Toll-like receptor 4 (TLR4) expression in human and murine pancreatic beta-cells affects cell viability and insulin homeostasis

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is widely recognized as an essential element in the triggering of innate immunity, binding pathogen-associated molecules such as Lipopolysaccharide (LPS), and in initiating a cascade of pro-inflammatory events. Evidence for TLR4 expression in non-immune cells, including pancreatic β-cells, has been shown, but, the functional role of TLR4 in the physiology of human pancreatic β-cells is still to be clearly established. We investigated whether TLR4 is present in β-cells purified from freshly isolated human islets and confirmed the results using MIN6 mouse insulinoma cells, by analyzing the effects of TLR4 expression on cell viability and insulin homeostasis.</p> <p>Results</p> <p>CD11b positive macrophages were practically absent from isolated human islets obtained from non-diabetic brain-dead donors, and TLR4 mRNA and cell surface expression were restricted to β-cells. A significant loss of cell viability was observed in these β-cells indicating a possible relationship with TLR4 expression. Monitoring gene expression in β-cells exposed for 48h to the prototypical TLR4 ligand LPS showed a concentration-dependent increase in TLR4 and CD14 transcripts and decreased insulin content and secretion. TLR4-positive MIN6 cells were also LPS-responsive, increasing TLR4 and CD14 mRNA levels and decreasing cell viability and insulin content.</p> <p>Conclusions</p> <p>Taken together, our data indicate a novel function for TLR4 as a molecule capable of altering homeostasis of pancreatic β-cells.</p

Integración de imágenes Aster y datos geofísicos aerotransportados para el reconocimiento de zonas de alteración hidrotermal en depósitos epitermales en el sur del Perú

El presente trabajo muestra una metodología para el procesamiento de imágenes satelitales ASTER y mapas geofísicos de reducción al Polo, y mapas radiométricos principalmente %K con los cuales se determinaron zonas de anomalías hidrotermales. Para corroborar los resultados se realizó la interpretación del espectro de una muestra de mano utilizando el PIMA/SP y el estudio de secciones delgadas, pulidas. El resultado del procesamiento de imágenes ASTER y datos geofísicos sirvió para identificar 3 zonas importantes las cuales fueron corroboradas. Zona A ubicada al noreste de la imagen y muestra una alteración del tipo argílica se encuentran los depósitos de Santa Rosa, Tucari y Cacachara. Zona B. Se encuentra al sur oeste en el sector de Charaque y finalmente zona C está al sureste y noroeste de la zona de estudio donde predomina la alteración propilítica

Rapid detection of mobilized colistin resistance using a nucleic acid based lab-on-a-chip diagnostic system

The increasing prevalence of antimicrobial resistance is a serious threat to global public health. One of the most concerning trends is the rapid spread of Carbapenemase-Producing Organisms (CPO), where colistin has become the last-resort antibiotic treatment. The emergence of colistin resistance, including the spread of mobilized colistin resistance (mcr) genes, raises the possibility of untreatable bacterial infections and motivates the development of improved diagnostics for the detection of colistin-resistant organisms. This work demonstrates a rapid response for detecting the most recently reported mcr gene, mcr−9, using a portable and affordable lab-on-a-chip (LoC) platform, offering a promising alternative to conventional laboratory-based instruments such as real-time PCR (qPCR). The platform combines semiconductor technology, for non-optical real-time DNA sensing, with a smartphone application for data acquisition, visualization and cloud connectivity. This technology is enabled by using loop-mediated isothermal amplification (LAMP) as the chemistry for targeted DNA detection, by virtue of its high sensitivity, specificity, yield, and manageable temperature requirements. Here, we have developed the first LAMP assay for mcr−9 - showing high sensitivity (down to 100 genomic copies/reaction) and high specificity (no cross-reactivity with other mcr variants). This assay is demonstrated through supporting a hospital investigation where we analyzed nucleic acids extracted from 128 carbapenemase-producing bacteria isolated from clinical and screening samples and found that 41 carried mcr−9 (validated using whole genome sequencing). Average positive detection times were 6.58 ± 0.42 min when performing the experiments on a conventional qPCR instrument (n = 41). For validating the translation of the LAMP assay onto a LoC platform, a subset of the samples were tested (n = 20), showing average detection times of 6.83 ± 0.92 min for positive isolates (n = 14). All experiments detected mcr−9 in under 10 min, and both platforms showed no statistically significant difference (p-value > 0.05). When sample preparation and throughput capabilities are integrated within this LoC platform, the adoption of this technology for the rapid detection and surveillance of antimicrobial resistance genes will decrease the turnaround time for DNA detection and resistotyping, improving diagnostic capabilities, patient outcomes, and the management of infectious diseases

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: Part 2 (treatment)

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP

Effect of Salvia hispanica L. (chia) on the physicochemical characteristics and antioxidant capacity of the Physalis peruviana drink (aguaymanto)

La importancia del consumo de bebidas funcionales elaboradas a partir de frutos promisorios pasa por su aporte nutracéutico, la misma que es esencial para la salud humana. El objetivo de la presente investigación fue elaborar una bebida funcional a partir de aguaymanto (Physalis peruviana) y chía (Salvia hispanica L.), para su posterior evaluación de las características fisicoquímicas y actividad antioxidante. El aguaymanto y la chía fueron provenientes de la provincia de Acobamba, Huancavelica-Perú. Para las determinaciones analíticas se acondicionó 04 tratamientos (T) de bebida funcional (BF): T1= BF + 0,0% de chía, T2= BF + 0,5% de chía, T3= BF + 1,0% de chía y T4= BF + 1,5% de chía. Para los análisis fisicoquímicos se emplearon métodos descritos por la AOAC y para la capacidad antioxidante el radical ABTS+. La bebida funcional de aguaymanto logró incrementar sus características fisicoquímicas y actividad antioxidante a partir de la incorporación de chía. La actividad antioxidante de la bebida funcional sin chía expreso 0,62 µmol de Eq. Trolox/mL (inhibición de ABTS), la adición de chía ocasionó su incremento hasta 1,45 µmol de Eq. Trolox/mL. Se concluye que la incorporación de chía en la bebida funcional de aguaymanto genera notable incremento de las cualidades nutracéuticas, obteniéndose un alimento con alto potencial antioxidante.The importance of the consumption of functional drinks made from promising fruits goes through their nutraceutical contribution, which is essential for human health. The objective of the present investigation was to elaborate a functional drink from aguaymanto (Physalis peruviana) and chia (Salvia hispanica L.), for its subsequent evaluation of the physicochemical characteristics and antioxidant activity. Aguaymanto and chia were from the province of Acobamba, Huancavelica-Peru. For the analytical determinations, 04 treatments (T) of functional drink (BF) were conditioned: T1 = BF + 0.0% of chia, T2 = BF + 0.5% of chia, T3 = BF + 1.0% of chia and T4 = BF + 1.5% of chia. For the physicochemical analyzes, methods described by the AOAC were used and for the antioxidant capacity the ABTS+ radical. Aguaymanto functional drink managed to increase its physicochemical characteristics and antioxidant activity from the incorporation of chia. The antioxidant activity of the functional drink without chia express 0.62 µmol of Eq. Trolox / mL (ABTS inhibition), the addition of chia caused its increase to 1.45 µmol of Eq. Trolox / mL. It is concluded that the incorporation of chia into the functional aguaymanto drink generates a significant increase in nutraceutical qualities, obtaining a food with high antioxidant potential

Handheld point-of-care system for rapid detection of SARS-CoV-2 extracted RNA in under 20 min

The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (<20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against extracted RNA from 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 91% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 ± 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n = 52), showing average detection times of 12.68 ± 2.56 min for positive samples (n = 34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geolocalization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: Part 1 (diagnosis)

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-fac

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women