Type I Kounis syndrome in a young woman without chest pain: a case report.

BACKGROUND: Kounis syndrome is defined as the concurrence of acute coronary syndromes in the setting of allergic or anaphylactic reactions. It primarily affects men aged 40-70 years and is often associated with chest pain. This syndrome is often unrecognized and undiagnosed in clinical practice due to a low level of awareness. Herein, we present a case of type I Kounis syndrome in a young woman without chest pain. CASE PRESENTATION: A 28-year-old Japanese woman with a history of atopic dermatitis received a glycyrrhizin, glutathione, and neurotropin preparation (a preparation of inflamed skin extract from rabbits inoculated with vaccinia virus) at a dermatology clinic to treat pruritus caused by atopic dermatitis. Immediately after the administration, the patient developed abdominal pain and generalized body wheals. The patient was diagnosed with anaphylaxis and was transported to our hospital. She had no chest pain on arrival at our hospital; however, a 12-lead electrocardiogram showed ST elevation in leads I, aVL, V2, and V3, and an echocardiogram showed decreased wall motion in the anterior and lateral walls of the left ventricle. Sublingual nitroglycerin administration improved ST-segment elevation and left ventricular wall motion abnormalities. The patient underwent emergency coronary angiography, which revealed no significant stenosis, and was diagnosed with type I Kounis syndrome. CONCLUSION: Kounis syndrome without chest pain is rare in young women. Since it can be fatal in cases with severe allergic symptoms such as anaphylaxis, the possibility of concurrent acute coronary syndrome should be considered when treating systemic allergic reactions, regardless of age, sex, or the presence or absence of chest symptoms.

Protein Classes Predicted by Molecular Surface Chemical Features: Machine Learning-Assisted Classification of Cytosol and Secreted Proteins.

Chemical structures of protein surfaces govern intermolecular interaction, and protein functions include specific molecular recognition, transport, self-assembly, etc. Therefore, the relationship between the chemical structure and protein functions provides insights into the understanding of the mechanism underlying protein functions and developments of new biomaterials. In this study, we analyze protein surface features, including surface amino acid populations and secondary structure ratios, instead of entire sequences as input for the classifier, intending to provide deeper insights into the determination of protein classes (cytosol or secreted). We employed a random forest-based classifier for the prediction of protein locations. Our training and testing data sets consisting of secreted and cytosol proteins were constructed using filtered information from UniProt and 3D structures from AlphaFold. The classifier achieved a testing accuracy of 93.9% with a feature importance ranking and quantitative boundary values for the top three features. We discuss the significance of these features quantitatively and the hidden rules to determine the protein classes (cytosol or secreted).

Why Is Surface-Enhanced Raman Scattering Insensitive to Liquid Water?

Surface-enhanced Raman scattering (SERS) is widely recognized as a remarkably powerful analytical technique that enables trace-level detection of organic molecules on a metal surface in aqueous systems with negligible spectral interference of water. This insensitivity of SERS to liquid water is violated in a restrictive manner under specific electrochemical conditions. However, the origin of such different SERS sensitivities to liquid water remains unclear. Here, we show that hydrogen-bond networks of water play a pivotal role in losing SERS enhancement for liquid water, and SERS detection of water requires local defects in the hydrogen-bond networks, which are formed around hydration shells of solute ions or on a polarized electrode surface. This work gives a new perspective on in situ SERS investigations in aqueous systems, including electrochemical and biological reactions.

Cranial hypertrophic pachymeningitis with myelodysplastic syndrome.

Hypertrophic pachymeningitis (HP) is a rare inflammatory disease characterized by thickening of the dura mater. HP develops with several inflammatory diseases. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and IgG4 related disease are reported as 2 major causes. With hematologic diseases, only 3 cases have been reported. We report the case of myelodysplastic syndrome (MDS) developing HP. Our case provides a thought-provoking hypothesis regarding the potential relationship between MDS and HP.

Increased Cerebrospinal Fluid Adenosine 5'-Triphosphate Levels in Patients with Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyneuropathy.

Background: Extracellular adenosine 5'-triphosphate (ATP) acts as a signaling molecule in the peripheral nerves, regulating myelination after nerve injury. The present study examined whether the cerebrospinal fluid (CSF) ATP levels in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are related to disease severity. Methods: CSF ATP levels in 13 patients with GBS and 18 patients with CIDP were compared with those in a control group of 16 patients with other neurological diseases (ONDs). In patients with CIDP, CSF ATP levels were compared before and after treatment. The correlations between CSF ATP levels and other factors, including clinical data and CSF protein levels, were also evaluated. Results: Median CSF ATP levels were significantly higher in patients with GBS and CIDP than in those with ONDs. When patients with CIDP were classified into two groups depending on their responsiveness to immunotherapy, median CSF ATP levels were significantly higher in good responders than in ONDs. CSF ATP levels tended to decrease after treatment in patients with CIDP. In patients with CIDP, there is a negative correlation between CSF ATP and CSF protein levels. Conclusions: CSF ATP levels were increased in patients with GBS and CIDP. In particular, CSF ATP levels tended to decrease following treatment in patients with CIDP. CSF ATP levels may be useful biomarkers for the diagnosis or monitoring of therapeutic effects in patients with GBS and CIDP.

Application of Machine Learning in the Quantitative Analysis of the Surface Characteristics of Highly Abundant Cytoplasmic Proteins: Toward AI-Based Biomimetics.

Proteins in the crowded environment of human cells have often been studied regarding nonspecific interactions, misfolding, and aggregation, which may cause cellular malfunction and disease. Specifically, proteins with high abundance are more susceptible to these issues due to the law of mass action. Therefore, the surfaces of highly abundant cytoplasmic (HAC) proteins directly exposed to the environment can exhibit specific physicochemical, structural, and geometrical characteristics that reduce nonspecific interactions and adapt to the environment. However, the quantitative relationships between the overall surface descriptors still need clarification. Here, we used machine learning to identify HAC proteins using hydrophobicity, charge, roughness, secondary structures, and B-factor from the protein surfaces and quantified the contribution of each descriptor. First, several supervised learning algorithms were compared to solve binary classification problems for the surfaces of HAC and extracellular proteins. Then, logistic regression was used for the feature importance analysis of descriptors considering model performance (80.2% accuracy and 87.6% AUC) and interpretability. The HAC proteins showed positive correlations with negatively and positively charged areas but negative correlations with hydrophobicity, the B-factor, the proportion of beta structures, roughness, and the proportion of disordered regions. Finally, the details of each descriptor could be explained concerning adaptative surface strategies of HAC proteins to regulate nonspecific interactions, protein folding, flexibility, stability, and adsorption. This study presented a novel approach using various surface descriptors to identify HAC proteins and provided quantitative design rules for the surfaces well-suited to human cellular crowded environments.

Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis.

Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.

Molecular Self-Assembly and Adsorption Structure of 2,2'-Dipyrimidyl Disulfides on Au(111) Surfaces.

The effects of solution concentration and pH on the formation and surface structure of 2-pyrimidinethiolate (2PymS) self-assembled monolayers (SAMs) on Au(111) via the adsorption of 2,2'-dipyrimidyl disulfide (DPymDS) were examined using scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS). STM observations revealed that the formation and structural order of 2PymS SAMs were markedly influenced by the solution concentration and pH. 2PymS SAMs formed in a 0.01 mM ethanol solution were mainly composed of a more uniform and ordered phase compared with those formed in 0.001 mM or 1 mM solutions. SAMs formed in a 0.01 mM solution at pH 2 were composed of a fully disordered phase with many irregular and bright aggregates, whereas SAMs formed at pH 7 had small ordered domains and many bright islands. As the solution pH increased from pH 7 to pH 12, the surface morphology of 2PymS SAMs remarkably changed from small ordered domains to large ordered domains, which can be described as a (4√2 × 3)R51° packing structure. XPS measurements clearly showed that the adsorption of DPymDS on Au(111) resulted in the formation of 2PymS (thiolate) SAMs via the cleavage of the disulfide (S-S) bond in DPymDS, and most N atoms in the pyrimidine rings existed in the deprotonated form. The results herein will provide a new insight into the molecular self-assembly behaviors and adsorption structures of DPymDS molecules on Au(111) depending on solution concentration and pH.

Lung Cancer Wherein Durvalumab Induced Both Anti-CRMP-5 Antibody-related Paraneoplastic Neurological Syndromes and Neurological Adverse Events.

A 68-year-old man with small-cell lung cancer developed anti-collapsin response-mediator protein (CRMP)-5 antibody-related paraneoplastic neurological syndrome (PNS) presenting with ataxia and chorea during treatment with durvalumab. As a result of steroid therapy, anti-CRMP-5 antibodies became negative, hyperintense lesions on brain magnetic resonance imaging disappeared, and neurological symptoms improved. After resuming durvalumab, he became unable to walk due to neurological adverse events (nAEs). There have been no reported cases manifesting PNSs and nAEs as a result of the same immune checkpoint inhibitors (ICIs) administered at different times. Resuming ICIs in patients diagnosed with PNSs should be performed with prudence.

Therapeutic plasma exchange for refractory Kawasaki disease in children weighing less than 10 kg.

INTRODUCTION: Therapeutic plasma exchange (TPE) is used for treating refractory Kawasaki disease (KD); however, there are few reports on its use in small children. METHODS: Nine children with refractory KD who underwent TPE between January 2010 and December 2022 were retrospectively investigated. Data on patient demographics, inflammatory markers, coronary artery lesions (CALs), TPE settings and complications, and outcomes were examined. RESULTS: A total of 37 TPE sessions were performed on nine patients, with 3-6 sessions per patient. The median body weight was 8.9 kg. C-reactive protein, white blood cell (WBC), and interleukin-6 levels significantly decreased (p < 0.05). Of the 33 coronary arteries with CALs before TPE, 44% and 3% had CALs at 1 month and 1 year after TPE, respectively. Minor complications, such as mild hypocalcemia and naturally recovering coagulopathy, occurred without serious complications. CONCLUSIONS: TPE for refractory KD may be safe and effective in preventing CALs.

Contribution of the retrosplenial cortex to route selection in a complex maze.

The retrosplenial cortex (RSC) is a region involved in navigation. In this study, we investigated the role of the RSC in navigation in a large-scale environment where the destination is not visible from the current location. We used a large maze where the routes could be freely designed by inserting and removing plates. In Experiment 1, rats learned a specific route in the maze and then were tested with a shortcut route in addition to the learned route. The rats with RSC lesions utilized the shortcut faster than those in the control group. In Experiment 2, rats were initially trained to follow a specific route, and subsequently, we tested the effects of a small change in the environment on their route-following behavior. In the test, the rats with RSC lesions demonstrated more errors than those in the control group. This suggests that lesions in the RSC make navigation to a goal unstable. These findings suggest that the RSC may be involved in the ability to perform appropriate behavior at a segment on a learned route in a large-scale environment, which drives habitually following the learned route.

Pregnancy and delivery after percutaneous embolization with a combination of microvascular plugs and hydrogel-coated coils for unilateral diffuse pulmonary arteriovenous malformations: a case report.

Background: Pulmonary arteriovenous malformations (PAVMs) are abnormal communications between the pulmonary arteries and veins; right-to-left shunts can cause hypoxaemia, emboli to systemic circulation, and brain abscesses. Cyanosis during pregnancy may increase the probability of premature birth or spontaneous abortion and may increase maternal cardiac complications. Case summary: We describe a case of a 24-year-old woman with diffuse multiple PAVMs localized to the left inferior lobe and chronic cyanosis. She had increased exertional fatigue and chronic headaches and was New York Heart Association class II, although her rest sitting peripheral oxygen saturation (SpO2) had remained unchanged at 83% over the past 20 years. She underwent percutaneous embolization with microvascular plugs and hydrogel-coated coils. A microvascular plug was placed as an anchor near the venous sac, followed by hydrogel-coated coil embolization of the proximal pulmonary artery. A total of six sessions of catheter intervention were performed. The embolization was successful, her hypoxaemia was relieved, and she was able to conceive and deliver. Three years have passed since the last session, and SpO2 97% has been maintained. Discussion: In the treatment of complex PAVMs, the combination of microvascular plugs and hydrogel-coated coils resulted in shorter procedure time, lower risk of migration of the embolus to the pulmonary veins, and less recanalization and revascularization. Percutaneous embolization of PAVMs resulted in safe delivery for the mother and child.

The Immunology of Takotsubo Syndrome.

Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully treated with anti-inflammatory therapies, supporting the importance of the inflammatory response in TTS. In this article, we provide a comprehensive review of the available clinical and pre-clinical literature on the immune response in TTS, in an effort to not only better understand the pathophysiology of TTS but also to generate insights on the treatment of patients with this disorder.

Recurrent Myocardial Injury Leads to Disease Tolerance in a Murine Model of Stress-Induced Cardiomyopathy.

Whereas the innate immune response to an initial episode of cardiac injury has been studied extensively, the response of the immune system to recurrent cardiac tissue injury is not well understood. Specifically, it is not known whether the immune system adapts to the initial episode of cardiac injury and whether any adaptations that occur lead to immune cell hypo-responsiveness or, alternatively, immune cell hyper-responsiveness. Here, we studied the role of adrenergic-mediated stress using a simple model of reversible stress-induced cardiomyopathy, and show that isoproterenol-induced tissue injury and inflammation are sufficient to protect the heart from the myopathic effects of a subsequent exposure to isoproterenol. Remarkably, pharmacological depletion of macrophages partially attenuated the isoproterenol-induced cytoprotective response, suggesting that immune-mediated tissue repair mechanisms confer tolerance to subsequent tissue damage.

Investigation of Hydration States of Ionic Liquids by Fourier Transform Infrared Absorption Spectroscopy: Relevance to Stabilization of Protein Molecules.

Among many kinds of ionic liquids, some hydrated ionic liquids (Hy ILs) have shown an exceptional capability to stabilize protein molecules and maintain their structure and functions over a long period. However, the complex IL-water interaction among these protein-stabilizing Hy ILs has yet to be elucidated clearly. In this work, we investigate the origin of the compatibility of ionic liquid with proteins from the viewpoint of hydration structure. We systematically analyzed the hydrogen-bonding state of water molecules around ionic liquid using Fourier transform infrared absorption (FT-IR) spectroscopy. We found that the native hydrogen-bonding network of water remained relatively unperturbed in the protein-stabilizing ILs. We also observed that the protein-stabilizing ILs have a strong electric field interaction with the surrounding water molecules and this water-IL interaction did not disrupt the water-water hydrogen-bonding interaction. On the other hand, protein-denaturing ILs perturb the hydrogen-bonding network of the water molecules to a greater extent. Furthermore, the protein-denaturing ILs were found to have a weak electric field effect on the water molecules. We speculate that the direct hydrogen bonding of the ILs with water molecules and the strong electric field of the ions lasting several hydration shells while maintaining the relatively unperturbed hydrogen-bonding network of the water molecules play an essential role in protein stabilization.

Investigation of Three-Dimensional Bacterial Adhesion Manner on Model Organic Surfaces Using Quartz Crystal Microbalance with Energy Dissipation Monitoring.

Bacterial biofilms reduce the performance and efficiency of biomedical and industrial devices. The initial step in forming bacterial biofilms is the weak and reversible attachment of the bacterial cells onto the surface. This is followed by bond maturation and secretion of polymeric substances, which initiate irreversible biofilm formation, resulting in stable biofilms. This implies that understanding the initial reversible stage of the adhesion process is crucial to prevent bacterial biofilm formation. In this study, we analyzed the adhesion processes of E. coli on self-assembled monolayers (SAMs) with different terminal groups using optical microscopy and quartz crystal microbalance with energy dissipation (QCM-D) monitoring. We found that a considerable number of bacterial cells adhere to hydrophobic (methyl-terminated) and hydrophilic protein-adsorbing (amine- and carboxy-terminated) SAMs forming dense bacterial adlayers while attaching weakly to hydrophilic protein-resisting SAMs [oligo(ethylene glycol) (OEG) and sulfobetaine (SB)], forming sparse but dissipative bacterial adlayers. Moreover, we observed positive shifts in the resonant frequency for the hydrophilic protein-resisting SAMs at high overtone numbers, suggesting how bacterial cells cling to the surface using their appendages as explained by the coupled-resonator model. By exploiting the differences in the acoustic wave penetration depths at each overtone, we estimated the distance of the bacterial cell body from different surfaces. The estimated distances provide a possible explanation for why bacterial cells tend to attach firmly to some surfaces and weakly to others. This result is correlated to the strength of the bacterium-substratum bonds at the interface. Elucidating how the bacterial cells adhere to different surface chemistries can be a suitable guide in identifying surfaces with a more significant probability of contamination by bacterial biofilms and designing bacteria-resistant surfaces and coatings with excellent bacterial antifouling characteristics.

Formation and Thermal Stability of Ordered Self-Assembled Monolayers by the Adsorption of Amide-Containing Alkanethiols on Au(111).

We examined the surface structure, binding conditions, electrochemical behavior, and thermal stability of self-assembled monolayers (SAMs) on Au(111) formed by N-(2-mercaptoethyl)heptanamide (MEHA) containing an amide group in an inner alkyl chain using scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and cyclic voltammetry (CV) to understand the effects of an internal amide group as a function of deposition time. The STM study clearly showed that the structural transitions of MEHA SAMs on Au(111) occurred from the liquid phase to the formation of a closely packed and well-ordered ß-phase via a loosely packed α-phase as an intermediate phase, depending on the deposition time. XPS measurements showed that the relative peak intensities of chemisorbed sulfur against Au 4f for MEHA SAMs formed after deposition for 1 min, 10 min, and 1 h were calculated to be 0.0022, 0.0068, and 0.0070, respectively. Based on the STM and XPS results, it is expected that the formation of a well-ordered ß-phase is due to an increased adsorption of chemisorbed sulfur and the structural rearrangement of molecular backbones to maximize lateral interactions resulting from a longer deposition period of 1 h. CV measurements showed a significant difference in the electrochemical behavior of MEHA and decanethiol (DT) SAMs as a result of the presence of an internal amide group in the MEHA SAMs. Herein, we report the first high-resolution STM image of well-ordered MEHA SAMs on Au(111) with a (3 × 2√3) superlattice (ß-phase). We also found that amide-containing MEHA SAMs were thermally much more stable than DT SAMs due to the formation of internal hydrogen networks in MEHA SAMs. Our molecular-scale STM results provide new insight into the growth process, surface structure, and thermal stability of amide-containing alkanethiols on Au(111).

Transcatheter Mitral Valve Repair Versus Transcatheter Mitral Valve Replacement in Patients with Mitral insufficiency.

AIMS: Mitral regurgitation (MR) is the most prevalent form of valvular heart disease. Transcatheter mitral valve repair (TMVr) and transcatheter mitral valve replacement (TMVR) have recently emerged as alternatives to open heart surgical repair or replacement. However, studies on the comparative outcomes of TMVr and TMVR are limited. This study aims to compare the demographics, complications and outcomes of TMVr and TMVR based on a real-world investigation of the National Inpatient Sample (NIS) database. METHODS AND RESULTS: From 2016-2018 in the NIS database, a total of 210 and 3370 patients who underwent TMVR and TMVr, respectively, were selected. The mean age of the patients was 75.99 years (TMVr) and 69.6 years (TMVR) (p <0.01). The mortality of patients who received TMVR was higher compared to that of patients who were treated with TMVr (8.1 vs. 1.9%, p <0.01). The patients who underwent TMVR were more likely to suffer perioperative complications including blood transfusions (16.2 vs. 5.0%, p <0.01) and acute kidney injury (22.9 vs. 13.3%, p <0.01). The average cost of treatment was higher (USD $278864 vs. USD $216845, p <0.01), and the average duration of hospitalization was longer (8.73 vs. 4.17 d, p <0.01) for TMVR compared to TMVr. When taking into account perioperative comorbidities and other factors, TMVR was associated with a worse adjusted in-hospital mortality (odds ratio [OR], 3.307 [95% CI, 1.533-7.136]; p <0.01). CONCLUSION: TMVr is associated with lower mortality, peri-procedural morbidity, and resource use compared to TMVR. A patient-centered approach can help guide decision-making about the choice of intervention for the individual patient and more studies evaluating the long-term outcomes and durability of TMVR are needed at present.