► Whey proteins can reduce postprandial glucose levels and stimulate insulin release. ► Administration of whey protein was associated with higher levels of intact incretins. ► Dipeptidyl peptidase-4 ...(DPP-4) is the main enzyme responsible for incretin degradation. ► β-Lactoglobulin is the major whey protein found in the milk of cows and other ruminants. ► Ile-Pro-Ala (IPA) is a bioactive peptide generated by proteolysis of bovine β-lactoglobulin. ► Our results showed that IPA can be regarded as a moderate DPP-4 inhibitor.
Preclinical and clinical studies suggest that whey proteins can reduce postprandial glucose levels and stimulate insulin release in healthy subjects and in subjects with type 2 diabetes by reducing dipeptidyl peptidase-4 (DPP-4) activity in the proximal bowel and hence increasing intact incretin levels. Our aim was to identify DPP-4 inhibitors among short peptides occurring in hydrolysates of β-lactoglobulin, the major whey protein found in the milk of ruminants. We proved that the bioactive peptide Ile-Pro-Ala can be regarded as a moderate DPP-4 inhibitor.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited disorder of the kidneys. It is characterized by enlargement of the kidneys caused by progressive development of renal ...cysts, and thus assessment of total kidney volume (TKV) is crucial for studying disease progression in ADPKD. However, automatic segmentation of polycystic kidneys is a challenging task due to severe alteration in the morphology caused by non-uniform cyst formation and presence of adjacent liver cysts. In this study, an automated segmentation method based on deep learning has been proposed for TKV computation on computed tomography (CT) dataset of ADPKD patients exhibiting mild to moderate or severe renal insufficiency. The proposed method has been trained (n = 165) and tested (n = 79) on a wide range of TKV (321.2-14,670.7 mL) achieving an overall mean Dice Similarity Coefficient of 0.86 ± 0.07 (mean ± SD) between automated and manual segmentations from clinical experts and a mean correlation coefficient (ρ) of 0.98 (p < 0.001) for segmented kidney volume measurements in the entire test set. Our method facilitates fast and reproducible measurements of kidney volumes in agreement with manual segmentations from clinical experts.
Background: Innate immune responses induced by in vitro stimulation of primary mammary epithelial cells (MEC) using Gram-negative lipopolysaccharide (LPS) and Gram-positive lipoteichoic acid (LTA) ...bacterial cell wall components are well- characterized in bovine species. The objective of the current study was to characterize the downstream regulation of the inflammatory response induced by Toll-like receptors in primary goat MEC (pgMEC). We performed quantitative real-time RT-PCR (qPCR) to measure mRNA levels of 9 genes involved in transcriptional regulation or antibacterial activity: Toll-like receptor 2 (TLR2), Toll-like receptor 4(TLR4), prostaglandin-endoperoxide synthase 2 (PTGS2), interferon induced protein with tetratricopeptide repeats 3(IFIT3), interferon regulatory factor 3 (IRF3), myeloid differentiation primary response 88 (MYD88), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1), Toll interacting protein (TOLLIP), and lactoferrin (LTF). Furthermore,we analyzed 7 cytokines involved in Toll-like receptor signaling pathways: C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 5 (CCL5), C-X-C motif chemokine ligand 6 (CXCL6), interleukin 8 (CXCL8), interleukin 1 beta (IL1B), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF).Results: Stimulation of pgMEC with LPS for 3 h led to an increase in expression of CCL2, CXCL6, IL6, CXCL8,PTGS2, IFIT3, MYD88, NFKB1, and TLR4 (P < 0.05). Except for IL6, and PTGS2, the same genes had greater expression than controls at 6 h post-LPS (P < 0.05). Expression of CCL5, PTGS2, IFIT3, NFKB1, TLR4, and TOLLIP was greater than controls after 3 h of incubation with LTA (P < 0.05). Compared to controls, stimulation with LTA for 6 h led to greater expression of PTGS2, IFIT3, NFKB1, and TOLLIP (P < 0.05) whereas the expression of CXCL6, CXCL8, and TLR4 was lower (P<0.05). At 3 h incubation with both toxins compared to controls a greater expression (P < 0.05) of CCL2, CCL5, CXCL6, CXCL8, IL6, PTGS2, IFIT3, IRF3, MYD88, and NFKB1 was detected. After 6 h of incubation with both toxins, the expression of CCL2, CXCL6, IFIT3, MYD88, NFKB1, and TLR4 was higher than the controls (P < 0.05).Conclusions: Data indicate that in the goat MEC, LTA induces a weaker inflammatory response than LPS.This may be related to the observation that gram-positive bacteria cause chronic mastitis more often than gram-negative infections.
Objectives
To evaluate the inter-rater agreement of chest X-ray (CXR) findings in coronavirus disease 2019 (COVID-19) and to determine the value of initial CXR along with demographic, clinical, and ...laboratory data at emergency department (ED) presentation for predicting mortality and the need for ventilatory support.
Methods
A total of 340 COVID-19 patients who underwent CXR in the ED setting (March 1–13, 2020) were retrospectively included. Two reviewers independently assessed CXR abnormalities, including ground-glass opacities (GGOs) and consolidation. Two scoring systems (
Brixia
score and percentage of lung involvement) were applied. Inter-rater agreement was assessed by weighted Cohen’s kappa (
κ
) or intraclass correlation coefficient (ICC). Predictors of death and respiratory support were identified by logistic or Poisson regression.
Results
GGO admixed with consolidation (
n
= 235, 69%) was the most common CXR finding. The inter-rater agreement was almost perfect for type of parenchymal opacity (
κ
= 0.90),
Brixia
score (ICC = 0.91), and percentage of lung involvement (ICC = 0.95). The
Brixia
score (OR: 1.19; 95% CI: 1.06, 1.34;
p
= 0.003), age (OR: 1.16; 95% CI: 1.11, 1.22;
p
< 0.001), PaO
2
/FiO
2
ratio (OR: 0.99; 95% CI: 0.98, 1;
p
= 0.002), and cardiovascular diseases (OR: 3.21; 95% CI: 1.28, 8.39;
p
= 0.014) predicted death. Percentage of lung involvement (OR: 1.02; 95% CI: 1.01, 1.03;
p
= 0.001) and PaO
2
/FiO
2
ratio (OR: 0.99; 95% CI: 0.99, 1.00;
p
< 0.001) were significant predictors of the need for ventilatory support.
Conclusions
CXR is a reproducible tool for assessing COVID-19 and integrates with patient history, PaO
2
/FiO
2
ratio, and SpO
2
values to early predict mortality and the need for ventilatory support.
Key Points
• Chest X-ray is a reproducible tool for assessing COVID-19 pneumonia.
•
The Brixia score and percentage of lung involvement on chest X-ray integrate with patient history, PaO
2
/FIO
2
ratio, and SpO
2
values to early predict mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.
Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive method sensitive to local water motion in the tissue. As a tool to probe the microstructure, including the presence and ...potentially the degree of renal fibrosis, DWI has the potential to become an effective imaging biomarker. The aim of this review is to discuss the current status of renal DWI in diffuse renal diseases. DWI biomarkers can be classified in the following three main categories: (i) the apparent diffusion coefficient-an overall measure of water diffusion and microcirculation in the tissue; (ii) true diffusion, pseudodiffusion and flowing fraction-providing separate information on diffusion and perfusion or tubular flow; and (iii) fractional anisotropy-measuring the microstructural orientation. An overview of human studies applying renal DWI in diffuse pathologies is given, demonstrating not only the feasibility and intra-study reproducibility of DWI but also highlighting the need for standardization of methods, additional validation and qualification. The current and future role of renal DWI in clinical practice is reviewed, emphasizing its potential as a surrogate and monitoring biomarker for interstitial fibrosis in chronic kidney disease, as well as a surrogate biomarker for the inflammation in acute kidney diseases that may impact patient selection for renal biopsy in acute graft rejection. As part of the international COST (European Cooperation in Science and Technology) action PARENCHIMA (Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease), aimed at eliminating the barriers to the clinical use of functional renal magnetic resonance imaging, this article provides practical recommendations for future design of clinical studies and the use of renal DWI in clinical practice.
In bovine species, β-casein (β-CN) is characterized by genetic polymorphism. The two most common protein variants are β-CN A² (the original one) and A¹, differing from A² for one amino acid ...substitution (Pro67 to His67). Several bioactive peptides affecting milk nutritional properties can originate from β-CN. Among them, β-casomorphin-7 (BCM7) ranging from amino acid 60 to 66 can be released more easily from β-CN variants carrying His67 (A¹ type) instead of Pro67 (A² type). Nowadays, "A2 milk" is produced in different countries claiming its potential benefits in human health. The aim of this study was to further develop and apply an isoelectric focusing electrophoresis (IEF) method to bulk and individual milk samples in order to improve its use for β-CN studies. We succeeded in identifying A2 milk samples correctly and quantifying the percentage of A², A¹, and B variants in bulk samples not derived from A2 milk as well as in individual milk samples. The method allows us to quantify the relative proportion of β-CN variants in whole milk without eliminating whey protein by acid or enzymatic precipitation of caseins. The aim of this study was also to study the different behavior of β-CN and β-lactoglobulin (β-LG) in the presence of trichloroacetic acid (TCA). The higher sensitivity of β-CN to TCA allows quantifying β-CN variants after TCA fixation because β-LG is not visible. Monitoring β-CN variation in cattle breeds is important in order to maintain a certain balance between Pro67 and His67 in dairy products. Overall, the debate between A1 and A2 milk needs further investigation.
Milk nutritional characteristics are especially interesting when donkey milk is aimed at consumption by children and the elderly. The aim of this study was to monitor the nutritional quality of ...Amiata donkey milk during lactation and productive season to provide information on the milk characteristics and to study action plans to improve milk yield and quality. Thirty-one pluriparous jennies belonging to the same farm were selected. Individual samples of milk from the morning milking were taken once per month starting from the d 30 of lactation until d 300. Milk yield and dry matter, fat, and ash content were constant throughout the experimental period. Milk total protein content showed a progressive decrease during the first 6mo of lactation; after this period, the protein percentages remained constant (1.50%). Caseins and lactose were lower until d 60 of lactation and remained constant thereafter. During summer and autumn, milk yield and casein and lactose contents were higher, whereas during the spring season, higher protein and ash contents were found. The percentages of fat and dry matter were stable as were most of the minerals in the milk, except for calcium, which was higher in the spring. In conclusion, Amiata donkey milk was found to be relatively stable during lactation. This is an advantage in terms of the production and trade of a food product with consistent characteristics. The different milk yield and quality during the productive seasons were probably related to better adaptability of the animals to warm and temperate periods.
•Severe COVID-19 survivors can still have chest CT abnormalities after discharge, even beyond three months after the disease onset.•The percentage of compromised lung volume on CT correlates with ...pulmonary function tests and dyspnea severity.•Pulmonary function tests indicate an impairment of diffusion capacity and a tendency toward restrictive physiology in most cases.•An underlying pulmonary vasculopathy is possibly implied in a minor proportion of patients.
To evaluate chest computed tomography (CT) and pulmonary function test (PFT) findings in severe COVID-19 patients after discharge and correlate CT pulmonary involvement with PFT results.
COVID-19 patients admitted to our hospital between February 25 and May 2, 2020, were retrospectively included according to the following criteria: (a) COVID-19 defined as severe based on the WHO interim guidance (i.e., clinical signs of pneumonia plus respiratory rate > 30 breaths/min, severe respiratory distress, and/or SpO2 < 90 % on room air); (b) chest radiograph in the acute setting; (c) post-discharge unenhanced chest CT; and (d) post-discharge comprehensive PFT. Imaging findings were retrospectively evaluated in consensus by two readers, and volume of abnormal lung was measured on CT using 3D Slicer software. Differences between demographics, comorbidities, acute radiographic findings, PFT, and post-discharge clinical and laboratory data of patients with normal and abnormal CT findings were assessed by Mann-Whitney or Fisher tests, and the compromised lung volume-PFT association by Pearson correlation after removing possible outliers.
At a median of 105 days from symptom onset, 74/91 (81 %) patients had CT abnormalities. The most common CT pattern was combined ground-glass opacity and reticular pattern (46/74, 62 %) along with architectural distortion (68/74, 92 %) and bronchial dilatation (66/74, 89 %). Compromised lung volume had a median value of 15 % 11–23, was higher in dyspneic patients, and negatively correlated with the percentage of predicted DLCO, VA, and FVC values (r = -0.39, -0.5, and -0.42, respectively). These PFT parameters were significantly lower in patients with CT abnormalities. Impairment of DLCO and KCO was found in 12 (13 %) cases, possibly implying an underlying pulmonary vasculopathy in this subgroup of patients.
Most severe COVID-19 survivors still had physiologically relevant CT abnormalities about three months after the disease onset, with an impairment of diffusion capacity on PFT. A pulmonary vasculopathy was suggested in a minor proportion of patients.
18
F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) is a widely used diagnostic tool that can detect and quantify pathophysiology, as assessed through changes in cerebral glucose ...metabolism.
18
F-FDG PET scans can be analyzed using voxel-based statistical methods such as Statistical Parametric Mapping (SPM) that provide statistical maps of brain abnormalities in single patients. In order to perform SPM, a “spatial normalization” of an individual’s PET scan is required to match a reference PET template. The PET template currently used for SPM normalization is based on
15
O-H
2
O images and does not resemble either the specific metabolic features of
18
F-FDG brain scans or the specific morphological characteristics of individual brains affected by neurodegeneration. Thus, our aim was to create a new
18
F-FDG PET aging and dementia-specific template for spatial normalization, based on images derived from both age-matched controls and patients. We hypothesized that this template would increase spatial normalization accuracy and thereby preserve crucial information for research and diagnostic purposes. We investigated the statistical sensitivity and registration accuracy of normalization procedures based on the standard and new template—at the single-subject and group level—independently for subjects with Mild Cognitive Impairment (MCI), probable Alzheimer’s Disease (AD), Frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). We found a significant statistical effect of the population-specific FDG template-based normalisation in key anatomical regions for each dementia subtype, suggesting that spatial normalization with the new template provides more accurate estimates of metabolic abnormalities for single-subject and group analysis, and therefore, a more effective diagnostic measure.
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