Strong plastic responses in aerenchyma formation in F1 hybrids of Imperata cylindrica under different soil moisture conditions.

Hybrids can express traits plastically, enabling them to occupy environments that differ from parental environments. However, there is insufficient evidence demonstrating how phenotypic plasticity in specific traits mediates hybrid performance. Two parental ecotypes of Imperata cylindrica produce F1 hybrids. The E-type in wet habitats has larger internal aerenchyma than the C-type in dry habitats. This study evaluated relationships between habitat utilisation, aerenchyma plasticity, and growth of I. cylindrica accessions. We hypothesize that plasticity in expressing parental traits explains hybrid establishment in habitats with various soil moisture conditions. Aerenchyma formation was examined in the leaf midribs, rhizomes and roots of two parental ecotypes and their F1 hybrids in their natural habitats. In common garden experiments, we examined plastic aerenchyma formation in leaf midribs, rhizomes and roots of natural and artificial F1 hybrids and parental ecotypes and quantified vegetative growth performance. In the natural habitats where soil moisture content varied widely, the F1 hybrids showed larger variation in aerenchyma formation in rhizomes than their parental ecotypes. In the common garden experiments, F1 hybrids showed high plasticity of aerenchyma formation in rhizomes, and their growth was similar to that of C-type and E-type under drained and flooded conditions, respectively. The results demonstrate that F1 hybrids of I. cylindrica exhibit plasticity in aerenchyma development in response to varying local soil moisture content. This characteristic allows the hybrids to thrive in diverse soil moisture conditions.

Magnetic structures and electronic properties of cubic-pyrochlore ruthenates from first principles.

The magnetic ground states ofR2Ru2O7andA2Ru2O7withR= Pr, Gd, Ho, and Er, as well asA= Ca, Cd are predicted devising a combination of the cluster-multipole (CMP) theory and spin-density-functional theory (SDFT). The strong electronic correlation effects are estimated by the constrained-random-phase approximation (cRPA) and taken into account within the dynamical-mean-field theory (DMFT). The target compounds feature d-orbital magnetism on Ru4+and Ru5+ions forRandA, respectively, as well as f-orbital magnetism on theRsite, which leads to an intriguing interplay of magnetic interactions in a strongly correlated system. We find CMP + SDFT is capable of describing the magnetic ground states in these compounds. The cRPA captures a difference in the screening strength betweenR2Ru2O7andA2Ru2O7compounds, which leads to a qualitative and quantitative understanding of the electronic properties within DMFT.

Caprylic acid enhances hydroxyhexylitaconic acid production in Aspergillus niger S17-5.

AIM: Aspergillus niger S17-5 produces two alkylitaconic acids, 9-hydroxyhexylitaconic acid (9-HHIA) and 10-hydroxyhexylitaconic acid (10-HHIA), which have cytotoxic and polymer building block properties. In this study, we characterized the production of 9-HHIA and 10-HHIA by addition of their expected precursor, caprylic acid, to a culture of A. niger S17-5, and demonstrated batch fermentation of 9-HHIA and 10-HHIA in a jar fermenter with DO-stat. METHODS AND RESULTS: Production titres of 9-HHIA and 10-HHIA from 3% glucose in a flask after 25 days cultivation were 0·35 and 1·01 g l-1 respectively. Addition of 0·22 g l-1 of caprylic acid to a suspension of resting cells of A. niger S17-5 led to 32% enhancement of total 9-HHIA and 10-HHIA production compared to no addition. No enhancement of the production of 9-HHIA or 10-HHIA by the addition of oxaloacetic acid was observed. Addition of caprylic acid to the culture at mid-growth phase was more suitable for 9-HHIA and 10-HHIA production due to less cell growth inhibition by caprylic acid. DO-stat batch fermentation with 3% glucose and 14·4 g l-1 of caprylic acid in a 1·5 l jar fermenter resulted in the production titres of 9-HHIA and 10-HHIA being 0·48 and 1·54 g l-1 respectively after 10 days of cultivation. CONCLUSIONS: Addition of caprylic acid to the culture of A. niger S17-5 enhances 9-HHIA and 10-HHIA production. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that 9-HHIA and 10-HHIA are synthesized with octanoyl-CoA derived from caprylic acid, and that the supply of octanoyl-CoA is a rate-limiting step in 9-HHIA and 10-HHIA production. To the best of our knowledge, this is the first report regarding the fermentation of naturally occurring itaconic acid derivatives in a jar fermenter.

Placental Gene Expression and Offspring Temperament Trajectories: Predicting Negative Affect in Early Childhood.

Exposure to prenatal stress increases offspring risk for long-term neurobehavioral impairments and psychopathology, such as Attention Deficit Hyperactivity Disorder (ADHD). Epigenetic regulation of glucocorticoid pathway genes may be a potential underlying mechanism by which maternal conditions 'program' the fetal brain for downstream vulnerabilities. The present study aims to investigate whether mRNA expression of glucocorticoid pathway genes in the placenta predict offspring negative affect during early childhood (between 6 and 24 months). Participants include 318 mother-child dyads participating in a longitudinal birth cohort study. Placental mRNA expression of glucocorticoid pathway genes (HSD11B1, HSD11B2, NR3C1, NCOR2) were profiled and negative affect traits of the offspring were measured at 6, 12, 18, and 24 months. HSD11B1 mRNA expression significantly predicted negative affect (ß = -.09, SE = .04; p = .036), and Distress to Limitations trajectories (ß = -.13, SE = .06; p = .016). NCOR2 mRNA expression significantly predicted Distress to Limitations (ß = .43, SE = .21; p = .047), and marginally predicted Sadness trajectories (ß = .39, SE = .21; p = .068). HSD11B2 and NR3C1 did not predict trajectories of Negative Affect or subscale scores. Infant negative affect traits were assessed via maternal self-report, and deviated from linearity across follow-up. mRNA expression of glucocorticoid pathway genes in the placenta may be a potentially novel tool for early identification of infants at greater risk for elevated negative affect. Further study is needed to validate the utility of mRNA expression of glucocorticoid pathway genes in the placenta.

The children of Superstorm Sandy: Maternal prenatal depression blunts offspring electrodermal activity.

We set out to examine the relations between prenatal exposure to the natural disaster Superstorm Sandy, maternal depression, and offspring electrodermal activity (EDA). EDA was measured via skin conductance response (SCR) magnitude in 198 children (M = 42.54 months, SD = 12.76) during a startle paradigm. In keeping with prior research, we expected prenatal depression to be associated with hyporeactive EDA and prenatal stress to be associated with hyperreactive EDA. SCR magnitude was lower in children prenatally exposed to depression alone, when compared to Superstorm Sandy, and controls. SCR magnitude of children prenatally exposed to both maternal depression and the storm was lower than that of all other groups. Our results emphasize the influence of maternal prenatal mental health, support targeted risk assessment for children who experienced an adverse prenatal environment, and highlight the need for a deeper understanding of the interactions between maternal mood and stress on the developing child.

Placental imprinted gene expression mediates the effects of maternal psychosocial stress during pregnancy on fetal growth.

Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn's growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.

Prenatal Exposure to Famine and Risk for Development of Psychopathology in Adulthood: A Meta-Analysis.

Prenatal famine, resulting in intrauterine malnutrition, impacts offspring psychopathology later in adulthood. In addition, the specific impact of intrauterine malnutrition of different psychopathology differs by the timing of the exposure. Using a meta-analysis, the current study assessed the specific risk of developing affective, psychotic, and personality disorders. Studies were identified using PubMed and PsycINFO. Studies met the following criteria for inclusion in the analysis: availability in peer-reviewed English journals, use of human subjects, prenatal exposure to famine, and psychopathology in adulthood defined by diagnostic criteria as an outcome. Fixed effect relative risks (RRs) were calculated for affective, psychotic, and personality domains. Furthermore, timing of exposure was assessed as an effect modifier in our analysis, defined by the index trimester at the height of famine. Our meta-analysis found that adults exposed in utero during the 1st trimester were at a significant increased risk of psychotic disorders (RR=1.46, 95% CI=1.08, 1.97, p=0.014), and personality disorders (RR=2.31, 95% CI=1.36, 3.92, p=0.002). Those exposed during the 2nd trimester were at a significant increased risk of affective disorders (RR=1.45, 95% CI=1.22, 1.72, p<0.0001), and psychotic disorders (RR=1.46, 95% CI=1.13, 1.89, p=0.004). Similarly, those exposed in the 3rd trimester were at a significant increased risk of affective disorders (RR=1.33, 95% CI=1.13, 1.57, p=0.0001), and psychotic disorders RR=1.47, 95% CI=1.10, 1.97, p=0.010). Our findings suggest that there is differential risk across the different domains of psychopathology by trimester of exposures. This meta-analysis underscores the need for further investigation into the mechanisms underlying prenatal maternal nutrition and offspring psychopathology where magnitude of elevated risk differs by the exposure timing during pregnancy.

Evaluation of the effect of lanthanum carbonate hydrate on the pharmacokinetics of roxadustat in non-elderly healthy adult male subjects.

WHAT IS KNOWN AND OBJECTIVE: Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor currently being investigated for the treatment of anemia in chronic kidney disease. Lanthanum carbonate is a phosphate binder that is commonly used to treat hyperphosphatemia in patients with chronic kidney disease. This study investigated the effect of lanthanum carbonate on the pharmacokinetics, safety and tolerability of a single oral dose of roxadustat in healthy non-elderly adult male subjects. METHODS: This was an open-label, randomized, two-period, two-sequence crossover study in non-elderly healthy adult males. Subjects randomized to Group 1 received roxadustat alone during Period 1 and roxadustat concomitantly with lanthanum carbonate during Period 2; subjects randomized to Group 2 received roxadustat concomitantly with lanthanum carbonate during Period 1 and roxadustat alone during Period 2. All subjects received a single oral dose of 100 mg roxadustat on Day 1 in both periods. Subjects receiving concomitant lanthanum carbonate received 750 mg lanthanum carbonate three times daily on Days 1 and 2. Pharmacokinetic assessments were conducted on Days 1-4 in both periods. The primary study outcomes were the area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf ), and maximum concentration (Cmax ); the geometric least squares mean ratio (GMR; roxadustat + lanthanum carbonate/roxadustat alone) and corresponding 90% confidence interval (CI) was calculated for AUCinf and Cmax . Safety was assessed by the occurrence of treatment-emergent adverse events (TEAEs), laboratory test results, vital signs and standard 12-lead electrocardiogram. RESULTS AND DISCUSSION: A total of 18 subjects were enrolled (Group 1, n = 9; Group 2, n = 9); no subjects discontinued from the study. Roxadustat was rapidly absorbed, reaching maximum plasma concentration between 1 and 4 hours. The GMRs for AUCinf and Cmax were 88.00% (90% CI: 84.01, 92.17) and 98.58% (90% CI: 92.92, 104.58), respectively. The 90% CIs for both parameters were within the no-effect boundaries of 80% and 125%, indicating a lack of effect of lanthanum carbonate on roxadustat absorption. No deaths or serious TEAEs occurred. WHAT IS NEW AND CONCLUSIONS: Concomitant administration of a single oral dose of 100 mg roxadustat and 750 mg lanthanum carbonate three times daily did not impact the AUCinf or Cmax of roxadustat and was considered safe and well tolerated in non-elderly healthy adult male Japanese subjects.

Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment.

Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood.

Quantitative Modeling and Simulation in PMDA: A Japanese Regulatory Perspective.

In Japan in October 2016, the Pharmaceuticals and Medical Devices Agency (PMDA) began to receive electronic data in new drug applications (NDAs). These electronic data are useful to conduct regulatory assessment of sponsors' submissions and contribute to the PMDA's research. In this article, we summarize the number of submissions of quantitative modeling and simulation (M&S) documents in NDAs in Japan, and we describe our current thinking and activities about quantitative M&S in PMDA.

Publisher's Note: Electronic Phase Separation and Dramatic Inverse Band Renormalization in the Mixed-Valence Cuprate LiCu_{2}O_{2} [Phys. Rev. Lett. 118, 176404 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.118.176404.

Electronic Phase Separation and Dramatic Inverse Band Renormalization in the Mixed-Valence Cuprate LiCu_{2}O_{2}.

We measured, by angle-resolved photoemission spectroscopy, the electronic structure of LiCu_{2}O_{2}, a mixed-valence cuprate where planes of Cu(I) (3d^{10}) ions are sandwiched between layers containing one-dimensional edge-sharing Cu(II) (3d^{9}) chains. We find that the Cu(I)- and Cu(II)-derived electronic states form separate electronic subsystems, in spite of being coupled by bridging O ions. The valence band, of the Cu(I) character, disperses within the charge-transfer gap of the strongly correlated Cu(II) states, displaying an unprecedented 250% broadening of the bandwidth with respect to the predictions of density functional theory. Our observation is at odds with the widely accepted tenet of many-body theory that correlation effects generally yield narrower bands and larger electron masses and suggests that present-day electronic structure techniques provide an intrinsically inappropriate description of ligand-to-d hybridizations in late transition metal oxides.

Liver transection using indocyanine green fluorescence imaging and hepatic vein clamping.

BACKGROUND: Three-dimensional (3D) imaging has facilitated liver resection with excision of hepatic veins by estimating the liver volume of portal and hepatic venous territories. However, 3D imaging cannot be used for real-time navigation to determine the liver transection line. This study assessed the value of indocyanine green (ICG) fluorescence imaging with hepatic vein clamping for navigation during liver transection. METHODS: Consecutive patients who underwent liver resection with excision of major hepatic veins between 2012 and 2013 were evaluated using ICG fluorescence imaging after clamping veins and injecting ICG. Regional fluorescence intensity (FI) values of non-veno-occlusive regions (FINon ), veno-occlusive regions (FIVO ) and ischaemic regions (FIIS ) were calculated using luminance analysing software. RESULTS: Of the 21 patients, ten, four and seven underwent limited resection, monosegmentectomy/sectionectomy and hemihepatectomy respectively, with excision of major hepatic veins. Median veno-occlusive liver volume was 80 (range 30-458) ml. Fluorescence imaging visualized veno-occlusive regions as territories with lower FI compared with non-veno-occlusive regions, and ischaemic regions as territories with no fluorescence after intravenous ICG injection. Median FIIS /FINon was lower than median FIVO /FINon (0·22 versus 0·59; P = 0·002). There were no deaths in hospital or within 30 days, and only one major complication. CONCLUSION: ICG fluorescence imaging with hepatic vein clamping visualized non-veno-occlusive, veno-occlusive and ischaemic regions. This technique may guide liver transection by intraoperative navigation, enhancing the safety and accuracy of liver resection.

Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study.

BACKGROUND: The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients. METHODS: This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis. RESULTS: Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708). CONCLUSIONS: The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

Rat white adipocytes activate p85/p110 PI3K and induce PM GLUT4 in response to adrenoceptor agonists or aluminum fluoride.

Adipocyte responses to adrenergic and ß-adrenoceptor(-AR) (adrenoceptor) regulation are not sufficiently understood, and information helpful for elucidating the adrenoceptor-responsive machinery is insufficient. Here we show by using immunoprecipitated kinase analysis with a phosphatidylinositol 3-kinase (PI3K) p85 antibody that PI3K activation was induced by treatment with 10 or 100 µM norepinephrine (NE) for 15 min or with 10 mM aluminum fluoride (AF, a guanosine triphosphate (GTP)-binding (G) protein activator) for 20 min in white adipocytes (rat epididymal adipocytes) and that treatment with pertussis toxin (PTX, a G-protein inactivator) inhibited PI3K activation induced by the 20-min treatment with AF in the cells. In addition, western blot analysis revealed that glucose transporter 4 (GLUT4) level in the adipocyte plasma membrane (PM) fraction was increased by treatment with 10 µM NE, 100 µM dobutamine (DOB, a ß1-AR agonist), or 0.1 µM CL316243 (CL, a ß3-AR agonist) for 30 min or with 10 mM AF for 20 min. NE or AF treatment triggered 2-deoxyglucose (2-DG) uptake into adipocytes under the above conditions. Our results advance the understanding of responses to adrenoceptor regulation in white adipocytes and provide possible clues for clarifying the machinery involved in adrenergic and ß-AR responses in the cells.

CL316243 induces phosphatidylinositol 3,4,5-triphosphate production in rat adipocytes in an adenosine deaminase-, pertussis toxin-, or wortmannin-sensitive manner.

The effect of beta(3)-adrenoceptor (beta(3)-AR) agonists on adipocytes treated or not treated with signaling modulators has not been sufficiently elucidated. Using rat epididymal adipocytes (adipocytes) labeled with [(32)P]orthophosphate, we found that treatment with the selective beta(3)-AR agonist CL316243 (CL; 1 microM) induces phosphatidylinositol (PI) 3,4,5-triphosphate (PI[3,4,5]P(3)) production and that this response is inhibited by adenosine deaminase (ADA, an adenosine-degrading enzyme; 2 U/ml), pertussis toxin (PTX, an inactivator of inhibitory guanine-nucleotide-binding protein; 1 microg/ml), or wortmannin (WT, a PI-kinase inhibitor; 3 microM). The results showed that CL induced PI(3,4,5)P(3) production in intact adipocytes and that this production was affected by signaling modulators. Taken together, our findings indicate that CL produces PI(3,4,5)P(3) in an ADA-sensitive, PTX-sensitive, or WT-sensitive manner and will advance understanding of the effect of beta(3)-AR agonists on adipocytes.

Computer-Assisted Detection of Cerebral Aneurysms in MR Angiography in a Routine Image-Reading Environment: Effects on Diagnosis by Radiologists.

BACKGROUND AND PURPOSE: Experiences with computer-assisted detection of cerebral aneurysms in diagnosis by radiologists in real-life clinical environments have not been reported. The purpose of this study was to evaluate the usefulness of computer-assisted detection in a routine reading environment. MATERIALS AND METHODS: During 39 months in a routine clinical practice environment, 2701 MR angiograms were each read by 2 radiologists by using a computer-assisted detection system. Initial interpretation was independently made without using the detection system, followed by a possible alteration of diagnosis after referring to the lesion candidate output from the system. We used the final consensus of the 2 radiologists as the reference standard. The sensitivity and specificity of radiologists before and after seeing the lesion candidates were evaluated by aneurysm- and patient-based analyses. RESULTS: The use of the computer-assisted detection system increased the number of detected aneurysms by 9.3% (from 258 to 282). Aneurysm-based analysis revealed that the apparent sensitivity of the radiologists' diagnoses made without and with the detection system was 64% and 69%, respectively. The detection system presented 82% of the aneurysms. The detection system more frequently benefited radiologists than being detrimental. CONCLUSIONS: Routine integration of computer-assisted detection with MR angiography for cerebral aneurysms is feasible, and radiologists can detect a number of additional cerebral aneurysms by using the detection system without a substantial decrease in their specificity. The low confidence of radiologists in the system may limit its usefulness.

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study.

BACKGROUND AND OBJECTIVE: A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. MATERIAL AND METHODS: A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. RESULTS: Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). CONCLUSIONS: It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis.