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Snakebite envenoming is a public health issue linked to high mortality and morbidity rates worldwide. Although antivenom has been the mainstay treatment for envenomed victims receiving medical care, the diverse therapeutic efficacy of the produced antivenom is a major limitation. Deinagkistrodon acutus is a venomous snake that poses significant concern of risks to human life in Taiwan, and successful production of antivenom against D. acutus envenoming remains a considerable challenge. Among groups of horses subjected to immunization schedules, few or none subsequently meet the quality required for further scale-up harvesting. The determinants underlying the variable immune responses of horses to D. acutus venom are currently unknown. In this study, we assessed the immunoprofiles of high-potency and low-potency horse plasma against D. acutus venom and explored the conspicuous differences between these two groups. Based on the results of liquid chromatography with tandem mass spectrometry (LC-MS/MS), acutolysin A was identified as the major component of venom proteins that immunoreacted differentially with the two plasma samples. Our findings indicate underlying differences in antivenoms with variable neutralization efficacies, and may provide valuable insights for improvement of antivenom production in the future.

The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming.

Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan.

OBJECTIVE: We have previously shown that bitter melon seed oil (BMSO), which is rich in cis-9, trans-11, trans-13 conjugated linolenic acid, is more potent than soybean oil in attenuating body fat deposition in high-fat diet-induced obese C57BL/6J mice. The aim of this study was to obtain a comprehensive insight into how white adipose tissue (WAT) is affected by BMSO administration and to explore the underlying mechanisms of the anti-adiposity effect of BMSO. METHODS AND RESULTS: A proteomic approach was used to identify proteins differentially expressed in the WAT of mice fed diets with or without BMSO for 11 wks. The WAT was also analyzed histologically for morphological changes. Two-dimensional gel electrophoresis (pH 4-7) revealed 32 spots showing a statistically significant difference (P2-fold change). Combined with histological evidence of macrophage infiltration and brown adipocyte recruitment, the proteomic and immunoblotting data showed that the WAT in mice subjected to long-term high dose BMSO administration was characterized by reduced caveolae formation, increased ROS insult, tissue remodeling/repair, mitochondria uncoupling, and stabilization of the actin cytoskeleton, this last change being putatively related to an increased inflammatory response. CONCLUSION: The anti-adiposity effect of BMSO is associated with WAT delipidation, inflammation, and browning. Some novel proteins participating in these processes were identified. In addition, the BMSO-mediated WAT browning may account for the increased inflammation without causing adverse metabolic effects.

Road networks are instrumental in resource allocation and preevacuation, and profoundly affect disaster response and recovery, particularly emergent-disaster logistics and island rescues. Disruptions to road networks impair daily operations, irrespective of whether they are damaged by external forces or failures in interacting elements. However, functional interdependency is absent from transportation vulnerability assessments. This study thus constructed a framework to assess the interdependent vulnerability of road network failures. Based on eleven fragile factors developed in the literature and an empirical case study in the Taipei metropolitan area, road network vulnerability is determined by fuzzy cognitive maps and geographic information systems for functional and spatial interactions, respectively. The analytical results indicate that road network vulnerability is underestimated if the interdependency is neglected. Delay time on the shortest substitution, level of service on adjacent links, and inaccessibility to hospital emergency centers significantly affect vulnerability. Whereas certain socioeconomic resilience is performed in the short term, spatial-functional interdependency dilutes those effects in the long term. The framework developed facilitates decision makers in understanding interdependent vulnerabilities and adopting appropriate strategies to improve vulnerability. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the antiadiposity effect of bitter melon seed oil (BMSO), which is rich in the c/s-9, trans-l 1, trans-]3 isomer of conjugated linolenicacid. In Expt. 1, C57BL/6J mice were feda butter-based, high-fat diet [HB; 29% butter + 1% soybean oil (SBO)l for 10 wk to induce obesity. They then continued to receive that diet or were switched to an SBO-based, high-fat diet alone (HS; 30% SBO) or containing bitter melon seed oil (BMSO) (HBM; 15% SBO -i-15% BMSO) for 5 wk. The body fat percentage was significantly lower in mice fed the HBM diet (21 %), but not the HS diet, compared with mice fed the HB diet. In Expt. 2, mice were fed an SBO-based, high-fat diet containing 0 (HS), 5 (LBM), 10 (MBM), or 15% (HBM) BMSO for 10 wk. In the LBM, MBM, and HBM groups, the body fat percentage was significantly lower by 32, 35, and 65%, respectively, compared with the HS control. The reduction in the HBM group was significantly greater than that in the LBM or MBM group. BMSO administration increased phosphorylation of acetyl-CoA carboxylase, cAMP-activated protein kinase (PKA), and signal transducer and activator of transcription 3 in the white adipose tissue (WAT), suggesting that PKA and leptin signaling might be involved in the BMSO-mediated reduction in lipogenesis and increase in thermogenesis and lipolysis. However, compared with the HS control, the HBM group had a significantly higher TNFa concentration in the WAT accompanied by TUNEL-positive nuclei. We conclude that BMSO is effective in attenuating body fat accumulation through mechanisms associated with PKA activation and programmed cell death in the WAT, but safety concerns need to be carefully addressed. [ABSTRACT FROM AUTHOR]

Different transport stakeholders have different needs for transport infrastructure and services. Meeting the needs of all stakeholders implies a trade-off of benefits and costs between supply and demand and creates transport diversity issues. However, the literature has largely ignored these issues. Transport diversity can assess the level to which important needs are satisfied equitably, and monitor whether transportation systems are moving towards sustainability by confirming the targets and basic level of quality of life. Based on the concept of transport diversity, this study utilizes fuzzy multi-objective programming to solve non-linear multi-objective problems involving urban public transit systems to determine the impact of resource allocation on needs satisfaction in relation to stakeholder behaviors. The proposed approach avoids problems of inefficient and inequitable resource allocation. A real-life case is presented to demonstrate the feasibility of applying the proposed methodology. Furthermore, empirical outcomes show that recent investments allocated to public transit systems considered equitable stakeholder satisfaction for both mass rapid transit (MRT) and bus, and also promoted transport diversity in the Taipei metropolitan area. [ABSTRACT FROM AUTHOR]

Different transport stakeholders have different needs for transport infrastructure and services. Meeting the needs of stakeholders implies a tradeoff of benefits and costs between supply and demand and creates issues of transport diversity. However, the literature has largely ignored these issues. This study aims to provide a framework evaluating transport diversity to promote quality of life. Transport diversity is defined as the satisfied level of stakeholder needs in this study and measured as the gap between the expected goal and present values of stakeholder needs in the form of the Shannon–Weaver index. Transport diversity can assess whether the level to which important needs are satisfied equitably, and monitor whether the transportation system is moving toward sustainability via confirming the targets and the basic level of quality of life. This study hopes that the conceptual framework developed can assist decision makers in understanding the relationship between transport diversity and sustainability, and provide a new assessment method for improvements in quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Seizure is a common poisoning-related neurological presentation in the emergency department (ED). Although brain computed tomography (CT) is recommended in patients presenting with first seizures, its role in patients with a suspected drug/substance-induced seizure (DSS) remains inconclusive. This study evaluated whether brain CT examination changes the management and outcome of DSS patients. Methods: We retrospectively reviewed adult patients presenting to the ED with a DSS in Linkou and Taipei Chang Gung Memorial Hospital, Taiwan, from January 2008 to December 2015. We also analyzed whether the brain CT examinations found meaningful acute abnormalities and their impact on subsequent management. We compared the differences between DSS patients undergoing CT scans or not to identify factors that affect the decision to arrange brain CT. Results: The study enrolled 97 patients (69 males). The most common cause of DSS was alcohol withdrawal (58.76%), followed by carbon monoxide (12.37%) and stimulants (8.25%). Eight (8.25%) patients developed status epilepticus, 15 (15.46%) were intubated, and 37 (37.76%) were admitted, including 12 (12.26%) to the intensive care unit. Brain CT was performed in 64 (66.0%) patients and four had abnormal reports that led to further imaging studies. The abnormal findings ultimately had no significant clinical impact. Patients who underwent CT scans had a worse Glasgow Coma Scale score (p = 0.024) and higher rate of status epilepticus (p = 0.031). Conclusion: Brain CT does not provide substantial information for the care of DSS patients. Multi-center prospective studies are needed to obtain stronger evidence. [ABSTRACT FROM AUTHOR]

Clinical Introduction: A 60-year-old man had a long history of chronic hepatitis C. He presented to the emergency department with 2 days of progressive dyspnoea. Clinical manifestations included respiratory distress, cyanosis, digital clubbing, spider naevi on the upper chest and shifting dullness in the abdomen (see online supplementary figure S1). The ECG showed sinus tachycardia and left axis deviation. The chest radiography depicted blunting of right costophrenic angle with small pleural effusions and bilateral prominent pulmonary vascular markings (see online supplementary figure S2). The dyspnoea was exacerbated by upright posture and improved with recumbency. The hypoxaemia could not be corrected with administration of 100% oxygen. Contrast-enhanced transthoracic echocardiography was performed with injection of agitated saline (see figure 1 and online supplementary video). CT scan of the chest revealed some vascular abnormalities (see online supplementary figure S3-S6).Question: Which of the following is the next best step in management?Catheter-based closure of intracardiac shuntLiver transplantationPulmonary angiography and embolisationThoracentesisTransjugular intrahepatic portosystemic shunt. [ABSTRACT FROM AUTHOR]