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Endosymbiotic Wolbachia bacteria are abundant in the filarial nematodes that cause onchocerciasis (river blindness), including the larvae (microfilariae) that migrate into the cornea. Using a mouse model of ocular onchocerciasis, we recently demonstrated that it is these endosymbiotic bacteria rather than the nematodes per se that induce neutrophil infiltration to the corneal stroma and loss of corneal clarity (Saint Andre et al., Science 295:1892-1895, 2002). To better understand the role of Wolbachia organisms in the pathogenesis of this disease, we examined the fate of these bacteria in the cornea by immunoelectron microscopy. Microfilariae harboring Wolbachia organisms were injected into mouse corneas, and bacteria were detected with antibody to Wolbachia surface protein. Within 18 h of injection, neutrophils completely surrounded the nematodes and were in close proximity to Wolbachia organisms. Wolbachia surface protein labeling was also prominent in neutrophil phagosomes, indicating neutrophil ingestion of Wolbachia organisms. Furthermore, the presence of numerous electron-dense granules around the phagosomes indicated that neutrophils were activated. To determine if Wolbachia organisms directly activate neutrophils, peritoneal neutrophils were incubated with either parasite extracts containing Wolbachia organisms, parasite extracts depleted of Wolbachia organisms (by antibiotic treatment of worms), or Wolbachia organisms isolated from filarial nematodes. After 18 h of incubation, we found that isolated Wolbachia organisms stimulated production of tumor necrosis factor alpha and CXC chemokines macrophage inflammatory protein 2 and KC by neutrophils in a dose-dependent manner. Similarly, these cytokines were induced by filarial extracts containing Wolbachia organisms but not by Wolbachia-depleted extracts. Taken together, these findings indicate that neutrophil activation is an important mechanism by which Wolbachia organisms contribute to the pathogenesis of ocular onchocerciasis.Wolbachia organisms infect filarial nematodes of importance to human health, including Wuchereria bancrofti and Brugia malayi, which cause lymphatic filariasis, and Onchocerca volvulus, which causes river blindness (10). The presence of intracytoplasmic bacteria in O. volvulus was first described by Kozek in 1977, who found Rickettsia-like bacteria in hypodermal lateral cords of male and female worms, in female reproductive organs, and in the first-stage larvae (microfilariae) (15). The bacteria appear to have an essential role in embryogenesis in these nematodes, as antibiotic treatment of infected individuals or experimental animals inhibits production of microfilariae (11-13).Using a murine model of ocular onchocerciasis, we recently demonstrated that O. volvulus extracts containing Wolbachia organisms induce pronounced corneal inflammation (characterized by neutrophil infiltration and development of corneal haze) when injected into the corneal stroma, whereas parasite extracts depleted of Wolbachia organisms by antibiotics do ...

Objective Describe the early impact of the COVID-19 pandemic on general surgery residency training nationwide. Design A 31-question electronic survey was distributed to general surgery program directors. Qualitative data underwent iterative coding analysis. Quantitative data were evaluated with summary statistics and bivariate analyses. Participants Eighty-four residency programs (33.6% response rate) with representation across US geographic regions, program affiliations, and sizes. Results Widespread changes were observed in the surgical training environment. One hundred percent of programs reduced the number of residents on rounds and 95.2% reduced the size of their in-hospital resident workforce; on average, daytime staffing decreased by nearly half. With telehealth clinics (90.5%) and remote inpatient consults (26.2%), both clinical care and resident didactics (86.9%) were increasingly virtual, with similar impact across all program demographics. Conversely, availability of some wellness initiatives was significantly higher among university programs than independent programs, including childcare (51.2% vs 6.7%), housing (41.9% vs 13.3%), and virtual mental health services (83.7% vs 53.3%). Conclusions Changes in clinical care delivery dramatically reduced in face-to-face learning opportunities for surgical trainees during the COVID-19 pandemic. While this effect had equal impact across all program types, sizes, and geographies, the same cannot be said for wellness initiatives. Though all programs initiated some strategies to protect resident health, the disparity between university programs and independent programs may be cause for action.

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