Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.

Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland "units." Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.

Acceptability and feasibility of SUCCEAT, an intervention for parents of adolescents with anorexia nervosa.

OBJECTIVE: "Supporting Carers of Children and Adolescents with Eating Disorders in Austria" (SUCCEAT), a skills training for parents, delivered via workshops (WS) or online modules (ONL), has been proven to be effective in terms of parental distress, caregiver skills, and adolescents' outcome. This study examined the adherence to and the acceptability and feasibility of SUCCEAT. METHOD: One-hundred parents (86% mothers) of adolescents with anorexia nervosa participated in the 8-week training. Parents were assigned to the WS (n = 50) or ONL (n = 50) format using a quasi-randomised design. Adherence, acceptability, and feasibility were assessed using self-report questionnaires. RESULTS: Adherence to the sessions was high (66%-98%) for both groups. The usage of the material was comparable between the groups. However, in the WS group, participants actively approached the coaches (71.8% vs. 48.9% often/very often) or other parents (63% vs. 4.4% often/very often) more often. Perceived helpfulness was high in both groups, overall satisfaction and practicability were higher in the WS group. CONCLUSIONS: Good adherence, acceptability, and feasibility were confirmed for both formats of SUCCEAT, with minimal advantages of the WS regarding satisfaction and contact with other parents and coaches. Thus, both formats can be recommended for implementation in clinical routine.

Psychological distress and caregiving experience during the first two years of the COVID-19 pandemic among parents of an offspring with anorexia nervosa.

OBJECTIVE: To compare different aspects of caregiving distress and experience in parents of patients with anorexia nervosa (AN) before and during the COVID-19 pandemic. METHODS: Three cohorts of parents of AN patients (cohort 1-pre-pandemic: N = 78, cohort 2-first pandemic year: N = 51, cohort 3-second pandemic year: N = 119) were recruited from child and adolescent psychiatry wards and cross-sectionally assessed as part of the clinical routine. Quantitative measures of psychological distress, psychopathology, eating disorder (ED)-related burden, expressed emotion and caregiver skills were obtained at the beginning of the child's inpatient or outpatient treatment. RESULTS: Cohort 2 showed lower levels of anxiety and a tendency of lower emotional overinvolvement and higher caregiving skills compared to the pre-pandemic cohort. In contrast, the levels of general psychological distress, depression, ED-related burden and criticism observed in cohort 3 significantly exceeded pre-pandemic levels. The prevalence of clinically relevant depression was higher in cohort 3 (41.5%) compared to cohorts 1 (24.4%) and 2 (21.6%). DISCUSSION: The pandemic effects on parents seem to be time-specific. Lower distress in the early phase of the pandemic may be associated with improvements in parent-child-relationships reported in previous studies. However, the pandemic may has negative consequences in the long-term emphasising the need of ongoing parental support.

The Maudsley model of anorexia nervosa treatment for adolescents and emerging adults: A multi-centre cohort study.

OBJECTIVE: The aim of this study was examining the efficacy of the Maudsley Model of Anorexia Nervosa Treatment for Adolescents and Young Adults (MANTRa) compared to individual psychotherapy that can be considered as standard in Austria (TAU-O). METHOD: In this cohort study, 92 patients between 13 and 21 years suffering from full-syndrome, atypical or weight-restored anorexia nervosa (AN) received either 24-34 individual MANTRa sessions (n = 45) or TAU-O (n = 47). Outcome variables were age- and sex-related BMI, eating disorder and comorbid psychopathology at 6-, 12- and 18-month post baseline as well as acceptability of treatment and therapeutic alliance. RESULTS: Both treatments resulted in significant improvements in age- and sex related BMI and reductions in eating disorder and comorbid psychopathology over time with significant differences between groups in favour of MANTRa. The percentage of participants with fully remitted AN was significantly higher in the MANTRa group compared to TAU-O at 18-month follow-up (MANTRa: 46% vs. TAU-O: 16%, p = 0.006). Satisfaction with both treatments was high. CONCLUSIONS: MANTRa is an effective treatment programme for adolescents and young adults with AN. Randomised controlled trials comparing MANTRa with existing treatments are necessary. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (Identifier: NCT03535714).

Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine.

OBJECTIVE: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. METHOD: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. RESULTS: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. CONCLUSIONS: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN.

Fathers in the spotlight: parental burden and the effectiveness of a parental skills training for anorexia nervosa in mother-father dyads.

PURPOSE: Research on the engagement of fathers in the treatment of childhood psychiatric disorders is scarce. This study aims to investigate differences between mothers and fathers of adolescents with anorexia nervosa regarding parental burden and effectiveness of a parental skills training. METHODS: Ninety-one mother-father dyads caring for a child with anorexia nervosa participated in an 8-week parental skills training and completed a set of questionnaires assessing parental psychopathology, eating disorder related burden, caregiver skills and expressed emotion at baseline and post-intervention. RESULTS: Fathers showed lower levels of general psychological distress, depression, anxiety and eating disorder related burden as well as lower emotional overinvolvement compared to mothers. The skills training was effective in reducing parental psychopathology, eating disorder-related burden and emotional overinvolvement as well as in increasing caregiver skills with no differences between mothers and fathers. However, session adherence and the willingness to practice skills between the sessions were slightly lower in fathers. CONCLUSIONS: These findings show that fathers are a great resource for the child's eating disorder treatment as they may counterbalance maternal emotional overinvolvement and over-protection. Furthermore, this is the first study demonstrating that fathers can profit from a parental skills training for anorexia nervosa in a similar way as mothers. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

A German version of the Caregiver Skills scale for caregivers of patients with anorexia nervosa.

OBJECTIVE: To investigate acceptance, reliability, convergent validity, factor structure and sensitivity to change of a German translation of the Caregiver Skills (CASK) scale measuring skills related to caring for patients with eating disorders. METHODS: Two hundred and thirty-three parents (76% female) of adolescent patients (mean age 15.1) with anorexia nervosa (AN) completed the 27 items of the CASK. We calculated item/scale characteristics, internal consistencies and bivariate correlations with other measures of caregiving burden. We evaluated goodness-of-fit of the 6-factor model using confirmatory factors analysis and explored the sensitivity to change following two skills-based trainings. RESULTS: The fit of the 6-factor model was acceptable (Root Mean Square Error of Approximation: 0.077, Standard Root Mean Square Residual: 0.080). Cronbach's alpha was excellent for the total (.94) and acceptable for all subscales (0.73-0.85). The total CASK score was 68.04 (max. 100) showing relatively high self-rated caregiver skills. Non-completion rates of most items were low (<3%) indicating high acceptance. Convergent validity was found with measures of psychological distress, depression, anxiety and expressed emotion. The total score significantly increased following an 8-week workshop/online skills training (d = 0.70) and a 2-day multi-family intervention (d = 0.47). DISCUSSION: The German CASK version is a useful instrument to assess caregiver skills in parents of patients with AN and to evaluate outcomes of skills-based trainings.

[Cost minimization analysis of flexible ENT-endoscopes]. / Kostenvergleichsanalyse von flexiblen HNO-Endoskopen.

BACKGROUND: Reprocessing of complex instruments like flexible ENT-endoscopes with and without working channel are challanging for clinics and private practices. Aim of the study was to analyse the costs of an examination with a reusable endoscope-system and to compare it with two single-use endoscope-systems. MATERIAL AND METHODS: A cost minimization analysis was performed at the Department of Otorhinolaryngology, Head and Neck Surgery of the University Medical Center in Mainz, Germany. The local reusable endoscopy-system was compared with two single-use endoscopy-systems of Ambu and Karl Storz. RESULTS: Overall costs per examination with a reusable-scope were 23.03 € (11.60 € investment costs + 5.09 € repair costs + 6.34 € reprocessing costs). The single-use Endoscopy-system of Ambu resulted in 120.43 € per examination (120.00 € acquisition costs + 0.43 € storage costs). Overall costs for the single-use endoscopy-system of Karl Storz were 223.44 € per examination (investment costs for monitors 3.01 € + 220.00 € acquisition costs + 0.43 € storage costs). DISCUSSION: Flexible single-use ENT-endoscopy-systems generate higher costs in comparison to conventional reusable ones. But there are also advantages from the medical and economical side. CONCLUSION: A smart mix of reusable and single-use endoscopy systems seems therefore usefull.

Prevalence and burden of headache in children and adolescents in Austria - a nationwide study in a representative sample of pupils aged 10-18 years.

BACKGROUND: Headache disorders are highly prevalent worldwide, but not so well investigated in children and adolescents as in adults: few studies have included representative nationwide samples. No data exist for Austria until now. In a representative sample of children and adolescents in Austria, we estimated the prevalence and attributable burden of headache disorders, including the new diagnostic category of "undifferentiated headache" (UdH) defined as mild headache lasting less than 1 hour. METHODS: Within the context of a broader national mental health survey, children and adolescents aged 10-18 years were recruited from purposively selected schools. Mediated self-completed questionnaires included sociodemographic enquiry (gender, age, socioeconomic status, family constellation, residence [urban or rural] and migration background). Prevalence and attributable burden of all headache, UdH, migraine (definite plus probable), tension-type headache (TTH: definite plus probable) and headache on ≥15 days/month (H15+) were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Health-related quality of life (HrQoL) was assessed using the KIDSCREEN questionnaire. RESULTS: Of 7643 selected pupils, 3386 (44.3%) completed the questionnaires. The 1-year prevalence of headache was 75.7%, increasing with age and higher in girls (82.1%) than in boys (67.7%; p < 0.001). UdH, migraine, TTH and H15+ were reported by 26.1%, 24.2%, 21.6% and 3.0% of participants. Attributable burden was high, with 42% of those with headache experiencing restrictions in daily activities. Medication use (50% overall) was highest in H15+ (67%) and still considerable in UdH (29%). HrQoL was reduced for all headache types except UdH. Participants in single parent or patchwork families had a higher probability of migraine (respectively, OR 1.5, p < 0.001; OR 1.5, p < 0.01). Participants with a migration background had a lower probability of TTH (OR 0.7, p < 0.01). CONCLUSIONS: Headache disorders are both very common and highly burdensome in children and adolescents in Austria. This study contributes to the global atlas of headache disorders in these age groups, and corroborates and adds knowledge of the new yet common and important diagnostic category of UdH. The findings call for action in national and international health policies, and for further epidemiological research.

Prevalence of emotional and behavioral problems and subthreshold psychiatric disorders in Austrian adolescents and the need for prevention.

PURPOSE: Epidemiological data are crucial to plan adequate prevention strategies. Thus, this study aims at obtaining the prevalence of mental health problems (MHP) and subthreshold psychiatric disorders based on a representative sample of Austrian adolescents. METHODS: Adolescents aged 10-18 were recruited from Austrian schools. Emotional and behavioral problems were determined using the Youth Self-Report (YSR); the point prevalence of subthreshold psychiatric disorders was assessed using structured diagnostic interviews. Sociodemographic variables including socioeconomic background, migration status, family structure, and place of residence were obtained. In addition, a non-school sample (unemployed adolescents, and child and adolescent psychiatry patients) was included to enhance representativeness and generalizability. RESULTS: 3446 students, 37 unemployed adolescents, and 125 child and adolescent psychiatric patients provided analyzable YSR data sets. In the school sample, 16.5% scored in the clinically relevant range, while internalizing problems were more prevalent (17.8%) than externalizing problems (7.4%). These prevalences increased by 0.7-2.0% when the non-school sample was taken into account. A low socioeconomic status (SES) and living in single parent families were associated with higher problem scores. Regarding the interviewed sample (377 students and 407 parents), subthreshold psychiatric disorders were observed in 12.7% of students. 92.5% of them have not yet received any kind of help. CONCLUSIONS: A significant proportion of Austrian adolescents are at risk for MHP. A non-responder analysis indicates that the observed prevalence may be even underestimated. These findings emphasize the urgent need for targeted prevention, especially for reducing anxiety and depressive symptoms and for adolescents in disadvantaged families.

Supporting Carers of Children and Adolescents with Eating Disorders in Austria (SUCCEAT): Study protocol for a randomised controlled trial.

Supporting Carers of Children and Adolescents with Eating Disorders in Austria (SUCCEAT) is an intervention for carers of children and adolescents with anorexia nervosa and atypical anorexia nervosa. This paper describes the study protocol for a randomised controlled trial including the process and economic evaluation. Carers are randomly allocated to one of the 2 SUCCEAT intervention formats, either 8 weekly 2-hr workshop sessions (n = 48) or web-based modules (n = 48), and compared with a nonrandomised control group (n = 48). SUCCEAT includes the cognitive-interpersonal model, cognitive behavioural elements, and motivational interviewing. The goal is to provide support for carers to improve their own well-being and to support their children. Outcome measures include carers' distress, anxiety, depression, expressed emotions, needs, motivation to change, experiences of caregiving, and skills. Further outcome measures are the patients' eating disorder symptoms, emotional problems, behavioural problems, quality of life, motivation to change, and perceived expressed emotions. These are measured before and after the intervention, and 1-year follow-up.

Mental health problems in Austrian adolescents: a nationwide, two-stage epidemiological study applying DSM-5 criteria.

This is a nationwide epidemiological study using DSM-5 criteria to assess the prevalence of mental disorders in a large sample of Austrian adolescents between 10 and 18 years including hard-to-reach samples. A sample of 3615 adolescents from four cohorts (school grades 5, 7, 9, 11; age range 10-18 years) was recruited from 261 schools, samples of unemployed adolescents (n = 39) and adolescents from mental health institutions (n = 137) were added. The Youth Self-Report and SCOFF were used to screen for mental health problems. In a second phase, the Childrens' Diagnostic Interview for Mental Disorders was used to make point and lifetime psychiatric diagnoses. Mental health service use was also assessed. Point prevalence and lifetime prevalence rates for at least one psychiatric disorder were 23.9% and 35.8%. The highest lifetime prevalence rates were found for anxiety disorders (15.6%), neurodevelopmental disorders (9.3%; ADHD 5.2%) and depressive disorders (6.2%). Forty-seven percent of adolescents with a lifetime psychiatric disorder had a second diagnosis. Internalising disorders were more prevalent in girls, while neurodevelopmental disorders and disruptive, impulse control and conduct disorders were more prevalent in boys. Of those with a lifetime psychiatric disorder, 47.5% had contacted mental health services. Of the residual 52.5% who had not contacted mental health services, 18.1% expressed an interest in treatment. DSM-5 mental health disorders are highly prevalent among Austrian adolescents. Over 50% had or were interested in accessing treatment. Early access to effective interventions for these problems is needed to reduce burden due to mental health disorders.

Prevalence of Eating Disorder Risk and Associations with Health-related Quality of Life: Results from a Large School-based Population Screening.

OBJECTIVE: The objective of this study was to investigate the prevalence of eating disorder (ED) risk as well as associated psychopathology and health-related quality of life (HrQoL) in a large population sample of Austrian adolescents. METHOD: A sample of 3610 adolescents aged 10-18 years was recruited from 261 schools representative for the Austrian population. The SCOFF questionnaire was used to identify participants at risk for EDs, and the Youth Self-Report and KIDSCREEN were used to assess general psychopathology and HrQoL. RESULTS: In total, 30.9% of girls and 14.6% of boys were screened at risk for EDs. SCOFF scores were significantly associated with internalising and externalising behavioural problems as well as HrQoL after controlling for sex, age and body mass index. The SCOFF score further turned out to be an independent predictor of HrQoL. DISCUSSION: The high prevalence of ED risk among Austrian adolescents points out the need for prevention in this field. Variables indicating eating pathology should be included in general mental health screenings.

The Mental Health in Austrian Teenagers (MHAT)-Study: preliminary results from a pilot study.

BACKGROUND: No epidemiological data on prevalence rates of mental disorders based on a representative sample are available for Austrian adolescents up to now. However, the knowledge of psychiatric disorders, related risk and protective factors is of great significance for treatment and prevention. The purpose of the MHAT-Study (Mental Health in Austrian Teenagers), the first epidemiological study on mental health in Austria, is to obtain prevalence rates of mental disorders and to examine risk factors, protective factors and quality of life in a representative sample of adolescents aged 10-18. Aims of this pilot study were to evaluate the feasibility and acceptability of the screening instruments, pre-estimate the frequency of mental health problems and estimate possible non-responder bias. METHODS: Twenty-one schools in eastern Austria were asked to participate. Data on mental health problems were derived from self-rating questionnaires containing standardized screening measures (Youth Self-Report, measuring emotional and behavioral problems and the SCOFF, indicating eating problems. Quality of life as well as related risk and protective factors were also obtained. RESULTS: Four hundred and eight adolescents of five schools were recruited. The prevalence of mental health problems was 18.9 % [CI 95 %: 14.9-22.7]. Moreover, emotional and behavioral problems were highly correlated with quality of life measures. A Non-Responder Analysis indicated that non-responders (16.7 %) differ from responders with regard of school related problems. CONCLUSIONS: The results demonstrate that mental health problems affect approximately one fifth of the adolescents. A Non-Responder Analysis suggests that the prevalence of behavioral and emotional problems is underestimated.

Comprehensive analysis of two hotspot codons in the TUBB4B gene and associated phenotypes.

Our purpose was to elucidate the genotype and ophthalmological and audiological phenotype in TUBB4B-associated inherited retinal dystrophy (IRD) and sensorineural hearing loss (SNHL), and to model the effects of all possible amino acid substitutions at the hotspot codons Arg390 and Arg391. Six patients from five families with heterozygous missense variants in TUBB4B were included in this observational study. Ophthalmological testing included best-corrected visual acuity, fundus examination, optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Audiological examination included pure-tone and speech audiometry in adult patients and auditory brainstem response testing in a child. Genetic testing was performed by disease gene panel analysis based on genome sequencing. The molecular consequences of the substitutions of residues 390 and 391 on TUBB4B and its interaction with α-tubulin were predicted in silico on its three-dimensional structure obtained by homology modelling. Two independent patients had amino acid exchanges at position 391 (p.(Arg391His) or p.(Arg391Cys)) of the TUBB4B protein. Both had a distinct IRD phenotype with peripheral round yellowish lesions with pigmented spots and mild or moderate SNHL, respectively. Yet the phenotype was milder with a sectorial pattern of bone spicules in one patient, likely due to a genetically confirmed mosaicism for p.(Arg391His). Three patients were heterozygous for an amino acid exchange at position 390 (p.(Arg390Gln) or p.(Arg390Trp)) and presented with another distinct retinal phenotype with well demarcated pericentral retinitis pigmentosa. All showed SNHL ranging from mild to severe. One additional patient showed a variant distinct from codon 390 or 391 (p.(Tyr310His)), and presented with congenital profound hearing loss and reduced responses in ERG. Variants at codon positions 390 and 391 were predicted to decrease the structural stability of TUBB4B and its complex with α-tubulin, as well as the complex affinity. In conclusion, the twofold larger reduction in heterodimer affinity exhibited by Arg391 substitutions suggested an association with the more severe retinal phenotype, compared to the substitution at Arg390.

Mental Health and Health-Related Quality of Life in Austrian Adolescents with Chronic Physical Health Conditions: Results from the MHAT Study.

Chronic physical health conditions (CPHC) are on the rise in younger age groups and might have a negative impact on children and adolescents. In a representative sample of Austrian adolescents aged 10-18 years, internalizing, externalizing, and behavioral problems were assessed cross-sectionally using the Youth Self-Report and health-related quality of life (HrQoL) using the KIDSCREEN questionnaire. Sociodemographic variables, life events, and chronic illness specific parameters were considered as associated variables with mental health problems in individuals with CPHC. Of 3469 adolescents, 9.4% of girls and 7.1% of boys suffered from a chronic pediatric illness. Of these individuals, 31.7% and 11.9% had clinically relevant levels of internalizing and externalizing mental health problems, respectively, compared to 16.3% and 7.1% adolescents without a CPHC. Anxiety, depression, and social problems were twice as high in this population. Medication intake due to CPHC and any traumatic life-event were related to mental health problems. All HrQoL domains were deteriorated in adolescents with a double burden of mental and CPHC, whereas adolescents with a CPHC without mental health problems did not differ significantly from adolescents without a chronic illness. Targeted prevention programs for adolescents with a CPHC are urgently needed to prevent mental health problems in the long term.

An investigation of the factor structure of a German version of the Eating Disorder Symptom Impact Scale (EDSIS) among parents of adolescents and young adults with anorexia nervosa.

The aim of this study was to explore the factor structure, scale characteristics and convergent validity of a German version of the Eating Disorder Symptom Impact Scale (EDSIS). A total of 335 parents of adolescents and young adults with anorexia nervosa in inpatient or outpatient treatment completed the 24-item German translation of the EDSIS and other measures of caregiving burden and psychological distress. We tested a 4 vs. 6-factor model of the EDSIS using confirmatory factor analyses. The 6-factor model treating items as ordinal variables showed the best fit to the data (CFI = 0.949, RMSEA = 0.064). Strong invariance of this model was shown between the sample of mothers and fathers. Internal consistencies of the EDSIS scales were in the acceptable-to-good range. Bottom effects were observed for the 'Binge-Purge-Impacts' subscale only. Mothers had significantly higher EDSIS scores compared to fathers. The EDSIS total score and most of the subscores showed substantial positive correlations with caregivers' psychological distress, level of depression, anxiety and expressed emotion as well as negative associations with the level of perceived caregiving skills. The German version of the EDSIS is a useful tool to assess caregiving burden in mothers and fathers of patients with anorexia nervosa.

Isoform-specific translational control is evolutionarily conserved in primates.

Alternative splicing (AS) alters messenger RNA (mRNA) coding capacity, localization, stability, and translation. Here we use comparative transcriptomics to identify cis-acting elements coupling AS to translational control (AS-TC). We sequenced total cytosolic and polyribosome-associated mRNA from human, chimpanzee, and orangutan induced pluripotent stem cells (iPSCs), revealing thousands of transcripts with splicing differences between subcellular fractions. We found both conserved and species-specific polyribosome association patterns for orthologous splicing events. Intriguingly, alternative exons with similar polyribosome profiles between species have stronger sequence conservation than exons with lineage-specific ribosome association. These data suggest that sequence variation underlies differences in the polyribosome association. Accordingly, single nucleotide substitutions in luciferase reporters designed to model exons with divergent polyribosome profiles are sufficient to regulate translational efficiency. We used position specific weight matrices to interpret exons with species-specific polyribosome association profiles, finding that polymorphic sites frequently alter recognition motifs for trans-acting RNA binding proteins. Together, our results show that AS can regulate translation by remodeling the cis-regulatory landscape of mRNA isoforms.