Upregulation of Angiogenic Factors via Protein Kinase C and Hypoxia-induced Factor-1α Pathways under High-glucose Conditions in the Placenta

Abnormal glucose metabolism during pregnancy is an established risk factor for preeclampsia (PE). Disruption of the balance between placental angiogenic factors is linked to PE pathophysiology. We examined whether hypoxia-induced factor-1α (HIF-1α) and protein kinase Cβ (PKCβ) are involved in the regulation of placental angiogenic factors under high-glucose conditions in vitro. The human choriocarcinoma cell lines BeWo and JEG-3, and the human trophoblast cell line HTR-8/SVneo were cultured with 10 and 25 mmol/L glucose [control glucose group (CG) and high-glucose group (HG), respectively]. We examined the changes in HIF-1α, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) expression in the CG and HG by real-time PCR and ELISA. PKC activation was also measured by ELISA. The expressions of HIF-1α, sFlt-1, PlGF, and VEGF were significantly higher in the HG than in the CG. PKC activity was significantly increased in the HG. High glucose affected the expression of angiogenic factors in choriocarcinoma cells via the PKCβ and HIF-1α pathways, suggesting their involvement in PE pathogenesis

Comparison of Kidney Function between Gestational Hypertension and Preeclampsia

Although gestational hypertension (GH) is thought to be different from preeclampsia (PE), in Japan GH and PE are usually treated as the same disease (i.e., pregnancy-induced hypertension). Here we sought to determine whether there are any differences in fetal growth and maternal kidney function between pregnancies with PE and those with GH. We retrospectively analyzed 61 GH patients and 60 PE patients with singleton pregnancies who delivered at Okayama University Hospital (2008-2015). We compared maternal and perinatal outcomes and maternal kidney function parameters between the GH and PE pregnancies. The mean values of maternal age (p=0.01), gestational age at delivery (p<0.0001), placental weight (p=0.002), birth weight and height (p<0.0001, p=0.0001), and head circumference standard deviation score (p=0.007) of newborns of the GH group were significantly higher than those of the PE group. The duration until termination of PE or GH was not significantly correlated with kidney function. The birth weight percentile was significantly correlated with kidney function in PE but not GH. However, GH patients with poor kidney function and small-for-gestational age infants showed perinatal outcomes similar to those of the PE group. Monitoring kidney function is thus important for determining the severity of PE and GH

Lung, gastric and colorectal cancer mortality by occupation and industry among working-aged men in Japan

We examined occupational and industrial differences in lung, gastric, and colorectal cancer risk among Japanese men of working age (25–64 years) using the 2010 Japanese national survey data for occupation and industry-specific death rates. Poisson regression models were used to estimate the age-adjusted incident rate ratios by lung, gastric, and colorectal cancers, with manufacturing used as the referent occupation or industry. Unemployed Japanese men and those in manufacturing had an 8–11-fold increased risk of lung, gastric and colorectal cancer. The highest mortality rates for lung and colorectal cancer by occupation were “administrative and managerial” (by occupation) and “mining” (by industry). For gastric cancer, the highest mortality rate was “agriculture” (by occupation) and “mining” (by industry). By occupation; Japanese men in service occupations, those in administrative and managerial positions, those in agriculture, forestry and fisheries, and those in professional and engineering categories had higher relative mortality risks for lung, gastric, and colorectal cancers. By industry; mining, electricity and gas, fisheries, and agriculture and forestry had the higher mortality risks for those cancers. Unemployed men had higher mortality rates than men in any occupation and industry for all three cancers. Overall, this study suggests that for Japanese men, occupations and industries may be a key social determinant of health

Successful Delivery after Abdominal Radical Trachelectomy, Using Transabdominal Cerclage in Early Pregnancy

Radical trachelectomy (RT) is a fertility-sparing surgery for cervical cancer. Postoperative pregnancies have a high risk of abortion and prematurity. To prevent this, a procedure involving transabdominal cerclage (TAC) was devised for shortened cervical canals post-RT. Here we describe the successful management of a pregnancy after abdominal RT (ART). The 34-year-old patient was gravida 1, para 0. When she was 27, she underwent ART for stage Ib1 cervical cancer, and she became pregnant 7 years later. Because her cervical canal was 16.7 mm during early pregnancy, we performed TAC at 12 weeks of pregnancy. Post-surgery, we administered an infusion of ritodrine hydrochloride for tocolysis. A selective caesarean section was performed at 36 weeks, with the delivery of a healthy infant

Relationship between Intracellular Signaling of the (Pro)renin Receptor and the Pathogenesis of Preeclampsia

An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-β and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-β, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-β, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-β, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia

Psychosocial factors at work and inflammatory markers: protocol for a systematic review and meta-analysis

Introduction Chronic inflammation may be a mediator for the development of cardiovascular disease (CVD), metabolic diseases and psychotic and neurodegenerative disorders. Meta-analytic associations between work-related psychosocial factors and inflammatory markers have shown that work-related psychosocial factors could affect the flexibility and balance of the immune system. However, few systematic reviews or meta-analyses have investigated the association between work-related psychosocial factors and inflammatory markers. Based on prospective studies, the present investigation will conduct a comprehensive systematic review and meta-analysis of the association between work-related psychosocial factors and inflammatory markers.Methods and analysis The systematic review and meta-analysis will include published studies identified from electronic databases (PubMed, EMBASE, PsycINFO, PsycARTICLES, Web of Science and Japan Medical Abstracts Society) according to recommendations of the Meta-analysis of Observational Studies in Epidemiology guideline. Inclusion criteria are studies that: examined associations between work-related psychosocial factors and increased inflammatory markers; used longitudinal or prospective cohort designs; were conducted among workers; provided sufficient data for calculating ORs or relative risk with 95% CIs; were published as original articles in English or Japanese; and were published up to the end of 2017. Study selection, data extraction, quality assessment and statistical syntheses will be conducted by 14 investigators. Any inconsistencies or disagreements will be resolved through discussion. The quality of studies will be evaluated using the Risk of Bias Assessment Tool for Non-randomized Studies.Ethics and dissemination The investigation study will be based on published studies, so ethics approval is not required. The results of this study will be submitted for publication in a scientific peer-reviewed journal. The findings may be useful for assessing risk factors for increased inflammatory markers in the workplace and determining future approaches for preventing CVD, metabolic diseases and psychotic and neurodegenerative disorders

A Case of Nager Syndrome Diagnosed Before Birth

Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly

On the stability of renormalizable expansions in three-dimensional gravity

Preliminary investigations are made for the stability of the $1/N$ expansion in three-dimensional gravity coupled to various matter fields, which are power-counting renormalizable. For unitary matters, a tachyonic pole appears in the spin-2 part of the leading graviton propagator, which implies the unstable flat space-time, unless the higher-derivative terms are introduced. As another possibility to avoid this spin-2 tachyon, we propose Einstein gravity coupled to non-unitary matters. It turns out that a tachyon appears in the spin-0 or -1 part for any linear gauges in this case, but it can be removed if non-minimally coupled scalars are included. We suggest an interesting model which may be stable and possess an ultraviolet fixed point.Comment: 32 pages. (A further discussion to avoid tachyons is included. To be Published in Physical Review D.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of exposure to long working hours and of the effect of exposure to long working hours on depression

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from depression attributable to exposure to long working hours, to inform the development of the WHO/ILO joint methodology. Objectives: We aim to systematically review studies on occupational exposure to long working hours (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of long working hours on depression (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework, conducting both systematic reviews in tandem and in a harmonized way. Data sources: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CISDOC and PsycINFO. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand search reference list of previous systematic reviews and included study records; and consult additional experts. Study eligibility and criteria: We will include working-age (≥15 years) participants in the formal and informal economy in any WHO and/or ILO Member State, but exclude child workers (&lt;15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative prevalence studies of relevant levels of occupational exposure to long working hours (i.e. 35–40, 41–48, 49–54 and ≥55 h/week) stratified by country, sex, age and industrial sector or occupation, in the years 2005–2018. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the relative effect of relevant level(s) of long working hours on the incidence of or mortality due to depression, compared with the theoretical minimum risk exposure level (i.e. 35–40 h/week). Study appraisal and synthesis methods: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO registration number: CRD42018085729The publication was prepared with financial support from the World Health Organization cooperative agreement with the Centres for Disease Control and Prevention National Institute for Occupational Safety and Health of the United States of America on implementing Resolution WHA 60.26 “Workers' Health: Global Plan of Action” (Grant 1 E11 OH0010676-02)