Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB). Objective. The primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin) and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (total n = 21) to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer's dementia. This trial is registered with ClinicalTrials.gov NCT01805518.

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We demonstrated for the first time Lipocurc™'s anti-apoptotic and neurotrophic effects in theDJ-1-KO rat model of PD. Our promising findings warrant randomized controlled trial of Lipocurc™ in translating the novel nanotechnology-based epigenetics-driven drug discovery platform toward efficacious therapeutics in PD.

Background:Methadone is associated with a statistically significant increase in BMI in the first 2 years of treatment.Objectives:To evaluate the changes of body composition (bone mass, % fat, % muscle mass, % water, and basal metabolic rate) related to this increase.Patients and Methods:Changes in body composition were monitored, via bioelectrical impedance, in 29 patients in methadone treatment for opiate dependency (age 18 to 44, mean = 29.3, SD = 7.0, 13 men, 16 women).Results:Within one year from admission to treatment, a statistically significant (t-tests, P < 0.05) increase was noted in their body mass index (BMI), % of body fat, average body mass, and average basal metabolic rate, and relative decrease in their % of muscle mass and % of bone mass. Neither absolute bone mass nor muscle mass changed significantly.Conclusions:Physicians involved in care of methadone patients should recommend dietary and lifestyle changes to improve their overall health.

The retrospective diagnosis of concussion is often missed by clinicians. We present a brief scale for retrospective assessment of the immediate concussion symptoms (ICS) to facilitate the diagnosis of patients without visible head injury or full loss of consciousness. We administered the scale to 90 survivors of car accidents (mean age 42.0, SD=13.6; 33 males, 57 females) at 2 to 33 months after their accident. Our scale consists of 6 items and these were endorsed by the following % of our respondents: feeling dazed (64.4% of our 90 respondents), stunned (73.3%), confused (70.0%), disoriented (62.2%), dizzy (57.8%), and loss of consciousness (22.2%). The statistical properties of the scale are satisfactory (Cronbach alpha = 0.74). The scale correlates with post-accident insomnia (r=0.28), depression (r=0.29), and also with Rivermead measure of the chronic post-concussion syndrome (r=0.34). The ICS scale could be used as a starting point in longitudinal research with brain imaging procedures to evaluate the stages of recovery from the initial concussion. Attached are the English, Spanish, French, German, Italian, Russian, and Czech versions of our scale.

In routine work, medical staff usually has to rely on the patient's self-reports of criminal activity and of recent involvement in fights. This study examines how these self-reports of crime correlate with the patients' routine urine tests and personality measures. Pearson correlations of these self-reports by 55 methadone patients (M age = 34.1 yr., SD = 9.1; 35 men, 20 women) were calculated to their urine screening tests (those for opiates, benzodiazepines, and cocaine) and to personality scores on the Symptom Checklist 90-Revised (SCL-90-R). Patients who reported being involved in recent illegal activities to obtain drugs had significantly higher scores on the SCL-90-R scale assessing obsessive-compulsive symptoms (r = .28) and had more frequent positive urine tests for cocaine (r = .35). Those who reported having engaged in fights within the last 12 mo. had higher scores on SCL-90-R measures of somatic complaints (r = .32), anxiety (r = .31), and depression (r = .29), and of overall psychopathology (r = .29), and they also had more often positive urine tests for cocaine (r = .28) than other patients. Studies on larger samples are needed to help clinicians to predict criminal or hostile behavior during methadone treatment.

Background: Feelings of hopelessness could be a potential sign of relapse in opiate addiction. Objectives: We investigated statistical relationship of self-reports of hopelessness by patients in methadone maintenance treatment (MMT) to concurrent drug abuse. Patients and Methods: Fifty-two MMT outpatients (34 men, 18 women, mean age 33.6, SD = 9.7) completed the Beck Hopelessness Scale (BHS) to describe how they felt within the last 7 days. Results of urine screening tests for opiates, cocaine, oxycodone, and benzodiazepines were also recorded for the last 7 days. Results: 67.3% of the patients scored within the normal BHS range (scores < 4), 21.2% within the mild category (BHS from 4 to 8), 9.6% within the moderate (BHS from 9 to 14), and one patient in the severe category (BHS > 14). On urine tests, 23.1% of the patients tested positive for opiates at least once in the last 7 days, 19.2 % for cocaine, and 17.3% for oxycodone. These three urine tests were neither significantly correlated (P > 0.05) with hopelessness scores, nor with gender or age. Only 4 patients tested positive for benzodiazepines (7.7 %). Conclusions: Mild to moderate reports of hopelessness among MMT patients were unrelated to their concurrent abuse of opiates, cocaine, and oxycodone.

Introduction: There is mounting evidence to suggest that hyper-homocysteinemia (eHct) correlates with cognitive decline severity and cortical atrophy in AD. Hydrogen Sulfide (H 2 S) exerts neuroprotection through regulating Homocysteine (eHcy) signaling. Elemental sulfur can mediate H 2 S neuroprotection through the trans-sulfuration pathway and correct the the dysregulation of H 2 S /Hct signaling in AD. Sublimed Sulfur, formulated as SULMEDOL and approved for the treatment of lactose intolerance, activates gut beta-galactosidase (GALAC). We repurpose Sulmedol from lactose intolerance to likely CNS effect, since gut GALAC cross-talks with senescence-related GALAC expression in the brain. In view of the known regulatory function of GALAC in CNS endosomal-lysosomal autophagy system , we propose that SULMEDOL may rescue aberrant autophagy in AD.