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Many questions remain about the prevalence and effects of SARS-CoV-2 infection in malaria-endemic African countries like Uganda, particularly in vulnerable groups such as pregnant women. We describe SARS-CoV-2 immunoglobulin (Ig)G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. From December 2020-February 2022, among 400 unvaccinated pregnant women enrolled at 12-20 weeks gestation and followed through delivery, 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time, consistent with affinity maturation of the antibody response in the cohort. No women experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infect (-1.54 versus -0.37 and -0.51, P = 0.009). These findings suggest that pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with transient shorter stature in early infancy. Further research should explore the significance of this finding and define targeted measures to prevent infection in pregnancy.

Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDCs LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance.

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5-19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10-20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

The rapid spread of SARS-CoV-2 caused the COVID-19 pandemic and accelerated vaccine development to prevent the spread of the virus and control the disease. Given the sustained high infectivity and evolution of SARS-CoV-2, there is an ongoing interest in developing COVID-19 serology tests to monitor population-level immunity. To address this critical need, we designed a paper-based multiplexed vertical flow assay (xVFA) using five structural proteins of SARS-CoV-2, detecting IgG and IgM antibodies to monitor changes in COVID-19 immunity levels. Our platform not only tracked longitudinal immunity levels but also categorized COVID-19 immunity into three groups: protected, unprotected, and infected, based on the levels of IgG and IgM antibodies. We operated two xVFAs in parallel to detect IgG and IgM antibodies using a total of 40 μL of human serum sample in

Introduction: Activation‐induced cytidine deaminase (AID) deficiency is a rare autosomal recessive inborn error of immunity (IEI) characterized by increased susceptibility to infections, autoimmunity, and/or autoinflammation. AID plays an important role in immunoglobulin class switching and somatic hypermutation. AID deficiency patients have very low or absent levels of IgG, IgA, and IgE, while IgM level is elevated. The disease is designated as type 2 hyperimmunoglobulin M syndrome (HIGM‐2). To date, around 130 patients with HIGM‐2 have been reported, none from Egypt. Methods: Four patients from three different consanguineous families with elevated serum IgM and low IgG and IgA were included in the study. After the exclusion of CD40 and/or CD40L deficiency by flow cytometry, patients' samples were tested by a panel covering 452 genes (four bases PID‐Pro) on the Illumina Miseq platform. Results: All patients suffered repeated infections since childhood. Patients 1–3 had inflammatory bowel disease‐like (IBD‐like) symptoms, while patient 4 did not have autoimmune manifestations. Patient 1 is the first HIGM‐2 patient to be reported to have renal amyloidosis as part of the autoinflammation. Patients 1–3 had the same pathogenic variant (NM_020661.4 (AID):c.406del, p.Ile136Ter), while patient 4 had another pathogenic variant (NM_020661.4 (AID):c.374G > A, p.Gly125Glu). The variant p.Ile136Ter was not reported before in any of the documented HIGM‐2 patients. Conclusion: HIGM‐2 is a rare IEI that can be overlooked; hence, patients' diagnosis is delayed. Autoimmune and autoinflammatory manifestations develop later in the disease course leading to significant morbidities. The diagnosis can be suspected after exclusion of CD40/CD40L deficiencies by flow cytometry, and the diagnosis can be confirmed by genetic testing. [ABSTRACT FROM AUTHOR]

Background: A strong association between multiple sclerosis (MS) and Epstein-Barr virus (EBV) has been established but the exact role of EBV in MS remains controversial. Recently, molecular mimicry between EBNA1 and specific GlialCAM, CRYAB and ANO2 peptides has been suggested as a possible pathophysiological mechanism. The aim of this study was to analyse anti-EBV antibodies in MS patients against (I) EBV lifecycle proteins, (II) putative cross-reactive peptides, and (III) during treatment. Methods: In this retrospective cross-sectional study, 258 serum samples were included consisting of EBV-negative (n = 25) and EBV-positive (n = 36) controls, 192 MS samples including untreated relapsing-remitting MS (RRMS) with and without relapses, secondary progressive MS (SPMS) and primary progressive MS (PPMS) patients, and 106 patients on 8 different treatment regimens. IgG and IgM antibody titers against EBV docking/fusion proteins (gp350, gh/gp42, gh/gL/gp42), immediate early antigen (BZLF1), early antigens (EA p85, EA P138, EA P54), capsid antigens (VCA P18, VCA P23, VCA gp125) and late antigens (EBNA1) were measured. Specific EBNA1 and GlialCAM, CRYAB and ANO2 peptides were synthesized and also incorporated in our custom magnetic bead based multiplex assay. Results: We observed significantly elevated IgG antibody titers in EBV-positive controls, RRMS with and without relapse, SPMS and PPMS patients for all lifecycle antigens except for several early antigens when compared to EBV-negative controls. Significantly higher IgG antibody titers were observed in RRMS patients for fusion proteins and EBNA1 peptides when compared to EBV-positive controls. An MS specific response was observed for ANO2 but not for GlialCAM or CRYAB. No significant treatment effects or a specific IgM response were detectable. Conclusion: The MS-specific, differential antibody response to EBV antigens confirms an altered immunological response to EBV in MS patients. EBV reactivation does not appear to play an important role in MS pathogenesis and no differential antibody signatures were observed between MS disease phases. The MS-specific anti-ANO2 antibody response suggests a potential role for EBNA1 as an antigenic driver, although the exact role of anti-ANO2 antibodies needs to be determined. The precise pathophysiological role of EBV in MS remains uncertain and requires further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Gynura procumbens (Lour.) Merr is a common traditional Chinese medicine with anti-tumor, anti-inflammatory and antioxidant activities. However, no related studies reported the potential application effect of Gynura procumbens on meat ducks. The study aims to investigate the potential effects of Gynura procumbens extract (GPE) supplementation on growth performance, carcass traits, antioxidant capacity, immunity and meat quality. Methods: A total of 480 21-day-old female healthy ducks were randomly allocated to four treatments, each treatment containing six replicates with 20 ducks per replicate. The groups received a corn-soybean basal diet supplemented with 0 mg/kg GPE (CON), 200 mg/kg GPE (GPE200), 400 mg/kg GPE (GPE400), and 600 mg/kg GPE (GPE600), respectively. The entire experiment lasted for 7 weeks. Results: The results showed that dietary supplementation with 600 mg/kg GPE significantly reduced the contents of serum urea nitrogen, triglyceride (TG) and total cholesterol (TC). GPE (200, 400, and 600 mg/kg) supplementation effectively reduced the contents of IL-2 and MDA. The levels of immunoglobulin M (IgM) as well as total antioxidative capacity (T-AOC) in GPE600 group dramatically elevated in comparison with the control group. Dietary GPE supplementation considerably increased the moisture content of the breast muscle. Furthermore, dietary supplementation with GPE markedly decreased the water loss rate and shear force. Discussion: With the ban of antibiotics in poultry production, traditional Chinese medicines have been widely used in livestock and poultry production due to their high efficiency and low toxicity. Gynura procumbens extract GPE as a natural plant origin contains a series of biologically active components, including flavonoids, polyphenols, saponin, tannin and terpenoid. This study indicated that dietary supplementation with GPE can increase serum total antioxidant capacity, regulate immune function and improve meat quality to some extent in meat ducks. The recommended optimal GPE level in the diet of meat ducks is 600 mg/kg according to the results in this study. [ABSTRACT FROM AUTHOR]

In this study, the effects of using the distiller's dried grains with solubles (DDGS) instead of soybean meal on rainbow trout (Oncorhynchus mykiss) were investigated. Four different experimental diets were prepared with isonitrogenous (43%) and isolipidic (19%) values, incorporating DDGS at levels of 0%, 10%, 20%, and 30%. Fish were weighed (18.5–20.2 g) and randomly distributed in 12 tanks (140 L water) with 22 fish in each tank. The feeding trial lasted 60 days and was conducted in triplicate. The best weight gain (WG), specific growth rate (SGR), and feed conversion ratio (FCR) were observed in the DDGS20 experimental group. While viscerosomatic index (VSI) and hepatosomatic index (HSI) values were found to be the highest in the DDGS30 experimental group, the spleen‐somatic index (SSI) was found to be the highest in the DDGS10 experimental group (p < 0.05). It was found that the nutrient digestibility ratio values and fish meat chemical composition values of the experimental diets were similar between the groups (p > 0.05). Additionally, it was analyzed that the use of DDGS protein sources in diets did not negatively affect the coloration of the experimental fish. While DDGS percentage increased in the diet, hepatocyte nucleus diameter was decreasing (p < 0.05). In the distal intestine, the DDGS10 and DDGS20 groups gave results that are more likely to be digestible, which depends on villi length. The results of the DDGS30 groups had no negative effects on both liver and distal intestine. The genes interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 8 (IL-8), and superoxide dismutase 2 (SOD2) exhibited higher fold changes when DDGS2 contribution was present in the liver, whereas the interleukin 1 beta (IL-1β) gene exhibited lower fold change. Furthermore, the mean fold changes increased with the proportion of the DDGS additive in the immunoglobulin M (IgM) heavy chain and immunoglobulin T (IgT) genes but decreased in the catalase (CAT) and glutathione peroxidase 1 (GPX1) genes. TNF-α and SOD2 genes showed the lowest fold changes in the head kidney in the presence of DDGS20, whereas IL-1β and GPX1 genes exhibited the highest fold changes in the presence of DDGS10. Moreover, the utilization of feed additives extracted from DDGS in feed formulations resulted in cost reductions, thereby positively influencing the production cost per kilogram of feed. Among the trials, the incorporation of DDGS20 had the most beneficial impact on the cost per kilogram of fish due to its comparatively lower cost. [ABSTRACT FROM AUTHOR]

Objective: COVID-19 has evolved into a seasonal coronavirus disease, characterized by prolonged infection duration and repeated infections, significantly increasing the risk of patients developing long COVID. Our research focused on the immune responses in asymptomatic and mild cases, particularly the critical factors influencing serum immunoglobulin G (IgG) levels and their predictive value. Methods: We conducted a retrospective analysis on data from 1939 asymptomatic or mildly symptomatic COVID-19 patients hospitalized between September 2022 and June 2023. Spearman methods were used to test the correlation between serum IgG and age, immunoglobulin M (IgM), procalcitonin (PCT), interleukin-6 (IL-6), nucleic acid conversion time, and BMI. Univariate and multivariate logistic regression analyses identified independent key factors influencing serum IgG levels, which were integrated and visualized in a nomogram. Finally, receiver operating characteristic (ROC) curves were plotted to predict the model's diagnostic performance by calculating the AUC. Results: Mild patients showed higher levels of IgG, IgM, and longer nucleic acid conversion times than asymptomatic patients, and a lower proportion of them had received ≥ 3 COVID-19 vaccine doses. Serum IgG was positively correlated with serum IgM and negatively correlated with age, PCT, IL-6, and BMI. Notably, it showed a moderate negative correlation with nucleic acid conversion time (r = -0.578, P < 0.001). Logistic regression results showed that younger age, lower IL-6 levels, ≥ 3 doses of vaccine, and no comorbidities were independent predictors of serum IgG levels ≥ 21.08 g/L. We used age, IL-6 levels, vaccine doses, and comorbidities to create a nomogram for predicting serum IgG levels, with the area under the ROC curve reaching 0.772. Conclusion: Age, IL-6 levels, vaccination status, and comorbidities were independent predictors of serum IgG levels in asymptomatic or mild COVID-19 patients, facilitating risk stratification and clinical decision-making. Notably, receiving ≥3 doses of the COVID-19 vaccine was the most beneficial factor for elevated serum IgG levels. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the potential of substituting fishmeal with American cockroach residue in the feed of juvenile Cyprinus carpio. Replacing up to 40% of fishmeal with American cockroach residue significantly improved growth performance, antioxidant capacity, and immune function in juvenile C. carpio. However, replacing more than 40% of fishmeal may adversely affect intestinal health. Therefore, determining the optimal replacement ratio is essential for maximizing growth and well-being in juvenile C. carpio. Five isonitrogenous and isolipidic diets (Diet 1–Diet 5, with Diet 1 as the control) were formulated to replace 0%, 20%, 40%, 60%, and 80% of fishmeal with American cockroach residue. Juvenile Cyprinus carpio (initial body weight approximately 74 g) were randomly assigned to these diets for a 10-week feeding trial. The Diet 3 group (40% replacement) showed significantly higher final body weight, weight gain rate, specific growth rate, and protein efficiency ratio compared to other groups. No significant differences were observed in crude protein, ash, and total amino acid content across the diets. Groups fed Diet 1 and Diet 2 exhibited higher intestinal trypsin, lipase, α-amylase, and hepatic trypsin activities. Serum triglyceride (TG) levels were highest in the Diet 5 group. Hepatic aspartate aminotransferase (AST) activity was significantly lower in the Diet 3 and Diet 5 groups compared to Diet 1. Serum urea nitrogen levels followed a non-linear trend, initially increasing, then decreasing, and rising again with increasing fishmeal replacement. No significant differences were found in serum total protein (TP) levels among the dietary groups. Intestinal villus number, muscle layer thickness, villus height, villus width, and crypt depth remained consistent across groups. However, goblet cell numbers were significantly reduced at the 60% replacement level, which could impair intestinal barrier function. Diet 3 showed higher serum and hepatic total superoxide dismutase (T-SOD) activity, while Diet 2 had the highest hepatic total antioxidant capacity (T-AOC) activity. Hepatic malondialdehyde (MDA) levels were lowest in the Diet 2 and Diet 5 groups. Immunoglobulin M (IgM) levels showed an increasing trend with higher fishmeal replacement levels. In conclusion, replacing fishmeal with American cockroach residue did not adversely affect growth performance or body composition in juvenile C. carpio. Substituting 20–40% of fishmeal with American cockroach residue enhanced antioxidant capacity and immune function in juvenile C. carpio. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the therapeutic effects of berberine (BBR) on Salmonella enteritis in broiler chickens and to elucidate its mechanisms of action preliminarily. Blood samples were collected from 21- to 35-day-old Sanhuang male chicks to measure immune and biochemical indicators and to calculate the organ coefficients for the liver, spleen, bursa of Fabricius, and thymus. The caecal microbiota was analysed through 16S ribosomal RNA (rRNA) gene sequencing, and transcriptome sequencing was conducted. Compared with the positive control group (S), the berberine-treated group (BS) presented increased serum immunoglobulin M (IgM) levels, serum IgG levels, and total antioxidant capacity; berberine ameliorated the increase in the thymus index caused by Salmonella administration. The addition of berberine to the diet increased the abundance of beneficial bacterial genera, including Bacteroides and Lactobacillus. It also decreased the abundance of harmful bacterial genera, including Faecalibacterium and Streptococcus. Transcriptome analysis revealed that gene expression in the S and BS groups was associated with T cell selection and B cell receptor signalling pathways, which are enriched primarily in multiple immune-related signalling pathways, including the B cell receptor signalling pathway, NF- κ B signalling pathway, intestinal immune network for IgA production, asthma, and African trypanosomiasis. The significantly expressed genes included ATAD5, ERP29, MGST2, PIK3CA, and HSP90AA1. The present study demonstrated that berberine has a good therapeutic effect on Salmonella infection in chicks, as it inhibits the occurrence and development of Salmonella -induced intestinal inflammation by regulating the balance of the gut microbiota and the expression of related genes, including ATAD5, ERP29, MGST2, PIK3CA, and HSP90AA1. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus suis serotype (cps) 2 is an important bacterial pathogen in piglet nurseries and an emerging zoonotic agent without effective vaccines available. Immunoglobulin (Ig)M plays an essential role in host defense against S. suis. In mice, non-conventional B-1 cells are a major source of protective IgM against encapsulated bacterial pathogens, such as S. pneumoniae. Two IgM+CD21− B-1-like cell subpopulations, distinguishable by CD11R1 expression, were described in pigs, but their properties and functions are poorly understood. This study aimed at a first characterization of the porcine early IgM B cell response against S. suis cps 2. Methods: We analyzed the same healthy pigs, naturally colonized by different S. suis serotypes, including cps 2, at four and eight weeks of age serologically and determined the frequency of different peripheral B cell subpopulations by flow cytometry. Furthermore, we isolated conventional IgM+CD21+ B-2 cells as well as non-conventional B-1-like cell subpopulations from peripheral blood of eight-weeks-old pigs to evaluate their potential of IgM secretion in response to innate and adaptive stimuli in vitro. Results: Between the fourth and eighth week of life, a characteristic increase of S. suis cps 2-binding serum IgM antibodies, restricting bacterial growth, was observed. Moreover, we show for the first time that the significant increase of anti- S. suis serum IgM is associated with a relative increase of peripheral non-conventional IgM+CD21− B-1-like cells in vivo , particularly of the IgM+CD21− CD11R1− subpopulation. Noteworthy, sorted IgM+CD21− CD11R1− B-1-like cells from eight-weeks-old pigs spontaneously secreted IgM in vitro. In addition, both non-conventional IgM+CD21− B cell subpopulations, in contrast to conventional IgM+CD21+ B-2 cells, produced anti- S. suis IgM upon toll-like receptor (TLR) stimulation underlining their innate-like characteristics. We furthermore observed that both B-1-like subpopulations secrete S. suis cps 2-binding IgM upon stimulation with T cell-associated factors with highest amounts in IgM+CD21−CD11R1− B-1-like cells even exceeding anti- S. suis IgM levels produced by B-2 cells. Conclusion: Porcine non-conventional B-1-like cells are a potent source of S. suis -binding IgM indicating a role in immunity during a critical phase of piglet rearing. [ABSTRACT FROM AUTHOR]

Objective: Hashimoto's thyroiditis (HT) is a common autoantibodies condition that impact on the thyroid gland. In this disorder, several autoantibodies play an essential role in the dysfunction of the thyroid, including the metabolism of 1,25-dihydroxyvitamin D3 (1,25 VitD3)-XP, and leading to contributed to the development of related autoimmune diseases. The aim of current study to explore the important correlation between 1,25 VitD3 deficiency and specific types of autoantibodies in the patients. Materials and Methods: The current involved 150 male's patients, aged 25-50 years, who were compared with same numbers and aged of as healthy controls. Various biomarkers to thyroid gland were measured, including thyroid-stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3). In additionally, anti-thyroid peroxidase (TPO), thyroglobulin (TG), TSH receptor antibodies (TRAbs) and 1,25VitD3 were measured. These biomarkers were measured by the electrochemiluminescence immunoassay technique (ECL). Furthermore, the level of antibodies against VitD3, extractable nuclear antigens m immunoglobulin G4 related disease (IgG4-RD), and glycoprotein 120 were assessed by IDS-system. Results: This study indicated that blood group B was most commonly associated with HT. Moreover, the concentration of the 1,25 VitD3 was significantly lower in the patient group compared to the control, with level of 3.5 ± 0.1, 35.9 ± 0.3 ng/mL, respectively. Furthermore, an inverse positive correlation in the increased concentrations of TRAbs, TG, and TPO (r=-0.98, -0.66, -0.75) autoantibodies and the low levels of 1,25 VitD3 were detected. Likewise, a strong direct correlation (r=+0.98) was observed in the increased concentrations of both anti-TSH and anti-VitD3. Finally, IgG4-RD had a significantly positive association with the concentrations of 1,25 VitD3-XP, and TSH in patients with a highly significant difference (p<0.001). Conclusion: The findings suggested a significant positive correlation between increased levels of autoantibodies, antibody-related diseases, and low 1,25 VitD3 levels. [ABSTRACT FROM AUTHOR]

Background. Naturally occurring human antibodies against glycans recognize and quickly eliminate infectious bacteria, viruses and aberrantly glycosylated neoplastic malignant cells, and they often initiate processes that involve the complement system. Methods. Using a printed glycan array (PGA) containing 605 glycoligands (oligo- and polysaccharides, glycopeptides), we examined which of the glycan-binding antibodies are able to activate the complement system. Using this PGA, the specificities of antibodies of the IgM and IgG classes were determined in the blood serum of healthy donors (suggested as mostly natural), and, then, using the same array, it was determined which types of the bound immunoglobulins were also showing C3 deposition. Results. It was found that about 30% of anti-glycan antibodies in human serum detected by the PGA did not activate the complement. They were mostly IgGs and directed to bacterial O-antigens; no apparent common structural motif within their target polysaccharides was found. Antibodies to blood group systems ABO and Forssman, xeno-antigens, a number of polysaccharides from various strains of S. enterica, E. coli and P. alcalifaciens, as well as small fragments of bacterial polysaccharides were recognized by complement-activating antibodies as expected. A complement-activating antibody was affinity-isolated on glycan-Sepharose from human serum, and, in the presence of the complement, it lysed red blood cells coated with the same glycan (kodecytes, where glycans expressed on biological membranes), while an isolated complement non-activating antibody did not, which confirms the validity of the solid-phase PGA results. Conclusions. Thus, ~30% of human anti-glycan antibodies lack the ability to activate the complement system. The function of the widely represented immunoglobulins that do not cause C3 deposition remains unclear. [ABSTRACT FROM AUTHOR]

Renal involvement of primary biliary cholangitis (PBC) usually presents as distal renal tubular acidosis. Proximal tubular (PT) dysfunctions in PBC were rarely reported with unclear clinicopathological characteristics and renal prognosis. We identified 11 cases of PBC with PT dysfunctions (PBC-PT). Their medical document, kidney pathology, and follow-up data were retrospectively reviewed and analyzed. The 11 PBC-PT patients were mainly middle-aged (57.8 ± 5.2 years) females (81.8%). Most of them were asymptomatic PBC (7, 63.6%) with a high prevalence of elevated serum immunoglobulin M (IgM, 81.8%) and G (IgG, 54.5%) levels. In the kidney, they had a mean estimated glomerular filtration rate (eGFR) level of 46.54 ± 23.03 ml/min/1.73m2, and 81.8% of them had eGFR below 60 ml/min/1.73m2. They showed different degrees of PT dysfunctions, including hyperuricosuria, hypouricemia, normoglycemic glycosuria, generalized aminoaciduria, hyperphosphaturia, and hypophosphatemia. Their kidney pathology showed tubulointerstitial nephritis with lymphoplasmacytic infiltrates, brush border defects, and proximal tubulitis. After glucocorticoids treatment, the PT dysfunctions manifesting as hypophosphatemia, hypouricemia, and renal glycosuria all recovered, and the eGFR levels were improved from 43.24 ± 19.60 ml/min/1.73m2 to 55.02 ± 21.14 ml/min/1.73m2 (p = 0.028), accompanied by significant improvements of serum IgM levels (from 5.97 ± 4.55 g/L to 2.09 ± 1.48 g/L, p = 0.019). The PT dysfunctions were rare in PBC patients, and glucocorticoids treatment could benefit the improvements of eGFR and tubular functions. [ABSTRACT FROM AUTHOR]

Ocular toxoplasmosis is the most common cause of infectious retinochoroiditis in humans. Atypical and unilateral presentations such as papillitis without vitritis are especially challenging for diagnosis. Here, we report a case of a 17-year-old man with unilateral Toxoplasma papillitis without vitritis. Fundus examination revealed unilateral inflammation in the right optic disc and peripapillary area. Toxoplasma immunoglobulin (Ig)M titer was positive and IgG negative. During the follow-up, while the IgM titer decreased, the IgG titer increased. After possible etiologies were excluded, the patient was diagnosed with presumed Toxoplasma papillitis with a complete absence of vitritis at presentation. The patient was treated with appropriate antiparasitic agents and good response was observed without recurrence. [ABSTRACT FROM AUTHOR]

Malondialdehyde (MDA) is a reactive carbonyl compound produced through lipid peroxidation during feed storage, which poses a significant threat to fish health. This study aimed to evaluate the effects of dietary MDA on the growth rate, gastrointestinal health, and muscle quality of striped catfish (Pangasianodon hypophthalmus). A basal diet (M0) containing 34% crude protein and 10.5% crude lipid was formulated. Each group was sprayed with malondialdehyde solution (0, 5, 10, 20, 40, and 80 mg/kg, on dietary crude lipid basis; 0, 0.53, 1.07, 2.13, 4.26, and 8.52 mg/kg, on dietary basis) before feeding, respectively. Each diet was randomly assigned to triplicates of 30 striped catfish (initial weight 31.38 g) per net cage. After 8 weeks, dietary inclusion of MDA regardless of level significantly depressed the growth rate and feed utilization. The extent of structural damage to the gastrointestinal tract increased progressively with increasing dietary MDA levels. The extent of damage to the intestinal biological barrier (intestinal microbial structure), chemical barrier (trypsin, lipase, amylase, and maltase activity), physical barrier (zonula occludent-2, occludin, claudin 7α, and claudin 12 relative expression), and immune barrier (contents of complement 4, complement 3, immunoglobulin M, and lysozyme activity) was dose-related to dietary MDA. Moreover, a linear decline in the activities of intestinal antioxidant enzymes (catalas, superoxide dismutase, et al.) and anti-inflammatory factor (transforming growth factor beta1, interleukin 10) relative expression was noted alongside an increase in dietary MDA content. In contrast, the relative expression levels of intestinal inflammatory factor (interleukin 8, transcription factor p65, tumor necrosis factor alpha) relative expression displayed an opposing trend. Additionally, dietary MDA exerted a linear influence on muscle color and texture characteristics. In conclusion, high doses of MDA (5–80 mg/kg) reduced the growth performance of striped catfish, attributed to linear damage to the gastrointestinal tract, a linear decrease in antioxidant function, and the occurrence of an inflammatory response. High doses of MDA (>40 mg/kg) were observed to significantly increase dorsal muscle b-value and induce muscle yellowing. [ABSTRACT FROM AUTHOR]

This study evaluated bioactive compounds in blood orange (Citrus sinensis (L.) Osbeck) peel (BOP) as dietary additives. An 8-week feeding trial was conducted to investigate the effects of dietary supplementation on the growth performance, body composition, digestive enzyme activity, antioxidant capacity, and immune response of juvenile black rockfish. A total of 1260 juvenile rockfish (1.4 ± 0.01 g) were randomly distributed into seven treatment groups, each with 50 fish per circular tank. The groups were fed seven different diets containing graded levels of 0 (control, BOP0), 1 (BOP1), 2 (BOP2), 3 (BOP3), 5 (BOP5), 7 (BOP7), and 10 (BOP10) g kg−1, respectively. The BOP10 diet significantly enhanced the final weight, weight gain, specific growth rate, protein efficiency ratio, and protein retention in fish. The BOP treatments notably affected the fishes' whole-body crude protein and lipid contents. Plasma total cholesterol levels of fish fed the BOP0 and BOP1 diets were significantly higher than those fed the BOP7 and BOP10 diets. The activities of trypsin and lipase were significantly affected by dietary BOP levels. The antioxidant enzyme activity in the plasma of fish fed the BOP10 diet was significantly higher than those fed the BOP0 diet. The lysozyme activity and levels of immunoglobulin M and G in fish fed the BOP0 diet were significantly lower than those in fish fed the BOP10 diet. In conclusion, dietary supplementation of BOP at 10 g kg−1 improved the growth performance and overall health of juvenile black rockfish. [ABSTRACT FROM AUTHOR]

Background: Pathogenic infections can significantly impact the health of livestock. Traditionally, antibiotic growth promoters (AGPs) have been used in feed to enhance growth performance and disease control. However, concerns regarding antibiotic resistance have led to the exploration of traditional herbal medicine as a natural alternative, guided by the principle of medicine-food homology. The Taguchi method was employed to optimize the culture formula for cordycepin production, an active component of Cordyceps militaris (C. militaris). The influences of C. militaris supplementing solid-state fermentation (CMSSF) in feed on the growth performance and immune responses of grower pigs were evaluated in the present study. Results: The C. militaris ethanol extract (CME) displayed potent free radical scavenging activity against 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) after undergoing fermentation. Additionally, the antibacterial testing revealed that CME effectively inhibits the growth of common pig pathogens such as Glaesserella parasuis, Pasteurella multocida, Staphylococcus hyicus, and Streptococcus suis. In lipopolysaccharide (LPS)-treated intestinal porcine enterocyte cell line (IPEC-J2), CME significantly suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6. In addition, higher antioxidative activity was detected as indicated by elevated concentration of superoxide dismutase (SOD) in pig serum. The levels of immunoglobulin M (IgM), IgA, and IgG antibodies, as well as classical swine fever virus (CSFV) antibodies (S/P ratio) in serum were all increased. Growth performance of pigs fed with dietary CMSSF supplementation was improved in comparison with the control. Conclusions: Results demonstrated that CMSSF has the potential to be used as a natural growth promoter to enhance immunity, antioxidation, as well as overall health and growth performance of grower pigs. [ABSTRACT FROM AUTHOR]

In most persons, human parvovirus B19 (B19) causes a mild respiratory illness, but infection can result in adverse health outcomes in persons who are pregnant, immunocompromised, or who have chronic hemolytic blood disorders. During the first quarter of 2024, several European countries reported increases in B19 activity. In the United States, there is no routine surveillance for B19. To assess increases in B19 activity in the United States, trends in testing and results from two independent populations were examined: 1) the presence of immunoglobulin (Ig) M antibodies, a marker of recent infection, in clinical specimens ordered by physicians and 2) B19 nucleic acid amplification testing (NAAT) in pooled donor source plasma from a large commercial laboratory during 2018–2024. The proportion of IgM-positive clinical specimens reached 9.9% in the second quarter (Q2) of 2024 after remaining <1.5% during 2020–2023 and was higher than Q2 peaks in 2018 (3.8%, p<0.001) and 2019 (5.1%, p<0.001). The prevalence of B19–NAAT-positive donor pools (512 donations per pool) reached 20% in June 2024 after remaining <2% during 2020–2023 and was higher than peaks in 2018 (6.7%, p<0.001) and 2019 (7.3%, p<0.001). Considering the B19 activity increase in the United States in 2024, promotion of measures to prevent respiratory viruses and monitor for adverse B19-related outcomes by health care providers and public health authorities might reduce adverse health outcomes in pregnant persons and others at increased risk. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of patients with immunoglobulin A nephropathy (IgAN). Methods: A retrospective analysis of clinicopathological data from 774 patients with primary IgAN at Hangzhou Hospital of Traditional Chinese Medicine between January 1, 2016, and December 31, 2018, was conducted. Patients were categorized into end-event and non-end-event groups according to whether they reached the renal composite endpoint, defined as a ≥ 50% decline in eGFR or progression to end-stage renal disease (ESRD). Risk factors for adverse renal outcomes were evaluated via univariate and multivariate Cox regression models. Patients were further divided into three groups on the basis of IgM deposition levels in the glomerular mesangial area: IgM-negative, low (IF < 2+), and high (IF ≥ 2+). Comparative analyses of clinical and histopathological characteristics, along with treatment regimens, were performed across these groups. Results: Compared with the IgM-negative and low-deposition groups, the high-IgM deposition group exhibited significantly lower serum albumin and eGFR levels and higher cholesterol, 24-hour urine protein, and blood immunoglobulin M levels. Multivariate Cox regression analysis identified immunosuppressant use as an independent protective factor for IgAN prognosis, whereas low serum albumin, T2 lesions, and nephropathological IgM deposits were recognized as independent risk factors for the 5-year prognosis of patients with IgAN. Kaplan‒Meier survival curves revealed that patients with high IgM deposition had markedly poorer prognoses than those with negative or low IgM deposition. Conclusion: In addition to low serum albumin and T2 lesions, IgM deposition in the mesangial region has emerged as an independent risk factor for the 5-year prognosis of patients with IgAN. [ABSTRACT FROM AUTHOR]

The aim of this research was to investigate the effects of adding moringa polysaccharides (MOP) on the growth performance, immune function, rumen tissue morphology, and rumen microbial community in early-weaned goat kids. Twenty-one 7-day-old Leizhou male goat kids weighing (3.05 ± 0.63) kg, were randomly divided into a control group (CON group), a low-dose group (LOW group), and a high-dose group (HIG group). MOP was added to the goat kids' milk replacer (MR) at 0, 0.15, and 0.3% (on dry matter basis),fed until 60 days of age, and four goat kids in each group with body weights close to the mean of each group were selected for slaughter. The results showed that, compared to the CON group, the MOP groups significantly improved final body weight, body measurements, daily weight gain, and feed intake of the early weaned goat kids; significantly reduced the content of propionic acid, butyric acid, valeric acid, and ammoniacal nitrogen; and in addition, the addition of MOP could significantly increase the height of rumen nipple, the content of immunoglobulin G (IgG) in the serum. The HIG group significantly increased rumen pH, rumen muscularis layer thickness, rumen wall thickness, and serum immunoglobulin A (IgA), and immunoglobulin M (IgM). In conclusion, the addition of MOP positively impacted the growth performance, serum immune function, and rumen tissue morphology in early-weaned goat kids. [ABSTRACT FROM AUTHOR]

The common carp (Cyprinus carpio), a major economic freshwater fish, is suffering from a variety of bacterial infectious diseases because of its high-density, factory and intensive farming patterns. Aeromonas veronii is the causative agent of high mortality in common carp, causing severe economic losses in aquaculture. However, the regulatory mechanisms involved in the response of common carp to this bacterial infection remain poorly understood. In this study, we compared mortality, blood serum LZM (Lysozyme) and IgM (Immunoglobulin M) levels and transcriptome patterns of head kidney tissues after infection with different concentrations of Aeromonas veronii. We observed that mortality increased progressively with an increasing pathogen concentration. The concentrations of blood serum LZM and IgM significantly increased after infection. A total of 13 and 925 differentially expressed genes (DEGs) were identified after infection with low (T4) and high (T9) concentrations of bacterial suspension, respectively. KEGG and GO analyses of the DEGs highlighted multiple immune-related signaling pathways. Weighted gene co-expression network analysis (WGCNA) revealed that 136 and 83 hub genes were related to blood serum LZM and IgM, respectively. Finally, the gene expression in the head kidney was validated via RT–qPCR to be consistent with the transcriptome. These results provide insights into the mechanisms of the immune response to infection with different concentrations of Aeromonas veronii and offer useful information for further studies on immune defense mechanisms in common carp. [ABSTRACT FROM AUTHOR]

Background: Gut microbiome dysbiosis and related immune dysfunction have been associated with the pathogenesis of Human Cytomegalovirus (HCMV) infection in infants with neonatal cholestasis (NC) as previously reported by us. However, the interaction of a perturbed microbiome, HCMV infection, and dysregulated immunity leading to exacerbation of disease severity has not been investigated so far. In this study, we examined the association of gut microbiome, host inflammatory and homeostatic markers that are likely to govern increased pathogenesis of NC in HCMV infected IgM positive infants (N = 15) compared to IgM negative (N = 15) individuals. Stool samples of HCMV infected infants and age-matched healthy controls (N = 10) were assessed for gut bacteria-derived metabolites like short-chain fatty acids (SCFAs), Lipopolysaccharide (LPS), cytokines and markers of gut barrier integrity. Data were correlated with previously determined gut microbiome composition and frequency of immune cell subsets. Finally, validation of clinical potential was undertaken by principal component analysis (PCA) of integrated data to delineate the spectrum of clinical pathology. Results: Significantly lower levels of SCFAs and elevated fecal levels of soluble inflammatory mediators were observed in IgM positive HCMV infected infants. Further, increased plasma LPS levels and markers of gut permeability, suggestive of microbial translocation due to a 'leaky gut' were observed in HCMV infected IgM positive group. PCA of integrated data revealed clearly disparate profiles representative of IgM positive, IgM negative, and uninfected healthy states. Conclusion: Our results suggest the utility of an integrated approach involving dysregulated microbiome-immune axis for gaining a better understanding of pathogenesis associated with HCMV infection in NC. [ABSTRACT FROM AUTHOR]

On April 24, 2023, the American Samoa Department of Health (ASDoH) declared a public health emergency amid concern about a possible measles outbreak given low 2-dose vaccination coverage at the time. ASDoH had received two positive measles immunoglobulin (Ig) M test results after Flag Day festivities 1 week earlier from vaccinated children. ASDoH performed active case finding, took actions to mitigate transmission, and requested technical assistance from CDC. ASDoH implemented a vaccination campaign to improve suboptimal coverage. Confirmatory molecular testing of specimens from these initial persons under investigation (PUIs) was not possible, but subsequent testing of specimens from additional PUIs by Hawaii State Laboratories Division and CDC ruled out measles. In settings with low measles prevalence, measles antibody testing results have low positive predictive value and can lead to difficulties with interpreting results. Testing for additional pathogens revealed a variety of viruses known to cause common childhood viral exanthems. Both molecular and serologic testing should be performed for all suspected measles cases. To decrease the probability of false-positive IgM results, testing should be reserved for cases that meet the Council of State and Territorial Epidemiologists measles case definition, especially those in persons with no evidence of immunity and with a history of recent international travel. In addition, maintaining high measles vaccination coverage can prevent future outbreaks. [ABSTRACT FROM AUTHOR]

Background: New feline erythrocyte antigens (FEAs) have been described based on the presence of naturally occurring alloantibodies (NOAb), but their immunogenicity and clinical relevance are poorly understood. Hypothesis/Objectives: Describe the immunogenicity of FEA 4 after sensitizing FEA 4–negative cats lacking NOAb and characterize anti–FEA 4 alloantibodies produced, including their rate of appearance, agglutination titer, and immunoglobulin class. Animals: Nineteen healthy type A cats were blood typed for FEAs 1 to 5 to identify suitable donor‐recipient pairs for FEA 4 sensitization. Methods: Four FEA 4–negative cats were transfused with FEA 4–positive red blood cells. Using a gel column technique, posttransfusion samples were screened daily for a week, weekly for a month, and monthly thereafter for anti–FEA 4 alloantibodies. Results: Alloantibodies were not detected in the first 3 recipients despite repeated transfusions (1 and 3 additional transfusions for 2 and 1 recipients, respectively). In the 4th recipient, alloantibodies against its donor red blood cells were detected 21 days postsensitization. However, they were not directed against FEA 4, but rather against a novel FEA not yet described. The alloantibodies, named anti–FEA 6, remained detectable for >4 months after sensitization and were determined to be mostly immunoglobulin M based on sulfhydryl treatment. Conclusions and Clinical Importance: Feline erythrocyte antigen 4 does not appear to be immunogenic because repeated sensitization of 4 cats failed to produce detectable anti–FEA 4 alloantibodies. A new immunogenic antigen, named FEA 6, has been discovered, but additional studies are needed to document its clinical importance. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is a common rickettsial infection endemic in India and is an important cause of acute febrile illness among children. Clinical manifestations vary from mild-to-severe affecting almost all organ systems with a high fatality rate. To reduce morbidity and mortality, a high index of suspicion, timely diagnosis, and treatment are crucial. However, due to lack of awareness, low index of suspicion among clinicians, and non-specific clinical presentation which overlaps with other tropical endemic infections of India such as dengue, chikungunya, malaria, and leptospirosis, scrub typhus is often underdiagnosed in our country. Aims and Objectives: (1) To find the prevalence of scrub typhus among children presenting with fever for the last 5 days, (2) To study their clinico-demographic profiles. Materials and Methods: Blood collected from children aged 1 month to 12 years of age presenting with fever for the last 5 days were tested for scrub typhus immunoglobulin M enzyme-linked immunosorbent assay. Clinical characteristics and laboratory parameters of the patients were collected. The results obtained were analyzed and interpreted. Results: Out of 865 pediatric patients presenting with fever, only 227 (26.24%) were positive for scrub typhus. Maximum cases (45.37%) were found in the age group >5-12 years. Fever was the presenting feature in all the cases. Other common presentations were hepatosplenomegaly, lymphadenopathy, pain abdomen, rash, and eschar. Conclusion: Although scrub typhus is an easily treatable disease, timely diagnosis and treatment are needed to avoid complications which require a high degree of suspicion among clinicians along with a robust laboratory setup with adequate diagnostic facilities. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of leptospirosis in humans is of great public health concern, particularly in tropical and subtropical regions. Objective: This study aimed to determine the seroprevalence of leptospiral antibodies and the distribution of serovars in livestock breeders and farmers in Golestan province. Methods: Seventy samples of serum collected from farmers and ranchers suspected of leptospirosis were examined using an ELISA method for surveying Immunoglobulin M (IgM) anti‐leptospiria. Also from samples, DNA was extracted and PCR was performed using by primers for 16s rRNA. Demographic properties of positive patients were analysed. Results: Chi‐square statistical test shows a statistically significant difference between the gender and prevalence leptospirosis (p‐value = 0.004). Also, by examining the age, it was shown that 68.57% of patients are in the middleaged rang. According to the results obtained from the study and investigation of blood serum IgM‐and Immunoglobulin G (IgG) in people suspected of leptospirosis, 3 cases of the patients had IgM higher than 11 and were known to be positive for leptospirosis. Also, by examining the IgG level of patients, 5 cases had intermediate results, and 2 cases were found to be positive for IgG. The PCR results showed that 41.42% of patients tested positive for the 16s rRNA. Conclusion: Leptospirosis is a common disease among farmers, and in Golestan province, considering traditional farming methods, it is considered an important infectious disease. Therefore, health and safety measures should be expanded to control and prevent this disease. Also, by employing mechanised agricultural methods, the prevalence of leptospirosis in this region can be significantly reduced. [ABSTRACT FROM AUTHOR]

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

Infection with Borrelia burgdorferi causes Lyme disease in humans. In small rodents, the natural reservoir species of this spirochete, infections lead to only modest disease manifestations, despite causing persistence infection. Although B cell responses are central for controlling bacterial tissue burden and disease manifestations, they lack classical aspects of T-dependent responses, such as sustained IgG affinity maturation and longevity, corresponding with a rapid collapse of germinal centers. Instead, the Ab response is characterized by strong and ongoing secretion of IgM, whose origins and impact on protective immunity to B. burgdorferi remain unknown. In this article, we demonstrate that B. burgdorferi infection-induced IgM in mice was produced continuously, mainly by conventional B, not B-1 cells, in a T-independent manner. Although IgM was passively protective and restricted early bacteremia, its production had no effects on bacterial dissemination into solid tissues, nor did it affect Borrelia tissue burden. The latter was controlled by the induction of bactericidal IgG, as shown comparing infections in wild type mice with those of mice lacking exclusively secreted IgM-/-, all class-switched Abs via deletion of aicda (AID-/-), and all secreted Abs (secreted IgM-/- × AID-/-). Consistent with the notion that B. burgdorferi infection drives production of IgM over more tissue-penetrable IgG, we demonstrated increased short- and long-term IgM Ab responses also to a coadministered, unrelated Ag. Thus, the continued production of IgM may explain the absence of B. burgdorferi in the blood.

Objective This study aims to evaluate the immunomodulatory effects of coconut oil extract (COE) in broilers experimentally infected with velogenic Newcastle disease virus (vNDV). Methods A total of 150 broiler birds (day-old) were equally divided into five study groups i.e., negative control, positive control, COE-1, COE-2, and COE-3. On day 10, broilers of groups COE-1, COE-2, and COE-3 were supplemented with 1, 2, and 3 mL of COE respectively per liter of drinking water for 15 days. On day 13, 0.1 mL/bird (10−5.25 ELD50) of vNDV was inoculated in broilers of positive control, COE-1, COE-2, and COE-3 groups intramuscularly. During this study, growth performance, morbidity, and mortality rates of each study group were recorded. The antibody titer against NDV was determined on days 7, 14, 21, 28, and 35. The levels of immunoglobulins (IgY and IgM) were also determined on the 7th, 14th, and 21st days post-sheep red blood cells (SRBCs) inoculation. On day 33, avian tuberculin was injected between the 1st and 2nd toes of the left side (intradermally) to measure lymphoproliferative responses. On day 35, the phagocytic activity in the blood was assessed through a carbon clearance assay by injecting carbon black ink into the right-wing vein. The visceral organs having gross lesions were also collected for histopathology. Results The COE significantly improved the growth performance, and lowered the morbidity and mortality rates of broilers. There was a significant rise in antibody titers against NDV and levels of IgY and IgM antibodies against SRBC in COE-supplemented broilers. The lymphoproliferative response and phagocytic activity were also enhanced. Among COE-supplemented groups, the broilers of the COE-3 group showed a significant increase in growth performance and boosted immune defense. Conclusion Coconut oil extract has the potential to boost the growth performance and immune status of broilers. It can be used effectively as a feed additive and alternative to antibiotics to prevent the spread of infectious poultry pathogens.

Abstract Background We investigated the associations between IgM, IgG, IgA, and IgE levels and all-cause mortality risk in Chinese centenarians. Methods All participants were from the China Hainan Centenarian Cohort Study. Eligible participants were divided into quartiles based on their IgM, IgG, IgA, and IgE levels. We used restricted cubic spline analyses, Cox regression analyses, and Kaplan–Meier survival curves to analyze associations between IgM, IgG, IgA, and IgE and all-cause mortality risk. Results A total of 906 centenarian participants were included in this study (81.2% female; median age, 102 years). During a median follow-up of 30.1 months, 838 (92.5%) participants died. Restricted cubic spline analysis revealed a nonlinear relationship (“L” type) between serum IgM level and all-cause mortality. Compared with the higher three quartiles of serum IgM level, the lowest quartile was associated with a higher risk of death (Q1 versus Q2-Q4: HR, 1.365; 95% CI, 1.166–1.598; P

Simple Summary: Increased reproductive performance in modern high-yielding sows often results in inadequate energy intake. Many recent studies have focused on the improvement of sow energy intake through the addition of different dietary energy source, but there have few studies on dietary energy concentration based on the net energy system. Our results suggest that increasing the dietary energy concentration can increase immunological substances in milk and improve milk quality and body health in primiparous lactating sows. This study aimed to determine the optimal dietary net energy concentration for the reproductive performance, immune function, milk composition, and gut microbiota of primiparous sows during lactation. Forty primiparous lactating sows (Landrace × Yorkshire) with similar body backfat thicknesses were randomly allocated into five treatment groups and fed diets with different dietary net energy concentrations of 10.05 MJ/kg, 10.47 MJ/kg, 10.89 MJ/kg, 11.30 MJ/kg, and 11.72 MJ/kg. The results showed that there were no differences in the performance of piglets, while there was a decrease in the daily feed intake of sows (p = 0.079, linear) as dietary net energy concentration increased. With the increasing dietary net energy concentration, the plasma insulin levels of sows increased (p < 0.01, linear), the plasma glucose levels tended to increase (p = 0.074, linear), and the blood urea nitrogen levels tended to decrease (p = 0.063, linear). Moreover, the plasma total superoxide dismutase activity of sows increased (p < 0.05, quadratic) and the plasma malondialdehyde content of sows decreased (p < 0.05, quadratic) by increasing the dietary net energy concentration. Interestingly, with the increase in dietary net energy concentration, the plasma immunoglobulin M content of sows increased, the milk immunoglobulin M, immunoglobulin G, immunoglobulin A and the percentage of milk fat increased (p < 0.05, linear), and the milk secretory immunoglobulin A content also increased (p < 0.05, linear and quadratic). The milk immunoglobulins and milk fat content of sows fed with net energy concentration of 11.72 MJ/kg were highest. Moreover, there were significant differences in the α-diversity, β-diversity, and relative abundance of gut microbiota in sows fed with different dietary net energy concentrations. At the phylum level, Spirochaetota and Bacteroidota in the gut microbiota of sows were mainly affected by increasing the dietary net energy concentration. Furthermore, the correlation analysis showed that milk immunoglobulin content had a significant negative correlation with the relative abundance of Bacteroidota, and plasma malondialdehyde content also had a significant negative correlation with the relative abundance of Spirochaetota. In summary, these results suggest that increasing the dietary net energy concentration to 11.72 MJ/kg can increase immunological substances in milk, improve milk quality, and alter the composition of gut microbiota in primiparous lactating sows. [ABSTRACT FROM AUTHOR]

Simple Summary: The addition of alternative feed sources such as Green Tea Powder to the feed of poultry, especially laying hens, has attracted attention due to its potential benefits. Therefore, the purpose of this study—with the addition of Green Tea Powder to the diet of laying hens—is, on the one hand, to explore the beneficial effects of Green Tea Powder on the production performance and physical function of laying hens and, on the other hand, to explore the utilization of Green Tea Powder and improve the utilization rate of biological resources. In conclusion, dietary supplementation of Green Tea Powder during the laying period can reduce the serum yolk weight of laying hens. The serum levels of immunoglobulin A and immunoglobulin M were increased, and the serum levels of malondialdehyde were decreased. Egg shell strength and shell thickness decreased, and egg yolk color deepened. Additionally, the percentage of amino acids in the eggs increased. It is beneficial to the health of laying hens to increase the diversity of intestinal flora and improve the structure of cecum flora. This study investigated the effects of Green Tea Powder supplementation on the performance and egg quality of laying hens and ultimately guided the development of more effective and scientific animal feeding strategies. This study was conducted to investigate the effects of different levels of Green Tea Powder on the performance, egg quality, serum immune and antioxidant indices, and cecal microflora of 300-day-old Chishui black-bone chickens during the peak laying period. A total of 360 Chishui black-bone chickens were selected as the experimental animals. They were randomly allocated into four groups: the control group (CON), trial group I (T1), trial group II (T2), and trial group III (T3), each group with six replicates and 15 hens in each replicate. The control group was fed a basal diet, and the experimental groups were fed a basal diet supplemented with 0.8%, 1.6%, and 2.4% Green Tea Powder, respectively. The accommodation period was 14 d, and the experimental period was 60 d. The statistical software SPSS was used to perform a one-way analysis of variance (ANOVA) on the experimental data, and Duncan's method was used to perform multiple comparisons among groups. The results showed the following: compared with those of the control group, the average daily gain of the laying hens significantly decreased in the 1.6% Green Tea Powder group (p < 0.05); adding Green Tea Powder significantly reduced the content of malondialdehyde in the serum (p < 0.05), and the addition of 0.8% tea leaves significantly increased the immunoglobulin M and immunoglobulin A contents (p < 0.05); the egg yolk weight, eggshell thickness, eggshell strength, and yolk color of the laying hens significantly decreased in the 1.6% Green Tea Powder group (p < 0.05), and the addition of Green Tea Powder at the level of 2.4% significantly increased the percentage of umami, essential, and total amino acids (p < 0.05); and the structure of intestinal microorganisms was improved, and the abundance of Bacteroidetes and Bacteroidaceae significantly increased, while the abundance of Firmicutes and Lachnospiraceae significantly decreased (p < 0.05). [ABSTRACT FROM AUTHOR]

Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause the emergence of escape mutants. We studied the humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged SARS-CoV-2 infection with a virus of lineage B.1.177.81. Following bamlanivimab treatment at an early stage of infection, the patient developed a bamlanivimab-resistant mutation, S:S494P. After five weeks of apparent genetic stability, the emergence of additional substitutions and deletions within the N-terminal domain (NTD) and the receptor binding domain (RBD) of S was observed. Notably, the composition and frequency of escape mutations changed in a short period with an unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until virus elimination. Routine serology revealed no evidence of an antibody response in the patient. A detailed analysis of the variant-specific immune response by pseudotyped virus neutralisation test, surrogate virus neutralisation test, and immunoglobulin-capture enzyme immunoassay showed that the onset of an IgM-dominated antibody response coincided with the appearance of escape mutations. The formation of neutralising antibodies against S:Delta141-4 E484K S494P correlated with virus elimination. One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in an increase in Omicron-reactive antibodies. In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the rapid emergence of various antibody escape mutants with known epidemiological relevance. Author summary: In the immunocompromised host, prolonged infection and insufficient antibody responses favour the emergence of highly mutated SARS-CoV-2 variants. To better understand the selective pressure exerted by antiviral antibodies, we characterised the variant-specific humoral immune response and resulting intra-host evolution of SARS-CoV-2 in a B-lymphocyte-depleted patient experiencing severe infection. Treatment with a monoclonal antibody early in infection led to the selection and outgrowth of resistant virus. As their B-cell function recovered, the patient mounted an IgM-dominated antiviral antibody response, the onset of which closely correlated with the appearance of additional escape mutations within the spike protein. The strength and breadth of this antibody response gradually increased, resulting in the selection of a variant carrying several escape mutations within spike. The formation of neutralising antibodies against this variant resulted in virus elimination. Our study provides new insights into the selection process of viral escape mutants in immunocompromised patients. The resuming humoral immunity against SARS-CoV-2 can be dominated by IgM. This immune response is poorly detectable with routine diagnostic procedures yet may trigger and drive substantial viral intra-host evolution. Determination of antiviral antibody responses and correlating them with intra-host evolution may provide a better picture of the adaptability of currently circulating SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background: We investigated the associations between IgM, IgG, IgA, and IgE levels and all-cause mortality risk in Chinese centenarians. Methods: All participants were from the China Hainan Centenarian Cohort Study. Eligible participants were divided into quartiles based on their IgM, IgG, IgA, and IgE levels. We used restricted cubic spline analyses, Cox regression analyses, and Kaplan–Meier survival curves to analyze associations between IgM, IgG, IgA, and IgE and all-cause mortality risk. Results: A total of 906 centenarian participants were included in this study (81.2% female; median age, 102 years). During a median follow-up of 30.1 months, 838 (92.5%) participants died. Restricted cubic spline analysis revealed a nonlinear relationship ("L" type) between serum IgM level and all-cause mortality. Compared with the higher three quartiles of serum IgM level, the lowest quartile was associated with a higher risk of death (Q1 versus Q2-Q4: HR, 1.365; 95% CI, 1.166–1.598; P < 0.001). Among individuals for whom IgM < 0.708 g/L (Q1), the risk of all-cause mortality was 36.5% higher. Kaplan–Meier analyses showed that centenarians with lower serum IgM levels had significantly shorter median survival time (Q1 versus Q2-Q4: 26 months versus 32 months, log-rank P = 0.001). Conclusion: Serum IgM levels in centenarians significantly correlated with the risk of death, suggesting that they are suitable for predicting the overall risk of death in centenarians and can be used as an independent predictor of death. [ABSTRACT FROM AUTHOR]

The IgM protease (IdeSsuis gene; Gene ID 8153996) of Streptococcus suis is a putative virulence factor that has been shown to be a protective vaccine antigen for pigs (Seele et al. Vaccine 33:2207–12, 2015). To assess its potential as a cross-protective antigen, the amino acid variability among prevalent clinical isolates in various regions and among various serotypes was investigated. Multi-sequence alignment of full-length amino acid sequences of S. suis IgM protease, available in the public domain (status Jan-2022) supplemented with in-house sequences, i.e. a total of 1999 sequences, revealed that the IgM protease of S. suis clusters into three main evolutionary distinct branches: groups A, B and C. Group A, 82% of the sequences in the database, was associated with clinical isolates of various serotypes. Group B, 6% of the strains in the database, was associated with clinical isolates mainly in the EU and mainly belonging to serotype (st) 9. Group C, 12% of the strains in the database, was largely associated with healthy carrier isolates, i.e. nose or tonsil isolates of various serotypes but in particular with st9 and un-typable strains. Within the groups A, B and C, high levels of amino acid identity were observed (> 75%), whereas between groups A and B, the percentage amino acid identity was approximately 30% and between groups A and C approximately 55%. Experimental Escherichia coli expressed recombinant subunit vaccines based on the IgM protease group A sequence of st1 strain B10-99, st2 strain 10 or st7 strain 14009-1, induced serotype independent protection in pigs against challenge with all group A strains tested, i.e. strains of different parts of the phylogenetic tree and of different serotypes including st1, 2, 9 and 14. Protection was observed after vaccination of piglets at 3 and 5 weeks of age and subsequent challenge at 7 weeks but also after vaccination of gilts at 6 and 2 weeks before anticipated parturition and challenge of the offspring up to at least 8 weeks of age. No protection was observed against challenge with st9 strain SZ2000-6264 having group B IgM protease. A recombinant subunit vaccine based on the group B IgM protease sequence, also did not protect against challenge with the homologous group B st9 challenge strain. The results indicate that a vaccine based on a group A IgM protease induces protection against all S. suis strains that express the group A IgM protease. Depending on the geographical region such a vaccine is expected to protect against 60–100% of the virulent S. suis strains. Since the novel proposed IgM protease classification is highly relevant, a PCR was developed and validated, to be able to classify clinical isolates into IgM protease groups A, B and C and predict the cross-protection that can be expected from a group A based IgM protease vaccine. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple sclerosis (PwMS) have an increased risk of infections. Objectives: To characterize incidence, clinical characteristics, outcomes and risk factors of infections, and serious infections (SIs) in ocrelizumab (OCR)-treated PwMS. Design: Post-hoc analysis of pooled data from 6155 patients in 13 clinical trials. Methods: Descriptive analyses of clinical characteristics and outcomes were reported over ⩽14 years. A Poisson Generalized Estimating Equation model was constructed to examine risk factors in a subgroup of patients with longer exposure to OCR (n = 2092). Results: Over a median (max) treatment period of 3.7 (13.9) years, 420/6155 patients (6.8%) experienced 583 SIs, excluding coronavirus disease 2019. Incidence rates in relapsing multiple sclerosis (RMS; 1.50 per 100 patient years [95% confidence interval (CI): 1.34–1.68]) and progressive multiple sclerosis (PMS; 3.70 [95% CI: 3.27–4.17]) remained stable over this period. Lower respiratory tract, urinary tract, abdominal and gastrointestinal, and skin infections were the most commonly reported SIs. Most SIs (~90%) resolved, and treatment with OCR was continued in >80% of cases. The presence of 1 or ⩾2 comorbidities (rate ratio = 1.66, 2.73, respectively), recent relapse activity (2.06), and Expanded Disability Status Scale (EDSS) score ⩾6.0 (2.02) were significant risk factors for SIs in patients with RMS treated over a median (max) period of 8.3 (11.2) years. In patients with primary PMS treated over a median (max) period of 7.1 (11.8) years, an EDSS score ⩾6.0 was associated with the greatest risk of SIs, a 4-fold increase (rate ratio, 4.31), followed by abnormal immunoglobulin (Ig)M levels (1.89), the presence of ⩾2 comorbidities (1.80), and having overweight/obesity (1.46). Time on OCR and abnormal IgG levels were not significantly associated with an increased SI risk. Conclusion: Continuous long-term treatment with OCR is associated with a manageable infection risk profile. Optimal disease control and addressing modifiable risk factors may reduce the risk of infections. Plain language summary: Is continued treatment with ocrelizumab associated with a higher risk of infections and serious infections in patients with multiple sclerosis? Patients with multiple sclerosis (PwMS) are at an increased risk of infections compared with the general population. Infections are also among the most frequently reported side effect in PwMS treated with ocrelizumab. Initial analyses have shown that serious infection (SI) rates in PwMS treated with ocrelizumab were stable over 6 years, but there is concern that this rate may increase with continued treatment. This study aimed to describe infections and SIs in PwMS treated with ocrelizumab and look into factors that increase patients' susceptibility to infections. We analyzed the largest population of PwMS ever treated with ocrelizumab, including 6155 patients from 13 clinical trials. Some of these patients received ocrelizumab for as long as 14 years. Approximately 7 out of every 100 patients experienced SIs, excluding COVID-19 infections, with no increase in yearly rates of SIs over time. Pneumonia and urinary tract infections were the most common SIs. Almost all patients recovered from their infections (>9 out of 10 cases), and continued treatment with ocrelizumab (>8 out of 10 cases). When looking at factors that made PwMS more prone to SIs, we found that patients with relapsing MS had an increased risk if they had experienced recent MS relapses, severe walking difficulties, or other health conditions like diabetes and bladder problems. Patients with primary progressive MS (PPMS) with severe walking difficulties were four times more likely to have SIs. Having other health conditions like heart or bladder problems, low levels of immunoglobulin M, or excess weight also increased the risk of SIs in patients with PPMS. In conclusion, continued treatment with ocrelizumab did not increase the risk of SIs, and most of those infections resolved without stopping ocrelizumab treatment. Addressing certain health conditions and achieving a good control of the MS disease may help to reduce the risk of SIs. [ABSTRACT FROM AUTHOR]

Background: Humoral bactericidal activity was first recognized nearly a century ago. However, the extent of inter-individual heterogeneity and the mechanisms underlying such heterogeneity beyond antibody or complement systems have not been well studied. Methods: The plasma bactericidal activity of five healthy volunteers were tested against 30 strains of Gram-negative uropathogens, Klebsiella pneumoniae and Escherichia coli, associated with bloodstream infections. IgG and IgM titers specific to K. pneumoniae strains KP13883 and KPB1 were measured by ELISA, and complement inhibitor was used to measure the contribution of complementinduced killing. Furthermore, MALDI-TOF mass spectrometry was conducted to determine the metabolomic components of plasma with bactericidal properties in 25 healthy individuals using Bayesian inference of Pearson correlation between peak intensity and colony counts of surviving bacteria. Results: Plasma bactericidal activity varied widely between individuals against various bacterial strains. While individual plasma with higher IgM titers specific to K. pneumoniae strain KP13883 showed more efficient killing of the strain, both IgM and IgG titers for K. pneumoniae strain KPB1 did not correlate well with the killing activity. Complement inhibition assays elucidated that the complement-mediated killing was not responsible for the inter-individual heterogeneity in either isolate. Subsequently, using MALDI-TOF mass spectrometry on plasmas of 25 healthy individuals, we identified several small molecules including gangliosides, pediocins, or saponins as candidates that showed negative correlation between peak intensities and colony forming units of the test bacteria. Conclusion: This is the first study to demonstrate the inter-individual heterogeneity of constitutive innate humoral bactericidal function quantitatively and that the heterogeneity can be independent of antibody or the complement system. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the effect of white noise intervention on sleep quality and immunological indicators of patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Methods: From January 2020 to December 2022, 104 newly diagnosed female patients (the number of people who met the inclusion criteria) with breast cancer who were confirmed to be preoperative NAC by puncture pathology were selected for a randomised single-blind trial. The patients were randomly divided into an observation group and a control group, with 52 cases in each group. The control group of patients received routine NAC treatment. The observation group played white noise at regular intervals every night on the basis of routine NAC, covering the entire treatment cycle. We evaluated the clinical efficacy, safety, sleep quality and immunological indicators of the two groups. Results: We found no statistically significant difference in the objective response rate between the two groups (P > 0.05). There was no statistically significant difference in the incidence of safety events between the two groups (P > 0.05). The total incidence of adverse reactions in the observation group was significantly lower than that in the control group (P < 0.05). After intervention, the sleep latency, subjective sleep quality, sleep duration, daytime function and sleep disorder scores of both groups decreased, and the observation group had significantly lower scores than the control group (P < 0.05). After intervention, both groups showed changes in immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), C-reactive protein and serum interleukin-6, but the differences between the groups were not statistically significant (P > 0.05). Conclusion: White noise intervention can improve the sleep quality of the NAC population with breast cancer and reduce the incidence of adverse reactions. In addition, it has no effect on the treatment efficacy, safety and immune indicators of patients. [ABSTRACT FROM AUTHOR]

Objectives: Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are significant global health concerns that contribute to acute viral hepatitis. This study aimed to investigate the prevalence of HAV, HEV, and co-infections in a tertiary care hospital setting in central India. Materials and Methods: This retrospective observational study analyzed 987 clinical specimens collected from suspected acute viral hepatitis cases over 5 years (2019–2023). Commercially available enzyme-linked immunosorbent assay kits were used to detect HAV and HEV immunoglobulin M antibodies. Statistical analysis: Demographic data and clinical information were collected and analyzed using Chi-square tests. P < 0.05 was considered statistically significant, indicating a significant association between the variables under investigation. Results: Overall, 32.72% of patients were seropositive for either HAV, HEV, or both. The prevalence of HAV was 22.9%, HEV was 9.83%, and co-infection was 3.24%. HAV infection was more prevalent in children (0–14 years), whereas HEV was more prevalent in adults. Both HAV and HEV infections were associated with elevated liver function markers, with the highest levels observed in co-infected cases. The monsoon season had the highest number of cases. Conclusions: This study revealed a substantial burden of HAV, HEV, and co-infections in central India. The observed sex—and age-specific prevalence patterns warrant further investigation. Effective public health strategies addressing sanitation, hygiene practices, and HAV vaccination programs are crucial to reducing the disease burden. [ABSTRACT FROM AUTHOR]

Background: The global demand for fish and fish products has increased due to population growth and healthier food choices. However, bacterial infections caused by Aeromonas species pose a challenge. Antibiotics are crucial for disease control, but multidrug resistance is a global concern. Eco-friendly disease management methods, like saffron, have been identified as potential treatments. Aim: The study investigated the effects of dietary supplementation with Saffron on Nile tilapia's growth performance, immune response, and disease resistance. Methods: 180 fish were acclimatized for 2 weeks and randomly allocated into three groups. The first group served as a control, while the other two groups were fed a basal diet supplemented with Saffron at 1.5 g/kg (T1) and 0.5 g/kg (T2), respectively, for 12 weeks. Biochemical blood parameters. Histopathology and immunohistochemical studies were performed on the gills, liver, and spleen tissues. Results: Following the feeding trial with Saffron supplement, especially at higher levels enhanced weight gain, Growth performance, plasma total protein, and globulin showed higher levels in fish groups with dietary with Saffron at 1.5 g/kg (T1) and 0.5 g/kg (T2) than in fish fed the control diet Regulate the immune response in lysozyme activity and immunoglobulin M (IgM). Regeneration of gills, liver, and spleen tissues was noticed Furthermore, saffron-treated organs exhibited immunoreactivity to TNF-a was mostly seen in the liver and gills, although it was also somewhat in the kidney and spleen and CD68, the group were challenged with Aeromonas hydrophila, improved its defenses against A. hydrophila, immunity, and disease resistance than the control group. Conclusion: The results showed that saffron supplementation significantly increased the survival rate of fish challenged with A. hydrophila. It also enhanced the immune response of fish, as evidenced by increased levels of serum immunoglobulins and lysozyme activity. These findings suggest that saffron supplementation could be a promising strategy for the prevention and treatment of bacterial infections in aquaculture. [ABSTRACT FROM AUTHOR]

The present study investigates the public health impact of flooding on leptospirosis incidence after Storm Daniel in Thessaly, Greece, in September 2023. A notable increase in cases was observed, with seven cases of female patients and a mean age of 40.2 years, indicating a significant risk among working-age adults. From the end of September to the beginning of November 2023, a total of 35 patients from flood-prone areas presented to the Emergency Department of the Tertiary University Hospital of Larissa. Diagnosis of leptospirosis was established by meeting the criteria suggested by the national public health organisation (EODY)-compatible clinical course, epidemiological exposure, molecular and serologic confirmation by the detection of immunoglobulin M antibodies to leptospira spp. using a commercially available enzyme-linked immunosorbent assay and real-time quantitative PCR for the molecular detection of leptospira. The larger part (84.6%) of leptospirosis cases were associated with contact with floodwater. The majority of these patients (71.4%) were from the prefecture of Larissa, followed by 14.3% from the prefecture of Karditsa, 8.6% from the prefecture of Trikala, and 5.7% from the prefecture of Magnesia. Occupational exposure and urbanisation were key risk factors. The most prevalent clinical feature was rash (69.2%), followed by fever (61.5%) and myalgia (30.7%). The findings emphasise the need for robust public health strategies, improved sanitation, rodent control, and protective measures for sanitation workers. The data highlight the broader implications of climate change on public health and the necessity for ongoing surveillance and community education to mitigate future outbreaks. [ABSTRACT FROM AUTHOR]

Background/Objectives: Neutrophils are emerging as promising candidates for cell-based nanodrug delivery to tumors due to their unique biological properties. This study aims to investigate the mechanisms of nanoparticle internalization by neutrophils, specifically focusing on liposomes, poly(lactic-co-glycolic acid) (PLGA), and magnetite nanoparticles. Understanding these mechanisms could enhance the efficiency of neutrophil-based nanodrug delivery for cancer treatment. Methods: Neutrophils were isolated from the peripheral blood of mice bearing 4T1 mammary adenocarcinoma. Confocal microscopy, transmission electron microscopy, and flow cytometry were employed to evaluate the uptake of liposomes, PLGA, and magnetite nanoparticles by neutrophils. The effects of cultivation conditions, such as the presence or absence of plasma in the growth medium, were also examined. Additionally, the roles of immunoglobulins (IgG/IgM) and cell surface receptors (Fc and scavenger receptors) in nanoparticle internalization were explored. Results: All types of nanoparticles were successfully internalized by neutrophils, though the mechanisms of uptake varied. Plasma presence in the medium significantly influenced nanoparticle binding, particularly for PLGA nanoparticles. Internalization of PLGA nanoparticles was found to depend on the presence of IgG/IgM in the medium and Fc receptors on neutrophil surfaces, while scavenger receptors were not involved. Conclusions: Understanding the distinct endocytosis pathways for different nanoparticles can improve the efficacy of neutrophil loading with nanodrugs, potentially advancing the development of neutrophil-based cancer therapies. The findings underscore the importance of the extracellular environment in modulating nanoparticle uptake. [ABSTRACT FROM AUTHOR]

(1) Background: We describe a model of primary mild-Clostridioides difficile infection (CDI) in a naïve host, including gut microbiota analysis, weight loss, mortality, length of colonization. This model was used in order to describe the kinetics of humoral (IgG, IgM) and mucosal (IgA) immune responses against toxins (TcdA/TcdB) and surface proteins (SlpA/FliC). (2) Methods: A total of 105 CFU vegetative forms of C. difficile 630Δerm were used for challenge by oral administration after dysbiosis, induced by a cocktail of antibiotics. Gut microbiota dysbiosis was confirmed and described by 16S rDNA sequencing. We sacrificed C57Bl/6 mice after different stages of infection (day 6, 2, 7, 14, 21, 28, and 56) to evaluate IgM, IgG against TcdA, TcdB, SlpA, FliC in blood samples, and IgA in the cecal contents collected. (3) Results: In our model, we observed a reproducible gut microbiota dysbiosis, allowing for C. difficile digestive colonization. CDI was objectivized by a mean weight loss of 13.1% and associated with a low mortality rate of 15.7% of mice. We observed an increase in IgM anti-toxins as early as D7 after challenge. IgG increased since D21, and IgA anti-toxins were secreted in cecal contents. Unexpectedly, neither anti-SlpA nor anti-FliC IgG or IgA were observed in our model. (4) Conclusions: In our model, we induced a gut microbiota dysbiosis, allowing a mild CDI to spontaneously resolve, with a digestive clearance observed since D14. After this primary CDI, we can study the development of specific immune responses in blood and cecal contents. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the immunomodulatory effects of coconut oil extract (COE) in broilers experimentally infected with velogenic Newcastle disease virus (vNDV). Methods: A total of 150 broiler birds (day-old) were equally divided into five study groups i.e., negative control, positive control, COE-1, COE-2, and COE-3. On day 10, broilers of groups COE-1, COE-2, and COE-3 were supplemented with 1, 2, and 3 mL of COE respectively per liter of drinking water for 15 days. On day 13, 0.1 mL/bird (10–5.25 ELD50) of vNDV was inoculated in broilers of positive control, COE-1, COE-2, and COE-3 groups intramuscularly. During this study, growth performance, morbidity, and mortality rates of each study group were recorded. The antibody titer against NDV was determined on days 7, 14, 21, 28, and 35. The levels of immunoglobulins (IgY and IgM) were also determined on the 7th, 14th, and 21st days post-sheep red blood cells (SRBCs) inoculation. On day 33, avian tuberculin was injected between the 1st and 2nd toes of the left side (intradermally) to measure lymphoproliferative responses. On day 35, the phagocytic activity in the blood was assessed through a carbon clearance assay by injecting carbon black ink into the right-wing vein. The visceral organs having gross lesions were also collected for histopathology. Results: The COE significantly improved the growth performance, and lowered the morbidity and mortality rates of broilers. There was a significant rise in antibody titers against NDV and levels of IgY and IgM antibodies against SRBC in COE-supplemented broilers. The lymphoproliferative response and phagocytic activity were also enhanced. Among COEsupplemented groups, the broilers of the COE-3 group showed a significant increase in growth performance and boosted immune defense. Conclusion: Coconut oil extract has the potential to boost the growth performance and immune status of broilers. It can be used effectively as a feed additive and alternative to antibiotics to prevent the spread of infectious poultry pathogens. [ABSTRACT FROM AUTHOR]

Simple Summary: The study evaluated the effects of Rumex nepalensis leaf powder (RNL) as a natural feed additive in broiler chickens. RNL @ 10 g/kg diet improved the body weight gain and feed conversion ratio of broilers. Total serum cholesterol was decreased when RNL was added @ 5 and 10 g/kg diet. Immunity of birds was better as depicted by increase in the serum levels of immunoglobulin G and immunoglobulin M levels in RNL supplemented groups. RNL @ 10 g/kg diet was found effective in enhancing the antioxidant enzyme status of birds in terms of increased serum superoxide dismutase and decreased malondialdehyde levels. Gut health of broilers improved by RNL as recorded by favorable results in cecal microbiology and intestinal histomorphology. Thus, RNL is a promising natural feed additive for improving the growth, immuno-antioxidant status and gut health of broiler chicken. The study investigated the impact of utilizing Rumex nepalensis leaf powder (RNL) as a phytogenic feed additive on performance, blood markers, intestinal microbiology and histomorphology in broiler chicken. One hundred eighty day-old Cobb broiler chicks were randomly divided into four treatment groups having three replicates with fifteen birds each. Four iso-caloric and iso-nitrogenous diets primarily based on maize–soybean were formulated, viz., CN (Control)—fed basal diet only; RNL2.5 (basal diet + 2.5 g/kg RNL); RNL5 (basal diet + 5 g/kg RNL); and RNL10 (basal diet + 10 g/kg RNL). The results revealed a significant (p < 0.05) increase in body weight gain and feed conversion ratio in dietary treatments compared to CN with best values in RNL10 followed by RNL5. The blood markers like glucose, total protein, creatinine, alanine transaminase (ALT) and aspartate transaminase (AST) showed no significance (p > 0.05) among all the treatments, however total cholesterol significantly (p < 0.05) decreased in RNL5 and RNL10 as against CN. Regarding immune parameters, immunoglobulin G (IgG) and immunoglobulin M (IgM) levels significantly (p < 0.05) enhanced in RNL5 and RNL10. Antioxidant enzyme status showed that superoxide dismutase (SOD) increased and malondialdehyde (MDA) decreased significantly (p < 0.05) in RNL10 compared to CN. Gut health in terms of cecal microbiology and histomorphology of duodenum and jejunum were altered by inclusion of RNL in the broiler diet. A significant decrease (p < 0.05) in coliform count was recorded by incorporation of dietary treatments with highest reduction in RNL10. Lactobacillus count and total viable count did not vary significantly (p > 0.05) among dietary treatments and CN. Duodenal and jejunal villus height and villus height/crypt depth ratio were significantly (p < 0.05) increased in RNL5 and RNL10 compared to RNL2.5 and CN. Thus, it could be concluded that inclusion of Rumex nepalensis leaf powder in the diet resulted in improved performance and better immuno-antioxidant status of broilers. Further, an improvement in the gut health was observed in terms of positive effects on cecal microbiota and intestinal histomorphology of broiler chickens. [ABSTRACT FROM AUTHOR]

Streptococcus suis (S. suis) is one of the most important porcine pathogens, causing severe pathologies such as meningitis or polyarthritis. It is also a very successful colonizer of mucosal surfaces. The IgM-degrading enzyme of S. suis (IdeSsuis) specifically cleaves porcine IgM, which results in complement evasion. On the basis of our previous finding that IdeSsuis also cleaves the IgM B cell receptor in vitro, we verified IgM B cell receptor cleavage ex vivo in whole regional lymph nodes and investigated the working hypothesis that this IgM B cell receptor cleavage results in a long-lasting impaired B cell function. The number of IgM-secreting cells was determined via ELISpot analysis after porcine peripheral blood mononuclear cells had initially been treated with different recombinant S. suis proteins and subsequently stimulated with interleukin-2 and the toll-like receptor 7/8 ligand R848. Compared with treatment with medium or recombinant muramidase-released protein, treatment with rIdeSsuis but also with a cleavage-deficient variant led to a reduction in the number of IgM-secreting cells as well as the level of secreted IgM. Flow cytometry analysis confirmed that the IgM B cell receptor was cleaved only by rIdeSsuis, and the receptor recovered to pretreatment levels on day 2 after treatment. Flow cytometry analysis of B and T cells incubated with fluorescein-labelled recombinant proteins revealed that different rIdeSsuis variants bind specifically to B cells, most prominently the cleavage-deficient variant. Our results indicate that in vitro interference of rIdeSsuis with the IgM B cell receptor results in long-lasting impaired IgM secretion by B cells after toll-like receptor activation. Further studies are warranted to prove that the modulation of B cell function by IdeSsuis could play a role in vivo. [ABSTRACT FROM AUTHOR]

COVID‐19 serological tests complement the molecular diagnostics and can be used as important tool for serosurveillance and vaccine efficiency evaluation. The aim of this study was to develop and evaluate the diagnostic performance of an in‐house ELISA for retrospective serosurveillance of SARS‐CoV‐2. Total IgG and IgM levels in sera of PCR positive SARS‐CoV‐2 patients (n = 50) from North Colombo Teaching Hospital were evaluated and compared with sera (n = 50) collected from prepandemic healthy individuals as controls. Patient sample collection was initiated before vaccination programme was widely started within the country. Seropositivity of 94.0% (n = 47/50) was observed for either IgG or IgM anti‐SARS‐CoV‐2 antibodies against receptor binding domain of spike protein or nucleocapsid protein in confirmed cases while none of controls were seropositive. In contrast, the seropositivity of only 48.0% (n = 24/50) was demonstrated with commercial ELISA kits for detection of IgG or IgM. All samples detected seropositive by commercially available kits remained seropositive with either in‐house IgM or IgG ELISA. Significant correlations (p ≤ 0.001) were observed between Ab levels and day of sampling from the onset of illness. The overall sensitivity values of the in‐house assays were 66.7%, 96.9%, and 100.0% for the first, second, and third week or longer after onset of symptoms for either in‐house IgM or IgG ELISAs. Majority of the patients (>80.0%) were seropositive, regardless of age (<60 vs. >60 years), gender (male vs. female), or clinical severity (mild vs. moderate/severe). These data suggest that the developed in‐house ELISAs can be applied to assess anti‐SARS‐CoV‐2 antibody levels induced by either natural infections or vaccination. [ABSTRACT FROM AUTHOR]

A core component of every blood program is the supply of safe blood and blood products. The elevated risk of transmission through these products is due to parvovirus B19 (B19V) resistance to the virus inactivation procedures. Our study aimed to screen asymptomatic blood donors for B19V at a tertiary care hospital in Chennai, Tamil Nadu, between September 2020 and June 2021. Sera from 106 healthy blood donors who tested negative for Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV), syphilis, and malaria were tested for anti-B19V IgM and IgG using a qualitative indirect enzyme-linked immunosorbent assay (ELISA). In the study population, 23.5% (n = 25) of donors tested IgM positive, 38.6% (n = 41) tested IgG positive, and 7.5% (n = 8) tested positive for both IgM and IgG. A proportion of 61.3% (n = 65) of the blood donors tested IgG negative, suggesting they had no past B19V infection. B19V DNA was not detected in any of the subjects. The high seroprevalence of IgM indicates that blood donors may have been recently exposed to B19V, potentially posing a risk to immunocompromised individuals and those with hematological stress. Further longitudinal studies with a larger sample size are recommended to better understand the risk of B19V transfusion transmission. [ABSTRACT FROM AUTHOR]