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Presenteeism is the loss of productivity due to a worker's health problems, despite the worker being present at the workplace. Although the association between presenteeism and insomnia complaints is well known, few studies have examined the association between insomnia severity and presenteeism. This study aimed to explore the association between insomnia severity and presenteeism. This study included 1925 participants (1543 males, 379 females, and three of other genders) in total. The mean age of the participants was 49.94 ± 9.82 years. The inclusion criteria were full-time employment, working 8 hr per day and 5 days per week, and having no night shifts. The insomnia severity was classified based on the Insomnia Severity Index and Athens Insomnia Scale criteria. Logistic regression analysis showed that moderate and severe insomnia severity were associated to a greater magnitude with presenteeism than mild insomnia severity. Severe insomnia severity was associated to a greater magnitude with presenteeism than moderate insomnia severity. In summary, logistic regression analysis showed that increased insomnia severity based on Insomnia Severity Index classification was associated with increased odds of presenteeism, but increased insomnia severity based on Athens Insomnia Scale classification was not fully consistent with increased odds of presenteeism. Because increased insomnia severity is associated with worsening of presenteeism, early detection of and early intervention against insomnia complaints are important for reducing presenteeism. This study was the first to examine the associations between presenteeism and insomnia severity classification of no insomnia, mild, moderate, and severe insomnia severity.

Background Sleep problems interfere with work performance. Decreased work productivity due to health problems is defined as presenteeism. Although empirical data on the improvement of presenteeism by sleep interventions have been published, a systematic review elucidating whether there is a difference in the improvement of presenteeism across various types of sleep interventions has not yet been published. This systematic review of studies aimed to clarify which sleep interventions are more likely to be effective in improving presenteeism. Methods The electronic databases PubMed, PsycINFO, and MEDLINE were used to perform a literature search (the start and end search dates were October 20, 2019, and March 11, 2020, respectively). A combination of terms such as “employee*,” “sleep,” “insomnia,” and “presenteeism” was used for the search. Both randomized and non-randomized control trials were included in this systematic review. Results Six types of sleep interventions were identified, including cognitive behavioral therapy for insomnia (CBT-I), sleep hygiene education, yoga, mindfulness, weight loss program, and changing the color temperature of fluorescent lights in the workplace. Only CBT-I improved both sleep problems and presenteeism compared with a control group. The results of this review also show that there is heterogeneity in the measurement of presenteeism. Conclusions The results of this systematic review suggested that CBT-I could be adapted for workers with sleep problems and presenteeism. We discussed whether CBT-I improved both sleep problems and presenteeism compared with other interventions. In addition, methods for measuring presenteeism in future research are proposed.

Aims We retrospectively analyzed the clinical outcome and prognostic parameters in patients with hepatocellular carcinoma (HCC) and bone metastases who had received treatment with zoledronic acid (ZOL). Methods Ninety-nine HCC patients with bone metastases who had been treated with ZOL were enrolled in this retrospective cohort study. We analyzed the prognostic factors, including serum N-telopeptide of type I collagen (NTX) levels, as bone metabolism markers. Results The median overall survival (OS) time was 11.5 months. Child–Pugh grade A (P = 0.004) and intrahepatic tumor stage (IHTS) T0–3 (P = 0.010) correlated significantly with favorable OS. In 46 patients with grade A and T0–3, receiver operating characteristic curve analysis defined 16 nmol BCE/L serum NTX as the cut-off level for median OS. Multivariate analysis identified baseline serum NTX

We report a 60-year-old male patient who developed extrahepatic metastases in bone, peritoneum, and lymph nodes (confirmed by computed tomography and positron emission tomography-computed tomography) after hepatectomy for hepatocellular carcinoma. He was treated with sorafenib (800 mg/day) but developed grade 3 hand-foot syndrome. He continued to be treated with sorafenib but at a lower dose (400 mg/week). The response to sorafenib therapy was graded as complete response at 6 months by the Response Evaluation Criteria in Solid Tumors. Sorafenib was continued for 8 months and the patient remained in complete response for 11 months. Further reporting of similar cases should help design treatment strategies and evaluate predictors of the response to sorafenib therapy.

Background: We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study. Methods: We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013. Results: During the observation period (median 50 months: range 13–224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17–141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3–6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8–50.0: P

Recently, treatments for chronic hepatitis C virus (HCV) infection have been drastically improved by the development of direct-acting antiviral agents. In September 2014, dual oral therapy using daclatasvir (DCV) and asunaprevir (ASV) was approved for the treatment of chronic HCV infection in Japan. We treated a patient with HCV-related liver cirrhosis with severe leg edema due to chronic renal dysfunction using this dual oral therapy. Although serum alanine aminotransferase increased rapidly during the first week of treatment, the antiviral therapy was able to continue, and liver function recovered spontaneously. After 1 month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased. Throughout the therapy, serum creatinine level nearly normalized, and leg edema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved. It has been reported that chronic HCV infection is associated with renal dysfunction and that HCV eradication can improve it. DCV and ASV combination therapy is safe for patients who have renal dysfunction and may be a suitable therapy for chronic hepatitis C patients with renal dysfunction.

Objectives This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). Methods We retrospectively examined 60 patients who received F-FDG PET-CT prior to hepatic resection for small HCC (≤30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. Results Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive α-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. Conclusions F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.

To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the a-fetoprotein (AFP) and des-y-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC.

We retrospectively analyzed the clinical outcome and prognostic parameters in patients with hepatocellular carcinoma (HCC) and bone metastases who had received treatment with zoledronic acid (ZOL).Ninety-nine HCC patients with bone metastases who had been treated with ZOL were enrolled in this retrospective cohort study. We analyzed the prognostic factors, including serum N-telopeptide of type I collagen (NTX) levels, as bone metabolism markers.The median overall survival (OS) time was 11.5 months. Child-Pugh grade A (P = 0.004) and intrahepatic tumor stage (IHTS) T0-3 (P = 0.010) correlated significantly with favorable OS. In 46 patients with grade A and T0-3, receiver operating characteristic curve analysis defined 16 nmol BCE/L serum NTX as the cut-off level for median OS. Multivariate analysis identified baseline serum NTX16 nmol BCE/L (P = 0.045) as the only significant and independent determinant of OS.Low baseline serum NTX level correlated with favorable outcome in bone metastatic HCC patients with Child-Pugh grade A and IHTS T0-3 treated with ZOL.

We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study.We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013.During the observation period (median 50 months: range 13-224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17-141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3-6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8-50.0: P 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6-7.2: P 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9-16.8: P 0.0001) as significant and independent risk factors for post-SVR HCC.Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.

Advanced glycation end products (AGE) and the receptor for AGE (RAGE) have been implicated in the chronic complications of diabetes mellitus (DM), and have been reported to play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we established a polyclonal anti-RAGE antibody, and examined the immunohistochemical localization of amyloid beta protein (Abeta), AGE, and RAGE in neurons and astrocytes from patients with AD and DM. Our anti-RAGE antibody recognized full-length RAGE (50 kd) and N-terminal RAGE (35 kd) in human brain tissue. Abeta-, AGE-, and RAGE-positive granules were identified in the perikaryon of hippocampal neurons (especially from CA3 and CA4) in all subjects. The distribution and staining pattern of these immunopositive granules showed good concordance with each antibody. In AD, most astrocytes contained both AGE-and RAGE-positive granules and their distribution was almost the same. Abeta-positive granules were less common, but Abeta-, AGE-, and RAGE-positive granules were colocalized in one part of a single astrocyte. In DM patients and control cases, AGE-and RAGE-positive astrocytes were very rare. These finding support the hypothesis that glycated Abeta is taken up via RAGE and is degraded through the lysosomal pathway in astrocytes. In addition to the presence of AGE, the process of AGE degradation and receptor-mediated reactions may contribute to neuronal dysfunction and promote the progression of AD.

The objective of this study was to assess the pathological role of advanced glycation end products (AGE) and the receptor for AGE (RAGE) in Creutzfeldt-Jakob disease (CJD). We immunohistochemically investigated the occipital lobe of three patients with CJD containing with prion protein (PrP) plaques using anti-AGE and RAGE antibodies. Many PrP-positive plaques were observed in these patients, and the PrP-positive prion plaques also showed immunoreactivity for the anti-AGE antibody. Furthermore, many astrocytes contained-PrP positive granules, and the same astrocytes also contained many AGE- and RAGE-immunopositive granules. The staining pattern of these granules showed good concordance with that of PrP. These findings suggest that there may be a RAGE-mediated PrP degradation pathway in CJD as is the case for beta-amyloid protein in Alzheimer's disease.

In this article, we have extensively studied and discussed the magnetic properties of acidic ferric hemoglobin and its isolated chains. The magnetic susceptibility, EPR and optical spectra of those samples were measured in the temperature region below 77 degrees K. By the magnetic susceptibility measurements, it could be made clear that at an acidic pH value, both ferric hemoglobin and its isolated chains were constituted of a mixture of two spin states (high-spin state S = 5/2 and low-spin state S = 1/2) and the ratio of this mixture varied in each protein sample, but was independent of the temperature change below 77 degrees K. The co-existence of these two components could be ascertained by the observation of EPR spectra at liquid hydrogen temperature. Acidic ferric hemoglobin and its isolated chains exhibited the two components of EPR spectra which corresponded to their magnetic susceptibility, and it was found that the relaxation time of the low-spin state was longer than that of the high-spin state. The low-spin component of EPR spectra was almost undetectable at liquid nitrogen temperature. The three principal g values of this low-spin were gz = 2.80, gy = 2.20, and gx = 1.70. At alkaline pH values these low-spin components and the high-spin component of EPR spectra were displaced by the different low-spin spectra which corresponded to the ferric hemoglobin-hydroxide complex. It seems that the magnetic properties of the high-spin component are the same as the acidic ferric myoglobin, and the fine structure of the iron ion also seems to be same. Optical spectroscopy also gave similar magnetic properties which corresponded to the magnetic measurements.

The temperature dependence of the paramagnetic anisotropy of a single deoxyhemoglobin crystal (Form II) was measured by the torque method with a sensitivity of 10−4 dyne·cm in the temperature range of 2 to 77 °K. Torque curves were measured in the three perpendicular planes of the crystal by a rotating magnetic field. The torque curves obtained were of a sinusoidal shape per half rotation of the magnetic field. The phases of the torque curves as well as the amplitudes changed with temperature. This means that the three principal values of magnetic susceptibility of heme depended on temperature and these temperature dependencies were not the same. The amplitude of the observed torque was very small when the magnetic field was rotated almost parallel to the heme planes in the unit cell, while it was very large when the magnetic field was rotated perpendicular to the heme planes. The directions of the magnetic field which gave zero torque values were nearly perpendicular and parallel to the heme plane. From these results, it was concluded that the magnetic susceptibility of heme in deoxyhemoglobin was fairly axially symmetrical, taking the axis to be nearly perpendicular to the plane of the heme, though in detail a small asymmetry in the heme plane existed. The temperature dependence of amplitude measured over a wide temperature range was analyzed on the basis of the spin Hamiltonian; H=DSZ2+E(SX2−Sy2)+βSgH. Experimental data were best represented by the theoretical curves which were calculated from the values of D = 5.3 and E = 0.9 cm−1. This study made it clear that the previously reported result of D = −18 cm−1 was incorrect (M. Kotani, Ann. N.Y. Acad. Sci., 158 (1969) 20).

To study the relationship between the fine structure of the electronic states of heme iron and its respiratory function, the temperature dependence of the magnetic susceptibility of deoxymyoglobin and deoxyhemoglobin were measured in different temperatures ranging from 2.0 to 77°K. The magnetic field dependence of the magnetization of these samples was also measured under a strong magnetic field with a super-conducting magnet up to 50 kOe. Results from these two measurements were consistent with each other. A theoretical analysis yielded the following conclusions: deoxymyoglobin and deoxyhemoglobin were of the high spin type, and the fine structure of the iron ion in these hemoproteins was expressed by spin Hamiltonian DS z 2 when D was chosen as 5 cm −1 . The difference in magnetic properties between myoglobin and hemoglobin was not detectable from these magnetic measurements.