Thirty-day mortality after palliative radiotherapy in advanced cancer patients: Optimizing end-of-life care in Asia.

INTRODUCTION: Evidence-based guidelines recommend hypofractionated palliative radiotherapy (PRT); nonetheless, many patients receive prolonged course of PRT. To identify patients with limited benefits from PRT in end-of-life care, we evaluated the pattern of PRT at an Asian institution and factors associated with 30-day mortality after PRT (30dM). METHODS: We retrospectively reviewed 228 patients who died after PRT in Yonsei Wonju Severance Christian hospital between October 2014 and March 2022. The associations between clinical factors and survival were assessed using the Cox proportional hazards method. Survival was analysed using the existing models to evaluate their performance in our cohort. RESULTS: The median PRT duration was 13 (IQR, 7-15) days. Only 11.4% of the patients were treated with hypofractionated radiotherapy. One-third of the patients (32.9%) could not complete PRT and 39 (17.1%) died during PRT. The 30dM was 31.6%. The median time from PRT to death was 17 (IQR, 11-23) days for the patients who died within 30 days. The number of involved organs (≤2 vs. >2; P < 0.001), albumin level (<3.3 vs. ≥3.3; P = 0.016), admission during PRT (P < 0.001), admission 3 months before PRT (P = 0.036) and ICU care during PRT (P < 0.001) were prognostic factors. A comparison of survival based on the existing models yielded unsatisfactory results in our cohort. CONCLUSION: Almost one-third of the patients received PRT in the last 30 days of life. The use of hypofractionation for PRT was low in this Asian population. Further research is necessary to develop a predictive model of early mortality, allowing tailored end-of-life care for Asian patients.

A tryptophan-based assay method to search regulatory compounds for transcriptionally controlled tumor protein.

Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find regulatory compounds. However, the molecular characteristics of TCTP made it difficult to search for chemicals interacting with it. In this study, a tryptophan-based assay method was designed and Y151W mutant TCTP was constructed to search binding chemicals. Since there is no tryptophan in the native sequence of TCTP, the incorporation of tryptophan in the Y151W mutant was very effective to establish the method. A flavonoid library was employed to the assay with the method. With the native and Y151W mutant TCTPs, three flavonoids such as morin, myricetin and isobavachalcone have been found to interact with TCTP. Combined with native gel electrophoresis, the binding region of isobavachalcone was suggested to be the flexible loop of TCTP. This approach can be easily applicable to find binding compounds of proteins with similar molecular characteristics of TCTP.

Amentoflavone, a potent natural matrix metalloproteinase 2 inhibitor.

Gelatinase A (MMP-2) has been studied and proven to play a vital role in the intrusion and metastasis of cancer. Flavonoids influence on molecular and cellular functions of MMP-2 and thus a systematic investigation of flavonoids against the metalloproteolytic activity of MMP-2 has been performed in this study. A fluorescence resonance energy transfer method was used to investigate the inhibitory activities of various flavonoids. Flavone, flavonol and isobavachalcone derivatives showed their inhibitory activity against MMP-2. Surprisingly, the most effective inhibitor was Amentoflavone and its blocking function was superior to other flavonoids. Its IC50 value was 0.689 µM. An induced-fit docking study was carried out to survey its extraordinary activity. The binding mode of Amentoflavone is quite similar to that of (2 ∼ {S})-2-[2-[4-(4-methoxyphenyl) phenyl] sulfanylphenyl] pentanedioic acid complexed with MMP-9. Amentoflavone interacts with the functional zinc and catalytic residue, Glu202. Therefore, the docking study reasonably confirmed the strong inhibitory activity of Amentoflavone.

Feasibility of artificial intelligence-driven interfractional monitoring of organ changes by mega-voltage computed tomography in intensity-modulated radiotherapy of prostate cancer.

PURPOSE: High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. MATERIALS AND METHODS: We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. RESULTS: Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. CONCLUSION: We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

Siraitia grosvenorii Extract Attenuates Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke and Lipopolysaccharide.

We studied the activities of Siraitia grosvenorii extracts (SGE) on airway inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) stimulated by cigarette smoke extract (CSE) and lipopolysaccharide (LPS), as well as in LPS-treated human bronchial epithelial cell line (BEAS-2B). SGE improved the viability of LPS-incubated BEAS-2B cells and inhibited the expression and production of inflammatory cytokines. SGE also attenuated the mitogen-activated protein kinase (MAPK)-nuclear factor-kappa B (NF-κB) signaling activated by LPS stimulation in BEAS-2B cells. In mice stimulated by CSE and LPS, we observed the infiltration of immune cells into the airway after COPD induction. SGE reduced the number of activated T cells, B cells, and neutrophils in bronchoalveolar fluid (BALF), lung tissue, mesenteric lymph node, and peripheral blood mononuclear cells, as well as inhibited infiltration into organs and mucus production. The secretion of cytokines in BALF and the expression level of pro-inflammatory cytokines, mucin 5AC, Transient receptor potential vanilloid 1, and Transient receptor potential ankyrin 1 in lung tissue were alleviated by SGE. In addition, to investigate the activity of SGE on expectoration, we evaluated phenol red secretions in the trachea of mice. SGE administration showed the effect of improving expectoration through an increase in phenol red secretion. Consequently, SGE attenuates the airway inflammatory response in CSE/LPS-stimulated COPD. These findings indicate that SGE may be a potential herbal candidate for the therapy of COPD.

Determination of the range of intervention timing for supernumerary teeth using the Korean health insurance review and assessment service database.

This study aimed to identify the frequency of complications during the diagnosis, observation, and treatment of supernumerary teeth or odontomas and evaluate the relationship between complications and the timing of surgical intervention. This study was conducted based on data from the Korea Health Insurance Review and Assessment Service between January 2008 and December 2019. A 2-year washout period was applied, and a follow-up period of at least 2 years was also included. During the observation period, the age at diagnosis of supernumerary teeth and odontomas was analyzed using major diagnostic codes, and the treatment codes were used to determine the interval between diagnosis and surgical intervention. The incidence rates of supernumerary teeth (1.21%) and odontomas (0.36%) were comparable to that reported in previous studies. The frequency of supernumerary teeth was the highest in the anterior region, followed by the premolar and molar regions. The average ages at diagnosis according to the location of the supernumerary teeth were 7.25, 13.98, and 16.11 years in the anterior, premolar, and molar regions, respectively. The age at diagnosis correlated with the maturity period of the teeth at the corresponding location. For the supernumerary tooth group, surgical intervention was more likely to occur when malocclusion (p < 0.0001) or tooth eruption disturbances (p < 0.0001) were present or dentigerous cysts were absent (p = 0.006). For the odontoma group, malocclusion (p = 0.251) was not correlated with surgical intervention. When tooth eruption disturbances (p = 0.002) and dentigerous cysts (p < 0.0001) were present, surgical intervention was more likely to occur. Pediatric dentists should conduct timely clinical checks and periodic follow-ups to prevent complications and unnecessary orthodontic treatments in patients with supernumerary teeth or odontomas.

Long-term motor outcomes of deep brain stimulation of the globus pallidus interna in Parkinson's disease patients: Five-year follow-up.

BACKGROUND: Deep brain stimulation (DBS) of globus pallidus interna (GPi) is an established treatment for advanced Parkinson's disease (PD). However, in contrast to subthalamic nucleus (STN)-DBS, long-term outcomes of GPi-DBS have rarely been studied. OBJECTIVE: We investigated the long-term motor outcomes in PD patients at 5 years after GPi-DBS. METHODS: We retrospectively analyzed the clinical data for PD patients who underwent GPi-DBS. Longitudinal changes of UPDRS scores from baseline to 5 years after surgery were assessed. RESULTS: Forty PD patients with a mean age of 59.5 ± 7.9 years at DBS surgery (mean duration of PD: 11.4 ± 3.4 years) were included at baseline and 25 patients were included in 5-year evaluation after DBS. Compared to baseline, sub-scores for tremor, levodopa-induced dyskinesia (LID), and motor fluctuation indicated improved states up to 5 years after surgery (p < 0.001). However, UPDRS Part 3 total score and sub-score for postural instability and gait disturbance (PIGD) gradually worsened over time until 5 years after surgery (p > 0.017 after Bonferroni correction). In a logistic regression model, only preoperative levodopa response was associated with the long-term benefits on UPDRS Part 3 total score and PIGD sub-score (OR = 1.20; 95% CI = 1.04-1.39; p = 0.015 and OR = 4.99; 95% CI = 1.39-17.89; p = 0.014, respectively). CONCLUSIONS: GPi-DBS provides long-term beneficial effects against tremor, motor fluctuation and LID, but PIGD symptoms gradually worsen. This selective long-term benefit has implications for the optimal application of DBS in PD patients.

Clinical factors and dopamine transporter availability for the prediction of outcomes after globus pallidus deep brain stimulation in Parkinson's disease.

We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson's disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [18F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD.

A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech's Artificial Intelligence (AI) technology, SOMAIPRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.

Optimal management of recurrent and metastatic upper tract urothelial carcinoma: Implications of intensity modulated radiation therapy.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is rare and the treatment for recurrent or metastatic UTUC is unclear. We evaluated the outcomes of salvage and palliative radiotherapy (RT) and prognostic factors in UTUC patients and find implications for salvage and palliative RT. METHODS: Between August 2006 and February 2021, 174 patients (median age, 68 years; range, 37-90) underwent salvage and palliative RT. Disease status at RT included initially diagnosed advanced disease (n = 8, 4.6%), local recurrence only (n = 56, 32.2%), distant metastasis only (n = 59, 33.9%), and local recurrence and distant metastasis (n = 51, 29.3%). The primary tumor location included the renal pelvis (n = 87, 50%), ureter (n = 77, 44.3%), and both (n = 10, 5.7%). Radical nephroureterectomy, chemotherapy, and immunotherapy were used in 135 (77.6%), 101 (58%), and 19 (10.9%) patients, respectively. Survival outcomes and prognostic factors were analysed using Cox and logistic regression analysis. RESULTS: Salvage RT and palliative RT was administered in 73 (42%) and 101 (58%) patients, respectively. The median radiation dose was 45 Gy (range, 15-65). Two-dimensional (2D) or three-dimensional (3D) RT and intensity modulated RT (IMRT) were used in 61 (35.1%) and 113 (64.9%) patients, respectively. The median follow-up was 7.8 months. The median duration of overall survival (OS) was 13.4 months, and the 1-year OS was 53.5%. The median progression-free survival (PFS) was 4.7 months, and the 6-month PFS was 41.9%. The 6-month infield PFS was 84%. In multivariate analysis, RT method (2D/3D vs. IMRT, p = 0.007) and RT response (p = 0.008) were independent prognostic factors for OS, and RT response correlated with PFS (p = 0.015). In subgroup analysis in patients with PD-L1 data, positive PD-L1 correlated with better PFS (p = 0.009). RT response-associated factors were concurrent chemotherapy (p = 0.03) and higher radiation dose (p = 0.034). Of 145 patients, 10 (6.9%) developed grade 3 acute or late toxicity. CONCLUSIONS: Salvage and palliative RT for UTUC are feasible and effective. Patients with RT response using IMRT may have survival benefit from salvage and palliative RT. Positive PD-L1 status might be related to radiosensitivity. High-dose radiation with concurrent chemotherapy may improve RT response.

The risk factors of intracerebral hemorrhage in deep brain stimulation: does target matter?

BACKGROUND: Although deep brain stimulation (DBS) is a relatively safe and effective surgery compared with ablative surgeries, intracerebral hemorrhage (ICH) is a serious complication during DBS that could result in a fatal prognosis. We retrospectively investigated whether ICH incidence differed between patients who underwent DBS in the subthalamic nucleus (STN) and in the globus pallidus interna (GPi), together with previously identified risk factors for ICH. METHODS: We retrospectively reviewed the medical records of 275 patients (527 DBS targets) who received DBS for Parkinson's disease or dystonia from April 2001 to December 2020. In cases that developed intra- or postoperative ICH, patients were classified as asymptomatic, symptomatic with temporary neurological deficit or symptomatic with permanent neurological deficit, according to patient clinical status. RESULTS: ICH occurred in 12 procedures (2.3%) among the 527 DBS procedures (275 patients) evaluated. In multivariable logistic regression analysis, the risk factor for all cases of ICH was systolic blood pressure (BP) during surgery (cut-off value 129.4 mmHg) (OR = 1.05, 95% CI = 1.01-1.09, P = 0.023). In addition, for ICH with permanent neurological deficit, STN target site (P = 0.024) and systolic BP during surgery (cut-off value: 148.3 mmHg) (P = 0.004) were identified as risk factors in univariable analyses. CONCLUSION: Even though the risk factor for all ICH in DBS was BP during surgery, when focused on ICH evoking permanent neurological deficit, the target location as well as systolic BP during surgery proved to be related.

Factors correlated with therapeutic effects of globus pallidus deep brain stimulation on freezing of gait in advanced Parkinson's disease: A pilot study.

INTRODUCTION: Deep brain stimulation (DBS) has showed variable therapeutic effect on freezing of gait (FOG) in Parkinson's disease (PD). It is unclear which factors associated with the effect of DBS on FOG in patients with advanced PD. In this study, we investigated the correlation of pre and postoperative factors with the therapeutic effect of globus pallidus interna (GPi) DBS on FOG in PD patients. METHODS: We retrospectively analyzed PD patients with FOG (N = 20) who underwent GPi DBS surgery. Postoperatively, video-based analysis for FOG severity was performed at the first DBS programming and patients were categorized into two groups according to DBS effect on FOG (11 FOG responders and 9 FOG non-responders) at medication-off state. We analyzed preoperative clinical characteristics, cognitive function, striatal dopamine transporter availability, postoperative DBS programming parameters, lead locations, and volume of tissue activated in functional subregions of GPi. Bootstrap enhanced Elastic-Net logistic regression was used to select pre and postoperative factors associated with the effect of GPi DBS. RESULTS: Therapeutic effect of GPi DBS on FOG were correlated with the disease duration of PD before DBS surgery, preoperative improvement in FOG severity by levodopa medication, and the distance from active contact of DBS electrode to the prefrontal region of GPi anatomical site. CONCLUSIONS: Our study results suggest that the effect of GPi DBS on FOG is correlated with disease duration, levodopa responsiveness on FOG before DBS surgery and DBS electrode location, providing useful information to predict FOG outcome after GPi DBS in PD patients.

Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer.

INTRODUCTION: Some patients with cancer may present with progressive or persistent disease at a limited number of sites following a period of treatment response. We evaluated the safety and effectiveness of metastasis-directed radiotherapy (MRT) for oligoprogressive or oligopersistent disease in patients receiving systemic treatment for metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC who received 5-fluorouracil, leucovorin, and oxaliplatin; 5-fluorouracil, leucovorin, and irinotecan; and/or capecitabine chemotherapy between 2011 and 2020 at a single institution were identified. Then, those who underwent MRT for five or fewer lesion sites while receiving systemic treatment for other metastases were categorized. The primary endpoint was time to change to systemic therapy. Secondary endpoints included MRT-related toxicity, overall survival, and local control. RESULTS: Among 4157 patients included, 91 (2%) received MRT to limited lesion sites (55 oligoprogressive and 36 oligopersistent) during systemic treatment following a period of treatment response. The median time to change to next-line systemic therapy was 5 months in the overall cohort (measured from the current chemotherapy session) and 9.5 (range, 6.0-40.6) months in the MRT group (measured from the MRT session). No severe toxicity or systemic treatment interruption was observed following MRT. The 1-year local control and overall survival rates were 69% and 99%, respectively. CONCLUSION: In patients with oligoprogressive or oligopersistent mCRC, MRT may be performed safely in conjunction with systemic treatment to maximize the benefit of systemic therapy and to prolong the time to change to systemic therapy. Further prospective studies should confirm these findings.

Management of non-obstetric traumatic vulvar haematoma: a retrospective review of 33 cases.

The cases of non-obstetric traumatic vulvar haematomas are rare, and there is a lack of consensus statements for the necessity of surgical intervention. We retrospectively analysed the data of 33 cases (mean age: 25.7 years) of non-obstetric traumatic vulvar haematoma (mean haematoma size: 8.4 cm). Women who underwent surgery (surgery group) were compared to those who received conservative management (conservative group). Twenty-four patients underwent surgery; most cases were of haematoma removal and primary closure. Nine patients received conservative management, such as ice bag application, antibiotics, or analgesia. The rate of deviation of the contralateral vulva because of haematoma was higher (54.2% versus 11.1%, p = .047) and the mean haematoma size was larger (9.5 versus 5.2 cm, p = .004) in the surgical than in the conservative group. While conservative management affects cases of minor vulvar haematoma, surgical evacuation of haematoma can be performed in cases of large haematoma (mean size: 9.5 cm), severe pain, distorted vulvar anatomy, and invisible urethral opening for indwelling urinary catheter.IMPACT STATEMENTWhat is already known on this subject? Cases of non-obstetric traumatic vulvar haematomas are rare. There are no consensus statements for the necessity of surgical intervention.What do the results of this study add? The study showed that surgical evacuation of haematoma can be performed in cases of large haematoma (mean size: 9.5 cm), severe pain, distorted vulvar anatomy, and invisible urethral opening for indwelling urinary catheter. Moreover, surgical management could hasten recovery.What are the implications of these findings for clinical practice and/or further research? The results of this study can be used in counselling non-obstetric traumatic vulvar haematomas. Further research is needed to confirm these findings.

Stepwise oxidations play key roles in the structural and functional regulations of DJ-1.

DJ-1 is known to play neuroprotective roles by eliminating reactive oxygen species (ROS) as an antioxidant protein. However, the molecular mechanism of DJ-1 function has not been well elucidated. This study explored the structural and functional changes of DJ-1 in response to oxidative stress. Human DJ-1 has three cysteine residues (Cys46, Cys53 and Cys106). We found that, in addition to Cys106, Cys46 is the most reactive cysteine residue in DJ-1, which was identified employing an NPSB-B chemical probe (Ctag) that selectively reacts with redox-sensitive cysteine sulfhydryl. Peroxidatic Cys46 readily formed an intra-disulfide bond with adjacent resolving Cys53, which was identified with nanoUPLC-ESI-q-TOF tandem mass spectrometry (MS/MS) employing DBond algorithm under the non-reducing condition. Mutants (C46A and C53A), not forming Cys46-Cys53 disulfide cross-linking, increased oxidation of Cys106 to sulfinic and sulfonic acids. Furthermore, we found that DJ-1 C46A mutant has distorted unstable structure identified by biochemical assay and employing hydrogen/deuterium exchange-mass spectrometry (HDX-MS) analysis. All three Cys mutants lost antioxidant activities in SN4741 cell, a dopaminergic neuronal cell, unlike WT DJ-1. These findings suggest that all three Cys residues including Cys46-Cys53 disulfide cross-linking are required for maintaining the structural integrity, the regulation process and cellular function as an antioxidant protein. These studies broaden the understanding of regulatory mechanisms of DJ-1 that operate under oxidative conditions.

Functional recovery by colon organoid transplantation in a mouse model of radiation proctitis.

Radiation proctitis is the collateral damage that occurs to healthy cells during radiation treatment of pelvic malignancies. Conservative treatment of radiation proctitis can mitigate inflammatory symptoms, but, to date, no therapeutic options are available for direct recovery of the damaged colonic epithelium. The present study assessed the ability of colon organoid-based regeneration to treat radiation proctitis. Radiation proctitis was induced in mice by irradiating their recta, followed by enema-based transplantation of mouse colon organoids. The transplanted colon organoids were found to successfully engraft onto the damaged rectal mucosa of the irradiated mice, reconstituting epithelial structure and integrity. Lgr5+ stem cells were shown to be pivotal to colon organoid mediated regeneration. Endoscopic examination showed the efficacy of localized transplantation of colon organoids with fibrin glue to irradiated sites. These findings provide useful insights into the use of colon organoid-based regenerative therapy for the treatment of radiation proctitis.

Effect of adenomyosis on adverse obstetrical outcomes in twin pregnancies achieved with assisted reproductive technology.

The incidence of twin pregnancy with adenomyosis (AD) is increasing due to advanced maternal age and infertility treatment. We retrospectively analysed the data of 45 dichorionic twin pregnancies complicated with AD in contrast to a control group of dichorionic twin pregnancies without AD (n = 130). Compared with those in the control group, the AD group had a higher overall foetal loss rate (8.9% vs. 0.8%; adjusted p = .031; odds ratio (OR), 13.6; 95% confidence interval (CI), 1.27-146.3), higher early preterm delivery rate (20% vs. 6.9%; adjusted p = .007; OR, 4.22; 95% CI, 1.47-12.13) and higher rate of hypertensive disorders of pregnancy (26.7% vs. 7.7%; adjusted p = .005; OR, 3.94; 95% CI, 1.5-10.2). Patients in the AD group were significantly more likely to require transfusion during or after delivery (17.8% vs. 5.4%; p = .026) and have smaller babies (2168 g vs. 2399 g; p = .004) compared with those in the control group. This is the first study to report that twin pregnancies with AD may be treated as high-risk for placental dysfunction and may need closer monitoring during pregnancy.Impact StatementWhat is already known on this subject? The incidence of twin pregnancy with adenomyosis (AD) is increasing due to advanced maternal age and infertility treatment. However, there are very few studies on the effect of AD on pregnancy outcomes.What the results of this study add? This is the first study to report that twin pregnancies with AD have higher rates of early preterm delivery, hypertensive disorders of pregnancy, and transfusion compared to controls.What the implications are of these findings for clinical practice and/or further research? The results of this study can be used in counselling twin pregnancies with AD. Further research is needed to confirm the current findings.

Are occupational and environmental noises associated with periodontitis? Evidence from a Korean representative cross-sectional study.

BACKGROUND: Evidences have shown that noise could be a risk factor for cardiovascular and metabolic diseases. Since periodontitis and CVD are characterized by inflammation, it is reasonable to doubt that occupational/environmental noise is a risk factor for periodontitis. The aim of this study was to examine the relationship between occupational/environmental noise and periodontitis in a nationally representative sample of Korean adults. METHODS: This cross-sectional study used data from the 7th Korean National Health and Nutrition Examination Survey. The study sample included 8327 adults aged 40 to 80 years old. Noise exposure and the duration of the exposure were assessed with self-report questionnaires. The dependent variable was periodontitis. Age, gender, place of residence, income, marital status, smoking, frequency of daily tooth brushing, recent dental checkup, and diabetes were included as covariates. Logistic regression analyses estimated the association between noise exposure and periodontitis. RESULTS: Those who were exposed to environmental noise during their lifetime had an increased prevalence of severe periodontitis (odds ratio [OR] 1.88; 95% confidence interval [CI] 1.05 to 3.40), and this association was strengthened as the duration of the environmental noise exposure was longer (OR of > 120 months 2.35 and OR of ≤120 months 1.49). There was a combined relationship for severe periodontitis between occupational and environmental noise exposure (OR of both exposures 2.62, OR of occupational exposure only 1.12, and OR of environmental exposure only 1.57). CONCLUSION: Our study shows that noise exposure is associated with periodontitis, and the association was higher in the synergism between occupational and environmental interaction.

Inhibition of d-glycero-ß-d-manno-heptose 1-phosphate adenylyltransferase from Burkholderia pseudomallei by epigallocatechin gallate and myricetin.

Flavonoids play beneficial roles in various human diseases. In this study, a flavonoid library was employed to probe inhibitors of d-glycero-ß-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei (BpHldC) and two flavonoids, epigallocatechin gallate (EGCG) and myricetin, have been discovered. BpHldC is one of the essential enzymes in the ADP-l-glycero-ß-d-manno-heptose biosynthesis pathway constructing lipopolysaccharide of B. pseudomallei. Enzyme kinetics study showed that two flavonoids work through different mechanisms to block the catalytic activity of BpHldC. Among them, a docking study of EGCG was performed and the binding mode could explain its competitive inhibitory mode for both ATP and ßG1P. Analyses with EGCG homologs could reveal the important functional moieties, too. This study is the first example of uncovering the inhibitory activity of flavonoids against the ADP-l-glycero-ß-d-manno-heptose biosynthesis pathway and especially targeting HldC. Since there are no therapeutic agents and vaccines available against melioidosis, EGCG and myricetin can be used as templates to develop antibiotics over B. pseudomallei.

Crystal structure of pharmaceutical-grade human serum albumin.

Human serum albumin (HSA) is the most abundant protein in human plasma and plays versatile biological role. HSA has been widely used to treat several diseases and develop biocompatible biomaterials for biomedical applications. However, pharmaceutical-grade HSA (p-HSA) showed the altered oxidative and ligand-binding properties compare to native HSA. To investigate the influences of the manufacturing process on the molecular state of HSA, we determined the first crystal structure of p-HSA using the commercial HSA solution without any defatting step and further purification and carried out mass spectrometry to identify bound ligands. The crystal structure of p-HSA revealed that medium- and long-chain fatty acids and tryptophan are bound to p-HSA and one free cysteine is oxidized to cysteine-sulfenic acid. The mass spectra of p-HSA also confirmed the existence of fatty acids and tryptophan in p-HSA. Our results enhance understanding of the molecular state of p-HSA and can be utilized to produce p-HSA solutions and HSA-based biomaterials that has a higher biorelevance.