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    Masking capacity of minimally invasive lithium disilicate restorations on discolored teeth-The impact of ceramic thickness, the material's translucency, and the cement color.

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    OBJECTIVES To evaluate minimally invasive restorations' capacity to mask discolored teeth and explore the impact of ceramic thickness, translucency, and cement color. MATERIALS AND METHODS Twenty-four assessment pairs of naturally colored and discolored bovine dentin samples were formed, using lithium disilicate specimens in six different thicknesses (0.3-0.8 mm), two different translucencies (high, low), and two cements (transparent, tooth-colored). Evaluators assessed the color differences in each assessment pair, and the threshold for detecting a color difference was determined using sequential testing and the Bonferroni-Holm method. RESULTS A thickness of 0.6 mm effectively masked color differences using high translucent ceramic with transparent cement, detectable differences were still observed at 0.7/0.8 mm. A threshold thickness of 0.4 mm was seen using high translucent ceramic and tooth-colored cement, with color differences still discernible at 0.5 and 0.8 mm. A threshold thickness of 0.4 mm was detected using low translucent ceramic and transparent cement, while detectable differences persisted at 0.5, 0.7, and 0.8 mm. A 0.5 mm threshold thickness was observed when using low translucent ceramic and tooth-colored cement, and no detectable color differences were detected beyond this thickness. CONCLUSIONS Masking can be achieved with a thickness of 0.4-0.5 mm using a low translucent material and tooth-colored cement. CLINICAL SIGNIFICANCE Understanding the impact of ceramic thickness, translucency, and cement color can aid clinicians in making informed decisions for achieving the best esthetic outcomes while preserving tooth structure. Effective masking can be accomplished with ceramic thicknesses starting at 0.4 mm, especially when employing a low translucent material and tooth-colored cement. However, clinicians should be aware that discolorations may still be detectable in certain scenarios when using minimally invasive lithium disilicate restorations

    Inhibition of the Renal Apical Sodium Dependent Bile Acid Transporter Prevents Cholemic Nephropathy in Mice with Obstructive Cholestasis.

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    BACKGROUND & AIMS Cholemic nephropathy (CN) is a severe complication of cholestasis-associated liver diseases, with no specific treatment. We revisited the pathophysiology to identify therapeutic strategies. METHODS Cholestasis was induced by bile duct ligation (BDL) in mice. Bile flux in kidneys and livers was visualized by intravital imaging, supported by MALDI-MSI and LC-MS/MS. The effect of AS0369, a systemically bioavailable apical sodium-dependent bile acid transporter (ASBT) inhibitor, was evaluated by intravital imaging, RNA-sequencing, histological, blood, and urine analyses. Translational relevance was assessed by ASBT immunostaining in kidney biopsies of CN patients, analysis of mice with humanized BA spectrum, and by analysis of serum bile acids (BA) and kidney injury molecule (KIM-1) in liver disease and hyperbilirubinemia patients. RESULTS Proximal tubular epithelial cells (TEC) reabsorbed and enriched BA, leading to oxidative stress and death of proximal TEC, casts in distal tubules and collecting ducts, peritubular capillaries leakiness, and glomerular cysts. Renal ASBT inhibition by AS0369 blocked BA uptake into TEC and prevented kidney injury up to 6 weeks after BDL. Similar results were obtained in mice with humanized BA composition. In advanced liver disease patients, serum BA were the main determinant of KIM-1 levels. ASBT expression in TEC was preserved in biopsies from CN patients, further highlighting the translational potential of targeting ASBT for treatment of CN. CONCLUSIONS BA enrichment in proximal TEC followed by oxidative stress and cell death is an early key event in CN. Inhibiting renal ASBT and consequently BA enrichment in TEC prevents CN and systemically decreases BA concentrations. IMPACT AND IMPLICATIONS Cholemic nephropathy (CN) is a severe complication of cholestasis with an unmet clinical need for therapy. We demonstrate that CN is triggered by the renal accumulation of bile acids (BA)- that are considerably increased in the systemic blood. Specifically, the proximal tubular epithelial cells (TEC) of the kidney take up BA via the apical sodium-dependent bile acid transporter (ASBT). We developed a therapeutic compound that blocks ASBT in the kidneys, prevents BA overload in TEC, and almost completely abolished all disease hallmarks in a CN mouse model. Renal ASBT inhibition represents a potential therapeutic strategy for CN patients

    Emergency front-of-neck access in infants: A pragmatic crossover randomized control trial comparing two approaches on a simulated rabbit model.

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    BACKGROUND Rapid-sequence tracheotomy and scalpel-bougie tracheotomy are two published approaches for establishing emergency front-of-neck access in infants. It is unknown whether there is a difference in performance times and success rates between the two approaches. AIMS The aim of this cross-over randomized control trial study was to investigate whether the two approaches were equivalent for establishing tracheal access in rabbit cadavers. The underlying hypothesis was that the time to achieve the tracheal access is the same with both techniques. METHODS Between May and September 2022, thirty physicians (pediatric anesthesiologists and intensivists) were randomized to perform front-of-neck access using one and then the other technique: rapid-sequence tracheotomy and scalpel-bougie tracheotomy. After watching training videos, each technique was practiced four times followed by a final tracheotomy during which study measurements were obtained. Based on existing data, an equivalence margin was set at ∆ = ±10 s for the duration of the procedure. The primary outcome was defined as the duration until tracheal tube placement was achieved successfully. Secondary outcomes included success rate, structural injuries, and subjective participant self-evaluation. RESULTS The median duration of the scalpel-bougie tracheotomy was 48 s (95% CI: 37-57), while the duration of the rapid-sequence tracheotomy was 59 s (95% CI: 49-66, p = .07). The difference in the median duration between the two approaches was 11 s (95% CI: -4.9 to 29). The overall success rate was 93.3% (95% CI: 83.8%-98.2%). The scalpel-bougie tracheotomy resulted in significantly fewer damaged tracheal rings and was preferred among participants. CONCLUSIONS The scalpel-bougie tracheotomy was slightly faster than the rapid-sequence tracheotomy and favored by participants, with fewer tracheal injuries. Therefore, we propose the scalpel-bougie tracheostomy as a rescue approach favoring the similarity to the adult approach for small children. The use of a comparable equipment kit for both children and adults facilitates standardization, performance, and logistics. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT05499273

    Association of results of the glutaraldehyde coagulation test with plasma acute phase protein concentrations and hematologic findings in hospitalized cows.

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    INTRODUCTION The glutaraldehyde test (GAT) allows for animal-side semi-quantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations. METHODS For the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and non-inflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations. RESULTS Shortened GAT coagulation times were more closely correlated to serum globulin (rs  = -0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs  = -0.64) and the Clauss method (rs  = -0.70). Cows with a markedly (≤3 min) or moderately (4-6 min) shortened coagulation time had higher (p < 0.001) plasma haptoglobin and SAA concentrations than cows with a negative test result. Total leukocyte, monocyte and neutrophil concentrations did not differ significantly between groups. An identified cut-off for the GAT coagulation time of ≤14 min had a sensitivity and specificity of 54.4 and 100%, respectively, for the prediction of an inflammatory state based on clinical findings and/or increased plasma haptoglobin or SAA concentrations. DISCUSSION In conclusion, this study demonstrates considerable diagnostic agreement between positive GAT results and increased plasma concentrations of haptoglobin and SAA. Despite high specificity, the test lacks sensitivity in case of acute inflammatory conditions indicating that plasma acute phase protein concentrations and hematologic findings can provide additional diagnostic information if the GAT is negative

    Prevalence and outcomes of heart failure phenotypes in patients with atrial fibrillation.

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    BACKGROUND Atrial fibrillation (AF) is common in patients with heart failure (HF). Real-world data about long-term outcomes and rhythm control interventions use in AF patients with and without HF remain scarce. METHODS AF patients from two prospective, multicentre studies were classified based on the HF status at baseline into: HF with preserved ejection fraction (HFpEF), HF with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF), and no HF. The prespecified primary outcome was risk of HF hospitalisation. Other outcomes of interest included mortality, cardiovascular events, AF progression, and quality of life. RESULTS A total of 1265 patients with AF were analysed (mean age 69.6 years, women 27.4%) with a median follow-up of 5.98 years. Patients with HFpEF (n = 126) had a 2.69-fold and patients with HFrEF/HFmrEF (n = 308) had a 2.12-fold increased risk of HF hospitalisation compared to patients without HF (n = 831, p < 0.001). Similar results applied for all-cause and cardiovascular mortality. The risk for AF progression was higher for patients with HFpEF and HFrEF/HFmrEF (6.30 and 6.79 per 100 patient-years, respectively) compared to patients without HF (4.20). The use of rhythm control strategies during follow-up was least in the HFpEF population (4.56 per 100 patient-years) compared to 7.74 in HFrEF/HFmrEF and 8.03 in patients with no HF. With regards to quality of life over time, this was worst among HFpEF patients. CONCLUSIONS The presence of HFpEF among patients with AF carried a high risk of HF hospitalisations and AF progression, and worse quality of life. Rhythm control interventions were rarely offered to HFpEF patients. These results uncover an unmet need for enhanced therapeutic interventions in patients with AF and HFpEF

    Gut-derived immune cells and the gut-lung axis in ARDS.

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    The gut serves as a vital immunological organ orchestrating immune responses and influencing distant mucosal sites, notably the respiratory mucosa. It is increasingly recognized as a central driver of critical illnesses, with intestinal hyperpermeability facilitating bacterial translocation, systemic inflammation, and organ damage. The "gut-lung" axis emerges as a pivotal pathway, where gut-derived injurious factors trigger acute lung injury (ALI) through the systemic circulation. Direct and indirect effects of gut microbiota significantly impact immune responses. Dysbiosis, particularly intestinal dysbiosis, termed as an imbalance of microbial species and a reduction in microbial diversity within certain bodily microbiomes, influences adaptive immune responses, including differentiating T regulatory cells (Tregs) and T helper 17 (Th17) cells, which are critical in various lung inflammatory conditions. Additionally, gut and bone marrow immune cells impact pulmonary immune activity, underscoring the complex gut-lung interplay. Moreover, lung microbiota alterations are implicated in diverse gut pathologies, affecting local and systemic immune landscapes. Notably, lung dysbiosis can reciprocally influence gut microbiota composition, indicating bidirectional gut-lung communication. In this review, we investigate the pathophysiology of ALI/acute respiratory distress syndrome (ARDS), elucidating the role of immune cells in the gut-lung axis based on recent experimental and clinical research. This exploration aims to enhance understanding of ALI/ARDS pathogenesis and to underscore the significance of gut-lung interactions in respiratory diseases

    Steatotic liver disease and HIV: an agenda for 2030.

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    People living with HIV are particularly susceptible to developing metabolic disorders, including metabolic dysfunction-associated steatotic liver disease and other forms of SLD. However, people living with HIV have been historically excluded from clinical trials and large cohort studies of SLD. Therefore, our understanding of the risk factors and natural history of SLD in this population is poor. Moreover, relevant knowledge gaps on the epidemiology and barriers for adequate health care, such as stigma, hamper adequate responses to the ongoing HIV and SLD syndemic. This Viewpoint provides a comprehensive perspective on how to tackle SLD in people living with HIV by examining the role of social determinants of health in the development of liver disease and metabolic syndrome comorbidities among this population, emphasising the importance of prioritising SLD management, summarising the most urgent needs in the field, and offering recommendations for advancing research to fill key data gaps and protect liver health of people living with HIV

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