A Simple Scoring System for Identifying Favorable Neurologic Outcomes Among Out-of-Hospital Cardiac Arrest Patients With Asystole.

STUDY OBJECTIVE: Asystole is the most common initial rhythm in out-of-hospital cardiac arrest (OHCA) but indicates a low likelihood of neurologic recovery. This study aimed to develop a novel scoring system to be easily applied at the time of emergency department arrival for identifying favorable neurologic outcomes in OHCA survivors with an asystole rhythm. METHODS: This study is a secondary analysis based on a previously collected nationwide database, targeting nontraumatic adult OHCA patients aged ≥18 years with an asystole rhythm who achieved return of spontaneous circulation (ROSC) between January 2016 and December 2020. The primary outcome was a favorable neurologic outcome defined as Cerebral Performance Categories scores of 1 or 2 at hospital discharge. A prediction model was developed through multivariable logistic regression analysis in a derivation cohort in the form of a scoring system (WBC-ASystole). The performance and calibration of the model were tested using an internal validation cohort. RESULTS: Among 19,803 OHCA patients with survival to hospital admission, 6,322 had asystole, and 285 (4.5%) achieved good neurologic outcomes. Factors associated with favorable outcomes included age, witness arrest, bystander cardiopulmonary resuscitation, time from call to hospital arrival, and out-of-hospital ROSC achievement. The WBC-ASystole score, totaling 11 points, exhibited a predictive performance with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval [CI] 0.76 to 0.83) and 0.79 (95% CI 0.74 to 0.83) in the derivation and validation cohorts, respectively. After categorizing patients into 3 groups based on probability for good neurologic outcomes, the sensitivity and specificity were as follows: 0.98 (95% CI 0.97 to 0.99) and 0.09 (95% CI 0.09 to 0.10) for the very low predicted probability group (WBC-ASystole ≤2), 0.85 (95% CI 0.82 to 0.89) and 0.54 (95% CI 0.53 to 0.55) for the low predicted probability group (WBC-ASystole 3 to 4), and 0.36 (95% CI 0.34 to 0.39) and 0.93 (95% CI 0.92 to 0.93) for fair predicted probability group (WBC-ASystole≥5), respectively. CONCLUSIONS: Although external validation studies must be performed, among OHCA patients with asystole, the WBC-ASystole scoring system may identify those patients who are likely to have a favorable neurologic outcome.

Cardiac Arrest Caused by Anaphylaxis Refractory to Prompt Management.

BACKGROUND: Anaphylaxis is a potentially life-threatening condition that occurs in the emergency department (ED). Although anaphylaxis is rapidly recognized and treated in the hospital compared with that in the community, in some cases, it does not respond to proper management. OBJECTIVE: The aim of this study is to describe our experience of cases of refractory anaphylaxis leading to cardiac arrest in hospital, to review their characteristics compared with those seen in the community, and to discuss the best management practices for anaphylaxis-induced cardiac arrest with a literature review. METHODS: We reviewed the medical records of patients referred to the ED with possible in-hospital anaphylaxis between January 2017 and May 2021. According to the anaphylaxis protocol, epinephrine, corticosteroid, and antihistamine were administered immediately on-site at our institution before the study period. Refractory anaphylaxis was defined as the development of anaphylaxis-induced cardiac arrest even after following the anaphylaxis protocol. RESULTS: A total of 246 cases were evaluated for possible anaphylaxis, with 236 cases meeting the criteria for a diagnosis of anaphylaxis. Among them, 178 patients showed the signs and symptoms of shock, and cardiac arrest occurred in 6 patients (2.5%). Of the six patients, three had a return of spontaneous circulation before admission to the ED, while two died due to refractory cardiac arrest despite resuscitation in the ED. Following post-cardiac arrest care, including temperature management, one patient who received extracorporeal cardiopulmonary resuscitation survived neurologically intact. CONCLUSION: We present our case series to highlight the risk of developing refractory anaphylaxis with subsequent in-hospital cardiac arrest. Patients may progress to cardiac arrest within minutes despite prompt recognition and management. If patients present with potentially fatal symptoms, a more aggressive approach, including intravenous adrenaline infusion, should be taken.

Cervical Spine Dysmorphism in Congenital Muscular Torticollis.

BACKGROUND: Congenital muscular torticollis is a common childhood musculoskeletal anomaly that might result in permanent craniofacial deformity, facial asymmetry, and changes in the cervical vertebrae, if not treated during early childhood. Although there have been many studies on cervical vertebral changes, their onset in children has not been previously studied. METHODS: Fifteen patients (aged <8 years) with a confirmed diagnosed of torticollis were included. Three-dimensional computed tomography scans were obtained, and segmentation of the cervical vertebrae was done. Division of the atlas and axis across the midsagittal plane was done to compare the anatomical changes. The volumes of each halves of the atlas and axis were measured. RESULTS: An apparent change was observed in the axis of the vertebral column when compared with that of the skull. There were progressive anatomical changes affecting the upper cervical vertebrae, which started to develop around the age of 8 months and became more evident in older children. The axis vertebra was the first to be affected. Rotational and bending deformities were the most likely changes to occur. Pearson correlation analysis showed a statistically significant trend in the volume and height changes for both halves of the atlas and axis (P < 0.001 and P < 0.001). CONCLUSIONS: Children with untreated congenital muscular torticollis show progressive anatomical changes of the cervical vertebrae which started at the age of 8 months. The severity of the deformity increased with the advance of age as well as with the severity of sternocleidomastoid tightness, which might result in permanent deformities.

Cervical Spine Deformity in Long-Standing, Untreated Congenital Muscular Torticollis.

BACKGROUND: Congenital muscular torticollis (CMT) is a benign condition. With early diagnosis and appropriate management, it can be cured completely, leaving no residual deformity. However, long-standing, untreated CMT can lead to permanent craniofacial deformities and asymmetry. METHODS: Four adult patients presented to the author with long-standing, untreated CMT. Initial clinical assessment demonstrated tightness of the sternocleidomastoid muscle on the affected side. Investigation of cervical spine using 3-dimensional computed tomography scans with cervical segmentation allowed a 3-dimensional module to be separately created for each vertebra to detect any anatomical changes. RESULTS: A change in the axis of the vertebral column was noted when compared to that of the skull. Also, there were apparent anatomical changes affecting the vertebrae, which were most noticeable at the level of the atlas and axis vertebrae. These changes decreased gradually till reaching the seventh cervical vertebra, which appeared to be normal in all patients. The changes in the atlas vertebra were mostly due to its intimate relation with the skull base. The changes of the axis were the most significant, affecting mainly the superior articular facet, the lamina, and the body. CONCLUSIONS: There were seemingly permanent changes along the cervical spine region in the adult patients with long-standing, untreated CMT in the form of bending and rotation deformities that might result in residual torticollis postoperatively.

Characteristics of patients with psoriatic arthritis in Korea: focusing on axial involvement.

BACKGROUND/AIMS: We aimed to clarify the clinical characteristics of psoriatic arthritis (PsA) in Korean patients focusing on PsA with axial involvement. METHODS: A retrospective medical chart review was performed to identify PsA patients at a single tertiary center. Cases of AS patients with psoriasis were recruited from a prospective AS registry of the same center. Demographics, laboratory findings, and radiologic characteristics were assessed. RESULTS: A total of 69 PsA patients were identified. In PsA patients, spondylitis (46.4%) was the most common form. Compared to AS patients with psoriasis, PsA patients with radiographic axial involvement were older (50.9 vs. 32.4 years; p < 0.001) and showed greater peripheral disease activity (peripheral arthritis 78.1 vs. 12.5%, p < 0.001; enthesitis 50.0 vs. 6.3%, p = 0.003). AS patients with psoriasis presented a higher rate of HLA-B*27 positivity (81.3 vs. 17.2%; p < 0.001) and a more frequent history of inflammatory back pain (100.0 vs. 75.0%; p = 0.039) than PsA patients with radiographic axial involvement. Significant proportions of PsA patients with radiographic axial involvement had cervical spine involvement (10/18, 55.6%) and spondylitis without sacroiliitis (10/23, 43.5%). CONCLUSION: We demonstrate that axial involvement is common in Korean PsA patients, and its characteristics can be distinct from those of AS.

Retinal degeneration increases susceptibility to myopia in mice.

PURPOSE: Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. METHODS: Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6b(rd1/rd1) (rd1), or Pde6b(rd10/rd10) (rd10) was measured weekly from 4 to 12 weeks of age and compared to age-matched wild-type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head-mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured with high-performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. RESULTS: The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (-6.14±0.62 and -7.38±1.46 diopter, respectively) compared to the WT mice (-2.41±0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. CONCLUSIONS: Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge.

Unveiling the Diversity of Hydnum in the Republic of Korea with One New Species, Hydnum paucispinum.

Hydnum is a genus of ectomycorrhizal fungi belonging to the Hydnaceae family. It is widely distributed across different regions of the world, including North America, Europe, and Asia; however, some of them showed disjunct distributions. In recent years, with the integration of molecular techniques, the taxonomy and classification of Hydnum have undergone several revisions and advancements. However, these changes have not yet been applied in the Republic of Korea. In this study, we conducted an integrated analysis combining the morphological and molecular analyses of 30 specimens collected over a period of approximately 10 years in the Republic of Korea. For molecular analysis, the sequence data of the internal transcribed spacer (ITS) region, the large subunit of nuclear ribosomal RNA gene (nrLSU), and a portion of translation elongation factor 1-α (TEF1) were employed as molecular markers. Through this study, we identified eight species that had previously not been reported to occur in the Republic of Korea, including one new species, Hydnum paucispinum. A taxonomic key and detailed descriptions of the eight Hydnum species are provided in this study.

HDAC2 overexpression confers oncogenic potential to human lung cancer cells by deregulating expression of apoptosis and cell cycle proteins.

Histone deacetylase 2 (HDAC2) is crucial for embryonic development, affects cytokine signaling relevant for immune responses, and is often significantly overexpressed in solid tumors, but little is known of its role in human lung cancer. In this study, we demonstrated the aberrant expression of HDAC2 in lung cancer tissues and investigated oncogenic properties of HDAC2 in human lung cancer cell lines. HDAC2 inactivation resulted in regression of tumor cell growth and activation of cellular apoptosis via p53 and Bax activation and Bcl2 suppression. In cell cycle regulation, HDAC2 inactivation caused induction of p21WAF1/CIP1 expression, and simultaneously suppressed the expressions of cyclin E2, cyclin D1, and CDK2, respectively. Consequently, this led to the hypophosphorylation of pRb protein in G1/S transition and thereby inactivated E2F/DP1 target gene transcriptions of A549 cells. In addition, we demonstrated that HDAC2 directly regulated p21WAF1/CIP1 expression in a p53-independent manner. However, HDAC1 was not related to p21WAF1/CIP1 expression and tumorigenesis of lung cancer. Lastly, we observed that sustained-suppression of HDAC2 in A549 lung cancer cells attenuated in vitro tumorigenic properties and in vivo tumor growth of the mouse xenograft model. Taken together, we suggest that the aberrant regulation of HDAC2 and its epigenetic regulation of gene transcription in apoptosis and cell cycle components play an important role in the development of lung cancer.

Crosstalk between cold response and flowering in Arabidopsis is mediated through the flowering-time gene SOC1 and its upstream negative regulator FLC.

The appropriate timing of flowering is pivotal for reproductive success in plants; thus, it is not surprising that flowering is regulated by complex genetic networks that are fine-tuned by endogenous signals and environmental cues. The Arabidopsis thaliana flowering-time gene SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) encodes a MADS box transcription factor and is one of the key floral activators integrating multiple floral inductive pathways, namely, long-day, vernalization, autonomous, and gibberellin-dependent pathways. To elucidate the downstream targets of SOC1, microarray analyses were performed. The analysis revealed that the soc1-2 knockout mutant has increased, and an SOC1 overexpression line has decreased, expression of cold response genes such as CBFs (for CRT/DRE binding factors) and COR (for cold regulated) genes, suggesting that SOC1 negatively regulates the expression of the cold response genes. By contrast, overexpression of cold-inducible CBFs caused late flowering through increased expression of FLOWERING LOCUS C (FLC), an upstream negative regulator of SOC1. Our results demonstrate the presence of a feedback loop between cold response and flowering-time regulation; this loop delays flowering through the increase of FLC when a cold spell is transient as in fall or early spring but suppresses the cold response when floral induction occurs through the repression of cold-inducible genes by SOC1.

Comparability studies of new 3rd generation recombinant human factor VIII GreenGene F after improvement of formulation and viral inactivation/removal process.

A new 3rd generation recombinant factor VIII (rFVIII), GreenGene F (WHO INN: beroctocog alfa), which is a highly homogenous B-domain deleted FVIII protein comprising of two peptides as heavy chain (A1 and A2 domain) and light chain (A3, C1, and C2 domain) at 80 and 90 kDa, was developed from its predecessor product GreenGene (2nd generation product previously approved by Korea FDA after clinical studies in South Korea) by process improvements of i) addition of Solvent/Detergent treatment for virus inactivation, ii) nanofiltration (20 nm pore size) for viral removal and iii) alterations to an albumin-free formulation to minimize the risk of viral contamination. An assessment of comparability between the two products was made to see if process improvements for safer product manufacturing affected the rFVIII structural and functional characteristics. Physicochemical and physiological characteristics were observed, in vivo efficacy following a single intravenous administration to FVIII knock-out mice and toxicity by various GLP in vivo tests were evaluated. All results showed equivalence, proving that no changes in protein characteristics of rFVIII occurred from process changes in formulation, viral inactivation, and viral removal which minimize the risk of pathogen transmission to enhance safety.

A Rare Case of Ankylosing Spondylitis Coexisting with Relapsing Polychondritis, Antiphospholipid Syndrome, and Myelodysplastic Syndrome.

Ankylosing spondylitis (AS) is rarely accompanied by other autoimmune diseases and/or hematologic disorders. We herein report a 46-year-old man with AS coexisting with relapsing polychondritis (RP), antiphospholipid syndrome (APS) and myelodysplastic syndrome (MDS). While receiving anti-TNF therapy for AS, the patient developed anemia and was diagnosed with MDS. After six months, he developed swelling and redness of the nose and both auricles. RP was diagnosed by an ear biopsy. Afterward, during the evaluation of a repeated fever, APS was diagnosed. This case of AS with multiple autoimmune diseases and hematologic malignancy successfully responded to a Janus kinase inhibitor (baricitinib).

Characterization of a Translucent Material Produced from Paulownia tomentosa Using Peracetic Acid Delignification and Resin Infiltration.

Paulownia tomentosa, a tree species that allows for efficient production of translucent wood, was selected as an experimental wood species in this study, and a two-step process of delignification and polymer impregnation was performed. For delignification, 2-4 mm thick specimens were immersed in peracetic acid for 8 h. The delignified-wood specimens were impregnated using epoxy, a commercial transparent polymer. To identify the characteristics of the resulting translucent wood, the transmittance and haze of each type of wood section (cross- and tangential) were measured, while bending strength was measured using a universal testing machine. The translucent wood varied in properties according to the wood section, and the total transmittance and haze were 88.0% and 78.5% for the tangential section and 91.3% and 96.2% for the cross-section, respectively. For the bending strength, untreated wood showed values of approximately 4613.5 MPa modulus of elasticity (MOE), while the epoxy impregnation to improve the strength of the wood had increased the MOE up to approximately 6089.9 MPa, respectively. A comparative analysis was performed in this study with respect to the substitution of balsa, which is used widely in the production of translucent wood. The results are anticipated to serve as baseline data for the functionalization of translucent wood.

Recurrent Cardiogenic Syncope From Extrinsic Organ Anomaly.

CASE PRESENTATION: A 40-year-old woman presented with recurrent syncope. She reported multiple (>20) episodes of non-prodromal loss of consciousness, periodically provoked by physical exertion. One episode resulted in a nasal fracture due to the abrupt nature of her syncope. The characterization of each episode was inconsistent with a neurogenic seizure. Other causes of syncope (vasovagal, situational, carotid hypersensitivity, and orthostasis) were also deemed unlikely. On physical examination, a low-pitched, brief adventitious sound was appreciated after each S2 sound in the right lower sternal border. The remainder of the physical examination was unremarkable. Initial workup, including complete blood count, comprehensive metabolic panel, cardiac enzymes, and ECG yielded normal results. The chest radiograph did not show any gross cardiac or pulmonary parenchymal pathologic condition (Fig 1). Telemetry did not demonstrate any malignant arrhythmias, and video-guided EEG did not document any seizure activity.

Stoichiometric Doping of Highly Coupled Cu2-xS Nanocrystal Assemblies.

The hole density of individual copper sulfide nanocrystals (Cu2-xS NCs) is determined from the stoichiometric mismatch (x) between copper and sulfide atoms. Consequently, the electronic properties of the material vary over a range of x. To exploit Cu2-xS NCs in devices, assemblies of NCs are typically required. Herein, we investigate the influence of x, referred to as the stoichiometric doping effect, on the structural, optical, electrical, and thermoelectric properties of electronically coupled Cu2-xS NC assemblies. The doping process is done by immersing the solid NC assemblies into a solution containing a Cu(I) complex for different durations (0-10 min). As Cu+ gradually occupied the copper-deficient sites of Cu2-xS NCs, x could be controlled from 0.9 to less than 0.1. Consequently, the near-infrared (NIR) absorbance of Cu2-xS NC assemblies changes systematically with x. With increasing x, electrical conductivity increased and the Seebeck coefficient decreased systematically, leading to the maximal thermoelectric power factor from a film of Cu2-xS NCs at an optimal doping condition yielding x = 0.1. The physical characteristics of the Cu2-xS NC assemblies investigated herein will provide guidelines for exploiting this emerging class of nanocrystal system based on doping.

Supporting High-Risk Percutaneous Coronary Interventions With Mechanical Devices.

The use of mechanical circulatory support to maintain appropriate hemodynamics in high risk percutaneous coronary intervention cases is a new frontier. Treatment of cases that were once considered prohibitive may now be possible. Due to a paucity of data, guidelines offer no guidance about the use of mechanical circulatory support in such cases. This case, the first documented case of extracorporeal membrane oxygenation support for percutaneous coronary intervention (PCI) of a vein graft supplying the entire coronary circulation, adds to the medical literature demonstrating a likely benefit in the use of mechanical support during high risk PCI in patients without shock. (Level of Difficulty: Intermediate.).

SOC1 translocated to the nucleus by interaction with AGL24 directly regulates leafy.

SUMMARY: Suppressor of overexpression of constans1 (SOC1) is one of the flowering pathway integrators and regulates the expression of LEAFY (LFY), which links floral induction and floral development. However, the mechanism by which SOC1, a MADS box protein, regulates LFY has proved elusive. Here, we show that SOC1 directly binds to the distal and proximal region of the LFY promoter where critical cis-elements are located. Intragenic suppressor mutant analysis shows that a missense mutation in the MADS box of SOC1 causes loss of binding to the LFY promoter as well as suppression of the flowering promotion function. The full-length SOC1 protein locates in the cytoplasm if expressed alone in protoplast transient expression assay, but relocates to the nucleus if expressed with AGAMOUS-LIKE 24 (AGL24), another flowering pathway integrator and a MADS box protein. The domain analysis shows that co-localization of SOC1 and AGL24 is mediated by the MADS box and the intervening region of SOC1. Finally, we show that LFY is expressed only in those tissues where SOC1 and AGL24 expressions overlap. Thus, we propose that heterodimerization of SOC1 and AGL24 is a key mechanism in activating LFY expression.

Effect of pH and precursor salts on in situ formation of calcium phosphate nanoparticles in methylcellulose hydrogel.

Thermo-reversible hydrogels have been widely studied in biomedical research fields, because of their potential performance in drug delivery and tissue engineering. In this study, a novel thermo-sensitive methylcellulose (MC) hydrogel based on calcium phosphate nanoparticles (CaP NPs) was prepared by in situ formation process in which precursor salts induced a salt-out effect in the MC solution. Based on the Hofmeister series, CaCl2, Na2HPO4, and NaH2PO4 precursor salts with a good salt-out effect were used as the precursor salts for CaP NPs. The gelation of MC solution was accelerated by the salt addition, and its effect varied with the salt type. When CaP precursor salts with two different Ca/P ratios (0.8/1 and 1.6/1) were added into the MC solution, more elastic MC hydrogel was formed at 1.6/1 Ca/P ratio. The CaP NPs were rectangular in shape (40-50 nm), and evenly distributed in the MC gel. The X-ray diffraction (XRD) observation indicates that dicalcium phosphate dehydrate (DCPD) and octacalcium phosphate (OCP) were synthesized at 0.8/1 Ca/P ratio, whereas DCPD was synthesized at 1.6/1 Ca/P ratio. This indicates that the CaP NPs with different crystalline phases were in situ synthesized in accordance with the Ca/P ratio and pH condition (pH 7.4, 9.0). Moreover, the DCPD and OCP crystalline phases were converted to the hydroxyapatite (HAP) crystalline phase, as the pH was changed to alkaline region. Therefore, the resulting MC composite hydrogel containing HAP NPs will be suitable for bone regeneration as an injectable hydrogel.

Effect of vitamin derivatives on gelation rate and gel strength of methylcellulose.

A thermo-sensitive methylcellulose (MC) hydrogel was prepared using three types of vitamin derivatives with or without phosphate groups. The gelation behavior of each MC hydrogel containing vitamin or vitamin derivatives was monitored using a rheometer. The gelation rate and mechanical strength of the MC hydrogels were improved by vitamin derivatives with phosphate groups due to their salting-out effects, whereas their injectabilities retained proper maximum forces. Also, the vitamin derivatives with phosphate groups were released slower from the MC hydrogel than the vitamins without phosphate groups due to higher physical crosslinking densities. Therefore, this thermo-responsive MC hydrogel containing vitamin derivatives has a great potential as an injectable hydrogel for drug delivery.

Analysis of the correlation between deformational plagiocephaly and neurodevelopmental delay.

BACKGROUND: Deformational plagiocephaly (DP) refers to cranial asymmetry resulting from uneven external forces. A strong association exists between DP and developmental delay. We investigated the effect of DP severity on developmental delay. METHODS: Between 2010 and 2016, data from 155 patients with DP were reviewed retrospectively. Two indices were used to evaluate the deformation quantitatively: cranial index (CI) and cranial vault asymmetry index (CVAI). The Bayley Scales of Infant Development-II was used to evaluate the neurodevelopment of patients. RESULTS: According to the CI of the study population, 2 patients showed scaphocephaly, 12 showed mesocephaly, and 141 showed brachycephaly. For CVAI, 10 patients showed values of <3.5, 10 patients showed mild deformity (3.5-6.25), 27 patients showed moderate deformity (6.25-8.75), and 108 patients showed severe deformity. The means of the mental development index (MDI) and psychomotor development index (PDI) were 91.69 ± 16.8 and 92.28 ± 17.59, respectively; after the exclusion of patients with confounding factors, the values were 96.26 and 92.9, respectively. The Spearman correlation coefficients between MDI and CI and CVAI were -0.019662 and 0.118916, respectively, whereas for PDI, the values were -0.195428 and -0.012386, respectively. CONCLUSIONS: There was a statistically significant neurodevelopmental delay in patients with DP. However, accelerated neurodevelopment was also encountered in many patients. MDI was found to be more affected by multiple confounding factors than PDI, whereas PDI was only affected by congenital anomalies. There was no definitive relationship between the severity of DP and the degree of developmental delay in our study group.

Dual effects of a CpG-DNAzyme targeting mutant EGFR transcripts in lung cancer cells: TLR9 activation and EGFR downregulation.

Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells. [BMB Reports 2018; 51(1): 27-32].