Aging disrupts the temporal organization of antioxidant defenses in the heart of male rats and phase shifts circadian rhythms of systolic blood pressure

Biogerontology - Aging is one of the main risk factors for cardiovascular diseases, and oxidative stress is a key element responsible for the development of age-related pathologies. In addition,...     

Fish navigation of large dams emerges from their modulation of flow field experience

Navigating obstacles is innate to fish in rivers, but fragmentation of the world’s rivers by more than 50,000 large dams threatens many of the fish migrations these waterways support. One limitation to mitigating the impacts of dams on fish is that we have a poor understanding of why some fish enter routes engineered for their safe travel around the dam but others pass through more dangerous routes. To understand fish movement through hydropower dam environments, we combine a computational fluid dynamics model of the flow field at a dam and a behavioral model in which simulated fish adjust swim orientation and speed to modulate their experience to water acceleration and pressure (depth). We fit the model to data on the passage of juvenile Pacific salmonids (Oncorhynchus spp.) at seven dams in the Columbia/Snake River system. Our findings from reproducing observed fish movement and passage patterns across 47 flow field conditions sampled over 14 y emphasize the role of experience and perception in the decision making of animals that can inform opportunities and limitations in living resources management and engineering design.Understanding how the design and management of civil infrastructure modifies the outcome of naturally evolved behavior in animals is critical for sustainably using limited environmental resources to spur economic development and maintain native species. The issue is particularly relevant for rivers, which make up only 0.0002% of water on Earth (1) but support more than 40% of the world’s human population (2, 3). River regulation to meet society’s needs has accelerated in the past two centuries (4), leaving over half of the world’s major rivers now fragmented by >50,000 large dams providing water, energy, flood control, and transportation (3, 5, 6). The demand for large hydropower continues, spurred by the need for economic development while limiting carbon use (7). However, dams impede the dispersal and migration of fish, a problem that, along with other factors, has contributed to the loss of populations and entire species (5). These losses have cultural, economic, and geopolitical repercussions (3, 8), because more than 40% of the world’s human population lives in internationally shared river basins (9) and declines in fish populations jeopardize the food security of hundreds of millions worldwide (10–12).In North America, the tension between economic development and living resource conservation is evident in the Columbia River basin. Flowing from Canada to the United States, the river once supported one of the world’s largest salmon runs, with annual returns of 10–16 million fish (13) sustaining tribal nations and ecosystems far from the ocean (14). However, years of overharvesting, land-use changes, ocean conditions, and dams have contributed to a decline in the annual return of salmon (15). To reverse the decline, millions of dollars are spent each year seeking a durable hydroelectric strategy to improve annual returns (1–2 million fish). A major emphasis in restoration is ensuring that millions of downstream migrating juvenile salmon reach the ocean where they grow before returning to the river as adults.Hydropower dams on the river provide three general routes of passage for downstream migrating fish: powerhouse turbines, a spillway, and often a bypass specifically designed for fish. These routes differ in their mortality effects on fish, so an understanding of how fish behavior determines route selection is important for mitigating the impacts of dams on the populations. However, route selection behavior is poorly understood. Not only has it been difficult to explain route passage patterns at one dam, but it has been even more difficult to explain why the pattern may be different at another dam with similar routes.     

Biocompatibility of silk-tropoelastin protein polymers

Blended polymers are used extensively in many critical medical conditions as components of permanently implanted devices. Hybrid protein polymers containing recombinant human tropoelastin and silk fibroin have favorable characteristics as implantable scaffolds in terms of mechanical and biological properties. A firefly luciferase transgenic mouse model was used to monitor real-time IL-1β production localized to the site of biomaterial implantation, to observe the acute immune response (up to 5 days) to these materials. Significantly reduced levels of IL-1β were observed in silk/tropoelastin implants compared to control silk only implants at 1, 2 and 3 days post-surgery. Subsequently, mice (n = 9) were euthanized at 10 days (10D) and 3 weeks (3W) post-surgery to assess inflammatory cell infiltration and collagen deposition, using histopathology and immunohistochemistry. Compared to control silk only implants, fewer total inflammatory cells were found in silk/tropoelastin (∼29% at 10D and ∼47% at 3W). Also fewer ingrowth cells (∼42% at 10D and ∼63% at 3W) were observed within the silk/tropoelastin implants compared to silk only. Lower IL-6 (∼52%) and MMP-2 (∼84%) (pro-inflammatory) were also detected for silk/tropoelastin at 10 days. After 3 weeks implantation, reduced neovascularization (vWF ∼43%), fewer proliferating cells (Ki67 ∼58% and PCNA ∼41%), macrophages (F4/80 ∼64%), lower IL-10 (∼47%) and MMP-9 (∼55%) were also observed in silk/tropoelastin materials compared to silk only. Together, these results suggest that incorporation of tropoelastin improves on the established biocompatibility of silk fibroin, uniquely measured here as a reduced foreign body inflammatory response.     

Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

Invasive Salmonella infections for which improved or new vaccines are being developed include enteric fever caused by Salmonella enterica serovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidal Salmonella (NTS) serovars, particularly S. enterica serovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developed in vitro assays to quantify serum bactericidal antibody (SBA) activity induced by S. Typhi, S. Paratyphi A, S. Typhimurium, and S. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. For S. Enteritidis, S. Typhimurium, and S. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast, S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administered S. Typhimurium, S. Enteritidis, and S. Paratyphi A but not S. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited by Salmonella vaccine candidates.     

Interferon‐γ, Interleukins‐6 and ‐4, and Factor XIII‐A as Indirect Markers of the Classical and Alternative Macrophage Activation Pathways in Chronic Periodontitis

Background: Macrophages account for 5% to 30% of the inflammatory infiltrate in periodontitis and are activated by the classic and alternative pathways. These pathways are identified by indirect markers, among which interferon (IFN)‐γ and interleukin‐6 (IL)‐6 of the classic pathway and IL‐4 of the alternative pathway have been studied widely. Recently, factor XIII‐A (FXIII‐A) was reported to be a good marker of alternative pathway activation. The aim of this study is to determine the macrophage activation pathways involved in chronic periodontitis (CP) by the detection of the indirect markers IFN‐γ, IL‐6, FXIII‐A, and IL‐4. Methods: Biopsies were taken from patients with CP (n = 10) and healthy individuals (n = 10) for analysis of IFN‐γ, IL‐6, IL‐4, and FXIII‐A by Western blot (WB), immunohistochemistry (IHC), and enzyme‐linked immunosorbent assay (ELISA). The same biopsies of healthy and diseased gingival tissue were used, and the expressions of these markers were compared between healthy individuals and those with CP. Results: The presence of macrophages was detected by CD68+ immunohistochemistry and their IFN‐γ, IL‐6, IL‐4, and FXIII‐A markers by WB, IHC, and ELISA in all samples of healthy and diseased tissue. IL‐6, IL‐4, and FXIII‐A were significantly higher in patients with CP, whereas FXIII‐A was higher in healthy individuals. Conclusion: The presence of IFN‐γ, IL‐6, IL‐4, and FXIII‐A in healthy individuals and in patients with CP suggests that macrophages may be activated by both classic and alternative pathways in health and in periodontal disease.     

Factors Associated with Physician Tolerance of Uncertainty: an Observational Study

BackgroundPhysicians need to learn and work amidst a plethora of uncertainties, which may drive burnout. Understanding differences in tolerance of uncertainty is an important research area.ObjectiveTo examine factors associated with tolerance of uncertainty, including well-being metrics such as burnout.DesignOnline confidential survey.SettingThe Massachusetts General Physicians Organization (MGPO).ParticipantsAll 2172 clinically active faculty in the MGPO.Main MeasuresWe examined associations for tolerance of uncertainty with demographic information, personal and professional characteristics, and physician well-being metrics.Key ResultsTwo thousand twenty (93%) physicians responded. Multivariable analyses identified significant associations of lower tolerance of uncertainty with female gender (OR, 1.23; 95% CI, 1.03–1.48); primary care practice (OR, 1.56; 95% CI, 1.22–2.00); years since training (OR, 0.99; 95% CI, 0.98–0.995); and lacking a trusted advisor (OR, 1.25; 95% CI, 1.03–1.53). Adjusting for demographic and professional characteristics, physicians with low tolerance of uncertainty had higher likelihood of being burned-out (OR, 3.06; 95% CI, 2.41–3.88), were less likely to be satisfied with career (OR, 0.37; 95% CI, 0.26–0.52), and less likely to be engaged at work (RR, 0.87; 95% CI, 0.84–0.90).ConclusionAt a time when concern about physician well-being is high, with much speculation about causes of burnout, we found a strong relationship between tolerance of uncertainty and physician well-being, across specialties. Particular attention likely needs to be paid to those with less experience, those in specialties with high rates of undifferentiated illness and uncertainty, such as primary care, and ensuring all physicians have access to a trusted advisor. These results generate the potential hypothesis that efforts focused in understanding and embracing uncertainty could be potentially effective for reducing burnout. This concept should be tested in prospective trials.KEY WORDS: uncertainty, burnout, well-being, faculty development, continuing medical education     

Use of Private Sector Workforce Respiratory Disease Short-Term Disability Claims to Assess SARS-CoV-2, Mexico, 2020

We examined respiratory disease short-term disability claims submitted to the Mexican Social Security Institute during 2020. A total of 1,631,587 claims were submitted by 19.1 million insured workers. Cumulative incidence (8.5%) was 3.6 times higher than that for January 2015‒December-2019. Workers in healthcare, social assistance, self-service, and retail stores were disproportionately affected.