Analysis of the status and content of consultations with a Cancer Consultation and Support Centre during the COVID-19 pandemic.

PURPOSE: Cancer Consultation and Support Centres (CCSCs) in Japan have been established at designated cancer hospitals nationwide and these centres provide information and consultation support for cancer care. The purpose of this study is to analyse the status and content of consultations during the COVID-19 pandemic using consultation record data from the Cancer Consultation Support Centre (CCSC) database from January 2020 to March 2021. METHODS: First, we examined the number and percentage of cases involving and not involving COVID-19 and compared the items of the entry forms between the groups. The comparison between the two groups suggests that the traditional consultation items used before the COVID-19 pandemic did not adequately cover the consultation content during the COVID-19 pandemic. Therefore, we categorised the content of consultation records related to COVID-19. RESULTS: As a result, the content was consolidated into 16 categories, which were appropriately captured from five different aspects. CONCLUSION: Using the resulting categories, we were able to create a complementary consultation entry form that could be operational during the COVID epidemic and consult consultants for the support they needed. TRIAL REGISTRATION: Not applicable.

Development of a Systematic Approach to Consultation Record Data from Cancer Consultation and Support Centers.

The purpose of this study is to extract features and structure them using text mining and to analyze changes over time on consultation records accumulated in a cancer consultation and support center database from 2009 to 2018. The text-mining approach worked effectively under conditions of expanding data, and a co-occurrence network revealed patterns and trends in the content of consultations.

Cryptococcus gattii evades CD11b-mediated fungal recognition by coating itself with capsular polysaccharides.

Cryptococcus gattii is a capsular pathogenic fungus causing life-threatening cryptococcosis. Although the capsular polysaccharides (CPs) of C. gattii are considered as virulence factors, the physiological significance of CP biosynthesis and of CPs themselves is not fully understood, with many conflicting data reported. First, we demonstrated that CAP gene deletant of C. gattii completely lacked capsule layer and its virulence, and that the strain was susceptible to host-related factors including oxidizing, hypoxic, and hypotrophic conditions in vitro. Extracellular CPs recovered from culture supernatant bound specifically to C. gattii acapsular strains, not to other fungi and immune cells, and rendered them the immune escape effects. In fact, dendritic cells (DCs) did not efficiently uptake the CP-treated acapsular strains, which possessed no visible capsule layer, and a decreased amount of phosphorylated proteins and cytokine levels after the stimulation. DCs recognized C. gattii acapuslar cells via an immune receptor CD11b- and Syk-related pathway; however, CD11b did not bind to CP-treated acapsular cells. These results suggested that CPs support immune evasion by coating antigens on C. gattii and blocking the interaction between CD11b and C. gattii cells. Here, we describe the importance of CPs in pathogenicity and immune evasion mechanisms of C. gattii.

Remarkable Potential of Zerumbone to Generate a Library with Six Natural Product-like Skeletons by Natural Material-Related Diversity-Oriented Synthesis.

Diversity-oriented synthesis (DOS) is an effective strategy for the quick creation of diverse and high three-dimensional compounds from simple starting materials. The selection of a starting material is the key to constructing useful, chemically diverse compound libraries for the development of new drugs. Here, we report a novel, general, and facile strategy for the creation of diverse compounds with high structural diversity from readily available natural products, such as zerumbone, as the synthetic starting material. Zerumbone is the major component of the essential oil from wild ginger, Zingiber zerumbet Smith. It is noteworthy that zerumbone has a powerful latent reactivity, partly because of its three double bonds, two conjugated and one isolated, and a double conjugated carbonyl group in an 11-membered ring structure. In fact, zerumbone has been shown to be a successful example of natural material-related DOS (NMRDOS). We will report that zerumbone can be converted in one chemical step from four zerumbone derivatives into rare and markedly different scaffolds by transannulation.

Characterization of metabolic phenotypes of mice lacking GPR61, an orphan G-protein coupled receptor.

AIMS: GPR61 is an orphan G protein-coupled receptor whose function remains unknown. The purpose of the present study is to elucidate the importance of GPR61 in metabolism by characterization of GPR61-deficient mice. MAIN METHODS: Male GPR61-deficient mice were characterized regarding various metabolic parameters, including food intake, body weight, oxygen consumption, body temperature, locomotor activity, and in a pair feeding study. Hypothalamic gene expression was analyzed using real-time quantitative RT-PCR. KEY FINDINGS: GPR61-deficient mice exhibited marked hyperphagia and heavier body weight than wild-type mice. Hyperphagia of GPR61-deficient mice was observed before the differences in body weight became apparent between the genotypes. When body weight difference did become apparent between genotypes, increases in visceral fat pad weight, liver weight, liver triglyceride (TG) content, plasma leptin, and plasma insulin were observed in GPR61-deficient mice, suggesting that GPR61 deficiency caused obesity associated with hyperphagia. Oxygen consumption, body temperature, and locomotor activity were not significantly different between GPR61-deficient and wild-type mice. Pair-fed GPR61-deficient mice had a greater fat mass than wild-type mice despite comparable body weight in both genotypes. The mRNA levels of proopiomelanocortin (POMC) and brain-derived neurotropic factor (BDNF) in the hypothalamus of GPR61-deficient mice were significantly lower than those of wild-type mice. SIGNIFICANCE: GPR61-deficient mice exhibited obesity associated with hyperphagia. These findings suggest that GPR61 is involved in the regulation of food intake and body weight, and may be of importance when considering GPR61 as a therapeutic target for obesity or eating disorders.

Socio-environmental factors associated with pubertal development in female adolescents: the role of prepubertal tobacco and alcohol use.

PURPOSE: Alcohol administered to laboratory animals has been shown to suppress puberty-related hormones and delay puberty by interfering with ovarian development and function. The effects of early substance use on human pubertal development are relatively unexplored. METHODS: This cross-sectional study of 3,106 female adolescents, aged 11-21 years, evaluated the association between prepubertal alcohol and tobacco use and the onset of puberty. Ages at initial breast development, body hair growth, and menarche were self-reported. Prepubertal alcohol and tobacco use were defined as the age at first use before the age of pubertal development and accompanied by regular use. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models. Logistic regression was used to estimate the association between substance use and delayed puberty, defined as lack of breast development by the age of 13 years. RESULTS: Unadjusted models indicated prepubertal tobacco use was associated with a longer time required for breast development (HR = 0.74; 95% CI, 0.65-0.85) and body hair growth (HR = 0.81; 95% CI, 0.71-0.93). Prepubertal alcohol use was associated with late breast development (HR = 0.71; 95% CI, 0.57-0.88). The direction of the observed associations remained consistent after adjusting for covariates, but the magnitude of effects were attenuated and the upper bound of the 95% CIs exceeded the null value. Girls who used alcohol before puberty had four times the odds of having delayed puberty (OR = 3.99; 95% CI, 1.94-8.21) as compared with nonusers. CONCLUSION: The results of this study suggest that the endocrine-disrupting effects of alcohol and tobacco use may alter the timing of pubertal development. These cross-sectional findings warrant further investigation.

Pharmacological effects of metabotropic glutamate receptor ligands on prepulse inhibition in DBA/2J mice.

Schizophrenic patients typically exhibit impairment of sensorimotor gating, which can be modeled in animals using acoustic prepulse inhibition of the startle. Both classical and atypical antipsychotics have been shown to improve prepulse inhibition in DBA/2J mice, a non-pharmacological model for impaired sensorimotor gating. The purpose of the present study was to clarify whether metabotropic glutamate receptors participate in control of sensorimotor gating. We evaluated various metabotropic glutamate receptor ligands on prepulse inhibition in DBA/2J mice. This basal level of prepulse inhibition in DBA/2J mice was increased by only the mGlu(1) receptor antagonists [2-cyclopropyl-5-[1-(2-fluoro-3-pyridinyl)-5-methyl-1H-1,2,3-triazol-4-yl]-2,3-dihydro-1H-isoindol-1-one] (CFMTI), 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-alpha]benzimidazole-2-carboxamide hydrochloride (YM-298198), and (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone (JNJ16259685). There was no effect after treatments with the mGlu(5) receptor antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), the mGlu(2/3) receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), the mGlu(2/3) receptor antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), the mGlu(7) receptor agonist N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the mGlu(7) receptor antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazonolo[4,5-c]pyridin-4(5H)-one (MMPIP), or the mGlu(8) receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG). These findings indicate that inhibition of mGlu(1) receptor selectively increases prepulse inhibition in DBA/2J mice and suggest that mGlu(1) receptor antagonists could be a novel treatment for some aspects of schizophrenia.

Deterrence theory and the role of shame in projected offending of college students against a ban on alcohol.

In the present study we advance previous research in deterrence theory by examining the perceived deterrent effects of a newly instituted dry policy on a college campus. A survey of 500 full-time undergraduate students between the ages of 18 and 26 was conducted 3 months following the ban on alcohol. Hypotheses are derived from deterrence theory and focus on both formal and informal sanctions as they predict projected offending. Findings indicate that perceived severity of the sanction does not predict deterrence against future policy violations. However, the informal deterrent of shame does lower projected offending. While these results suggest that a formal dry policy is not likely to deter future problem drinking behaviors among these college students, reductions may be achieved with the use of informal sanctions and the incorporation of principles from reintegrative shaming theory.

Pharmacological effects of the metabotropic glutamate receptor 1 antagonist compared with those of the metabotropic glutamate receptor 5 antagonist and metabotropic glutamate receptor 2/3 agonist in rodents: detailed investigations with a selective allosteric metabotropic glutamate receptor 1 antagonist, FTIDC [4-[1-(2-fluoropyridine-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide].

The functional roles of metabotropic glutamate receptor (mGluR) 1 in integrative brain functions were investigated using a potent and selective mGluR1 allosteric antagonist, FTIDC [4-[1-(2-fluoropyridine-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide], in comparison with the mGluR5 allosteric antagonist and the mGluR2/3 orthosteric agonist in rodents. FTIDC reduced maternal separation-induced ultrasonic vocalization and stress-induced hyperthermia without affecting behaviors in the elevated plus maze. An mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and an mGluR2/3 agonist, LY379268 [(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid], showed anxiolytic activities in these models, suggesting involvement of postsynaptic mGluR1 in stress-related responses comparable with mGluR5 and mGluR2/3. Analgesic effects of FTIDC were seen in the formalin test but not in the tail immersion test. FTIDC selectively blocked methamphetamine-induced hyperlocomotion and disruption of prepulse inhibition, whereas MPEP and LY379268 did not alter those behaviors, suggesting that pharmacological blockade of mGluR1 could result in antipsychotic-like effects. FTIDC did not elicit catalepsy or impair motor functions at 10 times higher dose than doses showing antipsychotic-like action. In conclusion, blockade of mGluR1 showed antipsychotic-like effects without impairing motor functions, whereas blockade of mGluR5 and activation of mGluR2/3 did not display such activities.