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A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.

Cyclooxygenase metabolizes dihomo-γ-linolenic acid and arachidonic acid to form prostaglandin (PG) E, including PGE1 and PGE2, respectively. Although PGE2 is well known to play an important role in the development and maintenance of hyperalgesia and allodynia, the role of PGE1 in pain is unknown. We confirm whether PGE1 induced pain using orofacial pain behavioral test in mice and determine the target molecule of PGE1 in TG neurons with whole-cell patch-clamp and immunohistochemistry. Intradermal injection of PGE1 to the whisker pads of mice induced a reduced threshold, enhancing the excitability of HCN channel-expressing trigeminal ganglion (TG) neurons. The HCN channel-generated inward current (Ih) was increased by 135.3 ± 4.8% at 100 nM of PGE1 in small- or medium-sized TG, and the action of PGE1 on Ih showed a concentration-dependent effect, with a median effective dose (ED50) of 29.3 nM. Adenylyl cyclase inhibitor (MDL12330A), 8-bromo-cAMP, and the EP2 receptor antagonist AH6809 inhibited PGE1-induced Ih. Additionally, PGE1-induced mechanical allodynia was blocked by CsCl and AH6809. PGE1 plays a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons, suggesting a potential therapeutic target in that PGE1 could be involved in pain as endogenous substances under inflammatory conditions.

Foreign direct investments (FDIs) influence insurance markets directly, through foreign insurers’ participation in domestic markets, and indirectly, through cross-sectoral spillover effects. This article focuses on the indirect effects and examines the relationship between greenfield FDIs and diversification in European insurance markets. Using panel data of 28 countries for the period 2004–2019, we find that greenfield FDIs induce greater diversification of insurance markets. Our results suggest a non-linear relationship and potential mediating effects of financial development on the FDI–insurance relationship. Robustness tests using different measures of market diversification, model specifications and averaging of the data show consistent results.

Purpose - The purpose of this paper is to examine insurance regulation theories, regulatory agency structures and measures.Design methodology approach - This study investigates significance of regulatory agency structure, key regulatory measures, political stability and cultural dimension in insurance markets of 56 developed and developing countries for 2005-2009.Findings - It was found that insurance consumption is lower in countries with an authority exclusively for insurance regulation but life insurance consumption is higher when the agency is part of government or when another agency is jointly responsible for insurance regulation. Market entry regulation leads to lower consumption whereas market exit regulation has the opposite effect. Solvency regulation and required use of standard forms for insurer financials lead to greater consumption of insurance. A positive impact on the nonlife market is observed for accounting regulation and regulator's intervention power.Practical implications - Price control regulation may lower consumption of insurance whereas tariff rating brings about a rise in the consumption. Regulation of insurance intermediaries or corporate governance may lower insurance consumption whereas the requirement that insurers employ an actuary or actuaries gives rise to the consumption.Originality value - The author found no difference between OECD and non-OECD countries. However, corruption-freeness and inflation impact insurance consumption. Using OECD country data only, a negative impact was found of the single agency structure and tariff regulation in the life insurance market and a positive impact of regulation by two or more agencies in the life insurance market and of price control regulation in the nonlife insurance market. Corruption-freeness positively affects the loss ratio in the life insurance market and the combined ratio in the nonlife insurance market.

The human capital attraction and retention challenges in the insurance industry intensify due to a combining effect of demographic, social, economic and market-specific factors. In addition, there is human capital obsolescence risk. The study findings indicate that: the financial services occupation group requires high competency in cognitive abilities, social perspectives, management knowledge and communication skills, but not much in technical, physical/sensory or engineering skills; the insurance industry and most insurance companies have not attained a high reputation; and insurance is not a widely recognised profession by the public and many college students. Based on our macro- and micro-spective investigation of the industry and university education, we recommend: more public relations activities, closer work with local universities and their faculties for adoption of the field as a major; better talent recruitment, training and retention programmes; and preparedness for talent morbidity across financial services sectors and countries.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major drawback in the use of chemotherapeutic agents for patients with cancer. Although studies have investigated a broad number of molecules that might be related to CIPN, the differences in the chemokine pathways between various chemotherapeutic agents, such as vincristine and oxaliplatin, which are some of the most widely used treatments, have not been fully elucidated. We confirmed that the administration (intraperitoneal injections for seven days) of vincristine (0.1 mg/kg) and oxaliplatin (3 mg/kg) induced pain by using the von Frey behavioral test. Subsequent applications with vincristine and oxaliplatin led to mechanical allodynia that lasted more than one week from the fifth day. After the induction of mechanical allodynia, the mRNA expression of CXCR2, CXCL1, CXCL3, and CXCL5 was examined in the dorsal root ganglia (DRG) and spinal cord of the CIPN models. As a result, the mRNA expression of CXCR2 robustly increased in the lumbar spinal cord in the oxaliplatin-treated mice. Next, to evaluate the involvement of CXCR2 in CIPN, reparixin, a CXCR1/2 inhibitor, was administered intrathecally or intraperitoneally with vincristine or oxaliplatin and was further verified by treatment with ruxolitinib, which inhibits Janus kinase 2 downstream of the CXCR1/2 pathway. Reparixin and ruxolitinib blocked oxaliplatin-induced allodynia but not vincristine-induced allodynia, which suggests that CXCR2-related pathways are associated with the development of oxaliplatin-induced neuropathy. Together with the above results, this suggests that the prevention of oxaliplatin-induced neuropathy by CXCR2 inhibition can lead to successful chemotherapy, and it is important to provide appropriate countermeasures against CIPN development for each specific chemotherapeutic agent.

This article introduces a government‐led insurance fraud detection program in Korea. The Insurance Fraud Recognition System (IFRS) uses policy and claims data from multi‐lines of insurance (life, automobile, and fire), employs a three‐stage statistical and link analysis to identify presumably fraudulent claims by claimant or by group, and generates system reports that the government regulator draws on to make decisions. The authors evaluate the system based on the fraud statistics and IFRS results for 2004, and offer recommendations for system improvement. This article examines existing studies about fraud, industry experiments using advanced technology, and government assistance to the insurance industry's fight against fraud in selected countries. It also provides a brief overview of the Korean insurance market, especially after the recent Asian economic crisis.

This article first investigates the microfinance—principally microinsurance—market at the global level and the business structure of over 600 microfinance institutions (MFIs) in 83 countries that were in operation during 1998-2007. It then empirically examines the impact of organisational, market and socio-cultural factors on the supply of insurance, lending and savings services by MFIs in developing countries. Findings from a series of probit analyses indicate that a rise in the financial expense ratio, loan repayments in arrears, years of operation, number of borrowers, woman borrower ratio, life insurance penetration ratio and family size positively affect MFIs' willingness to expand their operations, certainly to microinsurance business. In contrast, they are likely to stay away from the insurance market when their loan asset ratio, bad loan write-off ratio or average loan size in comparison to GNI per capita is on the rise. It seems MFIs focus on lending service in Muslim populous countries. Finally, we find no evidence that presence of insurance affects availability of savings service, and vice versa, in the microfinance market.

BackgroundAutoimmune hepatitis (AIH) can result in end-stage liver disease that requires inpatient treatment of the hepatic complications. Given this phenomenon, it is important to analyse the impact of gender and race on the outcomes of patients who are admitted with AIH using a national hospital registry.MethodsThe 2012–2017 National Inpatient Sample database was used to select patients with AIH, who were stratified using gender and race (Hispanics and blacks as cases and whites as reference). Propensity score matching was employed to match the controls with cases and compare mortality, length of stay and hepatic complications.ResultsAfter matching, there were 4609 females and 4609 males, as well as 3688 blacks and 3173 Hispanics with equal numbers of whites, respectively. In multivariate analysis, females were less likely to develop complications, with lower rates of cirrhosis, ascites, variceal bleeding, hepatorenal syndrome, encephalopathy and acute liver failure (ALF); they also exhibited lower length of stay (adjusted OR, aOR 0.96 95% CI 0.94 to 0.97). When comparing races, blacks (compared with whites) had higher rates of ALF and hepatorenal syndrome related to ALF, but had lower rates of cirrhosis-related encephalopathy; in multivariate analysis, blacks had longer length of stay (aOR 1.071, 95% CI 1.050 to 1.092). Hispanics also exhibited higher rates of hepatic complications, including ascites, varices, variceal bleeding, spontaneous bacterial peritonitis and encephalopathy.ConclusionMales and minorities are at a greater risk of developing hepatic complications and having increased hospital costs when admitted with AIH.

This paper provides empirical evidence consistent with the existence of adverse selection and moral hazard in the whole life and term life insurance market. We use life insurance companies' data to recognize adverse selection, moral hazard, and medical examination effects. Drawing on data from more than 1.3 million insurance policies in Japan, we find evidence that the mortality of the insured at policy inception is lower than that of the general public; with the selection of the insured via medical examination, we did not find adverse selection in new whole life and term life insurance risks. In the case of automatic renewal of term life policies where insurance companies set the price using the same regulated mortality table as that of optional renewal term life policies, the effectiveness of medical selection attenuates after approximately five years of the policy life, and the costs from adverse selection and the moral hazard from suicide begin to occur around the fifth year.