Varying Time Points Research Articles

Oxygen Nanoshuttles for Tumor Oxygenation and Enhanced Cancer Treatment

Oxygen Nanoshuttles for Tumor Oxygenation and Enhanced Cancer Treatment

Cardiovascular and respiratory safety evaluation of Musca Domestica larvae low molecular weight peptide in beagle dogs

Background: Many studies have demonstrated that the water extracts and low-molecular-weight peptide (LMWP) of the Musca domestica larvae contain significant biological activity. However, the cardiovascular and respiratory safety evaluations of LMWP are yet to be sufficiently investigated.Aim: This study focused on the cardiovascular and respiratory safety evaluations of the M. domestica larvae LMWP in beagle dogs.Methods: Direct cardiovascular and respiratory effects of three different doses of the M. domestica larvae LMWP were investigated following only once oral administration in conscious telemetered dogs, whereby ECG, arterial pressure, and respiratory data were collected using the Data Science International telemetric system.Results: The PR, QT, and QTcf intervals were significantly shortened in the medium-dose LMWP treatment group at 3 h after drug administration. Furthermore, no significant differences were observed in any of the corresponding indexes of other treatment groups at different time points compared to those of the control group. P wave, ST segment, R wave, systolic pressure, diastolic pressure, and mean pressure were significantly different, although these differences had no significant dose-effect relationship. Respiratory frequency significantly increased in the medium-dose LMWP treatment group at 8 h after drug administration compared to that of the control group. Respiratory rate and tidal volume showed no significant differences at varying time points among all LMWP treatment groups.Conclusions: No toxicological effects related to cardiovascular and respiratory safety in beagle dogs were observed at any dose level of the M. domestica larvae LMWP.

Urinary Cytokine Profile to Predict Response to Intravesical BCG with or without HS-410 Therapy in Patients with Non-muscle-invasive Bladder Cancer.

Despite extensive research to identify biomarkers of response in patients with non-muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC. Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG ± intradermal HS-410 therapy. Samples were collected at baseline, week 7, week 13, week 28, and at end of treatment. A total of 105 cytokines were analyzed in each sample. To predict outcome of time-to-event (recurrence or progression), univariate and multivariable Cox analyses were performed. Fifteen patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker versus nonsmoker status was associated with an improved response rate (HR 0.38; 95% confidence interval (CI), 0.14-0.99; P = 0.04). In the most clinically relevant model, the percent change (for 100 units) of IL18-binding protein-a (HR 1.995; 95% CI, 1.16-3.44; P = 0.01), IL23 (HR 1.12; 95% CI, 1.01-1.23; P = 0.03), IL8 (HR 0.27; 95% CI, 0.07-1.08; P = 0.06), and IFNγ-induced protein-10 (HR 0.95; 95% CI, 0.91-0.99; P = 0.04) at week 13 from baseline best predicted time to event. Urinary cytokines provided additional value to clinicopathologic features to predict response to immune-modulating agents in patients with NMIBC. This study serves as a hypothesis-generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.

025 Direct Determination of Kinetic and Equilibrium Binding of Flibanserin to 5HT1A and 5HT2A Receptors

Flibanserin is a 5HT1A receptor agonist and 5HT2A receptor antagonist that has been approved in the US and Canada for the treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. The most frequently experienced adverse events associated with flibanserin use include sedation-related symptoms. Activation of 5-HT1A receptors has been shown to generally promote wakefulness and inhibit sleep while inhibition of 5-HT2A receptors has been shown to reduce wakefulness. Previous receptor binding studies have indirectly estimated flibanserin’s equilibrium affinity constants to different receptors by using a second, more readily available radiolabeled ligand. Furthermore, dissociation rates of flibanserin from 5HT1A and 5HT2A receptors have not been described in the literature. The objective of this study was to directly characterize equilibrium binding and kinetic dissociation parameters of flibanserin for 5HT1A and 5HT2A receptors. Flibanserin binding was determined in membrane preparations of cell lines overexpressing human 5HT1A receptors or human 5HT2A receptors. Membranes were incubated with 100 nM flibanserin for 3 h at 37°C and dissociation was induced by 10-fold dilution and immediate addition of 400-fold molar excess of WAY100635 (5HT1A subtype-selective receptor antagonist) or eplivanserin (5HT2A subtype-selective receptor antagonist) and aliquots were removed at varying time points for measurement. For saturation binding studies, cell membranes were incubated with increasing concentrations of flibanserin in the absence or presence of at least 200-fold molar excess of either WAY100635 or eplivanserin for 3 h at 37°C to determine total and non-specific binding. Membranes were collected with vacuum onto polyethylenimine-treated glass fiber filters, washed and extracted. Flibanserin was quantified by liquid chromatography and tandem mass spectrometry using positive ion mode electrospray ionization.

Phylogenetic analyses of human 1/2/8/20 paralogons suggest segmental duplications during animal evolution.

Susumu Ohno hypothesized that the diversity of vertebrate gene families and genome is due to two rounds of whole genome duplications (also referred as 2R hypothesis). The quadruplicate paralogous blocks present on 1/2/8/20 chromosomes are taken as one of the evidences in favor of the 2R. In this study, we investigated that whether 2R has shaped the vertebrate evolution using gene families residing on chromosomes 1/2/8/20. Evolutionary history of 22 gene families (11 from the current study and 11 from the previous study) was evaluated by the phylogenetic analysis with triplicated or quadruplicated distribution on these human chromosomes 1/2/8/20. The phylogenetic analysis was performed using high-quality whole genomic sequence data of multiple species with neighbor-joining (NJ) and maximum likelihood (ML) methods. The phylogenetic tree topology of these gene families revealed variable duplication time points during invertebrate-vertebrate evolution. Topology comparison approach categorized 22 gene families into three groups. Tree topologies of ten gene families fell into Group 1 (duplications prior to invertebrate-vertebrate split), four in Group 2 (i.e., (AB) (C) (D), topology incongruent with 2R) and eight in Group 3 (((AB) (CD)), 2R congruent topology). Therefore, taken together the current and previous data of 1/2/8/20 paralogons, we propose that, in addition to whole genome duplications events, current developmental, morphological and genomic complexity of the vertebrate genomes may also have originated through segmental duplications occurring at varying time points during the course of animal evolution.

Preparation, in vitro release and antibacterial activity evaluation of rifampicin and moxifloxacin-loaded poly(D,L-lactide-co-glycolide) microspheres

Osteomyelitis is difficult to treat because infective bone is poorly accessible for intravenously administering antibiotics and biofilm formation increases bacterial resistance. In this study, microspheres prepared using poly(lactide-co-glycolide) (PLGA) and embedded with moxifloxacin (MOX–PLGA microspheres) and rifampicin/moxifloxacin (RIF/MOX–PLGA microspheres) using the water-in-oil-in-water double emulsion solvent evaporation technique were used for local delivery. Shape of MOX–PLGA microspheres and RIF/MOX–PLGA microspheres were spherical, mean particle size of them were 20.52 μm and 16.62 μm, respectively. Encapsulation efficiency of the MOX-PLGA microspheres was 17.35% ± 2.42%. However, the encapsulation efficiency for MOX and RIF in RIF/MOX–PLGA microspheres was 33.25% ± 7.51% and 49.0% ± 11.25%, respectively. Moxifloxacin and rifampicin were released slowly from microspheres. Both microspheres can efficiently release antibiotics in vitro. Antibacterial and bacterial biofilm-inhibition properties of the released solution were investigated from RIF/MOX–PLGA, MOX–PLGA, and blank PLGA microspheres at varying time points in vitro. RIF/MOX–PLGA microspheres demonstrated the strongest antibacterial activity and bacterial biofilm-inhibition property than the other two microspheres (p < .05). This study suggests that the novel RIF/MOX–PLGA microspheres can be used as a promising carrier for osteomyelitis treatment.

Assessing serum albumin concentration following exercise-induced fluid shifts in the context of the athlete biological passport.

The hydration status of an athlete at the time of a doping control sample collection is an important factor to consider when reviewing athlete biological passports (ABPs). Dehydration results in a reduction of the circulating plasma volume (PV), which may lead to artificially high values of some blood parameters. This study aimed to identify whether serum albumin could serve as a single marker of fluid shifts, which are not currently accounted for in the hematological passport. An additional marker could be used to assist experts when interpreting irregularities in the ABP. Twelve subjects underwent multiple controlled exercise trials designed to induce varying levels of PV shifts. Pre-exercise blood samples were collected to establish baseline values for individual passports. During exercise interventions, blood samples were collected before the start of exercise and at 10 minute, 1 hour, 2 hours, and 24 hours following exercise. Significant increases in hematological parameters - hemoglobin [Hb], hematocrit (HCT), albumin (ALB), and calculated OFF-score - were identified at varying time points following fluid shift-inducing exercise. Changes in ALB correlated strongly with changes in [Hb] (r=0.753) and with estimated PV shifts (r=-0.764). In analyzing ABPs, the resulting increases in Hb did not trigger any atypical findings at 99% specificity. Monitoring changes in ALB longitudinally may assist experts when reviewing PV shifts in the biological passport.

Sagittal Spinopelvic Alignment After Posterior Spinal Fusion in Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis.

A systematic review and meta-analysis. The aim of this study was to determine the differences in the sagittal spinopelvic parameters between the nonscoliotic controls, preoperative, and different time points postoperative in Lenke 1 and 5 adolescent idiopathic scoliosis (AIS). The postoperative changes in the sagittal profile of Lenke 1 and 5 AIS at varying time points after posterior spinal fusion (PSF) has not been rigorously demonstrated; studies performed have had conflicting results. Sagittal spinal and pelvic parameters, T5-T12 thoracic kyphosis (TK), L1-S1 lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), and sagittal vertical axis (SVA), for Lenke 1 and 5 preoperatively, at immediate, less than 2-year, and more than 2-year postoperatively, and for nonscoliotic adolescents were searched. Differences in the sagittal spinopelvic parameters between preoperative and the follow-ups and between the nonscoliotic and pre- and postoperative AIS subtypes were calculated through meta-analysis. A total of 22 studies on Lenke1 (1229 patients), 13 studies on Lenke5 (437 patients), and 18 studies on controls (1636 patients) were reviewed. Among all the measured variables, only PI in Lenke1 was significantly different between the final follow-up and controls, P < 0.05. In Lenke 1, SVA was significantly more anterior at the immediate postoperative than preoperative, but continued moving posteriorly up to 2-year postoperative resulting in no significant difference in the SVA position between the final follow-up and preoperative, P > 0.05. In Lenke 5, SVA was significantly more posterior at the immediate postoperative and more anterior at the final follow-up than the preoperative measurements, p < 0.05. Continuous changes in the sagittal spinal parameters should be expected after PSF. Normalization of the sagittal spinal parameters appears to be the rule after PSF, and watchful waiting appears to be appropriate in this population when viewing the lateral X-ray postoperatively. 4.

Effect of Yoga as an Add-on Therapy in the Modulation of Heart Rate Variability in Children with Duchenne Muscular Dystrophy.

Background:Duchene muscular dystrophy (DMD) is a progressive muscular disorder. Cardiac disorder is the second-most common cause of death in children with DMD, with 10%–20% of them dying of cardiac failure. Heart rate variability (HRV) is shown to be a predictor of cardio-autonomic function. Physiotherapy (PT) is advised for these children as a regular treatment for maintaining their functional status. The effect of yogic practices on the cardio-autonomic functions has been demonstrated in various neurological conditions and may prove beneficial in DMD.Materials and Methods:In this study, 124 patients with DMD were randomized to PT alone or PT with yoga intervention. Home-based PT and yoga were advised. Adherence was serially assessed at a follow-up interval of 3 months. Error-free, electrocardiogram was recorded in all patients at rest in the supine position. HRV parameters were computed in time and frequency domains. HRV was recorded at baseline and at an interval of 3 months up to 1 year. Repeated-measures ANOVA was used to analyze longitudinal follow-up and least significant difference for post hoc analysis and P < 0.05 was considered statistically significant.Results:In our study, with PT protocol, standard deviation of NN, root of square mean of successive NN, total power, low frequency, high-frequency normalized units (HFnu), and sympathovagal balance improved at varying time points and the improvement lasted up for 6–9 months, whereas PT and yoga protocol showed an improvement in HFnu during the last 3 months of the study period and all the other parameters were stable up to 1 year. Thus, it is evident that both the groups improved cardiac functions in DMD. However, no significant difference was noted in the changes observed between the groups.Conclusion:The intense PT and PT with yoga, particularly home-based program, is indeed beneficial as a therapeutic strategy in DMD children to maintain and/or to sustain HRV in DMD.

The role of CaMKII in neuropathic pain and fear memory in chronic constriction injury in rats

Purpose/Aim of the study In this study, we sought to observe the effects of Ca2+/calmodulin-dependent protein kinase II (CaMKII) on neuropathic pain and fear memory in a rat model of chronic constriction injury (CCI).Materials and methods Rats were randomly divided into the Sham, Control, CCI and m-AIP groups. In the m-AIP group, an intrathecal injection of m-AIP, the specific antagonist of CaMKII, was given either pretreatment or posttreatment in rats. Mechanical allodynia and thermal hyperalgesia tests were used to test pain behavior, and the passive avoidance test was used to measure fear memory in rats.Results The right side of hippocampus tissues were taken at varying time points. The expression levels of CaMKII-α, pCaMKII-α, CaMKII-β, pCaMKII-β, NR2A, pNR2A, NR2B and pNR2B were detected by Western blot analysis. Significant pain behaviors and impaired cognitive function were shown after CCI surgery, accompanied by the upregulation of proteins in the hippocampus. Pretreatment with m-AIP appeared to provide a temporary improvement in pain and fear memory and decreased the expression of the above proteins in the hippocampus seven days after surgery. Furthermore, postoperative treatment with m-AIP provided relief for pain behavior and protein expression but did not affect fear memory.Conclusions These data suggested that CaMKII played an important role in the crosstalk between neuropathic pain and fear memory, indicating that CaMKII may be a potential therapeutic target for neuropathic pain treatment.

Genetic Predictors of Behavioral Weight Loss: Current Status and Future Directions.

In this issue of Obesity, Hollensted and colleagues (1) report on their analysis of whether genetic loci previously implicated in childhood obesity predict the magnitude of weight loss with lifestyle intervention among 754 children and adolescents with overweight. Genetic risk scores combining 15 single-nucleotide polymorphisms (SNPs) from the most recent genome-wide association studies (GWAS) did not significantly predict change in BMI standard deviation score during the intervention. One of the 15 SNPs, LMX1B rs3829849, did predict weight loss independently. This study represents an important advance in understanding whether known genetic predictors of childhood BMI may inhibit children from losing weight with lifestyle methods. It is the largest study to date, tested a comprehensive list of the most recent genetic variants associated with childhood BMI, employed an evidence-based weight-loss intervention, and achieved a median weight loss of 0.20 BMI standard deviation score or roughly 10% weight loss. It should be noted that weight loss was reported at varying time points (follow-up: 6-24 months; median: 1.25 years). In addition, children who did not complete a minimum of 6 months of the program were excluded. These factors could have created variability in measurement of BMI and/or bias from excluding those who were not successful, potentially limiting the detection of genetic effects. Nonetheless, these results contribute to a growing literature indicating that SNPs related to BMI in GWAS largely do not appear to predict the magnitude of weight loss in behavioral interventions. Prominent examples include a lack of association of the FTO region with weight loss in a meta-analysis including 9,563 participants (2). In a joint analysis of the Action for Health in Diabetes (Look AHEAD) trial and the Diabetes Prevention Program (DPP), only one of a comprehensive list of 91 SNPs predicted magnitude of weight loss in the lifestyle interventions (3). MC4R mutations causing monogenic obesity also did not predict magnitude of weight loss with lifestyle intervention in children (4). That said, the progress in identifying genetic variation predictive of weight loss should be recognized. In the meta-analysis of Look AHEAD and DPP, the obesity-related allele of MTIF3 rs1885988 predicted greater weight loss. One copy of the obesity risk allele conferred an additional loss of 1.48 kg, and two copies predicted a 2.96-kg weight loss (3). Moreover, using a gene-centric assay, ABCB11 and RANK were shown to relate to magnitude of weight loss in Look AHEAD (5). In the Hollensted et al. paper, LMX1B rs3829849 also significantly predicted weight loss. Although not yet of sufficient magnitude to guide clinical recommendations, such findings provide a platform for replication and extension with increasing sample sizes and may ultimately be employed as part of a weight-loss genetic risk score. It is noteworthy that the search for genetic predictors of weight loss has been limited almost exclusively to SNPs related to BMI in GWAS. No genome-wide analysis of weight loss has been conducted, but it could lead to the discovery of novel genetic loci related to weight loss, as was observed for bariatric surgery (6). Such new discoveries could ultimately contribute to a genetic risk score sufficiently predictive of weight loss for clinical application. JMM reports personal fees from Weight Watchers, outside the submitted work.

Abstract P296: High Salt (NaCl) Induces Metabolic Modifications and Affects Classic and Alternative Macrophage Activation

High intake of dietary sodium is a risk factor for cardiovascular disease. Previously, we have shown that an increase in extracellular hypertonic sodium (+40 mM Na + ; HS) inhibits alternatively-activated M2 macrophage (M(IL4+IL13)) gene signature and function, while boosting classic M1 macrophage polarization (M(LPS)) and bacterial killing capacity. M1 macrophages predominantly rely on glycolysis, whereas M2 macrophages use oxidative phosphorylation, fueled by the oxidation of fatty acids, at a late phase of activation (24 h). The aim of this study was to elucidate the role of HS on the metabolic signature of M1 and M2 macrophages. Therefore, we quantified 13 C incorporation into intermediates of central carbon metabolism via GC-MS based pulsed stable isotope resolved metabolomics (pSIRM), and performed Seahorse analyses at varying time points during M1/M2-activation. After 24 h, LPS-induced increase in basal ECAR (extracellular acidification as surrogate parameter for glycolysis) and lactate production were further boosted under HS compared to isotonic salt conditions (NS), whereas mitochondrial respiration (OCR) was not affected. On the other hand, IL4+IL13-induced increase in OCR was decreased under HS compared to NS, while ECAR was not affected at this stage. Regarding TCA-cycle, we have found an early (1 h and 3 h post-stimulation) increase in citrate levels in M1 and M2 macrophages independent of HS, which further increased after 24 h in M1 and M1+HS. Interestingly, both in early and late phase of activation, glucose-derived 13 C incorporation into citrate was lower in HS-treated compared to NS-treated M0, M1 and M2 macrophages, suggesting an alternative replenishing source. Consistently, other TCA-cycle intermediates increased after 24h (especially in M1 and even further in M1+HS), whereas glucose-derived 13 C incorporation was minimal. Our data suggests that under hypertonic sodium macrophages re-direct TCA-cycle intermediates into the production of pro-inflammatory mediators (as described for late-phase M1 macrophages), whereas TCA-cycle itself is replenished by other alternative metabolic substrates. These HS-induced metabolic modifications might play an important role for macrophage activation and function.

Population-based Study Determining Predictors of Cancer-Specific Mortality and Survival in Pediatric High-grade Brainstem Glioma

Pediatric high-grade brainstem gliomas are aggressive tumors with dismal prognoses. Large-scale studies are needed to further characterize these tumors and determine factors influencing cancer-specific mortality and survival at varying time points. We used the SEER (Surveillance Epidemiology and End Results) database to conduct a population-based study of pediatric patients with histologically confirmed anaplastic astrocytoma or glioblastoma tumors located within the brainstem. Multivariate analyses incorporating patient demographics, tumor characteristics, and treatments were used to determine predictors of cancer-specific mortality and survival at 6 months, 9 months, 1 year, and 2 years. We included 154 patients from the SEER database: 72 patients with anaplastic astrocytoma (47%) and 82 (53%) with glioblastoma. Median survival for the entire cohort was 10.0 months. Glioblastoma histology, developmental stage, and large tumor size were significantly associated with cancer-specific mortality. Six-month, 9-month, 1-year, and 2-year survival was 75%, 57%, 42%, and 20%, respectively. Glioblastoma histology was associated with worsened survival at 6 months (odds ratio [OR], 0.19; P= 0.0081), 9 months (OR, 0.18; P < 0.001), 1 year (OR, 0.19; P < 0.001), and 2 years (OR, 0.14; P= 0.0055). Radiation therapy was associated with improved survival at 6 (OR, 8.53; P= 0.0012) and 9 months (OR, 3.58; P=0.035) but not at 1 or 2 years. Radiation therapy was associated with improved survival in glioblastoma (9.0 vs. 3.0 months; P < 0.001). This population-based study showed that glioblastoma histology is associated with a poor prognosis in pediatric patients with high-grade brainstem gliomas. Regardless of histology, radiation therapy improved survival at 6 and 9 months but not long-term.

Time to sputum culture conversion and treatment outcome among the first cohort of multidrug resistant tuberculosis patients in a high burden country

BackgroundSputum conversion considered the most important interim indicator of the efficacy of anti-tuberculosis treatment was assessed at varying time points among the first cohort of multidrug resistant tuberculosis (MDR-TB) patients in a National TB Control Programme. MethodsA retrospective study was conducted for the period between 2010 and 2013, at the premiere MDR-TB treatment center in Nigeria. Genexpert, culture and drug susceptibility tests were carried out. Total duration of treatment was 20 months. ResultsA total of 115 patients were studied consisting of 76 (66.1%) males and 39 (33.9%) females with ages ranging between 15 and 65 years. Median time to sputum conversion was 2.06 months (95% confident interval [CI] = 1.82, 2.30). At the end of the first month, 43 (37.4%) patients sputum converted, increasing to 104 (90.4%) at the end of three months. There was no significant interaction with Human Immunodeficiency Virus (HIV) status. Overall treatment success was 69.4%. The default rate was 8.7% (10/115) and 25 (21.7%) deaths were recorded. ConclusionThe treatment success rate in the study was high with most of cases with or without HIV infection, achieving sputum culture conversion within 2 months of commencing treatment. Expansion of MDR-TB treatment services is necessary to reduce the death rate.

Molecular dynamics of pancreatic transcription factors in bioengineered humanized insulin producing neoorgan

BackgroundThe present study has been aimed to identify molecular dynamics of pancreatic transcription factors (pTFs) during events of directed trans-differentiation of human hepatic progenitor cells (hHPCs) into insulin producing cells (InPCs) within bioengineered humanized neoorgan. The study demonstrates applicability of acellularized whole splenic scaffold (ASOS) to generate insulin producing humanized transplantable neoorgan through activation of pancreatic transcription factors. MethodsAn efficient acellularization process was developed for xenogeneic rat spleen using change in different gradients of reagents perfusion through splenic artery for varying time points. The acellularized xenogeneic spleen scaffold was characterized thoroughly for preservation of extra-cellular matrix and retention of organ specific vasculature and mechanical properties. Further scaffolds were sterilized and repopulated with hHPCs which were triggered using a stage wise induction with growth factors and hyperglycemic challenge for trans-differentiation into InPCs. Dynamics of pTFs alone or simultaneously during induction process was identified using gene expression analysis and immunological staining. ResultsThe cells within the engineered neoorgan respond to growth factors and extrinsic hyperglycemic challenge and generate large number of InPCs under controlled dynamic regulation of pTFs. Highly controlled regulation of pTFs generates higher percentage of Nkx-6.1+/C-peptide+ cells within the engineered splenic scaffolds. Generation of high percentage of insulin and C-peptide positive cells in three-dimensional organ architecture responded better to hyperglycemic stimuli and produced higher quantity of insulin than 2D-culture system. ConclusionThe present study provides a novel platform for designing effective regenerative strategies using whole organ scaffolds to control hyperglycemia under tight regulation of pTFs using humanized neoorgan system.

An Exploration of the Impact of Initial Timing of Physical Therapy on Safety and Outcomes After Concussion in Adolescents.

Physical therapy (PT) is a management strategy increasingly recognized to facilitate recovery after concussion. The purpose of this study was to investigate the safety and outcomes of multimodal impairment-based PT at varying time points after injury in youth diagnosed with concussion. Data were extracted retrospectively from medical records for patients who received PT for concussion-related impairments. Patient records were categorized into 3 cohorts on the basis of the timing of PT implementation: 0-20 days following injury (early intervention), 21 to 41 days following injury (middle intervention), and 42 or more days following injury (late intervention). The primary outcome measure was Post-Concussion Symptom Inventory score from the beginning to the end of the PT episode of care. Additional outcome measures included number of PT sessions, duration of PT episode of care (days), and occurrence of unplanned visits to a health care provider. A total of 120 patient records (mean age of 14.77 years) were analyzed. Thirty-three, 39, and 48 individuals were categorized into the early, middle, and late intervention cohorts, respectively. There were no significant differences between intervention cohorts with regard to symptom change on the Post-Concussion Symptom Inventory from the beginning to the end of the PT episode of care, unplanned health care visits, number of PT sessions, or duration of PT episode of care. Early initiation of PT may be safe and tolerable. Future prospective studies are needed to explore the efficacy of PT services administered early following injury to help characterize an optimal care plan for youth following concussion.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A210).

Never Quit Trying: Reengaging Tobacco Users in Statewide Cessation Services.

Tobacco dependence is well established as a chronic condition typically requiring numerous quit attempts. Tobacco users are unlikely to return to the same cessation program on their own. This program evaluation examined the effectiveness of using multiple outreach methods to reengage tobacco users in a statewide cessation program at varying time points after their initial program enrollment. Participants were randomized to receive or not receive reengagement outreach. We conducted outreach via phone, e-mail, and/or text (based on methods participants agreed to receive) at 1, 2, or 3 months post-initial engagement. Participants were offered the opportunity to reenroll in QUITPLAN Services. Minnesota's QUITPLAN Services PARTICIPANTS:: A total of 3020 tobacco users who enrolled in Minnesota's QUITPLAN Services and either received a 2-week starter kit of nicotine replacement therapy or completed 0-1 QUITPLAN Helpline calls. We explored group differences in the odds of reengagement (defined as enrolling in a phone cessation program or selecting 2 or more of nicotine replacement therapy starter kit, text messaging, e-mail program, or print materials), contributors to reengagement, and costs. 14.7% in the Reengagement Outreach (RO) group and 3.4% in the Comparison (no outreach) group reengaged. The majority (71%) reengaged during phone outreach. There were no significant differences in reengagement rates by follow-up time period (1, 2, or 3 months). Cost per reengagement was $546, mostly due to one-time setup costs; scaling to 10 000 tobacco users would cost approximately $101 per reengagement. Conducting proactive outreach through state-funded quitlines is an effective approach to reengaging tobacco users, yielding a 5-fold greater odds of reengagement compared with no outreach. Since most costs were for initial setup, the cost per reengagement would decrease as the outreach population size increases. Such outreach has the potential to foster treatment utilization and quit attempts.

Biomechanical and Histologic Evaluation of LifeMesh™: A Novel Self-Fixating Mesh Adhesive

Mesh fixation with the use of adhesives results in an immediate and total surface area adhesion of the mesh, removing the need for penetrating fixation points. The purpose of this study was to evaluate LifeMesh™, a prototype mesh adhesive technology which coats polypropylene mesh. The strength of the interface between mesh and tissue, inflammatory responses, and histology were measured at varying time points in a swine model, and these results were compared with sutures. Twenty Mongrel swine underwent implantation of LifeMesh™ and one piece of bare polypropylene mesh secured with suture (control). One additional piece of either LifeMesh™ or control was used for histopathologic evaluation. The implants were retrieved at 3, 7, and 14 days. Only 3- and 7-day specimens underwent lap shear testing. On Day 3, LifeMesh™ samples showed considerably less contraction than sutured samples. The interfacial strength of Day 3 LifeMesh™ samples was similar to that of sutured samples. At seven days, LifeMesh™ samples continued to show significantly less contraction than sutured samples. The strength of fixation at seven days was greater in the control samples. The histologic findings were similar in LifeMesh™ and control samples. LifeMesh™ showed significantly less contraction than sutured samples at all measured time points. Although fixation strength was similar at three days, the interfacial strength of LifeMesh™ remained unchanged, whereas sutured controls increased by day 7. With histologic equivalence, considerably less contraction, and similar early fixation strength, LifeMesh™ is a viable mesh fixation technology.

MP23-03 IL-6/STAT3 SIGNALING IS A HOST DETERMINANT OF UPEC VIRULENCE VIA ALTERED BACTERIAL INVASION AND INTRACELLULAR BACTERIAL COMMUNITY FORMATION

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II1 Apr 2018MP23-03 IL-6/STAT3 SIGNALING IS A HOST DETERMINANT OF UPEC VIRULENCE VIA ALTERED BACTERIAL INVASION AND INTRACELLULAR BACTERIAL COMMUNITY FORMATION Christina Ching, Sudipti Gupta, and Brian Becknell Christina ChingChristina Ching More articles by this author , Sudipti GuptaSudipti Gupta More articles by this author , and Brian BecknellBrian Becknell More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.735AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our understanding of bacterial virulence in urinary tract infection (UTI) is primarily limited to identification of bacteria-specific determinants. Host mediators are less well known. IL-6 is a cytokine that is induced during UTI and results in subsequent Stat3 phosphorylation, but without readily apparent functional significance. We sought to evaluate the impact of IL-6/Stat3 signaling on host susceptibility to UTI via urothelial bacterial invasion and intracellular bacterial community formation. METHODS We performed in vivo and in vitro studies in order to evaluate the impact of IL-6 and Stat3 in bacterial invasion. We infected 6 week old female wild type (WT) C57BL/6J, IL-6 knock out (KO), or tamoxifen-inducible Stat3 conditional KO mice transurethrally with UPEC. We evaluated bladder and urine bacterial burden at varying time points of sacrifice by serial plating of tissue homogenates on LB agar and IBC formation via beta-galactosidase staining. We similarly evaluated the impact of recombinant IL-6 rescue in IL-6 KO mice on IBC formation and antimicrobial formation. We evaluated the impact of recombinant IL-6 incubation and Stat3 inhibition on intracellular bacterial invasion with gentamicin protection assay in serum starved 5637 urothelial cells. Results were evaluated by Mann-Whitney U test with p <0.05 being significant. RESULTS We observed an early transient (6 hours post inoculation - hpi) increase in bladder bacterial burden in our IL-6 KO mice compared to the WT controls, with a subsequent and persistent increase in urine bacterial burden starting at 24 hpi. This matched an initial significant difference in bladder IBC number in the IL-6 KO vs. WT that resolved by 24 hpi and was confirmed in our Stat3 CKO mice. Recombinant intravesical IL-6 rescued this phenotype in the IL-6 KO mouse and also significantly increased antimicrobial peptide expression. Similarly, we found that there was a significant decrease in bacterial invasion in vitro when 5637 cells were preincubated with IL-6. Stat3 inhibition resulted in a reversal of this phenotype with an increase in bacterial invasion on par with if not above unstimulated cells. CONCLUSIONS IL-6 plays an important role in host susceptibility to UTI as a mediator of bacterial invasion and IBC formation, potentially via antimicrobial peptide formation. Given IBC formation represents a significant bottleneck in UPEC survival during cystitis, these findings could suggest a role of IL-6 in UTI persistence and chronicity. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e282 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Christina Ching More articles by this author Sudipti Gupta More articles by this author Brian Becknell More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Radiographic Local Tumor Control and Pain Palliation of Sarcoma Metastases within the Musculoskeletal System with Percutaneous Thermal Ablation.

To evaluate the effectiveness of percutaneous image-guided thermal ablation in achieving local tumor control and pain palliation of sarcoma metastases within the musculoskeletal system. Retrospective review of 64 sarcoma metastases within the musculoskeletal system in 26 women and 15 men (total = 41) treated with ablation between December 2011 and August 2016 was performed. Mean age of the cohort was 42.9years ± 16.0years. Two subgroups were treated: oligometastatic disease (n = 13) and widely metastatic disease (n = 51). A variety of sarcoma histologies were treated with average tumor volume of 42.5cm3 (range 0.1-484.7cm3). Pain scores were recorded before and 4weeks after therapy for 59% (38/64) of treated lesions. Follow-up imaging was evaluated for local control and to monitor sites of untreated disease as an internal control. Fifty-eight percent (37/64) were lost to imaging follow-up at varying time points over a year. Complication rate was 5% (3/64; one minor and two major events). One-year local tumor control rates were 70% (19/27) in all patients, 67% (12/18) in the setting of progression of untreated metastases, and 100% (10/10) in the setting of oligometastatic disease. Median pain scores decreased from 8 (interquartile range 5.0-9.0) to 3 (interquartile range 0.1-4.0) 1month after the procedure (P < 0.001). Image-guided percutaneous ablation is an effective option for local tumor control and pain palliation of metastatic sarcomas within the musculoskeletal system. Treatment in the setting of oligometastatic disease offers potential for remission. Level 4, Retrospective Review.