Growth differentiation factor 11 (GDF11) - a promising anti-ageing factor - is highly concentrated in platelets.

Recent research suggests that growth differentiation factor 11 (GDF11) could reverse age-related diseases and that its blood concentration decreases with age. This poses plasma from young donors as a therapeutic GDF11 source to treat age-related diseases. In addition, the tissue source of circulating GDF11 remains unknown. We analysed GDF11 levels in paired samples of serum, plasma and platelet lysate (PL) from 23 volunteers. Plasma and PL were collected by plateletpheresis. Here, we show that GDF11 is highly concentrated in platelets and that the circulating levels reported in previous studies could be biased as a result of serum sample manipulation.

Obesity is associated with more activated neutrophils in African American male youth.

BACKGROUND: There is emerging evidence suggesting the role of peripheral blood leukocytes in the pathogenesis of obesity and related diseases. However, few studies have taken a genome-wide approach to investigating gene expression profiles in peripheral leukocytes between obese and lean individuals with the consideration of obesity-related shifts in leukocyte types. METHOD: We conducted this study in 95 African Americans (AAs) of both genders (age 14-20 years, 46 lean and 49 obese). Complete blood count with differential test (CBC) was performed in whole blood. Genome-wide gene expression analysis was obtained using the Illumina HumanHT-12 V4 Beadchip with RNA extracted from peripheral leukocytes. Out of the 95 participants, 64 had neutrophils stored. The validation study was based on real-time PCR with RNA extracted from purified neutrophils. RESULTS: CBC test suggested that, in males, obesity was associated with increased neutrophil percentage (P=0.03). Genome-wide gene expression analysis showed that, in males, the majority of the most differentially expressed genes were related to neutrophil activation. Validation of the gene expression levels of ELANE (neutrophil elastase) and MPO (myeloperoxidase) in purified neutrophils demonstrated that the expression of these two genes--important biomarkers of neutrophils activation--were significantly elevated in obese males (P=0.01 and P=0.02, respectively). CONCLUSION: The identification of increased neutrophil percentage and activation in obese AA males suggests that neutrophils have an essential role in the pathogenesis of obesity-related disease. Further functional and mechanistic studies on neutrophils may contribute to the development of novel intervention strategies reducing the burden associated with obesity-related health problems.

Experience with anidulafungin in patients with allogeneic hematopoietic stem cell transplantation and graft-versus-host disease.

BACKGROUND: It is well known that both acute and chronic graft-versus-host disease (GVHD) are associated with invasive fungal disease (IFD). Because the galactomannan antigen diagnostic test has low specificity and sensitivity outside of the neutropenic period, many institutions use posaconazole or voriconazole for IFD prophylaxis during GVHD treatment. Moreover, several factors, mainly hepatic impairment, can limit the use of extended spectrum azoles, both in prophylaxis or treatment. METHODS: We retrospectively analyzed 25 patients with allogeneic hematopoietic stem cell transplantation (HSCT) and GVHD - grade III-IV acute GHVD (n = 15), progressive chronic GVHD (n = 7), and "overlap" GVHD (n = 3) - who received intravenous anidulafungin (200 mg on day 1, followed by 100 mg once daily). If necessary, anidulafungin treatment was followed by oral administration of 200 mg voriconazole twice a day or 200 mg posaconazole 3 times daily until patients were considered not at risk for IFD. RESULTS: Twenty-one patients (85%) received anidulafungin as prophylaxis and 5 patients (15%) received it as treatment. Median duration of intravenous anidulafungin administration was 8 days (range 6-17). Seven patients (28%) presented mild adverse effects, with no significant interactions with calcineurin inhibitors. Sequentially, 4 patients received voriconazole and 6 posaconazole. Two patients (8%) developed IFD after anidulafungin withdrawal: 1 with Candida albicans and the other with Mucor, 8 and 5 days after withdrawal, respectively. CONCLUSIONS: Our results are of interest owing to the absence of data in the literature on anidulafungin use in HSCT patients with GVHD, and suggest that anidulafungin, because of its spectrum, pharmacological profile, low toxicity, and absence of interactions with immunosuppressants, could be a drug of choice in this setting.

Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: a prospective non-randomized controlled trial.

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. STUDY: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.

Report by the Spanish Foundation of the Brain on the social impact of Alzheimer disease and other types of dementia. / Informe de la Fundación del Cerebro. Impacto social de la enfermedad de Alzheimer y otras demencias.

INTRODUCTION: Knowledge of the socioeconomic impact of dementia-related disorders is essential for appropriate management of healthcare resources and for raising social awareness. METHODS: We performed a literature review of the published evidence on the epidemiology, morbidity, mortality, associated disability and dependence, and economic impact of dementia and Alzheimer disease (AD) in Spain. CONCLUSIONS: Most population studies of patients older than 65 report prevalence rates ranging from 4% to 9%. Prevalence of dementia and AD is higher in women for nearly every age group. AD is the most common cause of dementia (50%-70% of all cases). Dementia is associated with increased morbidity, mortality, disability, and dependence, and results in a considerable decrease in quality of life and survival. Around 80% of all patients with dementia are cared for by their families, which cover a mean of 87% of the total economic cost, resulting in considerable economic and health burden on caregivers and loss of quality of life. The economic impact of dementia is huge and difficult to evaluate due to the combination of direct and indirect costs. More comprehensive programmes should be developed and resources dedicated to research, prevention, early diagnosis, multidimensional treatment, and multidisciplinary management of these patients in order to reduce the health, social, and economic burden of dementia.

The role of a computed tomography-based image registered navigation system for natural orifice transluminal endoscopic surgery: a comparative study in a porcine model.

BACKGROUND AND STUDY AIMS: Most natural orifice transluminal endoscopic surgery (NOTES) procedures have been performed in animal models through the anterior stomach wall, but this approach does not provide efficient access to all anatomic areas of interest. Moreover, injury of the adjacent structures has been reported when using a blind access. The aim of the current study was to assess the utility of a CT-based (CT: computed tomography) image registered navigation system in identifying safe gastrointestinal access sites for NOTES and identifying intraperitoneal structures. METHODS: A total of 30 access procedures were performed in 30 pigs: anterior gastric wall (n = 10), posterior gastric wall (n = 10), and anterior rectal wall (n = 10). Of these, 15 procedures used image registered guidance (IR-NOTES) and 15 procedures used a blind access (NOTES only). Timed abdominal exploration was performed with identification of 11 organs. The location of the endoscopic tip was tracked using an electromagnetic tracking system and was recorded for each case. Necropsy was performed immediately after the procedure. The primary outcome was the rate of complications; secondary outcome variables were number of organs identified and kinematic measurements. RESULTS: A total of 30 animals weighting a mean (± SD) of 30.2 ± 6.8 kg were included in the study. The incision point was correctly placed in 11 out of 15 animals in each group (73.3 %). The mean peritoneoscopy time and the number of properly identified organs were equivalent in the two groups. There were eight minor complications (26.7 %), two (13.3 %) in the IR-NOTES group and six (40.0 %) in the NOTES only group ( P = n. s.). Characteristics of the endoscope tip path showed a statistically significant improvement in trajectory smoothness of motion for all organs in the IR-NOTES group. CONCLUSION: The image registered system appears to be feasible in NOTES procedures and results from this study suggest that image registered guidance might be useful for supporting navigation with an increased smoothness of motion.

Effect of hypoxia on caveolae-related protein expression and insulin signaling in adipocytes.

Obesity is characterized by hypertrophy and hyperplasia of adipose tissue, which have been related to the development of hypoxia and insulin resistance. On the other hand, caveolin-1 (Cav-1), one of the main proteins of caveolae, promotes insulin receptor (IR) phosphorylation and the subsequent activation of insulin signaling. In this work we investigated the effect of hypoxia on Cav-1 regulation and the status of insulin signaling in 3T3-L1 adipocytes. Our results showed that hypoxia inhibited adipogenesis and insulin signaling in adipocytes. Furthermore, 48 h of hypoxia reduced insulin-induced glucose uptake while increased basal glucose uptake. This result was consistent with the upregulation of glucose transporter GLUT1 and the downregulation of GLUT4, which also showed defective translocation to plasma membrane when adipocytes were stimulated with insulin. In addition, the expression of caveolae-related proteins was reduced by hypoxia and chromatin immunoprecipitation assay demonstrated that Cav-1 transcription was directly regulated by HIF-1. These results strengthen the role of caveolae in insulin signaling and help to explain adipocyte response to hypoxia.

Estudio de brote COVID en centro residencial de mayores (CRM) de Alconchel: comparativa entre pacientes antes y después de la COVID / Study of the COVID outbreak in the elderly residential centre (CRM) of Alconchel: comparison between patients before and after COVID

JUSTIFICACIÓN: el 4,1 % de la población mayor en España vive en residencias; allí son más vulnerables a infecciones graves por COVID sufriendo altas tasas de mortalidad. En octubre del 2020 aparece un brote en el CRM de Alconchel Desde la farmacia ofrecemos el servicio de SPD y SFT. (AU)

Implantación del servicio de SPD y seguimiento farmacoterapéutico en centro residencial de mayores de Alconchel durante un brote por COVID-19 / Implementation of the SPD service and pharmacotherapeutic monitoring in a residential centre for the elderly in Alconchel during an outbreak of COVID-19

JUSTIFICACIÓN: el 4,1 % de la población mayor vive en residencias. Las personas que viven en estos centros son más vulnerables a las infecciones graves por SARS-CoV-2 y tienen altas tasas de mortalidad. El 31 de octubre de 2020 se detecta un brote en el centro residencial de mayores (CRM) de Alconchel. Desde la farmacia les ofrecemos el servicio de SPD y SFT.OBJETIVOS:• Ayudar a trabajadores y residentes del CRM con la organización de la medicación durante el brote de COVID.•Realizar RUM a residentes.•Caracterización de pacientes durante el brote y tras él.•Demostrar la utilidad del SPD en CRM.MATERIAL Y MÉTODOS: contactamos con el CRM para ofrecer el servicio de SPD y AF similar al que prestamos en la AFD. Realizamos un RUM. Contactamos telefónicamente con el MAP para subsanar PRM detectados. Elaboramos SPD según PNT de la guía de SEFAC-SEMERGEN. Análisis de datos con LibreOffice Calc.RESULTADOS: detectamos problemas de conservación e identificación en los medicamentos comprimidos cortados dentro de envase sin lotes y sin caducidad, envases caducados y PRM: pautas incorrectas, interacciones y duplicidades en 5 de 15 usuarios. Durante el brote hay 16 residentes (9 mujeres y 7 hombres), con 85,31 años de media. Dan positivo por COVID mas del 71 % de auxiliares y el 100 % de residentes; el 56 % ingresa en el hospital. El 25 % fallece. De los que superan la enfermedad el 1 7 % tiene secuelas. Tras el brote de COVID instauramos el servicio SPD en CRM. Actualmente hay 12 residentes con 85 años de media.CONCLUSIONES•Reducimos la carga de trabajo al personal auxiliar.•Se subsanan problemas de conservación e identificación de medicamentos y 7 PRM a nivel individual•El 71 % de las auxiliares y el 100 % de los residentes dieron positivo. Más del 56 % de los residentes ingresa en el hospital, el 25 % fallece. El 17 % de los que superan el COVID tienen secuelas. (AU)

Adaptación del tratamiento farmacológico de paciente con SPD tras sufrir accidente cardiovascular (ACV) / Adaptation of the pharmacological treatment of patients with SPD after suffering a cardiovascular accident (CVA)

PRESENTACIÓN: mujer de 87 años vive junto con su marido. Desde 2019 se encuentra en el programa de AFD del ayuntamiento de Alconchel. Presenta 11 problemas de salud (PS), toma 14 medicamentos, uno de ellos de uso hospitalario y tratamiento dietoterápico. El 6 de febrero de 2022, sufre un ACV, recibiendo el alta el 25 de febrero.EVALUACIÓN: se realiza conciliación del tratamiento con el informe de alta; suspenden triflusal e indapamida y prescriben insulina glargina; resto tratamiento sin cambios. Se recomienda dieta triturada y toma de líquido con espesantes.INTERVENCIÓN: realizamos RUM tras alta hospitalaria; comprobando con fichas técnicas (FT) y departamentos técnicos (DT) de los laboratorios la posibilidad de triturar los comprimidos porque presenta problemas de deglución:• Bisoprolol , alprazolam , simvastatina, sertralina y torasemida: están adaptados.• Vivace y tesavel: según FT no adaptado, tras consultar con el DT dan su aprobación.Todos podemos pulverizarlos y dispersarlos en 10 ml de agua.• Omeprazol: adaptado; recomendamos abrir la cápsula suspender gránulos en medio vaso de liquidos o alimentos blandos. Los gránulos no deben masticarse ni triturarse. Administrarlo inmediatamente, preferiblemente en ayunas.• Tramadol/paracetamol: no adaptado; sugerimos cambiarlo a bucodispersable.• Cinacalcet: No adaptado; tras consultar con el DT, no se pueden partir ni triturar. La cubierta es entérica. Su uso partido, triturado o reformulado sólo se ha descrito para derivar dosis atípicas y se han informado principalmente en pediatría.RESULTADOS: tras hablar con el MAP:• Seguir utilizando el tramadol/paracetamol comprimidos; triturarlos ya que los tolerará mejor que el bucodispersable. (AU)

Efficacy and safety of a combination of hyaluronic acid, chondroitin sulfate, and poloxamer 407 as a submucosal injection solution for endoscopic resection: pilot study on a swine model.

BACKGROUND AND AIMS: Endoscopic resection techniques require use of submucosal injection. The aim of this study was to assess a new solution that combines hyaluronic acid, chondroitin sulfate, and poloxamer 407 for submucosal injection. METHODS: A total of 48 gastric submucosal cushions were created in fresh porcine stomachs using gelafundin (n = 16) or the new solution diluted at 50 % (n = 16), or 80 % (n = 16). The duration of mucosal elevation was measured. In an in vivo model, 10 gastric submucosal cushions were created by injecting 2 mL of the new solution at 80 % and the animal was euthanized 30 minutes after the last injection. RESULTS: Submucosal cushions with the new solution at 80 % and 50 % concentration lasted longer than with gelafundin (23.13 ±â€Š15.57, 13.1 ±â€Š6.6, 3.94 ±â€Š1.53 minutes, respectively; P  = 0.000). In the in vivo study, no damage or necrosis was observed in the mucosa or muscularis propria. CONCLUSION: The combination of hyaluronic acid, chondroitin sulfate, and poloxamer 407 produces a long-lasting submucosal cushion and does not seem to induce acute damage in the tissue making it suitable for submucosal injection.

Explorando la nutrición en la farmacia comunitaria con nuevas herramientas. Ciclo de podcasts / Exploring nutrition in community pharmacy with new tools. Podcast series

JUSTIFICACIÓN: la farmacia comunitaria es lugar idóneo para tratar temas de salud relacionados con la nutrición. Muchas patologías y sus tratamientos precisan de consejo o intervención en el plano nutricional. La situación de pandemia actual ha obligado a buscar nuevas estrategias de formación y los podcasts han irrumpido como alternativa muy interesante.OBJETIVOS: formar a los farmacéuticos comunitarios en el área de Nutrición en farmacia comunitaria, mediante un ciclo de podcast. Potenciar la utilización de tecnologías de la información y comunicación (TIC) en el colectivo farmacéutico. Analizar y valorar el impacto de la herramienta de formación diseñada.MATERIAL Y MÉTODOS: los contenidos fueron desarrollados por farmacéuticos comunitarios, pertenecientes al grupo de Nutrición y Digestivo de SEFAC, con experiencia en los temas tratados y sometidos a una revisión por pares para garantizar la calidad. Posteriormente, los encargados de la creación de contenidos procedieron a su grabación con la participación de un periodista y finalmente fueron editados para su difusión a través de Ivoox, Spotify y Apple Podcasts.RESULTADOS: se grabaron un total de 11 podcasts con una duración media de 18 minutos sobre los títulos que se detallan a continuación relacionados con la nutrición y su aplicación en la farmacia comunitaria: La Vitamina D Proteína y salud muscular Desnutrición Ejercicio físico y salud. Prevenir la deshidratación. Interacción fármacos- nutrientes. Prevenir y tratar las úlceras de presión El rincón del mayor en la farmacia comunitaria. Desnutrición en procesos oncológicos Diabetes y nutrición ¿Es posible un servicio de nutrición en la farmacia comunitaria? Se procedió a su emisión en las plataformas mencionadas de febrero a diciembre de 2021 a razón de uno por mes. La media de escuchas de la colección fue a fecha 21 de febrero de 922. (AU)

Informe de la Fundación del Cerebro. Impacto social de la enfermedad de Alzheimer y otras demencias / Report by the Spanish Foundation of the Brain on the social impact of Alzheimer disease and other types of dementia

INTRODUCCIÓN: El conocimiento del alcance socioeconómico de las enfermedades que cursan con demencia es esencial para la planificación de recursos y la concienciación social. DESARROLLO: Se ha realizado una revisión de los datos publicados hasta el momento sobre la epidemiología, morbilidad, mortalidad, discapacidad, dependencia e impacto económico de la demencia y la enfermedad de Alzheimer en España. CONCLUSIONES: La mayoría de estudios en población mayor de 65 años estiman una prevalencia entre el 4% y el 9%. La prevalencia es mayor en mujeres en casi todos los grupos de edad. La enfermedad de Alzheimer es la causa de demencia más frecuente (50-70% del total). La demencia provoca un aumento de la morbilidad, mortalidad, discapacidad y dependencia de los pacientes, con una importante disminución de la calidad de vida y la supervivencia. El 80% de los enfermos es cuidado por sus familias, que asumen de media el 87% del coste total, con la consiguiente sobrecarga y menoscabo de la salud y calidad de vida de los cuidadores. El impacto económico de la demencia es enorme, y de evaluación compleja, por la mezcla de costes sanitarios y no sanitarios, directos e indirectos. Es necesario desarrollar programas globales e incrementar los recursos enfocados a fomentar la investigación, prevención, diagnóstico precoz, tratamiento multidimensional y abordaje multidisciplinario, que permitan reducir la carga sanitaria, social y económica de la demencia

INTRODUCTION: Knowledge of the socioeconomic impact of dementia-related disorders is essential for appropriate management of healthcare resources and for raising social awareness. METHODS: We performed a literature review of the published evidence on the epidemiology, morbidity, mortality, associated disability and dependence, and economic impact of dementia and Alzheimer disease (AD) in Spain. CONCLUSIONS: Most population studies of patients older than 65 report prevalence rates ranging from 4% to 9%. Prevalence of dementia and AD is higher in women for nearly every age group. AD is the most common cause of dementia (50%-70% of all cases). Dementia is associated with increased morbidity, mortality, disability, and dependence, and results in a considerable decrease in quality of life and survival. Around 80% of all patients with dementia are cared for by their families, which cover a mean of 87% of the total economic cost, resulting in considerable economic and health burden on caregivers and loss of quality of life. The economic impact of dementia is huge and difficult to evaluate due to the combination of direct and indirect costs. More comprehensive programmes should be developed and resources dedicated to research, prevention, early diagnosis, multidimensional treatment, and multidisciplinary management of these patients in order to reduce the health, social, and economic burden of dementia

Calcium- and voltage-activated potassium channels in adrenocortical cell membranes.

Current flowing through single Ca- and voltage-activated K channels has been recorded from cell-attached and inside-out excised membrane patches of cultured Y-1 adrenocortical cells. In intact cells, single-channel current amplitude and the time a channel stays in the open state increase with membrane depolarization. In excised patches bathed in symmetrical 130 mM K solutions, single-channel conductance is 170 pS. This value is constant in the membrane potential range of +/- 50 mV but decreases at larger hyper- and depolarizations. Channel open probability is heavily influenced by the concentration of ionic Ca at the inner surface of the membrane in the range between 0.01 and 10 microM. When internal Ca concentration is close to 0.01 microM, channels are usually closed even at large depolarizing voltages. With larger Ca concentrations, channel open probability increases and its voltage dependence is greater. These channels are uniformly distributed in the plasma membrane, since one to four channels were seen in more than 99% of the patches isolated in this study. There are previous reports suggesting a role for calcium ions in the secretory response of adrenocortical cells to ACTH. Therefore, it is possible that, as in other endocrine cells, these K channels modulate Ca influx across the plasma membrane and thus contribute to regulate steroid biosynthesis and release.

Proteolysis of Alzheimer's disease beta-amyloid precursor protein by factor Xa.

Amyloid beta-protein is a 4-kDa peptide which originates from proteolysis of a larger protein precursor (APP) and accumulates in senile plaques in brains of Alzheimer's disease (AD) patients. Since secreted APP inhibits factors IXa, Xa and XIa, and thrombin appears to play a role in APP secretion and proteolysis, a relationship between hemostasis system and APP metabolism seems to exist. In this work we investigate the susceptibility to proteolytic cleavage by factor Xa of a fusion construct containing full-length APP prepared in bacteria, and demonstrate that both APP695 and APP770 are substrates for this protease. Factor Xa was found to cleave APP after arginines 102, 268, 510, 573 and 601 (APP695 numeration); most of these sites appear to be common for different coagulation factors. In addition, APP incubation with factor Xa generates an array of six potentially amyloidogenic fragments. Comparative kinetic analysis of APP695 and APP770 cleavage by factor Xa suggests that Kunitz-type inhibitor-containing isoforms exert an inhibitory effect on the protease. However, this inhibition is far from complete even at a 5-fold molar excess of inhibitor. Our results raise the possibility that proteases from the coagulation cascade may contribute to APP proteolysis, and support the notion that these proteases play a role in AD pathogenesis.

Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO.

Human monocyte subsets, isolated from cultures of mononuclear cells, or freshly obtained from patients with multiple sclerosis, Graves' disease or pemphigus vulgaris, differed in phenotype, apoptotic features, mRNA levels of arginase II (A-II) and the inducible form of nitric oxide synthase (iNOS). Liver-type arginase I mRNA was present in all subsets. Apoptosis was followed by the expression of T cell intracellular antigen (TIA) and the simultaneous detection of DNA stainability by propidium iodine and annexin V binding. Apoptosis was practically absent both in activated CD14(++)CD33(++)DR(++)CD25(++)CD69(++)CD71(++/+) CD16(-) cells, expressing A-II mRNA and having arginase activity, but not iNOS mRNA, and in not fully mature large CD14(++)CD16(+)CD23(+)DR(++) monocytes, expressing simultaneously both mRNAs and having both enzyme activities. However, differentiated small CD14(+/++)CD16(+)CD69(+)CD25(+/-)CD71(++)CD23(+) DR(++) monocytes, expressing high levels of iNOS mRNA, exhibited apoptotic signs. Amounts of NO synthesised by monocytes co-expressing iNOS and arginase changed with the addition of arginine or an iNOS inhibitor; in that case a correlation of NO production and apoptotic features was observed. Data suggest a regulatory role for endogenous NO in apoptosis of stimulated and differentiated monocytes, and also that iNOS and A-II, when simultaneously present, could control the production of NO as a consequence of their competition for arginine.