Columbia College

Mediterranean diet (MeDi) has been linked to lower incidence of cardiovascular and neurodegenerative diseases, and overall mortality, in several prospective studies. There is limited data, however, regarding the relationship between MeDi and stroke subtypes. We hypothesized that MeDi would be associated with lower total, ischemic, and hemorrhagic stroke incidence. The California Teachers Study is a prospective cohort study that comprises 133,477 women who were educators and administrators enrolled in 1995-1996 and followed since. We identified incident strokes using linked California state hospitalization data and national death records from 1996-2020. The MeDi adherence score (range 0-9, higher score indicating better adherence) was calculated based on participants' response to the Block food frequency questionnaire at study baseline. Multivariable Cox proportional hazard models adjusted for socio-demographic, lifestyle and vascular risk variables were constructed to assess the association (hazard ratios and 95% confidence intervals, HR 95% CI) between MeDi score and risk of stroke and its subtypes. 105,614 participants were eligible and included in the final analytic cohort (mean age 52.5 ± 13.8 years). Over the follow-up period (average follow-up time was 20.5 years), there were 4,083 incident stroke events (3,358 ischemic; 725 hemorrhagic). In fully-adjusted models for all stroke, ischemic and hemorrhagic subtypes, there was a lower risk of stroke among those with MeDi scores of 6-9 compared to those with scores of 0-2 (all stroke HR 0.82, 95% CI 0.74-0.92; ischemic HR 0.84, 95% CI 0.75 - 0.95; hemorrhagic HR 0.75, 95% CI 0.58-0.97). Adherence to the MeDi is associated with lower risk of total, ischemic, and hemorrhagic stroke incidence among women. Potential study limitations include recall bias, misclassification bias, and residual confounding, which would bias our results to the null.

PurposeThe purpose of this study is to evaluate inter-eye asymmetry in refractive error (spherical equivalent, SE) and corneal curvature (mean keratometry, Km) following orthokeratology (ortho-k) in adolescents, and to identify clinical predictors of asymmetric treatment response using a paired-eye design.MethodsA retrospective analysis was conducted in 53 adolescents (106 eyes; ages 8-16 years) treated with orthokeratology for at least 6 months. Absolute inter-eye differences (oculus dexter - oculus sinister (|OD−OS|)) in SE and Km were calculated at baseline and post-treatment. Paired-samples t-tests assessed inter-eye differences, Pearson correlations evaluated bilateral symmetry, and linear regression models examined predictors of post-treatment asymmetry, including baseline asymmetry, age, sex, treatment duration, and interaction terms. Generalized estimating equations were used to evaluate predictors of annualized refractive progression while accounting for inter-eye correlation.ResultsMean baseline inter-eye asymmetry was 0.28 ± 0.34 D for SE and 0.37 ± 0.29 D for Km. Following treatment, asymmetry remained low (ΔSE: 0.22 ± 0.23 D; ΔKm: 0.15 ± 0.32 D), with no significant differences between the right and left eyes. Bilateral correlations were strong for all refractive and corneal measures. A minority of participants demonstrated higher asymmetry exceeding commonly used clinical thresholds. Linear regression analyses identified no significant predictors of post-treatment asymmetry, with low overall model explanatory power. In contrast, older age at treatment initiation and longer treatment duration were associated with slower annualized myopia progression, while baseline asymmetry and sex were not.ConclusionsOrthokeratology produces highly symmetric bilateral refractive and corneal responses in adolescents, with minimal inter-eye asymmetry and no identifiable predictors of asymmetric outcome. The consistency of treatment effects across eyes supports orthokeratology as a reliable and predictable myopia control strategy, including in pediatric populations managed in rural or underserved settings.

Background: There is sparse normative data on clitoral-vestibular bulb anatomy and how it changes with aging, despite growing evidence of the latter playing a notable role in female sexual function and other pelvic symptoms. Objective: To identify age differences in clitoral-vestibular bulb anatomy (dimensions, position, shape) among women across the adult lifespan. Study Design: This was a retrospective study of pelvic magnetic resonance images of women (≥18 years) without pelvic floor disorder/dysfunction symptom indications (pelvic organ prolapse, urinary incontinence/pain, fecal incontinence/pain, dyspareunia) and with normal pelvic anatomy (radiographically normal reproductive, genitourinary, or gastrointestinal systems). Participants were categorized into the following age groups: Young Adult (18-34 years), Early Midlife (35-49 years), and Older Adult (≥50 years). Axial images of participants in the supine position at rest were acquired for medical indications. The clitoral-vestibular bulb complex, vagina, and urethra were manually segmented to construct 3-dimensional anatomical models. Computational methods quantified clitoral-vestibular bulb dimensions, position, vaginal-urethral distances, and shape (given by principal component scores obtained from a statistical shape model). Age differences in clitoral-vestibular bulb measures were evaluated using Bonferroni-corrected one-way multivariate and univariate analyses of covariance, with adjustments for body mass index and parity. Age-related correlations were assessed using Spearman’s rank correlation. Results: A total of 134 women were analyzed (median [range] age, 39 [19-80] years): 47 Young Adult, 46 Early Midlife, and 41 Older Adult women. All Young Adult and Early Midlife women were premenopausal, whereas 27 (71%) of Older Adult women were postmenopausal. Older Adult women had a shorter clitoral body length than Early Midlife women (24.1 mm vs 27.9 mm; P=.006). Overall, smaller vestibular bulb volume was associated with increasing age (P=.04). Older Adult women had a more inferiorly positioned clitoral-vestibular bulb complex (lower in the pelvis) than Early Midlife women (-21.0 mm vs -17.6 mm; P<.001) and Young Adult women (-21.0 mm vs -17.9 mm; P<.001). Across the entire cohort, increasing age correlated with a shorter clitoral body length (ρ=-0.21; P=.01) and vestibular bulb volume (ρ=-0.20; P=.02), and a more posteriorly (ρ=-0.22; P=.01) and inferiorly (ρ=-0.43; P<.001) positioned clitoral-vestibular bulb complex, whereas clitoral volume remained unchanged (ρ=-0.03; P=.73). The shape analysis revealed that age predominantly affected the vestibular bulbs, which became more medially positioned (closer together) (ρ=-0.28; P=.001) and proportionally smaller relative to the clitoris (ρ=-0.28; P=.001) with advancing age. Conclusions: Older age was associated with reduced size and posterior-inferior descent of the clitoral-vestibular bulb complex, with aging primarily affecting the vestibular bulbs compared to the clitoris. Findings demonstrate age-related atrophy and descent of clitoral-vestibular bulb anatomy, which may contribute to sexual function and other pelvic symptoms.

Lichen planus (LP) is a rare, chronic inflammatory disorder affecting both skin and mucous membranes. LP has been associated with autoimmune conditions, glucose intolerance, dyslipidemia, and cardiovascular disorders; however, comprehensive data on these associations is limited. This study utilized data from the TrinetX Linked Network, comprising over 112 million patients, to assess the risk of comorbidities in LP patients from July 1, 2016, to December 9, 2024. LP patients were identified using International Classification of Diseases, 10th Revision, Clinical Modification codes, and propensity score matching was applied to compare comorbidity risks with a control cohort. The analysis revealed a significant association between LP and autoimmune dermatologic and rheumatologic conditions, including localized scleroderma, alopecia areata, vitiligo, psoriasis, lupus erythematous, Sjögren syndrome, autoimmune hepatitis, and autoimmune thyroiditis. Additionally, a lower risk was observed for hepatitis C and B infections in LP patients. The study highlights the stronger association between LP and autoimmune comorbidities, which could be linked to the higher prevalence of autoimmune diseases in women, explaining LP’s female predilection. These findings emphasize the need for heightened awareness of LP’s autoimmune nature. Limitations include diagnostic misclassification and potential geographic biases in the dataset.

Abstract Background Severe COVID-19 results in substantial economic burden and impacts quality of life. Assessing how non-hospitalized COVID-19 impacts health utilities during acute infection and long term is important to estimate the full economic impact of SARS-CoV-2 infection. Methods We analyzed EQ-5D-3L survey data from SARS-CoV-2 infected adults (aged ≥16 years) and children (aged 8-15 years) from three community and household cohorts in the United States (2020-2022). EQ-5D-3L scores were analyzed at three time points after symptom onset or first positive SARS-CoV-2 test result and converted to health utilities on a scale of 0-1 (1=perfect health). Among adults, regression models were used to compare differences in health utility by demographic/clinical characteristics. Results Among 538 SARS-CoV-2 non-hospitalized asymptomatic/symptomatic infections from 575 adults with EQ-5D-3L surveys, mean utilities were near 1 throughout the observation period. During 0-14 days, vaccinated participants had higher health utilities (Beta:0.57, 95% CI:0.07,1.07). Seeking medical care and having gastrointestinal symptoms (vs. none), were associated with lower health utilities (Beta, 95% CI:-0.96, −1.60, −0.31; and −0.76, −1.30, −0.21 respectively). During 15-30 days, unemployment was associated with lower health utility (Beta:-0.64, 95% CI:-1.15,-0.14). During 31-90 days, underlying conditions were associated with lower health utilities (Beta:-0.32, 95% CI:-0.54, −0.09). Results for children were similar to adults. Conclusion Non-hospitalized COVID-19 may have minimal overall impact on quality of life; however, health utilities differed by vaccination status, presence of gastrointestinal symptoms, employment status, and presence of underlying conditions. Vaccination may play an important role in minimizing illness impact from SARS-CoV-2 infection. Key points Severe COVID-19 illness causes substantial economic burden and impacts on quality of life; however, the incidence of non-hospitalized COVID-19 is far greater. Assessing how non-hospitalized COVID-19 impacts health during acute infection and long term is important to understand the full impact of SARS-CoV-2 infection. This study utilizes the EQ-5D-3L, a standardized generic preference-based instrument used in population health studies, to estimate health utilities at multiple time points following SARS-CoV-2 infection. The study also examines demographic/medical characteristics that are associated with health utility over time. While mean health utilities were high for all infection periods regardless of age, health utility was lower at varying time points post-infection among adults who sought medical care, reported gastrointestinal symptoms, were unemployed, and with underlying conditions. Vaccinated adults (vs. unvaccinated) had higher health utility and were less likely to report reduced health. Findings can be used as inputs for economic evaluation and assessing impact of interventions for non-hospitalized SARS-CoV-2 illness, such as vaccination.

Aberrant WNT/β-catenin signaling drives tumorigenesis and metastasis in cancer. Although enzymatic inhibitors of tankyrase (TNKS) effectively block AXIN degradation and stabilize the β-catenin destruction complex (DC), they have demonstrated limited efficacy in various cancer models. Here we demonstrate that, unexpectedly, the induction of AXIN puncta represents a major barrier to achieving therapeutic efficacy. Mechanistically, catalytic inhibition of TNKS prevents TNKS turnover and drives its accumulation in the DC, wherein the scaffolding function of TNKS induces AXIN puncta formation, rigidifies the DC, and impedes β-catenin turnover. Chemically induced degradation of TNKS overcomes this limitation by stabilizing AXIN without puncta formation, providing a deeper suppression of the WNT/β-catenin pathway activity and the proliferation of colorectal cancer cells harboring dysfunctional APC mutations. Collectively, these findings provide an explanation for the unsatisfactory outcomes of drugging the WNT/β-catenin signaling pathway by TNKS inhibitors and highlight TNKS degradation as a promising approach to treat WNT/β-catenin-driven cancers.

Autism is a heterogeneous set of neurodevelopmental conditions with a significant heritable component and perinatal origins. The earliest observable behavioural traits, with which a diagnosis can be made, emerge at 18 months of age. Previous studies have reported increased head circumference and brain growth in autistic children, but less is known about whether this extends to the wider spectrum of traits or to early brain development in the first 6 months of life. Data from two independent cohorts, the developing Human Connectome Project (dHCP) and Cambridge Human Imaging and Longitudinal Development (CHILD), were assessed in late fetal and early infancy for brain structure with MRI. Global and regional brain volumes in the dHCP, were studied prenatally (n = 106, mean age = 29.27 [SD = 3.8] gestational weeks) and postnatally (n = 454, mean age = 41.28 [SD = 1.93] weeks post-conception) in association with later autistic traits after 18 months of age, as captured on the parent-report Quantitative Checklist for Autism in Toddlers (‘Q-CHAT’). The results informed a region-of-interest analysis in the smaller independent CHILD cohort, where participants were scanned during pregnancy (mean = 31.98 weeks gestation, SD = 1.52) and postnatally (mean scan age = 50.45, SD = 2.8 weeks post-conception)(n = 27). After controlling for cohort covariates, such as maternal age, birth weight, sex and age post-conception at the time of scan, postnatal total brain volume, cortical grey matter volume, and white matter volume were all negatively associated with autistic traits in toddlerhood. This was found for postnatal volumes in both the dHCP and the CHILD cohort but was not apparent when assessing prenatal brain volume or perinatal growth rates of total brain volume in the same individuals. Regional analyses in the dHCP cohort, after controlling for total brain volume, showed patterns of note in the temporal lobe, which warrant further research. In conclusion, reduced total brain volume in the first two months of life is associated with a higher number of autistic traits, as reported by parents at 18 months of life. Further research is required to understand if this extends to later ages, to children later diagnosed with autism and how it affects the development and connectivity of specific regions, particularly in the temporal lobes.

PurposeMyopia is associated with increased near-work, time spent indoors, and urban environments. This may in part stem from the spatial frequency (SF) composition of the visual environment in such scenarios compared to nature. We investigated the SF content of natural and man-made environments and how the relative contrast experienced may be affected by viewing distance.DesignExperimental study of environmental contrast.Subjects, Participants, and ControlsDigital images (n = 594) from natural, mixed-urban, urban, and indoor environments across Singapore.MethodsThe fast Fourier transform was computed and radially averaged, and the slope of the amplitude spectra with SF was determined. The total contrast energy within each SF octave (f–2f) was measured to determine exposure deficits between environments and whether environmental contrast was scale invariant (unaffected by changes in viewing distance).Main Outcome MeasuresEnvironment differences in SF gradient, total contrast, and scale invariance.ResultsAs expected, indoor environments displayed the steepest SF gradients at –1.36 ± 0.1, more than urban (–1.22 ± 0.1, P < 0.01), mixed-urban (–1.09 ± 0.1, P < 0.01), and natural (–1.00 ± 0.1, P < 0.01) environments. Specifically, mixed-urban, urban, and indoor environments all lacked contrast at middle and higher SFs compared with natural scenes (P < 0.01 each). Contrast energy/octave was approximately equal for natural environments, signifying the relative SF composition was scale invariant. This was not true for man-made environments. Contrast energy/octave decreased as a function of SF in mixed-urban, urban, and most rapidly in indoor environments (P < 0.001 each), meaning the total contrast experienced in such environments is directly dependent on viewing distance. Consequently, halving viewing distance when indoors would reduce total perceived middle SF contrast by 35%, despite indoor environments already being deficient compared to nature.ConclusionsThe SF content of natural environments is consistent regardless of viewing distance, signifying scale invariance. This does not apply in man-made environments where contrast at all SFs directly depends on viewing distance. This implies that shorter viewing distances in man-made environments further exacerbate inherent deficits in middle and higher SF contrast, and thus these environments may fail to stimulate the eye with sufficient contrast compared to natural environments, possibly explaining why such environments induce myopia.Financial Disclosure(s)The authors have no proprietary or commercial interest in any materials discussed in this article.

ABCA7 (ATP-binding cassette sub-family A member 7) encodes a lipid transporter linked to Alzheimers disease (AD). While common variants confer modest risk in Europeans, a 44-base pair deletion (rs142076058; p.Arg578Alafs) is a strong risk factor in African Americans (AA). Despite this, the biological consequences of this ancestry-specific variant are not well understood. We expressed the truncated ABCA7 protein in HEK and HepG2 cells to assess localization and lipid metabolism. Additionally, induced pluripotent stem cell (iPSC)-derived neurons carrying the deletion were compared with isogenic controls. The truncated ABCA7 localized to the plasma membrane similarly to wild type but induced significant lipid droplet accumulation in HepG2 cells and iPSC-derived neurons. These findings show that the AA-specific ABCA7 deletion disrupts lipid regulation despite normal localization, suggesting a mechanistic link between impaired lipid homeostasis and increased AD risk. This work underscores the importance of ancestry-specific studies in AD research.

In transference-focused psychotherapy (TFP), an evidence-based treatment for patients with borderline personality disorder (BPD), the attention paid to establishing and tracking goals is both organizing and distinctive. The objective of this article is to describe TFP's unusual emphasis on first elucidating and then focusing on a patient's concrete, measurable personal goals. We review the critical distinction between the patient's goals and the therapist's goals. We also provide pertinent examples of material related to goals in TFP. The examination of the role of goals in the treatment of patients with BPD has significant salience given accumulating data that suggests that symptom remission does not reliably lead to enhanced functioning (sustained work/study performance, stable relations with a partner or parents) in this patient population.