Serum Concentrations Of Protein Research Articles

Взаимосвязь амилоидогенеза и таупатии с клиническими исходами ишемии головного мозга. Экспериментальное исследование

Currently, it has been established that increased formation of β-amyloid and tau protein play a significant role in the pathogenesis of cerebral ischemia. At the same time, these molecules can act as prognostic markers of the severity of cerebral ischemia. The aim of the study. To evaluate the peculiarities of changes in the concentration of β-amyloid and tau protein in blood serum and cerebrospinal fluid in rats with experimental subtotal cerebral ischemia, as well as to establish their relationship with the severity of post-ischemic clinical changes. Materials and methods. Subtotal cerebral ischemia was modeled by simultaneous occlusion of common carotid arteries in Wistar rats. The study assessed changes in neurological, sensorimotor and cognitive deficits. The content of β-amyloid and tau protein was assessed in blood serum and cerebrospinal fluid on the 1st, 3rd, 5th and 7th days of ischemia. During the analysis, species-specific kits for solid-phase enzyme immunoassay were used. Results. It was found that in animals with subtotal cerebral ischemia, as the duration of the ischemic period increases from day 1 to day 7, the concentration of β-amyloid and tau protein in both blood serum and cerebrospinal fluid progressively increases. It is worth noting that these changes strongly correlated with changes in the clinical manifestations of cerebral ischemia — neurological, sensorimotor and cognitive deficits.

Effects of Brewery Spent Grain (BSG) included poultry diet on growth performance and meat quality of New Hampshire chicken

An experiment was conducted to evaluate the inclusion effects of Dried Brewery Spent Grain (DBSG) to know its effect on growth performance and meat quality on poultry. Completely randomized design was used to compare the treatments in five replications. The treatments used were 15% DBSG (T1), 20% DBSG (T2), 25% DBSG (T3), Commercial feed (T4) and (0% DBSG) scavenging bird was used as a control. Each treatment contained 10 birds including 200 chickens in the whole investigation. The major factors body weight, carcasses and organs weight, cholesterol, total protein, albumin, and calcium were evaluated. Results showed that mean body weight of the experimental bird after 60 days was not significantly different (p>0.05) among the dietary treatments, i.e., T1 (781.46 g), T2 (738.36 g), T3 (728.91 g) and T4 (753.38 g). Carcass, breast muscle, thigh, wing, shank, liver and spleen were not significantly different (p>0.05) in weight between DBSG included diet and commercial feed. However, dressing percentage (59.3%) of T4 and gizzard (43.20 gm.) in T3 was significantly higher than other treatments. The significantly higher (p<0.05) amount of cholesterol found in T4 (312.01 mg/dl) followed by control diet (239.46 mg/dl), both of which were above than reference range (129-297 mg/dl). However, in other treatments i.e., T1, T2 and T3, the cholesterol content was in between the reference range. Similarly, same level (p>0.05) of total protein, albumin and calcium content in blood serum observed in BSG included diet and commercial diet. Hence, 15% to 20% inclusion of BSG could be the optimum level in diets of New Hampshire chickens.

Effect of WSSV-Infection on Relative Expression of Hemocyanin Genes in Litopenaeus Vannamei (Boone, 1931)

A Litopenaeus vannamei injected with the serum from the shrimps infected with WSSV-showed the typical symptoms of white spot syndrome at 48hpi. These include lethargy, lack of appetite, reduced and disoriented swimming activity. The negative control and serum from healthy shrimps did not show any band and the test samples contained a band corresponding to 310 bp which was like that of the positive control. Thus, the test samples were confirmed positive for the WSSV-infection. The mean serum protein concentration in healthy shrimp was 86.4 ± 6.3 mg/ml. on the other hand the serum protein concentration of WSSV-injected shrimps declined linearly and significantly to 58.8 ± 3.9, 46.2 ± 5.32, and 38.7 ± 6.7 mg/ml at 12, 24, and 48 hpi, respectively. Relative quantity of hemocyanin gene (I) expression in WSSV-injected shrimps increased gradually from 6 to 48 hpi. Analyses of relative quantification of hemocyanin gene (II) in the experimental groups showed that the relative quantity in WSSV- injected shrimps increased from 6 hpi up to 24 hpi, whereas at 48 hpi the WSSV-injected shrimps showed a decrease in relative quantity of hemocyanin gene (II). Analyses of relative quantification of hemocyanin gene (III) in the experimental groups showed that the relative quantity in WSSV-injected shrimps increased slowly from 6 to 12 hpi and the increase was found to be high at 24 and 48 hpi. The relative quantity increased in sham-injected shrimps. The melt curve analysis showed two peaks corresponding to 18S rRNA and hemocyanin gene I, II and III, respectively. The objective of the present study was directed towards the relative quantification of the hemocyanin genes (I, II and III) in L. vannamei upon WSSV-infection.

Normal Alpha-1-Antitrypsin Variants Display in Serum Allele-Specific Protein Levels.

Alpha-1-antitrypsin (A1AT or SERPINA1) has been proposed as a putative biomarker distinguishing healthy from diseased donors throughout several proteomics studies. However, the SERPINA1 gene displays high variability of frequent occurring genotypes among the general population. These different genotypes may affect A1AT expression and serum protein concentrations, and this is often not known, ignored, and/or not reported in serum proteomics studies. Here, we address allele-specific protein serum levels of A1AT in donors carrying the normal M variants of A1AT by measuring the proteoform profiles of purified A1AT from 81 serum samples, originating from 52 donors. When focusing on heterozygous donors, our data clearly reveal a statistically relevant difference in allele-specific protein serum levels of A1AT. In donors with genotype PI*M1VM1A, the experimentally observed ratio was approximately 1:1 (M1V/M1A, 1.00:0.96 ± 0.07, n = 17). For individuals with genotype PI*M1VM2, this ratio was 1:1.28 (M1V/M2, 1.00:1.31, ±0.19, n = 7). For genotypes PI*M1VM3 and PI*M1AM3, a significant higher amount of M3 was observed compared to the M1-subtypes (M1V/M3, 1.00:1.84 ± 0.35, n = 8; M1A/M3, 1.00:1.61 ± 0.33, n = 5). We argue that these observations are important and should be considered when analyzing serum A1AT levels before proposing A1AT as a putative serum biomarker.

Modification of the structural stability of human serum albumin in rheumatoid arthritis.

Differential scanning calorimetry (DSC) can indicate changes in structure and/or concentration of the most abundant proteins in a biological sample via heat denaturation curves (HDCs). In blood serum for example, HDC changes result from either concentration changes or altered thermal stabilities for 7-10 proteins and has previously been shown capable of differentiating between sick and healthy human subjects. Here, we compare HDCs and proteomic profiles of 50 patients experiencing joint-inflammatory symptoms, 27 of which were clinically diagnosed with rheumatoid arthritis (RA). The HDC of all 50 subjects appeared significantly different from expected healthy curves, but comparison of additional differences between the RA and the non-RA subjects allowed more specific understanding of RA samples. We used mass spectrometry (MS) to investigate the reasons behind the additional HDC changes observed in RA patients. The HDC differences do not appear to be directly related to differences in the concentrations of abundant serum proteins. Rather, the differences can be attributed to modified thermal stability of some fraction of the human serum albumin (HSA) proteins in the sample. By quantifying differences in the frequency of artificially induced post translational modifications (PTMs), we found that HSA in RA subjects had a much lower surface accessibility, indicating potential ligand or protein binding partners in certain regions that could explain the shift in HSA melting temperature in the RA HDCs. Several low abundance proteins were found to have significant changes in concentration in RA subjects and could be involved in or related to binding of HSA. Certain amino acid sites clusters were found to be less accessible in RA subjects, suggesting changes in HSA structure that may be related to changes in protein-protein interactions. These results all support a change in behavior of HSA which may give insight into mechanisms of RA pathology.

Efficiency of conventional and nanoparticle oxytetracycline in treatment of clinical endometritis in postpartum dairy cows

The incidence of clinical endometritis in dairy cows postpartum is one of the important reasons for financial losses in the dairy industry. The costs of treatment, milk losses, infertility, repeated breeding, and high annual culling rate of dairy cows present immediate losses in case of treatment failure. The commonly used therapeutic methods for clinical endometritis have not been successful nor have given definitive solutions to overcome the complications of the disease in dairy cows. Therefore, it was necessary to propose an innovative treatment program to overcome the reasons for the failure and lack of effectiveness of the treatment of clinical endometritis. This was tackled in the current study; oxytetracycline with different concentrations, oxytetracycline 5% (OTCC5%), oxytetracycline 20% (OTCC20%), and oxytetracycline 20% nanoparticles (OTC-NPs) were used for the treatment of clinical endometritis. Diagnosis of clinical endometritis was based on the assessment of high serum concentration of pro-inflammatory cytokines, acute phase protein, increased endometrium thickness, and intrauterine discharges with different degrees of echogenicity monitored by ultrasonography. Application of OTC-NPs revealed a decrease in serum concentration of pro-inflammatory cytokines (IL-1, IL-6, and TNF-α) and acute phase proteins compared to OTCC20% and OTCC5% groups. The improvement achieved by OTC-NPs may be attributed to the reduction of OTC particles into nano size which facilitates its tissue bioavailability, dispersion, penetration power to deeper tissues, and its more broad-spectrum activities. These activities were clearly apparent after the evacuation of uterine contents using a single dose of PGF2α. The OTC-NPs revealed a reduction in serum concentration of cytokines compared to OTCC20% and OTCC5% groups arranged as follows: 10.11, 25.45, 35.56 for IL-1; 99, 300, 319 for IL-6; 1.01, 4.40, 8.06 for CRP; and 46, 183, 266 for TNF-α. Furthermore, an increase in serum concentration of albumin (3.34) was obtained by OTC-NPs compared to OTCC5% (1.70). This improvement can be taken as evidence of liver resumption functions and inflammatory reactions. On the other side, globulin concentration recorded an increase like albumin and total proteins in OTC-NPs compared to others. A reduction in the endometrium thickness in OTC-NPs with the disappearance of intrauterine discharges was monitored by ultrasonography. This confirmed the subsiding of clinical endometritis in OTC-NPs group. Moreover, a significant improvement in conception and pregnancy rate in OTC-NPs compared to other groups were observed.

Identification of the most effective serovars to be included in the MAT antigen panel to optimize the serodiagnosis of Leptospira infection in Northern Italy.

The microscopic agglutination test (MAT) assay is adopted as a world-wide reference test for the serodiagnosis of leptospirosis in humans and animals. One of the main limitations of MAT is the lack of sensitivity and serodiagnostic antigens should be periodically updated with locally circulating serovars in order to optimise its performance. The aim of this study was to determine the need to implement the antigen panel currently adopted in Northern Italy for the diagnosis of Leptospira infection in dogs. For this purpose, a group of 288 dogs with and without clinical signs potentially consistent with Leptospira infection or found to have an increased C-reactive protein (CRP) serum concentration, sampled in 2013-2016 in Northern Italy, were tested by MAT comparing the results obtained with a nine antigens panel (Australis-Bratislava, Ballum-Ballum, Canicola-Canicola, Grippotyphosa-Grippotyphosa, Icterohaemorrhagiae-Copenhageni, Icterohaemorrhagiae-Icterohaemorrhagiae, Sejroe-Hardjo, Pomona-Pomona and Tarassovi-Tarassovi serovars) routinely adopted and a panel expanded to 27 antigens. In general, the antigen panel currently adopted in Northern Italy for the routine MAT assay resulted adequate for the diagnosis of Leptospira infection in dogs. The main exception concerns the Sejroe serogroup, with the Saxkoebing and Sejroe serovars that were more effective than Hardjo for diagnosis in dogs and whose inclusion in the antigen panel is recommended. Among other antigens evaluated in this study, Cynopteri serovar was detected with high frequency but its pathogenic role in dogs and as public health threat deserve further investigation.

Metabolic profile of transition period in ewes and its influence on passive immunity transference in lambs.

The intensification of ewe production, focusing on increasing prolificity, results in a higher incidence of metabolic disorders, especially in the transition period, which can lead to production losses with consequences for the health of the animals. The objective of this study was to evaluate the metabolic profile in transition period Lacaune ewes according to the parity and litter size born and its influence on the transference of passive immunity. Nineteen Lacaune ewes, with initial mean body weight of 76.36 ± 10.37kg (SD), kept in a semi-extensive system and receiving the same diet, were used. Ewes were classified according to parity (primiparous and multiparous) and the litter size born at parturition (1, 2, and 3). On days - 14, - 7, and - 4 of the expected date of parturition and on days 1, 4, 7, and 14days postpartum, blood sampling, the evaluation of the body condition score (BCS), and the weighing of animals were performed. Blood samples were taken from the lambs 48h after birth. Colostrum was collected up to 6h postpartum to determine the brix percentage. Serum concentrations of total plasma proteins (TPP), albumin, aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), paraoxonase (PON1), calcium (Ca), and magnesium (Mg) were evaluated. In lambs, the blood parameters evaluated were TPP, albumin, GGT, and PON1. Lamb plasma was used to estimate colostrum efficiency, brix percentage immunity, and total plasma protein (PPT). Productive data, pre- and postpartum metabolic variables for ewes, lambs, and those related to colostrum brix were analyzed. The BCS had a reduction (p < 0.0001) in the postpartum period, which is evidenced on days 7 and 14 (2.88 and 2.73, respectively). Serum concentration of BHB presented the highest concentrations in the prepartum period for ewes that gave birth to triplets, from day - 14, and for ewes that gave birth to twins on day - 4 (p = 0.0245). Serum concentration of NEFA demonstrated the highest value on day 14 in primiparous (1.07; p = 0.0402). Calcium had the lowest concentrations on day 1 (8.85mg/dl, p < 0.0001) and magnesium on day 3 (1.79mg/dl, p < 0.0001) postpartum. The multiparous with two lambs had higher brix percentages (30.5%), and the lowest value was observed in primiparous ewes that gave birth to a single lamb (27.06%; p = 0.0395). Triplet lambs had the lowest weight (3.73kg, p = 0.0007), and the best brix percentage in plasma was observed in twins (10.29%, p = 0.0174). Regardless of the parity, the ewes that presented the greatest metabolic challenge were those that gave birth to triplets, and these lambs presented the worst immunity and the lowest live weight. The quality of colostrum was influenced by the parity, and multiparous ewes that gave birth to triplets had the lowest brix percentage in the colostrum.

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury

To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.

Effects of a Single Intra-Articular Injection of 2% Lidocaine or 0.5% Bupivacaine on Synovial Fluid Acute Phase Protein Concentrations in Healthy Horses

The purpose of this study was to compare the extent of inflammation response in the middle carpal joints of healthy horses following intra-articular injection of 2% lidocaine, 0.5% bupivacaine, or 0.9% saline solution. The right middle carpal joint of 20 horses was injected with 5 mL of 0.5% bupivacaine (GB, n = 10) or 5 mL of 2% lidocaine (GL, n = 10). The left middle carpal joint of horses was used as a control (5 mL 0.9% saline). Serum and synovial fluid (SF) were aseptically collected before and at predetermined times after each injection. Serum and synovial fluid protein, albumin, transferrin, haptoglobin, ceruloplasmin, α1-antitripsin, and α1-acid glycoprotein concentrations were measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared among treatments. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student–Newman–Keuls test (P < .05). Both lidocaine and bupivacaine induced serum and SF changes indicative of inflammation, but the magnitude of those changes was more pronounced for lidocaine. Administration of 0.9% saline also induced an inflammatory reaction, but the magnitude of these changes was less pronounced than those caused by GB and GL. The results suggested that bupivacaine is safer than lidocaine for intra-articular injection in horses. Saline solution should not be used as an adjunct to intra-articular injections in horses.

Apolipoprotein A1 and serum amyloid A in dogs with sepsis and septic shock.

Apolipoprotein-A1 (Apo-A1) acts as a negative acute phase protein (APP) during inflammatory states, and has a potential prognostic value in people and dogs with sepsis. The aim of this retrospective study was to investigate the association of serum Apo-A1 concentration with disease severity, multiorgan dysfunction syndrome (MODS) and outcome in a population of dogs with sepsis, and to assess its correlation with major canine APPs. Ninety-nine dogs with uncomplicated sepsis (n = 78) or septic shock (n = 21) were included. The serum concentration of Apo-A1, C-reactive protein (CRP) and serum amyloid A (SAA) were recorded, alongside the canine acute patient physiologic and laboratory evaluation fast (APPLEfast) score and the presence of MODS. Dogs with septic shock had significantly lower serum Apo-A1 concentrations (106.3 ± 22.7 mg/dl; reference interval: 123.0-142.3 mg/dl), higher APPLEfast score (30, 13-38) and greater frequency of MODS (67%) compared to those with uncomplicated sepsis (117.9 ± 19.3 mg/dl; 25, 6-33 and 8%, respectively) (P = 0.0201; P = 0.0005; P < 0.0001, respectively). Similarly, dogs with MODS had significantly lower serum Apo-A1 concentrations (104.1 ± 4.6 mg/dl) and higher APPLEfast score values (31, 13-38) compared to those without MODS (118.32 ± 2.1 mg/dl and 26, 6-33, respectively) (P = 0.0050 and P = 0.0038, respectively). Conversely, neither CRP nor SAA were different between these groups. No difference in serum APPs concentrations was detected between survivors and non-survivors. Significant negative correlations were detected between serum Apo-A1 and SAA (P = 0.0056, r = -0.277), and between serum Apo-A1 and the APPLEfast score (P = 0.0027, r = -0.3). In this population, higher values of the APPLEfast score and the presence of MODS were independently associated with a higher risk of death. Our study shows that Apo-A1 is a useful biomarker of sepsis severity in dogs, since it is decreased in those with septic shock and MODS. Further prospective investigations are deemed to evaluate the applicability of Apo-A1 to predict sepsis course and response to treatment in septic dogs.

Sphingolipidomic profile and HDL subfractions in obese dyslipidemic type 2 diabetic patients

PurposeThe aim of the study was to investigate changes in serum sphingolipid levels and high density lipoprotein (HDL) subtypes with relation to low-density lipoprotein cholesterol (LDL-C), non-HDL-C and triglyceride (TG) levels in type 2 diabetes mellitus (T2DM) patients. MethodsBlood was obtained from 60 patients with T2DM. Levels of sphingosine-1-phosphate (S1P), C16-C24 sphingomyelins (SMs), C16-C24 ceramides (CERs), and C16 CER-1 P were determined by LC-MS/MS. Serum concentrations of cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-1 (apoA-I) were analyzed by enzyme-linked immunosorbent assay (ELISA). HDL subfraction analysis was performed by Disc polyacrylamide gel electrophoresis. ResultsC16 SM, C24 SM, C24-C16 CER and C16 CER-1 P levels were significantly increased in T2DM patients with LDL-C above 160 mg/dL, compared to those with LDL-C below 100 mg/dL. A significant correlation was observed between C24:C16 SM, C24:C16 CER ratios and LDL-C, non HDL-C levels. Higher serum levels of C24 SM, C24-C18 CER and C24:C16 SM ratio was seen in obese T2DM patients (BMI>30) compared to those with BMI 27–30. Patients with fasting TG levels below 150 mg/dL had significantly increased HDL-large and significantly decreased HDL-small fractions compared to those with fasting TG levels above 150 mg/dL. ConclusionObese dyslipidemic T2DM patients had increased levels of serum sphingomyelins, ceramides and HDL-small fractions. The ratio of serum C24:C16 SM, C24:C16 CER and long chain CER levels may be used as diagnostic and prognostic indicators of dyslipidemia in T2DM.

Can blood proteome diversity among fish species help explain perfluoroalkyl acid trophodynamics in aquatic food webs?

Per- and polyfluoroalkyl substances (PFAS) are a diverse family of industrially significant synthetic chemicals infamous for extreme environmental persistence and global environmental distribution. Many PFAS are bioaccumulative and biologically active mainly due to their tendency to bind with various proteins. These protein interactions are important in determining the accumulation potential and tissue distribution of individual PFAS. Trophodynamics studies including aquatic food webs present inconsistent evidence for PFAS biomagnification. This study strives to identify whether the observed variability in PFAS bioaccumulation potential among species could correspond with interspecies protein composition differences. Specifically, this work compares the perfluorooctane sulfonate (PFOS) serum protein binding potential and the tissue distribution of ten perfluoroalkyl acids (PFAAs) detected in alewife (Alosa pseudoharengus), deepwater sculpin (Myoxocephalus thompsonii), and lake trout (Salvelinus namaycush) of the Lake Ontario aquatic piscivorous food web. These three fish sera and fetal bovine reference serum all had unique total serum protein concentrations. Serum protein-PFOS binding experiments showed divergent patterns between fetal bovine serum and fish sera, suggesting potentially two different PFOS binding mechanisms. To identify interspecies differences in PFAS-binding serum proteins, fish sera were pre-equilibrated with PFOS, fractionated by serial molecular weight cut-off filter fractionation, followed by liquid chromatography–tandem mass spectrometry analysis of the tryptic protein digests and the PFOS extracts of each fraction. This workflow identified similar serum proteins for all fish species. However, serum albumin was only identified in lake trout, suggesting apolipoproteins are likely the primary PFAA transporters in alewife and deepwater sculpin sera. PFAA tissue distribution analysis provided supporting evidence for interspecies variations in lipid transport and storage, which may also contribute to the varied PFAA accumulation in these species. Proteomics data are available via ProteomeXchange with identifier PXD039145.

Tackling Neonatal Sepsis—Can It Be Predicted?

(1) Background: Early signs of sepsis in a neonate are often subtle and non-specific, the clinical course rapid and fulminant. The aim of our research was to analyse diagnostic markers for neonatal sepsis and build an application which could calculate its probability. (2) Methods: A retrospective clinical study was conducted on 497 neonates treated at the Clinical Department of Neonatology of the University Children's Hospital in Ljubljana from 2007 to 2021. The neonates with a diagnosis of sepsis were separated based on their blood cultures, clinical and laboratory markers. The influence of perinatal factors was also observed. We trained several machine-learning models for prognosticating neonatal sepsis and used the best-performing model in our application. (3) Results: Thirteen features showed highest diagnostic importance: serum concentrations of C-reactive protein and procalcitonin, age of onset, immature neutrophil and lymphocyte percentages, leukocyte and thrombocyte counts, birth weight, gestational age, 5-min Apgar score, gender, toxic changes in neutrophils, and childbirth delivery. The created online application predicts the probability of sepsis by combining the data values of these features. (4) Conclusions: Our application combines thirteen most significant features for neonatal sepsis development and predicts the probability of sepsis in a neonate.

Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor-associated neurotoxicity.

Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune-related adverse events (irAE). Especially ICI-mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing. A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut-off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed. nAE of any grade were observed in 31% of the patients (n= 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher-grade nAE had significantly elevated serum-concentrations of monocyte chemoattractant protein 1 (MCP-1) and brain-derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p< 0.01 and p< 0.05). Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP-1 and BDNF are potentially the first clinical-class nAE predictors for patients under ICI therapy.

Integrated multi-biomarker responses in Mozambique tilapia, Oreochromis mossambicus under acute and chronic Diazinon® exposures

ABSTRACT The pesticide ecosystem impacts are very diverse, and depending on their persistence could exert their intrinsic toxicity within an acute to a chronic timeframe. This study examined the toxic effects of Diazinon on haematological and biochemical endpoints in Oreochromis mossambicus after chronic exposure. After a prior range fining test, fishes were exposed to predetermined diazinon concentrations (T1-0.906 mg/L) and (T2-1.812 mg/L) and sampled after 28 days for toxicity endpoints. In Diazinon-exposed fish, haemoglobin content, Total Red Blood Cells, Total White Blood Cells, and MCH levels were substantially lower (p < 0.05) than in the control fish group. The total blood glucose concentrations in treated fish were substantially greater (p < 0.05) than in the control group, whereas serum protein concentrations were significantly lower (p < 0.05). Observation for most biomarkers revealed patterns of decreasing values with increasing toxicant concentration and exposure duration. The integrated indices (IBR and BRI) indexes were used to provide visual and understandable depictions of toxicity effects and emphasised the relativity of biomarkers in terms of sensitivity and magnitude or severity of responses under graded toxicant exposures. In acute and chronic diazinon exposure circumstances, the analysed metrics show significant impairment to Oreochromis mossambicus.

Effect of graded levels of dietary methionine on growth performance, carcass composition and physio-metabolic responses of genetically improved farmed tilapia (GIFT) juveniles reared in inland saline water of 10 ppt

The current study aimed to optimize dietary methionine level for improving growth performance, carcass composition and physio-metabolic responses of genetically improved farmed tilapia (GIFT) juveniles reared in inland saline water of 10 ppt. Seven isonitrogenous (∿370 g crude protein/kg), isolipidic (∿80 g lipid/kg) and isocaloric (∿19 MJ gross energy/kg) purified diets were made with graded levels of methionine viz., 4.9 (M4.9), 7.2 (M7.2), 9.9 (M9.9), 12.3 (M12.3), 15.1 (M15.1), 17.4 (M17.4) and 19.8 g/kg (M19.8) with a constant level of cystine (3.2 g/kg). Completely randomized designs were followed to constitute seven distinct experimental groups and each group comprised of three experimental units. Fifteen juveniles (3.16 ± 0.01 g) were randomly stocked in each experimental unit. During the 60-day feeding trial, juveniles were fed with their respective experimental diets thrice daily at an apparent satiation level. The results revealed that growth (weight gain percentage, thermal growth coefficient and specific growth rate) and feed and nutrient utilization (feed conversion ratio, protein efficiency ratio and apparent net protein retention) were improved significantly with an increment in dietary methionine levels up to 12.3 g/kg, and methionine supplementation beyond that did not give extra benefit in relation to growth performance. Dietary methionine supplementation at various levels had no effect (P > 0.05) on the body indices, survival, carcass moisture and ash content and carcass essential amino acid composition of GIFT juveniles. The carcass protein level increased with an increment in dietary methionine levels up to 12.3 g/kg and then declined with further increment of dietary methionine level. However, carcass lipid content displayed the inverse trend of carcass protein content. GIFT juveniles fed a diet containing 12.3 and 15.1 g methionine/kg displayed elevated activities of liver and muscle aminotransferases activities, while the activity of digestive enzymes was unchanged among dietary groups. An increment of methionine up to 12.3 g/kg of diet resulted in a significant rise in serum protein and globulin concentration. Based on broken-line linear and second-order polynomial regression analysis in relation to weight gain percentage and feed conversion ratio, the optimum methionine requirements for GIFT juveniles reared in inland saline water of 10 ppt ranged from 12.1 to 14.1 g/kg of diet (32.7–38.1 g/kg of dietary protein) with supplementation of cystine at 3.2 g/kg.

L-ficolin-MASP arm of the complement system in schizophrenia

The abnormal neurodevelopment secondary to in utero adversities, such as hypoxia, malnutrition and maternal infections, underlies schizophrenia (SZ) etiology. As the genes of MBL-associated serine proteases (MASP) of the complement lectin pathway, MASP1 and MASP2, are expressed in the developing cortex and are functionally important for neuronal migration, we hypothesize that the malfunction ofl-ficolin-MASP arm may also be involved in schizophrenia pathophysiology as it was shown for MBL-MASP complexes. We investigated serum l-ficolin and plasma MASP-2 levels, the activity of l-ficolin-bound MASP-2, as well as an array of the complement-related variables in chronic schizophrenic patients in the acute phase of the disease and controls without physical or mental diagnoses.The median concentration of l-ficolin in Armenian controls was 3.66 μg/ml and similar to those reported for other Caucasian populations. SZ-cases had ∼40 % increase in serum l-ficolin (median 5.08 μg/ml; P < 0.0024). In the pooled sample, l-ficolin level was higher in males than in females (P < 0.0031), but this gender dichotomy was not affecting the variable association with schizophrenia (P < 0.016). Remarkably, MASP-2 plasma concentration showed gender-dependent significant variability in the group of patients but not in controls. When adjusted for gender and gender*diagnosis interaction, a significantly high MASP-2 level in female patients versus female controls was observed (median: 362 ng/ml versus 260 ng/ml, respectively; P < 0.0020). A significant increase in l-ficolin-bound MASP-2 activity was also observed in schizophrenia (on the median, cases vs controls: 7.60 vs 6.50 RU; P < 0.021). Correlation analyses of the levels of l-ficolin and MASP-2, l-ficolin-(MASP-2) activity and the demographic data did not show any significant association with the age of individuals, family history, age at onset and duration of the illness, and smoking. Noteworthy, the levels of l-ficolin and MASP-2 in circulation were significantly associated with the type of schizophrenia (paranoid SZ-cases had much higher l-ficolin (P < 0.0035) and lower MASP-2 levels than the other types combined (P < 0.049)). Correlations were also found between: (i) the classical pathway functional activity and l-ficolin level (rs = 0.19, P < 0.010); (ii) the alternative pathway functional activity and MASP-2 level (rs = 0.26, P < 0.00035); (iii) the activity of l-ficolin-bound MASP2 and the downstream C2 component haemolytic activity (rs = −0.19, P < 0.017); and (iv) l-ficolin and the upstream C-reactive protein (CRP) serum concentrations (r = 0.28, P < 0.018).Overall, the results showed l-ficolin-related lectin pathway alterations in schizophrenia pathophysiology. It is likely that in addition to the MBL-MASP component over-activity reported previously, the alterations of the lectin pathway in schizophrenia also involve variations of l-ficolin-(MASP-2) on protein concentration and activity levels.

Study the effect of a drug depakene (Valproic acid) in the serum levels of immune proteins in albino male rats.

This study aimed to investigate the effect of administration of depakene (valproic acid)(VPA) (15 mg/Kg of body weight, orally) on serum protein levels, including immune proteins, because its functions and the importance of these proteins in the body and they are overlapping, and that was by measured protein levels before and after treatment as concentrations of total protein (Tp), albumin and globulin in normal male rats and in rats that treated with VPA drug along the period of experiment (30) days. The results showed a significant decrease (P&lt;0.05) in concentrations of total protein and albumin in comparison with normal control group, whereas did not observe significant differences (P&lt;0.05) in globulin concentration compared with normal control group, despite of, there was a little decrease in globulin concentration in rats group that administrated the drug under study but non-significant. It could be concluded of the present study that the VPA drug have an greater side effects on concentration and function of proteins in serum, and subsequently, may extending these effects to comprise its effect on the immunity, osmotic pressure, blood volume, nutrients exchange between the blood and tissues, glomerular infiltration rate, transport many of materials and hormones, and several of physiological and biochemical functions which correlated with the serum proteins

Inflammation and micronutrient deficiency as major risk factors for anemia in children with intestinal failure:A longitudinal cohort study.

Most data on anemia in children with intestinal failure (IF) have been obtained from studies in which the data were collected at a single point in time. We aimed to identify the frequency of anemia and factors associated with hemoglobin levels in children with IF during their course of home parenteral nutrition. We performed a longitudinal cohort study of patients with IF followed up at a pediatric intestinal rehabilitation center. Outcome variables were hemoglobin levels and prevalence of anemia during the follow-up period. The exposure variables were age, duration of parenteral nutrition, chronic disease, and serum concentrations of C-reactive protein, iron, copper, selenium, vitamins A, D, B12 , and folic acid. Twenty-five children with a median time of receiving parenteral nutrition of 40.7 months were included. A median (and interquartile range) of 40.7 (25.2-58) hemoglobin measurements were performed per patient. Mean (SD) hemoglobin was 10.7 (1.8) g/dL at baseline and 11.6 (0.9) g/dL in the last observation (paired t test, P = 0.07); 32% of patients had mean hemoglobin values below the lower limit for age. In a multivariable predictive model, having C-reactive protein >1 mg/dL was associated with a decrease of 0.57 g/dL in hemoglobin (95% CI, -0.90 to -0.24, P = 0.01), and an increase of 1 mg/L in vitamin A concentration was associated with the increase of 0.93 g/dL in Hb level (95% CI, 0.24-1.61; P = 0.008). Anemia affects almost one-third of children with IF and its frequency decreases during the follow-up period. Hemoglobin levels are associated with inflammatory response and serum micronutrient concentrations.