Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial.

Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6), in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171) were randomized (1:1) to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI) score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs) in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in) and/or short duration of treatment may have masked a potential beneficial effect on sleep quality.

Testing the Bivalent Fear of Evaluation Model of Social Anxiety: The Relationship between Fear of Positive Evaluation, Social Anxiety, and Perfectionism.

The Bivalent Fear of Evaluation (BFOE) model of social anxiety proposes that fear of negative evaluation (FNE) and fear of positive evaluation (FPE) play distinct roles in social anxiety. Research is however lacking in terms of how FPE is related to perfectionism and how these constructs interact to predict social anxiety. Participants were 382 individuals from the general community and included an oversampling of individuals with social anxiety. Measures of FPE, FNE, perfectionism, and social anxiety were administered. Results were mostly consistent with the predictions made by the BFOE model and showed that accounting for confounding variables, FPE correlated negatively with high standards but positively with maladaptive perfectionism. FNE was also positively correlated with maladaptive perfectionism, but there was no significant relationship between FNE and high standards. Also consistent with BFOE model, both FNE and FPE significantly moderated the relationship between maladaptive perfectionism and social anxiety with the relationship strengthened at high levels of FPE and FNE. These findings provide additional support for the BFOE model and implications are discussed.

Switching to a 10-day Mediterranean-style diet improves mood and cardiovascular function in a controlled crossover study.

OBJECTIVES: Even short-term adherence to a Mediterranean-style diet may benefit aspects of psychological functioning. The aim of the present study was to assess the effects of switching to a 10-d Mediterranean-style diet on mood, cognition, and cardiovascular measures. METHODS: Using a crossover design, 24 women were randomly assigned to either the diet change (where they switched to a Mediterranean-style diet) or no diet change (normal diet) condition for 10 days before switching to the other condition for the same duration. Mood, cognition, and cardiovascular measures of blood pressure, blood flow velocity, and arterial stiffness were assessed at baseline and at the completion of the two diets (days 11 and 22). RESULTS: Independent of whether the Mediterranean-style diet was undertaken before or after the crossover, it was associated with significantly elevated contentment and alertness, and significantly reduced confusion. Additionally, aspects of cognition, such as memory recall, improved significantly as a result of switching to the Mediterranean-style diet. Regarding cardiovascular measures, there was a significant reduction in augmentation pressure associated with the Mediterranean-style diet intervention, but blood flow velocity through the common carotid artery did not change. CONCLUSIONS: This Mediterranean-style diet has the potential to enhance aspects of mood, cognition, and cardiovascular function in a young, healthy adult sample.

Anti-stress effects of lemon balm-containing foods.

Lemon balm (Melissa officinalis) has been used historically and contemporarily as a modulator of mood and cognitive function, with anxiolytic effects following administration of capsules, coated tablets and topical application. Following a pilot study with lemon balm extract administered as a water based drink, which confirmed absorption of rosmarinic acid effects on mood and cognitive function, we conducted two similar double-blind, placebo-controlled, crossover studies. These evaluated the mood and cognitive effects of a standardised M. officinalis preparation administered in palatable forms in a beverage and in yoghurt. In each study a cohort of healthy young adults' self-rated aspects of mood were measured before and after a multi-tasking framework (MTF) administered one hour and three hours following one of four treatments. Both active lemon balm treatments were generally associated with improvements in mood and/or cognitive performance, though there were some behavioral "costs" at other doses and these effects depended to some degree on the delivery matrix.

Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial.

This study aimed to examine the acute and sub-chronic effects of cocoa polyphenols on cognition and mood. In a randomized, double-blind study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg or 0 mg of polyphenols (placebo) in a parallel-groups design. Participants consumed their assigned treatment once daily for 30 days. Cognition was measured with the Cognitive Drug Research system and self-rated mood with the Bond-Lader Visual Analogue Scale. Participants were tested at baseline, at 1, 2.5 and 4 h after a single acute dose and again after receiving 30 days of treatment. In total, 72 participants completed the trial. After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to placebo. Mood was unchanged by treatment acutely while cognition was unaffected by treatment at all time points. This randomized controlled trial is perhaps the first to demonstrate the positive effects of cocoa polyphenols on mood in healthy participants. This provides a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.

Validation of volume delivery with the use of heliox in mechanical ventilation.

Using a mixture of helium and oxygen (heliox) while mechanically ventilating patients to relieve lower airway obstruction is commonly practiced in intensive care units. The use of heliox with commercially available mechanical ventilators is usually accomplished by connecting the heliox mixture to the air inlet of the ventilator. Since most ventilators do not compensate for the difference in gas densities, particular attention to the delivered tidal volume (V T ) is required. We utilized a commercially available mechanical ventilator with an internal blending system that is capable of delivering heliox instead of medical air. It identifies and compensates for the gas mixture, theoretically enhancing stability in delivered and monitored parameters. Intubated, sedated male domestic pigs (n = 7) were ventilated with a mechanical ventilator equipped with an internal heliox blending system utilizing pressure assist control, pressure regulated volume control, and pressure support ventilation modes. Accuracy of volume delivery was assessed by comparing delivered V T measured at the patient wye using the variable orifice flow sensor connected to the ventilator and a heated 0-35 L/min pneumotachograph that was calibrated for flow, pressure, and volume, with a 0.80/0.20 heliox mix and 0.50 oxygen. A paired t-test was utilized with a P < 0.05. Pigs mean weight 9.0 ± 0.9 kg. Mean exhaled tidal volume for all modes and was 66 ± 16 mL. When comparing all modes for the 0.50 oxygen to the heliox mix, we found that exhaled tidal volume % difference increased when using heliox ( P ≤ 0.037). This study confirms that clinicians should be vigilant in monitoring delivered V T using a commercially available ventilator equipped with an internal heliox blending system. Accuracy of delivered V T can vary greatly with the use of heliox in this system, as well as other configurations.

MDMA and methamphetamine: some paradoxical negative and positive mood changes in an acute dose laboratory study.

RATIONALE: This study investigated the acute mood effects of oral MDMA, methamphetamine, and placebo in a double-blind laboratory study. METHODS: Fifty-two healthy participants comprised abstinent recreational users of stimulant drugs, 27 female and 25 male, mean age 24.8 years. Three test sessions involved acute 100 mg oral 3.4-methylendioxymethamphetamine (MDMA), 0.42 mg/kg oral methamphetamine, and matching placebo. Drug administration was counterbalanced, testing was double-blind, and medical supervision was present throughout. Car-driving performance on a laboratory simulator was assessed after 3 and 24 h, with the findings being presented elsewhere. Positive and negative moods (PANAS self-ratings) were completed before drug administration, 3, 4.5, and 24 h later. Blood samples were taken to monitor drug plasma levels. RESULTS: Following MDMA, there were no significant increases in positive moods, whereas negative moods were significantly higher than under placebo. Methamphetamine led to significant increases in both positive and negative moods. The MDMA findings contrast with the elated moods, typically noted by dance clubbers on Ecstasy. However, they are consistent with some previous laboratory findings, since a wide array of positive and negative mood changes have been demonstrated. One possible explanatory factor was the neutral environmental situation, particularly if a primary action of MDMA is to intensify ongoing psychological states. Other explanatory factors, such as dosage, gender, post-drug timing, neurohormonal aspects, and social factors, are also discussed. CONCLUSIONS: In the laboratory, acute methamphetamine led to significantly higher positive moods. However, against expectations, MDMA did not generate a significant increase in positive moods.

Healthy middle-aged individuals are vulnerable to cognitive deficits as a result of increased arterial stiffness.

OBJECTIVES: Whilst pulse pressure and pulse wave velocity have been shown to predict cognitive outcomes, the relationship between arterial stiffness and cognition has not yet been explored in an entirely healthy nonclinical population. Furthermore, the effects of arterial stiffness on cognition are yet to be examined with computerized cognitive test batteries sensitive to subtle differences in cognitive performance. The aim of the present study was to examine the relationship between arterial stiffness (pulse pressure and augmentation index) and specific domains of cognitive performance in a healthy middle-aged sample. INDIVIDUALS AND METHOD: The sample comprised 92 healthy individuals, aged between 40 and 65 years, with no history of cardiovascular disease, diabetes, stroke, hypertension, smoking and were free from medication. The cognitive drug research (CDR) computerized system was implemented to assess domains of cognitive performance, whereas pulse pressure and augmentation index were determined centrally by a noninvasive SphygmoCor device. RESULTS: Pulse pressure was an independent predictor of both episodic secondary memory performance (beta = -0.27, R change = 0.07, P < 0.05) and speed of memory retrieval (beta = 0.24, R change = 0.06, P < 0.05). Augmentation index was also an independent predictor of speed of memory (beta = 0.27, R change = 0.07, P < 0.01). Working memory, power of attention and continuity of attention were not predicted by pulse pressure or augmentation index. CONCLUSION: It was concluded that healthy middle-aged adults are vulnerable to memory deficits as a result of normal increases in pulse pressure associated with ageing.

A phase I and pharmacokinetic study of exisulind and docetaxel in patients with advanced solid tumors.

PURPOSE: Exisulind (sulindac sulfone, FGN-1, Aptosyn) is a sulindac metabolite that induces apoptosis via inhibition of cyclic GMP-phosphodiesterase. This agent demonstrated tumor growth inhibition in rodent models of colon, breast, prostate, and lung carcinogenesis. In an orthotopic model of human non-small-cell lung cancer, the combination of exisulind and docetaxel prolonged survival in athymic nude rats, forming the basis of this phase I combination study. EXPERIMENTAL DESIGN: This study evaluated the toxicity and pharmacokinetics of combining exisulind (150-250 mg) given orally twice daily and docetaxel (30-36 mg/m2) administered intravenously on days 1, 8, and 15 of a 4-week cycle. RESULTS: Twenty patients with a range of advanced solid tumors (median age, 59 years; age range, 35-77 years; median performance status, 1) received a total of 70 courses. Observed adverse events were mild to moderate, and there was no dose-limiting toxicity at any level. Grade 3 gastrointestinal toxicities were present in 10 of the 70 cycles (10%) and included nausea, vomiting, dyspepsia, and elevated alkaline phosphatase. Neutropenia was present in four cycles in patients treated with a docetaxel dose of 36 mg/m2. Pharmacokinetic analysis did not demonstrate a clear effect of exisulind on docetaxel pharmacokinetics and vice versa. Relationships were evident between the plasma concentration of exisulind and the development of grade 2 or greater toxicities. One third of patients maintained stable disease for 3 to 12 cycles, but no objective responses were observed. CONCLUSIONS: The combination of docetaxel (36 mg/m2, weekly) and exisulind (500 mg/d) was reasonably well tolerated, and it is undergoing phase II testing in patients with non-small-cell lung cancer.

Phase I and II study of exisulind in combination with capecitabine in patients with metastatic breast cancer.

PURPOSE: We studied the safety and clinical activity of exisulind in combination with capecitabine in 35 patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: All patients had received previous anthracycline and taxane chemotherapies. Two dose levels of exisulind were explored, 125 and 250 mg orally bid as continuous daily therapy, concomitant with capecitabine 2,000 mg/m2 for 14 days in 21-day cycles. In the phase I study, the dose-limiting toxicities were hand-foot syndrome and diarrhea. The 125-mg bid dose was selected for phase II testing. RESULTS: The most common nonhematologic grade 2 to 3 adverse events were hand-foot syndrome (57%) and fatigue (48%). The most frequent grade 2 to 3 laboratory abnormality was granulocytopenia. No death, unexpected adverse events, or cumulative toxicity were encountered. One complete and four partial responses were achieved (objective response rate, 16%) in the 31 patients assessable for response. The median duration of response was 31 weeks; three patients experienced stable disease longer than 26 weeks. Overall clinical benefit (complete response, partial response, or stable disease > 26 weeks) was 23%. Fourteen specimens were available for immunohistochemical assessment of phosphodiesterase-5 isoenzyme (PDE-5) and PDE-2 expression, which are the targets of exisulind. Eighty percent of tumors showed some expression of PDE-5 in the invasive cancer cells including 35% that showed moderate or strong staining. PDE-2 showed moderate or strong staining in 78% of tumors. There was no apparent association between tumor response and staining intensity. CONCLUSION: Exisulind (125 mg orally bid) in combination with capecitabine is well tolerated and the combination has anticancer activity similar to that of capecitabine alone in heavily pretreated patients with MBC.