Genetic Variations in TrkB.T1 Isoform and Their Association with Somatic and Psychological Symptoms in Individuals with IBS.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is often comorbid with somatic pain and psychological disorders. Dysregulated signaling of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), has been implicated in somatic-psychological symptoms in individuals with IBS. We investigated the association of 10 single nucleotide polymorphisms (SNPs) in the regulatory 3' untranslated region (UTR) of NTRK2 (TrkB) kinase domain-deficient truncated isoform (TrkB.T1) and BDNF Val66Met SNP with somatic and psychological symptoms and quality of life in a cohort from the United States (U.S.) (IBS n=464; healthy controls n=156). We found that the homozygous recessive genotype (G/G) of rs2013566 in individuals with IBS is associated with worsened somatic symptoms, including headache, back pain, joint pain, muscle pain, and somatization as well as diminished sleep quality, energy level and overall quality of life. Validation using United Kingdom BioBank (UKBB) data confirmed the association of rs2013566 with increased likelihood of headache. Several SNPs (rs1627784, rs1624327, rs1147198) showed significant associations with muscle pain in our U.S. cohort. These 4 SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Our findings suggest that genetic variation within the 3'UTR region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms impacting their quality of life. These findings advance our understanding of the genetic interaction between BDNF/TrkB pathways and somatic-psychological symptoms in IBS, highlighting the importance of further exploring this interaction for potential clinical applications. PERSPECTIVE: This study aims to understand the genetic effects on IBS-related symptoms across somatic, psychological, and quality of life domains, validated by UKBB data. The rs2013566 homozygous recessive genotype correlates with worsened somatic symptoms and reduced quality of life, emphasizing its clinical significance.

Effect of Strength and Plyometric Training on Kinematics in Female Novice Runners.

ABSTRACT: Harrison, K, Williams, DSB III, Darter, BJ, Zernicke, RF, Shall, M, and Finucane, S. Effect of strength and plyometric training on kinematics in female novice runners. J Strength Cond Res 38(6): 1048-1055, 2024-Both running performance and injury have been associated with running kinematics. Plyometric training improves run performance and reduces injury risk in court-sport and field-sport athletes. The aim of this study was to assess longitudinal changes in kinematics in novice runners before and after a typical beginners' running program, compared with those who perform a plyometric intervention before running. Fifty-seven novice female runners were assigned to the control group (8 weeks walking +8 weeks running) or the intervention group (8 weeks strength or plyometric training +8 weeks running). Kinematics were assessed at baseline, 8 weeks, and 16 weeks. Joint angles throughout the stride of those who completed the training ( n = 21) were compared between groups and assessment time points using a statistical parametric mapping 2-way analysis of variance, with group and study time point as independent variables. There was no interaction effect of group and study time point ( p > 0.05), indicating that both training programs had similar effects on running kinematics. There was a main effect of time for sagittal plane knee and hip kinematics ( p < 0.001); after training, subjects ran with a more extended leg, particularly during swing. Programs of 8 weeks of preparatory training, followed by 8 weeks of running, resulted in altered sagittal plane biomechanics, which have previously been related to improved running economy. A greater volume of plyometric, run training or concurrent plyometric and run training may be required to elicit changes in running form associated with lower injury risk.

Genetic Variations in TrkB.T1 Isoform and Their Association with Somatic and Psychological Symptoms in Individuals with IBS.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is often comorbid with somatic pain and psychological disorders. Dysregulated signaling of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), has been implicated in somatic-psychological symptoms in individuals with IBS. Thus, we investigated the association of 10 single nucleotide polymorphisms (SNPs) in the regulatory 3' untranslated region (UTR) of NTRK2 (TrkB) kinase domain-deficient truncated isoform (TrkB.T1) and the BDNF Val66Met SNP with somatic and psychological symptoms and quality of life in a U.S. cohort (IBS n=464; healthy controls n=156). We found that the homozygous recessive genotype (G/G) of rs2013566 in individuals with IBS is associated with worsened somatic symptoms, including headache, back pain, joint pain, muscle pain, and somatization as well as diminished sleep quality, energy level and overall quality of life. Validation using U.K. BioBank (UKBB) data confirmed the association of rs2013566 with increased likelihood of headache. Several SNPs (rs1627784, rs1624327, rs1147198) showed significant associations with muscle pain in our U.S. cohort. Notably, these SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Together, our findings suggest that genetic variation within the 3'UTR region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms that may influence their quality of life. These findings advance our understanding of the genetic interaction between BDNF/TrkB pathways and somatic-psychological symptoms in IBS, highlighting the importance of further exploring this interaction for potential clinical applications.

Factors Associated With Self-Selected Step Rate in High School Cross Country Runners.

ABSTRACT: Luedke, LE, Heiderscheit, BC, Williams, DSB, and Rauh, MJ. Factors associated with self-selected step rate in high school cross country runners. J Strength Cond Res 35(4): 1141-1148, 2021-Recommendations for step rate, or cadence, during distance running come from varying perspectives including performance, running economy, and injury risk. Studies of adult runners suggest that running experience and leg length may influence step rate, but limited evidence is available on factors that influence adolescent runner step rates. The purpose was to evaluate relationships between running experience, anthropometric factors, and lower extremity muscle strength with self-selected step rate in adolescent runners. Sixty-eight high school cross country runners (47 young women; age 16.2 ± 1.3 years) reported height, body mass, and running experience. Mean step rate was assessed at 3.3 m·s-1 and self-selected (mean 3.8 ± 0.5 m·s-1) speeds. Leg length and peak isometric strength of the hip abductors, knee extensors, and flexors were also measured. Step rates at 3.3 m·s-1 {r (95% confidence interval [CI]) = 0.44 [0.22, 0.61], p < 0.001} and self-selected (r [95% CI] = 0.45 [0.20, 0.66], p < 0.001) speeds were correlated with running experience. Step rates at 3.3 m·s-1 and self-selected speeds were inversely associated with body mass (r [95% CI] = -0.32 [-0.52, -0.09], p = 0.007 and r [95% CI] = -0.34 [-0.53, -0.11], p = 0.005, respectively), height (r [95% CI] = -0.40 [-0.58, -0.18], p = 0.01 and r [95% CI] = -0.32 [-0.52, -0.09], p = 0.008, respectively), and leg length (r [95% CI] = -0.48 [-0.64, -0.27], p < 0.001 and r [95% CI] = -0.35 [-0.52, -0.12], p = 0.004, respectively). No significant relationships were found between isometric strength values and step rate at either speed (p > 0.05). Adolescent runners with greater running experience displayed higher step rates. Hence, the lower step rates in runners with less experience may factor in the higher injury risk previously reported in novice runners. Runners with shorter leg length displayed higher step rates. Step rate recommendations should consider runner experience and anthropometrics.

An evaluation of a common elements treatment approach for youth in Somali refugee camps.

BACKGROUND: This paper reports on: (1) an evaluation of a common elements treatment approach (CETA) developed for comorbid presentations of depression, anxiety, traumatic stress, and/or externalizing symptoms among children in three Somali refugee camps on the Ethiopian/Somali border, and (2) an evaluation of implementation factors from the perspective of staff, lay providers, and families who engaged in the intervention. METHODS: This project was conducted in three refugee camps and utilized locally validated mental health instruments for internalizing, externalizing, and posttraumatic stress (PTS) symptoms. Participants were recruited from either a validity study or from referrals from social workers within International Rescue Committee Programs. Lay providers delivered CETA to youth (CETA-Youth) and families, and symptoms were re-assessed post-treatment. Providers and families responded to a semi-structured interview to assess implementation factors. RESULTS: Children who participated in the CETA-Youth open trial reported significant decreases in symptoms of internalizing (d  =  1.37), externalizing (d  =  0.85), and posttraumatic stress (d  =  1.71), and improvements in well-being (d  =  0.75). Caregivers also reported significant decreases in child symptoms. Qualitative results were positive toward the acceptability and appropriateness of treatment, and its feasibility. CONCLUSIONS: This project is the first to examine a common elements approach (CETA: defined as flexible delivery of elements, order, and dosing) with children and caregivers in a low-resource setting with delivery by lay providers. CETA-Youth may offer an effective treatment that is easier to implement and scale-up versus multiple focal interventions. A fullscale randomized clinical trial is warranted.

miR-711 upregulation induces neuronal cell death after traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of mortality and disability. MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression at post-transcriptional level and may be key modulators of neuronal apoptosis, yet their role in secondary injury after TBI remains largely unexplored. Changes in miRs after controlled cortical impact (CCI) in mice were examined during the first 72 h using miR arrays and qPCR. One selected miR (711) was examined with regard to its regulation and relation to cell death; effects of miR-711 modulation were evaluated after CCI and using in vitro cell death models of primary cortical neurons. Levels of miR-711 were increased in the cortex early after TBI and in vitro models through rapid upregulation of miR-711 transcription (pri-miR-711) rather than catabolism. Increases coincided with downregulation of the pro-survival protein Akt, a predicted target of miR-711, with sequential activation of forkhead box O3 (FoxO3)a/glycogen synthase kinase 3 (GSK3)α/ß, pro-apoptotic BH3-only molecules PUMA (Bcl2-binding component 3) and Bim (Bcl2-like 11 (apoptosis facilitator)), and mitochondrial release of cytochrome c and AIF. miR-711 and Akt (mRNA) co-immunoprecipitated with the RNA-induced silencing complex (RISC). A miR-711 hairpin inhibitor attenuated the apoptotic mechanisms and decreased neuronal death in an Akt-dependent manner. Conversely, a miR-711 mimic enhanced neuronal apoptosis. Central administration of the miR-711 hairpin inhibitor after TBI increased Akt expression and attenuated apoptotic pathways. Treatment reduced cortical lesion volume, neuronal cell loss in cortex and hippocampus, and long-term neurological dysfunction. miR-711 changes contribute to neuronal cell death after TBI, in part by inhibiting Akt, and may serve as a novel therapeutic target.

The placebo effect: From concepts to genes.

Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson's disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioral, neurobiological, and genetic influences on the placebo effect. Consistent with recent conceptualizations, the placebo effect is presented as the product of a general expectancy learning mechanism in which verbal, conditioned, and social cues are centrally integrated to change behaviors and outcomes. Examples of the integration of verbal and conditioned cues, such as instructed reversal of placebo effects are also incorporated into this model. We discuss neuroimaging studies that have identified key brain regions and modulatory mechanisms underlying placebo effects using well-established behavioral paradigms. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioral, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximize treatment outcomes in clinical settings.

Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established "chronic" schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.

Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death, reflecting the need for better understanding the oncogenesis, and developing new diagnostic and therapeutic targets for the malignancy. Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in tumorigenesis. Our recent study demonstrated that small nucleolar RNA 42 (SNORA42) was overexpressed in lung tumors. Here, we investigate the role of SNORA42 in tumorigenesis of NSCLC. We simultaneously assess genomic dosages and expression levels of SNORA42 and its host gene, KIAA0907, in 10 NSCLC cell lines and a human bronchial epithelial cell line. We then determine in vitro functional significance of SNORA42 in lung cancer cell lines through gain- and loss-of-function analyses. We also inoculate cancer cells with SNORA42-siRNA into mice through either tail vein or subcutaneous injection. We finally evaluate expression level of SNORA42 on frozen surgically resected lung tumor tissues of 64 patients with stage I NSCLC by using quantitative reverse transcriptase PCR assay. Genomic amplification and associated high expression of SNORA42 rather than KIAA0907 are frequently observed in lung cancer cells, suggesting that SNORA42 overexpression is activated by its genomic amplification. SNORA42 knockdown in NSCLC cells inhibits in vitro and in vivo tumorigenicity, whereas enforced SNORA42 expression in bronchial epitheliums increases cell growth and colony formation. Such pleiotropy of SNORA42 suppression could be achieved at least partially through increased apoptosis of NSCLC cells in a p53-dependent manner. SNORA42 expression in lung tumor tissue specimens is inversely correlated with survival of NSCLC patients. Therefore, SNORA42 activation could have an oncogenic role in lung tumorigenesis and provide potential diagnostic and therapeutic targets for the malignancy.

Effect of foot orthotics on rearfoot and tibia joint coupling patterns and variability.

The purpose of this study was to compare joint coupling patterns and variability of the rearfoot and tibia during running in subjects who were treated with two types of orthotic devices to that of controls. Eleven subjects with various lower extremity injuries were treated unsuccessfully with a standard orthotic, and then successfully with an inverted orthotic. Three-dimensional kinematic data were collected while subjects ran without orthoses and then in standard and inverted orthoses. Eleven healthy subjects ran without orthoses for comparison. The rearfoot inversion/eversion and tibial internal/external rotation joint coupling pattern and variability relationship was assessed using a vector coding technique. It was hypothesized that when the treated runners ran without orthotic devices, they would exhibit lower joint coupling angles and lower joint coupling variability compared to the controls. In addition, it was hypothesized that there would be no difference in the coupling angle or coupling variability between the standard and no orthotic conditions of the treated runners. Finally, it was hypothesized that coupling angle would decrease and variability would increase in the inverted versus the standard and non-orthotic conditions. No significant differences in joint coupling pattern or variability were observed between the treated and control subjects. In addition, no significant differences were noted between the orthotic conditions in the treated group. These results suggest that foot orthotic devices do not produce significant changes in rearfoot-tibial coupling. Therefore, the relief experienced with the inverted orthotic is likely due to factors other than alterations in this coupling.

High-arched runners exhibit increased leg stiffness compared to low-arched runners.

Leg stiffness between high-arched (HA) and low-arched (LA) runners was compared. It was hypothesized that high-arched runners would exhibit increased leg stiffness, increased sagittal plane support moment, greater vertical loading rates, decreased knee flexion excursion and increased activation of the knee extensor musculature. Twenty high-arched and 20 low-arched subjects were included in this study. Leg stiffness, knee stiffness, vertical loading rate and lower extremity support moment were compared between groups. Electromyographic data were collected in an attempt to explain differences in leg stiffness between groups. High-arched subjects were found to have increased leg stiffness and vertical loading rate compared to low-arched runners. Support moment at the impact peak of the vertical ground reaction force was related to leg stiffness across all subjects. High-arched subjects demonstrated decreased knee flexion excursion during stance. Finally, high-arched subjects exhibited a significantly earlier onset of the vastus lateralis (VL) than the low-arched runners. Differences exist in leg stiffness and vertical loading rate between runners with different foot types. Differences in lower extremity kinetics in individuals with different foot types may have implications for new treatment strategies or preventative measures.

Effect of inverted orthoses on lower-extremity mechanics in runners.

INTRODUCTION: Foot orthoses are recommended for individuals with injuries associated with abnormal lower-extremity mechanics. However, the biomechanical effect of these devices is not completely understood. Most clinicians and researchers believe that foot orthoses are effective in reducing some aspect of rearfoot motion. This is important as many injuries are suggested to be the result of increased pronation. Inverted orthoses are a more aggressive treatment in those whose symptoms do not respond to standard orthotics. They are likely to alter motion in all planes. However, no three-dimensional studies have assessed lower-extremity mechanics in individuals wearing inverted orthotics. PURPOSE: The purpose of this study was to compare the three-dimensional kinematics and kinetics of the rearfoot and knee during running while varying orthotic intervention. METHODS: Eleven subjects were initially fitted with standard foot orthoses and then with inverted orthoses. Three-dimensional kinematic and kinetic data were collected for conditions of no orthoses, standard orthoses, and inverted orthoses. RESULTS: There were no differences between conditions in peak rearfoot eversion or rearfoot eversion excursion. Peak rearfoot inversion moment and work were significantly reduced (P = 0.045 and P < 0.001, respectively) in the inverted orthotic condition suggesting a decreased demand on the soft tissue structures that control eversion. Significant differences were seen in tibial rotation (P = 0.043), knee adduction (P = 0.035), and knee abduction moment (P < 0.001) in the inverted orthotic condition, suggesting alterations were made further up the kinetic chain. CONCLUSIONS: The differences in kinetic parameters at the rearfoot may result in fewer injuries of the rearfoot soft tissue structures when using inverted orthotics. These alterations in lower-extremity mechanics associated with inverted orthoses provide clinicians some evidence for prescribing this device.

Gender differences in lower extremity mechanics during running.

OBJECTIVE: To compare differences in hip and knee kinematics and kinetics in male and female recreational runners. DESIGN: Gait analysis of 20 men and 20 women recreational runners. BACKGROUND: Female runners are reported to be more likely to sustain certain lower extremity injuries compared to their male counterparts. This has been attributed, in part, to differences in their structure and it has been postulated that these structural differences may lead to differences in running mechanics. It was hypothesized that females would exhibit greater peak hip adduction, hip internal rotation, knee abduction and decreased knee internal rotation compared to their male counterparts. It was also hypothesized that females would exhibit greater hip and knee negative work in the frontal and transverse planes compared to males. METHODS: Comparisons of hip and knee three-dimentional joint angles and negative work during the stance phase of running gait were made between genders. RESULTS: Female recreational runners demonstrated a significantly greater peak hip adduction, hip internal rotation and knee abduction angle compared to men. Female recreational runners also demonstrated significantly greater hip frontal and transverse plane negative work compared to male recreational runners. CONCLUSION: Female recreational runners exhibit significantly different lower extremity mechanics in the frontal and transverse planes at the hip and knee during running compared to male recreational runners. RELEVANCE: Understanding the differences in running mechanics between male and female runners may lend insight into the etiology of different injury patterns seen between genders. In addition, these results suggest that care should be taken to account for gender when studying groups of male and female recreational runners.

A comparison of four methods of obtaining a negative impression of the foot.

Four methods are currently available for taking a negative impression of the foot for the purpose of fabricating an orthotic device: nonweightbearing plaster casting, partial-weightbearing foam impressions, and partial-weightbearing and nonweightbearing laser scanning. This study compares the reliability and accuracy of these methods. Each impression method was performed three times on each foot of 15 subjects. Measures of rearfoot and forefoot width, forefoot-to-rearfoot relationship, and arch height were obtained from the negative impressions. Additionally, rearfoot and forefoot width and forefoot-to-rearfoot relationship were measured clinically for each subject. This study found that 1) foot measures are significantly influenced by the method used to obtain a negative foot impression; 2) the methods differ in reliability; and 3) plaster casting may be preferable to the other three methods when it is important to capture the forefoot-to-rearfoot relationship, as in fabricating a functional orthosis.

Family communication about sex: what are parents saying and are their adolescents listening?

CONTEXT: Communication between parents and adolescents about sex, particularly in minority families, has been understudied; more information is needed both on which sex-related topics are discussed and on how their content is transmitted. METHODS: Parent-adolescent communication about 10 sex-related topics was examined in a sample of 907 Hispanic and black 14-16-year-olds. Chi-square analyses were performed to test for significant differences across the 10 topics in discussions reported by the adolescents (with either parent) and by the mothers. The openness of communication, parent-adolescent agreement about communication of topics and differences by gender and ethnicity were also examined. RESULTS: Significantly higher proportions of mothers and adolescents reported discussions of HIV or AIDS (92% by mothers and 71% by adolescents, respectively) and STDs (85% and 70%, respectively) than of issues surrounding sexual behavior, contraceptive use and physical development (27-74% for these other eight topics as reported by mothers vs. 15-66% as reported by adolescents). The gender of the adolescent and of the parent holding the discussion, but not the family's ethnicity, significantly influenced findings, with adolescents of both sexes more likely to report discussions with mothers than with fathers, and with parents more likely to discuss any of the 10 topics with an adolescent of the same gender than of the opposite gender. The likelihood of a topic being discussed and of mother-adolescent agreement that a topic was discussed both increased with an increasing degree of openness in the communication process. CONCLUSIONS: Consistent with research among white samples, mothers of black and Hispanic adolescents are the primary parental communicators about sexual topics. To facilitate communication, educational programs for parents should cover not only what is discussed, but how the information is conveyed.

PIP: In the US, Black and Hispanic adolescents have an increased risk of a number of negative consequences of sexual activity, but most studies about parent-adolescent sex communication have been based on White samples, have failed to examine specific content of discussions, have considered the adolescent's perspective only, and have focused on whether (but not how) sexual information is transmitted. This analysis used data from interviews with 982 mother-adolescent pairs who took part in the 1993-94 Family Adolescent Risk Behavior and Communication Study. Sexual communication with either parent was measured by 10 questions to adolescents, sexual communication with adolescent was measured by rewording these questions for mothers, and another 10 questions measured the process of sexual communication. It was found that the topics of HIV/AIDS and sexually transmitted diseases were covered significantly more than other issues. Findings were influenced by the gender of the adolescent and the parent but not by ethnicity. Adolescents of both sexes were more likely to report discussions with mothers than with fathers, and parents were more likely to discuss the 10 topics with adolescents of the same gender. As openness in the communication process increased, so did the likelihood of a topic being discussed and of mother-adolescent agreement that the discussion took place. It was concluded that educational programs for parents should include the topic of how information is conveyed.

A neural network model for predicting pancreas transplant graft outcome.

OBJECTIVE: To compare the results of a neural network versus a logistic regression model for predicting early (0-3 months) pancreas transplant graft survival or loss. RESEARCH DESIGN AND METHODS: This study was a cross-sectional, secondary analysis of demographic and clinical data from 117 simultaneous pancreas-kidney (SPK), 35 pancreas-after-kidney (PAK), and 8 pancreas-transplant-alone (PTA) patients (n = 160). The majority of patients were men (57%) and were white (90.1%), with a mean age of 39 +/- 8.09 years. Of the patients, 23 (14.4%) experienced early graft loss, which included any loss owing to technical or immunological causes, and death with a functional graft. Data were analyzed with a logistic regression model for multivariate analysis and a backpropagation neural network (BPNN) model. RESULTS: A total of 12 predictor variables were chosen from literature and transplant surgeon recommendations. A logistic model with all predictor variables included correctly classified 93.53% of cases. Model sensitivity was 35.71%; specificity was 100% (pseudo-R2 0.24). Of the predictors, history of alcohol abuse (odds ratio [OR] 32.39; 95% CI 1.67-626.89), having a PAK or PTA (OR 13.6; 95% CI 2.20-84.01), and use of a nonlocal organ procurement center (OPO) (OR 4.51; 95% CI 0.78-25.96) were most closely associated with early graft loss. The BPNN model with the same 12 predictor variables correctly predicted 92.50% of cases (R2 0.71). Model sensitivity was 68%; specificity was 96%. Of the predictors, the three variables most closely associated with graft outcome in this model were recipient/donor weight difference >50 lb, having a PAK or PTA, and use of a nonlocal OPO. CONCLUSIONS: First, the BPNN model correctly predicted 92.5% of graft outcomes versus the logistic model (93.53%). Second, the BPNN model rendered more accurate predictions (>0.70 = loss; <0.30 = survival) versus the logistic model (>0.50 = loss; <0.50 = survival). Third, the BPNN model was more sensitive (68%) than the logistic model (35.71%) to graft failures and demonstrated an almost threefold increase in explained variance (R2 = 0.71 vs. 0.24). These results suggest that the BPNN model is a more powerful tool for predicting early pancreas graft loss than traditional multivariate statistical models.