Landscape-scale benefits of protected areas for tropical biodiversity.

The United Nations recently agreed to major expansions of global protected areas (PAs) to slow biodiversity declines1. However, although reserves often reduce habitat loss, their efficacy at preserving animal diversity and their influence on biodiversity in surrounding unprotected areas remain unclear2-5. Unregulated hunting can empty PAs of large animals6, illegal tree felling can degrade habitat quality7, and parks can simply displace disturbances such as logging and hunting to unprotected areas of the landscape8 (a phenomenon called leakage). Alternatively, well-functioning PAs could enhance animal diversity within reserves as well as in nearby unprotected sites9 (an effect called spillover). Here we test whether PAs across mega-diverse Southeast Asia contribute to vertebrate conservation inside and outside their boundaries. Reserves increased all facets of bird diversity. Large reserves were also associated with substantially enhanced mammal diversity in the adjacent unprotected landscape. Rather than PAs generating leakage that deteriorated ecological conditions elsewhere, our results are consistent with PAs inducing spillover that benefits biodiversity in surrounding areas. These findings support the United Nations goal of achieving 30% PA coverage by 2030 by demonstrating that PAs are associated with higher vertebrate diversity both inside their boundaries and in the broader landscape.

DNA Methylation and Histone H1 Jointly Repress Transposable Elements and Aberrant Intragenic Transcripts.

DNA methylation and histone H1 mediate transcriptional silencing of genes and transposable elements, but how they interact is unclear. In plants and animals with mosaic genomic methylation, functionally mysterious methylation is also common within constitutively active housekeeping genes. Here, we show that H1 is enriched in methylated sequences, including genes, of Arabidopsis thaliana, yet this enrichment is independent of DNA methylation. Loss of H1 disperses heterochromatin, globally alters nucleosome organization, and activates H1-bound genes, but only weakly de-represses transposable elements. However, H1 loss strongly activates transposable elements hypomethylated through mutation of DNA methyltransferase MET1. Hypomethylation of genes also activates antisense transcription, which is modestly enhanced by H1 loss. Our results demonstrate that H1 and DNA methylation jointly maintain transcriptional homeostasis by silencing transposable elements and aberrant intragenic transcripts. Such functionality plausibly explains why DNA methylation, a well-known mutagen, has been maintained within coding sequences of crucial plant and animal genes.

Mechanisms underpinning sympathoexcitation in hypoxia.

Sympathoexcitation is a hallmark of hypoxic exposure, occurring acutely, as well as persisting in acclimatised lowland populations and with generational exposure in highland native populations of the Andean and Tibetan plateaus. The mechanisms mediating altitude sympathoexcitation are multifactorial, involving alterations in both peripheral autonomic reflexes and central neural pathways, and are dependent on the duration of exposure. Initially, hypoxia-induced sympathoexcitation appears to be an adaptive response, primarily mediated by regulatory reflex mechanisms concerned with preserving systemic and cerebral tissue O2 delivery and maintaining arterial blood pressure. However, as exposure continues, sympathoexcitation is further augmented above that observed with acute exposure, despite acclimatisation processes that restore arterial oxygen content ( C a O 2 ${C_{{\mathrm{a}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Under these conditions, sympathoexcitation may become maladaptive, giving rise to reduced vascular reactivity and mildly elevated blood pressure. Importantly, current evidence indicates the peripheral chemoreflex does not play a significant role in the augmentation of sympathoexcitation during altitude acclimatisation, although methodological limitations may underestimate its true contribution. Instead, processes that provide no obvious survival benefit in hypoxia appear to contribute, including elevated pulmonary arterial pressure. Nocturnal periodic breathing is also a potential mechanism contributing to altitude sympathoexcitation, although experimental studies are required. Despite recent advancements within the field, several areas remain unexplored, including the mechanisms responsible for the apparent normalisation of muscle sympathetic nerve activity during intermediate hypoxic exposures, the mechanisms accounting for persistent sympathoexcitation following descent from altitude and consideration of whether there are sex-based differences in sympathetic regulation at altitude.

The interactive effects of posture and biological sex on the control of muscle sympathetic nerve activity during rhythmic handgrip exercise.

Body posture and biological sex exhibit independent effects on the sympathetic neural responses to dynamic exercise. However, the neural mechanisms (e.g., baroreflex) by which posture impacts sympathetic outflow during rhythmic muscular contractions, and whether biological sex affects posture-mediated changes in efferent sympathetic nerve traffic during exercise, remain unknown. Thus, we tested the hypotheses that increases in muscle sympathetic nerve activity (MSNA) would be greater during upright compared with supine rhythmic handgrip (RHG) exercise, and that females would demonstrate smaller increases in MSNA during upright RHG exercise than males. Twenty young (30 [6] yr; means [SD]) individuals (9 males, 11 females) underwent 6 min of supine and upright (head-up tilt 45°) RHG exercise at 40% maximal voluntary contraction with continuous measurements of MSNA (microneurography), blood pressure (photoplethysmography), and heart rate (electrocardiogram). In the pooled group, absolute MSNA burst frequency (P < 0.001), amplitude (P = 0.009), and total MSNA (P < 0.001) were higher during upright compared with supine RHG exercise. However, body posture did not impact the peak change in MSNA during RHG exercise (range: P = 0.063-0.495). Spontaneous sympathetic baroreflex gain decreased from rest to RHG exercise (P = 0.006) and was not impacted by posture (P = 0.347). During upright RHG exercise, males demonstrated larger increases in MSNA burst amplitude (P = 0.002) and total MSNA (P = 0.001) compared with females, which coincided with greater reductions in sympathetic baroreflex gain among males (P = 0.004). Collectively, these data indicate that acute attenuation of baroreflex-mediated sympathoinhibition permits increases in MSNA during RHG exercise and that males exhibit a greater reserve for efferent sympathetic neural recruitment during orthostasis than females.NEW & NOTEWORTHY The impact of posture and sex on cardiovascular control during rhythmic handgrip (RHG) exercise is unknown. We show that increases in muscle sympathetic nerve activity (MSNA) during RHG are partly mediated by a reduction in sympathetic baroreflex gain. In addition, males demonstrate larger increases in total MSNA during upright RHG than females. These data indicate that the baroreflex partly mediates increases in MSNA during RHG and that males have a greater sympathetic vasoconstrictor reserve than females.

Habitat modulates population-level responses of freshwater salmon growth to a century of change in climate and competition.

The impacts of climate change are widespread and threaten natural systems globally. Yet, within regions, heterogeneous physical landscapes can differentially filter climate, leading to local response diversity. For example, it is possible that while freshwater lakes are sensitive to climate change, they may exhibit a diversity of thermal responses owing to their unique morphology, which in turn can differentially affect the growth and survival of vulnerable biota such as fishes. In particular, salmonids are cold-water fishes with complex life histories shaped by diverse freshwater habitats that are sensitive to warming temperatures. Here we examine the influence of habitat on the growth of sockeye salmon (Oncorhynchus nerka) in nursery lakes of Canada's Skeena River watershed over a century of change in regional temperature and intraspecific competition. We found that freshwater growth has generally increased over the last century. While growth tended to be higher in years with relatively higher summer air temperatures (a proxy for lake temperature), long-term increases in growth appear largely influenced by reduced competition. However, habitat played an important role in modulating the effect of high temperature. Specifically, growth was positively associated with rising temperatures in relatively deep (>50 m) nursery lakes, whereas warmer temperatures were not associated with a change in growth for fish among shallow lakes. The influence of temperature on growth also was modulated by glacier extent whereby the growth of fish from lakes situated in watersheds with little (i.e., <5%) glacier cover increased with rising temperatures, but decreased with rising temperatures for fish in lakes within more glaciated watersheds. Maintaining the integrity of an array of freshwater habitats-and the processes that generate and maintain them-will help foster a diverse climate-response portfolio for important fish species, which in turn can ensure that salmon watersheds are resilient to future environmental change.

Exploring healthcare provider retention in a rural and frontier community in Northern Idaho.

BACKGROUND: A shortage of healthcare providers, particularly in primary care and mental health, exists in the predominately rural state of Idaho. There are also barriers to retaining healthcare providers to work in rural and remote communities. Limited research using U.S. samples has explored factors that may affect the retention of healthcare providers in rural areas. Additionally, due to differences between communities, it is important to conduct community-level investigations to better understand how these factors may affect retention in rural areas. Therefore, the purpose of this study was to explore factors affecting healthcare provider retention in a rural community in Northern Idaho. METHODS: A modified version of the Nursing Community Apgar Questionnaire (NCAQ) was completed by 30 healthcare providers in a rural and frontier community in Northern Idaho to assess factors influencing healthcare provider retention. Factors were classified into classes including geographic, economic, scope of practice, medical support, and facility and community support classes. Retention factors were assessed on their perceived importance to retention as well as whether they were perceived as an advantage or challenge to retention based on Likert scales. A "Community Apgar" score was also created by combining the importance and advantage/challenge factors. RESULTS: Overall, items in the medical support group had the highest importance of any other class and included factors such as nursing workforce. Additionally, the facility and community support class, which included factors such as televideo support, was rated the highest advantage class and had the highest Apgar score, indicating it contained the factor that healthcare providers identified as the most important advantage (i.e., medical reference resources). CONCLUSION: Our study identified multiple factors that healthcare providers deemed as important advantages or disadvantages to retaining healthcare providers in rural areas. Overall, facility and community support factors were found to have the highest advantage in the retention of rural providers. Rural healthcare organizations looking to increase healthcare provider retention should target retention efforts towards these factors. Additional research should also be conducted on other rural samples across the U.S. to make comparisons of findings.

Visual performance and patient preference with bilateral implantation of an extended depth of focus or combined implantation of an extended depth of focus/trifocal intraocular lens.

PURPOSE: Evaluate postoperative visual performance in patients with bilaterally implanted AT LARA or AT LARA/AT LISA tri (Carl Zeiss AG, Jena, Germany) intraocular lenses. METHODS: Multicentered, comparative, open-label, retrospective/prospective study. Post-IOL implantation, patients were prospectively enrolled into this study; preoperative patient data were collected retrospectively. Follow-up was at 2-4 and 5-8 months post-surgery. The primary endpoint was binocular best corrected distance visual acuity (CDVA). The study was retrospectively registered on clinicaltrials.gov (#NCT05462067). RESULTS: Seventy-one patients (142 eyes) were enrolled; 67 patients (134 eyes) have 5-8 months data. The mean binocular CDVA at 2-4 months was -0.10 ± 0.06 logMAR in the bilateral AT LARA group ("bilateral") and -0.11 ± 0.09 logMAR in the combined implantation AT LARA/ AT LISA tri group ("combined implantation"); (P = 0.4856). At 5-8 months, mean binocular CDVA was -0.13 ± 0.06 logMAR in the bilateral group and -0.11 ± 0.09 in the combined implantation group (P = 0.4003). At 5-8 months, more eyes in the bilateral group attained 0.2 logMAR or better binocular uncorrected intermediate VA (UIVA; 67 cm) than those in the combined implantation group (100% vs. 94%, respectively). The bilateral group achieved a mean of 0.24 ± 0.11 logMAR in uncorrected near VA (UCNVA), compared to a mean of 0.16 ± 0.12 logMAR in the combined implantation group at 5-8 months (P = 0.0041). CONCLUSIONS: A combined implantation approach (AT LARA in the distance dominant eye/AT LISA tri in the non-dominant eye) produced similar CDVA outcomes but better UCNVA as bilateral implantation with the AT LARA. UIVA was comparable between groups. No new safety concerns were reported.

Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics.

The spatial distribution of tumor-infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing tumors. Here, we present ST-FFPE, a spatial transcriptomics method for the analysis of formalin-fixed paraffin-embedded samples, which opens the possibility of interrogating archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser-capture, and can be used to study the cellular composition of tumor microenvironment. Focusing on triple-negative breast cancer (TNBC), we characterized T cells, B cells, dendritic cells, fibroblasts and endothelial cells in both stromal and intra-epithelial compartments. We found a highly variable spatial distribution of immune cell subsets among tumors. This analysis revealed that the immune repertoires of intra-epithelial T and B cells were consistently less diverse and more clonal than those of stromal T and B cells. T-cell receptor (TCR) sequencing confirmed a reduced diversity and higher clonality of intra-epithelial T cells relative to the corresponding stromal T cells. Analysis of the top 10 dominant clonotypes in the two compartments showed a majority of shared but also some unique clonotypes both in stromal and intra-epithelial T cells. Hyperexpanded clonotypes were more abundant among intra-epithelial than stromal T cells. These findings validate the ST-FFPE method and suggest an accumulation of antigen-specific T cells within tumor core. Because ST-FFPE is applicable for analysis of previously collected tissue samples, it could be useful for rapid assessment of intratumoral cellular heterogeneity in multiple disease and treatment settings.

Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study.

OBJECTIVE: To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND: CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS: This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS: A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.

Effect of Cannabidiol Oil on Post-ureteroscopy Pain for Urinary Calculi: A Randomized, Double-blind, Placebo-controlled Trial.

PURPOSE: Post-ureteroscopy stent placement carries significant morbidity which can interfere with daily life. This discomfort unfortunately leads to high utilization of opioid pain medications, which have a known risk of addiction. Cannabidiol oil represents an alternative analgesic that has proven anti-inflammatory and antinociceptive effects. The purpose was to evaluate the effect of a Food and Drug Administration-approved cannabidiol oil (Epidiolex) on pain control and opioid usage in the post-ureteroscopy setting. MATERIALS AND METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial at a tertiary care center. Ninety patients undergoing ureteroscopy with stent placement for urinary stone disease were randomized 1:1 to placebo or 20 mg cannabidiol oil daily for 3 days postoperatively. Both groups were prescribed a rescue narcotic, tamsulosin, oxybutynin, and phenazopyridine. Daily pain scores, medication usage, and ureteral stent symptoms using the validated Ureteral Stent Symptom Questionnaire were recorded postoperatively. RESULTS: Both the placebo and cannabidiol oil groups were not different in pre- and perioperative characteristics. There was no difference in pain scores or opioid usage between groups postoperatively. The level of discomfort with ureteral stents was also not different between groups when comparing physical activity, sleep, urination, and activities of daily life. CONCLUSIONS: This randomized, blinded, placebo-controlled trial showed that cannabidiol oil is safe but ineffective when compared to placebo in reducing post-ureteroscopic stent discomfort or opioid usage. Despite the availability of numerous analgesic agents, stent symptoms continue to be a dissatisfier for most patients, suggesting additional work needs to focus on novel interventions and pain control.

Barosensory vessel mechanics and the vascular sympathetic baroreflex: Impact on blood pressure homeostasis.

NEW FINDINGS: What is the topic of this review? We review barosensory vessel mechanics and their role in blood pressure regulation across the lifespan. What advances does it highlight? In young normotensive men, aortic unloading mechanics contribute to the resting operating point of the vascular sympathetic baroreflex; however, with advancing age, this contribution is removed. This suggests that barosensory vessel unloading mechanics are not driving the well-documented age-related increase in resting muscle sympathetic nerve activity. ABSTRACT: An age-associated increase in arterial blood pressure is evident for apparently healthy humans. This is frequently attributed to stiffening of the central arteries and a concurrent increase in sympathetic outflow, potentially mediated by a reduced ability of the baroreceptive vessels to distend. This is supported, in part, by a reduced mechanical component of the vascular sympathetic baroreflex (i.e., a reduction in distension for a given pressure). Previous characterization of the mechanical component has assessed only carotid artery distension; however, evidence suggests that both the aortic and carotid baroreflexes are integral to blood pressure regulation. In addition, given that baroreceptors are located in the vessel wall, the change in wall tension, comprising diameter, pressure and vessel wall thickness, and the mechanics of this change might provide a better index of the baroreceptor stimulus than the previous method used to characterize the mechanical component that relies on diameter alone. This brief review summarizes the data using this new method of assessing barosensory vessel mechanics and their influence on the vascular sympathetic baroreflex across the lifespan.

Predictive Molecular Design and Structure-Property Validation of Novel Terpene-Based, Sustainably Sourced Bacterial Biofilm-Resistant Materials.

Presented in this work is the use of a molecular descriptor, termed the α parameter, to aid in the design of a series of novel, terpene-based, and sustainable polymers that were resistant to biofilm formation by the model bacterial pathogen Pseudomonas aeruginosa. To achieve this, the potential of a range of recently reported, terpene-derived monomers to deliver biofilm resistance when polymerized was both predicted and ranked by the application of the α parameter to key features in their molecular structures. These monomers were derived from commercially available terpenes (i.e., α-pinene, ß-pinene, and carvone), and the prediction of the biofilm resistance properties of the resultant novel (meth)acrylate polymers was confirmed using a combination of high-throughput polymerization screening (in a microarray format) and in vitro testing. Furthermore, monomers, which both exhibited the highest predicted biofilm anti-biofilm behavior and required less than two synthetic stages to be generated, were scaled-up and successfully printed using an inkjet "valve-based" 3D printer. Also, these materials were used to produce polymeric surfactants that were successfully used in microfluidic processing to create microparticles that possessed bio-instructive surfaces. As part of the up-scaling process, a novel rearrangement was observed in a proposed single-step synthesis of α-terpinyl methacrylate via methacryloxylation, which resulted in isolation of an isobornyl-bornyl methacrylate monomer mixture, and the resultant copolymer was also shown to be bacterial attachment-resistant. As there has been great interest in the current literature upon the adoption of these novel terpene-based polymers as green replacements for petrochemical-derived plastics, these observations have significant potential to produce new bio-resistant coatings, packaging materials, fibers, medical devices, etc.

Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients with oesophageal adenocarcinoma.

OBJECTIVES: 2-deoxy-2[18F]Fluoro-D-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival. METHODS: Cohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy's and St Thomas' NHS Foundation Trust, London (2017-2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression. RESULTS: Optimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03-0.34; mTR HR 0.17 95% CI 0.06-0.48; pNR HR 0.17 95% CI 0.06-0.54; mNR HR 0.13 95% CI 0.02-0.66). CONCLUSIONS: Metabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival. KEY POINTS: • FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer. • Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection. • Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.

The role of spatial structure in at-risk metapopulation recoveries.

Metapopulations are often managed as a single contiguous population despite the spatial structure underlying their local and regional dynamics. Disturbances from human activities can also be spatially structured with mortality impacts concentrated to just a few local populations among the aggregate. Scale transitions between local and regional processes can generate emergent properties whereby the whole system can fail to recover as quickly as expected for an equivalent single population. Here, we draw on theory and empirical case studies to ask: what is the consequence of spatially structured ecological and disturbance processes on metapopulation recoveries? We suggest that exploring this question could help address knowledge gaps for managing metapopulations including: Why do some metapopulations recover quickly while others remain collapsed? And, what risks are unaccounted for when metapopulations are managed at aggregate scales? First, we used model simulations to examine how scale transitions among ecological and disturbance conditions interact to generate emergent metapopulation recovery outcomes. In general, we found that the spatial structure of disturbance was a strong determinant of recovery outcomes. Specifically, disturbances that unevenly impacted local populations consistently generated the slowest recoveries and highest conservation risks. Ecological conditions that dampened metapopulation recoveries included low dispersal, variable local demography, sparsely connected habitat networks, and spatially and temporally correlated stochastic processes. Second, we illustrate the unexpected challenges of managing metapopulations by examining the recoveries of three USA federally listed endangered species: Florida Everglade snail kites, California and Alaska sea otters, and Snake River Chinook salmon. Overall, our results show the pivotal role of spatial structure in metapopulation recoveries whereby the interplay between local and regional processes shapes the resilience of the whole system. With this understanding, we provide guidelines for resource managers tasked with conserving and managing metapopulations and identify opportunities for research to support the application of metapopulation theory to real-world challenges.

Physician-level determinants of HCV screening during pregnancy in a U.S. sample.

PURPOSE: The purpose of this study was to assess the association between select determinants and HCV screening guideline adherence among physicians who provide prenatal care. RESEARCH QUESTION: What factors may act as determinants of guideline adherence to HCV screening among physicians who provide prenatal care? METHODS: We surveyed a national sample of physicians who provided prenatal care in 2021. The survey included questions from the Clinician Guideline Determinant (CGD) questionnaire, demographic characteristics, and medical practice characteristics. We estimated odds ratios and 95% confidence intervals (CIs) using semi-Bayesian logistic regression for the association between determinants and guideline adherence. RESULTS: Participants included 224 physicians in the United States who reported providing prenatal care. Most physicians practiced in private practice (65%) and the majority were members of the American College of Obstetricians and Gynecologists (ACOG; 91%). Less than half (43%; 95% CI: 36%-49%) of physicians reported regular use of the HCV screening guideline. Physicians who reported general knowledge about HCV (OR = 9.0, 95% CI 3.1-30) or endorsed agreement with ease of implementation (OR = 8.0, 95% CI 2.7-25) had higher odds of adherence to the HCV screening guideline. CONCLUSION: Our study suggests that less than half of practicing prenatal care physicians adhere to HCV screening guidelines for pregnant patients. Our results may be useful as a preliminary screening of select determinants of guideline use for further investigation.

Health Literacy Correlates to HPV Vaccination Among US Adults Ages 27-45.

Human papillomavirus (HPV) vaccination is now available for adults aged 27-45 as a shared clinical decision. Health literacy skills (i.e., accessing, understanding, appraising, applying information) may facilitate vaccine decision-making for adults with a provider recommendation. This study assessed associations between health literacy skills and willingness to get a provider-recommended HPV vaccine among newly eligible US adults. In 2020, US participants (51% women), aged 27-45 years, were surveyed online (n = 691). The outcome was willingness (willing/not willing) to get the HPV vaccine with provider recommendation. Measures were adapted from Sørensen's multidimensional European Health Literacy Scale, which assesses health literacy among four domains (i.e., access, understanding, appraisal, application). Adjusted odds ratios were calculated for the outcome and each health literacy domain, adjusting for personal health determinants (e.g., age, sex). The sample consisted of primarily non-Hispanic (91.2%), White (74.4%), and married (60.7%) adults. Approximately 65% of participants were willing to get a provider-recommended HPV vaccine. Higher willingness to vaccinate with provider recommendation was significantly associated with increased HPV knowledge (understanding; aOR = 1.13, 95% CI 1.04, 1.24), ability to understand HPV information (understanding; aOR = 1.96, 95% CI 1.09, 3.52), increased perceived vulnerability to HPV-related cancer (appraising; aOR = 3.22, 95% CI 1.83, 5.69), and the need for more information on vaccine safety to seek vaccination (applying; aOR = 3.25; 95% CI 2.05, 5.16). Utilizing a multidimensional health literacy framework to evaluate facilitators to HPV vaccination uptake among adults aged 27-45 can help guide future interventions by targeting accurate, easy-to-understand HPV information that connects vaccination efficacy to reduction in HPV cancer risk.

Differential contributions of cardiac, coronary and pulmonary artery vagal mechanoreceptors to reflex control of the circulation.

Distinct populations of stretch-sensitive mechanoreceptors attached to myelinated vagal afferents are found in the heart and adjoining coronary and pulmonary circulations. Receptors at atrio-venous junctions appear to be involved in control of intravascular volume. These atrial receptors influence sympathetic control of the heart and kidney, but contribute little to reflex control of systemic vascular resistance. Baroreceptors at the origins of the coronary circulation elicit reflex vasodilatation, like feedback control from systemic arterial baroreceptors, as well as having characteristics that could contribute to regulation of mean pressure. In contrast, feedback from baroreceptors in the pulmonary artery and bifurcation is excitatory and elicits a pressor response. Elevation of pulmonary arterial pressure resets the vasomotor limb of the systemic arterial baroreflex, which could be relevant for control of sympathetic vasoconstrictor outflow during exercise and other states associated with elevated pulmonary arterial pressure. Ventricular receptors, situated mainly in the inferior posterior wall of the left ventricle, and attached to unmyelinated vagal afferents, are relatively inactive under basal conditions. However, a change to the biochemical environment of cardiac tissue surrounding these receptors elicits a depressor response. Some ventricular receptors respond, modestly, to mechanical distortion. Probably, ventricular receptors contribute little to tonic feedback control; however, reflex bradycardia and hypotension in response to chemical activation may decrease the work of the heart during myocardial ischaemia. Overall, greater awareness of heterogeneous reflex effects originating from cardiac, coronary and pulmonary artery mechanoreceptors is required for a better understanding of integrated neural control of circulatory function and arterial blood pressure.

Time-series transcriptomics reveals a BBX32-directed control of acclimation to high light in mature Arabidopsis leaves.

The photosynthetic capacity of mature leaves increases after several days' exposure to constant or intermittent episodes of high light (HL) and is manifested primarily as changes in chloroplast physiology. How this chloroplast-level acclimation to HL is initiated and controlled is unknown. From expanded Arabidopsis leaves, we determined HL-dependent changes in transcript abundance of 3844 genes in a 0-6 h time-series transcriptomics experiment. It was hypothesized that among such genes were those that contribute to the initiation of HL acclimation. By focusing on differentially expressed transcription (co-)factor genes and applying dynamic statistical modelling to the temporal transcriptomics data, a regulatory network of 47 predominantly photoreceptor-regulated transcription (co-)factor genes was inferred. The most connected gene in this network was B-BOX DOMAIN CONTAINING PROTEIN32 (BBX32). Plants overexpressing BBX32 were strongly impaired in acclimation to HL and displayed perturbed expression of photosynthesis-associated genes under LL and after exposure to HL. These observations led to demonstrating that as well as regulation of chloroplast-level acclimation by BBX32, CRYPTOCHROME1, LONG HYPOCOTYL5, CONSTITUTIVELY PHOTOMORPHOGENIC1 and SUPPRESSOR OF PHYA-105 are important. In addition, the BBX32-centric gene regulatory network provides a view of the transcriptional control of acclimation in mature leaves distinct from other photoreceptor-regulated processes, such as seedling photomorphogenesis.