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Objectives: The objectives of our study were to (1) determine if physical therapy (PT) impacts patient-reported outcomes (PROMs) after lumbar decompression surgery and (2) determine if PT impacts postsurgical readmissions or reoperations after lumbar decompression surgery. Methods: Patients >18 years of age who underwent primary one- or two-level lumbar decompression at our institution were identified. Patient demographics, surgical characteristics, surgical outcomes (all-cause 90 days readmissions and 90 days surgical readmissions), and patient-reported outcomes (PROMs) were compared between the groups. Multivariate linear regression was utilized to determine the individual predictors of 90 days readmissions and PROMs at the 1-year postoperative point. Alpha was set at P < 0.05. Results: Of the 1003 patients included, 421 attended PT postoperatively. On univariate analysis, PT attendance did not significantly impact 90-day surgical reoperations (P = 0.225). Although bivariate analysis suggests that attendance of PT is associated with worse improvement in physical function (P = 0.041), increased preoperative Visual Analogue Scale leg pain (0 = 0.004), and disability (P = 0.006), as measured by the Oswestry Disability Index, our multivariate analysis, which accounts for confounding variables found there was no difference in PROM improvement and PT was not an independent predictor of 90-day all-cause readmissions (P = 0.06). Instead, Charlson Comorbidity Index (P = 0.025) and discharge to a skilled nursing facility (P = 0.013) independently predicted greater 90-day all-cause readmissions. Conclusions: Postoperative lumbar decompression PT attendance does not significantly affect clinical improvement, as measured by PROMs or surgical outcomes including all-cause 90 days readmissions and 90-day surgical readmissions.

Abstract Background Evidence suggests lymphatic function mediates local rheumatoid arthritis (RA) flares. Yet biologics that target the immune system are dosed systemically via the subcutaneous (SC) administration route, thereby inefficiently reaching local lymphatic compartments. Nanotopography has previously been shown to disrupt tight cellular junctions, potentially enhancing local lymphatic delivery and potentially improving overall therapeutic efficacy. Method We first characterized nanotopography (SOFUSA™) delivery of an anti-TNF drug, etanercept, by comparing pharmacokinetic profiles to those obtained by conventional SC, intravenous (IV), and intradermal (ID) routes of administration, and assessed uptake of radiolabeled etanercept in draining lymph nodes (LNs) in single dosing studies. We then compared etanercept efficacy in a progressive rat model of collagen-induced arthritis (CIA), administered systemically via SC route of administration; via the regional lymphatics through ID delivery; or through a nanotopography (SOFUSA™) device at 10, 12, and 14 days post CIA induction. Measurements of hind limb swelling and near-infrared fluorescence (NIRF) imaging of afferent lymph pumping function and reflux were conducted on days 11, 13, and 18 post CIA induction and compared to untreated CIA animals. Univariate and multivariate analysis of variance were used to compare the group differences for percentage swelling and lymphatic contractile activity. Results Even though all three modes of administration delivered an equal amount of etanercept, SOFUSA™ delivery resulted in increased lymphatic pumping and significantly reduced swelling as compared to untreated, ID, and SC groups. Pharmacokinetic profiles in serum and LN uptake studies showed that using the nanotopography device resulted in the greatest uptake and retention in draining LNs. Conclusions Locoregional lymphatic delivery of biologics that target the immune system may have more favorable pharmacodynamics than SC or IV administration. Nanotopography may provide a more efficient method for delivery of anti-TNF drugs to reverse impairment of lymphatic function and reduce swelling associated with RA flares.

AtlA is the major peptidoglycan hydrolase of Enterococcus faecalis involved in cell division and cellular autolysis. The secreted zinc metalloprotease, gelatinase (GelE), has been identified as an important regulator of cellular function through post-translational modification of protein substrates. AtlA is a known target of GelE, and their interplay has been proposed to regulate AtlA function. To study the protease-mediated post-translational modification of AtlA, monoclonal antibodies were developed as research tools. Flow cytometry and Western blot analysis suggests that in the presence of GelE, surface-bound AtlA exists primarily as a N-terminally truncated form whereas in the absence of GelE, the N-terminal domain of AtlA is retained. We identified the primary GelE cleavage site occurring near the transition between the T/E rich Domain I and catalytic region, Domain II via N-terminal sequencing. Truncation of AtlA had no effect on the peptidoglycan hydrolysis activity of AtlA. However, we observed that N-terminal cleavage was required for efficient AtlA-mediated cell division while unprocessed AtlA was unable to resolve dividing cells into individual units. Furthermore, we observed that the processed AtlA has the propensity to localize to the cell septum on wild-type cells whereas unprocessed AtlA in the ΔgelE strain were dispersed over the cell surface. Combined, these results suggest that AtlA septum localization and subsequent cell separation can be modulated by a single GelE-mediated N-terminal cleavage event, providing new insights into the post-translation modification of AtlA and the mechanisms governing chaining and cell separation.

Post-transcriptional control provides bacterial pathogens a method by which they can rapidly adapt to environmental change. Dual exo- and endonucleolytic activities of RNase J enzymes contribute to Gram-positive RNA processing and decay. First discovered in Bacillus subtilis, RNase J1 plays a key role in mRNA maturation and degradation, while the function of the paralogue RNase J2 is largely unknown. Previously, we discovered that deletion of the Enterococcus faecalis rnjB gene significantly attenuates expression of a major virulence factor involved in enterococcal pathogenesis, the Ebp pili. In this work, we demonstrate that E. faecalis rnjB encodes an active RNase J2, and that the ribonuclease activity of RNase J2 is required for regulation of Ebp pili. To further investigate how rnjB affects E. faecalis gene expression on a global scale, we compared transcriptomes of the E. faecalis strain OG1RF with its isogenic rnjB deletion mutant (ΔrnjB). In addition to Ebp pili regulation, previously demonstrated to have a profound effect on the ability of E. faecalis to form biofilm or establish infection, we identified that rnjB regulates the expression of several other genes involved in bacterial virulence and fitness, including gls24 (a virulence factor important in stress response). We further demonstrated that the E. faecalis RNase J2 deletion mutant is more sensitive to bile salt and greatly attenuated in in vivo organ infection as determined by an IV-sublethal challenge infection mouse model, indicating that E. faecalis RNase J2 plays an important role in E. faecalis virulence.

Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions.We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increase any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two adimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation.

ABSTRACT The endocarditis and biofilm-associated pili (Ebp) are important in Enterococcus faecalis pathogenesis, and the pilus tip, EbpA, has been shown to play a major role in pilus biogenesis, biofilm formation, and experimental infections. Based on in silico analyses, we previously predicted that ATT is the EbpA translational start codon, not the ATG codon, 120 bp downstream of ATT, which is annotated as the translational start. ATT is rarely used to initiate protein synthesis, leading to our hypothesis that this codon participates in translational regulation of Ebp production. To investigate this possibility, site-directed mutagenesis was used to introduce consecutive stop codons in place of two lysines at positions 5 and 6 from the ATT, to replace the ATT codon in situ with ATG, and then to revert this ATG to ATT; translational fusions of ebpA to lacZ were also constructed to investigate the effect of these start codons on translation. Our results showed that the annotated ATG does not start translation of EbpA, implicating ATT as the start codon; moreover, the presence of ATT, compared to the engineered ATG, resulted in significantly decreased EbpA surface display, attenuated biofilm, and reduced adherence to fibrinogen. Corroborating these findings, the translational fusion with the native ATT as the initiation codon showed significantly decreased expression of β-galactosidase compared to the construct with ATG in place of ATT. Thus, these results demonstrate that the rare initiation codon of EbpA negatively regulates EbpA surface display and negatively affects Ebp-associated functions, including biofilm and adherence to fibrinogen. IMPORTANCE Enterococcus faecalis is among the leading causes of serious infections in the hospital setting, and the endocarditis and biofilm-associated pili (Ebp) have been shown to play significant roles in E. faecalis pathogenesis. Understanding the regulation of virulence is important for the development of new approaches to counteract multidrug-resistant pathogens. We previously predicted that ATT, which has been reported to start protein synthesis only in rare instances, is the most likely translational start codon of EbpA in E. faecalis. Here, we demonstrate that ATT is the initiation codon of EbpA and, relative to a constructed ATG start codon, results in smaller amounts of EbpA on the surface of the cells, attenuating biofilm formation and fibrinogen adherence, phenotypes associated with the ability of E. faecalis to cause infections. This provides the first example of pilus regulation through the use of an ATT initiation codon.

The endocarditis and biofilm-associated pilus (Ebp) operon is a component of the core genome of Enterococcus faecalis that has been shown to be important for biofilm formation, adherence to host fibrinogen, collagen and platelets, and in experimental endocarditis and urinary tract infection models. Here, we created single and double deletion mutants of the pilus subunits and sortases; next, by combining western blotting, immunoelectron microscopy, and using ebpR in trans to increase pilus production, we identified EbpA as the tip pilin and EbpB as anchor at the pilus base, the latter attached to cell wall by the housekeeping sortase, SrtA. We also confirmed EbpC and Bps as the major pilin and pilin-specific sortase, respectively, both required for pilus polymerization. Interestingly, pilus length was increased and the number of pili decreased by deleting ebpA, while control overexpression of ebpA in trans restored wild-type levels, suggesting a dual role for EbpA in both initiation and termination of pilus polymerization. We next investigated the contribution of each pilin subunit to biofilm formation and UTI. Significant reduction in biofilm formation was observed with deletion of ebpA or ebpC (P

Women are less likely to choose physical Science, Technology, Engineering, and Math (pSTEM) majors, partly because a lack of role models makes it hard for women to imagine themselves as successful in those fields. Possible self-interventions can help people imagine themselves having a successful future. Using social cognitive theory and expectancy-value framework, the current study explored virtual reality (VR; HTC Vive) as a space for a possible self-intervention to decrease stereotype threat and increase pSTEM motivation. Participants were 79 undergraduate women in California (46% Asian, 32% Latina, 14% white) who were randomly assigned to embody a future self either highly successful in pSTEM or highly successful in humanities. Following the virtual experience, women in the pSTEM condition differed significantly from women in the humanities condition regarding pSTEM value beliefs, anticipated stereotype threat, course motivation, and women-pSTEM implicit associations, after controlling for prior pSTEM-self implicit associations. However, this difference only occurred among women who identified with the experience. While women with high identification demonstrated an effect in the desired direction, women with low identification demonstrated reactance in the opposite direction. This speaks to the usefulness of identification as a moderator and implies that virtual reality might be a useful tool for future self-interventions among students.

Pronounced warming negatively impacts ecosystem resilience in modern oceans. To offer a long‐term geological perspective of the calcareous plankton response to global warming, we present an integrated record, from two Tethyan sections (northeastern Italy), of the planktic foraminiferal and calcareous nannofossil response to the Eocene Thermal Maximum 2 hyperthermal (ETM2, ∼54 Ma). Our study reveals pronounced changes in assemblage composition and a striking dwarfing of planktic foraminiferal tests of up to 40% during the event, impacting both surface and deeper dwellers. The increased abundance of small placoliths among calcareous nannofossils is interpreted as community size reduction. Literature and our foraminiferal size data from Sites 1263 and 1209 (Atlantic and Pacific Oceans) highlights that the pronounced dwarfism is restricted to the Tethyan area. The ETM2 is characterized by warm sea surface temperatures as indicated by our δ18O data, but this warming is of global extent and cannot explain the unique dwarfism. Excluding evolutionary modifications, other potential drivers of dwarfism (eutrophication, deoxygenation, metabolic adaptation) cannot explain the exceptional dwarfism by themselves. The smallest sizes are in close temporal association with peaks in volcanic derived Hg/Th‐Hg/Rb recorded just before and at the ETM2 which could not have been brought into our sections through weathering. In contrast, size reductions are absent below and above the ETM2 at Hg peaks where δ18O data do not show warm conditions. We speculate that the local input of toxic metals from submarine volcanic emissions could have acted synergistically to warming, causing the unique dwarfism. Key Points: Calcareous plankton size in the Tethys during the Eocene Thermal Maximum 2 (ETM2) reveals marked dwarfismPronounced dwarfism was restricted to the Tethyan area, highlighting the importance of local signals in interpreting hyperthermalsCalcareous plankton were highly unstable across the ETM2 but ultimately resilient [ABSTRACT FROM AUTHOR]