Evidence of Neutralizing and Non-Neutralizing Anti-Glucosaminidase Antibodies in Patients With S. Aureus Osteomyelitis and Their Association With Clinical Outcome Following Surgery in a Clinical Pilot.

Staphylococcus aureus osteomyelitis remains a very challenging condition; recent clinical studies have shown infection control rates following surgery/antibiotics to be ~60%. Additionally, prior efforts to produce an effective S. aureus vaccine have failed, in part due to lack of knowledge of protective immunity. Previously, we demonstrated that anti-glucosaminidase (Gmd) antibodies are protective in animal models but found that only 6.7% of culture-confirmed S. aureus osteomyelitis patients in the AO Clinical Priority Program (AO-CPP) Registry had basal serum levels (>10 ng/ml) of anti-Gmd at the time of surgery (baseline). We identified a small subset of patients with high levels of anti-Gmd antibodies and adverse outcomes following surgery, not explained by Ig class switching to non-functional isotypes. Here, we aimed to test the hypothesis that clinical cure following surgery is associated with anti-Gmd neutralizing antibodies in serum. Therefore, we first optimized an in vitro assay that quantifies recombinant Gmd lysis of the M. luteus cell wall and used it to demonstrate the 50% neutralizing concentration (NC50) of a humanized anti-Gmd mAb (TPH-101) to be ~15.6 µg/ml. We also demonstrated that human serum deficient in anti-Gmd antibodies can be complemented by TPH-101 to achieve the same dose-dependent Gmd neutralizing activity as purified TPH-101. Finally, we assessed the anti-Gmd physical titer and neutralizing activity in sera from 11 patients in the AO-CPP Registry, who were characterized into four groups post-hoc. Group 1 patients (n=3) had high anti-Gmd physical and neutralizing titers at baseline that decreased with clinical cure of the infection over time. Group 2 patients (n=3) had undetectable anti-Gmd antibodies throughout the study and adverse outcomes. Group 3 (n=3) had high titers +/- neutralizing anti-Gmd at baseline with adverse outcomes. Group 4 (n=2) had low titers of non-neutralizing anti-Gmd at baseline with delayed high titers and adverse outcomes. Collectively, these findings demonstrate that both neutralizing and non-neutralizing anti-Gmd antibodies exist in S. aureus osteomyelitis patients and that screening for these antibodies could have a value for identifying patients in need of passive immunization prior to surgery. Future prospective studies to test the prognostic value of anti-Gmd antibodies to assess the potential of passive immunization with TPH-101 are warranted.

Association between screen time and depression among US adults.

Epidemiological surveys conducted in general populations have found that the prevalence of depression is about 9% in the United States. World Health Organization has projected that depression will be leading cause of disease burden by the year 2030. Growing evidence suggests that sedentary lifestyle is an important risk factor of depression among adults. The relationship between television watching/computer use and depression in US adults is still unknown. The objective of this study was to assess the relationship between television watching/computer use and depression. This is a cross-sectional study that used the secondary data from the National Health and Nutritional Examination Survey (NHANES) (2011/2012). Participants were 3201 US adults who were 20 years or more. Self-reported Patient Health Questionnaire-9 [PHQ-9] was used to classify depression level; self-reported hours of watching TV and use of computer/day, and demographic information were obtained from NHANES data set. SAS®9.4was used to perform all statistical analyses and final model selection procedure. Depression was found to be significantly higher among female. Results showed that moderate or severe depression level was associated with higher time spent on TV watching and use of computer (> 6 h/day) (adjusted odds ratio: 2.3, 95% CI: 1.602-3.442). Duration of screen time was significantly associated when all covariates were adjusted. TV watching and computer use can predict the depression level among adults. Prospective studies and measurement of factors such as: work place sitting, social relationship, and family history of depression are warranted.