Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Epigenetics explained: a topic “primer” for the epilepsy community by the ILAE Genetics/Epigenetics Task Force

Epigenetics refers broadly to processes that influence medium to long‐term gene expression by changing the readability and accessibility of the genetic code. The Neurobiology Commission of the International League Against Epilepsy (ILAE) recently convened a Task Force to explore and disseminate advances in epigenetics to better understand their role and intersection with genetics and the neurobiology of epilepsies and their co‐morbidities, and to accelerate translation of these findings into the development of better therapies. Here, we provide a topic primer on epigenetics, explaining the key processes and findings to date in experimental and human epilepsy. We review the growing list of genes with epigenetic functions that have been linked with epilepsy in humans. We consider potential practical applications, including using epigenetic signals as biomarkers for tissue‐ and biofluid‐based diagnostics and the prospects for developing epigenetic‐based treatments for epilepsy. We include a glossary of terms, FAQs and other supports to facilitate a broad understanding of the topic for the non‐expert. Last, we review the limitations, research gaps and the next challenges. In summary, epigenetic processes represent important mechanisms controlling the activity of genes, providing opportunities for insight into disease mechanisms, biomarkers and novel therapies for epilepsy.     

Normal sleep and circadian rhythms: neurobiologic mechanisms underlying sleep and wakefulness.

Sleep is a vital, highly organized process regulated by complex systems of neuronal networks and neurotransmitters. Sleep plays an important role in the regulation of central nervous system and body physiologic functions. Sleep architecture changes with age and is easily susceptible to external and internal disruption. Reduction or disruption of sleep can affect numerous functions varying from thermoregulation to learning and memory during the waking state.     

Effects of 1.32-μm Nd-YAG laser on brain thermal and histological experimental data

Considering that the 1.32-μm Nd-YAG laser should have physicothermal properties close to those of the CO₂ laser, a series of experiments were conducted on rat cortex (N = 51). Three laser wavelengths were compared: CO₂ laser (10.6 μm), 1.06-μm Nd-YAG, and 1.32-μm Nd-YAG lasers. For each shot, temperature measurements were recorded with an infrared thermographic videocamera. The digitized signals were figured as thermal profiles and temperature developments. Ninety-five shots were correctly studied and analyzed: CO₂, N = 29; 1.06-μm Nd-YAG, N = 20; 1.32-μm Nd-YAG, N = 46. The histological lesions produced by these three lasers were compared on animals killed 24 hours (N = 20), 8 days (N = 20), and 30 days (N = 5) after the laser impacts. For equivalent densities of energy, the depth of cortical necrosis was comparable for the CO₂ laser (200–250 μm) and the 1.32-μm Nd-YAG laser (210–260μm) whatever the date of death; the 1.06-μm Nd-YAG laser shots were responsible for much more important damage (400–550μm). Because of its important absorption in water and nervous tissue, the authors consider the 1.32-μm Nd-YAG laser most suitable for neurosurgery, particularly because it is conducted through optic fibers, and therefore is easy to handle during neurosurgical procedures.     

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.