Time Trends in Perioperative Characteristics and Health Outcomes in Hispanic Patients Undergoing Primary Total Knee Arthroplasty.

OBJECTIVE: This study analyzed the yearly trends in procedure utilization, comorbidity profiles, hospital length of stay (LOS), and 30-day outcomes in Hispanic/Latino patients undergoing primary total knee arthroplasty (TKA). Risk stratification for the development of postsurgical adverse events (AEs) was also investigated. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was queried for all Hispanic/Latino patients who underwent primary, elective TKA between 2011 and 2017. Thirty-day outcomes and risk factors were determined using multivariate models that controlled for baseline and perioperative differences. RESULTS: A total of 12,767 Hispanic/Latino patients were identified. Over the study period, the rate of TKA utilization increased by 108%. During the same time, there were significant reductions in the rates of COPD (1.9% vs. 2.9%, p = 0.015), anemia (18.0% vs. 23.5%, p < 0.001), dyspnea (2.9% vs. 4.0%, p = 0.006), and procedure length > 100 min (35.2% vs. 39.4%, p < 0.001). Postoperatively, there was a significant decrease in LOS > 2 days (41.3% vs. 75.6%, p < 0.001), but there was an increase in the rate of developing 30-day AEs (5.8% vs. 4.7%, p = 0.046). Independent risk factors for 30-day AEs included age > 65 years, male sex, chronic steroid use, ASA > 2, diabetes, bleeding disorder, chronic kidney disease, and procedure length > 100 min. CONCLUSION: While the recent trends in procedure utilization, comorbidity profiles, and LOS in Hispanic/Latino patients undergoing primary TKA are reassuring, these have not been accompanied with improved postoperative safety. Patients with bleeding disorders, chronic steroid use, and those admitted from facilities other than home appear to be at highest risk for developing 30-day AEs.

Sex Differences in Remote Contextual Fear Generalization in Mice.

The generalization of fear is adaptive in that it allows an animal to respond appropriately to novel threats that are not identical to previous experiences. In contrast, the overgeneralization of fear is maladaptive and is a hallmark of post-traumatic stress disorder (PTSD), a psychiatric illness that is characterized by chronic symptomatology and a higher incidence in women compared to men. Therefore, understanding the neural basis of fear generalization at remote time-points in female animals is of particular translational relevance. However, our understanding of the neurobiology of fear generalization is largely restricted to studies employing male mice and focusing on recent time-points (i.e., within 24-48 h following conditioning). To address these limitations, we examined how male and female mice generalize contextual fear at remote time intervals (i.e., 3 weeks after conditioning). In agreement with earlier studies of fear generalization at proximal time-points, we find that the test order of training and generalization contexts is a critical determinant of generalization and context discrimination, particularly for female mice. However, tactile elements that are present during fear conditioning are more salient for male mice. Our study highlights long-term sex differences in defensive behavior between male and female mice and may provide insight into sex differences in the processing and retrieval of remote fear memory observed in humans.

RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss.

Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related Memory Loss. By exploring how this protein regulates the genomic landscape of the hippocampal circuit, we find that RbAp48 controls the expression of BDNF and GPR158 proteins, both critical components of osteocalcin (OCN) signaling in the mouse hippocampus. We show that inhibition of RbAp48 in the hippocampal formation inhibits OCN's beneficial functions in cognition and causes deficits in discrimination memory. In turn, disruption of OCN/GPR158 signaling leads to the downregulation of RbAp48 protein, mimicking the discrimination memory deficits observed in the aged hippocampus. We also show that activation of the OCN/GPR158 pathway increases the expression of RbAp48 in the aged dentate gyrus and rescues age-related memory loss.

Identification and Functional Assessment of Age-Dependent Truncations to Cx46 and Cx50 in the Human Lens.

PURPOSE: Many proteins in the lens undergo extensive posttranslational modifications (PTMs) with age, leading to alterations in their function. The extent to which lens gap junction proteins, Cx46 and Cx50, accumulate PTMs with aging is not known. In this study, we identified truncations in Cx46 and Cx50 in the human lens using mass spectrometry. We also examined the effect of truncations on channel function using electrophysiological measurements. METHODS: Human lenses were dissected into cortex, outer nucleus, and nucleus regions, and fiber cell membranes were subjected to trypsin digestion. Tryptic peptides were analyzed by liquid chromatography (LC)-electrospray tandem mass spectrometry (ESI/MS/MS). Effects of truncations on channel conductance, permeability, and gating were assessed in transfected cells. RESULTS: Cleavage sites were identified in the C-terminus, the cytoplasmic loop, and the N-terminus of Cx46 and Cx50. Levels of C-terminal truncations, which were found at residues 238 to 251 in Cx46 and at residues 238 to 253 and 274 to 284 in Cx50, were similar in different lens regions. In contrast, levels of truncations in cytoplasmic loop and N-terminal domains of Cx46 and Cx50 increased dramatically from outer cortex to nucleus. Most of the C-terminally truncated proteins were functional, whereas truncations in the cytoplasmic loop did not result in the formation of functional channels. CONCLUSIONS: Accumulation of cytoplasmic loop and N-terminal truncations in the core might lead to decreases in coupling with age. This reduction is expected to lead to an increase in intracellular calcium and a decrease in levels of glutathione in the nucleus. These changes may ultimately lead to age-related nuclear cataracts.