Physiological assessment of high glucose neurotoxicity in mouse and rat retinal explants

One of the tissues of the central nervous system most affected by diabetes is the retina. Despite a growing understanding of the biochemical processes involved in glucose toxicity, little is known about the physiological consequences of chronic high glucose (HG) on individual neurons and neuronal circuits. Electroretinogram recordings suggest that retinal bipolar cells (BCs), which filter and transmit photoreceptor output to the inner retina, are among the first cells affected by diabetic conditions, and may therefore serve as sensitive early biomarkers for incipient neuronal damage caused in diabetes. Here, we comparatively assessed retinal integrity, calcium responses, and the electrophysiological profiles of specific BC types of mouse and rat organotypic retinal explants after 1 to 3 weeks in tissue culture, under moderate glucose (MG) and HG conditions. While the retinal layers of both rodent species displayed a progressively reduced thickness in culture, BCs retained their electrophysiological profiles and remained morphologically identifiable for up to 2 weeks. Responses to glutamate and endogenous inhibitory responses were routinely observed, indicating that the retinal circuitry remained intact during this period. Significant physiological differences between MG and HG conditions were evident in calcium signals and in the time course of responses to glutamate, but the voltage-gated current profiles of BCs displayed only minor variations. Overall, rat retina appeared slightly more sensitive to HG levels compared with mouse. In conclusion, electrophysiological analysis of neuronal function in rodent retinal explants is useful for the study of early damage due to HG neurotoxicity.     

Advances in hereditary hemochromatosis

Hereditary hemocromatosis (HH) is a genetic disease with a recessive autosomic pattern, in which inadequate iron (Fe) absorption is made by the intestinal cell. As consequence of that process, takes place a progressive accumulation of metal in different organs, predominantly in the liver. This leads to an alteration of liver structure and function: cirrhosis and hepatocarcinoma (1). The gene implied in this pathology was identified (HFE) in 1996. This codes a similar molecule to the mayor histocompatibility complex type 1(MHC-T1 like) that can modulate the transport of PE binding the transferrin receptor. This progress allows a deep understanding of the molecular and cellular biology of the homeostasis of the Fe and its alterations in the NH. The diagnosis of disease by means of a genetic test let to carry out a familiar screening and to detect asymptomatic carriers. This makes possible to begin the appropriate treatment at early stages of the disease in order to avoid its consequences and offering a better quality of life to these patients.     

Addressing Burnout in Pharmacy Residency Programs

Addressing health care provider burnout has become a top priority for many health care systems. Unfortunately, a paucity of literature is available on preventing and managing burnout in pharmacy residents despite an increase in articles on the prevalence of pharmacy burnout. This limits the ability of pharmacy managers to understand and address burnout in this high-risk population. Until further investigation into the most beneficial, evidence-based strategies for managing burnout in this population is conducted, this commentary offers strategies to address and mitigate burnout in pharmacy residency training programs based on the available interdisciplinary literature.The authors have first-hand experience with burnout and aim to begin a paradigm shift to emphasize well-being and reshape the culture of postgraduate training. Dr. Potter has dedicated time to developing programming and founded an interprofessional well-being organization called Mindfulness in Newly Developing Students of Healthcare (MINDS) for health care students and providing recommendations for pharmacy residency programs. As a program director, Dr. Cadiz focuses on the development of realistic and effective strategies to eliminate burnout and foster well-being in her pharmacy residency training program.     

Evaluation of a training program for nurse supervisors who monitor nurses in an alternative-to-discipline program

Nurse alternative-to-discipline programs aim to protect the public from the harm of impaired practice and to support nurses in early recovery from substance use disorders. Supervisor observation of work behavior is one key monitoring activity that protects the public. We evaluate a supervisory training called "Fit to Perform" for nurse managers to help them monitor and manage nurses enrolled in an alternative-to-discipline program. We observed significant mean changes in knowledge, training utility, self-efficacy, and substance abuse stigma. The results suggest that the training positively affects knowledge about substance use disorders, confidence to supervise nurses enrolled in an alternative-to-discipline program, and reduces stigma, which may create a supportive workplace for nurses in recovery.     

Action of a serotonergic anorectic in meal-fed mice working for food

The aim of this study was to examine the effects of a serotonergic anorectic agent, dexnorfenfluramine (DNOR), on food intake in mice whose meals were constrained to specified periods each day and by effort. Mice were forced to adopt a human-like pattern of regular meals by making food available for four periods of 40 min/24-h period, mostly at night. They lived in behavior test chambers with a closed economy for food and were required to emit a fixed unit price (FUP) of either 2 or 25 nose pokes (FUP2, FUP25) to receive a 20 mg pellet of food. Once responding and intake were stable, mice were injected with a vehicle or DNOR (3 or 6 mg/kg) 1 h before a specified feeding opportunity. Food intake was dose-dependently suppressed at the next meal and to a greater extent when the cost of food was high (FUP25). Within a meal, the effect of the drug was the greatest in the first half of the available time. Therefore, the anorectic effect of DNOR was modified by the concurrent cost of food.     

Quasi-experimental evaluation of a substance use awareness educational intervention for nursing students

This article reports on a study that evaluated the effectiveness of an educational intervention, Addressing Nurse Impairment, for addressing nursing students' knowledge acquisition, changes in self-efficacy to intervene, and changes in substance abuse stigma. A gap exists in nursing students' education regarding the risks of addiction within the profession and how to handle a colleague suspected of having a substance use disorder. The seminar was adapted from an existing evidence-based prevention program called Team Awareness, as well as information from focus groups and a pilot test. A quasi-experimental pretest-posttest design was used to evaluate the effect of the seminar. When the control and experimental groups were compared, the results indicated that the seminar significantly affected knowledge and self-efficacy to intervene but did not significantly affect stigma. This research contributes to the body of evidence related to educational interventions for nursing students regarding substance abuse in the nursing profession.     

Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses

Herpes simplex virus 1 (HSV-1) and HSV-2 remain major human pathogens despite the development of anti-HSV therapeutics as some of the first antiviral drugs. Current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. We recently determined that certain natural troponoid compounds such as β-thujaplicinol readily suppress HSV-1 and HSV-2 replication. Here, we screened 26 synthetic α-hydroxytropolones with the goals of determining a preliminary structure-activity relationship for the α-hydroxytropolone pharmacophore and providing a starting point for future optimization studies. Twenty-five compounds inhibited HSV-1 and HSV-2 replication at 50 μM, and 10 compounds inhibited HSV-1 and HSV-2 at 5 μM, with similar inhibition patterns and potencies against both viruses being observed. The two most powerful inhibitors shared a common biphenyl side chain, were capable of inhibiting HSV-1 and HSV-2 with a 50% effective concentration (EC₅₀) of 81 to 210 nM, and also strongly inhibited acyclovir-resistant mutants. Moderate to low cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC₅₀] of 50 to >100 μM). Therapeutic indexes ranged from >170 to >1,200. These data indicate that troponoids and specifically α-hydroxytropolones are a promising lead scaffold for development as anti-HSV drugs provided that toxicity can be further minimized. Troponoid drugs are envisioned to be employed alone or in combination with existing nucleos(t)ide analogs to suppress HSV replication far enough to prevent viral shedding and to limit the development of or treat nucleos(t)ide analog-resistant mutants.     

Impact of molecular subtype and race on HR+, HER2− breast cancer survival

Purpose

There is an urgent need to understand the biological factors contributing to the racial survival disparity among women with hormone receptor-positive (HR+), HER2? breast cancer. In this study, we examined the impact of PAM50 subtype on 10-year mortality rate in women with HR+, HER2? breast cancer by race.

Methods

Women with localized, HR+, HER2? breast cancer diagnosed between 2002 and 2012 from two population-based cohorts were evaluated. Archival tumors were obtained and classified by PAM50 into four molecular subtypes (i.e., luminal A, luminal B, HER2-enriched, and basal-like). The molecular subtypes within HR+, HER2? breast cancers and corresponding 10-year mortality rate were compared between Black and Non-Hispanic White (NHW) women using Cox proportional hazard ratios and survival analysis, adjusting for covariates.

Results

In this study, 318 women with localized, HR+, HER2? breast cancer were included—227 Black (71%) and 91 NHW (29%). Young Black women (age?≤?50) had the highest proportion of HR+, non-luminal A tumors (47%), compared to young NHW (10%), older Black women (31%), and older NHW (30%). Overall, women with HR+, non-luminal A subtypes had a higher 10-year mortality rate compared to HR+, luminal A subtypes after adjustment for age, stage, and income (HR 4.21 for Blacks, 95% CI 1.74–10.18 and HR 3.44 for NHW, 95% CI 1.31–9.03). Among HR+, non-luminal A subtypes there was, however, no significant racial difference in 10-yr mortality observed (Black vs. NHW: HR 1.23, 95% CI 0.58–2.58).

Conclusion

Molecular subtype classification highlights racial disparities in PAM50 subtype distribution among women with HR+, HER2? breast cancer. Among women with HR+, HER2? breast cancer, racial survival disparities are ameliorated after adjusting for molecular subtype.