiological concentrations of folic acid, which may have an impact on cell metabolism. Using cell culture media with physiological levels of folic acid (25 nM), we uncover purine alterations in several human cell lines. HEK293T, Jurkat, and A549 cells accumulate 5'-aminoimidazole-4-carboxamide ribonucleotide (ZMP), an intermediary of the de novo biosynthetic pathway, at physiological levels of folic acid, but not with the artificially high levels (2200 nM) present in regular media. Interestingly, HEK293T and Jurkat cells do not accumulate high levels of ZMP when AICAr, the precursor of ZMP, is added to medium containing 2200 nM folate; instead, ATP levels are increased, suggesting an enhanced de novo synthesis. On the other hand, HeLa and EHEB cells do not accumulate ZMP at physiological levels of folic acid, but they do accumulate in medium containing AICAr plus 2200 nM folate. Expression of SLC19A1, which encodes the reduced folate carrier (RFC), is increased in HEK293T and Jurkat cells compared with HeLa and EHEB, and it is correlated with the total purine nucleotide content at high levels of folic acid or with ZMP accumulation at physiological levels of folic acid. In conclusion, tumoral cell lines show a heterogenous response to folate changes in the media, some of them accumulating ZMP at physiological levels of folic acid. Further research is needed to clarify the ZMP downstream targets and their impact on cell function.

Impact of a One-Stop Hematuria Clinic on Overall Survival and Bladder Tumor Recurrence.

BACKGROUND AND OBJECTIVE: One-stop clinics have emerged as a tool to optimize the therapeutic management of cancer patients. The main purpose of this study was to assess the role of the one-stop hematuria clinic (OSHC), as compared to a conventional clinic (CC), on the overall and disease-free survival of patients with bladder cancer. METHODS: A five-year follow-up retrospective and single-center study was conducted in patients with primary bladder tumor diagnosed between 2006 and 2015. The primary outcomes were five-year overall survival and one-year relapse rate. RESULTS: A total of 394 patients (160 in OSHC and 234 in CC) were included. No differences were observed in terms of age, sex, smoking habit or risk group between the OSHC and CC groups. The average times from first symptom to diagnosis (24.9 ± 29.1 vs. 100.7 ± 93.6 days) and from first symptom to treatment (70.2 ± 34.0 vs. 155.0 ± 102.9 days) were significantly lower in the OSHC group than in the CC group (p < 0.001 each). There was no significant difference in the five-year survival rate between OSHC and CC (103/160 vs. 150/234, respectively; p = 0.951), although the proportion of relapses during the first year was significantly lower in the OSHC group (35/139, 25.2%) than in the CC one (74/195, 38.0%; p = 0.02). CONCLUSIONS: OSHC significantly reduced the diagnosis and treatment times. The early-relapse rate was significantly lower in the OSHC group, although the five-year survival rate was similar.

Impact of a One-Stop Hematuria Clinic on Overall Survival and Bladder Tumor Recurrence

Background and Objective: One-stop clinics have emerged as a tool to optimize the therapeutic management of cancer patients. The main purpose of this study was to assess the role of the one-stop hematuria clinic (OSHC), as compared to a conventional clinic (CC), on the overall and disease-free survival of patients with bladder cancer. Methods: A five-year follow-up retrospective and single-center study was conducted in patients with primary bladder tumor diagnosed between 2006 and 2015. The primary outcomes were five-year overall survival and one-year relapse rate. Results: A total of 394 patients (160 in OSHC and 234 in CC) were included. No differences were observed in terms of age, sex, smoking habit or risk group between the OSHC and CC groups. The average times from first symptom to diagnosis (24.9 ± 29.1 vs. 100.7 ± 93.6 days) and from first symptom to treatment (70.2 ± 34.0 vs. 155.0 ± 102.9 days) were significantly lower in the OSHC group than in the CC group (p < 0.001 each). There was no significant difference in the five-year survival rate between OSHC and CC (103/160 vs. 150/234, respectively; p = 0.951), although the proportion of relapses during the first year was significantly lower in the OSHC group (35/139, 25.2%) than in the CC one (74/195, 38.0%; p = 0.02). Conclusions: OSHC significantly reduced the diagnosis and treatment times. The early-relapse rate was significantly lower in the OSHC group, although the five-year survival rate was similar (AU)

Impacto de los turnos de trabajo en la calidad del sueño del personal de enfermería en dos hospitales de tercer nivel de Canarias / Impact of shift work on the sleep quality of nursing staff attending two tertiary hospitals in the Canary Island

Fundamentos: Se sabe que las características de la actividad laboral influyen en la calidad del sueño de los trabajadores. Un elemento de la actividad laboral es la turnicidad. El objetivo de este estudio fue analizar la calidad del sueño del personal de enfermería de dos hospitales de tercer nivel en Canarias y su correlación con el turno de trabajo. Métodos: Estudio observacional, analítico y transversal, de una muestra no aleatoria de 275 enfermeros y técnicos en cuidados auxiliares de enfermería (TCAEs). Se midió calidad de sueño mediante el test de Pittsburgh Sleep Quality Index (PSQI) y características sociodemográficas y laborales con un cuestionario creado ad hoc. Resultados: El 65,8% del personal de enfermería tiene una mala calidad del sueño. Se observó que la turnicidad laboral afecta a la calidad del sueño. Los trabajadores con turno antiestrés (D/N) tienen mejor calidad de sueño (M=7,31; ±DE=4,0) comparado con el turno rotatorio (M/T/N) (M= 9,06; ± DE=4,3); p=0,01. Conclusiones: Las alteraciones del sueño son frecuentes entre el personal de enfermería, siendo el turno antiestrés (D/N) el que menos afecta a la calidad del sueño (AU)

Evaluation of the insertion parameters and complications of the i-gel Plus airway device for maintaining patent airway during planned procedures under general anaesthesia: a protocol for a prospective multicentre cohort study.

INTRODUCTION: Supraglottic airway devices represent a less invasive method of airway management than tracheal intubation during general anaesthesia. Their continued development is focused mainly on improvements in the insertion success rate and minimalisation of perioperative and postoperative complications. The i-gel Plus is a novel, anatomically preshaped supraglottic airway device which achieves a perilaryngeal seal due to a non-inflatable cuff made of a soft thermoplastic elastomer. The purpose of this cohort study is to assess the success rate of the i-gel Plus use during elective procedures under general anaesthesia, its intraoperative performance, and the degree of postoperative complications. METHODS AND ANALYSIS: This is a multicentre, prospective, interventional cohort study. The enrolment will take place in seven centres in four European countries. We plan to enrol 2000 adult patients in total, who are scheduled for elective surgery under general anaesthesia, and with an indication for use of a supraglottic airway device for management of their airway. The study is projected to run over a period of 18 months. The primary outcome of the study is the total success rate of the i-gel Plus insertion in terms of successful ventilation and oxygenation through the device. Secondary outcomes include perioperative parameters, such as insertion time, seal/leak pressures, number of insertion attempts and postoperative adverse events and complications. Postoperative follow-up will be performed at 1 hour, 24 hours in all patients, and for selected patients at 3 and 6 months. ETHICS AND DISSEMINATION: The cohort study has received the following ethical approvals: General University Hospital Prague, University Hospital Olomouc, University Military Hospital Prague, University Hospital Barcelona, University Hospital Lodz, Antrim Area Hospital, Craigavon Area Hospital, Office for Research Ethics Committees Northern Ireland. The results will be published in peer-reviewed journals and presented at relevant anaesthesia conferences. TRIAL REGISTRATION NUMBER: ISRCTN86233693;Pre-results.

Perinatal psychological interventions to promote breastfeeding: a narrative review.

BACKGROUND: Emotional distress in mothers inhibits the let-down reflex, thus affecting breastfeeding self-efficacy. A breastfeeding mother may have to cope with both physical discomfort and psychological distress. However, literature on initiatives to improve breastfeeding rates has focused mainly on providing community-based peer support, or social policies. The aim of this review is to assess evidence on the effectiveness of a broad range of psychological interventions to facilitate breastfeeding for mothers facing difficulties around the time of delivery. METHODS: The review of the literature is derived from a search on Cochrane Library, PubMed, EBSCOhost, and PsycINFO for papers published since 1980. The approach was to explore quantitative and qualitative parameters. Quantitative parameters included breastfeeding initiation, duration, and composition. Qualitative parameters recorded the evaluation of maternal perceptions on breastfeeding success. The high heterogeneity of the studies led to a narrative review; 20 selected papers that report on breastfeeding outcomes and psychological programs met the inclusion criteria. RESULTS: The evidence on breastfeeding support through psychotherapy is heterogeneous and scant. Out of the included studies, 11 were randomized controlled trials, two were non-randomised trials, and two used a quasi-experimental design. None of the studies reported an increase in adverse breastfeeding outcomes. Three studies failed to report an association between psychological procedures and improved breastfeeding outcomes. A literature review showed that 17 (85%) analyses support stress-releasing techniques to facilitate breastfeeding. CONCLUSIONS: This review suggests that relaxation interventions carefully tailored to address perinatal emotional distress may lead to important health benefits, including improvement in breastfeeding outcomes. There is also some indication that psychotherapy support while breastfeeding may have more impact than routine counselling. Conversely, this review did not find an association between self-hypnosis and breastfeeding outcomes. Data from this study can be used in designing prevention programs and future research with appropriate theoretical underpinning.

Brote de bacteriemia por Pantoea agglomerans en hemodiálisis. Una infección por un invitado no esperado / Bacteremia outbreak due to Pantoea agglomerans in hemodialysis, an infection by an unexpected guest

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CXCL12 blockade preferentially regenerates lost podocytes in cortical nephrons by targeting an intrinsic podocyte-progenitor feedback mechanism.

Insufficient podocyte regeneration after injury is a central pathomechanism of glomerulosclerosis and chronic kidney disease. Podocytes constitutively secrete the chemokine CXCL12, which is known to regulate homing and activation of stem cells; hence we hypothesized a similar effect of CXCL12 on podocyte progenitors. CXCL12 blockade increased podocyte numbers and attenuated proteinuria in mice with Adriamycin-induced nephropathy. Similar studies in lineage-tracing mice revealed enhanced de novo podocyte formation from parietal epithelial cells in the setting of CXCL12 blockade. Super-resolution microscopy documented full integration of these progenitor-derived podocytes into the glomerular filtration barrier, interdigitating with tertiary foot processes of neighboring podocytes. Quantitative 3D analysis revealed that conventional 2D analysis underestimated the numbers of progenitor-derived podocytes. The 3D analysis also demonstrated differences between juxtamedullary and cortical nephrons in both progenitor endowment and Adriamycin-induced podocyte loss, with more robust podocyte regeneration in cortical nephrons with CXCL12 blockade. Finally, we found that delayed CXCL12 inhibition still had protective effects. In vitro studies found that CXCL12 inhibition uncoupled Notch signaling in podocyte progenitors. These data suggest that CXCL12-driven podocyte-progenitor feedback maintains progenitor quiescence during homeostasis, but also limits their intrinsic capacity to regenerate lost podocytes, especially in cortical nephrons. CXCL12 inhibition could be an innovative therapeutic strategy in glomerular disorders.

Situación actual de la formación doctoral en la Facultad de Estomatología Raúl González Sánchez / Current background of the doctoral training at Raúl González Sánchez Dental School

Introducción: la cantidad de doctores en ciencias es un factor determinante en los procesos acreditativos de la calidad de las carreras universitarias. La Facultad de Estomatología de la Universidad de Ciencias Médicas de La Habana ha sido acreedora en dos oportunidades de la condición de carrera de excelencia. No obstante, la cantidad de doctores en ciencias es insuficiente con relación a los estándares de calidad. Objetivo: describir la situación actual de la formación doctoral en la Facultad de Estomatología de La Habana. Método: se realizó un estudio diagnóstico mediante el empleo de métodos teóricos y empíricos. Se revisaron documentos administrativos sobre el tema e informes de evaluación para la acreditación de la carrera. Se efectuó una lluvia de ideas con el consejo de dirección y algunos doctores en ciencias invitados, se confeccionó una matriz DAFO innovada para el análisis situacional de la formación doctoral en la Facultad. Resultados: el 7,5 por ciento del claustro son doctores en ciencias con un promedio de edad de 69,4 años. Muestra desde el 2012 una disminución progresiva. Las debilidades que más afectan la formación de doctores son: la carencia de una estrategia de captación temprana de aspirantes (11,7 por ciento), insuficiencias de la estrategia actual (11,2 por ciento) seguidas de la inadecuada estimulación a los doctores (11,2 por ciento) y la calidad de los procesos y control de la actividad (10,7 por ciento). Conclusiones: se identificó que la formación de doctores en la Facultad de Estomatología no avanza en correspondencia con sus potencialidades ni con los requerimientos de los procesos de certificación de la calidad(AU)

Introduction: the number of philosophy doctors is a determinant for the processes accrediting the quality of university majors. The Dental School of the University of Medical Sciences of Havana has been accredited in two opportunities with the condition of major of excellence. However, the number of philosophy doctors is insufficient in relation to quality standards. Objective: to describe the current situation of doctoral training in the Dental School of Havana. Method: adiagnostic study was carried out using theoretical and empirical methods. Administrative documents on the subject and evaluation reports for the major accreditation were reviewed. Brainstorming was carried out with the board of directors and some invited philosophy doctors. An innovated SWOT matrix was created for the situational analysis of doctoral training at the School. Results: 7.5 percent of the faculty are philosophy doctors, with an average age of 69.4 years. Since 2012, this has shown a progressive decrease. The weaknesses most affecting the training of philosophy doctors are the lack of a strategy of early recruitment for aspirants (11.7 percent), inadequacies of the current strategy (11.2 percent), followed by inadequate stimulation for physicians (11, 2 percent) and the quality of the processes and control of the activity (10.7 percent). Conclusions: the training of philosophy doctors in the Dental School was identifies as not advancing in correspondence with the potentials or the requirements of the quality certification processes(AU)

Simulación para formar en la competencia de valoración preanestésica: diseño común para residentes de primer año de anestesiología y enfermeras de anestesia / Simulation for training the competence pre-anesthetic assessment: a common design for first year anesthesia residents and anesthesia nurses

Introducción. La valoración preanestésica (VP) es una competencia compleja que debe adquirir el residente de anestesia tempranamente. La incorporación de enfermería especializada en la VP ha demostrado ser segura y eficaz. No existen recomendaciones para el entrenamiento en VP. La simulación puede ser una metodología apropiada para acortar el tiempo de adquisición de la competencia. Objetivo. Describir detalladamente el diseño y aplicación de un taller de simulación para formar residentes de anestesiología y enfermeras posgraduadas en la competencia VP. Sujetos y métodos. Taller de dos horas de duración con casos clínicos en formato video y ejecutados mediante técnica de role-playing. Los componentes fueron dos videos de grabación propia (el primero, de una VP con errores, y el otro, con una VP correctamente realizada), una plantilla para que cada alumno valorara en los videos los componentes técnicos y no técnicos de las competencias de la VP y una encuesta de satisfacción para alumnos e instructores. En el grupo de residentes se añadieron tres escenarios de VP de pacientes complejos. Resultados. Se analizaron las encuestas de los 10 residentes de dos promociones y de 60 enfermeras. La satisfacción de los dos tipos de alumnos y de los instructores sobre el aprendizaje fue muy alta. En el caso de las enfermeras, más del 85% de las alumnas de las promociones que recibieron el taller superaron la estación VP de la evaluación clínica objetiva estructurada (ECOE) frente a sólo el 20% de la promoción anterior. Conclusiones. El taller de VP con formato video y role-playing permite entrenar la competencia VP a residentes de anestesia y enfermeras posgraduadas, mejorando el rendimiento de éstas en la ECOE

Introduction. Preoperative anesthetic assessment (PA) is a complex competence that anesthesia residents should acquire early in their training. Participation of specialized nurses in the PA is increasing since it is safe and efficacious. There is not an established curriculum in PA. Simulation may be an adequate methodology to train PA. Aim. To describe in detail the design and application of a simulation workshop for training residents and postgraduate nurses in the competence PA. Subjects and methods. Workshop of 2 hours duration, with clinical cases combining videotapes and role-playing. Workshop components were two homemade videos, one with a PA with errors and the other one with a correct PA, a checklist in which each participant assesses technical and non-technical components of the PA and a satisfaction survey for students and instructors. Three simulation scenarios of PA in complex patients were added for residents. Results. 10 residents and 60 nurses participating in the workshop were surveyed. Satisfaction with the methodology applied was high for students and instructors. The percentage of passing the PA station of the final objective structured clinical examination (OSCE) of two promotions of nurses that had participated in the workshop was over 85% compared with only 20% of the previous promotion. Conclusions. A simulation workshop based on videos and role-playing allows to train the competence PA in anesthesia residents and postgraduate nurses, improving the performance of the latter in the OSC

The diabetes pandemic suggests unmet needs for 'CKD with diabetes' in addition to 'diabetic nephropathy'-implications for pre-clinical research and drug testing.

Curing 'diabetic nephropathy' is considered an unmet medical need of high priority. We propose to question the concept of 'diabetic nephropathy' that implies diabetes as the predominant cause of kidney disease, which may not apply to the majority of type 2 diabetics approaching end-stage kidney disease. With the onset of diabetes, hyperglycaemia/sodium-glucose co-transporter-2-driven glomerular hyperfiltration promotes nephron hypertrophy, which, however, on its own, causes proteinuria not before a decade later, probably because podocyte hypertrophy can usually accommodate an increase in the filtration surface. In contrast, precedent chronic kidney disease (CKD), that is, few nephrons per body mass, e.g. due to poor nephron endowment from birth, obesity, pregnancy, or renal ageing or injury-related nephron loss, usually precedes the onset of type 2 diabetes. This applies in particular in older adults, and each on its own, but especially in combination, further aggravates single nephron hyperfiltration and glomerular hypertrophy. Whenever this additional hyperglycaemia-driven enlargement of the glomerular filtration surface exceeds the capacity of podocytes for hypertrophy, podocytes detachment leads to glomerulosclerosis and nephron loss, i.e. CKD progression. Animal models of 'diabetic nephropathy' based only on hyperglycaemia do not mimic this aspect and therefore poorly predict outcomes of clinical trials usually performed on elderly CKD patients with type 2 diabetes. Thus, we advocate the use of renal mass (nephron) ablation in type 2 diabetic animals to better mimic the pathophysiology of 'CKD with diabetes' in the target patient population and the use of the glomerular filtration rate as a primary endpoint to more reliably predict trial outcomes.