Airway inflammatory changes in the lungs of patients with asthma-COPD overlap (ACO): a bronchoscopy endobronchial biopsy study.

BACKGROUND: Although asthma and chronic obstructive pulmonary disease (COPD) are two distinct chronic airway inflammatory diseases, they often co-exist in a patient and the condition is referred to as asthma-COPD overlap (ACO). Lack of evidence regarding the inflammatory cells in ACO airways has led to their poor prognosis and treatment. The objective of this endobronchial biopsy (EBB) study was to enumerate inflammatory cellular changes in the airway wall of ACO compared with asthma, COPD current smokers (CS) and ex-smokers (ES), normal lung function smokers (NLFS), and non-smoker controls (HC). METHODS: EBB tissues from 74 patients were immunohistochemically stained for macrophages, mast cells, eosinophils, neutrophils, CD8+ T-cells and CD4+ T-cells. The microscopic images of stained tissues were evaluated in the epithelium, reticular basement membrane (RBM) cells/mm RBM length, and lamina propria (LP) cells/mm2 up to a depth of 120 µM using the image analysis software Image-Pro Plus 7.0. The observer was blinded to the images and disease diagnosis. Statistical analysis was performed using GraphPad Prism v9. RESULTS: The tissue macrophages in ACO were substantially higher in the epithelium and RBM than in HC (P < 0.001 for both), COPD-ES (P < 0.001 for both), and -CS (P < 0.05 and < 0.0001, respectively). The ACO LP macrophages were significantly higher in number than COPD-CS (P < 0.05). The mast cell numbers in ACO were lower than in NLFS (P < 0.05) in the epithelium, lower than COPD (P < 0.05) and NLFS (P < 0.001) in RBM; and lower than  HC (P < 0.05) in LP. We noted lower eosinophils in ACO LP than HC (P < 0.05) and the lowest neutrophils in both ACO and asthma. Furthermore, CD8+ T-cell numbers increased in the ACO RBM than HC (P < 0.05), COPD-ES (P < 0.05), and NLFS (P < 0.01); however, they were similar in number in epithelium and LP across groups. CD4+ T-cells remained lower in number across all regions and groups. CONCLUSION: These results suggest that the ACO airway tissue inflammatory cellular profile differed from the contributing diseases of asthma and COPD with a predominance of macrophages.

Pathogenesis, clinical features of asthma COPD overlap, and therapeutic modalities.

Both asthma and COPD are heterogeneous diseases identified by characteristic symptoms and functional abnormalities, with airway obstruction common in both diseases. Asthma COPD overlap (ACO) does not define a single disease but is a descriptive term for clinical use that includes several overlapping clinical phenotypes of chronic airways disease with different underlying mechanisms. This literature review was initiated to describe published studies, identify gaps in knowledge, and propose future research goals regarding the disease pathology of ACO, especially the airway remodeling changes and inflammation aspects. Airway remodeling occurs in asthma and COPD, but there are differences in the structures affected and the prime anatomic site at which they occur. Reticular basement membrane thickening and cellular infiltration with eosinophils and T-helper (CD4+) lymphocytes are prominent features of asthma. Epithelial squamous metaplasia, airway wall fibrosis, emphysema, bronchoalveolar lavage (BAL) neutrophilia, and (CD8+) T-cytotoxic lymphocyte infiltrations in the airway wall are features of COPD. There is no universally accepted definition of ACO, nor are there clearly defined pathological characteristics to differentiate from asthma and COPD. Understanding etiological concepts within the purview of inflammation and airway remodeling changes in ACO would allow better management of these patients.

Differential airway remodeling changes were observed in patients with asthma COPD overlap compared to patients with asthma and COPD alone.

Management of patients with asthma COPD overlap (ACO) is clinically challenging due to insufficient evidence of pathological changes in these patients. In this cross-sectional study, we evaluated airway remodeling in endobronchial biopsies from a total of 90 subjects, which included 12 ACO, 14 patients with asthma, 12 COPD exsmokers (ES), 11 current smokers (CS), 28 healthy controls (HC), and 13 normal lung function smokers (NLFS). Tissue was stained with Masson's trichrome. Epithelium, goblet cells, reticular basement membrane (RBM), cellularity, lamina propria (LP), and smooth muscle (SM) changes were measured using Image-Pro Plus v7 software. Differential airway remodeling pattern was seen in patients with ACO. A limited change was noted in the ACO epithelium compared with other pathological groups. RBM was substantially thicker in patients with ACO than in HC (P < 0.0002) and tended to be thicker than in patients with asthma and NLFS. The total RBM cells were higher in ACO than in the HC (P < 0.0001), COPD-CS (P = 0.0559), -ES (P = 0.0345), and NLFS (P < 0.0002), but did not differ from patients with asthma. Goblet cells were higher in the ACO than in the HC (P = 0.0028) and COPD-ES (P = 0.0081). The total LP cells in ACO appeared to be higher than in HC, COPD-CS, and NLFS but appeared to be lower than in patients with asthma. Finally, SM area was significantly lower in the ACO than in patients with asthma (P = 0.001), COPD-CS (=0.0290), and NLFS (P = 0.0011). This first comprehensive study suggests that patients with ACO had distinguishable tissue remodeling that appeared to be more severe than patients with asthma and COPD. This study will help in informed decision-making for better patient management in clinical practice.

Putting the local back into planning-experiences and perceptions of state and district health functionaries of seven aspirational districts in India on an innovative planning capacity building approach.

District functionaries have ostensibly a major responsibility to develop evidence based plans. However, this responsibility is not commensurate with skills and expertise among functionaries in many Indian states. Vriddhi project-technical partner of the government, developed a planning tool for maternal and neonatal health programmes, called RMNCH + A Action Agenda using Strategic Approach (RAASTA), which was introduced in a workshop format in two states and attended by program officers. Qualitative feedback was obtained from selected participants to understand their experience of the workshop and of the planning tool. It emerged that previous planning process had little application of local evidence based solutions. Participants appreciated the alternative approach as RAASTA equipped them to use local evidence. Several action plans derived at the workshop were included in the state plan. At the same time, apprehension was expressed by participants about translating their learnings to practical application as planning was not a central priority in their scheme of duties and tasks. Enhanced support from states in refreshing district planners' skills would be an important step. One state government has scaled up the RAASTA tool while an electronic version is being developed for future use as it demonstrates great potential to equip and aid district officials in developing evidence based plans.

Nobiletin as a Molecule for Formulation Development: An Overview of Advanced Formulation and Nanotechnology-Based Strategies of Nobiletin.

Approximately 40% of compounds in clinical drug development suffer from solubility and bioavailability challenges. Evidence from literature demonstrates the growing interest to utilize flavonoids as potential compounds owing to their widespread therapeutic utility in various ailments. Nobiletin (NOB), one such dietary polymethoxylated flavonoid found in citrus fruits, has multiple pharmacological effects such as antioxidant, anti-microbial, anti-cancer, and anti-inflammatory. It is useful in cancer, inflammatory bowel diseases, atherosclerosis, obesity, and Alzheimer's disease. Although preclinical studies demonstrate the therapeutic utility of NOB, it suffers from serious biopharmaceutical limitations such as low aqueous solubility (below 1 µg/ml), poor permeability across biological barriers, and low bioavailability. To overcome these biopharmaceutical challenges associated with NOB, the use of advanced formulations and nanotechnology-based strategies appears to be a promising approach to potentiate its therapeutic action. Multiple reviews cover the various therapeutic benefits of NOB in various diseases; however, there is an absence of a comprehensive review that focuses on the formulation development strategies of NOB. The purpose of this review is to provide a concise perspective on NOB as a candidate molecule for formulation development. The manuscript covers various aspects related to NOB, such as its chemistry, physicochemical properties, and pharmacological effects. This is also a thorough review of various formulation development strategies with advances made in the past years to improve the solubility, bioavailability, and therapeutic efficacy of NOB. The review also contains information related to toxicity and patents involving NOB and its formulation.

A longitudinal exploration of perceptions of pharmacy practice preparedness among graduating pharmacy students and preceptors.

Graduating student pharmacists who are practice-ready is an essential responsibility of pharmacy programs and heavily emphasized by Accreditation Council of Pharmacy Education (ACPE), pharmacy education's accrediting body. Although several studies have examined students' readiness to engage in advanced pharmacy practice experiences (APPE), few studies examine graduating students' readiness to practice. The objective of this study was to examine national trends in graduating pharmacy students' and preceptors' perceptions of students' pharmacy practice preparedness across a six-year time frame (2016-2021) and trends in graduating students' overall impressions of their program and the pharmacy profession across the same time period. A longitudinal descriptive study to examine trends in graduating student and preceptor perception was conducted utilizing data from the 2016-2021 American Association of Colleges of Pharmacy (AACP) Graduating Student Surveys (GSS) (n = 65,461) and Preceptor Surveys (PS) (n = 41,951). Over six years of survey data analyzed, a large percentage of students at both public and private institutions reported they felt prepared for practice (96.5% vs 95.5% respectively, p < 0.001). There was overall agreement (>90%) among preceptors that graduating students were prepared to enter pharmacy practice based on responses, although preceptors had lower levels of agreement compared to students on most statements. Based on the findings, both graduating pharmacy students and preceptors feel that graduates are prepared to practice pharmacy, with consistent trends in perceptions over the last six years. However, results also indicate that a consistent downward trend in students' willingness to pursue pharmacy again, indicating decreased optimism of graduating students for the profession.

Large airway wall vascularity in patients with asthma-COPD overlap: a bronchoscopy study.

Large airway wall lamina propria in patients with asthma-COPD overlap is hypovascular with an increase in reticular basement membrane neoangiogenesis, reflecting smoking-related COPD-like pathology and potential epithelial-to-mesenchymal transition https://bit.ly/49DeoFX.

TGF-ß1, pSmad-2/3, Smad-7, and ß-Catenin Are Augmented in the Pulmonary Arteries from Patients with Idiopathic Pulmonary Fibrosis (IPF): Role in Driving Endothelial-to-Mesenchymal Transition (EndMT).

Background: We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim to quantify drivers of EndMT in IPF patients compared to normal controls (NCs). Methods: Lung resections from thirteen IPF patients and eleven NCs were immunohistochemically stained for EndMT drivers, including TGF-ß1, pSmad-2/3, Smad-7, and ß-catenin. Intima, media, and adventitia were analysed for expression of each EndMT driver in pulmonary arteries. Computer- and microscope-assisted Image ProPlus7.0 image analysis software was used for quantifications. Results: Significant TGF-ß1, pSmad-2/3, Smad-7, and ß-catenin expression was apparent across all arterial sizes in IPF (p < 0.05). Intimal TGF-ß1, pSmad-2/3, Smad-7, and ß-catenin were augmented in the arterial range of 100-1000 µm (p < 0.001) compared to NC. Intimal TGF-ß1 and ß-catenin percentage expression showed a strong correlation with the percentage expression of intimal vimentin (r' = 0.54, p = 0.05 and r' = 0.61, p = 0.02, respectively) and intimal N-cadherin (r' = 0.62, p = 0.03 and r' = 0.70, p = 0.001, respectively). Intimal TGF-ß1 and ß-catenin expression were significantly correlated with increased intimal thickness as well (r' = 0.52, p = 0.04; r' = 0.052, p = 0.04, respectively). Moreover, intimal TGF-ß1 expression was also significantly associated with increased intimal elastin deposition (r' = 0.79, p = 0.002). Furthermore, total TGF-ß1 expression significantly impacted the percentage of DLCO (r' = -0.61, p = 0.03). Conclusions: This is the first study to illustrate the involvement of active TGF-ß/Smad-2/3-dependent and ß-catenin-dependent Wnt signalling pathways in driving EndMT and resultant pulmonary arterial remodelling in patients with IPF. EndMT is a potential therapeutic target for vascular remodelling and fibrosis in general in patients with IPF.

Endothelial to mesenchymal transition is an active process in smokers and patients with early COPD contributing to pulmonary arterial pathology.

Background: We have previously reported pulmonary arterial remodelling in smokers and patients with early COPD, which can be attributed to endothelial to mesenchymal transition (EndMT). In this study, we aimed to evaluate if EndMT is an active mechanism in smokers and COPD. Methods: Immunohistochemical staining for the EndMT biomarkers CD31, N-cadherin, vimentin and S100A4 was done on lung resection tissue from 49 subjects. These comprised 15 nonsmoker controls (NC), six normal lung function smokers (NLFS), nine patients with small airway disease (SAD), nine current smokers with mild-moderate COPD (COPD-CS) and 10 ex-smokers with COPD (COPD-ES). Pulmonary arteries were analysed using Image ProPlus software v7.0. Results: We noted reduced junctional CD31+ endothelial cells (p<0.05) in the intimal layer of all smoking groups compared to NC. We also observed increased abundance of the mesenchymal markers N-cadherin (p<0.05) and vimentin (p<0.001) in all smoking groups and across all arterial sizes versus NC, except for N-cadherin in large arteries in COPD-CS. The abundance of S100A4 correlated with arterial thickness (small: r=0.29, p=0.05; medium: r=0.33, p=0.03; large: r=0.35, p=0.02). Vimentin in the small arterial wall negatively correlated with forced expiratory volume in 1 s/forced vital capacity (r= -0.35, p=0.02) and forced expiratory flow rate at 25-75% of forced vital capacity (r= -0.34, p=0.03), while increased cytoplasmic CD31 abundance in the intimal layer of medium and large arteries negatively correlated with predicted diffusing capacity of the lung for carbon monoxide (medium: r= -0.35, p=0.04; large: r= -0.39, p=0.03). Conclusion: This is the first study showing the acquisition of mesenchymal traits by pulmonary endothelial cells from NLFS, SAD and mild-moderate COPD patients through EndMT. This informs on the potential early origins of pulmonary hypertension in smokers and patients with early COPD.

Differential expression of mast cells in the small airways and alveolar septa of current smokers and patients with small airway disease and COPD.

Background: COPD patients suffer from dysregulated and suppressed immune functionality, determined by their loss of degranulating capacity. Here we provide crucial information on the presence of degranulated mast cells (MCs) in COPD airways and demonstrate their relationship to lung physiology and airway remodelling. Methods: Small airway lung resections from non-smoking controls (NC), normal lung function smokers (NLFS), small airway disease (SAD), and mild-to-moderate COPD current smokers (COPD-CS) and ex-smokers (COPD-ES) were dual immuno-stained with MC tryptase and degranulation marker lysosome-associated membrane protein (LAMP)-1. Total MCs, degranulating MCs and non-MCs were enumerated in small airway epithelium and subepithelium, and in alveolar septa. Results: In the small airway wall subepithelial areas, COPD-CS and COPD-ES patients had significantly lower MCs than the NC group (p<0.05), although the numbers were considerably higher in the small airway epithelium (p<0.01). Degranulating non-MCs were higher in SAD (p<0.05) than in COPD in the small airway subepithelium. In contrast, there were significant increases in total MCs (degranulated and non-degranulated) and degranulated non-MCs in the alveolar septum of COPD patients compared with the NC group (p<001). The lower numbers of MCs in the subepithelium correlated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (FEF25-75%), higher smoking rates in COPD patients, and increased small airway wall thickness and extracellular matrix. The increase in MCs in the alveolar septum negatively correlated with FEF25-75%. Conclusions: This study is the first to assess the differential pattern of MC, degranulating MC and non-MC populations in the small airways and alveoli of COPD patients. The spatial positioning of the MCs within the airways showed variable correlations with lung function.

Platelet Activating Factor Receptor and Intercellular Adhesion Molecule-1 Expression Increases in the Small Airway Epithelium and Parenchyma of Patients with Idiopathic Pulmonary Fibrosis: Implications for Microbial Pathogenesis.

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible lung fibrotic disorder of unknown cause. It has been reported that bacterial and viral co-infections exacerbate disease pathogenesis. These pathogens use adhesion molecules such as platelet activating factor receptor (PAFR) and intercellular adhesion molecule-1 (ICAM-1) to gain cellular entry, causing infections. Methods: Immunohistochemical staining was carried out for lung resections from IPF patients (n = 11) and normal controls (n = 12). The quantification of PAFR and ICAM-1 expression is presented as a percentage in the small airway epithelium. Also, type 2 pneumocytes and alveolar macrophages were counted as cells per mm2 of the parenchymal area and presented as a percentage. All image analysis was done using Image Pro Plus 7.0 software. Results: PAFR expression significantly increased in the small airway epithelium (p < 0.0001), type 2 pneumocytes (p < 0.0001) and alveolar macrophages (p < 0.0001) compared to normal controls. Similar trend was observed for ICAM-1 expression in the small airway epithelium (p < 0.0001), type 2 pneumocytes (p < 0.0001) and alveolar macrophages (p < 0.0001) compared to normal controls. Furthermore, the proportion of positively expressed type 2 pneumocytes and alveolar macrophages was higher in IPF than in normal control. Conclusions: This is the first study to show PAFR and ICAM-1 expression in small airway epithelium, type 2 pneumocytes and alveolar macrophages in IPF. These findings could help intervene microbial impact and facilitate management of disease pathogenesis.

A National Survey of Perceptions Around Conditions Associated With Pharmacy Faculty Workload Equity.

OBJECTIVE: To assess pharmacy faculty members' perceptions of conditions associated with workload equity and factors that can improve workload equity. METHODS: A 26-item survey instrument was developed and distributed via email to members of the American Association of Colleges of Pharmacy Council of Faculties. Questions pertained to the workload distribution, fairness in assignment, and perception of the conditions associated with workload equity (transparency, context, credit, clarity, norms, and accountability) as well as institutional and individual demographics. RESULTS: A total of 662 responses were obtained (response rate 15.9%). Respondents' demographics were comparable to available national data. Approximately 41% of respondents reported their institutions did not have a written faculty workload policy. Most respondents reported their workload assignment was fair (highest with research/scholarship) but reported only moderate alignment between assigned and actual workloads. The rating level for what domains the primary decision maker uses to assign workload was highest for context, followed by credit, clarity, and transparency. Transparency was reported as the most needed condition to improve faculty perception of workload equity. Respondents also rated increasing trust between leadership and faculty and increasing productivity and accountability as the most important reasons to minimize workload inequities. CONCLUSION: This was the first national survey of pharmacy faculty perceptions around the conditions associated with workload equity. Though additional research is needed in this area, programs can work to implement strategies associated with all of the conditions, particularly transparency, to improve faculty perceptions of equity.

Combining benefits of an adrenergic and a muscarinic blocker in a single formulation - a pharmacokinetic evaluation.

A pharmacokinetic bioequivalence study was conducted in Asian subjects, to compare a fixed dose combination capsule single oral dose of alpha adrenoceptor blocker-Alfuzosin hydrochloride 10mg extended release and muscarinic antagonists-Solifenacin succinate 5mg against individually administered Xatral XL 10mg tablets (Alfuzosin) of Sanofi Synthelabo Limited, United Kingdom (UK) and Vesicare 5mg tablets (Solifenacin) of Astellas Pharma Limited, UK under fed conditions. Blood samples were collected pre-dose up to 72 h post dose for determination of plasma Alfuzosin and Solifenacin concentrations and calculation of the pharmacokinetic parameters. ANOVA was performed on the log (natural)-transformed pharmacokinetic parameters. A 90% confidence interval for the ratios of the test and reference product averages (least square means) were calculated for alfuzosin and solifenacin. The 90% confidence intervals obtained for alfuzosin for Cmax, AUC0-t and AUC0-∞ were 102.74-122.75%, 95.84-116.96% and 95.82-116.76%, respectively. The 90% confidence intervals obtained for Solifenacin for Cmax, and AUC0-72 were 89.55-97.91% and 90.47-99.38%, respectively. Based on the results, the fixed dose combination was concluded to be bioequivalent to individually administered products.

Impact of Inhaled Epoprostenol in Patients on COVID-19 Acute Respiratory Distress Syndrome (ARDS).

Background: Coronavirus disease 2019 (COVID-19), a novel respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can progress to critical illness and the development of acute respiratory distress syndrome (ARDS). Variability in clinical presentation has led to 2 distinct theoretical classifications of COVID-19 ARDS based on different phenotypical presentations. The first of which follows closely to traditional ARDS presenting as severe hypoxemia with markedly reduced lung compliance, whereas the second presents as severe hypoxemia with preserved to high lung compliance. With uncertainty surrounding the specific pathological and mechanistic nature of COVID-19, we designed this study to elucidate the potential benefits of inhaled epoprostenol in COVID-19 ARDS. Methods: This was a retrospective, observational, cohort study conducted at a 425-bed teaching hospital. Chart reviews of patients' electronic medical records were conducted and the following data were documented on a password-protected spreadsheet: patient demographics, administration of intravenous fluids and/or corticosteroids, rate and duration of inhaled epoprostenol (0.01-0.05 mcg/kg/min over 7 mL/hr per dose), and ventilator settings while on inhaled epoprostenol, mortality, and intensive care unit (ICU) length of stay (LOS). The primary objective was to evaluate the effect of inhaled epoprostenol on the number of ventilator-free days in COVID-19 patients. Secondary objectives included assessing the effects on ventilator settings, mortality, and ICU LOS. Results: Over the span of 8 months, the charts of 848 patients diagnosed with COVID-19 were reviewed for inclusion in the study. Of those patients, 40 patients (intervention arm) who received at least 1 dose of inhaled epoprostenol (0.01-0.05 mcg/kg/min over 7 mL/hr per dose) were randomly selected for entry into the study. In the control arm, 40 patients with a diagnosis of COVID-19 who did not receive epoprostenol were randomly selected. There were no statistically significant differences in outcomes between the epoprostenol and control arms, in regard to ventilator-free days, ICU LOS, hospital LOS, and in-hospital mortality. Based on maximum ventilator settings during the first 3 days of inhaled epoprostenol use, there were no statistically significant differences between the 2 groups except for an unexpectedly lower oxygen saturation in the epoprostenol group. Conclusion: The use of inhaled epoprostenol did not have a statistically significant effect on ventilator-free days, ventilator settings, hospital and ICU LOS, and overall in-hospital mortality.

Gaps and Opportunities for Faculty Workload Policies in Pharmacy and Health Professions Education.

Faculty workload is difficult to delineate and quantify equitably because of the various factors and diverse roles that define faculty positions. This is especially true in health professions education, including pharmacy. Nonetheless, ensuring fair and transparent distribution of faculty workload is necessary for equity and engagement of the faculty workforce. While it is impossible to develop a uniform policy for all faculty, there can be a guide for how workload is developed and measured, especially for promotion or awarding of tenure, focusing on equity and transparency. Developing clear definitions of workload, setting mutually agreed expectations, and sharing transparent workload assignments and distribution within the institution may be needed. It is imperative to discuss an optimal policy for equitable and transparent workload in each institution and in academic pharmacy as a whole; a lack of this effort can create undue hardship for faculty, decrease productivity, potentially worsen faculty morale, and ultimately impair faculty retention.

F3 peptide functionalized liquid crystalline nanoparticles for delivering Salinomycin against breast cancer.

Salinomycin (Sal) is a potent veterinary antibiotic known to offer significant toxicity to the variety of neoplastic cells. Its therapeutic utility is limited due to its higher lipophilicity (logP 7.5) and poor hydrophilicity. Liquid crystalline nanoparticles (LCNPs) known to offer a suitable delivery platform for these kinds of drugs. The overexpressed nucleolin receptor on the cell surface and cytoplasm, could be selected as a target in cancer therapy. The present study involves the development and characterization of the F3 peptide functionalized LCNPs for delivering Sal (F3-Sal-NPs) for selectively targeting to the nucleolin receptor. The optimized LCNPs were characterized for particle size, zeta potential, surface morphology, drug release kinetics and stability. The LCNPs have a structure similar to nematic phases. In vitro drug release studies revealed sustained drug release characteristics (89.5 ± 1.5% at 120 h) with F3-Sal-NPs. The cytotoxicity results demonstrated that F3-Sal-NPs were 4.8, 2.6 and 5.5 folds more effective than naïve drug in MDA-MB-468, MDA-MB-231 and MCF-7 cells, respectively and the cell cycle was arrested in the S and G2/M phases. The expression of the gene responsible for the stemness (CD44 gene), apoptosis (BAX/Bcl-2 ration) and angiogenesis (LCN-2) was reduced by F3-Sal-NPs treatment. Ex vivo hemolytic toxicity was reduced (6.5 ± 1.5%) and the pharmacokinetics and bioavailability of Sal was improved with F3-Sal-NPs. The in vivo antitumor efficacy was tested in EAC bearing mice, where F3-Sal-NPs significantly reduced the tumor growth by 2.8-fold compared to pure Sal and induced necrosis of tumor cells. The results clearly demonstrate the outstanding performance of F3 peptide functionalized LCNPs for delivering Sal against breast cancer.

"Put me in Coach!" Engaging Faculty to Form a Winning Assessment Team.

This commentary uses the metaphor of an athletic team model to provide guidance when managing a successful assessment committee and assessment processes. To become a winning team, a joint effort must be exerted by players, coaches, and the athletic director. The topics of developing a team of productive members, creating, and implementing an assessment plan, forming a positive culture, and establishing leadership are discussed. Examples and advice are provided to assist with promoting an engaged faculty to form a well-rounded and productive assessment committee with clearly defined roles and responsibilities.

We Must Do Better to Ensure Equity, Transparency, and Clarity in Service Workload.

Assessment of faculty workload is challenging due to the diverse set of definitions and expectations at individual schools/colleges of pharmacy. The service component of faculty workload is complicated to assess and evaluate due to institutional variances in policies and procedures for assigning service commitments and lack of clarity in how service is regarded toward promotion and tenure decisions. This commentary discusses the challenges of service as a component of faculty workload including lack of clear definitions and time dedicated to service. The commentary also presents potential solutions that schools/colleges should consider in defining service expectations. These solutions include strategies on how administrators should: set expectations, engage faculty at all ranks and series, and measure outcomes to ensure equity of service workload to build a culture of collective citizenship.

A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of breast cancer with associated chemoresistance. The development of chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression of membrane proteins (transporters), epigenetic changes, and alteration of the cell signaling pathways/genes associated with the development of cancer stem cells (CSCs). AIM OF REVIEW: Due to the diverse and heterogeneous nature of TNBC, therapeutic response to the existing modalities offers limited scope and thus results in reccurance after therapy. To establish landmark therapeutic efficacy, a number of novel therapeutic modalities have been proposed. In addition, reversal of the resistance that developed during treatment may be altered by employing appropriate therapeutic modalities. This review aims to discuss the plethora of investigations carried out, which will help readers understand and make an appropriate choice of therapy directed toward complete elimination of TNBC. KEY SCIENTIFIC CONCEPTS OF REVIEW: This manuscript addresses the major contributory factors from the tumor microenvironment that are responsible for the development of chemoresistance and poor prognosis. The associated cellular events and molecular mechanism-based therapeutic interventions have been explained in detail. Inhibition of ABC transporters, cell signaling pathways associated with CSCs, and epigenetic modification offers promising results in this regard. TNBC progression, invasion, metastasis and recurrence can also be inhibited by blocking multiple cell signaling pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics and generating reactive oxygen species (ROS).

Perceptions and Practices for Evaluating Faculty Workload by Pharmacy Education Administration/Leadership.

OBJECTIVE: To assess how department chairs/administrators define, measure, and evaluate faculty workload to better understand practices within the Academy. METHODS: An 18-item survey was distributed to department chairs/administrators via American Association of Colleges of Pharmacy Connect. Participants identified if they are a primary decision maker for faculty workload, whether their program has a workload policy, how workload is calculated, and how faculty satisfaction with workload equity is measured. RESULTS: Of 71 participants initiating the survey, data from 64 participants from 52 colleges/schools were eligible for analysis. Leaders of practice departments reported that their faculty spend an average of 38% of their time on teaching (compared to 46% for non-practice departments), 13% on research (vs 37%), 12% on service (vs 16%), and 36% on clinical practice (vs 0%). Most survey participants (n = 57, 89%) are at schools/colleges with a tenure system, and about 24 participants reported that faculty workload metrics differ across departments/divisions. Teaching assignments and service are reportedly negotiable between faculty and supervisors, and workload expectations are widely variable. The majority indicated they do not analyze faculty satisfaction with workload fairness (n = 35) and faculty do not provide evaluative feedback on how supervisors assign faculty workload (n = 34). Of 6 priorities considered when determining workload, 'support college/school strategies and priorities' ranked highest (1.92) and 'trust between the chair and faculty' ranked lowest (4.87). CONCLUSION: Overall, only half of the participants reported having a clear, written process of quantifying faculty workload. The use of workload metrics may be needed for evidence-based decision-making for personnel management and resource allocation.