SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13.

Muco-obstructive lung diseases are typically associated with high risks of COVID-19 severity; however, allergic asthma showed reduced susceptibility. To investigate viral spread, primary human airway epithelial (HAE) cell cultures were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and host­virus interactions were examined via electron microscopy, immunohistochemistry, RNA in situ hybridization, and gene expression analyses. In HAE cell cultures, angiotensin-converting enzyme 2 (ACE2) expression governed cell tropism and viral load and was up-regulated by infection. Electron microscopy identified intense viral egress from infected ciliated cells and severe cytopathogenesis, culminating in the shedding of ciliated cells packed with virions, providing a large viral reservoir for spread and transmission. Intracellular stores of MUC5AC, a major airway mucin involved in asthma, were rapidly depleted, likely to trap viruses. To mimic asthmatic airways, HAE cells were treated with interleukin-13 (IL-13), which reduced viral titers, viral messenger RNA, and cell shedding, and significantly diminished the number of infected cells. Although mucus hyperproduction played a shielding role, IL-13­treated cells maintained a degree of protection despite the removal of mucus. Using Gene Expression Omnibus databases, bulk RNA-sequencing analyses revealed that IL-13 up-regulated genes controlling glycoprotein synthesis, ion transport, and antiviral processes (albeit not the typical interferon-induced genes) and down-regulated genes involved in cilial function and ribosomal processing. More precisely, we showed that IL-13 reduced ACE2 expression, intracellular viral load, and cell-to-cell transmission while increasing the cilial keratan sulfate coating. In conclusion, intense viral and cell shedding caused by SARS-CoV-2 infection was attenuated by IL-13, which affected viral entry, replication, and spread.

Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.

PURPOSE: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR). METHODS: We applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European ancestry. We performed analyses overall and by menopausal status. RESULTS: Genetically predicted BMI was positively associated with non-dense area (IVW: ß = 1.79; 95% CI = 1.58, 2.00; p = 9.57 × 10-63) and inversely associated with dense area (IVW: ß = - 0.37; 95% CI = - 0.51,- 0.23; p = 4.7 × 10-7). We observed weak evidence for an association of circulating sex hormone concentrations with mammographic density phenotypes, specifically inverse associations between genetically predicted testosterone concentration and dense area (ß = - 0.22; 95% CI = - 0.38, - 0.053; p = 0.009) and between genetically predicted estradiol concentration and non-dense area (ß = - 3.32; 95% CI = - 5.83, - 0.82; p = 0.009), although results were not consistent across a range of MR approaches. CONCLUSION: Our findings support a positive causal association between BMI and mammographic non-dense area and an inverse association between BMI and dense area. Evidence was weaker and inconsistent for a causal effect of circulating sex hormone concentrations on mammographic density phenotypes. Based on our findings, associations between circulating sex hormone concentrations and mammographic density phenotypes are weak at best.

Outcomes of Emergency Parastomal Hernia Repair in Older Adults: A Retrospective Analysis.

INTRODUCTION: Parastomal hernias are common and many are never repaired. Emergency parastomal hernia repair (PHR) is a feared complication following ostomy creation, yet the incidence and long-term outcomes of emergency PHR are unknown. MATERIALS AND METHODS: We performed a retrospective analysis of 100% Medicare claims data (2007-2015) to evaluate complications, readmissions, reoperations, hospitalizations, and mortality after emergency PHR. We used logistic regression and Cox proportional hazard models to determine the association of surgical approach, including repair with ostomy reversal, resiting, mesh, minimally invasive approach, or a myofascial flap. Analysis took place between June 2022 and February 2023. RESULTS: A total of 6658 patients underwent emergency PHR (mean [standard deviation] age, 75.9 [9.8] y; 4031 female individuals [60.5%]). Overall, 3433 (51.2%) patients underwent primary PHR, 1626 (24.4%) underwent PHR with ostomy resiting, and 1599 (24.0%) underwent PHR with ostomy reversal. In the 30 d after surgery, 4151 (62.3%) patients had complications and 55 (0.83%) underwent reoperation. Compared to local repair, the 30-d odds of complications were lower for patients who underwent ostomy resiting (odds ratio 0.82 [95% confidence interval 0.72-0.93]). Five y after surgery, the cumulative incidence of reoperation was 12.0% and was lowest for patients who underwent PHR with ostomy reversal (hazard ratio 0.15 [95% confidence interval 0.11-0.21]) when compared to local repair. CONCLUSIONS: Emergency PHR is associated with significant morbidity. However, technique selection may influence outcomes. Understanding the prognosis of emergency PHR may improve decision-making and patient counseling for patients living with this common disease.

Quantification of Hydrogen-Bond-Donating Ability of Biologically Relevant Compounds.

Hydrogen bonding is a key factor in the design of ligands for biological binding, including drug targets. Our group previously developed a method for experimentally assessing the hydrogen-bond-donating ability of an analyte using UV-vis titrations with a colorimetric sensor. Using this method, 79 new titrations were performed on weak hydrogen-bond donors, with a focus on heterocycles and pharmaceutically relevant motifs. The hydrogen-bond donating abilities of drug compounds and the substructures of drug compounds were also measured. These titrations will be used to build a database of hydrogen-bond donors.

Development and validation of time-to-event models to predict metastatic recurrence of localized cutaneous melanoma.

BACKGROUND: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. OBJECTIVE: To develop time-to-event risk prediction models for melanoma metastatic recurrence. METHODS: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. RESULTS: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. LIMITATIONS: Retrospective nature and cohort from one geography. CONCLUSIONS: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.

The Widened Pipe Model of plant hydraulic evolution.

Shaping global water and carbon cycles, plants lift water from roots to leaves through xylem conduits. The importance of xylem water conduction makes it crucial to understand how natural selection deploys conduit diameters within and across plants. Wider conduits transport more water but are likely more vulnerable to conduction-blocking gas embolisms and cost more for a plant to build, a tension necessarily shaping xylem conduit diameters along plant stems. We build on this expectation to present the Widened Pipe Model (WPM) of plant hydraulic evolution, testing it against a global dataset. The WPM predicts that xylem conduits should be narrowest at the stem tips, widening quickly before plateauing toward the stem base. This universal profile emerges from Pareto modeling of a trade-off between just two competing vectors of natural selection: one favoring rapid widening of conduits tip to base, minimizing hydraulic resistance, and another favoring slow widening of conduits, minimizing carbon cost and embolism risk. Our data spanning terrestrial plant orders, life forms, habitats, and sizes conform closely to WPM predictions. The WPM highlights carbon economy as a powerful vector of natural selection shaping plant function. It further implies that factors that cause resistance in plant conductive systems, such as conduit pit membrane resistance, should scale in exact harmony with tip-to-base conduit widening. Furthermore, the WPM implies that alterations in the environments of individual plants should lead to changes in plant height, for example, shedding terminal branches and resprouting at lower height under drier climates, thus achieving narrower and potentially more embolism-resistant conduits.

A cross-sectional survey of patient attitudes towards telemedicine in head and neck surgical oncology.

OBJECTIVE: To investigate patient attitudes towards desire for and barriers to utilizing telemedicine visits for head and neck oncology care. METHODS: This is a retrospective analysis of data from cross-sectional survey responses collected via prospectively administered questionnaire to 616 adult patients during their clinical visit to a tertiary care head and neck surgical oncology clinic. Responses to questions investigating interest in telemedicine and potential barriers were collated with patient demographics, measures of rurality, and insurance status. Interest in telemedicine appointments was the assessed primary outcome. RESULTS: Of 616 survey respondents, 315 (51 %) indicated interest in telemedicine visits. Limitations in access to technology (17.5 %) and lack of reliable internet connection (13.14 %) were identified as key barriers to telemedicine use. Lack of interest in telemedicine was associated with older age (OR 0.97 [95%CI 0.96-0.98]), governmental insurance (0.43 [0.31-0.60]) and, retired work status (0.48 [0.33-0.69]). Women (1.43 [1.04-1.97]) and patients who reported access to compatible electronic devices (41.05 [14.88-113.20]) and reliable internet connection (20.94 [8.34-52.60]) were more likely to be interested in telemedicine appointments. Respondents also indicated preference for a "hands on" examination over telemedicine appointments. CONCLUSION: Nearly 1 in 2 patients evaluated in a tertiary care head and neck surgical oncology clinic expressed reticence regarding telemedicine for clinical visits. Limited access to technology platforms and unreliable internet remain key concerns for these patients. Understanding the needs and attitudes of specific patient populations may be important for organizations pivoting to telemedicine platforms to ensure equity in healthcare access. LEVEL OF EVIDENCE: Retrospective analysis of prospectively collected cross-sectional survey.

Dermatofibrosarcoma Protuberans in "Slow Mohs-tion": Multidisciplinary Approach of A Pediatric Dermatofibrosarcoma Protuberans of the Scalp with Slow Mohs Micrographic Surgery and A Double Rotational-Advancement Scalp Flap.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue sarcoma with primary incidence of 4.1 per million person-years and accounts for 0.1% of all malignancies. In patients under the age of 19, DFSP comprises 6% of cases with an annual incidence of 1 in 1,000,000. It is a slow-growing malignancy with low metastatic potential. However, DFSP is notable for its high rates of local recurrence due to local invasion with its classic "finger-like" projections into normal tissue. We discuss a case of dermatofibrosarcoma protuberans on the scalp of a 14-year-old male with delayed diagnosis, which required extensive resection through slow Mohs Micrographic Surgery (sMMS). This resection created a sizeable scalp defect of nearly 100 cm 2 , which mandated creative reconstruction using a novel double rotational-advancement scalp flap to close the defect while maintaining the patient's hairline for optimal cosmesis.

BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance.

Airway mucociliary clearance (MCC) is required for host defense and is often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is associated with a reduction in the rate of MCC; however, how other secreted proteins impact the integrity of the mucus layer and MCC remains unclear. We previously identified the gene Bpifb1/Lplunc1 as a regulator of airway MUC5B protein levels using genetic approaches. Here, we show that BPIFB1 is required for effective MCC in vivo using Bpifb1 knockout (KO) mice. Reduced MCC in Bpifb1 KO mice occurred in the absence of defects in epithelial ion transport or reduced ciliary beat frequency. Loss of BPIFB1 in vivo and in vitro altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC. Finally, we detected colocalization of BPIFB1 and MUC5B in secretory granules in mice and the protein mesh of secreted mucus in human airway epithelia cultures. Collectively, our findings demonstrate that BPIFB1 is an important component of the mucociliary apparatus in mice and a key component of the mucus protein network.NEW & NOTEWORTHY BPIFB1, also known as LPLUNC1, was found to regulate mucociliary clearance (MCC), a key aspect of host defense in the airway. Loss of this protein was also associated with altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC.

Switchable Explosives: Performance Tuning of Fluid-Activated High Explosive Architectures.

We present our discovery of switchable high explosives (HEs) as a new class of energetic material that cannot detonate unless filled with a fluid. The performance of fluid-filled additive-manufactured HE lattices is herein evaluated by analysis of detonation velocity and Gurney energy. The Gurney energy of the unfilled lattice was 98% lower than that of the equivalent water-filled lattice and changing the fluid mechanical properties allowed tuning of the Gurney energy and detonation velocity by 8.5% and 13.4%, respectively. These results provide, for the first time since the development of HEs, a method to completely remove the hazard of unplanned detonations during storage and transport.

Hydrogen Bonding Parameters by Rapid Colorimetric Assessment: Evaluation of Structural Components Found in Biological Ligands and Organocatalysts.

Hydrogen bonding is a key molecular interaction in biological processes, drug delivery, and catalysis. This report describes a high throughput UV-Vis spectroscopic method to measure hydrogen bonding capacity using a pyrazinone sensor. This colormetric sensor reversibly binds to a hydrogen bond donor, resulting in a blue shift as additional equivalents of donor are added. Titration with excess equivalents of donor is used to determine the binding coefficient, ln(Keq ). Over 100 titrations were performed for a variety of biologically relevant compounds. This data enabled development a multiple linear regression model that is capable of predicting 95 % of ln(Keq ) values within 1 unit, allowing for the estimation of hydrogen bonding affinity from a single measurement. To show the effectiveness of the single point measurements, hydrogen bond strengths were obtained for a set of carboxylic acid bioisosteres. The values from the single point measurements were validated with full titrations.

The "η-sweet-spot" (ηmax) in liquid-assisted mechanochemistry: polymorph control and the role of a liquid additive as either a catalyst or an inhibitor in resonant acoustic mixing (RAM).

Resonant acoustic mixing (RAM) offers a simple, efficient route for mechanochemical synthesis in the absence of milling media or bulk solvents. Here, we show the use of RAM to conduct the copper-catalysed coupling of sulfonamides and carbodiimides. This coupling was previously reported to take place only by mechanochemical ball milling, while in conventional solution environments it is not efficient, or does not take place at all. The results demonstrate RAM as a suitable methodology to conduct reactions previously accessed only by ball milling and provide a detailed, systematic overview of how the amount of liquid additive, measured by the ratio of liquid volume to weight of reactants (η, in µL mg-1), can affect the course of a mechanochemical reaction and the polymorphic composition of its product. Switching from ball milling to RAM allowed for the discovery of a new polymorph of the model sulfonylguanidine obtained by catalytic coupling of di(cyclohexyl)carbodiimide (DCC) and p-toluenesulfonamide, and the ability to control reaction temperature in RAM enabled in situ control of the polymorphic behaviour of this nascent product. We show that the reaction conversion for a given reaction time does not change monotonically but, instead, achieves a maximum for a well-defined η-value. This "η-sweet-spot" of conversion is herein designated ηmax. The herein explored reactions demonstrate sensitivity to η on the order of 0.01 µL mg-1, which corresponds to an amount of liquid additive below 5 mol% compared to the reactants, and is at least one to two orders of magnitude lower than the η-value typically considered in the design of liquid-assisted ball milling mechanochemical reactions. Such sensitivity suggests that strategies to optimise liquid-assisted mechanochemical reactions should systematically evaluate η-values at increments of 0.01 µL mg-1, or even finer. At η-values other than ηmax the reaction conversion drops off, demonstrating that the same liquid additive can act either as a catalyst or an inhibitor of a mechanochemical reaction, depending on the amount.

Retrospective analysis of sepsis in cutaneous T-cell lymphoma reveals significantly greater risk in Black patients.

BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and resource utilization among patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVE: To characterize the demographic, clinical, and microbial attributes distinguishing patients with CTCL sepsis from other patients with non-Hodgkin lymphoma (NHL) sepsis and patients with CTCL in general. METHODS: Two-part retrospective cohort study at an academic medical center from 2001-2019 involving patients with CTCL (n = 97) and non-CTCL NHL (n = 88) admitted with sepsis, and a same-institution CTCL patient database (n = 1094). Overall survival was estimated by Kaplan-Meier analyses. RESULTS: Patients with CTCL sepsis were more likely to be older, Black, experience more sepsis episodes, die or be readmitted within 30 days of an inpatient sepsis episode, and develop Gram-positive bacteremia than patients with non-CTCL NHL sepsis. Staphylococcus aureus and Escherichia coli were the most frequently speciated organisms in CTCL (26%) and non-CTCL NHL (14%), respectively. No between-group differences were identified regarding sex, presence of central line, chemotherapy use, or disease stage. Compared with general patients with CTCL, patients with sepsis were Black and exhibited advanced-stage disease, higher body surface area involvement, and higher lactate dehydrogenase levels. LIMITATIONS: Single institution, retrospective nature may limit generalizability. CONCLUSION: Awareness of CTCL-specific risk factors is crucial for guiding sepsis prevention and improving patient outcomes.

Effect of use and dosage of p-follicle-stimulating hormone for ovarian superstimulation before ovum pick-up and in vitro embryo production in pregnant Holstein heifers.

The benefit of ovarian superstimulation using exogenous FSH before ovum pick-up (OPU) and in vitro embryo production (IVEP) has been the subject of conflicting results. The objective of the present study, therefore, was to evaluate the effect of use and dose of porcine FSH (p-FSH) before OPU/IVEP on ovarian response and embryo production in pregnant heifers. Pregnant Holstein heifers (n = 48) were randomly assigned to receive 0, 160, or 300 mg NIH-FSH-P1 in a crossover design. Ovum pick-up was performed at 49, 63, and 77 d of gestation with a 14 d "washout" between OPU sessions. Follicle ablation was performed on D 0 (p.m.) and p-FSH treatments, consisting of 4 decreasing dose injections administered 12 h apart, were initiated 36 h after follicle ablation (d 2 a.m.). Heifers underwent OPU on D 5 (a.m.), 40 h after the last p-FSH treatment, and cumulus oocyte complexes (COC) were subjected to IVEP procedures. Differences between treatment groups were evaluated using generalized linear mixed models. There were quadratic effects of treatment on both number and percentage of small (<6 mm), medium (6-10 mm), and large (>10 mm) follicles. Number and percentage of medium follicles increased with increasing p-FSH dosages, although the magnitude of the change was greater between 0 and 160 mg, than between 160 and 300 mg of p-FSH. Total number of follicles, number of COC recovered and number of viable COC increased linearly with increasing p-FSH dose. Conversely, there was no evidence for an effect of p-FSH dose on COC recovery percentage nor the percentage of viable COC. Cleavage percentage, number of cleaved oocytes, blastocyst percentage, and number of blastocysts increased linearly with increasing p-FSH dose. In conclusion, use of p-FSH before OPU resulted in greater superstimulatory response and oocyte competence which in turn increased IVEP. Furthermore, these effects were dose dependent such that use of a greater dose of p-FSH up to 300 mg progressively increased embryo yield.

Choline restores respiration in Psd1-deficient yeast by replenishing mitochondrial phosphatidylethanolamine.

Phosphatidylethanolamine (PE) is essential for mitochondrial respiration in yeast, Saccharomyces cerevisiae, whereas the most abundant mitochondrial phospholipid, phosphatidylcholine (PC), is largely dispensable. Surprisingly, choline (Cho), which is a biosynthetic precursor of PC, has been shown to rescue the respiratory growth of mitochondrial PE-deficient yeast; however, the mechanism underlying this rescue has remained unknown. Using a combination of yeast genetics, lipid biochemistry, and cell biological approaches, we uncover the mechanism by showing that Cho rescues mitochondrial respiration by partially replenishing mitochondrial PE levels in yeast cells lacking the mitochondrial PE-biosynthetic enzyme Psd1. This rescue is dependent on the conversion of Cho to PC via the Kennedy pathway as well as on Psd2, an enzyme catalyzing PE biosynthesis in the endosome. Metabolic labeling experiments reveal that in the absence of exogenously supplied Cho, PE biosynthesized via Psd2 is mostly directed to the methylation pathway for PC biosynthesis and is unavailable for replenishing mitochondrial PE in Psd1-deleted cells. In this setting, stimulating the Kennedy pathway for PC biosynthesis by Cho spares Psd2-synthesized PE from the methylation pathway and redirects it to the mitochondria. Cho-mediated elevation in mitochondrial PE is dependent on Vps39, which has been recently implicated in PE trafficking to the mitochondria. Accordingly, epistasis experiments placed Vps39 downstream of Psd2 in Cho-based rescue. Our work, thus, provides a mechanism of Cho-based rescue of mitochondrial PE deficiency and uncovers an intricate interorganelle phospholipid regulatory network that maintains mitochondrial PE homeostasis.

Treatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties via hydration.

QUESTION: Cystic fibrosis (CF) is characterised by the accumulation of viscous adherent mucus in the lungs. While several hypotheses invoke a direct relationship with cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction (i.e. acidic airway surface liquid (ASL) pH, low bicarbonate (HCO3 -) concentration, airway dehydration), the dominant biochemical alteration of CF mucus remains unknown. MATERIALS/METHODS: We characterised a novel cell line (CFTR-KO Calu3 cells) and the responses of human bronchial epithelial (HBE) cells from subjects with G551D or F508del mutations to ivacaftor and elexacaftor-tezacaftor-ivacaftor. A spectrum of assays such as short-circuit currents, quantitative PCR, ASL pH, Western blotting, light scattering/refractometry (size-exclusion chromatography with inline multi-angle light scattering), scanning electron microscopy, percentage solids and particle tracking were performed to determine the impact of CFTR function on mucus properties. RESULTS: Loss of CFTR function in Calu3 cells resulted in ASL pH acidification and mucus hyperconcentration (dehydration). Modulation of CFTR in CF HBE cells did not affect ASL pH or mucin mRNA expression, but decreased mucus concentration, relaxed mucus network ultrastructure and improved mucus transport. In contrast with modulator-treated cells, a large fraction of airway mucins remained attached to naïve CF cells following short apical washes, as revealed by the use of reducing agents to remove residual mucus from the cell surfaces. Extended hydration, but not buffers alkalised with sodium hydroxide or HCO3 -, normalised mucus recovery to modulator-treated cell levels. CONCLUSION: These results indicate that airway dehydration, not acidic pH and/or low [HCO3 -], is responsible for abnormal mucus properties in CF airways and CFTR modulation predominantly restores normal mucin entanglement.

Accuracy of tumor registry versus pharmacy dispensings for breast cancer adjuvant endocrine therapy.

PURPOSE: Accounting for endocrine therapy use for breast cancer treatment is important for studies of survivorship. We evaluated the accuracy of Surveillance, Epidemiology, and End Results (SEER) breast cancer endocrine therapy data compared with pharmacy dispensings from an integrated health system. METHODS: We included women with non-metastatic hormone receptor positive primary breast cancer diagnosed between 1995 and 2017 enrolled in Kaiser Permanente Washington, linking their data with SEER. We used pharmacy dispensings for endocrine therapy within one year following diagnosis as our reference standard. We calculated kappa (concordance), positive predictive value (PPV), and negative predictive values (NPV) overall and stratified by woman and tumor characteristics of interest. RESULTS: Of 5,055 women, mean age at diagnosis was 62 years (interquartile range = 53-71); 53% had localized stage, 56% received lumpectomy with radiation, and 31% received chemotherapy. SEER data alone identified 67% of women as having received endocrine therapy; this increased to 75% with pharmacy dispensings. SEER's concordance with pharmacy dispensings was 0.68 (PPV = 91%; NPV = 76%). PPV did not vary by tumor or women characteristics; however, NPV declined with younger age at diagnosis (64% in < 45 years vs. 86% in 75+ years), increasing tumor stage (49% in regional stage vs. 91% in DCIS), and chemotherapy treatment (41% in those with chemotherapy vs. 83% in those without chemotherapy). CONCLUSION: Pharmacy dispensings enable more complete endocrine therapy capture, particularly in women with more advanced tumors or who receive chemotherapy. We determined woman, tumor, and treatment characteristics that contribute to underascertainment of endocrine therapy use in tumor registries.

Trajectories of functioning in a population-based sample of veterans: contributions of moral injury, PTSD, and depression.

BACKGROUND: Although research has shown that exposure to potentially traumatic and morally injurious events is associated with psychological symptoms among veterans, knowledge regarding functioning impacts remains limited. METHODS: A population-based sample of post-9/11 veterans completed measures of intimate relationship, health, and work functioning at approximately 9, 15, 21, and 27 months after leaving service. Moral injury, posttraumatic stress, and depression were assessed at ~9 months post-separation. We used Latent Growth Mixture Models to identify discrete classes characterized by unique trajectories of change in functioning over time and to examine predictors of class membership. RESULTS: Veterans were assigned to one of four functioning trajectories: high and stable, high and decreasing, moderate and increasing, and moderate and stable. Whereas posttraumatic stress, depression, and moral injury associated with perpetration and betrayal predicted worse outcomes at baseline across multiple functioning domains, moral injury associated with perpetration and depression most reliably predicted assignment to trajectories characterized by relatively poor or declining functioning. CONCLUSIONS: Moral injury contributes to functional problems beyond what is explained by posttraumatic stress and depression, and moral injury due to perpetration and depression most reliably predicted assignment to trajectories characterized by functional impairment over time.

Variation in cloud immersion, not precipitation, drives leaf trait plasticity and water relations in vascular epiphytes during an extreme drought.

PREMISE: Epiphytes are abundant in ecosystems such as tropical montane cloud forests where low-lying clouds are often in contact with vegetation. Climate projections for these regions include more variability in rainfall and an increase in cloud base heights, which would lead to drier conditions in the soil and atmosphere. While recent studies have examined the effects of drought on epiphytic water relations, the influence that atmospheric moisture has, either alone or in combination with drought, on the health and performance of epiphyte communities remains unclear. METHODS: We conducted a 10-week drought experiment on seven vascular epiphyte species in two shadehouses, one with warmer and drier conditions and another that was cooler and more humid. We measured water relations across control and drought-treatment groups and assessed functional traits of leaves produced during drought conditions to evaluate trait plasticity. RESULTS: Epiphytes exposed to drought and drier atmospheric conditions had a significant reduction in stomatal conductance and leaf water potential and an increase in leaf dry matter. Nonsucculent epiphytes from the drier shadehouse had the greatest shifts in functional traits, whereas succulent epiphytes released stored leaf water to maintain water status. CONCLUSIONS: Individuals in the drier shadehouse had a substantial reduction in performance, whereas drought-treated individuals that experienced cloud immersion displayed minimal changes in water status. Our results indicate that projected increases in the cloud base height will reduce growth and performance of epiphytic communities and that nonsucculent epiphytes may be particularly vulnerable.

The Moral Injury Symptoms Scale-Military Version-Short Form: Further Scale Validation in a U.S. Veteran Sample.

This study assessed the Moral Injury Symptoms Scale - Military Version - Short Form's (MISS-M-SF) factor structure and construct validity. Participants included 3650 combat-deployed U.S. veterans who answered all 10 MISS-M-SF items from the sixth wave of The Veterans Metric Initiative (TVMI). EFA results suggested a two-factor solution, based on item wording, fit best. CFA results indicated a bifactor model (one general factor and two method factors, based on item wording) fit best. Further investigation revealed that a one-factor model could be used despite the data's multidimensionality. Item-level analyses revealed four items represented the general factor exceptionally well, potentially simplifying assessment in research and clinical applications. Construct validity was also demonstrated through moderate to high correlations with conceptually related measures.