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Quiet breathing in hindlimb casted mice
No full textThe hindlimb casting model was developed to study skeletal muscle reloading following a period of unloading. It is unknown if ventilation parameters of mice are affected by the casting model. We tested the hypothesis that hindlimb casted mice have similar ventilatory patterns compared to mice with the casts removed. Male CD-1 mice underwent 14 days of hindlimb immobilization via plaster casting. Breathing parameters were obtained utilizing unrestrained barometric plethysmography (UBP). Breathing traces were analyzed with Ponemah software for breathing frequency, tidal volume (TV), and minute ventilation (MV). Frequency, TV and MV did not show any differences in quiet breathing patterns during or post-casting in mice. Thus, the hindlimb casting model does not complicate breathing during and after casting and should not interfere with the unloading and reloading of skeletal muscle
Injectable Hydrogels for Localized Chemotherapy and Radiotherapy in Brain Tumors
No full textOverall survival of patients with newly diagnosed glioblastoma (GBM) remains dismal at 16 months with state-of-the-art treatment that includes surgical resection, radiation, and chemotherapy. GBM tumors are highly heterogeneous, and mechanisms for overcoming tumor resistance have not yet fully been elucidated. An injectable chitosan hydrogel capable of releasing chemotherapy (temozolomide [TMZ]) while retaining radioactive isotopes agents (iodine, [131I]) was used as a vehicle for localized radiation and chemotherapy, within the surgical cavity. Release from hydrogels loaded with TMZ or 131I was characterized in vitro and in vivo and their efficacy on tumor progression and survival on GBM tumors was also measured. The in vitro release of 131I was negligible over 42 days, whereas the TMZ was completely released over the first 48 h. 131I was completely retained in the tumor bed with negligible distribution in other tissues and that when delivered locally, the chemotherapy accumulated in the tumor at 10-fold higher concentrations than when delivered systemically. We found that the tumors were significantly decreased, and survival was improved in both treatment groups compared to the control group. Novel injectable chemo-radio-hydrogel implants may potentially improve the local control and overall outcome of aggressive, poor prognosis brain tumors
Pazopanib plus cetuximab in recurrent or metastatic head and neck squamous cell carcinoma: an open-label, phase 1b and expansion study
No full textBackground: Angiogenesis is a hallmark of head and neck squamous cell carcinoma (HNSCC), and a mechanism of resistance to EGFR inhibition. We investigated the safety and potential activity of pazopanib, an angiogenesis inhibitor, plus cetuximab, an EGFR inhibitor, in patients with recurrent or metastatic HNSCC. Methods: We did an open-label, single-centre, dose-escalation phase 1b trial using a standard 3 + 3 design, followed by an expansion cohort phase. Eligible participants were patients with histologically or cytologically confirmed recurrent or metastatic HNSCC, aged at least 18 years, had measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and an Eastern Cooperative Oncology Group performance status of 0–1. During dose escalation, pazopanib oral suspension was administered daily in 8-week cycles at doses of 200 mg/day, 400 mg/day, 600 mg/day, or 800 mg/day, with cetuximab given intravenously once per week (400 mg/m 2 first dose and 250 mg/m 2 in consecutive cycles). The primary endpoint was to determine the maximum tolerated dose or recommended phase 2 dose of pazopanib in combination with cetuximab. Analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT01716416, and it is ongoing but closed to accrual. Findings: Between June 5, 2013, and April 4, 2017, we enrolled 22 patients into the phase 1b, dose-escalation phase of the trial. A maximum tolerated dose of pazopanib in combination with cetuximab was not reached. Single dose-limiting toxic events (all grade 3) during dose escalation occurred with pazopanib 400 mg/day (neutropenia with infection), 600 mg/day (proteinuria), and 800 mg/day (fatigue). The established recommended phase 2 dose for the combination was 800 mg/day of pazopanib during cycles of 8 weeks each, plus cetuximab 400 mg/m 2 on day 1 of cycle 1, then cetuximab 250 mg/m 2 weekly. A further nine patients were enrolled into the expansion cohort and treated with the established recommended phase 2 dose. The most common (grade 3–4) adverse events for all patients were hypertension (ten [32%] of 31), lymphocyte count decrease (seven [23%]), and dysphagia (seven [23%]). There were no treatment-related deaths. 11 (35%; 95% CI 19·2–54·6) of 31 patients achieved an overall response, as assessed by the investigator; two (6%) had a complete response and nine (29%) a partial response. Tumour responses were also observed in six (55%) of 11 patients with platinum-naive and cetuximab-naive disease, three (25%) of 12 patients with cetuximab-resistant disease, and five (28%) of 18 patients with platinum-resistant disease. Interpretation: Pazopanib oral suspension at a dose of 800 mg/day was feasible to administer in combination with standard weekly cetuximab for patients with recurrent or metastatic HNSCC. Encouraging preliminary antitumour activity was observed with this combination therapy and warrants further validation in randomised trials. Funding: GlaxoSmithKline and Novartis
Comparative effectiveness of lipid-lowering treatments to reduce cardiovascular disease
No full textIntroduction: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a new treatment option for patients with hypercholesterolemia. The objective of this study was to systematically review the cost-effectiveness of lipid-lowering agents. Areas covered: Based on Pubmed, Embase, and Cochrane Database of Systematic Reviews, we identified 29 relevant articles. Studies found statins were cost-effective compared with placebo or no treatment in general. Atorvastatin was reported to be cost-effective against simvastatin. In most cases, rosuvastatin was more cost-effective than atorvastatin or simvastatin. Additionally, ezetimibe was considered to be cost-effective compared with no treatment for statin intolerant patients. For patients not meeting treatment goals with their statins, switching to ezetimibe plus simvastatin was consistently reported cost-effective. The cost-effectiveness of ezetimibe plus a hybrid of a statin varied by the source of clinical data and cost of ezetimibe. Finally, the cost-effectiveness of PCSK9 inhibitor plus a statin against statin monotherapy was uncertain. The PCSK9 inhibitor plus a stain was cost-ineffective compared with ezetimibe plus a statin. Expert commentary: Drug costs and treatment efficacy were the key drivers of the cost-effectiveness results in prior analyses. Future evaluations are warranted to reflect the decreasing drug prices and the long-term treatment effects of PCSK9 inhibitors
Faculty Research Incentive Program
No full textThe purpose of the Faculty Research Incentive Program is to reward faculty for sustained externally funded productivity and scholarly activities. This program will stimulate scholarly activity associated with performing externally funded research in all units.
As a means of encouraging active participation in competing for extramural support for research projects, University of Health Sciences and Pharmacy in St. Louis (UHSP) has developed guidelines for an incentive program (the “Program”) for faculty. The Program permits, within limits under the Program, a choice between a salary supplement or the establishment of a designated, discretionary research expense account to eligible principal investigators (PI) who have been awarded a competitive research grant or contract from outside funding sources and, according to the Program, who have earned a right to the funds. The Program is not a contract and is subject to change, with or without notice, at the University’s sole discretion.
All full-time faculty who have secured extramural funds while maintaining their other scholarly responsibilities are eligible for the Program
Burden of chronic conditions among patients from free clinics: A retrospective chart review of 2015
No full textIntroduction. There is limited research about the poor and uninsured patients who visit free clinics. Methods. We conducted a retrospective chart review of uninsured adult patients in four free clinics seen between January and December 2015. Prevalence of chronic conditions and their association with socioeconomic factors were investigated. Results. In 2015, 3,196 adult patients with chronic conditions were managed in four free clinics. Many of these patients were women (60.8%) and Hispanic (44.7%); the group had a mean age of 47.9 years (SD=14.1) and a median income of $14,400. The top five prevalent conditions were hypertension (33.6%), hyperlipidemia (20.7%), diabetes (14%), major depression (11.7%), and arthritis (8.7%). In the multivariable analysis, clinic site, age, marital status, employment status, and household size were significantly associated with the Disease Burden Index. Discussion. Public health prevention programs should focus on uninsured patients of free clinics who are mainly low-income, sicker, and unemployed, and often women and Hispanics
Temporal Patterns of Genetic Diversity in an Imperiled Population of the Eastern Massasauga Rattlesnake (Sistrurus catenatus)
No full textThe Eastern Massasauga (Sistrurus catenatus) is a small, grassland-dependent rattlesnake species declining throughout its native range, and is thus a species of high conservation priority. In Illinois, only a single population remains of a once widespread distribution. We documented genetic diversity in this population over a ten-year period and assessed levels of heterozygosity, allelic diversity, inbreeding (FIS), and effective population size (Ne). Neither heterozygosity nor levels of inbreeding differed significantly among periods. We identified 21 alleles that occurred in a single time period, some of which may have been lost from the population given our estimated detection probability of 93%. Effective population size (Ne) was numerically small and showed a decreasing trend through time. Despite small population size and a lack of connectivity, there was no significant decline in genetic diversity over the ten-year study. Aspects of life history, coupled with a preference for a historically patchy habitat, may mitigate the loss of genetic diversity in the species and promote their persistence in the fragmented habitats of the Anthropocene. However, continued genetic monitoring is recommended, and population recovery measures should be implemented as soon as possible to mitigate the deleterious effects of small population size
Curcumin and Melanoma: From Chemistry to Medicine
No full textMelanoma is the most deadly form of skin cancer, with about 48,000 deaths each year worldwide. Growing evidence suggests that individual nutrients or dietary patterns might have important roles in the prevention of melanoma. Considering that melanoma is a potentially life-threatening cancer, novel protective and adjuvant treatments are needed to improve its prognosis. Curcumin is a bioactive substance extracted from rhizome of Curcuma longa L. Its global market is expected to grow in the next few years, especially in the pharmaceutical industry, due to its numerous physiological and pharmacological properties. For this review, we collected the available data on the protective and therapeutic role of curcumin against melanoma. We also discuss the chemistry, dietary sources, bioavailability, and metabolism of curcumin, and the mechanisms of action of its potential anticancer effects at the molecular level. Current challenges and future directions for research are also critically discussed
Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma
No full textThe establishment of more effective treatments that can circumvent chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ) is one of the most potent proteasome inhibitors available, still possesses limitations related to dose limiting side effects. Several strategies have been developed to improve the delivery of chemotherapies to MM by targeting different moieties expressed on MM cells to nanoparticle delivery systems (NPs), which have failed mainly due to their heterogeneous expression on these cells. Our goal was to test CD38 targeted chitosan NPs as novel targeting moiety for MM to improve the potency and efficacy of BTZ in MM cells and reduce the side effects in healthy tissue. We have showed preferential BTZ release in tumor-microenvironment, specific binding to MM cells, and an improved drug cellular uptake through BTZ diffusion from the surface and endocytosed NPs, which translated in enhanced proteasome inhibition and robust cytotoxic effect on MM cells when BTZ was administered through anti-CD38 chitosan NPs. Furthermore, the anti-CD38 chitosan NPs specifically delivered therapeutic agents to MM cells improving therapeutic efficacy and reducing side effects in vivo. The anti-CD38 chitosan NPs showed low toxicity profile allowing enhancement of proteasome-inhibitory activity and specificity of BTZ by endocytosis-mediated uptake of CD38 representing a promising therapy in MM
Integrating innovative telehealth solutions into an interprofessional team-delivered chronic care management pilot program
No full textBACKGROUND: Pharmacist-delivered medication therapy management (MTM) services can improve patient outcomes, yet little is known about outpatient, interprofessional telepharmacy programs. OBJECTIVE: To evaluate an outpatient, interprofessional telehealth chronic care management (CCM) pilot program. METHODS: This 6-month program integrated family medicine providers, a university-based medication management telepharmacist, and an interprofessional care coordinator using telehealth solutions for CCM and pharmacy education services. A physician referred patients at risk for medicine-related problems to the telepharmacist. Eligible patients had 3 or more chronic conditions or took at least 5 medications, were aged 18 years and older, and had at least 1 appointment with their primary care provider during the program. The care coordinator met patients in person to facilitate these virtual clinic processes. The telepharmacist conducted a comprehensive medication review (CMR) via video-conferencing technology, providing CCM based on primary diagnosis, current medications and allergies, laboratory results, and previous chart notes. The consultation was documented in the electronic health record (EHR) for provider review and modification in real time. RESULTS: 69 patients received telepharmacy consultations and on-site registered nurse support during the program. Most patients were female (56.5%), aged 51-70 years (60.1%), Caucasian (72.4%), and non-Hispanic/ Latino (71.0%). Patients had 1-9 chronic conditions, such as hypertension (82.6%), diabetes (56.5%), hyperlipidemia (31.9%), depression (30.4%), and osteoporosis (29.0%). Most patients (94.2%) took at least 5 chronic disease medications, such as statins (11.2%), nonsteroidal anti-inflammatory drugs (8.4%), selective serotonin reuptake inhibitors (6.5%), beta blockers (6.5%), and calcium channel blockers (5.6%). The telepharmacist completed 200 interventions for safety (49.0%), vaccines (24.5%), care gaps per national consensus guidelines (13.5%), adherence (10.0%), and cost savings (3.0%). Patients\u27 providers accepted one third (n = 75, 37.5%) of the telepharmacist recommendations (e.g., monitoring and medication changes). CONCLUSIONS: This telehealth program constituted an added service for patients while simultaneously filling a gap in on-site pharmacist counseling services. Integrating the telepharmacist and registered nurse was crucial to clinical service provision. The results are encouraging; however, more research must examine the effectiveness of telehealth services in reaching underserved populations, improving patient care, and decreasing health care costs