Anti-spike protein antibody responses to BNT162b2 mRNA vaccine: A single-center survey in a COVID-19 non-epidemic area in Japan.

Background: There are a few reports on antibody responses after a two-dose BNT162b2 vaccination in non-epidemic areas. We evaluated this phenomenon. Methods: A total of 344 healthcare workers were vaccinated, and the serum anti-receptor-binding domain (RBD) antibody concentrations before and after two weeks following the two-dose BNT162b2 vaccination were measured using electro chemiluminescence immunoassay system. Results: Before vaccination, the antibody titers of all participants were less than 0.6 U/mL. After two doses of the BNT162b2 vaccine injection in 342 participants (2 excluded), a high seroconversion rate (99.7%) was observed. The average (±standard deviation) serum anti-RBD antibody titers were 2324 ± 1739 U/mL. Antibody levels in females and males were 2443 ± 1833 U/mL and 1908 ± 1287 U/mL, respectively (p = 0.037). Conclusion: In a non-epidemic area, two BNT162b2 doses induced a satisfactory antibody response, and the antibody concentrations in females were higher than in males.

Distribution of corticotropin-releasing factor neurons in the mouse brain: a study using corticotropin-releasing factor-modified yellow fluorescent protein knock-in mouse.

We examined the morphological features of corticotropin-releasing factor (CRF) neurons in a mouse line in which modified yellow fluorescent protein (Venus) was expressed under the CRF promoter. We previously generated the CRF-Venus knock-in mouse, in which Venus is inserted into the CRF gene locus by homologous recombination. In the present study, the neomycin phosphotransferase gene (Neo), driven by the pgk-1 promoter, was deleted from the CRF-Venus mouse genome, and a CRF-Venus∆Neo mouse was generated. Venus expression is much more prominent in the CRF-Venus∆Neo mouse when compared to the CRF-Venus mouse. In addition, most Venus-expressing neurons co-express CRF mRNA. Venus-expressing neurons constitute a discrete population of neuroendocrine neurons in the paraventricular nucleus of the hypothalamus (PVH) that project to the median eminence. Venus-expressing neurons were also found in brain regions outside the neuroendocrine PVH, including the olfactory bulb, the piriform cortex (Pir), the extended amygdala, the hippocampus, the neocortices, Barrington's nucleus, the midbrain/pontine dorsal tegmentum, the periaqueductal gray, and the inferior olivary nucleus (IO). Venus-expressing perikarya co-expressing CRF mRNA could be observed clearly even in regions where CRF-immunoreactive perikarya could hardly be identified. We demonstrated that the CRF neurons contain glutamate in the Pir and IO, while they contain gamma-aminobutyric acid in the neocortex, the bed nucleus of the stria terminalis, the hippocampus, and the amygdala. A population of CRF neurons was demonstrated to be cholinergic in the midbrain tegmentum. The CRF-Venus∆Neo mouse may be useful for studying the structural and functional properties of CRF neurons in the mouse brain.

Single session of high-intensity focused ultrasound for localized prostate cancer: treatment outcomes and potential effect as a primary therapy.

PURPOSE: To investigate the treatment outcomes of a single-session high-intensity focused ultrasound (HIFU) using the Sonablate(®) for patients with localized prostate cancer. METHODS: Biochemical failure was defined according to the Stuttgart definition [a rise of 1.2 ng/ml or more above the nadir prostate-specific antigen (PSA)] and the Phoenix definition (a rise of 2 ng/ml or more above the nadir PSA). Disease-free survival rate was defined using the Phoenix criteria and positive follow-up biopsy. RESULTS: A total of 171 patients were identified. Fifty-two (30.4 %) patients were identified to be with D'Amico low risk, 47 (27.5 %) with intermediate risk, and 72 (42.1 %) with high risk. In the median follow-up time of 43 months, there was 44 (25.7 %) and 36 (21.1 %) patients experienced biochemical failure for Stuttgart and Phoenix definition with mean (±SD) time to failure of 17.8 ± 2.1 and 19.4 ± 2.3 months, respectively. A total of 44 (25.7 %) patients were diagnosed as disease failure. Cox multivariate analysis revealed PSA nadir level (PSA cutoff = 0.2 ng/ml; HR = 9.472, 95 % CI 4.527-19.820, p < 0.001) and D'amico risk groups [HR = 3.132 (95 % CI 1.251-6.389), p = 0.033] were the predictor for failure in single-session HIFU. CONCLUSIONS: Single-session HIFU treatment using the Sonablate(®) seems to be potentially curative approach. When treated carefully with neoadjuvant hormonal therapy or preoperative transurethral resection of the prostate, higher-risk disease might be able to choose this minimally invasive procedure as primary therapy.

[Clinical features of nicotine dependence].

Nicotine dependence is characterized by weak dependence potential and less ability to produce psychotoxicity and social disturbance. A two-compartment model consisting of "dependence" and "dependence syndrome" was used to clarify clinical features of nicotine dependence. "Dependence" was defined by drug liking. "Dependence syndrome" was defined by a compulsion to take a drug, and drug-induced pathological symptoms (withdrawal syndrome and acute disorders) and social disturbance. Nicotine produced a mild or the least degree of drug liking and withdrawal syndrome, without any significant social disturbance, or acute disorders. Thus, nicotine dependence differed from other forms of drug dependence in that nicotine was not associated with "dependence syndrome". This review also introduced other current topics of nicotine dependence. First, adolescence is regarded as a risk factor for the development of nicotine dependence, whereas the involvement of gender difference (female) in this respect is controversial. Secondly, many smokers feel difficulties in quitting smoking in spite of the weak dependence potential of nicotine, which is known as the "nicotine paradox". Several working hypotheses have been presented to explain this phenomenon. For example, nicotine has relatively strong conditioning effects and/or dependence liability compared with other drugs of abuse. However, further studies should be carried out to clarify clinical characteristics of the "nicotine paradox".

Clinical features of nicotine dependence compared with those of alcohol, methamphetamine, and inhalant dependence.

A new clinical evaluation form was developed to compare the clinical features of nicotine dependence with those associated with other abused drugs. A new scoring system for clinical evaluation was developed. The form consisted of five scoring items: subjective effects, liking (of drug), withdrawal syndrome, acute psychic and physical disorders, and social disturbance. A preliminary clinical investigation was performed to test the validity of the evaluation form. Study subjects were those showing dependence on nicotine (cigarette smoking, n = 40), alcohol (n = 39), methamphetamine (n = 31), and inhalants (n = 30), who fulfilled the DSM-IV-TR criteria for drug dependence disregarding the state of "a maladaptive pattern of substance use, leading to clinically significant impairment or distress," and gave written informed consent for participation in the study. Nicotine caused a mild or the least degree of subjective effects, liking, and psychic and physical withdrawal symptoms, without any significant social disturbance or acute disorders. With alcohol, liking, withdrawal syndrome, and acute physical disorders were prominent. Methamphetamine produced the most serious acute psychic disorders, with intensive acute physical disorders and psychic withdrawal symptoms. Inhalants were characterized by an intensive degree of acute psychic disorders. As for social disturbance, alcohol, methamphetamine, and inhalants showed more significant influence than nicotine. Our study findings revealed that the clinical features of drug dependence could be evaluated by using the new clinical evaluation form. Further study is required to clarify the clinical features of nicotine dependence compared with those of other drugs of dependence.

[Studies on clinical characteristics of nicotine dependence using a two compartment model of drug dependence].

The purpose of the present study was to develop a new clinical evaluation form to compare the clinical characteristics of nicotine dependence with those associated with other drugs of abuse, using a two-compartment model consisting of "drug dependence" and "dependence syndrome". The evaluation form consisted of five scoring items: subjective effects, drug liking, withdrawal syndrome, acute psychic and acute physical disorders, and social disturbance. "Drug dependence" was defined by positive scores on the "drug liking" item. "Dependence syndrome" was defined by positive scores on drug-induced pathological symptoms (withdrawal syndrome, and acute psychic and physical disorders) and social disturbance. The subjects were dependent on nicotine (cigarette smoking) (n = 114), alcohol (n = 101), methamphetamine (n = 90), inhalants (n = 63), and benzodiazepines (n = 39). All subjects met the DSM-IV-TR criteria for drug dependence. Nicotine produced a mild or the least degree of drug liking and withdrawal syndrome, without any significant social disturbance, or acute disorders. The other four drugs produced more intensive degrees of withdrawal syndrome and acute psychic and physical symptoms, with more significant social disturbance than nicotine. The present study indicated that nicotine dependence differed from other forms of drug dependence in that nicotine was not associated with "dependence syndrome".

[Studies on clinical features of nicotine dependence in comparison with those of alcohol and methamphetamine dependence using a two compartment model of drug dependence].

The purpose of the present study was to develop a new clinical evaluation form to compare the clinical features of nicotine dependence with those associated with alcohol and methamphetamine dependence, using a two compartment model consisting of "drug dependence" and "dependence syndrome". The evaluation form consisted of six scoring items: subjective effects, tolerance, drug liking, social disturbance, withdrawal syndrome, and acute psychic and acute physical disorders. "Drug dependence" was defined by positive scores on the "drug liking" item. "Dependence syndrome" was defined by positive scores on drug-induced pathological symptoms (withdrawal syndrome, and acute psychic and physical disorders) and social disturbance. The subjects were dependent on nicotine (n = 68), alcohol (n = 62), or methamphetamine (n = 55). All subjects met DSM-IV diagnostic criteria for drug dependence. Nicotine produced a mild degree of drug liking and psychic withdrawal symptoms, but did not cause significant physical withdrawal symptoms, acute psychic or physical disorders or social disturbance. Alcohol and methamphetamine produced a moderate degree of drug liking and significant levels of withdrawal syndrome, acute disorders and social disturbance. Thus, in the present study, nicotine dependence differed from other forms of drug dependence in that nicotine was not associated with "dependence syndrome".