Pectus excavatum in motion: dynamic evaluation using real-time MRI.

OBJECTIVES The breathing phase for the determination of thoracic indices in patients with pectus excavatum is not standardized. The aim of this study was to identify the best period for reliable assessments of morphologic indices by dynamic observations of the chest wall using real-time MRI. METHODS In this prospective study, patients with pectus excavatum underwent morphologic evaluation by real-time MRI at 3 T between January 2020 and June 2021. The Haller index (HI), correction index (CI), modified asymmetry index (AI), and modified eccentricity index (EI) were determined during free, quiet, and forced breathing respectively. Breathing-related differences in the thoracic indices were analyzed with the Wilcoxon signed-rank test. Motion of the anterior chest wall was analyzed as well. RESULTS A total of 56 patients (11 females and 45 males, median age 15.4 years, interquartile range 14.3-16.9) were included. In quiet expiration, the median HI in the cohort equaled 5.7 (4.5-7.2). The median absolute differences (Δ) in the thoracic indices between peak inspiration and peak expiration were ΔHI = 1.1 (0.7-1.6, p .05 each). Furthermore, the dynamic evaluation revealed three distinctive movement patterns of the funnel chest. CONCLUSIONS Real-time MRI reveals patterns of chest wall motion and indicate that thoracic indices of pectus excavatum should be assessed in the end-expiratory phase of quiet expiration. KEY POINTS • The thoracic indices in patients with pectus excavatum depend on the breathing phase. • Quiet expiration represents the best breathing phase for determining thoracic indices. • Real-time MRI can identify different chest wall motion patterns in pectus excavatum

CD33 BiTE molecule-mediated immune synapse formation and subsequent T-cell activation is determined by the expression profile of activating and inhibitory checkpoint molecules on AML cells

Bispecific T-cell engager (BiTE) molecules recruit T cells to cancer cells through CD3ε binding, independently of T-cell receptor (TCR) specificity. Whereas physiological T-cell activation is dependent on signal 1 (TCR engagement) and signal 2 (co-stimulation), BiTE molecule-mediated T-cell activation occurs without additional co-stimulation. As co-stimulatory and inhibitory molecules modulate the strength and nature of T-cell responses, we studied the impact of the expression profile of those molecules on target cells for BiTE molecule-mediated T-cell activation in the context of acute myeloid leukemia (AML). Accordingly, we created a novel in vitro model system using murine Ba/F3 cells transduced with human CD33 ± CD86 ± PD-L1. T-cell fitness was assessed by T-cell function assays in co-cultures and immune synapse formation by applying a CD33 BiTE molecule (AMG 330). Using our cell-based model platform, we found that the expression of positive co-stimulatory molecules on target cells markedly enhanced BiTE molecule-mediated T-cell activation. The initiation and stability of the immune synapse between T cells and target cells were significantly increased through the expression of CD86 on target cells. By contrast, the co-inhibitory molecule PD-L1 impaired the stability of BiTE molecule-induced immune synapses and subsequent T-cell responses. We validated our findings in primary T-cell-AML co-cultures, demonstrating a PD-L1-mediated reduction in redirected T-cell activation. The addition of the immunomodulatory drug (IMiD) lenalidomide to co-cultures led to stabilization of immune synapses and improved subsequent T-cell responses. We conclude that target cells modulate CD33 BiTE molecule-dependent T-cell activation and hence, combinatorial strategies might contribute to enhanced efficacy

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Molecular and Supramolecular Control of the Work Function of an Inorganic Electrode with Self-Assembled Monolayer of Umbrella-Shaped Fullerene Derivatives

The surface properties of inorganic substrates can be altered by coating with organic molecules, which may result in the improvement of the properties suitable for electronic or biological applications. This article reports a systematic experimental study on the influence of the molecular and supramolecular properties of umbrella-shaped penta(organo)[60]fullerene derivatives, and on the work function and the water contact angle of indium–tin oxide (ITO) and gold surfaces. We could relate these macroscopic characteristics to single-molecular level properties, such as ionization potential and molecular dipole. The results led us to conclude that the formation of a SAM of a polar compound generates an electronic field through intermolecular interaction of the molecular charges, and this field makes the overall dipole of the SAM much smaller than the one expected from the simple sum of the dipoles of all molecules in the SAM. This effect, which was called depolarization and previously discussed theoretically, is now quantitatively probed by experiments. The important physical properties in surface science such as work function, ionization potential, and water contact angles have been mutually correlated at the level of molecular structures and molecular orientations on the substrate surface. We also found that the SAMs on ITO and gold operate under the same principle except that the “push-back” effect operates specifically for gold. The study also illustrates the ability of the photoelectron yield spectroscopy technique to rapidly measure the work function of a SAM-covered substrate and the ionization potential value of a molecule on the surface

Tracheal Tube Misplacement after Emergency Intubation in Pediatric Trauma Patients: A Retrospective, Exploratory Study

Inadvertent tracheal tube misplacement and particularly endobronchial intubation are well-known complications of emergency endotracheal intubation (ETI) in pediatric trauma patients, which require repositioning of the tube to avoid impairment of gas exchange. The main aim of study was to identify the frequency of tube misplacement and associated factors of pediatric trauma patients who received ETI either by prehospital physician-staffed emergency medical service (EMS), or at emergency department (ED) admission to a single level-1 trauma center. Sixty-five patients (median age 14 years and median injury severity score 29) were included. Of these, 30 underwent helicopter EMS ETI, 29 ground EMS ETI, and 6 ED ETI. Seventeen cases (26%) of tracheal tube misplacement were recognized. After multivariable analysis, tracheal tube misplacement was independently negatively associated with body weight (OR 0.86; 95% CI, 0.76–0.99; p = 0.032) and helicopter EMS ETI (OR 0.20; 95% CI, 0.04–0.97; p = 0.036). Two of nineteen patients received tube thoracostomy due to endobronchial intubation. Mortality and length of stay were comparable in patients with misplaced tubes and correctly placed tubes. The results suggest that particularly small children require attention to avoid tracheal tube misplacement, which emphasizes the need for special training. Helicopter EMS physicians’ expertise might be beneficial in prehospital pediatric trauma patients requiring advanced airway management

Epidemiological Analysis of the Emergency Vascular Access in Pediatric Trauma Patients: Single-Center Experience of Intravenous, Intraosseous, Central Venous, and Arterial Line Placements

Vascular access in severely injured pediatric trauma patients is associated with time-critical circumstances and low incidences, whereas only scarce literature on procedure performance is available. The purpose of this study was to analyze the performance of different vascular access procedures from the first contact at the scene until three hours after admission. Intubated pediatric trauma patients admitted from the scene to a single Level I trauma center between 2008 and 2019 were analyzed regarding intravenous (IV) and intraosseous (IO) accesses, central venous catheterization (CVC) and arterial line placement. Sixty-five children with a median age of 14 years and median injury severity score of 29 points were included, of which 62 (96.6%) underwent successful prehospital IV or IO access by emergency medical service (EMS) physicians, while it failed in two children (3.1%). On emergency department (ED) admission, IV cannulas of prehospital EMS had malfunctions or were dislodged in seven of 55 children (12.7%). IO access was performed in 17 children without complications, and was associated with younger age, higher injury severity and higher mortality. Fifty-two CVC placements (58 attempts) and 55 arterial line placements (59 attempts) were performed in 45 and 52 children, respectively. All CVC and arterial line placements were performed in the ED, operating room (OR) and intensive care unit (ICU). Ten mechanical complications related to CVC placement (17.8%) and seven related to arterial line placement (10.2%) were observed, none of which had outcome-relevant consequences. This case series suggests that mechanical issues of vascular access may frequently occur, underlining the need for special preparedness in prehospital, ED, ICU and OR environments

Electropolymerized Conjugated Polyelectrolytes with Tunable Work Function and Hydrophobicity as an Anode Buffer in Organic Optoelectronics

A new class of conductive polyelectrolyte films with tunable work function and hydrophobicity has been developed for the anode buffer layer in organic electronic devices. The work function of these films featuring a copolymer of ethylenedioxythiophene (EDOT), and its functionalized analogues were found to be easily tunable over a range of almost 1 eV and reach values as high as those of PEDOT:PSS. The new buffer material does not need the addition of any insulating or acidic material that might limit the film conductivity or device lifetime. Organic photovoltaic devices built with these films showed improved open-circuit voltage over those of the known PSS-free conductive EDOT-based polymers with values as high as that obtained for PEDOT:PSS. Furthermore, the surface hydrophobicity of these new copolymer films was found to be sensitive to the chemical groups attached to the polymer backbone, offering an attractive method for surface energy tuning

Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi

Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi