Human Olfactory Receptor Sensor for Odor Reconstitution.

Among the five human senses, light, sound, and force perceived by the eye, ear, and skin, respectively are physical phenomena, and therefore can be easily measured and expressed as objective, univocal, and simple digital data with physical quantity. However, as taste and odor molecules perceived by the tongue and nose are chemical phenomena, it has been difficult to express them as objective and univocal digital data, since no reference chemicals can be defined. Therefore, while the recording, saving, transmitting to remote locations, and replaying of human visual, auditory, and tactile information as digital data in digital devices have been realized (this series of data flow is defined as DX (digital transformation) in this review), the DX of human taste and odor information is not yet in the realization stage. Particularly, since there are at least 400,000 types of odor molecules and an infinite number of complex odors that are mixtures of these molecules, it has been considered extremely difficult to realize "human olfactory DX" by converting all odors perceived by human olfaction into digital data. In this review, we discuss the current status and future prospects of the development of "human olfactory DX", which we believe can be realized by utilizing odor sensors that employ the olfactory receptors (ORs) that support human olfaction as sensing molecules (i.e., human OR sensor).

How do medical journalists treat cancer-related issues?

Cancer patients can obtain information about their illness through a variety of media sources. Therefore, it is important to know how medical journalists treat cancer-related issues; to that end, we sent self-administered questionnaires to 364 journalists in 82 organisations who had reported on medical issues for the Japanese media, asking for their reasons for reporting on cancer-related issues and the difficulties they had faced. The most common reason for reporting on health-related issues was their personal interest in a particular issue (n = 36). They mainly covered conventional therapies (n = 33), healthcare policy (n = 30), new therapies (n = 25), and diagnosis (n = 25). All of the journalists that were surveyed experienced some difficulties in reporting health issues. Significant concerns included the quality of information (n = 36), social impact (n = 35), lack of technical knowledge (n = 35), and difficulty in understanding technical terms (n = 35). Journalists commonly used personal networks, including physicians, as information sources (n = 42), as well as social media (e.g., e-mail, Twitter and Facebook) (n = 32). Topic selection was biased, with 35 of 48 journalists having never reported on topics concerning hospices. Physicians were the most trusted source of information about cancer, and journalists attached high importance to interviewing them. As medical knowledge is advancing rapidly, journalists may have increasing difficulty covering cancer-related issues.

Cancer articles in weekly magazines: useful media to deliver cancer information to the public?

OBJECTIVE: Japanese weekly magazines, which have a circulation of over 2 700 000, play important roles in communicating with the public. They offer a wide range of information, entertainment, gossip, politics and economics, and often include articles on cancer. However, cancer articles in magazines have not been systematically analyzed. METHODS: We investigated cancer-related articles and advertisements in six major Japanese weekly magazines to demonstrate trends in public interest regarding cancer. RESULTS: The total number of articles assessed from July 2009 to December 2010 was 36 914, of which 696 (1.9%) were cancer articles. The total number of advertisements was 21 718, of which 340 (1.6%) were related to cancer. The number of cancer articles demonstrated an upward trend during the study period. Articles focused on lung (n = 145) and urogenital cancer (n = 122). The most common content comprised therapies and diagnosis (n = 340) and case reports on individual patients (n = 160). After a famous Japanese comedian revealed his prostate cancer diagnosis, the number of articles on prostate cancer increased from 2.0 to 6.6 per month. Immunotherapy including some dubious folk therapies was the most frequently reported cancer therapy in articles and advertisements (30.4%). A small group of oncologists were repeatedly referred to in comment sources; 35.6% of comments were presented by only five doctors. CONCLUSIONS: Cancer articles in weekly magazines are common paper media for providing cancer information to the public. However, the information provided might place emphasis on unestablished treatments or biased opinions.

Increased financial burden among patients with chronic myelogenous leukaemia receiving imatinib in Japan: a retrospective survey.

BACKGROUND: The financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML) who have been treated with imatinib. METHODS: A questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008. RESULTS: A total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15-94). A financial burden was felt by 41.2 % (28 of 68) of the patients treated with imatinib in 2000, 70.8 % (201 of 284) in 2005, and 75.8 % (400 of 528) in 2008. Overall, 182 patients (31.7 %) considered its discontinuation because of the financial burden and 15 (2.6 %) temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients' median annual household incomes were 49,615 US Dollars (USD), 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95-0.98, p ≪ 0.0001 for 1-year increments), and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85-0.99, p = 0.03 for 10,000 USD-increments) were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co-payments (OR = 2.21, 95 % CI: 1.28-4.28, p = 0.004 for 10,000 USD-increments) were more likely to have considered discontinuing their imatinib treatment. CONCLUSIONS: The proportion of CML patients who sensed a financial burden increased between 2000 and 2008. During this period, their annual incomes fell by 13,000 USD, although their medical expenses did not change. Financial support for patients being treated with expensive drugs remains a major problem in Japan.

Data mining of mental health issues of non-bone marrow donor siblings.

BACKGROUND: Allogenic hematopoietic stem cell transplantation is a curative treatment for patients with advanced hematologic malignancies. However, the long-term mental health issues of siblings who were not selected as donors (non-donor siblings, NDS) in the transplantation have not been well assessed. Data mining is useful in discovering new findings from a large, multidisciplinary data set and the Scenario Map analysis is a novel approach which allows extracting keywords linking different conditions/events from text data of interviews even when the keywords appeared infrequently. The aim of this study is to assess mental health issues on NDSs and to find helpful keywords for the clinical follow-up using a Scenario Map analysis. FINDINGS: A 47-year-old woman whose younger sister had undergone allogenic hematopoietic stem cell transplantation 20 years earlier was interviewed as a NDS. The text data from the interview transcriptions was analyzed using Scenario Mapping. Four clusters of words and six keywords were identified. Upon review of the word clusters and keywords, both the subject and researchers noticed that the subject has had mental health issues since the disease onset to date with being a NDS. The issues have been alleviated by her family. CONCLUSIONS: This single subject study suggested the advantages of data mining in clinical follow-up for mental health issues of patients and/or their families.

Internet-based survey on medical manga in Japan.

The more manga (Japanese graphic novels) communicate medical information, the more people are likely to be influenced by manga. We investigated through an Internet search using Google the characteristics of medical manga published in Japan, defined as those in which the main character is a medical professional and that occur in a medical setting. As of December 2008, 173 medical manga had been published. For a period of time after the first medical manga by Osamu Tezuka in 1970, the number of publications maintained a steady level, but increased rapidly in the mid 1980s. The professions of the protagonist were 134 doctors, 19 nurses, 3 dentists, 3 medical students, and 1 nursing student. Although the main character was mostly a doctor, manga featuring paramedical professionals have increased since 1990s. Medical manga may be a powerful tool for increasing the awareness of the public regarding medicine.

Structural problems of medical news reports in newspapers: a verification of news reports on an incident of mass nosocomial Serratia infection.

It is unclear how changes in the content and number of news reports over time affect the impressions made in the minds of newspaper readers. This study targeted news reports in major newspapers regarding an incident of mass nosocomial Serratia infection that occurred at one clinic. The trends in the total number of articles and total number of characters contained in the articles were congruent, with a peak on the day after the incident was disclosed and a rapid decrease thereafter. The numbers of articles and characters that appeared during the first 3 days corresponded to 45 and 51% of those that appeared during the entire study period. On day 9, it was published that Serratia liquefaciens propagated on medical instruments, and both the number of articles and the number of characters increased by approximately 40% in comparison to those published on the day after the initial report of the incident. The individual articles were deemed to be medically accurate; however, the main problem was that only part of the specific medical issue had been emphasized because of a poor balance in the number of news reports on this topic.

A study of the changes in how medically related events are reported in Japanese newspapers.

Media reports of medically related events have a major effect on the healthcare community but there have been few detailed investigations conducted to investigate their content. The Nikkei Telecom 21 database was used to investigate the number of reports concerning medically related events between 1992 and 2007 in Japan's 5 national newspapers. For this period, both the total number of articles and the number of articles containing medically-related keywords were determined. The number of reports relating to medically related occurrences increased sharply from 1999 to 2000 and displayed a decrease from 2003 before increasing again in 2008. As of 2008, such reports account for 0.17% of total newspaper articles. The use of the word 'iryokago' (medical professional negligence or error) drastically increased in 1999 but showed a consistent decrease from 2004. On the other hand the frequency of reports relating to 'litigation' and 'punishment' increased rapidly in 1999 before leveling off. Despite this, the number of articles relating to medically related occurrences that were caused by doctor shortages and system errors increased sharply between 2006 and the present. Results indicate that the manner in which newspapers report medically related events is undergoing major changes.

ERas is expressed in primate embryonic stem cells but not related to tumorigenesis.

The ERas gene promotes the proliferation of and formation of teratomas by mouse embryonic stem (ES) cells. However, its human orthologue is not expressed in human ES cells. This implies that the behavior of transplanted mouse ES cells would not accurately reflect the behavior of transplanted human ES cells and that the use of nonhuman primate models might be more appropriate to demonstrate the safety of human ES cell-based therapies. However, the expression of the ERas gene has not been examined in nonhuman primate ES cells. In this study, we cloned the cynomolgus homologue and showed that the ERas gene is expressed in cynomolgus ES cells. Notably, it is also expressed in cynomolgus ES cell-derived differentiated progeny as well as cynomolgus adult tissues. The ERas protein is detectable in various cynomolgus tissues as assessed by immunohistochemisty. Cynomolgus ES cell-derived teratoma cells, which also expressed the ERas gene at higher levels than the undifferentiated cynomolgus ES cells, did not develop tumors in NOD/Shi-scid, IL-2Rgamma(null) (NOG) mice. Even when the ERas gene was overexpressed in cynomolgus stromal cells, only the plating efficiency was improved and the proliferation was not promoted. Thus, it is unlikely that ERas contributes to the tumorigenicity of cynomolgus cells. Therefore, cynomolgus ES cells are more similar to human than mouse ES cells despite that ERas is expressed in cynomolgus and mouse ES cells but not in human ES cells.

Regional social system for specialized medical care in hematologic malignancies: a pilot study.

INTRODUCTION: The uneven distribution of physicians in Japan disadvantages rural and remote patients with hematological malignancies to the extent that they may not receive standard treatments. There are 7 core regional medical centers in Tokushima Prefecture. A Tokushima rural medical center's clinical hematology division experienced difficulty in treating patients due to a lack of physicians despite an increasing number of patients with hematological malignancies. The aim of this pilot study was to investigate the regional medical supply and demand associated with newly diagnosed hematological malignancies in Tokushima Prefecture, Japan. METHODS: The study investigated the home addresses of patients with newly diagnosed acute leukemia, malignant lymphoma and multiple myeloma who were hospitalized in the 7 core Tokushima centers in 2006. The surveyed patients were compared with the estimated number of patients with those diseases that were newly developed, based on a calculation of incidence and population by age group. The survey also investigated the number and distribution of hematologists. RESULTS: A total of 248 patients were newly hospitalized in the 7 core centers in Tokushima Prefecture during the 1 year period. The surveyed number of patients was similar to the estimated number of patients in all secondary medical areas, except for one area where there was active traffic to and from adjacent prefectures. More than 70% (median 80%; range 72-100%) of the patients received their treatments within a radius of approximately 25 km from their homes. There were 24 hematologists in November 2006 and 63% of these worked in the city with the largest population. The mean estimated number of patients per unit population was significantly higher in rural and remote areas than in urban areas (p <0.01). Three regional centers had only one or two hematologists. CONCLUSIONS: Most patients with newly developed hematological malignancies in Tokushima Prefecture received treatment from intra-prefectural hematologists within a 25 km distance of their homes. Rural areas had a shortage of hematologists who were localized in urban areas. It is recommended that functions of core medical centres and rural clinics are redesigned according the availability of specialized treatments, and to maximize cooperation between physicians at rural clinics and hematologists at urban hospitals.

Knockout serum replacement (KSR) has a suppressive effect on Sendai virus-mediated transduction of cynomolgus ES cells.

Sendai virus (SeV) vectors can introduce foreign genes efficiently and stably into primate embryonic stem (ES) cells. For the application of these cells, the control of transgene expression is important. Cynomolgus ES cells transduced with a SeV vector expressing the green fluorescent protein (GFP) gene were propagated in Knockout serum replacement (KSR)-supplemented medium, used widely for the serum-free culture of ES cells, and growth and transgene expression were evaluated. The SeV vector-mediated GFP expression was suppressed in the KSR-supplemented medium, although it was stable in regular fetal bovine serum (FBS)-supplemented medium. Propagation in the KSR-supplemented medium eventually resulted in a complete suppression of GFP expression and eradication of the SeV genome. The inhibitory effect of KSR on the transduction was attributable to the positive selection of untransduced ES cells in addition to the removal of the SeV vector from transduced cells. KSR also reduced the efficiency of the transduction. SeV vector-mediated transgene expression in ES cells was suppressed in the KSR-supplemented medium. Although the suppression is limited in specified cells such as ES cells, these findings will help elucidate how to control transgene expression.

Sustained macroscopic engraftment of cynomolgus embryonic stem cells in xenogeneic large animals after in utero transplantation.

Because embryonic stem (ES) cells are able to proliferate indefinitely and differentiate into any type of cell, they have the potential for providing an inexhaustible supply of transplantable cells or tissues. However, methods for the in vitro differentiation of human ES cells are still quite limited. One possible strategy would be to generate differentiated cells in vivo. In view of future clinical application, we investigated the possibility of using xenogeneic large animals for this purpose. We transplanted nonhuman primate cynomolgus ES cells into fetal sheep at 43-67 gestational days (full term 147 days, n=15). After birth, cynomolgus tissues, which were mature teratomas, had been engrafted in sheep when more than 1 x 10(6) ES cells were transplanted at <50 gestational days. Despite the sustained engraftment, both cellular and humoral immune responses against the ES cells were detected, and additional transplantation was not successful in the animals. At 2 weeks post-transplantation, the ES cell progeny proliferated when transplanted at 48 (<50) gestational days, whereas they were cleared away when transplanted at 60 (>50) gestational days. These results support the rapid development of the xenogeneic immunological barrier in fetal sheep after 50 gestational days. Notably, a large number of Foxp3(+) regulatory T cells were present around the ES cell progeny, but macrophages were absent when the transplant was conducted at <50 gestational days, implying that regulatory T cells and premature innate immunity might have contributed to the sustained engraftment. In conclusion, long-term macroscopic engraftment of primate ES cells in sheep is feasible despite the xenogeneic immunological barrier.

Characterization of acute graft-versus-host disease following reduced-intensity stem-cell transplantation from an HLA-identical related donor.

To investigate clinical features of acute graft-versus-host disease (GVHD) following reduced intensity stem-cell transplantation (RIST), we retrospectively investigated medical records of 65 patients with hematologic malignancies who underwent RIST from a matched related donor. Preparative regimen comprised fludarabine 30 mg/m(2) (n = 53) or cladribine 0.11 mg/kg (n = 12) for 6 days plus busulfan 4 mg/kg for 2 days. Twelve patients received rabbit antithymocyte globulin 2.5 mg/kg/day for 2-4 consecutive days. Grade II to IV acute GVHD was diagnosed in 36 patients (55%). Its median onset was day 58 (range, 17-109), while it was bimodal, peaking day 15-29 (early-onset GVHD, n = 18) and day 75-89 days (late-onset GVHD, n = 18). Variables that were more common in early-onset GVHD than late-onset GVHD included skin rash (89% vs. 61%) and noninfectious fevers (33% vs. 11%). Desaturation, pulmonary infiltrates and hyperbilirubinemia (>2.0 mg/dL) were more common in late-onset GVHD (6% vs. 22%, 0% vs. 17%, and 6% vs. 33%, respectively). All of the patients with early-onset GVHD given corticosteroid responded to it, while 5 of the 18 patients with late-onset GVHD failed to respond it. Patients with either early-onset or late-onset GVHD tended to have better progression-free survival (PFS) than those without it; however, there was no significant difference in PFS between patients with early-onset GVHD and those with late-onset GVHD. This study suggests that several etiologies might have contributed to the development of acute GVHD following RIST.