Pharmacological approaches to restoring lens transparency: Real world applications

Cataract is the most common cause of blindness and a major cause of visual impairment worldwide. As the world’s population ages, cataract-induced visual impairment is of increasing prevalence, and treatment is limited to those with access to surgical care. While cataracts are mainly a disease of the elderly, infantile cataracts lead to lifelong visual impairment if untreated. Even in those with surgical treatment early in life, visual prognosis is often guarded. Consequently, there is an increasing impetus for alternative therapeutic modalities. Makley and Zhao utilize two different experimental approaches to identify novel pharmacological substances able to improve lens transparency by reducing aggregation of crystalline proteins. These data support an alternative to surgical correction that may be applied to adult patients without access to surgical care as well as address the unique challenges of infantile cataracts.     

Bladder cancer cell lines adapt their aggressiveness profile to oxygen tension

During the process of tumor growth, cancer cells will be subjected to intermittent hypoxia. This results from the delay in the development of the vascular network in relation to the proliferation of cancer cells. The hypoxic nature of a tumor has been demonstrated as a negative factor for patient survival. To evaluate the impact of hypoxia on the survival and migration properties of low and high-grade bladder cancer cell lines, two low-grade (MGHU-3 and SW-780) and two high-grade (SW-1710 and T24) bladder cancer cell lines were cultured in normoxic (20% O₂) or hypoxic atmospheric conditions (2% O₂). The response of bladder cancer cell lines to hypoxic atmospheric cell culture conditions was examined under several parameters, including epithelial-mesenchymal transition, doubling time and metabolic activities, thrombospondin-1 expression, whole Matrix Metallo-Proteinase activity, migration and resistance to oxidative stress. The low-grade cell line response to hypoxia was heterogeneous even if it tended to adopt a more aggressive profile. Hypoxia enhanced migration and pro-survival properties of MGHU-3 cells, whereas these features were reduced for the SW-780 cell line cultured under low oxygen tension. The responses of tested high-grade cell lines were more homogeneous and tended to adopt a less aggressive profile. Hypoxia drastically changed some of the bladder cancer cell line properties, for example matrix metalloproteinases expression for all cancer cells but also switch in glycolytic metabolism of low grade cancer cells. Overall, studying bladder cancer cells in hypoxic environments are relevant for the translation from in vitro findings to in vivo context.     

The sensitivity of carpal bone indices to rotational malpositioning

We investigated the dependence of 20 radiographic carpal measurements (carpal indices) on rotational positioning errors in posteroanterior and lateral radiographs. The measurements were made from "true perspective" digitally reconstructed radiographs created from computed tomography data. Most posteroanterior indices were not affected by rotation. Carpal height, carpal height ratio, revised carpal height ratio, capitate-radius distance, and carpal ulnar translocation were particularly robust. Lateral-view indices involving the scaphoid were the most sensitive to simulated malpositioning: radioscaphoid, scapholunate, and scaphocapitate angles were reduced from 58 degrees, 48 degrees, and 56 degrees at true lateral to 30 degrees, 24 degrees, and 34 degrees, respectively, at 20 degrees external rotation. Observers were unable to estimate the degree of malpositioning accurately in either view. Our results support use of the "scaphopisocapitate" criterion for assessing correct positioning in lateral plain radiographs.     

Estrogen receptor alpha expression in normal human breast epithelium is consistent over time

If increased expression of estrogen receptor alpha (ER) in benign breast epithelium increases susceptibility to breast cancer, such overexpression should be stable over time. There are no published data regarding this important aspect of ER expression in breast epithelium. We examined the temporal consistency of ER expression in the normal breast tissue of 28 women who had 2 separate breast surgical procedures, at least 6 months apart (mean interval, 2.8 years). Paraffin embedded breast tissue blocks containing an adequate sample of normal breast epithelium and no cancer, were sectioned and processed using the 6F11 antibody and standard immunohistochemical techniques. The ER labelling index (ER LI) was calculated by counting a mean of 2,000 epithelial cells. The median ER LI at first sampling was 13.6 and at second sample 15.5, with R(2) = 0.34 and p = 0.001. The ER LI was categorized into high and low values, using a threshold of 10. Twenty-four women (85.7%) showed concordance of high and low expression between the 2 samples (p = 0.002). There were 11 women who were premenopausal at both time points. Among them, much of the variation in ER LI was explained by differences in the menstrual cycle day at the time of sampling and adding the day of cycle to the regression model substantially improved the correlation between first and second labeling indices. These data suggest that ER expression of normal breast tissue is fairly consistent over time and support the notion that overexpression of ER in normal epithelium is a constant feature of the high risk breast.     

Higher Undercarboxylated to Total Osteocalcin Ratio Is Associated With Reduced Physical Function and Increased 15-Year Falls-Related Hospitalizations: The Perth Longitudinal Study of Aging Women

Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15-year falls-related hospitalizations. Serum tOC and ucOC were assessed in 1261 older women (mean age 75.2 ± 2.7 years) forming the Perth Longitudinal Study of Aging Women (1998 to 2013). Timed-up-and-go (TUG) and grip strength were assessed at baseline and at 5 years. Falls-related hospitalizations (14.5-year follow-up) were captured by the Hospital Morbidity Data Collection, via the Western Australian Data Linkage System. At baseline, women with higher ucOC/tOC ratio (quartile 4) had slower TUG performance compared with quartile 1 (~0.68 seconds, p < .01). Grip strength and 5-year change of TUG and grip were not different (p > .05) between quartiles. Fear of falling limiting house, outdoor, and combined activities was significantly different across quartiles (p < .05). Higher ucOC/tOC was significantly associated with poorer TUG performance at baseline and 5-year change in performance, increased walking aid use, and fear of falling (all p < .05). Higher ucOC was related to lower grip strength at baseline (p < .05) but not 5-year change in strength. Those with the highest ucOC/tOC had greater falls-related hospitalizations (unadjusted log rank, p = .004) remaining significant after adjusting for key variables (hazard ratio [HR] = 1.31, 95% confidence interval [CI] 1.09–1.57, p = .004). We identified a large proportion of older women with high ucOC/tOC ratio who had reduced physical function, including its long-term decline and increased risk of falls-related hospitalizations. Early identification of women at higher risk can enable prevention and intervention strategies to occur, reducing risk for injurious falls. © 2020 American Society for Bone and Mineral Research (ASBMR)..     

Spontaneous resolution of Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative disorder of the immune system resulting in lymphohistiocytic proliferation, hemophagocytosis, and cytokine dysregulation. The most common infectious trigger in sHLH is Epstein–Barr virus (EBV‐HLH). Current treatment protocols for EBV‐HLH have a cure rate of approximately 75%; however, there are significant toxicities associated with these therapies. We present two patients with EBV‐HLH who experienced spontaneous resolution of their disease prior to the initiation of therapy, suggesting there may be a subgroup of patients with EBV‐HLH who do well with conservative management and can avoid potentially toxic therapies. Pediatr Blood Cancer. 2010;55:754–756. © 2010 Wiley‐Liss, Inc.     

Impact of the Out-of-School Nutrition and Physical Activity (OSNAP) Group Randomized Controlled Trial on Children’s Food,Beverage, and Calorie Consumption among Snacks Served

Background

Afterschool interventions have been found to improve the nutritional quality of snacks served. However, there is limited evidence on how these interventions affect children’s snacking behaviors.

Ethnic differences in all-cause and cardiovascular mortality by physical activity levels among older adults in the US

Aims: This study sought to determine whether the association between varying levels of physical activity (PA) and all-cause and cardiovascular mortality differ by race/ethnicity in older adults.

Methods: The sample comprised 2520 women and 2398 men drawn from National Health and Nutrition Examination Survey III (1988–1994) aged?≥?60 years. We used the metabolic equivalent (MET) of self-reported PA levels to define activity groups (inactive: those who did not report any PA; active: those who reported 3–6 METs for ≥5 times/week or >6 METs, ≥3 times/week; insufficiently active: those meeting neither criteria). Racial/Ethnic differences were modeled using proportional hazard regression (HR) adjusting for age, education, smoking, diabetes, and hypertension.

Results: Among those classified as inactive, Non-Hispanic Blacks (NHB) (HR: 0.72, 95% CI: 0.58–0.90) and Mexican Americans (HR: 0.59, 95%CI: 0.45–0.78) had a lower risk of all-cause mortality when compared to non-Hispanic Whites (NHW). Among those classified as insufficiently active, Mexican Americans (HR: 0.63, 95% CI: 0.51–0.77), but not NHB (HR: 0.81, (95% CI: 0.64–1.02) had a lower risk of all-cause mortality when compared to NHWs Similar results were observed for cardiovascular mortality.

Conclusion: Overall, PA in the elderly (either insufficient or active) is associated with a lower all-cause mortality across all race/ethnic groups as compared to NHW. Further investigation, including studies with larger sample, is needed to address the health consequences of varying degrees of PA in ethnically diverse populations.