Within the field of clinical research, reports on the stability of avian serum amyloid A (SAA) under varying storage conditions are currently scarce. In this study, avian plasma samples were evaluated for SAA, a major acute-phase protein in birds, to assess how varying storage periods and repeated freeze-thaw cycles impact the stability of SAA in the frozen samples. Seven plasma samples from two species and six plasma samples from three species stored at ‒20 °C were used to evaluate the time and temperature effects accordingly. A chicken-specific SAA ELISA kit was used for the measurements. Statistical analysis was performed using SPSS, and the Kruskal-Wallis test and Spearman\'s correlation coefficient were applied, with statistical significance set at P < 0.05. The SAA concentrations measured daily for 30 days showed no statistically significant differences over time. Freezing-thawing was repeated five times, and a significant negative relationship was confirmed over the cycles (r=‒0.8857, P < 0.05). Although no significance was observed between a decreased concentration and the number of cycles, a decrease in the concentration of > 10% was observed after the fourth cycle in four out of six samples. However, one to three freeze-thaw cycles did not result in a significant decline. Taken together, the results indicate that a negative correlation existed between the mean concentration and multiple freeze-thaw cycles, indicating that these should be avoided where possible.

The mammary gland is an exocrine gland whose main function is to produce milk. Breast morphogenesis begins in the embryonic period; however, its greatest development takes place during the lactation period. Studies have found the expression of serum amyloid A protein (SAA) in both breast cells and breast milk, yet the function of this protein in these contexts remains unknown. Insufficient milk production is one of the most frequent reasons for early weaning, a problem that can be related to the mother, the newborn, or both. This study aims to investigate the relationship between lactogenesis II (the onset of milk secretion) and the role of SAA in the human breast. To this end, mammary epithelial cell cultures were evaluated for the expression of SAA and the influence of various cytokines. Additionally, we sought to assess the activation pathway through which SAA acts in the breast, its glucose uptake capacity, and the morphological changes induced by SAA treatment. SAA expression was observed in mammary epithelial cells; however, it was not possible to establish its activation pathway, as treatments with inhibitors of the ERK1/2, p38MAPK, and PI3K pathways did not alter its expression. This study demonstrated that SAA can stimulate IL-6 expression, inhibit glucose uptake, and cause morphological changes in the cells, indicative of cellular stress. These mechanisms could potentially contribute to early breastfeeding cessation due to reduced milk production and breast involution.

Patients with small aortic annuli (SAAs) are predominantly women. We sought to compare gender-based and propensity-matched outcomes of index transcatheter aortic valve replacement (TAVR) in patients with SAAs. In this retrospective institutional analysis (2012 to 2023), primary stratification was by gender. SAA was defined as an aortic valve annulus diameter <23 mm and the 30-day and 1-year outcomes were compared between the groups. A total of 3,911 patients underwent TAVR. Of those, 661 patients had an SAA, of whom 23.8% were men and 76.2% were women. Propensity matching (1:1) identified 152 pairs. The mean age was 81 years. History of surgical or percutaneous coronary intervention was more prevalent in men (72.4% vs 48%, p <0.001). Men had a higher incidence of postoperative pacemaker implantation (8.6% vs 3.3%, p = 0.05), whereas only women had iliofemoral dissections (4.6% vs 0%, p = 0.007). The rates of moderate (23.0% vs 25.7%) and severe (2.6% vs 0.7%) prosthesis-patient mismatch was not statistically significantly different between the groups (p = 0.364). The 30-day mortality was 0%, whereas the 1-year mortality was 4.3%, with no difference between the groups. An increase in preoperative creatinine was associated with higher risk of death (hazard ratio 1.206, 95% confidence interval 1.025 to 1.418, p = 0.02), whereas gender was not. Kaplan-Meier survival estimates (Log rank, p = 0.768) and cumulative incidence of stroke readmission (p = 0.842) were similar in both groups. In conclusion, the outcomes of TAVR in SAAs do not differ by gender, with safety and efficacy evident in men and women.

Distinguishing inflammatory from non-inflammatory liver disease in cats may impact management. The study aim was to evaluate if certain diagnostic variables, including Serum Amyloid A (SAA), differ (1) between various clinical disease categories (Primary liver disease, Extrahepatic, Trauma and Inconclusive) and (2) between cytological findings of severe hepatic lipidosis and other cytological findings in cats with increased liver enzymes. Medical records from 5042 cats, where SAA had been measured, were reviewed, and 566 cats fulfilled inclusion criteria consisting of increased liver enzymes and available biochemical panel results. SAA was higher in cats diagnosed with trauma compared to other diseases (p = 0.008). Cytology results were available in 85 cats, and cats with severe lipidosis had lower serum SAA concentration (p < 0.0001) and were younger (p < 0.0002) compared to cats with other cytological findings. The study shows that SAA was higher in cats diagnosed with trauma compared to cats with other causes of increased liver enzymes and that SAA may be useful to distinguish cats with cytologic evidence of hepatic lipidosis from cats with other liver pathologies. Serum Amyloid A may be a valuable complement to liver cytology when investigating cats with increased liver enzymes.

BACKGROUND: Sepsis is triggered by pathogenic microorganisms, resulting in a systemic inflammatory response. Liver cirrhosis and sepsis create a vicious cycle: cirrhosis weakens immune function, raising infection risk and hindering pathogen clearance. Optimal treatment outcomes depend on understanding liver cirrhosis patients\' sepsis risk factors. Thus, preventing sepsis involves addressing these risk factors. Therefore, early identification and understanding of clinical characteristics in liver cirrhosis patients with sepsis are crucial for selecting appropriate antibiotics. A case-control study using logistic regression was conducted to examine the prognostic value of amyloid A/lactate level monitoring in identifying sepsis risk factors in liver cirrhosis patients.
METHODS: From March 2020 to March 2022, 136 liver cirrhosis patients treated at our hospital were divided into a sepsis group (n = 35) and a non-sepsis group (n = 101) based on sepsis complications. General clinical data were collected. Univariate analysis screened for liver cirrhosis patients\' sepsis risk factors. Multivariate logistic analysis was subsequently employed to evaluate the risk factors. Sepsis patients were followed up for a month. Based on prognosis, patients were categorized into a poor prognosis group (n = 16) and a good prognosis group (n = 19). Serum amyloid A (SAA) and blood lactic acid (BLA) levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of both individual and combined SAA/BLA monitoring.
RESULTS: Patient data, including age, diabetes history, liver cancer, hepatic artery embolization, recent antibiotic use, invasive procedures within two weeks, APACHE II Scoring, ALB and SAA and BLA levels, were compared between the sepsis and non-sepsis groups, showing significant differences (P < 0.05). Logistic regression identified factors such as age ≥ 70, recent antibiotic use, recent invasive procedures, history of liver cancer, hepatic artery embolization history, high APACHE II scores, decreased albumin, and elevated SAA and BLA levels as independent sepsis risk factors in liver cirrhosis patients (P < 0.05). Among the 35 sepsis patients, 16 had a poor prognosis, representing an incidence rate of 45.71%. Serum SAA and BLA levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). The AUC for serum SAA and BLA was 0.831 (95%CI: 0.738-0.924), 0.720 (95%CI: 0.600-0.840), and 0.909 (95%CI: 0.847-0.972), respectively. The combined diagnostic AUC was significantly higher than that of single factor predictions (P < 0.05). The predictive value ranked as follows: joint detection > SAA > BLA.
CONCLUSIONS: In treating liver cirrhosis, prioritize patients with advanced age, a history of hepatic artery embolization, recent invasive operations, history of liver cancer, recent antibiotic exposure, high APACHE II scores and low albumin. Closely monitoring serum SAA and BLA levels in these patients can offer valuable insights for early clinical prevention and treatment.

OBJECTIVE: Cryopyrin-Associated Periodic Syndromes (CAPS) encompasses a spectrum of Interleukin-1 (IL-1) driven systemic diseases with dramatic individual and societal burden. The study aimed to identify parameters and instruments to refine real-life Treat-to-Target (T2T) strategies and control CAPS disease activity.
METHODS: A single-centre, longitudinal study of consecutive children and adults diagnosed with CAPS and treated with anti-IL-1 therapy was performed. Demographics, clinical phenotype and NLRP3 gene variants in addition to serial inflammatory markers and Physician and Patient/Parent Global Assessments (PGA/PPGA) were captured. Effectiveness of anti-IL-1 T2T strategies and factors associated with therapy escalation were determined.
RESULTS: A total of 54 CAPS patients with 759 follow-up visits were included; 31/54 (57%) were children; the median follow-up was 108 months (12-620). The moderate CAPS phenotype was present in 89%; overall 59% had pathogenic/likely pathogenic NLRP3 variants. Therapy adjustments were documented in 50/759 visits including 35 therapy escalations and 15 reductions; 74% of the therapy escalation visits were for children. At time of visit, 63% showed moderate, 37% severe clinical disease activity. Inflammatory markers remained largely normal. Significant improvement was observed in both PGA/PPGA throughout the study (p< 0.01). At the last follow-up, 96% of patients achieved remission.
CONCLUSIONS: Guidance for refining real-life T2T strategies in CAPS cohorts can be drawn from serial assessments of PGA and PPGA reliably reflecting changes in disease activity. Individual parameters including age and NLRP3 gene variants are important predictors, while the sensitivity of inflammatory markers is limited due to the confounding anti-IL-1 therapy.

BACKGROUND: MG132, a proteasome inhibitor, is widely used to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity by proteasome-mediated degradation of IκB. It has been marketed as a specific, reversible, cell-permeable and low-cost inhibitor. However, adverse effects of the compound have been reported in the literature. We recently discovered and characterised a point mutation in the acute phase protein serum amyloid A (SAA) in chickens, by overexpressing the protein in chicken hepatocellular carcinoma (LMH) cells. This serine to arginine exchange at amino acid position 90 (SAA.R90S) leads to intra- and extracellular accumulation of SAA, which is surprisingly counteracted by MG132 treatment, independent of SAA\'s intrinsic promoter.
RESULTS: To test, whether low proteasomal degradation of SAA.R90S is responsible for the observed intra- and extracellular SAA accumulation, we intended to inhibit the proteasome in SAA wild type (SAA.WT) overexpressing cells with MG132. However, we observed an unexpected drastic decrease in SAA protein expression at the transcript level. NF-κB gene expression was unchanged by MG132 at the measured time point.
CONCLUSIONS: The observed results demonstrate that MG132 inhibits SAA expression at the transcript level, independent of its endogenous promoter. Further, the data might indicate that NF-κB is not involved in the observed MG132-induced inhibition of SAA expression. We, consequently, question in this brief report whether MG132 should truly be categorised as a specific ubiquitin proteasome inhibitor and recommend the usage of alternative compounds.

Virtual reality based physical stress (VRPS) paradigms could eliminate the influence of social factors on participants, and it may be a desirable tool to explore the impact of personality traits on stress levels. In this study, we attempt to explore the effects of VRPS on stress response among individuals with different personality traits. Forty male participants with an average age of 22.79 ± 0.41 years were divided into two groups based on Harm Avoidance (HA) scores of Tridimensional Personality Questionnaire (TPQ), referred to as the Low-HA group and the High-HA group. The stress levels of the participants were assessed using salivary α-amylase (sAA) activity and heart rate variability (HRV) indices pre- and post-stress. The influence of personality traits on stress response among different groups was analyzed. VRPS significantly affected the sAA activity and HRV indicators of both groups. During and after stress, there were significant differences in sAA activity and HRV indicators between the two groups. The sAA levels and HRV indices of the Low-HA group were lower than those of the High-HA group. Furthermore, sAA levels and HRV indices were correlated with the scores of TPQ. VRPS scenarios elicit different stress responses on individuals with different harm avoidance personality traits. Stress evaluation based on VR scenarios presents potential in personality trait assessments, particularly for distinguishing between individuals with low and high HA tendencies.

Alzheimer\'s disease (AD) pathology is defined by β-amyloid (Aβ) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed.
A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer\'s Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aβ and tau biomarkers, risk-factors, genetics, and cognitive trajectories.
SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala-predominant (60%) LB-pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher Aβ burden but lower CSF p-tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early-AD who were already AD biomarker positive.
SAA is a sensitive, specific marker for LB-pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of α-synuclein co-pathology in understanding AD\'s nature and progression.
SAA shows 79% sensitivity, 97% specificity for LB-pathology detection in AD. SAA positivity prevalence increases with disease stage and age. Higher Aβ burden, lower CSF p-tau181 linked with higher SAA+ rates in dementia. SAA+ impacts cognitive impairment in early disease stages. Study underpins need for wider LB-pathology screening in AD treatment.

UNASSIGNED: Cutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson\'s disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD.
UNASSIGNED: This study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies.
UNASSIGNED: We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy.
UNASSIGNED: P-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity.
UNASSIGNED: P-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.