From candidate to president: Donald Trump's effect on an executive coaching client.

Political events leading up to, and following the results of, the November, 2016 election have affected patients in psychotherapy as well as clients working with executive coaches. This article follows developments in coaching work with one male, middle-aged, highly successful but "interpersonally challenged" client that are traceable to the client's reactions to the election and to the president himself.

Effects of 7 days on an ad libitum low-fat vegan diet: the McDougall Program cohort.

BACKGROUND: Epidemiologic evidence, reinforced by clinical and laboratory studies, shows that the rich Western diet is the major underlying cause of death and disability (e.g, from cardiovascular disease and type 2 diabetes) in Western industrialized societies. The objective of this study is to document the effects that eating a low-fat (≤10% of calories), high-carbohydrate (~80% of calories), moderate-sodium, purely plant-based diet ad libitum for 7 days can have on the biomarkers of cardiovascular disease and type 2 diabetes. METHODS: Retrospective analysis of measurements of weight, blood pressure, blood sugar, and blood lipids and estimation of cardiovascular disease risk at baseline and day 7 from 1615 participants in a 10-day residential dietary intervention program from 2002 to 2011. Wilcoxon's signed-rank test was used for testing the significance of changes from baseline. RESULTS: The median (interquartile range, IQR) weight loss was 1.4 (1.8) kg (p < .001). The median (IQR) decrease in total cholesterol was 22 (29) mg/dL (p < .001). Even though most antihypertensive and antihyperglycemic medications were reduced or discontinued at baseline, systolic blood pressure decreased by a median (IQR) of 8 (18) mm Hg (p < .001), diastolic blood pressure by a median (IQR) of 4 (10) mm Hg (p < .001), and blood glucose by a median (IQR) of 3 (11) mg/dL (p < .001). For patients whose risk of a cardiovascular event within 10 years was >7.5% at baseline, the risk dropped to 5.5% (>27%) at day 7 (p < .001). CONCLUSIONS: A low-fat, starch-based, vegan diet eaten ad libitum for 7 days results in significant favorable changes in commonly tested biomarkers that are used to predict future risks for cardiovascular disease and metabolic diseases.

How evidence-based medicine biases physicians against nutrition.

Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease.

Identification of a new class of glucokinase activators through structure-based design.

Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high glucose concentrations. Glucose flux through GK also contributes to reducing hepatic glucose output. Because many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, compounds that can activate GK may serve as effective treatments for type 2 diabetes. Herein we report the identification and initial optimization of a novel series of allosteric glucokinase activators (GKAs). We discovered an initial thiazolylamino pyridine-based hit that was optimized using a structure-based design strategy and identified 26 as an early lead. Compound 26 demonstrated a good balance of in vitro potency and enzyme kinetic parameters and demonstrated blood glucose reductions in oral glucose tolerance tests in both C57BL/6J mice and high-fat fed Zucker diabetic fatty rats.

Are your patient's medically unexplained symptoms really "all in her head"?

Even though the definitions in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual were supposed to be descriptions of clinical syndromes, the third and later editions of the DSM have included diagnostic categories for conversion disorder and various forms of somatization disorder, which represent an assertion of causality, not an observation of a clinical syndrome. Although these "disorders" represent etiologic diagnoses, the definitions provide no validated method for establishing causality in individual cases. Nor is there any validated methodology for making a presumptive diagnosis. Thus, it is impossible to make a diagnosis of conversion disorder or a somatization disorder without making an error in reasoning. These diagnostic categories should therefore be excluded from the DSM-V.

Human papillomavirus: molecular and cytologic/histologic aspects related to cervical intraepithelial neoplasia and carcinoma.

Cervical cancer is unique among human cancers because it was the first cancer discovered to be virtually solely attributable to the effects of an infectious agent. Numerous epidemiologic and laboratory studies have confirmed a strong causal association between human papillomavirus infection and the development of premalignant and malignant lesions of the uterine cervix, and human papillomavirus-mediated malignant transformation is an ideal model system for the study of virally mediated carcinogenesis. Neoplastic transformation of affected cervical epithelium appears to be a direct consequence of the unregulated overexpression of viral oncoproteins that have central roles in the normal viral replicative cycle. This review is focused on the mechanisms that regulate the normal papillomavirus life cycle and on the mechanisms that appear to have central roles in malignant transformation of the cervical mucosa.

Phase II trial of weekly docetaxel/irinotecan combination in advanced pancreatic cancer.

BACKGROUND: Docetaxel and irinotecan have activity in pancreatic cancer. The combination of docetaxel and irinotecan is attractive because of preclinical evidence of synergy between the two drugs. We have previously demonstrated the safety of docetaxel 35 mg/m(2) and irinotecan 50 mg/m(2) given on days 1, 8, 15, and 21 of a 35-day schedule. PATIENTS AND METHODS: Patients who had unresectable or metastatic adenocarcinoma of the pancreas, bidimensionally measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and normal bilirubin levels were eligible. Tumor assessment was performed with computed tomography, computed tomographic angiography, or magnetic resonance imaging every 2 cycles. Response was graded according to World Health Organization criteria. RESULTS: We enrolled 37 eligible patients. Principal grade 3/4 toxicities were diarrhea (21%), neutropenia (30%), and hyperglycemia (30%). There were 3 patients with febrile neutropenia and no toxic deaths. There were 4 early deaths. Among 36 evaluable patients, 9 (24%) attained a partial response and 1 (3%) attained a complete response for an objective response rate of 27%. One patient enrolled because she had been deemed to have unresectable disease but then underwent resection with negative margins after attaining a confirmed partial response. Median survival for all eligible patients is 9.4 months (range 0-68+ months) with minimum follow-up for surviving patients of 23.4 months. One-year survival is 43%. The patient who attained a complete response is alive with recurrent disease at 68 months. CONCLUSIONS: The docetaxel/irinotecan combination given on a weekly schedule is an active treatment for advanced pancreatic cancer.

Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray.

BACKGROUND: Measures of vascular endothelial growth factor (VEGF) expression in pancreatic cancer typically have been qualitative or semiquantitative. The objective of this study was to use a series of algorithms called AQUA that quantitatively assesses protein expression on tissue microarrays (TMAs) to compare in situ expression of VEGF and its primary receptors, VEGF receptor 1 (FLT-1) and VEGF receptor 1 (FLK-1), on a pancreatic cancer TMA. METHODS: TMAs were constructed by arraying 1.5-mm cores from 76 samples of pancreatic adenocarcinoma (1996-2002) that were obtained from the archives of the Yale Department of Pathology. The staining for AQUA was similar to standard immunohistochemistry and involved antigen retrieval and the application of primary antibodies, but with epifluorescence detection. Slides were counterstained with 4',6-diamidino-2-phenylindole for nuclear visualization and cytokeratin for membrane visualization. The primary antibodies used were VEGF, FLT-1, FLK-1, and cytokeratin. RESULTS: Disease stage was highly prognostic for outcome, as expected. Total amounts of VEGF and its receptors were assessed within the tumor mask and were divided into quartiles. Kaplan-Meier survival curves showed that VEGF and FLK-1 were not associated clearly with outcome. However, the expression of FLT-1 was correlated significantly, and the patients who had tumors with the lowest expression FLT-1 levels had the worst survival (P = .0038). In multivariate analysis, FLT-1 expression was an independent prognostic factor for overall survival (P = .0044). CONCLUSIONS: VEGF and its 2 principal receptors were expressed to varying degrees in tumors of the pancreas. A significant association was found between low expression of FLT-1 and both poor prognosis and advanced stage, suggesting that tumor expression of this VEGF receptor is a marker of less aggressive disease.

Optimizing the gonadotrophin dose regimen.

The starting dose of gonadotrophin for controlled ovarian stimulation (COS) or ovulation induction (OI) must be individualized and has considerable impact on outcomes (pregnancy and adverse events). Five large randomized, controlled trials have compared fixed doses of recombinant follicle-stimulating hormone (rFSH) for COS for assisted reproductive technology (ART). Among young women, a fixed dosage of 200 IU/day (versus 100 IU/day) yielded more oocytes and more transferable embryos. Thus, if surplus embryos can be cryopreserved, it could result in a higher cumulative pregnancy rate. However, no clear dose-response relationship was evident among older women receiving either 150 or 250 IU/day. Another randomized, controlled trial showed that a low-dose step-up OI protocol with weekly increments of 25 IU/day of rFSH was more effective and more efficient than a regimen with 50-IU/day increments. Research to develop a normogram for the optimal starting dose of rFSH for individual patients is under way.