Kynurenine Pathway Dysregulation and Pain Perception in Acute Pancreatitis: Has the Connection Unraveled?

AIM: Tryptophan (TRP), an essential amino acid, undergoes catabolism through various pathways. Notably, the kynurenine pathway (KP), constituting one of these pathways, exhibits a unidirectional impact on immune response and energy metabolism. Nonetheless, its influence on pain sensation is characterized by biphasic dynamics. This study aims to scrutinize the influence of the KP pathway on pain sensation, particularly within the context of pancreatic inflammation. METHODS: Our prospective case-control study involved individuals diagnosed with acute pancreatitis and a control group matched for gender and age. The patient cohort was subsequently subdivided into severe and non-severe subgroups. To assess metabolites within KP, two blood samples were collected from the patient cohort, one at the time of diagnosis and another during the recovery phase. Furthermore, for pain quantification, daily pain scores utilizing the Visual Analog Scale (VAS) were extracted from the patients' medical records. RESULTS: The study incorporated 30 patients along with an equivalent number of controls. A noticeable distinction was evident between the patient and control groups, characterized by an increase in kynurenine levels and a decrease in the tryptophan/kynurenine ratio. Throughout the process of disease recovery, a uniform decrease was observed in all KP metabolites, excluding 3-Hydroxykynurenine. Elevated levels of Kynurenic acid (KYNA) were correlated with increased pain scores. Critically, no apparent distinctions in KP metabolites were discerned concerning pain severity in patients with comorbidities characterized by neural involvement. CONCLUSION: Based on our results, the kynurenine pathway (KP) is activated in instances of acute pancreatitis. Elevated levels of KYNA were found to be associated with heightened pain scores. The operative stages within the KP responsible for pain modulation are impaired in cases characterized by neuropathy-induced pain sensation.

Do Spiritual Well-Being and Pain Intensity Predict Physical or Mental Components of Health-Related Quality-of-Life Scale in Patients With Multiple Myeloma?

BACKGROUND: Multiple myeloma is a complex disease and supportive care is important for improving quality of life. Management of disease treatment symptoms, bone disease, renal dysfunction, infection, anemia, pain, and coagulation disorder are specific issues. Spirituality, or spiritual well-being, is one of the most fundamental and essential concepts for coping with the difficulties and stress caused by cancer. AIMS: This study explores whether spiritual well-being, pain, and other demographic factors predict the physical and mental components of quality of life in MM subjects. METHODS: This cross-sectional descriptive study was conducted with 92 multiple myeloma patients registered with the Cancer Warriors Association in Turkey. The data were collected using the Personal Information Form, The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale-12, the Numeric Rating Scale for Pain, and the Short Form-12 Health-Related Quality of Life Scale. RESULTS: The mean age of the patients was 54.4 ± 10.7 years. It was found that the mean total pain score in the previous week was 3.9 ± 2.6, while the mean total The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale-12 score was 28.1 ± 9.8. Their mean Short Form-12 total physical component score was 39.1 ± 25.4; whereas the Short Form-12 total mental component score was 45.5 ± 24.8. According to this model, 56.7% of the physical component score was explained by vertebroplasty, The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale-12 total score and subscale of peace and the pain intensity experienced in the previous week. According to multiple linear regression analysis, bone-sparing therapy and FACIT-Sp-12-Total and subscale peace significantly predicted the Mental component score (p < .05). CONCLUSIONS: Cancer pain remains undertreated, and patients with myeloma are no exception. Pain and spiritual well-being scores were significant predictors of physical and mental component scores of quality of life in this group of patients. According to this result, pain-reducing practices should be implemented to improve the quality of life in MM patients and the spiritual needs of the patients should be met.

Comparison of Labsan Tricell-1000 and Dirui FUS-2000 automated urine analyzers with manual microscopy.

Objectives: Urinalysis is a first-line test for screening for urinary tract infection. Several devices performing strip and sediment analysis have been introduced. The aim of this study was to compare the performance of Labsan Tricell-1000 and Dirui FUS-2000 automated urine analyzers with manual microscopy. Methods: 463 urine samples were analyzed. Digital image processing and particle recognition automatically display the cells in a flowing sheath fluid mixed monolayer urine sample, take the pictures of particles via digital camera, analyse these pics with a particle recognition software, transfer images of the formed elements to the screen and allow well-trained personnel to select, reclassify or remove them. Manual microscopy was used for comparison. Results: Agreement between Tricell-100 and manual microscopy was very good for RBC (Ï° = 0.80), and WBC (Ï° = 0.83); good for CaOx (Ï° = 0.69), SEC (Ï° = 0.80), YLC (Ï° = 0.72), HC (0.69) and LC (Ï° = 0.64); moderate for BAC (Ï° = 0.51), APC (Ï° = 0.43) and MT (Ï° = 0.55); fair for GC (Ï° = 0.39) and RTEC (Ï° = 0.32). Conclusions: Labsan Trion TriCell-1000 demonstrated satisfactory performance and can be used in routine urinalysis. In the case of low counts of RBC, presence of yeast, crystal, casts or cell clumping in urine sediment, characterization of urine particles should be performed by manual microscopy.

End-user verification results of two serum separator tubes for clinical chemistry analytes according to CLSI GP34-A and CLSI GP41-A6.

Tube manufacturers use different composition of gels and blood clot activator formulations in serum tube production. Our aim was to investigate the within-tube (repeatability) and between-tube variation, concordance between comparison results of BD and VacuSEL tubes. Blood samples were collected from control subjects (n = 20) and patients (n = 30) in accordance with the CLSI GP41-A6 and CLSI GP34-A guidelines. Twenty-three clinical chemistry parameters were analysed via Roche Cobas C702 Chemistry Analyzer on T0 (0 hour) and T24 (24 hour). Mean differences % were compared with Wilcoxon matched pair test. Clinical significance was evaluated based on desirable bias according to total allowable error (TEa). VacuSEL tubes demonstrated acceptable performance for the results of 20 parameters with regards to desirable bias % limits. Lactate dehydrogenase (LD) [mean difference % (%95 confidence intervals (CI) values of BD and VacuSEL tubes at T0 [6.41% (4.80-8.01%)]; sodium (Na) and total protein (TP) at T24 [-0.27% (-0.46 to -0.07%) and -1.39% (-1.87 to -0.91), respectively] were over the desirable bias limits (LD: 4.3%, Na: 0.23% and TP: 1.36%, respectively) but not exceeding total biological variation CV % [Na: 0.5 (0.0-1.0) % and TP: 2.6 (2.3-2.7) %). %95 confidence intervals (CI) of T0 LD values overlap with within-subject biological variation % (CI) limits (LD: 5.2 (4.9-5.4) %). The differences between two tubes were not medically significant and necessarily conclusive. VacuSEL serum tubes presented comparable performance with BD serum tubes.

Evaluation of Bone Turnover Markers Such as Osteoprotegerin, Sclerostin and Dickkopf-1 in Subclinical Hyperthyroidism.

In this study, it was aimed to assess effects of subclinical hyperthyroidism (SH) on bone metabolism using osteoprotegerin (OPG), sclerostin, Dickkopf-1 (DKK1) and biochemical parameters. This cross-sectional prospective study included 40 patients with SH and 40 euthyroid controls. Serum OPG, sclerostin, DKK-1, type-1 procollagen, C-terminal polypeptide (CTx) and 24-hours urine N-terminal telopeptide (NTx) were measures using ELISA kit. Bone mineral density measurements were performed using dual energy X-ray absorptiometry (DEXA). Risk for 10-years hip and major fracture was estimated by Turkish version of FRAX. No significant difference was detected in age, gender, body mass index, smoking and menopause rates between SH and control groups. The risk for 10-years hip fracture and major osteoporotic fracture were estimated as 4.45% and 0.55% in SH group, respectively. The OPG levels were significantly lower in patients with SH than controls (P = 0.017). No significant difference was detected in other bone formation and degradation parameters. No significant correlation was detected between OPG level and risk for major osteoporotic fracture (P > 0.05); however, a negative correlation was detected between OPG level and risk for hip fracture (rho = 0.233; P = 0.038). Serum OPG is markedly affected in patients with SH. In addition, OPG seemed to be associated with osteoporotic fracture risk. Available data show that SH is significantly associated with risk for fracture; thus, it is important to assess risk for fracture in patients with SH.

Twitter activity surrounding the Finnish green party's cannabis legalisation proposal: A mixed-methods analysis.

Background: In September 2021, a Finnish political party, the Greens, voted to include cannabis policy reform in their party programme, which would legalise the use, possession, manufacture and sale of cannabis. A rapid public discussion has emerged on different social media platforms, including Twitter. Methods: We downloaded 10 days of Twitter data and prepared it for further text analysis, including sentiment, topic modelling and thematic content analysis. Results: Before the proposal, the average daily number of tweets was approximately 140. However, during the week of the proposal, there was a significant increase in tweet volume, reaching a peak of 6,600 tweets on a single day, with a daily average of over 2,700 tweets. Sentiment analysis showed that during the public discussion, the sentiment scores of the tweets were more likely to be positive. Through topic modelling analysis, we obtained the weight of the topic for each tweet, which enabled us to identify the most representative tweets in our corpus. To narrow the sample size for content analysis, we selected tweets that had a topic percentage distribution of over 0.95 (N=188) for closer thematic content analysis. Several positive and negative themes emerged, which were then categorised under broader topics. Similar themes were identified in the most retweeted, liked and commented tweets, which came mainly from known public figures, including politicians, health experts and NGO leaders. Conclusion: Our results show that the discussion was not limited to cannabis legalisation, but instead covered a variety of topics related to drug policy.

Comparison of three chatbots as an assistant for problem-solving in clinical laboratory.

OBJECTIVES: Data generation in clinical settings is ongoing and perpetually increasing. Artificial intelligence (AI) software may help detect data-related errors or facilitate process management. The aim of the present study was to test the extent to which the frequently encountered pre-analytical, analytical, and postanalytical errors in clinical laboratories, and likely clinical diagnoses can be detected through the use of a chatbot. METHODS: A total of 20 case scenarios, 20 multiple-choice, and 20 direct questions related to errors observed in pre-analytical, analytical, and postanalytical processes were developed in English. Difficulty assessment was performed for the 60 questions. Responses by 4 chatbots to the questions were scored in a blinded manner by 3 independent laboratory experts for accuracy, usefulness, and completeness. RESULTS: According to Chi-squared test, accuracy score of ChatGPT-3.5 (54.4 %) was significantly lower than CopyAI (86.7 %) (p=0.0269) and ChatGPT v4.0. (88.9 %) (p=0.0168), respectively in cases. In direct questions, there was no significant difference between ChatGPT-3.5 (67.8 %) and WriteSonic (69.4 %), ChatGPT v4.0. (78.9 %) and CopyAI (73.9 %) (p=0.914, p=0.433 and p=0.675, respectively) accuracy scores. CopyAI (90.6 %) presented significantly better performance compared to ChatGPT-3.5 (62.2 %) (p=0.036) in multiple choice questions. CONCLUSIONS: These applications presented considerable performance to find out the cases and reply to questions. In the future, the use of AI applications is likely to increase in clinical settings if trained and validated by technical and medical experts within a structural framework.

Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by increased release of proinflammatory cytokines that are known to activate the indoleamine 2,3-dioxygenase (IDO-1) enzyme, which catalyzes the rate-limiting step of the kynurenine pathway (KP). This study aimed to measure KP metabolite levels in patients with SLE and investigate the relationship between disease activity, clinical findings, and KP. The study included 100 patients with SLE and 100 healthy controls. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QA) concentrations were measured with tandem mass spectrometry. Serum KYN, KYNA, 3HAA, 3HK, and QA levels of the patients with SLE were significantly higher than the control group. Serum QA levels were elevated in patients with neurological involvement (four patients with peripheral neuropathy and two patients with mononeuropathy), serum KYN levels and KYN/TRP ratio increased in patients with joint involvement, and serum KYN, 3HK, and 3HAA levels and the KYN/TRP ratio were increased in patients with renal involvement. Moreover, KYN and KYN/TRP ratios were positively correlated with the disease activity score. These findings indicated that imbalances in KP metabolites may be associated with the pathogenesis, activation, and clinical manifestations of SLE.

Exploring Political Mistrust in Pandemic Risk Communication: Mixed-Method Study Using Social Media Data Analysis.

BACKGROUND: This research extends prior studies by the Finnish Institute for Health and Welfare on pandemic-related risk perception, concentrating on the role of trust in health authorities and its impact on public health outcomes. OBJECTIVE: The paper aims to investigate variations in trust levels over time and across social media platforms, as well as to further explore 12 subcategories of political mistrust. It seeks to understand the dynamics of political trust, including mistrust accumulation, fluctuations over time, and changes in topic relevance. Additionally, the study aims to compare qualitative research findings with those obtained through computational methods. METHODS: Data were gathered from a large-scale data set consisting of 13,629 Twitter and Facebook posts from 2020 to 2023 related to COVID-19. For analysis, a fine-tuned FinBERT model with an 80% accuracy rate was used for predicting political mistrust. The BERTopic model was also used for superior topic modeling performance. RESULTS: Our preliminary analysis identifies 43 mistrust-related topics categorized into 9 major themes. The most salient topics include COVID-19 mortality, coping strategies, polymerase chain reaction testing, and vaccine efficacy. Discourse related to mistrust in authority is associated with perceptions of disease severity, willingness to adopt health measures, and information-seeking behavior. Our findings highlight that the distinct user engagement mechanisms and platform features of Facebook and Twitter contributed to varying patterns of mistrust and susceptibility to misinformation during the pandemic. CONCLUSIONS: The study highlights the effectiveness of computational methods like natural language processing in managing large-scale engagement and misinformation. It underscores the critical role of trust in health authorities for effective risk communication and public compliance. The findings also emphasize the necessity for transparent communication from authorities, concluding that a holistic approach to public health communication is integral for managing health crises effectively.

Relationship of tryptophan metabolites with the type and severity of multiple sclerosis.

BACKGROUND: Tryptophan is an essential amino acid primarily metabolized by the kynurenine pathway in mammals. Intermediate metabolites emerging in this pathway have been associated with many neurogenerative diseases. This study aimed to compare tryptophan pathway metabolite levels in patients with multiple sclerosis (MS) and healthy controls and reveal the relationship of tryptophan metabolites with disease subtype and the Expanded Disability Status Scale (EDSS) score. METHODS: The study included a total of 80 MS cases [53 with relapsing remitting MS (RRMS) and 27 with secondary progressive MS (SPMS)] and 41 healthy volunteers. The patients with RRMS were further divided into relapse (RRMS-attack) and non-attack (RRMS-stable) groups. Using liquid chromatography mass spectrometry, tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid levels were measured. The serum metabolite levels of the patient and control groups were compared. In addition, the link and relationship between the EDSS score and disease duration of the patients and their plasma tryptophan metabolite levels were examined. RESULTS: The tryptophan level of the patient group was significantly lower than that of the healthy controls (p<0.05). The kynurenine (105.38±65.43), quinolinic acid (10.42±3.56), kynurenine/tryptophan ratio (0.0218±0.019), and quinolinic acid/kynurenic acid ratio (1.7054±0.96141) of the patients with MS were significantly higher compared to the controls (p<0.05). In the receiver operating characteristic analysis of the power of kynurenine/tryptophan and quinolinic acid/kynurenic acid ratios in predicting the disease, both ratios predicted the diagnosis of MS (area under the curve: 0.793 and 0.645, respectively; p<0.05), albeit at low sensitivity and specificity. The parameters were similar between the RRMS-attack and RRMS-stable patient groups (p>0.05). There was also no significant difference between the RRMS and SPMS patient groups in terms of tryptophan metabolites (p>0.05). Lastly, no significant relationship was observed between tryptophan metabolites and MS subtype and the EDSS score. CONCLUSION: Our findings revealed that the kynurenine pathway involved in the tryptophan metabolism differed between the patients with MS and healthy controls, and this difference may be a limited guide in the diagnosis of MS, due to major overlaps in values for MS versus Controls, and is insufficient to determine the disease subtype.