Estudios de trasplante de microbiota fecal en síndrome metabólico, obesidad y diabetes, ¿dónde nos encontramos?

Fundamento: El trasplante de microbiota fecal (FMT) consiste en la transferencia de las heces de un donante sano a otro paciente con el objetivo de cambiar o restablecer la composición y función de su microbiota. Su única aplicación clínica actualmente aceptada es el tratamiento de infección recurrente por Clostridium difficile. No obstante, se está estudiando su empleo en enfermedades como la enfermedad inflamatoria intestinal, el autismo y las enfermedades metabólicas. En este último grupo encontramos el síndrome metabólico, la obesidad y la diabetes tipo 2, tres enfermedades relacionadas entre sí y cada vez más prevalentes en nuestro tiempo. Las tres se caracterizan por cursar con una disbiosis de la microbiota intestinal y en este contexto surge la idea del empleo del FMT para su tratamiento. El objetivo de este Trabajo de Fin de Grado es conocer los estudios que se han realizado para evaluar el efecto del FMT con donantes humanos en síndrome metabólico, obesidad y diabetes. Metodología: Se ha llevado a cabo una revisión sistemática utilizando la base de datos PubMed, realizando tres búsquedas por términos MeSH relacionando “fecal microbiota transplantation” con “obesity”, “diabetes” y “metabolic syndrome” y aplicando las metodologías PRISMA y PICO para seleccionar los resultados de interés. Resultados: Se han valorado siete artículos de intervención que evalúan el efecto del FMT con donantes humanos y receptores humanos o animales. Existen pocos resultados concluyentes sobre el efecto del FMT en la microbiota del receptor, debido a que los artículos son heterogéneos y valoran parámetros diferentes. Conclusión: El FMT supone un avance en el conocimiento de la relación entre la microbiota y las enfermedades metabólicas y, conforme obtenemos más información de los estudios de intervención realizados, nos acercamos a la posibilidad de aplicar este procedimiento en el tratamiento de otras enfermedades además de la infección por Clostridium difficile.Background: The fecal microbiota transplantation (FMT) consists in the transfer of gastrointestinal microbiota from a healthy individual to another in order to change or restore the composition and function of the recipient’s microbiota. Nowadays this method is only accepted as a therapeutic option for Clostridium difficile infection. However, there are many studies evaluating its applicability in other diseases such as inflammatory bowel disease, irritable bowel syndrome, autism and metabolic disorders, like obesity, diabetes or metabolic syndrome. In this project we are focusing on these three metabolic diseases, which incidence has increased rapidly worldwide. They are characterized by a dysbiosis of the intestinal microbiota and that is the reason why the idea of fecal microbiota transplantation as a possible therapeutic option arises. The main objective of this project is to analyse the currently available studies that evaluate the effect of fecal microbiota transplantation, from humans to either humans or animals, in the physiopathology of obesity, diabetes and metabolic syndrome. Methodology: A systematic review was carried out using the PubMed database with three independent searches using MeSH terms relating “fecal microbiota transplantation” and “obesity”, “diabetes” and “metabolic syndrome”. PRISMA and PICO methodologies were applied to select the studies of interest. Results: Seven articles from intervention studies that evaluate FMT with human donors and human or animal recipients have been included in this systematic review. To date, there are few conclusive results due to the heterogeneity of the studies. Conclusion: New studies on FMT represent an advance in the knowledge of the relationship between the microbiota and metabolic disorders. As we obtain more information regarding the applicability of this technique and its effect, we approach the possibility of applying it in the treatment of other diseases a part from infection by Clostridium difficile

Mediterranean lifestyle index and 24-h systolic blood pressure and heart rate in community-dwelling older adults

Specifc foods, nutrients, dietary patterns, and physical activity are associated with lower blood pressure (BP) and heart rate (HR), but little is known about the joint efect of lifestyle factors captured in a multidimensional score. We assessed the association of a validated Mediterranean-lifestyle (MEDLIFE) index with 24-h-ambulatory BP and HR in everyday life among community-living older adults. Data were taken from 2,184 individuals (51% females, mean age: 71.4 years) from the SeniorsENRICA-2 cohort. The MEDLIFE index consisted of 29 items arranged in three blocks: 1) Food consumption; 2) Dietary habits; and 3) Physical activity, rest, and conviviality. A higher MEDLIFE score (0–29 points) represented a better Mediterranean lifestyle adherence. 24-h-ambulatory BP and HR were obtained with validated oscillometric devices. Analyses were performed with linear regression adjusted for the main confounders. The MEDLIFEhighest quintile (vs Q1) was associated with lower nighttime systolic BP (SBP) (-3.17 mmHg [95% CI: -5.25, -1.08]; p-trend=0.011), greater nocturnal-SBP fall (1.67% [0.51, 2.83]; p-trend=0.052), and lower HR (-2.04 bpm [daytime], -2.33 bpm [nighttime], and -1.93 bpm [24-h]; all p-trend<0.001). Results were similar for each of the three blocks of MEDLIFE and by hypertension status (yes/no). Among older adults, higher adherence to MEDLIFE was associated with lower nighttime SBP, greater nocturnal-SBP fall, and lower HR in their everyday life. These results suggest a synergistic BP-related protection from the components of the Mediterranean lifestyle. Future studies should determine whether these results replicate in older adults from other Mediterranean and non-Mediterranean countriesThis work was supported by FIS grants 19/319, 20/00896, and 22/1164 from the Carlos III Health Institute, the Secretary of R+D+I, and the European Regional Development Fund/European Social Fund; and by International; REACT EU Program. Comunidad de Madrid and European Regional Development Fund (ERDF), European Union: FACINGLCOVID-CM project, Comunidad de Madrid and European Regional Development Fund (ERDF), European Union. MSP holds a Ramón y Cajal contract (RYC2018–025069-I) from the Spanish Ministry of Science, Innovation and Universitie

Novel N,N' -Disubstituted Acylselenoureas as Potential Antioxidant and Cytotoxic Agents

Selenium compounds are pivotal in medicinal chemistry for their antitumoral and antioxidant properties. Forty seven acylselenoureas have been designed and synthesized following a fragment-based approach. Different scaffolds, including carbo- and hetero-cycles, along with mono- and bi-cyclic moieties, have been linked to the selenium containing skeleton. The doseand time-dependent radical scavenging activity for all of the compounds were assessed using the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. Some of them showed a greater radical scavenging capacity at low doses and shorter times than ascorbic acid. Therefore, four compounds were evaluated to test their protective effects against H2O2-induced oxidative stress. One derivative protected cells against H2O2-induced damage, increasing cell survival by up to 3.6-fold. Additionally, in vitro cytotoxic activity of all compounds was screened against several cancer cells. Eight compounds were selected to determine their half maximal inhibitory concentration (IC50) values towards breast and lung cancer cells, along with their selectivity indexes. The breast cancer cells turned out to be much more sensitive than the lung. Two compounds (5d and 10a) stood out with IC50 values between 4.2 µM and 8.0 µM towards MCF-7 and T47D cells, with selectivity indexes greater than 22.9. In addition, compound 10b exhibited dual antioxidant and cytotoxic activities. Although further evidence is needed, the acylselenourea scaffold could be a feasible frame to develop new dual agents

Association between an oxidative balance score and mortality: a prospective analysis in the SUN cohort

We aimed to prospectively investigate the association of an overall oxidative balance score (OBS) with all-cause death and cause-specifc mortality among participants in the Seguimiento Universidad de Navarra (SUN) Study, a Mediterranean cohort of Spanish graduates. Methods Using baseline information on 12 a priori selected dietary and non-dietary lifestyle pro- and antioxidants exposures—vitamins C and E, β-carotenes, selenium, zinc, heme iron, polyphenols, total antioxidant capacity, body mass index, alcohol, smoking, and physical activity—we constructed an equally weighted OBS categorized into quartiles, with higher scores representing greater antioxidant balance. Cox proportional hazards models were ftted to evaluate the association between the OBS and mortality. Results A total of 18,561 participants (mean [SD] age, 38.5 [12.4] years; 40.8% males) were included in the analysis. During a median follow-up of 12.2 years (interquartile range 8.3–14.9), 421 deaths were identifed, including 80 deaths from cardiovascular disease (CVD), 215 from cancer, and 126 from other causes. After adjustment for potential confounders, the hazard ratios and 95% confdence interval (CIs) between the highest quartile (predominance of antioxidants) vs. the lowest quartile (reference category) were 0.35 (95% CI 0.22–0.54, P-trend<0.001) for all-cause mortality, 0.18 (95% CI 0.06–0.51, P-trend=0.001) for CVD mortality, 0.35 (95% CI 0.19–0.65, P-trend=0.002) for cancer mortality, and 0.45 (95% CI 0.20–1.02, P-trend=0.054) for other-cause mortality. Conclusion Our fndings suggest a strong inverse association between the OBS and all-cause, CVD, and cancer mortality. Individuals exposed to both antioxidant dietary and lifestyle factors may potentially experience the lowest mortality riskOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The SUN Project has received funding from the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, and G03/140), the Navarra Regional Government (27/2011, 45/2011, 122/2014), the Government Delegation for the National Drug Plan (2020/ 021) and the University of Navarra. Maria Soledad Hershey receives ERC traininggrant support (T42 OH008416

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Volteando la tortilla. Género y maíz en la alimentación actual de México.

Ante escenarios complejos, patriarcales y desoladores que dejan ver el neoliberalismo, la globalización agroalimentaria, el calentamiento global y las contaminaciones de granos nativos por la imposición de transgénicos, nos cuestionamos si existen algunas alternativas para preservar el maíz nativo como un recurso multiestratégico (alimentario, económico, cultural, ecológico y tecnológico) tomando en cuenta las condiciones actuales de desigualdades sociales de género, etnia, clases y edad que predominan en el campo mexicano. Para responder a algunos cuestionamientos, este libro presenta algunas alternativas a través de diversas experiencias femeninas y de relaciones de género en torno al maíz y la alimentación. Todas ellas muestran que es posible construir una masa crítica para salvaguardar el maíz nativo bajo esas condiciones desoladoras, pero siempre y cuando se “voltee la tortilla”, metáfora que da pie al inicio de otra realidad humanizada y en sincronía con la naturaleza.Proyecto realizado con financiamiento Conacy

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Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Unstable distal radius fracture: our experience in osteosynthesis with volar variable-angle locking plate

OBJECTIVE: assess the functional, subjective and radiological results obtained in patients treated with variable-angle locking plate for unstable distal radius fracture and compare these results with current studies. PATIENTS AND METHOD: From October of 2008 to July of 2011, 20 patients were included who had undergone intervention using the volar approach to the Flexor Carpi Radialis. The average follow up was 18 months. Both clinical and radiological results were analyzed. The Mayo Wrist Score and DASH questioner were used. RESULTS: The average age was 50 years; 50% men and 50% women. The consolidation of the fracture was verified in all cases. An average volar angle was obtained of 5º, radial inclination of 19º, radial height of 10.5 mm, and ulnar variance of -1 mm. The clinical assessment revealed an average dorsal flexion of 75º, palm flexion of 70º, supination of 75º and pronation of 73 º. The results for the DASH questionnaire showed an average of 17.8 and 82.7 for the Mayo Wrist Score. CONCLUSIONS: Our experience has provided some good results, both in functional and subjective as well as radio logical terms, similar to those found in studies with implants from the same generation.YesOBJETIVO: evaluar los resultados funcionales, subjetivos y radiológicos obtenidos en los pacientes tratados con placa volar de ángulo variable para fracturas inestables de radio distal y compararlos con estudios actuales. PACIENTES Y MÉTODOS: De octubre de 2008 a julio de 2011, se incluyeron 20 pacientes en los que se realizó abordaje volar de muñeca lateral al Flexor Carpi Radialis. Tuvieron un seguimiento promedio de 18 meses. Se evaluaron resultados clínicos y radiológicos, Mayo Wrist Score y cuestionario DASH. RESULTADOS: El promedio de edad fue de 50 años, 50% hombres y 50% mujeres. Se constató la consolidación de la fractura en todos los casos. Se obtuvo un promedio de angulación volar de 5º, inclinación radial de 19º, altura radial de 10,5mm, varianza cubital de -1mm. La valoración clínica arrojó un promedio de flexión dorsal de 75º, flexión palmar de 70º, supinación de 75º, pronación de 73º. Los resultados del cuestionario DASH mostraron un promedio de 17,8 y de 82,7 en cuando Mayo Wrist Score. CONCLUSIONES: Nuestra experiencia ha arrojado buenos resultados tanto funcionales y subjetivos, como radiológicos, similares a los encontrados en estudios con implantes de la misma generación

Post-Stroke Rehabilitation: A Necessary Step

A stroke is defined by the abrupt and sudden onset of neurological signs and symptoms that occur due to a disorder in cerebral blood circulation. Cerebrovascular diseases are a well-known cause of morbidity and mortality, being the second cause of mortality and disability throughout the world. Stroke treatment has improved substantially in recent years with the implementation of stroke units and revascularization therapies. The role of rehabilitation is to help improve deficits to regain functionality and to define the needs and care in patients with permanent disabilities. Stroke rehabilitation must start early and intensively and it must be carried out by a multidisciplinary team made up of neurologists, rehabilitation doctors, nurses, physiotherapists, occupational therapists, speech therapists, neuropsychologists, neurophysiologists, and social workers. Patients and families should be actively involved with this team, if possible, from the beginning and throughout the rehabilitation process. Functional recovery through comprehensive rehabilitation allows patients to remain in their usual environment, perform their work duties and carry out activities of daily life by themselves, reducing the need for institutionalization in long-term care facilities