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).     

An Evolutionary Perspective on Appearance Enhancement Behavior

Researchers have highlighted numerous sociocultural factors that have been shown to underpin human appearance enhancement practices, including the influence of peers, family, the media, and sexual objectification. Fewer scholars have approached appearance enhancement from an evolutionary perspective or considered how sociocultural factors interact with evolved psychology to produce appearance enhancement behavior. Following others, we argue that evidence from the field of evolutionary psychology can complement existing sociocultural models by yielding unique insight into the historical and cross-cultural ubiquity of competition over aspects of physical appearance to embody what is desired by potential mates. An evolutionary lens can help to make sense of reliable sex and individual differences that impact appearance enhancement, as well as the context-dependent nature of putative adaptations that function to increase physical attractiveness. In the current review, appearance enhancement is described as a self-promotion strategy used to enhance reproductive success by rendering oneself more attractive than rivals to mates, thereby increasing one’s mate value. The varied ways in which humans enhance their appearance are described, as well as the divergent tactics used by women and men to augment their appearance, which correspond to the preferences of opposite-sex mates in a heterosexual context. Evolutionarily relevant individual differences and contextual factors that vary predictably with appearance enhancement behavior are also discussed. The complementarity of sociocultural and evolutionary perspectives is emphasized and recommended avenues for future interdisciplinary research are provided for scholars interested in studying appearance enhancement behavior.

     

Heat Sink Effect on Tumor Ablation Characteristics as Observed in Monopolar Radiofrequency,Bipolar Radiofrequency,and Microwave,Using Ex Vivo Calf Liver Model

Thermal ablation of liver tumors near large blood vessels is affected by the cooling effect of blood flow, leading to incomplete ablation. Hence, we conducted a comparative investigation of heat sink effect in monopolar (MP) and bipolar (BP) radiofrequency ablation (RFA), and microwave (MW) ablation devices.With a perfused calf liver, the ablative performances (volume, mass, density, dimensions), with and without heat sink, were measured. Heat sink was present when the ablative tip of the probes were 8.0 mm close to a major hepatic vein and absent when >30 mm away. Temperatures (T1 and T2) on either side of the hepatic vein near the tip of the probes, heating probe temperature (T3), outlet perfusate temperature (T4), and ablation time were monitored.With or without heat sink, BP radiofrequency ablated a larger volume and mass, compared with MP RFA or MW ablation, with latter device producing the highest density of tissue ablated. MW ablation produced an ellipsoidal shape while radiofrequency devices produced spheres.Percentage heat sink effect in Bipolar radiofrequency : Mono-polar radiofrequency : Microwave was (Volume) 33:41:22; (mass) 23:56:34; (density) 9.0:26:18; and (relative elipscity) 5.8:12.9:1.3, indicating that BP and MW devices were less affected.Percentage heat sink effect on time (minutes) to reach maximum temperature (W) = 13.28:9.2:29.8; time at maximum temperature (X) is 87:66:16.66; temperature difference (Y) between the thermal probes (T3) and the temperature (T1 + T2)/2 on either side of the hepatic vessel was 100:87:20; and temperature difference between the (T1 + T2)/2 and temperature of outlet circulating solution (T4), Z was 20.33:30.23:37.5.MW and BP radiofrequencies were less affected by heat sink while MP RFA was the most affected. With a single ablation, BP radiofrequency ablated a larger volume and mass regardless of heat sink.     

Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED).

Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed.

Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0–4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0–4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0–100).

Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05–0.65; p?=?0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10–0.38; p?=?0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35–24.33; nominal p?=?0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51–16.70; p?<?0.0001).

Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed.

Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED.