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Abstract Background Cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) (K3)—a novel synthetic single-stranded DNA immune adjuvant for cancer immunotherapy—induces a potential Th1-type immune response against cancer cells. We conducted a phase I study of CpG ODN (K3) in patients with lung cancer to assess its safety and patients’ immune responses. Methods The primary endpoint was the proportion of dose-limiting toxicities (DLTs) at each dose level. Secondary endpoints included safety profile, an immune response, including dynamic changes in immune cell and cytokine production, and progression-free survival (PFS). In a 3 + 3 dose-escalation design, the dosage levels for CpG ODN (K3) were 5 or 10 mg/body via subcutaneous injection and 0.2 mg/kg via intravenous administration on days 1, 8, 15, and 29. Results Nine patients (eight non-small-cell lung cancer; one small-cell lung cancer) were enrolled. We found no DLTs at any dose level and observed no serious treatment-related adverse events. The median observation period after registration was 55 days (range: 46–181 days). Serum IFN-α2 levels, but not inflammatory cytokines, increased in six patients after the third administration of CpG ODN (K3) (mean value: from 2.67 pg/mL to 3.61 pg/mL after 24 hours). Serum IFN-γ (mean value, from 9.07 pg/mL to 12.7 pg/m after 24 hours) and CXCL10 levels (mean value, from 351 pg/mL to 676 pg/mL after 24 hours) also increased in eight patients after the third administration. During the treatment course, the percentage of T-bet-expressing CD8+ T cells gradually increased (mean, 49.8% at baseline and 59.1% at day 29, p = 0.0273). Interestingly, both T-bet-expressing effector memory (mean, 52.7% at baseline and 63.7% at day 29, p = 0.0195) and terminally differentiated effector memory (mean, 82.3% at baseline and 90.0% at day 29, p = 0.0039) CD8+ T cells significantly increased. The median PFS was 398 days. Conclusions This is the first clinical study showing that CpG ODN (K3) activated innate immunity and elicited Th1-type adaptive immune response and cytotoxic activity in cancer patients. CpG ODN (K3) was well tolerated at the dose settings tested, although the maximum tolerated dose was not determined. Trial registration UMIN-CTR number 000023276. Registered 1 September 2016, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000026649

Flowering is an important biological process through which plants determine the timing of reproduction. In rice, florigen mRNA is induced more strongly when the day length is shorter than the critical day length through recognition of 30-min differences in the photoperiod. Grain number, plant height, and heading date 7 (Ghd7), which encodes a CCT-domain protein unique to monocots, has been identified as a key floral repressor in rice, and Heading date 1 (Hd1), a rice ortholog of the Arabidopsis floral activator CONSTANS (CO), is another key floral regulator gene. The Hd1 gene product has been shown to interact with the Ghd7 gene product to form a strong floral repressor complex under long-day conditions. However, the mRNA dynamics of these genes cannot explain the day-length responses of their downstream genes. Thus, a real-time monitoring system of these key gene products is needed to elucidate the molecular mechanisms underlying accurate photoperiod recognition in rice. Here, we developed a monitoring system using luciferase (LUC) fusion protein lines derived from the Ghd7-LUC and Hd1-LUC genes. We successfully obtained a functionally complemented gene-targeted line for Ghd7-LUC. Using this system, we found that the Ghd7-LUC protein begins to accumulate rapidly after dawn and reaches its peak more rapidly under a short-day condition than under a long-day condition. Our system provides a powerful tool for revealing the accurate time-keeping regulation system incorporating these key gene products involved in rice photoperiodic flowering.

A dysphagia diet is important for patients with stroke to help manage their nutritional state and prevent aspiration pneumonia. Tongue pressure measurement is a simple, non-invasive, and objective method for diagnosing dysphagia. We hypothesized that tongue pressure may be useful in making a choice of diet for patients with acute stroke. Using balloon-type equipment, tongue pressure was measured in 80 patients with acute stroke. On admission, a multidisciplinary swallowing team including doctors, nurses, speech therapists, and management dietitians evaluated and decided on the possibility of oral intake and diet form; the tongue pressure was unknown to the team. Diet form was defined and classified as dysphagia diet Codes 0 to 4 and normal form (Code 5 in this study) according to the 2013 Japanese Dysphagia Diet Criteria. In multivariate analysis, only tongue pressure was significantly associated with the dysphagia diet form (p

INTRODUCTION: This study aimed to determine the prevalence of vertical HIV-1 transmission in the western region of the State of São Paulo, Brazil. METHODS: The study analyzed the medical records of HIV-1-infected mothers and infant pairs living in the municipalities of São Paulo Regional Health Departments DRS II (Araçatuba) and DRS XI (Presidente Prudente). From March 2001 to March 2006, blood samples were collected and referred to the Molecular Biology Unit of the Adolfo Lutz Institute (ALI), Presidente Prudente. HIV-1-RNA viral load was determined by bDNA assay. RESULTS: The number of births (109/217, 50.2%) and vertical HIV-1 transmissions (6/109, 5.5%) that occurred in DRS II was similar to births (108/217, 49.8%) and vertical transmissions (7/108, 6.5%) in DRS XI (p > 0.05). Although 80% (4/5) of the infected children were male in DRS II, while in DRS XI, 75% (6/8) were female, no differences between sex regarding infected and noninfected children in the regions of Araçatuba and Presidente Prudente were verified. The overall vertical HIV-1 transmission rate was 6%. No consistent reduction in the prevalence of vertical HIV-1 transmission occurred over the years. About 20% of mothers did not know the HIV-1 status of their newborns eight months after delivery. CONCLUSIONS: In the present study, MTCT prevalence rates were about 70% higher than those previously determined in the State of São Paulo, with noreduction throughout the period.Furthermore, a significant number of mothers did not know the HIV-status of their newborns eight months after delivery.

Aoi-no-Ue (Lady Aoi) is a play about a malevolent spirit, written in the fourteenth century Japan. The title is derived from a chapter of The Tale of Genji, written by Murasaki Shikibu. Aoi is the wife of Hikaru Genji who is the son of the emperor. One of Genji's lovers, Lady Rokujo, is consumed with hate and jealousy for Aoi who is pregnant with the child of her husband, and Rokujo's living spirit haunts and torments Aoi. Rokujo's self is divided: Her conscious self and her unconscious self as a spirit. Rokujo is a cultured woman and the late ex-emperor's wife, but her other self is a malevolent character who becomes an ogre. With the ogre mask, she is feared yet sympathized with, her laments bringing humanity to the horror expressed through the mask. In the original story, Aoi is killed by Rokujo's spirit after Aoi's childbirth. In the Noh version, Aoi survives, and Rokujo's spirit is healed by a spell incantation enacted by a Buddhist priest. The play is written from the viewpoint of Rokujo's other self though the title suggests it is named after Genji's wife. On stage, a bedridden Aoi is symbolized by a folded robe laid on the floor. What is seen (Aoi) is unseen, and what is unseen (Rokujo's spirit) is seen in human form by the audience. In the article, I would like to explore Rokujo's divided selves in Aoi-no-Ue comparing the play with the original story of The Tale of Genji. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the prevalence of vertical HIV-1 transmission in the western region of the State of São Paulo, Brazil., Methods: The study analyzed the medical records of HIV-1-infected mothers and infant pairs living in the municipalities of São Paulo Regional Health Departments DRS II (Araçatuba) and DRS XI (Presidente Prudente). From March 2001 to March 2006, blood samples were collected and referred to the Molecular Biology Unit of the Adolfo Lutz Institute (ALI), Presidente Prudente. HIV-1-RNA viral load was determined by bDNA assay., Results: The number of births (109/217, 50.2%) and vertical HIV-1 transmissions (6/109, 5.5%) that occurred in DRS II was similar to births (108/217, 49.8%) and vertical transmissions (7/108, 6.5%) in DRS XI (p > 0.05). Although 80% (4/5) of the infected children were male in DRS II, while in DRS XI, 75% (6/8) were female, no differences between sex regarding infected and noninfected children in the regions of Araçatuba and Presidente Prudente were verified. The overall vertical HIV-1 transmission rate was 6%. No consistent reduction in the prevalence of vertical HIV-1 transmission occurred over the years. About 20% of mothers did not know the HIV-1 status of their newborns eight months after delivery., Conclusions: In the present study, MTCT prevalence rates were about 70% higher than those previously determined in the State of São Paulo, with noreduction throughout the period.Furthermore, a significant number of mothers did not know the HIV-status of their newborns eight months after delivery.