A multicenter non-randomized,uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7–14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS.     

Spatial and elevational variation in fruiting phenology of a deciduous oak (Quercus crispula) and its effect on foraging behavior of the Asiatic black bear (Ursus thibetanus)

In habitats with elevational gradients, differences in the fruiting phenology of a single key food resource may affect the feeding behavior of an animal. The objectives of the present study were to assess (1) whether or not fruiting phenology and characteristics of Quercus crispula acorns differed with changes in altitude (900?C1,400?m asl) and area; (2) when bears foraged acorns in relation to their phenological development; and (3) where bears engaged in acorn foraging behavior with respect to acorn phenology. No difference in the fruiting phenology of acorns at various altitudes and locations was found, with the exception of changes in color and abscission period. Acorn abscission period occurred later at a site with an elevation of 1,200?m in Tochigi and at another with an elevation of 1,400?m in Gunma, making the available energy of acorns in the tree canopy (AET) greater and available for a longer time period at those two sites. Foraging of acorns by bears was observed at sites of moderate to high altitude between late September and mid-October. A threshold date when acorns became suitable for foraging by bears could not be identified, as the size and nutritional value of acorns increased continuously. Foraging activity of bears observed at moderate and high altitude sites corresponded with locations where AET was available in greater amounts and for a longer period of time for some sites; however, the small sample size precluded accurate assessment.     

The age-related tumor incidence in Wistar-Imamichi rat

The age-related incidences and types of spontaneous tumors were studied in 320 male and 354 female Wistar-Imamichi rats reared up to 130 weeks of age. The tumor incidence increased abruptly between 53 and 78 weeks of age, and 170 males and 269 females were shown to bear tumors during the observation period. Multiple tumors occurred in 62 males and 115 females. Most common were hypophyseal (male 69: female 224), mammary gland (29:99), testicular (74:0) and adrenal gland (26:21) tumors. The incidences of hypophyseal and testicular tumors increased with age. Tumors occurred in later stages of the observation period in the ovary, uterus and vagina (0:27), thyroid and parathyroid (13:12), skin (8:8), spleen and lymph nodes (8:7), pancreas (9:5), liver (3:7), lung (3:3), thymus (1:4), omentum and mesenterium (2:3), stomach and intestine (2:2), kidney and urinary bladder (1:2), right femur (0:1), and brain (0:1).     

Divergent synthesis of kinase inhibitor derivatives,leading to discovery of selective Gck inhibitors

We accomplished divergent synthesis of potent kinase inhibitor BAY 61-3606 (1) and 27 derivatives via conjugation of imidazo[1,2-c]pyrimidine and indole ring compounds with aromatic (including pyridine) derivatives by means of palladium-catalyzed cross-coupling reaction. Spleen tyrosine kinase (Syk) and germinal center kinase (Gck, MAP4K2) inhibition assays showed that some of the synthesized compounds were selective Gck inhibitors.