Understanding of pharmacy students' knowledge of cannabis use disorders in recreational vs non-recreational use states.

INTRODUCTION: Currently, the trend of legalizing recreational cannabis across the United States is experiencing rapid expansion. Cannabis Use Disorder (CUD) is a pattern of cannabis use leading to clinically significant impairment, manifested by at least two of the 11 criteria on DSM-5. The objective of this study is to compare the knowledge of CUD among pharmacy students attending pharmacy schools in recreational cannabis-legalized states to nonlegalized states. METHODS: This was a survey-based study using validated questionnaires distributed among students from ACPE-accredited pharmacy schools in the United States. The survey included a CUD knowledge section followed by section on student characteristics. Individual item knowledge scores for each question were assessed as well as the total knowledge score. Adjusted linear regression model was used to evaluate knowledge scores between legalized and nonlegalized states. RESULTS: A total of 513 students initiated the survey and 408 completed responses with 153 from recreational cannabis legalized states and 255 from nonlegalized states. The mean knowledge score in RC-legalized states was higher than nonlegalized states. After adjusting for covariates, the knowledge of pharmacy students in recreational cannabis legalized states were 40% higher than in nonlegalized states. CONCLUSION: For future patient requirements, it may be necessary for students to receive formal education in pharmacy schools regarding CUD so that they can proficiently assist with their patient needs. Given that pharmacy students might relocate to different states, it is essential to ensure that they possess a comprehensive understanding of the specific regulations CUD across the United States.

Harnessing an elastic flow instability to improve the kinetic performance of chromatographic columns.

Despite decades of research and development, the optimal efficiency of slurry-packed HPLC columns is still hindered by inherent long-range flow heterogeneity from the wall to the central bulk region of these columns. Here, we show an example of how this issue can be addressed through the straightforward addition of a semidilute amount (500 ppm) of a large, flexible, synthetic polymer (18 MDa partially hydrolyzed polyacrylamide, HPAM) to the mobile phase (1% NaCl aqueous solution, hereafter referred to as "brine") during operation of a 4.6 mm × 300 mm column packed with 10µm BEHTM 125 Å particles. Addition of the polymer imparts elasticity to the mobile phase, causing the flow in the interparticle pore space to become unstable above a threshold flow rate. We verify the development of this elastic flow instability using pressure drop measurements of the friction factor versus Reynolds number. In prior work, we showed that this flow instability is characterized by large spatiotemporal fluctuations in the pore-scale flow velocities that may promote analyte dispersion across the column. Axial dispersion measurements of the quasi non-retained tracer thiourea confirm this possibility: they reveal that operating above the onset of the instability improves column efficiency by greater than 100%. These experiments thereby suggest that elastic flow instabilities can be harnessed to mitigate the negative impact of trans-column flow heterogeneities on the efficiency of slurry-packed HPLC columns. While this approach has its own inherent limitations and constraints, our results lay the groundwork for future targeted development of polymers that can impart elasticity when dissolved in commonly used liquid chromatography mobile phases, and can thereby generate elastic flow instabilities to help improve the resolution of HPLC columns.

From foes to friends: rethinking the role of lymph nodes in prostate cancer.

Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly 'foes' or whether they are actually 'friends' in oncological care is an important idea to discuss.

Racial and Ethnic Disparity in Healthcare Expenditure and Resource Utilization Among Patients with Cardiovascular Diseases.

BACKGROUND: Despite extensive research, significant gaps remain in understanding racial disparity among individuals with cardiovascular diseases (CVD). These disparities, influenced by factors such as access to care and comorbid conditions, necessitate further investigation to develop targeted interventions. AIM: To evaluate the factors contributing to racial and ethnic disparities in healthcare resource utilization and total healthcare expenditure among individuals with CVD. METHODS: Using data from the Medical Expenditure Panel Survey spanning 2014-2021, total healthcare expenditure and having a CVD visit were compared among Hispanic, Black, and White adults with CVD. Descriptive analysis, linear regression, and logistic regression models were used to compare the results. Multivariable models were used to evaluate the effect of demographic and socioeconomic factors on total healthcare expenditure and the likelihood of having a CVD visit among different races. RESULTS: With a weighted sample of 17,722,706, the study found that Hispanic and Black cohorts had 23% and 11% lower healthcare expenditures (both p < 0.001). Hispanic and Black cohorts also had lower odds of having a CVD visit (odds ratio [OR] = 0.61, 95% confidence interval [CI]:0.55-0.68; OR = 0.58, 95% CI: 0.52-0.65, respectively) compared to the White cohort. Key predictors included physical and cognitive limitations, insurance status, income, region, and the year of data collection. CONCLUSION: This study highlights the need for targeted interventions to address healthcare disparities and promote health equity among minority populations with CVD.

Harnessing elastic instabilities for enhanced mixing and reaction kinetics in porous media.

Turbulent flows have been used for millennia to mix solutes; a familiar example is stirring cream into coffee. However, many energy, environmental, and industrial processes rely on the mixing of solutes in porous media where confinement suppresses inertial turbulence. As a result, mixing is drastically hindered, requiring fluid to permeate long distances for appreciable mixing and introducing additional steps to drive mixing that can be expensive and environmentally harmful. Here, we demonstrate that this limitation can be overcome just by adding dilute amounts of flexible polymers to the fluid. Flow-driven stretching of the polymers generates an elastic instability, driving turbulent-like chaotic flow fluctuations, despite the pore-scale confinement that prohibits typical inertial turbulence. Using in situ imaging, we show that these fluctuations stretch and fold the fluid within the pores along thin layers ("lamellae") characterized by sharp solute concentration gradients, driving mixing by diffusion in the pores. This process results in a [Formula: see text] reduction in the required mixing length, a [Formula: see text] increase in solute transverse dispersivity, and can be harnessed to increase the rate at which chemical compounds react by [Formula: see text]-enhancements that we rationalize using turbulence-inspired modeling of the underlying transport processes. Our work thereby establishes a simple, robust, versatile, and predictive way to mix solutes in porous media, with potential applications ranging from large-scale chemical production to environmental remediation.

Soft matter physics of the ground beneath our feet.

The soft part of the Earth's surface - the ground beneath our feet - constitutes the basis for life and natural resources, yet a general physical understanding of the ground is still lacking. In this critical time of climate change, cross-pollination of scientific approaches is urgently needed to better understand the behavior of our planet's surface. The major topics in current research in this area cross different disciplines, spanning geosciences, and various aspects of engineering, material sciences, physics, chemistry, and biology. Among these, soft matter physics has emerged as a fundamental nexus connecting and underpinning many research questions. This perspective article is a multi-voice effort to bring together different views and approaches, questions and insights, from researchers that work in this emerging area, the soft matter physics of the ground beneath our feet. In particular, we identify four major challenges concerned with the dynamics in and of the ground: (I) modeling from the grain scale, (II) near-criticality, (III) bridging scales, and (IV) life. For each challenge, we present a selection of topics by individual authors, providing specific context, recent advances, and open questions. Through this, we seek to provide an overview of the opportunities for the broad Soft Matter community to contribute to the fundamental understanding of the physics of the ground, strive towards a common language, and encourage new collaborations across the broad spectrum of scientists interested in the matter of the Earth's surface.

Influence of bacterial swimming and hydrodynamics on attachment of phages.

Bacteriophages ("phages") are viruses that infect bacteria. Since they do not actively self-propel, phages rely on thermal diffusion to find target cells-but can also be advected by fluid flows, such as those generated by motile bacteria themselves in bulk fluids. How does the flow field generated by a swimming bacterium influence how it encounters phages? Here, we address this question using coupled molecular dynamics and lattice Boltzmann simulations of flagellated bacteria swimming through a bulk fluid containing uniformly-dispersed phages. We find that while swimming increases the rate at which phages attach to both the cell body and flagellar propeller, hydrodynamic interactions strongly suppress this increase at the cell body, but conversely enhance this increase at the flagellar bundle. Our results highlight the pivotal influence of hydrodynamics on the interactions between bacteria and phages, as well as other diffusible species, in microbial environments.

Comparative analysis of brain language templates with primary language areas detected from presurgical fMRI of brain tumor patients.

INTRODUCTION: Functional brain templates are often used in the analysis of clinical functional MRI (fMRI) studies. However, these templates are mostly built based on anatomy or fMRI of healthy subjects, which have not been fully vetted in clinical cohorts. Our aim was to evaluate language templates by comparing with primary language areas (PLAs) detected from presurgical fMRI of brain tumor patients. METHODS: Four language templates (A-D) based on anatomy, task-based fMRI, resting-state fMRI, and meta-analysis, respectively, were compared with PLAs detected by fMRI with word generation and sentence completion paradigms. For each template, the fraction of PLA activations enclosed by the template (positive inclusion fraction, [PIF]), the fraction of activations within the template but that did not belong to PLAs (false inclusion fraction, [FIF]), and their Dice similarity coefficient (DSC) with PLA activations were calculated. RESULTS: For anterior PLAs, Template A had the greatest PIF (median, 0.95), whereas Template D had both the lowest FIF (median, 0.074), and the highest DSC (median, 0.30), which were all significant compared to other templates. For posterior PLAs, Templates B and D had similar PIF (median, 0.91 and 0.90, respectively) and DSC (both medians, 0.059), which were all significantly higher than that of Template C. Templates B and C had significantly lower FIF (median, 0.061 and 0.054, respectively) compared to Template D. CONCLUSION: This study demonstrated significant differences between language templates in their inclusiveness of and spatial agreement with the PLAs detected in the presurgical fMRI of the patient cohort. These findings may help guide the selection of language templates tailored to their applications in clinical fMRI studies.

Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors.

BACKGROUND AND PURPOSE: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors. MATERIALS AND METHODS: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. Three hundred seventeen patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI data set of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error-corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap maps in Montreal Neurological Institute standard space. The Wilcoxon signed-rank test was used to determine a significant difference in the maximum Dice coefficient for our atlas compared with a meta-analysis-based template with respect to expert-delineated primary language area activations. RESULTS: Probabilities of activating the left anterior primary language area and left posterior primary language area in the temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in the left anterior primary language area (0.351 and 0.326, respectively, P < .05) and the left posterior primary language area in the temporal lobe (0.274 and 0.244, respectively, P < .005). CONCLUSIONS: Brain tumor patient- and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients compared with the meta-analysis-based template.

Racial disparity in prostate cancer: an outlook in genetic and molecular landscape.

Prostate cancer (PCa) incidence, morbidity, and mortality rates are significantly impacted by racial disparities. Despite innovative therapeutic approaches and advancements in prevention, men of African American (AA) ancestry are at a higher risk of developing PCa and have a more aggressive and metastatic form of the disease at the time of initial PCa diagnosis than other races. Research on PCa has underlined the biological and molecular basis of racial disparity and emphasized the genetic aspect as the fundamental component of racial inequality. Furthermore, the lower enrollment rate, limited access to national-level cancer facilities, and deferred treatment of AA men and other minorities are hurdles in improving the outcomes of PCa patients. This review provides the most up-to-date information on various biological and molecular contributing factors, such as the single nucleotide polymorphisms (SNPs), mutational spectrum, altered chromosomal loci, differential gene expression, transcriptome analysis, epigenetic factors, tumor microenvironment (TME), and immune modulation of PCa racial disparities. This review also highlights future research avenues to explore the underlying biological factors contributing to PCa disparities, particularly in men of African ancestry.

Understanding Pharmacy Students' Preparedness towards Counseling over Cannabis Use Disorder.

The rise in cannabis use prompts significant concerns regarding pharmacy students' abilities to counsel patients over cannabis use disorder. This study aims to understand pharmacy students' preparedness to counsel patients with cannabis use disorder (CUD) and evaluate the relationship between knowledge, attitudes towards medical cannabis (MC) and recreational cannabis (RC), and behavior intention (BI) to counsel over CUD. A cross-sectional survey was administered to pharmacy students. Descriptive analyses of sample characteristics were assessed with the t-test and one-way ANOVA test. Pearson correlation and linear regression were conducted, measuring the strength and direction of relationships. The average scores for knowledge, attitudes towards MC use and RC, and behavioral intention were 81% (SD 16%), 4.13 (SD 0.75), 3.28 (0.80), and 2.74 (1.00). Significant correlations were observed between knowledge-attitudes toward MC, knowledge-attitudes towards RC, and attitudes towards RC-behavioral intentions. Linear regression indicated attitudes towards MC use and RC, academic year, awareness of MC use legality, obtained knowledge, and past patient interaction were significantly associated with behavioral intention on confidence in counseling over CUD. There is a gap in students' behavioral intention to counsel. These findings emphasize the importance of ample preparation that enables student pharmacists to address patient needs related to cannabis use confidently.

CD8+ T cell targeting of tumor antigens presented by HLA-E.

The nonpolymorphic major histocompatibility complex E (MHC-E) molecule is up-regulated on many cancer cells, thus contributing to immune evasion by engaging inhibitory NKG2A/CD94 receptors on NK cells and tumor-infiltrating T cells. To investigate whether MHC-E expression by cancer cells can be targeted for MHC-E-restricted T cell control, we immunized rhesus macaques (RM) with rhesus cytomegalovirus (RhCMV) vectors genetically programmed to elicit MHC-E-restricted CD8+ T cells and to express established tumor-associated antigens (TAAs) including prostatic acidic phosphatase (PAP), Wilms tumor-1 protein, or Mesothelin. T cell responses to all three tumor antigens were comparable to viral antigen-specific responses with respect to frequency, duration, phenotype, epitope density, and MHC restriction. Thus, CMV-vectored cancer vaccines can bypass central tolerance by eliciting T cells to noncanonical epitopes. We further demonstrate that PAP-specific, MHC-E-restricted CD8+ T cells from RhCMV/PAP-immunized RM respond to PAP-expressing HLA-E+ prostate cancer cells, suggesting that the HLA-E/NKG2A immune checkpoint can be exploited for CD8+ T cell-based immunotherapies.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Morphogenesis of bacterial colonies in polymeric environments.

Many bacteria live in polymeric fluids, such as mucus, environmental polysaccharides, and extracellular polymers in biofilms. However, lab studies typically focus on cells in polymer-free fluids. Here, we show that interactions with polymers shape a fundamental feature of bacterial life-how they proliferate in space in multicellular colonies. Using experiments, we find that when polymer is sufficiently concentrated, cells generically and reversibly form large serpentine "cables" as they proliferate. By combining experiments with biophysical theory and simulations, we demonstrate that this distinctive form of colony morphogenesis arises from an interplay between polymer-induced entropic attraction between neighboring cells and their hindered ability to diffusely separate from each other in a viscous polymer solution. Our work thus reveals a pivotal role of polymers in sculpting proliferating bacterial colonies, with implications for how they interact with hosts and with the natural environment, and uncovers quantitative principles governing colony morphogenesis in such complex environments.

Integrated curriculum in the United States pharmacy programs.

INTRODUCTION: In the last decade, significant changes in pharmaceutical sciences have influenced the delivery of pharmacy education in Pharmacy programs. Integrated curriculum is one such method considered. We aimed to describe the perceived level of integrated curriculum among PharmD programs in the US. METHODS: From October 26th, 2021, until January 18th, 2022, faculty administrators across 138 US pharmacy colleges were surveyed. Data was collected regarding each program's perceived curriculum integration and assessment integration. Characteristics of each college, including region and the type of school (public/private), were obtained from the PharmCAS website. Programs were categorized into high-integration and low-integration groups for analysis purposes. Descriptive and comparative analysis by the level of curriculum integration was performed. RESULTS: Overall, 60 colleges completed surveys (participation rate = 43.48%). Most schools were from the South region (38.33%) and public colleges (53.33%). The average perceived curriculum integration was 45% (SD = 23.69), while the average perceived assessment integration was 36% (SD = 25.52). Pharmacy practice [clinical sciences] (76.67%) was the most common discipline considered for integration, and the social and administrative sciences (21.67%) was the discipline least commonly considered for integration. Case-based learning (95%) was the most common pedagogy strategy to integrate knowledge from different disciplines. CONCLUSIONS: Integrated curriculum implementation in the US PharmD programs varied across colleges. While most programs integrated their clinical practice courses, social and administrative sciences was the course least commonly integrated. Very limited progress in assessment integration was perceived.

The role of implementing instructional design principles on learner experience with training in current good manufacturing practices (cGMP).

INTRODUCTION: The objective of the study was to assess if improvement of the learner experience could be achieved through the use of instructional design strategies in current Good Manufacturing Practices (cGMP) training. This is a novel application in a topic that is known to be boring but is critical to ensuring patient safety. METHODS: An experimental randomized controlled repeated measures cross-over design was utilized in a sample of pharmacy students to determine the effect of an intervention training strategy (which utilized a mix of strategies including weeding, signaling, use of multimedia, and optimized space and type) on the learner experience (Evaluation, Overall Satisfaction, Perceived Knowledge, and Future Recommendation) compared with a control. RESULTS: The sample of 52 pharmacy students that participated evaluated the intervention training strategy with higher scores than the control, with better overall satisfaction, perceived knowledge, and future recommendation scores than the control training strategy. Thus, an apparent effect which resulted from the use of instructional design strategies was seen for all learner experience variables (p < .01). CONCLUSION: Improvement in the learner experience can be achieved by using instructional design strategies in cGMP training. This indicates that similar results could be obtained in other topics where such techniques have not yet been applied.

Patterns of immunotherapy utilization for non-small cell lung cancer in Texas pre- and post-regulatory approval.

PURPOSE: Immunotherapy has shown remarkable benefits for non-small cell lung cancer (NSCLC) since approved by the US Food and Drug Administration (FDA). Texas, however, ranks below the national average in access to treatment for NSCLC. This retrospective cohort study assessed first-line immunotherapy treatment patterns and associated factors pre- and post-FDA approval in Texas. METHODS: Patients ≥18 years diagnosed with NSCLC from the Texas Cancer Registry database (2011-2018) and were stratified into pre- and post-FDA approval era. The rates of immunotherapy utilization were examined, and the average annual percent change (AAPC) in immunotherapy utilization across patient subgroups was compared. Multivariable logistic regression was used to identify associations of patient characteristics with immunotherapy utilization for patients with metastatic- and all-stage NSCLC. RESULTS: A total of 13,501 and 9509 patients with NSCLC were identified in pre-post-approval periods, respectively. Post-approval, immunotherapy utilization increased from 1.7 to 13.0%, and AAPC from 54.8 to 82.7%. Pre-approval, patients living in a county with ≥20% of households below the poverty level were less likely to receive immunotherapy (OR = 0.73, 95% CI = 0.61-0.94) while patients with private insurance were more likely to receive immunotherapy (OR = 1.56, 95% CI = 1.10-2.23). Post-approval, socioeconomic disparities were more prominent (10-19.9 and ≥20% of households below the poverty level: OR = 0.77, 95% CI = 0.66-0.90 and OR = 0.71, 95% CI = 0.60-0.86, respectively). Patients with metastatic NSCLC showed similar patterns of socioeconomic disparities pre- and post-approval. CONCLUSIONS: Our findings suggest that patients' socioeconomic status hinders immunotherapy utilization for NSCLC in Texas. This emphasizes the need for state health policy reforms such as Medicaid expansion and tailored cancer care strategies.

Interplay between environmental yielding and dynamic forcing modulates bacterial growth.

Many bacterial habitats-ranging from gels and tissues in the body to cell-secreted exopolysaccharides in biofilms-are rheologically complex, undergo dynamic external forcing, and have unevenly distributed nutrients. How do these features jointly influence how the resident cells grow and proliferate? Here, we address this question by studying the growth of Escherichia coli dispersed in granular hydrogel matrices with defined and highly tunable structural and rheological properties, under different amounts of external forcing imposed by mechanical shaking, and in both aerobic and anaerobic conditions. Our experiments establish a general principle: that the balance between the yield stress of the environment that the cells inhabit, σy, and the external stress imposed on the environment, σ, modulates bacterial growth by altering transport of essential nutrients to the cells. In particular, when σy<σ, the environment is easily fluidized and mixed over large scales, providing nutrients to the cells and sustaining complete cellular growth. By contrast, when σy>σ, the elasticity of the environment suppresses large-scale fluid mixing, limiting nutrient availability and arresting cellular growth. Our work thus reveals a new mechanism, beyond effects that change cellular behavior via local forcing, by which the rheology of the environment may modulate microbial physiology in diverse natural and industrial settings.