Multiplex Polymerase Chain Reaction Assay for Early Diagnosis of Viral Infection

Viral reactivation is one of the most serious complications for immunocompromised patients. Under immunosuppressive conditions, some viruses can be reactivated solely or simultaneously and may thus cause life-threatening infection. Therefore, the prompt and proper diagnosis of viral reactivation is important for the initiation of preemptive therapy. For this purpose, we recently developed a multiplex-virus polymerase chain reaction (PCR) assay. The multiplex PCR assay is designed to qualitatively measure the genomic DNA of 12 viruses at once: cytomegalovirus (CMV), human herpesvirus type 6 (HHV-6), HHV-7, HHV-8, Epstein-Barr virus (EBV), varicella-zoster virus (VZV), BK virus (BKV), JC virus (JCV), parvovirus B19 (ParvoB19), herpes simplex virus type 1 (HSV-1), HSV-2, and hepatitis B virus (HBV). When a specific PCR signal is obtained, the viral load is determined by a quantitative real-time PCR. The qualitative multiplex and quantitative real-time PCR procedures take only 3 hours to complete. With this assay system, we can identify viremia at the early stage and thereby prevent it from progressing to overt and symptomatic viral infection in immunocompromised patients, such as those receiving hematopoietic stem cell transplantation

Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation

CD4(+)Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs promptly respond to low concentrations of IL-2 through the constitutive expression of high-affinity IL-2 receptors. It has been reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD. Clinical studies of IL-2 therapy so far have mainly targeted patients in the chronic phase of transplantation when acute immune responses has subsided. However, the biological and clinical effects of exogenous IL-2 in an acute immune environment have not been well investigated. In the current study, we investigated the impact of exogenous IL-2 therapy on the post-transplant homeostasis of T cell subsets which influence the balance between GVHD and GVL in the acute phase, by setting the various immune environments early after HSCT in murine model. We initially found that 5,000 IU of IL-2 was enough to induce the active proliferation of Treg without influencing other conventional T cells (Tcons) when administered to normal mice. However, activated Tcons showed the response to the same dose of IL-2 in recipients after allogeneic HSCT. In a mild inflammatory environment within a threshold, exogenous IL-2 could effectively modulate Treg homeostasis with just limited influence to activated T cells, which resulted in an efficient GVHD suppression. In contrast, in a severely inflammatory environment, exogenous IL-2 enhanced activated T cells rather than Tregs, which resulted in the exacerbation of GVHD. Of interest, in an immune-tolerant state after transplant, exogenous IL-2 triggered effector T-cells to exert an anti-tumor effect with maintaining GVHD suppression. These data suggested that the responses of Tregs and effector T cells to exogenous IL-2 differ depending on the immune environment in the host, and the mutual balance of the response to IL-2 between T-cell subsets modulates GVHD and GVL after HSCT. Our findings may provide useful information in the optimization of IL-2 therapy, which may be personalized for each patient having different immune status

Personalization of Chemotherapy for Metastatic Pancreatic Cancer

Erlotinib is an approved drug for the treatment of advanced pancreatic cancer; however, its survival benefit is small and its cost is high, and the decision to use the drug may often be personalized according to the patient's background. A 72-year-old Asian man in good general condition chose gemcitabine monotherapy over combination therapy with gemcitabine plus erlotinib because the survival benefit of the latter was small. The cost of the drug did not appear to affect this decision. This report details the process of decision making with respect to whether a patient receives targeted therapy, and suggests that the use of molecular-targeted drugs must be personalized from many perspectives, including the patient's social situation

Developing a behaviour rubric for the practical model of ethical behaviour for clinical nursing

Abstract Aim The present study aimed to develop an ethical behaviour rubric for nurses and evaluate its reliability and validity. Method This study was to designed to construct a rubric and evaluate the reliability and validity. The ethical behaviour rubric was distributed to 241 nurses and 154 were completed and returned. The intra‐rater and inter‐rater reliability were evaluated by intraclass correlation coefficient (ICC) for all 10 items on the ethical behaviour rubric, and the internal consistency reliability was evaluated using Cronbach's α. Construct validity was tested with explanatory factor analysis, and criterion validity was tested using the known‐groups method. Results Intra‐rater reliability had a high interrater agreement (ICC = 0.9), and inter‐rater reliability had a high interrater agreement (ICC = 0.84). The Cronbach's α coefficient was 0.96. There was a linear correlation between the number of years of nursing experience and rubric scores p < 0.001. Exploratory factor analysis revealed 10 items loading on four factors. The result of factor analysis is that Cronbach's α was 0.93 for the first factor, 0.83 for the second factor, 0.91 for the third factor, and 0.77 for the fourth factor. Conclusions Our rubric was found to be a valid and reliable tool for the assessment of ethical behaviour among nurses in Japan

Status of radiotherapy in a multidisciplinary cancer board.

Multidisciplinary cancer boards (CBs) for making cancer treatment decisions have become popular in many countries; however, the status of radiotherapy in CBs and the influence of CBs on radiotherapy decisions have not been studied. To clarify these issues, we reviewed the minutes of our CBs from February 2010 to March 2012, and we classified planned treatments discussed at the CBs into five categories and analyzed decisions concerning radiotherapy in each category. The fraction of cases for which radiotherapy was recommended was 536/757 (71%). These cases included 478 cases (63%) for which radiation therapy was planned and four cases (0.5%) for which radiation therapy was unexpectedly recommended. On the other hand, radiation therapy was canceled in 21 cases (4%) for which radiation therapy had been planned. This study showed that radiotherapy was discussed in many cases at CBs and that CBs have a great influence on decisions concerning radiotherapy

Crystallization and preliminary X-ray analysis of the tumour necrosis factor α–tumour necrosis factor receptor type 2 complex

The formation, crystallization and preliminary X-ray diffraction analysis of the tumour necrosis factor α (TNF)–tumour necrosis factor receptor type 2 (TNFR2) complex are described. The initial electron-density map, which was calculated using only the phases of refined TNF trimer structures, could detect the main chains and side chains of TNFR2 around the TNF trimer

The current status of neglected tropical diseases in Japan: A scoping review.

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries