Cardiac Manifestations after Ingestion of a Commercial Desiccant: A Case Report.

Background and Objectives: The rise in suicidal attempts has led to an increase in unusual intoxication cases. The ingestion of anhydrous calcium chloride (CaCl2) causes direct injury to the gastrointestinal wall via a thermal burn. Therefore, previous reports on CaCl2 ingestion primarily considered the gastrointestinal injury. Severe CaCl2 intoxication can induce a hypercalcemic crisis, presenting with arrhythmia, acute pancreatitis, and acute kidney injury. This case report details a patient with hematemesis and hypercalcemia following the ingestion of a commercial desiccant. We aimed to report the progression of the case, with a focus on the electrocardiographic manifestations. Case Presentation: A 39-year-old female presented at a regional emergency center with blood in her vomit after the ingestion of a commercial desiccant. Bloody emesis was the initial symptom, and various electrolyte imbalances developed during admission. Electrocardiogram (ECG) changes occurred early after hospitalization and disappeared before the electrolyte levels normalized. The patient was maintained in an NPO (Nil Per Os) state throughout her hospital stay. The bloody emesis and abdominal pain resolved quite early, despite her minimal mention of symptoms, possibly due to her suspected negative psychiatric symptoms. Conclusions: In this case, we observed dynamic and prolonged multiple electrolyte imbalances along with the early-phase ECG changes, all of which responded well to supportive care. This report adds to the understanding of the diverse manifestations and management of CaCl2 intoxication.

Comparison of COVID-19 Pandemic-Related Stress among Frontline Medical Personnel in Daegu City, Korea.

Background and Objectives: Frontline medical staff usually experience high levels of stress, which could greatly impact their work output. We conducted a survey to investigate the level of stress and its association with job types, work departments, and medical centers among COVID-19 pandemic frontline medical personnel. Materials and Methods: We conducted a cross-sectional survey using a self-administered questionnaire among 307 frontline medical staff who cared for COVID-19 patients in Daegu city. We used a 33-item questionnaire to assess respondents' general characteristics, job stress, personal effects associated with the COVID-19 pandemic, and their stress level. A general health questionnaire-12 (GHQ-12) was included in our questionnaire. Results: Majority (74.3%) of the respondents were in the stress group. The mean GHQ-12 score was 14.31 ± 4.96. More females (67.4%, p < 0.05) and nurses (73.3%, p = 0.001) were in the stress group compared to males and doctors. Medical staff in the general ward considered the severity of the COVID-19 pandemic situation higher. Nurses perceived work changes (p < 0.05), work burden (p < 0.05), and personal impact (p < 0.05) more serious than doctors. Medical staff in Level 3 emergency department (ED) perceived a lack of real-time information (p = 0.012), a lack of resources, and negative personal impacts associated with the pandemic as more serious than staff in Level 1 and Level 2 EDs. Medical staff in the intensive care unit perceived work changes (p < 0.05), work burden (p < 0.05), and lack of personal protective equipment (p = 0.002) as more serious than staff in the ED and general ward. Conclusion: Providing real-time information and resources for reducing work burden and negative personal impact is central to maximizing the work output of the COVID-19 pandemic frontline medical staff. Supporting their mental health through regular programs and intervention is also imperative.

Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator.

The main pathway responsible for cellular regulation against oxidative stress is nuclear factor E2-related factor-2 (Nrf2) signaling. We previously synthesized and reported a novel vinyl sulfone (1) as an Nrf2 activator with therapeutic potential for Parkinson's disease (PD). In this study, we changed the vinyl sulfone to vinyl sulfonamide or vinyl sulfonate to improve Nrf2 activating efficacy. We observed that the introduction of vinyl sulfonamide led to a reduction of the effects on Nrf2 activation, whereas vinyl sulfonate compounds exhibited superior activity compared to the vinyl sulfone compounds. Among the vinyl sulfonates, 3c exhibited 6.9- and 83.5-fold higher effects on Nrf2 activation than the corresponding vinyl sulfone (1) and vinyl sulfonamide (2c), respectively. Compound 3c was confirmed to induce expression of the Nrf2-dependent antioxidant enzymes at the protein level in cells. In addition, 3c mitigated PD-associated behavioral deficits by protecting DAergic neurons in the MPTP-induced mouse model of PD.

Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer's disease.

Monoamine oxidase-B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer's disease (AD) because of its association with aberrant γ-aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC50 = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.

Risk Factors of Behavioral and Psychological Symptoms in Patients with Alzheimer Disease: The Clinical Research of Dementia of South Korea Study.

BACKGROUND: Few studies have evaluated risk factors for behavioral and psychological symptoms of dementia at the initial assessment for Alzheimer disease in large patient samples. In this study, the factors influencing Alzheimer disease were examined using the Clinical Research of Dementia of South Korea data. METHODS: This cross-sectional study was conducted using data of 1,128 patients with Alzheimer disease. The behavioral and psychological symptoms of dementia were examined using the Korean version of the Neuropsychiatric Inventory. Demographic characteristics, health-related behavior, neuropsychological tests, comorbidities, blood test results, and caregiver characteristics were assessed. Median logistic regression analysis with adjustment for covariates was conducted. RESULTS: The behavioral and psychological symptoms of dementia were negatively associated with memory (P=0.022) and frontal/executive (P<0.001) function in the Seoul Neuropsychological Screening Battery-dementia, Barthel Index for Activities of Daily Living (P<0.001), Korean version of the Mini-Mental State Examination score (P=0.003), and caregiver age (P=0.005) after adjustment for confounding factors, and positively associated with the Seoul-Instrumental Activities of Daily Living score (P<0.001), Clinical Dementia Rating Sum of Box (P<0.001), Global Deterioration Scale score (P<0.001), abnormality of free T4 level (P<0.001), anemia (P<0.001), and family history of stroke (P=0.001). Patients with female caregivers exhibited more severe behavioral and psychological symptoms of dementia than those with male caregivers. CONCLUSION: Behavioral and psychological symptoms of dementia in Alzheimer disease patients were associated with various risk factors including the inability to live independently and Alzheimer disease severity. These findings suggest that prevention and treatment strategies for the behavioral and psychological symptoms of dementia should be comprehensive.

Optimization of Vinyl Sulfone Derivatives as Potent Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators for Parkinson's Disease Therapy.

We previously developed a novel series of vinyl sulfones as nuclear factor erythroid 2-related factor 2 (Nrf2) activators with therapeutic potential for Parkinson's disease (PD). However, the previously developed lead compound (1) exhibited undesirable druglike properties. Here, we optimized vinyl sulfones by introducing nitrogen heterocycles to improve druglike properties. Among the synthesized compounds, 17e was the most promising drug candidate with good druglike properties. Compound 17e showed superior effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: half-maximal effective concentration (EC50) = 346 nM; 1: EC50 = 530 nM). Compound 17e was further confirmed to induce expression of Nrf2-dependent antioxidant enzymes at both mRNA and protein levels. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopositive dopaminergic neurons, suppressed microglial activation, and alleviated PD-associated motor dysfunction. Thus, 17e is a novel Nrf2 activator with excellent druglike properties and represents a potential therapeutic candidate for PD.

A film-based integrated chip for gene amplification and electrochemical detection of pathogens causing foodborne illnesses.

Given the increased interest in public hygiene due to outbreaks of food poisoning, increased emphasis has been placed on developing novel monitoring systems for point-of-care testing (POCT) to evaluate pathogens causing foodborne illnesses. Here, we demonstrate a pathogen evaluation system utilizing simple film-based microfluidics, featuring simultaneous gene amplification, solution mixing, and electrochemical detection. To minimize and integrate the various functionalities into a single chip, patterned polyimide and polyester films were mainly used on a polycarbonate housing chip, allowing simple fabrication and alignment, in contrast to conventional polymerase chain reaction, which requires a complex biosensing system at a bench-top scale. The individual integrated sensing chip could be manually fabricated in 10 min. Using the developed film-based integrated biosensing chip, the genes from the pathogens causing foodborne illnesses were simultaneously amplified based on multiple designed microfluidic chambers and Hoechst 33258, which intercalates into double-stranded DNA, to generate the electrochemical signal. The target pathogen gene was accurately analyzed by square wave voltammetry (SWV) within the 25 s, while the gel electrophoresis required about 30 min. Based on the developed integrated biosensing chip, the 1.0 × 101 and 1.0 × 102 colony-forming unit (CFU) of Staphylococcus aureus and Escherichia coli were sensitively detected with high reproducibility in the 25 s. On the basis of the significant features of the film-based molecular analysis platform, we expect that the developed sensor could be applied to the screening of various pathogens as a POCT device.

Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B inhibitors toward Parkinson's disease therapy.

Benzyloxyphenyl moiety is a common structure of highly potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and sembragiline. We synthesized 4-(benzyloxy)phenyl and biphenyl-4-yl derivatives including halogen substituents on the terminal aryl unit. In addition, we modified the carbon linker between amine group and the biaryl linked unit. Among synthesized compounds, 12c exhibited the most potent and selective MAO-B inhibitory effect (hMAO-B IC50: 8.9 nM; >10,000-fold selectivity over MAO-A) as a competitive inhibitor. In addition, 12c showed greater MAO-B inhibitory activity and selectivity compared to well-known MAO-B inhibitors such as selegiline, safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson's disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)-immunopositive DAergic neurons and attenuated the PD-associated behavioral deficits. This study suggests characteristic structures as a MAO-B inhibitor that may provide a good insight for the development of therapeutic agents for PD.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets.

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 102-105 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing.

A universal spring-probe system for reliable probing of electrochemical lab-on-a-chip devices.

For achieve sensitivity in lab-on-a-chip electrochemical detection, more reliable probing methods are required, especially for repeated measurements. Spring-probes are a promising candidate method which can replace needle-like probes and alligator clips that usually produce scratches on the surface of gold electrodes due to the strong physical contacts needed for electrochemical measurements. The superior reliability of amperometric measurements by a spring-probe system was compared with results by conventional probing methods. We demonstrated that a universal spring-probe system would be potentially suitable to achieve high performance in lab-on-a-chip devices using electrochemical detection.

Enzyme precipitate coatings of glucose oxidase onto carbon paper for biofuel cell applications.

Enzymatic biofuel cells (BFC) have a great potential as a small power source, but their practical applications are being hampered by short lifetime and low power density. This study describes the direct immobilization of glucose oxidase (GOx) onto the carbon paper in the form of highly stable and active enzyme precipitation coatings (EPCs), which can improve the lifetime and power density of BFCs. EPCs were fabricated directly onto the carbon paper via a three-step process: covalent attachment (CA), enzyme precipitation, and chemical crosslinking. GOx-immobilized carbon papers via the CA and EPC approaches were used as an enzyme anode and their electrochemical activities were tested under the BFC-operating mode. The BFCs with CA and EPC enzyme anodes produced the maximum power densities of 50 and 250 µW/cm(2) , respectively. The BFC with the EPC enzyme anode showed a stable current density output of >700 µA/cm(2) at 0.18 V under continuous operation for over 45 h. When a maple syrup was used as a fuel under ambient conditions, it also produced a stable current density of >10 µA/cm(2) at 0.18 V for over 25 h. It is anticipated that the direct immobilization of EPC on hierarchical-structured electrodes with a large surface area would further improve the power density of BFCs that can make their applications more feasible.