A Method for Analysis of Oxidized Phospholipids from Biological Samples Using Mass Spectrometry.

Oxidized phospholipids (oxPLs) are generated during innate immunity and inflammation, where they play a variety of biological roles, including regulation of autoimmunity and coagulation. Some are generated by enzymatic reactions, leading to stereo- and regiospecificity, while many others can be formed through nonenzymatic oxidation and truncation and can be used as biomarkers of oxidative stress. Mass spectrometry methods have been developed over many years for oxPL analysis, which can provide robust estimations of molecular species and amounts, where standards are available. Here we present a method used for the analysis of enzymatically-generated oxPL (eoxPL), which allows quantification of mono-hydroxy oxylipin-containing species. We also show profiling of many other partially characterized structures in tissue samples and provide typical chromatograms obtained.

Identifying Putative Biomarkers of Foodborne Pathogens Using a Metabolomic Approach.

Metabolomics is the study of low molecular weight biochemical molecules (typically <1500 Da) in a defined biological organism or system. In case of food systems, the term "food metabolomics" is often used. Food metabolomics has been widely explored and applied in various fields including food analysis, food intake, food traceability, and food safety. Food safety applications focusing on the identification of pathogen-specific biomarkers have been promising. This chapter describes a nontargeted metabolite profiling workflow using gas chromatography coupled with mass spectrometry (GC-MS) for characterizing three globally important foodborne pathogens, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica, from selective enrichment liquid culture media. The workflow involves a detailed description of food spiking experiments followed by procedures for the extraction of polar metabolites from media, the analysis of the extracts using GC-MS, and finally chemometric data analysis using univariate and multivariate statistical tools to identify potential pathogen-specific biomarkers.

Dual excitation channel ratiometric fluorescent probes for visual and fluorescent detection of anthrax spore biomarker and tetracycline hydrochloride.

Long-term and excessive use of tetracycline hydrochloride (TC) can lead to its accumulation in the environment, which can cause water contamination, bacterial resistance, and food safety problems. 2,6-Pyridine dicarboxylic acid (DPA) is a major biomarker of Bacillus anthracis spores, and its rapid and sensitive detection is of great significance for disease prevention and counter-terrorism. A bifunctional ratiometric fluorescent nanoprobe has been fabricated to detect DPA and TC. 3,5-dicarboxyphenylboronic acid (BOP) was intercalated into layered europium hydroxide (LEuH) by the ion-exchange method and exfoliated into nanosheets as a fluorescent nanoprobe (PNP). DPA and TC could significantly enhance the red fluorescence of Eu3+ through the antenna effect under different excitation wavelengths, while the fluorescence of BOP can be used as a reference based on the constant emission intensity, realizing ratiometric detection. A low limit of detection (LOD) for the target (DPA: 9.7 nM, TC: 21.9 nM) can be achieved. In addition, visual detection of DPA and TC was realized using color recognition software based on the obvious color changes. This is the first ratiometric fluorescent nanoprobe based on layered rare-earth hydroxide (LRH) for the detection of DPA and TC simultaneously, which opens new ideas in the design of multifunctional probes.

Advances in Chiral Metabolomic Profiling and Biomarker Discovery.

Chiral metabolomics entails the enantioselective measurement of the metabolome present in a biological system. Over recent years, it has garnered significant interest for its potential in discovering disease biomarkers and aiding clinical diagnostics. D-Amino acids and D-hydroxy acids, traditionally overlooked as unnatural, are now emerging as novel signaling molecules and potential biomarkers for a range of metabolic disorders, brain diseases, kidney disease, diabetes, and cancer. Despite their significance, simultaneous measurements of multiple classes of chiral metabolites in a biological system remain challenging. Hence, limited information is available regarding the metabolic pathways responsible for synthesizing D-amino/hydroxy acid and their associated pathophysiological mechanisms in various diseases. Capitalizing on recent advancements in sensitive analytical techniques, researchers have developed various targeted chiral metabolomic methods for the analysis of chiral biomarkers. Here, we highlight the pivotal role of chiral metabolic profiling studies in disease diagnosis, prognosis, and therapeutic interventions. Furthermore, we describe cutting-edge chromatographic and mass spectrometry methods that enable enantioselective analysis of chiral metabolites. These advanced techniques are instrumental in unraveling the complexities of disease biomarkers, contributing to the ongoing efforts in disease biomarker discovery.

A smartphone-based multichannel magnetoelastic immunosensor for acute aortic dissection supplementary diagnosis.

Some biomarkers of acute aortic dissection (AAD) can be used for the potential supplementary diagnosis of AAD, such as C-reactive protein (CRP), smooth muscle myosin heavy chain (SmMHC), and D-dimer (D-D). However, the current measurement methods for common markers primarily rely on sophisticated instruments. The operation process is complicated, and the reagents used are expensive. To provide chronic disease monitoring and home self-examination services for potential AAD patients in real time, we developed a smartphone-based multichannel magnetoelastic (ME) immunosensing device to detect protein levels. Our immunosensor reduced the aforementioned restrictions and demonstrated excellent performance for the supplementary diagnosis of AAD. In this paper, we successfully combined the intelligent terminal with the hardware system to sample the resonance frequency shift (RFS) on the multichannel ME immunosensor. According to the target detection objects with their respective antibodies in the immune binding response, multiple experiments were conducted to detect multiple groups of samples, and we found that a CRP concentration, a SmMHC concentration, and a D-D concentration in the range of 0.1-100µg/mL, 1-4ng/mL, and 0.25-5µg/mL were linearly proportional to the RFS of the ME immunosensor, respectively. For CRP, SmMHC, and D-D, the sensitivities were 13.37Hz/µg∙mL-1, 155.19Hz/ng∙mL-1, and 332.72Hz/µg∙mL-1, respectively, and the detection limits were 2.634×10-3µg/mL, 1.155×10-2ng/mL, and 3.687×10-3µg/mL, respectively. The experiments demonstrated that the accuracy and stability of our device were comparable to those of the vector network analyzer (VNA, Calibration instrument).

Lanthanide MOF-based luminescent sensor array for detection and identification of contaminants in water and biomarkers.

In today's society, heavy metal ions and antibiotic contaminants have caused great harm to water systems and human health. In this study, six isostructural lanthanide metal-organic frameworks [Ln(H3imda)2(TPA)(H2O)2](Tb for CUST-881, Eu for CUST-882, Dy for CUST-883, Er for CUST-884, Nd for CUST-885, Sm for CUST-886) were constructed by selecting terephthalic acid (TPA) and 4,5-Imidazoledicarboxylic acid (H3imda) and lanthanide metal ions via solvethermal method. Among them, CUST-881 and CUST-882 can selectively detect Fe3+, Cr2O72-, CrO42, and ceftriaxone sodium (CRO) in water systems and uric acid in urine. CUST-881 shows very low detection limits for these five substances. Furthermore, Principal Component Analysis (PCA) was used to distinguish Fe3+, Cr2O72-, CrO42-, and CRO in water. To our knowledge, this is the first time that they have been able to be simultaneously distinguished. In addition, the possible sensing mechanism was studied through UV-visible spectroscopy, Infrared spectroscopy, and PXRD analysis. Furthermore, the probe also showed satisfactory repeatability and recovery when applied to UA samples that simulated urine. Based on the above results, lanthanide metal-organic frameworks have great potential for practical monitoring of contaminants in water environments.

Recent advances in receptor-based optical biosensors for the detection of multiplex biomarkers.

Multiplex biosensors are highly sought-after tools in disease diagnosis. This technique involves the simultaneous sensing of multiple biomarkers, whose levels and ratios can provide a more comprehensive assessment of disease conditions compared to single biomarker detection. In most diseases like cancer due to its complexity, several biomarkers are involved in their occurrence. On the other hand, a single biomarker may be implicated in various diseases. Multiplex sensing employs various techniques, such as optical, electrochemical, and electrochemiluminescence methods. This comprehensive review focuses on optical multiplex sensing techniques, including surface plasmon resonance, localized surface plasmon resonance, fluorescence resonance energy transfer, chemiluminescence, surface-enhanced Raman spectroscopy, and photonic crystal sensors. The review delves into their mechanisms, materials utilized, and strategies for biomarker detection.

Efficacy of proinflamatory cytokines in the clinical and radiograpic outcomes of different primary molar pulpotomy agents: a comperative randomised study featuring a novel biomarker for pulpal diagnosis.

BACKGROUND: While the effect of biomaterials covering the pulp tissue is considered in the success of pulpotomy treatment, the level of pulpal inflammation is still very important for treatment success. The aim of this study was to compare IL-6 and IL-8 levels, known as good indicators of pulpal inflammation, with a new biomarker, presepsin, and to evaluate the impact of biomarker levels along with the pulp capping agents used in the treatment on the one-year success of pulpotomy treatment. METHODS: The study included 120 primary second molar teeth with pulpotomy indications from 75 children. To determine the pulpal inflammation status, pulpal bleeding samples were taken during treatment, and the levels of IL-6, IL-8, and presepsin were measured. During the pulpotomy treatment, MTA, NeoMTA™, and Biodentine™, and ZOE were randomly applied to groups of thirty teeth each. Patients were monitored for a period of 12 months post-treatment. RESULTS: IL-8, IL-6, and presepsin levels were significantly higher in teeth with pathology (p < 0.001). Biomarker levels were found to be higher in the NeoMTA and Biodentine groups, but this did not result in a statistically significant difference. (p > 0.05) Following pulpotomy treatment, the most successful material groups in order were MTA, ZOE, NeoMTA™, and Biodentine™. CONCLUSION: Presepsin may be a usable indicator in predicting the level of inflammation. At the end of the one-year follow-up of pulpotomy treatment, more pathology was observed in the NeoMTA and Biodentine groups, where biomarker levels were higher, while no pathology was found in the MTA group, where biomarker levels were lower. TRIAL REGISTRATION: NCT06398327/ 20,240,503.

Early Diagnosis of Bronchopulmonary Dysplasia with E-Nose: A Pilot Study in Preterm Infants.

Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm and is still associated with increased mortality and morbidity. The great interest lies in identifying early biomarkers that can predict the development of BPD. This pilot study explores the potential of e-nose for the early identification of BPD risk in premature infants by analyzing volatile organic compounds (VOCs) in the exhaled breath condensate (EBC). Fourteen mechanically ventilated very preterm infants were included in this study. The clinical parameters and EBC were collected within the first 24 h of life. The discriminative ability of breath prints between preterms who did and did not develop BPD was investigated using pattern recognition, a machine learning algorithm, and standard statistical methods. We found that e-nose probes can significantly predict the outcome of "no-BPD" vs. "BPD". Specifically, a subset of probes (S18, S24, S14, and S6) were found to be significantly predictive, with an AUC of 0.87, 0.89, 0.82, 0.8, and p = 0.019, 0.009, 0.043, 0.047, respectively. The e-nose is an easy-to-use, handheld, non-invasive electronic device that quickly samples breath. Our preliminary study has shown that it has the potential for early prediction of BPD in preterms.

Preliminary Assessment of Galectin-3 Expression in Serum and Follicular Fluid: Implications for Predicting In Vitro Fertilization Outcomes.

BACKGROUND: Galactin-3 has been found to be involved in oocyte maturation, folliculogenesis, implantation, and placentation. The expression of Galactin-3 in the endometrium of women who have successfully undergone in vitro fertilization (IVF) has been suggested as a potential biomarker for predicting successful embryo implantation. OBJECTIVES: To evaluate the expression of Galactin-3 in the sera and follicular fluid of women during IVF cycles. METHODS: This prospective research included 21 women undergoing IVF treatments. Blood samples were taken at four points: day 2 before starting stimulation, trigger day, day of oocyte retrieval, and day of the ß-human chorionic gonadotropin level test. In addition, follicular fluid samples were taken on the day of oocyte retrieval. Galactin-3 protein levels were measured in serum and follicular fluid using enzyme-linked immunosorbent assay. RESULTS: Galactin-3 levels on the stimulation day were positively correlated to estradiol levels on the day of the trigger (0.59, P = 0.02). Among women who achieved pregnancy compared to those who did not, Galectin-3 serum levels were higher on the day of the trigger (17.93 ± 4.35 ng/ml vs. 11.01 ± 3.73 ng/ml, P = 0.015). CONCLUSIONS: These findings may imply a potential role of Galectin-3 on the success of IVF treatments, underscoring the potential importance of inflammatory processes in fertility.

Increased CD14+HLA-DR-/low myeloid-derived suppressor cells can be regarded as a biomarker on disease severity and response to therapy in acute coronary syndrome.

Purpose: This study aimed to investigate the dynamic changes in monocytic myeloid-derived suppressor cells (M-MDSCs) and their implications in the pathogenesis of acute coronary syndrome (ACS), shedding light on potential therapeutic targets. Experimental Design: Peripheral blood samples were collected from 68 ACS patients, 35 stable angina pectoris (SAP) patients, and 30 healthy controls (HC). Multi-parameter flow cytometry was employed for analysis of M-MDSCs, explored with disease characteristics and progression. Results: ACS patients exhibited an increased frequency of circulating M-MDSCs compared to SAP patients and HC. M-MDSCs levels demonstrated associations with ACS type, coronary artery lesions, multi-vessel disease, and cardiac dysfunction severity. Higher M-MDSCs levels were found in obese patients. Notably, therapy led to a significant decrease in M-MDSCs frequency. Furthermore, ACS patients exhibited elevated levels of interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in the cytokine profile associated with M-MDSCs. Increased expression of arginase-1(Arg-1) was observed in ACS patients, with positive correlations between M-MDSCs levels and IL-6, GM-CSF, and Arg-1 expression. The diagnostic performance of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and M-MDSCs levels varied in predicting the severity of coronary artery stenosis, with TG showing higher specificity, HDL-C displaying higher sensitivity, and M-MDSCs levels demonstrating balanced sensitivity and specificity. Conclusions: Assessment of M-MDSCs frequency holds promise as a predictive marker for disease progression and therapy response of coronary artery stenosis. The elevated presence of M-MDSCs suggests their potential role in modulating ACS-related inflammation.

Oxidative damage biomarkers and antioxidant enzymes in saliva of patients with peri-implant diseases.

OBJECTIVES: 8-hydroxydeoxyguanosine (8-OHdG) and Malondialdehyde (MDA) are commonly used as markers to evaluate oxidative DNA and Lipid damage in disorders including chronic inflammatory diseases. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) protect tissues against oxidative injury from free oxygen radicals generated by various metabolic processes. The aim of this study was to evaluate 8-OHdG and MDA levels, and SOD and GPx activities in whole saliva of patients with peri-implant diseases. MATERIALS AND METHODS: A cross-sectional study was conducted on a sum of 60 age gender balanced; peri-implantitis (n = 20), peri-mucositis (n = 20) and healthy (n = 20) individuals. Unstimulated whole saliva samples were collected and to determine the clinical condition of each subject; the plaque index (PI), gingival index (GI), peri-implant probing pocket depth (PIPD), peri-implant presence of bleeding on probing (BOP) (with/without suppuration) and radiographic signs of crestal bone loss (BL) were measured. The salivary 8-OHdG level was measured using the ELISA method. SOD, GPx activities and MDA levels were determined spectrophotometrically. RESULTS: A total of 60 individuals had evaluations of 318 implants. In comparison to the peri-mucositis and peri-implantitis groups, the healthy group had significantly lower PI and GI scores (p < 0.001). The PIPD value differed amongst the groups, with the peri-implantitis group having the highest value (p < 0.001). Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher BL score (p < 0.001 and p < 0.001, respectively). The peri-implantitis group showed a significantly higher 8-OHdG level (p < 0.001; p < 0.001 respectively) than the peri-mucositis and control groups. Compared to the peri-mucositis and control groups, the peri-implantitis group had a significantly higher MDA level (p < 0.001 and p < 0.001, respectively). The peri-implantitis group had a significantly higher SOD level (p < 0.001 and p < 0.001, respectively) in comparison to the peri-mucositis and control groups. There was no significant difference in GPx levels between the peri-mucositis and control groups (p > 0.05), while the peri-implantitis group had significantly lower GPx levels than the peri-mucositis and control groups (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Elevated levels of oxidative stress in saliva may indicate the onset of pathological bone loss surrounding the implant and may be an indication of peri-implantitis. CLINICAL RELEVANCE: In peri-implant diseases, changes may occur in the levels of 8-OHdG, MDA, SOD and GPx in saliva, which may lead to a deterioration in the oxidant/antioxidant balance.

Denture microbiome shift and changes of salivary inflammatory markers following insertion of 3D printed removable partial PMMA denture: a pilot study.

BACKGROUND: The aim of this study was to investigate the microbiome shift of denture biofilm formation, the incidence of Candida and changes of salivary inflammatory markers following insertion of 3-dimensional printed PMMA denture. METHODS: This was a pilot study of 6 patients provided with 3D printed (test group) or conventionally heat-cured (control group) removable partial acrylic dentures followed up for 6 weeks. 3 denture swabs were collected at week 1, 3 and 6; and saliva samples were collected at baseline, week 1, 3 and 6 following denture insertion. Microbial DNA was isolated, and the 16S rRNA gene was amplified and sequenced to assess the denture microbiota. The presence of Candida was determined using PCR assay. The levels of salivary biomarkers lactoferrin (LTF) and histatin (HTN) were determined using ELISA. RESULTS: Denture microbiome of both groups exhibited similar microbial compositions at weeks 1, 3 and 6. However, the percentage of Streptococcus in the test group was significantly lower at week 1 (p < 0.05). Greater bacterial diversity was detected in the test group (p < 0.05; pairwise Wilcoxon) after 6 weeks. The presence of Candida was only detected in one sample of the 3D printed denture (test group) after 6 weeks. The level of LTF biomarkers increased in both groups after 6 weeks, however, the level of HTN increased only in the control group. CONCLUSIONS: Denture microbiome of both groups demonstrated similar microbial compositions. After 6 weeks, 3D printed denture demonstrated higher diversity with delayed microbiome shift compared to conventional heat cure dentures. 3D printed denture may be a viable alternative to conventional denture and it has a potential to delay microbial dysbiosis. CLINICAL RELEVANCE: Among wearers, 3D printed denture can potentially reduce the risk of denture stomatitis. A greater diversity may delay or slow the transition of denture microbiome to dysbiosis.

Clinical Significance of Faecal Calprotectin in Differentiating Inflammatory Bowel Disease from Irritable Bowel Syndrome.

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract with relapsing and remitting course. Recurrent abdominal pain and discomfort in association with abnormal defecation in the absence of structural abnormality of the gut is the key feature of irritable bowel syndrome (IBS). Faecal biomarker may be used a precise tool in the differentiation of IBD and IBS. The aim of this study was to measure faecal calprotectin (FC) in patients with IBD and IBS and compare between them. This was a cross-sectional study done in the department of Gastroenterology, BSMMU, Bangladesh from May 2017 to August 2018. IBD patients were diagnosed on the basis of compatible history, clinical examination, laboratory, radiological and endoscopic findings. IBS patients were selected by using the Rome IV criteria. Quantitative faecal calprotectin ELISA (BUHLMANN Quantum Blue) test was done and compared between IBD and IBS patients. In this study, ninety (90) patients were enrolled, 45 patients with IBD and 45 patients with IBS. Mean age of the IBD patients was 32.24±9.76 years and IBS patients was 33.80±9.70 years. There were 28(62.2%) male and 17(37.8%) female patients with IBD and 30(66.7%) male and 15(33.3%) female patients with IBS. We found faecal calprotectin (FC) level was 445.68±237.35µg/gm in IBD patients and 39.16±17.31µg/gm in IBS patients. There was a significant difference of faecal calprotectin level between IBD and IBS patients (p-value <0.001). The sensitivity and specificity of faecal calprotectin to differentiate IBD from IBS was 91.1% and 86.7% respectively. The test accuracy was 88.9%. Area under ROC was 0.959 (95% CI, 0.909 to 1.0). This study showed that faecal calprotectin appears to be clinically useful, non-invasive, rapid and reliable marker to differentiate IBD from IBS.

Higher hair cortisol levels associated with previous cardiovascular events and cardiovascular risks in a large cross-sectional population study.

BACKGROUND: Stress is today a common feature of patients seeking medical care and a growing public health issue in society. A method has been developed to measure biological chronic stress by Hair Cortisol Concentrations (HCC). This biomarker, for chronic stress, captures information about cumulative cortisol levels over the course of several months. Long-term stress might be one of the factors contributing to the onset of cardiovascular conditions and also affecting different risk factors. The aim of this study was to analyse the association between Hair Cortisol Concentrations and previous cardiovascular diseases and cardiovascular risk factors. METHODS: The method of measuring chronic stress by Hair Cortisol Concentration was applied in a large Swedish national observational cross-sectional study. A population-based random sample of N = 4,821 Swedish middle-aged men and women was analysed for hair cortisol levels in relation to diagnosed previous cardiovascular diseases and biologically measured cardiovascular risk factors. RESULTS: Long-term stress, measured by hair cortisol, was significantly associated with the classical cardiovascular risk factors hypertension and high cholesterol, but not smoking. Those with elevated HCC levels also had a significantly increased pre-history of myocardial infarction, type 2 diabetes, atrial fibrillation and by-pass surgery, but not regarding stroke, angina pectoris or sleep apnoea. Higher HCC was significantly associated (p < 0.001) with Body mass index and waist circumference, but only for females. HCC was also associated with the risk markers leukocytes, and high-sensitivity CRP, indicating a possible linkage between HCC and inflammation and hypothetically also the bodily immune defense. No association was found between perceived stress and HCC. CONCLUSIONS: An overall conclusion of our results is that health care should put more emphasis on patients reporting that they have been exposed to long term stress. Altogether, these analyses of Hair cortisol levels in a large middle-aged population show that chronically elevated cortisol levels represent a relevant and significant factor associated with cardiovascular diseases and classical cardiovascular risk factors.

Oral glucose tolerance test curve shape in Mexican children and adolescents with and without obesity.

OBJECTIVES: Mexican children with obesity are at a higher risk of developing type 2 diabetes mellitus (T2DM). The aim of the study was to compare oral glucose tolerance test (OGTT) characteristics: time of peak glucose, glucose level ≥155 mg/dL at 1 h, presence of metabolic syndrome (MetS), sensitivity, secretion, and oral disposition index (oDI) in children with and without obesity, according to oral glucose tolerance curve shape: monophasic or biphasic. METHODS: Cross-sectional study including 143 children. Groups were divided into (a) obese: biphasic (B-Ob) (n=55) and monophasic (M-Ob) (n=50), (b) without obesity: biphasic (B-NonOb) (n=20) and monophasic (M-NonOb) (n=18). RESULTS: Late glucose peak was more frequent in the M-Ob group (p<0.001). Glucose levels ≥155 mg/dL and MetS were more frequent in the M-Ob group but did not show significance. The groups with obesity (biphasic and monophasic) had higher indices of insulin resistance and insulin secretion compared to the nonobese groups (biphasic and monophasic) (p<0.001). AUC glucose was higher in the M-Ob group (p<0.05), and AUC insulin was higher in the M-NonOb group. oDI (Matsuda) was significantly lower in the M-Ob group compared to the other groups (p<0.001), and oDI-HOMA IR was higher in M-NonOb group (p=0.03). CONCLUSIONS: All OGTT parameters could help to identify Mexican children at increased risk of developing T2DM, not only fasting plasma glucose and 2 h glucose. M-Ob in non-T2DM Mexican children reflects an early defect in glucose metabolism. Higher level of IR indexes in M-NonOb vs. B-NonOb could indicate an increased risk for T2DM of genetic origin.

Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study.

INTRODUCTION: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier for better disease control. We aim to validate and recalibrate commonly used patient-reported symptom scores combined with a faecal calprotectin (FC) home test as non-invasive diagnostic tool for remote monitoring of IBD, both in daily practice and in a strict trial setting. Endoscopy will be used as the gold standard. METHODS AND ANALYSIS: In this multicentre prospective validation study, adult IBD patients are asked to fill out questionnaires regarding disease activity (Monitor IBD At Home, mobile Health Index, Manitoba IBD Index, IBD control and patient-HBI/patient-Simple Clinical Colitis Activity Index), perform a FC home test and collect a stool sample for routine laboratory FC measurement, before the start of the bowel preparation for the ileocolonoscopy. Endoscopic disease activity will be scored according to the simplified endoscopic score for Crohn's disease (CD) for CD patients or Ulcerative Colitis Endoscopic Index for Severity and Mayo Endoscopic Subscore for ulcerative colitis patients. The main study outcome is the diagnostic test accuracy of the various patient-reported scores to assess mucosal inflammation in combination with a FC home test. ETHICS AND DISSEMINATION: This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 03 March 2021 (METC 20-085) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05886322.

Group sequential testing of a treatment effect using a surrogate marker.

The identification of surrogate markers is motivated by their potential to make decisions sooner about a treatment effect. However, few methods have been developed to actually use a surrogate marker to test for a treatment effect in a future study. Most existing methods consider combining surrogate marker and primary outcome information to test for a treatment effect, rely on fully parametric methods where strict parametric assumptions are made about the relationship between the surrogate and the outcome, and/or assume the surrogate marker is measured at only a single time point. Recent work has proposed a nonparametric test for a treatment effect using only surrogate marker information measured at a single time point by borrowing information learned from a prior study where both the surrogate and primary outcome were measured. In this paper, we utilize this nonparametric test and propose group sequential procedures that allow for early stopping of treatment effect testing in a setting where the surrogate marker is measured repeatedly over time. We derive the properties of the correlated surrogate-based nonparametric test statistics at multiple time points and compute stopping boundaries that allow for early stopping for a significant treatment effect, or for futility. We examine the performance of our proposed test using a simulation study and illustrate the method using data from two distinct AIDS clinical trials.

The effect of diets with different inflammatory scores on inflammation and sleep in obese subjects: a randomized controlled trial.

OBJECTIVE: The aim of this study was to investigate the effect of different dietary inflammatory index diets on inflammatory markers, anthropometric measurements, and sleep quality in obese subjects. METHODS: This study was conducted in a public hospital in Turkey between November 2021 and May 2022. Participants with pro-inflammatory dietary habits were included in the study. Randomly divided into two groups of 33 participants, they were subjected to an anti-inflammatory diet or a control diet for 8 weeks. The study evaluated the anthropometric parameters, inflammatory biomarkers, and sleep quality indices of the diet groups. RESULTS: Significant reductions in body mass index were observed in both groups, more marked in the anti-inflammatory diet cohort. C-reactive protein levels, indicative of inflammation, also decreased substantially in both groups, with a more marked reduction in the anti-inflammatory diet cohort. Despite the improvement in sleep quality in both groups, the variation was not statistically significant. CONCLUSION: This study demonstrates the importance of anti-inflammatory diets in nutritional strategies for obesity by reducing body mass index and inflammation.

Caffeine mitigates tamoxifen-induced fatty liver in Wistar rats.

PURPOSE: Tamoxifen, a widely used drug for breast cancer treatment, is associated with adverse effects on the liver, including the development of fatty liver. This study aimed to investigate the potential protective effect of caffeine against tamoxifen-induced fatty liver in Wistar rats. METHODS: Rats were divided into normal control, tamoxifen + saline, and tamoxifen + caffeine. Plasma samples were assessed for biochemical markers related to oxidative stress, inflammation, liver function, and cell damage. Additionally, liver histopathology was examined to quantify the extent of fatty infiltration. RESULTS: In the tamoxifen + saline group, elevated levels of plasma malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT), cytokeratin 18, and soluble ST2 were observed compared to the normal control group, indicating increased oxidative stress, inflammation, and liver injury (p < 0.01). Moreover, histopathological examination revealed a significant increase in fatty infiltration (p < 0.001). However, in the tamoxifen + caffeine group, these markers were markedly reduced (p < 0.05, p < 0.01), and fatty infiltration was significantly mitigated (p < 0.001). CONCLUSIONS: The findings suggest that caffeine administration attenuates tamoxifen-induced fatty liver in rats by ameliorating oxidative stress, inflammation, liver injury, and cell damage. Histopathological evidence further supports the protective role of caffeine. This study highlights the potential of caffeine as a therapeutic intervention to counter tamoxifen-induced hepatic complications, contributing to the optimization of breast cancer treatment strategies.