Breeding animals able to effectively respond to stress could be a long-term, sustainable, and affordable strategy to improve resilience and welfare in livestock systems. In the present study, the ...concentrations of 29 plasma biomarkers were used as candidate endophenotypes for metabolic stress response in single-SNP, gene- and haplotype-based GWAS using 739 healthy lactating Italian Holstein cows and 88,271 variants. Significant genetic associations were found in all the 3 GWAS approaches for plasma γ-glutamyl transferase concentration on BTA17, for paraoxonase on BTA4, and for alkaline phosphatase and zinc on BTA2. On these chromosomes, single-SNP and gene-based chromosome-wide association studies were performed, confirming GWAS findings. The signals identified for paraoxonase, γ-glutamyl transferase, and alkaline phosphatase were in proximity of the genes coding for them. The heritability of these 4 biomarkers ranged from moderate to high (from 0.39 to 0.54). Plasma biomarkers are known to undergo large changes in concentration during metabolic stress in the transition period, with an inter-individual variability in the rate of change and recovery time. Genetics may account in part for these differences. To assess this, we studied a subset of 139 periparturient cows homozygous at 3 SNPs known to be respectively associated with concentration of plasma ceruloplasmin, paraoxonase and γ-glutamyl transferase. We compared the immune-metabolic profile measured in plasma at −7, +5 and +30 d relative to calving between groups of opposite homozygotes. A significant effect of the genotype was found on paraoxonase and γ-glutamyl transferase plasma concentration at all the 3 time points. No evidence for genotype effect was detected for ceruloplasmin. Understanding the genetic control underlying metabolic stress response may suggest new approaches to foster resilience in dairy cows.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pesticides are commonly used in agriculture and aquaculture. Triazophos, an organophosphate-based pesticide, is widely used in agriculture to control many insect pests. Due to its high photochemical ...stability and mode of action, Triazophos could persist in the aquatic ecosystem and cause toxic effects on non-target organisms. We have studied the potential toxic effects of Triazophos on L. rohita. Primarily, we determined the median lethal concentration (LC50) of Triazophos for 24 and 96 h. Next, we studied acute (96 h, LC50–96 h) toxicity. Then, we studied chronic (35 days, 1/10th LC50–24 h Treatment I: 0.609 mg/L, 1/5th LC50–96 h Treatment II: 1.044 mg/L) toxicity. We analyzed blood biomarkers such as hematology (Hb, Hct, RBC, WBC, MCV, MCH and MCHC), prolactin, cortisol, glucose and protein levels. Concurrently, we analyzed tissue biomarkers such as glycogen, GOT, GPT, LDH and histopathology. IBRv2 index assessment method was also to evaluate the Triazophos toxicity. Studied hematological, hormonal, biochemical and enzymological biomarkers were affected in Triazophos treated groups when compare to the control group. The changes in these biomarkers were statistically significant at the 0.05 alpha level. Triazophos exposed fish shown a severe degenerated primary and secondary lamellae, lamellar fusion, hypertrophy and telangiectasia in the gills. In the hepatic tissue, it caused moderate necrosis, blood congestion, distended sinusoids with minor vacuolation, prominent pyknotic nuclei, hypertrophy, cloudy swelling of cells, lipid accumulation and fibrotic lesions. In the renal tissue, Triazophos caused thickening of Bowman's capsule, hyaline droplets degeneration, irregular renal corpuscle, congestion, cellular swelling, degeneration of tubular epithelium, necrosis, shrunken glomerulus, vacuolated glomerulus, hypertrophy, exudate and edema. IBRv2 analysis suggested that tissue biomarkers are highly sensitive to Triazophos toxicity and prolonged exposure could cause serious health effects like acute toxicity in fish. Triazophos could cause multiorgan toxicity at studied concentrations.
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•Acute and chronic toxicity of Triazophos on non-target organism was studied.•Blood and tissue biomarkers were analyzed.•Triazophos cause negative impact on studied biomarkers.•IBRv2-analysis suggested, tissue is sensitive and prolonged exposure cause acute-effect.•Triazophos is a multi-organ toxic chemical.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The neuropathological confirmation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles (NFT) remains the gold standard for a definitive diagnosis of Alzheimer’s disease (AD). Nowadays, the in ...vivo diagnosis of AD is greatly aided by both cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Although highly accurate, their broad implementation is restricted by high cost, limited accessibility and invasiveness. We recently developed a high-performance, ultrasensitive immunoassay for the quantification of tau phosphorylated at threonine-181 (p-tau181) in plasma, which identifies AD pathophysiology with high accuracy. However, it remains unclear whether plasma p-tau181, measured years before the death, can predict the eventual neuropathological confirmation of AD, and successfully discriminates AD from non-AD dementia pathologies. We studied a unique cohort of 115 individuals with longitudinal blood collections with clinical evaluation at 8, 4 and 2 years prior to neuropathological assessment at death. The results demonstrate that plasma p-tau181 associates better with AD neuropathology and Braak staging than a clinical diagnosis 8 years before post-mortem. Moreover, while all patients had a diagnosis of AD dementia during life, plasma p-tau181 proved to discriminate AD from non-AD pathologies with high accuracy (AUC = 97.4%, 95% CI = 94.1–100%) even 8 years before death. Additionally, the longitudinal trajectory of plasma p-tau181 was assessed in all patients. We found that the main increases in plasma p-tau181 occurred between 8 and 4 years prior to death in patients with AD neuropathology and later plateauing. In contrast, non-AD pathologies and controls exhibited minor, albeit significant, increases in p-tau181 up until death. Overall, our study demonstrates that plasma p-tau181 is highly predictive and specific of AD neuropathology years before post-mortem examination. These data add further support for the use of plasma p-tau181 to aid clinical management in primary care and recruitment for clinical trials.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, ...it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this “silent” stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tau phosphorylated at threonine 181 (p-tau181) measured in blood plasma has recently been proposed as an accessible, scalable, and highly specific biomarker for Alzheimer's disease. Longitudinal ...studies, however, investigating the temporal dynamics of this novel biomarker are lacking. It is therefore unclear when in the disease process plasma p-tau181 increases above physiological levels and how it relates to the spatiotemporal progression of Alzheimer's disease characteristic pathologies. We aimed to establish the natural time course of plasma p-tau181 across the sporadic Alzheimer's disease spectrum in comparison to those of established imaging and fluid-derived biomarkers of Alzheimer's disease. We examined longitudinal data from a large prospective cohort of elderly individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 1067) covering a wide clinical spectrum from normal cognition to dementia, and with measures of plasma p-tau181 and an 18F-florbetapir amyloid-β PET scan at baseline. A subset of participants (n = 864) also had measures of amyloid-β1-42 and p-tau181 levels in CSF, and another subset (n = 298) had undergone an 18F-flortaucipir tau PET scan 6 years later. We performed brain-wide analyses to investigate the associations of plasma p-tau181 baseline levels and longitudinal change with progression of regional amyloid-β pathology and tau burden 6 years later, and estimated the time course of changes in plasma p-tau181 and other Alzheimer's disease biomarkers using a previously developed method for the construction of long-term biomarker temporal trajectories using shorter-term longitudinal data. Smoothing splines demonstrated that earliest plasma p-tau181 changes occurred even before amyloid-β markers reached abnormal levels, with greater rates of change correlating with increased amyloid-β pathology. Voxel-wise PET analyses yielded relatively weak, yet significant, associations of plasma p-tau181 with amyloid-β pathology in early accumulating brain regions in cognitively healthy individuals, while the strongest associations with amyloid-β were observed in late accumulating regions in patients with mild cognitive impairment. Cross-sectional and particularly longitudinal measures of plasma p-tau181 were associated with widespread cortical tau aggregation 6 years later, covering temporoparietal regions typical for neurofibrillary tangle distribution in Alzheimer's disease. Finally, we estimated that plasma p-tau181 reaches abnormal levels ∼6.5 and 5.7 years after CSF and PET measures of amyloid-β, respectively, following similar dynamics as CSF p-tau181. Our findings suggest that plasma p-tau181 increases are associated with the presence of widespread cortical amyloid-β pathology and with prospective Alzheimer's disease typical tau aggregation, providing clear implications for the use of this novel blood biomarker as a diagnostic and screening tool for Alzheimer's disease.
/Purpose: Acute appendicitis (AA) stands as the most prevalent cause of acute abdominal pain among children. The potential for morbidity escalates significantly when uncomplicated appendicitis (UA) ...progresses to complicated appendicitis (CA), which can encompass gangrenous, necrotic, or perforated appendicitis. Consequently, establishing an early and accurate diagnosis of AA, and effectively differentiating CA from UA, becomes paramount. This study explores the diagnostic utility of various blood biomarkers for distinguishing CA from UA in pediatric patients.
We conducted a retrospective review of medical records pertaining to pediatric patients who underwent surgery for AA. Patients were categorized as either having UA or CA based on histopathological examination of the appendix. The data collected and analyzed included demographic information, white blood cell (WBC) count, neutrophil proportion, lymphocyte proportion, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels upon admission.
Among the 192 pediatric patients who underwent surgery for AA, 150 were diagnosed with UA, while 42 were diagnosed with CA. The CA group exhibited significantly higher neutrophil proportions, NLRs, PLRs, and CRP levels, alongside lower lymphocyte proportions (all p < 0.01) compared to the UA group. Receiver operating characteristic (ROC) curve analysis disclosed that CRP exhibited the highest specificity, sensitivity, and positive and negative predictive values for predicting CA.
CRP emerges as a valuable biomarker for differentiating complicated appendicitis from uncomplicated appendicitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Rapid and accurate acute ischemic stroke (AIS) diagnosis is needed to expedite emergent thrombolytic and mechanical thrombectomy treatment. Changes in blood-based protein biomarkers during ...the first 24 h of AIS, the time window for treatment, could complement imaging techniques and facilitate rapid diagnosis and treatment. Methods We performed a systematic review according to PRISMA guidelines. MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies comparing levels of blood-based protein biomarkers in AIS patients with levels in healthy controls and stroke mimics. Protein biomarkers from the following pathophysiological categories were included: neurovascular inflammation (MMP-9, TNF-alpha), endothelial integrity (VCAM-1, ICAM-1), cell migration (E-Selectin, P-Selectin, L-Selectin), markers of glial and neuronal origin (GFAP, S100, S100B, NSE), and cardiac dysfunction (BNP, NT-proBNP). The literature search was limited to English-language publications before November 7th, 2023. Results A total of 61 studies from 20 different countries were identified, which included in total, 4,644 AIS patients, 2,242 stroke mimics, and 2,777 controls. Studies investigating TNF-alpha, MMP-9, VCAM-1, ICAM-1, E-Selectin, L-Selectin, GFAP, NSE, and S100B showed pronounced methodological heterogeneity, making between-study comparisons difficult. However, in 80% of NT-proBNP and BNP studies, and all P-selectin studies, higher biomarker levels were observed in AIS patients compared to healthy controls and/or patients with stroke mimics. Conclusion None of the biomarkers included showed sufficient evidence for additional diagnostic benefit for AIS. Comprehensive standardized global multicenter studies are needed to (1) permit comparability, (2) enable valid statements about protein-based biomarkers, and (3) reflect real-world scenarios.
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