The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40:1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria.

SETTING: Insulin resistance (IR) and compensatory hyperinsulinemia are considered contributing factors toward polycystic ovary syndrome (PCOS). OBJECTIVES: This study evaluates the frequency of metabolic abnormalities in PCOS patients and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio on hormonal and metabolic parameters. PARTICIPANTS: Thirty-four women with PCOS phenotype A (endocrine-metabolic syndrome [EMS-type 1]) between the ages of 20-40. DESIGN: Open prospective study with phenotype A (EMS-type I, n = 34) supplemented with 2,255 mg/day of inositol (MI and DCI in a 40:1 ratio) for 3 months. METHODS: The following were measured before and after treatment: serum levels of follicular stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), anti-Müllerian hormone, glucose, insulin, HOMA-IR, and body mass index (BMI). RESULTS: 55.9% of the enrolled patients were overweight or obese, 50% affected by IR, 17.6% with a history of gestational diabetes mellitus, and 61.8% had familial diabetes mellitus. At the conclusion of the study, BMI (p = 0.0029), HOMA-IR (p < 0.001) significantly decreased, along with decreased numbers of patients with elevated insulin levels. The supplementation resulted in decreased total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001); increased SHBG (p < 0.001) and estradiol (p < 0.001). LIMITATIONS: The present analysis was limited to a 12-week follow-up, which precluded a long-term evaluation of the effects of MI and DCI combination. Also, this period was insufficient to achieve and analyze clinical changes such as restoration of the menstrual cycle, restoration of reproductive function, and clinical manifestations of hyperandrogenism. CONCLUSIONS: Supplementation improved metabolic and hormonal profile in PCOS phenotype A (EMS-type I) patients. This builds upon previous work that demonstrated that combined inositol treatment may be effective in PCOS. The study presented herein, used a reduced concentration than in prior literature; however, a significant change in hormonal and metabolic parameters was still observed.

Exploring connections between pollinator health and human health.

Despite recent advances in understanding the role of biodiversity in ecosystem-service provision, the links between the health of ecosystem-service providers and human health remain more uncertain. During the past decade, an increasing number of studies have argued for the positive impacts of healthy pollinator communities (defined as functionally and genetically diverse species assemblages that are sustained over time) on human health. Here, we begin with a systematic review of these impacts, finding only two studies that concomitantly quantified aspects of pollinator health and human health. Next, we identify relevant research relating to four pathways linking pollinator health and human health: nutrition, medicine provisioning, mental health and environmental quality. These benefits are obtained through improved pollination of nutritious crops and an estimated approximately 28 000 animal-pollinated medicinal plants; the provisioning of pollinator-derived products such as honey; the maintenance of green spaces and biocultural landscapes that improve mental health; and cleaner air, water and food resulting from pollinator-centred initiatives to reduce agrochemical use. We suggest that pollinator diversity could be a proxy for the benefits that landscapes provide to human health. This article is part of the theme issue 'Natural processes influencing pollinator health: from chemistry to landscapes'.

Pyrazolopyrimide library screening in glioma cells discovers highly potent antiproliferative leads that target the PI3K/mTOR pathway.

The search for novel targeted inhibitors active on glioblastoma multiforme is crucial to develop new treatments for this unmet clinical need. Herein, we report the results from a screening campaign against glioma cell lines using a proprietary library of 100 structurally-related pyrazolopyrimidines. Data analysis identified a family of compounds featuring a 2-amino-1,3-benzoxazole moiety (eCF309 to eCF334) for their antiproliferative properties in the nM range. These results were validated in patient-derived glioma cells. Available kinase inhibition profile pointed to blockade of the PI3K/mTOR pathway as being responsible for the potent activity of the hits. Combination studies demonstrated synergistic activity by inhibiting both PI3Ks and mTOR with selective inhibitors. Based on the structure activity relationships identified in this study, five new derivatives were synthesized and tested, which exhibited potent activity against glioma cells but not superior to the dual PI3K/mTOR inhibitor and lead compound of the screening eCF324.

Development of Potent Inhibitors of Receptor Tyrosine Kinases by Ligand-Based Drug Design and Target-Biased Phenotypic Screening.

Pyrazolopyrimidines with potent antiproliferative properties were developed by an adaptive strategy that applies ligand-based design and phenotypic screening iteratively and is informed by biochemical assays. To drive development toward specific oncopathways, compounds were tested against cancer cells that overexpress, or not, AXL kinase. Identified phenotypic hits were found to inhibit oncotargets AXL, RET, and FLT3. Subsequent optimization generated antiproliferative lead compounds with unique selectivity profiles, including selective AXL inhibitors and a highly potent inhibitor of FLT3.

Global Expanded Nutrient Supply (GENuS) Model: A New Method for Estimating the Global Dietary Supply of Nutrients.

Insufficient data exist for accurate estimation of global nutrient supplies. Commonly used global datasets contain key weaknesses: 1) data with global coverage, such as the FAO food balance sheets, lack specific information about many individual foods and no information on micronutrient supplies nor heterogeneity among subnational populations, while 2) household surveys provide a closer approximation of consumption, but are often not nationally representative, do not commonly capture many foods consumed outside of the home, and only provide adequate information for a few select populations. Here, we attempt to improve upon these datasets by constructing a new model--the Global Expanded Nutrient Supply (GENuS) model--to estimate nutrient availabilities for 23 individual nutrients across 225 food categories for thirty-four age-sex groups in nearly all countries. Furthermore, the model provides historical trends in dietary nutritional supplies at the national level using data from 1961-2011. We determine supplies of edible food by expanding the food balance sheet data using FAO production and trade data to increase food supply estimates from 98 to 221 food groups, and then estimate the proportion of major cereals being processed to flours to increase to 225. Next, we estimate intake among twenty-six demographic groups (ages 20+, both sexes) in each country by using data taken from the Global Dietary Database, which uses nationally representative surveys to relate national averages of food consumption to individual age and sex-groups; for children and adolescents where GDD data does not yet exist, average calorie-adjusted amounts are assumed. Finally, we match food supplies with nutrient densities from regional food composition tables to estimate nutrient supplies, running Monte Carlo simulations to find the range of potential nutrient supplies provided by the diet. To validate our new method, we compare the GENuS estimates of nutrient supplies against independent estimates by the USDA for historical US nutrition and find very good agreement for 21 of 23 nutrients, though sodium and dietary fiber will require further improvement.

Imagery rescripting as a brief stand-alone treatment for depressed patients with intrusive memories.

Many depressed patients report intrusive and distressing memories of specific events in their lives. Where present, these memories are believed to act as a maintaining factor. A series of ten patients with major depressive disorder and intrusive memories, many of them reporting severe, chronic, or recurrent episodes of depression, were given an average of 8.1 sessions of imagery rescripting as a stand-alone treatment. Hierarchical linear modelling demonstrated large treatment effects that were well maintained at one year follow-up. Seven patients showed reliable improvement, and six patients clinically significant improvement. These gains were achieved entirely by working through patients' visual imagination and without verbal challenging of negative beliefs. Spontaneous changes in beliefs, rumination, and behaviour were nevertheless observed.

Patient expectations as predictors of outcome in patients with acute low back pain.

BACKGROUND: Few studies have evaluated the association between patient expectations for recovery and clinical outcomes, and no study has evaluated whether asking patients to choose their therapy modifies such an association. OBJECTIVE: To evaluate the association between patients' expectations and functional recovery in patients with acute low back pain (LBP), and to determine whether that association is affected by giving patients choice of therapy. DESIGN AND PARTICIPANTS: A secondary analysis of a randomized controlled trial comparing usual care alone to usual care plus choice of chiropractic, acupuncture, or massage in 444 adults with acute LBP, lasting less than 21 days. MEASUREMENTS AND MAIN RESULTS: Primary outcome was functional disability (Roland score) at 5 and 12 weeks. Patients' general expectations for improvement were associated with improvement in functional status (beta = 0.96, 95% CI = 0.56, 1.36). A 1-point increase in general expectations was associated with a 0.96-point improvement in Roland score. The association of expectation with outcome was 2-3 times greater in the usual care group than the choice group. However, these differences did not reach statistical significance. CONCLUSIONS: In patients with acute LBP, higher expectations for recovery are associated with greater functional improvement. Eliciting patient expectations for improvement may be a simple way to identify patients with the highest (or lowest) likelihood of experiencing functional improvement. Incorporating questions about patient expectations in future trials may clarify the role of this important correlate of clinical outcomes.

I'll believe it when I can see it: imagery rescripting of intrusive sensory memories in depression.

Intrusive sensory memories are a common feature of depression but these are not targeted in standard cognitive treatments. Imagery rescripting of distressing memories has so far been mainly used to treat trauma-related disorders and as a component of the treatment of personality disorders. We propose that this approach might also be effective in treating depression. This paper describes the initial application of imagery rescripting as a stand-alone treatment for two patients with a sole diagnosis of major depressive disorder. The two cases are described in detail and follow-up data are reported. Implications for the cognitive treatment of depression and for our theoretical understanding about the mechanisms of change in cognitive therapy are considered.

Intrusive images and memories in major depression.

Individuals with current major depression were interviewed to investigate the prevalence of distressing intrusive mental imagery among depressed patients and study the phenomenology of these intrusions. Of the 39 currently depressed patients, 17 experienced some form of repetitive intrusive imagery (i.e., either an intrusive memory or image), with intrusive memories being more common than images. The intrusive imagery was experienced as highly uncontrollable and interfered significantly with patients' everyday lives. The intrusions were experienced with a sense of 'nowness', as well as physical and emotional re-experiencing. Despite high levels of re-experiencing, levels of dissociation were very low. The intrusive imagery was in some patients part of a wider network of key defining autobiographical memories, consistent with the idea that it is likely to play a significant role in maintaining the patient's depressive mood. Interventions targeting these intrusions could potentially result in a positive shift in depressed mood.