Post-Transcriptional Induction of the Antiviral Host Factor GILT/IFI30 by Interferon Gamma.

Gamma-interferon-inducible lysosomal thiol reductase (GILT) plays pivotal roles in both adaptive and innate immunities. GILT exhibits constitutive expression within antigen-presenting cells, whereas in other cell types, its expression is induced by interferon gamma (IFN-γ). Gaining insights into the precise molecular mechanism governing the induction of GILT protein by IFN-γ is of paramount importance for adaptive and innate immunities. In this study, we found that the 5' segment of GILT mRNA inhibited GILT protein expression regardless of the presence of IFN-γ. Conversely, the 3' segment of GILT mRNA suppressed GILT protein expression in the absence of IFN-γ, but it loses this inhibitory effect in its presence. Although the mTOR inhibitor rapamycin suppressed the induction of GILT protein expression by IFN-γ, the expression from luciferase sequence containing the 3' segment of GILT mRNA was resistant to rapamycin in the presence of IFN-γ, but not in its absence. Collectively, this study elucidates the mechanism behind GILT induction by IFN-γ: in the absence of IFN-γ, GILT mRNA is constitutively transcribed, but the translation process is hindered by both the 5' and 3' segments. Upon exposure to IFN-γ, a translation inhibitor bound to the 3' segment is liberated, and a translation activator interacts with the 3' segment to trigger the initiation of GILT translation.

[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR CHILDREN WITH FOOD ALLERGY REPORTED BY PARENTS].

OBJECTIVE: No questionnaire aimed at evaluating the quality of life (QOL) of children with food allergies has been developed in Japan. Therefore, this study was aimed at developing a Japanese version of a QOL questionnaire for children with food allergies to be responded to by their parents. METHODS: A 59-question primary questionnaire was developed for parents of children aged 0 to 15 years who had food allergies. Responses to the primary questionnaire were collected, and question items were reduced using factor analysis. Then, a secondary questionnaire consisting of nine questions was developed. The secondary questionnaire, the Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF), and the parent-reported questionnaire on health-related quality of life in children and adolescents (KINDL) were administered to parents of children aged 3 to 15 years who had food allergies. RESULTS: Overall, 342 parents completed all questionnaires. The QOL scores of the secondary questionnaire were significantly correlated to those of the FAQLQ-PF (r=0.765) and weakly correlated to those of the KINDL (r=-0.358). In addition, QOL scores were significantly worse in patients with a history of anaphylaxis, who were prescribed an adrenaline auto-injector, and who were allergic to hen's eggs, cow milk, or wheat. CONCLUSION: We were able to develop a parent-reported validated Japanese version of the QOL questionnaire for children with food allergies.

Follow-up care compliance among patients diagnosed with unruptured intracranial aneurysms.

OBJECTIVES: Periodic imaging follow-up for patients with unruptured intracranial aneurysms (UIA) is crucial, as studies indicate higher rupture risk with aneurysm growth. However, few studies address patient adherence to follow-up recommendations. This study aims to identify compliance rates and factors influencing follow-up adherence. METHODS: Patients with a UIA were identified from our institution's database from 2011-2021. Follow-up imaging (CT/MR Angiogram) was advised at specific intervals. Patients were categorized into compliant and non-compliant groups based on first-year compliance. Factors contributing to compliance were assessed through multivariate logistic regression. Phone interviews were conducted with non-compliant patients to understand reasons for non-adherence. RESULTS: Among 923 UIA diagnosed patients, 337 were randomly selected for analysis. The median follow-up period was 1.4 years, with a 42% first-year compliance rate. The mean aneurysm size was 3.3 mm. Five patients had a rupture during follow-up, of which 4 died. Compared with patients consulting specialists at the initial diagnosis, those seen by non-specialists exhibited lower compliance (OR 0.25, p < 0.001). Loss to follow-up was greatest during transition from emergency service to specialist appointments. Patients who spoke languages other than English exhibited poorer compliance than those speaking English (OR 0.20, p = 0.01). CONCLUSIONS: Significant amounts of UIA patients at low rupture risk were lost to follow-up before seeing UIA specialists. Main non-compliance factors include inadequate comprehension of follow-up instructions, poor care transfer from non-specialists to specialist, and insurance barriers.

Cation-Stacking Approach Enabling Interconversion between Bis(xanthylium) and its Reduced Species.

Cyclophane-type dications with two units of xanthylium were designed, with the expectation that intramolecular interaction between cation units could induce changes in absorption and redox behavior. The desired dications were synthesized via the macrocyclic diketone as a key intermediate, which was efficiently obtained by a stepwise etherification. X-ray and UV/Vis measurements revealed that the cyclophane-type dications adopt a stacking structure in both the crystal and solution. Due to the intramolecular interaction caused by π-π stacking of the xanthylium units, a considerable blue shift compared to the corresponding monocations and a two-stage one-electron reduction process were observed in the dications. Furthermore, upon electrochemical reduction of dications, the formation of biradicals via radical cation species was demonstrated by UV/Vis spectroscopy with several isosbestic points at both stages. Therefore, the cation-stacking approach is a promising way to provide novel properties due to perturbation of their molecular orbitals and to stabilize the reduced species even though they have open-shell characters.

Glycemic control during TB treatment among Filipinos: The Starting Anti-Tuberculosis Treatment Cohort Study.

Poor TB treatment outcomes are observed in patients with type 2 diabetes mellitus (DM) comorbidity and glycemic control throughout treatment may play a role. The objective of this study was to investigate glycemic control longitudinally among Filipino adults undergoing TB treatment using mixed-effects linear and logistic regression. Analyses were conducted in 188 DM-TB patients out of 901 enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, with a median baseline glycosylated hemoglobin (HbA1c) of 8.2% (range 4.5-13.3%). Previous versus new DM diagnosis was associated with higher mean HbA1c (worse glycemic control) during treatment, with a smaller effect amongst those with central obesity (coefficient 0.80, 95% confidence interval [CI] 0.26, 1.57, P = 0.043) than amongst those without central obesity (coefficient 3.48, 95% CI 2.16, 4.80, P<0.001). In those with a new DM diagnosis, central obesity was associated with higher blood glucose (coefficient 1.62, 95% CI 0.72, 2.53, P = 0.009). Of 177 participants with ≥2 HbA1c results, 40% had uncontrolled glycemia (≥2 HbA1c results ≥8%). Of 165 participants with ≥3 HbA1c results, 29.9% had consistently-controlled glycemia, 15.3% had initially-uncontrolled glycemia, and 18.6% had consistently-uncontrolled glycemia. Previous versus new DM diagnosis and glucose-lowering medication use versus no use were associated with having uncontrolled versus controlled glycemia (adjusted odds ratio [aOR] 2.50 95%CI 1.61, 6.05, P = 0.042; aOR 4.78 95% CI 1.61,14.23, P<0.001) and more likely to have consistently-uncontrolled versus consistently-controlled glycemia (adjusted relative risk ratio [aRRR] 5.14 95% CI 1.37, 19.20, P = 0.015; aRRR 10.24 95% CI 0.07, 0.95, P = 0.003). Relapse cases of TB were less likely than new cases to have uncontrolled (aOR 0.20 95%CI 0.06, 0.63, P = 0.031) or consistently-uncontrolled (aRRR 0.25 95%CI 0.07, 0.95, P = 0.042) versus controlled glycemia. Those with long-term DM, suggested by previous diagnosis, glucose-lowering medication use and possibly central obesity, may require additional support to manage blood glucose during TB treatment.

Thermal Equilibrium Between Quinoid/Biradical Forms Enhancing Electrochemical Amphotericity.

Upon dibenzo annulation on Thiele's hydrocarbon (tetraphenyl-p-quinodimethane), the quinoid form and the biradical form adopt quite different geometries, and thus are no longer resonance structures. When these two forms can interconvert rapidly due to the small energy barrier (ΔG≠), the equilibrated mixture contains both forms in a ratio that is determined by the energy difference (ΔGo) between the two forms. For a series of tetrakis[5-(4-methoxyphenyl)-2-thienyl]-substituted derivatives, the more stable quinoid form and the metastable biradical form coexist in solution as an equilibrated mixture due to small ΔG≠ (<15 kcal mol-1) and ΔGo (1-4 kcal mol-1), in which the proportion of the two forms can be regulated by temperature. Since the biradical form can undergo easy two-electron (2e) oxidation to the corresponding dications as well as easy 2e-reduction to the dianions, it exhibits very high electrochemical amphotericity. This character with a record-small span for not only the first oxidation and reduction potentials but also the second those, [E1 sum≈E2 sum=E2 ox-E2 red=ca. 1.4 V], is attained through thermally enhanced conversion to the biradical form from the corresponding quinoid form, the latter of which is less amphoteric due to higher Eox and lower Ered values.

Impact of Target Artery Size on the Performance of Aspiration Thrombectomy: Insights from a Swine Model with Real-Time Visualization.

A novel swine model was developed to investigate the underlying reasons for the failure of aspiration thrombectomy. The model allows direct visualization of the target artery during thrombectomy in vessels of different sizes. The behavior of the target artery undergoing aspiration thrombectomy was recorded with high-resolution digital microscopy and fluoroscopic visualization, providing valuable insight into how the different sizes of treated arteries affect the effectiveness of mechanical thrombectomy.

Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines.

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

Stimuli-Induced Controls of Magnetic and Photophysical Properties Using Liquescent Open-Shell Ionic Molecular Systems.

This study explores the remarkable properties of liquescent open-shell ionic molecular systems, emphasizing the magnetic and photophysical characteristics arising from their associated structures in the condensed state under various conditions. Well-investigated open-shell molecules, namely, phenothiazine, dihydrophenazine, and tetrathiafulvalene radical cations, and bis(malononitriledithiolato)nickel(III) anionic complexes were examined, and the concept of liquescent open-shell ionic molecular systems was devised. Transformations in their associated structures are induced by external stimuli, resulting in significant variations in their physical properties. These experimental findings open new avenues for exploring and applying stimuli-responsive molecule-based materials.

Needlestick-Stimulation-Induced Conversion of Short-Wave Infrared-Light Transparency Using a Liquescent Radical Anion.

A liquescent salt consisting of a 7,7,8,8-tetracyanquinodimethane (TCNQ) radical anion and a tetra-n-decylammonium ion, 1+•TCNQ•-, exhibits rapid changes in the short-wave infrared (SWIR) light transparency at 1000-1400 nm upon the application of a one-shot needlestick-stimulus. Radical anion salt 1+•TCNQ•- transforms from a blue solid to a green liquid at 90 °C without decomposition under aerated conditions, and remains in the liquid state upon cooling to 70 °C. After applying pressure with a needlestick on a cover glass at 70 °C, the liquid transforms rapidly into the solid state over a timescale of seconds across a centimeter scale of area. Along with the liquid-solid transition, the SWIR-light transparency at 1200 nm completely switches from the "on" to the "off" states. Experimental results, such as electronic spectra and crystal structure analysis, indicates that the SWIR-light absorption in the solid state is due to the existence of a slipped-stacking π-dimer structure for TCNQ•-. The rapid rearrangement is induced by the formation of the π-dimer structures from the monomers of TCNQ•- and the subsequent generations of the solid-state seed.

High-throughput screening of small-molecules libraries identified antibacterials against clinically relevant multidrug-resistant A. baumannii and K. pneumoniae.

BACKGROUND: The current pipeline for new antibiotics fails to fully address the significant threat posed by drug-resistant Gram-negative bacteria that have been identified by the World Health Organization (WHO) as a global health priority. New antibacterials acting through novel mechanisms of action are urgently needed. We aimed to identify new chemical entities (NCEs) with activity against Klebsiella pneumoniae and Acinetobacter baumannii that could be developed into a new treatment for drug-resistant infections. METHODS: We developed a high-throughput phenotypic screen and selection cascade for generation of hit compounds active against multidrug-resistant (MDR) strains of K. pneumoniae and A. baumannii. We screened compound libraries selected from the proprietary collections of three pharmaceutical companies that had exited antibacterial drug discovery but continued to accumulate new compounds to their collection. Compounds from two out of three libraries were selected using "eNTRy rules" criteria associated with increased likelihood of intracellular accumulation in Escherichia coli. FINDINGS: We identified 72 compounds with confirmed activity against K. pneumoniae and/or drug-resistant A. baumannii. Two new chemical series with activity against XDR A. baumannii were identified meeting our criteria of potency (EC50 ≤50 µM) and absence of cytotoxicity (HepG2 CC50 ≥100 µM and red blood cell lysis HC50 ≥100 µM). The activity of close analogues of the two chemical series was also determined against A. baumannii clinical isolates. INTERPRETATION: This work provides proof of principle for the screening strategy developed to identify NCEs with antibacterial activity against multidrug-resistant critical priority pathogens such as K. pneumoniae and A. baumannii. The screening and hit selection cascade established here provide an excellent foundation for further screening of new compound libraries to identify high quality starting points for new antibacterial lead generation projects. FUNDING: BMBF and GARDP.

[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR PARENT BURDEN OF CHILDREN WITH FOOD ALLERGY].

OBJECTIVE: Quality of life (QOL) questionnaires for parents of children with food allergies have been developed in the United States and Europe. However, no original Japanese QOL questionnaire has been developed till date. We aimed to develop an original questionnaire to evaluate the QOL in parents of children with food allergies in Japan. METHODS: We collected QOL-related questions from parents of children with food allergies aged 0-15 years, and created a primary questionnaire. Responses to the primary questionnaire were obtained from the parents again, and question items were reduced using factor analysis to create a secondary questionnaire comprising eight items. In addition to the secondary questionnaire, responses to the Food Allergy QOL Questionnaire-Parent Form (FAQLQ-PF) Japanese version, Parent reported Health-Related QOL in children and adolescents (KINDL) and Health-related QOL (SF-8) were obtained from parents to assess the validity of the secondary questionnaire. RESULTS: A total of 407 parents completed all questionnaires. The secondary questionnaire scores were positively correlated with those of FAQLQ-PF and weakly negatively correlated with the KINDL and SF-8 mental component summary scores. Parents of children with food allergies with ≥3 culprit foods or severe reactions to daily foods, a history of anaphylaxis, and those carrying adrenaline autoinjectors scored higher and had lower QOL. CONCLUSION: The developed original questionnaire is a valid QOL questionnaire for Parents of children with food allergies.

Use of a large-bore 088 intracranial access support catheter for delivery of large intracranial devices: case series with the TracStar LDP in 125 cases.

BACKGROUND: The delivery of neuroendovascular devices requires a robust proximal access platform. This demand has previously been met with a 6Fr long sheath (8Fr guide) that is placed in the proximal internal carotid artery (ICA) or vertebral artery segments. We share our experience with the first 0.088 inch 8Fr guide catheter designed for direct intracranial access. METHODS: We retrospectively reviewed a prospectively maintained IRB-approved institutional database of the senior authors to identify all cases where the TracStar Large Distal Platform (LDP) was positioned within the intracranial vasculature, defined as within or distal to the petrous ICA, vertebral artery (V3) segments, or transverse sinus. Technical success was defined as safe placement of the TracStar LDP within or distal to the described distal vessel segments with subsequent complication-free device implantation. RESULTS: Over the 41-month study period from January 2020 to June 2023, 125 consecutive cases were identified in whom the TracStar LDP was navigated into the intracranial vasculature for triaxial delivery of large devices, 0.027 inch microcatheter and greater, for aneurysm treatment (n=108, 86%), intracranial angioplasty/stenting (n=15, 12%), and venous sinus stenting (n=2, 1.6%). All cases used a direct select catheter technique for initial guide placement (no exchange). Posterior circulation treatments occurred in 14.4% (n=18) of cases. Technical success was achieved in 100% of cases. No vessel dissections occurred in any cases. CONCLUSION: The TracStar LDP is an 0.088 inch 8Fr guide catheter that can establish direct intracranial access with an acceptable safety profile. This can be achieved in a wide range of neurointerventional cases with a high rate of technical success.

Temperature-Dependent Modulation of Short-Wave-Infrared Light Transparency Based on Associated Structures of a Liquescent Nickel(III) Complex.

A liquescent bis(malononitriledithiolato)nickel(III) complex with a bis(methoxyethyl)imidazolium cation, 1[Ni(mnt)2 ], exhibits three-stage thermochromic modulation of transparency/absorption in the short-wave-infrared (SWIR) region (1000-2500 nm), driven by associated structural changes. Upon heating, the electronic spectra of 1[Ni(mnt)2 ] in the SWIR region shift to shorter wavelengths accompanying with the solid-liquid phase transition at 76 °C. Further heating to over 109 °C induces a second transition of the electronic spectra, characterized by a blue-shift of the SWIR absorption in the liquid phase. The results of temperature-dependent electronic spectra and magnetic susceptibility indicated that the thermochromic changes can be attributed to the two-step dissociation of the associated structures of [Ni(mnt)2 ]- , occurring during the solid-liquid phase transition and the shift of dimer-monomer equilibrium in the liquid state. These changes can be visualized using an SWIR imaging camera under appropriate SWIR lights.

Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review.

Noonan syndrome-related myeloproliferative disorder (NS/MPD) and juvenile myelomonocytic leukemia (JMML) are rare MPDs that occur in young children. We herein report a case of NS/MPD with neonatal onset. The patient had a characteristic appearance and high monocyte count in the peripheral blood and bone marrow. Genetic testing showed the E139D mutation in PTPN11 ; however, the patient did not meet all the diagnostic criteria for JMML, and we thus diagnosed him with NS/MPD. Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.

Rescue therapy after thrombectomy for large vessel occlusion due to underlying atherosclerosis: review of literature.

In this review article, we summarized the current advances in rescue management for reperfusion therapy of acute ischemic stroke from large vessel occlusion due to underlying intracranial atherosclerotic stenosis (ICAS). It is estimated that 24-47% of patients with acute vertebrobasilar artery occlusion have underlying ICAS and superimposed in situ thrombosis. These patients have been found to have longer procedure times, lower recanalization rates, higher rates of reocclusion and lower rates of favorable outcomes than patients with embolic occlusion. Here, we discuss the most recent literature regarding the use of glycoprotein IIb/IIIa inhibitors, angioplasty alone, or angioplasty with stenting for rescue therapy in the setting of failed recanalization or instant/imminent reocclusion during thrombectomy. We also present a case of rescue therapy post intravenous tPA and thrombectomy with intra-arterial tirofiban and balloon angioplasty followed by oral dual antiplatelet therapy in a patient with dominant vertebral artery occlusion due to ICAS. Based on the available literature data, we conclude that glycoprotein IIb/IIIa is a reasonably safe and effective rescue therapy for patients who have had a failed thrombectomy or have residual severe intracranial stenosis. Balloon angioplasty and/or stenting may be helpful as a rescue treatment for patients who have had a failed thrombectomy or are at risk of reocclusion. The effectiveness of immediate stenting for residual stenosis after successful thrombectomy is still uncertain. Rescue therapy does not appear to increase the risk of sICH. Randomized controlled trials are warranted to prove the efficacy of rescue therapy.

On-Demand Control of Short-Wave Infrared Light Transparency Based on Stimuli-Responsive Association of Tetrathiafulvalene Radical Cations.

The light-transmissive properties of a solid-state tetrathiafulvalene radical cation-bis(trifluoromethanesulfonyl)imide, 1-C5 ⋅+ ⋅ NTf2 - , underwent instantaneous changes in the short-wave infrared (SWIR) region (1000-2500 nm) upon exposure to solvent vapor or the application of mechanostress at room temperature. The initial solid state of 1-C5 ⋅+ ⋅ NTf2 - exhibited strong absorption in the near-infrared (NIR; 700-1000 nm) and SWIR regions, whereas the absorption in the SWIR region was significantly diminished in the stimulated state induced by dichloromethane vapor. Upon cessation of vapor stimulation, the solid state spontaneously and promptly reverted to its original state, characterized by absorption bands in the NIR/SWIR region. Moreover, the SWIR absorption was absent upon the application of mechanical stress using a steel spatula. The reversal was fast and occurred within 10 s. These changes were visualized using a SWIR imaging camera under 1450-nm light irradiation. Experimental investigations demonstrated that the transparency to the SWIR light in the solid states was modulated through significant structural transformations of the associated radical cations, with transitions between columnar and isolated π-dimer structures under ambient and stimulated conditions, respectively.

Clitoral preputial edema can be mistaken for clitoromegaly: a clinical analysis of ten cases.

Background and objectives: We herein reported ten, female neonates with transient clitoral preputial edema, which was mistaken for clitoromegaly. Although it is well known that the clitoris is prominent in premature, female neonates, there are as of yet no reports of clitoral preputial edema in full-term neonates. The present study was conducted to clarify the clinical course of clitoral preputial edema. Methods: Seventeen, Japanese patients aged < 6 months with suspected clitoromegaly were enrolled, and their clinical course was analyzed retrospectively. Clitoral preputial edema was defined by 1) a normal clitoral glans despite edema; and 2) the absence of established differences of sexual development, such as 21-hydroxylase deficiency. Results: Ten of the 17 patients with suspected clitoromegaly had clitoral preputial edema; eight of the ten patients were full-term, and the remaining two were preterm neonates. The median age at the first visit was 8 days. Edema of the labia minora and labia majora, rugosity of the labia majora, and hymenal polyps often accompanied the clitoral preputial edema. Seven patients were examined at our division during the neonatal period, and three patients were examined in the post-neonatal period. Age at reduction of the clitoral width to < 7 mm ranged from 8 to 74 days in four of the seven neonatal patients. In the three post-neonatal patients, age to reduction in the clitoral width ranged from 107 to 243 days. Conclusions: Transient clitoral preputial edema is often mistaken for clitoromegaly. The key to diagnosing clitoral preputial edema lies in its characteristic appearance and improvement course.