Exploring experiences of people with knee osteoarthritis who received a physiotherapist-delivered dietary weight loss and exercise intervention: a mixed methods study.

OBJECTIVE: Explore the experiences of people with knee osteoarthritis who received a very low energy diet (VLED) and exercise program from a physiotherapist. METHODS: Mixed methods study involving questionnaires (n=42) and semi-structured interviews (n=22) with randomized control trial participants with knee osteoarthritis who had received a 6-month physiotherapist-delivered VLED weight loss and exercise intervention. Questionnaires measured participant satisfaction, and perceptions about physiotherapist's skills/knowledge in delivery of the dietary intervention (measured on 5-7 point Likert scales). Interviews explored participant's experiences and were analysed based on the principles of reflexive thematic analysis. RESULTS: Questionnaire response: 90%. Participants were satisfied with the program (95%), confident their physiotherapist had the required skills (84%) and knowledge (79%) to deliver the dietary intervention, felt comfortable talking to the physiotherapist about weight (74%), and would recommend others see a physiotherapist for the intervention they undertook (71%). Four themes were developed from the interviews: 1) one-stop-shop of exercise and diet; 2) physiotherapist-delivered weight loss works (unsure initially; successfully lost weight); 3) physiotherapists knowledge and skills (exercise is forte; most thought physiotherapists had the necessary weight loss skills/knowledge, but some disagreed); 4) physiotherapists have a role in weight loss (physiotherapists are intelligent, credible, and trustworthy; specific training in weight loss necessary). CONCLUSION: This study provides, to our knowledge, the first documented perspectives from people with osteoarthritis who have received a physiotherapist-delivered weight loss intervention. Findings suggest physiotherapists may have a role in delivering a protocolised dietary intervention for some people with knee osteoarthritis with overweight and obesity.

An educational approach to develop intercultural nursing care for refugees from Ukraine: A qualitative study.

AIM: To describe how nurses and nursing students in Poland and the United States perceive the practice of intercultural care of refugees from Ukraine. BACKGROUND: Millions of Ukrainian citizens sought safety in other countries when Russia invaded Ukraine in February 2022. INTRODUCTION: Nurses in Poland and the United States are positioned to provide nursing care for refugees from Ukraine yet lack intercultural knowledge, skills, and attitudes to meet refugee needs. METHODS: This education-focused qualitative description study was conducted in Spring 2023. Eighteen MSN and BSN students from one university in Poland and one university in the United States completed an international virtual exchange course that concentrated on the health and well-being of refugees from Ukraine. Students' reflection papers generated the data for this study. Content analysis was used to systematically structure the data, and themes were inductively derived for an initial understanding of intercultural care for refugees. The COREQ guidelines were followed for reporting study findings. RESULTS: Major themes were troubled communication, overlooked trauma-informed care, and compromised vaccine status. Language differences, a gap in nursing knowledge, and cultural variations impeded intercultural care. DISCUSSION: To address intercultural care for refugees from Ukraine, macro- and microlevel factors should be considered. Healthcare facilities need certified interpreters or adequate language-access technology for nurses. Nursing programs might evaluate content on trauma-informed care and cultural competency to meet the needs of war-affected refugees. Leaders from Ukrainian refugee communities could partner with nurses to deliver culturally relevant information to increase vaccine uptake. IMPLICATIONS: Nurses should advocate for inclusion of the WHO competency standards of care for refugees in healthcare policies with emphasis on communication and evidence-informed practice. Placing Ukrainian community leaders on health councils could bridge the gap between refugees and mainstream society.

Whole Genomes Reveal Evolutionary Relationships and Mechanisms Underlying Gene-Tree Discordance in Neodiprion Sawflies.

Rapidly evolving taxa are excellent models for understanding the mechanisms that give rise to biodiversity. However, developing an accurate historical framework for comparative analysis of such lineages remains a challenge due to ubiquitous incomplete lineage sorting and introgression. Here, we use a whole-genome alignment, multiple locus-sampling strategies, and summary-tree and SNP-based species-tree methods to infer a species tree for eastern North American Neodiprion species, a clade of pine-feeding sawflies (Order: Hymenopteran; Family: Diprionidae). We recovered a well-supported species tree that-except for three uncertain relationships-was robust to different strategies for analyzing whole-genome data. Nevertheless, underlying gene-tree discordance was high. To understand this genealogical variation, we used multiple linear regression to model site concordance factors estimated in 50-kb windows as a function of several genomic predictor variables. We found that site concordance factors tended to be higher in regions of the genome with more parsimony-informative sites, fewer singletons, less missing data, lower GC content, more genes, lower recombination rates, and lower D-statistics (less introgression). Together, these results suggest that incomplete lineage sorting, introgression, and genotyping error all shape the genomic landscape of gene-tree discordance in Neodiprion. More generally, our findings demonstrate how combining phylogenomic analysis with knowledge of local genomic features can reveal mechanisms that produce topological heterogeneity across genomes.

Associations between static foot posture, dynamic in-shoe plantar foot forces and knee pain in people with medial knee osteoarthritis: a cross-sectional exploratory study.

OBJECTIVE: To investigate relationships between static foot posture, dynamic plantar foot forces and knee pain in people with medial knee osteoarthritis (OA). DESIGN: Data from 164 participants with symptomatic, moderate to severe radiographic medial knee OA were analysed. Knee pain was self-reported using a numerical rating scale (NRS; scores 0-10; higher scores worse) and the Knee Injury and Osteoarthritis Outcome Score pain subscale (KOOS; scores 0-100; lower scores worse). Static foot posture was assessed using clinical tests (foot posture index, foot mobility magnitude, navicular drop). Dynamic plantar foot forces (lateral, medial, whole foot, medial-lateral ratio, arch index) were measured using an in-shoe plantar pressure system while walking. Relationships between foot posture and plantar forces (independent variables) and pain (dependent variables) were evaluated using linear regression models, unadjusted and adjusted for sex, walking speed, KL grade, shoe category, and body mass (for dynamic plantar foot forces). RESULTS: No measure of static foot posture was associated with any knee pain measure. Higher medial-lateral foot force ratio at midstance, and a higher arch index during overall stance, were weakly associated with higher knee pain on the NRS (regression coefficient=0.69, 95% confidence interval (CI) 0.09 to 1.28) and KOOS (coefficient=3.03, 95% CI 0.71 to 5.35) pain scales, respectively. CONCLUSION: Dynamic plantar foot forces, but not static foot posture, were associated with knee pain in people with medial knee OA. However, the amount of pain explained by increases in plantar foot force was small, thus these associations are unlikely to be clinically meaningful.

Hepatic OATP1B zonal distribution: Implications for rifampicin-mediated drug-drug interactions explored within a PBPK framework.

OATP1B facilitates the uptake of xenobiotics into hepatocytes and is a prominent target for drug-drug interactions (DDIs). Reduced systemic exposure of OATP1B substrates has been reported following multiple-dose rifampicin; one explanation for this observation is OATP1B induction. Non-uniform hepatic distribution of OATP1B may impact local rifampicin tissue concentrations and rifampicin-mediated protein induction, which may affect the accuracy of transporter- and/or metabolizing enzyme-mediated DDI predictions. We incorporated quantitative zonal OATP1B distribution data from immunofluorescence imaging into a PBPK modeling framework to explore rifampicin interactions with OATP1B and CYP substrates. PBPK models were developed for rifampicin, two OATP1B substrates, pravastatin and repaglinide (also metabolized by CYP2C8/CYP3A4), and the CYP3A probe, midazolam. Simulated hepatic uptake of pravastatin and repaglinide increased from the periportal to the pericentral region (approximately 2.1-fold), consistent with OATP1B distribution data. Simulated rifampicin unbound intracellular concentrations increased in the pericentral region (1.64-fold) compared to simulations with uniformly distributed OATP1B. The absolute average fold error of the rifampicin PBPK model for predicting substrate maximal concentration (Cmax) and area under the plasma concentration-time curve (AUC) ratios was 1.41 and 1.54, respectively (nine studies). In conclusion, hepatic OATP1B distribution has a considerable impact on simulated zonal substrate uptake clearance values and simulated intracellular perpetrator concentrations, which regulate transporter and metabolic DDIs. Additionally, accounting for rifampicin-mediated OATP1B induction in parallel with inhibition improved model predictions. This study provides novel insight into the effect of hepatic OATP1B distribution on site-specific DDI predictions and the impact of accounting for zonal transporter distributions within PBPK models.

Performance of a Wearable Ring in Controlled Hypoxia: A Prospective Observational Study.

BACKGROUND: Over recent years, technological advances in wearables have allowed for continuous home monitoring of heart rate and oxygen saturation. These devices have primarily been used for sports and general wellness and may not be suitable for medical decision-making, especially in saturations below 90% and in patients with dark skin color. Wearable clinical-grade saturation of peripheral oxygen (SpO2) monitoring can be of great value to patients with chronic diseases, enabling them and their clinicians to better manage their condition with reliable real-time and trend data. OBJECTIVE: This study aimed to determine the SpO2 accuracy of a wearable ring pulse oximeter compared with arterial oxygen saturation (SaO2) in a controlled hypoxia study based on the International Organization for Standardization (ISO) 80601-2-61:2019 standard over the range of 70%-100% SaO2 in volunteers with a broad range of skin color (Fitzpatrick I to VI) during nonmotion conditions. In parallel, accuracy was compared with a calibrated clinical-grade reference pulse oximeter (Masimo Radical-7). Acceptable medical device accuracy was defined as a maximum of 4% root mean square error (RMSE) per the ISO 80601-2-61 standard and a maximum of 3.5% RMSE per the US Food and Drug Administration guidance. METHODS: We performed a single-center, blinded hypoxia study of the test device in 11 healthy volunteers at the Hypoxia Research Laboratory, University of California at San Francisco, under the direction of Philip Bickler, MD, PhD, and John Feiner, MD. Each volunteer was connected to a breathing apparatus for the administration of a hypoxic gas mixture. To facilitate frequent blood gas sampling, a radial arterial cannula was placed on either wrist of each participant. One test device was placed on the index finger and another test device was placed on the fingertip. SaO2 analysis was performed using an ABL-90 multi-wavelength oximeter. RESULTS: For the 11 participants included in the analysis, there were 236, 258, and 313 SaO2-SpO2 data pairs for the test device placed on the finger, the test device placed on the fingertip, and the reference device, respectively. The RMSE of the test device for all participants was 2.1% for either finger or fingertip placement, while the Masimo Radical-7 reference pulse oximeter RMSE was 2.8%, exceeding the standard (4% or less) and the Food and Drug Administration guidance (3.5% or less). Accuracy of SaO2-SpO2 paired data from the 4 participants with dark skin in the study was separately analyzed for both test device placements and the reference device. The test and reference devices exceeded the minimum accuracy requirements for a medical device with RMSE at 1.8% (finger) and 1.6% (fingertip) and for the reference device at 2.9%. CONCLUSIONS: The wearable ring meets an acceptable standard of accuracy for clinical-grade SpO2 under nonmotion conditions without regard to skin color. TRIAL REGISTRATION: ClinicalTrials.gov NCT05920278; https://clinicaltrials.gov/study/NCT05920278.

Gelatin and Collagen from Sheepskin.

Abattoirs dispose of sheepskins as solid waste due to low price and poor demand for sheepskin leather. In principle, as an alternative to being disposed of in landfill, sheepskins can serve as a source of the protein collagen or the hydrolysis product, gelatin. In this research, sheepskins collected from abattoirs were used as a source of collagen. Three extraction methods were compared: acid extraction, acid with enzymes, and alkali extraction. The extracted material was characterized using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR), small angle X-ray scattering (SAXS), and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The collagen and gelatin extraction yield ranged from 3.1% to 4.8% with the product purity determined by hydroxyproline, ranging from 7.8% for the alkali process to 59% and 68% for the acid and acid-enzyme processes. SDS PAGE showed that the acid process produced fragments with molecular weights in the range 100 to >250 kDa, while acid-enzyme resulted in smaller fragments, below 30 kDa. The FTIR region of the amide I band at 1800-1550 cm-1, which was used as an indicator of the collagen and gelatin content, showed that the gelatin dominated in the acid extracts, and the alkaline extract contained a large portion of keratin. SAXS was found to be a sensitive method for showing the presence of intact collagen fibrils in materials from all of the extraction methods, albeit at low concentrations. Herein, sheepskin is shown to be a useful source for collagen-gelatin material of varying molecular weights.

Comparison of parent-reported motivators of non-vaccination for children 5-11 years old in Australia and Canada: Results of the iCARE study.

BACKGROUND: Despite COVID-19 infection being less severe in children compared to adults, vaccination for children from the age of 6 months onwards is recommended in many countries to reduce symptom severity and prevent severe disease. However, vaccination against COVID-19 for children remains controversial and uptake has been low. AIMS: To assess and compare the rate of change of parent-reported COVID-19 vaccine uptake in children aged 5 to 11 years and motivators of vaccine acceptance and non-vaccination among parents/guardians in Canada and Australia. METHODS: As part of the iCARE study, two cross-sectional representative samples in Canada and Australia were collected between May 20 and September 12, 2022 (i.e., 5 and 9 months after the COVID-19 vaccine rollout for children 5-11 years) using online panels. Parents/guardians reported the vaccine status of their children and motivators for vaccine acceptance and non-vaccination. General linear models were used to estimate differences between countries in terms of vaccine uptake and motivators across time. RESULTS: Parent-reported vaccine uptake for children 5-11 years didn't increase over the study period (T1 = 87 %,T2 = 86 %; OR = 0.83; 95 %CI = 0.45-1.54) and was overall lower in Canada (60.8 %) compared to Australia (71.6 %)(OR = 0.56; 95 %CI = 0.33-0.96). In both countries the socioeconomic characteristics of parents who didn't vaccinate their children were similar and having information on either the short- or long-term side effects of the vaccine were important motivators. However, vaccine effectiveness was more important in Canada and trust in the company that developed the vaccine and a recommendation from the child's doctor were more important motivators in Australia. CONCLUSION: Parent-reported vaccine uptake for children 5-11 years plateaued early in the vaccine rollout. The main motivators for parents of unvaccinated children varied between the two countries but information on vaccine safety and effectiveness were common to both countries. Findings may inform future tailored vaccine communication efforts and pandemic planning in Australia and Canada to optimize vaccine uptake for primary school children.

Combined Breast and Lung Cancer Screening Among Dual-Eligible Women: A Descriptive Study.

INTRODUCTION: Lung cancer is consistently the leading cause of cancer death among women in the United States, yet lung cancer screening (LCS) rates remain low. By contrast, screening mammography rates are reliably high, suggesting that screening mammography can be a "teachable moment" to increase LCS uptake among dual-eligible women. MATERIALS AND METHODS: This is a prospective survey study conducted at two academic institutions. Patients undergoing screening mammography were evaluated for LCS eligibility and offered enrollment in a pilot dual-cancer screening program. A series of surveys was administered to characterize participants' knowledge, perceptions, and attitudes about LCS before and after undergoing dual screening. Data were descriptively summarized. RESULTS: Between August 2022 and July 2023, 54 LCS-eligible patients were enrolled. The study cohort was 100% female and predominantly White (81%), with a median age of 57 y and median of 36 pack-y of smoking. Survey results showed that 98% felt they were at risk for lung cancer, with most (80%) motivated by early detection of potential cancer. Regarding screening barriers, 58% of patients lacked knowledge about LCS eligibility and 47% reported concerns about screening cost. Prior to undergoing LCS, 87% of patients expressed interest in combined breast and lung screening. Encouragingly, after LCS, 84% were likely or very likely to undergo dual screening again and 93% found the shared decision-making visit helpful or very helpful. CONCLUSIONS: Pairing breast and LCS is a feasible, acceptable intervention that, along with increasing patient and provider education about LCS, can increase LCS uptake and reduce lung cancer mortality.

Self-construal modulates default mode network connectivity in refugees with PTSD.

BACKGROUND: While self-construal and posttraumatic stress disorder (PTSD) are independently associated with altered self-referential processes and underlying default mode network (DMN) functioning, no study has examined how self-construal affects DMN connectivity in PTSD. METHODS: A final sample of 93 refugee participants (48 with DSM-5 PTSD or sub-syndromal PTSD and 45 matched trauma-exposed controls) completed a 5-minute resting state fMRI scan to enable the observation of connectivity in the DMN and other core networks. A self-construal index was calculated by substracting scores on the collectivistic and individualistic sub-scales of the Self Construal Scale. RESULTS: Independent components analysis identified 9 active networks-of-interest, and functional network connectivity was determined. A significant interaction effect between PTSD and self-construal index was observed in the anterior ventromedial DMN, with spatial maps localizing this to the left ventromedial prefrontal cortex (vmPFC), extending to the ventral anterior cingulate cortex. This effect revealed that connectivity in the vMPFC showed greater reductions in those with PTSD with higher levels of collectivistic self-construal. LIMITATIONS: This is an observational study and causality cannot be assumed. The specialized sample of refugees means that the findings may not generalize to other trauma-exposed populations. CONCLUSIONS: Such a finding indicates that self-construal may shape the core neural architecture of PTSD, given that functional disruptions to the vmPFC underpin the core mechanisms of extinction learning, emotion dysregulation and self-referential processing in PTSD. Results have important implications for understanding the universality of neural disturbances in PTSD, and suggest that self-construal could be an important consideration in the assessment and treatment of post-traumatic stress reactions.

A one health approach for monitoring antimicrobial resistance: developing a national freshwater pilot effort.

Antimicrobial resistance (AMR) is a world-wide public health threat that is projected to lead to 10 million annual deaths globally by 2050. The AMR public health issue has led to the development of action plans to combat AMR, including improved antimicrobial stewardship, development of new antimicrobials, and advanced monitoring. The National Antimicrobial Resistance Monitoring System (NARMS) led by the United States (U.S) Food and Drug Administration along with the U.S. Centers for Disease Control and U.S. Department of Agriculture has monitored antimicrobial resistant bacteria in retail meats, humans, and food animals since the mid 1990's. NARMS is currently exploring an integrated One Health monitoring model recognizing that human, animal, plant, and environmental systems are linked to public health. Since 2020, the U.S. Environmental Protection Agency has led an interagency NARMS environmental working group (EWG) to implement a surface water AMR monitoring program (SWAM) at watershed and national scales. The NARMS EWG divided the development of the environmental monitoring effort into five areas: (i) defining objectives and questions, (ii) designing study/sampling design, (iii) selecting AMR indicators, (iv) establishing analytical methods, and (v) developing data management/analytics/metadata plans. For each of these areas, the consensus among the scientific community and literature was reviewed and carefully considered prior to the development of this environmental monitoring program. The data produced from the SWAM effort will help develop robust surface water monitoring programs with the goal of assessing public health risks associated with AMR pathogens in surface water (e.g., recreational water exposures), provide a comprehensive picture of how resistant strains are related spatially and temporally within a watershed, and help assess how anthropogenic drivers and intervention strategies impact the transmission of AMR within human, animal, and environmental systems.

snpAIMeR: R package for evaluating ancestry informative marker contributions in non-model population diagnostics.

MOTIVATION: Single nucleotide polymorphism (SNP) markers are increasingly popular for population genomics and inferring ancestry for individuals of unknown origin. Because large SNP datasets are impractical for rapid and routine analysis, diagnostics rely on panels of highly informative markers. Strategies exist for selecting these markers, however, resources for efficiently evaluating their performance are limited for non-model systems. RESULTS: snpAIMeR is a user-friendly R package that evaluates the efficacy of genomic markers for the cluster assignment of unknown individuals. It is intended to help minimize panel size and genotyping effort by determining the informativeness of candidate diagnostic markers. Provided genotype data from individuals of known origin, it uses leave-one-out cross-validation to determine population assignment rates for individual markers and marker combinations. AVAILABILITY AND IMPLEMENTATION: snpAIMeR is available on CRAN (https://CRAN.R-project.org/package=snpAIMeR).

Somatic Factors Predict On-Road Driving Skills in Older Drivers and Drivers with Mild Cognitive Impairment.

BACKGROUND: On-road driving skills can be impaired in older drivers and drivers with mild cognitive impairment (MCI) due to different driving-relevant deficits. Among these deficits, somatic factors have received little attention so far. METHODS: In a prospective observational on-road driving study, we examined whether somatic factors can predict on-road driving skills in a mixed sample of healthy older drivers and drivers with MCI (n = 99) and whether the inclusion of age explains additional variance. Somatic factors included the number of prescribed drugs, visual acuity, peripheral visual field integrity, mobility of the cervical spine, and hearing impairment. A hierarchical regression analysis was used to predict on-road driving skills by adding the somatic factors in the first step and age in the second step. RESULTS: Results revealed that the combination of somatic factors significantly predicted on-road driving skills (R2adjusted = 0.439). The inclusion of age led to a significant increase of explained variance (R2adjusted = 0.466). CONCLUSIONS: Our results suggest that somatic factors can accurately predict on-road driving skills in healthy older drivers and drivers with MCI. In addition, our results suggest that there is a significant but rather small effect of age beyond somatic changes.

Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement.

The proliferation marker Ki67 has been attributed critical functions in maintaining mitotic chromosome morphology and heterochromatin organization during the cell cycle, indicating a potential role in developmental processes requiring rigid cell-cycle control. Here, we discovered that despite normal fecundity and organogenesis, germline deficiency in Ki67 resulted in substantial defects specifically in peripheral B and T lymphocytes. This was not due to impaired cell proliferation but rather to early lymphopoiesis at specific stages where antigen-receptor gene rearrangements occurred. We identified that Ki67 was required for normal global chromatin accessibility involving regulatory regions of genes critical for checkpoint stages in B cell lymphopoiesis. In line with this, mRNA expression of Rag1 was diminished and gene rearrangement was less efficient in the absence of Ki67. Transgenes encoding productively rearranged immunoglobulin heavy and light chains complemented Ki67 deficiency, completely rescuing early B cell development. Collectively, these results identify a unique contribution from Ki67 to somatic antigen-receptor gene rearrangement during lymphopoiesis.

ACR Appropriateness Criteria® Workup of Pleural Effusion or Pleural Disease.

Pleural effusions are categorized as transudative or exudative, with transudative effusions usually reflecting the sequala of a systemic etiology and exudative effusions usually resulting from a process localized to the pleura. Common causes of transudative pleural effusions include congestive heart failure, cirrhosis, and renal failure, whereas exudative effusions are typically due to infection, malignancy, or autoimmune disorders. This document summarizes appropriateness guidelines for imaging in four common clinical scenarios in patients with known or suspected pleural effusion or pleural disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

The role of neuroestrogens in the estrogen-induced gonadotropin surge in male monkeys.

Neuroestrogens locally synthesized in the brain are known to play a role in sexual behaviors. However, the question of whether neuroestrogens are involved in the regulation of the gonadotropin-releasing hormone (GnRH) release is just emerging. Because previous studies in this lab indicate that neuroestradiol is also important for the pulsatile release as well as the surge release of GnRH in female rhesus monkeys, in the present study, we examined whether neuroestradiol plays a role in the estrogen-induced LH surge in orchidectomized (ORX) male rhesus monkeys. Unlike in rodents, it is known that a high dose of estrogen treatment can result in the LH surge in ORX male rhesus monkeys. Results that the administration of the aromatase inhibitor, letrozole, failed to attenuate the estrogen-induced LH surge, suggest that unlike in ovariectomized females, neuroestrogens do not play a role in the LH surge experimentally induced by the exogenous estrogen treatment in ORX male monkeys.

Effects of PFAS on human liver transporters: implications for health outcomes.

Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in the production of various consumer and industrial goods. Research efforts continue to gauge the risk that historically used, and newly produced, PFAS may cause to human health. Numerous studies report toxic effects of PFAS on the human liver as well as increased serum cholesterol levels in adults. A major concern with PFAS, also dubbed "forever chemicals", is that they accumulate in liver and kidney and persist in serum. The mechanisms responsible for their disposition and excretion in humans are poorly understood. A better understanding of the interaction of PFAS with liver transporters, as it pertains to the disposition of PFAS and other xenobiotics, could provide mechanistic insight into human health effects and guide efforts toward risk assessment of compounds in development. This review summarizes the current state of the literature on the emerging relationships (e.g., substrates, inhibitors, modulators of gene expression) between PFAS and specific hepatic transporters. The adaptive and toxicological responses of hepatocytes to PFAS that reveal linkages to pathologies and epidemiological findings are highlighted. The evidence suggests that our understanding of the molecular landscape of PFAS must improve to determine their impact on the expression and function of hepatocyte transporters that play a key role in PFAS or other xenobiotic disposition. From here, we can assess what role these changes may have in documented human health outcomes.

Identification of the RSX interactome in a marsupial shows functional coherence with the Xist interactome during X inactivation.

The marsupial specific RSX lncRNA is the functional analogue of the eutherian specific XIST, which coordinates X chromosome inactivation. We characterized the RSX interactome in a marsupial representative (the opossum Monodelphis domestica), identifying 135 proteins, of which 54 had orthologues in the XIST interactome. Both interactomes were enriched for biological pathways related to RNA processing, regulation of translation, and epigenetic transcriptional silencing. This represents a remarkable example showcasing the functional coherence of independently evolved lncRNAs in distantly related mammalian lineages.

Race Adjustment of Pulmonary Function Tests in the Diagnosis and Management of COPD: A Scoping Review.

Aim: Increasing evidence suggests that the inclusion of self-identified race in clinical decision algorithms may perpetuate longstanding inequities. Until recently, most pulmonary function tests utilized separate reference equations that are race/ethnicity based. Purpose: We assess the magnitude and scope of the available literature on the negative impact of race-based pulmonary function prediction equations on relevant outcomes in African Americans with COPD. Methods: We performed a scoping review utilizing an English language search on PubMed/Medline, Embase, Scopus, and Web of Science in September 2022 and updated it in December 2023. We searched for publications regarding the effect of race-specific vs race-neutral, race-free, or race-reversed lung function testing algorithms on the diagnosis of COPD and COPD-related physiologic and functional measures. Joanna Briggs Institute (JBI) guidelines were utilized for this scoping review. Eligibility criteria: The search was restricted to adults with COPD. We excluded publications on other lung disorders, non-English language publications, or studies that did not include African Americans. The search identified publications. Ultimately, six peer-reviewed publications and four conference abstracts were selected for this review. Results: Removal of race from lung function prediction equations often had opposite effects in African Americans and Whites, specifically regarding the severity of lung function impairment. Symptoms and objective findings were better aligned when race-specific reference values were not used. Race-neutral prediction algorithms uniformly resulted in reclassifying severity in the African Americans studied. Conclusion: The limited literature does not support the use of race-based lung function prediction equations. However, this assertion does not provide guidance for every specific clinical situation. For African Americans with COPD, the use of race-based prediction equations appears to fall short in enhancing diagnostic accuracy, classifying severity of impairment, or predicting subsequent clinical events. We do not have information comparing race-neutral vs race-based algorithms on prediction of progression of COPD. We conclude that the elimination of race-based reference values potentially reduces underestimation of disease severity in African Americans with COPD.