Transcriptomic Analysis Reveals That Retinal Neuromodulation Is a Relevant Mechanism in the Neuroprotective Effect of Sitagliptin in an Experimental Model of Diabetic Retinopathy

Diabetic retinopathy; Sitagliptin; Synaptic signal transmissionRetinopatia diabètica; Sitagliptina; Transmissió del senyal sinàpticRetinopatía diabética; Sitagliptina; Transmisión de señal sinápticaSynaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Transcriptome analysis was performed, comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily and the retinas of 10 additional db/db mice that received vehicle eye drops. Ten non-diabetic mice (db/+) were used as a control group. The Gene Ontology (GO) and Reactome databases were used to perform the gene set enrichment analysis (GSEA) in order to explore the most enriched biological pathways among the groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission is the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesicle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of the macromolecule biosynthetic process with positive regulation of cell communication, which provides beneficial effects for the neuronal metabolism. This study suggests that topical administration of sitagliptin ameliorates the abnormalities on presynaptic and postsynaptic signal transmission during experimental DR and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.This research was funded by grants from the Ministerio de Economía y Competitividad (PID2019-104225RB-I00) and the Instituto de Salud Carlos III (DTS18/0163, PI19/01215 and ICI20/00129). The study funder was not involved in the design of the study

Perkembangan Teori Sewa Tanah dalam Perspektif Pemikiran Ekonomi

A history of Land Rent Theorities have several opinions, as mazhab of Physiocratic, classical tradition, and new. The different opponions can be understanding for knowing two factors that land value increasingly location to central bussines and fertile soil

Micro-to nano-scale characterisation of polyamide structures of the SW30HR RO membrane using advanced electron microscopy and stain tracers

The development of new reverse osmosis (RO) membranes with enhanced performance would benefit from a detailed knowledge of the membrane structures which participate in the filtration process. Here, we examined the hierarchical structures of the polyamide (PA) active layer of the SW30HR RO membrane. Scanning electron microscopy combined with focused ion beam milling (FIB-SEM) was used to obtain the 3-D reconstructions of membrane morphology with 5 nm cross-sectional resolution (comparable with the resolution of low magnification TEM imaging in 2D) and 30 nm slice thickness. The complex folding of the PA layer was examined in 3 dimensions, enabling the quantification of key structural properties of the PA layer, including the local thickness, volume, surface area and their derivatives. The PA layer was found to exhibit a much higher and convoluted surface area than that estimated via atomic force microscopy (AFM). Cross-sectional scanning transmission electron microscopy (STEM) was used to observe the distribution of a tracer stain under various conditions. The behaviour of stain in dry and wet PA indicated that the permeation pathways have a dynamic nature and are activated by water. High resolution STEM imaging of the stained PA nano-films revealed the presence of <1 nm pore-like structures with a size compatible with free volume estimations by positron annihilation lifetime spectroscopy (PALS). This study presents a comprehensive map of the active PA layer across different length scales (from micro- to sub-nanometre) and mechanistic insight into their role in the permeation process

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Synergistic Coupling of a Molybdenum Carbide Nanosphere with Pt Nanoparticles for Enhanced Ammonia Electro-Oxidation Activity in Alkaline Media

Ammonia will play a pivotal role in the future of zero carbon emitted sustainable fuel. The development of inexpensive efficient catalysts for ammonia electro-oxidation (AEO) is essential to its success. This study provides evidence that nanoparticles of earth-abundant elements, e.g., MoC, encapsulated in a doped-graphene shell (DG-MoC), are promising cocatalysts of Pt for AEO which significantly improve the catalyst cost and activity in comparison to the state-of-the-art platinum. DG-MoC, DG-MoC-supported Pt (Pt/DG-MoC), and nitrogen-doped-graphene (NG) catalysts were synthesized and characterized by Brunauer–Emmett–Teller (BET) surface area analysis, electrochemical techniques, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM) combined with energy-dispersive X-ray (EDX), scanning transmission electron microscopy (STEM), and electron energy loss (EEL) spectroscopy. The XRD analysis of DG-MoC disclosed that the presence of α-MoC1–x microscopy techniques demonstrates a close vicinity of Pt and MoC nanoparticles in Pt/DG-MoC. We report, for the first time, that Pt/DG-MoC particles reveal a large synergistic effect for AEO activity, while DG-MoC and NG showed no activity. Pt/DG-MoC gave a higher current density, lower half- and peak- potentials (28 mV and 14 mV, respectively), and greater resilience to ammonia poisoning than Pt/C as shown in the fall in the peak current density in the second voltammogram, i.e, approximately 3.6% compared to 20.7% for Pt/C. The XPS spectrum of the catalysts explained the source of this synergistic effect

"Painopeiton kaveriksi" : Painopeitto kehitysvammaisen rentoutumiseen toimintaterapiassa

Tämä on toiminnallinen opinnäytetyö, jonka tarkoituksena oli valmistaa painopeitto sekä löytää perusteet painopeiton käytön hyödyllisyyteen kehitysvammaiselle. Lisäksi painopeiton valmistamisesta tuotettiin kuvallinen vaiheittain etenevä ohjeistus. Painopeiton valmistus toteutettiin etelä-pohjanmaalla sijaitsevan Lehtimäen erityiskansanopiston toimintaterapiaan. Lehtimäen erityiskansanopisto on erityistä tukea ja ohjausta tarvitsevien henkilöiden oppilaitos. Tässä opinnäytetyössä tuodaan esille rentoutuminen osana ihmiselle merkityksellistä toimintaa, jonka viitekehyksenä on käytetty Kanadalaisen toiminnallisuuden ja sitoutumisen mallia, Canadian Model of Occupational Performance and Engagement, (CMOP-E). Rentoutumista mahdollistaa taktiiliset- ja proprioseptiviset aistimukset, jotka perustellaan sensorisen integraation teorian kautta. Painopeiton avulla kehitysvammaiselle voidaan tarjota taktilisia- ja proprioseptiivisia aistimuksia.The purpose of this functional thesis was to manufacture a weighted blanket and to find a basis for its usefulness for a mentally disabled patient. In addition, step by step visual instructions for the making of a weighted blanket were produced. The weighted blanket was made for the occupational therapy conducted at the Lehtimäki Special Folk High School located in Southern Ostrobothnia. The Lehtimäki Special Folk High School is an institution which caters for individuals in need of special support and guidance. This thesis raises relaxation as an important aspect of a person’s activities. Its theoretical basis originates from the Canadian Model of Occupational Performance and Engagement, (CMOP-E). Relaxation allows tactile and proprioceptive sensations which are justified by using the sensory integration theory. With the help of a weighted blanket, a mentally disabled person can be offered tactile and proprioceptive sensations