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of side effects was similar whether patients received empagliflozin or placebo. This included side effects that led to treatment being stopped as well as severe and serious side effects, including fractures and LLAs. Empagliflozin was not associated with a higher rate of hypoglycemia (low blood sugar) versus placebo, except in patients also treated with insulin and/or a sulfonylurea (31.5% vs. 30.2%, respectively). The risk of urinary tract infections was also similar for empagliflozin versus placebo (9.27 vs. 9.70/100 patient-years, respectively). However, genital infections, as anticipated, occurred more frequently in patients treated with empagliflozin than placebo (3.54 vs. 0.95/100 patient-years, respectively). Fimepinostat Overall, this analysis confirms the results of previous studies showing that empagliflozin is well tolerated in patients with T2DM.INTRODUCTION RLBP1 RP is an autosomal recessive form of retinitis pigmentosa (RP), characterized by night blindness, prolonged dark adaptation, constricted visual fields and impaired macular function. This study aimed to better understand the patient experience of RLBP1 RP and evaluate the content validity of existing patient reported outcome (PRO) instruments in this condition. METHODS Semi-structured concept elicitation and cognitive debriefing interviews were conducted with RLBP1 RP patients in Canada and Sweden. Interviews started with open-ended concept elicitation questioning, and then patients were cognitively debriefed on The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the Low Luminance Questionnaire (LLQ) and four light/dark adaptation items of the Visual Activities Questionnaire (VAQ). Qualitative interviews were also conducted with three expert clinicians. Anonymized, verbatim transcripts were analyzed using thematic analysis. RESULTS Twenty-one patients were interviewed (Canada n = 10; Sweden n = 11). Symptoms reported included night blindness (n = 21), difficulty adapting to changes in lighting (n = 21) and difficulties seeing in bright lighting (n = 18). Patients experienced substantial impacts on daily activities (n = 21) and physical functioning (n = 17). Patients had difficulty interpreting and selecting a response for some items in the NEI VFQ-25 and LLQ. Some items were not relevant to patients' disease experience. There were both gaps and overlaps in the conceptual coverage of the instruments. CONCLUSIONS Visual impairment due to RLBP1 RP has a substantial impact on physical functioning and daily activities. To adequately assess all important symptoms and associated functional impacts in RLBP1 RP, it is recommended to either modify one or more existing instruments or to develop a new non-syndromic RP specific instrument.Sidestream dark field (SDF) imaging enables direct visualisation of the microvasculature from which quantification of key variables is possible. The new MicroScan USB3 (MS-U) video-microscope is a hand-held SDF device that has undergone significant technical upgrades from its predecessor, the MicroScan Analogue (MS-A). The MS-U claims superior quality of sublingual microcirculatory image acquisition over the MS-A, however, this has yet to be robustly confirmed. In this manuscript, we therefore compare the quality of image acquisition between these two devices. The microcirculation of healthy volunteers was visualised to generate thirty video images for each device. Two independent raters, blinded to the device type, graded the quality of the images according to the six different traits in the Microcirculation Image Quality Score (MIQS) system. Chi-squared tests and Kappa statistics were used to compare not only the distribution of scores between the devices, but also agreement between raters. MS-U showed superior image quality over MS-A in three of out six MIQS traits; MS-U had significantly more optimal images by illumination (MS-U 95% optimal images, MS-A 70% optimal images (p-value 0.003)), by focus (MS-U 70% optimal images, MS-A 35% optimal images (p-value 0.002)) and by pressure (MS-U 72.5% optimal images, MS-A 47.5% optimal images (p-value 0.02)). For each trait, there was at least 85% agreement between the raters, and all the scores for each trait were independent of the rater (all p-values > 0.05). These results show that the new MS-U provides a superior quality of sublingual microcirculatory image acquisition when compared to old MS-A.BACKGROUND Coronary microvascular dysfunction (CMD) is present in various non-ischemic cardiomyopathies and in particular in those with left-ventricular hypertrophy. This study evaluated the diagnostic value of the novel cardiovascular magnetic resonance (CMR) parameter "myocardial transit-time" (MyoTT) in distinguishing cardiac amyloidosis from other hypertrophic cardiomyopathies. METHODS N = 20 patients with biopsy-proven cardiac amyloidosis (CA), N = 20 patients with known hypertrophic cardiomyopathy (HCM), and N = 20 control patients without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as first-pass perfusion acquisitions at rest for MyoTT measurement. MyoTT was defined as the blood circulation time from the orifice of the coronary arteries to the pooling in the coronary sinus (CS) reflecting the transit-time of gadolinium in the myocardial microvasculature. RESULTS MyoTT was significan (measured by native T1 and/or ECV) is more pronounced in HCM compared to CA-in spite of a higher absolute MyoTT value in CA patients. Hence, MyoTT may improve our understanding of the interplay between extracellular/intracellular and intravasal changes that occur in the myocardium during the disease course of different cardiomyopathies.Glucose arguably is the most important energy carrier, carbon source for metabolites and building block for biopolymers in all kingdoms of life. The proper function of animal organs and tissues depends on the continuous supply of glucose from the bloodstream. Most animals can resorb only a small number of monosaccharides, mostly glucose, galactose and fructose, while all other sugars oligosaccharides and dietary fibers are degraded and metabolized by the microbiota of the lower intestine. Bacteria, in contrast, are omnivorous. They can import and metabolize structurally different sugars and, as a consortium of different species, utilize almost any sugar, sugar derivative and oligosaccharide occurring in nature. Bacteria have membrane transport systems for the uptake of sugars against steep concentration gradients energized by ATP, the proton motive force and the high energy glycolytic intermediate phosphoenolpyruvate (PEP). Different uptake mechanisms and the broad range of overlapping substrate specificities allow bacteria to quickly adapt to and colonize changing environments. Here, we review the structures and mechanisms of bacterial representatives of (i) ATP-dependent cassette (ABC) transporters, (ii) major facilitator (MFS) superfamily proton symporters, (iii) sodium solute symporters (SSS) and (iv) enzyme II integral membrane subunits of the bacterial PEP-dependent phosphotransferase system (PTS). We give a short overview on the distribution of transporter genes and their phylogenetic relationship in different bacterial species. Some sugar transporters are hijacked for import of bacteriophage DNA and antibacterial toxins (bacteriocins) and they facilitate the penetration of polar antibiotics. Finally, we describe how the expression and activity of certain sugar transporters are controlled in response to the availability of sugars and how the presence and uptake of sugars may affect pathogenicity and host-microbiota interactions.Nax is a brain [Na+] sensor expressed in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT) in the brain. We previously demonstrated that Nax signals are involved in the control of water intake behavior through the Nax/TRPV4 pathway. Nax gene knockout mice showed significantly attenuated water intake after an intracerebroventricular (ICV) injection of a hypertonic NaCl solution; however, the induction of a certain amount of water intake still remained, suggesting that another unknown [Na+]-dependent pathway besides the Nax/TRPV4 pathway contributes to water intake. In the present study, we screened for novel [Na+] sensors involved in water intake control and identified SLC9A4 (also called sodium (Na+)/hydrogen (H+) exchanger 4 (NHE4)). SLC9A4 is expressed in angiotensin II (Ang II) receptor type 1a (AT1a)-positive neurons in the OVLT. Sodium-imaging experiments using cultured cells transfected with slc9a4 revealed that SLC9A4 was activated by increases in extracellular [Na+] ([Na+]o), but not osmolality. Moreover, the firing activity of SLC9A4-positive neurons was enhanced by increases in [Na+]o and Ang II. slc9a4 knockdown in the OVLT reduced water intake induced by increases in [Na+], but not osmolality, in the cerebrospinal fluid. ICV injection experiments of a specific inhibitor suggested that the increase in extracellular [H+] caused by SLC9A4 activation next stimulates acid-sensing channel 1a (AS1C1a) to induce water intake. Our results thus indicate that SLC9A4 in the OVLT functions as a [Na+] sensor for the control of water intake and that the SLC9A4 signal is independent of the Nax/TRPV4 pathway.This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal exposures are characterized by a spatially inhomogeneous irradiation of the body, which is potentially prolonged over large periods and variable over time, is particularly problematic for biological and electron paramagnetic resonance (EPR) dosimetry methods when compared with external exposures. The paper gives initially specific information about internal dosimetry methods, the most common cytogenetic techniques used in biological dosimetry and EPR dosimetry applied to tooth enamel. Based on real-case scenarios, dose estimates obtained from bioassay data as well as with biological and/or EPR dosimetry are compared and critically discussed. In most of the scenarios presented, concomitant external exposures were responsible for the greater portion of the received dose. As no assay is available which can discriminate between radiation of different types and different LETs on the basis of the type of damage induced, it is not possible to infer from these studies specific conclusions valid for incorporated radionuclides alone. The biological dosimetry assays and EPR techniques proved to be most applicable in cases when the radionuclides are almost homogeneously distributed in the body. No compelling evidence was obtained in other cases of extremely inhomogeneous distribution. Retrospective dosimetry needs to be optimized and further developed in order to be able to deal with real exposure cases, where a mixture of both external and internal exposures will be encountered most of the times.BACKGROUND This study aims to analyze risk factors, clinical profiles, treatment protocols, and disease outcomes in histologically proven resectable vulvar cancer (VC) patients according to tumor stage. This is a retrospective analysis of a prospectively collected database of 20 VC patients from May 2014 to June 2019. RESULTS The mean age of VC diagnosis was 55 years, with a range of 38-84 years. The incidence was four cases per year. The disease incidence was significantly more in post-menopausal (65%) and multiparous (90%) women. According to FIGO staging of vulvar cancer, stages I, II, and III were assigned to 6, 1, and 11 patients respectively. Two patients suffered from stage IVa vulvar melanoma. All patients had undergone surgical interventions. Patients treated with only nonsurgical (chemotherapy/radiotherapy/chemo-radiotherapy) treatment modalities were excluded from the study. Fifteen patients were treated with wide local excision (WLE), bilateral inguinofemoral dissection (B/L IFLND), and primary repair.