Search

BackgroundThymic epithelial tumors are rare malignant neoplasms that are frequently associated with paraneoplastic syndromes, especially myasthenia gravis. GTF2I is an oncogene mutated in a subgroup of thymomas that is reputed to drive their growth. However, for GTF2I wild-type tumors, the relevant mutations remain to be identified.MethodsWe performed a meta-analysis and identified 4,208 mutations in 339 patients. We defined a panel of 63 genes frequently mutated in thymic epithelial tumors, which we used to design a custom assay for next-generation sequencing. We sequenced tumor DNA from 67 thymomas of patients with myasthenia gravis who underwent resection in our institution.ResultsAmong the 67 thymomas, there were 238 mutations, 83 of which were in coding sequences. There were 14 GTF2I mutations in 6 A, 5 AB, 2 B2 thymomas, and one in a thymoma with unspecified histology. No other oncogenes showed recurrent mutations, while sixteen tumor suppressor genes were predicted to be inactivated. Even with a dedicated assay for the identification of specific somatic mutations in thymic epithelial tumors, only GTF2I mutations were found to be significantly recurrent.ConclusionOur evaluation provides insights into the mutational landscape of thymic epithelial tumors, identifies recurrent mutations in different histotypes, and describes the design and implementation of a custom panel for targeted resequencing. These findings contribute to a better understanding of the genetic basis of thymic epithelial tumors and may have implications for future research and treatment strategies.

Abstract Abnormal postprandial suppression of glucagon in Type 2 diabetes (T2DM) has been attributed to impaired insulin secretion. Prior work suggests that insulin and glucagon show an inverse coordinated relationship. However, dysregulation of α‐cell function in prediabetes occurs early and independently of changes in β‐cells, which suggests insulin having a less significant role on glucagon control. We therefore, sought to examine whether hepatic vein hormone concentrations provide evidence to further support the modulation of glucagon secretion by insulin. As part of a series of experiments to measure the effect of diabetes‐associated genetic variation in TCF7L2 on islet cell function, hepatic vein insulin and glucagon concentrations were measured at 2‐minute intervals during fasting and a hyperglycemic clamp. The experiment was performed on 29 nondiabetic subjects (age = 46 ± 2 years, BMI 28 ± 1 Kg/m2) and enabled post‐hoc analysis, using Cross‐Correlation and Cross‐Approximate Entropy (Cross‐ApEn) to evaluate the interaction of insulin and glucose. Mean insulin concentrations rose from fasting (33 ± 4 vs. 146 ± 12 pmol/L, p

Pancreatic β-cells are responsible for the synthesis and exocytosis of insulin in response to an increase in circulating glucose. Insulin secretion occurs in a pulsatile manner, with oscillatory pulses superimposed on a basal secretion rate. Insulin pulses are a marker of β-cell health, and secretory parameters, such as pulse amplitude, time interval and frequency distribution, are impaired in obesity, aging and type 2 diabetes. In this review, we detail the mechanisms of insulin production and β-cell synchronization that regulate pulsatile insulin secretion, and we discuss the challenges to consider when measuring fast oscillatory secretion in vivo. These include the anatomical difficulties of measuring portal vein insulin noninvasively in humans before the hormone is extracted by the liver and quickly removed from the circulation. Peripheral concentrations of insulin or C-peptide, a peptide cosecreted with insulin, can be used to estimate their secretion profile, but mathematical deconvolution is required. Parametric and nonparametric approaches to the deconvolution problem are evaluated, alongside the assumptions and trade-offs required for their application in the quantification of unknown insulin secretory rates from known peripheral concentrations. Finally, we discuss the therapeutical implication of targeting impaired pulsatile secretion and its diagnostic value as an early indicator of β-cell stress.

Abstract Background Interleukin-6 (IL-6) plays a central role in atherosclerosis and inflammation. It may improve risk prediction in patients at intermediate cardiovascular risk. Objective To analyze the impact of serum IL-6 in predicting early angiographic coronary artery disease in patients at intermediate cardiovascular risk with chest pain. Methods In a cross-sectional study, patients referred for coronary angiography due to suspected coronary artery disease (CAD) were included. Coronary artery disease was defined as the presence of at least 30% stenosis in one or more coronary artery. Severity of CAD was classified by the anatomic burden score. Performance of serum IL-6 assay was compared with ACC/AHA atherosclerotic cardiovascular disease (ASCVD) risk score and hs-CRP through receiver operating characteristic (ROC) curves. Results We have included 48 patients with a mean 10-year ASCVD risk of 10.0 ± 6.8%. The prevalence of CAD was 72.9%. The presence of CAD was associated with higher mean levels of IL-6 (p = 0.025). Patients with CAD had significantly more overweight than subjects without CAD. In 27% of patients, IL-6 was >1.0 pg/mL and 100% of these patients had CAD, while only 64% in those with IL-6 1.0 pg/mL were further reclassified into ASCVD high risk due to the presence of coronary lesions. Conclusion In intermediate risk patients referred for coronary angiography, a serum IL-6 level above 1 pg/mL is predictive of significant CAD. IL-6 determination may be useful to reclassify ASCVD intermediate risk patients into higher risk categories.

This study aimed to compare the effect of high-intensity interval training (HIIT) with moderate-intensity continuous training (MCT) on endothelial function, oxidative stress and clinical fitness in patients with type 1 diabetes. Thirty-six type 1 diabetic patients (mean age 23.5 ± 6 years) were randomized into 3 groups: HIIT, MCT, and a non-exercising group (CON). Exercise was performed in a stationary cycle ergometers during 40 min, 3 times/week, for 8 weeks at 50–85% maximal heart rate (HRmax) in HIIT and 50% HRmax in MCT. Endothelial function was measured by flow-mediated dilation (FMD) [endothelium-dependent vasodilation (EDVD)], and smooth-muscle function by nitroglycerin-mediated dilation [endothelium-independent vasodilation (EIVD)]. Peak oxygen consumption (VO2peak) and oxidative stress markers were determined before and after training. Endothelial dysfunction was defined as an increase < 8% in vascular diameter after cuff release. The trial is registered at ClinicalTrials.gov, identifier: NCT03451201. Twenty-seven patients completed the 8-week protocol, 9 in each group (3 random dropouts per group). Mean baseline EDVD was similar in all groups. After training, mean absolute EDVD response improved from baseline in HIIT: + 5.5 ± 5.4%, (P = 0.0059), but remained unchanged in MCT: 0.2 ± 4.1% (P = 0.8593) and in CON: −2.6 ± 6.4% (P = 0.2635). EDVD increase was greater in HIIT vs. MCT (P = 0.0074) and CON (P = 0.0042) (ANOVA with Bonferroni). Baseline VO2peak was similar in all groups (P = 0.96). VO2peak increased 17.6% from baseline after HIIT (P = 0.0001), but only 3% after MCT (P = 0.055); no change was detected in CON (P = 0.63). EIVD was unchanged in all groups (P = 0.18). Glycemic control was similar in all groups. In patients with type 1 diabetes without microvascular complications, 8-week HIIT produced greater improvement in endothelial function and physical fitness than MCT at a similar glycemic control.

Historically, open source agriculture (OSA) was based on grassroots technology generally manufactured by hand tools or with manual machining. The rise of distributed digital manufacturing provides an opportunity for much more rapid lateral scaling of open source appropriate technologies for agriculture. However, the most mature distributed manufacturing area is plastic, which has limited use for many OSA applications. To overcome this limitation with design, this study reports on of a completely 3D-printable planetary roller screw linear actuator. The device is designed as a parametric script-based computer aided design (CAD) package to allow for the easy adaption for a number of applications such as food processing at different scales. The planetary roller screw is fabricated in dishwasher-safe polyethylene terephthalate glycol (PETG) on an open source machine and tested using an open source testing platform to determine if it could maintain a constant load without slipping and the maximum force. Then, this output is compared to a direct screw press using the same materials. The results found that the maximum force is more than doubled for the roller screw actuator using the same materials, making them adequate for some food processing techniques. Future work is outlined to improve the performance and ease of assembly.

This study aimed to explore the application of infrared thermography in combination with ambulatory wearable monitoring of temperature and relative humidity, to assess the residual limb-to-liner interface in lower-limb prosthesis users. Five male traumatic transtibial amputees were involved, who reported no problems or discomfort while wearing the prosthesis. A thermal imaging camera was used to measure superficial thermal distribution maps of the stump. A wearable system for recording the temperature and relative humidity in up to four anatomical points was developed, tested in vitro and integrated with the measurement set. The parallel application of an infrared camera and wearable sensors provided complementary information. Four main Regions of Interest were identified on the stump (inferior patella, lateral/medial epicondyles, tibial tuberosity), with good inter-subject repeatability. An average increase of 20% in hot areas (P < 0.05) is shown after walking compared to resting conditions. The sensors inside the cuff did not provoke any discomfort during recordings and provide an inside of the thermal exchanges while walking and recording the temperature increase (a regime value is ~+1.1 ± 0.7 °C) and a more significant one (~+4.1 ± 2.3%) in humidity because of the sweat produced. This study has also begun the development of a reference data set for optimal socket/liner-stump construction.

BACKGROUND. Proglucagon can be processed to glucagon-like peptidel (GLP-1) within the islet, but its contribution to islet function in humans remains unknown. We sought to understand whether pancreatic GLP-1 alters islet function in humans and whether this is affected by type 2 diabetes. METHODS. We therefore studied individuals with and without type 2 diabetes on two occasions in random order. On one occasion, exendin 9-39, a competitive antagonist of the GLP-1 Receptor (GLP1R), was infused, while on the other, saline was infused. The tracer dilution technique ([3-[sup.3]H] glucose) was used to measure glucose turnover during fasting and during a hyperglycemic clamp. RESULTS. Exendin 9-39 increased fasting glucose concentrations; fasting islet hormone concentrations were unchanged, but inappropriate for the higher fasting glucose observed. In people with type 2 diabetes, fasting glucagon concentrations were markedly elevated and persisted despite hyperglycemia. This impaired suppression of endogenous glucose production by hyperglycemia. CONCLUSION. These data show that GLP1R blockade impairs islet function, implying that intra-islet GLP1R activation alters islet responses to glucose and does so to a greater degree in people with type 2 diabetes. TRIAL REGISTRATION. This study was registered at ClinicalTrials.gov NCT04466618. FUNDING. The study was primarily funded by NIH NIDDK DK126206. AV is supported by DK78646, DK116231 and DK126206. CDM was supported by MIUR (Italian Minister for Education) under the initiative 'Departments of Excellence' (Law 232/2016)., Introduction There are multiple strands of evidence that posttranslational processing of proglucagon in a-cells can yield glucagon-like peptidel (GLP-1) (1). Inflammation and caloric excess (2,3) induce prohormone convertase-1/3 (PC-1/3) in [...]

The T allele at rs7903146 in TCF7L2 increases the rate of conversion from prediabetes to type 2 diabetes. This has been associated with impaired β-cell function and with defective suppression of α-cell secretion by glucose. However, the temporal relationship of these abnormalities is uncertain. To study the longitudinal changes in islet function, we recruited 128 subjects, with 67 homozygous for the diabetes-associated allele (TT) at rs7903146 and 61 homozygous for the protective allele. Subjects were studied on two occasions, 3 years apart, using an oral 75-g glucose challenge. The oral minimal model was used to quantitate β-cell function; the glucagon secretion rate was estimated from deconvolution of glucagon concentrations. Glucose tolerance worsened in subjects with the TT genotype. This was accompanied by impaired postchallenge glucagon suppression but appropriate β-cell responsivity to rising glucose concentrations. These data suggest that α-cell abnormalities associated with the TT genotype (rs7903146) occur early and may precede β-cell dysfunction in people as they develop glucose intolerance and type 2 diabetes. Article Highlights: Diabetes-associated variation in TCF7L2 alters both α- and β-cell function, but the order in which these occur is uncertain. This study assessed whether α-cell dysfunction precedes β-cell dysfunction in people with diabetes-associated variation in TCF7L2. People with the diabetes-associated allele in TCF7L2 (rs7903146) developed increased postchallenge glucose concentrations, which were accompanied by an appropriate β-cell response to hyperglycemia and impaired glucagon suppression. The findings show that α-cell dysfunction occurs early in people with diabetes-associated variation in TCF7L2. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective The present study aimed to validate homeostasis model assessment of insulin resistance (HOMA-IR) in relation to the insulin tolerance test (ITT) in a model of insulin-resistance in Wistar rats induced by a 19-week high-fat diet. Materials and methods A total of 30 male Wistar rats weighing 200-300 g were allocated into a high-fat diet group (HFD) (55% fat-enriched chow, ad lib, n = 15) and a standard-diet group (CD) standard chow, ad lib, n = 15), for 19 weeks. ITT was determined at baseline and in the 19th week. HOMA-IR was determined between the 18-19th week in three different days and the mean was considered for analysis. Area under the curve (AUC-ITT) of the blood glucose excursion along 120 minutes after intra-peritoneal insulin injection was determined and correlated with the corresponding fasting values for HOMA-IR. Results AUC-ITT and HOMA-IR were significantly greater after 19th week in HFD compared to CD (p < 0.001 for both). AUC-OGTT was also higher in HFD rats (p = 0.003). HOMA-IR was strongly correlated (Pearson’s) with AUC-ITT r = 0.637; p < 0.0001. ROC curves of HOMA-IR and AUC-ITT showed similar sensitivity and specificity. Conclusion HOMA-IR is a valid measure to determine insulin-resistance in Wistar rats. Arch Endocrinol Metab. 2016;60(2):138-42

Open in new tab Download slide OBJECTIVES To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25–75% = 1–2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice. [ABSTRACT FROM AUTHOR]

Context The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated. Objective We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity. Methods Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations. One study involved a 2-step insulin clamp and the other study was a single step insulin clamp. For both studies the goal was to achieve plasma glucose concentrations of 95 mg/dL during the clamp irrespective of fasting glucose concentrations. The percent change in ISR from fasting to the end of the insulin clamp interval was the main outcome. Linear regression and analysis of covariance were used to test for the effects of insulin on ISR and to test for group differences. Results ISR was greater in obese volunteers (P <.001) under fasting and hyperinsulinemic clamp conditions. The change in plasma glucose from baseline to the end of the insulin clamp interval was highly correlated with the change in ISR (r = 0.61, P <.001). From baseline to the end of the clamp we observed a 27% (SD 20) suppression of ISR. The participants who underwent a 2-step insulin clamp had greater suppression of ISR during the second step than the first step (P <.001). The proportional suppression of ISR during euglycemic hyperinsulinemia was not different between nonobese and obese groups (P =.19). Conclusion Hyperinsulinemia suppresses endogenous insulin secretion and the relative change in insulin secretion produced by exogenous insulin did not differ between nonobese and obese people. [ABSTRACT FROM AUTHOR]

Abstract Methods This study assessed data from two cohorts of patients with alpha‐synucleinopathies (University of Brescia and University of Rome Tor‐Vergata cohorts). Consecutive participants with video‐polysomnography‐confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I‐FP‐CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I‐FP‐CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls. Results The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age‐matched controls. Individuals with iRBD were categorized as RBD‐DAT− (n = 32) and RBD‐DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD‐DAT− showed an early involvement of the left insula, which increased in RBD‐DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18–10.27]. Interpretation In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non‐pharmacological interventions.

Abstract Intestinal permeability has been related to colorectal cancer (CRC) development. Zonulin, a protein able to regulate tight junction function and intestinal permeability, emerges as a promising marker to elucidate the contribution of bacterial translocation in CRC. An Italian case-control study included 77 CRC cases, 72 intestinal adenoma and 76 healthy controls (for a total of 148 tumor-free subjects), aged 20–85. Serum zonulin levels were quantified by ELISA kit and blood 16S rRNA gene copies by DNA extraction and polymerase chain reaction. We applied logistic regression models adjusted for center, sex, age and education. There was a positive association between zonulin and CRC risk. The odds ratio (OR) of CRC for the highest versus lowest tertile of zonulin as compared to tumor-free subjects was 2.36 (95% confidence interval, 1.14–4.86). The ORs were similar in colon and rectal cancers. The OR of colon cancer for the highest versus lowest levels of both zonulin and 16S rRNA gene copies was 4.55. Circulating levels of zonulin were higher in CRC patients compared to tumor-free controls supporting the hypothesis of an interplay of gut barrier dysfunction and bacterial translocation in colorectal carcinogenesis. Zonulin may interact with 16S rRNA gene copies and serve as a further biomarker in the evaluation of CRC diagnosis.

Abstract Receptors for activated C kinases (RACKs) have been shown to coordinate PKC-mediated hypertrophic signalling in mice. However, little information is available on its participation in embryonic gene expression. This study investigated the involvement of RACK1 in the expression of embryonic genes in a zebrafish (ZF) ex vivo heart culture model by using phenylephrine (PE) or a growth factors cocktail (GFs) as a prohypertrophic/regeneration stimulus. Blebbistatin (BL) inhibition has also been studied for its ability to block the signal transduction actions of some PEs. qRT‒PCR and immunoblot analyses confirmed the upregulation of RACK1 in the PE- and GFs-treated groups. BL administration counteracted PE-induced hypertrophy and downregulated RACK1 expression. Immunohistochemical analyses of the heart revealed the colocalization of RACK1 and embryonic genes, namely, Gata4, Wt1, and Nfat2, under stimulation, whereas these genes were expressed at lower levels in the BL treatment group. Culturing ZF heart cells activated via GFs treatment increased the expression of RACK1. The overexpression of RACK1 induced by the transfection of recombinant RACK1 cDNA in ZF heart cells increased the expression of embryonic genes, especially after one week of GFs treatment. In summary, these results support the involvement of RACK1 in the induction of embryonic genes during cardiac hypertrophy/GFs stimulation in a fish heart model, which can be used as an alternative study model for mammals.

Abstract Historical landscapes in Italy have been slowly changing over the centuries and this is because their features, once fixed into specific shapes, were perpetuated until new economic and social developments occurred. Yet, in the Alpine region, this territorial organisation underwent sudden changes after World War II (WW II), resulting in a loss in population and traditional agropastoral production in favour of skiing plants and holiday houses. Moreover, the loss of traditional knowledge pertaining to environmental behaviour has resulted in the urbanisation of lands that are vulnerable to extreme events. In turn, this has hindered sustainable urban development. Nowadays, modern mapping technologies enable the state of the landscape to be assessed before, during, and after extreme events, the increased frequency of which may be related to climate change. The case study examined in this paper is the flood that hit Limone Piemonte, Italy, between the 2nd and 3rd October 2020. On that occasion, an aerial survey of the affected areas was carried out using Uncrewed Aerial Vehicles (UAV) a few weeks after the event. Spatial analyses were also performed based on very high-resolution satellite imagery acquired a few days after the event in order to determine where to plan more detailed three-dimensional (3D) surveys. This has enabled assessments of damages at different map scales to be performed. Thanks to the availability of pre-event multitemporal cartographic reference datasets, it was possible to monitor the historical evolution of the affected areas. It was possible to assess the vulnerable areas before the event, as well as to evaluate the morphological and settlement changes after the disaster. Therefore, one of the goals of this manuscript is to demonstrate that geoinformation systems are among the primary technical tools used to analyse environmental and climatic alterations that impact landscapes. Finally, a 3D model of the affected areas was produced, fulfilling another goal of the research by providing the public administration with a sustainable and innovative tool for territorial and landscape management, in accordance with the 11th pillar of the United Nations Sustainable Development Goals (UN SDGs).

Over the last two decades, we have witnessed great advancements in our understanding of the immunological pathways of asthma, leading to the development of targeted therapies, such as biologic drugs, that have radically and definitively changed the clinical outcomes of severe asthma. Despite the numerous therapeutic options available, ~4–10% of all people with asthma have severe or uncontrolled asthma, associated with an increased risk of developing chronic oral corticosteroid use, fixed airflow limitation, exacerbations, hospitalization and, finally, increased healthcare costs. The new concept of disease modification in asthma comes from the evolution of asthma management, which encompasses phenotyping patients with different inflammatory endotypes characterizing the disease, followed by the advent of more effective therapies capable of targeting the proximal factors of airway inflammation. This treat-to-target approach aims to achieve remission of the disease. Because the novel treatment paradigm for severe asthma with the advent of biologic therapies is no longer clinical control but rather clinical remission – a step closer to the concept of cure – a deeper and more accurate understanding of the critical causal mechanisms and endotypes of asthma is necessary to achieve the goal of clinical remission, which has the potential to generate real life-changing benefits for patients. This review aims to frame the evolution of the debated concept of clinical remission and provide clinicians with insights that may be helpful in achieving remission in the greatest number of patients.

The CoCrFeNiMnX (X = 5, 20, and 35 at.%) alloys, reinforced with 5 at.% SiC powder, were prepared by mechanical alloying and spark plasma sintering. This preparation method resulted in microstructural refinement of the FCC solid solution grains, while the SiC addition reacted with residual oxygen to form homogeneously distributed ultrafine SiO2 particles. Additionally, the alloys contained Cr7C3 carbides, which were significantly larger than the SiO2 particles and enriched with the alloy's elements, including Mn. Among the tested materials, the reinforced CoCrFeNiMn20 alloy exhibited the highest hardness and compressive yield strength (CYS), achieving 392 ± 9 HV30 or 476 ± 3 HVIT1 and 1024 ± 18 MPa, respectively. This alloy also maintained superior CYS (956 ± 35 MPa) even after 100 h of annealing at 800 °C. The reduction in CYS after annealing was smallest for the CoCrFeNiMn5 alloy (35 MPa) and increased with higher Mn content, highlighting Mn's significant role in diffusion-related processes. At elevated temperatures (600 and 800 °C), the CoCrFeNiMn5 alloy had the highest CYS of 190 ± 33 MPa, while the CoCrFeNiMn35 alloy had the lowest at 80 ± 6 MPa. This trend was also observed in wear rate tests, where the CoCrFeNiMn5 alloy had the lowest specific wear rate coefficient of 3.54 ± 0.09 × 10-4 mm³ N⁻1 m⁻1. This was due to matrix softening and oxide lubrication without significant spalling. Thus, the CoCrFeNiMn5 alloy demonstrated superior mechanical properties and wear resistance under various conditions, making it a promising candidate for applications requiring high strength and durability.

Magnetic resonance imaging is a novel imaging technique for guiding electrophysiology based ablation operations for atrial flutter and typical atrial fibrillation. When compared to standard electrophysiology ablation, this innovative method allows for better outcomes. Intra-procedural imaging is important for following the catheter in real time throughout the ablation operation while also seeing cardiac architecture and determining whether the ablation is being completed appropriately utilizing oedema sequences. At the same time, intra-procedural imaging allows immediate visualization of any complications of the procedure. We describe a case of a 67 year old male underwent an isthmus-cavo-tricuspid magnetic resonance-guided thermoablation procedure for atrial flutter episodes. During the procedure we noted an atypical focal thinning of the right atrial wall at the isthmus cava-tricuspidal zone. The post-procedural Black Blood T2 STIR showed an area of hyperintensity at the hepatic dome and glissonian capsule, which was consistent with intraparenchymal hepatic oedema, in close proximity to the atrial finding. Given the opportunity to direct monitoring of adjacent tissues, we aim to highlight with our case the ability of magnetic resonance-guided cardiac ablation to immediately detect peri-procedural complications in the ablative treatment of atrial fibrillation.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased β-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall β-cell function quantified by the Disposition Index was unchanged, the dynamic component of β-cell responsivity (/d) was decreased by Intralipid and glucose infusion (9 ± 1 vs. 16 ± 3 109, P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of β-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes. [ABSTRACT FROM AUTHOR]