Intrapulmonary administration of recombinant activated factor VII in pediatric, adolescent, and young adult oncology and hematopoietic cell transplant patients with pulmonary hemorrhage.

Introduction: Diffuse alveolar hemorrhage (DAH) is a devastating disease process with 50-100% mortality in oncology and hematopoietic cell transplant (HCT) recipients. High concentrations of tissue factors have been demonstrated in the alveolar wall in acute respiratory distress syndrome and DAH, along with elevated levels of tissue factor pathway inhibitors. Activated recombinant factor VII (rFVIIa) activates the tissue factor pathway, successfully overcoming the tissue factor pathway inhibitor (TFPI) inhibition of activation of Factor X. Intrapulmonary administration (IP) of rFVIIa in DAH is described in small case series with successful hemostasis and minimal complications. Methods: We completed a single center retrospective descriptive study of treatment with rFVIIa and outcomes in pediatric oncology and HCT patients with pulmonary hemorrhage at a quaternary hematology/oncology hospital between 2011 and 2019. We aimed to assess the safety and survival of patients with pulmonary hemorrhage who received of IP rFVIIa. Results: We identified 31 patients with pulmonary hemorrhage requiring ICU care. Thirteen patients received intrapulmonary rFVIIa, while eighteen patients did not. Overall, 13 of 31 patients (41.9%) survived ICU discharge. ICU survival (n=6) amongst those in the IP rFVIIa group was 46.2% compared to 38.9% (n=7) in those who did not receive IP therapy (p=0.69). Hospital survival was 46.2% in the IP group and 27.8% in the non-IP group (p=0.45). There were no adverse events noted from use of IP FVIIa. Conclusions: Intrapulmonary rFVIIa can be safely administered in pediatric oncology patients with pulmonary hemorrhage and should be considered a viable treatment option for these patients.

Object-based attention during scene perception elicits boundary contraction in memory.

Boundary contraction and extension are two types of scene transformations that occur in memory. In extension, viewers extrapolate information beyond the edges of the image, whereas in contraction, viewers forget information near the edges. Recent work suggests that image composition influences the direction and magnitude of boundary transformation. We hypothesize that selective attention at encoding is an important driver of boundary transformation effects, selective attention to specific objects at encoding leading to boundary contraction. In this study, one group of participants (N = 36) memorized 15 scenes while searching for targets, while a separate group (N = 36) just memorized the scenes. Both groups then drew the scenes from memory with as much object and spatial detail as they could remember. We asked online workers to provide ratings of boundary transformations in the drawings, as well as how many objects they contained and the precision of remembered object size and location. We found that search condition drawings showed significantly greater boundary contraction than drawings of the same scenes in the memorize condition. Search drawings were significantly more likely to contain target objects, and the likelihood to recall other objects in the scene decreased as a function of their distance from the target. These findings suggest that selective attention to a specific object due to a search task at encoding will lead to significant boundary contraction.

Leading beyond the Script: A Cross-Sectional Study Exploring Preparedness of Pharmacy Academic Administrators.

Limited research exists on the preparedness of pharmacy academic administrators for their roles. This cross-sectional survey aimed to explore the self-perceptions of pharmacy academic administrators, including deans, associate deans, assistant deans, department chairs, and directors, within United States-based Colleges or Schools of Pharmacy. Participants answered questions regarding their demographics, self-perceived readiness for administrative roles, self-perceived leadership skills, and strategies used to develop these skills. Data were analyzed using descriptive statistics, and subgroup comparisons were made using Student's t-test for normally distributed continuous variables, Mann-Whitney tests for ordinal variables or non-normally distributed continuous variables, and Chi-squared tests for nominal variables. A total of 193 responses were analyzed. Respondents reported feeling least prepared in two areas: entrepreneurial revenue and handling grievances and appeals. There were gender differences noted in preparedness to conduct performance reviews, manage unit finances, and develop entrepreneurial revenue, with men rating themselves significantly higher than women in all three areas. Despite high self-ratings of leadership skills in the overall cohort, significant gender differences were noted in micromanagement with men rating themselves lower than women. Seeking advice from senior colleagues was the most used development strategy, and women showed a significantly higher preference for programs facilitated by professional organizations. This study contributes valuable insights into the preparedness of pharmacy academic administrators to inform future strategies that better support individuals to be successful in their roles.

PROTOCOL FOR HUMAN EXPOSURE TO OPIOIDS AND CONCENTRATED MEDETOMIDINE USED IN FIELD APPLICATIONS.

Wildlife professionals routinely use potent sedatives and anesthetics when chemically immobilizing wildlife and zoo species in remote environments. Accidental exposure to these prescription veterinary drugs is rare but could be rapidly fatal. Commonly used agents include opioids and α2 adrenoreceptor agonists. These drugs can be reversed with specific antagonists; however, they are often not approved for human use. The protocol created here can be used by wildlife health professionals in a field setting with basic human emergency medical response training in coordination with local Emergency Medical Services (EMS). Key components include, building local relationships between EMS and wildlife professionals, focused EMS training, administering opioid and α2 adrenergic antagonists off label, and local evacuation procedures. This framework could allow wildlife management agencies or zoos to mitigate the risk of human exposures to these commonly used drugs, significantly improving occupational safety in an otherwise high-risk environment.

A Prospective, Randomized Controlled, Single-Blinded Study to Assess the Effect of a 33-Gauge Needle Versus a 34-Gauge Needle on Pain Experienced During Injection of Local Anesthetic on the Face.

BACKGROUND: Most pain experienced by patients during Mohs micrographic surgery is associated with the initial injection. Previous studies have shown that a smaller gauge needle (33-gauge vs 30-gauge) is associated with less patient-reported pain. OBJECTIVES: To evaluate patient-reported pain levels following injection with a 33-gauge versus a 34-gauge needle.  Methods: During this prospective, randomized, controlled, single-blinded study, 480 patients were randomized into a 33-gauge versus a 34-gauge needle group. Pain levels following needle insertion were recorded using the validated numerical rating scale (VNRS)-11 scale.  Results: Injection of local anesthetic with a 34-gauge needle is associated with significantly less pain compared to a 33-gauge needle across all subgroups (P=0.007, average pain level 0.49 [34-gauge group] vs 0.79 [33-gauge group] rated on a 0-10 pain scale). Females, first-time Mohs patients, patients under age 65, patients with basal cell carcinoma, and those with tumor locations on the nose experienced the most pain reduction with the use of a 34-gauge needle.  Limitations: This was a single-blinded study; thus, the injector was able to see which needle was being used. This knowledge could have subconsciously affected the angle, speed, or force used to insert the needle. CONCLUSIONS: Injections with a 33-gauge and a 34-gauge needle are both tolerated well and associated with minimal pain. While the pain reduction associated with using a 34-gauge needle is statistically significant, the use of a 34-gauge needle may be most clinically relevant for certain patient subgroups. J Drugs Dermatol. 2023;22(11): doi:10.36849/JDD.7689.

Impact of student-run clinic participation on empathy and interprofessional skills development in medical and pharmacy students.

Background: Students participating in student-run clinics (SRCs) have opportunities to develop and practice beneficial skill sets, including empathy and interprofessional collaboration. Objectives: This study aimed to assess whether participation in an underserved SRC impacts the development of empathy and interprofessional skills in pharmacy and medical students. Methods: This study assessed empathy and interprofessional skills development through a self-assessment survey. The survey included the Interpersonal Reactivity Index (IRI) to assess empathy, the Attitudes Towards Health Care Teams/Team Skills Scale (ATHCTS/TSS) to assess interprofessional team dynamics, and a free-text response section. Participants were grouped based on whether they participated in the SRC (intervention group) or did not participate in the SRC (control group). A subgroup analysis was performed based on the participants' discipline (medicine vs. pharmacy). To compare differences in IRI, ATHCTS, and TSS scores between study groups, independent samples t-tests were performed. A thematic analysis was used for qualitative data. Results: There were no statistically significant differences between intervention and control groups in IRI, ATHCTS, or TSS scores. Subgroup analyses showed no significant differences in scores of student pharmacists or medical students. For both disciplines, the thematic analysis revealed the most common positive themes identified were "real-world patient interaction and care," "impact on practice/career development." Alternatively, it revealed the highest reported negative themes identified as "time management and operational difficulties" and "concerns about the quality of/access to care". Conclusions: This study demonstrates that involvement in an SRC neither improves nor hinders a learner's development of empathy and interprofessional team skills. Qualitatively, students reported that participation in an SRC benefited their learning and helped develop their skills, like empathy and team dynamics, in an interprofessional setting. Future research with longitudinal monitoring or alternative assessment tools is recommended.

Association Between Sociodemographic Factors and Vision Difficulty in the National Health Interview Survey: A Population-Based Analysis.

PURPOSE: To investigate the relationship between social determinants of health with self-reported vision difficulty. DESIGN: Cross-sectional, population-based analysis. METHODS: The National Health Interview Survey (NHIS) is an annual survey based on the U.S. population ≥18 years of age. It provides self-reported data on demographic characteristics, socioeconomic factors, health status, and health care access. The 2021 NHIS database was used in this study. Adult participants of the NHIS who responded to the vision difficulty question "Do you have difficulty seeing, even when wearing glasses or contact lenses?" were included in this analysis. The outcome of interest was self-reported vision difficulty by participants. Analysis was done through univariable and multivariable logistic regression. RESULTS: Overall, there were 29,464 participants included in the analysis. Univariable logistic regression showed an increased odds of self-reported vision difficulty among female (odds ratio [OR] 1.28 [95% confidence interval {CI} 1.20-1.38]; P < .001), gay, lesbian, or bisexual participants (OR 1.24 [95% CI 1.04-1.49]; P = .02), those who possessed public compared with private insurance (OR 1.83 [95% CI 1.69-1.99]; P < .001), those with less than a high school education (OR 1.88 [95% CI 1.67-2.13]; P < .001), and those with an income below the poverty threshold (OR 2.22 [95% CI 1.96-2.51]; P < .001). Multivariable analysis revealed an increased risk of vision difficulty reported amongst non-Hispanic Black participants (OR 1.65 [95% CI 1.21-2.25]; P = .002). CONCLUSIONS: A multitude of sociodemographic factors are associated with self-reported vision difficulty in the U.S. POPULATION: Our findings emphasize the importance of considering factors of social determinants of health in clinical practice and policymaking for patients with vision loss.

Exploring the Relationship Between Imposter Phenomenon and Myers-Briggs Personality Types in Pharmacy Education.

OBJECTIVE: To investigate the relationship between imposter phenomenon (IP) and Myers-Briggs Type Indicator (MBTI) personality types in pharmacy students. METHODS: This was a retrospective, observational study of doctor of pharmacy students who had previously completed MBTI and Clance Imposter Phenomenon Scale (CIPS) assessments. CIPS scores and categories were compared between the 4 MBTI personality type dichotomies using independent samples t tests and chi-square. RESULTS: Mean CIPS score for included pharmacy students (N = 668) was 62.52 (SD 14.82). Clance Imposter Phenomenon Scale scores were significantly higher in students with MBTI of introversion (mean 64.14, SD 14.27), intuition (mean 63.80, SD 15.78), and perceiving (mean 64.38, SD 15.55) as compared to their dichotomous counterparts. No significant difference in mean CIPS scores was found within the thinking/feeling dichotomy. When analyzing IP risk associated with the various MBTI personality dichotomies, introverts were at a 1.8 times greater risk of high/severe IP than extroverts. Additionally, students with perceiving personality types were at a 1.4 times greater risk of high/severe IP than those with judging personality types. CONCLUSION: Our study suggests that pharmacy students with introversion, intuitive, and perceptive personality types exhibit higher CIPS scores, and those with introversion or perceptive personality types are at risk for high/severe IP. Given the common MBTI types and a high degree of IP in pharmacy students, our findings underlie the need for open, targeted discussions about IP and proactively incorporating strategies and resources within a curriculum to support students in normalizing and easing anxiety.

Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort : Rapid kidney function decline and heart failure in T2D.

BACKGROUND: Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors. METHODS: Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7-3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI). RESULTS: Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51-4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63-5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001). CONCLUSIONS: In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.

Operative expectations for Mohs surgery in patients with chronic lymphocytic leukemia: A multicenter retrospective cohort study.

Background: Patients with chronic lymphocytic leukemia (CLL) are immunocompromised and have both a higher incidence of and more aggressive skin cancers, often requiring treatment with Mohs micrographic surgery. Objective: Characterize operative expectations for Mohs surgery in patients with CLL. Methods: Multicenter retrospective cohort study. Results: One hundred fifty-nine tumors from 99 patients with CLL were matched 1:4 with controls. Cases had higher odds for requiring at least 3 stages during Mohs surgery compared to controls (odds ratio = 1.91; 95% CI [1.21-3.02]; P = .01). The mean number of Mohs stages in cases was 1.97 (±0.92) compared with 1.67 (±0.87) in controls (P = .0001). A regression analysis showed that cases had larger postoperative tumor areas (cm2) versus controls (mean = 5.57 vs 4.47; estimate difference Δß = 1.10 cm2; 95% CI [0.18-2.03]; P = .02). In logistic regression, cases were twice as likely to receive a flap repair compared to controls (odds ratio = 2.45; 95% CI [1.58-3.8]). Limitations: Retrospective cohort study and lack of histologic subtyping of tumors. Conclusion: Patients with CLL require more Mohs stages to attain clear surgical margins, have larger postoperative defect areas, and require more advanced repair techniques compared to a control population without CLL. These findings are essential for preoperative planning and patient counseling and further support the use of Mohs surgery in patients with CLL.

Confirmation, Disconfirmation, and Communal Coping for Joint Physical Activity in Romantic Dyads.

Most people in the United States do not engage in sufficient physical activity (PA). However, certain communication behaviors from romantic partners can motivate PA. Research indicates that confirming communication and communal coping (CC) in romantic relationships can increase PA efforts, but less research has examined the role of explicitly disconfirming communication or relationships between confirmation, disconfirmation, and CC on PA outcomes. We examined models in which shared PA appraisals mediate relationships between (a) confirmation and (b) disconfirmation and joint PA behavior in heterosexual, romantic dyads. Sex differences in actor and partner effects were also considered. Partners (N = 144) in 72 dyads completed assessments of key constructs. Results indicated that shared PA appraisals were critical in the confirmation model, mediating relationships between perceptions of confirmation and reports of joint PA. Unexpectedly, both partners' reports of partner disconfirmation were positively associated with their partners' reports of joint PA. Only one statistically significant sex difference emerged. Theoretical and pragmatic implications are discussed.

Objects are selected for attention based upon meaning during passive scene viewing.

While object meaning has been demonstrated to guide attention during active scene viewing and object salience guides attention during passive viewing, it is unknown whether object meaning predicts attention in passive viewing tasks and whether attention during passive viewing is more strongly related to meaning or salience. To answer this question, we used a mixed modeling approach where we computed the average meaning and physical salience of objects in scenes while statistically controlling for the roles of object size and eccentricity. Using eye-movement data from aesthetic judgment and memorization tasks, we then tested whether fixations are more likely to land on high-meaning objects than low-meaning objects while controlling for object salience, size, and eccentricity. The results demonstrated that fixations are more likely to be directed to high meaning objects than low meaning objects regardless of these other factors. Further analyses revealed that fixation durations were positively associated with object meaning irrespective of the other object properties. Overall, these findings provide the first evidence that objects are, in part, selected by meaning for attentional selection during passive scene viewing.

Biocatalytic synthesis of 2'-deoxynucleotide 5'-triphosphates from bacterial genomic DNA: Proof of principle.

2'-deoxynucleoside 5'-triphosphates (dNTPs) are the building blocks of DNA and are key reagents which are incorporated by polymerase enzymes during nucleic acid amplification techniques, such as polymerase chain reaction (PCR). These techniques are of high importance, not only in molecular biology research, but also in molecular diagnostics. dNTPs are generally produced by a bottom-up technique which relies on synthesis or isolation of purified small molecules like deoxynucleosides. However, the disproportionately high cost of dNTPs in low- and middle-income countries (LMICs) and the requirement for cold chain storage during international shipping makes an adequate supply of these molecules challenging. To reduce supply chain dependency and promote domestic manufacturing in LMICs, a unique top-down biocatalytic synthesis method is described to produce dNTPs. Readily available bacterial genomic DNA provides a crude source material to generate dNTPs and is extracted directly from Escherichia coli (step 1). Nuclease enzymes are then used to digest the genomic DNA creating monophosphorylated deoxynucleotides (dNMPs) (step 2). Design and recombinant production and characterization of E. coli nucleotide kinases is presented to further phosphorylate the monophosphorylated products to generate dNTPs (step 3). Direct use of the in-house produced dNTPs in nucleic acid amplification is shown (step 4) and their successful use as reagents in the application of PCR, thereby providing proof of principle for the future development of recombinant nucleases and design of a recombinant solid-state bioreactor for on-demand dNTP production.

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance.

BACKGROUND: Evidence guiding the management of cytologically indeterminate thyroid nodules with nondiagnostic (ND) or benign cytology on repeat fine-needle aspiration (FNA) is limited. This study evaluates the utility of molecular testing and estimates the risk of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and cancer among such nodules. METHODS: This was a retrospective single-institution review of thyroid nodules from adults that were classified as atypia of undetermined significance (AUS) or follicular neoplasm (FN) on initial FNA and underwent repeat FNA for cytology and Afirma testing (June 2013-July 2021). The association between repeat FNA cytology and RNA yield for Afirma was determined. Histologic outcomes were integrated with Afirma results to define end points for each nodule. RESULTS: A total of 691 AUS and FN nodules underwent repeat FNA and Afirma testing. Diagnostic Afirma results were obtained in 98% of cases overall and in 91% of nodules with ND cytology on repeat FNA. Using combined molecular and histologic end points, the NIFTP and/or cancer prevalence for nodules with ND cytology on repeat FNA was 9% (95% confidence interval [CI], 0.042-0.182), falling between those nodules classified as benign (5%; 95% CI, 0.029-0.094) and those classified as AUS or FN (18%; 95% CI, 0.140-0.218) on repeat FNA, although not reaching statistical significance from either subgroup (p = .38 and .10, respectively). CONCLUSIONS: AUS and FN nodules that are ND on repeat FNA have low but nonnegligible risk of NIFTP and/or cancer and may benefit from molecular testing, given the low test failure rate in this subgroup. Conversely, AUS and FN nodules reclassified as benign on repeat FNA have a very low risk of NIFTP and/or cancer and are unlikely to benefit from molecular testing.

Eukaryotic translation initiation factor eIF4E-5 is required for spermiogenesis in Drosophila melanogaster.

Drosophila sperm development is characterized by extensive post-transcriptional regulation whereby thousands of transcripts are preserved for translation during later stages. A key step in translation initiation is the binding of eukaryotic initiation factor 4E (eIF4E) to the 5' mRNA cap. In addition to canonical eIF4E-1, Drosophila has multiple eIF4E paralogs, including four (eIF4E-3, -4, -5, and -7) that are highly expressed in the testis. Among these, only eIF4E-3 has been characterized genetically. Here, using CRISPR/Cas9 mutagenesis, we determined that eIF4E-5 is essential for male fertility. eIF4E-5 protein localizes to the distal ends of elongated spermatid cysts, and eIF4E-5 mutants exhibit defects during post-meiotic stages, including a mild defect in spermatid cyst polarization. eIF4E-5 mutants also have a fully penetrant defect in individualization, resulting in failure to produce mature sperm. Indeed, our data indicate that eIF4E-5 regulates non-apoptotic caspase activity during individualization by promoting local accumulation of the E3 ubiquitin ligase inhibitor Soti. Our results further extend the diversity of non-canonical eIF4Es that carry out distinct spatiotemporal roles during spermatogenesis.

Reactance to Healthy Eating and Physical Activity Messages: Face Threat and Face Management Strategies in Memorable Daily Conversations Among Couples.

Most adults in the United States (U.S.) fail to meet guidelines for physical activity (PA) and nutrition outlined by the Centers for Disease Control. One important predictor of engagement in healthy behavior is support from one's romantic partner. However, messages from partners may fail to motivate healthy behavior if they threaten recipients' face and cause reactance. The present study examines face-threatening acts (FTAs) and face management strategies (FMSs) in conversations between romantic couples and their associations with reactance, healthy eating, and PA behaviors. Cohabitating couples (N = 70) were recruited, and one member of the couple completed a 10-day diary survey in which they reported on daily memorable conversations they had with their partner about PA and/or healthy eating. Participants completed measures of positive and negative face threat, as well as the extent to which they engaged in healthy eating and PA that day. Trained raters assessed reported conversations for positive and negative face threat as well as positive and negative FMSs. Results indicate that both participant and trained raters' reports of positive face threat were associated with increased reactance, whereas only participants' reports of negative face threat were associated with increased reactance. Both positive and negative FMSs were associated with reduced reactance. Reactance was negatively associated with healthy eating and PA. Results are discussed in terms of implications for reactance and politeness theories, as well as pragmatic implications for the millions of partnered individuals in the U.S. seeking to improve their health.