Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury.

Sensory axons degenerate following separation from their cell body, but partial injury to peripheral nerves may leave the integrity of damaged axons preserved. We show that an endogenous ligand for the natural killer (NK) cell receptor NKG2D, Retinoic Acid Early 1 (RAE1), is re-expressed in adult dorsal root ganglion neurons following peripheral nerve injury, triggering selective degeneration of injured axons. Infiltration of cytotoxic NK cells into the sciatic nerve by extravasation occurs within 3 days following crush injury. Using a combination of genetic cell ablation and cytokine-antibody complex stimulation, we show that NK cell function correlates with loss of sensation due to degeneration of injured afferents and reduced incidence of post-injury hypersensitivity. This neuro-immune mechanism of selective NK cell-mediated degeneration of damaged but intact sensory axons complements Wallerian degeneration and suggests the therapeutic potential of modulating NK cell function to resolve painful neuropathy through the clearance of partially damaged nerves.

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.

Effect of intra-alveolar delivery of Frondoside A on inflammatory response of delayed tooth replantation.

BACKGROUND/AIM: Frondoside A is a sea cucumber extract which is well known for its anti-inflammatory and immunomodulatory properties. The purpose of this study was to evaluate the effect of Frondoside A application in the alveolar socket on inflammatory responses after delayed replantation in rat teeth. MATERIALS AND METHODS: Human periodontal ligament cells were cultured and exposed to Frondoside A. Cell-counting kit-8 assay was performed to evaluate the cell viability and nitric oxide assay was performed to assess the anti-inflammatory effect of Frondoside A. Molars were extracted from 32 Sprague-Dawley rats and randomly divided into control and Frondoside A groups. After 30 min of extra-oral dry time, molars were replanted. In the Frondoside A group, Frondoside A solution was applied in the alveolar socket before replantation. The animals were sacrificed after 28 days and histologically and immunohistochemically evaluated. RESULTS: 0.5 µM Frondoside A showed higher cellular viability at 6 h and lower production of nitric oxide compared with other Frondoside A solutions (p < .05). The Frondoside A group demonstrated lower inflammatory resorption scores in both middle 1/3 and apical 1/3 of root compared to the control group (p < .05). The Frondoside A group showed lower levels of expression in both cathepsin K and CD45 compared with the control group (p < .05). CONCLUSIONS: Within the limits of this study, intra-alveolar delivery of Frondoside A alleviates inflammatory root resorption in delayed replantation of rat teeth.

Anti-acne activity of carnitine salicylate and magnolol through the regulation of exfoliation, lipogenesis, bacterial growth and inflammation.

BACKGROUND: Salicylic acid has been used as an anti-acne agent with its comedolytic property and antimicrobial activity. However, there is a limit to use for leave-on cosmetics because of the transient skin irritation and low efficacy at neutral pH condition. We prepared a salicylic acid-based ionic pair with L -carnitine (we named, IP-BHA) overcoming the limitation of salicylic acid. We examined the effect of IP-BHA as well as the combination effect with magnolol, a bioactive organic lignan, in order to clarify their efficacy as anti-acne agents. METHODS: After verifying the structure of IP-BHA, we confirmed anti-acne activities including the regulation of exfoliation, lipogenesis, bacterial growth, and inflammation with IP-BHA and/or magnolol. RESULTS: The antibacterial activity of IP-BHA and magnolol was evaluated by determining the minimum antibacterial inhibitory concentration. Magnolol showed strong activity against Cutibacterium acnes, which was better than a medical antibiotic acne drug, clindamycin. The combined application with IP-BHA was more effective in antibacterial activity by 2.5 times. It was confirmed that testosterone-induced lipogenesis was significantly inhibited by treatment with IP-BHA and magnolol, while single treatment had no significant inhibitory effect. Interestingly, MMP-1 and VEGF were induced by C. acnes lysate in human keratinocytes. We found that these inflammatory molecules were completely inhibited by combined application of IP-BHA and magnolol. Through ex vivo test, the dose-dependent exfoliation effect of IP-BHA was confirmed at pH 5.5, and the synergic exfoliation effect was shown in the combined application of IP-BHA and magnolol. When topically applied, the emulsion containing IP-BHA and magnolol relieved the sodium dodecyl sulfate-induced erythema and improved inflamed acne with papule and pustule. CONCLUSION: Our data demonstrate that the ionic paired salicylic acid with L -carnitine can overcome the limitations of salicylic acid at low concentration and natural skin pH. Based on the dual administration effects, we suggest that IP-BHA and magnolol may be the potential agent for acne by improving inflammatory skin condition.

Effect of Home-Based Self-Management Intervention for Community-Dwelling Patients with Early Parkinson's Disease: A Feasibility Study.

PURPOSE: This study aimed to evaluate the effect of a home-based self-management intervention in community-dwelling patients with early Parkinson's diseases (PD). DESIGN: A randomized-controlled design. METHODS: Thirty-two patients participated (15=intervention, 17=control), and the intervention group received 16 weeks of the intervention. FINDINGS: Physical activity and non-motor symptoms improved more in the intervention group than in the control group. CONCLUSION: Home-based self-management intervention was effective in improving physical activity and non-motor symptoms for them. CLINICAL EVIDENCE: Home-based intervention - comprising education, telephone counseling, smartphone-based message and information, and smart wearable devices - was feasible for patients with early PD.

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.

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.

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.

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.

Dimerization Tendency of 3CLpros of Human Coronaviruses Based on the X-ray Crystal Structure of the Catalytic Domain of SARS-CoV-2 3CLpro.

3CLpro of SARS-CoV-2 is a promising target for developing anti-COVID19 agents. In order to evaluate the catalytic activity of 3CLpros according to the presence or absence of the dimerization domain, two forms had been purified and tested. Enzyme kinetic studies with a FRET method revealed that the catalytic domain alone presents enzymatic activity, despite it being approximately 8.6 times less than that in the full domain. The catalytic domain was crystallized and its X-ray crystal structure has been determined to 2.3 Å resolution. There are four protomers in the asymmetric unit. Intriguingly, they were packed as a dimer though the dimerization domain was absent. The RMSD of superimposed two catalytic domains was 0.190 for 182 Cα atoms. A part of the long hinge loop (LH-loop) from Gln189 to Asp197 was not built in the model due to its flexibility. The crystal structure indicates that the decreased proteolytic activity of the catalytic domain was due to the incomplete construction of the substrate binding part built by the LH-loop. A structural survey with other 3CLpros showed that SARS-CoV families do not have interactions between DM-loop due to the conformational difference at the last turn of helix α7 compared with others. Therefore, we can conclude that the monomeric form contains nascent enzyme activity and that its efficiency increases by dimerization. This new insight may contribute to understanding the behavior of SARS-CoV-2 3CLpro and thus be useful in developing anti-COVID-19 agents.

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.

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.

Effect of mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease: Randomized controlled trial.

OBJECTIVES: To evaluate the effects of a mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease. METHODS: A randomized controlled design was used. The participants were randomly assigned to an intervention or a control group. The intervention group (n = 20) received mobile health intervention comprising mobile applications, smartwatches, smartphone-based short text messages and information, and telephone counselling; whereas the control group (n = 23) received short text messages and telephone counselling for 16 weeks. RESULTS: After 16 weeks, self-efficacy and non-motor symptom scores in the intervention group significantly improved compared to those in the control group. However, no significant differences were observed in the motor symptoms, self-management, and quality of life between the groups. CONCLUSIONS: The mobile health intervention for self-management is effective for self-efficacy and non-motor symptoms in people with Parkinson's disease.

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.

A study of inhibitors of d-glycero-ß-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei as a potential antibiotic target.

d-Glycero-ß-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei (BpHldC) is the fourth enzyme in the ADP-l-glycero-ß-d-manno-heptose biosynthesis pathway producing a lipopolysaccharide core. Therefore, BpHldC is an anti-melioidosis target. Three ChemBridge compounds purchased from ChemBridge Corporation (San Diego, CA) were found to have an effective inhibitory activity on BpHldC. Interestingly, ChemBridge 7929959 was the most effective compound due to the presence of the terminal benzyl group. The enzyme kinetic study revealed that most of them show mixed type inhibitory modes against ATP and ßG1P. The induced-fit docking indicated that the medium affinity of ChemBridge 7929959 is originated from its benzyl group occupying the substrate-binding pocket of BpHldC. The inhibitory role of terminal aromatic groups was proven with ChemBridge 7570508. Combined with the previous study, ChemBridge 7929959 is found to work as a dual inhibitor against both HldC and HddC. Therefore, three ChemBridge compounds can be developed as a potent anti-melioidosis agent with a novel inhibitory concept.

A triple-targeting inhibitory activity of Rose Bengal on polysaccharide biosynthesis of Burkholderia pseudomallei.

Sugar nucleotidyltransferases (SNTs) participate in various biosynthesis pathways constructing polysaccharides in Gram-negative bacteria. In this study, a triple-targeting inhibitory activity of Rose Bengal against SNTs such as d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC), d-glycero-ß-d-manno-heptose-1-phosphate adenylyltransferase (HldC), and 3-deoxy-d-manno-oct-2-ulosonic acid cytidylyltransferase (KdsB) from Burkholderia pseudomallei is provided. Rose Bengal effectively suppresses the nucleotidyltransferase activity of the three SNTs, and its IC50 values are 10.42, 0.76, and 5.31 µM, respectively. Interestingly, Rose Bengal inhibits the three enzymes regardless of their primary, secondary, tertiary, and quaternary structural differences. The experimental results indicate that Rose Bengal possesses the plasticity to shape its conformation suitable to interact with the three SNTs. As HddC functions in the formation of capsular polysaccharides and HldC and KdsB produce building blocks to constitute the inner core of lipopolysaccharide, Rose Bengal is a potential candidate to design antibiotics in a new category. In particular, it can be developed as a specific antimelioidosis agent. As the mortality rate of the infected people caused by B. pseudomallei is quite high, there is an urgent need for specific antimelioidosis agents. Therefore, a further study is being carried out with derivatives of Rose Bengal.

Transabdominal fetal reduction: a report of 124 cases.

To prevent fetal loss, preterm delivery, and perinatal morbidity of multifetal pregnancies (MPs), fetal reduction (FR) is offered to some patients. We retrospectively analysed the data of 124 MPs that underwent transabdominal FR to twin (n = 63) and singleton (n = 61) pregnancies at a mean gestational age of 12 + 6 weeks between December 2006 and January 2018. FR was performed transabdominally with the injection of potassium chloride into the intracardiac or intrathoracic space of the fetus or fetuses after ultrasound screening for nuchal translucency and anatomical defects. The initial number of embryos were 48 twins, 63 triplets, 11 quadruplets, and 2 quintuplets. The procedure-related pregnancy loss rate was 0.8% (1/124), the overall pregnancy loss rate was 2.4% (3/124), the fetal loss rate was 1.6% (2/124), and the neonatal death rate was 0.8% (1/124). The baby take-home rates were 96% for twin pregnancies and 96.7% for singletons. This study shows that transabdominal FR is an effective and safe procedure with a pregnancy loss rate of 2.4%.Impact statementWhat is already known on this subject? The incidence of multifetal pregnancies has increased over the years. Because multifetal pregnancies increase perinatal morbidity and mortality due to prematurity, fetal reduction is offed to some patients.What the results of this study add? The results of this study add to the growing body of research on fetal reduction. The study showed that transabdominal fetal reduction is a safe procedure with a pregnancy loss rate of 2.4%.What the implications are of these findings for clinical practice and/or further research? The results of this study can be used in counselling couples with multifetal pregnancies who are considering fetal reduction. Further research is needed to confirm the current findings.

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.

In vivo evaluation of scaffolds compatible for colonoid engraftments onto injured mouse colon epithelium.

Colon organoids (colonoids) are known to be similar to colon tissue in structure and function, which makes them useful in the treatment of intestinal de-epithelialized disease. Matrigel, which is used as a transplantation scaffold for colonoids, cannot be used in clinical applications because of its undefined composition and tumorigenicity. This study identifies clinically available scaffolds that are effective for colonoid transplantation in damaged intestinal mucosa. The colon crypt was isolated and cultured from C57BL/6-Tg[CAG enhanced green fluorescent protein (EGFP)131Osb/LeySopJ mice into EGFP + colonoids and subsequently transplanted into the EDTA colitis mouse model using gelatin, collagen, or fibrin glue scaffolds. To identify scaffolds suitable for colonoid engraftment in injured colon mucosa, the success rates of transplantation and secondary EGFP colonoid formation were measured, and the scaffolds' mediated toxicity in vitro and in vivo was observed in recipient mice. When colonoids were transplanted with gelatin, collagen, and fibrin glue into the EDTA colitis mouse model, all groups were found to be successfully engrafted. Fibrin glue, especially, showed significant increase in the engrafted area compared with Matrigel after 4 wk. The scaffolds used in the study did not induce colonic toxicity after transplantation into the recipients' colons and were thus deemed safe when locally administrated. This study suggests new methods for and provides evidence of the safety and utility of the clinical application of colonoid-based therapeutics. Furthermore, the methods introduced in this study will be helpful in developing cell treatment using the esophagus or a stomach organoid for various digestive-system diseases.-Jee, J., Jeong, S. Y., Kim, H. K., Choi, S. Y., Jeong, S., Lee, J., Ko, J. S., Kim, M. S., Kwon, M.-S., Yoo, J. In vivo evaluation of scaffolds compatible for colonoid engraftments onto injured mouse colon epithelium.

Treatment of superimposed preeclampsia on chronic hypertension in a twin pregnancy with automatic continuous positive airway pressure: a case report.

BACKGROUND: Obstructive sleep apnoea (OSA) is related with adverse pregnancy outcomes, including preeclampsia. However, there are small studies about treatment of OSA with automatic continuous positive airway pressure (CPAP) in adverse obstetric outcomes. CASE PRESENTATION: We introduce a case of 34 year old twin pregnant woman diagnosed with superimposed preeclampsia on chronic hypertension at 28 + 1/7 weeks of gestation. A level III polysomnography showed obstructive sleep apnoea, and automatic CPAP was applied. After the CPAP treatment concomitant with an antihypertensive drugs, both blood pressure and urinary protein concentration were reduced. The pregnancy safely continued for 49 days (to 35 + 1/7 weeks), with stable blood pressure, allowing prolongation of gestation of the foetuses. CONCLUSION: This is the first case to report OSA with preeclampsia in a twin pregnancy. Our results suggest that automatic CPAP as an adjunct treatment to antihypertensive drugs may be beneficial in controlling blood pressure in early-onset preeclampsia associated with OSA.