Renal medulla in hypertension

Abstract: Studies have found that blood flow to the renal medulla is an important determinant of pressure-natriuresis and the long-term regulation of arterial pressure. First, a brief review of methods developed enabling the study of the medullary circulation is presented. Second, studies performed in rats are presented showing medullary blood flow plays a vital role in the pressure-natriuresis relationship and thereby in hypertension. Third, it is shown that chronic reduction of medullary blood flow results in hypertension and that enhancement of medullary blood flow reduces hypertension hereditary models of both salt-sensitive rats and salt-resistant forms of hypertension. The key role that medullary nitric oxide production plays in protecting this region from ischemic injury associated with circulating vasoconstrictor agents and reactive oxygen species is presented. The studies cited are largely the work of my students, research fellows, and colleagues with whom I have performed these studies dating from the late 1980s to more recent years.

Cost-effectiveness of population-wide genomic screening for Lynch Syndrome and Polygenic Risk Scores to inform Colorectal Cancer screening.

INTRODUCTION: Genomic screening to identify individuals with Lynch Syndrome (LS) and those with a high polygenic risk score (PRS) promises to personalize Colorectal Cancer (CRC) screening. Understanding its clinical and economic impact is needed to inform screening guidelines and reimbursement policies. METHODS: We developed a Markov model to simulate individuals over a lifetime. We compared LS+PRS genomic screening to standard of care (SOC) for a cohort of US adults at age 30. The Markov model included health states of "no CRC", CRC stages (A-D) and death. We estimated incidence, mortality, and discounted economic outcomes of the population under different interventions. RESULTS: Screening 1000 individuals for LS+PRS resulted in 1.36 fewer CRC cases and 0.65 fewer deaths compared to SOC. The incremental cost-effectiveness ratio (ICER) was $124,415 per quality-adjusted life-year (QALY); screening had a 69% probability of being cost-effective using a willingness to pay threshold of $150,000/QALY. Setting the PRS threshold at the 90th percentile of the LS+PRS screening program to define individuals at high risk was most likely to be cost-effective compared to 95th, 85th, and 80th percentiles. CONCLUSION: Population-level LS+PRS screening is marginally cost-effective and a threshold of 90th percentile is more likely to be cost-effective than other thresholds.

Unlocking the potential of cultivated meat through cell line engineering.

Cultivated meat has the potential to revolutionize food production, but its progress is hindered by fundamental shortcomings of mammalian cells with respect to industrial-scale bioprocesses. Here, we discuss the essential role of cell line engineering in overcoming these limitations, highlighting the balance between the benefits of enhanced cellular traits and the associated regulatory and consumer acceptance challenges. We believe that careful selection of cell engineering strategies, including both genetic and non-genetic modifications, can address this trade-off and is essential to advancing the field.

Cation induced changes to the structure of cryptophane cages.

Here the monocation complexes of seven anti-cryptophanes are examined with high-resolution ion-mobility mass spectrometry. The relative size of the [cation + cryptophane]+ complexes were compared based on their measured mobilities and derived collisional cross sections. A paradoxical trend of structural contraction was observed for complexes of increasing cation size. Density functional theory confirmed encapsulation occurs for cation = Na+, K+, Rb+, Cs+ and NH4+. However, cation = Li+ preferred oxygen coordination at a linker over encapsulation within the cavity, leading to a slightly larger gas phase structure overall. Protonated cryptophanes yielded much larger collision cross sections via imploded cryptophane structures. Thus, competing physical effects led to the observed non-periodic size trend of the complexes. Trends in complexation from isothermal titration calorimetry and other condensed phase techniques were borne out by the gas phase studies. Further, predicted cavity sizes compared with the gas phase experimental findings reveal more about the encapsulation mechanisms themselves.

Conductive Polypropylene Additive Manufacturing Feedstock: Application to Aqueous Electroanalysis and Unlocking Nonaqueous Electrochemistry and Electrosynthesis.

Additive manufacturing electrochemistry is an ever-expanding field; however, it is limited to aqueous environments due to the conductive filaments currently available. Herein, the production of a conductive poly(propylene) filament, which unlocks the door to organic electrochemistry and electrosynthesis, is reported. A filament with 40 wt % carbon black possessed enhanced thermal stability, excellent low-temperature flexibility, and high conductivity. The filament produced highly reproducible additive manufactured electrodes that were electrochemically characterized, showing a k0 of 2.00 ± 0.04 × 10-3 cm s-1. This material was then applied to three separate electrochemical applications. First, the electroanalytical sensing of colchicine within environmental waters, where a limit of detection of 10 nM was achieved before being applied to tap, bottled, and river water. Second, the electrodes were stable in organic solvents for 100 cyclic voltammograms and 15 days. Finally, these were applied toward an electrosynthetic reaction of chlorpromazine, where the electrodes were stable for 24-h experiments, outperforming a glassy carbon electrode, and were able to be reused while maintaining a good electrochemical performance. This material can revolutionize the field of additive manufacturing electrochemistry and expand research into a variety of new fields.

Targeting the EGFR pathway in chemotherapy-resistant triple-negative breast cancer - a phase II study.

PURPOSE: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance and inhibition of the EGFR pathway sensitizes TNBC to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175). PATIENTS AND METHODS: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after 4 cycles of AC. were eligible for this study and received panitumumab (2.5 mg/kg IV, Q1 week x 13), paclitaxel (80mg/m2 IV Q1 week x 12), and carboplatin (AUC=4 IV, Q3 weeks x 4) as the second phase of NAT. A two-stage Gehan-type design was employed to detect an improvement in the pCR/residual cancer burden class I (RCB-I) rate from 5% to 20%. Whole exome sequencing was performed on diagnostic tumor biospecimens, where available. RESULTS: From 11/3/2016 through 8/3/2021, 43 patients with AC-resistant TNBC were enrolled. The combined pCR/RCB-I rate was 30.2%. The most common treatment-related adverse events were neutropenia (72%) and anemia (61%), with 7 (16%), 16 (37%), and 8 (19%) patients experiencing grade 4 neutropenia, grade 3 neutropenia, and grade 3 anemia, respectively. No new safety signals were observed. CONCLUSIONS: This study met its primary endpoint (pCR/RCB-I=30.2% vs. 5% in historical controls), suggesting that panitumumab should be evaluated as a component of neoadjuvant therapy in patients with chemotherapy-resistant TNBC in a larger, randomized clinical trial.

Temporal trends and outcomes of acute ischaemic strokes in patients hospitalised for percutaneous coronary intervention.

BACKGROUND: Acute ischaemic stroke (AIS) after percutaneous coronary intervention (PCI) is a rare, but debilitating, complication. However, contemporary data from real-world unselected patients are scarce. AIMS: We aimed to explore the temporal trends, outcomes and variables associated with AIS as well as in-hospital all-cause mortality in a nationwide cohort. METHODS: A retrospective analysis of healthcare records from 2006-2021 was implemented. Patients were stratified according to the occurrence of AIS in the setting of PCI. The temporal trends of AIS were analysed. A stepwise regression model was used to identify variables associated with AIS and in-hospital all-cause mortality. RESULTS: A total of 4,910,430 PCIs were included for the current analysis. AIS occurred in 4,098 cases (0.08%). An incremental increase in the incidence of AIS after PCI from 0.03% to 0.14% per year was observed from 2006-2021. The strongest associations with AIS after PCI included carotid artery disease, medical history of stroke, atrial fibrillation, presentation with an ST-segment elevation myocardial infarction (STEMI) or non-STEMI and coronary thrombectomy. For patients with AIS, a higher in-hospital all-cause mortality (18.11% vs 3.29%; p<0.001) was documented. With regard to all-cause mortality, the strongest correlations in the stroke cohort were found for cardiogenic shock, dialysis and clinical presentation with a STEMI. CONCLUSIONS: In an unselected nationwide cohort of patients hospitalised for PCI, a gradual increase in AIS incidence was noted. We identified several variables associated with AIS as well as with in-hospital mortality. Hereby, clinicians might identify the patient population at risk for a peri-interventional AIS as well as those at risk for an adverse in-hospital outcome after PCI.

Age-related differences in the prevalence of premature ejaculation: taking a second and more detailed look.

Background: Research indicates an inconsistent relationship between age and the prevalence of premature ejaculation (PE), with studies reporting an increase, decrease, or no change with age. Aim: To reexamine the possible relationship between age and PE prevalence, implementing methodological improvements that enhance the likelihood of detecting real effects. Methods: From a sample of 2772 men, we analyzed a subset of 418 classified as having probable or definite PE based on the Premature Ejaculation Diagnostic Tool. We not only analyzed men with lifelong PE (LPE; n = 316) and acquired PE (APE; n = 102) separately but assessed prevalence differences across age groups using an omnibus measure to establish PE status and specific PE diagnostic criteria, individually and in multifactorial combination. Outcome: Prevalence of PE in younger vs older men. Results: LPE, but not APE, showed age-related differences in prevalence, with LPE being lower in the higher age group. This pattern was most discernible when a multifactorial approach was used to establish PE status. Clinical Translation: Older men may be less distressed about their dysfunction or may benefit from diminishing ejaculatory function with age. Strengths and Limitations: This cross-sectional study used an improved methodology to detect age-related differences in PE prevalence. Future studies would benefit from a larger sample size that enables a breakdown of prevalence using a greater number of age categories. Conclusion: According to an improved methodology, men with LPE showed a decline in prevalence with aging. A methodology aimed at exploring this relationship should-at the very least-not only distinguish between LPE and APE subtypes but also consider using a multifactorial method of determining PE status that includes a measure of bother/distress.

Risk and Reward: Nationwide Analysis of Cardiac Transplant Center Variation in Organ Travel Distance and the Effects on Outcomes.

BACKGROUND: The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change. METHODS: The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021. Transplant centers were grouped by average donor heart travel distance based on whether they received more or less than 50% of organs from >250 miles away. Descriptive statistics were provided for waitlisted and transplanted patients. Regression analyses modeled waitlist mortality, incidence of transplant, overall survival, and graft survival. RESULTS: Centers with a longer average travel distance had a higher mean annual transplant volume with a reduction in total days on a waitlist (86.6 vs. 149.2 days), an increased cold ischemic time (3.6 vs. 3.2 h), with no significant difference in post-transplant overall survival or graft survival. CONCLUSIONS: The benefits of reducing waitlist time while preserving post-transplant outcomes extend broadly. The trends observed in this investigation will be useful as we revise organ transplant policy in the era of new organ procurement and preservation techniques.

Genes associated with fitness and disease severity in the pan-genome of mastitis-associated Escherichia coli.

Introduction: Bovine mastitis caused by Escherichia coli compromises animal health and inflicts substantial product losses in dairy farming. It may manifest as subclinical through severe acute disease and can be transient or persistent in nature. Little is known about bacterial factors that impact clinical outcomes or allow some strains to outcompete others in the mammary gland (MG) environment. Mastitis-associated E. coli (MAEC) may have distinctive characteristics which may contribute to the varied nature of the disease. Given their high levels of intraspecies genetic variability, virulence factors of commonly used MAEC model strains may not be relevant to all members of this group. Methods: In this study, we sequenced the genomes of 96 MAEC strains isolated from cattle with clinical mastitis (CM). We utilized clinical severity data to perform genome-wide association studies to identify accessory genes associated with strains isolated from mild or severe CM, or with high or low competitive fitness during in vivo competition assays. Genes associated with mastitis pathogens or commensal strains isolated from bovine sources were also identified. Results: A type-2 secretion system (T2SS) and a chitinase (ChiA) exported by this system were strongly associated with pathogenic isolates compared with commensal strains. Deletion of chiA from MAEC isolates decreased their adherence to cultured bovine mammary epithelial cells. Discussion: The increased fitness associated with strains possessing this gene may be due to better attachment in the MG. Overall, these results provide a much richer understanding of MAEC and suggest bacterial processes that may underlie the clinical diversity associated with mastitis and their adaptation to this unique environment.

Set Up and Utilization of a Three-Dimensional In Vitro Bioreactor System for Human Intestinal Studies and Microbial Co-Cultures.

The study of human intestinal physiology and host-microbe interactions is crucial for understanding gastrointestinal health and disease. Traditional two-dimensional cell culture models lack the complexity of the native intestinal environment, limiting their utility in studying intestinal biology. Here, we present a detailed protocol for the set up and utilization of a three-dimensional (3D) in vitro bioreactor system for human intestinal studies and bacterial co-culture. This article outlines the design and assembly of the bioreactor system, scaffold fabrication, bacterial culture techniques, analysis methods, and troubleshooting tips. By providing step-by-step instructions, the goal is to enable other laboratories to utilize physiologically relevant tissue models of the human intestine, incorporating key features, such as nutrient flow, multiple human cell types, 3D architecture, and microbial communities. The incorporation of commensal bacteria into the bioreactor system allows for the investigation of complex host-microbe interactions, providing insight into gastrointestinal health and pathology. This article serves as a comprehensive resource for scientists seeking to advance their understanding of intestinal biology toward the development of novel therapeutic strategies for gastrointestinal disorders. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Scaffold design Basic Protocol 2: Intestinal cell culture: Caco2 cells Basic Protocol 3: Intestinal cell culture: organoids Basic Protocol 4: Bioreactor design and set up Basic Protocol 5: Bacteria in 3D bioreactor set up Basic Protocol 6: Bacteria and drug dosing.

Operative treatment of clavicle fractures results in more opioids prescribed as compared to non-operative management.

PURPOSE: The operative treatment of mid-shaft clavicle fractures shows benefit in union rates, return to work, and lower pain scores relative to non-operative treatment. We sought to determine if the surgical treatment of isolated mid-shaft clavicle fractures would result in fewer opioids prescribed as compared to those managed non-operatively. METHODS: All mid-shaft clavicle fractures treated at a Level 1 trauma center were identified from 2012 to 2016. Demographics, fracture characteristics, surgical complications/outcomes, non-operative outcomes, and all narcotics prescribed for 6 months post-injury were collected. Narcotic prescriptions, in morphine equivalents (ME), were obtained through the state prescription drug monitoring program (PDMP). RESULTS: One hundred and ten operative and 48 non-operative patients were included. Age, gender, previous alcohol, tobacco or drug use, and final range of motion were similar between groups. Pre-treatment fracture shortening (1.8 cm vs. 0.7 cm, p < 0.001) and displacement (150% vs. 70%, p < 0.001) were greater in the operative group. Total ME's (604 vs. 187, p < 0.001) and post-operative ME's (420 vs. 187, p < 0.001) were greater for the operative group. In either group, no other variable influenced ME's prescribed. CONCLUSION: Clavicles treated operatively receive substantially more opiates than those treated non-operatively, despite data suggesting that operative treatment makes clavicle fractures less painful. The total amount of narcotic analgesics obtained by operatively treated patients was over three times that obtained by non-operatively managed patients, which equates to 55 5 mg oxycodone pills or 85 5 mg hydrocodone pills per patient. While there may certainly be advantages to the operative treatment of clavicle fractures, they must be weighed against the risks of a significant increase in opiate prescribing and potential consumption.

Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.

BACKGROUND: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration. METHODS: Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. RESULTS: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001). CONCLUSION: Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines.

Bow Hunter Phenomenon From Advanced Cerebrovascular Disease Treated With Subclavian Artery Stenting and Carotid Endarterectomy.

Bow Hunter syndrome (BHS) is a rare disorder characterized by mechanical occlusion of the vertebral artery (VA) during neck rotation, resulting in symptomatic, transient, and positional vertebrobasilar insufficiency. We describe a case of a 76-year-old female who presented with dizziness and right ear tinnitus triggered by right head rotation. Her symptoms would immediately resolve upon returning her head to the neutral position. CT angiogram showed 80% stenosis of the left subclavian artery origin, 50%-70% stenosis of the proximal right internal carotid artery (ICA), and near occlusive stenoses of the origins of the bilateral VAs. After failing conservative management, the patient was treated with left subclavian artery stenting, followed by a right carotid endarterectomy (CEA) 6 weeks later. Follow-up at 1 month showed resolution of paroxysmal symptoms and no neurological sequelae. To our knowledge, there have not yet been reported cases of patients with concurrent BHS, subclavian artery stenosis, and carotid artery stenosis. We suggest that global revascularization via subclavian artery stenting and CEA may be considered as treatment for patients with BHS complicated by other cerebrovascular disease secondary to stenoses of the ICA and subclavian artery. This approach obviates the need for more complex surgery or endovascular intervention of the VA.

Walking away from depression: the mediating role of walking activity in depression impacting blood glucose levels of people with diabetes or prediabetes.

Introduction: Depression can exacerbate diabetes by impairing self-care behaviors and increasing the risk of complication; however, the underlying mechanism is still unclear. Given the suggested associations between walking activity, depression status, and blood glucose levels this study explores the intricate relationship between depression and blood glucose (BG) control, with a focus on walking activity as a behavioral mediator. The purpose of this study is to examine walking activity's mediating role in depression's impact on BG levels, investigating and validating the non-linear association between BG levels and walking activity. This retrospective real-world study demonstrates the potential of regular walking activity as a simple and accessible intervention to mitigate the negative effects of depression on BG levels in T2D and prediabetes. Methods: A cohort of 989 users with T2D and prediabetes, who regularly tracked their steps levels and BG levels for 12 months using the Dario digital health platform was evaluated. The mediating role of the monthly average number of steps on the relationship between the self-reported depression status and lagged monthly average BG was assessed. Additionally, the association between monthly walking activity and monthly average BG was tested using a piecewise linear mixed effects model. Results: Users with self-reported depression demonstrated increased BG levels compared to users without depression (B=8.00, P=.01). The association between depression and monthly average number of steps was significant (B=-.27, P<.005) and monthly average number of steps significantly predicted the following months' average BG (B=-.81, P=.001), adjusting for depression. The monthly average number of steps significantly mediated the effect of self-reported depression on the following month's average BG (M=.22, P<.005). Further sensitivity analysis demonstrated model robustness over various periods. Finally, non-linear dynamics of walking activity over time was validated using unseen data showing a decrease in monthly average BG for users with over an average of 400 steps per day (B=-1.87, P<.01). Discussion: This study shows how regular walking may reduce the negative impact of depression on BG levels in people with T2D. Our findings advocate for the integration of walking activity into treatment protocols as a cost-effective, accessible intervention strategy to improve glycemic management and depressive symptoms in this population.

Overview of ADNI MRI.

The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi-platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex. To remain technically current, the ADNI MRI protocol has changed substantially over the past two decades. The ADNI 4 protocol contains nine different imaging types (e.g., three dimensional [3D] T1-weighted and fluid-attenuated inversion recovery [FLAIR]). Our view is that the ADNI MRI data are a greatly underutilized resource. The purpose of this paper is to educate the scientific community on ADNI MRI methods and content to promote greater awareness, accessibility, and use. HIGHLIGHTS: The MRI Core provides multi-platform standardized protocols, carefully curated image data, and quantitative analysis by expert groups. The ADNI MRI protocol has undergone major changes over the past two decades to remain technically current. As of April 25, 2024, the following numbers of image series are available: 17,141 3D T1w; 6877 FLAIR; 3140 T2/PD; 6623 GRE; 3237 dMRI; 2846 ASL; 2968 TF-fMRI; and 2861 HighResHippo (see Table 1 for abbreviations). As of April 25, 2024, the following numbers of quantitative analyses are available: FreeSurfer 10,997; BSI 6120; tensor based morphometry (TBM) and TBM-SYN 12,019; WMH 9944; dMRI 1913; ASL 925; TF-fMRI NFQ 2992; and medial temporal subregion volumes 2726 (see Table 4 for abbreviations). ADNI MRI is an underutilized resource that could be more useful to the research community.

Craniofacial and Velopharyngeal Dimensions in Infants 0-12 Months: Between- and Within-Group Differences Based on Age and Sex.

PURPOSE: The purpose of the present study is to (a) provide quantitative data on the growth of levator veli palatini (LVP), velopharyngeal (VP), and craniofacial dimensions in children under 12 months while controlling for corrected age and sex and (b) compare variability within age and sex groups. METHOD: Magnetic resonance imaging scans of 75 infants between 0 and 12 months were measured and divided into four age groups. These data were obtained as part of a larger retrospective study. Following exclusion criteria, scans were analyzed, and dependent variables were obtained. RESULTS: There was a statistically significant (p < .0001) difference between corrected age groups on LVP muscle, VP, and craniofacial variables while controlling for sex. Significant growth effects were observed for LVP length (p < .0001), extravelar length (p < .0001), intravelar length (p = .048), midline thickness (p = .0001), origin-origin distance (p < .0001), velar length (p < .0001), velar thickness (p = .003), nasion-sella turcica distance (p < .0001), sella turcica-basion distance (p < .0001), and hard palate length (p < .0001). Significant sex effects were observed for pharyngeal depth (p = .026) and effective VP ratio (p = .014). When age was treated as a continuous variable, similar results were observed for all variables except pharyngeal depth. Within-group comparisons revealed the most variability occurs between 3 and 5.99 months for LVP and craniofacial variables and between 9 and 11.99 months of age for VP variables. Male participants demonstrated greater variability than female participants. CONCLUSIONS: Differences were observed in LVP, VP, and craniofacial variables in children under 12 months while controlling for sex. Males demonstrated larger values and greater variability for most variables.

Efficient genetic code expansion without host genome modifications.

Supplementing translation with noncanonical amino acids (ncAAs) can yield protein sequences with new-to-nature functions but existing ncAA incorporation strategies suffer from low efficiency and context dependence. We uncover codon usage as a previously unrecognized contributor to efficient genetic code expansion using non-native codons. Relying only on conventional Escherichia coli strains with native ribosomes, we develop a plasmid-based codon compression strategy that minimizes context dependence and improves ncAA incorporation at quadruplet codons. We confirm that this strategy is compatible with all known genetic code expansion resources, which allowed us to identify 12 mutually orthogonal transfer RNA (tRNA)-synthetase pairs. Enabled by these findings, we evolved and optimized five tRNA-synthetase pairs to incorporate a broad repertoire of ncAAs at orthogonal quadruplet codons. Lastly, we extend these resources to an in vivo biosynthesis platform that can readily create >100 new-to-nature peptide macrocycles bearing up to three unique ncAAs. Our approach will accelerate innovations in multiplexed genetic code expansion and the discovery of chemically diverse biomolecules.

Impact of quality indicators on variability of keratometry measurements using a swept-source OCT based optical biometer.

PURPOSE: To characterize the variability of keratometry measurements on the IOLMaster 700, and relate it to device image quality indicators (QI). SETTING: Two academic centers and one private practice. DESIGN: Multicenter, retrospective consecutive case series. METHODS: Measurements from three sites, obtained between December, 2015 and July, 2023 were included. Surgery-naïve phakic eyes with same-day sequential measurements on the same eye were identified. Repeat measurement pairs were grouped by IOLMaster QIs (success vs. warning), and changes in mean standard (∆Kmean) and total (∆TKmean) keratometry as well as standard (∆Kastig) and total (∆TKastig) astigmatism vectors were calculated. RESULTS: Analysis was performed on 3,222 eyes of 1,890 patients. Measurement 'success' was associated with a smaller ΔKmean (0.09 ± 0.14 D) and ΔTKmean (0.11 ± 0.16 D) when compared to pairs in which both measurements had a 'warning' [0.25 ± 0.32 D and 0.14 ± 0.17 D, respectively; (p < 0.0001)]. A similarly smaller ∆Kastig (0.26 ± 0.28 D) and ∆TKastig (0.28 ± 0.30 D) was observed with measurement 'success' versus 'warning' [0.77 ± 0.79 D and 0.42 ± 0.41 D, respectively (p < 0.0001)]. Even when both measurements were successful, the proportion of measurement pairs that had a ∆Kastig > 0.50 D increased from 14% to 24% to 32% when Kmean standard deviation (SD) was ≥ 0.01, 0.05, and 0.10 D, respectively. CONCLUSIONS: When measurement quality is poor, total keratometry varies less than standard keratometry measurements. Clinicians may use the SD of Kmean/TKmean to estimate the repeatability of measurements and balance this against their tolerance for performing repeat measurements.