Aging-associated decrease of PGC-1α promotes pain chronification.

Aging is generally associated with declining somatosensory function, which seems at odds with the high prevalence of chronic pain in older people. This discrepancy is partly related to the high prevalence of degenerative diseases such as osteoarthritis in older people. However, whether aging alters pain processing in the primary somatosensory cortex (S1), and if so, whether it promotes pain chronification is largely unknown. Herein, we report that older mice displayed prolonged nociceptive behavior following nerve injury when compared with mature adult mice. The expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in S1 was decreased in older mice, whereas PGC-1α haploinsufficiency promoted prolonged nociceptive behavior after nerve injury. Both aging and PGC-1α haploinsufficiency led to abnormal S1 neural dynamics, revealed by intravital two-photon calcium imaging. Manipulating S1 neural dynamics affected nociceptive behavior after nerve injury: chemogenetic inhibition of S1 interneurons aggravated nociceptive behavior in naive mice; chemogenetic activation of S1 interneurons alleviated nociceptive behavior in older mice. More interestingly, adeno-associated virus-mediated expression of PGC-1α in S1 interneurons ameliorated aging-associated chronification of nociceptive behavior as well as aging-related S1 neural dynamic changes. Taken together, our results showed that aging-associated decrease of PGC-1α promotes pain chronification, which might be harnessed to alleviate the burden of chronic pain in older individuals.

Recent Trends in "Manels" and Gender Representation Among Panelists at North American Annual Radiation Oncology Meetings.

PURPOSE: Achieving gender equity in radiation oncology is an important goal, as a smaller proportion of women enter radiation oncology residency compared with those graduating from medical school. As invited speaking opportunities at academic medical conferences are vital for promotion/tenure, we investigated the prevalence of all-men panels ("manels") at American Society for Radiation Oncology (ASTRO) and Canadian Society of Radiation Oncology (CARO) annual meetings. METHODS AND MATERIALS: Using ASTRO and CARO online meeting programs, 2018 to 2021 faculty information was obtained, including gender, panel role (chair vs nonchair), type of session, and topic. Primary outcomes included percentage of manels and proportion of female panelists over time. Representation of women among chairs was also evaluated. RESULTS: Over the 4-year study period across both conferences, a total of 765 panel sessions were held with 2973 faculty members, of whom 1287 (43.3%) were women. Of these sessions, 127 of 765 (16.6%) were manels. ASTRO meetings had 1169 of 2742 (42.6%) female faculty members and held 107 of 680 (15.7%) manels, whereas CARO meetings had 118 of 231 (51.1%) female faculty and held 20 of 85 manels (23.5%). From 2018 to 2021, the proportion of manels decreased at ASTRO and CARO meetings from 25.6% to 8.2% (P < .001) and from 29.6% to 15.0% (P = .130), respectively. The role of chair was majority male in every year from 2018 to 2021 at ASTRO meetings (58.6% overall), but more balanced at CARO meetings (48.0% overall). Among session types, the highest proportion of manels was observed for scientific sessions (19.1%, P = .011) at ASTRO meetings and leadership sessions (29.4%, P = .533) at CARO meetings. The lowest proportion of female panelists was on genitourinary cancer topics at ASTRO meetings (31.9%, P = .018) and physics topics at CARO meetings (40.4%, P = .085). CONCLUSIONS: During the study period, the proportion of female panelists increased with a corresponding decrease in manels. ASTRO and CARO should strive for further involvement of women and the elimination of manels whenever possible.

US Cancer Mortality Trends Among Hispanic Populations From 1999 to 2020.

Importance: Advances in cancer research and treatment access have led to decreasing cancer mortality in the US; however, cancer remains the leading cause of death among Hispanic individuals. Objective: To evaluate longitudinal cancer mortality trends from 1999 to 2020 among Hispanic individuals by demographic characteristics and to compare age-adjusted cancer death rates between the Hispanic population and other racial and ethnic populations during 2000, 2010, and 2020. Design, Setting, and Participants: This cross-sectional study obtained age-adjusted cancer death rates among Hispanic individuals of all ages between January 1999 and December 2020, using the Centers for Disease Control and Prevention WONDER database. Cancer death rates in other racial and ethnic populations were extracted for 2000, 2010, and 2020. Data were analyzed from October 2021 to December 2022. Exposures: Age, gender, race, ethnicity, cancer type, and US census region. Main Outcomes and Measures: Trends and average annual percent changes (AAPCs) in age-adjusted cancer-specific mortality (CSM) rates among Hispanic individuals were estimated by cancer type, age, gender, and region. Results: From 1999 to 2020, 12 644 869 patients died of cancer in the US, of whom 690 677 (5.5%) were Hispanic; 58 783 (0.5%) were non-Hispanic American Indian or Alaska Native; 305 386 (2.4%), non-Hispanic Asian or Pacific Islander; 1 439 259 (11.4%), non-Hispanic Black or African American; and 10 124 361 (80.1%), non-Hispanic White. For 26 403 patients (0.2%), no ethnicity was stated. The overall CSM rate among Hispanic individuals decreased by 1.3% (95% CI, 1.2%-1.3%) annually. Overall CSM rate decreased more for Hispanic men (AAPC, -1.6%; 95% CI, -1.7% to -1.5%) compared with women (AAPC, -1.0%; 95% CI, -1.0% to -0.9%). While death rates among Hispanic individuals decreased for most cancer types, mortality rates for liver cancer (AAPC, 1.0%; 95% CI, 0.6%-1.4%) increased among Hispanic men, and rates of liver (AAPC, 1.0%; 95% CI, 0.8%-1.3%), pancreas (AAPC, 0.2%; 95% CI, 0.1%-0.4%), and uterine (AAPC, 1.6%; 95% CI, 1.0%-2.3%) cancers increased among Hispanic women. Overall CSM rates increased for Hispanic men aged 25 to 34 years (AAPC, 0.7%; 95% CI, 0.3%-1.1%). By US region, liver cancer mortality rates increased significantly in the West for both Hispanic men (AAPC, 1.6%; 95% CI, 0.9%-2.2%) and Hispanic women (AAPC, 1.5%; 95% CI, 1.1%-1.9%). There were differential findings in mortality rates when comparing Hispanic individuals with individuals belonging to other racial and ethnic populations. Conclusions and Relevance: In this cross-sectional study, despite overall CSM decreasing over 2 decades among Hispanic individuals, disaggregation of data demonstrated that rates of liver cancer deaths among Hispanic men and women and pancreas and uterine cancer deaths among Hispanic women increased from 1999 to 2020. There were also disparities in CSM rates among age groups and US regions. The findings suggest that sustainable solutions need to be implemented to reverse these trends among Hispanic populations.

Figure of eight suture technique in aortic valve replacement decreases prosthesis-patient mismatch.

BACKGROUND: While the pledget suture technique has been the standard for surgical aortic. valve replacement (AVR), discussion continues regarding the possibility of the nonpledget suture technique to produce superior structural and hemodynamic parameters. This study aims to assess the effectiveness of the figure-of-eight suture technique in AVR, as determined by the incidence of prosthesis-patient mismatch (PPM). METHODS: We reviewed records of patients (N = 629) who underwent a surgical AVR procedure between January 2011 and July 2018 at a single institution. Indexed effective orifice area values and PPM incidence were calculated from implanted valve size and patient body surface area. Incidence of none, moderate, and severe PPM was compared across AVR suture techniques. RESULTS: A total of 570 pledget and 59 figure-of-eight patients were compared for incidence of PPM. Patients who received AVR with the pledget suture technique had significantly lower echocardiographic measurements of baseline ejection fraction than patients who had received AVR with the figure-of-eight suture technique (p = 0.003). Patients who received the figure-of eight suture had a 14% decrease in moderate PPM compared to patients who received the pledget suture (p = 0.022). Patients who received the figure-of-eight suture also had a significantly higher rate of no PPM (p = 0.044). CONCLUSIONS: The use of the figure-of-eight suture technique in AVR can reduce the incidence of moderate PPM. While the pledget suture is the standard technique in AVR, the figure-of-eight suture technique may offer better structural and hemodynamic outcomes, especially for patients with a smaller aortic annulus.