John E Nestler’s research while affiliated with Virginia Commonwealth University and other places

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

Background Effective patient provider communication skills can be difficult and time‐consuming to teach. Deliberate practice of communication skills through improvisational theatre exercises, with structured debriefing, can provide a solution for teaching patient‐centred communication skills in time‐limited settings. The objective of this study was to determine if improvisational theatre exercises improved the ratings of patient satisfaction and empathetic communication by standardised patients. Methods This was a randomised controlled trial looking at the effect of improvisational theatre exercises on ratings of patient satisfaction and empathetic communication. Third‐year medical students (n = 188) participated in a formative team‐based standardised patient (SP) experience. Prior to the SP experience, teams of students were randomly assigned to receive a 45‐minute communication‐focused improvisation intervention (immediately before the SP experience) or to a control arm without intervention. All teams then participated in the SP experience; the SPs (blinded to team randomisation assignment) then assessed each team's empathetic communication and completed patient satisfaction questions focused on physician behaviours derived from Press GaneyTM and the Hospital Consumer Assessment of Healthcare Providers and System SurveysTM. Fifty teams of three or four students participated; 20 teams in the intervention arm and 30 teams in the control arm. Results Student teams in the improvisation intervention group had increased measures of empathetic communication (p = 0.04) compared to the control group. The intervention group had increased patient satisfaction survey ratings of ‘ability to listen carefully’ (p = 0.001) and of ‘physician skills’ compared to control groups (p = 0.03). Discussion Improv exercises with students increased students’ empathetic communication and patient satisfaction as assessed by standardised patients.

Introduction: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). Areas covered: In view of the recent knowledge, changes in nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplemenation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. Expert opinion: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.

It is well known that myo-inositol (MI) and D-chiro-inositol (DCI) are insulin-sensitizing agents, and MI is of proven utility in polycystic ovary syndrome (PCOS). In addition, MI plays a pivotal role in the physiology of reproduction, and has beneficial effects on the development of oocytes, spermatozoa, and embryos. By contrast, DCI has little effect on spermatozoa, but high concentrations in the ovary can negatively affect the quality of oocytes and the blastocyst. Overall, the evidence in the literature supports the beneficial effects of MI in both female and male reproduction, warranting clinical use of MI in assisted reproductive treatment (ART).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Introduction: This Experts’ opinion aims to offer an updated scientific support for the therapeutic use of Inositols in Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM), providing a practical support for gynecologists, obstetricians, endocrinologists, nutritionists, developmental and system biologists, neurologists and general practitioners. Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI) and their therapeutic role, also for in vitro fertilization. The document highlights some deep differences between the physiological functions of MI and DCI, taking also in consideration the safety and intestinal absorption. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, as well as the innovative approach based on alpha-lactalbumin to overcome the therapeutic decreased efficacy of Inositols in some patients. Expert opinion: The available evidence suggests that MI, alone or in combination with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and d-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle-stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. Moreover, MI enhances the effect of metformin and clomiphene on the fertility of PCOS women seeking pregnancy. As impaired intestinal transport may lead to unsuccessful inositol treatment, we also discuss new data on the use of alpha-lactalbumin to boost inositol absorption. Overall, the physiological activities of MI and DCI dictate the dosages and timing of inositol supplementation in the treatment of PCOS.