Occupational stress is associated with job performance among pregnant women in Japan: comparison with similar age group of women.

BACKGROUND: Pregnancy results in physical and psychological changes in women; however, pregnant women hesitate to take a break from work even when they feel the need. Since working while physically ill leads to decreased job performance, it is important to determine the factors that lead to this phenomenon. AIM: To study the occupational stress associated with job performance and absenteeism of pregnant women compared with non-pregnant women. METHODS: In 2019, non-pregnant and pregnant employed women in their 20-40 s in Japan completed an online survey examining job performance (Work Limitation Questionnaire - Short Form), absenteeism, occupational stress (Brief Job Stress Questionnaire), and working situations. RESULTS: Of 918 respondents who met the inclusion criteria, 904 were included in the final analysis (454 non-pregnant and 450 pregnant women). Logistic regression analyses showed that absenteeism was significantly higher for pregnant women. However, for women who were absent, there was no significant difference between non-pregnant and pregnant women. After adjusting for attributes and working conditions, pregnant women had significantly higher (p < .001) work productivity losses than non-pregnant women, but only in the physical tasks domain; their physical stress response was also higher compared to non-pregnant women (p = .048). However, pregnant women reported significantly less interpersonal conflict stress (p < .001) and psychological stress (p = .026), as well as better workplace support as a buffering factor for stress (p = .021), than non-pregnant women. CONCLUSION: Clarifying the physical burden associated with pregnancy and assisting women in coordinating their work duties while considering the physical demands of pregnancy may minimize work productivity losses among pregnant women.

Factors Associated With the Work Productivity of Japanese Working Pregnant Women: A Cross-Sectional Study.

OBJECTIVES: Working pregnant women experience physical and psychosocial changes, which are associated with two aspects of work productivity: presenteeism and absenteeism. We examined the factors that affect these two aspects. METHODS: This cross-sectional study was conducted in April to May 2019 through an online survey. Participants were 450 working women who were pregnant for the first time. RESULTS: Occupational stress (job overload sß: 0.14, suitable jobs sß: 0.16); physical conditions, such as pregnancy complications (sß: 0.32) and gestational period (sß: 0.18); and adjustment status in the workplace due to pregnancy, such as pregnancy disclosure (sß: 0.11) and pregnancy discrimination (sß: 0.18), were related to presenteeism. Meanwhile, pregnancy complications were the only factor associated with absenteeism (sß: 0.32; all P < 0.05). CONCLUSIONS: In addition to physical condition support, support for psychosocial conditions in the workplace is required.

Identification by differential tissue proteome analysis of talin-1 as a novel molecular marker of progression of hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is characterized by a multistage process of tumor progression. This study addressed its molecular features to identify novel protein candidates involved in HCC progression. METHODS: Using liquid chromatography-tandem mass spectrometry, proteomes of 4 early HCCs and 4 non-HCC tissues derived from 2 cases of liver transplant surgery were compared with respect to the separation profiles of their tryptic peptides. Immunohistochemistry was performed on 106 HCC nodules to confirm the results of the proteomic analysis. RESULTS: Statistical analysis of the profiles selected the peptide peaks differentiating HCC from non-HCC. A database search of the tandem mass spectrometry data from those peptide peaks identified 61 proteins, including a cytoskeletal protein, talin-1, as upregulated in HCC. Talin-1 expression levels in HCC nodules were significantly associated with the dedifferentiation of HCC (p = 0.001). A follow-up survey of the examined clinical cases revealed a correlation between talin-1 upregulation and a shorter time to recurrence after resection (p = 0.039), which may be related to the higher rate of portal vein invasion in HCCs with talin-1 up-regulation (p = 0.029). CONCLUSIONS: Proteomic analysis led to identification of talin-1 as a promising HCC marker. Talin-1 upregulation is associated with HCC progression and may serve as a prognostic marker.

Proteomic biomarkers for acute interstitial lung disease in gefitinib-treated Japanese lung cancer patients.

Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10(-25)), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control.

i-RUBY: a novel software for quantitative analysis of highly accurate shotgun-proteomics liquid chromatography/tandem mass spectrometry data obtained without stable-isotope labeling of proteins.

We developed a novel software named i-RUBY (identification-Related qUantification-Based strategY algorithm for liquid chromatography/tandem mass spectrometry (LC/MS/MS) data) that enables us to perform fully automatic ion current-based spectral feature analysis of highly accurate data obtained by LC/MS/MS. At the 1st step, this software utilizes accurate peptide/protein identification information for peak detection and peak matching among measurements. Then, at the 2nd step, it picks yet unidentified peaks and matches them to the peaks identified at the 1st step by a linear interpolation algorithm. The analysis of human plasma externally spiked with a known amount of yeast alcohol dehydrogenase 1 showed a good linear relationship between the amount of protein spiked and the quantitative values obtained by i-RUBY analysis. Experiment using human plasma digests spiked with a mixture of known amounts of synthetic peptides derived from two yeast proteins, alcohol dehydrogenase 1 and glucose-6-phospate isomerase, showed the expansion by the 2nd step of i-RUBY of the lower quantification limits to 1/10 to 1/1000 of those reached only by identified peaks at the 1st step. Good correlations between the i-RUBY results and the amount of proteins were confirmed by the analysis of real samples, i.e., sera of normal subjects and cancer patients, by comparing quantitative values of acute-phase proteins obtained by i-RUBY analysis of LC/MS/MS data with those obtained by an immunological method using Bio-Plex. These results taken together show that i-RUBY is a useful tool for obtaining dependable quantitative information from highly accurate shotgun-proteomics LC/MS/MS data.

Selected reaction monitoring by linear ion-trap mass spectrometry can effectively be applicable to simultaneous quantification of multiple peptides.

Selected reaction monitoring (SRM) mass spectrometry (MS) is becoming a popular approach for targeted quantitative proteomics. Triple-quadrupole mass spectrometers have been historically considered as the instrument of choice for this type of quantitative analysis. Recently, however, it has been reported that the SRM MS with a linear ion-trap (LIT) mass spectrometer is rather more appropriate for quantitative analysis of large peptides than the triple-quadrupole ones. In this study, we demonstrate that the SRM MS performed with a LIT mass spectrometer can simultaneously analyze multiple peptides and can quantify specific peptides in biological specimens without the use of stable isotope (SI)-labeled standard peptides. Firstly, a mixture of 10 synthesized peptides derived from yeast proteins and bovine serum albumin (BSA) was simultaneously analyzed by the LIT SRM. The ion peak areas of the 10 peptides were linearly correlated with the input amounts between 1 fmol and 10 pmol. Furthermore, the same peptide mixture spiked into human plasma was analyzed, and a linear response was found. Next, the amount of a BSA tryptic peptide was quantified by using an SI-labeled or a non SI-labeled peptide as an external reference standard. The difference in the quantified amounts of the BSA tryptic peptide was less than 10% between the 2 methods, suggesting that the "externally pulsed" non SI-labeled standard peptides derived from another species are useful. These results indicate that the SRM MS conducted with a LIT mass spectrometer is applicable to targeted quantitative proteomics of peptides at least up to 10 in number.

Genetic deficiency of a mitochondrial aldehyde dehydrogenase increases serum lipid peroxides in community-dwelling females.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a major role in acetaldehyde detoxification. The alcohol sensitivity is associated with a genetic deficiency of ALDH2. We and others have previously reported that such a deficiency influences the risk for late-onset Alzheimer's disease (LOAD), hypertension, and myocardial infarction. Then we tried to find phenotypes to which the ALDH2 polymorphism contributes by conducting several evaluations including biochemical and functional analyses of various tissues in a community-dwelling population. Several serum proteins, lipids, and lipid peroxides (LPO) levels showed differences between the nondefective (ALDH2*1/1) and defective (ALDH2*1/2 and ALDH2*2/2) ALDH2 individuals. However, alcohol-drinking behavior is known to affect these evaluations. Thus, we excluded the effects of alcohol-drinking behavior from the association with the ALDH2-deficient genotype through correction and found that the concentration of LPO was significantly lower in the nondefective ALDH2 females than the defective females. The effect of frequent alcohol-drinking behavior in males seems to override the phenotype of the high serum LPO level. These results indicate that the ALDH2 deficiency may enhance oxidative stress in vivo. Thus, these findings suggest that ALDH2 functions as a protector against oxidative stress and the decrease in protection may influence the onset of AD, hypertension, and myocardial infarction.

The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients.

We evaluated the relationship of an alanine or valine polymorphism at amino acid sequence 16 [Val(16)Ala] of manganese superoxide dismutase (Mn-SOD) with diabetes and diabetic nephropathy in Japanese type 2 diabetic patients. Val(16)Ala genotyping of Mn-SOD was done by polymerase chain reaction-restriction fragment length polymorphism with a restriction enzyme ( Bsaw I) in 478 Japanese type 2 diabetic patients and 261 nondiabetic Japanese healthy subjects. The genotype distribution of diabetic and nondiabetic subjects was then compared, and the association of genotype with diabetic nephropathy was evaluated in the diabetic patients. The allele frequency and genotype of the diabetic patients were not different from those of the healthy nondiabetic subjects. The VV type showed a significantly higher frequency in the diabetic patients with nephropathy than did the AA or VA type [VV type: normoalbuminuria 70.8%, microalbuminuria 84.8% (P = 0.0057), macroalbuminuria 84.1% (P = 0.0128)]. Furthermore, logistic regression analysis showed that this polymorphism is associated with diabetic nephropathy independently (odds ratio = 0.461925, P = 0.03). Accordingly, the Val(16)Ala polymorphism of Mn-SOD may be unrelated to the etiology of type 2 diabetes, but it seems to be associated with diabetic nephropathy in Japanese type 2 diabetic patients.