BioID-based intact cell interactome of the Kv1.3 potassium channel identifies a Kv1.3-STAT3-p53 cellular signaling pathway.

Kv1.3 is a multifunctional potassium channel implicated in multiple pathologies, including cancer. However, how it is involved in disease progression is not fully clear. We interrogated the interactome of Kv1.3 in intact cells using BioID proximity labeling, revealing that Kv1.3 interacts with STAT3- and p53-linked pathways. To prove the relevance of Kv1.3 and of its interactome in the context of tumorigenesis, we generated stable melanoma clones, in which ablation of Kv1.3 remodeled gene expression, reduced proliferation and colony formation, yielded fourfold smaller tumors, and decreased metastasis in vivo in comparison to WT cells. Kv1.3 deletion or pharmacological inhibition of mitochondrial Kv1.3 increased mitochondrial Reactive Oxygen Species release, decreased STAT3 phosphorylation, stabilized the p53 tumor suppressor, promoted metabolic switch, and altered the expression of several BioID-identified Kv1.3-networking proteins in tumor tissues. Collectively, our work revealed the tumor-promoting Kv1.3-interactome landscape, thus opening the way to target Kv1.3 not only as an ion-conducting entity but also as a signaling hub.

Evaluating When Subscores Add Value in Psychological and Health Applications.

Many scales used in psychological and health research are designed to yield subscores, yet it is common to see total scores reported instead. One challenge of using subscores is they can lack adequate reliability due to their shortened length. However, methods originally developed for educational measurement have shown that augmenting subscores can improve reliability estimates. Augmented subscores blend the individual score with other sources of information. The present study sought to understand (a) the costs of ignoring subscores in favor of total scores and (b) the extent to which augmentation can help alleviate challenges encountered when using subscores. Data were simulated to examine when subscores should be preferred to total scores and the magnitude of improvement from using augmented subscores over non-augmented subscores. Results suggested that when a scale is designed to yield subscores, there is practical benefit to using them. In situations where subscore reliability is low, we recommend using augmentation.

American society for metabolic and bariatric surgery: intra-operative care pathway for minimally invasive Roux-en-Y gastric bypass.

BACKGROUND: Clinical care pathways help guide and provide structure to clinicians and providers to improve healthcare delivery and quality. The Quality Improvement and Patient Safety Committee (QIPS) of the American Society for Metabolic and Bariatric Surgery (ASMBS) has previously published care pathways for the performance of laparoscopic sleeve gastrectomy (LSG) and pre-operative care of patients undergoing Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This current RYGB care pathway was created to address intraoperative care, defined as care occurring on the day of surgery from the preoperative holding area, through the operating room, and into the postanesthesia care unit (PACU). METHODS: PubMed queries were performed from January 2001 to December 2019 and reviewed according to Level of Evidence regarding specific key questions developed by the committee. RESULTS: Evidence-based recommendations are made for care of patients undergoing RYGB including the pre-operative holding area, intra-operative management and performance of RYGB, and concurrent procedures. CONCLUSIONS: This document may provide guidance based on recent evidence to bariatric surgeons and providers for the intra-operative care for minimally invasive RYGB.

Discovery, Expression, and In Silico Safety Evaluation of Honey Truffle Sweetener, a Sweet Protein Derived from Mattirolomyces terfezioides and Produced by Heterologous Expression in Komagataella phaffii.

Honey truffle sweetener (HTS), a 121 amino acid protein is identified as a high-intensity sweetener found naturally occurring in the Hungarian Sweet Truffle Mattirolomyces terfezioides, an edible mushroom used in regional diets. The protein is intensely sweet, but the truffle is difficult to cultivate; therefore, the protein was systematically characterized, and the gene coding for the protein was expressed in a commonly used host yeast Komagataella phaffii. The heterologously expressed protein maintained the structural characteristics and sweet taste of the truffle. Preliminary safety evaluations for use as a food ingredient were performed on the protein including digestibility and in silico approaches for predicting the allergenicity and toxicity of the protein. HTS is predicted to be nonallergenic, nontoxic, and readily digestible. This protein is readily produced by precision fermentation of the host yeast, making it a potential replacement for both added sugars and small molecule high-intensity sweeteners in food.

Sphingosine kills intracellular Pseudomonas aeruginosa and Staphylococcus aureus.

Sphingosine has been previously shown to kill many strains of pathogenic bacteria including Pseudomonas aeruginosa, Staphyloccus aureus, Acinetobacter, and atypical mycobacteria. However, these studies were performed on isolated or extracellular bacteria and it is unknown whether sphingosine also targets intracellular bacteria. Here, we demonstrate that exogenously-added sphingosine directly binds to extracellular P. aeruginosa and S. aureus, but also targets and binds to intracellular bacteria. Intracellular sphingosine and bacteria were identified by sequential immunostainings. We further show that exogenously-added sphingosine also kills intracellular P. aeruginosa and S. aureus using modified gentamycin assays. Intracellular killing of P. aeruginosa and S. aureus by sphingosine is not mediated by improved phagosomal-lysosomal fusion. In summary, our data indicate that sphingosine binds to and most likely also directly kills extra- and intracellular P. aeruginosa and S. aureus.

The Society of Black Academic Surgeons membership survey: Insights on demographics, engagement, and opportunities for improvement.

BACKGROUND: The Society of Black Academic Surgeons (SBAS) sought to understand who constitutes its membership and obtain feedback to improve the organization. METHODS: SBAS conducted a 25-question survey amongst members. RESULTS: The response rate was 19 â€‹% (n â€‹= â€‹132/685) with an even gender breakdown (male n â€‹= â€‹64, female n â€‹= â€‹68). The majority identified as Black or African American (85 â€‹%), followed by White (12 â€‹%). Fifty-two percent identified as trainees, while the rest were practicing surgeons specializing in burn/trauma/critical care (19 â€‹%), oncology (19 â€‹%), and general surgery (13 â€‹%). Half joined SBAS within the last 3 years. Satisfaction was reported at a mean of 3.7/5. Lack of awareness (41 â€‹%), time (13 â€‹%), or interest (5 â€‹%) limited committee participation. Networking (83 â€‹%), mentorship/sponsorship/allyship (71 â€‹%), and leadership development (46 â€‹%) were most valued benefits with job boards, webinars, and grants least valuable. CONCLUSION: SBAS is a unique organization uniting both new and lifetime members and opportunities exist to enhance current membership and improve participation.

Toward better outcome measurement for insomnia in children with autism spectrum disorder.

LAY ABSTRACT: Insomnia, trouble falling asleep or staying asleep, is common in autistic children. In a previous report, we described the results of focus groups with parents of autistic children toward the development of the Pediatric Autism Insomnia Rating Scale. In this article, we report on the steps taken to complete the Pediatric Autism Insomnia Rating Scale. With help from the Simons Foundation registry, we collected information from parents on 1185 children with autism spectrum disorder to test the new measure. These results were evaluated using standard statistical methods such as factor analysis. To confirm the validity of the new measure, we enrolled a separate sample of 134 autistic children for a detailed assessment by video conference. This step showed that the Pediatric Autism Insomnia Rating Scale is clearly measuring symptoms of insomnia in children with autism spectrum disorder and not related problems such as hyperactivity, repetitive behavior, or anxiety. We also showed that the total score on the Pediatric Autism Insomnia Rating Scale is stable when repeated over a brief period of time. This is important because a measure that is not stable over a brief period of time would not be suitable as an outcome measure. In summary, the Pediatric Autism Insomnia Rating Scale is a brief and valid measure of insomnia in children with autism spectrum disorder that provides reliable scores.

Caprini guideline indicated venous thromboembolism (VTE) prophylaxis among inpatient surgical patients: are there racial/ethnic differences in practice patterns and outcomes?

BACKGROUND: While racial disparity in surgical mortality due to venous thromboembolism (VTE) has improved, a gap persists. Our study aim was to determine differences in VTE prevention practices and their impact on outcomes among racial surgical cohorts. METHODS: Elective surgeries performed between 1.1.2016 and 5.31.2021 were included. Racial/ethnic cohorts were propensity-matched 1:1 to non-Hispanic White (NHW) patients, and outcomes were compared using unadjusted logistic regression. Match cohort balance was assessed using absolute standardized mean differences and linear model analysis of variance (ANOVA). Pearson's Chi-square tests evaluated bi-variate associations. Conditional logistic regression to compare outcomes between matched groups. Odds ratios, 95 â€‹% confidence intervals, and p-values are reported. Analyses were performed using R version 4.1.2 and the R package Matchit. RESULTS: Non-Hispanic other race (NHOR) (vs. NHW) patients were less likely to receive inpatient prophylaxis (OR 0.86, CI:0.76-0.98). Appropriate prophylaxis resulted in similar VTE for NHB (p â€‹= â€‹0.71) and Hispanic (p â€‹= â€‹0.06), compared to NHW patients. Inpatient bleeding was higher in Hispanic patients with a higher likelihood of receiving appropriate prophylaxis (OR 1.94, CI:1.16-3.32) and NHOR patients with a lower likelihood (OR 1.90, CI:1.10-3.36) CONCLUSION: Postoperative VTE was similar for minority patients receiving appropriate prophylaxis, compared to NHW patients. Inpatient bleeding was more likely in Hispanic and NHOR patients but may not be related to receiving appropriate prophylaxis. NHOR patients were less likely to receive inpatient thromboprophylaxis.

Symmetry of the left and right tibial plafond; a comparison of 75 distal tibia pairs.

PURPOSE: Tibia plafond or pilon fractures present a high level of complexity, making their surgical management challenging. Three-Dimensional Virtual Planning (3DVP) can assist in preoperative planning to achieve optimal fracture reduction. This study aimed to assess the symmetry of the left and right tibial plafond and whether left-right mirroring can reliably be used. METHODS: Bilateral CT scans of the lower limbs of 75 patients without ankle problems or prior fractures of the lower limb were included. The CT images were segmented to create 3D surface models of the tibia. Subsequently, the left tibial models were mirrored and superimposed onto the right tibia models using a Coherent Point Drift surface matching algorithm. The tibias were then cut to create bone models of the distal tibia with a height of 30 mm, and correspondence points were established. The Euclidean distance was calculated between correspondence points and visualized in a boxplot and heatmaps. The articulating surface was selected as a region of interest. RESULTS: The median left-right difference was 0.57 mm (IQR, 0.38 - 0.85 mm) of the entire tibial plafond and 0.53 mm (IQR, 0.37 - 0.76 mm) of the articulating surface. The area with the greatest left-right differences were the medial malleoli and the anterior tubercle of the tibial plafond. CONCLUSION: The tibial plafond exhibits a high degree of bilateral symmetry. Therefore, the mirrored unfractured tibial plafond may be used as a template to optimize preoperative surgical reduction using 3DVP techniques in patients with pilon fractures.

Robotic Versus Laparoscopic Sleeve Gastrectomy Outcome Trends Over Time: Are We Improving?

BACKGROUND: Sleeve gastrectomy (SG) is an effective treatment option for patients with obesity. Robotic sleeve gastrectomy (RSG) is reported to have worse short-term patient outcomes compared to laparoscopic SG (LSG), but prior studies may not have accounted for evolving technology, including stapler utilization. OBJECTIVE: This study compared RSG and LSG outcomes over different time periods. SETTING: Academic Hospital. MATERIAL AND METHODS: The 2015 to 2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Project (MBSAQIP) databases were used. Matched cohort analyses compared adverse outcomes within 30 days for the 2015-2018 and 2019-2021 cohorts. Bivariate and regression models compared cohorts using Stata/MP 17.0. RESULTS: Seven hundred sixty-eight thousand and sixty-nine SG were analyzed. Over the 7-year study period, all patient outcomes, operation length (OL), and length of stay (LOS) trended downward for RSG, except surgical site infection (SSI). In the 2015-2018 cohort, leak was significantly higher with RSG (OR 1.53), and OL and LOS longer (p < 0.001). In the 2019-2021 cohort which corelated with a significant increase in robotic cases, leak (OR 1.36), SSI (OR 1.46), and morbidity (OR 1.11) were higher with RSG. While the mean difference in OL and LOS decreased between the two time periods, they remain longer for RSG (p < 0.001). CONCLUSION: While RSG and LSG are safe with similar mortality, RSG continues to be associated with higher rates of morbidity, leak, and SSI, as well as longer OL, hospital LOS, and higher cost. The study is limited by the ability to account for the impact of surgeon experience and stapler utilization on outcomes.

Thirty day outcomes for laparoscopic versus robotic sleeve gastrectomy: Does the stapler matter?

BACKGROUND: Sleeve gastrectomy (SG) remains a safe and effective treatment for severe obesity. The number of robotic SG (RSG) has steadily increased from 2015 to 2021. Prior studies have shown higher rates of some adverse outcomes with RSG but have not accounted for staplers used. OBJECTIVE: The aim of this study is to compare outcomes for RSG compared to laparoscopic sleeve gastrectomy (LSG), accounting for stapler type used. SETTING: National hospital derived administrative data. METHODS: The PINC AI Healthcare Database was used for the current study. Analyzed cohort included elective LSG or RSG performed between January 1, 2019, and December 31, 2021. Patient, hospital, billing, provider, insurance, and operative data were captured. Bleeding, leak, and other outcomes were identified by ICD-10-CM diagnosis codes. Propensity score matching (PSM) compared outcomes between RSG with SureForm stapler vs. LSG with powered stapler. RESULTS: 56,013 LSG and 13,832 RSG were analyzed. RSG increased from 15 % in 2019 to 25 % in 2021 with an absolute 27 â€‹% increase in robotic stapler utilization for RSG. PSM analysis compared, 5434 RSG with SureForm Stapler vs. 5434 LSG with powered staplers showed equivalent complication rates, shorter LOS, but longer operative time with RSG. CONCLUSIONS: When stapler type used is accounted for, patient outcomes following RSG and LSG are equivalent.

A comprehensive analysis of health care Inequities in randomized clinical trials following bariatric surgeries.

BACKGROUND: Obesity is a global epidemic, leading to an increasing focus on interventions like bariatric surgeries. Despite this, there's a noticeable gap in understanding the demographic distribution of patients in clinical trials for bariatric surgery. METHODS: We conducted a comprehensive analysis of 117 registered randomized clinical trials related to bariatric surgery on ClinicalTrials.gov. We extracted demographic information, including age, sex, race, and ethnicity, and performed descriptive statistical analyses. RESULTS: The analysis covered 8,418 participants. The mean age was 43.8 years, with a substantial majority (93.8 â€‹%) falling within the 18-65 age group. Females comprised 74.9 â€‹% of participants, surpassing real-world estimates. Racially, 65.3 â€‹% of participants were White, while African Americans represented 18.5 â€‹%, Asians 1.2 â€‹%, Native Hawaiians 0.2 â€‹%, and American Indians 0.1 â€‹%, indicating an underrepresentation of diverse racial groups, notably lower compared to real-world demographic data. In terms of ethnicity, only 17.6 â€‹% were Hispanic. CONCLUSIONS: This study reveals significant demographic disparities in patients undergoing bariatric surgeries in clinical trials. This suggests a lack of generalizability, emphasizing the need for inclusive recruitment strategies to enhance health equity.

County health ranking: untangling social determinants of health and other factors associated with short-term bariatric surgery outcomes.

BACKGROUND: The complex interplay of the social determinants of health, race/ethnicity, and traditional surgical risk factors on outcomes following metabolic surgery is poorly understood. OBJECTIVE: To evaluate the relationship between the social determinants of health as measured by county health ranking (CHR) and short-term metabolic surgery outcomes. SETTING: Five accredited bariatric program sites at a national academic health system. METHODS: Data were collected from 5 sites of a single health system from 2010 to 2021. Current procedural terminology codes identified primary and revisional cases. Patient characteristics, procedural data, and 30-day occurrences were collected. CHRs for health factors were determined by ZIP Code and stratified into best, middle, and worst terciles. The primary outcome was 30-day complications, readmissions, or reinterventions/reoperations. Logistic regression assessed the correlation between CHR tercile and morbidity. RESULTS: We analyzed 4,315 primary and 370 revisional metabolic surgery cases. Overall, 64.0%, 27.4%, and 8.6% of patients lived in the best, middle, and worst CHR terciles, respectively. Patients in the middle and worst CHR terciles were more commonly older; non-Hispanic Black or Hispanic; suffered from preexisting chronic obstructive pulmonary disease or hypertension, were dialysis dependence, were on therapeutic anticoagulation, or had inferior vena cava filters. Middle and worst CHR tercile patients were more likely to undergo index sleeve gastrectomy or robotic-assisted surgery and have surgery performed by a self-designated general surgeon. Thirty-day outcomes were similar across CHR terciles. Racial disparity in multiple short-term outcomes persisted despite adjustment for CHR tercile. CONCLUSION: Higher-risk patients are more likely to be from counties with lower CHRs, but CHR was not independently associated with 30-day outcomes after metabolic surgery.

Out-of-Pocket Costs among Commercially Insured Individuals with type 2 Diabetes and Obesity: Comparison between Ozempic and Sleeve Gastrectomy.

OBJECTIVE: Determine out-of-pocket (OOP) costs two years after sleeve gastrectomy (SG) or initiating Ozempic for patients with type 2 diabetes (T2D) and obesity. SUMMARY BACKGROUND DATA: Individuals with obesity and T2D have a variety of treatment options. Risks and benefits of these treatment options are becoming more well documented; however, the real-world patient costs of these options are not known. METHODS: Adults with body mass index (BMI) 35 kg/m2 or higher, and T2D who had an SG or used Ozempic were identified in the employer-based retrospective claims database Merative™ (previously Truven IBM Marketscan) from 2017 to 2021. SG cohort was defined as having a SG (without filling a prescription for Ozempic) and Ozempic cohort was defined as continuously filling a prescription for Ozempic for at least 2 years (and not having any bariatric surgery). Individuals in each cohort were 1:1 propensity matched on demographics, obesity-related comorbidities, and baseline OOP costs. in the year before treatment. OOP costs were compared in the two years after treatment using paired t-tests. RESULTS: 302 SG were matched to 302 Ozempic patients (mean age 50, mean baseline BMI 40, 41% male). OOP healthcare costs were similar for the SG ($2,267) and Ozempic ($2,131) cohorts 1-year after index date (difference=$136, P=0.19). OOP healthcare costs were significantly lower in the SG cohort ($1,155 vs. $2,084, P<0.01) 2-years after index date. CONCLUSIONS: Within 2 years of starting treatment, OOP healthcare costs were significantly lower among individuals who had a SG versus those treated with Ozempic.

Measurement Invariance in Intellectual and Developmental Disability Research.

Measurement invariance (MI) is a psychometric property of an instrument indicating the degree to which scores from an instrument are comparable across groups. In recent years, there has been a marked uptick in publications using MI in intellectual and developmental disability (IDD) samples. Our goal here is to provide an overview of why MI is important to IDD researchers and to describe some challenges to evaluating it, with an eye towards nudging our subfield into a more thoughtful and measured interpretation of studies using MI.

Troubling complaint: Addressing hepatitis C-related stigma and discrimination through complaint mechanisms.

The need to grapple with hepatitis C-related stigma and discrimination in Australian health-care settings has been recognised in public policy, and work is underway to address it. But how likely are people to raise a complaint when they experience stigma or discrimination? And how effective and accessible are complaints mechanisms? Given complaint procedures are considered important parts of the delivery of safe and ethical health care, these are important questions that have yet to be substantially explored. Drawing on interviews with people with lived experience of hepatitis C (n = 30), this article considers how affected people feel about complaints processes and the act of complaining. Alongside these perspectives, we discuss complaint mechanisms, and the views of stakeholders who work with hepatitis C-affected communities in policy, health, legal and advocacy roles (n = 30) on the institutional and cultural dynamics of complaint. We draw on Sara Ahmed's Complaint! and Fraser et al.'s work on drug-related stigma to analyse these concerns that have yet to be researched, and argue that the (unlikely) prospect of successful complaint is a key part of the network of forces that perpetuate stigma, discrimination and disadvantage among people who have (lived with) hepatitis C. Although people with lived experience are often powerful advocates and acutely aware of the deficiencies in the quality of their treatment, our interviews suggest that the obstacles they face to accessing health care are seen as commonplace, intractable and insurmountable; and, that mechanisms for addressing them-where they exist at all-treat complaints in narrowly individualising terms and expose complainants to dismissal. Following Ahmed, we call for a 'troubling' of complaints-responding to them not as individual problems but rather as collective, structural concerns, necessitating new approaches.

Prevalence of Rotational Malalignment After Infrapatellar Versus Suprapatellar Intramedullary Nailing of Tibial Shaft Fractures.

Background: Up to 30% of patients with a tibial shaft fracture sustain iatrogenic rotational malalignment (RM) after infrapatellar (IP) nailing. Although IP nailing remains the management of choice for most patients, suprapatellar (SP) nailing has been gaining popularity. It is currently unknown whether SP nailing can provide superior outcomes with regard to tibial RM. The aim of this study was to compare the differences in the prevalence of RM following IP versus SP nailing. Methods: This retrospective study included 253 patients with a unilateral, closed tibial shaft fracture treated with either an IP or SP approach between January 2009 and April 2023 in a Level-I trauma center. All patients underwent a postoperative, protocolized, bilateral computed tomography (CT) scan for RM assessment. Results: RM was observed in 30% and 33% of patients treated with IP and SP nailing, respectively. These results indicate no significant difference (p = 0.639) in the prevalence of RM between approaches. Furthermore, there were no significant differences in the distribution (p = 0.553) and direction of RM (p = 0.771) between the 2 approaches. With the IP and SP approaches, nailing of left-sided tibial shaft fractures resulted in predominantly internal RM (85% and 73%, respectively), while nailing of right-sided tibial shaft fractures resulted in predominantly external RM (90% and 80%, respectively). The intraobserver reliability for the CT measurements was 0.95. Conclusions: The prevalence of RM was not influenced by the entry point of tibial nailing (i.e., IP versus SP). Hence, the choice of surgical approach should rely on factors other than the risk of RM. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

An Illustrated Scoping Review of the Magnetic Resonance Imaging Characteristics of Canine and Feline Brain Tumors.

Magnetic resonance imaging (MRI) is used pervasively in veterinary practice for the antemortem diagnosis of intracranial tumors. Here, we provide an illustrated summary of the published MRI features of primary and secondary intracranial tumors of dogs and cats, following PRISMA scoping review guidelines. The PubMed and Web of Science databases were searched for relevant records, and input from stakeholders was solicited to select data for extraction. Sixty-seven studies of moderate to low-level evidence quality describing the MRI features of pathologically confirmed canine and feline brain tumors met inclusion criteria. Considerable variability in data inclusion and reporting, as well as low case numbers, prohibited comparative data analyses. Available data support a holistic MRI approach incorporating lesion number, location within the brain, shape, intrinsic signal appearances on multiparametric sequences, patterns of contrast enhancement, and associated secondary changes in the brain to prioritize differential imaging diagnoses, and often allows for accurate presumptive diagnosis of common intracranial tumors. Quantitative MRI techniques show promise for improving discrimination of neoplastic from non-neoplastic brain lesions, as well as differentiating brain tumor types and grades, but sample size limitations will likely remain a significant practical obstacle to the design of robustly powered radiomic studies. For many brain tumor variants, particularly in cats, there remains a need for standardized studies that correlate clinicopathologic and neuroimaging data.

Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheeze. There are few mechanistic data linking chromosome 17q12-q21 to wheezing illness. OBJECTIVE: We investigated whether 17q12-q21 risk alleles were associated with impaired interferon responses to rhinovirus. METHODS: In a population-based birth cohort of European ancestry, we stimulated peripheral blood mononuclear cells with rhinovirus A1 (RV-A1) and rhinovirus A16 (RV-A16) and measured IFN and IFN-induced C-X-C motif chemokine ligand 10 (aka IP10) responses in supernatants. We investigated associations between virus-induced cytokines and 6 SNPs in 17q12-q21. Bayesian profile regression was applied to identify clusters of individuals with different immune response profiles and genetic variants. RESULTS: Five SNPs (in high linkage disequilibrium, r2 ≥ 0.8) were significantly associated with RV-A1-induced IFN-ß (rs9303277, P = .010; rs11557467, P = .012; rs2290400, P = .006; rs7216389, P = .008; rs8079416, P = .005). A reduction in RV-A1-induced IFN-ß was observed among individuals with asthma risk alleles. There were no significant associations for RV-A1-induced IFN-α or CXCL10, or for any RV-A16-induced IFN/CXCL10. Bayesian profile regression analysis identified 3 clusters that differed in IFN-ß induction to RV-A1 (low, medium, high). The typical genetic profile of the cluster associated with low RV-A1-induced IFN-ß responses was characterized by a very high probability of being homozygous for the asthma risk allele for all SNPs. Children with persistent wheeze were almost 3 times more likely to be in clusters with reduced/average RV-A1-induced IFN-ß responses than in the high immune response cluster. CONCLUSIONS: Polymorphisms on chromosome 17q12-q21 are associated with rhinovirus-induced IFN-ß, suggesting a novel mechanism-impaired IFN-ß induction-links 17q12-q21 risk alleles with asthma/wheeze.