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Vaccination is crucial for preventing the spread of COVID-19. Vaccination for COVID-19 was implemented in Japan in community units, and community pharmacists were engaged in vaccine preparation. Capturing the knowledge, attitudes, and practices (KAP) of pharmacists regarding COVID-19 infection control is important for developing future community health action strategies and plans. We conducted a cross-sectional study among 141 pharmacists who were members of a pharmacist association in the Shinagawa Ward of Tokyo (1–31 July 2021) using a Google online questionnaire. The questionnaire included demographic information and KAP questions regarding COVID-19. A correlation test was used for analyzing KAP scores. Significant correlations were found among all KAP scores. Stepwise logistic regression analysis showed “age” as a significant knowledge factor and “marriage”, “pharmacist careers”, “information source: official government website”, and “information source: word of mouth from family and friends” as significant attitude factors. Good KAP scores were recorded in this study, indicating increased comprehension of infection control measures and increased knowledge scores, as pharmacy pharmacists were practically involved in COVID-19 infection control measures through vaccine preparation. Policymakers should understand the value of pharmacists as healthcare professionals and should enhance public health through the effective use of pharmacists.

This study aimed to determine psychological and physical differences in elementary and junior high school teachers during COVID-19. This questionnaire-based cross-sectional study was conducted among 427 teachers in Tokyo, Japan (between 15 and 30 October 2020). The questionnaire explored school type (elementary and middle schools), sex, age, and COVID-19 changes (psychological changes, physical changes, impact on work, and infection control issues perceived to be stressed). Post hoc tests for I cannot concentrate on work at all, found a significant difference for no change–improved and male teacher in elementary school female teacher in junior high school (p = 0.03). Regarding stress situation due to implementation of COVID-19 infection control, there were significant differences for disinfection work by teachers between male teachers in elementary school female teachers in junior high school (p = 0.04) and female teachers in elementary school female teachers in junior high school (p = 0.03). COVID-19 produced differences in psychological and physical changes between male and female teachers in elementary and junior high schools. Some experienced psychological and physical stress, whereas others showed improvement. Given that teachers’ mental health also affects students’ educational quality, it is important to understand and improve teachers’ psychological and physical circumstances and stress.

Objectives: Patients' adherence to enteral administration of nutrients is influenced by their feeling during administration. The present study compared the taste of commercially prepared ice cream with that of enteral nutrient ice cream, using a sensory test. Additionally, the factors influencing the comprehensive evaluation of enteral nutrient ice cream and commercially prepared ice cream were identified. Methods: A sensory test was performed by 30 pharmacists, on commercially prepared ice cream and enteral nutrient ice cream using the Semantic Differential Method. The factors related to comprehensive evaluation were extracted, and those influencing the comprehensive evaluation of ice cream were analyzed by Covariance structure analysis. Results: No significant differences were observed in the comprehensive evaluation of enteral nutrient ice cream and commercially prepared ice cream (p = 0.08, 95% CI = −0.78 to 0.04). Covariance structure analysis identified five factors related to Easy-to-intake (i.e., Taste, Ease to ingest, Continuity, Peculiar flavor, and Familiarity), which strongly influenced Comprehensive evaluation (standardized estimated value: 0.88). In addition, four factors related to discomfort factor (i.e., Feeling of heaviness, Concentration of taste, Greasiness, and Milky smell) were found not to influence Comprehensive evaluation directly but were correlated with Ease-to-intake (standardized estimate: 0.64). Conclusion: It is important for healthcare professionals to understand the factors involved in the comprehensive evaluation of enteral nutrients, and they should provide appropriate information about it.

To understand the mechanism of cadmium accumulation, it is important to know the precise mechanisms of transport systems for other metals. Recently, utilization of genomics and metallomics has clarified the involvement of specific metal transporter(s) in cadmium uptake. Studies with metallothionein (MT)-null cadmium-resistant cells have revealed the involvement of the manganese/zinc transport system in cadmium uptake. Genomic studies of strain differences in sensitivity to cadmium-induced testicular hemorrhage revealed that a zinc transporter, Zrt-, Irt-related protein (ZIP) 8 encoded by slc39a8, is responsible for the strain difference. Ectopic expression of ZIP8 in various cells enhanced the uptake of cadmium, manganese, and zinc. ZIP8-transgenic mice showed high expression of ZIP8 in the vasculature of testis and apical membrane of proximal tubules in kidney, and exhibited enhanced cadmium accumulation and toxicity when treated with cadmium. The expression of ZIP8 was found to be down-regulated in MT-null cadmium-resistant cells, in which the uptake rates of both cadmium and manganese were decreased. These data suggest that ZIP8 plays an important role in the uptake of both cadmium and manganese in mammalian cells. The role of ZIP14 in the uptake of cadmium and manganese is also discussed.

Context: Genetic factors are important for the development of obesity. However, the genetic background of obesity still remains unclear. Objective: Our objective was to search for obesity-related genes using a large number of gene-based single-nucleotide polymorphisms (SNPs). Design and Setting: We conducted case-control association analyses using 94 obese patients and 658 controls with 62,663 SNPs selected from the SNP database. SNPs that possessed P ≤ 0.02 were further analyzed using 796 obese and 711 control subjects. One SNP (rs3764220) in the secretogranin III (SCG3) gene showed the lowest P value (P = 0.0000019). We sequenced an approximately 300-kb genomic region around rs3764220 and discovered SNPs for haplotype analyses. SCG3 was the only gene within a haplotype block that contained rs3764220. The functions of SCG3 were studied. Patients: Obese subjects (body mass index ≥ 30 kg/m2, n = 890) and control subjects (general population; n = 658, body mass index ≤ 25kg/m2; n = 711) were recruited for this study. Results: Twelve SNPs in the SCG3 gene including rs3764220 were in almost complete linkage disequilibrium and significantly associated with an obesity phenotype. Two SNPs (rs16964465, rs16964476) affected the transcriptional activity of SCG3, and subjects with the minor allele seemed to be resistant to obesity (odds ratio, 9.23; 95% confidence interval, 2.77–30.80; χ2 = 19.2; P = 0.0000067). SCG3 mRNA and immunoreactivity were detected in the paraventricular nucleus, lateral hypothalamic area, and arcuate nucleus, and the protein coexisted with orexin, melanin-concentrating hormone, neuropeptide Y, and proopiomelanocortin. SCG3 formed a granule-like structure together with these neuropeptides. Conclusions: Genetic variations in the SCG3 gene may influence the risk of obesity through possible regulation of hypothalamic neuropeptide secretion.

Objective: Gap-junctional communication (GJC) plays critical roles in cell growth and differentiation. Several studies have demonstrated the involvement of GJC in myogenesis and osteogenesis; however, the role of GJC in adipogenesis has not been fully studied. Thus, we investigated the role of GJC in adipogenesis. Research Methods and Procedures: 3T3-L1 preadipocytes were differentiated in the presence of gap junction inhibitor, 18-α-glycyrrhetinic acid (AGA), and accumulation of cytoplasmic triglycerides was measured. 3T3-L1 cells were transfected with 100 nM small interfering RNA duplexes targeting connexin (Cx) 43. The mRNA levels of CCAAT/enhancer-binding protein (C/EBP) α, peroxisome proliferator-activated receptor γ, glucose transporter 4, C/EBPβ, and Cx43 were measured by real-time polymerase chain reaction. The protein levels of C/EBPβ were quantitated by Western blotting. The cell proliferation was measured by counting cell numbers, and DNA synthesis was measured by bromodeoxyuridine incorporation. Results: AGA inhibited adipocyte differentiation dose-dependently. The lipid accumulation and the mRNA levels of C/EBPα, peroxisome proliferator-activated receptor γ, and glucose transporter 4 were markedly reduced in AGA-treated adipocytes. The mRNA levels of C/EBPβ did not decrease; however, C/EBPβ [liver-enriched transcriptional activator protein (LAP)] expression and the C/EBPβ (LAP)-to-C/EBP [liver-enriched transcriptional inhibitory protein (LIP)] ratio were reduced by AGA treatment. The increase in both cell number and DNA synthesis, which occurs during mitotic clonal expansion, was reduced by AGA in a dose-dependent fashion. The major component of gap junctions in 3T3-L1 cells was Cx43. Down-regulation of Cx43 using small interfering RNA reduced the expression of C/EBPβ (LAP) and inhibited adipogenesis. Discussion: Our data suggest that GJC plays some important roles in adipogenesis through inhibiting mitotic clonal expansion and modulating C/EBPβ (LAP) expression.

The mechanism of cellular cadmium (Cd) uptake has been poorly understood. Recently, we developed Cd-resistant cell lines from metallothionein null mouse cells and showed that the Cd resistance of these cells was conferred primarily by a reduced Cd accumulation. Surprisingly, the uptake rate of manganese (Mn) was also markedly reduced in Cd-resistant cells. Subsequent studies on the kinetics of Cd and Mn uptake by Cd-resistant and parental cells revealed that the Mn transport system with high affinity for Mn is used for cellular Cd uptake, and that this pathway is suppressed in Cd-resistant metallothionein null cells. This is the first indication that the transport system for Mn is used for Cd uptake in mammalian cells. Divalent metal transporter 1 (DMT1) is the only known mammalian transporter involved in the uptake of both Cd and Mn. However, the high-affinity Mn/Cd transport system we found seems to be distinct from DMT1 because of the difference in optimal pH and substrate specificity. On the other hand, various types of Mn transporters have been shown to play an important role in cellular Cd uptake in non-mammalian species such as yeast, plants and bacteria, suggesting the existence of Mn transporters other than DMT1 in mammals.

Primary cultured embryonic cells derived from mice with disrupted metallothionein (MT) I and II genes and from control mice were transformed with a plasmid encoding the simian virus 40 (SV40) large T antigen. The resulting MT-/- and MT+/+ cell strains showed similar cell morphology, cell cycle and no significant differences in glutathione levels or in the activities of glutathione-related enzymes and antioxidant enzymes. The MT-/- cells were more sensitive to Cd than MT+/+ cells, though no increase in the sensitivity to Zn, Cu, Hg or Ni were observed in MT-/- cells. MT+/+ cells accumulated more Cd than MT-/- cells but showed less lesion, suggesting the role of MT induced by Cd in MT+/+ cells as a scavenger of toxic Cd ion. These results suggest a dominant protective role of MT against Cd compared with other metals. SV40-transformed MT-/- cells seem to be a useful tool for the investigation of cellular function of MT.

Effects of glutathione (GSH) depletion on nephrotoxicity of cis-diamminedichloroplatinum(II) (cis-DDP) and induction of renal metallothionein (MT) synthesis elicited by cis-DDP treatment has been studied using mice. Pretreatment with L-buthionine-SR-sulfoximine (BSO) reduced the GSH level in the kidneys to 20% of the control level at the time of cis-DDP administration. Administration of 45 μmol/kg cis-DDP did not change the blood urea nitrogen (BUN) level, determined as an indicator of nephrotoxicity, until 96 h after administration, whereas BSO pretreatment raised the BUN level as early as 48 h after cis-DDP (45 μmol/kg) treatment. The level of renal MT was also increased in the GSH-depleted mice and was changed in parallel with the BUN level after cis-DDP treatment. Level of plasma fibrinogen, one of acute phase proteins, increased by cis-DDP in GSH-depleted mice. The increase was reduced by dexamethasone pretreatment, although the renal MT level increased by BSO and cis-DDP was not changed by dexamethasone pretreatment. These results suggest that the induction of renal MT synthesis by cis-DDP in BSO-pretreated mice was not related with the acute phase responses such as cytokines induction. Although the mechanism of the induction of MT synthesis by cis-DDP in GSH-depleted mice is unclear, it is possible that MT is induced as an antidote against oxidative stress, which may be a major cause for nephrotoxicity of cis-DDP enhanced by GSH depletion. © 1995 Wiley-Liss, Inc.

The mechanism of cellular entry of cadmium remains unclear. We have previously established cadmium-resistant cells from mouse embryonic cells of metallothionein (MT)-null mice, and demonstrated that the down-regulation of a zinc transporter, Zrt/Irt-related protein (ZIP) 8, was responsible for the reduced cadmium incorporation into cells. In the present study, we developed cadmium-resistant cells (A + 70 and B + 70) from mouse embryonic cells of MT-expressing wild-type mice. The LC 50 values of CdCl 2 for A + 70 and B + 70 cells were about 200 μM while that of the parental cells was 30 μM. We found that the cadmium resistance of these cells was conferred not only by enhanced expression of MT, but also by a decrease in cadmium accumulation. Since the uptake rates of cadmium into A + 70 and B + 70 cells were lowered, we determined the expression levels of the metal transporters and channels potentially involved in the cellular uptake of cadmium. We found a down-regulation of multiple transport systems, including ZIP8, divalent metal transporter 1 (DMT1), and α 1 subunits of L-type (Ca V 1.2) and T-type (Ca V 3.1) voltage-dependent calcium channels, in A + 70 and B + 70 cells. Furthermore, A + 70 and B + 70 cells exhibited cross-resistance to cytotoxicity of MnCl 2 , probably due to a marked decrease in manganese uptake in these cells. These results suggest that the suppressed expression of ZIP8 and DMT1, which are known to have affinities for both cadmium and manganese, may be responsible for the reduction in the uptake, and consequently the cytotoxicity, of cadmium and manganese in A + 70 and B + 70 cells.

Genetic factors are clearly involved in the development of obesity, but the genetic background of obesity remains largely unclear. Starting from 62 663 gene-based single-nucleotide polymorphisms (SNPs) in three sequential case-control association studies, we identified a replicated association between the obesity phenotype (BMI > or =30 kg/m(2)) and a SNP (rs2293855) located in the myotublarin-related protein 9 (MTMR9) gene in the chromosomal segment 8p23-p22. P-values (minor allele dominant model) of the first set (93 cases versus 649 controls) and the second set (564 cases versus 562 controls) were 0.008 and 0.0002, respectively. The association was replicated in the third set [394 cases versus 958 controls, P = 0.005, odds ratio (95% CI) =1.40 (1.11-1.78)]. The global P-value was 0.0000005. A multiple regression analysis revealed that gender, age BMI and rs2293855 genotype (minor allele dominant model) were significantly associated with both systolic and diastolic blood pressures. MTMR9 was shown to be the only gene within the haplotype block that contained SNPs associated with obesity. Both the transcript and protein of MTMR9 were detected in the rodent lateral hypothalamic area as well as in the arcuate nucleus, and the protein co-existed with orexin, melanin concentrating hormone, neuropeptide Y and proopiomelanocortin. The levels of MTMR9 transcript in the murine hypothalamic region increased after fasting and were decreased by a high-fat diet. Our data suggested that genetic variations in MTMR9 may confer a predisposition towards obesity and hypertension through regulation of hypothalamic neuropeptides.

Metallothionein (MT) is known to play a predominant role in the protection of cells from cadmium (Cd) toxicity. To investigate other factors involved in Cd resistance, we established Cd-resistant cell lines from simian virus 40-transformed MT null fibroblasts. Cd-resistant MT null cells, Cd-rA7 and Cd-rB5, developed approximately 10-fold resistance to Cd compared to parental cells, but showed no cross-resistance to Zn, Cu, Hg, Ni, As, cisplatin or H 2 O 2 . Accumulation of Cd in the resistant cells was 13–18% of that of parental cells after treatment with Cd for 24 h. A short-term experiment revealed that the rate of Cd incorporation into the Cd-resistant cells was suppressed, and the rate of Cd release was enhanced in the resistant cells compared with that of parental cells. These results indicate that the altered transport of Cd, slow uptake and rapid release, may confer resistance to Cd on the Cd-resistant cells established from MT null fibroblasts.

The effect of Glutathione (GSH) depletion on the induction of metallothionein (MT) synthesis by paraquat (PQ) was examined in ICR mice. An increase in hepatic MT level in mice was observed after a single PQ administration. Pretreatment of mice with L-buthionine-SR-sulfoximine (BSO), an inhibitor of GSH synthesis, enhanced the induction of hepatic and renal MT synthesis by PQ depending on the decreased tissue GSH level. A similar result was obtained by pretreatment with diethylmaleate, a GSH depleting agent. The ratio of hepatic MT-I to MT-II induced by PQ was not changed by BSO pretreatment. An increase in the hepatic MT level in GSH depleted mice was observed from 3 hr to 24 hr after PQ administration. An increase in the hepatic MT-I mRNA level after treatment with PQ was observed prior to hepatic MT induction in BSO pretreated mice. Pretreatment with actinomycin D, an inhibitor of mRNA synthesis, inhibits the PQ-induced increase in hepatic MT and MT-I mRNA levels in BSO pretreated mice. Pretreatment with BSO did not affect the induction of MT synthesis by zinc, cadmium or dexamethasone. Pretreatment with dexamethasone, an anti-inflammatory agent, enhanced the hepatic MT induction by PQ treatment in GSH depleted mice, while dexamethasone reduced the MT induction by turpentine oil, which is known to induce inflammation and hepatic MT synthesis. These findings suggest that GSH depletion enhances the induction of MT synthesis by PQ because of an increase in the transcription rate, and this enhancement of MT synthesis is not due to an inflammatory response caused by PQ.