Peptidoglycan-Targeted [18F]3,3,3-Trifluoro-d-alanine Tracer for Imaging Bacterial Infection.

Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([111In]-WBC SPECT, [18F]FDG PET) techniques are used in clinical practice but lack specificity for the causative microorganisms themselves. To meet this challenge, many groups have developed imaging methods that target pathogen-specific metabolism, including PET tracers integrated into the bacterial cell wall. We have previously reported the d-amino acid derived PET radiotracers d-methyl-[11C]-methionine, d-[3-11C]-alanine, and d-[3-11C]-alanine-d-alanine, which showed robust bacterial accumulation in vitro and in vivo. Given the clinical importance of radionuclide half-life, in the current study, we developed [18F]3,3,3-trifluoro-d-alanine (d-[18F]-CF3-ala), a fluorine-18 labeled tracer. We tested the hypothesis that d-[18F]-CF3-ala would be incorporated into bacterial peptidoglycan given its structural similarity to d-alanine itself. NMR analysis showed that the fluorine-19 parent amino acid d-[19F]-CF3-ala was stable in human and mouse serum. d-[19F]-CF3-ala was also a poor substrate for d-amino acid oxidase, the enzyme largely responsible for mammalian d-amino acid metabolism and a likely contributor to background signals using d-amino acid derived PET tracers. In addition, d-[19F]-CF3-ala showed robust incorporation into Escherichia coli peptidoglycan, as detected by HPLC/mass spectrometry. Based on these promising results, we developed a radiosynthesis of d-[18F]-CF3-ala via displacement of a bromo-precursor with [18F]fluoride followed by chiral stationary phase HPLC. Unexpectedly, the accumulation of d-[18F]-CF3-ala by bacteria in vitro was highest for Gram-negative pathogens in particular E. coli. In a murine model of acute bacterial infection, d-[18F]-CF3-ala could distinguish live from heat-killed E. coli, with low background signals. These results indicate the viability of [18F]-modified d-amino acids for infection imaging and indicate that improved specificity for bacterial metabolism can improve tracer performance.

Pleiotropy, epistasis and the genetic architecture of quantitative traits.

Pleiotropy (whereby one genetic polymorphism affects multiple traits) and epistasis (whereby non-linear interactions between genetic polymorphisms affect the same trait) are fundamental aspects of the genetic architecture of quantitative traits. Recent advances in the ability to characterize the effects of polymorphic variants on molecular and organismal phenotypes in human and model organism populations have revealed the prevalence of pleiotropy and unexpected shared molecular genetic bases among quantitative traits, including diseases. By contrast, epistasis is common between polymorphic loci associated with quantitative traits in model organisms, such that alleles at one locus have different effects in different genetic backgrounds, but is rarely observed for human quantitative traits and common diseases. Here, we review the concepts and recent inferences about pleiotropy and epistasis, and discuss factors that contribute to similarities and differences between the genetic architecture of quantitative traits in model organisms and humans.

Reoperation Following Primary Greater Occipital Nerve Decompression Surgery: Incidence, Risk Factors and Outcomes.

BACKGROUND: Although nerve decompression surgery is an effective treatment for refractory occipital neuralgia (ON), a proportion of patients experience recurrence of pain and undergo reoperation. This study analyzes the incidence, risk factors, and outcomes of reoperation following primary greater occipital nerve (GON) decompression. METHODS: 215 patients who underwent 399 primary GON decompressions were prospectively enrolled. Data included patient demographics, past medical and surgical history, reoperation rates, intraoperative findings, surgical technique, and postoperative outcomes in terms of pain frequency (days/month), duration (hours/day), intensity (scale 0-10), and migraine headache index (MHI). Bivariate analyses, univariable and multivariable logistic regression analysis was performed. RESULTS: 27 (6.8%) GON decompressions required reoperation with neurectomy at a median follow-up time of 15.5 months (9.8-40.5). Cervical spine disorders on imaging that did not warrant surgical intervention (OR, 4.88; 95% 1.61-14.79; p<0.01) and radiofrequency ablation (RFA) (OR, 4.20; 95% CI, 1.45-15.2; p<0.05) were significantly associated with higher rates of reoperation. At 12 months postoperatively, patients who underwent reoperation achieved similar mean reductions in pain frequency, duration, intensity and MHI, as compared to patients who underwent only primary decompression (p>0.05). CONCLUSION: Patients with ON who have a history of cervical spine disorders or RFA should be counseled that primary decompression has a higher risk of reoperation, but outcomes are ultimately comparable.

Evolution of laparoscopic ileal pouch-anal anastomosis: impact of enhanced recovery program, medication changes, and staged approaches on outcomes.

BACKGROUND: Although laparoscopic Ileal pouch-anal anastomosis (IPAA) has become the gold standard in restorative proctocolectomy, surgical techniques have experienced minimal changes. In contrast, substantial shifts in perioperative care, marked by the enhanced recovery program (ERP), modifications in steroid use, and a shift to a 3-staged approach, have taken center stage. METHODS: Data extracted from our prospective IPAA database focused on the first 100 laparoscopic IPAA cases (historic group) and the latest 100 cases (modern group), aiming to measure the effect of these evolutions on postoperative outcomes. RESULTS: The historic IPAA group had more 2-staged procedures (92% proctocolectomy), whereas the modern group had a higher number of 3-staged procedures (86% proctectomy) (P < .001). Compared with patients in the modern group, patients in the historic group were more likely to be on steroids (5% vs 67%, respectively; P < .001) or immunomodulators (0% vs 31%, respectively; P < .001) at surgery. Compared with the historic group, the modern group had a shorter operative time (335.5 ± 78.4 vs 233.8 ± 81.6, respectively; P < .001) and length of stay (LOS; 5.4 ± 3.1 vs 4.2 ± 1.6 days, respectively; P < .001). Compared with the modern group, the historic group exhibited a higher 30-day morbidity rate (20% vs 33%, respectively; P = .04) and an elevated 30-day readmission rate (9% vs 21%, respectively; P = .02). Preoperative steroids use increased complications (odds ratio [OR], 3.4; P = .01), whereas 3-staged IPAA reduced complications (OR, 0.3; P = .03). ERP was identified as a factor that predicted shorter stays. CONCLUSION: Although ERP effectively reduced the LOS in IPAA surgery, it failed to reduce complications. Conversely, adopting a 3-staged IPAA approach proved beneficial in reducing morbidity, whereas preoperative steroid use increased complications.

Structural flexibility of favipiravir and its structural analogues in solutions: experimental and computational insight.

Combined UV-vis and quantum chemical studies of the structural flexibility and tautomerism of 6-R-3-hydroxy-2-pyrazine carboxamides in solutions revealed that their keto-enol transformations are accompanied by the deprotonation of enol tautomers and the formation of the corresponding anionic species. Both the solvent and the 6-R substituent strongly influence the relative abundance of the above forms in solutions. Anions are not formed in 1,2-dichloroethane (DCE), but the probability of deprotonation in neutral water and N,N-dimethylformamide (DMF) increases in the order R = H < F < NO2. Only enol tautomers of all solutes are found in DCE. DMF stabilizes keto forms only moderately and assists much strongly in the deprotonation of all three compounds. Water tends to stabilize both keto tautomers and deprotonated anions: the keto form dominates in the case of R = H (antiviral drug T-1105), the anions are found exclusively for R = NO2, and the aqueous solution of another antiviral drug, favipiravir (R = F), contains both the keto tautomer and the anionic form. The results of quantum chemical free energy calculations are in agreement with the experimental observations.

Toll-like receptor 4 in pancreatic damage and immune infiltration in acute pancreatitis.

Acute pancreatitis is a complex inflammatory disease resulting in extreme pain and can result in significant morbidity and mortality. It can be caused by several factors ranging from genetics, alcohol use, gall stones, and ductal obstruction caused by calcification or neutrophil extracellular traps. Acute pancreatitis is also characterized by immune cell infiltration of neutrophils and M1 macrophages. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that has been noted to respond to endogenous ligands such as high mobility group box 1 (HMGB1) protein and or exogenous ligands such as lipopolysaccharide both of which can be present during the progression of acute pancreatitis. This receptor can be found on a variety of cell types from endothelial cells to resident and infiltrating immune cells leading to production of pro-inflammatory cytokines as well as immune cell activation and maturation resulting in the furthering of pancreatic damage during acute pancreatitis. In this review we will address the various mechanisms mediated by TLR4 in the advancement of acute pancreatitis and how targeting this receptor could lead to improved outcomes for patients suffering from this condition.

Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using interpretable machine learning.

Osteoarthritis (OA) is increasing in prevalence and has a severe impact on patients' lives. However, our understanding of biomarkers driving OA risk remains limited. We developed a model predicting the five-year risk of OA diagnosis, integrating retrospective clinical, lifestyle and biomarker data from the UK Biobank (19,120 patients with OA, ROC-AUC: 0.72, 95%CI (0.71-0.73)). Higher age, BMI and prescription of non-steroidal anti-inflammatory drugs contributed most to increased OA risk prediction ahead of diagnosis. We identified 14 subgroups of OA risk profiles. These subgroups were validated in an independent set of patients evaluating the 11-year OA risk, with 88% of patients being uniquely assigned to one of the 14 subgroups. Individual OA risk profiles were characterised by personalised biomarkers. Omics integration demonstrated the predictive importance of key OA genes and pathways (e.g., GDF5 and TGF-ß signalling) and OA-specific biomarkers (e.g., CRTAC1 and COL9A1). In summary, this work identifies opportunities for personalised OA prevention and insights into its underlying pathogenesis.

Robotic modified Sugarbaker technique for parastomal hernia repair: a standardized approach.

Parastomal hernia (PSH) is a prevalent long-term morbidity associated with stoma construction, and the optimal operative management remains uncertain. This study addresses the need for a standardized approach to symptomatic PSH repair, focusing on the robotic-assisted modified Sugarbaker technique with composite permanent mesh. The study, conducted in a high-volume colon and rectal surgery referral practice, outlines a systematic approach to patient selection, surgical procedures, and postoperative care. Preoperative evaluations include detailed medical and surgical histories, impact assessments of PSH, and oncological history reviews. The surgical technique involves the Da Vinci Xi™ robotic platform for adhesiolysis, hernia content reduction, stoma revision if needed, narrowing of the enlarged stoma trephine, lateralization of the stoma limb of bowel, and securing the mesh to the abdominal wall. Outcomes are reported for 102 patients undergoing robotic parastomal hernia repair from January 2021 to July 2023. Conversion to open surgery occurred in only one case (0.9%). Postoperative complications affected 39.2% of patients, with ileus being the most frequent (24.5%). Recurrence was observed in 5.8% of cases during an average follow-up of 10 months. In conclusion, parastomal hernia, a common complication post-stoma creation, demands surgical intervention. The robotic-assisted modified Sugarbaker repair technique, as outlined in this paper, offers promising results in terms of feasibility and outcomes.

The SagA of E. faecium.

An enzyme that remodels the cell wall of Enterococcus faecium helps these gut bacteria to divide and generate peptide fragments that enhance the immune response against cancer.

Transcript-specific enrichment enables profiling rare cell states via scRNA-seq.

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing (scRNA-seq) identifies many rare populations of interest that express specific marker transcript combinations, traditional flow sorting limits our ability to enrich these populations for further profiling, including requiring cell surface markers with high-fidelity antibodies. Additionally, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers. To address these limitations, we describe Programmable Enrichment via RNA Flow-FISH by sequencing (PERFF-seq), a scalable assay that enables scRNA-seq profiling of subpopulations from complex cellular mixtures defined by the presence or absence of specific RNA transcripts. Across immune populations (n = 141,227 cells) and fresh-frozen and formalin-fixed paraffin-embedded brain tissue (n = 29,522 nuclei), we demonstrate the sorting logic that can be used to enrich for cell populations via RNA-based cytometry followed by high-throughput scRNA-seq. Our approach provides a rational, programmable method for studying rare populations identified by one or more marker transcripts.

Future Directions: The Phenomenology of Irritable Mood and Outbursts: Hang Together or Hang Separately1.

Recognition of the importance of irritable mood and outbursts has been increasing over the past several decades. This "Future Directions" aims to develop a set of recommendations for future research emphasizing that irritable mood and outbursts "hang together," but have important distinctions and thus also need to "hang separately." Outbursts that are the outcome of irritable mood may be quite different from outbursts that are the trigger or driving force that make youth and his/her environment miserable. What, then, is the relation between irritable mood and outbursts? As the field currently stands, we not only cannot answer this question, but we may also lack the tools to effectively do so. Here, we will propose recommendations for understanding the phenomenology of irritable mood and outbursts so that more directed and clinically useful assessment tools can be designed. We discuss the transdiagnostic and treatment implications that relate to improvements in measurement. We describe the need to do more than repurpose our current assessment tools, specifically interviews and rating scales, which were designed for different purposes. The future directions of the study and treatment of irritable mood and outbursts will require, among others, using universally accepted nomenclature, supporting the development of tools to measure the characteristics of each irritable mood and outbursts, understanding the effects of question order, informant, development and longitudinal course, and studying the ways in which outbursts and irritable mood respond to treatment.

A RANGE-WIDE ECTOPARASITE SURVEY FOR ALLEGHENY WOODRATS (NEOTOMA MAGISTER).

Allegheny woodrats (Neotoma magister) are karst-specializing rodents that are rare or in conservation need in many states within their current range. Parasitism and habitat fragmentation have been suggested as primary reasons for declining populations. The presence, prevalence, and impact of ectoparasites, including fleas, ticks, and bots, is not fully understood rangewide. We collected Allegheny woodrat ectoparasites across 8 states in their range, identifying parasites via morphological and genetic means. Across contributions from 8 states, we discovered 2 woodrat-specific fleas parasitizing Allegheny woodrats: Orchopeas pennsylvanicus (all contributing states, n = 228) and Epitedia cavernicola (Indiana only, n = 9). The former was a new state record in New Jersey and Ohio. Woodrat specialists Ixodes woodi were morphologically identified as the dominant tick species (n = 38), and our contributions to genetic databases may ease confusion in future efforts. Three generalist species of ticks representing 8 individuals were identified as Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis. Only 2 bot fly species were recognized in Allegheny woodrats: 1 squirrel bot (Cuterebra emasculator) and 10 individuals of Cuterebra sp. not genetically conspecific to any known eastern U.S. rodent bot. The host specificity for fleas is not surprising, given that previous small-scale surveys and ticks primarily appear to be a mix of genus-specific (Ixodes woodi) and generalist species. There remains uncertainty with bots via morphological and genetic analyses. Our survey presents a wide-ranging baseline survey for Allegheny woodrats across their range, emphasizing the diversity (or specificity) of parasite groups for this species. An understanding of Allegheny woodrats and the health impact of ectoparasites is imperative because they face myriad challenges rangewide, especially considering the bot-driven demise of 1 woodrat in our study. Ectoparasites can have a marked impact on already-declining woodrat populations across their range and should not be overlooked in future surveys.

Evaluating and Predicting the Performance of Sorghum Lines in an Elite by Exotic Backcross-Nested Association Mapping Population.

Maintaining or introducing genetic diversity into plant breeding programs is necessary for continual genetic gain; however, diversity at the cost of reduced performance is not something sought by breeders. To this end, backcross-nested association mapping (BC-NAM) populations, in which the recurrent parent is an elite line, can be employed as a strategy to introgress diversity from unadapted accessions while maintaining agronomic performance. This study evaluates (i) the hybrid performance of sorghum lines from 18 BC1-NAM families and (ii) the potential of genomic prediction to screen lines from BC1-NAM families for hybrid performance prior to phenotypic evaluation. Despite the diverse geographical origins and agronomic performance of the unadapted parents for BC1-NAM families, many BC1-derived lines performed significantly better in the hybrid trials than the elite recurrent parent, R.Tx436. The genomic prediction accuracies for grain yield, plant height, and days to mid-anthesis were acceptable, but the prediction accuracies for plant height were lower than expected. While the prediction accuracies increased when including more individuals in the training set, improvements tended to plateau between two and five lines per family, with larger training sets being required for more complex traits such as grain yield. Therefore, genomic prediction models can be optimized in a large BC1-NAM population with a relatively low fraction of individuals needing to be evaluated. These results suggest that genomic prediction is an effective method of pre-screening lines within BC1-NAM families prior to evaluation in extensive hybrid field trials.

[The impact of social media on youths with anorexia nervosa]. / De impact van sociale media op anorexia nervosa.

OBJECTIVE: To describe the impact of social media on youths with severe anorexia nervosa. DESIGN: Qualitative study. METHOD: Through semi-structured interviews with eleven youths diagnosed with anorexia nervosa, opinions and experiences surrounding the impact of social media on anorexia nervosa were collected, coded and analyzed using thematic analysis. RESULTS: Social media are often used to compensate for social isolation or misunderstandings about anorexia nervosa from friends and family. Motivated youths experience recovery communities as helpful against social isolation and a good place to find motivation for recovery. Negative aspects of social media include the idealization of unhealthy body types, the competition to have the most severe anorexia and the ease with which pro-ana content is found online and imposes itself. CONCLUSION: Preventive measures, including education about the dangers of social media can protect youths with anorexia nervosa in their social media use. Isolation from social media may lead to further social isolation.

Deterministic epidemic models overestimate the basic reproduction number of observed outbreaks.

The basic reproduction number, R0, is a well-known quantifier of epidemic spread. However, a class of existing methods for estimating R0 from incidence data early in the epidemic can lead to an over-estimation of this quantity. In particular, when fitting deterministic models to estimate the rate of spread, we do not account for the stochastic nature of epidemics and that, given the same system, some outbreaks may lead to epidemics and some may not. Typically, an observed epidemic that we wish to control is a major outbreak. This amounts to implicit selection for major outbreaks which leads to the over-estimation problem. We formally characterised the split between major and minor outbreaks by using Otsu's method which provides us with a working definition. We show that by conditioning a 'deterministic' model on major outbreaks, we can more reliably estimate the basic reproduction number from an observed epidemic trajectory.

In vitro characterization of [125I]HY-3-24, a selective ligand for the dopamine D3 receptor.

Introduction: Dopamine D3 receptor (D3R) ligands have been studied for the possible treatment of neurological and neuropsychiatric disorders. However, selective D3R radioligands for in vitro binding studies have been challenging to identify due to the high structural similarity between the D2R and D3R. In a prior study, we reported a new conformationally-flexible benzamide scaffold having a high affinity for D3R and excellent selectivity vs. D2R. In the current study, we characterized the in vitro binding properties of a new radioiodinated ligand, [125I]HY-3-24. Methods: In vitro binding studies were conducted in cell lines expressing D3 receptors, rat striatal homogenates, and rat and non-human primate (NHP) brain tissues to measure regional brain distribution of this radioligand. Results: HY-3-24 showed high potency at D3R (Ki = 0.67 ± 0.11 nM, IC50 = 1.5 ± 0.58 nM) compared to other D2-like dopamine receptor subtypes (D2R Ki = 86.7 ± 11.9 nM and D4R Ki > 1,000). The Kd (0.34 ± 0.22 nM) and Bmax (38.91 ± 2.39 fmol/mg) values of [125I]HY-3-24 were determined. In vitro binding studies in rat striatal homogenates using selective D2R and D3R antagonists confirmed the D3R selectivity of [125I]HY-3-24. Autoradiography results demonstrated that [125I]HY-3-24 specifically binds to D3Rs in the nucleus accumbens, islands of Calleja, and caudate putamen in rat and NHP brain sections. Conclusion: These results suggest that [125I]HY-3-24 appears to be a novel radioligand that exhibits high affinity binding at D3R, with low binding to other D2-like dopamine receptors. It is anticipated that [125I]HY-3-24 can be used as the specific D3R radioligand.

Primary fit tracheoesophageal puncture in primary versus salvage laryngectomy: Short-term and long-term complications and functional outcomes.

BACKGROUND: Primary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary-fit TEP in the setting of salvage laryngectomy. METHODS: A retrospective, single-center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short-term and long-term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy. RESULTS: In this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes. CONCLUSION: Primary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.

Inhibitory regulation of FoxO1 in PPARδ expression drives mitochondria dysfunction and insulin resistance.

Forkhead box protein O1 (FoxO1) regulates muscle growth, but the metabolic role of FoxO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FoxO1 in skeletal muscle, we generated skeletal muscle-specific FoxO1 inducible knockout (mFoxO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFoxO1 iKO mice, and assessed the correlation between FoxO1 and mitochondrial-related protein in the skeletal muscle of diabetic patients. Obese mFoxO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FoxO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle and deletion of PPARδ abolished the beneficial effects of FoxO1 deficiency. FoxO1 protein levels were higher in the skeletal muscle of diabetic patients and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FoxO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FoxO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ.

Evaluation of ChatGPT and Gemini large language models for pharmacometrics with NONMEM.

To assess ChatGPT 4.0 (ChatGPT) and Gemini Ultra 1.0 (Gemini) large language models on NONMEM coding tasks relevant to pharmacometrics and clinical pharmacology. ChatGPT and Gemini were assessed on tasks mimicking real-world applications of NONMEM. The tasks ranged from providing a curriculum for learning NONMEM, an overview of NONMEM code structure to generating code. Prompts in lay language to elicit NONMEM code for a linear pharmacokinetic (PK) model with oral administration and a more complex model with two parallel first-order absorption mechanisms were investigated. Reproducibility and the impact of "temperature" hyperparameter settings were assessed. The code was reviewed by two NONMEM experts. ChatGPT and Gemini provided NONMEM curriculum structures combining foundational knowledge with advanced concepts (e.g., covariate modeling and Bayesian approaches) and practical skills including NONMEM code structure and syntax. ChatGPT provided an informative summary of the NONMEM control stream structure and outlined the key NONMEM Translator (NM-TRAN) records needed. ChatGPT and Gemini were able to generate code blocks for the NONMEM control stream from the lay language prompts for the two coding tasks. The control streams contained focal structural and syntax errors that required revision before they could be executed without errors and warnings. The code output from ChatGPT and Gemini was not reproducible, and varying the temperature hyperparameter did not reduce the errors and omissions substantively. Large language models may be useful in pharmacometrics for efficiently generating an initial coding template for modeling projects. However, the output can contain errors and omissions that require correction.

Pain catastrophizing moderates the relationship between pain sensitivity and clinical pain in adolescents with functional abdominal pain.

Pain catastrophizing has been linked to amplified pain sensitivity assessed using quantitative sensory testing (QST) in adults; pediatric data is limited, particularly in youth with functional abdominal pain (FAP). With increasing use of QST to evaluate somatosensory function and predict pain outcomes, we examined the associations between QST and clinical pain in adolescents with FAP and tested the moderating effects of pain catastrophizing. Seventy-seven adolescents (mean age 16.6 years, 85.7% female, 72.7% White, 90.8% non-Hispanic) who fulfilled diagnostic criteria for FAP completed QST assessment (pressure pain threshold and tolerance, heat pain threshold, conditioned pain modulation) and measures of abdominal pain intensity, pain interference and pain catastrophizing. Adjusting for age and sex, only higher heat pain threshold was associated with higher abdominal pain intensity (Beta per 1-SD = 0.54, P = 0.026). Contrary to hypothesis, for youth with higher pain catastrophizing, higher pressure pain tolerance was associated with greater abdominal pain intensity, but associations were not significant for youth with lower catastrophizing (P = 0.049). Similarly, for those with higher pain catastrophizing (in contrast to lower pain catastrophizing), higher pressure pain thresholds and tolerance were associated with higher pain interference (P = 0.039, 0.004, respectively). Results highlight the need to investigate the influence of pain catastrophizing on QST. PERSPECTIVE: This study demonstrated unexpected findings of pain catastrophizing moderating the relationships between pressure pain threshold and tolerance, and clinical pain in adolescents with FAP. This raised questions regarding our understanding of psychological contributions to QST findings in pediatric populations with chronic pain.