Low Serum Concentrations Research Articles

Molecular confirmation of alpha 1-antitrypsin deficiency in liver transplant setting: A province-wide experience.

Patients suspected of Alpha 1-Antitrypsin (A1AT) abnormality based on low serum concentration are routinely confirmed through polymerase chain reaction (PCR) testing of peripheral blood. Genotyping formalin-fixed paraffin-embedded (FFPE) tissue is a novel approach that could aid in detecting variant A1AT. We performed qPCR on FFPE liver explants with Periodic Acid Schiff after Diastase (PASD)- and A1AT-positive globules to confirm and estimate the frequency of A1AT deficiency in transplant cases. Eighteen (12.68%) of 142 patients with end-stage liver disease showed PASD/A1AT positive globules. FFPE of the explants was tested through qPCR to detect S and Z alleles. A second age- and sex-matched control group consisting of five liver transplant patients with negative globules was included in the study. qPCR assay was successful with all the samples meeting QC parameters. All patients included in the study elucidated Z allele variants; 2 homozygous (11.1%) and 16 heterozygous (88.9%). The control group demonstrated normal wild-type MM allele. Screening for A1AT deficiency using serum levels is not sufficiently sensitive to detect deficiency, especially in carriers. If A1AT testing was not performed preoperatively and the risk is high based on the PASD/A1AT-positive globules in the explants, then molecular testing of FFPE tissue can be a viable method for confirming the diagnosis.

Indole Family and Neomycin Sulfate: Inductors of Differentiation in C2C12 and RD cell Lines

Rhabdomyosarcoma (RMS) is a highly aggressive tumor primarily affecting the pediatric population, that generally originates from a failure in the embryonic differentiation of myogenic precursor cells. Standard treatment involves surgery, chemotherapy and radiation therapy, with a poor prognosis, especially when it spreads to other parts of the body, highlighting the need for new treatment approaches. In this study, cellular differentiation was investigated as a potential therapeutic approach for an embryonal subtype of RMS (eRMS) employing a human eRMS cell line, RD; and comparing it with a normal murine myoblast cell line, C2C12. We observed that not only a serum free or a low serum concentration in the cultured medium induce morphological changes towards differentiations, but also staurosporine, bisindolylmaleimide, and neomycin sulfate (direct or indirect protein kinase inhibitors) induces differentiation in RD and C2C12 cell lines, suggesting a crucial role of PKC, PLC and its signaling pathways in a proliferation/differentiation switch. These findings underscore the importance of exploring cellular differentiation as a therapeutic strategy against RMS and highlight the need for further research into the underlying mechanisms of kinase inhibitor-induced cellular differentiation as a potential cancer treatment.

Interaction of a caffeine overdose with clinical doses of contraceptive ethinyl estradiol in a young woman.

The overdose of caffeine, a cytochrome P450 1A2 probe, in young women has become a problem. The aim of this study was to evaluate possible drug interactions between intentionally overdosed caffeine (12 g) and oral contraceptive doses of ethinyl estradiol prescribed to a young woman in a suicide attempt. The serum concentrations of caffeine in the patient and the time-dependent ethinyl estradiol inhibition of caffeine oxidation invitro were evaluated. The serum concentration of caffeine 4 h after overdose was 136 μg/mL; from the data obtained between 4 and 28 h after overdose, the half-life was estimated to be 33 h, which is many times larger than the normal value. Prescribed ethinyl estradiol prolonged caffeine elimination invivo and inhibited paraxanthine formation, as evidenced by the low serum concentrations. In human liver microsomes, ethinyl estradiol (50 nM) inhibited half of caffeine N 3 -demethylation. Pre-incubation of human liver microsomes with ethinyl estradiol resulted in a powerful time-dependent inhibitory effect on caffeine N 3 -demethylation in human liver microsomes. These results suggest that a prescription history of contraceptives at clinical doses may have a strong effect on the pharmacokinetics of overdosed caffeine in young women, resulting in dangerous drug interactions.

Antibody-dependent enhancement and neutralization against CVB4 investigated in vitro and in silico through an agent-based model.

The infection with coxsackievirus B4 (CVB4) can be enhanced in vitro by antibodies directed against the viral capsid protein VP4. In peripheral blood mononuclear cells, antibody-dependent enhancement (ADE) of CVB4 infection leads to the production of interferon alpha (IFN-α). To investigate ADE of CVB4-induced production of IFN-α, an agent-based model was constructed with enhancing and neutralizing antibodies. The model recapitulates viral neutralization and ADE in silico. The enhancing and neutralizing activities of serum samples were evaluated in vitro to confront the model predictions with experimental results. Increasing the incubation time of CVB4 with serum samples improves virus neutralization in silico as well as in vitro. It also results in ADE at lower antibody numbers in silico, which is confirmed in vitro with IFN-α production at lower serum concentrations. Furthermore, incubation of CVB4 with serum at a low temperature does not induce IFN-α production in vitro. Thus, taken together our results suggest that enhancing antibodies bind cryptic epitopes, more accessible with longer incubation time and at higher temperature due to changes in capsid conformation, consistent with previous results indicating that enhancing antibodies are anti-VP4 antibodies.

Quantitative bile acid profiling in healthy adult dogs and pups from serum, plasma, urine, and feces using LC-MS/MS.

Synthesis and secretion of bile acids (BA) is a key physiological function of the liver. In pathological conditions like portosystemic shunt, hepatic insufficiency, hepatitis, or cirrhosis BA metabolism and secretion are disturbed. Quantification of total serum BA is an established diagnostic method to assess the general liver function and allows early detection of abnormalities, liver disease progression and guidance of treatment decisions. To date, data on comparative BA profiles in dogs are limited. However, BA profiles might be even better diagnostic parameters than total BA concentrations. On this background, the present study analyzed and compared individual BA profiles in serum, plasma, urine, and feces of 10 healthy pups and 40 adult healthy dogs using ultra-high performance liquid chromatography coupled to electrospray ionization mass spectrometry. Sample preparation was performed by solid-phase extraction for serum, plasma, and urine samples or by protein precipitation with methanol for the feces samples. For each dog, 22 different BA, including unconjugated BA and their glycine and taurine conjugates, were analyzed. In general, there was a great interindividual variation for the concentrations of single BA, mostly exemplified by the fact that cholic acid (CA) was by far the most prominent BA in blood and urine samples of some of the dogs (adults and pups), while in others, CA was under the detection limit. There were no significant age-related differences in the BA profiles, but pups showed generally lower absolute BA concentrations in serum, plasma, and urine. Taurine-conjugated BA were predominant in the serum and plasma of both pups (68%) and adults (74-75%), while unconjugated BA were predominant in the urine and feces of pups (64 and 95%, respectively) and adults (68 and 99%, respectively). The primary BA chenodeoxycholic acid and taurocholic acid and the secondary BA deoxycholic acid and lithocholic acid were the most robust analytes for potential diagnostic purpose. In conclusion, this study reports simultaneous BA profiling in dog serum, plasma, urine, and feces and provides valuable diagnostic data for subsequent clinical studies in dogs with different kinds of liver diseases.

Association between circulating antioxidants and sleep disorders: comprehensive results from NHANES 2017-2018.

Background: Oxidative stress plays an important role in the occurrence and pathological process of numerous human diseases. A bidirectional relationship was found between sleep disorders and oxidative stress. However, the association between circulating antioxidant levels and the risk of sleep disorders at the population-scale has yet to be determined. Methods: We used the dataset from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 data release cycle and included 3062 adult participants aged 25-75 years. The circulating antioxidants levels in serum were measured, and the sleep status was assessed by self-reported sleep disorder questionnaire tests. We investigated the association and exposure-response relationship between the 12 main circulating antioxidants and sleep disorders using a generalized additive model (GAM), multiple linear, binary logistic, and restricted cubic spline (RCS) regression models. Multiple sensitivity analyses were conducted to validate the results of our study. Results: Significantly lower serum concentrations of ten antioxidants were observed in the group which had trouble sleeping symptoms compared to the control group. After adjusting for all the covariates, the binary logistic regression models indicated that six of the circulating antioxidants including alpha-carotene, alpha-cryptoxanthin, trans-beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and vitamin C, showed a significant association with the risk of overall trouble sleeping symptoms, with odds ratios corresponding to 0.88 (95% CI: 0.80-0.96), 0.74 (95% CI: 0.62-0.87), 0.87 (95% CI: 0.79-0.97), 0.85 (95% CI: 0.75-0.95), 0.72 (95% CI: 0.61-0.84), and 0.83 (95% CI: 0.74-0.93), respectively. The GAM and multiple linear regression revealed similar associations whereas the RCS regression models further confirmed their significant negative exposure-response relationship. Conclusions: The circulating carotenoids and vitamin C levels were negatively correlated with the risk of sleep disorders. Higher circulating antioxidant levels were significantly associated with a lower risk of sleep disorders. The potential health risk of low circulating antioxidants levels was higher in the female population than in the male population.

CYSLTR1 antagonist inhibits Th17 cell differentiation by regulating the NF-κB signaling for the treatment of psoriasis.

Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.

Supplementation of Multistrain Probiotics Improves Milk Production, Blood Metabolites, Digestibility, and Rectal Microbiota during the Prepartum and Early Lactation Stages in Crossbred Cows

The current study aimed to study the effects of administration with a multistrain probiotic formulation (MPF) initiated from the prepartum stage on lactation performance, digestibility, rectal microbiota, and blood metabolites of postpartum dairy cows. A total of 30 multiparous crossbred (Holstein Friesian × Balady) dairy cows were randomized into three groups: control (no MPF supplementation), MPF1 (0.5 g MPF/cow/d), and MPF2 (1 g MPF/cow/d). The administration of MPF started 28 days before calving and continued for 84 days after. The results revealed that cows in the MPFI and MPF2 groups had higher milk production, 3.5% FCM, and ECM than those in the control group. The MPF‐supplemented cows had significantly greater milk energy output, DMI, and yields of solids‐not‐fat, lactose, total solids, ash, fat, and protein. The MPF supplementation significantly enhanced feed conversion and significantly interacted with milk solids‐not‐fat, lactose, total solids, and protein. Hematological indicators did not significantly alter between the MPF and control groups. However, cows receiving MPF supplements had higher levels of Hct. Serum biochemical measurements showed lower serum concentrations of LDL, total cholesterol, and VLDL in MPF‐fed cows than in the control group. The digestibility of organic and dry matter tended to be higher in MPF‐supplemented cows. The populations of lactobacillus, bacillus, and total bacterial count increased due to MPF administration, while the count of Clostridium, Salmonella, E. coli, and coliforms decreased in MPF‐fed cows. In summary, administering MPF during late gestation and early lactation period improved milk production, fecal microbial composition, and overall health of dairy cows.

Comparison of the Effects of Adductor Canal and Femoral Nerve Blocks on Postoperative Opioid Consumption and Inflammatory Factor Levels in Elderly Patients After Total Knee Arthroplasty: A Prospective Observational Study.

Total Knee Arthroplasty (TKA) is a highly invasive procedure causing severe postoperative pain, which hampers early mobility. Effective pain management is crucial for optimal recovery. This study aimed to evaluate how adductor canal block (ACB) and femoral nerve block (FNB) affect opioid use and inflammation factor levels in elderly TKA patients. This prospective observational study included 120 patients who received TKA, and divided them into three groups, based on the different nerve block technique: ACB, FNB, and no intervention before general anesthesia (CON). Postoperative opioid consumption, pain assessment, inflammation factor, knee function recovery and other clinical indicators were recorded. The CON group had significantly higher cumulative sufentanil consumption compared to the ACB and FNB groups at both 12 h and 48h postoperative (P<0.001). Compared with the CON group, the ACB and FNB groups persistently had lower pain scores until 12 h at rest and 24 h during motion after surgery. The ACB group showed significantly lower serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) compared to the CON group at 24 h postoperative (P=0.017, P=0.009), and IL-6 levels remained significantly lower at 72 h postoperative (P=0.005). Both ACB and FNB groups achieved earlier ambulation compared to the CON group (P=0.002). On the first day postoperative, both the ACB and FNB groups showed significantly better knee motion (P<0.001), quadriceps strength (P<0.001), and daily mobilization (P<0.001) compared to the CON group. Additionally, the ACB group exhibited superior quadriceps strength (P<0.001) and daily mobilization (P<0.001) compared to the FNB group. The ACB and FNB groups exhibited comparable clinical efficacy outcomes in terms of pain scores and opioid consumption. However, the ACB group experienced reduced postoperative inflammation and improved knee recovery, especially in quadriceps strength.

Serum Calcium and Magnesium Levels, Not 25-Hydroxyvitamin D, Are Associated With Sleep Quality in Airline Pilots.

Despite the vulnerability of airline pilots (APs) to sleep disturbances, the biological underpinnings responsible for this phenomenon are still not entirely elucidated. However, there is an increasing amount of evidence indicating an association between 25-hydroxyvitamin D, Ca2+, and Mg2+ levelsand sleep health. In this cross-sectional study, we sought to examine the potential associations between serum levels of these biomarkers and the occurrence of poor sleep among APs. We examined a convenience sample of 100male APs who underwent the Pittsburgh Sleep Quality Index (PSQI) to assess their sleep quality. Those who scored 5 or higher on the PSQI were labeled as poor sleepers. Serum levels of 25-hydroxyvitamin D, Ca2+, and Mg2+ were quantified in all participants. Out of the 100 APs, 58 (58%) and 42 (42%) were classified as good and poor sleepers, respectively, based on the PSQI scores. We defined vitamin D deficiency as serum 25-hydroxyvitamin D levels below 10 ng/mL and insufficiency as levels ranging from 10 to 30 ng/mL. The results revealed no significant differences in serum levels of 25-hydroxyvitamin D between the two groups, and there was no evidence of vitamin D deficiency or insufficiency. However, poor sleepers exhibited significantly lower levels of both Mg2+ (1.8 ± 0.1 mg/dLversus2.0 ± 0.1 mg/dL, respectively) and Ca2+ (8.5 ± 0.4mg/dLversus9.1 ± 0.5 mg/dL, respectively) compared to good sleepers (P < 0.001 for both). Logistic regression analysis identified both Mg2+ and Ca2+ as independent biomarkers associated with poor sleep quality in APs (P < 0.001 for both). Lower serum concentrations of Mg2+ and Ca2+, not 25-hydroxyvitamin D, may be associated with poor sleep in APs.

Reduced period from follicular wave emergence to luteolysis generated greater steroidogenic follicles and estrus intensity in dairy cows

The onset of productive life in dairy cattle, concomitant to parturition, is accompanied by a substantial decrease in fertility in comparison with non-lactating, nulliparous heifers. Follicular growth patterns differ between parous and nulliparous dairy cattle. Nulliparous heifers ovulate follicles with reduced antral age (RAA). This study aimed to exogenously reduce ovulatory follicle age in lactating dairy cows from 7 to 5 days old. Cows (n = 80) had their estrous cycles synchronized with the Double-Ovsynch program. At the final portion of this program, luteolysis was induced at either 5 (RAA) or 7 (Control) days following follicular wave emergence. RAA outcomes were estimated in comparison with Controls. RAA resulted in smaller follicles 2 days post-treatment. Despite lower serum concentrations of 17β-estradiol before treatment compared with Controls, the rate of increase in this hormone was greater for the RAA treatment. There was no difference in luteolysis rates between treatments. Proestrus (luteolysis onset to estrus onset) was prolonged in RAA cows. Cows with RAA had more intense estruses. Collectively, these results indicate that decreasing the age of the ovulatory follicle may improve the steroidogenic capacity of the dominant follicle and estrus expression intensity in lactating dairy cows.

Hydrogen attenuates endothelial glycocalyx damage associated with partial cardiopulmonary bypass in rats.

Cardiopulmonary bypass (CPB) causes systemic inflammation and endothelial glycocalyx damage. Hydrogen has anti-oxidant and anti-inflammatory properties; therefore, we hypothesized that hydrogen would alleviate endothelial glycocalyx damage caused by CPB. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 7 per group), as follows: sham, control, 2% hydrogen, and 4% hydrogen. The rats were subjected to 90 minutes of partial CPB followed by 120 minutes of observation. In the hydrogen groups, hydrogen was administered via the ventilator and artificial lung during CPB, and via the ventilator for 60 minutes after CPB. After observation, blood collection, lung extraction, and perfusion fixation were performed, and the heart, lung, and brain endothelial glycocalyx thickness was measured by electron microscopy. The serum syndecan-1 concentration, a glycocalyx component, in the 4% hydrogen group (5.7 ± 4.4 pg/mL) was lower than in the control (19.5 ± 6.6 pg/mL) and 2% hydrogen (19.8 ± 5.0 pg/mL) groups (P < 0.001 for each), but it was not significantly different from the sham group (6.2 ± 4.0 pg/mL, P = 0.999). The endothelial glycocalyces of the heart and lung in the 4% hydrogen group were thicker than in the control group. The 4% hydrogen group had lower inflammatory cytokine concentrations (interleukin-1β and tumor necrosis factor-α) in serum and lung tissue, as well as a lower serum malondialdehyde concentration, than the control group. The 2% hydrogen group showed no significant difference in the serum syndecan-1 concentration compared with the control group. However, non-significant decreases in serum and lung tissue inflammatory cytokine concentrations, as well as in serum malondialdehyde concentration, were observed. Administration of 4% hydrogen via artificial and autologous lungs attenuated endothelial glycocalyx damage caused by partial CPB in rats, which might be mediated by the anti-inflammatory and anti-oxidant properties of hydrogen.

A low thrombospondin-1 serum concentration is related to increased bacteremia risk in lymphoma patients treated with BeEAM/BEAM conditioning regimen and autologous stem cell transplantation.

Infectious complications of autologous hematopoietic stem cell transplantation (AHSCT) are the most common adverse effects of the therapy, resulting in prolonged hospitalization and deterioration of patient well-being. Identifying predictors of these complications is essential for improving patient outcomes and guiding clinical management. This study aimed to examine thrombospondin-1 (THBS-1) serum levels as a potential biomarker for predicting bacteremia in AHSCT recipients. Blood samples were collected from 30 patients undergoing BeEAM/BEAM (bendamustine/carmustine, etoposide, cytarabine, melphalan) conditioning regimen at subsequent time points during AHSCT. THBS-1 levels were quantified using ELISA kits. Patients who developed bacteremia (n = 11) during the AHSCT course had lower THBS-1 concentration compared with those without (n = 19) (22.88 ± 11.53µg/mL vs. 15.24 ± 5.62µg/mL, p = .0325). The ROC curve analysis revealed that THBS-1 serum concentration at the first day of BeEAM/BEAM regimen had an area under the curve of 0.732 (95%CI: 0.5390.925, p = .0186) with an optimal cut-off value of 16.5µg/ml resulting in 82% Sensitivity and 53% Specificity for predicting bacteremia with a median of 11 days before its occurrence. Patients with lower THBS-1 concentrations experienced febrile neutropenia significantly earlier, with a median difference of 5 days (p = .0037). Patients with a low concentration of THBS-1 had a higher risk of bacteremia and a shorter time to febrile neutropenia, indicating its potential value as a complications biomarker. Patients with lower serum THBS-1 concentrations, indicating an increased risk, may be more suitable for an inpatient AHSCT procedure, where close monitoring and immediate intervention are accessible.

Correlation of bioactive marker compounds of an orally applied Morus alba root bark extract with toxicity and efficacy in BALB/c mice.

Introduction: In traditional Chinese medicine, the root bark of Morus alba L. is used to treat respiratory infections. Recently, anti-inflammatory and multiple anti-infective activities (against influenza viruses, corona virus 2, S. aureus, and S. pneumoniae) were shown in vitro for a standardized root bark extract from M. alba (MA60). Sanggenons C and D were identified as major active constituents of MA60. The aim of the present preclinical study was to evaluate, whether these findings are transferable to an in vivo setting. Methods: MA60 was orally administered to female BALB/c mice to determine 1) the maximum tolerated dose (MTD) in an acute toxicity study and 2) its anti-influenza virus and anti-inflammatory effects in an efficacy study. A further aim was to evaluate whether there is a correlation between the obtained results and the amount of sanggenons C and D in serum and tissues. For the quantitation of the marker compounds sanggenons C and D in serum and tissue samples an UPLC-ESI-MS method was developed and validated. Results: In our study setting, the MTD was reached at 100mg/kg. In the efficacy study, the treatment effects were moderate. Dose-dependent quantities of sanggenon C in serum and sanggenon D in liver samples were detected. Only very low concentrations of sanggenons C and D were determined in lung samples and none of these compounds was found in spleen samples. There was no compound accumulation when MA60 was administered repeatedly. Discussion: The herein determined low serum concentration after oral application once daily encourages the use of an alternative application route like intravenous, inhalation or intranasal administration and/or multiple dosing in further trials. The established method for the quantitation of the marker sanggenon compounds in tissue samples serves as a basis to determine pharmacokinetic parameters such as their bioavailability in future studies.

INTERRELATION RECURRENCE RATE OF CHEILITIS FROM THE LEVELS OF VITAMIN D

Vitamin D deficiency is a widespread problem among carriers, people living in acute lack of sunlight in northern latitude regions, this is the result of low serum concentrations of the vitamin. Chronic lip fissure and meteorological cheilitis are the most common forms of cheilitis among residents of the Far North. The role of vitamin D deficiency has not been studied in patients with these diagnoses. The purpose of the study is to measure the level of vitamin D in the blood serum in patients with chronic lip fissure and meteorological cheilitis, as well as to dynamically study the dependence cases of disease recurrence on the concentration vitamin D. The study was conducted in 79 residents of the Murmansk region for 12 months. Diagnostic results have established that low serum vitamin D concentrations support the recurrence of meteorological cheilitis and chronic cleft lip. The use of vitamin D to maintain a normal level of vitamin in the blood serum improves the regenerative ability of the lip skin, maintains the barrier function of the epithelium, and reduces cheilitis recurrence rate. The study found that in the conditions of the Far North one of the mandatory components of the prevention and pathogenetic therapy of meteorological cheilitis and chronic lip fissure should be vitamin therapy with cholecalciferol preparations.

Intrapartum trends of NT-proBNP and hs-cTnT in patients with severe features of preeclampsia

BackgroundPreeclampsia with severe features (SPE) is a multisystem syndrome associated with long-term cardiovascular morbidity. Serum concentrations of N-terminal B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin-T (hs-cTnT) are sensitive markers of cardiac stretch and ischemia, respectively. ObjectiveOur aim was to examine NT-proBNP and hs-cTnT in patients with SPE during labor. We hypothesized that patients with severe preeclampsia would have increased serum concentrations of these analytes as compared with normotensive laboring patients.Study Design.This was a prospective cohort study of intrapartum patients with SPE and normotensive controls. Patients were recruited at the time of SPE diagnosis or admission to the labor unit, and those with medical conditions that could predispose to baseline cardiac dysfunction were excluded. Serum from venous blood was collected for NT-proBNP and hs-cTnT measurement at three time points: 0–2 h, 4 h, and 12 h after admission. A mixed random effects regression model was used to compare analyte levels at each time point and to compare trends over time. The primary outcome was NT-proBNP concentration at each collection time point in patients with severe preeclampsia as compared to normotensive controls. Power analysis yielded a goal sample of 25 patients with a 12 h and at least 1 other sample in each arm. Two-tailed P values less than 0.05 were considered statistically significant. P value adjustment for multiple comparisons was performed. ResultsOf 78 patients analyzed, 36 had severe preeclampsia and 42 were normotensive controls with 25 in each cohort having a 12 h and at least 1 other sample. The NT-proBNP trend was significantly different in the two cohorts (P < 0.001). After adjustment for multiple comparisons, the mean serum concentration of NT-proBNP was elevated in the severe preeclampsia group at 0–2 and 4 h, but not at 12 h. After similar adjustment, detectable serum concentrations of hs-cTnT were more frequent in patients with severe preeclampsia at all three timepoints. ConclusionIntrapartum serum concentrations of NT-proBNP were elevated nearly twofold in patients with SPE when compared with normotensive controls, with the most pronounced differences found during early labor. Detectable but low serum concentrations of hs-cTnT were more common in women with severe preeclampsia as compared with normotensive controls. These findings suggest cardiac dysfunction with SPE may be present at the time of admission and contribute to features of maternal cardiovascular morbidity and mortality.

Effects of Season, Productive State, Age and Agro-ecology on Blood Biochemical Characteristics of Dromedary Camels (Camelus dromedarius) in Natural Browsing Environment

Background: Blood biochemistry and reference intervals assist in distinguishing between healthy and productive camels as well as providing information for nutritional conditions, evaluation and monitoring when they are allowed to browse naturally; nevertheless, these intervals are frequently collected from animals of varying ages. The nutritional condition and biochemical markers of dromedary camels in pastoral systems in southern Ethiopia were investigated in this study, which took season, animal status, age and environmental variables into consideration. Methods: A total of 36 camels were divided into three groups based on their age ( greater than 8 years, 5-8 years, or less than 5 years) and productive state (milking, pregnant and young) in two environments (two herds in arid and semi-arid areas). Blood samples were collected from animals’ neck jugular veins, centrifuged and frozen for analysis. The samples were centrifuged (3000 rpm for 10 min) immediately after their arrival at the laboratory. Serum concentrations of glucose, protein, urea, creatinine, triglycerides and cholesterol were measured using spectrophotometry. Result: This study shows that glucose (91.33+7.30 mg/dl), total protein (7.17+0.15 mg/dl) and triglyceride (75.28+5.38 mg/dl) concentrations were significantly higher (P less than 0.05) during the rainy season, whereas urea (32.06+1.18 mg/l) and creatinine levels were significantly higher during the dry season. The study reveals increased glucose, total protein and triglyceride concentrations in camels during the rainy season, while urea and creatinine levels were higher during the dry season. Arid camels had lower serum concentrations of total protein and urea. Milking and pregnant camels had lower total serum protein, triglyceride and cholesterol levels.

A comparative study of performance of first trimester FMF algorithm for prediction of preeclampsia in singleton and twin pregnancies in coastal Karnataka

Preeclampsia is one of the most common disorders of pregnancy known to complicate 5-10% of all the pregnancies, and it is a component of the deadly triad (along with haemorrhage and infection), that contributes greatly to maternal morbidity and mortality rates. The prevalence of preeclampsia in twin pregnancy is 3-4 fold compared to singleton pregnancy. Timely diagnosis and prevention of this condition is therefore critical. Multiple maternal factors and placental biomarkers have shown to predict preeclampsia in singleton pregnancies. Previous Studies have shown that the proposed algorithms for preeclampsia screening in singletons can also be applied in twins, but with slight modifications and lower accuracy. To study the various parameters included in FMF screening algorithm in first trimester for preeclampsia in singleton and twin pregnancies. To find diagnostic accuracy of screening parameters to predict preeclampsia later in second and third trimester. To study sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in singleton and twin pregnancy. This prospective observational cohort study conducted in department of Obstetrics and Gynecology, Kasturba Medial College, Hospital, Manipal. Patients were recruited from August 2021 to November 2022. A total of 295 pregnant women were included of which 255 were singleton gestation and 40 were twin gestation. All parameters mentioned in FMF algorithm were obtained between 11week to 13+6 weeks. Patients were followed until delivery for occurrence of pre-eclampsia. Individual parameters of first trimester FMF algorithm of pre-eclampsia screening were analyzed in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in both singleton and twin study subjects and results were then compared among the groups. In this study a total of 295 pregnant women were recruited. 255 were single gestation of which 47 had preeclampsia and 40 were twin gestation of which 4 had preeclampsia. In the cohort of singleton pregnant women with pre-eclampsia, mean age was noted to be higher (32.77±4.27). They had higher BMI (mean 27.61±3.74) and first trimester MAP was also higher. Similarly, cohort of twin pregnancy with preeclampsia had higher mean of maternal age, BMI and MAP (30.33 ±4.46, 22.83 ± 2.93 and 90.40 ± 1.45 respectively). The Preeclampsia group in both singleton and twin subjects had lower serum concentration and lower MoM values of PAPP-A and PlGF while higher values of free beta HCG and uterine artery PI. Therefore the FMF algorithm for first trimester screening of preeclampsia was found to be a good predictor in both singleton and twin pregnancy. The first trimester FMF algorithm for preeclampsia screening had similar utility in the prediction of preeclampsia in both singleton and twin pregnancy with its individual parameters and combined risk model. However, its accuracy was slightly lesser among twins. Therefore, same screening model can be applicable in singleton and twin gestation.

Use of machine learning to predict mortality in patients with type 2 diabetes mellitus, according to socioeconomic status

Abstract Introduction Patients with Type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease (CVD) that adversely affects prognosis. Socioeconomic deprivation may be associated with lifestyle choices that contribute to adverse outcomes. The influence of social deprivation on the prognosis of T2DM is rarely investigated in large cohorts. Therefore, we assessed the associations between socioeconomic status and survival in patients with T2DM by applying conventional statistical methods and state-of-the-art, machine learning (ML) models. Methods We obtained routinely collected, linked administrative data for individuals with T2DM aged &amp;gt;50 years from the National Health Service (NHS) Scotland, including demographic data, laboratory measurements, prescriptions, death records and primary and secondary care diagnostic codes. We developed a random survival forest model for predicting all-cause mortality, overall and for each quintile of socioeconomic status using the Scottish Index of Multiple Deprivation (SIMD), which is based on postcodes that reflect a combination of income, employment, local crime rates, education, housing and health. We used Cox proportional hazards models to investigate the risk between the most and least deprived quintiles. Subsequently, we applied Shapely Additive Explanations (SHAP), a state-of-the-art ML interpretability method, to identify key prognostic factors that influence the survival probability prediction score for each sub-group. Results 30,495 people had a newly recorded diagnosis of T2DM between 2009-2019, of whom 4,300 died within 10 years. Table 1 shows the c-index (global assessment of model discrimination) and time-brier score (measure of calibration for time-dependent probability prediction) for the whole cohort and for each SIMD quintile: use of loop diuretics, older age, lower serum concentrations of albumin and alanine transaminase (ALT) and estimated glomerular function rate (eGFR) were strong predictors of death for all quintiles. Prevalence of chronic obstructive pulmonary disease (COPD) was strongly associated with mortality for the most deprived quintile (Q1, whilst strokes were strongly associated with mortality for the most affluent (Q5). A history of heart failure, in addition to use of loop diuretics, predicted a higher risk, in 3 of the 5 quintiles. Overall Q1 had a 36% higher mortality than Q5 (HR: adjusted for age and sex 1.36 [95% CI 1.24 – 1.50 (&amp;lt;0.005)]). Conclusion Greater socioeconomic deprivation is associated with a worse prognosis in patients with T2DM. Results of commonly measured blood tests, allied to readily available patient characteristics (including heart failure and use of loop diuretics) predict mortality risks across all deprivation groups for people with T2DM.Table:Predictors of Mortality in T2DM

ACNE AND INSULIN RESISTANCE: A SYSTEMATIC REVIEW

Acne is a skin disorder that is characterized by persistent inflammation and involves the folliculopilosebaceous unit. It has an impact on a sizeable portion of the general population. Acne affects a disproportionate number of females and teenagers, especially those between the ages of 15 and 24, who are most susceptible to the condition. In recent times, there has been seen to be a growing interest in the possible connection between acne and insulin resistance (IR). This attention has been seen, and it is appreciated. It would appear that IR has a strong connection to acne, which is a persistent skin condition that can lead to inflammation. Research has been conducted on a wide variety of etiopathological factors that have been associated with the progression of IR. It would appear that obesity is one of the most common. Additionally, it would appear that factors such as chronic inflammation, hypertriglyceridemia, low HDL serum concentration, mitochondrial dysfunction, gut microbiota, and the excess activity of antagonistic hormones such as cortisol, glucagon, and thyroid hormones all play a significant role in the development of this condition. We identified a linkage between insulin resistance and severe acne vulgaris, which was reported to have a positive link with insulin resistance. On the basis of these findings, it is a legitimate assumption to hypothesize that medications that are now utilized for the treatment of insulin resistance would also be helpful for the treatment of severe acne vulgaris.