THE EFFECT OF INTRAWOUND VANCOMYCIN POWDER ON SURGICAL SITE INFECTIONS IN POSTERIOR INSTRUMENTED SPINAL ARTHRODESES

Summary: We reviewed 371 consecutive patients from Oct. 2008 to Sept. 2011 who underwent posterior instrumented spinal arthrodesis and received intrawound vancomycin powder prior to closure and compared their acute, deep infection rate to 371 consecutive patients from Oct. 2008 to Apr. 2005 who underwent posterior spinal instrumented arthrodesis and did not receive intrawound vancomycin. We found the use of vancomycin powder decreased the acute, deep Staphylococcus infection rate from 2.05% to 0 (p=0.008). Vancomycin powder is an effective way to decrease acute, deep S. aureus infections following spine surgery. Introduction: Surgical site infection is a serious complication for patients undergoing instrumented spinal surgery. Staphylococcus aureus is the most common causative agent associated with post-op wound infections. Recent studies have reported a decreased infection rate with intrawound vancomycin use in spine surgeries. We sought to determine if intrawound vancomycin would decrease the rates of acute, deep S. aureus infections in our posterior instrumented spinal arthrodesis patients. Methods: This is a historical cohort study. All procedures were performed by a single surgeon. 371 consecutive patients undergoing posterior instrumented spinal arthrodesis received intrawound vancomycin in addition to standard antimicrobial prophylaxis beginning in Oct. 2008 through Sept. 2011 (Vanco cohort). We compared them to 371 consecutive patients from Oct. 2008 to Apr. 2005 who did not receive intrawound vancomyin (Historical cohort). We excluded any superficial infection (above the lumbosacral fascia) or any infection occurring after 90 days. Infection rates were analyzed with Fisher exact test. Results: We found 8 (2.4%) acute, deep infections in the Historical cohort: 1 Enterococcus and 7 (2.05%) Staphylococcus (6 of which were S. aureus). We found 4 (1.2%) acute, deep infections in the Vanco group, none of which were S. aureus. There were 2 E.coli, 1 Klebsiella oxytoca, and 1 anaerobic Streptococcus. The difference in total acute, deep infection rate between the Historical cohort and Vanco cohort was not significant (p= 0.262), but the decrease in Staphylococcus infection rate in the Vanco group was significant (p=0.008). Conclusion: Intrawound vancomycin powder has decreased the rate of acute, deep Staphylococcus infections in our posterior instrumented spinal fusion patient population from 2.05% to 0. Our Vanco cohort was significantly older but otherwise similar in terms of risk factors to the Historical cohort, though had fewer infections. This work is adding to the growing body of evidence in support of this effective adjuvant to standard antimicrobial prophylaxis

Chapter 26: the temporal dynamics of emotional responding: implications for well-being and health from the MIDUS

In this chapter findings are reviewed from the MIDUS Neuroscience Project that underscore the value in examining the temporal dynamics of responses to brief emotional provocation for understanding linkages among emotions and factors contributing to health and well-being across the MIDUS study. This rich dataset has allowed the exploration of associations between individual differences in the affective chronometry of negative and positive emotional responses in vulnerable vs. resilient profiles. Findings from functional magnetic resonance imaging (fMRI) as well as electromyographic recordings (EMG) of the facial muscles to objectively measure emotional responses demonstrate that the temporal dynamics of emotional responses to affective stimuli are associated with aging, personality, psychopathology, stress exposure, biomarkers, and well-being. Overall, these findings suggest that variation in health and well-being are differentially predicted by specific temporal parameters of the emotional response, such as the magnitude of the immediate response to the presence of a stimulus (i.e., reactivity), residual activity and its duration after stimulus offset (i.e., recovery), as well as the change in response – or habituation - across repeated presentations of similarly-valenced stimuli. Besides the seemingly obvious import of recovering quickly from negative or unpleasant provocations, the chronometry of positive emotional responses appears to be particularly vital for determining how emotional processes may take a physiological toll or promote resiliency in the face of stress and disease. By examining such temporal dynamics in response to affective stimuli in MIDUS, a better understanding of the brain-behavior associations underlying emotion, and how emotions “get under the skin” to impact well-being and health across the lifespan is gained

Individual differences in naturalistic learning link negative emotionality to the development of anxiety

Organisms learn from prediction errors (PEs) to predict the future. Laboratory studies using small financial outcomes find that humans use PEs to update expectations and link individual differences in PE-based learning to internalizing disorders. Because of the low-stakes outcomes in most tasks, it is unclear whether PE learning emerges in naturalistic, high-stakes contexts and whether individual differences in PE learning predict psychopathology risk. Using experience sampling to assess 625 college students\u27 expected exam grades, we found evidence of PE-based learning and a general tendency to discount negative PEs, an optimism bias. However, individuals with elevated negative emotionality, a personality trait linked to the development of anxiety disorders, displayed a global pessimism and learning differences that impeded accurate expectations and predicted future anxiety symptoms. A sensitivity to PEs combined with an aversion to negative PEs may result in a pessimistic and inaccurate model of the world, leading to anxiety

Relationships between changes in sustained fronto-striatal connectivity and positive affect with antidepressant treatment in major depression

Objective: Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. Method: Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during per- formance of an emotion regulation para- digm in 21 depressed patients before and after 2 months of antidepressant treat- ment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. Results: After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when control- ling for negative affect. None of these associations were observed in healthy comparison subjects. Conclusions: Treatment-induced change in the sustained engagement of fronto- striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a va- riety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to under- stand changes in daily positive affect

The Power of Community: The Role of Community-Based Organizations in Mitigating COVID-19-Related Impacts on Well-Being Among South Florida's Minoritized Populations

The rapid closure of schools and businesses during the COVID-19 pandemic has had a significant impact in South Florida, highlighting diverse challenges to community well-being. Community-based organizations (CBOs) have served as a source of support for community members, particularly in stressful times. Using a combination of quantitative and qualitative methods, and in collaboration with Breakthrough Miami, a CBO committed to addressing the educational opportunity gap in Miami-Dade County, we conducted a study to assess challenges to the well-being of systematically minoritized families during the heart of the COVID-19 pandemic. The study included longitudinal survey data collected via ecological momentary assessment and in-depth interviews with Breakthrough Miami families to gather richer and nuanced data regarding indicators of well-being and CBO engagement. Quantitative results indicated that as perceived stress increased over time, so too did emotional and informational support. Follow-up qualitative interviews indicated that 100% of families identified Breakthrough Miami as a source of academic support during the pandemic. Additionally, families cited the important role Breakthrough Miami played beyond their standard academic programs and services in coping with the most significant sources of stress reported through the pandemic: meeting basic needs and threats to socioemotional well-being. Implications for CBOs are addressed

The Power of Community: The Role of Community-Based Organizations in Mitigating COVID-19-Related Impacts on Well-Being Among South Florida's Minoritized Populations

The rapid closure of schools and businesses during the COVID-19 pandemic has had a significant impact in South Florida, highlighting diverse challenges to community well-being. Community-based organizations (CBOs) have served as a source of support for community members, particularly in stressful times. Using a combination of quantitative and qualitative methods, and in collaboration with Breakthrough Miami, a CBO committed to addressing the educational opportunity gap in Miami-Dade County, we conducted a study to assess challenges to the well-being of systematically minoritized families during the heart of the COVID-19 pandemic. The study included longitudinal survey data collected via ecological momentary assessment and in-depth interviews with Breakthrough Miami families to gather richer and nuanced data regarding indicators of well-being and CBO engagement. Quantitative results indicated that as perceived stress increased over time, so too did emotional and informational support. Follow-up qualitative interviews indicated that 100% of families identified Breakthrough Miami as a source of academic support during the pandemic. Additionally, families cited the important role Breakthrough Miami played beyond their standard academic programs and services in coping with the most significant sources of stress reported through the pandemic: meeting basic needs and threats to socioemotional well-being. Implications for CBOs are addressed

Nmp4/CIZ suppresses the response of bone to anabolic parathyroid hormone by regulating both osteoblasts and osteoclasts

How parathyroid hormone (PTH) increases bone mass is unclear, but understanding this phenomenon is significant to the improvement of osteoporosis therapy. Nmp4/CIZ is a nucleocytoplasmic shuttling transcriptional repressor that suppresses PTH-induced osteoblast gene expression and hormone-stimulated gains in murine femoral trabecular bone. To further characterize Nmp4/CIZ suppression of hormone-mediated bone growth, we treated 10-week-old Nmp4-knockout (KO) and wild-type (WT) mice with intermittent human PTH(1–34) at 30 μg/kg daily or vehicle, 7 days/week, for 2, 3, or 7 weeks. Null mice treated with hormone (7 weeks) gained more vertebral and tibial cancellous bone than WT animals, paralleling the exaggerated response in the femur. Interestingly, Nmp4/CIZ suppression of this hormone-stimulated bone formation was not apparent during the first 2 weeks of treatment. Consistent with the null mice enhanced PTH-stimulated addition of trabecular bone, these animals exhibited an augmented hormone-induced increase in serum osteocalcin 3 weeks into treatment. Unexpectedly, the Nmp4-KO mice displayed an osteoclast phenotype. Serum C-terminal telopeptide, a marker for bone resorption, was elevated in the null mice, irrespective of treatment. Nmp4-KO bone marrow cultures produced more osteoclasts, which exhibited elevated resorbing activity, compared to WT cultures. The expression of several genes critical to the development of both osteoblasts and osteoclasts was elevated in Nmp4-KO mice at 2 weeks, but not 3 weeks, of hormone exposure. We propose that Nmp4/CIZ dampens PTH-induced improvement of trabecular bone throughout the skeleton by transiently suppressing hormone-stimulated increases in the expression of proteins key to the required enhanced activity and number of both osteoblasts and osteoclasts

Negative Interpretation Bias Connects to Real-World Daily Affect: A Multistudy Approach

Negative interpretation bias, the tendency to appraise ambiguous stimuli as threatening, shapes our emotional lives. Various laboratory tasks, which differ in stimuli features and task procedures, can quantify negative interpretation bias. However, it is unknown whether these tasks globally predict individual differences in real-world negative (NA) and positive (PA) affect. Across two studies, we tested whether different lab-based negative interpretation bias tasks predict daily NA and PA, measured via mobile phone across months. To quantify negative interpretation bias, Study 1 (N = 69) used a verbal, self-referential task whereas Study 2 (N = 110) used a perceptual, emotional image task with faces and scenes. Across tasks, negative interpretation bias was linked to heightened daily NA. However, only negative interpretation bias in response to ambiguous faces was related to decreased daily PA. These results illustrate the ecological validity of negative interpretation bias tasks and highlight converging and unique relationships between distinct tasks and naturalistic emotion

Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication