Assessing causality with an event such as a nightmare is difficult because of the high incidence of nightmares in the healthy population. Using qualitative, quantitative, and possible pharmacologic mechanism criteria, it appears that sedative/hypnotics, beta-blockers, and amphetamines are the therapeutic modalities most frequently associated with nightmares. These drug classes have a plausible pharmacologic mechanism to explain this effect. Dopamine agonists also have evidence of causality, with dopamine receptor stimulation as a possible pharmacologic mechanism.
The rat is widely used in studies of the metabolic and physiological effects of physical exercise. The most commonly used form of exercise is running on treadmills or mechanically driven running wheels. Rats will not voluntarily run significant distances, under normal circumstances. If rats are exposed to running wheels with food freely available, only very limited activity normally occurs. When rats with access to a running wheel are restricted to a fixed amount of food, presented once per day, consistent running occurs. The running is spontaneous and very sensitive to the amount of food provided. Six 6-wk-old rats of 197 g mean body wt were induced to run for 139 days. The distance run increased rapidly over a 20-day initial period on a food supply of 15 g/day (vs. 19.5 g/day consumption by sedentary controls). From day 20 to day 139 the mean distance run was described by the regression equation distance (m/day) = 10,410 - 37.9 X days. Food provided was varied according to distance run, ranging from 15 to 18 g/day, and was normally 17.5 g/day. Thus a food deprivation of 10% of normal consumption will result in mean distances run of approximately 8,000 m/day. The use of pair-fed control animals without access to a wheel allows the conduct of experiments to test the effects of chronic long-distance running. The running is spontaneous; thus the technique avoids the complications accompanying techniques that force running.
The safety and efficacy of direct‐acting oral anticoagulants (DOACs) and reversal strategies are not well established in the solid organ transplant population. This was a survey of pharmacists to assess DOAC and urgent reversal practices among adult transplant programs in the United States. A 27‐question survey was distributed to members of transplant pharmacy organization listservs between 5/28/19 and 6/30/19. A total of 115 responses were received from kidney (43.5%), heart (20.0%), lung (18.3%), liver (13.9%), and pancreas (4.4%) transplant programs. DOAC use prior to transplant was mostly prohibited in thoracic programs (77.3%) but more permissive in kidney transplant programs (64.0%). If permitted, apixaban (57.8%) was most preferred. At transplant surgery, reversal of DOAC was performed “as needed” (20.9%) or was not routine (18.3%). DOAC use post‐transplant was more permissive (94.3%). A majority of responders follow FDA recommended dosing in the setting of drug‐drug interactions (51.1%). Major factors influencing DOAC prescribing decisions included renal function, drug‐drug interactions, and insurance. High clinical practice variability exists regarding DOAC utilization and urgent reversal strategies in pre‐, peri‐, and post‐transplant stages. While more research is needed to refine the clinical landscape, many institutions are using DOAC therapy under the perception that they pose a similar risk of bleeding compared to a non‐transplant population.
The increased proliferation of cancer cells is directly dependent on the increased activity of the endoplasmic reticulum (ER) machinery which is responsible for protein folding, assembly, and transport. In fact, it is so critical that perturbations in the endoplasmic reticulum can lead to apoptosis. This carefully regulated organelle represents a unique target of cancer cells while sparing healthy cells. In this study, a standardized mangosteen fruit extract (MFE) was evaluated for modulating ER stress proteins in prostate cancer. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells (PrECs) procured from two patients undergoing radical prostatectomy were treated with MFE. Flow cytometry, MTT, BrdU and Western blot were used to evaluate cell apoptosis, viability, proliferation and ER stress. Next, we evaluated MFE for microsomal stability and anti-cancer activity in nude mice. MFE induced apoptosis, decreased viability and proliferation in prostate cancer cells. MFE increased the expression of ER stress proteins. Interestingly, MFE selectively promotes ER stress in prostate cancer cells while sparing PrECs. MFE suppressed tumor growth in a xenograft tumor model without obvious toxicity. Mangosteen fruit extract selectively promotes endoplasmic reticulum stress in cancer cells while sparing non-tumorigenic prostate epithelial cells. Furthermore, in an in vivo setting mangosteen fruit extract significantly reduces xenograft tumor formation.
Introduction: Early emergency department and hospital re-admissions are common in renal transplant recipients, but data are lacking in unique populations. Study Aim: The purpose of this study was to identify patient risk factors for multiple acute care utilization events within the first year of renal transplantation. Design: This was a single-center, retrospective cohort study of adult renal transplant recipients between 9/2013-9/2016. Patients were compared across number of emergency department visits and by hospital re-admissions. Diagnoses were categorized. Univariate and multivariate logistic regression was used to assess risk for multiple acute care utilization events within the first 12 months post-transplant. Results: A total of 216 patients were analyzed and were on average 50.5 (SD 13.9) years old, redominantly Black (49.77%) with an average body mass index of 33.33 (9.8) and were recipients of deceased donor renal transplants (61.11%). A total of 105 (48.6%) patients visited the emergency epartment and 119 (55.1%) patients had a hospital readmission. Patients having a body mass index >35 kg/m2 did not differ across emergency department visit or hospitalization groups. Delayed graft function (OR 2.86, 95% CI 1.07-7.65) and previous renal transplant (OR 2.77, 95% CI 1.04-7.39) were significantly associated with multiple acute care utilizations. Discussion: Acute care utilization following renal transplantation was similar to previously reported experiences. Obesity did not impact use of acute care resources or patient outcomes. Strategies addressing potential preventable emergency visits and hospital re-dmissions should be promoted.
Background. Tacrolimus demonstrates wide intrapatient and interpatient variability requiring therapeutic drug monitoring. The utility of tacrolimus time in therapeutic range (TTR) after renal transplantation (RT) under an early corticosteroid withdrawal (ECSWD) protocol is unknown. The purpose of this study is to assess the impact of tacrolimus TTR in an ECSWD RT population. Materials. A retrospective analysis of adult RT recipients maintained on tacrolimus was conducted. Patients were excluded if they were on nonstandard protocol immunosuppression agents <12 months post-RT. Tacrolimus TTR was calculated using the Rosendaal method. Patients were divided into high (TTR-H) and low (TTR-L) TTR groups based on cohort median. The primary outcome was to compare the incidence of acute rejection 12 months post-RT. Secondary outcomes included comparing rejection subtypes, incidence of donor-specific antibody (DSA) and de novo DSA (dnDSA), risk factors for acute rejection and dnDSA development, and allograft function (serum creatinine and estimated glomerular filtration rate). Results. A total of 193 patients were analyzed (TTR-H = 98 and TTR-L = 95). There was no difference in the incidence of acute rejection (TTR-H 20.4% versus TTR-L 20.0%; P = 0.944). Positive DSA posttransplant (odds ratio [OR], 3.62; 95% confidence interval [CI], 1.41-9.26; P = 0.007) was associated with a higher acute rejection at 12 months posttransplant. Mycophenolate dose reduction (OR, 2.82; 95% CI, 1.13-6.97; P = 0.025) and acute rejection (OR, 2.99; 95% CI, 1.09-8.18; P = 0.032) were associated with dnDSA formation. No difference in serum creatinine or estimated glomerular filtration rate was observed ( P > 0.05). Conclusions. Tacrolimus TTR was not significantly different with regards to acute rejection in an ECSWD population. Future studies are still needed to determine tacrolimus TTR thresholds post-RT and identify populations that may benefit from this intrapatient variability monitoring parameter.
Clinical research is a skill that can be honed and cultivated in the right educational environment. Creating experiences to maximize growth and interest in clinical research can occur both during pharmacy school and throughout postgraduate training. The purpose of this “how‐to” guide is to assist pharmacists, as well as their students and residents, with effectively structuring experiences and programs that instill and cultivate a lifelong desire to contribute to the medical literature. The overarching areas of focus are threefold: (1) identifying trainees and mentors, (2) crafting research training experiences, and (3) supporting continued interest and growth in research after completion of the initial experience. Early introduction of a positive research culture in the trainee experience through structured and thoughtful curricula and experiences can maximize learner potential. Several thoughtful steps and recommendations can maximize these experiences and opportunities for learners and new practitioners. Instilling and cultivating a lifelong desire to contribute to the medical literature in pharmacy trainees remains a challenge that is both worthy and necessary to pursue for the sakes of our profession, patients, and trainees.
Background Due to the mechanisms of action of conventional catecholamine vasopressors, there is increased risk of renal allograft injury and adverse events in transplant recipients with fluid‐refractory distributive shock during the perioperative period. As such, mechanistically alternative vasopressors like angiotensin II (ATII) may avoid these complications, but there is an absence of data supporting use in this population. Methods This was a single‐center, single‐arm, open‐label, phase 4 study conducted as a 1‐year pilot of 20 adult renal transplant recipients receiving ATII as their first continuous infusion vasopressor in the perioperative period. The study aim was to systematically assess the safety and hemodynamic effects of ATII. Safety was assessed based on the incidence of adverse events. Hemodynamic effect was assessed by the achievement of per protocol hemodynamic goals (i.e., SBP ≥120 mmHg) and the need for adjunct vasopressors. Results Most cases involved deceased donors (70%), with a corresponding mean (SD) cold ischemia time of 14.7 (8.6) h. Over a surgery duration of 5.3 (1.2) h, subjects received 3.2 (2.0) L of total volume resuscitation prior to ATII initiation. No adverse events were directly related to ATII administration. Throughout this period, ATII was utilized for a median of 1.0 (IQR, 1.5) h intraoperatively (N = 7), 26.5 (IQR, 84.8) h postoperatively (N = 4), and 63.8 (IQR, 57.8) h in subjects who required ATII both intra‐ and postoperatively (N = 9). Only one of the 20 patients needed adjunct continuous infusion vasopressors in addition to ATII. Conclusions Based on the observations of this pilot study, ATII is a safe and effective vasopressor option for renal transplant recipients requiring perioperative hypotension reversal.
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