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Child's Nervous System : ChNS :... Jul 2024Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent,...
Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.
PubMed: 38960918
DOI: 10.1007/s00381-024-06502-9 -
Current Microbiology Jul 2024Imidazole-chalcone compounds are recognised for their broad-spectrum antimicrobial properties. Probiotic-friendly, selective new-generation antimicrobials prove to be...
Imidazole-chalcone compounds are recognised for their broad-spectrum antimicrobial properties. Probiotic-friendly, selective new-generation antimicrobials prove to be more efficient in combating gastrointestinal system pathogens. The aim of this study is to identify imidazole-chalcone derivatives that probiotics tolerate and evaluate their in vitro synergistic antimicrobial effects on pathogens. In this study, fifteen previously identified imidazole-chalcone derivatives were analyzed for their in vitro antimicrobial properties against gastrointestinal microorganisms. Initially, the antimicrobial activity of pathogens was measured using the agar well diffusion method, while the susceptibility of probiotics was determined by microdilution. The chosen imidazole-chalcone derivatives were assessed for synergistic effects using the checkerboard method. Four imidazole-chalcone derivatives to which probiotic bacteria were tolerant exhibited antibacterial and antifungal activity against the human pathogens tested. To our knowledge, this study is the first to reveal the fractional inhibitory concentration (FIC) of combinations of imidazole-chalcone derivatives. Indeed, the minimum inhibitory concentrations (MIC) for morpholinyl- (ZDO-3f) and 4-ethylpiperazinyl- (ZDO-3 m) imidazole-chalcones were notably low when tested against E. coli and B. subtilis, with values of 31.25 μg/mL and 125 μg/mL, respectively. The combination of morpholinyl- and 4-ethylpiperazinyl derivatives demonstrated an indifferent effect against E. coli, but an additive effect was observed for B. subtilis. Additionally, it was observed that imidazole-chalcone derivatives did not exhibit any inhibitory effects on probiotic organisms like Lactobacillus fermentum (CECT-5716), Lactobacillus rhamnosus (GG), and Lactobacillus casei (RSSK-591). This study demonstrates that imidazole-chalcone derivatives that are well tolerated by probiotics can potentially exert a synergistic effect against gastrointestinal system pathogens.
Topics: Probiotics; Imidazoles; Microbial Sensitivity Tests; Drug Synergism; Chalcone; Anti-Bacterial Agents; Chalcones; Gastrointestinal Tract; Humans; Bacteria; Antifungal Agents
PubMed: 38960917
DOI: 10.1007/s00284-024-03788-5 -
Journal of Gastric Cancer Jul 2024The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with...
PURPOSE
The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type.
MATERIALS AND METHODS
We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications.
RESULTS
Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months.
CONCLUSIONS
Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.
Topics: Humans; Male; Adenocarcinoma; Female; Stomach Neoplasms; Middle Aged; Esophagogastric Junction; Retrospective Studies; Aged; Esophageal Neoplasms; Prognosis; Gastrectomy; Adult; Survival Rate; Esophagectomy; Aged, 80 and over
PubMed: 38960886
DOI: 10.5230/jgc.2024.24.e20 -
Academic Radiology Jul 2024Hyperpolarized xenon (Xe) MRI is a noninvasive method to assess pulmonary structure and function. To measure lung microstructure, diffusion-weighted imaging-commonly the...
RATIONALE AND OBJECTIVES
Hyperpolarized xenon (Xe) MRI is a noninvasive method to assess pulmonary structure and function. To measure lung microstructure, diffusion-weighted imaging-commonly the apparent diffusion coefficient (ADC)-can be employed to map changes in alveolar-airspace size resulting from normal aging and pulmonary disease. However, low signal-to-noise ratio (SNR) decreases ADC measurement certainty, and biases ADC to spuriously low values. Further, these challenges are most severe in regions of the lung where alveolar simplification or emphysematous remodeling generate abnormally high ADCs. Here, we apply Global Local Higher Order Singular Value Decomposition (GLHOSVD) denoising to enhance image SNR, thereby reducing uncertainty and bias in diffusion measurements.
MATERIALS AND METHODS
GLHOSVD denoising was employed in simulated images and gas phantoms with known diffusion coefficients to validate its effectiveness and optimize parameters for analysis of diffusion-weighted Xe MRI. GLHOSVD was applied to data from 120 subjects (34 control, 39 cystic fibrosis (CF), 27 lymphangioleiomyomatosis (LAM), and 20 asthma). Image SNR, ADC, and distributed diffusivity coefficient (DDC) were compared before and after denoising using Wilcoxon signed-rank analysis for all images.
RESULTS
Denoising significantly increased SNR in simulated, phantom, and in-vivo images, showing a greater than 2-fold increase (p < 0.001) across diffusion-weighted images. Although mean ADC and DDC remained unchanged (p > 0.05), ADC and DDC standard deviation decreased significantly in denoised images (p < 0.001).
CONCLUSION
When applied to diffusion-weighted Xe images, GLHOSVD improved image quality and allowed airspace size to be quantified in high-diffusion regions of the lungs that were previously inaccessible to measurement due to prohibitively low SNR, thus providing insights into disease pathology.
PubMed: 38960843
DOI: 10.1016/j.acra.2024.06.029 -
Journal of Clinical and Experimental... Jul 2024Alemtuzumab is recommended as first-line and second-line therapies for T-cell prolymphocytic leukemia (T-PLL). This study retrospectively evaluated the efficacy and...
Alemtuzumab is recommended as first-line and second-line therapies for T-cell prolymphocytic leukemia (T-PLL). This study retrospectively evaluated the efficacy and safety of alemtuzumab in nine Japanese patients with T-PLL at five participating institutions who were treated between January 2015 and August 2023. The median age at first administration of alemtuzumab was 72 years (range, 39 to 78). Two patients were treatment naïve, and seven had been treated with a median of one (range, 1 to 3) prior systemic therapy. Six patients were refractory to their most recent therapy. Three patients completed 12 weeks of treatment. The overall response rate and the complete response (CR) rate were 78% and 11%, respectively. Among the six patients who achieved a partial response, two achieved clinical CR but did not undergo bone marrow examination. One patient also achieved clinical CR but did not undergo CT or bone marrow examination for response evaluation. The median progression-free survival time was 8.1 months (95% confidence interval, 0.9 to 18.6). Three patients received readministration of alemtuzumab monotherapy after disease progression. There were no treatment-related deaths. The grade 3 or 4 nonhematologic adverse events included infusion reaction (grade 3, n = 2), cytomegalovirus reactivation (grade 3, n = 2), and pulmonary edema (grade 3, n = 1). One patient experienced Epstein‒Barr virus-positive diffuse large B-cell lymphoma 15 months after the last dose of alemtuzumab. These results confirm that the efficacy and safety of alemtuzumab monotherapy in Japanese patients are comparable to those previously reported.
PubMed: 38960696
DOI: 10.3960/jslrt.24028 -
Internal Medicine (Tokyo, Japan) Jul 2024Herein, we report a case of 72-year-old man who had L858R EGFR-mutated lung adenocarcinoma. Chest computed tomography revealed a large lung mass that had completely...
Herein, we report a case of 72-year-old man who had L858R EGFR-mutated lung adenocarcinoma. Chest computed tomography revealed a large lung mass that had completely replaced the right upper lobe. Although the mass dramatically shrank after initiating chemotherapy, non-malignant pleural effusion appeared. Because diffuse pleural thickening and shrinking of the thoracic cage gradually became apparent, the patient was diagnosed with trapped lung. Despite the stabilization of his lung cancer, he experienced severe dyspnea and significant weight loss, ultimately leading to a decreased performance status. Chest physicians should recognize that trapped lung can develop as a sequela of dramatic tumor shrinkage in lung cancer.
PubMed: 38960688
DOI: 10.2169/internalmedicine.3704-24 -
Internal Medicine (Tokyo, Japan) Jul 2024Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytosis. Although 20% of patients with RDD have spontaneous remission, some cases with central...
Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytosis. Although 20% of patients with RDD have spontaneous remission, some cases with central nervous system (CNS) involvement require surgery or systemic treatment. We encountered a case of RDD in which hypertrophic pachymeningitis was diffuse, eliminating the need for surgical intervention. A 72-year-old Japanese man was diagnosed with RDD based on pathological lymph node findings. Repeated intravenous methylprednisolone (IVMP) administration resolved and stabilized the hypertrophic pachymeningitis without any sequelae. If surgery or anticancer medications are contraindicated, repeated IVMP may be a good therapeutic option for CNS-associated RDD.
PubMed: 38960687
DOI: 10.2169/internalmedicine.3884-24 -
Journal of Psychiatry & Neuroscience :... 2024Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have...
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults.
METHODS
We applied diffusion-weighted spherical deconvolution tractography to dissect the cerebellar peduncles of male adults with ADHD (including those who did or did not respond to methylphenidate, based on at least 30% symptom improvement at 2 months) and controls. We investigated differences in tract metrics between controls and the whole ADHD sample and between controls and treatment-response groups using sensitivity analyses. Finally, we analyzed the association between the tract metrics and cliniconeuropsychological profiles.
RESULTS
We included 60 participants with ADHD (including 42 treatment responders and 18 nonresponders) and 20 control participants. In the whole ADHD sample, MCP fractional anisotropy (FA; = 3.24, = 0.002) and hindrance modulated orientational anisotropy (HMOA; = 3.01, = 0.004) were reduced, and radial diffusivity (RD) in the right ICP was increased ( = -2.84, = 0.006), compared with controls. Although case-control differences in MCP FA and HMOA, which reflect white-matter microstructural organization, were driven by both treatment response groups, only responders significantly differed from controls in right ICP RD, which relates to myelination ( = 3.14, = 0.003). Hindrance modulated orientational anisotropy of the MCP was significantly positively associated with hyperactivity measures.
LIMITATIONS
This study included only male adults with ADHD. Further research needs to investigate potential sex- and development-related differences.
CONCLUSION
These results support the role of the cerebellar networks, especially of the MCP, in adult ADHD pathophysiology and should encourage further investigation.
CLINICAL TRIAL REGISTRATION
NCT03709940.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Male; Adult; Methylphenidate; Diffusion Tensor Imaging; Cerebellum; Central Nervous System Stimulants; Young Adult; Anisotropy; White Matter; Neural Pathways; Nerve Net; Case-Control Studies
PubMed: 38960626
DOI: 10.1503/jpn.230146 -
American Journal of Preventive Medicine Jul 2024The number of US adults who own and carry a firearm for self-defense is rising. Research has established that owning or carrying a firearm increases the risk of injury...
INTRODUCTION
The number of US adults who own and carry a firearm for self-defense is rising. Research has established that owning or carrying a firearm increases the risk of injury and death for firearm owners and the people in their lives. The present study sought to better understand this paradox by estimating associations of perceived specific and diffuse threats with firearm behaviors among US adults.
METHODS
The team used data from the 2023 National Firearm Attitudes and Behaviors Study, a nationally representative cross-sectional survey of US adults. Binary and ordinal logistic regression estimated associations of perceived specific (fear of attack in the community, fear of someone breaking into the home) and diffuse threats (belief in a dangerous world) with firearm ownership and carriage frequency, overall and stratified by gender. Adjusted models controlled for violence exposures and demographic characteristics. The team conducted analyses in 2024.
RESULTS
Among all US adults, the perceived specific threat of someone breaking into the home was associated with firearm ownership (aORs: 1.09[0.98, 1.23]). Among firearm-owning adults, the diffuse threat of belief in a dangerous world was associated with firearm carriage frequency (1.11[0.98, 1.25]). Both associations persisted among men (aORs=1.27[1.05-1.52] and 1.15[1.01-1.31], respectively), and analyses found no associations between perceived threats and firearm behaviors among women.
CONCLUSIONS
Perceived threats are associated with firearm behaviors among US men, even after accounting for the actual violence they report experiencing or witnessing.
PubMed: 38960293
DOI: 10.1016/j.amepre.2024.06.024 -
European Journal of Pharmaceutics and... Jul 2024We have used pulsed field gradient (PFG)-NMR diffusion experiments, also known as DOSY, in combination with small angle X-ray scattering measurements to investigate...
Molecular localization and exchange kinetics in pharmaceutical liposome and mRNA lipoplex nanoparticle products determined by small angle X-ray scattering and pulsed field gradient NMR diffusion measurements.
We have used pulsed field gradient (PFG)-NMR diffusion experiments, also known as DOSY, in combination with small angle X-ray scattering measurements to investigate structure and molecular exchange dynamics between pharmaceutical lipid nanoparticles and the bulk phase. Using liposomes and lipoplexes formed after complexation of the liposomes with messenger mRNA as test systems, information on dynamics of encapsulated water molecules, lipids and excipients was obtained. The encapsulated fraction, having a diffusivity similar to that of the liposomes, could be clearly identified and quantified by the NMR diffusion measurements. The unilamellar liposome membranes allowed a fast exchange of water molecules, while sucrose, used as an osmolyte and model solute, showed very slow exchange. Upon interactions with mRNA a topological transition from a vesicular to a lamellar organization took place, where the mRNA was inserted in repeating lipid bilayer stacks. In the lipoplexes, a small fraction of tightly bound water molecules was present, with a diffusivity that was influenced by the additional presence of sucrose. This extended information on dynamic coherencies inside pharmaceutical nanoparticle products, provided by the combined application of SAXS and PFG-NMR diffusion measurements, can be valuable for evaluation of quality and comparability of nanoscaled pharmaceuticals.
PubMed: 38960290
DOI: 10.1016/j.ejpb.2024.114380