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This investigation aimed to assess the safety and efficacy of NeoLight's Skylife phototherapy device for the treatment of hyperbilirubinemia. A prospective, two-arm, randomized, unblinded controlled investigation compared total serum bilirubin (TSB) levels at baseline and discharge for a new phototherapy device (Skylife) with an existing phototherapy treatment in newborn infants. The repeated-measures analysis of variance (RM-ANOVA) indicated a significant main effect for the treatment condition, F (1, 54) = 4.041, P =.049. Post hoc findings showed that the Skylife group had significantly lower TSB levels following treatment (n = 28, Mean = 11.36, SD = 1.69) compared with the standard of care group (n = 28, Mean = 12.37, SD = 2.08), t (54) = 2.01, P =.049). The Skylife phototherapy device was as effective as the currently used therapy, with a shift toward a more rapid decline in bilirubin levels. Using this device may potentially decrease the length of therapy and hospitalization. Clinical Trial Registration Comparison of Phototherapy Using Neolight Skylife Versus Standardized Phototherapy for Hyperbilirubinemia in Newborns is registered at clinicaltrials.gov as NCT03599258 [ABSTRACT FROM AUTHOR]

Purpose: There are several pathways by which zinc may be a modifiable factor to slow age-related cognitive decline. We investigated the associations between serum and dietary zinc and cognitive impairment in a longitudinal cohort. Methods: We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort (n = 30,239) and the REGARDS Trace Element Study (n = 2666). Baseline serum zinc concentrations (2003–2007) were measured using inductively coupled plasma mass spectrometry. Baseline dietary zinc intake was measured via the Block food frequency questionnaire. Serum zinc concentrations and dietary zinc intake were categorized into quartiles. The outcome of interest was impairment on the Six-Item Screener (SIS), a measure of global cognitive functioning administered annually. The Enhanced Cognitive Battery (ECB), a more comprehensive series of tests assessing memory and fluency, was administered every two years and considered a secondary outcome. Associations between zinc and incident impairment were assessed using multivariable logistic regression. Results: Among 2065 participants with serum zinc data, 184 individuals developed impairment over 10 years of follow-up. In adjusted models, there was no significant association between serum zinc and impairment as assessed by the SIS or the ECB. Among 18,103 participants who had dietary data, 1424 experienced incident impairment on the SIS. Dietary zinc intake was not significantly associated with impairment as assessed by the SIS or the ECB in adjusted models. Conclusion: Findings from this U.S. cohort did not support the hypothesis that serum zinc concentration or dietary zinc intake is associated with the risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

The serum (1,3)-beta- d -glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (–1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. Twenty-two C. auris , 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379–648) for C. auris , 1080 pg/mL (IQR 830–1276) for C. albican s, and 755 pg/mL (IQR 511–930) for C. parapsilosis , with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15–161) and 57 pg/mL (IQR 18–332), vs. 372 pg/mL (IQR 102–520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18–64) in case of C. auris , 30% (95% CI, 8–65) C. parapsilosis and 78% (95% CI, 49–94) C. albicans candidemia. In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans , with a potential impact on serum BDG performance for the diagnosis of candidemia. [ABSTRACT FROM AUTHOR]

Objective: Diabetes retinopathy (DR) is one of the top listed world health issues. Screening is usually advised for diabetic cases on a routine basis. However, there is only partial access to ophthalmologists in all parts of the world. Irisin is a myokine that is being investigated for this reason. Our study aims to assess the role of irisin in detecting DR. Methods and materials: In a cross-sectional study, 140 diabetes cases, including 70 patients with diabetic retinopathy and 70 patients free from diabetic retinopathy, were enrolled. Demographic and anthropometric data were gathered, and the patients underwent physical examination. Also, microalbuminuria and serum irisin levels were assessed in both groups. The results were compared between the two study groups. Results: Among the enrolled cases, 55 (39.28%) were men, and 85 (60.72%) were women. The disease duration (p = 0.016) and the serum level of HBA1c (p = 0.014) were significantly higher in the diabetic retinopathy group compared to the group free from diabetic retinopathy. Moreover, irisin was significantly higher in the patients free from diabetic retinopathy (p = 0.007). Conclusion: Irisin may have value in screening diabetic retinopathy; however, further studies are needed for this proposal. [ABSTRACT FROM AUTHOR]

Context Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome–targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear. Objectives This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population. Data Source A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD. Data Extraction Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies. Data Analysis A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], −10.21; 95% confidence interval [CI], −13.29, −7.14; P < 0.001), aspartate aminotransferase (AST; ES, −8.86; 95%CI, −11.39, −6.32; P < 0.001), and γ-glutamyltransferase (ES, −5.56; 95%CI, −7.92, −3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, −8.69; 95%CI, −11.01, −6.37; P < 0.001) and ALT (ES, −9.82; 95%CI, −11.59, −8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, −11.40; 95%CI, −13.91, −8.88; P < 0.001) and ALT (ES, −11.87; 95%CI, −13.80, −9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, −2.96; 95%CI, −8.12, 2.18, P = 0.259; and ES, −4.69; 95%CI, −13.53, 4.15, P = 0.299, respectively). Conclusion Gut microbiome–targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome–targeted therapies in the treatment of the NAFLD population. Systematic Review Registration PROSPERO registration no. CRD42022346998. [ABSTRACT FROM AUTHOR]

Our study investigated the impact on male mouse fertility and reproduction of long‐term (14 weeks) exposure to triethylene glycol dimethacrylate (TEGDMA), a co‐monomer of resin‐based compounds, at doses of 0.01, 0.1, 1, and 10 ppm. Test and control mice were then paired with sexually mature untreated female mice and their fertility evaluated. Females paired with males exposed to all TEGDMA doses exhibited a significant decline in pregnancy rates, and significant increases in the total embryonic resorption‐to‐implantation ratio, except for males exposed to 0.01 ppm TEGDMA. Males in the highest dose group (10 ppm) showed significant increases in seminal vesicle and preputial gland weights. They also had significantly higher serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) than the controls, and the 0.01 ppm dosage group for FSH levels. TEGDMA exposure resulted in notable histopathological alterations in the testis, with detachment of germ cells and shedding of germinal epithelium into the tubule lumen. These results strongly indicate that TEGDMA exposure has detrimental consequences on the reproductive abilities and functions in male mice through disruption of the standard hormonal regulation of the reproductive system, leading to changes in spermatogenesis and ultimately leading to decreased fertility. [ABSTRACT FROM AUTHOR]

Objective: This study aimed at assessing the effectiveness of cognitive‐behavioural therapy (CBT) integrated with psychoeducation in a group of hypertensive patients with clinically significant psychopathological symptoms. Methods: One hundred hypertensive patients completed the Symptom Checklist‐90‐Revised. Of them, 17 scored above the clinical range (cut‐off = 0.75) on the Global Severity Index and were included in the study. Psychological distress was assessed again after the intervention (T1) and 6 months after the end of treatment (T2). In addition, the cortisol dosage and the heart rate (HR) measurement were collected at both T0 and T2. Then, mediation analyses were carried out to calculate whether psychopathological distress might predict HR through elevated serum cortisol levels, at both T0 and T2. Results: The psychological intervention (CBT integrated with psychoeducation) reduced most of the psychopathological symptoms (anxiety, depression, somatisations, obsessions and compulsions, hostility, interpersonal sensitivity and paranoid ideation) but not cortisol dosage and HR measurement. However, psychological distress indirectly predicted HR via cortisol at T0 but not at T2. Conclusion: These results suggest and encourage the replicability of data in larger sample sizes and the comparison with a control group. Nevertheless, these results highlight a need for a multidimensional assessment of disorders affecting the mental and physical spheres of patients to support their overall well‐being. [ABSTRACT FROM AUTHOR]

Background: Limited studies are available on vitamin D supplementation in dogs. This study evaluates the effect of a commercial vitamin D3 supplement on serum 25-hydroxy vitamin D as well as selected biochemical and hematological parameters in healthy dogs. Eight intact male adult dogs with a mean body weight of 20 kg from mixed breeds were included in the study. After adaptation period, dogs received vitamin D3 supplement at the dose of 50 IU/kg body weight per day. Blood samples were collected on days 0, 14, 28 and 42 of supplementation. Food was used for analysis of vitamin D3 content. Results: Significant increase in serum level of 25-hydroxy vitamin D3 was detected since day 14 of supplementation. Changes in serum 25-hydroxy vitamin D3 concentration during time showed an upward significance (p < 0.05). Vitamin D3 content of the food was 2900 IU/kg dry matter. Changes in serum phosphorus levels were upward significant. No dog showed calcium or phosphorus levels above the highest reference level. Liver and kidney parameters remained in the reference range during the experiment. A gradual significant increase was observed in hemoglobin and hematocrit which was started from day 14. Vitamin D3 supplementation had no significant effect on neutrophils, monocytes and lymphocytes percent during the study. Conclusions: Vitamin D3 supplementation at 50 IU/kg BW daily, increases serum levels of 25-hydroxy vitamin D in healthy dogs fed with a diet containing proper amount of this vitamin. It also increases hemoglobin and hematocrit levels in a time dependent manner without inducing adverse effects. [ABSTRACT FROM AUTHOR]

Background: Peste des Petits Ruminants (PPR) is a world organization for animal health (WOAH) notifiable and economically important transboundary, highly communicable viral disease of small ruminants. PPR virus (PPRV) belongs to the genus Morbillivirus of the family Paramyxoviridae. Aim: The present cross-sectional epidemiological investigation was accomplished to estimate the apparent prevalence and identify the risk factors linked with peste des petits ruminants (PPR) in the previously neglected northern border regions of Pakistan. Method: A total of 1300 samples (serum = 328; swabs = 972) from 150 flocks/herds were compiled from sheep (n = 324), goats (n = 328), cattle (n = 324), and buffaloes (n = 324) during 2020–2021 and tested using ELISA for detection of viral antibody in sera or antigen in swabs. Results: An overall apparent prevalence of 38.7% (504 samples) and an estimated true prevalence (calculated by the Rogan and Gladen estimator) of 41.0% (95% CI, 38.0–44 were recorded in the target regions. The highest apparent prevalence of 53.4% (85 samples) and the true prevalence of 57.0%, 95% Confidence Interval (CI) were documented in the Gilgit district and the lowest apparent prevalence of 53 (25.1%) and the true prevalence of 26.0%, 95% Confidence Interval (CI), 19.0–33.0) was reported in the Swat district. A questionnaire was designed to collect data about associated risk factors that were put into a univariable logistic regression to decrease the non-essential assumed risk dynamics with a P-value of 0.25. ArcGIS, 10.8.1 was used to design hotspot maps and MedCalc's online statistical software was used to calculate Odds Ratio (OR). Some of the risk factors significantly different (P < 0.05) in the multivariable logistic regression were flock/herd size, farming methods, nomadic animal movement, and outbreaks of PPR. The odds of large-sized flocks/herds were 1.7 (OR = 1.79; 95% Confidence Interval (CI) = 0.034–91.80%) times more likely to be positive than small-sized. The odds of transhumance and nomadic systems were 1.1 (OR = 1.15; 95% Confidence Interval (CI) = 0.022–58.64%) and 1.0 (OR = 1.02; 95% Confidence Interval (CI) = 0.020–51.97%) times more associated to be positive than sedentary and mixed farming systems, respectively. The odds of nomadic animal movement in the area was 0.7 (OR = 0.57; 95% Confidence Interval (CI) = 0.014–38.06%) times more associated to be positive than in areas where no nomadic movement was observed. In addition, the odds of an outbreak of PPR in the area were 1.0 (OR = 1.00; 95% Confidence Interval (CI) = 0.018–46.73%) times more associated to be positive than in areas where no outbreak of PPR was observed. Conclusions: It was concluded that many northern regions considered endemic for PPR, large and small ruminants are kept and reared together making numerous chances for virus transmission dynamic, so a big threats of disease spread exist in the region. The results of the present study would contribute to the global goal of controlling and eradicating PPR by 2030. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusion\nCLINICAL SIGNIFICANCEBladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC.In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively.Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 − 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05).The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Wooden breast myopathy is an abnormality that affects heavyweight, rapidly growing broilers' breast muscle. The understanding of the exact cause of this muscle pathology remains incomplete, necessitating further investigation. Blood biochemical analysis is used to diagnose pathologies and understand disease processes. Therefore, the objective of this research was to determine and compare the changes in the blood serum biochemical parameters of broilers without myopathy and those affected by myopathy. Blood samples were collected from male and female 43-day-old broilers with an average live weight of 2.98–3.09 kg. The research results showed that birds with wooden breast had higher levels of creatine kinase, potassium, and alanine aminotransferase. Increased alanine aminotransferase indicated possible liver injury alongside wooden breast myopathy. Elevated creatine kinase and potassium suggested muscle damage, indicating CK as a potential biomarker for WB. Wooden breast (WB) myopathy is a pathology of the pectoralis major muscle. Wooden breast is caused by multiple factors. The exact etiopathogenesis of this myodegenerative pathology is still unclear. Fast-growing commercial lines of broilers that are selected for high breast muscle yields are more susceptible to this myopathy. The biochemical analysis of blood is used to diagnose pathologies and understand disease processes. Therefore, the objective of this research was to determine and compare the changes in the blood serum biochemical parameters of Ross 308 chicken broilers without myopathy and those affected by WB myopathy. Blood samples were collected from male and female Ross 308 broilers that were 43 days old, with an average live weight of 2.98–3.09 kg. Representative blood samples were selected from broilers with WB (n = 33) and without WB (n = 33). In the laboratory, the blood was centrifugated, and biochemical tests were performed with an automated computerized biochemistry analyzer. The research results showed that broilers with WB had elevated blood serum levels of creatine kinase (CK) (p = 0.018), potassium (p = 0.010), and alanine aminotransferase (ALT) (p = 0.012). In conclusion, elevated serum levels of CK and potassium indicated that skeletal muscle cells were damaged. Moreover, increased ALT levels suggested a possible association between WB myopathy and liver damage. Additionally, these research findings underscore the diagnostic significance of CK and hint at its potential as a WB biomarker. [ABSTRACT FROM AUTHOR]

Simple Summary: This study thoroughly investigated viral pathogens associated with bovine respiratory disease complex (BRDC) in Serbian cattle using serum and nasal swab samples. Conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding ones with vaccinated cattle, this study categorized the farms by their size: small, medium, and large. Serum samples from adult cattle were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3, while nasal swabs from respiratory-symptomatic animals were PCR-tested for viral genome detection. The results showed seropositivity for all four viruses on all of the farms, with BPIV3 being universally positive. Medium-sized and large farms exhibited higher levels of seropositivity for BRSV and BHV-1 compared to small farms (p < 0.05). Our true seroprevalence estimates were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3 at the animal level. A PCR analysis of the nasal swabs detected BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%), with no Influenza D virus found. This study provides crucial insights into viral pathogen prevalence and circulation in Serbian cattle with BRDC, emphasizing the importance of surveillance and control measures to manage respiratory diseases in cattle populations. Bovine respiratory disease complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding farms with vaccinated cattle. The farms were categorized by their livestock count: small (≤50 animals), medium (51–200 animals), and large (>200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from the animals with respiratory signs were tested using PCR for viral genome detection. The results showed seropositivity for all four viruses across all of the farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher levels of seropositivity for BRSV and BHV-1 compared to small farms (p < 0.05). Our true seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. A PCR analysis of the nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of the samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations. [ABSTRACT FROM AUTHOR]

Simple Summary: Leishmania infantum is a single-celled trypanosomatid responsible for canine leishmaniasis, a serious disease that causes a generalized inflammatory reaction including, among others, lymphadenopathy, hepatomegaly, and splenomegaly in dogs. Increasing information on leishmaniasis in wildlife shows that many mammalian species can act as reservoirs, being a serious threat to domestic dog populations and public health. Our case describes a female wolf suffering from lameness due to an ulcerative wound on the right forepaw, with hyper-gammaglobulinemia, high serum GPT levels, and positive ELISA tests for antibodies to Leishmania infantum antigens as confirmed by PCR. The wolf responded positively to conventional treatment of leishmaniasis, and all altered parameters were restored. Leishmaniasis in wild canids is a vector-borne disease caused in Europe by the protozoan parasite Leishmania infantum. To date, there is limited information on clinical signs and laboratory abnormalities in wolves due to leishmaniasis. The current clinical case report described a female Iberian wolf (Canis lupus signatus) housed in semi-captivity conditions at the Centro del Lobo Ibérico "Félix Rodríguez de la Fuente", in Robledo de Sanabria, Zamora (Spain), with an interdigital ulcerous wound at the right forepaw, hyper-gammaglobulinemia, and abnormal liver blood parameters. Definitive serodiagnosis of leishmaniasis was established using antileishmanial serum antibodies and PCR analysis of different biological samples. A gold-standard anti-L. infantum treatment protocol consisting in subcutaneous meglumine antimoniate and oral allopurinol combination was installed. However, the presence of pain at the site of injection due to meglumine antimoniate administration forced its substitution by oral miltefosine. A progressive reduction of the levels of anti-L. infantum serum antibodies and the concentrations of gamma-globulin fraction was detected after antileishmanial treatment as well as a decline of liver GPT. To our knowledge, this is the first case of leishmaniasis diagnosed in a wolf housed in semi-captivity conditions, with the condition subsequently treated and successfully cured. [ABSTRACT FROM AUTHOR]

Simple Summary: The synchronization process of yak estrus plays a crucial role in enhancing the reproductive success rate of yaks and safeguarding the continuation of the species. Metabolomics, a branch of bio-chemistry, primarily focuses on the quantitative analysis of all metabolites within an organism, aiming to identify the relative relationships between metabolites and physiological changes. It serves as a valuable tool for delving into the molecular mechanisms and responses of metabolic pathways under various perturbations. In this study, metabolomics methods were utilized to analyze blood samples collected from non-estrus yaks as well as those that underwent hormonally induced synchronized estrus to identify differential metabolites. The research results provide a theoretical basis for the optimization and application of synchronized estrus technology in yaks, promoting the healthy development of the yak industry. The yak is a unique species of livestock found in the Qinghai-Tibet Plateau and its surrounding areas. Due to factors such as late sexual maturity and a low rate of estrus, its reproductive efficiency is relatively low. The process of estrus synchronization in yaks plays a crucial role in enhancing their reproductive success and ensuring the continuation of their species. In order to clarify the characteristics of the serum metabolites of yak estrus synchronization, the yaks with inactive ovaries were compared with the estrus synchronization yaks. In this study, yaks were divided into the inactive ovaries group (IO), gonarelin-induced yak estrus group (GnRH), and chloprostenol sodium-induced yak estrus group (PGF). After the completion of the estrus synchronization treatment, blood samples were collected from the jugular veins of the non-estrus yaks in the control group and the yaks with obvious estrus characteristics in the GnRH and PGF groups. Metabolites were detected by ultra-high performance liquid chromatography-mass spectrometry, and differential metabolites were screened by multivariate statistical analysis. The results showed that a total of 70 significant differential metabolites were screened and identified in the GnRH vs. IO group, and 77 significant differential metabolites were screened and identified in the PGF vs. IO group. Compared with non-estrus yaks, 36 common significant differential metabolites were screened out after the induction of yak estrus by gonarelin (GnRH) and cloprostenol sodium (PGF), which were significantly enriched in signaling pathways such as the beta oxidation of very long chain fatty acids, bile acid biosynthesis, oxidation of branched chain fatty acids, steroidogenesis, steroid biosynthesis, and arginine and proline metabolism. This study analyzed the effects of gonadotropin releasing hormone (GnRH) and prostaglandin F (PGF) on the reproductive performance of yaks treated with estrus synchronization, which provides a theoretical basis for the optimization and application of yak estrus synchronization technology and promotes the healthy development of the yak industry. [ABSTRACT FROM AUTHOR]

Mixed-mode high-performance liquid chromatography (HPLC) is increasingly used for the analysis of ionic and highly hydrophilic drugs, which are difficult to separate by conventional single-mode HPLC. In the former case, chromatographic separation is achieved using one of the several commercially available mixed-mode stationary phases, typically combinations of reversed and ion-exchange phases. Moreover, mixed-mode stationary phases can be used as solid-phase extraction (SPE) sorbents. This review focuses on the recent applications of mixed-mode stationary phases in the chromatographic analysis of bioactive compounds, such as drugs, herbicides, and pesticides. Specifically, we briefly summarize HPLC methods utilizing mixed-mode stationary phases and SPE pretreatment procedures utilizing mixed-mode sorbents developed in the last decade, thus providing a reference work for overcoming the difficulties in analyzing ionized or hydrophilic drugs by conventional reversed-phase chromatography. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies against a lot of nuclear components. Despite many studies on the genetic background of this disease, the pathogenesis remains unclear. The aim of the study is to comprehensively evaluate the polymorphism of the IL-10 promoter gene, its mRNA expression, and the serum IL-10 concentration of SLE female patients and females age-matched controls. Analyzing the association between the level of the tested cytokine and the polymorphism genotype-1082; -819; -592, we found statistically higher serum IL-10 levels in SLE patients compared to in healthy controls (11.9 ± 2.2 pg/mL vs. 9.4 ± 1.7 pg/mL, accordingly; p < 0.0001). We did not find statistically significant differences in the gene polymorphism of IL-10 among SLE patients and controls. The most significant observation derived from our study is that IL-10 mRNA transcripts are upregulated in SLE patients compared to in healthy controls (p < 0.0001). According to our results, the presence of the IL-10 genetic polymorphism has no clinical significance for the development of SLE, and subsequent differences in mRNA and IL-10 concentration results from the influence of other factors which should be the subject of further research. [ABSTRACT FROM AUTHOR]

Accurate measurement of endogenous steroid hormones in serum is a powerful tool for understanding the status of human adrenal diseases. Isotope dilution–liquid chromatography–tandem mass spectrometry is the most commonly used method for determination of steroids in serum. In this study, we used a laboratory-constructed quadrupole-linear ion trap (Q-LIT) tandem mass spectrometer to develop a new method for the quantification of five steroid hormones in serum. A simple and efficient pretreatment was improved, wherein the serum was extracted once by a mixed solvent of 1.0 mL of ethyl acetate and n-hexane. Using the optimized method, the regression coefficients of the calibration curves were all higher than 0.99, the limits of detection were from 0.31 to 1.25 ng mL−1, and the limits of quantification were between 1.00 and 2.50 ng mL−1. The intra-day (n = 3) relative standard deviations ranged from 4.24% to 13.79%, and the inter-day (n = 3) relative standard deviations from 3.99% to 11.43%. After internal standard correction, the relative recoveries of all steroids were from 86.08% to 106.60%. Twenty-two serum samples were analyzed by Q-LIT, which was compared with commercial triple quadrupole mass spectrometer. The results of the instruments had high consistency. Therefore, Q-LIT accurately quantified steroid hormones in human samples and may be used for clinical diagnosis and monitoring of hormone-dependent diseases. [ABSTRACT FROM AUTHOR]

Background: Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes. Methods: A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected. Results: Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71–1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible. Conclusions: This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years. Systematic review registration: PROSPERO CRD42022308006 [ABSTRACT FROM AUTHOR]

Background: Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies. Methods: In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes. Results: Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors—kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10− 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)—and three protective factors—3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14–0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20–0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51–0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA. Conclusion: Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies. [ABSTRACT FROM AUTHOR]

Background: M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN. Methods: This retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model. Results: After a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26–0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62–0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601–0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587–0.824), thus, demonstrating robustness. Conclusions: Cyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) has significant potential as a biomarker for diagnosis of ovarian cancer in female patients because it is present throughout all phases of the illness. Regrettably, there is not a clinically useful test for this biomarker yet. In this work, an ultra‐detection of LPA molecule by Raman spectroscopy‐based molecularly imprinted polymer (MIP) in serum samples is reported. β‐CD was synthesized to facilitate the collection of Raman spectroscopy and combined with MIP to denote it as β‐CD‐MIP for the adsorption of LPA with high sensitivity and selectivity. Linear regression model in serum samples shows peaks at 1100 and 1116 cm−1, respectively. A satisfactory linear fit was seen with LPA concentration log I = 3.7 log C + 1255.74 and with spiked serum log I = 4.6 log C + 327.22, respectively. The literature survey suggests the threshold LPA level in healthy person is 1.50 μM/L whereas the LPA level rises in patients with benign ovarian cancer tumor as 7.90 μM/L. This LPA level rises to 16.99 μM/L in ovarian cancer patients. On the basis of the band intensity, the limit of detection of the β‐CD‐MIP sensor for LPA was recorded as 0.003 μM/L. The binding constant of β‐CD‐MIP for LPA in serum was 0.031–0.003 μM/L, respectively. β‐CD‐MIP gel was optimized, characterized, and successfully applied on spiked serum samples. The findings of this research show that this substrate has a lot of potential for ultradetection of trace amounts of LPA molecule from the serum samples. The MIP sensor is robust, recyclable, efficient, and selective. [ABSTRACT FROM AUTHOR]

• RSVpreF immunogenicity, safety, and tolerability were evaluated in healthy adults. • Equivalence in immunogenicity was assessed across 3 RSVpreF lots. • All 3 RSVpreF lots elicited strong immune responses 1 month after vaccination. • Lot-pair comparisons met the 1.5-fold equivalence criterion for both RSV A and RSV B. • RSVpreF single doses were safe and well tolerated, with safety similar across lots. Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots. This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18–49-year-old adults. Participants received a single 120-µg injection of 1 of 3 RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667–1.5 interval). Safety and tolerability were assessed. Of 992 participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671–1795; RSV B 1358–1429) to 1 month after RSVpreF vaccination (RSV A, 24,131–25,238; RSV B, 19,238–21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots. These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208). [ABSTRACT FROM AUTHOR]

Background: The association between the systemic immune-inflammation index (SII) and the serum soluble-Klotho concentration (pg/ml) in osteoarthritis (OA) patients is unknown. This study aimed to investigate the relationship between the SII and serum soluble-Klotho levels in OA patients. Methods: All study data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (n = 1852 OA patients; age range = 40–79 years). The SII and serum Klotho measurement data are from the NHANES mobile examination centre. The SII values were divided into quartiles (Q1-4: 0.02–3.36, 3.36–4.78, 4.79–6.70, and 6.70–41.75). A multivariate linear regression model was constructed to evaluate the association between the SII and serum Klotho levels in OA patients; interaction tests were conducted to test the stability of the statistical results. Results: Multivariate linear regression revealed a negative linear relationship between the SII and serum Klotho concentration in OA patients (β = -6.05; 95% CI: -9.72, -2.39). Compared to Q1, Q4 was associated with lower serum Klotho concentrations (β = -59.93; 95% CI: -96.57, -23.28). Compared with that of Q1, the β value of Q2-Q4 showed a downwards trend as the SII increased (Ptrend <0.001). The stratified analysis results indicated that the SII had a greater sensitivity in predicting serum Klotho concentrations in OA patients aged 60–79 years (Pinteraction = 0.028). Conclusions: There was a significant negative linear correlation between the SII and serum Klotho concentration in OA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in OA patients. Klotho may be a potential anti-inflammatory drug for OA treatment. [ABSTRACT FROM AUTHOR]

Heat exposure exceeding the ISO7243:1989 standard limit can contribute to health problems among employees in a variety of workplaces. Ignoring heat standard requirements in hot working conditions such as bakeries results in physiologic and health problems, as well as an elevated risk of later illnesses. In this analytical case-control study, the serum levels of four inflammatory factors (interleukin-1 beta, interleukin-6, tumor necrosis factor-α, and C-reactive protein) were assessed using an enzyme-linked immunosorbent assay. 105 male artisan bakers (in four job classifications in bakeries and staff) were compared based on demographic characteristics and inflammatory factors. The findings of the study showed correlations between serum interleukin-1β, interleukin-6, and C-reactive protein levels and thermal exposure in the occupational environment and employment type. Moreover, some differences in serum level of interleukin-1β and job type were observed. Heat overexposure affected the increase of interleukin-1β and C-reactive protein secretion. As a result of years of working in high-temperature conditions, inflammation can lead to subsequent diseases in workers. To protect their health from this occupational hazard, additional safeguards are needed. Our recommendations could also be applied to overly hot work environments that may cause heat stress in workers. [ABSTRACT FROM AUTHOR]

We evaluated different sample preparation methods for one-dimensional proton nuclear magnetic resonance metabolomics analysis of beef cattle ruminal fluid and serum. After collecting and pooling samples from five bulls (all of which received the same diet and were subjected to the same management conditions), we prepared the samples with the following methods: metabolite extraction using methanol and chloroform (M + C); metabolite extraction using methanol, chloroform and acetone (M + C + A); filtering with a 3-kDa filter; and filtering with a 2-μm filter. We evaluated the methods based on the spectral quality, reproducibility, ease of processing, speed and relative cost. The use of 2-μm filters did not produce good-spectra quality for serum samples, but it was a promising method for ruminal fluid. The yields of metabolites were similar for the the solvent extractions (22 metabolites for ruminal fluid and 29 for serum samples), but lower compared with the filter methods (31 metabolites for ruminal fluid and 47 for serum samples). The filters resulted in a higher concentration of metabolites and better reproducibility. In conclusion, the 2-μm and 3-kDa filter methods represent a suitable way to prepare biological samples from beef cattle for nuclear magnetic resonance – based metabolomics. [ABSTRACT FROM AUTHOR]

Background: Chemokine‐like factor 1 (CKLF1) may be involved in the inflammatory response and secondary brain injury after severe traumatic brain injury (sTBI). We determined serum CKLF1 levels of sTBI patients to further investigate the correlation of CKLF1 levels with disease severity, functional prognosis, and 180‐day mortality of sTBI. Methods: Serum CKLF1 levels were measured at admission in 119 sTBI patients and at entry into study in 119 healthy controls. Serum CKLF levels of 50 patients were also quantified at days 1–3, 5, and 7 after admission. Glasgow coma scale (GCS) scores and Rotterdam computerized tomography (CT) classification were utilized to assess disease severity. Extended Glasgow outcome scale (GOSE) scores were recorded to evaluate function prognosis at 180 days after sTBI. Relations of serum CKLF1 levels to 180‐day poor prognosis (GOSE scores of 1–4) and 180‐day mortality were analyzed using univariate analysis, followed by multivariate analysis. Receiver‐operating characteristic (ROC) curve was built to investigate prognostic predictive capability. Results: Serum CKLF1 levels of sTBI patients increased at admission, peaked at day 2, and then gradually decreased; they were significantly higher during the 7 days after sTBI than in healthy controls. Differences of areas under ROC curve (areas under the curve [AUCs]) were not significant among the six time points. Multivariate analysis showed that serum CKLF1 levels were independently correlated with GCS scores, Rotterdam CT classification, and GOSE scores. Serum CKLF1 levels were significantly higher in non‐survivors than in survivors and in poor prognosis patients than in good prognosis patients. Serum CKLF1 levels independently predicted 180‐day poor prognosis and 180‐day mortality, and had high 180‐day prognosis and mortality predictive abilities, and their AUCs were similar to those of GCS scores and Rotterdam CT classification. Combination model containing serum CKLF1, GCS scores, and Rotterdam CT classification performed more efficiently than any of them alone in predicting mortality and poor prognosis. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Conclusion: Serum CKLF1 levels are significantly associated with disease severity, poor 180‐day prognosis, and 180‐day mortality in sTBI patients. Hence, complement CKLF1 may serve as a potential prognostic biomarker of sTBI. [ABSTRACT FROM AUTHOR]

Erythrodermic psoriasis (EP) is a rare and life‐threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, and potential intervention strategies. To gain a better understanding of the mechanisms of EP and explore the serum metabolic signature of EP, we conducted an untargeted metabolomics analysis from 20 EP patients and 20 healthy controls. Furthermore, targeted metabolomics for focused metabolites were identified in the serum samples of 30 EP patients and 30 psoriasis vulgaris (PsV) patients. In the untargeted analysis, a total of 2992 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Principal component analysis (PCA), orthogonal partial least squares‐discriminant analysis (OPLS‐DA) revealed significant difference between groups. After screening, 98 metabolites were found to be significantly dysregulated in EP, including 67 down‐regulated and 31 up‐regulated. EP patients had lower levels of L‐tryptophan, L‐isoleucine, retinol, lysophosphatidylcholine (LPC), and higher levels of betaine and uric acid. KEGG analysis showed differential metabolites were enriched in amino acid metabolism and glycerophospholipid metabolism. The targeted metabolomics showed lower L‐tryptophan in EP than PsV with significant difference and L‐tryptophan levels were negatively correlated with the PASI scores. The serum metabolic signature of EP was discovered. Amino acid and glycerophospholipid metabolism were dysregulated in EP. The metabolite differences provide clues for pathogenesis of EP and they may provide insights for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: Trophoblast-derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. Human Leukocyte Antigen-G (HLA-G) belongs to the non-classical human major histocompatibility complex (MHC-I) molecule and has membrane-bound and soluble forms. HLA-G is primarily expressed by extravillous cytotrophoblasts located in the placenta between the maternal and fetal compartments and plays a pivotal role in providing immune tolerance. The aim of this study was to establish a relationship between concentrations of soluble HLA-G (sHLA-G) in maternal serum and amniotic fluid at 16–22 weeks of gestation and the sonographic measurements of fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices, were determined in 41 singleton pregnancies with no complications. The level of sHLA-G (U/mL) was tested with a sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: The sHLA-G levels were unchanged both in amniotic fluid and serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β = 0.63, p < 0.01). Serum sHLA-G level was significantly correlated with abdominal measurements (β = 0.41, p < 0.05) and estimated fetal weight (β = 0.41, p < 0.05). Conversely, amniotic sHLA-G level and placental perfusion (VI: β = −0.34, p < 0.01 and VFI: β = −0.44, p < 0.01, respectively) were negatively correlated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = −0.102, p < 0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator of placental function, whereas the sHLA-G level in serum can be a prognostic factor for feto-placental insufficiency. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction (ED) stands out as one of the most prevalent sexual disorders in men, with its incidence progressively escalating with age. As delineated by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, the prevalence of ED among men under 40 years is estimated to be within the range of 1–10%. The aim of this study was to determine the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men with and without erectile dysfunction. Materials and methods: The retrospective cohort study included 152 men who underwent total hip arthroplasty for hip osteoarthritis at the Department of Orthopaedic Traumatology and Musculoskeletal Oncology at the Pomeranian Medical University in Szczecin. Certain exclusion criteria were applied to ensure the integrity of the study. These included individuals with diabetes, a history of cancer, alcohol abuse, liver or kidney failure, New York Heart Association (NYHA) class III or IV heart failure, and those taking medications that affect bone metabolism, such as mineral supplements, neuroleptics, chemotherapeutic agents, immunosuppressants, corticosteroids, or antidepressants. Patients with hypogonadism or infertility were excluded from the study. Results: The study showed an association between bioT concentrations and Cu concentrations in both patients with and without erectile dysfunction. A correlation between bioactive testosterone and Cr concentrations was also observed in both groups. Patients with erectile dysfunction showed a relationship between bioT concentration and Zn concentration, TT concentration and Mn concentration, FT concentration and Zn concentration, and E2 concentration and Cr concentration. An analysis of elemental concentrations in bone tissue showed an association between FT and Mg and Mn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between FT and Cu concentrations. A correlation was also observed between bioT concentrations and Mg, Mn, and Zn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between bioT and Cu concentrations. Conclusions: Studying the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men may be important in explaining the etiology of the problem. The study of the concentration of Zn and Cu in bone tissue and serum showed that these two elements, regardless of the place of accumulation, may be related to the concentration of androgens in men. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the utility of pretreatment DKI parameters and serum SCC-Ag in evaluating the early therapeutic response of cervical cancer to radiotherapy. Materials and methods: A total of 33 patients diagnosed with cervical cancer, including 31 cases of cervical squamous cell carcinoma and two cases of adenosquamous carcinoma, participated in the study. All patients underwent conventional MRI and DKI scans on a 3T magnetic resonance scanner before radiotherapy and after ten sessions of radiotherapy. The therapeutic response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were categorized into a response group (RG), comprising Complete Remission (CR) and Partial Remission (PR), and a non-response group (NRG), comprising Stable Disease (SD) and Progressive Disease (PD). LASSO was employed to select pretreatment DKI parameters, and ROC curves were generated for the selected parameters and serum SCC-Ag. Results: Significant differences were observed in pretreatment MD, Da, Dr, MK, Ka, Kr, and SCC-Ag between the RG and NRG groups (P < 0.01). However, no significant differences were noted for FA and FAK (P = 0.441&0.928). The two selected parameters (MD and MK) demonstrated area under the curve (AUC), sensitivity, and specificity of 0.810, 0.769, 0.850 and 0.827, 0.846, 0.750, respectively. The combination of MD and MK exhibited an improved AUC of 0.901, sensitivity of 0.692, and specificity of 1.000, with a higher Youden index compared to the individual parameters. Conversely, the AUC, sensitivity, and specificity of the combination of MD, MK, and SCC-Ag were 0.852, 0.615, and 1.000, with a Youden index of 0.615. Conclusion: Pretreatment MD, MK, and SCC-Ag demonstrate potential clinical utility, with the combined application of MD and MK showing enhanced efficacy in assessing the early therapeutic response of cervical cancer to radiotherapy. The addition of SCC-Ag did not contribute further to the assessment efficacy. [ABSTRACT FROM AUTHOR]

Background: The study aimed to evaluate the immunological response of layer chickens to live Newcastle disease virus vaccine using a newly developed vaccine schedule administered via the ocular route, as well as assess the persistence of passive antibodies in layer chickens and the effectiveness of protection against strains of the virus. Methods: A total of 140‐day‐old Lohmann Brown chicks were randomly divided into seven groups, 20 chicks each. Groups 1–3 received a single eye instillation of the vaccine at ages 5, 26 and 54 days, respectively, whereas groups 4–6 received a double eye instillation. Group 7 served as non‐vaccinated control group. Ten days after immunization, samples were taken from hens that had received the vaccine at ages 15, 36 and 64, as well as from control chickens that had not received the vaccine at ages 5, 15, 21 and 31. Results: A total of 10 serum samples from all chickens exhibited protective antibodies, and booster doses resulted in the highest haemagglutination inhibition titre. No significant change in antibody production was observed among layer hens (p > 0.05). The study found that the La Sota (GMT ± SD: 6.71 ± 4.96), La Sota (GMT ± SD: 8.00 ± 0.00) and thermostable I2 (GMT ± SD: 7.60 ± 6.02), vaccination schedules provided the maximum immune response in single eye instillation, whereas the HB1 (GMT ± SD: 7.11 ± 4.77), La Sota (GMT ± SD: 7.83 ± 5.76) and La Sota (GMT ± SD: 7.60 ± 6.02), combination was the second‐best vaccination schedule in double eye instillation. Furthermore, maternally‐derived antibodies were maintained up to 31 days of age, indicating the level of passive immunity prior to vaccination. Characteristic lesions, such as edematous and diphtheria mucosal membranes of the trachea, along with petechial and necrotic haemorrhages of the proventriculus, were observed during the necropsy of the birds that died from the challenged virus. Conclusion: This study suggests that subsequent live virus vaccine by ocular route immunization is required to effectively protect against velogenic viscerotropic Newcastle disease infection. The results also highlight the importance of developing effective vaccination schedules and routes to enhance immunity against ND in layer chickens. [ABSTRACT FROM AUTHOR]

Context: Timely pregnancy diagnosis is critical for reducing non-production days and improving the reproductive efficiency of sheep flocks. Aims: The aim of this study was to investigate the serum proteomic profile of ewes in different gestational stages and explore the potential of differentially expressed proteins as biomarkers for early gestation. Methods: Serum samples were collected from two groups: pregnant sheep (n = 4) and non-pregnant sheep (n = 4) on Day 14 after mating. The differentially expressed proteins were detected using tandem mass-tag (TMT) labelling with liquid chromatography tandem-mass spectrometry. The differentially expressed proteins were confirmed using enzyme-linked immunosorbent assay (ELISA). Furthermore, six selected proteins were evaluated in ewes (n = 35) on Day 14 from mating by using ELISA to assess their potential as biomarkers for early pregnancy. Receiver-operating characteristic (ROC) curves were used to analyse the diagnostic accuracy of these proteins. Key results: Twenty proteins, of a total of 555 proteins detected, showed differential expression between pregnant and non-pregnant sheep. From the ROC-curve data, CHI3L1 (AUC = 0.992), PSMB4 (AUC = 0.976) and LGALS3BP (AUC = 0.844) had high predictive value in the diagnosis of early pregnancy. Conclusions: In this study, CHI3L1, PSMB4 and LGALS3BP were found to be differentially expressed proteins in the serum of pregnant sheep. Therefore, these three proteins carry a high probability as candidate biomarkers for early gestational embryo attachment in ewes. Implications: Early pregnancy diagnosis enables timely identification of non-pregnant ewes, resulting in optimised resource allocation and enhanced economic benefits for farmers by reducing production costs. The present study enables to advance the diagnosis of pregnancy in ewes to the first oestrous period after breeding. The differentially expressed protein in serum was found to be a highly specific and sensitive biomarker for early pregnancy diagnosis in ewes. Its application in production can reduce the number of days of mating loss in ewes, reduce production costs and improve economic efficiency. [ABSTRACT FROM AUTHOR]

Background: Serum copper and zinc are measured to assess deficiency and toxicity. Atomic absorption spectrophotometry and mass spectrometry methods are expensive and require highly trained staff. Colorimetric assays are available from Randox which are inexpensive and can be automated. We validated serum copper and zinc colorimetric assays on the Binding Site Optilite analyser including comparison with flame atomic absorption spectrophotometry (FAAS) and inductively coupled plasma-mass spectrometry (ICP-MS). Methods: Accuracy, imprecision, lower limit of quantitation, and linearity were ascertained. The impact of triglycerides, bilirubin, nickel, and iron on assay performance was also investigated. Comparison of results from colorimetric analysis of patient and external quality assurance samples with those obtained by FAAS and ICP-MS was undertaken. Results: Intra-, and inter-assay imprecision was <9%. Serum copper and zinc assays were linear between 1.8–35.6 and 2.3–45.7 µmol/L, respectively. Agreement was good between colorimetry and FAAS (intercept = -0.7, slope = 1.04) and ICP-MS (intercept = 0.6, slope = 0.99) for serum copper in patients' samples. For serum zinc, agreement was poor between colorimetry and FAAS (intercept = 2.2, slope = 0.87) and ICP-MS (intercept = 1.9, slope = 0.98) in patients' samples. There was a poor concordance in assessment of hypozincaemia between colorimetry and FAAS/ICP-MS. Conclusion: The Randox colorimetric assay for serum copper on the Optilite is simple to perform, has a short analysis time, and measured concentrations compare well with FAAS and ICP-MS. Due to poor agreement with FAAS and ICP-MS, colorimetry is not suitable for the measurement of serum zinc. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effect of Alfalfa polysaccharide (APS) on the growth performance and immune responses of broilers. A total of 400 1-day-old Avian broiler chicks were randomly divided into four treatment groups and administered intranasal with different levels of APS (0, 2.5, 5.0 or 10.0 mg/dose) on day 1 and day 14. Growth performance, phagocytic activity, T lymphocyte transformation, and serum antibody titers against the Newcastle disease virus (NDV) vaccine were examined. During the study period of 42 days, no significant differences were observed in food intake among treatment groups (P>0.05). The APS administered groups displayed a low FCR, especially the 2.5 mg groups (P<0.05). Broilers with 2.5 mg APS displayed a much higher phagocytic activity than the control group (P<0.05). At the same time, APS enhanced the T lymphocyte transformation in response to phytohaemagglutinin (PHA). The antibody titer to NDV was not influenced by APS on day 14, while it improved on day 28 and day 42, especially in the 2.5 mg group (P<0.05). And the above data suggest that APS could improve innate and cellular immune responses in broilers. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints. Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre‐ and post‐treatment from the Trial of Anti–B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class‐switched memory B cells within the SG. Furthermore, rituximab significantly down‐regulated genes involved in immune‐cell recruitment, lymphoid organization alongside antigen presentation, and T cell co‐stimulatory pathways. In the peripheral compartment, rituximab down‐regulated immunoglobulins and auto‐antibodies together with pro‐inflammatory cytokines and chemokines. Interestingly, patients classified as responders according to STAR displayed significantly higher baseline levels of C‐X‐C motif chemokine ligand‐13 (CXCL13), interleukin (IL)‐22, IL‐17A, IL‐17F, and tumor necrosis factor‐α (TNF‐α), whereas a longitudinal analysis of serum T cell–related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS‐responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ‐receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. Conclusion: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate inflammatory responses to lipopolysaccharide (LPS) injection in layers. ANIMALS 33 40-week-old laying hens were used. METHODS 30 laying hens were divided into 2 groups: the first group was injected with 8 mg/kg LPS, while the second group was injected with sterile saline. At the start of the study, 3 birds served as a baseline and were used as the time 0 controls for both the saline and LPS-treated groups. Blood and spleen tissues were collected at 0 (before) and 1, 2, 3, 4, and 6 hours after injection. RESULTS LPS administration increased splenic mRNA levels of IL-1β, IL-2, IL-6, IL-8, IL-10, interferon-γ, and tumor necrosis factor-α (P < .001) and serum IL-6 levels (P < .01) compared to saline injection. The mRNA expression of most cytokine genes increased rapidly toward peak values within 2 hours after the LPS injection, and then the difference between the saline and LPS treatments got smaller as time went on; serum IL-6 reached its highest concentration 2 hours after LPS administration. The magnitude of LPS-induced upregulation of gene expression was the highest for IL-6, followed by IL-1β and IL-8, and tumor necrosis factor-α was the least affected. CLINICAL RELEVANCE The temporal and quantitative profile of these inflammatory mediators generated from this study provides valuable information in identifying the optimal time window and appropriate biomarkers for LPS-induced inflammation, which has significant implications in evaluating the effects of interventions on the immune system of chickens. [ABSTRACT FROM AUTHOR]

Aminophylline (AMP) is a bronchodilator. The therapeutic and toxic doses are very close. Therefore, therapeutic drug monitoring (TDM) of AMP is essential in clinical practice. Microgels were synthesized by free radical precipitation polymerization. Silver@poly(N -isopropyl acrylamide) (Ag@PNIPAM) hybrid microgels were obtained by loading silver (Ag) nanoparticles into the three-dimensional network of the microgels by in situ reduction. The microgel is a three-dimensional reticular structure with tunable pore size, large specific surface area, and good biocompatibility, which can be used as a sorbent for solid-phase extraction (SPE) of target molecules in complex matrices and as a surface-enhanced Raman spectroscopy (SERS) substrate. We optimized the conditions affecting SERS enhancement, such as silver nitrate (AgNO3) concentration and SPE time, according to the SERS strategy of Ag@PNIPAM hybrid microgels to achieve label-free TDM for trace AMP in human serum. The results showed good linearity between the logarithmic concentration of AMP and its SERS intensity in the range of 1–1.1 × 102 µg/mL, with a correlation coefficient (R 2) of 0.9947 and a low detection limit of 0.61 µg/mL. The assay accuracy was demonstrated by spiking experiments, with recoveries ranging from 93.0 to 101.8%. The method is rapid, sensitive, reproducible, requires simple sample pretreatment, and has good potential for use in clinical treatment drug monitoring. [ABSTRACT FROM AUTHOR]

Thymic epithelial tumors (TET) patients are at high risk of autoimmune and hypoimmune complications. Limited evidence is available on the potential risk of immune-related and inflammatory reactions induced by SARS-Cov-2 vaccine in this patient population. In order to identify subjects at higher risk for vaccine complications, we prospectively evaluated a panel of serum biomarkers related to inflammation (TNF-α, IL-1β, −6, −10, −12, and −17A, IFN-α, β and γ, MPO, MMP-9), and vascular damage (E- and P-selectin, VEGF-A, P-ANCA and MCP-1) in 44 TET patients and in 30 healthy controls along the whole SARS-Cov-2 vaccine cycle. About 50 % of subjects (either TET and controls) showed an increase of serum biochemical markers of inflammation and endothelial damage with a large heterogeneity of values. Such increase appeared early, after the first dose in control subjects and later, after the second dose in TET patients (in which we observed mainly an increase of inflammatory biomarkers). The values normalized after about 3 months and did not increase after the third, booster dose. No autoimmune or vascular complications were observed in the study subjects and no difference was observed in terms of vaccine response among subjects showing serum biomarkers increase and those who experienced no changes. Our data highlight the relevance of Sars-Cov-2 vaccine in TET patients, as it resulted safe and prevented severe COVID-19. However, further studies are awaited to explore the mechanisms and the potential consequences of the observed increase of serum inflammatory and vascular damage biomarkers. [ABSTRACT FROM AUTHOR]

The standardization of cystatin C (CysC) measurement has received increasing attention in recent years due to its importance in estimating glomerular filtration rate (GFR). Mass spectrometry-based assays have the potential to provide an accuracy base for CysC measurement. However, a precise, accurate and sustainable LC–MS/MS method for CysC is still lacking. The developed LC–MS/MS method quantified CysC by detecting signature peptide (T3) obtained from tryptic digestion. Stable isotope labeled T3 peptide (SIL-T3) was spiked to control matrix effects and errors caused by liquid handling. The protein denaturation, reduction and alkylation procedures were combined into a single step with incubation time of 1 h, and the digestion lasted for 3.5 h. In the method validation, digestion time-course, imprecision, accuracy, matrix effect, interference, limit of quantification (LOQ), carryover, linearity, and the comparability to two routine immunoassays were evaluated. No significant matrix effect or interference was observed with the CysC measurement. The LOQ was 0.21 mg/L; the within-run and total imprecision were 1.33–2.05 % and 2.18–3.90 % for three serum pools (1.18–5.34 mg/L). The LC–MS/MS method was calibrated by ERM-DA471/IFCC and showed good correlation with two immunoassays traceable to ERM-DA471/IFCC. However, significant bias was observed for immunoassays against the LC–MS/MS method. The developed LC–MS/MS method is robust and simpler and holds the promise to provide an accuracy base for routine immunoassays, which will promote the standardization of CysC measurement. [ABSTRACT FROM AUTHOR]

Aims: Dolutegravir increases serum creatinine by inhibiting its renal tubular secretion and elimination. We investigated determinants of early changes in serum creatinine in a southern African cohort starting first‐line dolutegravir‐based antiretroviral therapy (ART). Methods: We conducted a secondary analysis of data from participants in a randomized controlled trial of dolutegravir, emtricitabine and tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF) (ADVANCE, NCT03122262). We assessed clinical, pharmacokinetic and genetic factors associated with change in serum creatinine from baseline to Week 4 using linear regression models adjusted for age, sex, baseline serum creatinine, HIV‐1 RNA concentration, CD4 T‐cell count, total body weight and co‐trimoxazole use. Results: We included 689 participants, of whom 470 had pharmacokinetic data and 315 had genetic data. Mean change in serum creatinine was 11.3 (SD 9.9) μmol.L−1. Factors that were positively associated with change in serum creatinine at Week 4 were increased log dolutegravir area under the 24‐h concentration–time curve (change in creatinine coefficient [β] = 2.78 μmol.L−1 [95% confidence interval (CI) 0.54, 5.01]), TDF use (β = 2.30 [0.53, 4.06]), male sex (β = 5.20 [2.92, 7.48]), baseline serum creatinine (β = −0.22 [−0.31, −0.12]) and UGT1A1 rs929596 A→G polymorphism with a dominant model (β = −2.33 [−4.49, −0.17]). The latter did not withstand correction for multiple testing. Conclusions: Multiple clinical and pharmacokinetic factors were associated with early change in serum creatinine in individuals initiating dolutegravir‐based ART. UGT1A1 polymorphisms may play a role, but further research on genetic determinants is needed. [ABSTRACT FROM AUTHOR]

Objective: We investigated the correlation between serum C1q/TNF-related protein 4 (CTRP4) level and flow-mediated dilation (FMD) in patients with type 2 diabetes mellitus (T2DM), and evaluated the biological effects of CTRP4 on human umbilical vein endothelial cells (HUVECs). Methods: A group of 165 patients diagnosed with T2DM were included in this study. Endothelial function was measured with the examination of brachial artery FMD. ELISA kit was used to measure the levels of CTRP4 in serum. HUVECs were stimulated with recombinant CTRP4 protein to assess its biological functions. Results: The levels of CTRP4 showed a significant variation among three groups based on FMD tertiles (p = 0.001). What's more, FMD had a significant difference among three CTRP4 tertile groups (p < 0.05) and was negatively related to serum CTRP4 levels (r = −0.270, p < 0.001). In T2DM patients, logistic regression analysis demonstrated that CTRP4 was the primary influence factor of low FMD (p < 0.01). In receiver operating characteristic curve analysis, the area under the curve of CTRP4 for predicting low FMD was 0.66 (95%CI 0.58–0.75). When stimulated HUVECs with recombinant CTRP4 protein, we found that CTRP4 could concentration-dependently ameliorate proliferation and migration of HUVECs in wounding healing and transwell assay. This protein could also decrease the expression of IL-6 and TNF-α and promote the release of NO in HUVEC supernatants, with suppression of NF-κB and STAT3 phosphorylation. Conclusions: Serum CTRP4 concentrations were negatively associated with FMD. CTRP4 alleviated proliferation, migration and inflammation in HUVECs through the suppression of NF-κB and STAT3 signaling pathways. [ABSTRACT FROM AUTHOR]

Rimegepant is a calcitonin gene‐related peptide receptor antagonist approved for migraine treatment. This phase 1, open‐label, single‐center, fixed‐sequence study evaluated the effect of rimegepant on the pharmacokinetics (PK) of metformin. Twenty‐eight healthy participants received metformin 500 mg twice daily from Days 1 to 4 and Days 7 to 10, and once daily on Days 5 and 11. Rimegepant, 75 mg tablet, was administered once daily from Days 9 to 12. At pre‐specified time points, plasma metformin concentration, serum glucose levels, and safety and tolerability were evaluated. A 16% increase in the area under the plasma metformin concentration‐time curve (AUC) for 1 dosing interval (AUC0‐τ,ss), a statistically insignificant increase in maximum and minimum steady‐state metformin concentration (Cmax,ss and Cmin,ss), and a decrease in metformin renal clearance were observed on Day 11 following metformin‐rimegepant coadministration compared with metformin alone; however, the changes were not clinically relevant. Additionally, coadministration of rimegepant with metformin did not induce clinically meaningful change in the maximum observed glucose concentration (Gmax) or AUCgluc compared with metformin alone. Overall, rimegepant and metformin coadministration did not result in clinically relevant changes in metformin PK, renal clearance, or the antihyperglycemic effects of metformin. Rimegepant is considered safe for use with metformin. [ABSTRACT FROM AUTHOR]

This study intended to investigate the impact of long‐term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)‐infected patients with low‐risk of kidney injury. The observational study involving 100 HIV‐infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine β2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood β2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood β2 microglobulin was statistically significant at month 6 and months 12‐30 (P <.05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine β2 microglobulin fluctuated from 0.5 (0.3‐1.1) to 0.8 (0.5‐1.35) mg/L at months 18‐30, which was higher than 0.41 (0.18‐1.1) mg/L at month 0 (P <.05). The abnormal concentration proportion of urine β2 microglobulin fluctuated from 72.7% to 81.3% at months 18‐30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood β2 microglobulin, urine β2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = −0.008, r3 = −0.165, P >.05). Long‐term TDF antiviral regimen in low‐risk of kidney injury HIV‐infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine β2 microglobulin levels may be helpful in screening for renal dysfunction. [ABSTRACT FROM AUTHOR]

PF‐06817024 is a high affinity, humanized antibody that binds interleukin‐33, a proinflammatory type 2 cytokine, and thereby has the potential to inhibit downstream type 2 inflammation. This Phase 1, randomized, placebo‐controlled study was conducted in 3 parts to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics of escalating single and limited repeat PF‐06817024 doses in healthy participants (Part 1), a single dose of PF‐06817024 in participants with chronic rhinosinusitis with nasal polyps (Part 2), and repeat doses of PF‐06817024 in participants with moderate to severe atopic dermatitis (atoptic dermatitis; Part 3). PF‐06817024 was generally well tolerated in all participant populations. Most participants experienced a treatment‐emergent adverse event (healthy participants, 78.4% and 100%; participants with chronic rhinosinusitis with nasal polyps, 90.9% and 88.9%; and participants with atoptic dermatitis, 60.0% and 62.5% in the PF‐06817024 and placebo groups, respectively). No substantial deviations from dose proportionality were observed for single intravenous doses of 10‐1000 mg, indicating linear PK in healthy participants. Mean terminal half‐life ranged from 83 to 94 days after single intravenous administration in healthy participants and was similar to that observed after administration in the studied patient populations. Incidences of antidrug antibodies in the studied populations were 10.8%, 9.1%, and 5.0% for healthy participants, participants with chronic rhinosinusitis with nasal polyps, and participants with atoptic dermatitis, respectively. In addition, dose‐dependent increases were observed in total serum interleukin‐33 levels of treated participants, indicating target engagement. Overall, the PK and safety profile of PF‐06817024 supports further investigation of the drug as a potential treatment for allergic diseases. [ABSTRACT FROM AUTHOR]

To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively. We performed a nationwide population-based matched cohort study (Denmark, 1993–2021). We included 52 200 Bb-seropositive individuals (stratified as only Bb- IgM-seropositive [ n = 26 103], only Bb- IgG-seropositive [ n = 18 698], and Bb- IgM-and-IgG-seropositive [ n = 7399]) and two age- and sex-matched comparison cohorts: 104 400 Bb-seronegative individuals and 261 000 population controls. We investigated the risk associated with being tested for serum Bb antibodies and being Bb seropositive. Outcomes were atrioventricular block and other conduction disorders. We calculated short-term odds ratios (aOR) (within 1 month), and long-term hazard ratios (aHR) (after 1 month) adjusted for age, sex, diabetes, chronic heart failure, and kidney disease with 95% CI. Compared with population controls, individuals tested for Bb antibodies had increased short- and long-term risks of atrioventricular block (aOR 47.9, 95% CI: 30.0–76.7, aHR 1.3, 95% CI:1.2–1.3), and other conduction disorders (aOR 18.2, 95% CI: 10.1–32.8, aHR 1.2, 95% CI: 1.1–1.4). Compared with Bb -seronegative individuals, only Bb- IgM-and-IgG-seropositive individuals had increased short-term risk of atrioventricular block (aOR: 2.1, 95% CI: 1.5–3.1). The results suggest that Bb antibody testing is included in the diagnostic work-up of conduction disorders. Finally, that Bb seropositivity is not associated with other conduction disorders than atrioventricular block or with increased long-term risk of conduction disorders. [ABSTRACT FROM AUTHOR]

There are estimated 300 million people afflicted with chronic hepatitis B (CHB) worldwide. The risk of liver cirrhosis and hepatocellular carcinoma (HCC) increases considerably with chronic hepatitis B infection. While current therapeutics are effective in controlling hepatitis B virus (HBV) infection and disease progression, a cure for HBV infection remains unattainable due to an intranuclear replicative intermediate known as covalently closed circular DNA (cccDNA). It has recently been shown that serum HBV RNA is a non‐invasive biomarker that reflects cccDNA transcriptional activity. This review provides a comprehensive overview and the latest updates on the molecular characteristics and clinical significance of serum HBV RNA, such as species of serum HBV RNA, forms of serum HBV RNA carriers and predictive value for relapses in CHB patients after nucleos(t)ide analogues (NAs) discontinuation and development of liver fibrosis and HCC. Furthermore, we summarize standardized assays for testing serum HBV RNA, the dynamic changes of serum HBV RNA levels in treatment‐naïve CHB patients and those under NAs therapy, as well as the host and viral influencing factors of serum HBV RNA levels. Finally, we discuss the future perspectives in studies of serum HBV RNA. [ABSTRACT FROM AUTHOR]

• Twenty-one PFASs levels in human serum, blood and urine of patients with liver diseases were analyzed. • Higher total PFAS concentrations were detected in hepatocellular carcinoma (HCC) patients than in non-HCC patients. • Significant correlation between PFAS concentrations in patients and their demographic characteristics (including gender, age, and BMI) were found. • Serum PFNA and PFBS concentrations were associated with elevated liver function biomarkers ALP and GGT. Studies have shown that per- and polyfluoroalkyl substances (PFASs) may be hepatotoxic in animals or humans. However, data on clinical epidemiology are very limited. In this study, 21 PFASs were determined in patients with liver diseases, with the highest median concentrations detected in the serum sample (26.7 ng/mL), followed by blood (10.7 ng/mL) and urine (5.02 ng/mL). Higher total PFAS concentrations were found in hepatocellular carcinoma (HCC) patients compared to non-HCC patients, with significant discrepancies in serum and blood samples. Besides, significant correlations were also found among PFAS concentrations and age, gender, body mass index (BMI), and liver function biomarkers levels. For example, PFAS concentrations are significantly higher in males than in females; Several serum PFASs concentrations increase with age and BMI, while the serum perfluorohexane sulfonic acid (PFHxS) concentrations are negatively correlated with age. In addition, multiple regression models adjusted for age, gender and BMI found that increased serum perfluorobutane sulfonic acid (PFBS), perfluoroheptane sulfonic acid (PFHpS) and perfluorohexylphosphonic acid (PFHxPA) conentrations are correlated with elevated alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP) (p < 0.05). Our results provide epidemiological support for the future study on the potential clinical hepatotoxicity of PFAS. [Display omitted] [ABSTRACT FROM AUTHOR]

Bovine tuberculosis is usually diagnosed using tuberculin skin tests or at post-mortem. Recently, we have developed a serological test for bovine tuberculosis in cattle which shows a high degree of accuracy using serum samples. Here, we have assessed the performance of the test using individual bovine milk samples. The diagnostic specificity estimate using the high sensitivity setting of the test was 99.7% (95% CI: 99.2–99.9). This estimate was not altered significantly by tuberculin boosting. The relative sensitivity estimates of the test using the high sensitivity setting in milk samples from comparative skin test positive animals was 90.8% (95% CI: 87.1–93.6) with boosting. In animals with lesions, the relative sensitivity was 96.0% (95% CI: 89.6–98.7). Analysis of paired serum and milk samples from skin test positive animals showed correlation coefficients ranging from 0.756–0.955 for individual antigens used in the test. Kappa analysis indicated almost perfect agreement between serum and milk results, while McNemar marginal homogeneity analysis showed no statistically significant differences between the two media. The positive and negative likelihood ratio were 347.8 (95% CI: 112.3–1077.5) and 0.092 (95% CI: 0.07–0.13) respectively for boosted samples from skin test positive animals. The results show that the test has high sensitivity and specificity in individual milk samples and thus milk samples could be used for the diagnosis of bovine tuberculosis. [ABSTRACT FROM AUTHOR]

Pneumococcal carriage is the primary reservoir for transmission and a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage. We vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA). PCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not. This study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection. [ABSTRACT FROM AUTHOR]