Lower Extremity Growth according to AI Automated Femorotibial Length Measurement on Slot-Scanning Radiographs in Pediatric Patients.

Background Commonly used pediatric lower extremity growth standards are based on small, dated data sets. Artificial intelligence (AI) enables creation of updated growth standards. Purpose To train an AI model using standing slot-scanning radiographs in a racially diverse data set of pediatric patients to measure lower extremity length and to compare expected growth curves derived using AI measurements to those of the conventional Anderson-Green method. Materials and Methods This retrospective study included pediatric patients aged 0-21 years who underwent at least two slot-scanning radiographs in routine clinical care between August 2015 and February 2022. A Mask Region-based Convolutional Neural Network was trained to segment the femur and tibia on radiographs and measure total leg, femoral, and tibial length; accuracy was assessed with mean absolute error. AI measurements were used to create quantile polynomial regression femoral and tibial growth curves, which were compared with the growth curves of the Anderson-Green method for coverage based on the central 90% of the estimated growth distribution. Results In total, 1874 examinations in 523 patients (mean age, 12.7 years ± 2.8 [SD]; 349 female patients) were included; 40% of patients self-identified as White and not Hispanic or Latino, and the remaining 60% self-identified as belonging to a different racial or ethnic group. The AI measurement training, validation, and internal test sets included 114, 25, and 64 examinations, respectively. The mean absolute errors of AI measurements of the femur, tibia, and lower extremity in the test data set were 0.25, 0.27, and 0.33 cm, respectively. All 1874 examinations were used to generate growth curves. AI growth curves more accurately represented lower extremity growth in an external test set (n = 154 examinations) than the Anderson-Green method (90% coverage probability: 86.7% [95% CI: 82.9, 90.5] for AI model vs 73.4% [95% CI: 68.4, 78.3] for Anderson-Green method; χ2 test, P < .001). Conclusion Lower extremity growth curves derived from AI measurements on standing slot-scanning radiographs from a diverse pediatric data set enabled more accurate prediction of pediatric growth. © RSNA, 2024 Supplemental material is available for this article.

Contextual fear conditioning in zebrafish: Influence of different shock frequencies, context, and pharmacological modulation on behavior.

Contextual fear conditioning is a protocol used to assess associative learning across species, including fish. Here, our goal was to expand the analysis of behavioral parameters that may reflect aversive behaviors in a contextual fear conditioning protocol using adult zebrafish (Danio rerio) and to verify how such parameters can be modulated. First, we analyzed the influence of an aversive stimulus (3 mild electric shocks for 5 s each at frequencies of 10, 100 or 1000 Hz) on fish behavior, and their ability to elicit fear responses in the absence of shock during a test session. To confirm whether the aversive responses are context-dependent, behaviors were also measured in a different experimental environment in a test session. Furthermore, we investigated the effects of dizocilpine (MK-801, 2 mg/kg, i.p.) on fear-related responses. Zebrafish showed significant changes in baseline activity immediately after shock exposure in the training session, in which 100 Hz induced robust contextual fear responses during the test session. Importantly, when introduced to a different environment, animals exposed to the aversive stimulus did not show any differences in locomotion and immobility-related parameters. MK-801 administered after the training session reduced fear responses during the test, indicating that glutamate NMDA-receptors play a key role in the consolidation of contextual fear-related memory in zebrafish. In conclusion, by further exploring fear-related behaviors in a contextual fear conditioning task, we show the effects of different shock frequencies and confirm the importance of context on aversive responses for associative learning in zebrafish. Additionally, our data support the use of zebrafish in contextual fear conditioning tasks, as well as for advancing pharmacological studies related to associative learning in translational neurobehavioral research.

Generalizing Diffusion Tensor Imaging of the Physis and Metaphysis.

BACKGROUND: Current methods to predict height potential are inaccurate. Predicting height by using MRI of the physeal cartilage has shown promise but the applicability of this technique in different imaging setups has not been well-evaluated. PURPOSE: To assess variability in diffusion tensor imaging of the physis and metaphysis (DTI-P/M) of the distal femur between different scanners, imaging parameters, tractography software, and resolution. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Eleven healthy subjects (five males and six females ages 10-16.94). FIELD STRENGTH/SEQUENCE: 3 T; DTI single shot echo planar sequences. ASSESSMENT: Physeal DTI tract measurements of the distal femur were compared between different scanners, imaging parameters, tractography settings, interpolation correction, and tractography software. STATISTICAL TESTS: Bland-Altman, Spearman correlation, linear regression, and Shapiro-Wilk tests. Threshold for statistical significance was set at P = 0.05. RESULTS: DTI tract values consistently showed low variability with different imaging and analysis settings. Vendor to vendor comparison exhibited strong correlation (ρ = 0.93) and small but significant bias (bias -5.76, limits of agreement [LOA] -24.31 to 12.78). Strong correlation and no significant difference were seen between technical replicates of the General Electric MRI scanner (ρ = 1, bias 0.17 [LOA -1.5 to 1.2], P = 0.42) and the Siemens MRI scanner (ρ = 0.89, bias = 0.56, P = 0.71). Different voxel sizes (1 × 1 × 2 mm3 vs. 2 × 2 × 3 mm3) did not significantly affect DTI values (bias = 1.4 [LOA -5.7 to 8.4], P = 0.35) but maintained a strong correlation (ρ = 0.82). Gap size (0 mm vs. 0.6 mm) significantly affects tract volume (bias = 1.8 [LOA -5.4 to 1.8]) but maintains a strong correlation (ρ = 0.93). Comparison of tractography algorithms generated significant differences in tract number, length, and volume while maintaining correlation (ρ = 0.86, 0.99, 0.93, respectively). Comparison of interobserver variability between different tractography software also revealed significant differences while maintaining high correlation (ρ = 0.85-0.98). DATA CONCLUSION: DTI of the pediatric physis cartilage shows high reproducibility between different imaging and analytic parameters. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

First-attempt awake tracheal intubation success rate using a hyperangulated unchannelled videolaryngoscope vs. a channelled videolaryngoscope in patients with anticipated difficult airway: a randomised controlled trial.

INTRODUCTION: There is uncertainty about the optimal videolaryngoscope for awake tracheal intubation in patients with anticipated difficult airway. The use of channelled and unchannelled videolaryngoscopy has been reported, but there is a lack of evidence on which is the best option. METHODS: We conducted a randomised clinical trial to compare the efficacy of the C-MAC D-Blade® vs. Airtraq® in adult patients (aged ≥ 18 y) scheduled for elective or emergency surgery under general anaesthesia with anticipated difficult airway who required awake tracheal intubation under local anaesthesia and conscious sedation. The primary endpoint was the first-attempt tracheal intubation success rate. Secondary outcomes included the overall success rate; number of tracheal intubation attempts; Cormack and Lehane glottic view; level of difficulty (visual analogue score); patient discomfort (visual analogue score); and incidence of complications. RESULTS: Ninety patients (70/90 male (78%); mean (SD) age 65 (12) y) with anticipated difficult airways were randomly allocated to C-MAC D-Blade or Airtraq videolaryngoscopy. First-attempt successful tracheal intubation rate was higher in patients allocated to the C-MAC D-Blade group compared with those allocated to the Airtraq group (38/45 (84%) vs. 28/45 (62%), respectively; p = 0.006). The proportion of patients' tracheas that were intubated at the second and third attempt was 4/45 (9%) and 3/45 (7%) in those allocated to the C-MAC D-Blade group compared with 14/45 (31%) and 1/45 (2%) in those allocated to the Airtraq group (p = 0.006). There was no significant difference in overall tracheal intubation success rate (C-MAC D-Blade group 45/45 (100%) vs. Airtraq group 43/45 (96%), p = 0.494). DISCUSSION: In patients with anticipated difficult airway, first-attempt awake tracheal intubation success rate was higher with the C-MAC D-Blade compared with Airtraq laryngoscopy. No difference was found between the two videolaryngoscopes in overall tracheal intubation success rate.

Diffusion tensor imaging shows increased physis organization after growth hormone initiation in hypophosphatasia.

Hypophosphatasia is a rare heritable disorder of bone mineralization, with a spectrum of severity based on age of initial presentation. We describe the case of a 14-year-old boy with gene-confirmed inherited hypophosphatasia and growth hormone deficiency, who presented with short stature, unremarkable radiographs, and only minor physeal and metaphyseal changes on magnetic resonance (MR) imaging. Diffusion tensor imaging (DTI) before growth hormone initiation revealed abundant, non-parallel tracts in the physes and metaphyses with loss of the typical columnar organization. After 8 months of growth hormone treatment, DTI scans revealed realigned, nearly parallel, longer physeal tracts; duplication of tract volume; and decreased and more typical fractional anisotropy values. DTI can thus visualize physeal tract changes over time, could be a more sensitive diagnostic technique in milder physeal abnormality cases, and may be a potential marker of growth hormone treatment response.

Reasons for Provider-to-Provider Synchronous Teleconsultations Between Nurses in Primary Care: A Cross-Sectional Study of TelessaúdeRS-UFRGS Service.

Introduction: Nurses have proven to be fundamental for the expansion and consolidation of primary health care (PHC), as well as the development of digital health strategies. We explored the results of a synchronous telephone teleconsultations service between professionals for nurses in Brazil. Methods: This is a cross-sectional study. We retrieved data from teleconsultations registry. All teleconsultations answered by the team of nurses between September 2018 and July 2021 were analyzed regarding the reasons (according to International Classification of Primary Care, 2nd edition-ICPC-2) and decisions of the teleconsultation. Results: There were 9,273 phone teleconsultations registered in the period, requested by 3,125 nurses from all states throughout the country, of which 56.9% called once and 15.9% used the teleconsultations at least 4 times. We found 362 different reasons for solicitations, which were classified according to the ICPC-2 chapters. The most frequent codes were respiratory (25.9%), general and unspecified (21.2%), and skin (21.2%), which corresponded to 68% of the total sample. Most teleconsultations (66.9%) had as outcome the maintenance of the case at PHC. Conclusion: Teleconsultations are widely used and address a broad number of situations. This service may improve the quality of Brazilian PHC and promote the development of clinical reasoning and critical thinking by nurses.

Real-world application of PBPK in drug discovery.

The utility of PBPK models in support of drug development has been well documented. During the discovery stage, PBPK has increasingly been applied for early risk assessment, prediction of human dose, toxicokinetic dose projection and early formulation assessment. Previous review articles have proposed model building and application strategies for PBPK-based first in human predictions with comprehensive descriptions of the individual components of PBPK models. This includes the generation of decision trees, based on comprehensive literature reviews, to guide the application of PBPK in the discovery setting. The goal of this mini review is to provide additional guidance on the real-world application of PBPK, in support of the discovery stage of drug development. In this mini review, our goal is to provide guidance on the typical steps involved in the development and application of a PBPK model during drug discovery to assist in decision making. We have illustrated our recommended approach through description of case examples, where PBPK has been successfully applied to aid in human PK projection, candidate selection and prediction of drug interaction liability for parent and metabolite. Through these case studies, we have highlighted fundamental issues, including pre-verification in preclinical species, the application of empirical scalars in the prediction of in vivo clearance from in vitro systems, in silico prediction of permeability and the exploration of aqueous and biorelevant solubility data to predict dissolution. In addition, current knowledge gaps have been highlighted and future directions proposed. Significance Statement Through description of three case studies, we have highlighted the fundamental principles of PBPK application during drug discovery. These include pre-verification of the model in preclinical species, application of empirical scalars where necessary in the prediction of clearance, in silico prediction of permeability, and the exploration of aqueous and biorelevant solubility data to predict dissolution. In addition, current knowledge gaps have been highlighted and future directions proposed.

Obesity and its chronic inflammation as pain potentiation factor in rats with osteoarthritis.

BACKGROUND: Obesity produces the accumulation of adipose tissue and a chronic inflammatory process, while osteoarthritis (OA) is also an inflammatory disorder. OBJECTIVES: to evaluate whether obesity associated to OA may be a factor that increases inflammation and pain. METHODS: Male animals (M) were divided into groups: control (CM), OA-induced pain (MP), obese (OM) and obese with OA-induced pain (OMP). Similarly, females (F) were divided into groups: control (CF), OA-induced pain (FP), obese (OF) and obese with OA-induced pain (OFP). All the groups except for control and obese groups were submitted to OA induction by sodium monoiodoacetate injection and monitored until day 65. Their adiposity index, thermal, mechanical and spontaneous pain nociceptive profile were investigated. At the end of the experiment (t = 65 days) hematological parameters, biochemical parameters, andcytokines were assessed. RESULTS: Rats with obesity induction showed alterations in mechanical and thermal nociceptive profile, and increase in systemic inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-8 and leptin) with reduction in anti-inflammatory cytokines (adiponectin and IL-10). These profile changes were investigated by principal component analysis (PCA), in which the first two principal components explained near 90% of the data variability. Obesity, when present together with OA in OMP and OFP groups, yielded the highest levels of inflammatory cytokines and pain scores and the lowest levels on anti-inflamatory cytokines. CONCLUSION: Obesity modified the nociceptive profile when inflammatory process is produced. When obesity occurs concomitantly with OA, inflammatory progression is intensified, yelding increase in pain scores.

Traceless N-Polyfluoroalkylation of Weakly Nucleophilic Nitrogen Containing Compounds.

Here we report an efficient access to high-value N-polyfluoroalkyl anilines, primary polyfluoroalkylamines and N,N-bis(polyfluoroalkyl)amines, via N-polyfluoroalkylation of sulfonamides and phthalimide derivatives using sulfuryl fluoride (SO2 F2 ). The in situ formation of polyfluoroalkyl fluorosulfonates from commercially available fluorinated alcohols and economical sulfuryl fluoride is highly advantageous given that some polyfluoroalkyl halides are ozone-depleting substances (ODS) regulated by the Montreal protocol. This general method is applied to the polyfluoroalkylation of a variety of sulfonamides, N-sulfonyl carbamates and phthalimide with a wide tolerance of functional groups. The process thus provides viable access for industry to N-(polyfluoroalkyl)anilines as well as primary and secondary N-(polyfluoroalkyl)amines, which are very valuable but not easily accessible building blocks for life science applications.

Quetiapine for the Treatment of Pediatric Delirium.

BACKGROUND: Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. OBJECTIVE: The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. METHODS: A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. RESULTS: This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. CONCLUSION AND RELEVANCE: Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Fibrous hamartoma of infancy: imaging findings.

BACKGROUND: Fibrous hamartoma of infancy is a benign tumor that typically arises within the first 2 years of life in the subcutaneous and lower dermal layers. Diagnosis can be challenging as it is a rare tumor, and the imaging appearance is not well known. OBJECTIVE: To describe the imaging features in 4 cases of fibrous hamartoma of infancy focusing on ultrasound (US) and magnetic resonance (MR) findings. MATERIALS AND METHODS: In this retrospective IRB-approved study, informed consent was waived. We searched patient charts for histopathology-confirmed fibrous hamartoma of infancy diagnosis between November 2013 and November 2022. We found four cases, three boys and one girl, and the mean age was 1.4 years (5 months-3 years). The lesions were located in the axilla, posterior elbow, posterior neck, and lower back. All four patients underwent ultrasound evaluation of the lesion, and two patients also underwent MRI evaluation. The imaging findings were reviewed by consensus by two pediatric radiologists. RESULTS: US imaging revealed subcutaneous lesions with variably defined hyperechoic regions and intervening hypoechoic bands resulting in a linear "serpentine" pattern or a "multiple semicircle" pattern. MR imaging evidenced heterogeneous soft tissue masses, localized in the subcutaneous fat, and showed hyperintense fat interspersed with hypointense septations on both T1- and T2-weighted images. CONCLUSION: Fibrous hamartoma of infancy has a suggestive appearance on US with heterogeneous, echogenic subcutaneous lesions with intervening hypoechoic portions, in parallel or circumferential arrangement that can be seen as a serpentine or semicircular pattern. On MRI, interspersed macroscopic fatty components show high signal intensity on T1- and T2-weighted images and reduced signal on fat-suppressed inversion recovery images, with irregular peripheral enhancement.

Diffusion tensor imaging of the physis: the ABC's.

The physis, or growth plate, is the primary structure responsible for longitudinal growth of the long bones. Diffusion tensor imaging (DTI) is a technique that depicts the anisotropic motion of water molecules, or diffusion. When diffusion is limited by cellular membranes, information on tissue microstructure can be acquired. Tractography, the visual display of the direction and magnitude of water diffusion, provides qualitative visualization of complex cellular architecture as well as quantitative diffusion metrics that appear to indirectly reflect physeal activity. In the growing bones, DTI depicts the columns of cartilage and new bone in the physeal-metaphyseal complex. In this "How I do It", we will highlight the value of DTI as a clinical tool by presenting DTI tractography of the physeal-metaphyseal complex of children and adolescents during normal growth, illustrating variation in qualitative and quantitative tractography metrics with age and skeletal location. In addition, we will present tractography from patients with physeal dysfunction caused by growth hormone deficiency and physeal injury due to trauma, chemotherapy, and radiation therapy. Furthermore, we will delineate our process, or "DTI pipeline," from image acquisition to data interpretation.

Impact of early memories and current experiences of warmth and safeness on adolescents' psychological distress.

A variable-centered and a person-centered approach were performed to examine the role of early memories of warmth and safeness (EMWS) and current experiences of warmth and safeness (CEWS) on depressive and anxious symptoms among adolescents from community and residential youth care (RYC) settings. Variable-centered results revealed EMWS were only indirectly (through CEWS) associated with depressive and anxious symptoms. Person-centered outcomes allowed to identify four different profiles based on EMWS and CEWS, which differed on depressive and anxious symptoms. EMWS and CEWS seem to play an important role in psychological distress during adolescence. CEWS seem to have a protective role on RYC adolescents' psychological distress, even when EMWS were poor.

The paradoxical position of nurses regarding euthanasia and its legalisation: A descriptive quantitative study.

AIMS AND OBJECTIVES: To learn about the attitudes of nurses working in the Andalusian Public Health System regarding euthanasia and its legalisation. BACKGROUND: Euthanasia often finds itself in the crosshairs of ethical and political debate on an international scale. Currently, the Spanish Organic Law 3/2021 of 24 March, 2021, recognises euthanasia as a fundamental right in Spain. It is of particular interest to know about the views, attitudes and stances that Andalusian nurses have of euthanasia as they are key players within the framework of euthanasia and administration of life-ending drugs. They play a central role in guiding patients through the euthanasia application process. DESIGN: Observational descriptive study. METHODS: A study of Andalusian Public Health System nurses was carried out using non-probability convenience sampling. 518 nurses with an average age of 44.75 years answered in a questionnaire that was distributed on an online platform. Socio-demographic and occupational variables were assessed, together with the Death Anxiety Scale and the Euthanasia Attitude Scale. A bivariate analysis and a multivariate linear regression model were performed. The STROBE checklist was used. RESULTS: The mean score obtained on the Euthanasia Attitude Scale was 75.95 (SD = 16.53). The mean score obtained on the Death Anxiety Scale was 7.56 (SD = 3.05). The variables age and work experience were negatively correlated with the total scores of the Euthanasia Attitude Scale and the categories 'Ethical considerations', 'Practical considerations' and 'Treasuring life'. On the other hand, there was a significant positive correlation between age and work experience and 'Spiritual beliefs' category. CONCLUSIONS: The current situation shows a worrying paradox. There is a stark difference between positive professional attitudes towards euthanasia and the desire to participate in its application. RELEVANCE TO CLINICAL PRACTICE: It is vital that educational and healthcare institutions make the necessary efforts to ensure that nurses develop sound moral judgement, displaying the moral conscience and ethical commitment required of this established profession. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

SO2F2-Mediated N-Alkylation of Imino-Thiazolidinones.

The N-alkylation of ambident and weakly nucleophilic imino-thiazolidinones has been developed via substitution with alkyl fluorosulfonates. These reactive electrophiles are obtained through the transformation of nontoxic, economic, and commercially available alcohol derivatives on exposure to SO2F2 gas. The use of electron-withdrawing groups and DMAc as solvent affords a (Z)- and N-endocyclic selectivity for the easy introduction of a variety of alkyl and polyfluoroalkyl chains.

Prophylactic thoracic duct obliteration and resection during esophagectomy: What is the impact on perioperative risks and long-term survival? A systematic review and meta-analysis.

There is no agreement whether prophylactic thoracic duct ligation (TDL), with or without resection, during esophagectomy for patients with cancer is beneficial. The effects of these procedures on postoperative complications and overall survival remain unclear. This systematic review included 16 articles. TDL did not influence short- and long-term outcomes. However, thoracic duct resection increased postoperative chylothorax and overall complications, with no improvement in survival.

Catalytic Nitrous Oxide Reduction with H2 Mediated by Pincer Ir Complexes.

Reduction of nitrous oxide (N2O) with H2 to N2 and water is an attractive process for the decomposition of this greenhouse gas to environmentally benign species. Herein, a series of iridium complexes based on proton-responsive pincer ligands (1-4) are shown to catalyze the hydrogenation of N2O under mild conditions (2 bar H2/N2O (1:1), 30 °C). Among the tested catalysts, the Ir complex 4, based on a lutidine-derived CNP pincer ligand having nonequivalent phosphine and N-heterocyclic carbene (NHC) side donors, gave rise to the highest catalytic activity (turnover frequency (TOF) = 11.9 h-1 at 30 °C, and 16.4 h-1 at 55 °C). Insights into the reaction mechanism with 4 have been obtained through NMR spectroscopy. Thus, reaction of 4 with N2O in tetrahydrofuran-d8 (THF-d8) initially produces deprotonated (at the NHC arm) species 5NHC, which readily reacts with H2 to regenerate the trihydride complex 4. However, prolonged exposure of 4 to N2O for 6 h yields the dinitrogen Ir(I) complex 7P, having a deprotonated (at the P-arm) pincer ligand. Complex 7P is a poor catalytic precursor in the N2O hydrogenation, pointing out to the formation of 7P as a catalyst deactivation pathway. Moreover, when the reaction of 4 with N2O is carried out in wet THF-d8, formation of a new species, which has been assigned to the hydroxo species 8, is observed. Finally, taking into account the experimental results, density functional theory (DFT) calculations were performed to get information on the catalytic cycle steps. Calculations are in agreement with 4 as the TOF-determining intermediate (TDI) and the transfer of an apical hydrido ligand to the terminal nitrogen atom of N2O as the TOF-determining transition state (TDTS), with very similar reaction rates for the mechanisms involving either the NHC- or the P-CH2 pincer methylene linkers.

Ammonia-Borane Dehydrogenation Catalyzed by Dual-Mode Proton-Responsive Ir-CNNH Complexes.

Metal complexes incorporating proton-responsive ligands have been proved to be superior catalysts in reactions involving the H2 molecule. In this contribution, a series of IrIII complexes based on lutidine-derived CNNH pincers containing N-heterocyclic carbene and secondary amino NHR [R = Ph (4a), tBu (4b), benzyl (4c)] donors as flanking groups have been synthesized and tested in the dehydrogenation of ammonia-borane (NH3BH3, AB) in the presence of substoichiometric amounts (2.5 equiv) of tBuOK. These preactivated derivatives are efficient catalysts in AB dehydrogenation in THF at room temperature, albeit significantly different reaction rates were observed. Thus, by using 0.4 mol % of 4a, 1.0 equiv of H2 per mole of AB was released in 8.5 min (turnover frequency (TOF50%) = 1875 h-1), while complexes 4b and 4c (0.8 mol %) exhibited lower catalytic activities (TOF50% = 55-60 h-1). 4a is currently the best performing IrIII homogeneous catalyst for AB dehydrogenation. Kinetic rate measurements show a zero-order dependence with respect to AB, and first order with the catalyst in the dehydrogenation with 4a (-d[AB]/dt = k[4a]). Conversely, the reaction with 4b is second order in AB and first order in the catalyst (-d[AB]/dt = k[4b][AB]2). Moreover, the reactions of the derivatives 4a and 4b with an excess of tBuOK (2.5 equiv) have been analyzed through NMR spectroscopy. For the former precursor, formation of the iridate 5 was observed as a result of a double deprotonation at the amine and the NHC pincer arm. In marked contrast, in the case of 4b, a monodeprotonated (at the pincer NHC-arm) species 6 is observed upon reaction with tBuOK. Complex 6 is capable of activating H2 reversibly to yield the trihydride derivative 7. Finally, DFT calculations of the first AB dehydrogenation step catalyzed by 5 has been performed at the DFT//MN15 level of theory in order to get information on the predominant metal-ligand cooperation mode.

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment.

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.

Neuronavigation-assisted bedside placement of bolt external ventricular drains in the intensive care setting: a technical note.

BACKGROUND: The insertion of bolt external ventricular drains (EVD) on the intensive care unit (ICU) has enabled rapid cranial cerebrospinal fluid (CSF) diversion. However, bolt EVDs tend to be perceived as a more challenging technique, particularly when dealing with small ventricles or when there is midline shift distorting the ventricular morphology. Furthermore, if neuronavigation guidance is felt to be necessary, this usually assumes a transfer to an operating theatre. In this technical note, we describe the use of electromagnetic neuronavigation for bolt EVD insertion on the ICU and assess the protocol's feasibility and accuracy. METHODS: Case series of neuronavigation-assisted bolt EVD insertion in ICU setting, using Medtronic Flat Emitter for StealthStation EM. RESULTS: Neuronavigation-guided bolt EVDs were placed at the bedside in n = 5 patients on ICU. Their widest frontal ventricular horn diameter in the coronal plane ranged from 11 to 20 mm. No procedural complications were encountered. Post-procedural CT confirmed the optimal placement of the EVDs. CONCLUSIONS: Electromagnetic neuronavigation is feasible at the ICU bedside and can assist the insertion of bolt EVDs in this setting. The preference for a bolt EVD to be inserted in ICU-as is standard practice at this unit-should not prohibit patients from benefitting from image guidance if required.