The association of dietary total flavonoids and their subclasses with the risk of type 2 diabetes: a prospective cohort study.

BACKGROUND: Data from mechanistic studies suggest flavonoids may benefit glucose metabolism, but their associations with type 2 diabetes (T2D) remain unclear. This study examined the prospective associations of dietary intake of total, classes, and individual flavonoids, as well as their source foods, with T2D in the CArdioVascular disease Association Study (CAVAS). METHODS: A total of 16,666 Korean men and women were enrolled at baseline, and 953 were newly diagnosed with T2D over a median follow-up of 5.96 years. Intake of flavonoids was cumulatively averaged using all food frequency questionnaires before the censoring events. A Poisson regression model was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: Women with higher total flavonoid, flavonol, isoflavone, and proanthocyanidin intake had a lower risk of T2D (fourth vs. first quartile, IRR 0.62; 95% CI 0.44-0.89; P for linearity and non-linearity < 0.05 for total flavonoids), while in men, flavanones, anthocyanins, and proanthocyanidins, but not total flavonoids, were inversely associated with T2D risk (all P interaction for sex > 0.05). The key source foods contributing to flavonoid intake were also different between men and women, except for apples: tangerines and strawberries in men and green leafy vegetables and soy products in women. CONCLUSIONS: A higher intake of total flavonoids, particularly from vegetables, soybeans, and apples, may be associated with lower risk of T2D in women. However, flavonoids from fruits, rather than total flavonoids, may be inversely associated in men. The association between flavonoid intake and the risk of T2D may be contingent upon the dietary sources of flavonoids consumed.

Habitual intake of iron, copper, and zinc and the risk of type 2 diabetes in a prospective cohort: The CAVAS (Cardiovascular Disease Association Study).

BACKGROUND AND AIMS: Unlike iron, evidence of the association between dietary copper and zinc intake and type 2 diabetes (T2D) risk is limited. This study aimed to examine the prospective associations of dietary intake of iron (total, plant-based, and animal-based), copper, and zinc with T2D risk among adults aged ≥40 years. METHODS AND RESULTS: For 16,666 participants, dietary intakes (baseline, cumulative average, and most recent) of iron, copper, and zinc were calculated from repeated food frequency questionnaires; a modified Poisson regression model with a robust error estimator was conducted. In men, positive associations between T2D and baseline dietary intake of Cu and Zn, cumulative average dietary intake of Fe (total and animal-based), Cu and Zn, and most recent dietary intake of Fe (total, plant-based, and animal-based), Cu, and Zn [most recent diet: for total Fe, IRR(95%CI) = 1.93 (1.41-2.64); for plant-based Fe, 1.56 (1.15-2.11); for animal-based Fe, 1.44 (1.09-1.90); for Cu, 3.17 (2.33-4.30); for Zn, 2.18 (1.64-2.89)] were observed, where as in women, there were positive associations of only cumulative average dietary Zn intake and most recent dietary intake of plant-based Fe, Cu, and Zn [most recent diet: for plant-based Fe, 1.30 (1.01-1.68); for Cu, 1.62 (1.27-2.08); for Zn, 2.07 (1.61-2.66)]. CONCLUSION: Dietary intakes of iron (total, plant-based, and animal-based), copper, and zinc may be positively associated with T2D risk. These positive associations are predominantly observed in most recent diet and appear to be stronger compared to baseline and cumulative average diet.

Mycobacterium potentiates protection from colorectal cancer by gut microbial alterations.

Not only are many Mycobacteria pathogens, but they can act as strong non-specific immunopotentiators, generating beneficial effects on the pathogenesis of some diseases. However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat-killed Mycobacterial tuberculosis and live Mycobacterium bovis (Bacillus Calmette-Guérin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the Reg3 family genes. Furthermore, interleukin-22 production by T helper cells contributed to the anti-inflammatory activity of Mycobacteria. Our results revealed a novel role of Mycobacteria involving gut microbial alterations in dampening inflammation-associated CRC and an immunological mechanism underlying the interaction between microbes and host immunity.

An aptamer-based magnetic resonance imaging contrast agent for detecting oligomeric amyloid-ß in the brain of an Alzheimer's disease mouse model.

The oligomeric amyloid-ß (oAß) is a reliable feature for an early diagnosis of Alzheimer's disease (AD). Therefore, the objective of this study was to demonstrate imaging of oAß deposits using our developed DNA aptamer called ob5 conjugated with gadolinium (Gd)-dodecane tetraacetic acid (DOTA) as a contrast agent for early diagnosis of AD using MRI. An oAß-specific aptamer was developed by amide bond formation and conjugated to Gd-DOTA MRI contrast agent and/or cyanine5 (cy5). We verified the performance of our new contrast agent with an AD mouse model using in vivo and ex vivo fluorescent imaging and animal MRI experiments. The presence of soluble Aß in 3xTg AD mice was detected using GdDOTA-ob5-cy5 probe ex vivo. Fluorescence intensities of the GdDOTA-ob5-cy5 contrast agent were high in the brains of 3xTg-AD mice, but relatively low in the brains of control mice. The GdDOTA-ob5 contrast agent had higher relaxivity than a clinically available contrast agent. T1-weighted MRI signals in 5-month-old 3xTg AD mice increased at 5 min, were prolonged until 10 min, then decreased 15 min after injecting the GdDOTA-ob5 contrast agent. Our targeted DNA aptamer GdDOTA-ob5 contrast agent could be potentially useful for validating the efficacy of a novel diagnostic contrast agent for selectively targeting neurotoxic oAß. It could ultimately be used for early diagnosis of AD.

Comparison of Proportional Mortality Between Korean Atomic Bomb Survivors and the General Population During 1992-2019.

BACKGROUND: Atomic bombs dropped on Hiroshima and Nagasaki in Japan in August 1945 were estimated to have killed approximately 70,000 Koreans. In Japan, studies on the health status and mortality of atomic bomb survivors compared with the non-exposed population have been conducted. However, there have been no studies related to the mortality of Korean atomic bomb survivors. Therefore, we aimed to study the cause of death of atomic bomb survivors compared to that of the general population. METHODS: Of 2,299 atomic bomb survivors registered with the Korean Red Cross, 2,176 were included in the study. In the general population, the number of deaths by age group was calculated from 1992 to 2019, and 6,377,781 individuals were assessed. Causes of death were categorized according to the Korean Standard Classification of Diseases. To compare the proportional mortality between the two groups, the P value for the ratio test was confirmed, and the Cochran-Armitage trend test and χ² test were performed to determine the cause of death according to the distance from the hypocenter. RESULTS: Diseases of the circulatory system were the most common cause of death (25.4%), followed by neoplasms (25.1%) and diseases of the respiratory system (10.6%) in atomic bomb survivors who died between 1992 and 2019. The proportional mortality associated with respiratory diseases, nervous system diseases, and other diseases among atomic bomb survivors was higher than that of the general population. Of the dead people between 1992 and 2019, the age at death of survivors who were exposed at a close distance was younger than those who were exposed at a greater distance. CONCLUSION: Overall, proportional mortality of respiratory diseases and nervous system diseases was high in atomic bomb survivors, compared with the general population. Further studies on the health status of Korean atomic bomb survivors are needed.

Cumulative average nut consumption in relation to lower incidence of hypertension: a prospective cohort study of 10,347 adults.

PURPOSE: Maintaining optimal blood pressure (BP) levels can be an effective preventive strategy for reducing disease burden. Nut consumption may play a preventive role against hypertension, which is a lifelong condition. We aimed to prospectively examine the association between cumulative average nut consumption and the incidence of hypertension in Korean adults aged 40 years and older. METHODS: A total of 10,347 participants who were free of hypertension at baseline, were included. Hypertension was defined as having a physician diagnosis and taking antihypertensive medications or having abnormal BP (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg). As an exposure, cumulative average nut consumption was calculated using repeated food-frequency questionnaires (mean: 2.1). We used a modified Poisson regression model with a robust error estimator to estimate the incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for hypertension. RESULTS: We identified 2047 incident cases of hypertension during 44,614 person-years of follow-up. Among both men and women, an average nut consumption of ≥ 1 serving/week (15 g/week]) was inversely associated with hypertension incidence (IRR = 0.74, 95% CI = 0.58-0.96, p for trend = 0.013 for men; IRR = 0.72, 95% CI = 0.59-0.88, p for trend = 0.002 for women) and these significant associations were consistently observed across the strata of potential confounders. CONCLUSION: An average consumption of at least one serving (15 g) per week of peanuts, almonds, and/or pine nuts may be inversely associated with the risk of hypertension among Korean adults aged 40 years and older, in a dose-response manner.

Genome-wide gene and serum ferritin interaction in the development of type 2 diabetes in adults aged 40 years or older.

BACKGROUND AND AIMS: Elevated serum ferritin is associated with incident Type 2 diabetes (T2D), but the interactions between serum ferritin and genetic factors which may improve understanding underlying mechanism in the development of T2D are still unclear. We determined the gene-ferritin interactions on the development of T2D by genome-wide gene-ferritin interaction analyses. METHODS AND RESULTS: A total of 3405 participants from two prospective cohorts of community living residents were included, and the median follow-time was 3.99 years. Genome-wide gene-ferritin interactions were analyzed using the joint test with two degrees of freedom and the interaction test with one degree of freedom. There were 18 SNPs selected in the joint test. Finally, four independent variants [rs355140 (LINC00312), rs4075576 (nearby PDGFA), rs1332202 (PTPRD), and rs713157 (nearby LINC00900)] with low pairwise linkage disequilibrium (r2<0.2) and located at least 1000 kb from the index SNP showed interactions with serum ferritin level. In the association analyses between serum ferritin levels (tertiles of ferritin and ferritin status) and the incidence of T2D according to genotype, the Incidence Rate Ratios (IRRs) in the highest tertile of ferritin level (vs. the lowest tertile) were greater for participants with heterozygotes of risk alleles of each of the four SNP than IRRs for those with wild type. Compared with the normal group, the elevated ferritin group also had a higher risk of T2D for all genetic variants of risk alleles, particularly its homozygotes. CONCLUSION: Serum ferritin level interacts with genetic variants (rs355140, rs4075576, rs1332202, and rs713157) in the development of T2D.

Pregnancy loss and Income in the Republic of Korea using National Health Insurance Service Data, 2008-2014.

BACKGROUND: Although unintentional pregnancy loss is common, national representative statistics are lacking in high-income East Asian countries undergoing rapid demographic changes. It is necessary to confirm the income inequality of pregnancy loss even in universal national health insurance. METHOD: Using National Health Insurance Service data between 2008 and 2014, the annual prevalence of pregnancy loss was enumerated, and differences in pregnancy loss according to age and income levels were assessed by multivariable Poisson regression. Joint-point regression was used to examine the trend of pregnancy loss. RESULT: On average, there was a 15.0% annual pregnancy loss among 3,941,020 pregnancy cases from 2008 to 2014. Pregnancy loss inequality increased stepwise with income levels except for the highest income group. After adjusting for income levels, the annual percent change of age-standardized prevalence significantly increased by 2.6% every year since 2011. CONCLUSION: Even in high-income countries with universal national health insurance, income inequality in pregnancy loss is observed. Further appraisal is needed to explain the increasing trend of pregnancy loss between 2011 and 2014 even after adjusting income.

Prevalence and risk factors of maternal depression among women who participated in a home visitation program in South Korea.

PURPOSE: The psychosocial health of mother is crucial for healthy prenatal period and early childhood. We investigated the prevalence and risk factors of maternal depression during pregnancy and postpartum among women who participated in a home visitation program in Seoul, South Korea (Seoul Healthy First Step Project, SHFSP). METHODS: We analyzed 80,116 women who participated in the SHFSP, which was launched by Seoul metropolitan government in 2013, and defined peripartum depression as a score ≥ 10 on the Korean version of the Edinburgh Postnatal Depression Scale (EPDS). Sociodemographic factors and psychosocial health status were evaluated through a standardized questionnaire completed by participants upon program registration. We calculated the prevalence of women at risk for peripartum depression and evaluated associated factors by multivariable logistic regression analysis. RESULTS: Prevalence of women at risk for peripartum depression was 17.7% (prepartum depression: 14.2%, postpartum depression: 24.3%). Younger maternal age, low income (OR 2.40, 95% CI 2.03-2.84), disability (2.61, 1.96-3.47), single parenthood (3.27, 2.69-3.99), and smoking (2.02, 1.44-2.83) increased the peripartum depression risk. Furthermore, experience of stress, change, or loss over the past 12 months (3.36, 3.22-3.50), history of treatment for emotional issues (2.47, 2.27-2.70), experience of child abuse (1.91, 1.74-2.11), and domestic violence (2.25, 1.81-2.80) increased the risk for peripartum depression, whereas having helpers for the baby (0.62, 0.58-0.67), having someone to talk with (0.31, 0.27-0.35), and considering oneself confident (0.30, 0.29-0.31) decreased the risk. CONCLUSIONS: Policies to reduce and manage peripartum depression should be strengthened, with a focus on high-risk pregnant and puerperal women.

Measurements of Interleukin-8 and Matrix Metalloproteinases-9 in Cervicovaginal Fluid in Women with Preterm Labor: A Direct Comparison with Amniotic Fluid.

OBJECTIVE: We aimed to evaluate the correlation and agreement of interleukin (IL)-8 and matrix metalloproteinases (MMP-9) levels between cervicovaginal (CVF) and amniotic fluids (AF) in women with preterm labor (PTL) and to determine the clinical values of these proteins in CVF compared with those in AF. STUDY DESIGN: We designed a retrospective cohort study of 85 singleton pregnant women with PTL at 23 to 34 weeks, who underwent amniocentesis. The AF was cultured, and CVF samples were collected at the time of amniocentesis. Paired AF and CVF samples were assayed for IL-8 and MMP-9 by enzyme-linked immunoassay (ELISA) in duplicate on a single plate, using similar dilution ratios. RESULTS: A significant but weak correlation was found for IL-8 levels between AF and CVF (r = 0.333), while no correlation was found for MMP-9 levels between AF and CVF (r = -0.039). Intra-class correlation coefficient for the agreement of IL-8 levels between CVF and AF was 0.4335 and -0.279 for MMP-9, indicating a poor-to-fair level of agreement between the two measured values, respectively. IL-8 and MMP-9 levels in CVF were not associated with the risk of either microbial invasion of the amniotic cavity (MIAC) or spontaneous preterm delivery (SPTD) within 7 days, whereas those in AF provided good-to-excellent predictive values for these two outcomes (area under the curve [AUCs]: 0.82-0.95). AUCs for IL-8 and MMP-9 were significantly larger using AF rather than using CVF for the prediction of MIAC and SPTD. CONCLUSIONS: In women with PTL, IL-8 and MMP-9 levels in CVF do not precisely reflect the levels of the corresponding proteins in AF. IL-8 and MMP-9 levels in CVF had poor predictive values for the risk of MIAC and SPTD and were significantly inferior to those in AF. KEY POINTS: · IL-8 and MMP-9 levels in CVF do not precisely reflect levels of the corresponding proteins in AF.. · Diagnostic accuracy of IL-8 and MMP-9 in CVF alone is not sufficient to predict MIAC and SPTD.. · IL-8 and MMP-9 levels in AF provide good-to-excellent predictive values for these two outcomes..

Validity and reliability of a Korean version of the Consultation and Relational Empathy (CARE) measure.

BACKGROUND: No validated tool is available to assess patients' perception of physician empathy in Korea. The objective of this study was to establish a Korean version of the Consultation and Relational Empathy (CARE) measure-originally developed in English and widely used internationally-and to examine its reliability and validity. METHODS: The CARE measure was translated into Korean and tested on 240 patients from one secondary care hospital and one tertiary care hospital in Korea. Internal consistency by Cronbach's alpha, exploratory analysis, and confirmatory factor analysis were conducted to verify the 10 items of the Korean CARE measure. RESULTS: The Korean CARE measure demonstrated high acceptability and face validity, excellent internal reliability (Cronbach's alpha = 0.97) and moderate test-retest reliability (Pearson correlation coefficient = 0.53; Spearman correlation coefficient = 0.51). Distribution of scores showed negative skewedness. Corrected item-total correlations ranged from 0.77-0.92, indicating homogeneity. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.949, and Bartlett's test of sphericity was good (χ2 = 3157.11, P < 0.001). Factor analysis yielded a single dimensional structure of physician empathy with all factor loadings exceeding 0.80 and showing excellent goodness of fit. CONCLUSION: This study supports the reliability and validity of the Korean CARE measure in a university hospital setting in Korea.

TNF-α-Mediated RIPK1 Pathway Participates in the Development of Trigeminal Neuropathic Pain in Rats.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) participates in the regulation of cellular stress and inflammatory responses, but its function in neuropathic pain remains poorly understood. This study evaluated the role of RIPK1 in neuropathic pain following inferior alveolar nerve injury. We developed a model using malpositioned dental implants in male Sprague Dawley rats. This model resulted in significant mechanical allodynia and upregulated RIPK1 expression in the trigeminal subnucleus caudalis (TSC). The intracisternal administration of Necrosatin-1 (Nec-1), an RIPK1 inhibitor, blocked the mechanical allodynia produced by inferior alveolar nerve injury The intracisternal administration of recombinant rat tumor necrosis factor-α (rrTNF-α) protein in naive rats produced mechanical allodynia and upregulated RIPK1 expression in the TSC. Moreover, an intracisternal pretreatment with Nec-1 inhibited the mechanical allodynia produced by rrTNF-α protein. Nerve injury caused elevated TNF-α concentration in the TSC and a TNF-α block had anti-allodynic effects, thereby attenuating RIPK1 expression in the TSC. Finally, double immunofluorescence analyses revealed the colocalization of TNF receptor and RIPK1 with astrocytes. Hence, we have identified that astroglial RIPK1, activated by the TNF-α pathway, is a central driver of neuropathic pain and that the TNF-α-mediated RIPK1 pathway is a potential therapeutic target for reducing neuropathic pain following nerve injury.

Different associations of specific non-alcoholic beverages with elevated high-sensitivity C-reactive protein in Korean adults: results from the Korea National Health and Nutrition Examination Survey (2015-2016).

This study examined the associations between specific non-alcoholic beverages and high-sensitivity C-reactive protein (hs-CRP) and their interactions with obesity. The study participants were 4,999 adults aged 19-64 years from the 2015-2016 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable logistic regression analyses. In women, there was an inverse linear trend between coffee and hs-CRP status (p trend = 0.0137), and a positive linear trend for soda was also found (≥1/week vs never or almost never, OR = 1.79, 95% CI 1.23-2.61, p trend = 0.0127). In the stratification analyses, the associa-tions were only observed in obese women. The associations were inverse for coffee and tea but linearly positive for soda in obese women (p trend<0.05). In men, an inverted J-shaped association between commercial fruit juice/drink and hs-CRP status was found; but after stratification by obesity, the association was linear only in obese men (p trend<0.05, OR = 2.44, 95% CI 1.44-4.16 in ≥1/week vs never or almost never). Coffee and tea in women may be beneficially associated with hs-CRP status, but soda in women and commercial fruit juice/drink in men may be adversely, particularly for obese adults.

Neuroprotective Effects of Sodium Butyrate through Suppressing Neuroinflammation and Modulating Antioxidant Enzymes.

The discovery of effective therapeutic agents against neurodegenerative diseases (NDDs) remains challenging. Neurotoxicity, inflammations, and oxidative stress are associating factors of NDDs. Sodium butyrate (NaB) is a short-chain fatty acid found in diet and produced in the gut that reportedly protects cancer, inflammation, obesity and so on. Previously, SH-SY5Y cells were studied as in vitro models of cerebral diseases. We have investigated the neuroprotective effects of NaB in SH-SY5Y cells stimulated with TNF-α. The expression of inflammatory mediators, including iNOS, COX-2, and mitogen-activated protein kinases (MAPK) and the apoptotic regulators, including P-53, Bcl-2 associated X (BAX) Protein, and caspase-3 were analyzed by western blot analysis. The anti-apoptotic gene Bcl-2 and the pro-apoptotic gene BAX translocation were also investigated. Our results showed that NaB attenuated cell death and inhibited the NO production and decreased the expression of iNOS and COX-2 in TNF-α-stimulated SH-SY5Y cells. NaB notably ameliorated apoptotic regulatory proteins p-53, Caspase-3 and caspase-1 level, and reversed phosphorylation of extracellular signal-regulated kinases and p-38 proteins. NaB ameliorated Glucocorticoid receptor and NLRP3 inflammasome expressions. NaB also suppressed the BAX nuclear translocation and modulated Nrf-2, HO-1 and MnSOD expression in neuroblastoma cells. In addition, NaB substantially reversed the reactive oxygen species in H2O2 induced SH-SY5Y cells. Altogether, our results suggest that sodium butyrate has potential therapeutic effects against NDDs.

Mast cell tryptase-PAR2 pathway in proliferation of prostatic stromal cells reacted with Trichomonas vaginalis.

We investigated whether tryptase released from mast cells activated by prostate stromal cells (PSC) reacted with Trichomonas vaginalis (Tv) promoted the proliferation of PSC through protease- activated receptor 2 (PAR2). Conditioned medium of PSC was prepared by stimulating them with Tv (Trichomonad-conditioned medium (TCM)), and mast cell-conditioned medium were prepared by incubating them with TCM (mast cell-TCM (M-TCM)). Mast cells incubated with TCM migrated more efficiently and produced more ß-hexosaminidase and tryptase. M-TCM containing tryptase increased the proliferation of PSC, while inhibition of tryptase decreased proliferation. Expression of signalling molecules such as PAR2, p-ERK, COX-2, 15d-PGJ2 and PPARγ, known to be involved in the tryptase-PAR2 pathway, increased in response to M-TCM, and blocking any of these signals decreased proliferation, indicating that tryptase-PAR2 signalling is involved in the proliferation of PSC. Inhibition of tryptase and PAR2 led to reduced expression of PAR2, p-ERK, COX-2, 15d-PGJ2 and PPARγ, while inhibition of ERK or COX-2 reduced the expression of COX-2, 15d-PGJ2 and PPARγ indicating that the tryptase-PAR2 pathway proceeds in the order p-ERK, COX-2, 15d-PGJ2 , and PPARγ. These results show that interaction between PSC stimulated with Tv and mast cells causes proliferation of PSC through the tryptase-PAR2 pathway.

Impact of a screening protocol for blood pressure level for hypertension in the Korean community health survey.

PURPOSE: A community program is an efficient model for improving the management of chronic diseases such as hypertension, diabetes, and dyslipidemia. A specific blood pressure (BP) measurement protocol was developed for community settings in which BP was measured by the interviewer at the interviewee's home. MATERIALS AND METHODS: In the 2018 Korean Community Health Survey, BP was measured twice at a five-minute interval after a five-minute resting period at the beginning of the survey. In 2019, BP was measured at the end of the survey after a two-minute rest and was obtained as three measurements at one-minute intervals. As factors related to BP level, stressful stimuli within 30 min before BP measurement such as smoking, caffeine, and/or exercise; duration of rest; and survey year were analysed. RESULTS: The mean age of participants was 55.2 years, and females accounted for 55.4% of the participants (n = 399,838). Stressful stimuli were observed in 21.9% of the participants in 2018 (n = 188,440) and 11.3% in 2019 (n = 211,398). Duration of rest was 0 min (2.1%), two minutes (55.0%), and five minutes (47.9%). When adjusted for age, sex, body mass index, antihypertensive medication, the arm of measurement, survey year (beta= -4.092), stressful stimuli (beta = 0.834), and resting time (beta = -1.296 per one minute of rest) were significant factors for mean systolic BP. A two-minute rest was not a significant factor in mean BP. The differences in adjusted mean systolic BPs were significant for rest times of five minutes vs. two minutes (3.1 mmHg, p < 0.0001), for stressful stimuli (0.8 mmHg, p < 0.0001), and for survey year (127.8 ± 0.2 mmHg vs. 122.2 ± 0.3 mmHg for 2018 vs. 2019, p < 0.0001). CONCLUSION: For the community-based home visit survey, avoidance of stressful stimuli, five-minute rest, and allocation of BP measurement in the last part of the survey was useful for obtaining a stable BP level.

Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes.

BACKGROUND: We sought to determine whether lipopolysaccharide binding protein (LBP), pentraxin 3, resistin, and insulin-like growth factor binding protein (IGFBP)-3 in plasma and amniotic fluid (AF) can predict microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI in women with preterm premature rupture of membranes (PPROM). METHODS: This was a retrospective cohort study involving 168 singleton pregnant women with PPROM. AF obtained via amniocentesis was cultured and assayed for interleukin (IL)-6 to define IAI and for IL-8 to compare with AF biomarkers. Plasma samples were collected at the time of amniocentesis, and C-reactive protein (CRP) levels in serum were compared with plasma biomarkers. The stored plasma and AF samples were assayed for LBP, pentraxin 3 (PTX3), resistin, and IGFBP-3 by ELISA. RESULTS: Multivariate logistic regression analysis revealed that: 1) elevated plasma and AF levels of LBP were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 2) elevated AF, but not plasma, PTX3, and resistin levels were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 3) decreased IGFBP-3 levels in the plasma were independently associated with only IAI, whereas those in the AF were associated with only microbial-associated IAI. Among the tested biomarkers, AF PTX3 and resistin had the highest predictive performance for MIAC, IAI, and microbial-associated IAI (area under the curves [AUC] = 0.85-0.95), which is similar to the performance of AF IL-8. The AUCs of the plasma LBP and IGFBP-3 were similar to that of serum CRP with respect to IAI. CONCLUSION: Maternal plasma LBP and IGFBP-3 are potential biomarkers for the non-invasive identification of IAI in women with PPROM, with a similar accuracy to the serum CRP level. AF LBP, PTX3, resistin, and IGFBP-3 may be involved in the intra-amniotic inflammatory responses in PPROM complicated by MIAC.

Complement Activation Fragments in Cervicovaginal Fluid Are Associated with Intra-Amniotic Infection/Inflammation and Spontaneous Preterm Birth in Women with Preterm Premature Rupture of Membranes.

OBJECTIVE: We sought to determine whether the levels of complement and other inflammatory and angiogenic mediators in cervicovaginal fluid (CVF) are independently associated with intra-amniotic infection and/or inflammation (IAI) and imminent spontaneous preterm birth (SPTB, £48 hours of sampling) in women with preterm premature rupture of membranes (PPROM). STUDY DESIGN: This was a retrospective study consisting of 85 singleton pregnant women with PPROM at 200/7 to 336/7 weeks. Amniotic fluid (AF) obtained via amniocentesis was cultured and assayed for interleukin-6. CVF samples collected at the time of amniocentesis were assayed for complement C3a, C4a, and C5a, HSP70 (heat shock protein 70), M-CSF (macrophage colony-stimulating factor), M-CSF-R (macrophage colony-stimulating factor-receptor), S100 A8, S100 A9, thrombospondin-2, VEGF (vascular endothelial growth factor-receptor), and VEGFR-1 (vascular endothelial growth factor-receptor 1) by enzyme-linked immunosorbent assay. RESULTS: Multivariate logistic regression analyses revealed that elevated CVF concentrations of complement C3a, 4a, and 5a were significantly associated with an increased risk of IAI and imminent SPTB, whereas those of M-CSF were associated with IAI, but not imminent SPTB (p = 0.063), after adjustment for baseline covariates (e.g., gestational age at sampling). However, univariate, and multivariate analyses showed that the CVF concentrations of angiogenic (thrombospondin-2, VEGF, and VEGFR-1) and inflammatory (HSP70, M-CSF-R, S100 A8, and S100 A9) proteins were not associated with either IAI or imminent SPTB. CONCLUSION: In women with PPROM, elevated CVF concentrations of complement C3a, C4a, and C5a are independently related to an increased risk of IAI and imminent SPTB. These findings suggest that complement activation in CVF is significantly involved in mechanisms underlying preterm birth and in the host response to IAI in the context of PPROM. KEY POINTS: · Elevated CVF levels of C3a, 4a and 5a are associated with IAI and SPTB.. · CVF C3a, 4a and 5a have better predictability for SPTB, compared to AF WBC.. · Elevated CVF levels of M-CSF were associated with IAI, but not SPTB..

The Osteogenic Differentiation of Human Dental Pulp Stem Cells through G0/G1 Arrest and the p-ERK/Runx-2 Pathway by Sonic Vibration.

Mechanical/physical stimulations modulate tissue metabolism, and this process involves multiple cellular mechanisms, including the secretion of growth factors and the activation of mechano-physically sensitive kinases. Cells and tissue can be modulated through specific vibration-induced changes in cell activity, which depend on the vibration frequency and occur via differential gene expression. However, there are few reports about the effects of medium-magnitude (1.12 g) sonic vibration on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). In this study, we investigated whether medium-magnitude (1.12 g) sonic vibration with a frequency of 30, 45, or 100 Hz could affect the osteogenic differentiation of HDPSCs. Their cell morphology changed to a cuboidal shape at 45 Hz and 100 Hz, but the cells in the other groups were elongated. FACS analysis showed decreased CD 73, CD 90, and CD 105 expression at 45 Hz and 100 Hz. Additionally, the proportions of cells in the G0/G1 phase in the control, 30 Hz, 45 Hz, and 100 Hz groups after vibration were 60.7%, 65.9%, 68.3%, and 66.7%, respectively. The mRNA levels of osteogenic-specific markers, including osteonectin, osteocalcin, BMP-2, ALP, and Runx-2, increased at 45 and 100 Hz, and the ALP and calcium content was elevated in the vibration groups compared with those in the control. Additionally, the western blotting results showed that p-ERK, BSP, osteoprotegerin, and osteonectin proteins were upregulated at 45 Hz compared with the other groups. The vibration groups showed higher ALP and calcium content than the control. Vibration, especially at 100 Hz, increased the number of calcified nodes relative to the control group, as evidenced by von Kossa staining. Immunohistochemical staining demonstrated that type I and III collagen, osteonectin, and osteopontin were upregulated at 45 Hz and 100 Hz. These results suggest that medium magnitude vibration at 45 Hz induces the G0/G1 arrest of HDPSCs through the p-ERK/Runx-2 pathway and can serve as a potent stimulator of differentiation and extracellular matrix production.

The Identification of Immune-Related Plasma Proteins Associated with Spontaneous Preterm Delivery and Intra-Amniotic Infection in Women with Premature Cervical Dilation or an Asymptomatic Short Cervix.

BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm). METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17-29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures. RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection. CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.