Associations Between Vitamin D Deficiency/Insufficiency and Depression Expose Health Disparities in Older Rural West Texans: A Project FRONTIER Study.

Objective: To determine associations between Vitamin D (VD) levels and clinical depression through the Geriatric Depression Scale (GDS) and its questions and subdomains, stratified by demographics and Hispanic/Latino ethnicity (HLE).

Design, Setting, And Participants: A cohort of 299 Project FRONTIER participants aged 62.6 ± 11.

Healthy brain aging and delayed dementia in Texas rural elderly.

Healthy aging is the process of preserving and enhancing one's independence, physical and mental well-being, and overall quality of life. It involves the mental, emotional, and cognitive wellness. Although biological and genetic factors have a significant influence on the process of aging gracefully, other adjustable factors also play a crucial role.

Urgent needs of caregiving in ageing populations with Alzheimer's disease and other chronic conditions: Support our loved ones.

The ageing process begins at birth. It is a life-long process, and its exact origins are still unknown. Several hypotheses attempt to describe the normal ageing process, including hormonal imbalance, formation of reactive oxygen species, DNA methylation & DNA damage accumulation, loss of proteostasis, epigenetic alterations, mitochondrial dysfunction, senescence, inflammation, and stem cell depletion.

Comprehensive Understanding of Hispanic Caregivers: Focus on Innovative Methods and Validations.

Alzheimer's disease (AD) and Alzheimer's disease-related disorders (ADRD) are late-onset, age-related progressive neurodegenerative disorders, characterized by memory loss and multiple cognitive impairments. Current research indicates that Hispanic Americans are at an increased risk for AD/ADRD and other chronic conditions such as diabetes, obesity, hypertension, and kidney disease, and given their rapid growth in numbers, this may contribute to a greater incidence of these disorders. This is particularly true for the state of Texas, where Hispanics are the largest group of ethnic minorities.

Refractory Shock Secondary to Denosumab-induced Severe Hypocalcaemia.

Unlabelled: Denosumab is one of the most commonly used antiresorptive drugs for osteoporosis treatment and the prevention of skeletal-related events in cancer patients. The purpose of this case report is to highlight potentially life-threatening severe hypocalcaemia as a side effect of denosumab complicated by refractory shock that failed to respond to medical management including intravenous calcium, vasopressors and inotropes in an elderly man with a history of prostatic cancer.

Learning Points: Denosumab is a commonly used antiresorptive drugs for the treatment of osteoporosis and to prevent skeletal-related events in patients with cancer.

Phosphorylated Tau in Alzheimer's Disease and Other Tauopathies.

Alzheimer's disease (AD) is the leading cause of dementia in elderly people. Amyloid beta (Aβ) deposits and neurofibrillary tangles are the major pathological features in an Alzheimer's brain. These proteins are highly expressed in nerve cells and found in most tissues.

Role of Nrf2 in aging, Alzheimer's and other neurodegenerative diseases.

Nuclear Factor-Erythroid Factor 2 (Nrf2) is an important transcription factor that regulates the expression of large number of genes in healthy and disease states. Nrf2 is made up of 605 amino acids and contains 7 conserved regions known as Nrf2-ECH homology domains. Nrf2 regulates the expression of several key components of oxidative stress, mitochondrial biogenesis, mitophagy, autophagy and mitochondrial function in all organs of the human body, in the peripheral and central nervous systems.

The Role of Obesity and Diabetes in Dementia.

Chronic conditions such as obesity, diabetes, and dementia are increasing in the United States (US) population. Knowledge of these chronic conditions, preventative measures, and proper management tactics is important and critical to preventing disease. The overlap between obesity, diabetes, and dementia is becoming further elucidated.

Establishing an Ehlers-Danlos Syndrome Clinic: Lessons Learned.

In a large academic medical center, patient requests from the community and internal referrals for evaluation of suspected hypermobility conditions were being denied consultation because services specific to this condition were not available. We identified this gap and developed a comprehensive evaluation for this unique patient population. The objective of this paper is to demonstrate a solution for improving outcomes in a neglected patient population by establishing an innovative outpatient clinic specifically tailored for patients with EDS.

Prediction Accuracy of Production ADMET Models as a Function of Version: Activity Cliffs Rule.

As with many other institutions, our company maintains many quantitative structure-activity relationship (QSAR) models of absorption, distribution, metabolism, excretion, and toxicity (ADMET) end points and updates the models regularly. We recently examined version-to-version predictivity for these models over a period of 10 years. In this approach we monitor the goodness of prediction of new molecules relative to the training set of model version V before they are incorporated in the updated model V+1.

MegaSyn: Integrating Generative Molecular Design, Automated Analog Designer, and Synthetic Viability Prediction.

Generative machine learning models have become widely adopted in drug discovery and other fields to produce new molecules and explore molecular space, with the goal of discovering novel compounds with optimized properties. These generative models are frequently combined with transfer learning or scoring of the physicochemical properties to steer generative design, yet often, they are not capable of addressing a wide variety of potential problems, as well as converge into similar molecular space when combined with a scoring function for the desired properties. In addition, these generated compounds may not be synthetically feasible, reducing their capabilities and limiting their usefulness in real-world scenarios.

Teaching methods fostering enjoyment and creativity in medical education.

The journey towards becoming a physician has always been a test of diligence and patience in perfecting the science and art of treating patients. This learning continues well-beyond medical school, requiring a life-long pursuit for acquiring and refining medical knowledge with advances in science and technology. After completing medical school and residency, however, many clinicians report feelings of dissatisfaction and disillusionment with their career path citing lack of autonomy, increased government regulations, and long hours.

Current Status of Healthy Aging and Dementia Research: A Symposium Summary.

The purpose of the 'First Regional Healthy Aging and Dementia Research Symposium' was to discuss the latest research in healthy aging and dementia research, public health trends related to neurodegenerative diseases of aging, and community-based programs and research studying health, nutrition, and cognition. This symposium was organized by the Garrison Institute on Aging (GIA) of the Texas Tech University Health Sciences Center (TTUHSC), and was held in Lubbock, Texas, October 24-25, 2018. The Symposium joined experts from educational and research institutions across the United States.

The Role of Sex Hormones in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelination disorder with an immune-mediated pathophysiology that affects the central nervous system (CNS). Like other autoimmune conditions, it has a predilection for female gender. This suggests a gender bias and a possible hormonal association.

Absolute configuration assignment of (+)-fluralaner using vibrational circular dichroism.

The absolute configurations of the separated enantiomers of fluralaner, a racemic animal health product used to prevent fleas and ticks, have been assigned using vibrational circular dichroism (VCD). The crystallographic structure of the active enantiomer (+)-fluralaner has previously been shown to have the (S) configuration using small molecule crystallography. We sought a faster analytical method to determine the absolute configuration of the separated enantiomers.

Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type.

Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT) through the use of the sex determination test (SDT).

Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter.

White Matter Deterioration May Foreshadow Impairment of Emotional Valence Determination in Early-Stage Dementia of the Alzheimer Type.

In Alzheimer Disease (AD), non-verbal skills often remain intact for far longer than verbally mediated processes. Four (1 female, 3 males) participants with early-stage Clinically Diagnosed Dementia of the Alzheimer Type (CDDAT) and eight neurotypicals (NTs; 4 females, 4 males) completed the emotional valence determination test (EVDT) while undergoing BOLD functional magnetic resonance imaging (fMRI). We expected CDDAT participants to perform just as well as NTs on the EVDT, and to display increased activity within the bilateral amygdala and right anterior cingulate cortex (r-ACC).

Clinical Aspects of Glucose Metabolism and Chronic Disease.

The burden of chronic disease is an emerging world health problem. Advances made in the treatment of individual disease states often fail to consider multimorbidity patterns in clinical research models. Adjusting for age as a confounder ignores its contribution as a powerful risk factor for most chronic diseases.

Iterative Focused Screening with Biological Fingerprints Identifies Selective Asc-1 Inhibitors Distinct from Traditional High Throughput Screening.

N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer's disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine-serine-cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs.

Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine.

In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2, we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent (20, cAMP+HS IC50=0.67 nM), and selective compound (hERG IC50=19 μM) with favorable rodent pharmacokinetics (F=100%, t1/2=7h) is described.

Synthesis and Evaluation of 5-Fluoro-2-aryloxazolo[5,4-b]pyridines as β-Amyloid PET Ligands and Identification of MK-3328.

5-Fluoro-2-aryloxazolo[5,4-b]pyridines were synthesized and investigated as potential (18)F containing β-amyloid PET ligands. In competition binding assays using human AD brain homogenates, compounds 14b, 16b, and 17b were identified as having favorable potency versus human β-amyloid plaque and were radiolabeled for further evaluation in in vitro binding and in vivo PET imaging experiments. These studies led to the identification of 17b (MK-3328) as a candidate PET ligand for the clinical assessment of β-amyloid plaque load.

Medications in long-term care: when less is more.

Attention has been drawn to the potential risks of several medications in the long-term care setting. Most of these medications deemed as inappropriate affect the central nervous system and are indicated only for select populations with specific conditions. Many of these drugs are prescribed without clear indications and continued indefinitely without critical decision-making about the potentially salutary effects of discontinuing medications.