Rapid Characterization of Undeclared Pharmaceuticals in Herbal Preparations by Ambient Ionization Mass Spectrometry for Emergency Care.

In Asia, some herbal preparations have been found to be adulterated with undeclared synthetic medicines to increase their therapeutic efficiency. Many of these adulterants were found to be toxic when overdosed and have been documented to bring about severe, even life-threatening acute poisoning events. The objective of this study is to develop a rapid and sensitive ambient ionization mass spectrometric platform to characterize the undeclared toxic adulterated ingredients in herbal preparations. Several common adulterants were spiked into different herbal preparations and human sera to simulate the clinical conditions of acute poisoning. They were then sampled with a metallic probe and analyzed by the thermal desorption-electrospray ionization mass spectrometry. The experimental parameters including sensitivity, specificity, accuracy, and turnaround time were prudently optimized in this study. Since tedious and time-consuming pretreatment of the sample is unnecessary, the toxic adulterants could be characterized within 60 s. The results can help emergency physicians to make clinical judgments and prescribe appropriate antidotes or supportive treatment in a time-sensitive manner.

An Ultra-Broadband High Efficiency Polarization Beam Splitter for High Spectral Resolution Polarimetric Imaging in the Near Infrared.

A broadband, high efficiency polarized beam splitter (PBS) metagrating based on integrated resonant units (IRUs) to enable simultaneous polarization analysis, spectral dispersion, and spatial imaging in the near infrared (NIR) is developed. A PBS metagrating with a diameter of 60 mm is the key technology component of the high-resolution multiple-species atmospheric profiler in the NIR (HiMAP-NIR), which is a spaceborne instrument concept crafted to be a core payload of NASA's new generation Earth System Observatory. HiMAP-NIR will enable the aerosol profiling in Earth's planetary boundary layer (from surface to2 km altitude) by simultaneously measuring four spatial-spectral-polarimetric images from 680 to 780 nm. Through detailed optimization of hybridized resonant modes in IRUs, the PBS metagrating shows a diffraction efficiency of 70% (or better) for all four linear-polarized incident light, and polarization contrasts between orthogonal states are 0.996 (or better) from 680 to 780 nm. It meets the stringent performance required by the HiMAP-NIR exploiting a new paradigm for the broad applications of metasurfaces.

Gastrointestinal discomfort and hypotension in a patient with Reutealis trisperma seeds intoxication: A case report.

RATIONALE: Reutealis trisperma is a plant belonging to the Euphorbiaceae family and Reutealis genus and is often mistaken for a plant of the genus Aleurites. Accidental ingestion of R trisperma seeds is relatively rare in Taiwan than that of Vernicia fordii. Mostly, the clinical course of R trisperma seed poisoning is similar to that of V fordii poisoning. Recent studies have shown that the median lethal dose 50 of R trisperma seeds in mice is approximately 4954 mg/kg. R trisperma seed extract has a significant effect on the autonomic nervous system by causing ptosis and disrupting breathing, and affects the central nervous system by reducing motor activity. PATIENT CONCERNS: A 51-year-old man with underlying gout and hepatitis B picked several seeds of R trisperma, which he misidentified at chestnuts, at an elementary school. He prepared soup by boiling 3 to 4 seeds and consumed it. He experienced abdominal pain, vomiting, and watery diarrhea with hypotension. DIAGNOSIS: R trisperma seeds intoxication. INTERVENTIONS: The patient was given a soft diet, input and output were recorded, and intravenous fluid supplements were administered. OUTCOMES: The patient was discharged after 3 days of hospitalization, once a relatively stable condition was achieved. LESSONS: Human poisoning by accidental consumption of R trisperma seeds is relatively rare in Taiwan. It may cause gastrointestinal symptoms and even hypotension. Patients can recover within 2 to 3 days of receiving proper treatment and intravenous fluid infusion.

Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells.

BACKGROUND: Pathogenic coronaviruses include Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. These viruses have induced outbreaks worldwide, and there are currently no effective medications against them. Therefore, there is an urgent need to develop potential drugs against coronaviruses. METHODS: High-throughput technology is widely used to explore differences in messenger (m)RNA and micro (mi)RNA expression profiles, especially to investigate protein-protein interactions and search for new therapeutic compounds. We integrated miRNA and mRNA expression profiles in MERS-CoV-infected cells and compared them to mock-infected controls from public databases. RESULTS: Through the bioinformatics analysis, there were 251 upregulated genes and eight highly differentiated miRNAs that overlapped in the two datasets. External validation verified that these genes had high expression in MERS-CoV-infected cells, including RC3H1, NF-κB, CD69, TNFAIP3, LEAP-2, DUSP10, CREB5, CXCL2, etc. We revealed that immune, olfactory or sensory system-related, and signal-transduction networks were discovered from upregulated mRNAs in MERS-CoV-infected cells. In total, 115 genes were predicted to be related to miRNAs, with the intersection of upregulated mRNAs and miRNA-targeting prediction genes such as TCF4, NR3C1, and POU2F2. Through the Connectivity Map (CMap) platform, we suggested potential compounds to use against MERS-CoV infection, including diethylcarbamazine, harpagoside, bumetanide, enalapril, and valproic acid. CONCLUSIONS: The present study illustrates the crucial roles of miRNA-mRNA interacting networks in MERS-CoV-infected cells. The genes we identified are potential targets for treating MERS-CoV infection; however, these could possibly be extended to other coronavirus infections.

Calibration of the SHERLOC Deep Ultraviolet Fluorescence-Raman Spectrometer on the Perseverance Rover.

We describe the wavelength calibration of the spectrometer for the scanning of habitable environments with Raman and luminescence for organics and chemicals (SHERLOC) instrument onboard NASA's Perseverance Rover. SHERLOC utilizes deep ultraviolet Raman and fluorescence (DUV R/F) spectroscopy to enable analysis of samples from the Martian surface. SHERLOC employs a 248.6 nm deep ultraviolet laser to generate Raman-scattered photons and native fluorescence emission photons from near-surface material to detect and classify chemical and mineralogical compositions. The collected photons are focused on a charge-coupled device and the data are returned to Earth for analysis. The compact DUV R/F spectrometer has a spectral range from 249.9 nm to 353.6 nm (∼200 cm-1 to 12 000 cm-1) (with a spectral resolution of 0.296 nm (∼40 cm-1)). The compact spectrometer uses a custom design to project a high-resolution Raman spectrum and a low-resolution fluorescence spectrum on a single charge-coupled device. The natural spectral separation enabled by deep ultraviolet excitation enables wavelength separation of the Raman/fluorescence spectra. The SHERLOC spectrometer was designed to optimize the resolution of the Raman spectral region and the wavelength range of the fluorescence region. The resulting illumination on the charge-coupled device is curved, requiring a segmented, nonlinear wavelength calibration in order to understand the mineralogy and chemistry of Martian materials.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection induces dysregulation of immunity: in silico gene expression analysis.

Highly pathogenic coronaviruses (CoVs) induce acute respiratory distress syndrome, and the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused a pandemic since late 2019. The diversity of clinical manifestations after SARS-CoV-2 infection results in great challenges to diagnose CoV disease 2019 (COVID-19). There is a growing body of published research on this topic; however, effective medications are still undergoing a long process of being assessed. In the search for potential genetic targets for this infection, we applied a holistic bioinformatics approach to study alterations of gene signatures between SARS-CoV-2-infected cells and mock-infected controls. Two different kinds of lung epithelial cells, A549 with angiotensin-converting enzyme 2 (ACE2) overexpression and normal human bronchial epithelial (NHBE) cells, were infected with SARS-CoV-2. We performed bioinformatics analyses of RNA-sequencing in this study. Through a Venn diagram, Database for Annotation, Visualization and Integrated Discovery, Gene Ontology, Ingenuity Pathway Analysis, and Gene Set Enrichment Analysis, the pathways and networks were constructed from commonly upregulated genes in SARS-CoV-2-infected lung epithelial cells. Genes associated with immune-related pathways, responses of host cells after intracellular infection, steroid hormone biosynthesis, receptor signaling, and the complement system were enriched. Dysregulation of the immune system and malfunction of interferon contribute to a failure to kill SARS-CoV-2 and exacerbate respiratory distress in severely ill patients. Current findings from this study provide a comprehensive investigation of SARS-CoV-2 infection using high-throughput technology.

Plastic wrap combined with alcohol wiping is an effective method of preventing bacterial colonization on mobile phones.

INTRODUCTION: Using mobile phones for communication in emergency departments is a common practice; however, several studies have demonstrated that they may act as vectors for bacteria and viruses. This study evaluated the effectiveness of plastic wrapping in decreasing bacterial contamination on mobile phone surfaces. METHOD: We used culture dishes and a luminometer to detect bacterial colonies and contamination on the phone surfaces. RESULT: Our experiment showed that bacterial colonies exist on mobile phones before and after work. We found that wiping with 75% alcohol sanitizers effectively reduces the number of colonies on either a mobile phone or a temporary plastic covering. In addition, we found that bacterial colonies do not contaminate or adhere to plastic wrap any easier than to mobile phones. CONCLUSION: These results demonstrated the effectiveness of plastic wrap for protecting mobile phone surfaces against bacterial colonization. In addition, applying a layer of plastic wrap protects the phone from potential damage due to the alcohol.

Survey on perceived work stress and its influencing factors among hospital staff during the COVID-19 pandemic in Taiwan.

This study aimed to investigate the perceived work stress and its influencing factors among hospital staff during the novel coronavirus (COVID-19) pandemic in Taiwan. A web-based survey was conducted at one medical center and two regional hospitals in southern Taiwan, targeting physicians, nurses, medical examiners, and administrators. The questionnaire included items on the demographic characteristics of hospital staff and a scale to assess stress among healthcare workers caring for patients with a highly infectious disease. A total of 752 valid questionnaires were collected. The hospital staff reported a moderate level of stress and nurses had a highest level of stress compared to staff in the other three occupational categories. The five highest stress scores were observed for the items "rough and cracked hands due to frequent hand washing and disinfectant use," "inconvenience in using the toilet at work," "restrictions on eating and drinking at work," "fear of transmitting the disease to relatives and friends," and "fear of being infected with COVID-19." Discomfort caused by protective equipment was the major stressor for the participants, followed by burden of caring for patients. Among participants who experienced severe stress (n = 129), work stress was higher among those with rather than without minor children. The present findings may serve as a reference for future monitoring of hospital staff's workload, and may aid the provision of support and interventions.

Gene signatures of SARS-CoV/SARS-CoV-2-infected ferret lungs in short- and long-term models.

Coronaviruses (CoVs) consist of six strains, and the severe acute respiratory syndrome coronavirus (SARS-CoV), newly found coronavirus (SARS-CoV-2) has rapidly spread leading to a global outbreak. The ferret (Mustela putorius furo) serves as a useful animal model for studying SARS-CoV/SARS-CoV-2 infection and developing therapeutic strategies. A holistic approach for distinguishing differences in gene signatures during disease progression is lacking. The present study discovered gene expression profiles of short-term (3 days) and long-term (14 days) ferret models after SARS-CoV/SARS-CoV-2 infection using a bioinformatics approach. Through Gene Ontology (GO) and MetaCore analyses, we found that the development of stemness signaling was related to short-term SARS-CoV/SARS-CoV-2 infection. In contrast, pathways involving extracellular matrix and immune responses were associated with long-term SARS-CoV/SARS-CoV-2 infection. Some highly expressed genes in both short- and long-term models played a crucial role in the progression of SARS-CoV/SARS-CoV-2 infection, including DPP4, BMP2, NFIA, AXIN2, DAAM1, ZNF608, ME1, MGLL, LGR4, ABHD6, and ACADM. Meanwhile, we revealed that metabolic, glucocorticoid, and reactive oxygen species-associated networks were enriched in both short- and long-term infection models. The present study showed alterations in gene expressions from short-term to long-term SARS-CoV/SARS-CoV-2 infection. The current result provides an explanation of the pathophysiology for post-infectious sequelae and potential targets for treatment.

Ventricular Fibrillation Caused by Primary Carnitine Deficiency.

BACKGROUND: Primary carnitine deficiency (PCD) is a rare but potentially life-threatening genetic disorder if left untreated. Although some patients remain asymptomatic lifelong, a few patients present with hepatic encephalopathy, hypoglycemia, cardiomyopathy, dysrhythmia, and even sudden death. CASE REPORT: A 25-year-old woman with PCD collapsed suddenly while eating lunch. Bystander cardiopulmonary resuscitation (CPR) was performed for 8 min, with automated external defibrillation once before admission. Upon arrival at our emergency department (ED), she was unresponsive without a pulse or spontaneous breathing. The initial heart rhythm on the electrocardiogram monitor was ventricular fibrillation (VF). The medical staff continued CPR with defibrillation for sustained VF. Return of spontaneous circulation (ROSC) was achieved after a total resuscitation time of 14 min, with defibrillation twice after cardiac arrest. The heart rhythm after ROSC was atrial fibrillation, with a rapid ventricular rate initially and subsequent progression to sinus tachycardia with diffuse ST segment depression and a prolonged QT interval. Her low carnitine level was consistent with her underlying disease. Cardiac magnetic resonance imaging and sonography for detection of cardiomyopathy showed no significant findings. With carnitine supplementation for a few days, her plasma carnitine level returned to 30 µM, with no recurrence of ventricular dysrhythmia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: PCD is rare but could be life-threatening, and compiling detailed histories may help emergency physicians to determine the cause of sudden cardiac death after resuscitation. This information may be used to correct potential underlying problems and prevent recurrence of the condition after treatment.

Upper Gastrointestinal Bleeding With Hemobilia Caused by Gallstones.

BACKGROUND: Hemobilia refers to bleeding in the biliary tract, commonly due to iatrogenic, traumatic, and neoplastic causes. It is a rare source of upper gastrointestinal hemorrhage, but it can be severe and fatal. However, gallstones account for 5%-15% of hemobilia cases. CASE REPORT: A 60-year-old woman with diabetes mellitus and chronic kidney disease visited the emergency department with complaints of epigastric pain and vomiting of coffee ground-like content for 2 days. Physical examination revealed epigastric tenderness and hyperactive bowel sounds. Laboratory tests showed anemia with a hemoglobin count of 10.7 mg/dL and elevated liver function tests with total and direct bilirubin levels of 3.6 mg/dL and 2.5 mg/dL, respectively. Panendoscopy showed oozing of coffee ground-like material at the orifice of the ampulla of Vater and second portion of the duodenum, leading to suspicion of hemobilia. After admission, endoscopic retrograde cholangiopancreatography revealed common bile duct (CBD) dilatation with choledocholithiasis, biliary sludge, and filling defect at the middle section of the CBD. Endoscopic sphincterotomy with balloon lithotripsy was performed. After biliary decompression and broad-spectrum antibiotic administration, abdominal pain was relieved, and liver enzyme and total bilirubin levels improved. Symptoms of hemobilia depend on the bleeding rate and presence of bile duct obstructions due to clots. Minor and slow bleeding tend to form clots and cause biliary obstruction. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although minor hemobilia may remain asymptomatic and tends to resolve spontaneously, the cause of hemobilia must be corrected to prevent recurrent bleeding or obstruction.

Identification of the Potential Prognostic Markers from the miRNA-lncRNA-mRNA Interactions for Metastatic Renal Cancer via Next-Generation Sequencing and Bioinformatics.

The survival rate in patients with metastatic renal cell carcinoma (RCC) is low. In addition, metastatic RCC resists traditional treatment. Therefore, identification of novel biomarkers, signaling pathways, and therapeutic targets is an important issue. The aim of the present study is to identify novel prognostic markers from the miRNA-mediated network for the regulation of metastasis of RCC. To address this issue, the RNA of human RCC cell lines, 786-O and ACHN, derived from primary and metastatic sites, respectively, were collected and subjected to RNA sequencing and small RNA sequencing. The bioinformatic analysis revealed that the pathways of the genes with different expressions were related to tumor progression, and identified miRNA and miRNA-long non-coding RNA (lncRNA) interactions, and mRNA. The results revealed that the expressions of seven miRNAs were associated with the overall survival rate of patients with RCC. Furthermore, the expressions of two lncRNA and three protein-coding genes (mRNA) were significantly associated with the increased or decreased disease-free survival rate. Although the detailed regulatory mechanism between miRNAs and targeted genes was not fully understood, our findings present novel prognostic markers and novel insight on miRNA-mediated pathways for metastatic RCC.

Hexavalent chromium intoxication induces intrinsic and extrinsic apoptosis in human renal cells.

Hexavalent chromium [Cr(VI)], is a well­known toxic form of the heavy metal chromium in the natural environment. Clinical evidence has indicated that exposure to Cr(VI) can cause severe renal damage. The production of reactive oxygen species (ROS) due to intracellular reduction of Cr(VI) is the main mechanism underlying the induction of cellular dysfunction and apoptosis. The present study aimed to investigate in detail the apoptotic pathways induced by Cr(VI)­exposure in a human immortalized proximal tubular epithelial cell line HK­2, in order to understand the mechanism involved therein. Exposure to 10 µM potassium dichromate (K2Cr2O7), a toxic compound of Cr(VI), significantly decreased cell viability after 24 and 48 h of incubation and induced intracellular ROS generation. The expression levels of markers that activate the apoptotic pathway including cleaved caspase­3 and poly (ADP­ribose) polymerase were significantly upregulated in K2Cr2O7­exposed HK­2 cells. In addition, the induction of intrinsic and extrinsic apoptotic markers was detected in K2Cr2O7­exposed HK­2 cells. In summary, the present study described for the first time the novel apoptotic mechanism of Cr(VI)­toxicity in human renal cells which may be beneficial in designing optimal clinical treatment for renal damage caused by acute Cr(VI) toxicity.

Rapid identification of organophosphorus pesticides on contaminated skin and confirmation of adequate decontamination by ambient mass spectrometry in emergency settings.

RATIONALE: Dermal exposure to pesticides may cause severe intoxication and even result in a fatal outcome. To expedite rescue in the emergency department, it is mandatory to develop a point-of-care analytical method for immediate identification of pesticides on the skin of exposed personnel, and to perform immediate dermal decontamination to prevent further harm and optimize the chance for full clinical recovery. METHODS: Four of the most commonly used highly toxic pesticides that contaminate the skin were rapidly characterized by thermal desorption electrospray ionization mass spectrometry. The technique was also applied to confirm the completeness of pesticide decontamination from the skin. Pesticide sampling, desorption, ionization, and detection altogether took less than 30 s. In addition, different fabrics of protective garments worn by farmers were assessed with this efficient ambient mass spectrometric technique for their protective capabilities against dermal exposure to pesticides, and scanning electron microscopy was used to observe their different microstructures. The decontaminating efficacies of different cleansing agents for these skin contaminants were also evaluated by this technical platform. RESULTS: The repeatability of this method had a low relative standard deviation (<22%) for the detection of pesticides on the surface of swine skin. The detection limits of the pesticides in solution were found to be in the range of 3-20 ng/mL. Linearity was observed between the signal intensities and the concentrations of the four pesticides in solution within the range of 50 ng/mL to 50 µg/mL (R2 between 0.9921 and 0.9966). In addition, it was found that PVC fabric is optimal in preventing skin contamination by fenthion and detergent had the best efficiency for fenthion decontamination. CONCLUSIONS: Since the whole analytical process is extremely fast, this technique allows early point-of-care identification of contaminating pesticides on the skin of exposed patients in the emergency room, as well as rapid assessment of the adequacy of decontamination.

6-Shogaol Suppresses 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b] Pyridine (PhIP)-Induced Human 786-O Renal Cell Carcinoma Osteoclastogenic Activity and Metastatic Potential.

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) which can be detected in processed meats and red meats, is a potential carcinogen for renal cell carcinoma (RCC). Approximately 30% of patients with metastatic RCC have bone metastases, and the prognosis of RCC with bone metastases is poor. Thus, the aim of the present study was to investigate whether PhIP induced bone metastases and to develop novel therapeutic agents. Our data revealed that PhIP pre-treatment increased the production of parathyroid hormone-related protein (PTHrP) in human 786-O renal cell carcinoma cells. Subsequently, the cultures of human osteoblasts with PhIP-stimulated condition medium of 786-O increased the expression of the macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL), and decreased the expression of osteoprotegerin (OPG). In addition, PhIP-mediated PTHrP up-regulated as well as increased IL-8 secretion in 786-O cells, and then contributed to 786-O-mediated bone resorption. Furthermore, 6-shogaol, which is an active ingredient in ginger, showed suppressive effects on PhIP-mediated bone resorption. In summary, this is the first study to demonstrate that PhIP pre-treatment increases the stimulatory effect of human renal cell carcinoma 786-O on osteoclastogenesis activity directly by PTHrP. In addition, 6-shogaol treatment reverses PhIP-mediated bone resorption. It suggests that 6-shogaol treatment results in bone resorption activity in the RCC model in vitro.

Pneumatosis intestinalis and pneumoretroperitoneum post steroid use in a patient with superior mesenteric artery syndrome.

Pneumatosis intestinalis (PI) refers to the presence of gas within the wall of the small or large intestine. PI can be both asymptomatic and life-threatening. The patient was a 50-year-old man with previous cervical spine abscess and osteomyelitis post debridement 4 years ago, with a heroin abuse history. He presented with abdominal distension ongoing for 4 days and vomiting for 3 times with fluid content. Abdominal computed tomography revealed pneumatosis with pneumoretroperitoneum. A surgeon was contacted and antibiotic treatment was started. The patient was kept on nothing per os and intravenous fluid supply. A drainage tube was inserted into retroperitoneum space on the same day. Tracing back his history, our patient was discharged from the hospital recently with a diagnosis of superior mesenteric artery dyndrome (SMAS), hypersensitivity pneumonitis, and asbestosis with soft tissue pleural plaques and calcified pleural plaques. During the hospitalization period, hydrocortisone dexamethasone and methylprednisolone were prescribed for hypersensitivity pneumonitis. Steroid use and SMAS maybe the cause of PI. Finally, he was discharged 5 days later with a nasojejunal and drainage tubes and was arranged for OPD follow-up. PI can be asymptomatic or life-threatening, and patient management varies based on the clinical condition. Although in this case PI was found in the emergency department, a patient's past history of underlying disease and medication should be reviewed to find the most possible etiology.