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Myeloid-derived suppressor cells (MDSCs) are markedly increased in cancer patients and tumor-bearing mice and promote tumor growth and survival by inhibiting host innate and adaptive immunity. In this study, we generated and characterized MDSCs from murine-induced pluripotent stem cells (iPSCs). The iPSCs were co-cultured with OP9 cells, stimulated with GM-CSF, and became morphologically heterologous under co-culturing with hepatic stellate cells. Allogeneic and OVA-specific antigen stimulation demonstrated that iPS-MDSCs have a T-cell regulatory function. Furthermore, a popliteal lymph node assay and autoimmune hepatitis model showed that iPS-MDSCs also regulate immune responsiveness in vivo and have a therapeutic effect against hepatitis. Taken together, our results demonstrated a method of generating functional MDSCs from iPSCs and highlighted the potential of iPS-MDSCs as a key cell therapy resource for transplantation and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background Schizophrenia is characterized by prominent cognitive deficits, impacting on memory and learning; these are strongly associated with the prefrontal cortex. Objective/hypothesis To combine two interventions, transcranial direct current stimulation (tDCS) over the prefrontal cortex and cognitive training, to examine change in cognitive performance in patients with schizophrenia. Methods A double blind, sham-controlled pilot study of 49 patients with schizophrenia, randomized into real or sham tDCS stimulation groups. Subjects participated in 4 days of cognitive training (days 1, 2, 14, 56) with tDCS applied at day-1 and day-14. The primary outcome measure was change in accuracy on working memory and implicit learning tasks from baseline. The secondary outcome measure was the generalization of learning to non-trained task, indexed by the CogState neuropsychological battery. Data analysis was conducted using multilevel modelling and multiple regressions. Results 24 participants were randomized to real tDCS and 25 to sham. The working memory task demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 (b = 0.68, CI 0.14–1.21; p = 0.044) and at day-56 (b = 0.71, 0.16–1.26; p = 0.044). There were no significant effects of tDCS on implicit learning. Trend evidence of generalization onto untrained tasks of attention and vigilance task (b = 0.40, 0.43–0.77; p = 0.058) was found. Conclusions This is the first study to show a significant longer-term effect of tDCS on working memory in schizophrenia. Given the current lack of effective therapies for cognitive deficits, tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to prospectively evaluate the use of daily 2-mm bolus in patients undergoing postmastectomy radiation without reconstruction using optically stimulated luminescence dosimetry and weekly assessment of skin toxicity. Methods and materials We prospectively collected data from the first 49 women treated with a daily 2-mm Superflab bolus during their postmastectomy radiation therapy from 2013 to 2016 at The University of Chicago Comprehensive Cancer Center at Silver Cross. Within the first 3 days of starting radiation therapy, we measured the surface dose in vivo at 5 anatomical locations under the 2-mm bolus on the chest wall. We assessed weekly the acute skin toxicity during radiation using the National Cancer Institute Common Toxicity Criteria. Patients with reconstruction before radiation therapy were excluded. Results Forty-nine women with a mean age of 54.3 years were treated with daily 2-mm bolus to the chest wall following mastectomy. Median follow-up was 32.7 weeks. The mean percentages of prescribed dose (standard deviation) for the median, central, lateral, superior, and inferior optically stimulated luminescence dosimeters were 100.1% (5.6%), 108.1% (6.7%), 98.1% (6.5%), 102.6% (8.9%), and 106.3% (6.6%), respectively. The majority (71.4%) of women experienced a maximum acute National Cancer Institute Common Toxicity Criteria skin toxicity score of 2, with only 12.2% experiencing a score of 3. There were no grade 4 toxicities. There were no local recurrences during our follow-up period. Conclusions A daily 2-mm bolus is a feasible regimen for chest wall bolus during postmastectomy radiation therapy with acceptable dose buildup and skin toxicity. [ABSTRACT FROM AUTHOR]

Background: Left cardiac sympathetic denervation (LCSD) provides an additive or potentially alternative treatment option for patients with life-threatening cardiac channelopathies/cardiomyopathies.Objective: We sought to examine the effects of LCSD on quality of life (QOL).Methods: From November 2005 to May 2013, 109 patients who underwent LCSD were subsequently sent postoperative QOL surveys.Results: Of 109 patients, 8 (7%) could not be contacted. Of the remaining 101 patients, 62 returned surveys (response rate 61%). There were an average of 4.1 ± 1.8 self-reported side effects immediately after LCSD. The most common anticipated side effects included unilateral hand dryness, color or temperature variance between sides of the face, and abnormal sweating. Although parent-reported pediatric physical QOL scores were lower than national norms, there were no differences in psychosocial QOL or disability scores (P = .09 and .33, respectively). QOL scores for adult patients were not significantly different from a US normative sample. Adult LCSD patients reported less disability than a US normative sample (P < .01). There was no correlation between QOL scores and the presence of anticipated side effects. However, among the subset of pediatric patients who continued to receive ventricular fibrillation-terminating implantable cardioverter-defibrillator shocks after LCSD, there was a correlation between their disability scores and the number of reported shocks (Spearman correlation = 0.56). The majority of patients/parents reported that they were very or somewhat satisfied with their surgery (or their child's surgery) and would definitely or probably recommend LCSD to another patient.Conclusion: Despite the anticipated side effects associated with LCSD, patients are satisfied with their surgery and indicate that they would recommend the surgery to another patient. [ABSTRACT FROM AUTHOR]

In the fall of 2009, the autlwrs conducted a limited ground-penetrating radar survey in Prairie du Chien, Wisconsin on the remains of the First Fort Crawford (47CR249). First Fort Crawford was built in 1816 and abandoned in 1832. In the 1930s, the fort was accidentally rediscovered. At that time, Leland R. Cooper of Hamline University excavated a majority of the fort's rooms as a Works Progress Administration project. Largely undocumented, these excavations have left us without an accurate idea of the extent of the excavations and, more to the point, what was not excavated. Sketchy surviving records suggest that tire powder magazine and latrines were either not located or not excavated at the time. Comparing forts with similar architecture offered clues as to where to look for those features. Cooper's accession books and photographs allowed us to reconstruct much of the excavation and its features. Geophysical Survey Systems SIR-3000 ground-penetrating radar was used in an attempt to relocate these features for future excavation and to determine the extent of previous excavations. The results of these investigations indicate that there are intact rooms and features that were not previously excavated. [ABSTRACT FROM AUTHOR]

Light is a potent circadian entraining agent. For many people, daily light exposure is fundamentally dysregulated with reduced light during the day and increased light into the late evening. This lighting schedule promotes chronic disruption to circadian physiology resulting in a myriad of impairments. Developmental changes in sleep-wake physiology suggest that such light exposure patterns may be particularly disruptive for adolescents and further compounded by lifestyle factors such as early school start times. This narrative review describes evidence that reduced light exposure during the school day delays the circadian clock, and longer exposure durations to light-emitting electronic devices in the evening suppress melatonin. While home lighting in the evening can suppress melatonin secretion and delay circadian phase, the patterning of light exposure across the day and evening can have moderating effects. Photic countermeasures may be flexibly and scalably implemented to support sleep-wake health; including manipulations of light intensity, spectra, duration and delivery modality across multiple contexts. An integrative approach addressing physiology, attitudes, and behaviors will support optimization of light-driven sleep-wake outcomes in adolescents. [ABSTRACT FROM AUTHOR]

IMPORTANCE Forward models predict the sensory consequences of planned actions and permit discrimination of self- and non-self-elicited sensation; their impairment In schizophrenia is implied by an abnormality in behavioral force-matching and the flawed agency judgments characteristic of positive symptoms, including auditory hallucinations and delusions of control. OBJECTIVE To assess attenuation of sensory processing by self-action in individuals with schizophrenia and its relation to current symptom severity. DESIGN, SETTING, AND PARTICIPANTS Functional magnetic resonance imaging data were acquired while medicated Individuals with schizophrenia (n = 19) and matched controls (n = 19) performed a factorially designed sensorimotor task in which the occurrence and relative timing of action and sensation were manipulated. The study took place at the neuroimaging research unit at the Institute of Cognitive Neuroscience, University College London, and the Maudsley Hospital. RESULTS In controls, a region of secondary somatosensory cortex exhibited attenuated activation when sensation and action were synchronous compared with when the former occurred after an unexpected delay or alone. By contrast, reduced attenuation was observed in the schizophrenia group, suggesting that these individuals were unable to predict the sensory consequences of their own actions. Furthermore, failure to attenuate secondary somatosensory cortex processing was predicted by current hallucinatory severity. CONCLUSIONS AND RELEVANCE Although comparably reduced attenuation has been reported in the verbal domain, this work Implies that a more general physiologic deficit underlies positive symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Limited exposure and visualization and technical complexity have affected resident training in mitral valve surgery. We propose simulation-based learning to improve skill acquisition in mitral valve surgery. Methods: After reviewing instructional video recordings of mitral annuloplasty in porcine and plastic models, 11 residents (6 integrated and 5 traditional) performed porcine model mitral annuloplasty. Video-recorded performance was reviewed by attending surgeon providing audio formative feedback superimposed on video recordings; recordings were returned to residents for review. After 3-week practice with plastic model, residents repeated porcine model mitral annuloplasty. Performance assessments initially (prefeedback) and at 3 weeks (postfeedback) were based on review of video recordings on 5-point rating scale (5, good; 3, average; 1, poor) of 11 components. Ratings were averaged for composite score. Results: Time to completion improved from mean 31 ± 9 minutes to 25 ± 6 minutes after 3-week practice (P = .03). At 3 weeks, improvement in technical components was achieved by all residents, with prefeedback scores varying from 2.4 ± 0.6 for needle angles to 3.0 ± 0.5 for depth of bites and postfeedback scores of 3.1 ± 0.8 for tissue handling to 3.6 ± 0.8 for suture management and tension (P ≤ .001). Interrater reliability was greater than 0.8. In this sample, composite scores of first-year integrated and traditional residents were lower than those of senior level residents; comparatively, third-year integrated residents demonstrated good technical proficiency. Conclusions: Simulation-based learning with formative feedback results in overall improved performance of simulated mitral annuloplasty. In complex surgical procedures, simulation may provide necessary early graduated training and practice. Importantly, a “passing” grade can be established for proficiency-based advancement. [Copyright &y& Elsevier]

This study evaluated the safety and efficacy of chlorine dioxide (ClO2) fed into the incoming main water line to control Legionella bacteria in two hospital water systems. In both hospitals A and B, positivity of all distal outlets (sinks and showers) for Legionella decreased from 60% to ≤ 10% after the ClO2 treatment. In hospital B, the heterotrophic plate count bacteria in hot water were reduced from 15,400 cfu/mL to 2,900 cfu/mL after ClO2 treatment. Mean concentrations of ClO2 and chlorite (ClO2-) in cold and hot water did not exceed the maximum residual disinfection level of 0.8 mg/L and the maximum contaminant level of 1.0 mg/L, respectively. No cases of healthcare acquired legionellosis have been identified in the postdisinfection period in these two hospitals. The study indicates that ClO2 is a promising disinfectant for controlling not only Legionella, but also other microorganisms in drinking water. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is the leading cause of skin and soft tissue infections and is a major health burden due to the emergence of antibiotic-resistant strains. To address the unmet need of alternative treatments to antibiotics, a better understanding of the protective immune mechanisms against S. aureus skin infection is warranted. Here, we report that tumor necrosis factor (TNF) promoted protection against S. aureus in the skin, which was mediated by bone marrow-derived immune cells. Furthermore, neutrophil-intrinsic TNF receptor (TNFR) signaling directed immunity against S. aureus skin infections. Mechanistically, TNFR1 promoted neutrophil recruitment to the skin, whereas TNFR2 prevented systemic bacterial dissemination and directed neutrophil antimicrobial functions. Treatment with a TNFR2 agonist showed therapeutic efficacy against S. aureus and Pseudomonas aeruginosa skin infections, which involved increased neutrophil extracellular trap formation. Our findings revealed nonredundant roles for TNFR1 and TNFR2 in neutrophils for immunity against S. aureus and can be therapeutically targeted for protection against bacterial skin infections.