Computer-aided drug design to generate a unique antibiotic family.

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS).

Factors associated with fall risk increasing drug use in older black and white men and women: the Health ABC Study.

Background: Most older adults use medications that may increase falls, often defined as fall risk increasing drugs or "FRIDs". Two definitions for FRIDs, the Centers for Disease Control and Prevention's (CDC) Stopping Elderly Accidents, Deaths & Injuries (STEADI-R) and Swedish National Board of Health and Welfare (SNBHW) definitions, are widely accepted, though include different FRIDs in their definitions. Whether factors associated with FRID use in older adults differ by definition is unknown.

Serial gait speed measurements over time and dynamic survival prediction in older adults.

Background: A one-time gait speed measurement predicts mortality risk. A framework for updating a clinician's mortality risk perception with new information from each clinic visit is needed. We used joint modeling of longitudinal and survival data for dynamic prediction of mortality risk.

All-Cause Mortality and Cause-Specific Death in U.S. Long-Lived Siblings: Data From the Long Life Family Study.

Background: This study compared the mortality risk of long-lived siblings with the U.S. population average and their spouse controls, and investigated the leading causes of death and the familial effect in death pattern.

Medicare Fee-For-Service Spending for Fall Injury and Nonfall Events: The Health, Aging, and Body Composition Study.

Background And Objectives: Fall injuries are prevalent in older adults, yet whether higher spending occurs after nonfracture (NFFI) and fracture is unknown. We examined whether incident fall injuries, including NFFI and fractures, were associated with higher Medicare spending in 12 months after incident events in older adults.

Research Design And Methods: The Health, Aging, and Body Composition Study included 1 595 community-dwelling adults (53% women, 37% Black; 76.

Plasma proteomic signature of human longevity.

The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead of longevity. We leveraged two large population-based prospective cohorts with long follow-ups to evaluate the proteomic signature of longevity defined by survival to 90 years of age.

Bone Mineral Density During and After Lactation: A Comparison of African American and Caucasian Women.

During lactation, changes in maternal calcium metabolism are necessary to provide adequate calcium for newborn skeletal development. The calcium in milk is derived from the maternal skeleton through a process thought to be mediated by the actions of parathyroid hormone-related protein (PTHrP) in combination with decreased circulating estrogen concentrations. After weaning, bone lost during lactation is rapidly regained.

Association of a Blood-Based Aging Biomarker Index With Death and Chronic Disease: Cardiovascular Health Study.

Background: A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration.

Peripheral bone structure, geometry, and strength and muscle density as derived from peripheral quantitative computed tomography and mortality among rural south Indian older adults.

Multiple studies have observed a relationship of bone mineral density (BMD) measured by Dual energy X-ray absorptiometry (DXA) and mortality. However, areal BMD (aBMD) measured by DXA is an integrated measure of trabecular and cortical bone and does not measure the geometry of bone. Peripheral Quantitative Computed Tomography (pQCT) provides greater insights on bone structure, geometry and strength.

Role of Perceived Physical and Mental Fatigability Severity on Prospective, Recurrent, and Injurious Fall Risk in Older Men.

Background: Falls occur annually in 25% of adults aged ≥65 years. Fall-related injuries are increasing, highlighting the need to identify modifiable risk factors.

Methods: Role of fatigability on prospective, recurrent, and injurious fall risk was examined in 1 740 men aged 77-101 years in the Osteoporotic Fractures in Men Study.

Effectiveness of a behavioral lifestyle intervention on weight management and mobility improvement in older informal caregivers: a secondary data analysis.

Background: Older informal caregivers are prone to sedentary behavior and obesity. With great caregiving burdens and frequent physical and mental distress, older informal caregivers may have low adherence and poor results in behavioral intervention for weight management. This study examined whether overweight or obese older informal caregivers could benefit from a behavioral weight management program as much as non-caregivers.

Development of a Novel Accelerometry-Based Performance Fatigability Measure for Older Adults.

Introduction: Efforts to study performance fatigability have been limited because of measurement constrains. Accelerometry and advanced statistical methods may enable us to quantify performance fatigability more granularly via objective detection of performance decline. Thus, we developed the Pittsburgh Performance Fatigability Index (PPFI) using triaxial raw accelerations from wrist-worn accelerometer from two in-laboratory 400-m walks.

Lower Leg Power and Grip Strength Are Associated With Increased Fall Injury Risk in Older Men: The Osteoporotic Fractures in Men Study.

Background: Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly nonfracture fall injuries.

Methods: In the Osteoporotic Fractures in Men Study (baseline: N = 5 994; age 73.7 ± 5.

Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites.

Introduction: Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Aβ) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses.

Methods: We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Aβ-mediated neurotoxicities in AD.  Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD.

Changes in Objectively Measured Physical Activity Are Associated With Perceived Physical and Mental Fatigability in Older Men.

Background: Lower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established.

Methods: Community-dwelling older men (N = 1 113, age = 84.

Digitally generated Trail Making Test data: Analysis using hidden Markov modeling.

The Trail Making Test (TMT) is a neuropsychological test used to assess cognitive dysfunction. The TMT consists of two parts: TMT-A requires connecting numbers 1 to 25 sequentially; TMT-B requires connecting numbers 1 to 12 and letters A to L sequentially, alternating between numbers and letters. We propose using a digitally recorded version of TMT to capture cognitive or physical functions underlying test performance.

The Association Between Severity of Radiographic Knee OA and Recurrent Falls in Middle and Older Aged Adults: The Osteoarthritis Initiative.

Background: Knee osteoarthritis (KOA) is the most prevalent type of OA and a leading cause of disability in the United States. Falls are a major public health concern in older adults. Our aim was to examine how the severity of radiographic KOA affects recurrent falls in a cohort of middle-aged and older individuals enrolled in the Osteoarthritis Initiative.

Prospective Associations Between Physical Activity and Perceived Fatigability in Older Men: Differences by Activity Type and Baseline Marital Status.

Background: Lower physical activity has been cross-sectionally associated with greater perceived fatigability, defined as self-reported fatigue anchored to activity intensity and duration. The temporality of this relationship, and whether it differs by activity type or marital status, remains unclear.

Methods: In the Osteoporotic Fractures in Men Study (N = 1 759), self-reported total, exercise, and household activity were assessed using the Physical Activity Scale for the Elderly across 7 visits (2000-2016).

Distribution of 54 polygenic risk scores for common diseases in long lived individuals and their offspring.

A surprising and well-replicated result in genetic studies of human longevity is that centenarians appear to carry disease-associated variants in numbers similar to the general population. With the proliferation of large genome-wide association studies (GWAS) in recent years, investigators have turned to polygenic scores to leverage GWAS results into a measure of genetic risk that can better predict the risk of disease than individual significant variants alone. We selected 54 polygenic risk scores (PRSs) developed for a variety of outcomes, and we calculated their values in individuals from the New England Centenarian Study (NECS, N = 4886) and the Long Life Family Study (LLFS, N = 4577).

Perceived Physical Fatigability Predicts All-Cause Mortality in Older Adults.

Background: Perceived physical fatigability is highly prevalent in older adults and associated with mobility decline and other health consequences. We examined the prognostic value of perceived physical fatigability as an independent predictor of risk of death among older adults.

Methods: Participants (N = 2 906), mean age 73.

Relationship Between Personality Measures and Perceived Mental Fatigability.

Objective: Examine the association between personality measures and perceived mental fatigability.

Methods: We performed a cross-sectional analysis in =1670 men, age 84.3±4.

Relationship between socioeconomic status, exposure to airborne pollutants, and chronic rhinosinusitis disease severity.

Background: Air pollution directly interacts with airway mucosa, yet little is known about how pollutants affect upper airway inflammation. Studies have shown increased incidence of chronic rhinosinusitis (CRS), rhinitis, and asthma in areas with higher traffic pollution, and these neighborhoods are often associated with lower socioeconomic status (SES). The Area Deprivation Index (ADI) assesses neighborhood-level SES by zip code.

Perceived physical fatigability improves after an exercise intervention among breast cancer survivors: a randomized clinical trial.

Background: Among breast cancer populations, exercise interventions resulted in positive but relatively small improvements on fatigue, which may be due to insensitive measures of global fatigue. Perceived fatigability-whole-body tiredness anchored to standardized tasks/activities of a specific intensity and duration-may help to detect effective exercise interventions reducing fatigue in oncology. We examined whether perceived physical fatigability improved after an exercise intervention.