Randomized control trial comparing genetic counseling service delivery models in an underserved population.

This randomized controlled trial compares outcomes of telephone versus in-person genetic counseling service models in underserved, bilingual patient populations referred for cancer genetic counseling. Between 2022 and 2023, a two-arm (telephone vs. in-person genetic counseling) prospective, randomized controlled study with 201 participants was conducted at two county hospital cancer genetics clinics. Primary outcomes included comparison of pre- and post-genetic counseling genetics knowledge (Multi-dimensional Model of Informed Choice, MMIC), genetic counseling visit satisfaction (Genetic Counseling Satisfaction Scale, GCSS), and genetic counseling visit completion rates. Secondary outcomes included comparison of genetic testing attitudes and informed choice (MMIC), genetic counseling-specific empowerment (Genomic Outcomes Scale, GOS), and genetic testing completion and cancellation/failure rates, using linear regression models (significance ≤0.05). There were no statistically significant differences between arms in pre/post-genetic counseling MMIC knowledge and attitude, GOS or GCSS scores or genetic counseling completion. While more participants in the telephone versus in-person arm made an informed choice about testing (52.5% v. 39.0%, p = 0.0552), test completion was lower (74% v. 100%, p < 0.05) for this group. Genetic counseling completion rates and MMIC knowledge and attitude, GOS, and GCSS scores suggest telephone genetic counseling is comparable to in-person genetic counseling for underserved populations. Higher informed choice scores and significantly lower testing completion rates for telephone visits require further study.

Recent Advances and Prospects of Nucleic Acid Therapeutics for Anti-Cancer Therapy.

Nucleic acid therapeutics are promising alternatives to conventional anti-cancer therapy, such as chemotherapy and radiation therapy. While conventional therapies have limitations, such as high side effects, low specificity, and drug resistance, nucleic acid therapeutics work at the gene level to eliminate the cause of the disease. Nucleic acid therapeutics treat diseases in various forms and using different mechanisms, including plasmid DNA (pDNA), small interfering RNA (siRNA), anti-microRNA (anti-miR), microRNA mimics (miRNA mimic), messenger RNA (mRNA), aptamer, catalytic nucleic acid (CNA), and CRISPR cas9 guide RNA (gRNA). In addition, nucleic acids have many advantages as nanomaterials, such as high biocompatibility, design flexibility, low immunogenicity, small size, relatively low price, and easy functionalization. Nucleic acid therapeutics can have a high therapeutic effect by being used in combination with various nucleic acid nanostructures, inorganic nanoparticles, lipid nanoparticles (LNPs), etc. to overcome low physiological stability and cell internalization efficiency. The field of nucleic acid therapeutics has advanced remarkably in recent decades, and as more and more nucleic acid therapeutics have been approved, they have already demonstrated their potential to treat diseases, including cancer. This review paper introduces the current status and recent advances in nucleic acid therapy for anti-cancer treatment and discusses the tasks and prospects ahead.

Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States (US); little is known about pregnancy outcomes with modulator use. This retrospective study aims to determine the impact of CFTR modulators on maternal outcomes. RESEARCH QUESTION: Does pregnancy differentially impact outcomes in females with CF with and without CFTR modulators? STUDY DESIGN AND METHODS: We collected data on pregnancies from 2010-2021 from 11 US adult CF centers. We conducted multivariable longitudinal regression analysis to assess whether changes in percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), and Pseudomonas aeruginosa prevalence differed from before, during, and after pregnancy by CFTR modulator use, while adjusting for confounders. We also describe infant outcomes based on maternal modulator use. RESULTS: Among 307 pregnancies, mean age at conception was 28.5 years (range: 17-42), pre-pregnancy ppFEV1 was 74.2 and BMI was 22.3 kg/m2. One hundred and fourteen pregnancies (37.1%) had CFTR modulator exposure during pregnancy (77 with highly effective modulator therapy [HEMT] and 37 with other modulators). The adjusted mean change in ppFEV1 from pre- to during pregnancy was -2.36 (95%CI: -3.56, -1.16) in the unexposed group and +2.60(95%CI: 0.23, 4.97) in the HEMT group, with no significant change from during to one-year post-pregnancy. There was an overall decline in ppFEV1 from pre- to post-pregnancy in the no modulator group (-2.56; 95%CI:-3.62, -1.49) that was not observed in the HEMT group (1.10; 95%CI: -1.13, 3.34). PEx decreased from pre- to post-pregnancy in the HEMT group and BMI increased from pre- to during pregnancy in all groups but without a significant change post-pregnancy. Missing infant outcome data precluded firm conclusions. INTERPRETATION: We observed superior pregnancy and post-pregnancy pulmonary outcomes in individuals who used HEMT, including a preservation of ppFEV1, compared with those unexposed to HEMT.

Protective effect of recombinant interleukin-10 on newborn rat lungs exposed to short-term sublethal hyperoxia.

BACKGROUND: Lung injury imposed by hyperoxia is the main cause of bronchopulmonary dysplasia in newborns. These injuries are generated from the early stage of hyperoxia through the main biologic effects of cell death and inflammatory response. Interleukin (IL)-10 is a potent anti-inflammatory cytokine that may have the inhibitory effects on these biologic actions induced by hyperoxia. PURPOSE: Based on our former in vitro studies investigating the effect of recombinant IL-10 (rIL-10) on protecting cultured alveolar type II cells exposed to short-term hyperoxia, we performed the in vivo study to investigate the effect of rIL-10 in newborn rats aged P4 exposed to hyperoxia. METHODS: Rats were classified into 3 groups; the control group exposed to normoxia for 24 hours; the hyperoxia group exposed to 65% hyperoxia for 24 hours; and the IL10 group treated with intratracheal instillation of rIL-10 prior to exposure to 65% hyperoxia for 24 hours. Following each treatment, the rats were euthanized. Individual lobes of the right lung were prepared for hematoxyling and eosin (H&E) staining and immunohistochemical staining for thyroid transcription factor-1 (TTF1). Bronchoalveolar lavage (BAL) was performed in the left lung to analyze cell counts and cytokines. RESULTS: The IL10 group showed preserved air spaces similar to the control group, with decreased cellularity compared to the hyperoxia group, whereas the hyperoxia group showed markedly reduced air spaces with increased cellularity compared to the IL10 group. And, the IL10 group showed more TTF1-positive cells, which represented alveolar type II cells, compared to the hyperoxia group. Inflammatory cells, such as neutrophils and lymphocytes and proinflammatory cytokines of tumor necrosis factor-α, IL-1α, IL-8, and macrophage inflammatory protein-1α were significantly lower in BAL fluid of the IL10 group compared to the hyperoxia group. CONCLUSION: These results indicate that rIL-10 may be a promising pharmaceutical measure for protecting newborn lungs from injury induced at the early stage of hyper oxia.

Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial.

BACKGROUND: The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. METHODS: We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at three health systems from March 2018 to September 2021. Outcomes of interest were early-stage HCC detection (ie, screening benefit) and diagnostic evaluation for false positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. RESULTS: Of 125 patients diagnosed with HCC (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan Criteria. Early tumor detection did not significantly differ between the outreach and usual care arms (64.2% vs 79.3%, p = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%, p = .95) with 5.9% in both arms having mild harms, 4.0% and 3.8% respectively with moderate harms, and 0.9% and 1.0% respectively with severe harms. CONCLUSION: Most patients enrolled in HCC screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not significantly increase early HCC detection or physical harms compared to usual care. CLINICAL TRIALS NUMBER: NCT02582918 and NCT03756051.

Assessing the health impacts of parenthood on people with cystic fibrosis: the HOPeCF prospective cohort protocol.

INTRODUCTION: People with cystic fibrosis (CF) are living longer and healthier lives with a growing number considering and pursuing parenthood. The decision of whether to become a parent is complex for people with CF, and CF is a major factor in reproductive decision-making. Unfortunately, in people with CF who become parents, there are no prospective studies of disease trajectory, no data on the impact of parenthood on mental health, disease self-management, or quality of life, and no research regarding non-genetic parenthood. METHODS AND ANALYSIS: Health Outcomes of Parents with CF (HOPeCF) is a prospective, multicentre observational cohort study which will enrol 146 new parents with CF of children less than 5 years of age. The primary aim of this 60-month study is to assess the rate of lung function decline as impacted by mental health, parental stress and responsibility, and the use of CF transmembrane conductance regulator modulators. In addition, we will conduct dyadic interviews with a subset of study participants and their key supports (partner/family/friend) to inform future interventions. ETHICS AND DISSEMINATION: This longitudinal, observational multicentre study is a necessary and timely step in understanding parental health outcomes in CF and will provide data essential for care guidance to people with CF, their partners, and healthcare providers. The University of Pittsburgh Institutional Review Board approved this study (STUDY23080161). As people with a variety of paediatric-onset chronic diseases are living longer and considering parenthood, these results may have widespread applicability and will be distributed at international meetings and submitted to peer-reviewed journals.

Estimating minimal clinically important difference (MCID) for gastrointestinal symptoms in cystic fibrosis.

BACKGROUND: Minimal clinically important difference (MCID) is important to establish as a meaningful outcome in research when using patient reported outcome measures (PROMs). We determined the MCID using the distribution-based approach for three measurements used as part of the GALAXY study, which is an observational prospective study on gastrointestinal (GI) symptoms in cystic fibrosis (CF). METHODS: Four hundred and two persons with cystic fibrosis (PwCF) participated in the GALAXY study, all with baseline values available for all questionnaires. Mean age was 20.9 years (2.1- 61.1) with 75 females and 94 males under the age of 18 (42.04 %) and 118 females and 115 males aged 18 or older (57.99 %). MCID was measured for Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL) and their subscales. Two distribution-based approaches, defined as multiplications of the standard deviation (SD) or standard error of the mean (SEM), were used to approximate the MCID. RESULTS: The two distribution-based approaches for determining the MCID estimates produced comparable results in trends in MCIDs across the subscales and total scores. In general, MCID estimates of subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire are as follows: PAC-SYM: 0.26 and 0.14; PAGI-SYM: 0.32 and 0.15; PAC-QOL: 0.27 and 0.18, respectively. CONCLUSION: This paper establishes initial MCIDs estimated by the distribution-based approach for the PAC-SYM, PAGI-SYM and PAC-QOL that can now be used to evaluate interventional studies that may impact gastrointestinal symptoms in PwCF.

Changes in the Perceptions of the Neighborhood Environment and Physical Activity Patterns Among Mexican Americans on the Texas-Mexico Border.

INTRODUCTION: Little research on the association of neighborhood environment with physical activity in resource-poor communities has been done. This study assessed changes in perceptions of the neighborhood environment and the association between those perceptions and physical activity in Mexican Americans on the Texas-Mexico border in an area where there would be community efforts to enhance pedestrian and cycling infrastructure and programming. METHODS: We analyzed data from a population-based cohort of Mexican American individuals on the Texas-Mexico border. From 2008 to 2018, interviewer-administered questionnaires were used to collect perceptions of neighborhood environment and physical activity at baseline, 5- and 10-year follow-ups, and at other ancillary study visits, with an average of 3 data points per participant. We conducted multivariable longitudinal logistic regression analyses to assess if the changes in odds of positive perceptions of the neighborhood environment over the study years differed by physical activity patterns. RESULTS: The sample (n = 1036) was mostly female (71%), born in Mexico (70%), and had no health insurance (69%). We saw improvements in the perceptions of several neighborhood environment attributes from 2008 to 2018, though we saw different longitudinal trajectories in these perceptions based on an individual's longitudinal physical activity patterns. By 2014-2018, we saw significantly higher positive perceptions of the neighborhood environment for those who consistently met physical activity guidelines compared with those who did not (adjusted rate ratio = 1.12, P = .049). DISCUSSION: We found that perceptions of many neighborhood environment attributes improved between 2008 and 2018, and that overall positive perceptions were associated with consistently meeting physical activity guidelines over time.

Oxidative and carbonyl stress induced AMD and Codonopsis lanceolata ameliorates AMD via controlling oxidative and carbonyl stress.

Age-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 µM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 µg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 µM A2E and 20 mW/cm2 blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent.

Nanosized DNA Hydrogel Functionalized with a DNAzyme Tetrahedron for Highly Efficient Gene Silencing.

DNAzymes are DNA oligonucleotides that have catalytic activity without the assistance of protein enzymes. In particular, RNA-cleaving DNAzymes were considered as ideal candidates for gene therapy due to their unique characteristics. Nevertheless, efforts to use DNAzyme as a gene therapeutic agent are limited by issues such as their low physiological stability in serum and intracellular delivery efficiency. In this study, we developed a nanosized synthetic DNA hydrogel functionalized with a DNAzyme tetrahedron (TDz Dgel) to overcome these limitations. We observed remarkable improvement in the gene-silencing effect as well as intracellular uptake without the support of gene transfection reagents using TDz Dgel. The improved catalytic activity of the DNAzyme resulted from the combination of the cell-penetrating DNA tetrahedron structure and high stability of DNA hydrogel. We envision that this approach will become a convenient and efficient strategy for gene-silencing therapy using DNAzyme in the future.

Sex Differences After Treatment With Ivacaftor in People With Cystic Fibrosis.

BACKGROUND: Historically, studies show that female patients with cystic fibrosis (CF) have worse pulmonary outcomes than male patients, including decreased life expectancy. It is unknown whether this disparity persists in the new era of highly effective modulator therapies. Ivacaftor has been available in the United States for > 10 years, allowing for the opportunity to understand the impact this therapy may have on sex disparities in CF. We hypothesized that female patients will continue to show worse outcomes because we suspect that the disparity is not driven solely by ion channel dysfunction. RESEARCH QUESTION: Does a difference in outcomes between male and female patients persist after the initiation of ivacaftor in people with CF? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using the CF Foundation Patient Registry comparing changes in pulmonary exacerbation rate, lung function (FEV1 % predicted), and presence of Pseudomonas aeruginosa among male patients vs female patients before and after initiation of treatment with the highly effective modulator ivacaftor. RESULTS: The cohort comprised 1,900 people with CF who were treated with ivacaftor between 2010 and 2017; 928 patients (48.84%) were male and 972 patients (51.16%) were female with a mean age of 33.09 years. Male patients showed a significant decrease in pulmonary exacerbations after ivacaftor treatment (from 0.38 to 0.34; adjusted rate ratio, 0.89; P = .028), whereas female patients did not (from 0.48 to 0.45; adjusted rate ratio, 0.95; P = .174). FEV1 % predicted similarly decreased in both male and female patients before vs after ivacaftor treatment. P aeruginosa prevalence decreased to a similar extent in both male and female patients after ivacaftor treatment. INTERPRETATION: Our findings demonstrate that sex disparities in CF persist in those treated with ivacaftor because of differences in pulmonary exacerbations. More research is needed to determine the specific pathophysiologic drivers of this disparity.

Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis. METHODS: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses. RESULTS: All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage. CONCLUSION: Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions. TRIAL REGISTRATION NUMBER: NCT02582918.

An expanded chronic care management approach to multiple chronic conditions in Hispanics using community health workers as community extenders in the Rio Grande Valley of Texas.

INTRODUCTION: The synergistic negative effects of type 2 diabetes (T2DM) and hypertension increases all-cause mortality and the medical complexity of management, which disproportionately impact Hispanics who face barriers to healthcare access. The Salud y Vida intervention was delivered to Hispanic adults living along the Texas-Mexico Border with comorbid poorly controlled T2DM and hypertension. The Salud y Vida multicomponent intervention incorporated community health workers (CHWs) into an expanded chronic care management model to deliver home-based follow-up visits and provided community-based diabetes self-management education. METHODS: We conducted multivariable longitudinal analysis to examine the longitudinal intervention effect on reducing systolic and diastolic blood pressure among 3806 participants enrolled between 2013 and 2019. Participants were compared according to their program participation as either higher (≥ 10 combined educational classes and CHW visits) or lower engagement (<10 encounters). Data was collected between 2013 and 2020. RESULTS: Baseline mean systolic and diastolic blood pressure were 138 and 81 mmHg respectively. There were overall improvements in systolic (-6.49; 95% CI = [-7.13, -5.85]; p < 0.001) and diastolic blood pressure (-3.97; 95% CI = [-4.37, -3.56]; p < 0.001). The higher engagement group had greater systolic blood pressure reduction at 3 months (adjusted mean difference = -1.8 mmHg; 95% CI = [-3.2, -0.3]; p = 0.016) and at 15 month follow-up (adjusted mean difference = -2.3 mmHg; 95% CI = [-4.2, -0.39]; p = 0.0225) compared to the lower engagement group. CONCLUSION: This intervention, tested and delivered in a real-world setting, provides an example of how CHW integration into an expanded chronic care model can improve blood pressure outcomes for individuals with co-morbidities.

Concentrations of dehydroepiandrosterone-sulphate (DHEA-S) in people with cystic fibrosis on and off elexacaftor-tezacaftor-ivacaftor.

BACKGROUND: Levels of sulfated Dehydroepiandrosterone (DHEA-S) are unknown in people with Cystic Fibrosis (pwCF). DHEA-S is reported to have an inverse association with inflammation and warrants evaluation in pwCF. METHODS: We compared differences in DHEA-S and other hormones between pwCF (n = 180) and without CF (n = 180) and DHEA-S association with percent predicted forced expiratory volume in one second (ppFEV1). We also evaluated DHEA-S levels in people with CF on elexacaftor-tezacaftor-ivacaftor (ETI) (n = 145). RESULTS: PwCF (not on ETI) had lower DHEA-S levels compared to healthy non-CF controls. DHEA-S levels in individuals with CF on ETI were similar to those without CF. Lower DHEA-S levels were associated with lower ppFEV1. CONCLUSIONS: PwCF (not on ETI) have lower levels of DHEA-S than people without CF or people with CF on ETI. Additional studies are needed to investigate the impact of DHEA-S on the health of pwCF and mechanisms involved.

Beyond the Diagnosis: Evaluation of Quality-of-Life Measures and Family Functioning in SLC6A1-Related Neurodevelopmental Disorder.

BACKGROUND: SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD) is a rare genetic disorder linked to autism spectrum disorder, epilepsy, and developmental delay. In preparation for future clinical trials, understanding how the disorder impacts patients and their families is critically important. Quality-of-life (QoL) measures capture the overall disease experience of patients. This study presents QOL findings from our SLC6A1-NDD clinical trial readiness study and the Simons Searchlight SLC6A1-NDD registry. METHODS: We compiled QoL data from participants with SLC6A1-NDD enrolled in our clinical trial readiness study (n = 20) and the Simons Searchlight registry (n = 32). We assessed the distribution of scores on the Quality-of-Life Inventory-Disability (QI Disability), Quality of Life of Childhood Epilepsy (QOLCE-55), and Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM) administered to caregivers. RESULTS: In our cohort of 52 participants, the mean QI Disability total score was 73 ± 12.3, the QOLCE-55 mean total score was 49 ± 17.1, and the mean total PedsQL score was 51 ± 17.6. Longitudinal QoL scores for a subset of participants (n = 7) demonstrated a reduction in the Family Relationship domain of PedsQL-FIM (Δ-10.0, P = 0.035). Bootstrap resampling of total scores displays nonoverlapping 95% confidence intervals for the 10th, 50th, and 90th percentiles on all three measures. CONCLUSIONS: This is the first study to investigate QoL measures for SLC6A1-NDD. Findings suggest that scores within the 10th percentile's confidence interval could be clinically significant, referring to QI-Disability scores of <61, QOLCE-55 scores of <46, and PedsQL-FIM scores of <42. Future validation studies are needed.

Associations of Ambulatory Blood Pressure Measurements With High-Sensitivity Troponin and Natriuretic Peptide Levels in SPRINT.

BACKGROUND: Nighttime blood pressure (BP) has greater prognostic importance for cardiovascular disease (CVD) than daytime BP, but less is known about nighttime and daytime BP associations with measures of subclinical CVD. METHODS: Among 897 Systolic Blood Pressure Intervention Trial Study (SPRINT) participants with 24-hour ambulatory BP monitoring obtained near the 27-month study visit, 849 (95%) had N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measured at the 24-month study visit. Multivariable linear regression analyses were performed to evaluate the associations of nighttime and daytime BP with cardiac biomarker levels. RESULTS: The mean age was 69 ±â€…12 years, 28% were African American, and mean nighttime and daytime SBP were 121 ±â€…16 mm Hg and 132 ±â€…14 mm Hg, respectively. In multivariable models, compared with the lowest tertile of nighttime systolic BP, the highest tertile was associated with 48% higher NT-proBNP levels (adjusted geometric mean ratio [GMR] = 1.48, 95% CI: 1.22, 1.79), and 19% higher hs-cTnT levels (adjusted GMR = 1.19, 95% CI: 1.07, 1.32). In contrast, the highest vs. lowest tertile of daytime systolic BP was not associated with NT-proBNP (adjusted GMR = 1.09, 95% CI: 0.88, 1.34), but was associated with 16% higher hs-cTnT levels (adjusted GMR = 1.16, 95% CI: 1.04, 1.30). Similar results were observed using diastolic BP. CONCLUSIONS: In SPRINT, both higher nighttime and daytime BP were independently associated with higher hs-cTnT levels, but only higher nighttime BP was associated with higher NT-proBNP levels.

Risk of Obstructive Sleep Apnea, Chronic Dizziness, and Sleep Duration.

BACKGROUND: Although it is recommended that obstructive sleep apnea (OSA) be screened for using a validated self-report questionnaire in patients experiencing dizziness, there is still a lack of research on the relationship between high risk of OSA and chronic dizziness. OBJECTIVES: The study aimed to examine the relationship between the high risk of OSA and chronic dizziness and investigate how this relationship is affected by sleep duration. METHODS: This cross-sectional study used data from the 8th Korea National Health and Nutrition Examination Survey (2019-2021). Adults aged 40 years or older were included and divided into two groups using the STOP-Bang Questionnaire (SBQ): a high-risk group for OSA or not. Complex samples logistic regression analyses were performed to examine the odds ratios of chronic dizziness based on the national population estimates. RESULTS: Our findings showed that individuals in the high-risk group for OSA were significantly more likely to experience chronic dizziness. Specifically, among subgroups based on sleep duration, the high-risk group for OSA with a short sleep duration of ≤5 hours demonstrated the highest odds of chronic dizziness, showing a significantly 2.48-fold increased likelihood compared to the non-high risk for OSA with a sleep duration of 5-9 hours. DISCUSSION: The SBQ can be beneficial when other causes do not explain chronic dizziness, helping to rule in the possibility of OSA. Educating individuals suspected of having OSA or who have been diagnosed with OSA about the importance of adequate sleep duration may help reduce the risk of chronic dizziness.

Dynamic Hyperspectral Holography Enabled by Inverse-Designed Metasurfaces with Oblique Helicoidal Cholesterics.

Metasurfaces are flat arrays of nanostructures that allow exquisite control of phase and amplitude of incident light. Although metasurfaces offer new active element for both fundamental science and applications, the challenge still remains to overcome their low information capacity and passive nature. Here, by integrating an inverse-designed-metasurface with oblique helicoidal cholesteric liquid crystal (ChOH), simultaneous spatial and spectral tunable metasurfaces with a high information capacity for dynamic hyperspectral holography, are demonstrated. The inverse design facilitates a single-phase map encoding of ten independent holographic images at different wavelengths. ChOH provides precise spectral modulation with narrow bandwidth and wide tunable regime in response to programmed stimuli, thus enabling dynamic switching of the multicolor holography. The results provide simple and generalizable principles for the rational design of interactive metasurfaces that will find numerous applications, including security platform.

Association of in-line digestive enzyme cartridge with enteral feeds on improvement in anthropometrics among pediatric patients with cystic fibrosis.

BACKGROUND: Approximately 85% of patients with cystic fibrosis (CF) have exocrine pancreatic insufficiency (EPI) with 10% requiring supplemental nighttime enteral tube feedings. Administration of pancreatic enzyme replacement therapy (PERT) with nighttime feedings is fraught with challenges. RELiZORB (Alcresta Therapeutics, Inc), an in-line lipase cartridge, delivers PERT continuously with enteral feedings. Outcomes related to the use of this in-line lipase cartridge are lesser known. This project evaluated anthropometrics related to in-line lipase cartridge use among pediatric patients with CF already receiving oral PERT therapy prior to nighttime enteral feedings. METHODS: Retrospective chart review was performed on 29 patients with CF and EPI receiving supplemental tube feedings and utilizing in-line lipase cartridge for a continuous 12 month period between 2015 and 2019. Anthropometrics were evaluated 12 months before and after initiation of in-line lipase cartridge. RESULTS: Compared with mean height z score at 6-months pre-in-line lipase cartridge, mean height z score at 6-months post-in-line-lipase cartridge (adjusted mean difference [AMD] = 0.2540; 95% CI = [0.0487, 0.4592]; P = 0.0153) and mean height z score at 12-months post-in-line lipase cartridge (AMD = 0.2684; 95% CI = [0.0203, 0.5166]; P = 0.0340) were significantly higher. Mean weight z score at 12-months post-in-line-lipase-cartridge neared statistical significance compared with 6-months pre-in-line lipase cartridge (AMD = 0.2816; 95% CI = [-0.0003, 0.5634]; P = 0.0502) when excluding seven patients with advanced lung disease (forced expiratory volume in the first second of expiration of 40%). Weight-for-length or body mass index did not significantly differ compared with pre-in-line lipase cartridge. CONCLUSION: Use of in-line lipase cartridge with enteral feeds improved anthropometrics, especially height, in pediatric patients with CF.