Polyphenol oxidases exhibit promiscuous proteolytic activity

Tyrosinases are an industrially significant class of polyphenol oxidase. Here, two tyrosinases are shown to cleave a specific peptide bond in a carboxylesterase, yielding a truncated product with higher catalytic activity than the full-length enzyme

Effectiveness of Compounded Bioidentical Hormone Replacement Therapy: An Observational Cohort Study

<p>Abstract</p> <p>Background</p> <p>Bioidentical Hormone Replacement Therapy (BHRT) is believed it to be a safer and equally effective alternative to Conventional Hormone Therapy for the relief of menopausal symptoms; however, data are needed to support these claims. The objective of this study is to evaluate the effectiveness of compounded BHRT provided in six community pharmacies.</p> <p>Methods</p> <p>This was an observational cohort study of women between the ages of 18-89 who received a compounded BHRT product from January 1, 2003 to April 30, 2010 in six community pharmacies. Data included patient demographics, comorbidities, therapeutic outcomes, and hormone therapies. Women self-rated menopausal symptoms as absent, mild, moderate, or severe. Descriptive statistics were used to characterize the patient population, BHRT use, and adverse events. Patient symptom severity was compared at baseline and 3 to 6 months follow-up using the Wilcoxon signed-rank test.</p> <p>Results</p> <p>Women (n = 296) receiving BHRT at Oakdell Pharmacy had a mean (standard deviation) age of 52 (9) years. The most common BHRT dosage forms utilized were topical (71%) and oral (43%). Compounded BHRT regimens were generally initiated at low doses regardless of route. Women experienced a 25% decrease in emotional lability (p < 0.01), a 25% decrease in irritability (p < 0.01), and a 22% reduction in anxiety (p = 0.01) within 3 to 6 months. These women also experienced a 14% reduction in night sweats (p = 0.09) and a 6% reduction in hot flashes (p = 0.50).</p> <p>Conclusions</p> <p>This study demonstrates that compounded BHRT improves mood symptoms. Larger studies are needed to examine the impact on vasomotor symptoms, myocardial infarction and breast cancer.</p

Development and Validation of Automated Magnetic Resonance Parkinsonism Index 2.0 to Distinguish Progressive Supranuclear Palsy-Parkinsonism From Parkinson's Disease

Background: Differentiating progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) is clinically challenging. Objective: This study aimed to develop an automated Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.0) algorithm to distinguish PSP-P from PD and to validate its diagnostic performance in two large independent cohorts. Methods: We enrolled 676 participants: a training cohort (n&nbsp;=&nbsp;346; 43 PSP-P, 194 PD, and 109 control subjects) from our center and an independent testing cohort (n&nbsp;=&nbsp;330; 62 PSP-P, 171 PD, and 97 control subjects) from an international research group. We developed a new in-house algorithm for MRPI 2.0 calculation and assessed its performance in distinguishing PSP-P from PD and control subjects in both cohorts using receiver operating characteristic curves. Results: The automated MRPI 2.0 showed excellent performance in differentiating patients with PSP-P from patients with PD and control subjects both in the training cohort (area under the receiver operating characteristic curve [AUC]&nbsp;=&nbsp;0.93 [95% confidence interval, 0.89–0.98] and AUC&nbsp;=&nbsp;0.97 [0.93–1.00], respectively) and in the international testing cohort (PSP-P versus PD, AUC&nbsp;=&nbsp;0.92 [0.87–0.97]; PSP-P versus controls, AUC&nbsp;=&nbsp;0.94 [0.90–0.98]), suggesting the generalizability of the results. The automated MRPI 2.0 also accurately distinguished between PSP-P and PD in the early stage of the diseases (AUC&nbsp;=&nbsp;0.91 [0.84–0.97]). A strong correlation (r&nbsp;=&nbsp;0.91, P &lt; 0.001) was found between automated and manual MRPI 2.0 values. Conclusions: Our study provides an automated, validated, and generalizable magnetic resonance biomarker to distinguish PSP-P from PD. The use of the automated MRPI 2.0 algorithm rather than manual measurements could be important to standardize measures in patients with PSP-P across centers, with a positive impact on multicenter studies and clinical trials involving patients from different geographic regions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Abnormal electroencephalographic rhythms from quiet wakefulness to light sleep in Alzheimer\u27s disease patients with mild cognitive impairment

\ua9 2025 International Federation of Clinical NeurophysiologyObjectives: Alzheimer\u27s disease patients with mild cognitive impairment (ADMCI) show abnormal resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms (8–12 Hz) and may suffer from daytime sleepiness. Our exploratory study tested the hypothesis that they may present characteristic EEG rhythms from quiet wakefulness to light sleep during diurnal recordings. Methods: Datasets of 34 ADMCI and 22 matched healthy elderly (Nold) subjects were obtained from international archives. EEG recordings lasted approximately 30 min. Transitions of EEG activity from quiet wakefulness (alpha-dominant) to light sleep (theta-dominant ripples) were scored according to Hori\u27s vigilance stages. Cortical source activities were computed using the eLORETA software. Results: ADMCI (t-ADMCI, N = 18) over Nold (t-Nold, N = 11) participants were characterized by greater frontal EEG delta source activities and a lesser reduction (reactivity) in the posterior alpha source activities from quiet wakefulness to ripples. Notably, EEG delta source activities during quiet wakefulness were also greater in the ADMCI group transitioning to light sleep as compared to patients without said vigilance reduction. Conclusions: These results suggest that ADMCI patients with a greater susceptibility to daytime sleepiness may show characteristic EEG delta and alpha rhythms in the transition from quiet vigilance to daytime sleep. Significance: Our study showed a derangement of EEG rhythms during the transition to sleep possibly specific to AD

Resting-State EEG Alpha Rhythms Are Related to CSF Tau Biomarkers in Prodromal Alzheimer's Disease

: Patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show abnormally high delta (&lt;4 Hz) and low alpha (8-12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid-tau biomarkers in ADMCI patients. An international database provided clinical-demographic-rsEEG datasets for cognitively unimpaired older (Healthy; N = 45), ADMCI (N = 70), and noADMCI (N = 45) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. Posterior rsEEG alpha source activities were reduced in the ADMCI group compared not only to the Healthy group but also to the noADMCI group (p &lt; 0.001). Negative associations between the CSF phospho-tau and total tau levels and posterior rsEEG alpha source activities were observed in the ADMCI group (p &lt; 0.001), whereas those with CSF amyloid beta 42 levels were marginal. These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through rsEEG alpha rhythms are mainly affected by brain tauopathy in ADMCI patients

Resting-state electroencephalographic rhythms depend on sex in patients with dementia due to Parkinson\u27s and Lewy Body diseases: An exploratory study

\ua9 2025 The Authors. Parkinson\u27s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (&lt; 4 Hz) and low alpha (8–10 Hz) rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient\u27s sex. An international database provided clinical-demographic-rsEEG datasets for cognitively unimpaired older (Healthy; N = 49; 24 females), PDD (N = 39; 13 females), and DLB (N = 38; 15 females) participants. Each group was stratified into matched female and male subgroups. The rsEEG rhythms were investigated across the individual rsEEG delta, theta, and alpha frequency bands based on the individual alpha frequency peak. The eLORETA freeware was used to estimate cortical rsEEG sources. In the Healthy group, widespread rsEEG alpha source activities were greater in the females than in the males. In the PDD group, widespread rsEEG delta source activities were lower and widespread rsEEG alpha source activities were greater in the females than in the males. In the DLB group, central-parietal rsEEG delta source activities were lower, and posterior rsEEG alpha source activities were greater in the females than in the males. These results suggest sex-dependent hormonal modulation of neuroprotective-compensatory neurophysiological mechanisms in PDD and DLB patients underlying the generation of rsEEG delta and alpha rhythms, which should be considered in the treatment of vigilance dysregulation in those patients

Resting-State EEG Alpha Rhythms Are Related to CSF Tau Biomarkers in Prodromal Alzheimer\u27s Disease

\ua9 2025 by the authors. Patients with mild cognitive impairment due to Alzheimer’s disease (ADMCI) typically show abnormally high delta (&lt;4 Hz) and low alpha (8–12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid–tau biomarkers in ADMCI patients. An international database provided clinical–demographic–rsEEG datasets for cognitively unimpaired older (Healthy; N = 45), ADMCI (N = 70), and noADMCI (N = 45) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. Posterior rsEEG alpha source activities were reduced in the ADMCI group compared not only to the Healthy group but also to the noADMCI group (p &lt; 0.001). Negative associations between the CSF phospho-tau and total tau levels and posterior rsEEG alpha source activities were observed in the ADMCI group (p &lt; 0.001), whereas those with CSF amyloid beta 42 levels were marginal. These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through rsEEG alpha rhythms are mainly affected by brain tauopathy in ADMCI patients

Prevalence and Subtypes of Mild Cognitive Impairment in Parkinson's Disease.

The current study examined the prevalence and subtypes of Mild Cognitive Impairment (MCI) in an Australian sample of people with Parkinson's Disease (PD). Seventy participants with PD completed neuropsychological assessments of their cognitive performance, using MDS Task Force Level II diagnostic criteria for PD-MCI. A cut-off score of less than one standard deviation (SD) below normative data determined impaired performance on a neuropsychological test. Of 70 participants, 45 (64%) met Level II diagnostic criteria for PD-MCI. Among those with PD-MCI, 42 (93%) were identified as having multiple domain impairment (28 as amnestic multiple domain and 14 as nonamnestic multiple domain). Single domain impairment was less frequent (2 amnestic/1 nonamnestic). Significant differences were found between the PD-MCI and Normal Cognition groups, across all cognitive domains. Multiple domain cognitive impairment was more frequent than single domain impairment in an Australian sample of people with PD. However, PD-MCI is heterogeneous and current prevalence and subtyping statistics may be an artifact of variable application methods of the criteria (e.g., cut off scores and number of tests). Future longitudinal studies refining the criteria will assist with subtyping the progression of PD-MCI, while identifying individuals who may benefit from pharmacological and nonpharmacological interventions

Attention/working memory and executive function in Parkinson's disease: review, critique, and recommendations

Background: Cognitive impairment in Parkinson's disease (PD) is a well‐established non‐motor complication that significantly affects the quality of life and well‐being of both patients and care partners. To optimally detect mild cognitive impairment or dementia, extensive neuropsychological assessment is essential. A wide range of cognitive tests and clinical outcome assessments have been used in clinical settings, often without regard to their clinimetric quality. Methods: We performed a literature review of tests assessing attention/working memory and executive domains in PD (tests on other domains are included in an accompanying review). The selected tests were evaluated for their clinimetric properties and categorized by a panel of experts as “recommended,” “recommended with caveats,” “suggested,” or “listed” according to the International Parkinson and Movement Disorder Society Clinical Outcome Assessment Scientific Evaluation Committee guidelines. Results: A total of 30 tests were reviewed. Eight tests were “recommended,” including four tests assessing attention/working memory abilities (WAIS‐IV Digit Span, Coding and Symbol Search subtests, and Trail Making Test) and four tests assessing executive abilities (WAIS‐IV Similarities, Wisconsin Card Sorting Test, Fluency Tests, and Stroop Color‐Word Test). These tests demonstrated good to excellent levels of reliability and validity, have normative datasets, and are sensitive to change. Eight other tests were “recommended with caveats”, eleven were “suggested,” and three were “listed.” Conclusions: The recommended tests for attention/working memory and executive functioning in PD can guide PD cognitive assessment. Other tests were identified as potentially useful; however, caution is advised due to their clinimetric limitations. Further validation studies are required for these tests