Emphysematous cholecystitis

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Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.AIMS/HYPOTHESIS: Ageing can lead to reduced insulin sensitivity and loss of pancreatic beta cell function, predisposing individuals to the development of diabetes. The aim of this study was to assess the contribution of microRNAs (miRNAs) to age-associated beta cell dysfunction. METHODS: The global mRNA and miRNA profiles of 3- and 12-month-old rat islets were collected by microarray. The functional impact of age-associated differences in miRNA expression was investigated by mimicking the observed changes in primary beta cells from young animals. RESULTS: Beta cells from 12-month-old rats retained normal insulin content and secretion, but failed to proliferate in response to mitotic stimuli. The islets of these animals displayed modifications at the level of several miRNAs, including upregulation of miR-34a, miR-124a and miR-383, and downregulation of miR-130b and miR-181a. Computational analysis of the transcriptomic modifications observed in the islets of 12-month-old rats revealed that the differentially expressed genes were enriched for miR-34a and miR-181a targets. Indeed, the induction of miR-34a and reduction of miR-181a in the islets of young animals mimicked the impaired beta cell proliferation observed in old animals. mRNA coding for alpha-type platelet-derived growth factor receptor, which is critical for compensatory beta cell mass expansion, is directly inhibited by miR34a and is likely to be at least partly responsible for the effects of this miRNA. CONCLUSIONS/INTERPRETATION: Changes in the level of specific miRNAs that occur during ageing affect the proliferative capacity of beta cells. This might reduce their ability to expand under conditions of increased insulin demand, favouring the development of type 2 diabetes.Swiss National Science FoundationFondation Francophone pour la Recherche sur le DiabèteWellcome Trust Senior Investigator AwardMRC Programme GrantRoyal Society Wolfson Research Merit AwardWellcome Trust project gran

Old and new calcimimetics for treatment of secondary hyperparathyroidism: Impact on biochemical and relevant clinical outcomes

Secondary hyperparathyroidism (SHPT) is associated with increased bone turnover, risk of fractures, vascular calcifications, and cardiovascular and all-cause mortality. The classical treatment for SHPT includes active vitamin D compounds and phosphate binders. However, achieving the optimal laboratory targets is often difficult because vitamin D sterols suppress parathyroid hormone (PTH) secretion, while also promoting calcium and phosphate intestinal absorption. Calcimimetics increase the sensitivity of the calcium-sensing receptor, so that even with lower levels of extracellular calcium a signal can still exist, leading to a decrease of the set-point for systemic calcium homeostasis. This enables a decrease in plasma PTH levels and, consequently, of calcium levels. Cinacalcet was the first calcimimetic to be approved for clinical use. More than 10 years since its approval, cinacalcet has been demonstrated to effectively reduce PTH and improve biochemical control of mineral and bone disorders in chronic kidney patients. Three randomized controlled trials have analysed the effects of treatment with cinacalcet on hard clinical outcomes such as vascular calcification, bone histology and cardiovascular mortality and morbidity. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Etelcalcetide is a new second-generation calcimimetic with a pharmacokinetic profile that allows thrice-weekly dosing at the time of haemodialysis. It was recently approved in Europe, and is regarded as a second opportunity to improve outcomes by optimizing treatment for SHPT. In this review, we summarize the impact of cinacalcet with regard to biochemical and clinical outcomes. We also discuss the possible implications of the new calcimimetic etelcalcetide in the quest to improve outcomes

An innovative thermal protective clothing system for firefighters

Nowadays, despite the evolution of personal protective equipment (PPE), the number of firefighters injured and burned during fire extinguishing operations is still very high, leading in some cases to loss of life. Therefore, the research and development of new solutions to minimize firefighters' heat load and skin burns, with consecutive improvements of commercial firefighters' suits, is of extreme importance. The integration of phase change materials (PCMs) in a protective clothing system has been used to significantly reduce the incoming heat flux from the fire environment. This study consists in the development of a protective clothing system composed by a vest, specially designed to protect the torso (back, chest and abdomen) with a layer of PCM pouches, to be worn over a fire-resistant jacket - selection and design based on numerical models' predictions. Therefore, several mockups were made, varying the number of PCM pouches and their distribution in the vest, allowing the creation of air ducts to increase the breathability of the vest. The most promising solutions are being evaluated in a real controlled environment, at a Portuguese National School of Firefighters (ENB) simulation site, using a fire manikin and thermocouples to monitor vest temperature during heat and flame exposure, and consequently to verify PCMs influence in heat protection. Results regarding the development of a PCM vest will be presented, focusing on the integration of PCM pouches and the thermal performance of the most promising solutions

Evaluation of vineyard growth under four irrigation regimes using vegetation and soil on-the-go sensors

Precision agriculture is a useful tool to assess plant growth and development in vineyards. The present study focused on spatial and temporal analysis of vegetation growth variability, in four irrigation treatments with four replicates. The research was carried out in a vineyard located in the southwest of Spain during the 2012 and 2013 growing seasons. Two multispectral sensors mounted on an all-terrain vehicle (ATV) were used in the different growing seasons/stages in order to calculate the vineyard normalized difference vegetation index (NDVI). Soil apparent electrical conductivity (ECa) was also measured up to 0.8m soil depth using an on-the-go geophysical sensor. All measured data were analysed by means of principal component analysis (PCA). The spatial and temporal NDVI and ECa variations showed relevant differences between irrigation treatments and climatological conditions

Human IgG2- and IgG4-expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age

The mechanisms involved in sequential immunoglobulin G (IgG) class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on blood mononuclear cells from young children and adults as models for primary and secondary immunological memory. Additional sequencing and detailed immunophenotyping with IgG subclass-specific antibodies was performed on purified IgG+ memory B-cell subsets. In both children and adults, SHM levels were higher in transcripts involving more downstream-located IGHG genes (esp. IGHG2 and IGHG4). In adults, SHM levels were significantly higher than in children, and downstream IGHG genes were more frequently utilized. This was associated with increased frequencies of CD27+ IgG+ memory B cells, which contained higher levels of SHM, more IGHG2 usage, and higher expression levels of activation markers than CD27-IgG+ memory B cells. We conclude that secondary immunological memory accumulates with age and these memory B cells express CD27, high levels of activation markers, and carry high SHM levels and frequent usage of IGHG2. These new insights contribute to our understanding of sequential IgG subclass switching and show a potential relevance of using serum IgG2 levels or numbers of IgG2-expressing B cells as markers for efficient generation of memory responses

Particle separation in surface acoustic wave microfluidic devices using reprogrammable, pseudo-standing waves

We report size and density/compressibility-based particle sorting using on-off quasi-standing waves based on the frequency difference between two ultrasonic transducers. The 13.3 MHz fundamental operating frequency of the surface acoustic wave microfluidic device allows the manipulation of particles on the micrometer scale. Experiments, validated by computational fluid dynamics, were carried out to demonstrate size-based sorting of 5–14.5 lm diameter polystyrene (PS) particles and density/compressibility-based sorting of 10 lm PS, iron-oxide, and poly(methyl methacrylate) particles, with densities ranging from 1.05 to 1.5 g/cm3 . The method shows a sorting efficiency of >90% and a purity of >80% for particle separation of 10 lm and 14.5 lm, demonstrating better performance than similar sorting methods recently published (72%–83% efficiency). The sorting technique demonstrates high selectivity separation of particles, with the smallest particle ratio being 1.33, compared to 2.5 in previous work. Density/compressibility-based sorting of polystyrene and iron-oxide particles showed an efficiency of 97 6 4% and a purity of 91 6 5%. By varying the sign of the acoustic excitation signal, continuous batch acoustic sorting of target particles to a desired outlet was demonstrated with good sorting stability against variations of the inflow rate

Smart firefighters PPE: Impact of phase change materials

Considering the high level of heat and flame exposure firefighters encounter while performing their work activities, personal protective equipment (PPE) is of the utmost importance to enhance their safety. Phase change materials (PCMs) are known as advanced materials able to absorb high amounts of thermal energy, with the potential to increase the thermal performance of protective clothing. In this work, a PCM-vest was developed for the first time, and its thermal performance was evaluated. A three-stage approach was followed: (1) at a small scale in the laboratory, the effect of different encapsulated PCMs on a multilayer assembly performance was evaluated; (2) in the laboratory, the essential requirements of heat and flame tests were assessed; and (3) in a simulated urban fire, the thermal performance of three different PCM-vests (different textiles and designs) was studied. As the main conclusions, the PCMs significantly affected the heating rate of the multilayer assembly, particularly when a PCM with higher latent heat was used. In some cases, the heat transfer index (HTI) doubled by comparison with the sample without PCMs. As a drawback and as expected, the cooling time was increased. The PCM-vest sample ensured the requirements of the heat and flame tests. Through this study, the positive impact of using PCMs to enhance the heat protection of conventional PPE can be highlighted

Adenovirus Infection in a Kidney–Pancreatic Transplant Recipient: Case Report

Adenovirus infection in transplant recipients may present from asymptomatic viremia to multisystemic involvement. Most frequently, it occurs in the first year after a kidney transplant, and it is secondary to the reactivation of latent disease. However, primary infection may occur, and disseminated disease is more common when related to primary infection. Kidney involvement may be confirmed by biopsy, although diagnosis may be presumptive. Reduction of immunosuppression and supportive care are important components of therapy. CASE DESCRIPTION: A 41-year-old female renal-pancreatic recipient 12 years before with chronic renal graft dysfunction and a functional pancreatic graft had a history of cytomegalovirus and polyoma virus infection 2 years after transplantation. She was taking tacrolimus, mycophenolate mofetil, and prednisolone. The patient was admitted after persistent uncharacteristic diarrhea 3 weeks before hospitalization without any relevant epidemiologic context. She was dehydrated, and the lab results showed worsened kidney function and leucocytosis. The viral culture revealed adenovirus. Vigorous hydration was implemented, and the mycophenolate mofetil dose was reduced. The patient was discharged, and renal function returned to previous values. DISCUSSION AND CONCLUSION: Adenovirus infection has a wide clinical presentation, and multisystemic involvement may occur in transplant recipients. Supportive care is paramount. The clinical features and viral culture confirm the diagnosis, although tissue samples and quantitative polymerase chain reaction may be required in more severe cases.info:eu-repo/semantics/publishedVersio