The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans.

Eukaryotic cells regulate 5'-triphosphorylated RNAs (ppp-RNAs) to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR-1 (phosphatase that interacts with RNA and ribonucleoprotein particle 1) family of RNA polyphosphatases remove both the ß and γ phosphates from ppp-RNAs. Here, we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RNA-dependent RNA polymerases (RdRPs) and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in both somatic and germline development. Our findings suggest that PIR-1 modulates both Dicer-dependent and Dicer-independent Argonaute pathways and provide insight into how cells and viruses use a conserved RNA phosphatase to regulate and respond to ppp-RNA species.

Exosomal miR-155-5p drives ibrutinib resistance in B-cell lymphoma.

Ibrutinib, a Bruton Tyrosine Kinase (BTK) inhibitor, has shown effectiveness against various B-cell lymphoid malignancies. However, prolonged usage can induce resistance, affecting treatment outcomes. The oncogenic microRNA, miR-155-5p, is associated with poor prognosis in B-cell lymphomas, prompting our investigation into the mechanism of acquired ibrutinib resistance in these cells. We generated ibrutinib-resistant OCI-Ly1 cells (OCI-Ly1-IbtR) through continuous exposure to 1 µM and 2 µM of ibrutinib. We conducted microRNA profiling of OCI-Ly1-IbtR and isolated exosomes via ultracentrifugation. Comparative studies of microRNA levels in cells and exosomes, as well as exploration of targets of up-regulated microRNAs in OCI-Ly1-IbtR, were performed. Target validation involved transfection of candidate microRNAs, and co-culture experiments utilized OCI-Ly1 cells with exosomes from OCI-Ly1-IbtR. Elevated levels of miR-155-5p were observed in OCI-Ly1-IbtR and its exosomes, correlating with AKT and NF-κB activation. Transfection of miR-155-5p induced AKT/NF-κB pathway activation in OCI-Ly1, resulting in ibrutinib resistance, enhanced colony formation, and sustained BTK activity. Primary cell lines from ibrutinib-refractory B-cell lymphoma patients exhibited similar signaling protein activation. Target evaluation identified KDM5B and DEPTOR as miR-155-5p targets, confirmed by downregulation after transfection. We observed KDM5B and DEPTOR enrichment in Ago2 during ibrutinib resistance and miR-155-5p transfection. Co-culture experiments demonstrated exosome-mediated transfer of miR-155-5p, inducing ibrutinib resistance and KDM5B/DEPTOR downregulation in OCI-Ly1. Our findings suggest that miR-155-5p overexpression is associated with AKT and NF-κB pathway activation in ibrutinib-resistant cells, proposing a potential role for acquired miR-155-5p upregulation in B-cell lymphoma ibrutinib resistance.

Ion Selectivity, Current, and Water Flow Regulation in Ti3C2 MXene Nanopores.

Recent years have seen a growing interest in zero-dimensional (0D) transport phenomena occurring across two-dimensional (2D) materials for their potential applications to nanopore technology such as ion separation and molecular sensing. Herein, we investigate ion transport through 1 nm-wide nanopores in Ti3C2 MXene using molecular dynamics simulations. The high polarity and fish-bone arrangement of the Ti3C2 MXene offer a built-in potential and an atomic-scale distortion to the nanopore, causing an adsorption preference for cations. Our observation of variable cation-specific ion selectivity and Coulomb blockade highlights the complex interplay between adsorption affinity and cation size. The cation-specific ion selectivity can induce both the ion current and electro-osmotic water transmission, which can be regulated by tailoring the ions' preferential pathways through electric field tilting. Our finding underscores the pivotal role of the atomic arrangement of MXenes in 0D ion transport and provides fundamental insight into the application of 2D material in nanopores-based technologies.

PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma.

BACKGROUND: Although a combination of immune checkpoint inhibitors (ICIs) is recommended as the first line treatment option for metastatic renal cell carcinoma (mRCC), several immune-related adverse events (irAEs) occur, especially hepatitis. We explored the therapeutic benefits and safety profile of combining oncolytic vaccinia virus, JX-594, with a programmed cell death protein-1 (PD-1) inhibitor. METHODS: We used early-stage and advanced-stage orthotopic murine mRCC models developed by our group. PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with either JX-594 or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor were systemically injected through the peritoneum. An immunofluorescence analysis was performed to analyze the tumor immune microenvironment (TIME). irAEs were assessed in terms of hepatitis. RESULTS: In the early-stage mRCC model mice, the combination of JX-594 and a PD-1 inhibitor significantly decreased the primary tumor size and number of lung nodules, compared with the ICI combination, but the JX-594 and PD-1 inhibitor combination and ICI combination did not differ significantly in the advanced-stage mRCC model mice. The JX-594 and PD-1 inhibitor combination induced tumor-suppressing TIME changes in both the early- and advanced-stage mRCC models. Furthermore, mice treated with the ICI combination had significantly greater hepatic injuries than those treated with the JX-594 and PD-1 inhibitor combination which was evaluated in early-stage mRCC model. CONCLUSIONS: The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity.

Selection of Catechin Biosynthesis-Related Genes and Functional Analysis from Chromosome-Level Genome Assembly in C. sinensis L. Variety 'Sangmok'.

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.

Efficacy of Asymmetric siRNA Targeting Androgen Receptors for the Treatment of Androgenetic Alopecia.

Asymmetric small interfering RNAs (asiRNAs) that mediate RNA interference have been investigated for therapeutic use in various tissues, including skin tissue. Androgenetic alopecia (AGA) is caused by a combination of genetic factors, resulting in sensitivity to dihydrotestosterone (DHT), which binds to the androgen receptor (AR) to mediate a series of biomolecular changes leading to hair loss. This study aimed to evaluate the therapeutic potential of a cell-penetrating, AR-targeting asiRNA (cp-asiAR) for AGA treatment, which was designed to silence the AR gene. AGA mouse models were developed by stimulation with DHT, and ex vivo human scalp tissues were also used for analysis. Cp-asiAR-mediated changes in mRNA expression and protein levels of AR were assessed along with the examination of phenotypic improvements in mouse model of AGA. We also assessed downstream signaling associated with AR in primary human dermal papilla (DP) cells. Several cp-asiARs were screened for selecting the optimal sequence of AR using cell lines in vitro. A cholesterol-conjugated, chemically modified cp-asiAR candidate was optimized under passive uptake conditions in vitro. Intradermal cp-asiAR injection efficiently reduced mRNA and protein levels corresponding to AR in mouse models. Moreover, cp-asiAR injection promoted hair growth in mouse models with DHT-induced AGA. In ex vivo human hair follicle culture, the proportion of telogen hair decreased, and the mean hair bulb diameter increased in the cp-asiAR-treated group. In isolated primary human DP cells, AR expression was effectively downregulated by cp-asiAR. Furthermore, cp-asiAR attenuated DHT-mediated increases in interleukin-6, transforming growth factor-ß1, and dickkopf-1 levels. No significant toxicity was observed in DP cells after cp-asiAR treatment. Cp-asiAR treatment showed effective downregulation of AR expression and prevention of DHT-mediated alterations in the hair cycle and hair diameter, indicating its potential as a novel therapeutic option for AGA.

Discovery of GCC5694A: A potent and selective sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes.

Sodium-dependent glucose co-transporter 2 (SGLT2) has emerged as a promising drug target for the treatment of type 2 diabetes, and recently, several SGLT2 inhibitors have been approved for clinical use. A series of molecules with a C-aryl glucoside scaffold was designed and synthesized for biological evaluation. Among the molecules tested, a dihydrobenzofuran-containing analog, 14g (GCC5694A), exhibited excellentin vitro activity against SGLT2 (IC50 = 0.460 nM), good selectivity for SGLT1, and good metabolic stability. Data from further evaluation of the compound in animal models showed that this molecule is a promising candidate for development as an anti-diabetic agent.

Smart Homes Supporting the Wellness of One or Two-Person Households.

The reduction in face-to-face contact and the increase in time spent at home during the ongoing coronavirus disease pandemic have resulted in increasing interest and demand for smart homes. Further, the rapid increase in the number of one-person and two-person households in Korea recently has led to these becoming representative household types. This study identifies the wellness characteristics of such households and proposes a direction for smart home development to help them lead healthy, happy lives. It focuses on mapping residents' perceptions and experiences to scenarios and on identifying the functions required in smart homes and the technologies needed to provide these functions. It uses data from a survey to investigate and analyze the wellness characteristics of one- and two-person households in five dimensions and develops five scenarios of representative household types. By analyzing the developed scenarios, this study proposes smart homes that support the wellness of such households in six categories: exercise/sports, hobby/entertainment, social communications, occupation/work, self-development/education, and energy conservation. These households are exposed to digital environments from an early age and are familiar with the internet and technologies. Therefore, they are likely to adopt innovative technologies in housing. Thus, the smart home development proposed in this study is a promising strategic approach to housing planning.

Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study.

BACKGROUND: Alcohol consumption is a major risk factor for esophageal cancer; however, a high incidence of esophageal cancer is observed particularly among Eastern Asians, although they consume relatively less alcohol, presumably due to the high frequency of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms. Nevertheless, the association between ALDH2 polymorphisms and esophageal cancer remains under debate. In the present study, we evaluated the association between ALDH2 rs671 polymorphisms and the risk of esophageal cancer in the South Korean population. METHODS: This study included 783 hospital based-cases and 8732 population-based controls. Information on smoking history and alcohol consumption was obtained from the medical records or interview questionnaires. Age-adjusted logistic regression analysis was performed to assess the association between ALDH2 rs671 polymorphisms and esophageal cancer. RESULTS: Odds ratios (ORs) for esophageal cancer in men with GA and AA genotypes were 2.75 (95% confidence interval [CI]: 2.34-3.23) and 0.08 (95% CI: 0.00-0.35), respectively; whereas, in women, these ratios were 2.99 (95% CI: 1.43-6.34) and 6.18 (95% CI: 1.40-19.62), respectively, taking subjects with the ALDH2 GG genotype as a reference. In men, the association between ALDH2 polymorphisms and esophageal cancer was modified by alcohol consumption. CONCLUSION: In Eastern Asians, ALDH2 rs671 polymorphisms are associated with esophageal cancer, which may be linked to acetaldehyde accumulation.

Effect of the Nanotube Radius and the Volume Fraction on the Mechanical Properties of Carbon Nanotube-Reinforced Aluminum Metal Matrix Composites.

By using the advantages of carbon nanotubes (CNTs), such as their excellent mechanical properties and low density, CNT-reinforced metal matrix composites (MMCs) are expected to overcome the limitations of conventional metal materials, i.e., their high density and low ductility. To understand the behavior of composite materials, it is necessary to observe the behavior at the molecular level and to understand the effect of various factors, such as the radius and content of CNTs. Therefore, in this study, the effect of the CNT radius and content on the mechanical properties of CNT-Al composites was observed using a series of molecular dynamics simulations, particularly focusing on MMCs with a high CNT content and large CNT diameter. The mechanical properties, such as the strength and stiffness, were increased with an increasing CNT radius. As the CNT content increased, the strength and stiffness increased; however, the fracture strain was not affected. The behavior of double-walled carbon nanotubes (DWNTs) and single-walled carbon nanotubes (SWNTs) was compared through the decomposition of the stress-strain curve and observations of the atomic stress field. The fracture strain increased significantly for SWNT-Al as the tensile force was applied in the axial direction of the armchair CNTs. In the case of DWNTs, an early failure was initiated at the inner CNTs. In addition, the change in the elastic modulus according to the CNT content was predicted using the modified rule of mixture. This study is expected to be useful for the design and development of high-performance MMCs reinforced by CNTs.

Mitochondrial division inhibitor (mdivi-1) decreases oxidative metabolism in cancer.

BACKGROUND: Previous studies suggested that mdivi-1 (mitochondrial division inhibitor), a putative inhibitor of dynamin-related protein (DRP1), decreased cancer cell proliferation through inducing mitochondrial fusion and altering oxygen consumption. However, the metabolic reprogramming underlying the DRP1 inhibition is still unclear in cancer cells. METHODS: To better understand the metabolic effect of DRP1 inhibition, [U-13C]glucose isotope tracing was employed to assess mdivi-1 effects in several cancer cell lines, DRP1-WT (wild-type) and DRP1-KO (knockout) H460 lung cancer cells and mouse embryonic fibroblasts (MEFs). RESULTS: Mitochondrial staining confirmed that mdivi-1 treatment and DRP1 deficiency induced mitochondrial fusion. Surprisingly, metabolic isotope tracing found that mdivi-1 decreased mitochondrial oxidative metabolism in the lung cancer cell lines H460, A549 and the colon cancer cell line HCT116. [U-13C]glucose tracing studies also showed that the TCA cycle intermediates had significantly lower enrichment in mdivi-1-treated cells. In comparison, DRP1-WT and DRP1-KO H460 cells had similar oxidative metabolism, which was decreased by mdivi-1 treatment. Furthermore, mdivi-1-mediated effects on oxidative metabolism were independent of mitochondrial fusion. CONCLUSIONS: Our data suggest that, in cancer cells, mdivi-1, a putative inhibitor of DRP1, decreases oxidative metabolism to impair cell proliferation.

Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk. Among categories of NAFLD, hepatic fibrosis is most likely to affect mortality. Myocardial function and its energy metabolism are tightly linked, which might be altered by an insulin resistant condition such as NAFLD. We investigated whether hepatic steatosis and fibrosis were associated with myocardial dysfunction relative to myocardial glucose uptake. METHODS: A total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a tertiary care hospital. Myocardial glucose uptake was evaluated at fasted state using [18F]-fluorodeoxyglucose-positron emission tomography (18FDG-PET). Hepatic steatosis and fibrosis were assessed by transient liver elastography (Fibroscan®) with controlled attenuation parameter, which quantifies hepatic fat and by surrogate indices (fatty liver index and NAFLD fibrosis score). Cardiac structure and function were examined by echocardiogram. RESULTS: Compared to those without NAFLD, patients with NAFLD had alterations in cardiac remodeling, manifested by increased left ventricular mass index, left ventricular end-diastolic diameter, and left atrial volume index (all p <0.05). Hepatic steatosis was significantly associated with left ventricular filling pressure (E/e' ratio), which reflects diastolic dysfunction (p for trend <0.05). Those without NAFLD were more likely to have higher myocardial glucose uptake compared to those with NAFLD. Significant hepatic fibrosis was also correlated with diastolic dysfunction and impaired myocardial glucose uptake. Using multivariable linear regression, E/e' ratio was independently associated with hepatic fibrosis (standardized ß = 0.12 to 0.27; all p <0.05). Association between hepatic steatosis and E/e' ratio was also significant (standardized ß = 0.10 to 0.15; all p <0.05 excluding the model adjusted for adiposity). CONCLUSIONS: Hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction. This association is linked with myocardial glucose uptake evaluated by 18FDG-PET. LAY SUMMARY: Non-alcoholic fatty liver disease is associated with an increased risk of cardiovascular disease. More severe forms of non-alcoholic fatty liver disease, where hepatic fibrosis occurs, are linked to increased mortality. In this study, we have shown that hepatic steatosis and fibrosis are associated with subclinical myocardial dysfunction. This association is linked to altered myocardial glucose uptake.

Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses.

Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that are efficacious against major drivers of influenza-like disease, including influenza viruses and respiratory syncytial virus (RSV), are urgently needed. Using a dual-pathogen high-throughput screening protocol for influenza A virus (IAV) and RSV inhibitors, we have identified N4-hydroxycytidine (NHC) as a potent inhibitor of RSV, influenza B viruses, and IAVs of human, avian, and swine origins. Biochemical in vitro polymerase assays and viral RNA sequencing revealed that the ribonucleotide analog is incorporated into nascent viral RNAs in place of cytidine, increasing the frequency of viral mutagenesis. Viral passaging in cell culture in the presence of an inhibitor did not induce robust resistance. Pharmacokinetic profiling demonstrated dose-dependent oral bioavailability of 36 to 56%, sustained levels of the active 5'-triphosphate anabolite in primary human airway cells and mouse lung tissue, and good tolerability after extended dosing at 800 mg/kg of body weight/day. The compound was orally efficacious against RSV and both seasonal and highly pathogenic avian IAVs in mouse models, reducing lung virus loads and alleviating disease biomarkers. Oral dosing reduced IAV burdens in a guinea pig transmission model and suppressed virus spread to uninfected contact animals through direct transmission. Based on its broad-spectrum efficacy and pharmacokinetic properties, NHC is a promising candidate for future clinical development as a treatment option for influenza-like diseases.

sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation.

OBJECTIVE AND DESIGN: The receptor for advanced glycation endproducts (RAGE) is an innate immunity receptor that has been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, the possibility that RAGE-mediated signaling is involved in angiotensin II (Ang II)-induced cardiac left ventricular hypertrophy has yet to be investigated. We therefore determined whether RAGE has a role in regulating pathological cardiac hypertrophy. MATERIALS AND SUBJECTS: Protein abundance was estimated using Western blotting and intracellular ROS level and phospho-p65 were detected using fluorescence microscopy. Enzyme-linked immunosorbent assay was used to detect HMGB1 and IL-1ß. All in vitro experiments were performed using H9C2 cells. TREATMENTS: To induce cardiomyocyte hypertrophy, 300 nM Ang II was treated for 48 h and 2 µg/ml sRAGE was treated 1 h prior to addition of Ang II. RESULTS: sRAGE attenuated Ang II-induced cardiomyocyte hypertrophy by downregulating RAGE and angiotensin II type 1 receptor expression. Secretion levels of high motility group box 1 and interleukin-1ß, estimated from a cell culture medium, were significantly reduced by sRAGE. Activated PKCs and ERK1/2, important signals in left ventricular hypertrophy (LVH) development, were downregulated by sRAGE treatment. Furthermore, we found that nuclear factor-κB and NOD-like receptor protein 3 (NLRP3) were associated with RAGE-mediated cardiomyocyte hypertrophy. CONCLUSIONS: In the context of these results, we conclude that RAGE induces cardiac hypertrophy through the activation of the PKCs-ERK1/2 and NF-κB-NLRP3-IL1ß signaling pathway, and suggest that RAGE-NLRP3 may be an important mediator of Ang II-induced cardiomyocyte hypertrophy. In addition, we determined that inhibition of RAGE activation with soluble RAGE (sRAGE) has a protective effect on Ang II-induced cardiomyocyte hypertrophy.

Botulinum toxin type A for neuropathic pain in patients with spinal cord injury.

OBJECTIVE: To evaluate the analgesic effect of botulinum toxin type A (BTX-A) on patients with spinal cord injury-associated neuropathic pain. METHODS: The effect of BTX-A on 40 patients with spinal cord injury-associated neuropathic pain was investigated using a randomized, double-blind, placebo-controlled design. A 1-time subcutaneous BTX-A (200U) injection was administered to the painful area. Visual analogue scale (VAS) scores (0-100mm), the Korean version of the short-form McGill Pain Questionnaire, and the World Health Organization WHOQOL-BREF quality of life assessment were evaluated prior to treatment and at 4 and 8 weeks after the injection. RESULTS: At 4 and 8 weeks after injection, the VAS score for pain was significantly reduced by 18.6 ± 16.8 and 21.3 ± 26.8, respectively, in the BTX-A group, whereas it was reduced by 2.6 ± 14.6 and 0.3 ± 19.5, respectively, in the placebo group. The pain relief was associated with preservation of motor or sensory function below the neurological level of injury. Among the responders in the BTX-A group, 55% and 45% reported pain relief of 20% or greater at 4 and 8 weeks, respectively, after the injection, whereas only 15% and 10% of the responders in the placebo group reported a similar level of pain relief. Improvements in the score for the physical health domain of the WHOQOL-BREF in the BTX-A group showed a marginal trend toward significance (p = 0.0521) at 4 weeks after the injection. INTERPRETATION: These results indicate that BTX-A may reduce intractable chronic neuropathic pain in patients with spinal cord injury.

DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors.

Pediatric posterior fossa (PF) tumor survivors experience long-term motor deficits. Specific cerebrocerebellar connections may be involved in incidence and severity of motor dysfunction. We examined the relationship between long-term ataxia as well as fine motor function and alteration of differential cerebellar efferent and afferent pathways using diffusion tensor imaging (DTI) and tractography. DTI-based tractography was performed in 19 patients (10 pilocytic astrocytoma (PA) and 9 medulloblastoma patients (MB)) and 20 healthy peers. Efferent Cerebello-Thalamo-Cerebral (CTC) and afferent Cerebro-Ponto-Cerebellar (CPC) tracts were reconstructed and analyzed concerning fractional anisotropy (FA) and volumetric measurements. Clinical outcome was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Kinematic parameters of fine motor function (speed, automation, variability, and pressure) were obtained by employing a digitizing graphic tablet. ICARS scores were significantly higher in MB patients than in PA patients. Poorer ICARS scores and impaired fine motor function correlated significantly with volume loss of CTC pathway in MB patients, but not in PA patients. Patients with pediatric post-operative cerebellar mutism syndrome showed higher loss of CTC pathway volume and were more atactic. CPC pathway volume was significantly reduced in PA patients, but not in MB patients. Neither relationship was observed between the CPC pathway and ICARS or fine motor function. There was no group difference of FA values between the patients and healthy peers. Reduced CTC pathway volumes in our cohorts were associated with severity of long-term ataxia and impaired fine motor function in survivors of MBs. We suggest that the CTC pathway seems to play a role in extent of ataxia and fine motor dysfunction after childhood cerebellar tumor treatment. DTI may be a useful tool to identify relevant structures of the CTC pathway and possibly avoid surgically induced long-term neurological sequelae.

Subjective taste to polyethylene glycol is associated with efficacy of right colon preparation.

AIM: A prospective observational trial with preparations using polyethylene glycol (PEG) to compare patient compliance and adverse events according to individual subjective taste. METHODS: A total of 299 outpatients (mean ± standard deviation [SD] 56.5 ± 13.8 years, 172 males) were recruited for our study. We assessed the efficacy of bowel preparation, subjective taste to their regimens, compliance and adverse events during the preparation. RESULTS: We achieved adequate preparation in 267 (89.3%). A total of 124 patients (41.5%) had 'unacceptable taste' to their regimens. The patients with acceptable taste had better compliance than the patients with unacceptable taste (p = .009). The patients with unacceptable taste had more frequent adverse events such as nausea, vomiting and abdominal bloating than the patients with acceptable taste (all p < .001, Table 2). Patients with unacceptable taste (16.1%) had more frequent inadequate preparation in overall colon than patients with acceptable taste (6.9%, p = .011). There was a significant difference in the efficacy of preparation of right colon between the two groups (p = .004). CONCLUSION: Subjective taste to PEG is associated with efficacy of right colon preparation. In addition, subjective taste to PEG is associated with compliance and adverse events.

Ultrasound Dimensions of the Rotator Cuff and Other Associated Structures in Korean Healthy Adults.

In evaluating patients complaining of shoulder pain, ultrasonography is an emerging imaging tool due to convenience, low cost, high sensitivity and specificity. However, normative values of ultrasound dimensions of the shoulder to be compared with pathologic findings in Korean adults are not provided yet. We evaluated the ultrasound dimensions of the rotator cuff, long head of biceps tendon, deltoid muscle and acromioclavicular joint in Korean healthy adults. Shoulder ultrasonography was performed on 200 shoulders from 100 healthy adults. The dimensions of the thickness of rotator cuff (supraspinatus, infraspinatus, subscapularis tendon), deltoid muscle, long head of biceps tendon, subacromial subdeltoid bursa, and acromioclavicular joint interval were measured in a standardized manner. Differences in measurements among sex, age, and dominant arms were compared. The thickness of rotator cuff tendons (supraspinatus, infraspinatus, subscapularis) and deltoid muscle were significantly different between men and women. The thickness of subacromial subdeltoid bursa was significantly different between men and women for non-dominant side. In rotator cuff tendon measurements, the differences between dominant and non-dominant shoulders were not significant, which means the asymptomatic contralateral shoulder can be used to estimate the normal reference values. When stratified by age divided by 10 years, the measurements of supraspinatus, subscapularis and deltoid thickness showed tendency of increase with the age. The acromioclavicular joint interval, on the other hand, revealed decreasing tendency. This report suggests normative values of ultrasound dimensions of healthy Korean population with varying age, and can be useful as reference values in evaluating shoulder pathology, especially in rotator cuff tendon pathology.

Anatomical localization of the motor entry point in the thyroarytenoid muscle.

INTRODUCTION: The aim of this study was to localize the motor entry point (MEP) of the thyroarytenoid muscle. METHODS: Eight cadaver larynges were dissected. A virtual plane was used to represent the MEP in a coordinate (X/Y/Z) system. The inferior border of the thyroid cartilage was linked to the center of the anterior arc of the cricoid cartilage (the Y-axis). The X-axis was set perpendicular to the Y-axis; the Z-axis passed through the posterior border of the thyroid lamina from the height of the insertion point. RESULTS: The mean X, Y, and Z coordinates were 6.2 mm, 9.1 mm, and 11.0 mm, respectively. The calculated angles of the lateral and superior deflections were 29.4° and 35.8°, respectively. The calculated insertion depth, that is, the distance from the insertion point to the MEP, was 15.6 mm. CONCLUSIONS: These results may help to improve the accuracy of needle insertion during diagnostic laryngeal electromyography or laryngeal electromyography-guided injections.

Comparative study of biological activity of four botulinum toxin type A preparations in mice.

BACKGROUND: Units of available botulinum toxin preparations are not interchangeable, and the dose-conversion ratios between such preparations remain controversial. OBJECTIVE: To compare the efficacy and safety of four botulinum toxin type A preparations. MATERIALS AND METHODS: Murine gastrocnemius compound muscle action potentials (CMAPs) were recorded before and after injecting the four botulinum toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, new botulinum toxin, and incobotulinumtoxinA). RESULTS: In all preparations, CMAP amplitudes decreased until 4 days after receiving the injection and then gradually recovered. On postinjection day 84, the amplitudes returned to baseline in all groups except the high-dose groups. CMAP amplitude in the contralateral limb also decreased up to postinjection days 4 to 7 and then gradually returned to baseline by postinjection day 28. CONCLUSION: The dose-conversion ratio between onabotulinumtoxinA and abobotulinumtoxinA was determined to be 1:2.6; previous reports of 1:3 were considered too high. A dose-conversion ratio between onabotulinumtoxinA and new botulinum toxin of 1:1 was deemed appropriate. OnabotulinumtoxinA and incobotulinumtoxinA demonstrated a dose-conversion ratio of 1:1.07. The efficacy of incobotulinumtoxinA was slightly lower than that of onabotulinumtoxinA. These dose-conversion ratios are applicable solely from an efficacy standpoint and not for safety. This study was conducted in mice, so it may not translate perfectly to human applications.