Lipid-Targeted Atherosclerotic Risk Reduction in Older Adults: A Review.

Aggressive lipid-lowering lifestyle modifications and pharmacologic therapies are the cornerstones of the primary and secondary prevention of atherosclerotic cardiovascular disease events. While statins are highly effective, inexpensive, and generally well-tolerated medications, many clinicians and patients express uncertainty regarding the necessity of statin treatment in older adults. Citing concerns such as polypharmacy, muscle symptoms, and even potential cognitive changes with statins, many patients and health care providers elect to de-intensify or discontinue statin therapy during the process of aging. A lack of clear representation of older individuals in many clinical trials and practice guidelines may contribute to the ambiguity. However, the recently prevailing data and practice patterns supporting the benefits, safety, and tolerability of a variety of lipid-lowering therapeutics in older adults are discussed here, with particular mention of a potential protective effect from incident dementia among a statin-treated geriatric population and an admonishment of the historical concept of "too-low" low-density lipoprotein cholesterol (LDL-C) levels.

Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms.

Individual mammalian cells exhibit large variability in cellular volume, even with the same absolute DNA content, and so must compensate for differences in DNA concentration in order to maintain constant concentration of gene expression products. Using single-molecule counting and computational image analysis, we show that transcript abundance correlates with cellular volume at the single-cell level due to increased global transcription in larger cells. Cell fusion experiments establish that increased cellular content itself can directly increase transcription. Quantitative analysis shows that this mechanism measures the ratio of cellular volume to DNA content, most likely through sequestration of a transcriptional factor to DNA. Analysis of transcriptional bursts reveals a separate mechanism for gene dosage compensation after DNA replication that enables proper transcriptional output during early and late S phase. Our results provide a framework for quantitatively understanding the relationships among DNA content, cell size, and gene expression variability in single cells.

Motor vehicle crash-related injury causation scenarios for spinal injuries in restrained children and adolescents.

OBJECTIVE: Motor vehicle crash (MVC)-related spinal injuries result in significant morbidity and mortality in children. The objective was to identify MVC-related injury causation scenarios for spinal injuries in restrained children. METHODS: This was a case series of occupants in MVCs from the Crash Injury Research and Engineering Network (CIREN) data set. Occupants aged 0-17 years old with at least one Abbreviated Injury Scale (AIS) 2+ severity spinal injury in vehicles model year 1990+ that did not experience a rollover were included. Unrestrained occupants, those not using the shoulder portion of the belt restraint, and those with child restraint gross misuse were excluded. Occupants with preexisting comorbidities contributing to spinal injury and occupants with limited injury information were also excluded. A multidisciplinary team retrospectively reviewed each case to determine injury causation scenarios (ICSs). Crash conditions, occupant and restraint characteristics, and injuries were qualitatively summarized. RESULTS: Fifty-nine cases met the study inclusion criteria and 17 were excluded. The 42 occupants included sustained 97 distinct AIS 2+ spinal injuries (27 cervical, 22 thoracic, and 48 lumbar; 80 AIS-2, 15 AIS-3, 1 AIS-5, and 1 AIS-6), with fracture as the most common injury type (80%). Spinal-injured occupants were most frequently in passenger cars (64%), and crash direction was most often frontal (62%). Mean delta-V was 51.3 km/h±19.4 km/h. The average occupant age was 12.4±5.3 years old, and 48% were 16- to 17-year-olds. Thirty-six percent were right front passengers and 26% were drivers. Most occupants were lap and shoulder belt restrained (88%). Non-spinal AIS 2+ injuries included those of the lower extremity and pelvis (n=56), head (n=43), abdomen (n=39), and thorax (n=36). Spinal injury causation was typically due to flexion or lateral bending over the lap and or shoulder belt or child restraint harness, compression by occupant's own seat back, or axial loading through the seat pan. Nearly all injuries in children<12 years occurred by flexion over a restraint, whereas teenage passengers had flexion, direct contact, and other ICS mechanisms. All of the occupants with frontal flexion mechanism had injuries to the lumbar spine, and most (78%) had associated hollow or solid organ abdominal injuries. CONCLUSIONS: Restrained children in nonrollover MVCs with spinal injuries in the CIREN database are most frequently in high-speed frontal crashes, of teenage age, and have vertebral fractures. There are age-specific mechanism patterns that should be further explored. Because even moderate spinal trauma can result in measurable morbidity, future efforts should focus on mitigating these injuries.