Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype.

Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in the future. Stress responses are established by an interplay between genetics, environment, and life experiences. Psychosocial stress is particularly impactful during adolescence, a critical period for the development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, the "internalizing" bred Low Responder (bLR) line versus the "externalizing" bred High Responder (bHR) line, to investigate how genetic temperament and adolescent environment impact future responses to social interactions and psychosocial stress, and how these determinants of stress response interact. Male bLR and bHR rats were exposed to social and environmental enrichment in adolescence prior to experiencing social defeat and were then assessed for social interaction and anxiety-like behavior. Adolescent enrichment caused rats to display more social interaction, as well as nominally less social avoidance, less submission during defeat, and resilience to the effects of social stress on corticosterone, in a manner that seemed more notable in bLRs. For bHRs, enrichment also caused greater aggression during a neutral social encounter and nominally during defeat, and decreased anxiety-like behavior. To explore the neurobiology underlying the development of social resilience in the anxious phenotype bLRs, RNA-seq was conducted on the hippocampus and nucleus accumbens, two brain regions that mediate stress regulation and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory activity were enriched with differential expression in both regions, with a particularly large effect on gene sets that regulate social behaviors. Our findings provide further evidence that adolescent enrichment can serve as an inoculating experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipulating their environment has translational implications, as it underscores the feasibility of intervention strategies targeted at genetically vulnerable adolescent populations.

Adolescent environmental enrichment induces social resilience and alters neural gene expression in a selectively bred rodent model with anxious phenotype.

Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in the future. Stress responses are established by an interplay between genetics, environment, and life experiences. Psychosocial stress is particularly impactful during adolescence, a critical period for the development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, the "internalizing" bred Low Responder (bLR) line versus the "externalizing" bred High Responder (bHR) line, to investigate how genetic temperament and adolescent environment impact future responses to social interactions and psychosocial stress, and how these determinants of stress response interact. Male bLR and bHR rats were exposed to social and environmental enrichment in adolescence prior to experiencing social defeat and were then assessed for social interaction and anxiety-like behavior. Adolescent enrichment caused rats to display more social interaction, as well as nominally less social avoidance, less submission during defeat, and resilience to the effects of social stress on corticosterone, in a manner that seemed more notable in bLRs. For bHRs, enrichment also caused greater aggression during a neutral social encounter and nominally during defeat, and decreased anxiety-like behavior. To explore the neurobiology underlying the development of social resilience in the anxious phenotype bLRs, RNA-seq was conducted on the hippocampus and nucleus accumbens, two brain regions that mediate stress regulation and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory activity were enriched with differential expression in both regions, with a particularly large effect on gene sets that regulate social behaviors. Our findings provide further evidence that adolescent enrichment can serve as an inoculating experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipulating their environment has translational implications, as it underscores the feasibility of intervention strategies targeted at genetically vulnerable adolescent populations.

Contemporary Outcomes of Elective Parastomal Hernia Repair in Older Adults.

Importance: Parastomal hernia is a challenging complication following ostomy creation; however, the incidence and long-term outcomes after elective parastomal hernia repair are poorly characterized. Objective: To describe the incidence and long-term outcomes after elective parastomal hernia repair. Design, Setting, and Participants: Using 100% Medicare claims, a retrospective cohort study of adult patients who underwent elective parastomal hernia repair between January 1, 2007, and December 31, 2015, was performed. Logistic regression and Cox proportional hazards models were used to evaluate mortality, complications, readmission, and reoperation after surgery. Analysis took place between February and May 2022. Exposures: Parastomal hernia repair without ostomy resiting, parastomal hernia repair with ostomy resiting, and parastomal hernia repair with ostomy reversal. Main Outcomes and Measures: Mortality, complications, and readmission within 30 days of surgery and reoperation for recurrence (parastomal or incisional hernia repair) up to 5 years after surgery. Results: A total of 17 625 patients underwent elective parastomal hernia repair (mean [SD] age, 73.3 [9.1] years; 10 059 female individuals [57.1%]). Overall, 7315 patients (41.5%) underwent parastomal hernia repair without ostomy resiting, 2744 (15.6%) underwent parastomal hernia repair with ostomy resiting, and 7566 (42.9%) underwent parastomal hernia repair with ostomy reversal. In the 30 days after surgery, 676 patients (3.8%) died, 7088 (40.2%) had a complication, and 1740 (9.9%) were readmitted. The overall adjusted 5-year cumulative incidence of reoperation was 21.1% and was highest for patients who underwent parastomal hernia repair with ostomy resiting (25.3% [95% CI, 25.2%-25.4%]) compared with patients who underwent parastomal hernia repair with ostomy reversal (18.8% [95% CI, 18.7%-18.8%]). Among patients whose ostomy was not reversed, the hazard of repeat parastomal hernia repair was the same for patients whose ostomy was resited vs those whose ostomy was not resited (adjusted hazard ratio, 0.93 [95% CI, 0.81-1.06]). Conclusions and Relevance: In this study, more than 1 in 5 patients underwent another parastomal or incisional hernia repair within 5 years of surgery. Although this was lowest for patients who underwent ostomy reversal at their index operation, ostomy resiting was not superior to local repair. Understanding the long-term outcomes of this common elective operation may help inform decision-making between patients and surgeons regarding appropriate operative approach and timing of surgery.

Comparative Outcomes of Groin Hernia Repair by Sex Among Medicare Beneficiaries.

OBJECTIVE: To compare the rates of operative recurrence between male and female patients undergoing groin hernia repair. BACKGROUND DATA: Groin hernia repair is common but understudied in females. Limited prior work demonstrates worse outcomes among females. METHODS: Using Medicare claims, we performed a retrospective cohort study of adult patients who underwent elective groin hernia repair between January 1, 2010 and December 31, 2017. We used a Cox proportional hazards model to evaluate the risk of operative recurrence up to 5 years following the index operation. Secondary outcomes included 30-day complications following surgery. RESULTS: Among 118,119 patients, females comprised the minority of patients (n=16,056, 13.6%). Compared with males, female patients were older (74.8 vs. 71.9 y, P <0.01), more often white (89.5% vs. 86.7%, P <0.01), and had a higher prevalence of nearly all measured comorbidities. In the multivariable Cox proportional hazards model, we found that female patients had a significantly lower risk of operative recurrence at 5-year follow-up compared with males (aHR 0.70, 95% CI 0.60-0.82). The estimated cumulative incidence of recurrence was lower among females at all time points: 1 year [0.68% (0.67-0.68) vs. 0.88% (0.88-0.89)], 3 years [1.91% (1.89-1.92) vs. 2.49% (2.47-2.5)], and 5 years [2.85% (2.82-2.88) vs. 3.7% (3.68-3.75)]. We found no significant difference in the 30-day risk of complications. CONCLUSIONS: We found that female patients experienced a lower risk of operative hernia recurrence following elective groin hernia repair, which is contrary to what is often reported in the literature. However, the risk of operative recurrence was low overall, indicating excellent surgical outcomes among older adults for this common surgical condition.

Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features.

CONTEXT: Noninvasive encapsulated follicular variant of papillary thyroid cancer was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in January 2017. The impact of this nomenclature change at a population level remains unknown. OBJECTIVE: Examine use of NIFTP across different US regions and populations. DESIGN: Descriptive epidemiology study using SEER-22 data (2000-2019). PARTICIPANTS: Individuals diagnosed with papillary or follicular thyroid cancer (2000-2019) or NIFTP (2017-2019). MAIN OUTCOME MEASURES: Annual incidence rates of thyroid cancer by subtype and NIFTP. Using 2018-2019 data, (1) rates of NIFTP at the 17 SEER-22 sites and (2) comparison of demographics for patients diagnosed with NIFTP vs papillary and follicular thyroid cancer. RESULTS: NIFTP comprised 2.2% and 2.6% of cases in 2018 and 2019, respectively. Between 2018 and 2019, large heterogeneity was observed in the regional use of NIFTP diagnosis, with site-specific incidence rates between 0.0% and 6.2% (median 2.8%, interquartile range 1.3-3.6%). A diagnosis of NIFTP (vs papillary and follicular thyroid cancer) in 2018 and 2019 was significantly associated with older age (P = 0.012 and P = 0.009, respectively), Black race (both Ps < 0.001), and non-Hispanic ethnicity (both Ps < 0.001). CONCLUSIONS: Marked variation exists in the use of the NIFTP diagnosis. The recent 2021 coding change that resulted in NIFTP, a tumor with uncertain malignant potential and for which there is no long-term outcome data available, no longer being a reportable diagnosis to SEER will disproportionately affect vulnerable patient groups such as older patients and Black patients, in addition to patients who reside in regions with higher rates of NIFTP diagnoses.