Exploring Healthcare Provider Recruitment in a Rural and Frontier Community in Northern Idaho.

Limited U.S. research has been conducted examining factors affecting healthcare provider recruitment in rural settings, necessitating community-level investigations due to community differences. The aim of this study was to explore the factors involved in healthcare provider recruitment in a rural community in Northern Idaho. A retooled version of the Nursing Community Apgar Questionnaire (NCAQ) was used to collect data from 50 healthcare providers to assess items influencing provider recruitment. Items were categorized into five factors: geographic, economic, scope of practice, medical support, and facility and community support classes. Healthcare providers ranked items based on perceived importance and how advantageous or challenging it was to recruitment. A "Community Apgar" score is a composite score calculated using the advantage/challenge and importance scores. In our sample, medical support was rated as the most important class. Additionally, facility and community support was rated as the highest advantage class and had the most impactful Apgar scores, meaning it contained the most important advantage and challenge. Our findings suggest that these classes contain dominant factors related to the recruitment of providers in rural areas. Rural healthcare organizations seeking to improve the recruitment of healthcare providers should consider the potential impact of these factors on their population. Further investigations should be conducted on diverse rural samples across the U.S. to enable comparisons of research findings.

Chronic Thromboembolic Pulmonary Hypertension: Clinical and Imaging Evaluation.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and is an important cause of pulmonary hypertension. As a clinical entity, it is frequently underdiagnosed with prolonged diagnostic delays. This study reviews the clinical and radiographic findings associated with CTEPH to improve awareness and recognition. Strengths and limitations of multiple imaging modalities are reviewed. Accompanying images are provided to supplement the text and provide examples of important findings for the reader.

Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms.

A central challenge in developing personalized cancer cell immunotherapy is the identification of tumor-reactive T cell receptors (TCRs). By exploiting the distinct transcriptomic profile of tumor-reactive T cells relative to bystander cells, we build and benchmark TRTpred, an antigen-agnostic in silico predictor of tumor-reactive TCRs. We integrate TRTpred with an avidity predictor to derive a combinatorial algorithm of clinically relevant TCRs for personalized T cell therapy and benchmark it in patient-derived xenografts.

Accuracy of Toric Intraocular Lens Formulas With Measured Posterior Corneal Astigmatism of Different Orientations.

PURPOSE: To assess whether the use of measured posterior corneal astigmatism (PCA) values improves the prediction accuracy of toric intraocular lens power formulas, compared to predicted PCA values, when the orientation of the steep axis of PCA is non-vertical. DESIGN: Retrospective observational cohort study. METHODS: Four hundred eighteen eyes of 344 patients were included in the study. Prediction errors (PE) for postoperative refractive astigmatism at 4 weeks postoperatively were determined using vector analysis and compared for the following toric intraocular lens power formulas: Barrett Toric with predicted posterior corneal astigmatism (PPCA); Barrett Toric with measured posterior corneal astigmatism (MPCA); EVO Toric PPCA; EVO Toric MPCA; Holladay I with Abulafia-Koch regression. Subgroup analysis compared PEs for eyes with a vertically orientated steep axis of PCA (60-120°) to eyes with a non-vertically orientated steep axis of PCA. SETTING: Cathedral Eye Clinic, Belfast, United Kingdom and Tan Tock Seng Hospital, Singapore. RESULTS: Standard keratometry was with-the-rule in 48% of eyes, while the steep PCA axis was vertically orientated in 91% of eyes. For all eyes, EVO-PPCA had a smaller mean absolute error than Barrett-MPCA, Barrett-PPCA, and Abulafia-Koch (P < .01 for all). EVO-PPCA had the highest percentage of eyes within 0.50D of predicted postoperative astigmatism for eyes with vertical PCA (61%), while EVO-MPCA had the highest percentage for eyes with non-vertical PCA (54%). EVO-MPCA had the smallest centroid error for all eyes, and the subgroups (P < .01 for all). Eyes with non-vertical PCA had a lower percentage within 0.50D than eyes with vertical PCA when using PPCA (43% vs 61%, P = .034), but there was no significant difference between these groups when MPCA is used for eyes with non-vertical PCA (54% vs 61%, P = .40). CONCLUSIONS: When the steep axis of posterior corneal astigmatism is not vertically orientated, the use of measured posterior keratometry values improves prediction accuracy.

Enantioselective de novo synthesis of 14-hydroxy-6-oxomorphinans.

The enantioselective de novo synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using this route and their biological activities against the opioid receptors were measured.

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 remains unknown. Thus, we tested the hypotheses that increases in muscle sympathetic nerve activity (MSNA) would be greater during upright compared to supine rhythmic handgrip (RHG) exercise, and that females would demonstrate smaller increases in MSNA during upright RHG exercise than males. Twenty young (30 [6] years; mean [SD]) individuals (9 males, 11 females) underwent 6-minutes 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 to 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 to females, that coincided with greater reductions in sympathetic baroreflex gain (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.

Physiological condition infers habitat choice in juvenile sockeye salmon.

The amount of time that juvenile salmon remain in an estuary varies among and within populations, with some individuals passing through their estuary in hours while others remain in the estuary for several months. Underlying differences in individual physiological condition, such as body size, stored energy and osmoregulatory function, could drive individual variation in the selection of estuary habitat. Here we investigated the role of variation in physiological condition on the selection of estuarine and ocean habitat by sockeye salmon (Oncorhynchus nerka) smolts intercepted at the initiation of their 650-km downstream migration from Chilko Lake, Fraser River, British Columbia (BC). Behavioural salinity preference experiments were conducted on unfed smolts held in fresh water at three time intervals during their downstream migration period, representing the stage of migration at lake-exit, and the expected timing for estuary-entry and ocean-entry (0, 1 and 3 weeks after lake-exit, respectively). In general, salinity preference behaviour varied across the three time periods consistent with expected transition from river to estuary to ocean. Further, individual physiological condition did influence habitat choice. Smolt condition factor (K) and energy density were positively correlated with salinity preference behaviour in the estuary and ocean outmigration stages, but not at lake-exit. Our results suggest that smolt physiological condition upon reaching the estuary could influence migratory behaviour and habitat selection. This provides evidence on the temporally dependent interplay of physiology, behaviour and migration in wild juvenile Pacific salmon, with juvenile rearing conditions influencing smolt energetic status, which in turn influences habitat choice during downstream migration. The implication for the conservation of migratory species is that the relative importance of stopover habitats may vary as a function of initial condition.

CamTrapAsia: A dataset of tropical forest vertebrate communities from 239 camera trapping studies.

Information on tropical Asian vertebrates has traditionally been sparse, particularly when it comes to cryptic species inhabiting the dense forests of the region. Vertebrate populations are declining globally due to land-use change and hunting, the latter frequently referred as "defaunation." This is especially true in tropical Asia where there is extensive land-use change and high human densities. Robust monitoring requires that large volumes of vertebrate population data be made available for use by the scientific and applied communities. Camera traps have emerged as an effective, non-invasive, widespread, and common approach to surveying vertebrates in their natural habitats. However, camera-derived datasets remain scattered across a wide array of sources, including published scientific literature, gray literature, and unpublished works, making it challenging for researchers to harness the full potential of cameras for ecology, conservation, and management. In response, we collated and standardized observations from 239 camera trap studies conducted in tropical Asia. There were 278,260 independent records of 371 distinct species, comprising 232 mammals, 132 birds, and seven reptiles. The total trapping effort accumulated in this data paper consisted of 876,606 trap nights, distributed among Indonesia, Singapore, Malaysia, Bhutan, Thailand, Myanmar, Cambodia, Laos, Vietnam, Nepal, and far eastern India. The relatively standardized deployment methods in the region provide a consistent, reliable, and rich count data set relative to other large-scale pressence-only data sets, such as the Global Biodiversity Information Facility (GBIF) or citizen science repositories (e.g., iNaturalist), and is thus most similar to eBird. To facilitate the use of these data, we also provide mammalian species trait information and 13 environmental covariates calculated at three spatial scales around the camera survey centroids (within 10-, 20-, and 30-km buffers). We will update the dataset to include broader coverage of temperate Asia and add newer surveys and covariates as they become available. This dataset unlocks immense opportunities for single-species ecological or conservation studies as well as applied ecology, community ecology, and macroecology investigations. The data are fully available to the public for utilization and research. Please cite this data paper when utilizing the data.

Interoceptive signals from the heart and coronary circulation in health and disease.

This review considers interoceptive signalling from the heart and coronary circulation. Vagal and cardiac sympathetic afferent sensory nerve endings are distributed throughout the atria, ventricles (mainly left), and coronary artery. A small proportion of cardiac receptors attached to thick myelinated vagal afferents are tonically active during the cardiac cycle. Dependent upon location, these mechanoreceptors detect fluctuations in atrial volume and coronary arterial perfusion. Atrial volume and coronary arterial signals contribute to beat-to-beat feedback control and physiological homeostasis. Most cardiac receptors are attached to thinly myelinated or nonmyelinated C fibres, many of which are unresponsive to the cardiac cycle. Of these, there are many chemically sensitive cardiac receptors which are activated during myocardial stress by locally released endogenous substances. In contrast, some tonically inactive receptors become activated by irregular ventricular wall mechanics or by distortion of the ischaemic myocardium. Furthermore, some are excited both by chemical mediators of ischaemia and wall abnormalities. Reflex responses arising from cardiac receptors attached to thinly myelinated or nonmyelinated are complex. Impulses that project centrally through vagal afferents elicit sympathoinhibition and hypotension, whereas impulses travelling in cardiac sympathetic afferents and spinal pathways elicit sympathoexcitation and hypertension. Two opposing cardiac reflexes may provide a mechanism for fine-tuning a composite haemodynamic response during myocardial stress. Sympathetic afferents provide the primary pathway for transmission of cardiac nociception to the central nervous system. However, activation of sympathetic afferents may increase susceptibility to life-threatening arrhythmias. Notably, the cardiac sympathetic afferent reflex predominates in pathophysiological states including hypertension and heart failure.

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.

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.

Effects of human disturbances on wildlife behaviour and consequences for predator-prey overlap in Southeast Asia.

Some animal species shift their activity towards increased nocturnality in disturbed habitats to avoid predominantly diurnal humans. This may alter diel overlap among species, a precondition to most predation and competition interactions that structure food webs. Here, using camera trap data from 10 tropical forest landscapes, we find that hyperdiverse Southeast Asian wildlife communities shift their peak activity from early mornings in intact habitats towards dawn and dusk in disturbed habitats (increased crepuscularity). Our results indicate that anthropogenic disturbances drive opposing behavioural adaptations based on rarity, size and feeding guild, with more nocturnality among the 59 rarer specialists' species, more diurnality for medium-sized generalists, and less diurnality for larger hunted species. Species turnover also played a role in underpinning community- and guild-level responses, with disturbances associated with markedly more detections of diurnal generalists and their medium-sized diurnal predators. However, overlap among predator-prey or competitor guilds does not vary with disturbance, suggesting that net species interactions may be conserved.

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.

Comparison of non-pharmaceutical treatments for evaporative dry eye: a randomised controlled study protocol.

INTRODUCTION: The lipid layer of the tear film is critical to maintaining the integrity of the tear film and absence in the tear film lipid layer (TFLL) is one of the main causes of evaporative dry eye (EDE) in dry eye disease patients, resulting in excessive evaporation (so-called hyperevaporative dry eye). This study protocol will be designed to assess and compare the effects of intense pulsed light (IPL), heated eye mask (HEM), vectored thermal pulsation system (VTPS) and eyelid massage device (EMD) for improving signs and symptoms of EDE. METHODS AND ANALYSIS: Patients with EDE will be randomly divided into IPL, HEM, VTPS and EMD groups and will be followed up for 6 weeks. The primary outcome measure will be non-invasive tear breakup time (NITBUT). The secondary outcome measures will include, TFLL score, meibomian gland quality and expressibility change from baseline conjunctivocorneal staining with fluorescein and lissamine, tear meniscus height, conjunctival hyperaemia (redness score) and ocular surface disease index questionnaire. Additionally, adverse events will be monitored and documented. ETHICS AND DISSEMINATION: Ethics approval number: IRB(2023)K019.01. The findings will be shared regardless of the effect's direction. TRIAL REGISTRATION NUMBER: NCT05923528.

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.

Activation of endogenous glucocorticoids by HSD11B1 inhibits the antitumor immune response in renal cancer.

Although immune-based therapies have revolutionized the management of cancer, novel approaches are urgently needed to improve their outcome. We investigated the role of endogenous steroids in the resistance to cancer immunotherapy, as these have strong immunomodulatory functions. Using a publicly available database, we found that the intratumoral expression of 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1), which regenerates inactive glucocorticoids into active glucocorticoids, was associated with poor clinical outcome and correlated with immunosuppressive gene signatures in patients with renal cell carcinoma (RCC). HSD11B1 was mainly expressed in tumor-infiltrating immune myeloid cells as seen by immunohistochemistry in RCC patient samples. Using peripheral blood mononuclear cells from healthy donors or immune cells isolated from the tumor of RCC patients, we showed that the pharmacological inhibition of HSD11B1 improved the response to the immune checkpoint inhibitor anti-PD-1. In a subcutaneous mouse model of renal cancer, the combination of an HSD11B1 inhibitor with anti-PD-1 treatment increased the proportion of tumor-infiltrating dendritic cells. In an intrarenal mouse tumor model, HSD11B1 inhibition increased the survival of mice treated with anti-PD-1. In addition, inhibition of HSD11B1 sensitized renal tumors in mice to immunotherapy with resiquimod, a Toll-like receptor 7 agonist. Mechanistically, we demonstrated that HSD11B1 inhibition combined with resiquimod increased T cell-mediated cytotoxicity to tumor cells by stimulating the antigen-presenting capacity of dendritic cells. In conclusion, these results support the use of HSD11B1 inhibitors to improve the outcome of immunotherapy in renal cancer and highlight the role of the endogenous glucocorticoid metabolism in the efficacy of immunotherapy.

Thoracic Applications of Spectral CT Scan.

TOPIC IMPORTANCE: Thoracic imaging with CT scan has become an essential component in the evaluation of respiratory and thoracic diseases. Providers have historically used conventional single-energy CT; however, prevalence of dual-energy CT (DECT) is increasing, and as such, it is important for thoracic physicians to recognize the utility and limitations of this technology. REVIEW FINDINGS: The technical aspects of DECT are presented, and practical approaches to using DECT are provided. Imaging at multiple energy spectra allows for postprocessing of the data and the possibility of creating multiple distinct image reconstructions based on the clinical question being asked. The data regarding utility of DECT in pulmonary vascular disorders, ventilatory defects, and thoracic oncology are presented. A pictorial essay is provided to give examples of the strengths associated with DECT. SUMMARY: DECT has been most heavily studied in chronic thromboembolic pulmonary hypertension; however, it is increasingly being used across a wide spectrum of thoracic diseases. DECT combines morphologic and functional assessments in a single imaging acquisition, providing clinicians with a powerful diagnostic tool. Its role in the evaluation and treatment of thoracic diseases will likely continue to expand in the coming years as clinicians become more experienced with the technology.