Daprodustat: A Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor for Anemia of Chronic Kidney Disease.

OBJECTIVE: The objective was to review the safety and efficacy of daprodustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) in the treatment of anemia of chronic kidney disease (CKD). DATA SOURCES: A literature search was conducted in MEDLINE, EMBASE, and ClinicalTrials.gov using the keywords "daprodustat," "GSK1278863," and "hypoxia-inducible factor-prolyl hydroxylase inhibitors" from January 2010 through November 2023. STUDY SELECTION AND DATA EXTRACTION: Literature was included if it evaluated pharmacology, pharmacokinetics, efficacy, and/or safety of daprodustat in human subjects and was reported in English. The manufacturer's product monograph was also utilized. DATA SYNTHESIS: Daprodustat significantly increased hemoglobin levels in CKD patients on dialysis (difference 0.18 g/dL) and not on dialysis (difference 0.08 g/dL) over 52-week treatment periods compared with erythropoiesis stimulating agents (ESA) in Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat (ASCEND)-D and ASCEND-ND, respectively. First occurrence of major adverse cardiovascular events (MACEs) was similar between daprodustat and ESAs in both trials. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Daprodustat can be used in patients with CKD on dialysis and already receiving an ESA for at least 6 weeks to further increase serum hemoglobin levels without increasing the risk of MACE. Adverse effects of daprodustat that may occur more than ESAs include headache, emesis, and thrombosis. CONCLUSIONS: Daprodustat is a novel oral, non-iron therapy for treatment of anemia of CKD. It was Food and Drug Administration approved in 2023 in patients already receiving dialysis for at least 4 months but not in non-dialysis patients. Long-term data for safety and additional benefits are pending.

Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells.

Despite the success of BCMA-targeting CAR-Ts in multiple myeloma, patients with high-risk cytogenetic features still relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell surface antigen in high risk myeloma tumors. We use a structure-guided design to define a CD27-based anti-CD70 CAR-T design that outperforms all tested scFv-based CARs, leading to >80-fold improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key transcription factors and transcriptional networks driving CD70 upregulation in high risk myeloma. Dual-targeting CAR-Ts against either CD70 or BCMA demonstrate a potential strategy to avoid antigen escape-mediated resistance. Together, these findings support the promise of targeting CD70 with optimized CAR-Ts in myeloma as well as future clinical translation of this approach.

Trauma-informed care in school-based health centers: A mixed methods study of behavioral health screening and services.

An explanatory, parallel mixed method design was used to examine trauma screening and behavioral health service rates in urban school-based health centers (SBHCs) and SBHC personnel's experiences providing culturally responsive, trauma-informed care. Logistic regressions were performed with electronic medical records from N = 4,794 patients ages 12-22 receiving care in a SBHC using trauma screening rates and service use as dependent variables. Quantitative analyses were supplemented with semistructured interviews with medical providers and behavioral health clinicians (N = 9) from eight SBHCs. The overall trauma screening rate across the SBHCs was 69.2%. Screening rates were higher for older and Spanish-speaking youth. The rate of behavioral health use was 32.9%, with higher rates among students screened for trauma at a prior medical visit, recent immigrant, and female youth. This suggests that trauma screening is feasible and facilitates access. Additionally, English-speaking youth were more likely to use behavioral health services than Spanish-speakers. Qualitative analyses suggested a strong sense of mission, collaboration, and beliefs that trauma screening facilitated access to care all facilitated trauma-focused screening. Barriers included staffing shortages and language translation challenges. Analysis also highlighted the importance of culturally responsive practices (e.g., interpreters, culture-specific assessment tools, knowledge of population needs). Mixed methods integrative analysis highlighted the ways in which barriers and facilitators aligned with the overall rates of access to screening and behavioral health care, and factors that helped the SBHCs tailor care to diverse youth. Limitations and implications for practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Evaluation of an individual examination remediation policy in a professional pharmacy course.

INTRODUCTION: Maintaining institutional remediation policies is required for pharmacy education accreditation, but specific policies and students' perceptions of remediation are not well described in the literature. The purpose of this research was to determine whether the individual examination remediation policy utilized in a biomedical literature evaluation course was a viable approach to ensuring positive student experiences and success. METHODS: This study utilized a pre-/post-quantitative survey design. An 11-item pre-remediation questionnaire was offered to all students enrolled in the course in 2022. A matched post-survey was administered to students eligible to remediate individual examinations. Survey items were assessed using a five-point Likert rating. Remediation examination grades were analyzed in aggregate. Descriptive statistics were utilized as appropriate. RESULTS: One hundred of the 108 (92.5%) enrolled students completed the pre-remediation survey. Students strongly agreed they would prefer to remediate individual examinations instead of taking one cumulative course remediation examination (median 5) and that remediating would improve their understanding of course material (median 5). Nineteen (44%) of 43 students eligible for individual examination remediation chose to remediate, and 16 (37%) responded to the post-remediation survey. Among those eligible, the most common reason for remediating was desire to receive a better score. Significantly more students improved their examination scores through remediation. CONCLUSIONS: Students in the course preferred to remediate individual examinations, but only 44% of students eligible to remediate chose to do so. Future studies with larger sample sizes and course outcome data are warranted to further explore examination remediation in professional pharmacy courses.

Unique Variant of Zieve Syndrome With a Normal Reticulocyte Count.

Zieve syndrome is a rare diagnosis seen in patients with chronic alcohol use which consists of a distinct clinical triad of hyperlipidemia, hemolytic anemia, and jaundice. Patients typically have an elevated reticulocyte count due to the hemolytic nature of the anemia. We present the case of a 44-year-old female who was discovered to have an unusual variant of Zieve syndrome with a normal reticulocyte count, which was believed to be due to suppression of bone marrow from excessive alcohol consumption. She was treated with steroids and complete alcohol cessation, with remarkable improvement on subsequent follow-up. An exhaustive literature review of 31 documented cases of Zieve syndrome was conducted to better understand the clinical presentation and overall prognosis of these patients. This case report and literature review aimed to improve patient outcomes through increased recognition of this underrecognized syndrome.

"It's going to help me in life": Forms, sources, and functions of social support for youth in natural mentoring relationships.

Social support is associated with positive physical and psychological health outcomes for youth. We took a qualitative approach to examine the sources, forms, and functions of social support youth receive from natural mentoring relationships in their lives. Based on in-depth interviews with 40 adolescents participating in a study of youth-adult relationships and natural mentoring processes, we found that (1) different types of adults had the capacity to provide different types of support and were likely to provide overlapping supports; (2) emotional, informational, and instrumental support qualitatively differed depending on the adult's role (e.g., teacher), while companionship and validation were consistent across adults; and (3) youth were able to identify benefits attached to the social support received from adults. Our findings contribute to a more nuanced understanding of aspects and characteristics of effective youth-adult mentoring processes and call for fuller assessments of social support in youths' lives so we may better meet their developmental needs.

A computational musculoskeletal arm model for assessing muscle dysfunction in chronic obstructive pulmonary disease.

Computational models have been used extensively to assess diseases and disabilities effects on musculoskeletal system dysfunction. In the current study, we developed a two degree-of-freedom subject-specific second-order task-specific arm model for characterizing upper-extremity function (UEF) to assess muscle dysfunction due to chronic obstructive pulmonary disease (COPD). Older adults (65 years or older) with and without COPD and healthy young control participants (18 to 30 years) were recruited. First, we evaluated the musculoskeletal arm model using electromyography (EMG) data. Second, we compared the computational musculoskeletal arm model parameters along with EMG-based time lag and kinematics parameters (such as elbow angular velocity) between participants. The developed model showed strong cross-correlation with EMG data for biceps (0.905, 0.915) and moderate cross-correlation for triceps (0.717, 0.672) within both fast and normal pace tasks among older adults with COPD. We also showed that parameters obtained from the musculoskeletal model were significantly different between COPD and healthy participants. On average, higher effect sizes were achieved for parameters obtained from the musculoskeletal model, especially for co-contraction measures (effect size = 1.650 ± 0.606, p < 0.001), which was the only parameter that showed significant differences between all pairwise comparisons across the three groups. These findings suggest that studying the muscle performance and co-contraction, may provide better information regarding neuromuscular deficiencies compared to kinematics data. The presented model has potential for assessing functional capacity and studying longitudinal outcomes in COPD.

Assessment of Truck-Mounted Area-Wide S-methoprene Applications to Manage West Nile Virus Vector Species in the Suburbs of Chicago, IL, USA.

West Nile virus remains the leading cause of arboviral neuroinvasive disease in the United States, despite extensive efforts to control the mosquito vectors involved in transmission. In this study, we evaluated the effectiveness of Altosid SR-20 (active ingredient, S-methoprene 20%) larvicide applications using truck-mounted ultra-low volume (ULV) dispersal equipment to target Culex pipiens Linnaeus (Diptera: Culicidae) and Cx. restuans (Theobald)larvae. A combination of emergence bioassays, open-field measurements of deposited S-methoprene and spray distribution using gas chromatography-mass spectrometry, and assessments of adult Culex spp. populations in response to applications were conducted over the summer of 2020 within the North Shore Mosquito Abatement District (IL, USA). Open-field applications revealed that dispersed Altosid SR-20 using ULV equipment was effective (75% emergence inhibition in susceptible lab strain Cx. pipiens larvae) up to 53 m. In suburban neighborhood applications, we found that S-methoprene deposition and larval emergence inhibition (EI) in front yards did not differ significantly from backyards. An overall EI of 46% and 28% were observed for laboratory strain Cx. pipiens and wild Cx. restuans larvae respectively, and both had an EI significantly higher than the untreated control group. The EI of exposed wild Cx. pipiens larvae did not differ from the untreated controls, suggesting an increased tolerance to S-methoprene. No difference in abundance of gravid or host-seeking adult Culex spp. post-application was detected between treated and untreated sites. These results document the ability of area-wide application to distribute S-methoprene, but this strategy will need further modifications and evaluation for Culex spp. management.

Factors Associated With Repeat Emergency Department Visits for Low Back Pain.

Background Low back pain represents 2-3% of Emergency Department (ED) visits. In this study, we aimed to identify patient and treatment-related variables that contributed to repeat visits to the ED for low back pain within a 12-month period. Methodology We conducted a retrospective review of adult patients presenting to the ED of one hospital over a two-year period with the primary diagnosis of low back pain. The primary outcome included return to the ED within 12 months with the same complaint, and the secondary outcome included return to the ED within 30 days or six months. Results A total of 793 patients met the inclusion criteria. The rate of return to the ED with the same complaint within 30 days, six months, and 12 months of the first visit was 7%, 11%, and 14%, respectively. Patients who received opioids at discharge were more likely to return within 12 months (68% vs. 55%; p = 0.0075) and six months (68% vs. 56%; p = 0.0184) compared to those who did not receive opioids at discharge. Undergoing an X-ray decreased the odds of a 30-day return visit by 70% (p = 0.0067), and by 59% within 12 months (p = 0.0032). Receiving opioids at discharge also doubled the odds of return within 12 months (odds ratio = 2.030, p = 0.0183), while receiving nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the odds by 60% (p = 0.0028). Conclusions Patients who received opioids at discharge were more likely to have a return visit for low back pain within six and 12 months. Patients who underwent X-rays at the index visit and were prescribed NSAIDs at discharge were less likely to return to the ED for low back pain.

Online racial discrimination and the role of white bystanders.

Black college students attending historically and predominantly White institutions are increasingly encountering online racial discrimination. This exposure may increase psychological distress and undermine academic performance. Although White bystanders may be well-positioned to challenge racist posts, limited research has examined interventions to increase White students' willingness to confront online racial discrimination. The present study used multiple methodologies to characterize the nature and frequency of online racial discrimination college students face, understand its impact on Black students, and increase challenges to online discrimination among White bystanders. Study data include content scraped from campus-related social media platforms over a 3-month period, transcripts from 8 focus groups conducted separately with Black (n = 35) and White (n = 33) college students, and data from an online experiment with 402 White college students. Taken together, study findings indicated that Black students encounter online racial discrimination with nontrivial frequency and are harmed by this exposure. Black students noted, however, that harm is mitigated when online racial discrimination is challenged by their White peers. Further, findings indicated that White students may be more likely to publicly confront racist posts if they (a) are aware of the harm it causes their Black peers; (b) perceive social norms that support confronting discrimination; and (c) receive guidance on what to say. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

From Apathy to Vigilance: Young Adolescents' Reactions to the Unite the Right Rally in Charlottesville.

The present study examined middle school students' responses to the 2017 Unite the Right rally in Charlottesville, Virginia. Using a consensual qualitative research approach, we analyzed interviews from 73 local, seventh-grade students (58% female; 55% students of color) to explore the range of students' emotional responses and cognitive engagement with the events. The resulting six profiles document heterogeneity in meaning-making and personal impacts across youth. Individual and social factors including race and ethnic identity varied across profiles. Many students of color expressed fear and vigilance toward racial violence while many White students expressed sadness and sympathy. We discuss the role of developmental factors in students' reactions as well as implications for supporting early adolescents in the wake of bias-motivated violence.

Targeting Obesity-Induced Macrophages during Preneoplastic Growth Promotes Mammary Epithelial Stem/Progenitor Activity, DNA Damage, and Tumor Formation.

Obesity enhances breast cancer risk in postmenopausal women and premenopausal women with genetic or familial risk factors. We have shown previously that within breast tissue, obesity increases macrophage-driven inflammation and promotes expansion of luminal epithelial cell populations that are hypothesized to be the cells of origin for the most common subtypes of breast cancer. However, it is not clear how these changes within the microenvironment of the breast alter cancer risk and tumor growth. Using a high-fat diet to induce obesity, we examined preneoplastic changes associated with epithelial cell-specific loss of Trp53. Obesity significantly enhanced the incidence of tumors of diverse histotypes and increased stromal cells within the tumor microenvironment. Obesity also promoted the growth of preneoplastic lesions containing elevated numbers of luminal epithelial progenitor cells, which were surrounded by macrophages. To understand how macrophage-driven inflammation due to obesity enhances tumor formation, mice were treated with IgG or anti-F4/80 antibodies to deplete macrophages during preneoplastic growth. Unexpectedly, depletion of macrophages in obese mice enhanced mammary epithelial cell stem/progenitor activity, elevated expression of estrogen receptor alpha, and increased DNA damage in cells. Together, these results suggest that in obesity, macrophages reduce epithelial cells with DNA damage, which may limit the progression of preneoplastic breast lesions, and uncovers complex macrophage function within the evolving tumor microenvironment. Understanding how obesity alters the function of macrophages during tumor formation may lead to chemoprevention options for at-risk obese women. SIGNIFICANCE: Understanding how obesity impacts early tumor growth and response to macrophage-targeted therapies may improve therapeutics for obese patients with breast cancer and identify patient populations that would benefit from macrophage-targeted therapies.

Biophysical model-based parameters to classify tumor recurrence from radiation-induced necrosis for brain metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is used for local control treatment of patients with intracranial metastases. As a result of SRS, some patients develop radiation-induced necrosis. Radiographically, radiation-induced necrosis can appear similar to tumor recurrence in magnetic resonance (MR) T1 -weighted contrast-enhanced imaging, T2 -weighted MR imaging, and Fluid-Attenuated Inversion Recovery (FLAIR) MR imaging. Radiographic ambiguities often necessitate invasive brain biopsies to determine lesion etiology or cause delayed subsequent therapy initiation. We use a biomechanically coupled tumor growth model to estimate patient-specific model parameters and model-derived measures to noninvasively classify etiology of enhancing lesions in this patient population. METHODS: In this initial, preliminary retrospective study, we evaluated five patients with tumor recurrence and five with radiation-induced necrosis. Longitudinal patient-specific MR imaging data were used in conjunction with the model to parameterize tumor cell proliferation rate and tumor cell diffusion coefficient, and Dice correlation coefficients were used to quantify degree of correlation between model-estimated mechanical stress fields and edema visualized from MR imaging. RESULTS: Results found four statistically relevant parameters which can differentiate tumor recurrence and radiation-induced necrosis. CONCLUSIONS: This preliminary investigation suggests potential of this framework to noninvasively determine the etiology of enhancing lesions in patients who previously underwent SRS for intracranial metastases.

"It's like all of his attention is on you": A mixed methods examination of attachment, supportive nonparental youth-adult relationships, and self-esteem during adolescence.

The purpose of this mixed methods study was to examine the relationship between attachment, supportive nonparental youth-adult relationships, and self-esteem during adolescence. First, in a quantitative path analysis, we found that perceived social support from nonparental adults partially mediated the relationship between adolescent attachment and self-esteem. In our follow-up mixed methods analysis, we analyzed youth reflections of support experienced in relationships with significant non-parental adults (VIPs). As compared to youth with positive attachment models, youth with negative attachment models reported fewer instances of emotional support but more instances of validation support. The youth with negative attachment models described (1) the importance of trust and (2) receiving emotional support specific to their needs. In instances of validation support, these youth described how their VIPs (1) provided them with honest and realistic feedback, (2) challenged their negative thinking and (3) created opportunities for them to recognize and showcase their strengths. Our findings underscore the importance of considering youths' individual attributes in the context of their ongoing relationships in order to gain a more nuanced understanding of the role and dynamics of supportive nonparental youth-adult relationships in youths' lives.

Understanding mutuality: Unpacking relational processes in youth mentoring relationships.

Evidence suggests that a close interpersonal bond is important for the success of youth-adult mentoring relationships. Mutuality has been suggested to be important for developing a close interpersonal bond (Rhodes, 2002, 2005), but mutuality remains an abstract construct, difficult to understand and cultivate. Using thematic analysis of mentor and mentee (n = 42) interviews, we investigate how mentoring pairs reflect on mutuality. Results suggest that mutuality is understood as a combination of 2 dimensions: shared relational excitement and experiential empathy. Shared relational excitement is felt when there is a genuine desire by both the mentor and the mentee to invest in the relationship. Experiential empathy is the process through which mentors connect with, advise, and normalize the experiences of their mentees by sharing their own relevant experiences. This work has implications for mentor training, program development, and future research on youth-adult relationships.

An Operational Evaluation of 3 Methoprene Larvicide Formulations for Use Against Mosquitoes in Catch Basins.

Effectiveness in controlling mosquitoes in storm water catch basins in the North Shore Mosquito Abatement District (northeastern Cook County, Illinois) was determined for 3 formulations of methoprene-based larvicides (Altosid XR 150-day Briquets, Altosid 30-day Pellets, Altosid 30-day Granules) in 2017 using a pass/fail evaluation criterion, in which emergence of a single adult from pupae collected from the basin constituted a control failure. Over the course of the 16-week study, basins receiving the 150-day briquets were treated once and basins receiving the pellet and granular formulations were treated every 4 weeks, with the first treatment occurring during the last week of May. Untreated basins were also observed for comparison with the treated basins. Over the course of the study, adult mosquitoes emerged from pupae collected in 94.2% of the untreated basins that contained pupae. All of the formulations evaluated in the study demonstrated some degree of control compared with the untreated basins, with pupae successfully emerging as adults in 64.6%, 55.5%, and 21.8% of samples from 150-day briquet, 30-day tablet, and 30-day pellet-treated basins that contained pupae, respectively. Pellets reapplied every 28 days provided significantly more effective control than the other formulations. The simple pass/fail criterion for evaluating control effectiveness proved to be a useful procedure for comparing effectiveness to untreated basins and among treatments.

Standardized Operational Evaluations of Catch Basin Larvicides from Seven Mosquito Control Programs in the Midwestern United States During 2017.

During June to September 2017, 7 mosquito control programs in the midwestern United States evaluated a total of 9 catch basin larvicide formulations using similar protocols. Treated basins were monitored among study sites to observe when larvicides failed to control mosquitoes in 25% or more basins within a site. Overall, when monitoring occurred within the maximum label duration of the larvicides, sites treated with a single larvicide tablet or briquet surpassed the 25% fail threshold more often than pellet and granular larvicide formulations. In 438 of the study basins, the depth from sump bottom to catch basin lid was measured. In basins that were deeper than 5 ft (1.5 m), larvicides failed to control mosquitoes significantly more often than those 5 ft or shallower.

Visual Behavior Differences in Drivers Across the Lifespan: A Digital Billboard Simulator Study.

Driver distraction is implicated in a significant portion of motor vehicle collisions; evidence has suggested that billboards can contribute to such distraction, but many knowledge gaps remain. The purpose of this study was to evaluate the effects of various types of billboards (static, 250-foot digital transition, 500-foot digital transition, and a control [no billboard] condition) and age group (teen, middle, and older) on visual behavior through the use of a driving simulator. To address gaps in the existing literature, the effects of age group and billboard type on the following visual attention variables were considered: percent of time participants looked at billboards, average glance length, number of glances, and glance pattern activity. Significant main effects of age group were found, suggesting that teen drivers exhibited significantly different visual behavior as compared to drivers in the other age groups. An Age Group x Billboard Type interaction for one outcome provided some evidence that percent of time spent looking at billboards significantly increased as billboard transition time increased for drivers, except for older adults, who spent more time looking at static billboards. This study helps lay the groundwork for future studies that may consider how young drivers' differential scanning patterns impact driving safety.

Distracted Driving in Teens With and Without Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: This study is among the first to examine the effect of talking on a cell phone or text messaging while driving in teens with and without attention deficit/hyperactivity disorder (ADHD). METHOD: Teens (average age 17years) with a diagnosis of ADHD (N=16) were matched with typically developing controls (N=18). All participants operated a driving simulator while (1) conversing on a cell phone, (2) text messaging, and (3) with no distraction during a baseline condition. Six indicators of driving performance were recorded: (a) time to complete the drive; (b) lane deviations; (c) variability in lane position (i.e., root mean square [RMS]); (d) reaction time; (e) motor vehicle collisions; and, (f) speed fluctuation. RESULTS: Significantly greater variation in lane position occurred in the texting task compared to no task and the cell phone task. While texting, in particular, teens with ADHD took significantly less time to complete the scenario. No significant main effects of group were found. CONCLUSIONS: Generally, those with ADHD did not differ in regard to driving performance, when compared to controls, with the exception of one outcome: time to complete scenario. These findings suggest that distracted driving impairs driving performance of teen drivers, regardless of ADHD status. Texting while driving had the greatest negative impact on driving performance, particularly with regard to variability in lane position (i.e., RMS). This study sheds light on key issues regarding injury prevention, with the intent of providing pediatric care providers with the knowledge to inform teen drivers of risks associated with distracted driving which will ultimately result in reduced rates of motor vehicle crashes and concomitant injuries.

Does skipping a meal matter to a butterfly's appearance? Effects of larval food stress on wing morphology and color in monarch butterflies.

In animals with complex life cycles, all resources needed to form adult tissues are procured at the larval stage. For butterflies, the proper development of wings involves synthesizing tissue during metamorphosis based on the raw materials obtained by larvae. Similarly, manufacture of pigment for wing scales also requires resources acquired by larvae. We conducted an experiment to test the effects of food deprivation in the larval stage on multiple measures of adult wing morphology and coloration of monarch butterflies (Danaus plexippus), a species in which long-distance migration makes flight efficiency critical. In a captive setting, we restricted food (milkweed) from late-stage larvae for either 24 hrs or 48 hrs, then after metamorphosis we used image analysis methods to measure forewing surface area and elongation (length/width), which are both important for migration. We also measured the brightness of orange pigment and the intensity of black on the wing. There were correlations between several wing features, including an unexpected association between wing elongation and melanism, which will require further study to fully understand. The clearest effect of food restriction was a reduction in adult wing size in the high stress group (by approximately 2%). Patterns observed for other wing traits were ambiguous: monarchs in the low stress group (but not the high) had less elongated and paler orange pigmentation. There was no effect on wing melanism. Although some patterns obtained in this study were unclear, our results concerning wing size have direct bearing on the monarch migration. We show that if milkweed is limited for monarch larvae, their wings become stunted, which could ultimately result in lower migration success.