Prenatal Exposure to Maternal Mood Entropy Is Associated With a Weakened and Inflexible Salience Network in Adolescence.

BACKGROUND: Fetal exposure to maternal mood dysregulation influences child cognitive and emotional development, which may have long-lasting implications for mental health. However, the neurobiological alterations associated with this dimension of adversity have yet to be explored. Here, we tested the hypothesis that fetal exposure to entropy, a novel index of dysregulated maternal mood, would predict the integrity of the salience network, which is involved in emotional processing. METHODS: A sample of 138 child-mother pairs (70 females) participated in this prospective longitudinal study. Maternal negative mood level and entropy (an index of variable and unpredictable mood) were assessed 5 times during pregnancy. Adolescents engaged in a functional magnetic resonance imaging task that was acquired between 2 resting-state scans. Changes in network integrity were analyzed using mixed-effect and latent growth curve models. The amplitude of low frequency fluctuations was analyzed to corroborate findings. RESULTS: Prenatal maternal mood entropy, but not mood level, was associated with salience network integrity. Both prenatal negative mood level and entropy were associated with the amplitude of low frequency fluctuations of the salience network. Latent class analysis yielded 2 profiles based on changes in network integrity across all functional magnetic resonance imaging sequences. The profile that exhibited little variation in network connectivity (i.e., inflexibility) consisted of adolescents who were exposed to higher negative maternal mood levels and more entropy. CONCLUSIONS: These findings suggest that fetal exposure to maternal mood dysregulation is associated with a weakened and inflexible salience network. More broadly, they identify maternal mood entropy as a novel marker of early adversity that exhibits long-lasting associations with offspring brain development.

Analysis and comparison of SARS-CoV-2 variant antibodies and neutralizing activity for 6 months after a booster mRNA vaccine in a healthcare worker population.

Introduction: In the context of recurrent surges of SARS-CoV-2 infections, a detailed characterization of antibody persistence over a 6-month period following vaccine booster dose is necessary to crafting effective public health policies on repeat vaccination. Methods: To characterize the SARS-CoV-2 antibody profile of a healthcare worker population over a 6-month period following mRNA vaccination and booster dose. 323 healthcare workers at an academic medical center in Orange County, California who had completed primary vaccination and booster dose against SARS-CoV-2 were recruited for the study. A total of 690 blood specimens over a 6-month period were collected via finger-stick blood and analyzed for the presence of antibodies against 9 SARS-CoV-2 antigens using a coronavirus antigen microarray. Results: The primary outcome of this study was the average SARS-CoV-2 antibody level as measured using a novel coronavirus antigen microarray. Additional outcomes measured include levels of antibodies specific to SARS-CoV-2 variants including Delta, Omicron BA.1, and BA.2. We also measured SARS-CoV-2 neutralization capacity for a subset of the population to confirm correlation with antibody levels. Although antibodies against SARS-CoV-2 wane throughout the 6-month period following a booster dose, antibody levels remain higher than pre-boost levels. However, a booster dose of vaccine based on the original Wuhan strain generates approximately 3-fold lower antibody reactivity against Omicron variants BA.1 and BA.2 as compared to the vaccine strain. Despite waning antibody levels, neutralization activity against the vaccine strain is maintained throughout the 6-month period. Discussion: In the context of recurrent surges of SARS-CoV-2 infections, our data indicate that breakthrough infections are likely driven by novel variants with different antibody specificity and not by time since last dose of vaccination, indicating that development of vaccinations specific to these novel variants is necessary to prevent future surges of SARS-CoV-2 infections.

Risk factors for SARS-CoV-2 seropositivity in a health care worker population during the early pandemic.

BACKGROUND: While others have reported severe acute respiratory syndrome-related coronavirus 2(SARS-CoV-2) seroprevalence studies in health care workers (HCWs), we leverage the use of a highly sensitive coronavirus antigen microarray to identify a group of seropositive health care workers who were missed by daily symptom screening that was instituted prior to any epidemiologically significant local outbreak. Given that most health care facilities rely on daily symptom screening as the primary method to identify SARS-CoV-2 among health care workers, here, we aim to determine how demographic, occupational, and clinical variables influence SARS-CoV-2 seropositivity among health care workers. METHODS: We designed a cross-sectional survey of HCWs for SARS-CoV-2 seropositivity conducted from May 15th to June 30th 2020 at a 418-bed academic hospital in Orange County, California. From an eligible population of 5,349 HCWs, study participants were recruited in two ways: an open cohort, and a targeted cohort. The open cohort was open to anyone, whereas the targeted cohort that recruited HCWs previously screened for COVID-19 or work in high-risk units. A total of 1,557 HCWs completed the survey and provided specimens, including 1,044 in the open cohort and 513 in the targeted cohort. Demographic, occupational, and clinical variables were surveyed electronically. SARS-CoV-2 seropositivity was assessed using a coronavirus antigen microarray (CoVAM), which measures antibodies against eleven viral antigens to identify prior infection with 98% specificity and 93% sensitivity. RESULTS: Among tested HCWs (n = 1,557), SARS-CoV-2 seropositivity was 10.8%, and risk factors included male gender (OR 1.48, 95% CI 1.05-2.06), exposure to COVID-19 outside of work (2.29, 1.14-4.29), working in food or environmental services (4.85, 1.51-14.85), and working in COVID-19 units (ICU: 2.28, 1.29-3.96; ward: 1.59, 1.01-2.48). Amongst 1,103 HCWs not previously screened, seropositivity was 8.0%, and additional risk factors included younger age (1.57, 1.00-2.45) and working in administration (2.69, 1.10-7.10). CONCLUSION: SARS-CoV-2 seropositivity is significantly higher than reported case counts even among HCWs who are meticulously screened. Seropositive HCWs missed by screening were more likely to be younger, work outside direct patient care, or have exposure outside of work.

Adolescent use and co-use of tobacco and cannabis in California: The roles of local policy and density of tobacco, vape, and cannabis retailers around schools.

Adolescent tobacco use (particularly vaping) and co-use of cannabis and tobacco have increased, leading some jurisdictions to implement policies intended to reduce youth access to these products; however, their impacts remain unclear. We examine associations between local policy, density of tobacco, vape, and cannabis retailers around schools, and adolescent use and co-use of tobacco/vape and cannabis. We combined 2018 statewide California (US) data on: (a) jurisdiction-level policies related to tobacco and cannabis retail environments, (b) jurisdiction-level sociodemographic composition, (c) retailer locations (tobacco, vape, and cannabis shops), and (d) survey data on 534,176 middle and high school students (California Healthy Kids Survey). Structural equation models examined how local policies and retailer density near schools are associated with frequency of past 30-day cigarette smoking or vaping, cannabis use, and co-use of tobacco/vape and cannabis, controlling for jurisdiction-, school-, and individual-level confounders. Stricter retail environment policies were associated with lower odds of past-month use of tobacco/vape, cannabis, and co-use of tobacco/vape and cannabis. Stronger tobacco/vape policies were associated with higher tobacco/vape retailer density near schools, while stronger cannabis policies and overall policy strength (tobacco/vape and cannabis combined) were associated with lower cannabis and combined retailer densities (summed tobacco/vape and cannabis), respectively. Tobacco/vape shop density near schools was positively associated with tobacco/vape use odds, as was summed retailer density near schools and co-use of tobacco, cannabis. Considering jurisdiction-level tobacco and cannabis control policies are associated with adolescent use of these substances, policymakers may proactively leverage such policies to curb youth tobacco and cannabis use.

Experiences of COVID-19-Related Racism and Impact on Depression Trajectories Among Racially/Ethnically Minoritized Adolescents.

PURPOSE: In 2020, racially/ethnically minoritized (REMD) youth faced the "dual pandemics" of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic). METHODS: A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%). RESULTS: REMD adolescents' depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date. DISCUSSION: REMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth.

Quantitative cone contrast threshold testing in patients with differing pathophysiological mechanisms causing retinal diseases.

BACKGROUND: Cone contrast threshold testing (CCT) provides quantitative measurements of color and contrast function to reveal changes in vision quality that are not standard endpoints in clinical trials. We utilize CCT to measure visual function in patients with multiple sclerosis (MS), age-related macular degeneration (AMD), epiretinal membrane (ERM), and retinal vein occlusion (RVO). METHODS: Retrospective data was gathered from 237 patients of the Gavin Herbert Eye Institute. Subjects included 17 patients with MS, 45 patients with AMD, 41 patients with ERM, 11 patients with RVO, and 123 healthy controls. Patients underwent the primary measurement outcome, CCT testing, as well as Sloan visual acuity test and spectral domain optical coherence tomography during normal care. RESULTS: Color and contrast deficits were present in MS patients regardless of history of optic neuritis. AMD with intermediate or worse disease demonstrated reduced CCT scores. All 3 stages of ERM demonstrated cone contrast deficits. Despite restoration of visual acuity, RVO-affected eyes demonstrated poorer CCT performance than unaffected fellow eyes. CONCLUSIONS: CCT demonstrates color and contrast deficits for multiple retinal diseases with differing pathophysiology. Further prospective studies of CCT in other disease states and with larger samples sizes is warranted.

Health-Related Social Control and Perceived Stress Among High-Risk Latina Mothers with Type 2 Diabetes and Their At-Risk Adult Daughters.

BACKGROUND: Diabetes-related multi-morbidity and cultural factors place Latinas with diabetes at increased risk for stress, which can threaten illness management. Families provide an ideal focus for interventions that seek to strengthen interpersonal resources for illness management and, in the process, to reduce stress. The current study sought to examine whether participating in a dyadic intervention was associated with reduced perceived stress and, furthermore, whether this association was mediated by persuasion and pressure, two forms of health-related social control. METHOD: Latina mothers with diabetes and their at-risk adult daughters participated in either (1) a dyadic intervention that encouraged constructive collaboration to improve health behaviors and reduce stress, or (2) a usual-care minimal control condition. Actor-partner interdependence model analysis was used to estimate the effect of the intervention on dyads' perceived stress, and mother-daughter ratings of health-related social control as potential mediators. RESULTS: Results revealed that participating in the intervention was associated with significantly reduced perceived stress for daughters, but not for mothers (ß = - 3.00, p = 0.02; ß = - 0.57, p = 0.67, respectively). Analyses also indicated that the association between the intervention and perceived stress was mediated by persuasion, such that mothers' who experienced more health-related persuasion exhibited significantly less post-intervention perceived stress (indirect effect = - 1.52, 95% CI = [- 3.12, - 0.39]). Pressure exerted by others, however, did not evidence a mediating mechanism for either mothers or daughters. CONCLUSION: These findings buttress existing research suggesting that persuasion, or others' attempts to increase participants' healthy behaviors in an uncritical way, may be a driving force in reducing perceived stress levels.

Correlations of disease severity outcome measures in inclusion body myositis.

This study aimed to evaluate the correlation between various outcome measures used to assess disease severity and progression in inclusion body myositis (IBM) clinical trials. A cross-sectional study, involving 51 IBM patients meeting the European Neuromuscular Center (ENMC) 2011 criteria for clinically defined or probable IBM, was completed at the University of California, Irvine. Clinical details, demographic data, and functional data including timed get up (TGU), manual muscle testing, hand grip, pinch dynamometry, as well as IBM functional rating scale (IBMFRS), modified Rankin score, forced vital capacity (FVC), and modified ocular bulbar facial respiratory scale (mOBFRS) were collected on all patients. Descriptive statistics and Pearson's r correlation were performed to analyze the data. Age of the patient did not correlate with any of the outcome measures. Greater severity of IBMFRS scores correlated with longer disease duration as well as greater severity for FVC, strength outcomes, TGU, modified Rankin, and mOBFRS. Additionally, TGU strongly correlated with muscle strength measurements, modified Rankin, and mOBFRS. mOBFRS moderately correlated with IBMFRS, muscle strength, FVC, TGU and modified Rankin score. We demonstrate moderate to strong correlations among the disease severity outcome measures in this study.

Correcting for selection bias in HIV prevalence estimates: an application of sample selection models using data from population-based HIV surveys in seven sub-Saharan African countries.

INTRODUCTION: Population-based biomarker surveys are the gold standard for estimating HIV prevalence but are susceptible to substantial non-participation (up to 30%). Analytical missing data methods, including inverse-probability weighting (IPW) and multiple imputation (MI), are biased when data are missing-not-at-random, for example when people living with HIV more frequently decline participation. Heckman-type selection models can, under certain assumptions, recover unbiased prevalence estimates in such scenarios. METHODS: We pooled data from 142,706 participants aged 15-49 years from nationally representative cross-sectional Population-based HIV Impact Assessments in seven countries in sub-Saharan Africa, conducted between 2015 and 2018 in Tanzania, Uganda, Malawi, Zambia, Zimbabwe, Lesotho and Eswatini. We compared sex-stratified HIV prevalence estimates from unadjusted, IPW, MI and selection models, controlling for household and individual-level predictors of non-participation, and assessed the sensitivity of selection models to the copula function specifying the correlation between study participation and HIV status. RESULTS: In total, 84.1% of participants provided a blood sample to determine HIV serostatus (range: 76% in Malawi to 95% in Uganda). HIV prevalence estimates from selection models diverged from IPW and MI models by up to 5% in Lesotho, without substantial precision loss. In Tanzania, the IPW model yielded lower HIV prevalence estimates among males than the best-fitting copula selection model (3.8% vs. 7.9%). CONCLUSIONS: We demonstrate how HIV prevalence estimates from selection models can differ from those obtained under missing-at-random assumptions. Further benefits include exploration of plausible relationships between participation and outcome. While selection models require additional assumptions and careful specification, they are an important tool for triangulating prevalence estimates in surveys with substantial missing data due to non-participation.

Persistence of SARS-CoV-2 Antibodies in Vaccinated Health Care Workers Analyzed by Coronavirus Antigen Microarray.

Recent studies provide conflicting evidence on the persistence of SARS-CoV-2 immunity induced by mRNA vaccines. Here, we aim to quantify the persistence of humoral immunity following vaccination using a coronavirus antigen microarray that includes 10 SARS-CoV-2 antigens. In a prospective longitudinal cohort of 240 healthcare workers, composite SARS-CoV-2 IgG antibody levels did not wane significantly over a 6-month study period. In the subset of the study population previously exposed to SARS-CoV-2 based on seropositivity for nucleocapsid antibodies, higher composite anti-spike IgG levels were measured before the vaccine but no significant difference from unexposed individuals was observed at 6 months. Age, vaccine type, or worker role did not significantly impact composite IgG levels, although non-significant trends towards lower antibody levels in older participants and higher antibody levels with Moderna vaccine were observed at 6 months. A small subset of our cohort were classified as having waning antibody titers at 6 months, and these individuals were less likely to work in patient care roles and more likely to have prior exposure to SARS-CoV-2.

Breathing Room: Industrial Zoning and Asthma Incidence Using School District Health Records in the City of Santa Ana, California.

Background: Traffic and industrial emissions are associated with increased pediatric asthma morbidity. However, few studies have examined the influence of city industrial zoning on pediatric asthma outcomes among minoritized communities with limited access to air monitoring. Methods: In this cross-sectional analysis of 39,974 school-aged students in Santa Ana, CA, we investigated the effect of proximity to areas zoned for industrial use on pediatric asthma prevalence, physical fitness, school attendance, and standardized test scores. Results: The study population was 80.6% Hispanic, with 88.2% qualifying for free/reduced lunch. Compared to students living more than 1 km away from industrial zones, those living within 0.5 km had greater odds of having asthma (adjusted OR 1.21, 95% CI 1.09 to 1.34, p < 0.001). Among children with asthma, those living between 0.5−1.0 km had greater odds of being overweight or obese (aOR 1.47, 95% CI 1.00, 2.15, p = 0.047). Industrial zone proximity was not significantly associated with worse fitness and academic outcomes for students with asthma. Conclusion: These findings suggest that industrial zone proximity is associated with increased pediatric asthma in a predominantly Latino community in Southern California.

Analysis of port-wine birthmark vascular characteristics by location: Utility of optical coherence tomography mapping.

INTRODUCTION: Port-wine birthmarks (PWBs) are congenital capillary malformations that can be located on any area of the body. Vascular features include vessel size, depth, and density, which can greatly differ between patients, individual lesions, and even sites within the same lesion. Previous studies have determined that the location of PWB lesions has impacted their clinical response to laser treatment. OBJECTIVE: We utilized dynamic optical coherence tomography (D-OCT) to measure in vivo vessel diameter, density, and superficial plexus depth in patients of all ages with PWB on various sites of the body. We hypothesized that these vascular characteristics would differ according to body location. MATERIALS AND METHODS: Patients who had a PWB and presented to clinic at three sites for treatment with the pulsed dye laser (PDL) were enrolled into the study. A D-OCT scanner was utilized for noninvasive, in vivo imaging of PWB lesions. The depth of the top portion of the superficial vascular plexus was estimated as the depth at which the vessel density reaches 50% of the maximum. Vessel diameter and density were calculated by incorporated software algorithm. RESULTS: A total of 108 patients were enrolled into the study. There was a total of 204 measurements of PWB lesions. Of all patients, 56.5% (n = 61) reported having a previous treatment with PDL. Of all D-OCT scans, 62.3% (n = 127) were located on the head, 14.2% (n = 29) the upper extremities, 8.3% (n = 17) the lower extremities, 7.8% (n = 16) the trunk, and 7.8% (n = 15) the neck. All locations were compared for each vascular characteristic. For superficial plexus depth, lesions on the head were significantly shallower than those on the upper extremities (217 vs. 284 µm; p < 0.001) and lower extremities (217 vs. 309 µm; p < 0.001). For vessel diameter, lesions on the head had significantly larger vessels than those on the upper extremities (100 vs. 72 µm; p = 0.001). For vessel density, lesions on the head had significantly denser vessels than those on the trunk (19% vs. 9.6%; p = 0.039) and upper extremities (19% vs. 9.3%; p < 0.001) CONCLUSIONS: PWB lesions have distinct vascular characteristics, which can be associated with their body location. This includes superficial vascular plexus depth as well as vessel diameter and density.

The acute and persisting impact of COVID-19 on trajectories of adolescent depression: Sex differences and social connectedness.

BACKGROUND: The COVID-19 era is a time of unprecedented stress, and there is widespread concern regarding its short- and long-term mental health impact. Adolescence is a sensitive period for the emergence of latent psychopathology vulnerabilities, often activated by environmental stressors. The present study examined COVID-19's impact on adolescent depression and possible influences of different domains of social connectedness (loneliness, social media use, social video game time, degree of social activity participation). METHODS: A community sample of 175 adolescents (51% boys, mean age = 16.01 years) completed questionnaires once before and twice during the COVID-19 pandemic. Piecewise growth modeling examined the acute (7 weeks) and persistent (8 months) effects of COVID-19 on depressive symptoms, and differences across sex and social connectedness. RESULTS: Significant increases in depressive symptoms followed pandemic onset for boys and girls. However, this increase was earlier and more pronounced among girls than boys, whose depression only increased significantly during the persistent period and to a lesser degree. Trajectories of depression were influenced by loneliness and social connections. LIMITATIONS: Most participants had economic stability and minimal exposure to the virus. Exacerbation of depressive symptoms may be more severe in higher risk populations. CONCLUSIONS: Adolescent depression levels have increased during COVID-19, and are higher for girls and those who are lonely. Enhanced screening and management for adolescent depression and social connectedness could play a critical role in mitigating the negative mental health fallout of COVID-19 and future pandemics within this population.

Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.

This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.

Early life adversity in male mice sculpts reward circuits.

Early life adversity (ELA) comprises a wide variety of negative experiences during early life and has been linked to cognitive impairments, reduced experiences of pleasure (anhedonia), and other long-term consequences implying that ELA impacts the reward circuitry. In this study, we focused on the projections from the dorsal raphe (DR) to the ventral tegmental area (VTA) and on to the nucleus accumbens (NAcc), an important pathway within the reward circuit. We hypothesized that ELA alters connectivity within the DR-VTA-NAcc pathway, associated with deficient reward seeking behaviors in adulthood. We used the limited bedding and nesting model to induce ELA in mice and measured reward-related behaviors in adulthood using the three-chamber social interaction and sucrose preference tests. High resolution ex vivo diffusion tensor imaging (DTI) was acquired and processed for regional DTI metrics, including tractography to assess circuit organization. We found brain-wide changes in radial diffusivity (RD) and altered connectivity of the reward circuit in the ELA group. DR-VTA-NAcc circuit tractography and axial diffusivity (AD) along this tract exhibited dispersed organization where AD was increased in the VTA segment. Behaviorally, ELA elicited a social anhedonia-like phenotype in adulthood with decreased direct social approach and time spent with peers in the three-chamber task, and no overt differences in sucrose preference. Our findings suggest that reward circuits, assessed using DTI, are altered following ELA and that these changes may reflect enduring reward deficits.

Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis.

OBJECTIVE: Platinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic signatures that predict platinum resistance in patients receiving chemotherapy for gynecologic cancers. METHODS: In this study 47 patients with adenocarcinoma of the ovary or uterus who were candidates for carboplatin plus paclitaxel submitted blood for quantitation of metabolites and surgical specimens for the isolation 3-dimensional organoids used to measure individual patient platinum resistance, ex vivo. Results were correlated with response, time to progression and survival. RESULTS: Of 47 patients, 27 (64.3%) achieved complete remission with a mean time to progression of 1.9 years (± 1.5), disease-free survival of 1.7 years (± 1.4) and overall survival of 2.6 years (± 1.6) and a mean cisplatin lethal concentration 50% (LC50) = 1.15 µg/ml (range 0.4-3.1). Cisplatin LC50's correlated with a non-significant decrease in complete remission (RR [95% CI] =0.76 [0.46-1.27]), diminished disease-free survival (median: 1.15 vs. 2.99 years, p = 0.038) and with biochemical signatures of 186 metabolites. Receiver operating curves (ROC) of lipid ratios, branched chain amino acids and the tryptophan to kynurenine ratio identified patients at the highest risk of relapse and death (AUC = 0.933) with a sensitivity of 92.0% and specificity of 86.0% (p < 0.001). CONCLUSIONS: Metabolic signatures in gynecologic cancer identify patients at the highest risk of relapse and death offering new diagnostic and prognostic tools for management of the advanced gynecologic tumors.

Vascular characteristics of port wine birthmarks as measured by dynamic optical coherence tomography.

BACKGROUND: Port wine birthmarks (PWBs) are congenital capillary malformations. Vessel characteristics, such as diameter and depth, may impact presentation and outcomes. They can be imaged using dynamic optical coherence tomography, a high-resolution, noninvasive imaging method. PURPOSE: We conducted a cross-sectional observational study to measure in vivo vascular characteristics as a function of PWB color. METHODS: Patients undergoing treatment for PWB were recruited from 3 sites. PWBs were classified by color. Dynamic optical coherence tomography images with calculations were obtained. RESULTS: One hundred eight patients were enrolled. Mean age correlated with PWB color, with birthmarks being lighter in younger patients and darker in older patients (P < .01). Mean superficial plexus depth was significantly shallower in purple PWBs than in pink PWBs. Color was not associated with significant differences in mean superficial vessel density or diameter. Among pink PWBs, each 10-year increase in age was associated with a 10.6-µm increase in superficial plexus depth. Among purple PWBs, each 10-year increase in age was associated with a 16.2-µm reduction in superficial plexus depth. In lesions without prior treatment, vessel density was 12.7% lower in purple PWBs than in pink PWBs. CONCLUSION: Superficial vessels of purple PWBs were significantly closer to the epidermis than those of pink PWBs, which might impact optimal laser parameters.

Is Interview Length Associated With Blood Test Participation? Evidence From Three Population-Based HIV Impact Assessment Surveys Conducted From 2016 to 2017.

BACKGROUND: High response rates in surveys are critical to ensuring that findings are unbiased and representative of the target population. Questionnaire length affects response rates, with long interviews associated with partially complete surveys, higher item nonresponse ("don't know" and "refuse" responses), and willingness to participate in future surveys. Our aim is to determine the impact of questionnaire length on blood test participation in population-based HIV surveys. METHODS: Data are from population-based HIV impact assessments conducted in Zambia, Eswatini, and Lesotho in 2016-2017. The population-based HIV impact assessments consist of an interview followed by a blood draw. Consent for blood draw was obtained before the interview in Eswatini and after the interview in Zambia and Lesotho. Interview length was measured by the survey tablet as the time to complete the survey (interview duration) and the number of questions answered by the participant (questionnaire length). We assessed the effects of questionnaire length and interview duration on blood test participation using logistic regression. RESULTS: Across all 3 surveys, the median interview duration was 16 minutes and the median number of questions was 77. In adjusted analyses, there was a negative impact of interview duration on blood draw consent for individuals with unknown status in Lesotho and a positive relationship between questionnaire length and blood draw consent in Zambia for those with HIV-negative and unknown status. CONCLUSION: Although interview length is an important consideration to reduce respondent burden, a longer questionnaire does not necessarily result in lower consent rates for blood testing.

Two-Photon Microperimetry: A Media Opacity-Independent Retinal Function Assay.

Purpose: Compare results obtained using infrared two-photon microperimetry (2PM-IR) with conventional visual function tests in healthy subjects of varying ages with and without simulated media opacities. Methods: Subjects from two separate cohort studies completed cone contrast threshold (CCT) testing, conventional microperimetry, visible light microperimetry from a novel device (2PM-Vis), and infrared two-photon microperimetry. The first cohort study, which consisted of six healthy volunteers (23 to 29 years of age), evaluated the effects of simulated media opacities on visual performance testing. Subjects underwent testing on four visual function devices nine separate times under the following conditions: no filter, red filter, green filter, blue filter, light brown filter, dark brown filter, polarized black filter (0° rotation), and polarized black filter (90° rotation). Subjects subsequently performed 2PM-IR and 2PM-Vis testing without a filter in the mydriatic state. The second cohort study evaluated the effect of age on visual test performance in 42 healthy subjects split between two groups (ages 20-40 years and 60-80 years). Results: Retinal sensitivity measured by 2PM-IR demonstrated lower variability than all other devices relying on visible spectrum stimuli. Retinal sensitivity decreased proportionally with the transmittance of light through each filter. CCT scores and retinal sensitivity decreased with age in all testing modalities. Visible spectrum testing modalities demonstrated larger test result differences between young and old patient cohorts; this difference was inversely proportional to the wavelength of the visual function test. Conclusions: 2PM-IR mitigates media opacities that may mask small differences in retinal sensitivity when tested with conventional visual function testing devices. Translational Relevance: Conventional visual function tests that emit visible light may not detect differences in retinal function during the early stages of age-related diseases due to the confounding effects of cataracts. Infrared light, which has greater transmittance through ocular tissue, may reliably quantify retinal sensitivity and thereby detect degenerative changes early on.