Colonic bacterial diversity and dysbiosis in active microscopic colitis as compared to chronic diarrhoea and healthy controls: effect of polyethylene glycol after bowel lavage for colonoscopy.

BACKGROUND: Most microbiota studies in microscopic colitis patients are performed after diagnostic colonoscopy without considering the potential effect of colonic lavage. Patients may achieve clinical remission after colonoscopy and it is unknown whether lavage-induced changes play a role. AIM: To assess the effect of polyethylene glycol (PEG) colonic lavage on clinical remission rate, microbial diversity, microbial dysbiosis index and specific microbial changes in patients with active microscopic colitis as compared to other diarrhoeal diseases and healthy controls. METHODS: Fifty-five consecutive patients presenting chronic watery diarrhoea and 12 healthy controls were included. Faecal samples were collected three days before and 30 days after PEG in patients and controls for microbiome analysis. RESULTS: Clinical remission was observed in 53% of microscopic colitis patients, and in 32% of non-microscopic colitis patients (p = 0.16). Considering patients with persisting diarrhoea after colonoscopy, 71% of non-microscopic colitis patients had bile acid diarrhoea. Baseline Shannon Index was lower in diarrhoea groups than in healthy controls (p = 0.0025); there were no differences between microscopic colitis, bile-acid diarrhoea and functional diarrhoea. The microbial dysbiosis index was significantly higher in microscopic colitis than in bile acid diarrhoea plus functional diarrhoea (p = 0.0095), but no bacterial species showed a significantly different relative abundance among the diarrheal groups. CONCLUSIONS: Dysbiosis is a feature in active microscopic colitis, but loss of microbial diversity was similar in all diarrheal groups, suggesting that faecal microbial changes are not due to microscopic colitis itself but associated with stool form. A considerable number of microscopic colitis patients achieved clinical remission after colonoscopy, but we were unable to demonstrate related PEG-induced changes in faecal microbiome.

Impact of the COVID-19 pandemic on the activity of advanced-practice nurses on a reference unit for inflammatory bowel disease / Impacto de la pandemia por COVID-19 en la actividad de la enfermera de práctica avanzada, en enfermedad inflamatoria intestinal en una unidad de referencia

Objective: To report the impact of the COVID-19 pandemic on the activity of nurses working on an inflammatory bowel disease (IBD) unit and to identify reasons for telehealth care and its relationship to certain characteristics. Background: The COVID-19 pandemic had led to an increase in demand for remote care in patients with inflammatory bowel disease who require monitoring and frequent access to health services. Design – methods: A retrospective study of all activity (in person and by phone call or email) done on the unit during the acute phase of the pandemic at a reference hospital in Spain. Numbers of activities done by nurses, reasons for telehealth care and sociodemographic and clinical data were collected. Statistical analysis was performed using frequency, chi-squared and analysis of variance tests. Results: A total of 1095 activities for 561 patients who received care were reported. Among them, 1042 (95.2%) were telemedicine activities, amounting to a 47.3% increase over the prior year. COVID-19-related activities numbered 588 (59.5%). Consultations due to disease flare-up numbered 134 (13.7%), representing a 145% increase compared to 2019. Significant differences were found between reasons for using telemedicine and diagnosis, occupational status, contact week and treatment. Conclusion: The acute phase of the pandemic has changed the activity managed by the nursing staff on the unit. Identifying and analysing these changes has yielded valuable information to achieve more efficient management and better care quality for patients in special situations.(AU)

Objetivos: Describir el impacto de la pandemia por COVID-19 en la actividad de la enfermera, en enfermedad inflamatoria intestinal (EII) de la unidad, e identificar las razones de la asistencia telemática y la relación con las variables recogidas. Antecedentes: La pandemia de COVID-19 ha dado lugar a un aumento en la demanda de atención remota en pacientes con EII que requieren un seguimiento y un acceso frecuente a los servicios de salud. Diseño y métodos: Estudio retrospectivo de toda la actividad (presencia, llamada telefónica o correo electrónico), realizado en la unidad durante la fase aguda de la pandemia, en un hospital de referencia en España. Se recogió el número de actividades llevadas a cabo por la enfermera, motivo de asistencia telemática y datos sociodemográficos y clínicos. El análisis estadístico se realizó utilizando la prueba de frecuencia, χ2 y el análisis de varianza. Resultados: Fueron registradas 1.095 actividades por 561 pacientes atendidos, siendo 1.042 (95,2%) actividades de telemedicina, lo que supuso un incremento del 47,3% con respecto al año anterior. Las demandas relacionadas con COVID-19 fueron 588 (59,5%). Por otro lado, 134 (13,7%) fueron consultas por brote de su enfermedad, un 145% más que en 2019. Se han encontrado diferencias significativas entre los motivos del uso de la telemedicina y el diagnóstico, la situación laboral, la semana en que se realizó el contacto y el tratamiento. Conclusión: La fase aguda de la pandemia ha cambiado la actividad gestionada por enfermería en la unidad. Identificar y analizar estos cambios nos ha proporcionado información para conseguir una gestión más eficiente y de calidad al cuidado de los pacientes en situaciones excepcionales.(AU)

Sucrosomial Iron Supplementation for the Treatment of Iron Deficiency Anemia in Inflammatory Bowel Disease Patients Refractory to Oral Iron Treatment.

Iron deficiency anemia (IDA) is a common manifestation of Inflammatory Bowel Disease (IBD). Oral iron supplements are the treatment of choice, but are not always well tolerated. Sucrosomial® iron (SI) may represent an alternative. This prospective study assessed the tolerability and effectiveness of SI, and quality of life (QoL) of IDA-IBD patients who were intolerant to oral iron salts. The study included 52 individuals treated with 1 capsule/day for 12 weeks. Tolerability was assessed through a gastrointestinal symptom severity questionnaire. Hemoglobin (Hb) levels and clinical symptoms of IDA were analyzed. QoL was assessed using IBDQ-9 and EuroQoL questionnaires. The percentage of patients with excellent/good health increased from 42.9% to 94.3%. Mean Hb concentration significantly increased at all follow-up visits (p < 0.05). Almost all participants (96.9%) were adherent to the study medication. Patients' QoL improved (IBDQ-9: from 60.9 to 65.5). Patients also improved in mobility (71.8% to 78.1%), usual activities (51.3% to 68.7%), pain/discomfort (41.0% to 53.1%), and extreme depression/anxiety problems (7.7% to 3.2%); they worsened in self-care (100% to 90.6%), but perceived an enhancement in their global health [EQ-VAS score: 61.9 (±26.1) to 66.9 (±20.3)]. SI was well tolerated and improved IDA symptoms, IBD activity, and patients' QoL. In conclusion, SI should be considered in IDA-IBD patients.

Impact of the COVID-19 pandemic on the activity of advanced-practice nurses on a reference unit for inflammatory bowel disease.

OBJECTIVE: To report the impact of the COVID-19 pandemic on the activity of nurses working on an inflammatory bowel disease (IBD) unit and to identify reasons for telehealth care and its relationship to certain characteristics. BACKGROUND: The COVID-19 pandemic had led to an increase in demand for remote care in patients with inflammatory bowel disease who require monitoring and frequent access to health services. DESIGN - METHODS: A retrospective study of all activity (in person and by phone call or email) done on the unit during the acute phase of the pandemic at a reference hospital in Spain. Numbers of activities done by nurses, reasons for telehealth care and sociodemographic and clinical data were collected. Statistical analysis was performed using frequency, chi-squared and analysis of variance tests. RESULTS: A total of 1095 activities for 561 patients who received care were reported. Among them, 1042 (95.2%) were telemedicine activities, amounting to a 47.3% increase over the prior year. COVID-19-related activities numbered 588 (59.5%). Consultations due to disease flare-up numbered 134 (13.7%), representing a 145% increase compared to 2019. Significant differences were found between reasons for using telemedicine and diagnosis, occupational status, contact week and treatment. CONCLUSION: The acute phase of the pandemic has changed the activity managed by the nursing staff on the unit. Identifying and analysing these changes has yielded valuable information to achieve more efficient management and better care quality for patients in special situations.

Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment.

BACKGROUND: Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. AIM: To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. METHODS: Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. RESULTS: Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. TREATMENT: with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. CONCLUSIONS: One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.

Patient preferences for inflammatory bowel disease treatment objectives.

BACKGROUND: There is currently little evidence about what treatment objectives most interest patients with inflammatory bowel disease (IBD). AIMS: To determine patient preferences regarding IBD treatment objectives, specially the attributes they value most and the symptoms to be controlled as a priority. METHODS: Prospective, observational, anonymous study conducted in 117 outpatients with Crohn's disease or ulcerative colitis. RESULTS: The most important treatment objectives from the patients' perspective were: improving quality of life (40.2% of patients), and completely resolving symptoms (33.3%). Only 12.8% of patients indicated having a completely normal colonoscopy as a preferred objective. The symptoms the patients considered to be most important when prioritizing their control were: abdominal pain (23.1% of patients), and bowel movement urgency (17.1%). The preferred treatment objectives were similar for Crohn's disease and ulcerative colitis patients. CONCLUSIONS: Improving quality of life and completely controlling symptoms are the priority treatment objectives for IBD patients, with abdominal pain being the most important symptom. Conversely, therapeutic objective target goals proposed by physicians, such as healing the mucosal lesions, are not a priority for most patients. This indicates that there are discrepancies between patient and physician expectations, which should be taken into account if a patient-centered care model is to be implemented.

Iron Deficiency in the Absence of Anemia Impairs the Perception of Health-Related Quality of Life of Patients with Inflammatory Bowel Disease.

BACKGROUND: Anemia is a common complication of inflammatory bowel disease (IBD) and contributes to the deterioration of health-related quality of life (HRQOL). Iron deficiency (ID) is a prevalent underlying factor, present in up to 90% of patients. In the absence of anemia, it is unclear as to what extent ID can affect HRQOL in patients with IBD. Our aim was to determine whether ID without anemia negatively affects normal perception of HRQOL in patients with IBD in remission. METHODS: We conducted a prospective, cross-sectional study in patients with IBD in remission without anemia. Blood samples were obtained to determine iron status, and patients completed the Inflammatory Bowel Disease Questionnaire-36. ID was defined on serum ferritin <30 ng/mL and transferrin saturation <16%. Restoration of HRQOL was defined as ≥209 on the Inflammatory Bowel Disease Questionnaire-36. RESULTS: One hundred-four patients with IBD in clinical remission were included; 45 patients were iron deficient and 59 had normal iron status. All patients were in clinical remission, with a median Harvey-Bradshaw Index ≤0 and Simple Clinical Colitis Activity Index ≤0. Median hemoglobin was 12.8 g/dL in the ID group and 13.9 g/dL in the normal iron status group (P < 0.05). Prevalence of female patients was higher in the ID group (odds ratio, 4.45; 95% CI, 1.7-11.7; P < 0.01). The median global value of Inflammatory Bowel Disease Questionnaire-36 was not different between the groups (219 in the ID group versus 230 in the normal iron status group, P = not significant), but restoration of health was significantly less frequent in patients with ID (odds ratio, 2.83; 95% CI, 1.22-6.6; P < 0.05). CONCLUSIONS: ID in absence of anemia negatively impacts normal perception of HRQOL in patients with IBD in remission. Correction of ID may be a new target in the treatment of these patients.

Predictive value of early restoration of quality of life in Crohn's disease patients receiving antitumor necrosis factor agents.

BACKGROUND AND AIM: Crohn's disease (CD) impairs patients' health-related quality of life (HRQoL), therefore a goal of treatment is to improve their health. Recently, a more ambitious therapeutic target has been proposed, to reestablish patients' HRQoL to normal standards. There is no information on long-term prognostic value of restoring the health of patients with CD. Our aim was to determine if early restoration of HRQoL with antitumor necrosis factor (anti-TNF) agents is associated with long-term clinical remission. METHODS: Retrospective longitudinal study in patients with active CD treated with anti-TNF agents. Patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ)-36 at baseline and weeks 2, 6, 14, 28, and 52. Early restoration of health was defined as an IBDQ-36 score > 209 at week 14, and long-term clinical remission as a Cohn's disease activity index (CDAI) score < 150 maintained through week 52. RESULTS: Ninety-four patients were included. Sixty-three patients maintained long-term remission, with 47 (75%) of them achieving early restoration of HRQoL. Of the 31 patients who did not maintain long-term remission, only 4 (13%) restored their HRQoL early (P < 0.01). There was a strong negative correlation between the IBDQ-36 at week 14 and CDAI values at week 52 (rs = - 0.64, P < 0.01). Ninety-two percent of patients with early restoration of HRQoL maintained long-term remission versus 37% who did not restore their HRQoL (P < 0.01). To predict long-term remission, the cutoff point of 209 of the early IBDQ-36 had an area under the receiver operating characteristic (AUROC) curve of 0.87. CONCLUSION: Achieving early restoration of HRQoL with anti-TNF agents is associated with sustained long-term remission. This could be a therapeutic goal of treatment in clinical trials and daily practice.

Crosstalk between PI(4,5)P2and CK2 modulates actin polymerization during endocytic uptake.

A transient burst of actin polymerization assists endocytic budding. How actin polymerization is controlled in this context is not understood. Here, we show that crosstalk between PI(4,5)P2and the CK2 catalytic subunit Cka2 controls actin polymerization at endocytic sites. We find that phosphorylation of the myosin-I Myo5 by Cka2 downregulates Myo5-induced Arp2/3-dependent actin polymerization, whereas PI(4,5)P2cooperatively relieves Myo5 autoinhibition and inhibits the catalytic activity of Cka2. Cka2 and the PI(4,5)P2-5-phosphatases Sjl1 and Sjl2, the yeast synaptojanins, exhibit genetic interactions indicating functional redundancy. The ultrastructural analysis of plasma membrane invaginations in CK2 and synaptojanin mutants demonstrates that both cooperate to initiate constriction of the invagination neck, a process coupled to the remodeling of the endocytic actin network. Our data demonstrate a holoenzyme-independent function of CK2 in endocytic budding and establish a robust genetic, functional, and molecular link between PI(4,5)P2and CK2, two masters of intracellular signaling.

Questionnaries for measuring fatigue and its impact on health perception in inflammatory bowel disease.

INTRODUCTION: fatigue impacts perceived health, but its importance in inflammatory bowel disease is not known. OBJECTIVES: to define the applicability of the fatigue measurement questionnaires and analyze it in patients with Crohn´s disease and ulcerative colitis. MATERIAL AND METHODS: in a first phase, the psychometric properties of 3 fatigue measurement questionnaires were determined in 99 patients: Daily Fatigue Impact Scale, Fatigue Severity Scale, and Modified Fatigue Impact Scale. In a second phase, fatigue status and its relationship to disease and quality of life was determined in 127 patients and 69 healthy controls. RESULTS: the first part of the study showed the applicability of the questionnaires listed in inflammatory bowel disease, the Daily Fatigue Impact Scale (DFIS) having the best correlation with the quality of life and clinical activity. In the second phase, significantly higher levels of fatigue were observed in active disease than in disease in remission and healthy controls (p < 0,05). The severity of fatigue was significantly correlated with quality of life (r = -0.66 and -0.72 between IBDQ-9 and DFIS and in Crohn´s disease and ulcerative colitis, respectively) and with disease activity (r = 0.25 and Crohn´s disease and ulcerative colitis, respectively, p < 0.05). CONCLUSIONS: in inflammatory bowel disease, fatigue measurement questionnaires have good properties and show that fatigue is an important manifestation of the disease, which has a significant impact on quality of life of patients.

Cuestionarios de medida e impacto de la fatiga en la percepción de salud en la enfermedad inflamatoria intestinal / Questionnaires for measuring fatigue and its impact on health perception in inflammatory bowel disease

Introducción: la fatiga repercute en la salud percibida, pero se desconoce su relevancia en la enfermedad inflamatoria intestinal. Objetivos: definir la aplicabilidad de cuestionarios de medida de fatiga y analizarla en pacientes con enfermedad de Crohn y colitis ulcerosa. Material y métodos: en una primera fase, en 99 pacientes se determinaron las propiedades psicométricas de 3 cuestionarios de medida de fatiga: Escala del Impacto Diario de Fatiga, Escala de Gravedad de la Fatiga y Escala Modificada del Impacto de Fatiga. En una segunda fase, se determinó el estado de fatiga y su relación con la enfermedad y la calidad de vida en 127 pacientes y 69 controles sanos. Resultados: la primera parte del estudio, demostró la aplicabilidad de los cuestionarios citados en la enfermedad inflamatoria intestinal, siendo la Escala del Impacto Diario de Fatiga (EIDF) el de mejor correlación con la calidad de vida y la actividad clínica. En la segunda fase, se objetivaron unos niveles significativamente superiores de fatiga en la enfermedad activa que en la enfermedad en remisión y los controles sanos (p < 0,05). La intensidad de la fatiga se correlacionó de forma significativa con la calidad de vida (r = -0,66 y -0,72 entre el IBDQ- 9 y EIDF en enfermedad de Crohn y colitis ulcerosa respectivamente) y con la actividad de la enfermedad (r = 0,25 y 0,33 en la enfermedad de Crohn y colitis ulcerosa respectivamente, p < 0,05). Conclusiones: en la enfermedad inflamatoria intestinal los cuestionarios de medida de fatiga tienen propiedades adecuadas y demuestran que la fatiga es una manifestación importante de la enfermedad, que repercute de forma significativa en la calidad de vida de los pacientes(AU)

Introduction: fatigue impacts perceived health, but its importance in inflammatory bowel disease is not known. Objectives: to define the applicability of the fatigue measurement questionnaires and analyze it in patients with Crohn’s disease and ulcerative colitis. Material and methods: in a first phase, the psychometric properties of 3 fatigue measurement questionnaires were determined in 99 patients: Daily Fatigue Impact Scale, Fatigue Severity Scale, and Modified Fatigue Impact Scale. In a second phase, fatigue status and its relationship to disease and quality of life was determined in 127 patients and 69 healthy controls. Results: the first part of the study showed the applicability of the questionnaires listed in inflammatory bowel disease, the Daily Fatigue Impact Scale (DFIS) having the best correlation with the quality of life and clinical activity. In the second phase, significantly higher levels of fatigue were observed in active disease than in disease in remission and healthy controls (p < 0,05). The severity of fatigue was significantly correlated with quality of life (r = -0.66 and -0.72 between IBDQ-9 and DFIS and in Crohn’s disease and ulcerative colitis, respectively) and with disease activity (r = 0.25 and Crohn’s disease and ulcerative colitis, respectively, p < 0.05). Conclusions: in inflammatory bowel disease, fatigue measurement questionnaires have good properties and show that fatigue is an important manifestation of the disease, which has a significant impact on quality of life of patients(AU)

Mucosal healing restores normal health and quality of life in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a debilitating immune disorder that impairs function and health-related quality of life (HRQOL). A goal of IBD treatment is mucosal healing, but it is not known whether it achieves normalization of the patients' perception of health. This can be assessed by using a cut-off scoring threshold of the Inflammatory Bowel Disease Questonnaire-36 (IBDQ-36). AIMS: To determine whether patients with Crohn's disease (CD) and ulcerative colitis (UC) in clinical remission and with mucosal healing normalize their HRQOL. METHODS: This is a multicentric, prospective, observational, cross-sectional study of patients who are in stable clinical remission and having mucosal healing. Patients completed the IBDQ-36, the EuroQol-5D, and the Daily Fatigue Impact Scale fatigue questionnaires. Complete restoration of health was believed to have occurred when the global score in the IBDQ-36 was at least 209 points. RESULTS: A total of 115 patients (48 with CD, 67 with UC) were included. The median activity index (the Harvey-Bradshaw or the colitis activity index) was 1.0 and the median endoscopic index (Simple Endoscopic Score for Crohn's disease or Mayo) was 0. Eighty percent of the patients (79% in CD and 82% in UC patients, P=NS) normalized their HRQOL. Type of treatment was not related to normalization of HRQOL. The lack of restoration of health was significantly related to fatigue and anxiety/depression. CONCLUSION: Mucosal healing is associated with a normalization of the perception of health by most IBD patients independently of treatment. However, a significant group of patients do not achieve restoration of HRQOL, which reinforces the necessity of a global care addressed to all patient concerns to achieve patients' complete health restoration.

Restoration of quality of life of patients with inflammatory bowel disease after one year with antiTNFα treatment.

BACKGROUND: Inflammatory bowel disease impairs patients' health related quality of life (HRQOL). AntiTNFα agents control disease activity effectively. An ambitious goal of treatment is to achieve the normalization of health. This can be assessed by using a cut-off scoring threshold of the IBDQ-36 questionnaire. It has not been established if antiTNFα treatment is able to restore to normal patients' HRQOL. AIMS: To determine whether patients with Crohn's disease (CD) and ulcerative colitis (UC) in clinical remission after one year treatment with antiTNFα agents achieve normalization of their HRQOL. METHODS: Observational and cross-sectional study in patients treated with antiTNFα for one year and in sustained clinical remission. Patients completed the specific questionnaire IBDQ-36. Complete restoration of health was considered achieved when global score of IBDQ-36 was higher than 209 points. RESULTS: 54 patients (43 with CD and 11 with UC) were included. Thirty patients received adalimumab and 24 infliximab. Median global score of the IBDQ-36 was 231, without differences between CD and UC (228 vs 235 respectively, p=ns). Normalization of HRQOL was achieved in all 11 UC patients and in 29 out of 43 CD patients (67%). In our sample population, restoration of health was significantly more frequent in UC than in CD (p<0.05). CONCLUSIONS: One-year clinical remission induced by antiTNFα treatment restores perception of health to normal in most patients with IBD.

Statistical errors in microleakage studies in operative dentistry. A survey of the literature 2001-2009.

The aim of this study was to assess the literature on microleakage of direct restorations in operative dentistry indexed in the ISI Web of Science, in order to assess the robustness of the statistical methodology used. Our database included 226 scientific papers (published between 2001 and 2009 in 22 journals) from the journal citation report categories 'Dentistry, Oral Surgery and Medicine' and 'Materials Science, Biomaterials'. We reviewed all articles to find potential mistakes that are commonly made at different stages in the scientific research process. Microleakage was assessed quantitatively in 50 (22.2%) studies and qualitatively in 176 (77.8%) studies. In all studies reviewed the statistical methods used were appropriate for the category attributed to the outcome variable, but in 13% of the total, the chi-square test or parametric methods were inappropriately used afterwards. When the appropriate statistical methods were applied in studies that had originally employed inappropriate methods to analyse their data, and in which the authors provided raw data, an alteration of the conclusions was necessary in 15.4% of these re-analysed studies. This survey also showed that the statistical methodology applied varies considerably for similar experimental designs. This could have an effect on statistical results; hence, a more standardized methodology should be implemented.

Calmodulin dissociation regulates Myo5 recruitment and function at endocytic sites.

Myosins-I are conserved proteins that bear an N-terminal motor head followed by a Tail Homology 1 (TH1) lipid-binding domain. Some myosins-I have an additional C-terminal extension (C(ext)) that promotes Arp2/3 complex-dependent actin polymerization. The head and the tail are separated by a neck that binds calmodulin or calmodulin-related light chains. Myosins-I are known to participate in actin-dependent membrane remodelling. However, the molecular mechanisms controlling their recruitment and their biochemical activities in vivo are far from being understood. In this study, we provided evidence suggesting the existence of an inhibitory interaction between the TH1 domain of the yeast myosin-I Myo5 and its C(ext). The TH1 domain prevented binding of the Myo5 C(ext) to the yeast WIP homologue Vrp1, Myo5 C(ext)-induced actin polymerization and recruitment of the Myo5 C(ext) to endocytic sites. Our data also indicated that calmodulin dissociation from Myo5 weakened the interaction between the neck and TH1 domains and the C(ext). Concomitantly, calmodulin dissociation triggered Myo5 binding to Vrp1, extended the myosin-I lifespan at endocytic sites and activated Myo5-induced actin polymerization.

Multilocus sequence typing of oenological Saccharomyces cerevisiae strains.

This study describes the application of a multilocus sequence typing (MLST) analysis for molecular discrimination at the strain level of Spanish wine yeast strains. The discrimination power of MLST is compared to mitochondrial RFLP analysis. Fragments of the ADP1, ACC1, RPN2, GLN4, and ALA1 genes were amplified by PCR from chromosomal DNA of 18 wine Saccharomyces cerevisiae strains. Ten polymorphic sites were found in the five loci analyzed showing 13 different genotypes, with 11 of them represented by only one strain. RFLP analysis of the same 18 wine yeast strains showed seventeen different mitochondrial patterns. Phylogenetic relationships among the strains analyzed, inferred by MLST data, showed wine isolates of S. cerevisiae as a rather homogeneous group. The discrimination potential of mitochondrial RFLP analysis was superior to the MLST scheme used in this work. However, MLST analysis allowed an easy construction of reliable phylogenetic trees. MLST analysis offers the possibility of typing wine S. cerevisiae strains simultaneously to the study of the genetic relationship among them.

Comparación de los efectos de carvedilol y bisoprolol sobre la clase funcional y la función ventricular en pacientes con insuficiencia cardiaca congestiva / Comparative effects of carvedilol and bisoprolol on functional class and ventricular function in patients with heart failure

Ensayos clínicos demuestran que el bloqueo beta produce mejoría hemodinámica y sintomática en pacientes con insuficiencia cardíaca y reduce de manera importante la mortalidad y reingresos hospitalarios. Enrolamos 480 pacientes con insuficiencia cardíaca con fracción de eyección igual o menor de 35 por ciento en clase funcional I a III de la Asociación Americana del Corazón en un programa estratificado para recibir dosis crecientes de Carvedilol comparada con Bisoprolol y medir su efecto sobre la capacidad funcional y función ventricular determinada por ecocardiograma. Grupo Carvedilol: 18 pacientes en clase funcional III, 176 en clase II y 126 en clase I. La fracción de eyección mejoró 1 a 10 por ciento. Grupo Bisoprolol: 28 pacientes en clase funcional III, 82 en clase II y 50 en clase I. La fracción de eyección mejoró 2 a 6 por ciento. Ambos medicamentos producen mejoría en la clase funcional, evitan progresión de síntomas y mejoran fracción de eyección. Los efectos de Carvedilol sobre la mejoría pueden ser diferentes al observado con Bisoprolol debido a sus propiedades adicionales: bloquea receptores adrenérgicos alfa-1 y beta-2, reduce niveles cardiacos de norepinefrina, no aumenta los receptores beta cardíacos y tiene efectos antioxidantes protectores contra la pérdida de miocitos que caracterizan el progreso de la insuficencia cardíaca