An assessment of radiology resident competency in identifying suppurative retropharyngeal lymphadenitis: an examination using the WIDI SIM platform.

BACKGROUND AND PURPOSE: Suppurative retropharyngeal lymphadenitis is a retropharyngeal space infection almost exclusively seen in the young (4-8 years old) pediatric population. It can be misdiagnosed as a retropharyngeal abscess, leading to unnecessary invasive treatment procedures. This retrospective study aims to assess radiology residents' ability to independently identify CT imaging findings and make a definitive diagnosis of suppurative retropharyngeal lymphadenitis in a simulated call environment. MATERIALS AND METHODS: The Wisdom in Diagnostic Imaging Emergent/Critical Care Radiology Simulation (WIDI SIM) is a computer-aided emergency imaging simulation proven to be a reliable method for assessing resident preparedness for independent radiology call. The simulation included 65 cases across various imaging modalities of varying complexity, including normal studies, with one case specifically targeting suppurative retropharyngeal adenitis identification. Residents' free text responses were manually scored by faculty members using a standardized grading rubric, with errors subsequently classified by type. RESULTS: A total of 543 radiology residents were tested in three separate years on the imaging findings of suppurative retropharyngeal lymphadenitis using the Wisdom in Diagnostic Imaging simulation web-based testing platform. Suppurative retropharyngeal lymphadenitis was consistently underdiagnosed by radiology residents being tested for call readiness irrespective of the numbers of years in training. On average, only 3.5% of radiology residents were able to correctly identify suppurative retropharyngeal lymphadenitis on a contrast-enhanced computed tomography (CT). CONCLUSIONS: Our findings underscore a potential gap in radiology residency training related to the accurate identification of suppurative retropharyngeal lymphadenitis, highlighting the potential need for enhanced educational efforts in this area.

Discovery of N-(5-amido-2-methylphenyl)-5-methylisoxazole-3-carboxamide as dual CSF-1R/c-Kit Inhibitors with improved stability and BBB permeability.

This study explores the potential of CSF-1R inhibitors as therapeutic agents for neurodegenerative diseases. CSF-1R, a receptor tyrosine kinase primarily expressed in macrophage lineages, plays a pivotal role in regulating various cellular processes. Recent research highlights the significance of CSF-1R inhibition in mitigating neuroinflammation, particularly in Alzheimer's disease, where microglial overactivation contributes to neurodegeneration. The research reveals a series of N-(5-amido-2-methylphenyl)-5-methylisoxazole-3-carboxamide CSF-1R inhibitors, where compounds 7d, 7e, and 9a exhibit outstanding inhibitory activities and selectivity, with IC50 values of 33, 31, and 64 nM, respectively. These most promising compounds in this series were profiled for cellular potency and subjected to in vitro pharmacokinetic profiling. These inhibitors exhibit minimal cytotoxicity, even at higher concentrations, and possess promising blood-brain barrier permeability, making them potential candidates for central nervous system diseases. The investigation into the in vitro ADME properties, including plasma and microsomal stability, reveals that these CSF-1R inhibitors maintain their structural integrity and plasma concentration. This resilience positions them for further development as therapeutic agents for neurodegenerative diseases.

Impact of Nutritional Status on Total Brain Tissue Volumes in Preterm Infants.

Preterm infants bypass the crucial in utero period of brain development and are at increased risk of malnutrition. We aimed to determine if their nutritional status is associated with brain tissue volumes at term equivalent age (TEA), applying recently published malnutrition guidelines for preterm infants. We performed a single center retrospective chart review of 198 infants < 30 weeks' gestation between 2018 and 2021. We primarily analyzed the relationship between the manually obtained neonatal MR-based brain tissue volumes with the maximum weight and length z-score. Significant positive linear associations between brain tissue volumes at TEA and weight and length z-scores were found (p < 0.05). Recommended nutrient intake for preterm infants is not routinely achieved despite efforts to optimize nutrition. Neonatal MR-based brain tissue volumes of preterm infants could serve as objective, quantitative and reproducible surrogate parameters of early brain development. Nutrition is a modifiable factor affecting neurodevelopment and these results could perhaps be used as reference data for future timely nutritional interventions to promote optimal brain volume.

Incidence of New-Onset Inflammatory Bowel Disease, Oral and Gastrointestinal Candidiasis, Herpes Zoster, Pulmonary Tuberculosis, and Major Cardiovascular Events in Patients with Moderate-to-Severe Psoriasis Exposed to Biologics.

The multicenter, retrospective cohort study was aimed at examining adverse events in biologic-treated patients with moderate-to-severe psoriasis by using a real-world database. Thus, we analyzed exposure-adjusted incidence rates for new-onset inflammatory bowel disease (IBD), oral and gastrointestinal candidiasis, pulmonary tuberculosis, herpes zoster, and major cardiovascular events (MACEs) in biologic-treated patients with moderate-to-severe psoriasis. Overall, 2085 patients were found to have been exposed to tumor necrosis factor (TNF)-α, interleukin (IL)-12/23, IL-17, and IL-23 inhibitors (n = 463, 540, 635, and 447, respectively). No patient developed new-onset IBD. The incidence rates of oral and gastrointestinal candidiasis were comparable between patients treated with IL-23 and IL-17 inhibitors (5.6 and 5.3 per 1000 PY, respectively). None treated with IL-17 or IL-23 inhibitors reported pulmonary tuberculosis. The incidence rate of herpes zoster was the highest in patients treated with TNF-α inhibitors (17.0 per 1000 PY), followed by IL-17, IL-23, and IL-12/23 inhibitors (13.3, 7.8, and 2.7 per 1000 PY, respectively). MACEs were not reported in patients treated with IL-17 inhibitors but were reported in those treated with TNF-α, IL-23, and IL-12/23 inhibitors (incidence: 5.6, 3.8, and 1.8 per 1000 PY, respectively). The study indicated favorable safety profiles of biologics in Korean patients with moderate-to-severe psoriasis.

Capacitance Contribution of NIH/3T3 Cells Existing on and between Electrodes of an Impedance Biosensor.

In this study, an impedance biosensor capable of real-time monitoring of the growth and drug reactions using NIH/3T3 cells was fabricated through a semiconductor process. With the fabricated impedance biosensor, the cell growth and drug reaction states are monitored in real-time, showing the validness of the developed biosensor. By using the developed impedance biosensor, we have investigated the capacitance contribution of NIH/3T3 cells existing on electrodes and between electrodes. To compare the capacitance value contributions of the cells on and between electrodes, wide- and narrow-gap electrode patterns are manufactured with 3.7 and 0.3 mm electrode gap spacings, respectively. From the detailed analysis, the capacitance contributions of NIH/3T3 cells existing on electrodes are estimated around less than 20 percent compared to the cells existing between electrodes. In other words, a minimized electrode area with maximized electrode spacing is the promising impedance biosensor design guide for accurate cell capacitance measurements.

Rhythm-based assessment and training for children with attention deficit hyperactivity disorder (ADHD): a feasibility study protocol.

Background: The timing-related deficits in individuals with attention deficit hyperactivity disorder (ADHD) contribute to the symptom-related difficulties and cognitive impairments. Current assessment and training measurement only target specific aspects of the timing ability, highlighting the need for more advanced tools to address timing deficits in ADHD. The aim of this study is to develop and validate a rhythm-based assessment and training (RAT) program, which intends to provide a comprehensive understanding of and enhancement to the time-related abilities of children with ADHD, thereby demonstrating its clinical efficacy. Methods: We will use randomized crossover trials in this study, with participants being randomly assigned to either start with the RAT and then proceed to cognitive training or start with cognitive training and then proceed to the RAT. Both groups will undergo pre- and post- evaluations. The evaluation will be administered immediately before and after the 4-week training period using diagnostic questionnaires, cognitive evaluation tools, and resting electroencephalography (EEG) measurements. Notably, EEG measurements will be conducted concurrently with the RAT evaluations. Discussion: This study develops and evaluates the feasibility and effectiveness of a RAT while using EEG measurements to elucidate the underlying therapeutic mechanism of auditory rhythm at varying levels of complexity. The study will investigate the potential of RAT as a supplementary or alternative approach for managing ADHD. The multifaceted data collected will yield valuable insights to customize training agendas based on individual developmental stages and prognoses.

Do the Clinical Characteristics of Lipomas Influence the Incision Length During Minimal Incision Extraction?

BACKGROUND: Minimal incision extraction technique is widely accepted for the surgical removal of lipomas, but no consensus for the incision length has been made yet. OBJECTIVE: To investigate the clinical characteristics of lipomas which affect the minimal incision length during the minimal incision extraction. METHODS: We retrospectively analyzed 50 patients who underwent minimal incision extraction for 55 medium-sized (3-5 cm) or large lipomas (> 5 cm) between March 2020 and May 2022. If the mass is not fully dissected, or adequate visual field for hemostasis was not provided through the initial one-third incision, the incision was extended to the minimal extent. RESULTS: There were 33 males and 17 females with a mean age of 53.5 ± 12.7 years. There was no statistical difference in the minimal % incision length, defined as [(incision length) / (tumor diameter)] x 100, between the medium-sized (n = 31) and large lipomas (n = 24). Lipomas of the long incision group (minimal % incision length ≥66.7%, n = 21) had a higher frequency of head and neck location than lipomas of the short incision group (minimal % incision length <66.7%, n = 34) (odds ratio = 14.5, P < .05). However, no association was found between the tumor diameter or depth and the minimal % incision length. The occurrence of postoperative complications was not associated also (P = .296). CONCLUSION: The minimal % incision length for lipoma removal does not show statistical difference between medium-sized and large lipomas, and is affected by its anatomical location, but not by tumor diameter or depth.

Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease.

Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC50 < 1.0 nM) and excellent selectivity over other protein kinases including isoforms JNK1 (>300 fold) and JNK2 (∼10 fold). Based on in vitro biological activity and DMPK properties, the lead compounds were selected for further in vivo studies. We confirmed that repeat administration of JNK3 inhibitors improved cognitive memory in APP/PS1 and the 3xTg mouse model. Overall, our results show that JNK3 could be a potential target protein for AD.

Novel 1,4,5,6-tetrahydrocyclopenta[d]imidazole-5-carboxamide-based JNK3 inhibitors: Design, synthesis, molecular docking, and therapeutic potential in neurodegenerative diseases.

JNK3 is a key factor driving the pathophysiology of neuronal apoptosis. Since demonstrating the therapeutic potential of JNK3 inhibitors in Alzheimer's disease, we aimed to broaden their chemical diversity for drug development. In continuation with our previous research, a series of compounds with the tetrahydrocyclopenta[d]imidazole scaffold as a core moiety was developed as JNK3 inhibitors based on in silico modeling analysis. The biochemical kinase assay results revealed that the JNK3 inhibitory effects and isoform selectivity of the compounds developed in this study were significantly higher than that of previously developed inhibitors. In particular, the IC50 values of compounds 18c, 19c, 22b, and 26c, which exhibited excelled isoform selectivity, against JNK3 were 0.716, 0.564, 0.379, and 0.779 nM, respectively, which were more potent than those of any known JNK3 inhibitors. Additionally, compounds 18c, 18c, 22b, and 22c effectively protected the neuronal cells against amyloid beta-induced apoptosis. Docking studies indicated that the tetrahydrocyclopenta[d]imidazole scaffold retained all the optimal interactions. Meanwhile, BBB PAMPA and ADME prediction suggested that the tested compounds had a favorable BBB permeability and pharmacokinetic profile. Therefore, the tetrahydrocyclopenta[d]imidazole scaffold is a promising candidate for developing JNK3 inhibitors. In particular, compound 22b is a potential starting point for the preclinical optimization of novel JNK3 inhibitors.

Physicochemical Properties of Yanggaeng with Added Tempeh Powder.

In this study, we investigated the physicochemical and antioxidative properties of the traditional Korean confectionery, Yanggaeng, when various amounts of tempeh powder (TP) were added. We replaced a portion of the white bean paste in Yanggaeng with TP at percentages of 0% (CON), 2% (TP2), 4% (TP4), and 6% (TP6) by total weight. The proximate composition results showed that TP6 exhibited the highest crude ash and crude protein contents, but its moisture content and carbohydrate content were the lowest compared to the CON. Tempeh addition altered the colorimetric properties by increasing the L* value, b* value, and browning index; however, tempeh addition did not alter the a* value. The results also showed that tempeh addition gradually decreased the pH of Yanggaeng. The Brix value was the highest in TP2; in TP4 and TP6, the Brix value gradually decreased, and these formulations exhibited lower Brix values than the CON. Furthermore, tempeh addition gradually induced antioxidative capacities, as evidenced by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities. The results of this study demonstrate that the addition of tempeh to Yanggaeng alters its physicochemical properties and antioxidative capacity.

Increased Brain-Derived Neurotrophic Factor Levels in Cerebrospinal Fluid During the Acute Phase in TBI-Induced Mechanical Allodynia in the Rat Model.

BACKGROUND: The present study aimed to develop a rat model for mechanical allodynia after traumatic brain injury (TBI) and to investigate the expression of brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) using this model. METHODS: A total of 180 rats were randomly allocated into three groups: a control group (group C), a sham-operated group (group S), and a controlled cortical impact induced TBI group (group T), 60 in each group. Von Frey test was performed to evaluate mechanical withdrawal thresholds. An enzyme-linked immunosorbent assay was performed to quantify BDNF level in CSF. RESULTS: The 50% withdrawal thresholds of group T were lower than those of group C and group S at all measuring points except for the preoperative period (P = 0.026, <0.001, and <0.001 for POD1, POD7, and POD14, respectively). The BDNF level of group T was higher than those of group C and group S at POD1 (P = 0.005). CONCLUSION: Upregulation of the BDNF expression in CSF was observed in rats who developed mechanical allodynia on the day after TBI. Based on our findings, to elucidate the relationship between TBI-induced neuropathic pain and BDNF expression in CSF, further research should be carried out through a multifaceted approach to a broad spectrum of pain behavior models.

Rational design and synthesis of 2-(1H-indazol-6-yl)-1H-benzo[d]imidazole derivatives as inhibitors targeting FMS-like tyrosine kinase 3 (FLT3) and its mutants.

Fms-like tyrosine kinase 3 (FLT3) has been verified as a therapeutic target for acute myeloid leukaemia (AML). In this study, we report a series of 2-(1H-indazol-6-yl)-1H-benzo[d]imidazol-5-yl benzamide and phenyl urea derivatives as potent FLT3 inhibitors based on the structural optimisation of previous FLT3 inhibitors. Derivatives were synthesised as benzamide 8a-k, 8n-z, and phenyl urea 8l-m, with various substituents. The most potent inhibitor, 8r, demonstrated strong inhibitory activity against FLT3 and FLT3 mutants with a nanomolar IC50 and high selectivity profiles over 42 protein kinases. In addition, these type II FLT3 inhibitors were more potent against FLT3 mutants correlated with drug resistance. Overall, we provide a theoretical basis for the structural optimisation of novel benzimidazole analogues to develop strong inhibitors against FLT3 mutants for AML therapeutics.

Incidental operating room fire from a breathing circuit warmer system: a case report.

BACKGROUND: An airway-associated fire in an operating room can have devastating consequences for patients. Breathing circuit warmers (BCWs) are widely used to provide heated and humidified anesthetic gases and eventually prevent hypothermia during general anesthesia. Herein, we describe a case of a BCW-related airway fire. CASE PRESENTATION: In this case, an electrical short within a BCW wire caused a fire inside the circuit. Simultaneously, the fire was extinguished, ventilation was stopped, and the endotracheal tube was disconnected from the BCW. The patient was exposed to the fire for less than 10 s, resulting in burns to the trachea and bronchi. Immediately after airway burn, bronchoscopy showed no edema or narrowing except for soot in the trachea and both main bronchus. After the inhalation burn event, prophylactic antibiotics, bronchodilator, mucolytics nebulizer, and corticosteroid nebulizer were started. On bronchoscopy 3 days after the inhalation burn, mucosal erythematous edema was observed and the inflammatory reaction worsened. The inflammatory reaction showed aggravation for up to 2 weeks, and then gradually recovered, and the epithelium and mucous membrane of the upper respiratory tract returned to normal after 4 weeks. Eventually, the patient recovered without long-term complications and was successfully discharged. CONCLUSIONS: This is the first report of a fire caused by BCW. We wanted to share our experience of how we responded to an airway-related fire in an OR and treated the patient. It cannot be overemphasized that the electrical medical appliance associated with the airways are fatal to the patient in the event of a fire, so caution should always be exercised.

Growth and Drug Interaction Monitoring of NIH 3T3 Cells by Image Analysis and Capacitive Biosensor.

Capacitive biosensors are manufactured on glass slides using the semiconductor process to monitor cell growth and cell-drug interactions in real time. Capacitance signals are continuously monitored for each 10 min interval during a 48 h period, with the variations of frequency from 1 kHz to 1 MHz. The capacitance values showed a gradual increase with the increase in NIH 3T3 cell numbers. After 48 h of growth, 6.67 µg/mL puromycin is injected for the monitoring of the cell-drug interaction. The capacitance values rapidly increased during a period of about 10 h, reflecting the rapid increase in the cell numbers. In this study, we monitored the state of cells and the cell-drug interactions using the developed capacitive biosensor. Additionally, we monitored the state of cell behavior using a JuLiTM Br&FL microscope. The monitoring of cell state by means of a capacitive biosensor is more sensitive than confluence measuring using a JuLiTM Br&FL microscope image. The developed capacitive biosensor could be applied in a wide range of bio-medical areas; for example, non-destructive real-time cell growth and cell-drug interaction monitoring.

Formation of a tris(catecholato) iron(III) complex with a nature-inspired cyclic peptoid ligand.

Siderophore-mimicking macrocyclic peptoids were synthesized. Peptoid 3 with intramolecular hydrogen bonds showed an optimally arranged primary coordination sphere leading to a stable catecholate-iron complex. The tris(catecholato) structure of 3-Fe(iii) was determined with UV-vis, fluorescence, and EPR spectroscopies and DFT calculations. The iron binding affinity was comparable to that of deferoxamine, with enhanced stability upon air exposure.

Helicity Modulation Improves the Selectivity of Antimicrobial Peptoids.

The modulation of conformational flexibility in antimicrobial peptides (AMPs) has been investigated as a strategy to improve their efficacy against bacterial pathogens while reducing their toxicity. Here, we synthesized a library of helicity-modulated antimicrobial peptoids by the position-specific incorporation of helix-inducing monomers. The peptoids displayed minimal variations in hydrophobicity, which permitted the specific assessment of the effect of conformational differences on antimicrobial activity and selectivity. Among the moderately helical peptoids, the most dramatic increase in selectivity was observed in peptoid 17, providing more than a 20-fold increase compared to fully helical peptoid 1. Peptoid 17 had potent broad-spectrum antimicrobial activity that included clinically isolated multi-drug-resistant pathogens. Compared to pexiganan AMP, 17 showed superior metabolic stability, which could potentially reduce the dosage needed, alleviating toxicity. Dye-uptake assays and high-resolution imaging revealed that the antimicrobial activity of 17 was, as with many AMPs, mainly due to membrane disruption. However, the high selectivity of 17 reflected its unique conformational characteristics, with differential interactions between bacterial and erythrocyte membranes. Our results suggest a way to distinguish different membrane compositions solely by helicity modulation, thereby improving the selectivity toward bacterial cells with the maintenance of potent and broad-spectrum activity.

Effect of side chain hydrophobicity and cationic charge on antimicrobial activity and cytotoxicity of helical peptoids.

Peptoids are peptidomimetic polymers that are resistant to proteolysis and less prone to immune responses; thus, they can provide a practical alternative to peptides. Among the various therapeutic applications that have been explored, cationic amphipathic peptoids have demonstrated broad-spectrum antibacterial activity, including activity towards drug-resistant bacterial strains. While their potency and activity spectrum can be manipulated by sequence variations, bacterial selectivity and systemic toxicity need to be improved for further clinical development. To this aim, we incorporated various hydrophobic or cationic residues to improve the selectivity of the previously developed antibacterial peptoid 1. The analogs with hydrophobic residues demonstrated non-specific cytotoxicity, while those with an additional cationic residue showed improved selectivity and comparable antibacterial activity. Specifically, compared to 1, peptoid 7 showed much lower hemolysis and cytotoxicity, while maintaining the antibacterial activity. Therefore, we believe that peptoid 7 has the potential to serve as a promising alternative to current antimicrobial therapies.