Liquid-like condensates that bind actin drive filament polymerization and bundling.

Liquid-like protein condensates perform diverse physiological functions. Previous work showed that VASP, a processive actin polymerase, forms condensates that polymerize and bundle actin. To minimize their curvature, filaments accumulated at the inner condensate surface, ultimately deforming the condensate into a rod-like shape, filled with a bundle of parallel filaments. Here we show that this behavior does not require proteins with specific polymerase activity. Specifically, we found that condensates composed of Lamellipodin, a protein that binds actin but is not an actin polymerase, were also capable of polymerizing and bundling actin filaments. To probe the minimum requirements for condensate-mediated actin bundling, we developed an agent-based computational model. Guided by its predictions, we hypothesized that any condensate-forming protein that binds actin could bundle filaments through multivalent crosslinking. To test this idea, we added an actin-binding motif to Eps15, a condensate-forming protein that does not normally bind actin. The resulting chimera formed condensates that drove efficient actin polymerization and bundling. Collectively, these findings broaden the family of proteins that could organize cytoskeletal filaments to include any actin-binding protein that participates in protein condensation.

Intercostal artery aneurysm presenting as a spontaneous hemothorax in a patient with neurofibromatosis.

Beyond the commonly known clinical presentation of neurofibromatosis, vascular pathologies are increasingly becoming a known complication. We present a case of a 41-year-old adult with neurofibromatosis type 1 who came with a right-sided spontaneous hemothorax due to a ruptured 13-mm fusiform aneurysm of the right posterior T9 intercostal artery. Patient underwent a transcatheter angiographic embolization with subsequent video-assisted thoracic surgery (VATS) for a retained hemothorax. Patient was discharged home on Hospital Day 5, and follow-up imaging demonstrated a complete resolution of the hemothorax. This presented case contributes to literature by demonstrating intra-arterial embolization as a viable option to obtain hemostasis in fragile vessels. However, this may not always result in hemostasis, and VATS should be considered to achieve and ensure complete hemostasis.

Interprofessional Education and Older Adults in the Shared Virtual Classroom: Lessons Learned During the COVID-19 Pandemic.

The current article provides an overview of an interprofessional service-learning course that became virtual in the setting of the coronavirus disease 2019 pandemic. Telehealth video technologies were used to build an intergenerational, virtual classroom and increase engagement of older adults with interdisciplinary health professional students. The virtual classroom involved group health education sessions, individualized Medicare wellness visits, and a clinical huddle. The course addressed the public health need for reliable health information during the early days of the pandemic, social connection, and meeting the educational goals for health care students and older adults in a novel virtual setting. Lessons learned for the interdisciplinary team and for engaging older adults included the need for preparation reading, team building exercises, training videos, and telehealth competency checklists. Beyond the pandemic, adoption of virtual methods enables hybrid approaches to interprofessional education and builds competencies for delivery of telehealth and computer-based visits in professional practice settings. [Journal of Gerontological Nursing, 48(8), 52-56.].

Senior Care Pharmacists, Audiologists, and Otologists: Improving Hearing Health for Older Patients Through Interprofessional Collaboration.

The purpose of this manuscript is to provide pharmacists with education on hearing loss that colleagues in audiology believe is most critical for pharmacists. As well as highlighting insightful interventions pharmacists can make in collaboration with hearing professionals, such as audiologists, otolaryngologists, and otologists, to improve patient care. This project was initiated by professional students at the University of Maryland in both Baltimore and College Park campuses, after completing the interprofessional elective course IPE Care in Geriatrics. Upon completion of the course, the authors performed an extensive literature search and reviewed publications pertaining to pharmacy, audiology, and their integration.Hearing loss can have a significant impact on a patient's quality of life. Older people are at an increased risk for experiencing hearing impairment, but often do not seek help from health care providers. Collaboration between audiologists, otolaryngologists, and pharmacists has the potential to improve patients' access to hearing health and break barriers for patients. Important interventions that pharmacists can make to better serve their patients with hearing loss include screening, enhancing communication, and hearing aid assistance. This article also provides guidance on identifying patients who would be candidates for over-the-counter hearing aids and patients who should be referred to a hearing professional. This skill will become increasingly relevant with the emergence of over-the-counter hearing aids.

Postinduction therapy pulmonary function retesting is necessary before surgical resection for non-small cell lung cancer.

OBJECTIVE: Pretreatment-predicted postoperative diffusing capacity of the lung for carbon monoxide (DLCO) has been associated with operative mortality in patients who receive induction therapy for resectable non-small cell lung cancer (NSCLC). It is unknown whether a reduction in pulmonary function after induction therapy and before surgery affects the risk of morbidity or mortality. We sought to determine the relationship between induction therapy and perioperative outcomes as a function of postinduction pulmonary status in patients who underwent surgical resection for NSCLC. METHODS: We retrospectively reviewed data for 1001 patients with pathologic stage I, II, or III NSCLC who received induction therapy before lung resection. Pulmonary function was defined according to American College of Surgeons Oncology Group major criteria: DLCO ≥50% = normal; DLCO <50% = impaired. Patients were categorized into 5 subgroups according to combined pre- and postinduction DLCO status: normal-normal, normal-impaired, impaired-normal, impaired-impaired, and preinduction only (without postinduction pulmonary function test measurements). Multivariable logistic regression was used to quantify the relationship between DLCO categories and dichotomous end points. RESULTS: In multivariable analysis, normal-impaired DLCO status was associated with an increased risk of respiratory complications (odds ratio, 2.29 [95% CI, 1.12-4.49]; P = .02) and in-hospital complications (odds ratio, 2.83 [95% CI, 1.55-5.26]; P < .001). Type of neoadjuvant therapy was not associated with an increased risk of complications, compared with conventional chemotherapy. CONCLUSIONS: Reduced postinduction DLCO might predict perioperative outcomes. The use of repeat pulmonary function testing might identify patients at higher risk of morbidity or mortality.

Assessment of histological characteristics, imaging markers, and rt-PA susceptibility of ex vivo venous thrombi.

Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ, which prohibits mechanistic investigation of lytic resistance or the development of diagnostic indicators for treatment outcomes. In this study, thrombus samples extracted from venous thromboembolism patients were analyzed ex vivo to determine their histological properties, susceptibility to lytic therapy, and imaging characteristics. A wide range of thrombus morphologies were observed, with a dependence on age and etymology of the specimen. Fibrinolytic inhibitors including PAI-1, alpha 2-antiplasmin, and TAFI were present in samples, which may contribute to the response venous thrombi to catheter-directed thrombolytics. Finally, a weak but significant correlation was observed between the response of the sample to lytic drug and its magnetic microstructure assessed with a quantitative MRI sequence. These findings highlight the myriad of changes in venous thrombi that may promote lytic resistance, and imaging metrics that correlate with treatment outcomes.

Identifying and Bridging the Gaps in Antimicrobial Stewardship in Post-Acute and Long-Term Care.

National organizations have developed guidelines and tools for antimicrobial stewardship (AMS) in post-acute and long-term care (PALTC), but there is a need to effectively translate these into actionable, measurable, and impactful programs. An electronic needs assessment survey was developed and distributed to health care providers and administrators involved with AMS activities in PALTC facilities in Maryland. The results of this survey were used to develop a statewide initiative to improve AMS in nursing facilities. The survey revealed that barriers to implementing AMS include limited access or poor utilization of experts in AMS and infectious disease, adverse event data collection tools, and locally developed protocols and guidelines. Strategies to improve AMS included the provision of free continuing education to a multidisciplinary audience and improved access to individuals with expertise in infectious disease and the development of an adverse drug event tool. Continuing to provide meaningful tools and resources that address the specific needs of nursing facilities should lead to improved compliance with regulations and ultimately improved resident outcomes. [Journal of Gerontological Nursing, 46(1), 8-13.].

Students' perceptions of interprofessional education in geriatrics: A qualitative analysis.

Interprofessional education (IPE) is critical for ensuring that students are prepared to collaborate with team members across disciplines once they enter clinical practice; particularly, in the complex care of the geriatric population. This qualitative study explored the experiences of interdisciplinary students in a clinical based IPE experience at a senior housing residence. Reflective journals were examined from students (n = 23) in nursing, social work, pharmacy, and medicine participating in an IPE program. Four core themes emerged in the analysis: exposure to geriatrics, IPE advantages for students, IPE advantages for older adults, and IPE challenges. Findings from this study confirmed advantages of IPE in a real-world clinical setting in terms of students learning the value and scope of practice of interdisciplinary team members. The exposure to geriatrics helped students to gain an in-depth understanding of issues affecting older adults in the community and increase professional confidence in their future clinical practice.

Long-Term Results After Lung Volume Reduction Surgery: A Single Institution's Experience.

BACKGROUND: The National Emphysema Treatment Trial (NETT) showed a clear survival and quality of life benefit for patients selected for lung volume reduction surgery (LVRS). However, long-term outcomes after LVRS are still lacking. The aim of this study was to evaluate overall mortality and functional durability in this single-institution cohort of patients undergoing LVRS. METHODS: A single-institution registry identified all patients who had undergone LVRS from January 2006 through August 2017. Records were retrospectively reviewed, and data were collected to include pulmonary functions test values, he University of California, San Diego shortness of breath questionnaire and complication and mortality rate. RESULTS: LVRS was performed in 135 patients with a 2.2% 90-day mortality rate (n = 3). Estimated 1-, 2- and 5-year survival was 0.94 (95% confidence interval [CI], 0.88 to 0.97), 0.91 (95% CI, 0.83 to 0.95), and 0.71 (95% CI, 0.57 to 0.81), respectively. Mean improvement in forced expiratory volume in 1 second% predicted from preoperative baseline at 1 and 2 years was 5.3 (95% CI, 3.1 to 7.4) and 4.3 (95% CI, 1.9 to 6.6), respectively. There was a mean improvement in maximum workload of 5.2 W (95% CI, 0.9 to 9.4) at 1 year. Also, shortness of breath questionnaire scores had a mean decrease of -17.3 points (95% CI, -21.8 to -13) at 6 months and -13.9 points (95% CI, -18.4 to -9.3) at 1 year. CONCLUSIONS: LVRS is an effective operation with overall improvement in functional status and quality of life in appropriately selected patients.

Robotic Resection of Ectopic Parathyroid Glands in the Superior Posterior Mediastinum.

Background: Ectopic parathyroid glands can present in a challenging location in the superior posterior mediastinum. Methods: Two patients with primary hyperparathyroidism were operated on for ectopic paraesophageal parathyroid glands in the superior posterior mediastinum. Sestamibi scan, computed tomography (CT) scan, and photon emission CT were used to identify the exact location of these glands. We describe a minimally invasive resection using a three-arm robotic-assisted thoracoscopic technique. Results: Both lesions were completely resected with using the port-based robotic approach with expedited recovery. There was no perioperative morbidity. Patient had low postoperative pain scores and improved symptomatically. Conclusion: Robotic approach for resection of superior posterior mediastinal parathyroids is safe and effective in this challenging operative location.

How Consultant Pharmacists Gained Access to Maryland's Health Information Exchange.

The Chesapeake Regional Information System for our Patients (CRISP) is a health information exchange in Maryland that is designed to improve communication among members of the health care team including physicians, nurses, and other health professionals. Senior care pharmacists gained access to CRISP through successful collaborative efforts at both the state and national levels. This involved efforts to address medication-related problems that continue to be a concern during transitions of care, especially for older, vulnerable adults. Having access to recent clinical data assists the senior care pharmacist in providing medication therapy management services during transitions of care-the movement of a patient from one setting of care to another.This article highlights the importance of collaboration and advocacy between state and national leadership of the American Society of Consultant Pharmacists (ASCP) with key stakeholders to negotiate and gain access to such information for senior care pharmacists working in the post-acute and long-term care settings in Maryland.

Overexpression of miR-199a-5p decreases esophageal cancer cell proliferation through repression of mitogen-activated protein kinase kinase kinase-11 (MAP3K11).

Studies examining the oncogenic or tumor suppressive functions of dysregulated microRNAs (miRs) in cancer cells may also identify novel miR targets, which can themselves serve as therapeutic targets. Using array analysis, we have previously determined that miR-199a-5p was the most downregulated miR in two esophageal cancer cell lines compared to esophageal epithelial cells. MiR-199a-5p is predicted to bind mitogen-activated protein kinase kinase kinase 11 (MAP3K11) mRNA with high affinity. In this study, we observed that MAP3K11 is markedly overexpressed in esophageal cancer cell lines. Forced expression of miR-199a-5p in these cells leads to a decrease in the mRNA and protein levels of MAP3K11, due to decreased MAP3K11 mRNA stability. A direct binding interaction between miR-199a-5p and MAP3K11 mRNA is demonstrated using biotin pull-down assays and heterologous luciferase reporter constructs and confirmed by mutational analysis. Finally, forced expression of miR-199a-5p decreases proliferation of esophageal cancer cells by inducing G2/M arrest. This effect is mediated, in part, by decreased transcription of cyclin D1, due to reduced MAP3K11-mediated phosphorylation of c-Jun. These findings suggest that miR-199a-5p acts as a tumor suppressor in esophageal cancer cells and that its downregulation contributes to enhanced cellular proliferation by targeting MAP3K11.

Discontinuation of acetylcholinesterase inhibitor treatment in the nursing home.

BACKGROUND: Dementia treatment guidelines are not consistent in determining how long to continue acetylcholinesterase inhibitor (AChEI) treatment in patients with Alzheimer's disease. OBJECTIVE: Our aim was to examine reasons for AChEI discontinuation in a nursing home to better understand how practitioners actually decide when to stop treatment. METHODS: A retrospective chart review was done on 107 deceased nursing home veterans who had been taking an AChEI to determine the time between discontinuation and death. RESULTS: In the majority of residents (n = 67; 63%), the AChEI was continued into the week preceding death. Reasons for discontinuation were dying or death (n = 56; 52%), admission to hospice (n = 13; 12.2%), and admission to the nursing home (n = 5; 4.7%). Admission to hospice (P = 0.01), hospice length of stay (P = 0.0004), and length of stay at Minnesota Veterans Home (P = 0.02) were significantly associated with discontinuation of AchEI before the last week of life. CONCLUSION: Our study showed that residents were significantly more likely to have their AChEI discontinued if they were either admitted to hospice, stayed longer in hospice, or stayed longer in the nursing home. In addition, the majority of residents continued AChEI treatment until sometime during the week before death occurred.