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This article discusses the development of topical therapeutics for the treatment of UV-induced skin hyperpigmentary disorders. The researchers used a screening tool to identify compounds that inhibit melanogenesis, the process of melanin synthesis. They engineered small-molecule analogues of a compound called altiratinib, which showed dose-dependent inhibitory action on melanogenesis but had cytotoxicity at higher concentrations. The researchers designed new compounds that demonstrated comparable or better efficacy in reducing melanin content without cytotoxicity. These compounds also showed enhanced skin permeability and were effective in reducing melanin content in mouse and human skin cultures. The findings suggest that these compounds have the potential to be developed into safe and potent topicals for the treatment of hyperpigmentary diseases. [Extracted from the article]

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof‐of‐principle evidence is presented that a cell‐penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene‐addicted cancer cells through transcription activity‐independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2‐p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome‐wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C‐resistant cancers. This study enhances the understanding of ACP52C‐induced cancer‐specific apoptosis induction and supports the use of ACP52C in anticancer drug development. [ABSTRACT FROM AUTHOR]

Composite solid electrolytes (CSE) are promising candidate materials that can complement the ionic conductivity and thermal and electrochemical stabilities of solid polymer electrolytes. In this study, the ionic conductivity, Li migration characteristics, and electrochemical stability are investigated of "polymer‐in‐ceramic"‐structured CSE sheet into which polyethylene glycol polymer is introduced. PEG10 CSE exhibits ionic conductivity twice as high as PEG0 CSE at 50 °C and shows high oxidation potential stability of 5.2 V. In addition, PEG10 CSE has high interfacial compatibility with Li metal, and LiFePO4/PEG10 CSE/Li cell evaluation confirms that PEG10 CSE has high discharge capacity, C‐rate performance, and cycle stability at 45 °C. [ABSTRACT FROM AUTHOR]

Changes in mitochondrial morphology are associated with nutrient utilization, but the precise causalities and the underlying mechanisms remain unknown. Here, using cellular models representing a wide variety of mitochondrial shapes, we show a strong linear correlation between mitochondrial fragmentation and increased fatty acid oxidation (FAO) rates. Forced mitochondrial elongation following MFN2 over‐expression or DRP1 depletion diminishes FAO, while forced fragmentation upon knockdown or knockout of MFN2 augments FAO as evident from respirometry and metabolic tracing. Remarkably, the genetic induction of fragmentation phenocopies distinct cell type‐specific biological functions of enhanced FAO. These include stimulation of gluconeogenesis in hepatocytes, induction of insulin secretion in islet β‐cells exposed to fatty acids, and survival of FAO‐dependent lymphoma subtypes. We find that fragmentation increases long‐chain but not short‐chain FAO, identifying carnitine O‐palmitoyltransferase 1 (CPT1) as the downstream effector of mitochondrial morphology in regulation of FAO. Mechanistically, we determined that fragmentation reduces malonyl‐CoA inhibition of CPT1, while elongation increases CPT1 sensitivity to malonyl‐CoA inhibition. Overall, these findings underscore a physiologic role for fragmentation as a mechanism whereby cellular fuel preference and FAO capacity are determined. Synopsis: Metabolic fuel preference is associated with mitochondrial architecture, yet the mechanisms that connect shape and function remain unknown. This study demonstrates selective coupling between mitochondrial architecture and fatty acid (FA) utilization, uncovering an unexpected connection between mitochondrial fusion and fission, and fuel choice.Long‐chain FA oxidation capacity increases upon mitochondrial fragmentation and decreases upon mitochondrial elongation.Activity of CPT1, a rate‐limiting enzyme in fatty acid oxidation, is inhibited by the elongation of mitochondria, but enhanced by their fragmentation.Mitochondrial fragmentation reduces CPT1's sensitivity to its endogenous inhibitor, malonyl‐CoA, which is a product of pyruvate metabolism and the first metabolite in FA synthesis.Fragmentation‐induced FA utilization has cell type‐specific functional consequences, causing increased hepatic gluconeogenesis, induction of insulin secretion at non‐stimulatory glucose levels, and enhanced survival of OXPHOS‐dependent lymphoma cells. [ABSTRACT FROM AUTHOR]

Although many efforts are undertaken to treat peripheral demyelinating neuropathies based on biochemical interventions, unfortunately, there is no approved treatment yet. Furthermore, previous studies have not shown improvement of the myelin membrane at the biomolecular level. Here, an electroceutical treatment is introduced as a biophysical intervention to treat Charcot‐Marie‐Tooth (CMT) disease—the most prevalent peripheral demyelinating neuropathy worldwide—using a mouse model. The specific electrical stimulation (ES) condition (50 mV mm−1, 20 Hz, 1 h) for optimal myelination is found via an in vitro ES screening system, and its promyelinating effect is validated with ex vivo dorsal root ganglion model. Biomolecular investigation via time‐of‐flight secondary ion mass spectrometry shows that ES ameliorates distribution abnormalities of peripheral myelin protein 22 and cholesterol in the myelin membrane, revealing the restoration of myelin membrane integrity. ES intervention in vivo via flexible implantable electrodes shows not only gradual rehabilitation of mouse behavioral phenotypes (balance and endurance), but also restored myelin thickness, compactness, and membrane integrity. This study demonstrates, for the first time, that an electroceutical approach with the optimal ES condition has the potential to treat CMT disease and restore impaired myelin membrane integrity, shifting the paradigm toward practical interventions for peripheral demyelinating neuropathies. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the biological activities of sweet potato tips and tubers. Antioxidant activity of 2,2‐azino‐bis 93‐ethlbenzothiazoline‐6‐sulphonic acid) diammonium salt (ABTS) and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging activities had the highest value of 32.45 mg, AAE/g, and 15.10 mg AAE/g, respectively, in 'Pungwonmi' tips. Angiotensin converting enzyme I inhibitory activity ranged between 47.72% in 'Sinjami' tubers and 62.25% in 'Pungwonmi' tips. α‐Glucosidase inhibitory activity had the highest value of 78.81% and 62.93% in 'Pungwonmi' tips and 'Juhwangmi' tubers, respectively. In particular, 'Pungwonmi' tips had the most effective inhibiting effect on intracellular reactive oxygen species levels in HepG2 cells. Wound healing assay result revealed that 'Sinjami' showed 75% wound healing effect. For skin whitening, 'Pungwonmi' tips showed 63% activity at 10 mg/ml. These results suggest that sweet potato tips and tubers can be used to develop functional food and cosmetic materials. [ABSTRACT FROM AUTHOR]

This study investigated the physicochemical properties of rice flour suspensions under ultrahigh hydrostatic pressure (UHP) treatment. Rice flour suspensions were subjected to 200, 400, and 600 MPa of pressure for 10 min, and heat treatment was used as a control. Proximate characteristics of different rice cultivar were analyzed to amylose, damage starch content, and particle size. Changes in physicochemical properties of rice flour suspensions according to UHP treatment were analyzed to microscopic structure, iodine reaction, α-amylase hydrolysis rate, and resistant starch content. Microscopic structural analyses showed that the structures of the rice flours were altered under both heat and 600 MPa treatment conditions. Water absorption rates were highest under heat treatment (467.53–554.85%), followed by 600 MPa treatment (269.55–334.57%). Iodine reaction values increased with increasing applied pressure. α-Amylase hydrolysis rates and resistant starch contents were highest under heat treatment and increased with increasing applied pressure. Based on these results, 600 MPa treatment of rice flour suspensions was shown to be comparable to heat treatment; as a result, the development of the new rice processing method with different physicochemical properties is expected from rice cultivars treated under UHP processing methods. [ABSTRACT FROM AUTHOR]

Background: Ganglionated plexuses (GPs) are implicated in atrial fibrillation (AF). Endocardial high‐frequency stimulation (HFS) delivered within the local atrial refractory period can trigger ectopy and AF from specific GP sites (ET‐GP). The aim of this study was to understand the role of ET‐GP ablation in the treatment of AF. Methods: Patients with paroxysmal AF indicated for ablation were recruited. HFS mapping was performed globally around the left atrium to identify ET‐GP. ET‐GP was defined as atrial ectopy or atrial arrhythmia triggered by HFS. All ET‐GP were ablated, and PVs were left electrically connected. Outcomes were compared with a control group receiving pulmonary vein isolation (PVI). Patients were followed‐up for 12 months with multiple 48‐h Holter ECGs. Primary endpoint was ≥30 s AF/atrial tachycardia in ECGs. Results: In total, 67 patients were recruited and randomized to ET‐GP ablation (n = 39) or PVI (n = 28). In the ET‐GP ablation group, 103 ± 28 HFS sites were tested per patient, identifying 21 ± 10 (20%) GPs. ET‐GP ablation used 23.3 ± 4.1 kWs total radiofrequency (RF) energy per patient, compared with 55.7 ± 22.7 kWs in PVI (p = <.0001). Duration of procedure was 3.7 ± 1.0 and 3.3 ± 0.7 h in ET‐GP ablation group and PVI, respectively (p =.07). Follow‐up at 12 months showed that 61% and 49% were free from ≥30 s of AF/AT with PVI and ET‐GP ablation respectively (log‐rank p =.27). Conclusions: It is feasible to perform detailed global functional mapping with HFS and ablate ET‐GP to prevent AF. This provides direct evidence that ET‐GPs are part of the AF mechanism. The lower RF requirement implies that ET‐GP targets the AF pathway more specifically. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the distribution of phenolic compounds in the peanut skins of various cultivars, as well as their antioxidant and anti‐inflammatory effect (Arachishypogaea L. cv. K‐Ol, cv. Sinpalkwang, cv. Daan, cv. Heuksaeng) and extraction solvent. The major components of red peanut cultivars (K‐Ol, Sinpalkwang, and Daan) were identified as proanthocyanidin, catechin, gallic acid, coumaric acid, and hesperidine, whereas the major components of black peanut cultivar (Heuksaeng) were identified as anthocyanin, ferulic acid, and quercetin. The DPPH and ABTS radical scavenging activities, and FRAP values were the highest in Daan followed by Sinpalkwng, K‐Ol, and Heuksang. Furthermore, the skin extracts of red peanuts effectively improved cell viability, reactive oxygen species generation, MDA concentration, and antioxidant enzyme activity (GR, GPx, CAT, and superoxide dismutase) in oxidative stress‐induced HepG2 cells, and reduced the expression of pro‐inflammatory factors (NO, TNF‐α, IL‐6, and IL‐1β) in LPS‐stimulated RAW 264.7 macrophages. These results suggest that red peanut skin extracts could effectively mediate physiological activity and provide valuable information for the use of peanut byproducts as functional food materials. [ABSTRACT FROM AUTHOR]

LMX1A, encoding the LIM homeobox transcription factor, is essential for inner ear development. Despite previous reports of three human LMX1A variants with nonsyndromic hearing loss (NSHL) in the literature, functional characterization of these variants has never been performed. Encouraged by identification of a de novo, heterozygous, missense variant (c.595A > G; p.Arg199Gly) located in the homeodomain of LMX1A in a subject with congenital severe‐to‐profound deafness through Exome sequencing, we performed luciferase assay to evaluate transcriptional activity of all LMX1A variants reported in the literature including p.Arg199Gly. Resultantly, p.Arg199Gly manifesting the most severe NSHL showed the biggest reduction of transcriptional activity in contrast with moderately reduced activity of p.Cys97Ser and p.Val241Leu associated with less severe progressive NSHL, proposing a genotype–phenotype correlation. Further, our dominant LMX1A variant exerted pathogenic effects via haploinsufficiency rather than dominant‐negative effect. Collectively, we provide a potential genotype–phenotype correlation of LMX1A variants as well as the pathogenic mechanism of LMX1A‐related NSHL. [ABSTRACT FROM AUTHOR]

DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for synthesizing the lagging strand of DNA. Single heterozygous POLD1 mutations in domains with polymerase and exonuclease activities have been reported to cause syndromic deafness as a part of multisystem metabolic disorder or predisposition to cancer. However, the phenotypes of diverse combinations of POLD1 genotypes have not been elucidated in humans. We found that five members of a multiplex family segregating autosomal recessive nonsyndromic sensorineural hearing loss (NS‐SNHL) have revealed novel compound heterozygous POLD1 variants (p.Gly1100Arg and a presumptive null function variant, p.Ser197Hisfs*54). The recombinant p.Gly1100Arg polymerase δ showed a reduced polymerase activity by 30–40%, but exhibited normal exonuclease activity. The polymerase activity in cell extracts from the affected subject carrying the two POLD1 mutant alleles was about 33% of normal controls. We suggest that significantly decreased polymerase δ activity, but not a complete absence, with normal exonuclease activity could lead to NS‐SNHL. [ABSTRACT FROM AUTHOR]

BACKGROUND: The ability of heat treatment with a soaking solvent to increase soluble phenolic compounds due to the liberation or breakdown of the cell matrix has been investigated in various plants. This study investigated the changes in phenolic compounds and antioxidant activities of 12 sweet potato cultivars after heat treatment with distilled water or prethanol A. RESULTS: The highest total polyphenol content (134.67 mg gallic acid equivalents/g extract residue) and flavonoid content (65.43 mg catechin equivalents/g extract residue) was observed in the 'Jami' (JM) cultivar after heat treatment with prethanol A. Higher polyphenol and flavonoid content was generally observed in the purple sweet potato cultivars. Salicylic acid was the major phenolic acid, followed by protocatechuic acid or chlorogenic acid in almost all untreated sweet potato cultivars. The salicylic acid, vanillic acid, gallic acid, and caffeic acid content of the sweet potatoes increased after the heat treatment, whereas the protocatechuic acid and chlorogenic acid content decreased. The highest 1,1‐Diphenyl‐2‐picrylhydrazyl (DPPH) and 2,2‐azinobis(3‐ethyl benzothiazoline)‐6‐sulfonic acid (ABTS) radical scavenging activity levels were observed in the JM cultivar subjected to heat treatment with prethanol A (48.15 and 80.00 mg TE/g extract residue, respectively). CONCLUSION: These results suggest that heat treatment with a soaking solvent is an efficient method to enhance the antioxidant characteristics of Korean sweet potato cultivars. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remain poorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G > C and p.Gln589ArgfsX55 [NM_144672.3]). The pathogenic potential of c.1320 + 5 G > C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild‐type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol‐specific phospholipase C‐induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI‐anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI‐anchorage. [ABSTRACT FROM AUTHOR]

Introduction: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence atrioventricular (AV) dissociation. Methods and Results: High frequency stimulation was delivered through a Smart‐Touch catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. Three dimensional locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia, or no effect. CARTO maps were exported, registered, and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated (AVD‐GP) effects. There were 10 AVD‐GPs (interquartile range, 11.5) per patient. Eighty percent (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups was very similar. Highest probability of AVD‐GPs (>20%) was identified in: inferoseptal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%). Conclusion: It is feasible to map the entire left atrium for AVD‐GPs before AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD‐GPs, identified three regions with a higher likelihood for finding AVD‐GPs and these matched the histological descriptions. This approach could be used to better characterize the autonomic network. [ABSTRACT FROM AUTHOR]

Abstract: Background: The MYO6 gene, if altered, can cause nonsyndromic hearing loss (NSHL) either in an autosomal dominant (AD) (DFNA22) or recessive form. The present study identified MYO6 variants in the cohort of Korean AD NSHL families and investigated the audiological phenotypes of DFNA22 with respect to suggesting clinical guides for the counseling of DFNA22. Methods: A retrospective cohort study was performed on 81 AD NSHL families in two hospitals. Among them, five families (SH21, SB60, SB247, SB290 and SB305) segregating with MYO6 variant were genetically and clinically assessed. Results: We identified two novel missense variants of MYO6: p.G223R (SB290) and p.T158R (SB305). A known heterozygous truncation variant, p.R205X, reported previously (SH21, SB60), was identified (SB247). The overall frequency of DFNA22 among such cases was 6.2%. Specifically, we found p.R205X from three of five DFNA22 families (60%). Five DFNA22 families demonstrated extremely diverse audiogram configurations and age of onset with even intrafamilial variations, whereas the severity of hearing loss mostly ranged within moderate. Conclusions: We report a recurring predominant allele and two new missense variants of MYO6, highlighting the significant contribution of MYO6 to AD NSHL in the Korean population. Extremely diverse audiological configurations of DFNA22 suggest that MYO6 should be considered in future genetic studies of patients with AD NSHL. Gradual progression with a good speech audiometry score could provide physicians with clinical insight with respect to advising patients to use hearing aids or consider middle ear implants, whereas, in the case of certain exceptional circumstances, physicians could provide patients with the option to consider a cochlear implant. [ABSTRACT FROM AUTHOR]

Abstract: Thermoreception is an important cutaneous sense, which plays a role in the maintenance of our body temperature and in the detection of potential noxious heat stimulation. In this study, we investigated event‐related fields (ERFs) and neural oscillatory activities, which were modulated by warmth stimulation. We developed a warmth stimulator that could elicit a warmth sensation, without pain or tactile sensation, by using a deep‐penetrating 980‐nm diode laser. The index finger of each participant (n = 24) was irradiated with the laser warmth stimulus, and the cortical responses were measured using magnetoencephalography (MEG). The ERFs and oscillatory responses had late latencies (∼1.3 s and 1.0–1.5 s for ERFs and oscillatory responses, respectively), which could be explained by a slow conduction velocity of warmth‐specific C‐fibers. Cortical sources of warmth‐related ERFs were seen in the bilateral primary and secondary somatosensory cortices (SI and SII), posterior part of the anterior cingulate cortex (pACC), ipsilateral primary motor, and premotor cortex. Thus, we suggested that SI, SII, and pACC play a role in processing the warmth sensation. Time–frequency analysis demonstrated the suppression of the alpha (8–13 Hz) and beta (18–23 Hz) band power in the bilateral sensorimotor cortex. We proposed that the suppressions in alpha and beta band power are involved in the automatic response to the input of warmth stimulation and sensorimotor interactions. The delta band power (1–4 Hz) increased in the frontal, temporal, and cingulate cortices. The power changes in delta band might be related with the attentional processes during the warmth stimulation. [ABSTRACT FROM AUTHOR]

This study investigated the changes in the functional components of three cultivars (Kunalbori, Dahan, and Hinchalssalbori) over a 6 day germination period; these cultivars were selected because of their varied characteristics and applications. Barley produced from the cultivars was subjected to 6 days of germination. Germinated barley was analyzed for total polyphenol, total flavonoid, hordenine, total arabinoxylan, soluble arabinoxylan, y-aminobutyric acid, and y-oryzanol contents. The total polyphenol content increased with germination period, corresponding to 1.47-3.83, 1.41-3.42, and 1.59-2.82 mg/g in barley produced from the three cultivars, respectively. The corresponding total flavonoid contents were 0.35-0.44, 0.31-0.48, and 0.22-0.37 mg/g. The hordenine contents in the barley produced from the three cultivars increased from not detected for nongerminated barley to 1.52, 1.09, and 1.34 mg/100 g, respectively, at germination day 6. The y-aminobutyric acid content significantly increased until germination day 4, followed by a decrease, and the highest content was observed for barley produced from the Kunalbori cultivar at germination day 4. The total arabinoxylan and soluble arabinoxylan contents increased with germination period. Results indicated that the germination period is crucial for increasing the functional components. These results are expected to be beneficial during food product manufacturing. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare and evaluate, through histomorphometric and radiological analysis, the effects of UV photofunctionalization on an implant placed over a critical defect area with and without a bone graft. Four female beagle dogs were first divided into control and bone graft groups. Each group was then subdivided into UV-treated and UV-untreated groups. The mandibular premolars in each dog were extracted. 12 weeks after extraction, implants were placed according to the condition of each group. Four and 12 weeks after implantation on left and right mandible, the dogs were sacrificed. The specimens were prepared for histomorphometric and micro-computed tomographic analysis. In both 4-week and 12-week groups, UV-treated implant surfaces showed better osseointegration than SA implant surfaces. Also, with implant surfaces placed over the critical defect with bone graft, UV photofunctionalization increased bone-to-implant contact (BIC) and new bone formation at the initial stage (4 weeks). Based on the results of this study, it can be suggested that UV photofunctionalization on the surface of implants placed over large critical defects with bone graft aids initial osseointegration and osteogenesis. [ABSTRACT FROM AUTHOR]

Background The symptoms of phosphoribosyl pyrophosphate synthetase 1 ( PRPS1) deficiency diseases have been reported to be alleviated by medication. In the present study, we report biochemical data that favor PRPS1 deficiency-related hearing loss as a potential target for pharmaceutical treatment. Methods We recruited 42 probands from subjects aged less than 15 years with a moderate degree of nonsyndromic autosomal-recessive or sporadic sensorineural hearing loss (SNHL) in at least one side. Molecular genetic testing, including targeted exome sequencing (TES) of 129 genes for deafness, and in silico prediction were performed. Results A strong candidate variant (p.A82P) of PRPS1 is co-segregated with SNHL in X-linked recessive inheritance from one Korean multiplex SNHL family. Subsequent measurement of in vitro enzymatic activities of PRPS1 from erythrocytes of affected and unaffected family members, as well as unrelated normal controls, confirmed a pathogenic role of this variant. In detail, compared to normal hearing controls (0.23-0.26 nmol/ml/h), the proband, the affected sibling and their normal hearing mother demonstrated a significantly decreased PRPS1 enzymatic activity (0.07, 0.03 and 0.11 nmol/ml/h, respectively). This novel loss-of-function mutation of PRPS1 (p.A82P) is the ninth and sixth most reported mutation in the world and in Asia, respectively. Conclusions DFNX1 was found to account for approximately 2.4% (1/42) of moderate SNHL in a Korean pediatric population. Confirmation of PRPS1 activity deficiency and an audiologic phenotype that initially begins in a milder form of SNHL, as in our family, should indicate the need for rigorous genetic screening as early as possible. [ABSTRACT FROM AUTHOR]

A kinetic study on nucleophilic substitution reactions of 4-pyridyl benzoate ( 2a) and O-4-pyridyl thionobenzoate ( 2b) with a series of cyclic secondary amines in acetonitrile at 25.0°C is reported. Plots of pseudo-first-order rate constant ( kobsd) vs. [amine] are linear and pass through the origin for the reactions of 2a but curve upward for those of 2b. The upward curvature observed for the reactions of 2b is typical for reactions that proceed through a stepwise mechanism with a zwitterionic intermediate T±, which decomposes to the products via uncatalyzed and catalyzed routes competitively. The reaction of 2a has been suggested to proceed through a stepwise mechanism with T±, in which expulsion of the leaving group occurs in the rate-determining step on the basis of a linear Brønsted-type plot with βnuc = 0.77. The catalyzed reaction of 2b from T± has been proposed to proceed through a concerted mechanism with a six-membered cyclic transition state rather than via a stepwise pathway with an anionic intermediate T−. Factors influencing reactivity and reaction mechanism are discussed in detail. [ABSTRACT FROM AUTHOR]

Pseudo-first-order rate constants ( kobsd) for nucleophilic substitution reaction of O-2-pyridyl thionobenzoate ( 7) with a series of secondary amines in MeCN at 25.0 ± 0.1°C have been measured spectrophotometrically. The plots of kobsd vs. [amine] curve upward, indicating that the reaction proceeds through a stepwise mechanism with a zwitterionic tetrahedral intermediate (T±), which decomposes to the products through uncatalyzed and catalyzed routes. It has been proposed that the uncatalyzed reaction proceeds through a six-membered cyclic transition state ( TS), in which expulsion of the leaving group occurs in the rate-determining step. The catalyzed reaction from T± proceeds through a concerted mechanism with a six-membered cyclic TS rather than via a stepwise pathway with an anionic intermediate T−. This is in contrast to the report that the corresponding reaction of 2-pyridyl benzoate ( 6, a CO analogue of 7) proceeds through a forced concerted mechanism. Comparison of the second-order rate constants for the uncatalyzed reaction of 7 with those reported previously for the corresponding reaction of 6 has revealed that 7 is much more reactive than 6. Factors that affect the reactivity and reaction mechanism are discussed in detail. [ABSTRACT FROM AUTHOR]

Aim This empirical research aimed to identify relationships between nurses' unit tenure, nursing unit tenure diversity and medication errors. Background Research examining medication errors has paid little attention to the effects of multilevel precursors. Method In total, 567 registered nurses (from 36 nursing units) completed a survey questionnaire at a university hospital during September 2012. Of these, 334 (completed by nurses from 22 nursing units) were eligible for multilevel analysis. Results The average frequency of self-reported medication errors per registered nurse in the preceding 6 months was 0.98. Multilevel analysis showed that medication errors were significantly negatively associated with nurses' unit tenure at individual level ( B = −0.64, P = 0.002) and nursing unit tenure diversity at unit level ( B = −0.69, P < 0.001). Furthermore, nursing unit tenure diversity moderated the relationship between nurses' unit tenure and medication errors ( B = 0.48, P = 0.012). Conclusion This study provided evidence indicating that novice nurses made a higher number of medication errors relative to experienced nurses, and that including a mixture of novice and experienced nurses in a nursing unit attenuated novice nurses' medication errors. Implications for nursing management The development of staffing strategies that enhance nursing unit tenure diversity is required. [ABSTRACT FROM AUTHOR]

Sebaceous carcinoma is a rare malignant tumor of the skin. Although this tumor is not completely understood due to its rarity and the paucity of published reports, it is known to be an aggressive tumor with a high incidence in Asia. Sebaceous carcinomas occur preferentially in the periocular region and require attention not to miss the associated Muir- Torre syndrome. In the case of localized disease, a wide local excision with clear margin followed by adjuvant radiation therapy is usually considered the standard treatment strategy but there is no agreed treatment strategy or standard chemotherapeutic regimen for recurrent metastatic sebaceous carcinoma. We report here two cases of recurrent metastatic sebaceous carcinoma patients who responded to 5-fluorouracil and cisplatin combination chemotherapy, and review the literature. We suggest that 5-fluorouracil-cisplatin can be considered a feasible and effective treatment modality for recurrent sebaceous carcinoma. [ABSTRACT FROM AUTHOR]

Second-order rate constants ( kN) for nucleophilic displacement reactions of phenyl Y-substituted phenyl carbonates ( 7a-7l) with 1,8-diazabicyclo[5.4.0]undec-7-ene ( DBU) in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 oC have been measured spectrophotometrically. The Brønsted-type plot for the reactions of 7a-7l with DBU is linear with βlg = -0.48, indicating that the reactions proceed through a concerted mechanism, which is in contrast to the stepwise mechanism reported previously for the corresponding reactions with ethylamine (a primary amine) and piperidine (a secondary amine). The Hammett plots correlated with σ− and σo constants exhibit many scattered points. In contrast, the Yukawa-Tsuno plot results in an excellent linear correlation with ρY = 1.27 and r = 0.57, implying that a negative charge develops partially on the O atom of the leaving group in the transition state. The bulky DBU is less reactive than the primary and secondary amines toward substrates possessing a weakly basic leaving group. It has been concluded that steric hindrance exerted by DBU in the plausible intermediate (T±) forces the reactions to proceed through a concerted mechanism because expulsion of the leaving group from T± could reduce the steric hindrance. [ABSTRACT FROM AUTHOR]

Second-order rate constants ( kN3−) for SNAr reactions of 1-(Y-substituted-phenoxy)-2,4-dinitrobenzenes ( 2a-2h) with [ABSTRACT FROM AUTHOR]

Second-order rate constants () for alkaline hydrolysis of 2,4-dinitrophenyl X-substituted benzenesulfonates ( 1a-1f) and Y-substituted phenyl 4-nitrobezenesulfonates ( 2a-2g) have been measured spectrophotometrically. Comparison of with the values reported previously for the corresponding reactions with has revealed that OH is only 103-fold more reactive than , although the former is 11 p Ka units more basic than the latter. The Yukawa-Tsuno plot for the reactions of 1a-1f results in an excellent linear correlation with ρX = 2.09 and r = 0.41. The Brønsted-type plot for the reactions of 2a-2g is linear with βlg = −0.51, which is typical for reactions reported to proceed through a concerted mechanism. The Yukawa-Tsuno plot for the reactions of 2a-2g exhibits excellent linearity with ρY = 1.85 and r = 0.25, indicating that a partial negative charge develops on the O atom of the leaving group in the transition state. Thus, the alkaline hydrolysis of 1a-1f and 2a-2g has been concluded to proceed through a concerted mechanism. Comparison of the ρX and βlg values for the reactions with ions suggests that the reactions with hydroxide ion proceed through a tighter transition-state structure than those with azide ion. [ABSTRACT FROM AUTHOR]

Second-order rate constants ( kquin) have been measured spectrophotometrically for the reactions of O-3,4-dinitrophenyl thionobenzoate ( 1a) with a series of quinuclidine derivatives and of O-4-nitrophenyl X-substituted thionobenzoates ( 2a-2f) with quinuclidine in 80 mol% H2O/20 mol% DMSO at 25.0 ± 0.1 °C. Quinuclidine is less reactive toward the thione esters than less basic benzylamine. Steric hindrance exerted by the tertiary amine is responsible for the decreased reactivity. The Hammett plot for the reactions of 2a-2f with quinuclidine consists of two intersecting straight lines, while the Yukawa-Tsuno plot for the same reactions exhibits an excellent linear correlation with ρ X = 1.10 and r = 0.71. This indicates that the nonlinear Hammett plot is not due to a change in the rate-determining step but is caused by ground-state stabilization of substrates possessing an electron-donating group in the thionobenzoyl moiety through resonance interactions. Brønsted-type plot for the reactions of 1a with quinuclidines is linear with βnuc = 0.89, which is typical for reactions reported to proceed through a stepwise mechanism. However, the reactions have been concluded to proceed through a forced concerted mechanism. Instability of a plausible intermediate T± forces the reactions to proceed through such a mechanism. [ABSTRACT FROM AUTHOR]

The second-order rate constants for reactions of 2,4-dinitrophenyl X-substituted-benzenesulfonates ( 4a-4f) and Y-substituted-phenyl-4-nitrobenzenesulfonates ( 5a-5f) with [ABSTRACT FROM AUTHOR]

Second-order rate constants ( kN) have been measured spectrophotometrically for reactions of Y-substituted-phenyl picolinates ( 7a-7i) with a series of quinuclidines in 80 mol% H2O/20 mol% DMSO at 25.0 ± 0.1 °C. The Brønsted-type plot for the reactions of 7a-7i with quinuclidine is linear with βlg = −0.80. The Yukawa-Tsuno plot exhibits an excellent linear correlation with ρY = 2.37 and r = 0.52, indicating that a negative charge develops partially on the O atom of the leaving group in the rate-determining transition state ( TS). The Brønsted-type plot for the reactions of 2-chloro-4-nitrophenyl picolinate ( 7a) with a series of quinuclidines is also linear with βnuc = 0.83. Thus, it was concluded that the reactions proceed through a stepwise mechanism, in which expulsion of the leaving group occurs in the rate-determining step. Comparison of the current kinetic data with those reported previously for the corresponding reactions with piperidine revealed that quinuclidine is ca. 102-fold less reactive than piperidine. This is in contrast to the reports that quinuclidines are more reactive than isobasic secondary amines toward diaryl carbonates and related esters. Effects of amine nature on reactivity and TS structures are discussed. [ABSTRACT FROM AUTHOR]

Scientific research on the relationship between suppression and aggression is rather scarce. Consequently, practitioners searching for means to reduce workplace aggression do not have adequate data on which factors are related to aggressive behavior in the workplace. To shed light on this relationship, this study investigated emotional suppression in a sample of 17 participants by using functional magnetic resonance imaging ( fMRI) and examined their aggressive behavior by using an inventory assessing five types of aggressive behavior. Results of fMRI analysis suggest that the insula, cingulate cortex, and calcarine sulcus are involved in suppression. When the blood-oxygen-level-dependent signals of all the significant regions were tested for correlation with the ratings of the five types of aggression given by the participants' significant others (e.g. family members and/or close friends), a significant correlation was found between activation in the calcarine sulcus during suppression and property aggression. The findings not only indicate the potential neural correlates of observed aggressive behaviors but also emphasise the detrimental effect of unsuccessful, superficial emotion regulation on organisations. [ABSTRACT FROM AUTHOR]

Second-order rate constants ( kquin) for the reactions of O- Y-substituted phenyl thionobenzoates ( 3a-3i) with quinuclidine have been measured spectrophotometrically. Comparison of kquin with the rate constants reported previously for the corresponding reactions with benzylamine ( kBzNH2) has revealed that quinuclidine is less reactive than benzylamine toward 3a-3i although the former is 2.1 p Ka units more basic than the latter. Steric hindrance exerted by quinuclidine has been suggested to be responsible for the decreased reactivity of the tertiary amine. The Brønsted-type plot for the reactions of 3a-3i with quinuclidine is linear with βlg = −0.37. The Hammett plot correlated with [ABSTRACT FROM AUTHOR]

Second-order rate constants ( kOH-) for alkaline hydrolysis of Y-substituted phenyl picolinates ( 6a-6i) have been measured spectrophotometrically. A linear Brønsted-type plot is obtained with βlg = −0.34, which is typical for reactions reported previously to proceed through a stepwise mechanism with formation of an addition intermediate being the rate-determining step ( RDS). However [ABSTRACT FROM AUTHOR]

We report here the first observation of alkali-metal ion catalysis and inhibition in SNAr reactions. The plot of kobsd versus [alkali-metal ethoxide] exhibits downward curvature for the reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene with EtOLi, EtONa, and EtOK, but upward curvature for the corresponding reaction with EtOK in the presence of 18-crown-6-ether (18C6). Dissection of kobsd into the second-order rate constants for the reactions with the dissociated EtO− and the ion-paired EtOM (i.e., k [ABSTRACT FROM AUTHOR]

Background The incretin effect is known to be decreased in type 2 diabetes. However, there are limited data on the incretin effect in non- Caucasian subjects. Because Asian patients with type 2 diabetes are characterized by decreased insulin secretion, this study set out to examine the incretin effect in Korean subjects with normal glucose tolerance ( NGT) or type 2 diabetes. Methods We performed 75-g oral glucose tolerance tests ( OGTTs) and corresponding isoglycaemic intravenous glucose infusion ( IIGI) studies in Korean subjects with NGT ( n = 14) or type 2 diabetes ( n = 16). The incretin effect was calculated based on the incremental area under the curves ( iAUCs) of the plasma levels of insulin, C-peptide or insulin secretion rate ( ISR). The plasma levels of total glucagon-like peptide-1 ( GLP-1) and glucose-dependent insulinotropic polypeptide ( GIP) were measured by ELISA. Results The incretin effect was not different between the subjects with NGT and type 2 diabetes (43 ± 6% vs 47 ± 4%, P = 0·575 by insulin; 29 ± 7% vs 38 ± 4%, P = 0·253 by C-peptide; 28 ± 7% vs 35 ± 5%, P = 0·372 by ISR, respectively). However, the gastrointestinally mediated glucose disposal ( GIGD) was markedly decreased in type 2 diabetes (28·5 ± 4·2% vs 59·0 ± 4·3%, P < 0·001). The plasma levels of the total GLP-1 and GIP during the OGTTs were comparable between the two groups. Conclusion In Koreans, the secretion of GLP-1 or GIP during OGTTs and the incretin effect were comparable between subjects with NGT and type 2 diabetes, whereas the GIGD was significantly decreased in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

R5948 --> 634.18 --> Thyroglossal duct (TGD) plays an important role in guiding the embryonic development and migration of the thyroid gland down the midline of the trachea. By the tenth week of gestation, TGD is completely obliterated with the thyroid gland in its proper position. In about 7% of the population, TGD persists and forms a thyroglossal duct cyst (TGDC) within the midline of the pretracheal neck region and often presents as the most common congenital midline neck mass. A rare finding of TGD from posterior base of the tongue to left‐lateral pyramidal lobe, outside its normal midline pathway, was observed in a 92‐year‐old male during routine cadaver dissection of first year medical student's curriculum at Oakland University William Beaumont School of Medicine. Upon further inspection of the thyroid, there was no evidence of hyperplasia or lesion in the thyroid or the thyroglossal duct itself. The thyroid and associated structures were studied by first year medical students during dissection in 25 formalin fixed cadavers (13 male, 12 female, average age of 76‐years‐old). Four of the 25 cadavers did not present with a thyroid due to previous thyroidectomy. The pyramidal lobe was observed in four of the 25 cadavers (19.05%), and a thyroglossal duct was observed in 3 of the 4 cadavers in the pyramidal lobe subgroup. Within this subgroup, only one cadaver displayed a left‐sided thyroglossal duct. Currently, clinical literature suggest findings of TGDCs in four general regions of intralingual, suprahyoid, thyrohyoid, and suprasternal, but all within the midline pathway of TGD. This case finding reinforces the importance of CT scanning when treating patients with TGDC by surgical removal. [ABSTRACT FROM AUTHOR]

Power delivery systems that use power lines can communicate with other electrical systems, monitor the quality of electrical energy and provide an economical solution for automatic meter reading (AMR). Energy meters can be connected to a low‐voltage power system by power line carriers for all consumers. Illegal electricity usage in the power delivery system can be easily detected if AMR is installed in the system, which consists of a terminal smart meter (TSM) and a gateway smart meter (GSM). This study proposes a novel remote detection method for illegal electricity usage that uses both TSM and GSM, where the TSM and the GSM are installed on the power system of each consumer and on the node of the power system feeder, respectively. TSM and GSM simultaneously disconnect an electrical source for a very short period of time. After this, the proposed detection method sends a low‐voltage signal with a high frequency from the TSM to the GSM during the time of disconnection. Once the signal has passed, the proposed detection method detects illegal electricity usage by measuring the amount of time it was disconnected. This study presents the structure of the proposed detection method as well as the mathematical model, proof, simulation and experimental results. [ABSTRACT FROM AUTHOR]

Introduction It is important to understand the presence of Martin-Gruber anastomosis in patients with complete ulnar neuropathy at the elbow. Case Report: We describe a patient with complete ulnar neuropathy at the elbow and Martin-Gruber anastomosis in the forearm, mimicking incomplete ulnar neuropathy with complete conduction block in the forearm segment. Ultrasonography of the ulnar nerve around the elbow demonstrated severe swelling of the ulnar nerve, which was compatible with severe ulnar neuropathy at the elbow. Conclusions: This case report demonstrates that combination of ultrasonography with electrophysiological studies can provide more detailed information about the changes of nerve structures and lesion sites. Muscle Nerve, 2013 [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a potent mutagen and an important risk factor for hepatocellular carcinoma (HCC) in humans. Transgenic mouse strains and cells in culture have been used to detect different types of mutations caused by AFB1 and investigate the molecular determinants of their location and frequency. The AFB1 mutational spectrum in the gpt gene was markedly different in AS52 cells compared with the liver in gpt delta B6C3F1 transgenic mice. The results demonstrate the importance of metabolism, chromosomal location, transcription and selection conditions on mutational spectra. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article focuses on a research on palladium-catalyzed asymmetric hydrosilylation of styrene and its derivatives with chiral phosphoramidite ligands containing chiral ferrocenyl amine. Topics include examining the reactivity and enantioselectivity of the hydrosilylation of styrene using diastereomeric ferrocenyl phosphoramidite ligands; high catalytic activity and enantioselectivity for hydrosilylation of styrene and its derivatives; and synthesis of chiral ferrocenyl secondary amines.

Dendropanax morbifera Leveille (Araliaceae) is well known in Korea traditional medicine for a variety of diseases. The methanol extract of the lower stem parts of D. morbifera was investigated for its activity against chloroquine-sensitive strains of Plasmodium falciparum using the parasite lactate dehydrogenase assay method. Two cycloartane-type glycosides oleifoliosides A (1) and B (2), and dendropanoxide (3), β-amyrin (4), α-amyrin (5) have been isolated from the stem parts of D. morbifera. All five compounds were evaluated for in vitro antiplasmodial activities as well as their cytotoxic potential on SK-OV-3 cancer cell lines. Compounds 2 and 3 showed notable growth inhibitory activity against chloroquine-sensitive strains of Plasmodium falciparum with IC50 values of 6.2 and 5.3 µ m. This compound showed no significant cytotoxicity (IC50 > 150 µ m) evaluated using SK-OV-3 cancer cell lines. This is the first report on the antiplasmodial activity of the compounds from D. morbifera. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether microcurrent therapy is therapeutically effective in infants with torticollis. Design: Prospective, unblinded, controlled trial. Setting: Bundang CHA Hospital. Subjects: Fifteen infants were included in this study who received torticollis treatment from April to July 2008. The control group (CG) included 8 infants (3 male, 5 female) with a mean age of 7.1 months. The experimental group (EG) included 7 infants (6 male, one female) with a mean age of 10 months. Methods: The CG underwent stretching exercises for 30 minutes after ultrasound therapy and the EG underwent stretching exercises for 2 minutes after microcurrent therapy for 30 minutes. Each group received 3 treatments per week for 2 consecutive weeks. Main Outcome Measures: Measurements included head tilting angle at supine (TA) and neck rotation range of motion to the affected side (RR) at the first day and the 14th day of treatment. The incidence of crying during therapy also was recorded. The results were assessed by Mann-Whitney U and the Fisher exact tests. Results: In the CG, 4 infants showed TA improvement, one infant showed RR improvement, and 8 infants cried during therapy. In the EG, 6 infants showed TA improvement, 5 infants showed RR improvement, and 3 infants cried during therapy. In the CG, mean TA was 16.3 ± 9.2° at the first day and 13.9 ± 8.2° at the 14th day of treatment. In the EG, mean TA was 15.7 ± 8.2° at the first day and 6.7 ± 4.3° at the 14th day of treatment. TA improvement was greater in the EG (P < .01) as compared with the CG. In the CG, mean RR was 65.0 ± 24.6° at the first day and 66.3 ± 25.7° at the 14th day of treatment. In the EG, mean RR was 70.0 ± 11.5° at the first day and 80.7 ± 6.7° at the 14th day of treatment. RR showed greater improvement in the EG (P < .05). The incidence of crying during therapy was significantly lower in the EG (P < .05). Conclusion: Microcurrent therapy in infants with torticollis appears more effective in improving TA and RR and shows better therapeutic compliance than traditional therapy. [Copyright &y& Elsevier]

Oligonol is a polyphenol formulation enriched with catechin-type oligomers. As an initial approach to assess the chemopreventive potential of Oligonol, the study investigated the effects of Oligonol on the inhibition of lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice. Oligonol, which is abundantly found in plants, vegetables and fruits, was found to possess antimetastatic activity against B16F-10 melanoma cells. Continued consumption of Oligonol, even at high doses, for long periods does not seem to cause any toxic symptoms because excess Oligonol is stored in adipose tissue rather than in the liver. However, the mechanism by which Oligonol exerts its antimetastatic activity remains unclear. Further investigations are required to clarify the exact role of Oligonol in such B16F-10 melanoma regulation. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An epidemiologic study was performed to determine the genetic variability of rotaviruses in Seoul, South Korea. In 3,174 stool specimens from children with acute diarrhea at five referral hospitals, 571 (18%) possessed the antigen of group A rotavirus detectable by ELISA-10.8% in 2004 and 28.1% in 2005. VP7 genotyping revealed that the G3 type was found in 25.6% of all typed isolates, G4 in 23.8%, G2 in 21.6%, and G1 in 17.6%. VP4 genotyping showed that the P[8] type was detected in 66.7%, P[6] in 15.6%, P[4] in 13.0%, and P[9] in 0.2%. Because the variant P[8] type could not be amplified initially by conventional P typing primers (1T-1), PCR were performed using newly designed 1T-1S primer, which revealed that 307 specimens were the variant P[8] type. Uncommon combinations such as G4P[6] and G2P[8] were also found with relatively high prevalence, 14.6% and 12.8%, respectively. Variant P[8] types were associated with an outbreak of rotavirus in 2005. J. Med. Virol. 80:1661-1665, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]