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Having a realistic perception of one's motor abilities is important for successful aging. We used two different motor tasks, carrying a tray with cube-towers (study 1; n = 20 young adults; n = 20 older adults), and stepping over a crossbar (study 2; n = 23 young adults; n = 21 older adults), to investigate how physical risk influences task-difficulty choices. We also investigated the effect of wearing an age simulation suit on young adults. For the tray-carrying task, older adults were more risk-tolerant in their task-difficulty choices. When stepping over the crossbar, older adults left a larger "safety-buffer" than young adults. When wearing the age suit, young adults adopted a more careful strategy in the stepping task. We conclude that healthy older adults flexibly adjust their strategies to postural risks, and that young adults' strategy-choices can be influenced by experimentally inducing some of the sensory-motor constraints of old age.

Aging is known to lead to decrements in sensory and cognitive functioning and motor performance. The purpose of the present experiment was twofold: a) We assessed the influence of wearing an age simulation suit on motor sequence learning, cognitive speed tasks and far visual acuity in healthy, younger adults. b) We evaluated the interaction of cognitive aging and declining motor sequence learning in older adults. In a between-subjects design we tested 11 younger adults (M age  = 23.6 years) without the age suit, 12 younger adults wearing the age suit (M age  = 23.2 years), and 23 older adults (M age  = 72.6 years). All participants learned a simple, spatial-temporal movement sequence on two consecutive days, and we assessed perceptual processing speed (Digit Symbol Substitution test and Figural Speed test) and far visual acuity. Wearing an age simulation suit neither affected the learning of the simple motor sequence nor the performance at the cognitive speed tasks in younger adults. However, far visual acuity suffered from wearing the suit. Younger adults with and without the suit showed better motor sequence learning compared to older adults. The significant correlations between the cognitive speed tests and the motor learning performance in older adults indicated that cognitive aging partially explains some of the variance in age-related motor learning deficits., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Opioid dependency has been a persistent issue in the United States over the past two decades. Increased efforts have been made to reduce opioid prescribing. Our objective was to quantify at-home opioid requirements following radical prostatectomy. Methods: Written questionnaires were administered to patients 1 week following robot-assisted laparoscopic radical prostatectomy (RALP). Patients provided data on opioid use, pain levels, and demographic characteristics. Results: Sixty-five patients were included. Median age (interquartile range [IQR]) was 69 (62-72) years. The majority were white (85%) and hispanic (67%). Prescriptions ranged from 6 to 15 pills of 5-mg oxycodone equivalents. Twenty-two percent (145/663) of the prescribed pills in the study were consumed. Fifty-four percent (35/65) of patients did not take opioids. Of the 30 patients who took opioids, median use (IQR) was 4.5 (3-6) pills. Forty-six percent (30/65) reported catheter-related pain. Patients who took opioids reported higher levels of pain. On generalized linear regression, younger age, lower levels of education, and living with a family member were factors associated with increased risk for opioid use (all p  < 0.05). Conclusions: Despite the Florida Department of Health's restriction on narcotic prescriptions to 3-day supplies, opioids are still overprescribed in our region. The majority of patients do not require opioids after RALP, and patients who do require an opioid analgesic can be adequately managed with less than 6 pills of 5-mg oxycodone equivalents.

Premedical students typically pursue undergraduate specialization in basic biological and other sciences, learning to understand living systems at a microscopic, genetic, or molecular level. However, curricula in the basic sciences do not traditionally include courses that enable students to learn about living systems at the macro level-understanding individuals within their environment, as well as understanding and managing the health of populations, especially those with underlying conditions or the underserved. This disconnect can be bridged by creating novel curricular programs intersecting medicine and business. Population health management is a multidisciplinary field that aims to improve the patient experience, reduce health care costs, and improve treatment outcomes. Though related to public health, the 2 fields differ in significant ways. Population health management emphasizes health outcomes and their measurements and seeks to improve health outcomes based on a full understanding of risk, behaviors, lifestyle, environment, and all social determinants of health. A shift in premedical education that connects the medical sciences with business requires curricular reform with the emerging field of population health management at their intersection, allowing students to be better prepared for future medical practices and to understand expectations, benchmarks, business, and economics in a new value-based health care system.

The integration of medical schools and clinical partners is effectively established through the formation of academic medical centers (AMCs). The tripartite mission of AMCs emphasizes the importance of providing critical clinical services, medical innovation through research, and the education of future health care leaders. Although AMCs represent only 5% of all hospitals, they contribute substantially to serving disadvantaged populations of patients, including an estimated 37% of all charity care and 26% of all Medicaid hospitalizations. Currently, most AMCs use a business model centered upon revenue generated from hospital services and/or practice plans. In the last decade, mounting financial demands have placed significant pressure on AMC finances because of the rising costs associated with complex clinical care and operating diverse graduate medical education programs. A shift toward population health-centric health care management strategies will profoundly influence the predominant forms of health care delivery in the United States in the foreseeable future. Health systems are increasingly pursuing new strategies to manage financial risk, such as forming Accountable Care Organizations and provider-sponsored plans to provide value-based care. Refocusing research and operational capacity toward population health management fosters collaboration and enables reintegration with hospital and clinical partners across care networks, and can potentially create new revenue streams for AMCs. Despite the benefits of population health integration, current literature lacks a blueprint to guide AMCs in the transformation toward sustainable population health management models. The purpose of this paper is to propose a modern conceptual framework that can be operationalized by AMCs in order to achieve a sustainable future.

Background/study Context: We assessed the influence of wearing an Age Simulation Suit (GERT) on gross motor, fine motor and cognitive performance in healthy young adults., Methods: In a within-subjects design, we tested 20 young adults ( M age  = 22.3 years) with and without the Age Simulation Suit. We assessed gross motor (Functional Fitness test) and fine motor (Purdue Pegboard test) functioning, cognitive performance (Digit Symbol Substitution test), and questionnaires on perceived physical state and mood. Gross and fine motor tests provided norms for large samples of older adults., Results: Wearing the Age Simulation Suit leads to significant performance reductions in all task dimensions, with large effect sizes. Depending on the subtest, participants' performances were reduced to the level of mid-50- to 85-years-olds for almost all tests of gross and fine motor performance. Mood and perceived physical state also declined while wearing the suit., Conclusion: We argue that the GERT suit offers an attractive possibility to experimentally simulate the effects of aging-related sensory and motor losses and propose future studies with this paradigm, in the context of cognitive-motor dual-tasking or motor learning.

Background: In Florida, 2.4 million people have diabetes and 5.8 million are pre-diabetic. Not only has the prevalence of diabetes doubled over the past 20 years from 5.2 in 1992 to 11.2 in 2014, but the Centers for Disease Control and Prevention expects 1 out of every 3 adults will have diabetes by the year 2050. In addition, in every year since 1996, Florida well exceeds the national levels in terms of prevalence of diabetes, and the gap is getting wider. A study was conducted to gather information from key physician stakeholders as to how to address unmet needs of patients at risk for, or whom already have, diabetes in a tri-county region of South Florida where the prevalence of diabetes is very high., Objective: The goal was to catalyze innovation and generate solutions for high quality and affordable diabetes care by convening community physicians in South Florida and querying them about solutions for delivering value-based care., Methods: A physician-led task force of community physicians was convened to uncover unmet needs in the diabetes care continuum, identify areas of improvement for coordinating care across the continuum and effectively accessing specialty care. Focus groups were convened with 30 participants to capture qualitative data relative to unmet needs, utilizing the Rapid Ideation Technique. A survey instrument was designed and administered to the twenty-one community clinicians on the task force to augment the qualitative data with quantitative data. The first part of the survey captured characteristics of the participating clinicians, their practices, their diabetes services and management approaches. The second part of the survey captured individual ratings of the importance and merit of needs and/or potential solutions generated., Results: The focus groups generated a wealth of information regarding challenges, issues, areas of opportunities, and potential solutions that could be organized within eight main themes: care coordination and integration; patient engagement, education and behavioral change; physician and practice support; EMR and data issues; telehealth solutions; health informatics and data analytics; and access to care. The surveys culminated in the formation of a Call-For-Action Agenda for immediate work., Conclusions: The ultimate goal of the taskforce was to catalyze innovation and generate solutions for high quality and affordable care. This article reports the findings and provides a roadmap for the future., Competing Interests: Conflicts of Interest The authors declare they have no conflicts of interest., (© 2020 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Research has indicated that older adults perform movement sequences more slowly than young adults. The purpose of the present experiment was to compare movement sequence learning in young and older adults when the time to perform the sequence was extended, and how the elderly's cognitive status (Montreal Cognitive Assessment [MoCA]) interacted with sequence learning. The task was to minimize the difference between a target sequence pattern and the sequence produced by elbow extension-flexion movements. On Day 1, participants (28 young adults; 28 older adults) practiced the sequence under two time windows: 1300 ms or 2000 ms. On Day 2, retention performance and the cognitive status were assessed. The results demonstrated that young adults performed superior compared to older adults. Additional time to perform the sequence did not improve retention performance for the older adults. The correlation between the error score and the MoCA score of r = - .38 ( p < .05) in older adults indicated that a better cognitive status was associated with performance advantages in sequence learning.

Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly.

SOX2 is an embryonic stem cell marker that in prostate cancer has been associated not only with tumorigenesis but also metastasis. Furthermore hypoxia in primary tumors has been linked to poor prognosis and outcomes in this disease. The goal of the present study was to investigate the impact of hypoxia on SOX2 expression and metastasis-associated functions in prostate cancer cells. A tissue microarray of 80 samples from prostate cancer patients or healthy controls was employed to examine the expression of HIF-1α and its correlation with SOX2. The role of SOX2 and HIF-1/2α in the regulation of cell invasion and sphere formation capacity under hypoxic conditions was investigated in vitro using short hairpin RNA (shRNA)-mediated knockdown in three human prostate cancer cell lines. HIF-1α expression was significantly elevated in malignant prostate tissue compared to benign or normal tissue, and in tumor samples its expression was highly correlated with SOX2. In prostate cancer cells, acute and chronic exposures to hypoxia that resulted in elevated expression levels of HIF-1α and HIF-2α, respectively, also induced SOX2. Genetic depletion of SOX2 attenuated hypoxia-induced cell functions. Knockdown of HIF-1α, but not HIF-2α, decreased acute hypoxia-mediated cell invasion and SOX2 up-regulation, whereas only HIF-2α gene silencing reduced sphere formation capacity and chronic hypoxia-mediated SOX2 up-regulation. Enhanced SOX2 expression and HIF-1α or HIF-2α associated phenotypes are dependent on the time duration of exposure to hypoxia. The present results indicate that SOX2 may be a key mediator of hypoxia-induced metastasis-associated functions and hence may serve as a potential target for therapeutic interventions for metastatic prostate cancer.

Purpose: In murine and human hyperoxaluric conditions macrophages can be seen surrounding renal calcium oxalate crystal deposits. We hypothesized that macrophages have a role in degrading and destroying these deposits. We investigated the inflammatory response and phagocytic mechanisms when macrophages were exposed to human kidney stones and inorganic crystals., Materials and Methods: Human monocytes were differentiated into resting, fully differentiated macrophages by treatment with recombinant human macrophage colony-stimulating factor (M-CSF) or GM-CSF (granulocyte M-CSF) for 6 days. After confirming phenotype by flow cytometry the macrophages were exposed for 20 hours to fragments of sterile human calcium oxalate stones or calcium oxalate crystals. Crystal uptake was determined, and supernatant cytokine and chemokine profiles were analyzed using antibody arrays. Quantitative reverse transcriptase-polymerase chain reaction was done to validate mRNA profile expression., Results: Under direct vision fluorescence microscopy activated human macrophages were noted to surround stone fragments and synthesized crystals, and destroy them in a step-by-step process that involved clathrin mediated endocytosis and phagocytosis. An inflammatory cascade was released by macrophages, including the chemokines chemokine ligand (CCL)2, CCL3, interleukin (IL)-1 receptor antagonist (IL-1ra), complement component C5/C5a and IL-8. Response patterns to stone and crystal material depended on macrophage phenotype and activation status., Conclusions: In our in vitro study macrophages differentiated with M-CSF showed greater ability to phagocytize crystal deposits than those treated with GM-CSF. Following clathrin mediated endocytosis macrophages released a number of cytokines that are crucial for the inflammatory immune response. This suggests that tissue macrophages have an important role in preventing kidney stone disease by removing and digesting interstitial renal crystal deposits., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The development and management of pressure ulcers (PUs) among hospital and nursing home patients is one of the greatest preventable challenges to healthcare worldwide. For over 50 years, pressure mapping and subjective comfort has been the primary indicators for mattress selection. Our research demonstrates that mattress/patient interface pressure and relative blood/oxygen perfusion do not inversely correlate and pressure is not a meaningful, real-time indicator of tissue ischemia and risk of pressure ulcer development. Developed in our research is a real-time sensor system to simultaneously measure and record these parameters over the anatomical sites at risk for PUs. Measurements focused on the heel, sacrum, trochanter, ischium, scapula and occipital. A modified pressure mapping system is used for interface pressure measurements and integrated with multiple near-infrared sensors to measure specific deep tissue hemoglobin saturated oxygen or rSO2. Testing and mattress design development was done during the period of 2008 to present. Over 200 human tests of commercially available mattresses were conducted in supine, 30 degree, and 70 degree positions, ranging in times of up to four hours. During this time period, we utilized 20 test subjects-eight female and 12 male-with ages ranging from 18 to 65 years. The result of this proprietary off-loading device evaluation and design system shows that the new Oxy-Mat™ (Off-Loading Technologies, Tarrytown, NY) Non-Powered Mattress System consistently provides optimized tissue perfusion as measured by natural deep tissue oxygen saturation levels. In extensive laboratory and clinical evaluations, the Oxy-Mat™ was shown to be functionally superior to CMS Group 2 powered mattresses. Another outcome of our research was that a powered mattress system may not be appropriate for most sensate and semi-ambulatory patients. Further research is underway.

Purpose: Clinical practice guidelines are increasingly being used by leading organizations to promote high quality evidence-based patient care. However, the methodological quality of clinical practice guidelines developed by different organizations varies considerably. We assessed published clinical practice guidelines on the treatment of localized prostate cancer to evaluate the rigor, applicability and transparency of their recommendations., Materials and Methods: We searched for English based clinical practice guidelines on treatment of localized prostate cancer from leading organizations in the 15-year period from 1999 to 2014. Clinical practice guidelines limited to early detection, screening, staging and/or diagnosis of prostate cancer were excluded from analysis. Four independent reviewers used the validated AGREE II instrument to assess the quality of clinical practice guidelines in 6 domains, including 1) scope and purpose, 2) stakeholder involvement, 3) rigor of development, 4) clarity of presentation, 5) applicability and 6) editorial independence., Results: A total of 13 clinical practice guidelines met inclusion criteria. Overall the highest median scores were in the AGREE II domains of clarity of presentation, editorial independence, and scope and purpose. The lowest median score was for applicability (28.1%). Although the median score of editorial independence was high (85.4%), variability was also substantial (IQR 12.5-100). NICE and AUA clinical practice guidelines consistently scored well in most domains., Conclusions: Clinical practice guidelines from different organizations on treatment of localized prostate cancer are of variable quality and fall short of current standards in certain areas, especially in applicability and stakeholder involvement. Improvements in these key domains can enhance the impact and implementation of clinical practice guidelines., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We identified structural abnormalities in the spermatic cord nerves that may explain how microsurgical denervation of the spermatic cord provides pain relief in patients with chronic orchialgia., Materials and Methods: We retrospectively reviewed a prospective database to compare spermatic cord biopsy specimens from 56 men treated with a total of 57 procedures for microsurgical denervation of the spermatic cord for chronic orchialgia vs a control group of men without pain treated with cord surgery, including varicocelectomy in 4 and radical orchiectomy in 6. Tissue biopsies were obtained from mapped regions of the spermatic cord in all cases. Biopsies stained with hematoxylin and eosin were examined by an independent pathologist. Three human cadaveric spermatic cords were dissected to confirm localization of the nerve distribution identified on pathological mapping., Results: We identified a median of 25 small diameter (less than 1 mm) nerve fibers in the spermatic cord. Of the 57 procedures for orchialgia 48 (84%) showed wallerian degeneration in 1 or more of these nerves but only 2 of 10 controls (20%) had such degeneration (p = 0.0008). In decreasing order of nerve density the 3 primary sites (trifecta nerve complex) of these changes were the cremasteric muscle fibers (19 nerves per patient), perivasal tissues and vasal sheath (9 nerves per patient), and posterior cord lipomatous/perivessel tissues (3 nerves per patient). Cord nerve distribution mapped by the biopsies was confirmed by cadaveric dissection., Conclusions: In men with chronic orchialgia there appears to be wallerian degeneration in reproducible patterns in the spermatic cord nerve fibers. Transection of these nerves may explain the effect of the denervation procedure., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Cancer stem cells (CSC) represent a malignant subpopulation of cells in hierarchically organized tumors. They constitute a subpopulation of malignant cells within a tumor mass and possess the ability to self-renew giving rise to heterogeneous tumor cell populations with a complex set of differentiated tumor cells. CSC may be the cause of metastasis and therapeutic refractory disease. Because few markers exist to identify and isolate pure CSC, we used cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) to create DNA aptamers that can identify novel molecular targets on the surfaces of live CSC. Out of 22 putative DNA sequences, 3 bound to ~90% and 5 bound to ~15% of DU145 prostate cancer cells. The 15% of cells that were positive for the second panel of aptamers expressed high levels of E-cadherin and CD44, had high aldehyde dehydrogenase 1 activity, grew as spheroids under nonadherent culture conditions, and initiated tumors in immune-compromised mice. The discovery of the molecular targets of these aptamers could reveal novel CSC biomarkers., (Copyright © 2012 UICC.)

Purpose: Chemokines are involved in cancer-related inflammation and malignant progression. In this study, we evaluated expression of CCR8 and its natural cognate ligand CCL1 in patients with urothelial carcinomas of bladder and renal cell carcinomas., Experimental Design: We examined CCR8 expression in peripheral blood and tumor tissues from patients with bladder and renal carcinomas. CCR8-positive myeloid cells were isolated from cancer tissues with magnetic beads and tested in vitro for cytokine production and ability to modulate T-cell function., Results: We show that monocytic and granulocytic myeloid cell subsets in peripheral blood of patients with cancer with urothelial and renal carcinomas display increased expression of chemokine receptor CCR8. Upregulated expression of CCR8 is also detected within human cancer tissues and primarily limited to tumor-associated macrophages. When isolated, CD11b(+)CCR8(+) cell subset produces the highest levels of proinflammatory and proangiogenic factors among intratumoral CD11b myeloid cells. Tumor-infiltrating CD11b(+)CCR8(+) cells selectively display activated Stat3 and are capable of inducing FoxP3 expression in autologous T lymphocytes. Primary human tumors produce substantial amounts of the natural CCR8 ligand CCL1., Conclusions: This study provides the first evidence that CCR8(+) myeloid cell subset is expanded in patients with cancer. Elevated secretion of CCL1 by tumors and increased presence of CCR8(+) myeloid cells in peripheral blood and cancer tissues indicate that CCL1/CCR8 axis is a component of cancer-related inflammation and may contribute to immune evasion. Obtained results also implicate that blockade of CCR8 signals may provide an attractive strategy for therapeutic intervention in human urothelial and renal cancers., (©2013 AACR.)

Both cancer-related inflammation and tumor-induced immune suppression are associated with expansion of myeloid cell subsets including myeloid-derived suppressor cells. However, little known regarding characteristics of myeloid cells in patients with bladder cancer. In this study, we analyzed myeloid cells from peripheral blood (PBMC) and tumor tissue that were collected from patients with superficial noninvasive and invasive urothelial carcinomas. Our results demonstrate that PBMC from bladder cancer patients contain two major CD11b myeloid cell subsets: granulocyte-type CD15(high) CD33(low) cells and monocyte-type CD15(low) CD33(high) cells. The number of circulating granulocytic but not monocytic myeloid cells in cancer patients was markedly increased when compared to healthy individuals. Both myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G-CSF, IL-8 and IL-6. Granulocytic myeloid cells were able to inhibit in vitro T cell proliferation through induction of CD4(+) Foxp3(+) T regulatory cells. Analysis of bladder cancer tissues revealed that tumors were infiltrated with monocyte-macrophage CD11b(+) HLA-DR(+) and granulocytic CD11b(+) CD15(+) HLA-DR(-) myeloid cells. Collectively, this study identifies myeloid cell subsets in patients with bladder cancer. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer., (Copyright © 2011 UICC.)