The influence of decision-making in tree ring-based climate reconstructions.

Tree-ring chronologies underpin the majority of annually-resolved reconstructions of Common Era climate. However, they are derived using different datasets and techniques, the ramifications of which have hitherto been little explored. Here, we report the results of a double-blind experiment that yielded 15 Northern Hemisphere summer temperature reconstructions from a common network of regional tree-ring width datasets. Taken together as an ensemble, the Common Era reconstruction mean correlates with instrumental temperatures from 1794-2016 CE at 0.79 (p < 0.001), reveals summer cooling in the years following large volcanic eruptions, and exhibits strong warming since the 1980s. Differing in their mean, variance, amplitude, sensitivity, and persistence, the ensemble members demonstrate the influence of subjectivity in the reconstruction process. We therefore recommend the routine use of ensemble reconstruction approaches to provide a more consensual picture of past climate variability.

Results of a randomized phase I dose-finding trial of several doses of isoflavones in men with localized prostate cancer: administration prior to radical prostatectomy.

The purpose of this phase I dose-finding randomized controlled trial was to evaluate the safe and effective dose of isoflavones to be used in future clinical trials for prostate cancer prevention. Forty-five eligible men were supplemented with 40, 60, and 80 mg of purified isoflavones or no supplement from biopsy to prostatectomy. Compliance with the study agent, toxicity, and changes in plasma isoflavones, serum steroid hormones, prostate-specific antigen (PSA), and tissue Ki-67 were analyzed from baseline to completion of the study. Forty-four subjects completed the study with a duration of intervention of 30 (+/- 3) days. We observed significant increases in plasma isoflavones with treatment for all doses compared with controls without producing any toxicity. Significant increases in serum total estradiol were observed in the 40 and 60 mg isoflavone-treated arms. However, a significant increase in serum free testosterone was observed in the 60 mg isoflavone-treated arm. Changes in serum sex hormone-binding globulin, PSA, and percentage of tissue Ki-67 were not statistically significant with treatment for this sample size and duration of intervention. Our results identify a safe dose of purified isoflavones for future clinical trials and establish the need for further definitive, well-powered trials to examine the role of isoflavones in prostate carcinogenesis.

Results of a Randomized Clinical Trial of the Action of Several Doses of Lycopene in Localized Prostate Cancer: Administration Prior to Radical Prostatectomy.

PURPOSE: The purpose of this Phase II randomized-controlled trial was to evaluate the safety and effect of administering several doses of lycopene to men with clinically localized prostate cancer, on intermediate endpoint biomarkers implicated in prostate carcinogenesis. METHODS: Forty-five eligible men with clinically localized prostate cancer were supplemented with 15, 30 or 45 mg of lycopene or no supplement from biopsy to prostatectomy. Compliance to study agent, toxicity, changes in plasma lycopene, serum steroid hormones, PSA and tissue Ki-67 were analyzed from baseline to completion of intervention. RESULTS: Forty-two of forty-five five subjects completed the intervention for approximately 30 days from the time of biopsy until prostatectomy. Plasma lycopene increased from baseline to post treatment in all treatment groups with greatest increase observed in the 45 mg lycopene-supplemented arm compared to the control arm without producing any toxicity. Overall, subjects with prostate cancer had lower baseline levels of plasma lycopene similar to those observed in previous studies in men with prostate cancer. Serum free testosterone decreased with 30 mg lycopene supplementation and total estradiol increased significantly with 30 mg and 45 mg supplementation from baseline to end of treatment, with no significant increases in serum PSA or tissue Ki-67. These changes were not significant compared to the control arm for this sample size and duration of intervention. CONCLUSIONS: Although antioxidant properties of lycopene have been hypothesized to be primarily responsible for its beneficial effects, our study suggests that other mechanisms mediated by steroid hormones may also be involved.

A Phase II randomized, placebo-controlled clinical trial of purified isoflavones in modulating steroid hormones in men diagnosed with localized prostate cancer.

Our purpose was to evaluate the safety and effectiveness of purified isoflavones in producing an increase in plasma isoflavones and a corresponding change in serum sex hormone binding globulin (SHBG) and steroid hormone levels in men diagnosed with early stage prostate cancer. In this Phase II randomized, double-blinded, placebo-controlled trial, 53 prostate cancer patients with a Gleason score of 6 or below were supplemented with 80 mg purified isoflavones or placebo for 12 weeks. Changes in plasma isoflavones, serum steroid hormones, and safety markers were analyzed from baseline to 12 wk. A total of 50 subjects completed the study. Although significant increases in plasma isoflavones (P < 0.001) was observed with no clinical toxicity, the corresponding modulation of serum SHBG, total estradiol, and testosterone in the isoflavone-treated group compared to men receiving placebo was nonsignificant. Increasing plasma isoflavones failed to produce a corresponding modulation of serum steroid hormone levels in men with localized prostate cancer. The study establishes the need to explore other potential mechanisms by which prolonged and consistent purified isoflavone consumption may modulate prostate cancer risk.

Safety of purified isoflavones in men with clinically localized prostate cancer.

Our purpose was to evaluate the safety of 80 mg of purified isoflavones administered to men with early stage prostate cancer. A total of 53 men with clinically localized prostate cancer, Gleason score of 6 or below, were supplemented with 80 mg purified isoflavones or placebo for 12 wk administered in 2 divided doses of 40 mg to provide a continuous dose of isoflavones. Compliance, changes in plasma isoflavones, and clinical toxicity were analyzed at baseline, 4, and 12 wk. A total of 50 subjects completed the 12-wk intervention. A continuous, divided-dose administration of 80 mg/day of purified isoflavones at amounts that exceeded normal American dietary intakes significantly increased (P < 0.001) plasma isoflavones in the isoflavone-treated group compared to placebo and produced no clinical toxicity. With the current evidence on the cancer preventive properties of isoflavones, these results are significant and offer promise for these phytochemicals to be developed as potent agents to prevent cancer progression.

Perioperative herbal supplement use in cancer patients: potential implications and recommendations for presurgical screening.

BACKGROUND: Products made from botanicals that are used to maintain or improve health are known as herbal supplements, botanicals, or phytomedicines. Many herbs have a long history of use and claimed health benefits. However, many herbal supplements and botanicals have potent pharmacologic activity that can contribute to adverse effects and drug interactions. The use of herbal supplements by cancer patients in the perioperative period is common and consistent with the substantial increase in the use of alternative medical therapies. METHODS: We reviewed the literature to examine the constituents, safety, pharmacokinetics, and pharmacodynamics of those herbal supplements that are predominantly used by cancer patients. RESULTS: Different supplements possess antiplatelet activity, adversely interact with corticosteroids and central nervous system depressant drugs, have gastrointestinal manifestations, produce hepatotoxicity and nephrotoxicity, and produce additive effects when used with opioid analgesics. CONCLUSIONS: With the increasing use of herbal supplements by cancer patients, surgical staff need to screen patients pre-surgically for use of these supplements. Clinical practice guidelines are needed for screening and prevention of herbal supplement usage to prevent potential adverse events that may arise from herbal medications taken alone or combined with conventional therapies during the perioperative period.

A case-control study evaluating the association of purposeful physical activity, body fat distribution, and steroid hormones on premenopausal breast cancer risk.

The objective of this case-control study was to investigate the relationship between purposeful physical activity, body fat distribution, body mass index, and steroid hormones. These factors are known to be implicated in modulating breast cancer risk in premenopausal women. A total of 112 newly diagnosed, premenopausal breast cancer patients and 106 age-matched premenopausal disease-free controls were admitted to the study. Information regarding personal, medical, hormonal, and reproductive history, smoking and alcohol use, physical activity history, and anthropometric measurements was obtained. Serum samples for steroid hormone assays were collected and analyzed. Disease-free premenopausal controls had a significantly higher physical activity index (PAI) (p

The specific role of isoflavones in reducing prostate cancer risk.

AIMS: To evaluate the effectiveness of supplementing a group of early stage prostate cancer patients, with 60 mg of soy isoflavones in producing a change in hormonal and proliferative risk parameters that are implicated in prostate cancer promotion. METHODS: Seventy six eligible prostate cancer patients with a Gleason score of 6 or below, between ages 50 and 80 were admitted and supplemented with soy isoflavones or placebo for a 12 week period and changes in PSA and steroid hormones were analyzed at baseline and post intervention. RESULTS: Fifty-nine patients completed the 12-week intervention. Serum free testosterone was reduced or showed no change in 61% of subjects in the isoflavone group compared to 33% in the placebo group. Serum total PSA decreased or was unchanged in 69% of the subjects in the isoflavone treated group compared to 55% in the placebo group. However, we did not see an increase in SHBG levels. Nineteen percent of subjects receiving soy isoflavones reduced total PSA by two points or more during the intervention period. CONCLUSIONS: These data suggest that supplementing early stage prostate cancer patients with soy isoflavones, even in a study of short duration, altered surrogate markers of proliferation such as serum PSA and free testosterone in a larger number of subjects in the isoflavone supplemented group than the group receiving placebo. The study establishes the need to explore further the effects of prolonged and consistent soy consumption, which could potentially delay onset of histologic disease in this patient population.

Use of complementary/integrative nutritional therapies during cancer treatment: implications in clinical practice.

BACKGROUND: The objectives of this study were to determine the prevalence and characterize the use of complementary/integrative nutritional therapies (CINTs) by patients during cancer treatment. METHODS: This retrospective review used data collected as a part of standard clinical care provided by the registered clinical dietitians and included nutritional history, demographic variables, anthropometrics, prevalence of use, and the specific integrative nutritional therapies used by these patients during cancer treatment. RESULTS: Twenty-nine percent of 820 patients reported use of CINTs not prescribed by their physician. Caucasians and patients over age 60 were the principal users of CINTs during treatment. Modular vitamins were the most frequently reported additive (86.9%), followed by botanicals/biologics (43.8%) and mineral supplements (28.6%). CONCLUSIONS: A considerable proportion of cancer patients use unproven CINTs during cancer treatment. The health professional should become more aware of the complementary/integrative therapies that their patients are using during cancer treatment.

The specific role of isoflavones on estrogen metabolism in premenopausal women.

BACKGROUND: There is increasing evidence that dietary factors may play a role in the production, metabolism, and bioavailability of sex hormones and their impact on target tissues. The specific objective of this study was to evaluate the effectiveness of supplementing a group of premenopausal women who were free of breast carcinoma with a dietary supplement of isoflavones (40 mg per day) in producing a change in steroid hormones and menstrual cycle length. METHODS: Sixty-eight consecutively recruited, premenopausal, omnivorous women of all races and ethnicities between the ages of 25 years and 55 years were admitted to the study and randomized to an experimental group supplemented with soy (40 mg genistein per day) or to a control group that consumed a placebo for a 12-week period. Changes in their anthropometric, nutritional, and hormonal biomarkers from early follicular phase were analyzed at baseline and post-intervention. RESULTS: Serum-free estradiol and estrone levels decreased moderately in the experimental group. Serum hormone-binding globulin levels increased in 41.4% of women in the experimental group compared with 37.5% of women in the placebo group. Free estradiol decreased in 53.85% of women in the experimental group compared with 37.5% of women in the placebo group. Estrone decreased in 55.56% of women in the experimental group compared with 42.86% in the placebo group. Those women in the experimental group who were consuming soy had their mean menstrual cycle length increased by 3.52 days compared with a mean decrease of 0.06 days for women in the placebo group (P = 0.04) from baseline to the third menstrual cycle. In addition, women who were taking soy had their mean follicular phase increase by 1.46 days compared with a mean increase of 0.14 days for women who were taking the placebo (P = 0.08). CONCLUSIONS: These data suggest that increased isoflavone intake affects estrogen metabolism by altering the steroid hormone concentrations and menstrual cycle length, thereby demonstrating a potential to reduce the risk for breast carcinoma.