A proprietary blend of standardized Punica granatum fruit rind and Theobroma cocoa seed extracts mitigates aging males' symptoms: A randomized, double-blind, placebo-controlled study.

Objective: We evaluated the safety and efficacy of a novel combination of Punica granatum fruit rind and Theobroma cocoa seed extracts (LN18178 or Tesnor®) in enhancing serum testosterone level and reducing aging males' symptoms (AMS) in a randomized, double-blind, placebo-controlled investigation (CTRI Reg. No. CTRI/2019/02/017506). Methods: One hundred twenty healthy male participants (age 36-55 years) were randomized (n=40) to placebo, 200 or 400 mg of LN18178 for a period of fifty-six consecutive days of supplementation. The primary efficacy parameter was the AMS score. The secondary parameters were serum testosterone (free and total) levels, hand-grip strength, and perceived stress scale (PSS-10) score. Measurement of other hormones included in the study was serum dihydrotestosterone (DHT), cortisol, and 17ß-estradiol (E2). Total blood chemistry parameters, vital signs, and urinalysis were parts of the safety assessment. Results: Both doses of LN18178 significantly reduced the mean AMS scores after 56 days of supplementation. Furthermore, it significantly improved general, psychological, and sexual well-being. Serum levels of free testosterone and total testosterone levels were significantly increased in LN18178 supplemented (200 and 400 mg) participants compared to the baseline and placebo. Significant improvements in hand-grip strength and reduced PSS-10 scores were also observed. Conclusion: LN18178 supplementation reduced AMS scores and improved sexual performance. Also, LN18178 groups exhibited superior muscular strength and reduction in perceived stress. Total blood chemistry and urine analysis demonstrated the broad-spectrum safety.

Spreading depolarization may represent a novel mechanism for delayed fluctuating neurological deficit after chronic subdural hematoma evacuation.

OBJECTIVE: Most patients with chronic subdural hematoma (cSDH) recover after surgical evacuation with a straightforward course. There is a subset of patients who develop transient and fluctuating deficits not explained by seizures, stroke, or mass effect after evacuation. The objective of this study was to investigate whether these postoperative neurological deficits may be related to temporary brain dysfunction caused by cortical spreading depolarizations (SDs). METHODS: The authors conducted a prospective observational study of 40 patients who underwent cSDH evacuation. At the time of surgery, a 1 × 6 subdural electrode strip was placed on the cortex parallel to the subdural drain. Clinical outcomes were assessed utilizing the Markwalder Grading Scale, need for clinical EEG for new deficit, and presence of new deficits. RESULTS: Definitive SD was detected in 6 (15%) of 40 patients. Baseline and cSDH characteristics did not differ between patients with and without SD. More patients experienced postoperative neurological deterioration if they had SD (50%) compared to those without SD (8.8%; p = 0.03). Only 2 patients in the entire cohort demonstrated early neurological deterioration, both of whom had SD. One of these cases demonstrated a time-locked new focal neurological deficit (aphasia) at the start of a series of multiple clusters of SD. CONCLUSIONS: This is the first observation of SD occurring after cSDH evacuation. SD occurred at a rate of 15% and was associated with neurological deterioration. This may represent a novel mechanism for otherwise unexplained fluctuating neurological deficit after cSDH evacuation. This could provide a new therapeutic target, and SD-targeted therapies should be evaluated in prospective clinical trials.

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (p<0.01). Fewer readers could lateralize seizure-onset (p<0.05). The confidence measures of the assignments were low (probable-unlikely), but increased using AR2 (p<0.05). The ICC for identifying the time of seizure-onset was 0.15 (95% confidence interval (CI), 0.11-0.18) using AR1 and 0.26 (95% CI 0.21-0.30) using AR2.  The EEG interpretations were often consistent with behavioral, neurophysiological, and neuro-radiological findings, with left sided assignments correct in 95.9% (CI 85.7-98.9%, n=4) of cases using AR2, and 91.9% (77.0-97.5%) (n=4) of cases using AR1. Conclusions: EEG artifact reduction methods for localizing seizure-onset does not result in high rates of interpretability, reader confidence, and inter-reader agreement. However, the assignments by groups of readers are often congruent with other clinical data. Utilization of the AR2 software method may improve the validity of ictal EEG artifact reduction.