Leading Across Health Professions: Reflections on Opportunities and Challenges.

Pharmacy leaders are well equipped to serve as academic leaders overseeing additional health profession programs and/or faculty. Organizing multiple health professions programs under one umbrella offers a number of opportunities, such as efficiencies in financial and human resources, expanded and more diverse leadership talent which offers advantages in succession planning, organizational effectiveness in its operations, expanded opportunities for interprofessional education and collaborations in research and scholarship, greater visibility as a partner for establishing pipeline agreements and clinical partners affiliations, and personal professional development and growth for those in senior leadership positions. However, pharmacy academic leaders with oversight over multiple health professions programs and faculty also face challenges in understanding the professional identities and culture of their faculty, complexities of equity of workload across numerous departments, mistrust from departments other than pharmacy, and their own increased workload and possible burnout. AACP has recently established a new Multi-Professional Healthcare Administrative Leaders Connect Community, which should be further promoted to increase membership. Programming to allow additional networking, sharing of best practices, mentorship and professional development of leaders who oversee, or aspire to oversee, multiple health professions programs can be beneficial. Further research can describe different models of organizing multiple health professions programs and identify best practices for successful organizational and operational structures.

Ultrasound Contrast Agents: Current Role in Adults and Children for Various Indications.

Intravenous contrast-enhanced ultrasound (CEUS) is a rapidly evolving imaging technique that uses a microbubble contrast agent to enhance ultrasonographic images by augmenting characterization of blood vessels and organ perfusion. CEUS is considered as a useful problem-solving tool and as an indicated first-line imaging modality in select settings. CEUS technique has an inherent advantage over its predecessor B-mode and Doppler imaging. This article reviews different approved and off-label use of CEUS in the pediatric and adult population and also discusses Food and Drug Administration-approved contrast agents in the United States, their reported side effects, and ongoing efforts in the field.

A congenital periocular leiomyosarcoma in a dairy calf.

A mass was removed surgically from the right orbit of a 1-d-old Holstein calf. Grossly, the mass filled the rostral part of an enlarged orbit and compressed the globe toward the caudal pole of the orbit. The brown, 6-cm tumor had central yellow and brown areas, and a smooth, glistening cut surface. Microscopically, the neoplasm was highly cellular and composed of spindle cells arranged in irregular, broad, interlacing streams and bundles, forming a herringbone pattern and supported by a sparse collagenous matrix. Neoplastic cells infiltrated surrounding soft tissues and compressed the globe. The neoplastic cells had positive immunolabeling for α-smooth muscle actin, desmin, and vimentin, and negative immunolabeling for factor VIII, myoglobin, cytokeratin, and skeletal muscle actin. Histopathology and immunohistochemistry results confirmed a diagnosis of leiomyosarcoma. To our knowledge, congenital periocular leiomyosarcoma has not been reported in cattle previously. This rare tumor could be included as a differential diagnosis in newborn calves with periocular masses.

Photodynamic therapy with Photoditazine increases microviscosity of cancer cells membrane in cellulo and in vivo.

Photodynamic therapy (PDT) is a minimally invasive method for cancer treatment, one of the effects of which is the oxidation of membrane lipids. However, changes in biophysical properties of lipid membranes during PDT have been poorly explored. In this work, we investigated the effects of PDT on membrane microviscosity in cancer cells in the culture and tumor xenografts. Membrane microviscosity was visualized using fluorescence lifetime imaging microscopy (FLIM) with a viscosity-sensitive rotor BODIPY2. It was found that PDT using chlorine e6-based photosensitizer Photoditazine caused a quick, steady elevation of membrane microviscosity both in cellulo and in vivo. The proposed mechanisms responsible for the increase in microviscosity was lipid peroxidation by reactive oxygen species that resulted in a decrease of phosphatidylcholine and the fraction of unsaturated fatty acids in the membranes. Our results suggest that the increased microviscosity is an important factor that contributes to tumor cell damage during PDT.

Age-associated clonal B cells drive B cell lymphoma in mice.

Although cancer is an age-related disease, how the processes of aging contribute to cancer progression is not well understood. In this study, we uncovered how mouse B cell lymphoma develops as a consequence of a naturally aged system. We show here that this malignancy is associated with an age-associated clonal B cell (ACBC) population that likely originates from age-associated B cells. Driven by c-Myc activation, promoter hypermethylation and somatic mutations, IgM+ ACBCs clonally expand independently of germinal centers and show increased biological age. ACBCs become self-sufficient and support malignancy when transferred into young recipients. Inhibition of mTOR or c-Myc in old mice attenuates pre-malignant changes in B cells during aging. Although the etiology of mouse and human B cell lymphomas is considered distinct, epigenetic changes in transformed mouse B cells are enriched for changes observed in human B cell lymphomas. Together, our findings characterize the spontaneous progression of cancer during aging through both cell-intrinsic and microenvironmental changes and suggest interventions for its prevention.

Kazakhstan Has an Unexpected Diversity of Medicinal Plants of the Genus Acorus (Acoraceae) and Could Be a Cradle of the Triploid Species A. calamus.

The Acorus calamus group, or sweet flag, includes important medicinal plants and is classified into three species: A. americanus (diploid), A. verus (tetraploid), and A. calamus (sterile triploid of hybrid origin). Members of the group are famous as components of traditional Indian medicine, and early researchers suggested the origin of the sweet flag in tropical Asia. Subsequent research led to an idea of the origin of the triploid A. calamus in the Amur River basin in temperate Asia, because this was the only region where both diploids and tetraploids were known to co-occur and be capable of sexual reproduction. Contrary to this hypothesis, triploids are currently very rare in the Amur basin. Here, we provide the first evidence that all three species occur in Kazakhstan. The new records extend earlier data on the range of A. verus for c. 1800 km. Along the valley of the Irtysh River in Kazakhstan and the adjacent Omsk Oblast of Russia, A. verus is recorded in the south, A. americanus in the north, and A. calamus is common in between. We propose the Irtysh River valley as another candidate for a cradle of the triploid species A. calamus. It is possible that the range of at least one parent species (A. americanus) has contracted through competition with its triploid derivative species, for which the Irtysh River floods provide a tool for downstream range expansion. We refine our earlier data and show that the two parent species have non-overlapping ranges of variation in a quantitative metric of leaf aerenchyma structure.

Conventional and Contrast-enhanced US of the Lung: From Performance to Diagnosis.

In recent years, lung US has evolved from a marginal tool to an integral component of diagnostic chest imaging. Contrast-enhanced US (CEUS) can improve routine gray-scale imaging of the lung and chest, particularly in diagnosis of peripheral lung diseases (PLDs). Although an underused tool in many centers, and despite inherent limitations in evaluation of central lung disease caused by high acoustic impedance between air and soft tissues, lung CEUS has emerged as a valuable tool in diagnosis of PLDs. Owing to the dual arterial supply to the lungs via pulmonary and bronchial (systemic) arteries, different enhancement patterns can be observed at lung CEUS, thereby enabling accurate differential diagnoses in various PLDs. Lung CEUS also assists in identifying patients who may benefit from complementary diagnostic tests, including image-guided percutaneous biopsy. Moreover, lung CEUS-guided percutaneous biopsy has shown feasibility in accessible subpleural lesions, enabling higher histopathologic performance without significantly increasing either imaging time or expenses compared with conventional US. The authors discuss the technique of and basic normal and pathologic findings at conventional lung US, followed by a more detailed discussion of lung CEUS applications, emphasizing specific aspects of pulmonary physiology, basic concepts in lung US enhancement, and the most commonly encountered enhancement patterns of different PLDs. Finally, they discuss the benefits of lung CEUS in planning and guidance of US-guided lung biopsy. ©RSNA, 2024 Supplemental material is available for this article.

Renal bleeding: imaging and interventions in patients with tumors.

In patients with cancer, spontaneous renal bleeding can stem from a range of underlying factors, necessitating precise diagnostic tools for effective patient management. Benign and malignant renal tumors are among the primary culprits, with angiomyolipomas and renal cell carcinomas being the most common among them. Vascular anomalies, infections, ureteral obstructions, and coagulation disorders can also contribute to renal-related bleeding. Cross-sectional imaging techniques, particularly ultrasound and computed tomography (CT), play pivotal roles in the initial detection of renal bleeding. Magnetic resonance imaging and CT are preferred for follow-up evaluations and aid in detecting underlying enhancing masses. IV contrast-enhanced ultrasound can provide additional information for active bleeding detection and differentiation. This review article explores specific disorders associated with or resembling spontaneous acute renal bleeding in patients with renal tumors; it focuses on the significance of advanced imaging techniques in accurately identifying and characterizing renal bleeding in these individuals. It also provides insights into the clinical presentations, imaging findings, and treatment options for various causes of renal bleeding, aiming to enhance the understanding, diagnosis, and management of the issue.

A Deeper Reflection on the Integration of the Pharmacists' Patient Care Process.

OBJECTIVE: Given the importance of developing student understanding and application of the Pharmacists' Patient Care Process (PPCP), programs may be able to use successful approaches from other institutions to enhance their curricular and experiential learning and assessment of student outcomes. The study objective was to explore successful methods of integrating the PPCP and outline areas of challenge. METHODS: This study used a qualitative study design with semistructured interviews to gain insight from participants' lived experiences. Pharmacy faculty members participating in a national survey or who were authors of articles about PPCP initiatives were recruited to provide greater detail about building successful and innovative curricula. Thematic analysis identified commonalities and differences among the interviewed participants. RESULTS: A total of 10 interviews were conducted. The following 4 overarching themes arose from the data: discussions around intentional integration of the PPCP across multiple core courses may foster innovations in teaching strategies; intentional integration alone does not equate to PPCP integration across the curriculum; intentional integration may enhance program assessment; and PPCP data from experiential coursework may not be widely used in curricular continuous quality improvement. CONCLUSION: Pharmacy programs will ideally involve the entire faculty, including experiential and basic and social/administrative science members, in weaving the PPCP throughout the curriculum. Rigorous assessment can better inform interventions related to student competency in various steps of the PPCP. Pharmacy programs should also clarify how data obtained from preceptors observing student performance in each of the PPCP steps are used to assess student mastery of this critical skill.

Ultrasound evaluation of portal venous gas and its mimics.

Portal venous gas on abdominal ultrasound classically represents an indirect indicator of bowel ischemia, a critical condition which poses a high patient mortality and therefore warrants emergent corrective action. While the classic appearance of portal venous gas on ultrasound is well-described in the literature, the characteristic descriptors are nonspecific and may actually represent other less emergent mimics. Therefore, while radiologists should remain vigilant for the detection of findings corresponding to portal venous gas, they should also be aware of similar-appearing entities in order to provide the most accurate diagnosis. This pictorial essay will open with imaging examples of true portal venous gas attributable to bowel ischemia and describe the classic features which should alert radiologists to this specific diagnosis. Subsequently, this pictorial essay will provide imaging examples of other various other clinical entities which on ultrasound may share similar imaging characteristics. An important objective of this pictorial essay is to highlight distinguishing imaging features along with specific clinical circumstances for each pathological entity which can direct radiologists into identifying the correct diagnosis.

Multimodality Imaging of Postmastectomy Breast Reconstruction Techniques, Complications, and Tumor Recurrence.

For women undergoing mastectomy, breast reconstruction can be performed by using implants or autologous tissue flaps. Mastectomy options include skin- and nipple-sparing techniques. Implant-based reconstruction can be performed with saline or silicone implants. Various autologous pedicled or free tissue flap reconstruction methods based on different tissue donor sites are available. The aesthetic outcomes of implant- and flap-based reconstructions can be improved with oncoplastic surgery, including autologous fat graft placement and nipple-areolar complex reconstruction. The authors provide an update on recent advances in implant reconstruction techniques and contemporary expanded options for autologous tissue flap reconstruction as it relates to imaging modalities. As breast cancer screening is not routinely performed in this clinical setting, tumor recurrence after mastectomy and reconstruction is often detected by palpation at physical examination. Most local recurrences occur within the skin and subcutaneous tissue. Diagnostic breast imaging continues to have a critical role in confirmation of disease recurrence. Knowledge of the spectrum of benign and abnormal imaging appearances in the reconstructed breast is important for postoperative evaluation of patients, including recognition of early and late postsurgical complications and breast cancer recurrence. The authors provide an overview of multimodality imaging of the postmastectomy reconstructed breast, as well as an update on screening guidelines and recommendations for this unique patient population. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Irreversible inhibition of estrogen receptor α signaling and the emergence of hormonal resistance in MCF7 breast cancer cells induced by DNA damage agents.

Combining chemotherapy and hormone therapy is a prevalent approach in breast cancer treatment. While the cytotoxic impact of numerous chemotherapy drugs stems from DNA damage, the exact role of these DNA alterations in modulating estrogen receptor α (ERα) machinery remains elusive. The present study aimed to analyze the impact of DNA damage agents on ERα signaling in breast cancer cells and assess the signaling pathways mediating the influence of DNA damage drugs on the ERα machinery. Cell viability was assessed using the MTT method, while the expression of signaling proteins was analyzed by immunoblotting. ERα activity in the cells treated with various drugs (17ß-estradiol, tamoxifen, 5-fluorouracil) was assessed through reporter gene assays. In vitro experiments were conducted on MCF7 breast cancer cells subjected to varying durations of 5-fluorouracil (5-FU) treatment. Two distinct cell responses to 5-FU were identified based on the duration of the treatment. A singular dose of 5-FU induces pronounced DNA fragmentation, temporally suppressing ERα signaling while concurrently activating AKT phosphorylation. This suppression reverses upon 5-FU withdrawal, restoring normalcy within ten days. However, chronic 5-FU treatment led to the emergence of 5-FU-resistant cells with irreversible alterations in ERα signaling, resulting in partial hormonal resistance. These changes mirror those observed in cells subjected to UV-induced DNA damage, underscoring the pivotal role of DNA damage in shaping estrogen signaling alterations in breast cancer cells. In summary, the results of the present study suggested that the administration of DNA damage agents to cancer cells can trigger irreversible suppression of estrogen signaling, fostering the development of partial hormonal resistance. This outcome may ultimately impede the efficacy of combined or subsequent chemo- and hormone therapy strategies.

The Determination of the Biocompatibility of New Compositional Materials, including Carbamide-Containing Heterocycles of Anti-Adhesion Agents for Abdominal Surgery.

Due to traumatic injuries, including those from surgical procedures, adhesions occur in over 50% of cases, necessitating exclusive surgical intervention for treatment. However, preventive measures can be implemented during abdominal organ surgeries. These measures involve creating a barrier around internal organs to forestall adhesion formation in the postoperative phase. Yet, the effectiveness of the artificial barrier relies on considerations of its biocompatibility and the avoidance of adverse effects on the body. This study explores the biocompatibility aspects, encompassing hemocompatibility, cytotoxicity, and antibacterial and antioxidant activities, as well as the adhesion of blood serum proteins and macrophages to the surface of new composite film materials. The materials, derived from the sodium salt of carboxymethylcellulose modified by glycoluril and allantoin, were investigated. The research reveals that film materials with a heterocyclic fragment exhibit biocompatibility comparable to commercially used samples in surgery. Notably, film samples developed with glycoluril outperform the effects of commercial samples in certain aspects.

Evaluation of Inactivation Methods for Rift Valley Fever Virus in Mouse Microglia.

Rift Valley fever phlebovirus (RVFV) is a highly pathogenic mosquito-borne virus with bioweapon potential due to its ability to be spread by aerosol transmission. Neurological symptoms are among the worst outcomes of infection, and understanding of pathogenesis mechanisms within the brain is limited. RVFV is classified as an overlap select agent by the CDC and USDA; therefore, experiments involving fully virulent strains of virus are tightly regulated. Here, we present two methods for inactivation of live virus within samples derived from mouse microglia cells using commercially available kits for the preparation of cells for flow cytometry and RNA extraction. Using the flow cytometry protocol, we demonstrate key differences in the response of primary murine microglia to infection with fully virulent versus attenuated RVFV.

Audiogenic kindling activates glutamatergic system in the hippocampus of rats with genetic predisposition to audiogenic seizures.

Temporal lobe epilepsy (TLE) development is associated with dysregulation of glutamatergic transmission in the hippocampus; however, detailed molecular mechanisms of pathological changes are still poorly understood. In the present study, we performed the complex analysis of glutamatergic system in the hippocampus of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). Daily AGS stimulations (audiogenic kindling) were used to reproduce the dynamics of TLE development. Naïve KM rats were used as a control. After 14 AGS, at the stage of developing TLE, KM rats demonstrated significant upregulation of extracellular signal-regulated kinases (ERK) 1 and 2, cAMP response element-binding protein (CREB), and c-Fos in the hippocampus indicating activation of the hippocampal cells. These changes were accompanied with an increase in glutaminase and vesicular glutamate transporter (VGLUT) 2 suggesting the activation of glutamate production and loading into the synaptic vesicles. After 21 AGS, when TLE was fully-established, alterations were similar but more pronounced, with higher activation of glutaminase, increase in glutamate production, upregulation of VGLUT1 and 2, and Fos-related antigen 1 (Fra-1) along with c-Fos. Analysis of glutamate receptors showed variable changes. Thus, after 14 AGS, simultaneous increase in metabotropic glutamate receptor mGluR1 and decrease in ionotropic N-methyl-D-aspartate (NMDA) receptors could reflect compensatory anti-epileptic mechanism, while further kindling progression induced upregulation of ionotropic receptors, probably, contributing to the hippocampal epileptization. However, we revealed practically no alterations in the expression of synaptic proteins. Altogether, obtained results suggested that overactivation of glutamate production in the hippocampus strongly contributed to TLE development in KM rats.

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.

TIME-seq reduces time and cost of DNA methylation measurement for epigenetic clock construction.

Epigenetic 'clocks' based on DNA methylation have emerged as the most robust and widely used aging biomarkers, but conventional methods for applying them are expensive and laborious. Here we develop tagmentation-based indexing for methylation sequencing (TIME-seq), a highly multiplexed and scalable method for low-cost epigenetic clocks. Using TIME-seq, we applied multi-tissue and tissue-specific epigenetic clocks in over 1,800 mouse DNA samples from eight tissue and cell types. We show that TIME-seq clocks are accurate and robust, enriched for polycomb repressive complex 2-regulated loci, and benchmark favorably against conventional methods despite being up to 100-fold less expensive. Using dietary treatments and gene therapy, we find that TIME-seq clocks reflect diverse interventions in multiple tissues. Finally, we develop an economical human blood clock (R > 0.96, median error = 3.39 years) in 1,056 demographically representative individuals. These methods will enable more efficient epigenetic clock measurement in larger-scale human and animal studies.

Electrospinning of biomimetic materials with fibrinogen for effective early-stage wound healing.

Electrospun biomimetic materials based on polyester of natural origin poly-3-hudroxybutyrate (PHB) modified with hemin (Hmi) and fibrinogen (Fbg) represent a great interest and are potentially applicable in various fields. Here, we describe formulation of the new fibrous PHB-Fbg and PHB-Hmi-Fbg materials with complex structure for biomedical application. The average diameter of the fibers was 3.5 µm and 1.8 µm respectively. Hmi presence increased porosity from 80 % to 94 %, significantly reduced the number of defects, ensured the formation of a larger number of open pores, and improved mechanical properties. Hmi presence significantly improved the molding properties of the material. Hmi facilitated effective Fbg adsorption on the of the PHB wound-healing material, ensuring uniform localization of the protein on the surface of the fibers. Next, we evaluated cytocompatibility, cell behavior, and open wound healing in mice. The results demonstrated that PHB-Fbg and PHB-Hmi-Fbg electrospun materials had pronounced properties and may be promising for early-stage wound healing - the PHB-Hmi-Fbg sample accelerated wound closure by 35 % on the 3rd day, and PHB-Hmi showed 45 % more effective wound closure on the 15th day.