QSAR model to develop newer generation GSK-3β inhibitors targeting Alzheimer

In the year 2022 most of the patients affected by the disease was around 65 year age. Among total number of patients, 73% were near 75 year or older age. It was also stated that maximum numbers of patients were women. Black Americans were more affected by Alzheimer than white Americans. GSK-3β was also linked with hyperphosphorylation of tau protein followed by the increasing number of amyloid-beta plaques and other inflammatory responses followed by activation of microglial cells to develop neurotoxic inflammatory factors along with reducing the concentration of acetylcholine; these factors cumulatively create Alzheimer disease. GSK-3β modulated the inflammatory stress related to endoplasmic reticulum and mitochondrial abnormalities. But all the molecules those were used in the treatment not so much effective to fully cure the patient. So, to break this jinx to develop of newer generation anti Alzheimer drug molecules, computational approaches played an essential role. The most effective QSAR model was pIC50 = -5.47052 +2.60572 IC1 +1.64642 GATS2e +2.088 mindssC -0.01441 ATSC7s -13.5191 AVP-0 +0.16712 minssNH -0.15369 minaaN +0.01777 VR2_Dt +1.52684 MATS8s +0.04725 nAtomP with all necessary acceptance criteria Q^2: 0.60111, r^2: 0.65711, |r0^2-r'0^2|: 0.07866, k: 0.99121 [(r^2-r0^2)/r^2] 0.00543 or k': 0.92437 [(r^2-r'0^2)/r^2] 0.12513. It can be easily concluded that if in near future we want to develop a small molecule effective as GSK-3β inhibitor active against Alzheimer disease, this QSAR model will work as a boon for the mankind

The academy for future science faculty:randomized controlled trial of theory-driven coaching to shape development and diversity of early-career scientists

Background: Approaches to training biomedical scientists have created a talented research community. However, they have failed to create a professional workforce that includes many racial and ethnic minorities and women in proportion to their representation in the population or in PhD training. This is particularly true at the faculty level. Explanations for the absence of diversity in faculty ranks can be found in social science theories that reveal processes by which individuals develop identities, experiences, and skills required to be seen as legitimate within the profession. Methods/Design: Using the social science theories of Communities of Practice, Social Cognitive Career Theory, identity formation, and cultural capital, we have developed and are testing a novel coaching-based model to address some of the limitations of previous diversity approaches. This coaching intervention (The Academy for Future Science Faculty) includes annual in-person meetings of students and trained faculty Career Coaches, along with ongoing virtual coaching, group meetings and communication. The model is being tested as a randomized controlled trial with two cohorts of biomedical PhD students from across the U.S., one recruited at the start of their PhDs and one nearing completion. Stratification into the experimental and control groups, and to coaching groups within the experimental arms, achieved equal numbers of students by race, ethnicity and gender to the extent possible. A fundamental design element of the Academy is to teach and make visible the social science principles which highly influence scientific advancement, as well as acknowledging the extra challenges faced by underrepresented groups working to be seen as legitimate within the scientific communities. Discussion: The strategy being tested is based upon a novel application of the well-established principles of deploying highly skilled coaches, selected and trained for their ability to develop talents of others. This coaching model is intended to be a complement, rather than a substitute, for traditional mentoring in biomedical research training, and is being tested as such

Saliva testing as a means to monitor therapeutic lithium levels in patients with psychiatric disorders: Identification of clinical and environmental covariates, and their incorporation into a prediction model.

ObjectiveThe narrow therapeutic window of lithium medications necessitates frequent serum monitoring, which can be expensive and inconvenient for the patient. Compared to blood, saliva collection is easier, non-invasive, requires less processing, and can be done without the need for trained personnel. This study investigated the utility of longitudinal salivary lithium level monitoring.MethodsWe measured salivary lithium levels using ICP-OES in n = 169 passive drool samples, collected both as single observations and longitudinally for up to 18 months, from a multi-center cohort of n = 75 patients with bipolar disorder or other psychiatric conditions.ResultsSaliva and serum lithium levels were highly correlated. Adjustment for daily lithium dose, diabetes, and smoking improved this relationship (r = 0.77). Using the adjusted intersubject equation and a patient's salivary lithium value, we observed a strong correlation between the predicted vs. observed serum lithium levels (r = 0.70). Most patients had highly stable saliva/serum ratios across multiple visits, with longitudinal variability significantly greater with age. Use of the intrasubject saliva/serum ratio from a single prior observation had similar predictive power to the use of the adjusted intersubject equation. However, the use of the mean intrasubject ratio from three prior observations could robustly predict serum lithium levels (predicted vs. observed r = 0.90).ConclusionsThese findings strongly suggest that saliva could be used for lithium monitoring, and open the door for the development and implementation of a point-of-care salivary lithium device for use at home or the clinic. We propose that the use of saliva will dramatically improve treatment opportunities for patients with mood disorders