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The co-occurrence of subacute thyroiditis (SAT) and Graves' disease (GD) is rare. A 62-year-old Japanese man presented with shifting neck pain and elevated thyroid hormone level. The patient tested positive for thyroid-stimulating hormone receptor antibodies. Additionally, thyroid hormone levels did not decrease during treatment with prednisolone for SAT. Consequently, concurrent GD was suspected, and diagnostic assistance was obtained by confirming increased uptake on 99m Technetium thyroid scintigraphy. A genetic analysis of human leukocyte antigen (HLA) revealed genotypes associated with susceptibility to SAT (HLA-B*35:01) and GD (HLA-DPB1*05:01). Furthermore, the possibility of coronavirus disease 2019 as a related environmental factor cannot be ruled out in this case.

We presented a control strategy for tablet manufacturing processes based on continuous direct compression. The work was conducted by the experts of pharmaceutical companies, machine suppliers, academia, and regulatory authority in Japan. Among different items in the process, the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing. The control and management of the Loss in Weight (LIW) feeder were deemed the most important, and the Residence Time Distribution (RTD) model were regarded effective for setting the control range and for controlling of the LIW feeder. Based on these ideas, the concept of process control using RTD was summarized. The presented contents can serve as a solid fundament for adopting a new control method of continuous direct compression processes in and beyond the Japanese market., (© 2020 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

Background: Patients with rare tumors may lack approved treatments and clinical trial access. Although each rare tumor is uncommon, cumulatively they account for approximately 25% of cancers. We recently initiated a Rare Tumor Clinic that emphasized a precision medicine strategy., Materials and Methods: We investigated the first 40 patients presenting at the Rare Tumor Clinic. Next-generation sequencing (NGS) of tissue and plasma-derived, circulating-tumor DNA (ctDNA), and protein markers were assessed., Results: Median age was 58 years (range, 31-78 years); 70% (28/40) were women; median number of previous systemic therapies was 2 (range 0-7). The most common diagnoses were sarcoma ( n  = 7) for solid tumors and Erdheim-Chester disease ( n  = 5) for hematologic malignancies. Twenty distinct diagnoses were seen. Examples of ultrarare tumors included ameloblastoma, yolk sac liver tumor, ampullary cancer, and Castleman's disease. Altogether, 32 of 33 patients (97%) with tissue NGS and 15 of 33 (45%) with ctDNA sequencing harbored ≥1 alteration. Overall, 92.5% of patients (37/40) had ≥1 actionable target based on either genomic ( n  = 32) or protein ( n  = 27) markers. In total, 52.5% (21/40) received matched therapy; 52.4% (11/21) achieved stable disease (SD) ≥6 months ( n  = 3), partial remission (PR; n  = 6), or complete remission (CR; n  = 2). Matched therapy resulted in significantly longer progression-free survival compared with last prior unmatched therapy (hazard ratio 0.26, 95% confidence interval 0.10-0.71, p  = .008)., Conclusion: Identifying genomic and protein markers in patients with rare/ultrarare tumors was feasible. When therapies were matched, >50% of patients attained SD ≥6 months, PR, or CR. Further precision medicine clinical investigations focusing on rare and ultrarare tumors are urgently needed., Implications for Practice: Although rare tumors are infrequent by definition, when all subtypes of rare cancers are combined, they account for approximately 25% of adult malignancies. However, patients with rare tumors may lack approved treatments and clinical trial access. This paper describes an institutional a Rare Tumor Clinic focused on a precision medicine strategy. Performing genomics and protein analyses was feasible amongst patients with rare cancers. Over 50% of patients attained SD ≥6 months, PR, or CR when they received matched therapy (genomically targeted and/or immunotherapy). Further studies investigating the efficacy of the precision therapy approach among rare tumors are warranted., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

Membrane protein crystallography is notoriously difficult due to challenges in protein expression and issues of degradation and structural stability. We have developed a novel method for large-scale screening of native sources for integral membrane proteins that have intrinsic biochemical properties favorable for crystallization. Highly expressed membrane proteins that are thermally stable and nonaggregating in detergent solutions were identified by mass spectrometry from Escherichia coli, Saccharomyces cerevisiae, and Sus scrofa cerebrum. Many of the membrane proteins identified had been crystallized previously, supporting the promise of the approach. Most identified proteins have known functions and include high-value targets such as transporters and ATPases. To validate the method, we recombinantly expressed and purified the yeast protein, Yop1, which is responsible for endoplasmic reticulum curvature. We demonstrate that Yop1 can be purified with the detergent dodecylmaltoside without aggregating., (© 2015 The Protein Society.)

The lyase activity toward Se-methylated selenoamino acids and the demethylase activity toward methylselenol in the metabolism of selenium were characterized in vitro. The beta- and gamma-lyase activities toward selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys), respectively, were compared under exactly identical conditions by incubating 77Se-SeMet and 76Se-MeSeCys simultaneously in a liver supernatant, and then estimated by the decreases in the labeled starting selenoamino acids (MeSeCys and SeMet), and also by the increases in the labeled enzyme products (methylselenol and selenide) after oxidation to methylseleninic acid (MSA(IV)) and selenite, respectively, by HPLC-inductively coupled plasma-mass spectrometry (ICP-MS). Only 76Se-MeSeCys was decreased and only 76Se-selenite was produced, suggesting that conversion of MeSeCys to methylselenol by beta-lyase followed by that of methylselenol to selenide by demethylase actively occurred in the liver supernatant. The demethylase activity was characterized by incubating 77Se-methylselenol produced in situ from 77Se-MSA(IV) and glutathione in a partially purified enzyme preparation. It was found that demethylation takes place directly through an attack by a hydroxide anion on the methyl group of methylselenol producing selenide and methanol, selenide being detected on HPLC-ICP-MS after oxidation to selenite, and methanol on GC-MS. It was concluded that beta- but not gamma-lyase activity could be detected in a liver supernatant, and that the resulting methylselenol product is demethylated through hydrolysis, with methanol and selenide being produced (MeSeCys-->CH3SeH-->HSeH + CH3OH).

Nutritional selenocompounds are transformed into the assumed common intermediate selenide, which is utilized for the synthesis of selenoenzymes or transformed into methylated metabolites for excretion. Hence, selenocompound metabolites can be traced only with labeled selenium. Here we applied a new tracer method for the metallomics of biometals using simultaneous speciation of each metallome labeled with different homo-elemental isotopes to metabolism and availability of selenium. Rats were depleted of endogenous natural abundance selenium by feeding a single selenium stable isotope ((82)Se-selenite) and then administered (76)Se-selenite and (77)Se-selenomethionine ((77)Se-SeMet)simultaneously. Biological samples were subjected to quantification and speciation analysis by HPLC-ICPMS. Metabolites of the labeled (76)Se and (77)Se and interaction with endogenous selenium were traced and examined without interference from the corresponding endogenous natural abundance isotopes. Differences in the distribution and metabolism among organs and between the two nutritional selenocompounds were compared under exactly identical biological and analytical conditions: (1) selenite was distributed more efficiently than SeMet in organs and body fluids except the pancreas. (2) SeMet was taken up by organs in its intact form. (3) Selenium of SeMet origin was distributed selectively in the pancreas and mostly bound to a protein together with intact SeMet. (4) Selenosugars A and B but not trimethylselenonium (TMSe) were detected in the liver. (5) Selenosugar B and TMSe were detected in the kidneys.

Methylseleninic acid (MSA(IV)) [CH(3)Se(O)OH] is readily reducible to methylselenol [CH(3)SeH], the assumed lyase metabolite and the proposed biologically active form of methylated selenoamino acids. At the same time, MSA(IV) is an oxidation product of the major urinary metabolite selenosugar. (77)Se-Enriched MSA(IV) was injected intravenously into rats (25 microg Se/kg body weight), and urine, blood and liver were obtained at five time points after the injection. Time-related changes in the concentration of (77)Se were determined together with speciation analysis of the labeled metabolites. (77)Se was mostly moved into red blood cells (RBCs) within 10 min, and then redistributed into organs within 30 min. Excessive (77)Se taken up by the liver was first detected as selenosugar A and then as B, suggesting that MSA(IV) was transformed to selenide, and then to selenosugar A followed by methylation to selenosugar B (urinary metabolite). (77)Se was incorporated also into selenoproteins (most efficiently to plasma selenoprotein P that is synthesized in liver), suggesting that MSA(IV) is utilized for the synthesis of selenosugar (for excretion) and selenoproteins (for utilization) through selenide. In vitro experiments with simultaneous incubation of (77)Se-MSA(IV) and (82)Se-selenite in a RBC suspension revealed the precise difference in the metabolism between MSA(IV) and selenite in RBCs. (77)Se excreted into the urine was mostly detected as selenosugar but with a distinct amount of trimethylselenonium, suggesting that selenosugar and trimethylselenonium are produced depending on the capacity to transform methylselenol to selenide. MSA(IV) was suggested to be reduced to methylselenol (allowing the production of a proposed active form of selenium), and then transformed (demethylated) to selenide for utilization and excretion.

Once selenium (Se) is absorbed by the body, it is excreted mostly into the urine and the major metabolite is 1beta-methylseleno-N-acetyl-d-galactosamine (selenosugar) within the required to low-toxic range. Selenosugar plateaus with a dose higher than 2.0 microg Se/ml water or g diet, and trimethylselenonium (TMSe) starts to increase, indicating that TMSe can be a biomarker of excessive and toxic doses of Se. Here, we show dose-related changes in the two urinary Se metabolites to clarify the relationship between the dose and urinary metabolites by feeding selenite to rats. It was also examined whether the metabolites are related to age, and further whether a possible exogenous source of the N-acetyl-d-galactosamine moiety, chondroitin 4-sulfate, affects the urinary metabolites. Selenite in drinking water was fed ad libitum to male Wistar rats of 36 and 5 weeks of age, and the concentrations of Se in the urine and organs were determined together with speciation of the urinary Se metabolites. In young rats, selenosugar was always the major urinary metabolite and TMSe increased with a dose higher than 2.0 microg Se/ml drinking water. On the other hand, in adult rats, TMSe increased only marginally despite that the rats suffered much more greatly from the Se toxicity, suggesting that TMSe cannot be a biomarker of Se toxicity. The results suggest that sources of the sugar moiety of selenosugar are more abundant in adult rats than in young rats. Chondroitin 4-sulfate did not affect the ratio of the two urinary metabolites, suggesting that the sugar source is of endogenous origin and that it increases with age.

Two issues led me into the area of cross-cultural psychiatric epidemiology in the 1980s. The National Institute of Mental Health funded the Epidemiological Catchment Area Studies. One of them included a study of a Caucasian and Hispanic populations in Los Angeles. Dr Masaaki Kato, then the Director of the National Institute of Mental Health of Japan, was the consultant for a JAICA-funded project in Lima, Peru. He was interested in fostering psychiatric research there, so I suggested an epidemiological study. This study was done in two phases with Drs Shunichiro Hayashi, Kimpei Minobe and Alberto Perales. Because it is extraordinarily expensive to undertake epidemiological studies in the USA, I met with colleagues regarding psychiatric epidemiological studies in Asia, Dr Chung-kyoon Lee at the Seoul National University in Korea, Dr Eng-Kung Yeh of the National Taiwan University in Taipei,Taiwan, Dr Char-nie Chen of the Chinese University of Hong Kong, and Dr Masaaki Kato in Japan. Studies have been completed in Korea, Taiwan, Hong Kong, but not in Japan. In the meantime, very small pilot studies among Asian groups in Los Angeles were performed. The very recent results of the study of Chinese in Los Angeles, California, with the Composite International Diagnostic Interview are now available to compare the prevalence of selected psychiatric disorders among the Chinese in Los Angeles and the data from the National Co-Morbidity Study.

Objective: The authors' goal was to estimate the lifetime and 12-month rates of major depressive episodes and dysthymia for Chinese Americans who reside in Los Angeles. This effort, the Chinese American Psychiatric Epidemiological Study, is the first large-scale community psychiatric epidemiological study on an Asian American ethnic group that used DSM-III-R criteria for major depressive episodes and dysthymia., Method: A multi-stage sampling design was used to select respondents for participation in the survey. The sample included 1,747 adults, 18-65 years of age, who resided in Los Angeles County and who spoke English, Mandarin, or Cantonese., Results: Approximately 6.9% of the respondents had experienced an episode of major depression and 5.2% had had dysthymia in their lifetime. The 12-month rates of depressive episode and dysthymia were 3.4% and 0.9%, respectively. The most consistent correlate of lifetime and 12-month depressive episode and dysthymia was social stress, measured by past traumatic events and recent negative life events., Conclusions: The Chinese American Psychiatric Epidemiological Study provides a rare opportunity to investigate the heterogeneity within a single Asian American ethnic group, Chinese Americans, and to identify the subgroups among Chinese Americans who may be most at risk for mental health problems.

This study examined the prevalence and clinical features of ICD-10-defined neurasthenia (NT) in Chinese-Americans and its relations to other psychiatric disorders. In this community epidemiological survey, the enhanced Composite International Diagnostic Interview [CIDI], with a supplemental NT module, was administered to 1,747 Chinese-Americans, selected with a stratified cluster sampling method. The SCL-90-R was also used for measuring psychiatric morbidity and symptoms. Dimensions of social stress and social support were measured by established instruments. A total of 112 ICD-10 NT subjects (6.4%) were identified. Of these, 63 (56.3%) did not experience any current and lifetime DSM-III-R diagnoses, yielding a 12-month or lifetime prevalence rate of "pure" NT of 3.61%. This rate was much higher than any of the other psychiatric disorders in this sample. Compared with normal subjects, "pure" NT subjects had significantly higher SCL-90-R total and factor scores, experienced more psychosocial stress, and perceived less social support (P < .05 or .01). Compared with subjects with depression and anxiety disorders, "pure" NT cases reported significantly less SCL-90-R psychological symptoms (P < .05 or .01), but had a strikingly similar elevation in the somatization subscale score. These data suggest that NT is a distinctive clinical condition overlapping only partially with the other better recognized diagnostic entities. In view of its high prevalence and the salience of its impact on the health of those afflicted, it is imperative that concerted research efforts be made to further elucidate the temporal stability, natural course, and outcome of such a condition.

Parents whose children were identified as being at-risk for academic difficulties following a transfer into a new school were involved in either a school-based tutoring program or a school-based tutoring program with a parent training component. When parents actively worked with their elementary school age children at home, the children evidenced better grades at the end of the school year. A variety of other social adjustment measures also indicated that when parents and school-based personnel worked together in the preventive effort, the outcomes were more favorable.