An asynchronous, hands-off workflow for looking time experiments with infants.

The study of infant gaze has long been a key tool for understanding the developing mind. However, labor-intensive data collection and processing limit the speed at which this understanding can be advanced. Here, we demonstrate an asynchronous workflow for conducting violation-of-expectation (VoE) experiments, which is fully "hands-off" for the experimenter. We first replicate four classic VoE experiments in a synchronous online setting, and show that VoE can generate highly replicable effects through remote testing. We then confirm the accuracy of a state-of-the-art gaze annotation software, iCatcher+ in a new setting. Third, we train parents to control the experiment flow based on the infant's gaze. Combining all three innovations, we then conduct an asynchronous automated infant-contingent VoE experiment. The hands-off workflow successfully replicates a classic VoE effect: infants look longer at inefficient actions than efficient ones. We compare the resulting effect size and statistical power to the same study run in-lab and synchronously via Zoom. The hands-off workflow significantly reduces the marginal cost and time per participant, enabling larger sample sizes. By enhancing the reproducibility and robustness of findings relying on infant looking, this workflow could help support a cumulative science of infant cognition. Tools to implement the workflow are openly available. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Racial and Ethnic Disparities in Allergen Immunotherapy Prescription for Allergic Rhinitis.

BACKGROUND: Racial and ethnic differences exist in the severity of various atopic diseases including allergic rhinitis (AR). Patients of under-represented races and ethnicities may be subjected to disparate subcutaneous allergen immunotherapy (SCIT) prescription practices. OBJECTIVE: To explore the racial and ethnic disparities in the use of SCIT among patients with AR. METHODS: In this retrospective matched cohort study, we used the TriNetX US Collaborative Network, a multicenter electronic health record-based database to identify patients with AR 18 years and older. Patients were grouped according to their racial and ethnic identification. Study groups were matched for baseline demographics, atopic comorbidities, heart diseases and utilization of ß-blockers, and angiotensin-converting enzyme inhibitors. The proportion of patients of under-represented racial and ethnic groups started on SCIT was contrasted to the non-Hispanic White cohort. RESULTS: We identified 1,038,000 patients with AR; the mean age (±standard deviation) at the index was 49.7 (±16.1) years, and 64.6% were female. Ethnicity information was available from 87.3% of patients, and the majority (92.3%) were non-Hispanic. Over a 3-year observation period, fewer Black patients (relative risk [RR], 0.40; 95% confidence interval [CI], 0.33-0.48) and Hispanic patients (RR, 0.80; 95% CI, 0.64-0.99) were started on SCIT compared with non-Hispanic White patients. The proportions of Asian patients who were initiated on SCIT tended to be lower when compared with non-Hispanic White patients (RR, 0.69; 95% CI, 0.47-1.009). CONCLUSIONS: In the United States, differences in SCIT prescription exist between Black and Hispanic patients relative to White patients. Barriers to treatment should be explored and mitigated.

Impact of Medication Reconciliation by a Dialysis Pharmacist.

Integrating a pharmacist into a hemodialysis unit significantly reduced medication discrepancies and medication-related problems over time.Medication reconciliation for the Centers for Medicare and Medicaid Services End-Stage Renal Disease Quality Incentive Program can be optimally performed by a dialysis pharmacist.

Brain Prehabilitation for Oncologic Surgery.

PURPOSE OF REVIEW: This review aims to summarize the current research on postoperative cognitive complications, such as delirium and cognitive dysfunction. This includes discussion on preoperative preventive strategies, such as physical and nutritional prehabilitation as well as up-to-date information on neuroprehabilitation. RECENT FINDINGS: Current recommendations for prevention of postoperative delirium have focused on multicomponent interventions. The optimal composition of surgical prehabilitation programs targeting exercise and nutrition has not yet been established. The Neurobics Trial shows that cognitive prehabilitation improves cognitive reserve and may be a useful addition to multimodal surgical prehabilitation. Perioperative management of oncologic patients is often associated with a myriad of challenges, such as the management of tumor-related pathologies, adverse events from neoadjuvant therapy, and chronic metabolic and immunological changes associated with malignancy. In addition, oncologic patients are at increased risk of developing frailty, which adversely affects postoperative recovery and further cancer treatment. As a result, oncologic patients are at considerable risk of developing postoperative cognitive complications, such as delirium and cognitive dysfunction. In this review, we discuss the effect of prehabilitation on postoperative cognitive outcomes.

Breakthrough SARS-CoV-2 infections after COVID-19 immunization.

As no vaccines are 100% effective at preventing illness, COVID-19 vaccine breakthrough cases are expected. We here aim to review the most recent literature on COVID-19 vaccine breakthrough infections. SARS-CoV-2 breakthrough infections are, in general, rare. Age may still be a factor in SARS-CoV-2 infections in immunized individuals.

Concurrent Inhibition of ERK and Farnesyltransferase Suppresses the Growth of HRAS Mutant Head and Neck Squamous Cell Carcinoma.

Human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide with an unmet need for more effective, less toxic treatments. Currently, both the disease and the treatment of HNSCC cause significant mortality and morbidity. Targeted therapies hold new promise for patients with HPV-negative status whose tumors harbor oncogenic HRAS mutations. Recent promising clinical results have renewed interest in the development of farnesyltransferase inhibitors (FTIs) as a therapeutic strategy for HRAS-mutant cancers. With the advent of clinical evaluation of the FTI tipifarnib for the treatment of HRAS-mutant HNSCC, we investigated the activity of tipifarnib and inhibitors of HRAS effector signaling in HRAS-mutant HNSCC cell lines. First, we validated that HRAS is a cancer driver in HRAS-mutant HNSCC lines. Second, we showed that treatment with the FTI tipifarnib largely phenocopied HRAS silencing, supporting HRAS as a key target of FTI antitumor activity. Third, we performed reverse-phase protein array analyses to profile FTI treatment-induced changes in global signaling, and conducted CRISPR/Cas9 genetic loss-of-function screens to identify previously unreported genes and pathways that modulate sensitivity to tipifarnib. Fourth, we determined that concurrent inhibition of HRAS effector signaling (ERK, PI3K, mTORC1) increased sensitivity to tipifarnib treatment, in part by overcoming tipifarnib-induced compensatory signaling. We also determined that ERK inhibition could block tipifarnib-induced epithelial-to-mesenchymal transition, providing a potential basis for the effectiveness of this combination. Our results support future investigations of these and other combination treatments for HRAS mutant HNSCC.

Pre-excitation Due to Fascicular-Ventricular Pathway: An Electrocardiographic Diagnosis: A Case Report.

A 79-year-old Caucasian male was referred to cardiology clinic because the electrocardiogram showed premature atrial complexes and pre-excitation (delta waves) thought to be consistent with Wolff-Parkinson-White (WPW) syndrome. He did not report symptoms of palpitations or syncope. Careful analysis of the electrocardiogram revealed a fascicular-ventricular pathway (FVP) responsible for pre-excitation. Differentiating FVP from WPW syndrome is essential as the risk profile is different with each. Electrocardiographic observations that could help identify the presence of an FVP and its diagnostic, prognostic, and therapeutic implications are presented.

Learning and Attention Deficit/Hyperactivity Disorders as Risk Factors for Prolonged Concussion Recovery in Children and Adolescents.

OBJECTIVE: Examine pre-existing learning disorders (LD) and attention deficit/hyperactivity disorders (ADHD) as risk factors for prolonged recovery and increased symptomology following pediatric mild traumatic brain injury (mTBI). METHODS: We conducted a retrospective cohort study of children/adolescents (5-17 years) with mTBI who presented to a Children's Minnesota Concussion Clinic between April 2018 and March 2019. Differences across strata of pre-existing conditions (present vs. absent) in time to recovery measures were estimated via Kaplan-Meier and Cox proportional hazards analyses and differences in symptom trajectories were examined via linear mixed-effects regression models. Regression models were adjusted for age, sex and other confounders. RESULTS: In our cohort of 680 mTBI patients, those with LD (n = 70) or ADHD (n = 107) experienced significantly longer median durations of symptoms (58 and 68 days, respectively) than those without (43 days). Accordingly, LD was significantly associated with delayed symptom recovery (adjusted hazard ratio (aHR) = 1.63, 95% CI: 1.16-2.29), return to school (1.47, 1.08-2.00), and return to physical activity (1.50, 1.10-2.04). Likewise, ADHD was associated with delayed recovery (1.69, 1.28-2.23), return to school (1.52, 1.17-1.97) and physical activity (1.55, 1.19-2.01). Further, patients with LD or ADHD reported, on average, significantly more concussion symptoms and higher vision symptom scores throughout recovery versus those without. There was no evidence that concussion or vision symptom recovery trajectories varied over time between those with/without LD or ADHD (joint P-interactions > 0.05). CONCLUSION: Pre-existing LD and ADHD are risk factors for prolonged and more symptomatic mTBI recovery in youth. These results can inform clinical concussion management and recovery expectations.

Prenatal Cannabis Use and Infant Birth Outcomes in the Pregnancy Risk Assessment Monitoring System.

OBJECTIVES: To examine the association of prenatal cannabis use and adverse infant outcomes in a nationally representative cohort and consider the impact of concurrent cigarette exposure. STUDY DESIGN: We conducted a retrospective cohort study on 32 583 new mothers from the 2017-2019 Pregnancy Risk Assessment Monitoring System. Cannabis use was evaluated as a binary variable (use or no use) as well as ordinal categories (no, light, moderate, heavy use). We used multivariable logistic regression to examine the relationship between prenatal cannabis exposure and low birthweight (LBW), preterm birth, and small for gestational age. RESULTS: Prenatal cannabis use was associated with significantly greater odds of LBW (aOR, 1.27; 95% CI, 1.05-1.54) and small for gestational age (aOR, 1.35; 95% CI, 1.09-1.68) but not preterm birth. Compared with nonusers, heavy users (weekly or more) were twice as likely to deliver a LBW infant (aOR, 2.07; 95% CI, 1.46-2.94) or small for gestational age infant (aOR, 2.14; 95% CI, 1.38-3.30). When examining combined cannabis and cigarette use, prenatal exposure to both substances increased the likelihood of LBW (aOR, 2.27; 95% CI, 1.71-3.01), preterm birth (aOR, 1.61; 95% CI, 1.12-2.31), and small for gestational age (aOR, 3.29; 95% CI, 2.39-4.55) compared with no use, and the increased odds were greater than for either substance alone. CONCLUSIONS: Our results suggest that cannabis use during pregnancy may harm fetal development, and recommendations to improve birth outcomes should address co-use of cannabis and tobacco.

Pharmacist intervention on prescribing errors: Use of a standardized approach in the inpatient setting.

PURPOSE: The objective of this study was to implement a standardized process across health systems to determine the prevalence and clinical relevance of prescribing errors intercepted by pharmacists. METHODS: This prospective, multicenter, observational study was conducted across 11 hospitals. Pharmacist-intercepted prescribing errors were collected during inpatient order verification over 6 consecutive weeks utilizing a standardized documentation process. The potential harm of each error was evaluated using a modified National Coordinating Council for Medication Error Reporting and Prevention (NCC-MERP) index with physician validation, and errors were stratified into those with potentially low, serious, or life-threatening harm. Endpoints included the median error rate per 1,000 patient days, error type, and potential harm with correlating cost avoidance. RESULTS: Pharmacists intervened on 7,187 errors, resulting in a mean error rate of 39 errors per 1,000 patient days. Among the errors, 46.6% (n = 3,349) were determined to have potentially serious consequences and 2.4% (n = 175) could have been life-threatening if not intercepted. This equates to $874,000 in avoided cost. The top 3 error types occurring with the highest frequency were "wrong dose/rate/frequency" (n = 2,298, 32.0%), "duplicate therapy" (n = 1,431, 19.9%), and "wrong timing" (n = 960, 13.4%). "Wrong dose/rate/frequency" (n = 49, 28%), "duplicate therapy" (n = 26, 14.9%), and "drug-disease interaction" (n = 24, 13.7%) errors occurred with the highest frequency among errors with potential for life-threatening harm. "Wrong dose/rate/frequency" (n = 1,028, 30.7%), "wrong timing" (n = 573, 17.1%), and "duplicate therapy" (n = 482, 14.4%) errors occurred with the highest frequency among errors with potentially serious harm. CONCLUSION: Documentation of pharmacist intervention on prescribing errors via a standardized process creates a platform for multicenter analysis of prescribing error trends and an opportunity for development of system-wide solutions to reduce potential harm from prescribing errors.

Combined Knockout of Lrrk2 and Rab29 Does Not Result in Behavioral Abnormalities in vivo.

BACKGROUND: Coding mutations in the LRRK2 gene, encoding for a large protein kinase, have been shown to cause familial Parkinson's disease (PD). The immediate biological consequence of LRRK2 mutations is to increase kinase activity, suggesting that inhibition of this enzyme might be useful therapeutically to slow disease progression. Genome-wide association studies have identified the chromosomal loci around LRRK2 and one of its proposed substrates, RAB29, as contributors towards the lifetime risk of sporadic PD. OBJECTIVE: Considering the evidence for interactions between LRRK2 and RAB29 on the genetic and protein levels, we set out to determine whether there are any consequences on brain function with aging after deletion of both genes. METHODS: We generated a double knockout mouse model and performed a battery of motor and non-motor behavioral tests. We then investigated postmortem assays to determine the presence of PD-like pathology, including nigral dopamine cell count, astrogliosis, microgliosis, and striatal monoamine content. RESULTS: Behaviorally, we noted only that 18-24-month Rab29-/- and double (Lrrk2-/-/Rab29-/-) knockout mice had diminished locomotor behavior in open field compared to wildtype mice. However, no genotype differences were seen in the outcomes that represented PD-like pathology. CONCLUSION: These results suggest that depletion of both LRRK2 and RAB29 is tolerated, at least in mice, and support that this pathway might be able to be safely targeted for therapeutics in humans.

K2P2.1 (TREK-1) potassium channel activation protects against hyperoxia-induced lung injury.

No targeted therapies exist to counteract Hyperoxia (HO)-induced Acute Lung Injury (HALI). We previously found that HO downregulates alveolar K2P2.1 (TREK-1) K+ channels, which results in worsening lung injury. This decrease in TREK-1 levels leaves a subset of channels amendable to pharmacological intervention. Therefore, we hypothesized that TREK-1 activation protects against HALI. We treated HO-exposed mice and primary alveolar epithelial cells (AECs) with the novel TREK-1 activators ML335 and BL1249, and quantified physiological, histological, and biochemical lung injury markers. We determined the effects of these drugs on epithelial TREK-1 currents, plasma membrane potential (Em), and intracellular Ca2+ (iCa) concentrations using fluorometric assays, and blocked voltage-gated Ca2+ channels (CaV) as a downstream mechanism of cytokine secretion. Once-daily, intra-tracheal injections of HO-exposed mice with ML335 or BL1249 improved lung compliance, histological lung injury scores, broncho-alveolar lavage protein levels and cell counts, and IL-6 and IP-10 concentrations. TREK-1 activation also decreased IL-6, IP-10, and CCL-2 secretion from primary AECs. Mechanistically, ML335 and BL1249 induced TREK-1 currents in AECs, counteracted HO-induced cell depolarization, and lowered iCa2+ concentrations. In addition, CCL-2 secretion was decreased after L-type CaV inhibition. Therefore, Em stabilization with TREK-1 activators may represent a novel approach to counteract HALI.

Concussion symptomology and recovery in children and adolescents with pre-existing anxiety.

OBJECTIVE: To examine pre-existing anxiety disorders as a risk factor for increased concussion symptomology and prolonged recovery in children and adolescents. METHODS: In this retrospective cohort study, we abstracted medical record data for 637 children/adolescents (5-17 years) presenting to three tertiary concussion clinics between April 2018 and March 2019. Primary outcomes were mean concussion symptom and vision symptom severity scores measured at clinic visits. Linear mixed-effects regression models were employed to investigate differences in average symptom load, vision symptom score and symptom recovery trajectories across anxiety strata, adjusted for random effects (time), age and sex. Secondary outcomes, time to concussion symptom recovery and time to return to academics and sports, respectively, were examined via log-rank tests and multivariable Cox regression. RESULTS: Among 637 eligible concussion patients, 155 (24%) reported pre-existing anxiety. On average, patients with anxiety reported an additional 2.64 (95% CI 1.84 to 3.44) concussion symptoms and 7.45 (95% CI 5.22 to 9.68) higher vision symptom severity scores throughout recovery versus those without, after adjusting for age and sex. There was no evidence that concussion or vision symptom trajectories varied over time between those with/without anxiety after accounting for baseline dissimilarities in symptom scores (all pinteraction >0.05). Anxiety was significantly associated with delayed symptom recovery (adjusted HR 3.34, 95% CI 2.18 to 5.12), return to school (adjusted HR 2.01, 95% CI 1.59 to 2.53) and return to physical activity (adjusted HR 1.88, 95% CI 1.49 to 2.37). CONCLUSIONS: Pre-existing anxiety disorders were associated with more severe symptomology and prolonged recovery after concussion in children and adolescents. These results can be referenced by providers to manage patients' recovery expectations.

Does early physical therapy intervention reduce opioid burden and improve functionality in the management of chronic lower back pain?

INTRODUCTION: Chronic lower back pain is a leading cause of disability in US adults. Opioid use continues to be controversial despite the Centers for Disease Control and Prevention guidance on chronic pain management to use nonpharmacologic and nonopioid pharmacologic interventions. The objectives of the study were to assess the impact of early physical therapy (PT) intervention on improving functionality and reducing opioid burden in patients with chronic lower back pain. METHODS: A single-center, retrospective chart review of patients receiving ≥6 PT visits and treated with either opioids first (OF) or PT first (PTF) therapy for chronic lower back pain were evaluated. Concomitant use of nonopioid and nonpharmacologic therapy was permitted. The Oswestry Disability Index (ODI), a survey measuring functionality, was recorded for PTF group. Pain scores and medication use including opioids were collected at treatment initiation and completion. RESULTS: One hundred and eighty patients were included in three groups: OF group (n = 60), PTF group (n = 60), and PTF + ODI group (n = 60). The PTF + ODI group had mean ODI reduction of 11.9% (P < .001). More OF patients were lost to follow up (68.3%) or failed PT (60%) compared to the PTF group, 38.3% and 3.3% (P < .001). Reduction in both opioid and nonopioid medications as well as pain scores were observed but not statistically significant. DISCUSSION: Early PT resulted in improved functionality, decreased pain, and reduced medication use upon PT completion. These findings suggest PT, along with nonopioid modalities, are a viable first-line option for the management of chronic lower back pain.

Assessment of the Research Interests and Perceptions of First-Year Medical Students at 4 Colleges of Osteopathic Medicine.

CONTEXT: There are limited data regarding the experiences of and attitudes toward research participation among osteopathic medical students despite rapidly increasing enrollment and expansion of the number of osteopathic medical schools. OBJECTIVE: To assess first-year osteopathic medical students' experience with research, their interest in it, their perceptions of its value, and barriers to participation. METHODS: An anonymous, online survey was sent to 868 medical students in the class of 2021 at 4 colleges of osteopathic medicine. The survey consisted of 14 multiple-choice items (7 of which offered the option of a written response) and 1 open-ended item that asked them to report their age. The survey remained open for 2 weeks, with 1 reminder email sent on the last day of the survey. Incomplete responses were excluded from the analysis. RESULTS: A total of 328 participants were included, for a response rate of 38%. A majority of respondents reported previous research experience (261 [79.6%]), consistent with a strong perception that research participation is important (315 [96.0%]). Fewer students (177 [54.0%]) were either currently participating in research or affirmed interest in performing research during medical school, with the highest level of interest in clinical research (259 [79.0%]) followed by basic science (166 [50.6%]). Regarding incentives that might encourage participation in research, students preferred monetary compensation (213 [64.9%]) or extra credit in courses (195 [59.5%]). A commonly reported barrier to performing research during medical school was the possibility of a negative impact on performance in coursework (289 [88.1%]). CONCLUSION: First-year osteopathic medical students are interested in research, view research experience as valuable, and consider research experience as beneficial to future career development. This study's findings highlight opportunities for increasing student participation in research through incentives or removal of perceived barriers.

Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses.

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the mannose receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182-mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206high patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased cancer cell phagocytosis by reprogrammed TAMs.

Quantification of ultraviolet (UV) radiation in the shade and in direct sunlight.

Ultraviolet (UV) radiation is associated with negative health effects, including sun damage and skin cancer. The purpose of this study is to compare the protective effects of the shade provided by a sun umbrella versus that provided by a tree. Sun sensors that register the level and dose of UV radiation were placed in the shade and in direct sunlight. Measurements were recorded every half hour between the hours of 12:30 p.m. and 3:00 p.m. in Sacramento, California. The results suggest that the level of UV radiation in the shade is not zero. The sensors located in tree shade indicated that over 5% of UV radiation was detected in the shade. The sensors located in sun-umbrella shade showed that greater than 17% of UV radiation reached the shade. The sun sensors used in our study collected UV radiation data relevant to UV index; however, they did not differentiate between UVA, UVB, visible, and infrared light. The amount of UV radiation detected in the shade is not zero, thus regular sunscreen use and other sun protective practices should be followed to reduce the risk of sun damage and skin cancer.

Postpartum Nurses' Experience Caring for Infants With Neonatal Abstinence Syndrome.

OBJECTIVES: In previous years, otherwise healthy infants with neonatal abstinence syndrome (NAS) in our hospital were transferred to the NICU and frequently treated with medication. Currently, infants with NAS room-in with their mothers and rarely require medication. We sought to understand the lived experience of nurses on maternity and well-newborn units caring for infants with NAS. METHODS: We conducted focus groups of registered nurses on postpartum units at 2 hospitals using qualitative methodology. Themes were identified through consensus, and the focus groups were stopped when no new themes were identified. RESULTS: Seventeen postpartum nurses participated in 5 focus groups. The following major themes emerged: (1) managing the expectations of parents of newborns with NAS, (2) current NAS protocol (positive aspects of rooming-in and challenges with withdrawal scoring tool), (3) inconsistencies in care and communication, (4) perceived increase in nursing workload on the postpartum unit, and (5) nurses' emotional response to the care of infants with NAS. CONCLUSIONS: We highlight the perspectives of nursing staff on the well-newborn unit who were previously unaccustomed to caring for infants with NAS. With increasing numbers of infants with NAS and longer stays on the well-newborn unit, hospitals must prepare to better support staff and implement protocols that offer consistency in practice.