We describe a case of novel use of trametinib in treating arrythmia without concomitant cardiomyopathy. Our patient is a two-year-old female born with Costello syndrome due to heterozygous mutations in the HRAS gene c34 G > T p (G12C). Shortly after birth, she was diagnosed with multifocal atrial tachyarrhythmia. Her imaging studies have shown no hypertrophy or CHD. There was poor arrhythmia control despite triple antiarrhythmic therapy. Trametinib, a MEK1 and MEK2 inhibitor, was used in treating her isolated atrial arrythmia, allowing her to wean off other antiarrhythmics. Other case reports have shown trametinib to benefit certain RASopathy patients with lymphatic abnormalities, hypertrophic cardiomyopathy, and concurrent arrhythmias. This case demonstrates effective treatment of isolated arrhythmia without cardiomyopathy, broadening the potential indications for use of trametinib in certain RASopathy patients.

Tight focusing with very small f-numbers is necessary to achieve the highest at-focus irradiances. However, tight focusing imposes strong demands on precise target positioning in-focus to achieve the highest on-target irradiance. We describe several near-infrared, visible, ultraviolet and soft and hard X-ray diagnostics employed in a ∼1022 W/cm2 laser–plasma experiment. We used nearly 10 J total energy femtosecond laser pulses focused into an approximately 1.3-μm focal spot on 5–20 μm thick stainless-steel targets. We discuss the applicability of these diagnostics to determine the best in-focus target position with approximately 5 μm accuracy (i.e., around half of the short Rayleigh length) and show that several diagnostics (in particular, 3$\omega$ reflection and on-axis hard X-rays) can ensure this accuracy. We demonstrated target positioning within several micrometers from the focus, ensuring over 80% of the ideal peak laser intensity on-target. Our approach is relatively fast (it requires 10–20 laser shots) and does not rely on the coincidence of low-power and high-power focal planes.

Obestatin is a gastrointestinal peptide having wide-ranging effects on cell proliferation; however, its mechanism of action remains poorly understood. Thus, the aim of the study was to elucidate the effect of exogenous obestatin on the postnatal structural development of the small intestine. Seven-day-old piglets with an average BW of 1.56 ± 0.23 kg were divided into four groups (n = 10) that received intragastrically obestatin (2, 10 or 15 μg/kg BW) or vehicle. After a 6-day experimental period, morphological analysis of gastrointestinal tract and small intestine wall (mitosis and apoptosis indexes, histomorphometry of mucosa and muscularis layers) was performed. The study revealed a seemingly incoherent pattern of the histological structure of the small intestine among the experimental groups, suggesting that the effect of obestatin is both intestinal segment specific and dose dependent. Histomorphometric analysis of the small intestine showed that higher doses of obestatin seem to promote the structural development of the duodenum while simultaneously hindering the maturation of more distal parts of the intestine. Intragastric administration of obestatin increased the crypt mitotic index in all segments of the small intestine with the strongest pro-mitotic activity following the administration of obestatin at a dose of 10 and 15 μg/kg BW. The significant differences in the number of apoptotic cells in the intestinal villi among the groups were observed only in proximal jejunum and ileum. In conclusion, it seems that obestatin shows a broad-spectrum of activity in the gastrointestinal tract of newborn piglets, being able to accelerate its structural development. However, the varied effect depending on the intestinal segment or the concentration of exogenous obestatin causes that further research is needed to clarify the exact mechanism of this phenomenon.

We present a case of SLE psychosis with a characteristic symptom mainly concernd to time dysorientation.

A lady of 17 years old without any previous history is hospitalised to Jichi Medical University Hospital, because of covulsion. After this problem is disappeared, she became inactive, however, sometimes irritated without any specific reason. Brain imaging (MRI, CT) was normal, but EEG revealed slow waves as basal rhythme. Her physical state and labodatas fulfilled the criteria of SLE. She was treated with Steroid-pulse therapy (Methylpredonisolone 1.000 mg/day for 3 days), predonisolone 90mg/day (for two weeks) and finally betamethasone 8mg/day (for three weeks) which made her consciousness clear, and her behavior coherent.

During the periode of the steroid pulse therapy and the start of betamethasone, this patient repeated to say "the date is wrong". She believed that one year had already passed since her admission. She appeared to be perplexed continuously between the two different time standards (wrong standard of her own and the right one of common world). We could not correct her misunderstanding until her consciousness became clear.

This symptom of misunderstanding and perplexion derives from continuous dysorientation. We may call this "time gap experience". We could observe this type of dysorientation in a very slight consciousness clouding which continues stably during certain period. Therefore, “time gap experience” can be a key to find a psychosis based on somatic disease like SLE.

The syndrome of emotional burnout is developed in people whose profession requires a lot of communication, and the effectiveness of their work depends on its quality. The aim of our study was to determine the influence of burnout on relational maintenance strategies.8 professors of università della Svizzera italiana, Lugano, Switzerland participated in this research. We used Maslach Burnout Inventory and The relational maintenance strategies scale. Moderate level of emotional exhaustion was detected in the majority of the participants. This condition is characterized by the urge towards finding a place to stay alone and get some rest from everything and everybody. It is accompanied by the feeling of emptiness, depression, and apathy. These indicate pronounced tiredness, disappointment, and unwillingness to work among our participants. The high level of Lack of personal accomplishments phase is being developed in all the participants. It indicates the pronounced doubts in the necessity to keep performing the work and in the fact that the work is needed and recognized by other people. We demonstrated that among the professors with burnout such strategies as conflict management, openness, assurances and positivism are the most widespread. Our data indicate that the readiness to work together on certain project or scientific problem (Openness), the willingness to support a student (Advice Giving) and the help to find necessary support outside of current academic environment (Social Networks) decreases with the development of emotional burnout. Understating the level of one's self-appraisal, observed during the development of burnout, ruins effective collaboration between professors and their PhD students, and formalizes their relationships. Thus, burnout is an important mediating variable between interpersonal aspects of work environment.

Diabetes mellitus is a global epidemic, characterised as a heterogeneous group of metabolic disorders associated with high risk of CVD. Green banana biomass, which is composed of resistant starches (RS) and cannot be hydrolysed by amylases, delays gastric emptying and modulates insulin sensitivity, thus contributing to improve metabolic disorders. The aim of the present study was to investigate the effects of consumption of RS from green banana biomass on body composition, fasting plasma glucose, glycated Hb (HbA1c) and homeostasis model assessment of insulin resistance in subjects with pre-diabetes or type 2 diabetes on top of treatment. Middle-aged subjects (n 113) of both sexes with pre-diabetes (HbA1c: 5·7–6·4 %) or diabetes (HbA1c ≥ 6·5 %) were randomised to receive nutritional support plus green banana biomass (40 g) (RS: approximately 4·5 g, G1, n 62) or diet alone (G2, n 51) for 24 weeks. Body composition, biochemical analyses and dietary intake were evaluated at the beginning and end of the study. In the experimental group (G1), consumption of RS was associated with reduction in HbA1c (P = 0·0001), fasting glucose (P = 0·021), diastolic blood pressure (P = 0·010), body weight (P = 0·002), BMI (P = 0·006), waist and hip circumferences (P < 0·01), fat mass percentage (P = 0·001) and increase in lean mass percentage (P = 0·011). In controls (G2), reductions were observed in waist and hip circumferences (P < 0·01), HbA1c (P = 0·002) and high-density lipoprotein-cholesterol (P = 0·020). In pre-diabetes or diabetes, non-significant differences were observed in the percentage reduction in HbA1c and fasting glucose in exploratory analyses. Our results indicate that the consumption of bioactive starches is a good dietary strategy to improve metabolic control and body composition.

The naturalization of alien Reeves's muntjacs (Muntiacus reevesi) on Izu-Oshima Island, Tokyo, Japan, has proceeded intensively over the last five decades. To clarify whether the gastrointestinal helminths of these animals were brought from their original endemic area or were newly acquired in Japan, 32 Reeves's muntjacs trapped on the island were parasitologically examined. In addition to Gongylonema pulchrum in the oesophagus (34.4% prevalence), Chabaudstrongylus ninhae (Dróżdż, 1967) (Trichostrongylidae: Cooperiinae) and Oesophagostomum muntiacum Jian, 1989 (Chabertiidae: Oesophagostominae) were prevalent in the small (28.1%) and large (46.9%) intestines, respectively. For the first time, these trichostrongylid or chabertiid worms were genetically characterized based on partial nucleotide sequences of the nuclear ribosomal RNA gene (rDNA) and mitochondrial DNA cytochrome c oxidase subunit 1 gene (cox-1), and the phylogenetic relationships with other members of their family were explored. Since these two intestinal nematode species are inherent in muntjacs, this study demonstrates a new distribution of exotic helminth species in Japan in accordance with the naturalization of alien mammalian hosts. The molecular genetic data collected here could assist the taxonomic assessment of morphological variants in different Muntiacus spp. and/or of different geographical origins. Furthermore, our data may help to define the phylogenetic relationships among such isolates.

The number of tests performed is an important surveillance indicator. We illustrate this point using HIV surveillance data, focusing on Tokyo and Okinawa, two prefectures with high HIV notification rates in Japan. Restricting to data reported from local public health centres and affiliate centres where testing data are accessible, we assessed HIV surveillance data during 2007–2014, based on the annual HIV notification rate (per 100 000 population), HIV testing rate (per 100 000 population) and proportion testing HIV-positive (positivity). Nationally, testing activity and positivity showed an inverse relationship; in 2008, the testing rate peaked, but positivity was lowest. While notification rates were higher for Tokyo (median = 0.98, range = 0.89–1.33) than Okinawa (median = 0.61, range = 0.42–1.09), Okinawa had slightly higher testing rates (median = 187, range = 158–274) relative to Tokyo (median = 172, range = 163–210). Positivity was substantially lower in Okinawa (median = 0.34%, range = 0.24–0.45%) compared with Tokyo (median = 0.57%, range = 0.46–0.67%). Relative to the national testing rate (median = 85, range = 80–115) and positivity (median = 0.34%, range = 0.28–0.36%), Tokyo had higher positivity, despite more testing. In 2014 in Okinawa, all three indicators increased, providing a strong reason to be concerned as positivity increased despite more testing. Together with other information, accounting for testing and positivity improve interpretation of surveillance data to guide public health assessments.

Watanabeite Cu4(As,Sb)2S5, in which As>Sb, is a new copper sulphosalt that occurs with quartz in a hydrothermal vein at the Teine mine, Sapporo, Hokkaido, Japan. It is silvery lead-grey in colour with lead-grey streak. VHN100 = 253-306 kg/mm2, brittle. It has no cleavage and the fracture is uneven. The measured density = 4.66(2) g/cm3. The mean of six microprobe analyses gave Cu 41.1, Ag 0.1, Mn 0.3, As 15.4, Sb 14.3, Bi 2.4, S 26.2, a total of 99.8 wt.%, corresponding to: (Cu3.94Mn0.03− Ag0.01)∑3.98(As1.25Sb0.72Bi0.07)∑2.04S4.98 (basis: total atoms = 11), or ideally, Cu4(As,Sb)2S5, with As > Sb. The X-ray powder pattern resembles that of tetrahedrite but has subsidiary diffractions and is similar to that of synthetic Cu24As12S31 (Maske and Skinner, 1971). It is indexed on an orthorhombic cell with a = 14.51 Å, b = 13.30 Å, c = 17.96 Å (all ± 0.01 Å), and Z = 16. Calculated density is 4.66 g/ cm3. It is optically similar to tetrahedrite but is grey and weakly bireflectant. No internal reflections were observed. The maximum and minimum reflectance values in air and in oil (nD = 1.515) for the COM wavelengths are: 470 nm −32.5, 31.5; 17.7, 17.0, 546 nm −32.0, 31.1; 17.0, 16.3,589 nm −31.1, 30.3; 16.1 m 15.5, 650 nm −30.0, 29.3; 15.0, 14.5%, respectively. Watanabeite forms masses composed of aggregates of minute grains up to 50 μm in diameter. Apart from some minute inclusions of emplectite, native bismuth and tennantite, it is almost monominerallic.

Tsugaruite, Pb4As2S7, is a new Pb-As sulphosalt from the Yunosawa mine, Aomori Prefecture, northern Japan. X-ray studies indicated it to be orthorhombic Pnn2 or Pnnm, a 15.179(1), b 38.195(1), c 8.0745(1) Å, Z = 16 [Pb4As2S7] with a subcell with c′ = 1/2c. The six strongest diffractions in the X-ray powder pattern [d (in Å), (I), (hkl)] are: 4.47 (30) (340), 3.705 (34) (1.10.0), 3.395 (100) (450), 2.870 (34) (192), 2.819 (53) (550), and 2.739 (48) (560, 2.13.0). The average of seven electron microprobe analyses gave Pb 68.70, Tl 0.13, As 12.45, S 18.64, total 99.92 wt.%. The empirical formula calculated on the basis of total atoms = 13 is Pb3.99Tl0.01As2.00S7.00, corresponding to the ideal formula Pb4As2S7. The calculated density is 6.83 g/cm3 for the ideal formula.

Tsugaruite is opaque with a metallic lustre and lead-grey streak. No cleavage was observed. It is brittle with uneven fracture. VHN25 is 75.4–94.9 kg/mm2, mean 86.4 (n) = 4), corresponding to 2.5–3 in Mohs' hardness scale. In reflected plane-polarised light in air, it is white with a greenish tint, more greenish than jordanite. Bireflectance and pleochroism are weak, weaker than those of jordanite; and anisotropism is weak to moderate, weaker than that of jordanite. No internal reflections. The reflectance spectra are tabulated in the text.

Tsugaruite was found in a thin baryte veinlet exposed in the wall of a small open cut of the Yunosawa mine. It forms radiating groups of long tabular tapering crystals elongated along c and tabular to b, up to 0.04 mm wide and 2 mm long. The associated minerals are jordanite, which formed earlier than tsugaruite, and galena. The chemical similarity of tsugaruite and jordanite and their intergrown character indicates that earlier jordanite analyses may also include analyses of tsugarite.

Chemical analyses of bannisterite from the Kamo mine, Toba City, Mie Prefecture, Japan, give Ba : Ca = 69:31–55:45, yielding the ideal formula with Ba > Ca, i.e. (Ba,Ca)(K,H3O)(Mn2+ · Mg,Fe2+)21 (Si,Al)32(O,OH)92 · nH2O, where Ba > Ca, Mn2+ > Mg, Fe2+,Si ≫ Al, and O > OH. The unit cell parameters calculated after the indexing of the X-ray powder pattern are: a = 22.95, b = 16.52, c = 25.66 Å, β = 94.2°. It occurs as dark brown veinlets cutting massive caryopilite-rhodochrosite ore, which is also cut by veinlets of manganoan chlorite (Mn/(Mg + Mn + Fe) = c. 0.30–0.39) with minor barian orthoclase (Ba/(K+ Ba) = 0.05 ∼ 0.06).