Mitigating biomass composition uncertainties in flux balance analysis using ensemble representations.

The biomass equation is a critical component in genome-scale metabolic models (GEMs): it is used as the de facto objective function in flux balance analysis (FBA). This equation accounts for the quantities of all known biomass precursors that are required for cell growth based on the macromolecular and monomer compositions measured at certain conditions. However, it is often reported that the macromolecular composition of cells could change across different environmental conditions and thus the use of the same single biomass equation in FBA, under multiple conditions, is questionable. Herein, we first investigated the qualitative and quantitative variations of macromolecular compositions of three representative host organisms, Escherichia coli, Saccharomyces cerevisiae and Cricetulus griseus, across different environmental/genetic variations. While macromolecular building blocks such as RNA, protein, and lipid composition vary notably, changes in fundamental biomass monomer units such as nucleotides and amino acids are not appreciable. We also observed that flux predictions through FBA is quite sensitive to macromolecular compositions but not the monomer compositions. Based on these observations, we propose ensemble representations of biomass equation in FBA to account for the natural variation of cellular constituents. Such ensemble representations of biomass better predicted the flux through anabolic reactions as it allows for the flexibility in the biosynthetic demands of the cells. The current study clearly highlights that certain component of the biomass equation indeed vary across different conditions, and the ensemble representation of biomass equation in FBA by accounting for such natural variations could avoid inaccuracies that may arise from in silico simulations.

Anger-Related Characteristics According to Chronotypes in Bipolar or Depressive Disorders.

OBJECTIVE: Though anger was highly associated with eveningness in general population, there is no study on the relationship between chronotype and anger-related characteristics in bipolar or depressive disorders. This study aimed to investigate the difference of anger-related characteristics according to chronotypes in bipolar or depressive disorders. METHODS: Patients with bipolar or depressive disorders (n=238) were included in this study. Their chronotypes and anger-related characteristics were assessed with a self-evaluation of the Composite Scale of Morningness (CSM), the State Trait Anger Expression Inventory (STAXI) and the Anger Coping Scale (ACS). RESULTS: The eveningness group in patients with mood disorders showed the highest scores of anger-trait (p<0.001), anger-expression (p=0.002) and anger-in (p<0.001) in STAXI subscales, verbal aggression (p=0.010) in ACS subscales among three groups, but the morningess group showed the lowest scores of these subscales among three groups. However, there were no significant differences in all subscales of the STAXI and ACS according to diagnostic subtypes in the Friedman test. CONCLUSION: The results of this study suggested that eveningness in patients with mood disorders might be related to anger proneness and maladaptive anger coping. To manage anger emotion in the patients with mood disorders, therapeutic interventions to modulate eveningness might be helpful.

Genome scale metabolic models and analysis for evaluating probiotic potentials.

Probiotics are live beneficial microorganisms that can be consumed in the form of dairy and food products as well as dietary supplements to promote a healthy balance of gut bacteria in humans. Practically, the main challenge is to identify and select promising strains and formulate multi-strain probiotic blends with consistent efficacy which is highly dependent on individual dietary regimes, gut environments, and health conditions. Limitations of current in vivo and in vitro methods for testing probiotic strains can be overcome by in silico model guided systems biology approaches where genome scale metabolic models (GEMs) can be used to describe their cellular behaviors and metabolic states of probiotic strains under various gut environments. Here, we summarize currently available GEMs of microbial strains with probiotic potentials and propose a knowledge-based framework to evaluate metabolic capabilities on the basis of six probiotic criteria. They include metabolic characteristics, stability, safety, colonization, postbiotics, and interaction with the gut microbiome which can be assessed by in silico approaches. As such, the most suitable strains can be identified to design personalized multi-strain probiotics in the future.

Quantitative analysis of radiation dosage and image quality between digital breast tomosynthesis (DBT) with two-dimensional synthetic mammography and full-field digital mammography (FFDM).

PURPOSE: Currently in diagnostic setting for breast cancer, FFDM and DBT are performed conjunctively. However, performing two imaging modalities may increase radiation exposure by double. Two-dimensional reconstructed images created from DBT with 2DSM, has a potential to replace conventional FFDM in concerning both radiation dosage and image quality. With increasing concerns for individual radiation exposure, studies analyzing radiation dosage in breast imaging modalities are needed. This study compared radiation dosage and image quality between DBT + 2DSM versus FFDM. METHODS AND MATERIALS: 374 patients (mean age 52 years) who underwent both DBT and FFDM were retrospectively reviewed. Radiation dosage data were obtained by radiation dosage scoring and monitoring program Radimetrics (Bayer HealthCare, Whippany, NJ). Entrance dose and mean glandular doses in each breast were obtained for both modalities. To compare image quality of DBT + 2DSM and FFDM, a 5-point scoring system for lesion clarity was assessed. The parameters of radiation dosage (entrance dose, mean glandular dose) and image quality (lesion clarity scoring) were compared. RESULTS: For entrance dose, DBT had lower mean dosage (14.8 mGy) compared with FFDM (21.8 mGy, p-value < 0.0001). Mean glandular doses for both breasts were lower in DBT (Left 1.74, Right 2.1) compared with FFDM (Left 2.85, Right 2.74, p-value < 0.0001). Lesion clarity score was higher in DBT with 2DSM (mean score 4.03) compared with FFDM (3.82, p-value < 0.0001). CONCLUSION: DBT showed lower radiation entrance dose and mean glandular doses to both breasts compared with FFDM. DBT + 2DSM had better image quality than FFDM, suggesting that DBT with 2DSM has potential as an alternative to FFDM.

Protein Kinase C Activity and Delayed Recovery of Sleep-Wake Cycle in Mouse Model of Bipolar Disorder.

OBJECTIVE: Previous studies reported the delayed recovery group after circadian rhythm disruption in mice showed higher quinpiroleinduced locomotor activity. This study aimed to compare not only Protein Kinase C (PKC) activities in frontal, striatal, hippocampus and cerebellum, but also relative PKC activity ratios among brain regions according to recovery of circadian rhythm. METHODS: The circadian rhythm disruption protocol was applied to eight-week-old twenty male Institute Cancer Research mice. The circadian rhythm recovery patterns were collected through motor activities measured by Mlog system. Depressive and manic proneness were examined by forced swim test and quinpirole-induced open field test respectively. Enzyme-linked immunosorbent assay was employed to measure PKC activities. RESULTS: The delayed recovery group presented greater locomotor activities than the early recovery group (p=0.033). The delayed recovery group had significantly lower frontal PKC activity than the other (p=0.041). The former showed lower frontal/cerebellar PKC activity ratio (p=0.047) but higher striatal/frontal (p=0.038) and hippocampal/frontal (p=0.007) PKC activities ratios than the latter. CONCLUSION: These findings support potential mechanism of delayed recovery after circadian disruption in bipolar animal model could be an alteration of relative PKC activities among mood regulation related brain regions. It is required to investigate the PKC downstream signaling related to the delayed recovery pattern.

Can Residual Symptoms During Inter-Episode Period after Partial Remission in Bipolar I Disorder Have Cyclic Patterns with Specific Frequencies?

This case report aimed to describe cyclic patterns of residual mood symptoms in partially remitted bipolar I patient. In a 24-year-old woman with bipolar I disorder, residual mood symptoms measured by self-rated daily mood chart for 18 months were analyzed using wavelet analysis. A 146-day periodicity was prominent for the first 100 days after discharge. Between 100-200 days, 146-day periodicity was progressively diminished and 21- and 8-day periodicity was prominent. Between 200-516 days, 21-day periodicity was diminished and 85-day periodicity became prominent. This case suggest that bipolar patients might have cyclic residual symptoms with specific frequencies.

Psychometric Properties of the Coping Inventory for Stressful Situations in Korean Adults.

OBJECTIVE: The Coping Inventory for Stressful Situations (CISS) is a globally recognized measure of stress coping methods. However, research into the applicability of the CISS in a Korean context is still in its infancy. The aim of this study is to assess and report the validity of the CISS in Korean adults for the first time. METHODS: Three hundred and two Korean adults who currently have no distressing problems requiring psychiatric treatment completed the Korean version of the CISS. Principal component analysis was used to extract factors in the process of exploratory factor analysis. RESULTS: The result displayed a clear pattern matrix, and a high level of internal consistency was shown by Chronbach's alpha. The items classified under task-oriented and emotion-oriented coping presented adequate factorial validity, and only three items grouped under avoidance-oriented coping loaded poorly or loaded onto factors differing from the original. CONCLUSION: These results seem to indicate that the CISS may indeed be both applicable and useful in gauging the coping styles of Korean adults. However, the ambiguous meanings of certain items under avoidance-oriented coping would require adjustment for the purposes of future study.

Ridge preservation of extraction sockets with chronic pathology using Bio-Oss® Collagen with or without collagen membrane: an experimental study in dogs.

OBJECTIVES: This study aimed to evaluate the dynamics of newly bone formation and dimensional change in diseased extraction sockets using Bio-Oss® Collagen with or without a collagen membrane. MATERIAL AND METHODS: In six beagle dogs, right and left 3rd and 4th mandibular premolars were hemisected and the distal roots were removed. Combined endodontic-periodontic lesions were induced in all sites using black silk, collagen sponge, endodontic files, and application of Porphyromonas gingivalis. After 4 months, among 4 premolars, three teeth were randomly selected per dog and allocated to the following experimental groups: Control group (no treatment but debridement), Test 1 group (only Bio-Oss® Collagen graft), and Test 2 group (Bio-Oss® Collagen graft with a collagen membrane). After 7 months from the baseline, the beagle dogs were sacrificed for histomorphometric and Micro-CT analysis. RESULTS: The vertical distance between buccal and lingual crests in the Control group (2.22 ± 0.26 mm) and Test 2 group (1.80 ± 0.16 mm) was significantly different. The socket of the Test 2 group (27.04 ± 5.25%) was occupied by a greater quantity of bone graft compared to the Test 1 group (18.49 ± 2.11%). CONCLUSION: Ridge preservation in diseased extraction sockets could compensate for buccal bone resorption by contact osteogenesis surrounding the bone graft particles at the bucco-coronal area during socket healing, and the application of a collagen membrane at the entrance of the socket is useful for preserving graft material at the coronal part of the socket.

Post-operative intravenous patient-controlled analgesic efficacy of morphine with ketorolac versus nefopam after laparoscopic gynecologic surgery: a randomized non-inferiority trial.

BACKGROUND: Nefopam is a non-opioid non-steroidal centrally acting analgesic. This study was conducted to assess the analgesic efficacy of intravenous patient-controlled analgesia (IV-PCA) using nefopam alone, compared with a combination of morphine and ketorolac, after laparoscopic gynecologic surgery. METHODS: Sixty patients undergoing laparoscopic gynecologic surgery received IV-PCA. Group A (n = 30) received IV-PCA with a combination of morphine 60 mg and ketorolac 180 mg, while group B (n = 30) received nefopam 200 mg (basal rate 1 ml/h, bolus 1 ml, and lockout time 15 min for both). The primary outcome evaluated was analgesic efficacy using the visual analogue scale (VAS). Other evaluated outcomes included the incidence rate of postoperative nausea and vomiting (PONV), patient satisfaction of pain control, percentage of patients requiring additional opioids, and incidence rate of postoperative adverse effects. RESULTS: Group B was not inferior to group A in relation to the VAS in the post-anesthesia care unit, and at 12, 24, and 48 h after surgery (mean difference [95% confidence interval], 0.50 [-0.43 to 1.43], -0.30 [-1.25 to 0.65], -0.05 [-0.65 to 0.55], and 0.10 [-0.55 to 0.75], respectively). The incidence rate of nausea was lower in group B than in group A at 12 and 24 h after surgery (P = 0.004 and P = 0.017, respectively). There were no significant differences in the other outcomes between groups. CONCLUSIONS: IV-PCA using nefopam alone has a non-inferior analgesic efficacy and produces a lower incidence of PONV in comparison with IV-PCA using a combination of morphine and ketorolac after laparoscopic gynecologic surgery.

The relationship between chronotype and mood fluctuation in the general population.

There is a lack of evidence for the relationship between chronotype and subthreshold mood fluctuation. The present study aims to investigate the relationship between chronotypes and mood fluctuation in the general population. Participants (n=302) who have had no experience of major mood episodes were included. The Korean version of the Composite Scale of Morningness (CSM) was used to classify participants according to three chronotypes. Mood fluctuation was measured using the Mood Disorder Questionnaire (MDQ) and the Bipolar Spectrum Diagnostic Scale (BSDS). Mean scores achieved by the three chronotype groups on the MDQ and the BSDS were compared. There were no significant differences in the frequency of positive responses on the MDQ for the three chronotype groups. However, there was a significant group difference in total BSDS scores. The eveningness group had significantly higher BSDS-D scores than did either the morningness or the intermediate group have. In addition, the eveningness group had significantly higher BSDS-M scores than the morningness group. After adjusting for age by the analysis of covariance (ANCOVA), there were still significant group differences in total BSDS scores. The present results suggest that eveningness may be more related to mood fluctuation than morningness. The eveningness may be an important factor related to soft bipolarity or mood fluctuation.

Characteristics of stress-coping behaviors in patients with bipolar disorders.

Appropriate stress-coping strategies are needed to improve the outcome in the treatment of bipolar disorders, as stressful life events may aggravate the course of the illness. The aim of this study was to compare stress-coping behaviors between bipolar patients and healthy controls. A total of 206 participants comprising 103 bipolar patients fulfilling the Diagnostic and Statistical Manual for Axis I disorder fourth edition (DSM-IV) diagnostic criteria for bipolar I and II disorders and controls matched by age and sex were included in this study. Stress-coping behaviors were assessed using a 53-item survey on a newly-designed behavioral checklist. The characteristics of stress-coping behaviors between the two groups were compared by using t-test and factor analysis. Social stress-coping behaviors such as 'journey', 'socializing with friends', and 'talking something over' were significantly less frequent in bipolar patients than controls. On the other hand, pleasurable-seeking behaviors such as 'smoking', 'masturbation', and 'stealing' were significantly more frequent in bipolar patients than controls. These results suggest that bipolar patients may have more maladaptive stress-coping strategies than normal controls. It is recommended to develop and apply psychosocial programs to reduce maladaptive stress-coping behaviors of bipolar patients.