Learning induces unique transcriptional landscapes in the auditory cortex.

Learning can induce neurophysiological plasticity in the auditory cortex at multiple timescales. Lasting changes to auditory cortical function that persist over days, weeks, or even a lifetime, require learning to induce de novo gene expression. Indeed, transcription is the molecular determinant for long-term memories to form with a lasting impact on sound-related behavior. However, auditory cortical genes that support auditory learning, memory, and acquired sound-specific behavior are largely unknown. Using an animal model of adult, male Sprague-Dawley rats, this report is the first to identify genome-wide changes in learning-induced gene expression within the auditory cortex that may underlie long-lasting discriminative memory formation of acoustic frequency cues. Auditory cortical samples were collected from animals in the initial learning phase of a two-tone discrimination sound-reward task known to induce sound-specific neurophysiological and behavioral effects. Bioinformatic analyses on gene enrichment profiles from bulk RNA sequencing identified cholinergic synapse (KEGG rno04725), extra-cellular matrix receptor interaction (KEGG rno04512), and neuroactive receptor interaction (KEGG rno04080) among the top biological pathways are likely to be important for auditory discrimination learning. The findings characterize candidate effectors underlying the early stages of changes in cortical and behavioral function to ultimately support the formation of long-term discriminative auditory memory in the adult brain. The molecules and mechanisms identified are potential therapeutic targets to facilitate experiences that induce long-lasting changes to sound-specific auditory function in adulthood and prime for future gene-targeted investigations.

Learning induces unique transcriptional landscapes in the auditory cortex.

Learning can induce neurophysiological plasticity in the auditory cortex at multiple timescales. Lasting changes to auditory cortical function that persist over days, weeks, or even a lifetime, require learning to induce de novo gene expression. Indeed, transcription is the molecular determinant for long-term memories to form with a lasting impact on sound-related behavior. However, auditory cortical genes that support auditory learning, memory, and acquired sound-specific behavior are largely unknown. This report is the first to identify in young adult male rats (Sprague-Dawley) genome-wide changes in learning-induced gene expression within the auditory cortex that may underlie the formation of long-lasting discriminative memory for acoustic frequency cues. Auditory cortical samples were collected from animals in the initial learning phase of a two-tone discrimination sound-reward task known to induce sound-specific neurophysiological and behavioral effects (e.g., Shang et al., 2019). Bioinformatic analyses on gene enrichment profiles from bulk RNA sequencing identified cholinergic synapse (KEGG 04725), extra-cellular matrix receptor interaction (KEGG 04512) , and neuroactive ligand-receptor interaction (KEGG 04080) as top biological pathways for auditory discrimination learning. The findings characterize key candidate effectors underlying changes in cortical function that support the initial formation of long-term discriminative auditory memory in the adult brain. The molecules and mechanisms identified are potential therapeutic targets to facilitate lasting changes to sound-specific auditory function in adulthood and prime for future gene-targeted investigations.

Do Patient Expectations Influence Patient-Reported Outcomes and Satisfaction in Total Hip Arthroplasty? A Prospective, Multicenter Study.

BACKGROUND: The relationship between patient expectations and patient-reported outcomes (PROs) in total hip arthroplasty (THA) patients is controversial. The purpose of this study was to examine the impact of preoperative patient expectations on postoperative PROs and patient satisfaction. METHODS: This was a prospective multicenter observational cohort study of primary THA patients. Preoperatively, patients completed Hospital for Special Surgery (HSS) Hip Replacement Expectations Survey (expectations), 12 item Short Form Survey (SF-12), University of California, Los Angeles (UCLA) activity score, and Hip Disability and Osteoarthritis Score (HOOS). Postoperatively at 6 months and 1 year, patients completed the Hospital for Special Surgery Hip Replacement Fulfillment of Expectations Survey (fulfillment of expectations), a satisfaction survey, and the same PROs as preoperatively. Stepwise multivariate regression models were created. RESULTS: A total of 207 patients were enrolled. Follow-up rate was 91% at 6 months and 92% at 1 year. Being employed and lower baseline HOOS predicted higher expectations (employment status: B = -7.5, P = .002; HOOS: B = -0.27, P = .002). Higher preoperative expectations predicted greater improvements in UCLA activity, SF-12 physical component score, and HOOS at 6 months (UCLA activity: B = 0.03, P = .001; SF-12 physical component score: B = 0.15, P = .001; HOOS: B = 0.20; P = .008) and UCLA activity at 1 year (B = 0.02, P = .004). Furthermore, higher expectations predicted higher postoperative satisfaction and fulfillment of expectations at 6 months (satisfaction: B = 0.21, P < .001; fulfillment of expectations: B = 0.30, P < .001) and higher fulfillment of expectations at 1 year (B = 0.17, P = .006). CONCLUSION: In patients undergoing THA, being employed and worse preoperative hip function predict of higher preoperative expectations of surgery. Higher expectations predict greater improvement in PROs, greater patient satisfaction, and the fulfillment of expectations. These findings can be used to guide patient counseling and shared decision making preoperatively.

Higher Patient Expectations Predict Higher Patient-Reported Outcomes, But Not Satisfaction, in Total Knee Arthroplasty Patients: A Prospective Multicenter Study.

BACKGROUND: The relationship between patient expectations, patient-reported outcomes (PROs), and satisfaction in total knee arthroplasty (TKA) patients is not well understood. METHODS: We prospectively evaluated patients who underwent primary TKA at 4 institutions. Demographics were collected. Preoperatively, patients completed the Hospital for Special Surgery Knee Replacement Expectations Survey (HSS-KRES), SF-12, UCLA activity, and Knee Disability and Osteoarthritis Score. At 6 months and 1 year postoperatively, patients completed the Hospital for Special Surgery Knee Replacement Fulfillment of Expectations Survey (HSS-KRFES), a satisfaction survey, and PROs. Step-wise multivariate regression models were created. RESULTS: Eighty-three patients were enrolled. At 6 months and 1 year postoperatively, the follow-up rate was 84.3% and 92.7%, respectively. No demographics or preoperative PROs were predictive of HSS-KRES. Preoperative HSS-KRES did not predict postoperative satisfaction, but higher HSS-KRES predicted higher HSS-KRFES at 1 year, greater improvement in UCLA activity at 6 months and 1 year, and SF-12 Physical Composite Scale and Knee Disability and Osteoarthritis Score at 6 months. Higher HSS-KRFES predicted higher satisfaction at 6 months and 1 year. CONCLUSION: In TKA patients, preoperative expectations are not influenced by patient demographics or preoperative function. Higher preoperative expectations predict greater postoperative improvement in PROs and fulfillment of expectations. These findings highlight the importance of preoperative patient expectations on postoperative outcome.

Preoperative Reduction of Opioid Use Before Total Joint Arthroplasty.

BACKGROUND: The purpose of this study was to assess whether weaning of opioid use in the preoperative period improved total joint arthroplasty (TJA) outcomes. METHODS: Forty-one patients who regularly used opioids and successfully weaned (defined as a 50% reduction in morphine-equivalent dose) before a primary total knee or hip arthroplasty were matched with a group of TJA patients who did not wean and a matched control group of TJA patients who did not use opioids preoperatively. The difference between preoperative and postoperative (at 6-12 months follow-up) patient-reported outcomes were assessed using the change in University of California, Los Angeles (UCLA) activity score, SF12v2, and The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Paired t tests and 1-way repeated measures analysis of variance were performed to assess differences in TJA outcomes between groups. RESULTS: Patients using opioids who successfully weaned had greater improvements in both disease-specific and generic measures of health outcomes than patients who did not wean (WOMAC 43.7 vs 17.8, P < .001; SF12v2 Physical Component Score 10.5 vs 1.85, P = .003; UCLA activity score 1.49 vs 0, P < .001). There was no statistical difference between the 2 groups on SF12v2 Mental Component Score 2.48 vs 4.21, P = .409. Patients who successfully weaned from opioids had similar outcomes to control patients who did not use opioids: WOMAC 39.0 vs 43.7, P = .31; SF12v2 Physical Component Score 12.5 vs 10.5, P = .35; SF12v2 Mental Component Score 3.08 vs 2.48, P = .82; UCLA activity 1.90 vs 1.49, P = .23. CONCLUSION: Patients with a history of chronic opioid use who successfully decreased their use of opioids before surgery had substantially improved clinical outcomes that were comparable to patients who did not use opioids at all.

Trends in total knee arthroplasty implant utilization.

The incidence of total knee arthroplasty (TKA) has increased alongside our knowledge of knee physiology, kinematics, and technology resulting in an evolution of TKA implants. This study examines the trends in TKA implant utilization. Data was extracted from The Orthopedic Research Network to evaluate trends in level of constraint, fixed vs. mobile bearing, fixation, and type of polyethylene in primary TKAs. In 2012, 88% used cemented femoral and tibial implants, and 96% involved patellar resurfacing. 38% of implants were cruciate retaining, 53% posterior stabilized or condylar stabilized, 3% constrained. 91% were fixed-bearing, 7% mobile-bearing. 52% of tibial inserts were HXLPE. TKA implant trends demonstrate a preference for cemented femoral and tibial components, patellar resurfacing, fixed-bearing constructs, metal-backed tibial components, patellar resurfacing, and increased usage of HXLPE liners.

Paraoxonase polymorphism in northwestern Indians.

OBJECTIVE: The aim of this study was to distinguish paraoxonase phenotypes by dual substrate method. SUBJECTS AND METHODS: 166 unrelated healthy northwestern Indian Punjabis were studied for basal paraoxonase activity (P), in presence of 1 M NaCl (salt-activated) using paraoxon as substrate and arylesterase activity (A) using phenylacetate as substrate. RESULTS: The mean (+ SD) activity of these in population was 70.43 (+/-30.41), 103.11 (+/-42.87) nmol/min/ml plasma and 36.81 (+/- 9.87) micromol/min/ml plasma, respectively, with no significant difference in sexes. Based on the ratio of SAP activity to A activity, 3 distinct phenotypes could be determined with gene frequencies of PON*A and PON*B being 0.845 and 0.155, respectively. Between P and A, and SAP and A in both A and AB phenotypes, significant correlation was observed (A = r 0.34 and 0.62, p < 0.01; B = r 0.31 and 0.81, p > 0.01), suggesting that both enzymes belong to the same group. CONCLUSIONS: Though northwestern Indian Punjabis have trimodal paraoxonase activity, the majority is either low homozygous (AA) or heterozygous (AB) type with enzyme activity lower than Europids.

In vivo function of surfactants containing phosphatidylcholine analogs.

Increased phospholipase A2 activity demonstrated in some forms of lung injury may contribute to surfactant dysfunction. Phospholipase A2-resistant analogs of dipalmitoylphosphatidylcholine (DPPC) with surfactant properties might therefore be useful lipid components of treatment surfactants for certain lung injuries. The in vivo function of surfactants containing DPPC or the phospholipase-resistant analogs dihexadecylphosphatidylcholine (DEPC) or dihexadecylphosphonotidylcholine (DEPnC), with or without surfactant proteins B and C (SP-B+C), was thus evaluated in preterm rabbits (27 days' gestation). Rabbits randomly received one of seven surfactants (DPPC, DEPC, DEPnC, DPPC+SP-B+C, DEPC+SP-B+C, DEPnC+SP-B+C, or lipid extract surfactant [LES]) or 0.45% NaCl (control) and were ventilated for 30 min. Lipid-only surfactants decreased ventilatory pressures (peak inspiratory pressures minus positive end-expiratory pressure) relative to control (p < 0.05). Addition of SP-B+C further decreased ventilatory pressures to levels similar to LES (p < 0.01 versus control, lipid-only surfactants). Lung dynamic compliances and postventilation pressure-volume curves improved in the following order: LES, SP-B+C lipid surfactants > lipid-only surfactants > control (p < 0.05). All surfactant preparations decreased intravascular 125I-albumin recoveries in the lungs relative to control (p < 0.01 for all surfactants versus control). These results indicate that DEPC and DEPnC were as effective as DPPC as lipid components of synthetic surfactants. And like DPPC, the analogs interacted with isolated SP-B+C and improved in vivo function to levels comparable to LES.