1,721,045 research outputs found
Vitamin D Deficiency in Cushing’s Disease: Before and After Its Supplementation
Full text linkBackground: The primary objective of the study was to assess serum 25-hydroxyvitamin D [25(OH)D] values in patients with Cushing’s disease (CD), compared to controls. The secondary objective was to assess the response to a load of 150,000 U of cholecalciferol. Methods: In 50 patients with active CD and 48 controls, we evaluated the anthropometric and biochemical parameters, including insulin sensitivity estimation by the homeostatic model of insulin resistance, Matsuda Index and oral disposition index at baseline and in patients with CD also after 6 weeks of cholecalciferol supplementation. Results: At baseline, patients with CD showed a higher frequency of hypovitaminosis deficiency (p = 0.001) and lower serum 25(OH)D (p < 0.001) than the controls. Six weeks after cholecalciferol treatment, patients with CD had increased serum calcium (p = 0.017), 25(OH)D (p < 0.001), ISI-Matsuda (p = 0.035), oral disposition index (p = 0.045) and decreased serum PTH (p = 0.004) and total cholesterol (p = 0.017) values than at baseline. Multivariate analysis showed that mean urinary free cortisol (mUFC) was independently negatively correlated with serum 25(OH)D in CD. Conclusions: Serum 25(OH)D levels are lower in patients with CD compared to the controls. Vitamin D deficiency is correlated with mUFC and values of mUFC > 240 nmol/24 h are associated with hypovitaminosis D. Cholecalciferol supplementation had a positive impact on insulin sensitivity and lipids
Nutritional Intervention in Cushing's Disease: The Ketogenic Diet's Effects on Metabolic Comorbidities and Adrenal Steroids
Full text linkBackground: a very low-calorie ketogenic diet (VLCKD) is associated with improvement of metabolic and cardiovascular disorders. We aimed to evaluate the effects of a VLCKD in patients with Cushing's disease (CD) as adjunctive therapy to treatment for the primary disease. Methods: we evaluated clinical, hormonal and metabolic parameters in 15 patients with CD and 15 controls at baseline after 1 week and 3 weeks of VLCKD and, further, after 2 weeks of a low-carbohydrate ketogenic diet (LCKD). Results: after 5 weeks of diet, a significant decrease in BMI (p = 0.002), waist circumference (WC) (p = 0.024), systolic blood pressure (p = 0.015), diastolic blood pressure (p = 0.005), ACTH (p = 0.026), cortisone (p = 0.025), total cholesterol (p = 0.006), LDL cholesterol (p = 0.017), triglycerides (p = 0.016) and alkaline phosphatase (p = 0.008) and a significant increase in HDL cholesterol (p = 0.017), vitamin D (p = 0.015) and oral disposition index (oDI) (p = 0.004) was observed in the CD patients. A significant decrease in BMI (p = 0.003), WC (p = 0.002), systolic blood pressure (p = 0.025), diastolic (p = 0.007) blood pressure and total cholesterol (p = 0.026) and an increase in HDL cholesterol (p = 0.001) and oDI (p < 0.001) was observed in controls. Conclusions: the current study confirms that a ketogenic diet is effective in improving metabolic disorders in CD and shows that a nutritional approach may be combined with conventional CD therapy in order to improve metabolic and cardiovascular comorbidities
Setting up of a machine learning algorithm for the identification of severe liver fibrosis profile in the general US population cohort
No full textBackground
The progress of digital transformation in clinical practice opens the door to transforming the current clinical line for liver disease diagnosis from a late-stage diagnosis approach to an early-stage based one. Early diagnosis of liver fibrosis can prevent the progression of the disease and decrease liver-related morbidity and mortality. We developed here a machine learning (ML) algorithm containing standard parameters that can identify liver fibrosis in the general US population.
Materials and methods
Starting from a public database (National Health and Nutrition Examination Survey, NHANES), representative of the American population with 7265 eligible subjects (control population n = 6828, with Fibroscan values E < 9.7 KPa; target population n = 437 with Fibroscan values E ≥ 9.7 KPa), we set up an SVM algorithm able to discriminate for individuals with liver fibrosis among the general US population. The algorithm set up involved the removal of missing data and a sampling optimization step to managing the data imbalance (only ∼ 5 % of the dataset is the target population).
Results
For the feature selection, we performed an unbiased analysis, starting from 33 clinical, anthropometric, and biochemical parameters regardless of their previous application as biomarkers of liver diseases. Through PCA analysis, we identified the 26 more significant features and then used them to set up a sampling method on an SVM algorithm. The best sampling technique to manage the data imbalance was found to be oversampling through the SMOTE-NC. For final model validation, we utilized a subset of 300 individuals (150 with liver fibrosis and 150 controls), subtracted from the main dataset prior to sampling. Performances were evaluated on multiple independent runs.
Conclusions
We provide proof of concept of an ML clinical decision support tool for liver fibrosis diagnosis in the general US population. Though the presented ML model represents at this stage only a prototype, in the future, it might be implemented and potentially applied to program broad screenings for liver fibrosis
Improvement of a rapid direct blood culture microbial identification protocol using MALDI-TOF MS and performance comparison with SepsiTyper kit
No full textFast diagnosis of pathogens is critical to guarantee the most adequate therapy for infections; bacterial culture methods, which constitute the actual gold standard, are precise and sensitive but rather slow. Today, new methods have been made available to enable faster diagnosis, with the Matrix-Assisted Laser Desorption Ionization–Time Of Flight Mass Spectrometry (MALDI-TOF MS) technique being the most promising. Even if simpler and faster than traditional bacterial culture methods, analysis of positive blood cultures via MALDI-TOF MS requires a preliminary extraction process of samples. In this study, we compared two extraction protocols for bacterial identification directly from positive blood cultures using the Bruker MALDI Biotyper system (Bruker Daltonics, Billerica, MA). In particular, we evaluated the time employed and the overall performance for their accurate identification. In this work, the performances of a commercial extraction kit, named SepsiTyperTM Kit, and those of the protocol developed by Treibmann et al. were evaluated and proven to be similar. However, the SELTERS method represents the best compromise price/performance. Lastly, an in-house developed analysis protocol has been tested, and the introduced optimizations granted a performance level equal if not better than the SepsiTyper kit, a reduced processing time and reduced costs
Occurrence of illicit drugs in two wastewater treatment plants in the South of Italy
No full textIn this study the occurrence and the behavior of illicit drugs and their metabolites have been investigated for two wastewater treatment plants (WWTPs) (namely, WWTP-1 and WWTP-2) located in Sicily (island of Italy). Samples were analyzed for methamphetamine, cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA), methadone (METH), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), 3,4-methylenedioxy amphetamine (MDA); 3,4-methylenedioxy ethylamphetamine (MDEA), 11-nor-9-carboxy-Î9-tetrahydrocannabinol (THC-COOH) and Benzoylecgonine (BEG). The BEG, COC, MOR and THC-COOH were found at the highest concentration in both WWTPs. The Wastewater-based epidemiology calculation for BEG, COC, cannabinoids and THC-COOH was performed. On average, for both plants, population consumes 1.6 and 23.4 dose 1000 inhâ1dayâ1of cocaine and cannabis, respectively. For WWTP-1 negative removals of illicit drugs were observed. For WWTP-2 the following average removal efficiencies were obtained: BEG (77.85%), COC (92.34%), CODEINE (64.75%), MOR (90.16%) and THC-COOH (68.64%)
Exploring Oral and Vaginal Probiotic Solutions for Women's Health from Puberty to Menopause: A Narrative Review
No full textThe vaginal microbiota (VMB) plays a crucial role in women's health from puberty to menopause. Traditional studies have focused on the microorganisms present within the vaginal environment and their roles in disease onset. However, the dynamic relationship between the VMB and its host remains underexplored. Common narratives emphasize the presence of Lactobacilli spp. as an indicator of vaginal health, yet this does not fully explain the occurrence of asymptomatic yet significant dysbiosis. Moreover, a wide array of bacterial types can inhabit the vaginal environment, suggesting that probiotic Lactobacilli could offer a natural, safe solution for balancing vaginal microbiota. This review examines the current literature on VMB, key factors affecting its composition, and the changes it undergoes during different life stages. Given the health-promoting potential of probiotics, we also examine their role in maintaining a healthy VMB and overall women's health throughout life
Cigarette Smoke Extract Induces p38 MAPK-Initiated, Fas-Mediated Eryptosis
Full text linkEryptosis is a physiological mechanism for the clearance of senescent or damaged erythrocytes by phagocytes. Excessive eryptosis is stimulated under several pathologies and associated with endothelial injury and thrombosis. Cigarette smoke (CS) is an established risk factor for vascular diseases and cigarette smokers have high-levels of eryptotic erythrocytes. This study, for the first time, investigates the mechanism by which CS damages red blood cells (RBCs). CS extract (CSE) from commercial cigarettes was prepared and standardized for nicotine content. Cytofluorimetric analysis demonstrated that treatment of human RBCs with CSE caused dose-dependent, phosphatidylserine externalization and cell shrinkage, hallmarks of apoptotic death. CSE did not affect cellular levels of Ca2+, reactive oxygen species (ROS) or glutathione (GSH). Immununoprecipitation and immunoblotting revealed the assembly of the death-inducing signaling complex (DISC) and oligomerization of Fas receptor as well as cleaved caspase-8 and caspase-3 within 6 h from the treatment. At the same time-interval, CSE elicited neutral sphyngomielinase (nSMase) activity-dependent ceramide formation and phosphorylation of p38 MAPK. Through specific inhibitors’ nSMase, caspase-8 or p38 MAPK activities, we demonstrated that p38 MAPK activation is required for caspase-8-mediated eryptosis and that ceramide generation is initiator caspase-dependent. Finally, ex vivo analysis detected phosphorylated p38 MAPK (p-p38) and Fas-associated signaling complex in erythrocytes from cigarette smokers. In conclusion, our study demonstrates that CSE exposure induces in erythrocytes an extrinsic apoptotic pathway involving p38 MAPK-initiated DISC formation followed by activation of caspase-8/caspase-3 via ceramide formation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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