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.     

Bemiparin as a long-term treatment for venous thrombosis in cancer patients: the ELEBAMA study

Clinical and Translational Oncology - Low-molecular-weight heparin (LMWH) is the standard treatment for cancer-associated venous thromboembolism (VTE). There have been no specific studies...