Targeted protein degradation using heterobifunctional proteolysis-targeting chimera (PROTAC) compounds, which recruit E3 ligase machinery to a target protein, is increasingly becoming an attractive pharmacologic strategy. PROTAC compounds are often developed from existing inhibitors, and assessing selectivity is critical for understanding on-target and off-target degradation. We present here an in-depth kinetic degradation study of the pan-kinase PROTAC, TL12-186, applied to 16 members of the cyclin-dependent kinase (CDK) family. Each CDK family member was endogenously tagged with the 11-amino-acid HiBiT peptide, allowing for live cell luminescent monitoring of degradation. Using this approach, we found striking differences and patterns in kinetic degradation rates, potencies, and Dmax values across the CDK family members. Analysis of the responses revealed that most of the CDKs showed rapid and near complete degradation, yet all cell cycle-associated CDKs (1, 2, 4, and 6) showed multimodal and partial degradation. Further mechanistic investigation of the key cell cycle protein CDK2 was performed and revealed CDK2 PROTAC-dependent degradation in unsynchronized or G1-arrested cells but minimal loss in S or G2/M arrest. The ability of CDK2 to form the PROTAC-mediated ternary complex with CRBN in only G1-arrested cells matched these trends, despite binding of CDK2 to TL12-186 in all phases. These data indicate that target subpopulation degradation can occur, dictated by the formation of the ternary complex. These studies additionally underscore the importance of profiling degradation compounds in cellular systems where complete pathways are intact and target proteins can be characterized in their relevant complexes. Ménière's Disease (MD) is a chronic condition where patients suffer recurrent vertigo attacks. Evidence for treatment concepts are to this date low. To evaluate the therapeutic effect of intratympanic lidocaine injections to reduce the number of attacks. Twenty patients diagnosed with definitive MD that were treated with 34 intratympanic lidocaine injections were included. Main outcome measures were the number of vertigo attacks in the previous four weeks, the attack free period and the subjective improvement of the condition. Mean follow up after first lidocaine injection was 25.3 months (±22.2; range 1.9-79.7). Patients expressed subjective improvement in overall situation, vertigo, and aural fullness. The number of vertigo attacks before each assessment decreased from 7.1 (±5.9; range 2-20) per months at baseline to 1.9 (±3.8; range 0-15). 25% of the patients suffered no further attacks, the other patients had an average attack free period of 7.8 months (±15.4; range 0.2-58.4). Purmorphamine Hearing thresholds remained unaffected. Repetitive injections proved effective. Intratympanic lidocaine is an effective nonsurgical and non-ablative therapy for MD. When patients experience an increase of attacks repetitive injections promise improvement.Intratympanic lidocaine is an effective nonsurgical and non-ablative therapy for MD. When patients experience an increase of attacks repetitive injections promise improvement.Split thickness skin grafting is a common reconstructive technique which carries unavoidable donor site morbidity. The aim of this systematic review and meta-analysis is to present the evidence for the use of platelet rich plasma as an adjunct to donor site wound healing. A comprehensive literature search was performed, according to PRISMA guidelines from inception to August 2020, for studies regarding platelet rich plasma and skin graft donor site healing. Animal studies, case series of less than three cases and studies reporting histological outcomes only were excluded. The literature search identified 114 articles. After applying the exclusion criteria, four randomised control trials and two case-control studies remained, incorporating a total of 218 wounds in 139 patients. Four out of six studies reported total healing times for donor site wounds. Pooled analysis showed a significant reduction in healing time when donor wounds were treated with PRP versus controls [MD 5.95, 95% CI 5.04-6.85, p  less then  0.001]. Of the five studies which reported pain at dressing change, four showed significantly reduced pain scores for the platelet rich plasma treated wounds versus control. There were no significant complications recorded in the treated wounds. The current evidence basis for platelet rich plasma in donor site healing is limited by heterogeneous methodology and reporting outcomes and low powered studies. Nevertheless, the preponderance of data supports its use for accelerating wound healing and reducing pain at dressing change. These preliminary findings need to be substantiated with higher powered randomised controlled trials with standardised PRP manufacture and reporting structures.The blood-brain barrier (BBB), a dynamic interface between blood and brain constituted mainly by endothelial cells of brain microvessels, robustly restricts the entry of potentially harmful blood-sourced substances and cells into the brain, however, many therapeutically active agents concurrently cannot gain access into the brain at effective doses in the presence of an intact barrier. On the other hand, breakdown of BBB integrity may involve in the pathogenesis of various neurodegenerative diseases. Besides, certain diseases/disorders such as Alzheimer's disease, hypertension, and epilepsy are associated with varying degrees of BBB disruption. In this review, we aim to highlight the current knowledge on the cellular and molecular composition of the BBB with special emphasis on the major transport pathways across the barrier type endothelial cells. We further provide a discussion on the innovative brain drug delivery strategies in which the obstacle formed by BBB interferes with effective pharmacological treatment of neurodegenerative diseases/disorders. The aim of this research was to evaluate the effects of adding 10 g of cocoa-rich chocolate (99%) to the habitual diet on cognitive performance in postmenopausal women. Following a randomised controlled parallel clinical trial, a total of 140 postmenopausal women aged 50-64 were recruited. The intervention group (  = 73) consumed daily 10 g of chocolate (99% cocoa) in addition to their usual food intake for 6 months, whereas the control group (  = 67) did not receive any intervention. Attention and executive functions, verbal memory, working memory, phonological fluency, category fluency and clinical variables were assessed at baseline and 6 months. Trail Making Test B execution time showed a decreased of -12.08 s (95% CI -23.99, -0.18;  = 0.047) in the intervention group compared to the control group, after adjusting for age, educational level, time elapsed from the beginning of menopause and daily energy consumption (Cohen's  = -0.343). Attention, immediate or delayed verbal memory, phonological or category fluency, and working memory remained unchanged.