Determination of paroxetine in serum treated with simple pretreatment by pre-column high-performance liquid chromatography using 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride as a fluorescent labeling reagent.

The therapeutic drug monitoring of paroxetine could be used to optimize the pharmacological treatment of depressed patients. A simple and sensitive high-performance liquid chromatography procedure was developed for the determination of paroxetine in serum. After simple pretreatment of serum (50 μL) with acetonitrile and o-phthalaldehyde, paroxetine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70°C for 20 min in borate buffer (0.1 mol/L, pH 8.0) to produce a fluorescent product. The derivative was separated on a reversed-phase column at 40°C for stepwise elution with (A) acetic acid (10 mmol/L) and (B) acetonitrile. The flow rate was 1.0 mL/min. The fluorescence intensity was monitored at excitation and emission wavelengths of 320 and 400 nm, respectively. The within-day and day-to-day relative standard deviations were 3.0-3.4 and 2.7-8.3%, respectively. The detection limit of paroxetine was 8.3 fmol at a signal-to-noise ratio of 3. As the proposed method that only requires a small quantity of serum (50 μL) is simple, sensitive and reproducible, it would be useful for clinical and biochemical research as well as drug monitoring.The therapeutic drug monitoring of paroxetine could be used to optimize the pharmacological treatment of depressed patients. A simple and sensitive high-performance liquid chromatography procedure was developed for the determination of paroxetine in serum. After simple pretreatment of serum (50 μL) with acetonitrile and o-phthalaldehyde, paroxetine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70°C for 20 min in borate buffer (0.1 mol/L, pH 8.0) to produce a fluorescent product. The derivative was separated on a reversed-phase column at 40°C for stepwise elution with (A) acetic acid (10 mmol/L) and (B) acetonitrile. The flow rate was 1.0 mL/min. The fluorescence intensity was monitored at excitation and emission wavelengths of 320 and 400 nm, respectively. The within-day and day-to-day relative standard deviations were 3.0-3.4 and 2.7-8.3%, respectively. The detection limit of paroxetine was 8.3 fmol at a signal-to-noise ratio of 3. As the proposed method that only requires a small quantity of serum (50 μL) is simple, sensitive and reproducible, it would be useful for clinical and biochemical research as well as drug monitoring

Geoscience Teaching Using Local Geological Materials (7) : Slump Structures in the Cretaceous Takada Rhyolites Distributed in Oshiba Jima Island, Higashi-hiroshima, SW Japan

In this paper, internal structure of slump beds distributed in Oshiba Jima Island, Higashi-hiroshima were described from a viewpoint of their form, and were considered in the context of teaching materials. The Oshiba Jima Island consists mainly of the H7 Rhyolite Member of Haigamine Formation of Cretaceous Takada Rhyolites. The slump beds were found out from the mudstone and tufaceous sandstone intercalated with welded tuff beds of the H7 Rhyolite Member. The form of asymmetric slump folds and thrusts on an outcrop are not difficult to describe. When used in combination of some analogue experiments, morphological characteristics of the slump beds have the potential to be a learning tool to improve the understanding of geologic structures.本研究の一部に科学研究費補助金基盤研究（A）課題番号25242015および同基盤研究（C）課題番号26350235を使用した

Screening of tick-borne pathogens in argasid ticks in Zambia : Expansion of the geographic distribution of Rickettsia lusitaniae and Rickettsia hoogstraalii and detection of putative novel Anaplasma species

Ticks (Ixodidae and Argasidae) are important arthropod vectors of various pathogens that cause human and animal infectious diseases. Many previously published studies on tick-borne pathogens focused on those transmitted by ixodid ticks. Although there are increasing reports of viral pathogens associated with argasid ticks, information on bacterial pathogens they transmit is scarce. The aim of this molecular study was to detect and characterize Rickettsia and Anaplasmataceae in three different argasid tick species, Ornithodoros faini, Ornithodoros moubata, and Argas walkerae collected in Zambia. Rickettsia hoogstraalii and Rickettsia lusitaniae were detected in 77 % (77/100) of Ar. walkerae and 10 % (5/50) of O. faini, respectively. All O. moubata pool samples (n = 124) were negative for rickettsial infections. Anaplasmataceae were detected in 63 % (63/100) of Ar. walkerae and in 82.2 % (102/124) of O. moubata pools, but not in O. faini. Phylogenetic analysis based on the concatenated sequences of 16S rRNA and groEL genes revealed that Anaplasma spp. detected in the present study were distinct from previously validated Anaplasma species, indicating that the current knowledge on the diversity and vector range of Anaplasma spp. is incomplete. Our findings highlight new geographical records of R. lusitaniae and R. hoogstraalii and confirm that the wide geographic distribution of these species includes the African continent. The data presented here increase our knowledge on argasid tick-borne bacteria and contribute toward understanding their epidemiology

Neoadjuvant androgen-deprivation therapy with radical prostatectomy for prostate cancer in association with age and serum testosterone

Background: We aimed to identify the candidate prostate cancer patients suitable for neoadjuvant androgen-deprivation therapy (ADT) with radical prostatectomy (RP). Materials and methods: This study included 711 Japanese patients with clinically localized prostate cancer who were treated with RP between 2000 and 2013. Patients were treated with or without neoadjuvant ADT before RP. The prognostic significance of neoadjuvant ADT on biochemical recurrence (BCR) was analyzed according to various clinicopathological characteristics. Results: BCR occurred in 186 (26.2%) of 711 patients. The group treated with neoadjuvant ADT showed higher levels of prostate-specific antigen at diagnosis and advanced clinical T-stage, but suppressed pathological T-stage. Neoadjuvant ADT was not associated with the risk of BCR. In subgroup analysis, neoadjuvant ADT was significantly associated with increased BCR in patients aged >65 years [hazard ratio (95% confidence interval), 2.04 (1.13–3.43), P = 0.020]. Among the 53 patients with available serum testosterone levels, neoadjuvant ADT was associated with the risk of BCR according to serum testosterone levels. Conclusion: This study demonstrated that neoadjuvant ADT showed potential deleterious effects in older patients and patients with lower serum testosterone levels, while a possible improved prognosis in patients with high serum testosterone levels treated with neoadjuvant ADT was suggested, warranting further exploration. Keywords: Age, Neoadjuvant androgen-deprivation therapy, Prostate cancer, Radical prostatectomy, Testosteron

A single‐center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan

Abstract Background Melanoma brain metastasis (MBM) has a poor prognosis, although recent treatments, including immune checkpoint inhibitors and targeted therapy, have improved the prognosis. However, these systemic therapies have been reported to be less efficient for Asian patients. We investigated the survival of Asian patients with MBM and the effectiveness of systemic therapies. Methods We retrospectively reviewed the survival rates of patients diagnosed with MBM between January 2011 and December 2021 at the National Cancer Center Hospital in Tokyo, Japan. In addition, we identified factors associated with survival using Cox regression analysis. Results A total of 135 patients were included. The median overall survival (OS) after an MBM diagnosis was 7.8 months (95% confidence interval [CI] 6.1–9.6). The 6‐month and 1‐year survival rates were 60.7% and 34.8%, respectively. We identified the prognostic factors of MBM, including non‐acral primary location, low serum LDH levels, systemic therapy of single‐agent immune checkpoint inhibitors (ICIs) or targeted therapies (TTs), and radiotherapy of stereotactic irradiation (STI). We found no significant difference in effectiveness between single‐agent ICIs, the combination of Nivolumab and Ipilimumab (COMBI‐ICI), and TTs (COMBI‐ICI vs. single‐agent ICI, hazard ratio 0.71, 95% confidence interval 0.27–1.88, p = 0.49; COMBI‐ICI vs. TT: hazard ratio 0.46, 95% confidence interval 0.14–1.55, p = 0.21). Conclusions Systemic therapy and radiotherapy have improved the survival of MBM patients, but the survival of Asian patients remains poor. Our findings suggest that COMBI‐ICIs are not significantly more effective than single‐agent ICI or TT in treating MBM