Inflammatory Biomarkers Research Articles

Proliferative vitreoretinopathy and its relationship with inflammatory serum biomarkers.

To analyze if a relationship between levels of inflammatory serum biomarkers and severity of primary proliferative vitreoretinopathy (PVR) exists. A retrospective case-control study. The healthy adult patients with rhegmatogenous retinal detachment and primary PVR were included in the PVR group. For the control group, healthy adults who underwent cataract surgery were included. The grade of PVR was classified according to the Retinal Society Terminology Committee. Blood samples were obtained before surgery, and processed in MYTHIC 18. Measures of interest were neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), the time between the decrease in visual acuity and surgery, PVR grade, type of surgery, final best corrected visual acuity, and rate of re-detachment. Totally 240 patients were included, 120 in each group, 79 (65.8%) and 56 (46.7%) were male in the PVR and control group, respectively. PVR A had greater levels of monocytes (0.28±0.18 vs 0.12±0.32, P=0.002), neutrophils (4.59±1.51 vs 3.92±1.27, P=0.006), and LMR (9.32±4.42 vs 7.43±3.90, P=0.01). PVR B had a greater monocyte count (0.30±0.13 vs 0.12±0.32, P=0.001), and PVR C demonstrated higher levels in monocytes (0.27±0.12 vs 0.12±0.32, P=0.004), neutrophils (4.39±1.13 vs 3.92±1.27, P=0.004), and LMR (9.63±3.24 vs 7.43±3.90, P=0.002) compared to control, respectively. An LMR cut-off value of 9.38 predicted PVR with a sensibility of 54.2% and specificity of 77.5% and NLR cut-off of 1.70 predicted PVR with a sensibility of 62% and specificity of 54.2%. Patients with primary PVR demonstrate greater neutrophil, monocyte, and LMR levels than the control group. Cut-off values obtained from ratios could be useful in a clinical setting when no posterior view of the fundus is possible due to media opacity.

Effects of Some Olive Fruits-Derived Products on Oxidative Stress and Cardiovascular Biomarkers on Experimental Diabetes Mellitus

The aim of this study is to assess the possible effect of olive seed oil (OSO) and destoned and dehydrated olive oil (DDOO), in comparison with extra-virgin olive oil (EVOO), on some cardiovascular biomarkers in an experimental model of diabetes mellitus. Diabetic animals showed evident alterations in biomarkers involved in the evolution of diabetic vasculopathy, marked by increases in biomarkers that favor vascular damage, which was between 1.5 and five times as many as those in non-diabetic animals, and a smaller number of biomarkers that protect against such damage (25–75% less than in healthy controls) was observed. The three oils administered decreased the concentration of biomarkers of vascular damage (35–45% in the serum lipid profile, 15–40% in early biomarkers of vascular inflammation and 20–60% in platelet aggregation and in thromboxane/prostacyclin imbalance). The greatest effect was by the antioxidant, both in the inhibition of lipid peroxidation and in the increase of glutathione. DDOO showed a significantly greater effect on oxidative stress and on thromboxane/prostacyclin imbalance than those shown by OSO and EVOO. This greater effect may possibly be explained by its higher triterpenoid content (913 mg/kg, compared to 113 mg/kg in OSO and 75 mg/kg in EVOO). We conclude, in the light of the results of this study, that these oils meet two basic conditions: they could improve the yield of the olive industry, and they equal, and may even increase, the beneficial effects of EVOO on cardiovascular disease.

Targeted proteomics of cerebrospinal fluid in treatment naïve multiple sclerosis patients identifies immune biomarkers of clinical phenotypes

Multiple sclerosis (MS) is an inflammatory demyelinating disease with heterogeneous clinical presentations and variable long-term disability accumulation. There are currently no standard criteria to accurately predict disease outcomes. In this study we investigated the cross-sectional relationship between disease phenotype and immune-modulating cytokines and chemokines in cerebrospinal fluid (CSF). We analyzed CSF from 20 DMT-naïve MS patients using Olink Proteomics’ Target 96 Inflammation panel and correlated the resulting analytes with respect to (1) disease subtype, (2) patient age and sex, (3) extent of clinical disability, and (4) MRI segmental brain volumes. We found that intrathecal IL-4 correlated with higher Expanded Disability Status Scale (EDSS) scores and longer 25-foot walk times, and CD8A correlated with decreased thalamic volumes and longer 9-hole peg test times. Male sex was associated with higher FGF-19 expression, and Tumefactive MS with elevated CCL4. Several inflammatory markers were correlated with older age at the time of LP. Finally, higher intrathecal IL-33 correlated with increased MS lesion burden and multi-compartment brain atrophy. This study confirms immune heterogeneity underlying CSF profiles in MS, but also identifies several inflammatory protein biomarkers that may be of use for predicting clinical outcomes in future algorithms.

Flexible, Electrochemical Skin-Like Platform for Inflammatory Biomarker Monitoring.

Addressing global challenges in wound management has greatly encouraged the emergence of home diagnosis and monitoring devices. This technological shift has accelerated the development of new skin patch sensors for continuous health monitoring. A key requirement is the creation of flexible platforms capable of mimicking human skin features. Here, for the first time, an innovative, highly adaptable electrochemical biosensor with molecularly imprinted polymers (MIPs) is customized for the detection of the inflammatory biomarker interleukin-6 (IL-6). The 3-electrode gold pattern is geometrically standardized onto a 6µm thick polyimide flexible membrane, an optically transparent, and biocompatible polymeric substrate. Subsequently, a biomimetic sensing layer specifically designed for the detection of IL-6 target is produced on these transducers. The obtained MIP biosensor shows a good linear response within the concentration range 50pgmL-1-50ngmL-1, with a low limit of detection (8pgmL-1). X-ray photoelectron spectroscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy characterizations confirm the modifications of the flexible gold transducer. After optimization, the biosensing device shows remarkable potential in terms of sensitivity, selectivity, and reproducibility. Overall, the integration of a low-cost electrochemical sensor on biocompatible flexible polymers opens the way for a new generation of monitoring tools with higher accuracy, less invasiveness, and greater patient comfort.

Effects of intermittent fasting and caloric restriction on inflammatory biomarkers in individuals with obesity/overweight: A systematic review and meta-analysis of randomized controlled trials.

Obesity is characterized by chronic low-grade inflammation. This study presents an updated systematic review and meta-analysis on the effect of caloric restriction (CR) and intermittent fasting (IF) on plasma inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) in individuals with obesity/overweight compared with unrestricted or ad libitum feeding. PubMed, Web of Science, and SCOPUS databases were searched for randomized controlled trials (RCTs) reporting inflammatory biomarkers after at least 8 weeks of intervention. Standardized mean differences (SMDs) were calculated using a fixed effect model. Heterogeneity was determined using I2 statistics. Sensitivity analysis was conducted using the "leave-one-out" approach. Relatively few RCTs have investigated the effect of IF on inflammatory biomarkers than with CR (6 vs. 15). Analysis of pooled data showed that CR was associated with a significant reduction in CRP with low heterogeneity (SMD -0.15 mg/L [95% CI -0.30 to -0.00], p = 0.04; I2= 0%, p = 0.69) and IL-6 with high heterogeneity (SMD -0.31 pg/mL [95% CI -0.51 to -0.10], p = 0.004; I2= 73%, p = 0.001). IF was associated with a significant decrease in TNF-alpha with moderate heterogeneity (SMD -0.32 pg/mL [95% CI -0.63 to -0.02], p = 0.04; I2= 44%, p = 0.13). No associations were detected between IF and CRP or IL-6 and CR and TNF-alpha. CR may be more effective in reducing chronic low-grade inflammation than IF. However, there were some concerns regarding the included studies' randomization and allocation sequence concealment process.

Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model.

Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body's metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20-30g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30days. In contrast, group 2 (DiNP group), received 50mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P < 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (P < 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death.

Multifaceted neuroprotective approach of Trolox in Alzheimer's disease mouse model: targeting Aβ pathology, neuroinflammation, oxidative stress, and synaptic dysfunction

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. The accumulation of these aggregated proteins causes memory and synaptic dysfunction, neuroinflammation, and oxidative stress. This research study is significant as it aims to assess the neuroprotective properties of vitamin E (VE) analog Trolox in an Aβ1 − 42-induced AD mouse model. Aβ1 − 42 5μL/5min/mouse was injected intracerebroventricularly (i.c.v.) into wild-type adult mice brain to induce AD-like neurotoxicity. For biochemical analysis, Western blotting and confocal microscopy were performed. Remarkably, intraperitoneal (i.p.) treatment of Trolox (30 mg/kg/mouse for 2 weeks) reduced the AD pathology by reducing the expression of Aβ, phosphorylated tau (p-tau), and β-site amyloid precursor protein cleaving enzyme1 (BACE1) in both cortex and hippocampus regions of mice brain. Furthermore, Trolox-treatment decreased neuroinflammation by inhibiting Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (pNF-κB) and interleukin-1β (IL-1β), and other inflammatory biomarkers of glial cells [ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)]. Moreover, Trolox reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (NRF2) and heme oxygenase 1 (HO1). Similarly, Trolox-induced synaptic markers, including synaptosomal associated protein 23 (SNAP23), synaptophysin (SYN), and post-synaptic density protein 95 (PSD-95), and memory functions in AD mice. Our findings could provide a useful and novel strategy for investigating new medications to treat AD-associated neurodegenerative diseases.

Analytical Validation of Cxbladder® Detect, Triage, and Monitor: Assays for Detection and Management of Urothelial Carcinoma

Background: Cxbladder® assays are reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tests incorporating five genetic biomarkers (CDK1, MDK, IGFBP5, HOXA13, and CXCR2) to provide risk stratification for urothelial carcinoma (UC) in patients with hematuria or undergoing surveillance for recurrent disease. This study evaluated the analytical validity of the Cxbladder Detect, Triage, and Monitor assays. Methods: Pre-specified acceptance criteria, including the assays’ fundamental aspects (sample and reagent stability, RNA extraction quality, RT-qPCR linearity, and analytical sensitivity and specificity), accuracy and precision, and reproducibility between laboratories. Results: Cxbladder had an analytical sensitivity of 12.5–31.1 RNA copies/mL urine for the CDK1, MDK, IGFBP5, and HOXA13 UC biomarkers and 68.9 RNA copies/mL for the inflammatory biomarker CXCR2. All the pre-specified analytical criteria were met. Cxbladder had diagnostic sensitivity, specificity, positive predictive value, and negative predictive values of 77%, 94%, 68%, and 96%, respectively, for Detect; 95%, 46%, 20%, and 98% for Triage; and 91%, 39%, 21%, and 96% for Monitor. Cxbladder had high analytical accuracy (≤10.63% inaccuracy across all biomarkers) and good reproducibility (&gt;85% concordance between laboratories). Conclusions: Cxbladder accurately and reproducibly detects UC biomarker expression and can aid clinicians in risk stratification of hematuria patients or those undergoing surveillance for recurrent UC.

Inflammatory protein associations with brain MRI measures: Framingham Offspring Cohort.

Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study. Dementia and stroke-free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross-sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations. Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex-stratified analyses, associations were observed exclusively among males. We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups. Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV. Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV. Higher levels of SCF and TWEAK, were associated with larger TCBV. Significance diminished in models adjusting for CVD risk factors. Associations were observed exclusively in males.

Hematological biomarkers of systemic inflammation in predicting long-term treatment response of temporomandibular disorders

BackgroundChronic systemic inflammation has been proposed as the underlying mechanism of pain chronicity in several pain conditions. In spite of the growing evidence supporting the role of systemic inflammatory markers as a diagnostic tool, their role has not been analyzed in a well-defined group of temporomandibular disorders (TMD) patients until now. This study aimed to investigate the association between various clinical features and comorbidity levels of TMD in relation to hematological markers and seek its association with long-term treatment response.MethodsClinical features and hematological indices including those for systemic inflammation were assessed in TMD patients (n = 154). Examinations were re-done after 6 months of conservative treatment. Patients were divided into pain improved and unimproved groups based on ≥ 2 numeric rating scale improvement in pain intensity at 6 months for final analysis.ResultsThe portion of patients with low lymphocyte-to-monocyte ratio (p = 0.026), total protein (p = 0.014), hemoglobin (p = 0.040), and mean corpuscular hemoglobin concentration (p = 0.042) values showed significant differences according to prognosis groups. Low hemoglobin levels were significantly associated with unfavorable response to long-term treatment (β = 1.706, p = 0.018). High pre-treatment pain intensity (β=-0.682, p < 0.001) and low Graded Chronic Pain Scale (β = 1.620, p = 0.002) could predict significant pain improvement with long-term treatment.ConclusionsHematologic assessment could be considered in addition to clinical examination to better determine long-term prognosis in TMD patients.

Methods for phenotyping adult patients with acute kidney injury: a systematic review.

Acute kidney injury (AKI) is a multifaceted disease characterized by diverse clinical presentations and mechanisms. Advances in artificial intelligence have propelled the identification of AKI subphenotypes, enhancing our capacity to customize treatments and predict disease trajectories. We conducted a systematic review of the literature from 2017 to 2022, focusing on studies that utilized machine learning techniques to identify AKI subphenotypes in adult patients. Data were extracted regarding patient demographics, clustering methodologies, discriminators, and validation efforts from selected studies. The review highlights significant variability in subphenotype identification across different populations. All studies utilized clinical data such as comorbidities and laboratory variables to group patients. Two studies incorporated biomarkers of endothelial activation and inflammation into the clinical data to identify subphenotypes. The primary discriminators were comorbidities and laboratory trajectories. The association of AKI subphenotypes with mortality, renal recovery and treatment response was heterogeneous across studies. The use of diverse clustering techniques contributed to variability, complicating the application of findings across different patient populations. Identifying AKI subphenotypes enables clinicians to better understand and manage individual patient trajectories. Future research should focus on validating these phenotypes in larger, more diverse cohorts to enhance their clinical applicability and support personalized medicine in AKI management.

Dexmedetomidine leads to the amelioration of stress response to surgery

Objectives: To determine the impact of intravenous Dexmedetomidine (Dex) administered perioperatively on stress response markers in patients undergoing ENT surgeries. Methods: This randomized interventional study was conducted at POFs Hospital and NUMS affiliated WMC, Wah Cantt, in collaboration with IIMC Rawalpindi, Pakistan, from October 2021 to April 2022. One hundred patients aged between 15-60 years, after satisfying the inclusion standards were randomly divided into two groups C and D. Group-C (n=50) received normal saline in addition to the standard anesthesia protocol. The intervention Group-D (n=50) was administered 1µg/kg dexmedetomidine hydrochloride intravenously over 10 minutes just before the induction followed 0.5μg/kg/hr as maintenance dose till the end of surgery. Serum inflammatory biomarkers (interleukins-6, TNF-α and cortisol) were measured in blood samples in both groups, taken at 0 (T0), 30 minutes(T1), and two hours (T2) time intervals and analyzed by using Enzyme-linked immunosorbent assay (ELISA). Data was statistically analyzed using SPSS 23. Results: The patients receiving Dex showed marked decrease in serum levels of cortisol, TNF- α and interleukins-6, from 139.73 to10.18, 99.51 to 0.96 and 85.09 to 0.96 respectively. Comparison between C and D groups revealed significant differences (p≤0.05) in these serum biomarkers. Conclusions: In the present study, intravenous Dex suppressed the intraoperative rise in levels of cytokine secretion and enhanced smooth recovery with no incidence of nausea and vomiting. These effects could be attributed to the anti-inflammatory effects of dexmedetomidine. Iranian Registry of Clinical Trials reference: IRCT20230824059251N1. Abbreviation:ENT: Ear, Nose and Throat, BMI: Body Mass Index, MAC: Monitored Cared Anesthesia, ASA: American Society of Anesthesiologists, SPSS: Statistical Package for Social Sciences, SD: Standard Deviation, PONV: Postoperative Nausea and Vomiting, OT: Operation Theater, POFs: Pakistan Ordinance Factories, WMC: Wah Medical College, IIMC: Islamic International Medical College, NUMS: National University of Medical Sciences. doi: https://doi.org/10.12669/pjms.40.9.8792 How to cite this: Ajmal K, Waheed A, Farooqi R, Mansoor Q. Dexmedetomidine leads to the amelioration of stress response to surgery. Pak J Med Sci. 2024;40(9):---------. doi: https://doi.org/10.12669/pjms.40.9.8792 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Role of Zinc Supplementation in Alleviating Inflammatory Biomarkers in Patients Undergoing Hemodialysis: A Randomized Placebo Controlled, Crossover Trial

Background: Chronic kidney disease (CKD), which progresses to end-stage renal disease (ESRD) and requires maintenance hemodialysis (MHD), is a global health issue. Inflammation in MHD patients is associated with increased mortality and cardiovascular events. Zinc, essential for immune function and possessing anti-inflammatory properties, is frequently deficient in these patients and could potentially help mitigate inflammation. Objectives: This study aims to assess the impact of zinc supplementation on inflammatory biomarkers, specifically (CRP) and the neutrophil-to-lymphocyte ratio (NLR), in MHD patients. Methods: In a double-blind, randomized controlled crossover trial conducted at Labafinejad Hospital, Tehran, MHD patients with zinc deficiency were initially allocated to either a zinc supplementation group or a placebo group. After 30 days, the groups were crossed over, with patients initially receiving zinc now receiving a placebo and vice versa. The primary outcome was changes in serum zinc levels, while secondary outcomes focused on CRP and NLR levels. Results: Significant changes in serum zinc levels were observed in both groups from baseline to Month 2 (drug-placebo group: Mean change -15.9±10.33 µg/dL, P &lt; 0.05; placebo-drug group: Mean change -14.70 ± 12.58 µg/dL, P &lt; 0.05). A significant initial reduction in CRP levels at Month 1 (P = 0.045) was not sustained at Month 2 (P = 0.812). No statistically significant changes in NLR were noted. Improvements in quality of life, including reductions in muscle pain and skin dryness, were significant in the drug-placebo group (P &lt; 0.05). Conclusions: Zinc supplementation in MHD patients significantly improved serum zinc levels and initially reduced CRP levels, highlighting its potential role in managing inflammation. Although the impact on NLR was not significant, overall patient outcomes and quality of life showed promising improvements.

PSIV-6 Blood biomarkers of oxidative stress in offspring from dams infected with bovine viral diarrhea virus during late-term gestation

Abstract The objective of this experiment was to examine the impact of dams infected with bovine viral diarrhea virus (BVDV) during late gestation on inflammatory blood biomarkers in their offspring. Fetal infection with BVDV before d 125 to 150 of gestation results in the birth of immunotolerant, persistently infected (PI) calves. Infection of BVDV during late gestation results in transient fetal infections (TI). It was hypothesized that offspring of dams transiently infected with BVDV on d 175 of gestation would have greater inflammatory blood biomarkers than control offspring. Unvaccinated, yearling Hereford heifers (n = 24), seronegative for antibodies to BVDV1 and BVDV2 were bred by artificial insemination with X chromosome-bearing sperm from an Angus sire. On d 175 of pregnancy, heifers were intranasally inoculated with either Dulbecco’s Modified Eagle Medium + 2% horse serum (sham control) or 4.0 log TCID50 noncytopathic type 2 BVDV to generate control and transient infected calves, respectively. All BVDV-inoculated dams seroconverted by d 14 post-inoculation and all sham-inoculated control dams remained seronegative. Twelve, seronegative control heifer calves were born to the control dams, and 11 seropositive (to type 2 BVDV) TI heifer calves were born to BVDV-inoculated dams. All offspring were raised on pasture until weaning. At weaning, all calves were transported to our feedlot research facility, housed in one group feedlot pen, and transitioned to a high-energy concentrate-based diet until reaching an approximate body weight (BW) of 600 kg. Upon arrival, all animals received a standard heifer growth implant containing 200 mg of testosterone propionate and 20 mg of estradiol benzoate, a modified live viral vaccine containing IBR-BRSV-PI3, and were dewormed. Jugular blood samples were obtained every 28 d until harvest (280 d on feed) and analyzed for biomarkers of inflammation. Data were analyzed as a randomized block design with the MIXED procedures of SAS. There was a treatment x time interaction (P &amp;lt; 0.05) for plasma ceruloplasmin and the oxidized form of glutathione. On d 0 and 28 of the feeding period, all biomarkers were similar across treatments. By d 56 of the feeding period, ceruloplasmin (P &amp;lt; 0.03) and the oxidized form of glutathione (P &amp;lt; 0.01), indicators of chronic inflammation, were increased in plasma samples from TI heifers compared with controls. These parameters remained greater in TI heifers compared with controls throughout the feeding period. There were no treatment or treatment x time interactions for plasma interferon (INF)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and haptoglobin. These data suggest that TI heifers may be experiencing a greater level of oxidative stress later in the finishing period. This research was supported by USDA-NIFA Grant #2019-67015-29866.

Salivary Calprotectin Levels and Bone Mineral Density in Post-Menopausal Women With and Without Chronic Periodontitis - An Evaluative Study.

Menopause is a normal developmental stage in a woman's life marking the permanent cessation of menstruation. Periodontitis and osteoporosis are noteworthy health concerns in post-menopausal women. Calprotectin is an inflammatory biomarker for precise diagnosis of periodontal disease. This study was performed to evaluate the variations in salivary calprotectin levels and bone mineral density in post-menopausal women with and without chronic periodontitis. The study included 24 post-menopausal women aged 45-57 years and was divided into group 1 (12 post-menopausal women without chronic periodontitis) and group 2 (12 post-menopausal women with chronic periodontitis). Unstimulated salivary samples, panoramic radiographs and clinical examination were performed. The collected samples were combined with CALPRO antibody with horseradish peroxide (HRP) that results in the formation of antigen-antibody complex. Tetramethylbenzidine (TMB) solution was added that turned blue. Colour change was measured at 450nm. A human ELISA kit was used. Data collected were sent for statistical analysis. There was a statistically significant difference in salivary calprotectin levels between groups 1 and 2 (P = 0.016) and no statistical difference in mean bone mineral density levels between the two groups (P = 0.235). A positive correlation was seen between salivary calprotectin levels and bone mineral density in group 2 (P = 0.013).

Sexual behavior is linked to changes in gut microbiome and systemic inflammation that lead to HIV-1 infection in men who have sex with men

Pathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A. muciniphila, B. caccae, B. fragilis, B. uniformis, Bacteroides spp., Butyricimonas spp., and Odoribacter spp., and a potential increase in the abundance of Dehalobacterium spp. and Methanobrevibacter spp. in stools of MSM with the highest number of sexual partners. These differences in microbiota, together with a reduction in the pairwise correlations among commensal and short-chain fatty acid-producing bacteria with a number of sexual partners, support an increase in gut dysbiosis with the number of sexual partners. These results demonstrate the interconnectedness of sexual behavior, immune response, and microbiota composition, notably among MSM participating in high-risk sexual behaviors.

307 Use of defatted black soldier fly larvae meal (BSFLM) as an alternative and functional ingredient in canine nutrition

Abstract Black soldier fly (Hermetia illucens) larvae meal (BSFLM) is an alternative, sustainable, and nutrient-rich ingredient for pet foods. However, limited information is available on optimal inclusion levels and its functional properties. The objective of the study was to evaluate the effects of incremental levels of BSFLM (15% or 30%) as a partial or full substitute for chicken by-product meal (CM) in extruded diets. Three complete and balanced diets were formulated and extruded: Control, 15% BSFLM, and 30% BSFLM. The effects of the diets on nutrient digestibility, fecal metabolites and microbiota, and serum oxidative stress and inflammatory biomarkers in adult dogs were examined. A complete randomized design was used with adult Beagles (n = 10/treatment). The experimental period lasted 70 d, consisting of a 14-d adaptation to the control diet followed by 56-d test period. Data were analyzed using SAS Proc Mixed 9.4 with P ≤ 0.05 significance. All diets were well-accepted by the dogs; food intake and fecal output were not affected (P &amp;gt; 0.05) by treatment. Apparent total tract digestibility (ATTD) of dry matter, crude protein, and fat did not differ among treatments, whereas ATTD of organic matter (81.2%) and total dietary fiber (18.9%) was less (P &amp;lt; 0.05) for dogs fed 30% BSFLM in contrast with the Control group (83.2% and 30.3%, respectively). Fecal concentrations of total short-chain fatty acids and total phenols were less (P &amp;lt; 0.05) for dogs fed 30% BSFLM relative to dogs fed Control. No treatment effect was observed for serum biomarkers of oxidative stress and inflammation. Fecal microbial diversity differed between Control and 30% BSFLM groups. Overall, extruded diets containing 15% or 30% were well-digested by dogs as demonstrated by similar ATTD coefficients compared with Control. Intrinsic presence of chitin in BSFLM, and other insect-derived ingredients, can behave like insoluble dietary fiber in a food matrix, which would explain the decreased ATTD for organic matter and total dietary fiber, as well as less fecal concentration of total short-chain fatty acids. The inclusion of 30% BSFLM may have decreased protein hindgut fermentation due to less fecal concentration of total phenols. Altogether, the inclusion of 15% BSFLM resulted in similar physiological responses in comparison with dogs fed the Control diet. Greater inclusion levels of BSFLM may impact ATTD, however, it also has the potential to modulate fecal metabolites and microbiota, without negatively affecting fecal microbial richness.

296 Saccharomyces cerevisiae derived postbiotic modulates inflammatory response and gut microbiota in large breed dogs exposed to endurance exercise and transport stress

Abstract Postbiotic supplements have been used in various livestock species to mitigate the negative effects of stress. This study aimed to determine if similar responses are seen in canine companion animals. We evaluated the effects of a Saccharomyces cerevisiae (S. cerevisiae) postbiotic supplement on inflammatory biomarkers, cortisol, and microbiota dysbiosis index in Labrador Retrievers exposed to exercise and transport stress. Dogs [n = 36; 3.52 ± 0.21 yr old and body weight (BW) = 27.6 ± 2.97 kg] were blocked by sex, age, and BW and assigned to receive 1 of 3 daily top-dressed treatments: 1) 15 g ground corn germ (Control, n = 12); 2) 7.5 g S. cerevisiae yeast postbiotic (Low, n = 12); or 3) 15 g of S. cerevisiae yeast postbiotic (High, n = 12). Dogs were given 1 wk to acclimate to treatments before beginning a 7-wk exercise regimen consisting of twice weekly 4.8 km guided runs. Dogs were exposed to a transportation stressor in wk 8. Fecal samples from d 0 and 56 were analyzed for calprotectin, calgranulin C (S100A12), α1-protease inhibitor, immunoglobulin A, and microbiota dysbiosis index. Blood was collected on d 0 and 63 for serum chemistries and complete blood counts. Blood collection was also performed prior to and 18 to 20 h after first and final runs of the exercise regimen for analysis of inflammatory cytokines. The Four Rivers Kennel (FRK) Gait Inflammation Index score was assessed prior to and 24 hours after the first and last exercise runs with the Gait4Dogs pressure mat system. Saliva cortisol was measured before and after transportation. Blood chemistry did not differ among treatments (P ≥ 0.19), but Control dogs had increased eosinophils (P = 0.01) and tended to have increased white blood cells (P = 0.08) and lymphocytes (P = 0.08) compared with dogs receiving postbiotic. Dogs fed Low dose had elevated monocyte chemoattractant protein-1 (P = 0.01) and maintained Interleukin (IL) -8 after the initial run (P = 0.03). Males in the Low group had increased IL-10 (P = 0.02). Fecal biomarkers and microbiota dysbiosis index score did not differ among treatments by d 56 (P ≥ 0.19). Blautia abundance was decreased in High (P = 0.04). Fusobacterium abundance tended to be reduced in High and increased in Control and Low (P = 0.07). Clostridium hiranonis tended to be greater in Low compared with Control (P = 0.07). The FRK Total Gait Inflammation Index scores decreased over time with acclimation to running (P &amp;lt; 0.01). Saliva cortisol concentrations did not differ among treatments (P ≥ 0.20). The Saccharomyces cerevisiae-based postbiotic tested in this study has potential as a functional ingredient to modulate immune function, improve muscle recovery shortly after exercise and positively change diversity of the gut microbiome in canine companion animal diets.

Psoriasis treatment and biologic switching: The association with clinical characteristics and laboratory biomarkers over a 13-year retrospective study.

The advent of biologics has greatly improved patient outcomes, yet some patients are compelled to switch therapies. Predicting these therapeutic failures is important; however, the factors associated with switching biologics have not been fully explored. This study examined patterns and determinants of biologics switching in psoriasis treatment retrospectively over 13 years. We focused on the association between clinical characteristics, basal laboratory data, and frequency of biologics switching. The findings revealed that elevated Psoriasis Area Severity Index scores and the presence of arthritis were observed in patients who experienced two or more treatment switches compared with those without treatment switches. Moreover, neutrophil to lymphocyte ratio was associated with higher biologics switching rates, indicating that systemic inflammation significantly impacts treatment adherence. A treatment approach, taking into account both the clinical presentation and inflammatory biomarkers, may be important for optimizing patient management in psoriasis.

No replicating evidence for anti-amyloid-β autoantibodies in cerebral amyloid angiopathy-related inflammation.

Elevated levels of anti-amyloid-β (anti-Aβ) autoantibodies in cerebrospinal fluid (CSF) have been proposed as a diagnostic biomarker for cerebral amyloid angiopathy-related inflammation (CAA-RI). We aimed to independently validate the immunoassay for quantifying these antibodies and evaluate its diagnostic value for CAA-RI. We replicated the immunoassay to detect CSF anti-Aβ autoantibodies using CSF from CAA-RI patients and non-CAA controls with unrelated disorders and further characterized its performance. Moreover, we conducted a literature review of CAA-RI case reports to investigate neuropathological and CSF evidence of the nature of the inflammatory reaction in CAA-RI. The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (rsp = 0.51, p = 0.02). Assay levels were not elevated in CAA-RI patients (n = 6) compared to non-CAA controls (n = 20; p = 0.64). Literature review indicated only occasional presence of B-lymphocytes and plasma cells (i.e., antibody-producing cells), alongside the abundant presence of activated microglial cells, T-cells, and other monocyte lineage cells. CSF analysis did not convincingly indicate intrathecal IgG production. We were unable to reproduce the reported elevation of anti-Aβ autoantibody concentration in CSF of CAA-RI patients. Our findings instead support nonspecific detection of IgG levels in CSF by the assay. Reviewed CAA-RI case reports suggested a widespread cerebral inflammatory reaction. In conclusion, our findings do not support anti-Aβ autoantibodies as a diagnostic biomarker for CAA-RI.