Altered development of structural MRI connectome hubs at near-term age in very and moderately preterm infants.

Preterm infants may exhibit altered developmental patterns of the brain structural network by endogenous and exogenous stimuli, which are quantifiable through hub and modular network topologies that develop in the third trimester. Although preterm brain networks can compensate for white matter microstructural abnormalities of core connections, less is known about how the network developmental characteristics of preterm infants differ from those of full-term infants. We identified 13 hubs and 4 modules and revealed subtle differences in edgewise connectivity and local network properties between 134 preterm and 76 full-term infants, identifying specific developmental patterns of the brain structural network in preterm infants. The modules of preterm infants showed an imbalanced composition. The edgewise connectivity in preterm infants showed significantly decreased long- and short-range connections and local network properties in the dorsal superior frontal gyrus. In contrast, the fusiform gyrus and several nonhub regions showed significantly increased wiring of short-range connections and local network properties. Our results suggested that decreased local network in the frontal lobe and excessive development in the occipital lobe may contribute to the understanding of brain developmental deviances in preterm infants.

Recombinant expression and tryptophan-assisted analysis of human sweet taste receptor T1R3's extracellular domain in sweetener interaction studies.

The human palate can discern multiple tastes; however, it predominantly perceives five fundamental flavors: sweetness, saltiness, sourness, bitterness, and umami. Sweetness is primarily mediated through the sweet taste receptor, a membrane-bound heterodimeric structure comprising T1R2-T1R3. However, unraveling the structural and mechanistic intricacies of the sweet taste receptor has proven challenging. This study aimed to address this knowledge gap by expressing an extracellular N-terminal domain encompassing the cysteine-rich domain of human hT1R3 (hT1R3-TMD) in Escherichia coli. The expressed protein was obtained as inclusion bodies, purified by metal affinity chromatography, and refolded using the dilution-refolding method. Through rigorous analysis, we confirmed the successful refolding of hT1R3-TMD and elucidated its structural characteristics using circular dichroism spectroscopy. Notably, the refolded protein was found to exist as either a monomer or a dimer, depending on its concentration. A tryptophan fluorescence quenching assay revealed that the dissociation constants for sucrose, sucralose, and brazzein were >9500 µM, 2380 µM and 14.3 µM, respectively. Our findings highlight the utility of this E. coli expression system for producing functional hT1R3-TMD for investigations and demonstrate the efficacy of the tryptophan fluorescence quenching assay in revealing complex interactions between sweet taste receptors and various sweeteners.

Functional significance of serine 13 in the active site of glutathione S-transferase F3 from Oryza sativa.

Plant glutathione S-transferase (GST, EC 2.5.1.18) is an enzyme that detoxifies various electrophilic compounds including herbicides and organic pollutants by catalyzing the formation of conjugates with reduced glutathione (GSH). Although the structure and function of the GST subunits in rice, an important food in Asia, are not well understood, they are crucial for herbicide development. To investigate the role of active site residues in rice Phi-class GSTF3 (OsGSTF3), evolutionarily conserved serine residues were replaced with alanine using site-directed mutagenesis to obtain the mutants S13A, S38A, S69A, and S169A. These four mutants were expressed in Escherichia coli and purified to electrophoretic homogeneity using immobilized GSH affinity chromatography. Mutation of Ser13 to Ala resulted in substantial reductions in specific activities and kcat/Km values for the GSH-[1-chloro-2,4-dinitrobenzene (CDNB)] conjugation reaction. In contrast, mutations of Ser38, Ser69, and Ser169 to Ala had little effect on the activities and kinetic parameters. Additionally, the mutation of Ser13 to Ala significantly affected the KmGSH and I50 values of S-hexylglutathione and S-(2,4-dinitrophenyl)glutathione, which compete with GSH and the product of GSH-CDNB conjugation, respectively. A pH-log (kcat/KmCDNB) plot was used to estimate the pKa value of GSH in the enzyme-GSH complex of the wild-type enzyme, which was approximately 6.9. However, the pKa value of GSH in the enzyme-GSH complex of the S13A mutant was approximately 8.7, which was about 1.8 pK units higher than that of the wild-type enzyme. OsGSTF3 was also crystallized for crystallographic study, and the structure analyses revealed that Ser13 is located in the active site and that its side chain is in close proximity to the thiol group of glutathione bound in the enzyme. Based on these substitution effects on kinetic parameters, the dependence of kinetic parameters on the pH and 3-dimensional structure, it was suggested that Ser13 in rice OsGSTF3 is the residue responsible for catalytic activity by lowering the pKa of GSH in the enzyme-GSH complex and enhancing the nucleophilicity of the GSH thiol in the active site.

Multiple functions of pyruvate kinase M2 in various cell types.

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.

A Survey of the Criteria Used for the Selection of Alternative Comparator Products by Participating Regulators and Organizations of the International Pharmaceutical Regulators Programme.

The safety and efficacy of a generic product are partly based on demonstrating bioequivalence to the innovator product; however, when the innovator product is no longer available as a comparator product, a survey conducted within the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP) indicated that the criteria for selecting an alternative comparator product varies. For most members of the BEWGG, an existing marketed generic that was approved based on a comparison with the locally registered innovator product can be used, contingent on criteria that ranges from allowing any generic to be used, to allowing only specific criteria-defined generics to be used. Notwithstanding the acceptability of a generic as an alternative comparator, it is not always the preferred comparator for several jurisdictions. Some jurisdictions require the use of a locally sourced alternative innovator comparator (e.g., the same medicinal ingredient manufactured by a different company) or a foreign innovator comparator. Unlike the other members of the BEWGG, the European Union (EU) has no such options available, rather mechanisms are in place to allow manufacturers to develop a new comparator. The criteria described herein regarding the use of an alternative comparator product can also be applied to scenarios where a specific strength of a series of strengths or an innovative fixed dose combination are discontinued. The results of the survey demonstrate that while criteria for selecting alternative comparator products are not harmonized among the BEWGG participants, the common concern for all jurisdictions is to select a comparator product that meets the safety and efficacy standards of the original innovator product.

Systems approaches to uncovering the contribution of environment-mediated drug resistance.

Cancer drug response is heavily influenced by the extracellular matrix (ECM) environment. Despite a clear appreciation that the ECM influences cancer drug response and progression, a unified view of how, where, and when environment-mediated drug resistance contributes to cancer progression has not coalesced. Here, we survey some specific ways in which the ECM contributes to cancer resistance with a focus on how materials development can coincide with systems biology approaches to better understand and perturb this contribution. We argue that part of the reason that environment-mediated resistance remains a perplexing problem is our lack of a wholistic view of the entire range of environments and their impacts on cell behavior. We cover a series of recent experimental and computational tools that will aid exploration of ECM reactions space, and how they might be synergistically integrated.

Altered muscle recruitment patterns during isometric shoulder abduction in individuals with chronic upper trapezius pain: a cross sectional study.

BACKGROUND: Upper trapezius (UT) pain with myofascial trigger points (MTrPs) can affect movement at the glenohumeral joint as well as at the scapulothoracic joint. The investigation of muscle recruitment patterns can discern motor control strategies. The purpose of this study was to compare shoulder muscle recruitment patterns and muscle activity according to various loads between individuals with and without chronic UT pain. METHODS: In this cross-sectional study, twenty-four participants that had UT pain with MTrPs and sex, age, body weight matched 24 controls with no UT pain were recruited. Surface EMG electrodes were attached to the UT, the serratus anterior (SA), the lower trapezius (LT) and the middle deltoid (MD). All participants performed isometric shoulder abduction with a load of 25%, 50%, or 75% of the maximum strength at 60° of shoulder abduction. The EMG activity, the activity ratio (SA/UT, LT/UT, MD/UT), and the relative contribution of each muscle activity were calculated. RESULTS: MD activity was significantly decreased in the UT pain group compared to that in the control group (p < 0.05). The EMG activity ratio of SA/UT (p < 0.025) and the relative contribution of SA activity to shoulder abduction (p < 0.05) were significantly greater in the UT pain group than in the control group in the 25% loading condition. CONCLUSION: The results of present study showed that UT pain with MTrPs may increase the relative contribution of SA activity and decrease MD activity at low loads. Altered recruitment patterns of scapular upward rotators can be altered in the proper scapular position, which results in decreased MD activity. Clinicians should consider altered recruitment patterns when managing UT pain. TRIAL REGISTRATION: Clinical Research Information Service: Clinical Research Information Service (KCT0007370; 08/06/2022).

Characterization of antigenic variant infectious bursal disease virus strains identified in South Korea.

Infectious bursal disease (IBD) is one of the most important immunosuppressive diseases of young chickens, causing considerable economic losses to the poultry industry. More than 30 years ago, an antigenic variant (av) pathotype of the IBD virus (IBDV) was reported to originate in, and subsequently spread among, poultry farms in the USA. Recently, a novel avIBDV lineage was identified in China and was shown to exhibit clear differences in its pathogenicity as well as molecular characteristics compared with the previously isolated variant strains. In this study, we conducted a passive surveillance of chicken carcasses submitted to our research division from June-December 2019, and detected the IBDV strains by reverse transcription PCR. Five avIBDV strains were isolated, and their pathogenicity was determined by necropsy and molecular analysis. Additionally, a coinfection field case involving an avIBDV strain and a very virulent IBDV (vvIBDV) strain was identified. Multiple sequence alignment and phylogenetic analysis of partial viral protein 1 (VP1) and hypervariable region (hv) VP2 genes revealed that those strains originated from two different avIBDV lineages. The co-occurrence of two sub-groups of avIBDVs in South Korea confirms for the first time the evolution of antigenic variant IBDV strains, and highlights the urgency for the development of new strategies for IBDV intervention in South Korea.RESEARCH HIGHLIGHTS Five avIBDV strains were identified in South Korea by passive surveillance test in 2019.A coinfection between two IBDV strains from different genogroups was reported in a field case.By phylogenetic analysis, Korean avIBDVs belonged to two distinct lineages of antigenic variant genogroup.

The clinical features and outcomes of Tolosa-Hunt syndrome.

BACKGROUND: The objective of this study was to investigate the clinical features and outcomes of Tolosa-Hunt syndrome (THS). METHODS: A retrospective review of the medical records was performed on patients with THS between March 2016 and January 2020. A total of eleven patients fulfilling the International Classification of Headache Disorders (ICHD-3 beta) diagnostic criteria for THS were included in this study. RESULTS: The average age of the patients with THS was 57.18 ± 15.32 years and the mean duration of recovery was 26.91 ± 24.35 days. All eleven patients had orbital or periorbital pain as the first symptom followed by diplopia. Ptosis was found in five patients (45.45 %) in the involved eye. Sixth cranial nerve (CN) palsy was most common (eight cases, 72.73 %), followed by third and fourth CN palsy (five cases, 45.45 %, respectively), optic neuritis (two cases, 18.18 %), and trigeminal nerve and facial nerve palsy (one case, 9.09 %, respectively). One patient with optic neuritis failed to recover visual acuity and the other ten patients completely recovered their ocular motor limitation. All patients were initially treated with steroids. One patient relapsed after five weeks and one patient had a history of THS five years earlier. CONCLUSIONS: THS responded well to steroid treatment, but if it was accompanied by optic neuritis as optic nerve involvement, we suggest follow-up with high dose steroid treatment especially was important.

Comparison of the Shoulder External Rotator Strength and Asymmetry Ratio Between Workers With and Without Shoulder Impingement Syndrome.

ABSTRACT: Kim, J-H, Kwon, O-Y, Hwang, U-J, Jung, S-H, Ahn, S-H, and Kim, H-A. Comparison of shoulder external rotator strength and the asymmetry ratio between workers with and without shoulder impingement syndrome. J Strength Cond Res 35(12): 3364-3369, 2021-Shoulder impingement syndrome (SIS) is the most common shoulder problem causing shoulder pain. Several studies have indicated that shoulder external rotator muscles provide dynamic stability to the shoulder joint. However, the relationship of SIS to changes in shoulder external rotator muscle strength remains controversial. The purpose of the study was to compare the shoulder external rotator strength and asymmetry ratio between workers with SIS and the normal group in a side-lying position. Twelve male industrial workers with SIS and the normal group of 12 workers participated in this study. A pulling sensor measured shoulder external rotator muscle strength in a side-lying position with the shoulder at 0° and 90° of flexion. The asymmetry ratio was calculated by a specific formula using the shoulder external rotator muscle strength of the dominant side and the unaffected side. Two-way analysis of variance was used to determine between-group differences in shoulder external rotator muscle strength and the asymmetry ratio among the 2 positions. Subjects with SIS did not exhibit significant differences in shoulder external rotator muscle strength in the side-lying position with the shoulder at 0° and 90° of flexion relative to the normal group. However, subjects with SIS had a significantly increased asymmetry ratio of shoulder external rotation strength in the side-lying position with the shoulder at 90° of flexion compared with the normal group. In conclusion, workers with SIS had an asymmetry of shoulder external rotator strength in side-lying with the shoulder at 90° of flexion.

Diagnosis and management of three optic neuropathies: a national survey.

BACKGROUND: We aimed to evaluate the current practice patterns of neuro-ophthalmologists in diagnosis and management of three optic neuropathies using a national survey in South Korea and to further compare the practices of neuro-ophthalmologists divided into junior and senior groups based on their clinical practice experience. METHODS: An anonymous, 15-question survey on the diagnosis and treatment of traumatic optic neuropathy (TON), nonarteritic anterior ischemic optic neuropathy (NAION), and Leber's hereditary optic neuropathy (LHON) was sent to all neuro-ophthalmologists registered with the Korean Neuro-ophthalmology Society. The questions addressed physician's practice duration as neuro-ophthalmologist, choices of MRI scans and laboratory tests for the diagnosis in suspected optic neuropathy, clinical experiences with steroids (e.g., side effects), and choices of treatment modalities and reason in in each optic neuropathy. All participants were classified into senior (≥ 10 years) and junior (< 10 years) groups. RESULTS: A total of 63 responders (response rate 78.8%) answered the questionnaire. All responders performed the basic blood tests and brain imaging for evaluating optic neuropathy. Observation was the most preferred option for TON (47.6%) and NAION (63.5%). Steroid use was the second most preferred, and the most selected indication of steroid was "when the patient wants" (58.7%) for TON and "severe visual loss or last eye" (66%) for NAION. The most preferred treatment for LHON was "prescribing idebenone" (69.7%) with a dose of 900 mg/day (63.8%). Forty-nine respondents (77.8%) experienced side effects of steroids. There was no significant difference between the senior and junior groups in all questionnaire answers (all p > 0.05). CONCLUSION: Optic neuropathies are being managed similarly by the two groups in South Korea, and many of them still use steroids. We provided reliable reasons for our results compared with other countries.

Application of laser-induced breakdown spectroscopy for detection of elements in flowback water samples from shale gas wells.

Laser-induced breakdown spectroscopy (LIBS) was applied to rapidly detect elements in flowback water samples from shale gas wells in Oklahoma. Two types of LIBS systems (aerosolization and collection on a substrate) were used. The LIBS with an aerosolization system provided rapid determination of elements in flowback water, but moisture present in the chamber and variation in the water droplet size could make quantification difficult. In the substrate collection system, a comparison among substrate types showed that a hydrophilic cellulose filter gave the most homogeneous sample distribution after drying and provided the best performance. The elements in flowback water samples were also determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES). ICP-OES data showed spatial variations for the elements among the different wells. Among the elements, K showed the highest variation (relative standard ${\rm deviation} = {62.8}\% $deviation=62.8%) and Mg the lowest (relative standard ${\rm deviation} = {39.1}\% $deviation=39.1%). Good correlations (${ r} = {0.98 - 0.99}$r=0.98-0.99) were observed between Ca, K, Mg, and Na LIBS peak areas determined using the cellulose filter and their mass concentrations (ppm) measured by ICP-OES for aqueous solutions. The limits of detection for Ca, K, Mg, and Na by LIBS were 122 ppm, 68 ppm, 36 ppm, and 142 ppm, respectively. Both the LIBS and ICP-OES data showed that element concentrations in the flowback water samples were in the order of Na, Ca, Mg, and K from highest to lowest. Our data suggest that the LIBS technique could rapidly detect elements in flowback water samples on site. However, accurate quantification of elements present in low concentrations in water samples is limited.

Factors associated with myopia in Korean children: Korea National Health and nutrition examination survey 2016-2017 (KNHANES VII).

BACKGROUND: To evaluate the prevalence and risk factors associated with myopia and high myopia in children in South Korea. METHODS: A total of 983 children 5-18 years of age who participated in the Korean National Health and Nutrition Examination Survey 2016-2017 (KNHANES VII), a nationwide population-based cross-sectional study, were evaluated. Myopia and high myopia were defined as a spherical equivalent (SE) ≤ - 0.5 diopters (D) and SE ≤ --6.0 D. The association between refractive errors and potential risk factors for myopia was analyzed. RESULTS: The prevalence of myopia and high myopia was 65.4 and 6.9%, respectively. Older age and parental myopia were significantly associated with both myopia and high myopia, while higher body mass index (BMI) was associated with high myopia only. Although the proportion of subjects who spent more time on near work activities (≥4 h/day) was sequentially increased with increased refractive error, this tendency was not statistically significant by multivariable logistic regression. CONCLUSIONS: Korean children had a high prevalence of myopia and high myopia. In this age group, the risk of myopia increased with aging and parental myopia. Higher BMI may be associated with high myopia.

Red Chinese Cabbage Transcriptome Analysis Reveals Structural Genes and Multiple Transcription Factors Regulating Reddish Purple Color.

Reddish purple Chinese cabbage (RPCC) is a popular variety of Brassica rapa (AA = 20). It is rich in anthocyanins, which have many health benefits. We detected novel anthocyanins including cyanidin 3-(feruloyl) diglucoside-5-(malonoyl) glucoside and pelargonidin 3-(caffeoyl) diglucoside-5-(malonoyl) glucoside in RPCC. Analyses of transcriptome data revealed 32,395 genes including 3345 differentially expressed genes (DEGs) between 3-week-old RPCC and green Chinese cabbage (GCC). The DEGs included 218 transcription factor (TF) genes and some functionally uncharacterized genes. Sixty DEGs identified from the transcriptome data were analyzed in 3-, 6- and 9-week old seedlings by RT-qPCR, and 35 of them had higher transcript levels in RPCC than in GCC. We detected cis-regulatory motifs of MYB, bHLH, WRKY, bZIP and AP2/ERF TFs in anthocyanin biosynthetic gene promoters. A network analysis revealed that MYB75, MYB90, and MYBL2 strongly interact with anthocyanin biosynthetic genes. Our results show that the late biosynthesis genes BrDFR, BrLDOX, BrUF3GT, BrUGT75c1-1, Br5MAT, BrAT-1, BrAT-2, BrTT19-1, and BrTT19-2 and the regulatory MYB genes BrMYB90, BrMYB75, and BrMYBL2-1 are highly expressed in RPCC, indicative of their important roles in anthocyanin biosynthesis, modification, and accumulation. Finally, we propose a model anthocyanin biosynthesis pathway that includes the unique anthocyanin pigments and genes specific to RPCC.

Effect of Abdominal Electrical Muscle Stimulation Training With and Without Superimposed Voluntary Muscular Contraction on Lumbopelvic Control.

CONTEXT: Electrical muscle stimulation (EMS) was designed for artificial muscle activation or superimposed training. OBJECTIVES: To compare the effects of 8 weeks of superimposed technique (ST; application of electrical stimulation during a voluntary muscle action) and EMS on the cross-sectional area of the rectus abdominis, lateral abdominal wall, and on lumbopelvic control. SETTING: University research laboratory. DESIGN: Randomized controlled trial. PARTICIPANTS: Fifty healthy subjects were recruited and randomly assigned to either the ST or EMS group. INTERVENTION: The participants engaged with the electrical stimulation techniques (ST or EMS) for 8 weeks. MAIN OUTCOME MEASURES: In all participants, the cross-sectional area of the rectus abdominis and lateral abdominal wall was measured by magnetic resonance imaging and lumbopelvic control, quantified using the single-leg and double-leg lowering tests. RESULTS: There were no significant differences in the cross-sectional area of the rectus abdominis (right: P = .70, left: P = .99) or lateral abdominal wall (right: P = .07, left: P = .69) between groups. There was a significant difference between groups in the double-leg lowering test (P = .03), but not in the single-leg lowering test (P = .88). There were significant differences between the preintervention and postintervention in the single-leg (P < .001) and double-leg lowering tests (P < .001). CONCLUSIONS: ST could improve lumbopelvic control in the context of athletic training and fitness.

Comparison of MRI cross-sectional area and functions of core muscles among asymptomatic individuals with and without lumbar intervertebral disc degeneration.

BACKGROUND: Previous studies suggested that patients with symptomatic intervertebral disc degeneration (IDD) of lumbar spine have reduced cross-sectional area (CSA) and functions of core muscles. However, reduced CSA and functions of core muscles have been observed not only in patients with symptomatic IDD but also in patients with other subgroups of low back pain (LBP). Thus, it is uncertain whether reduced CSA and functions of core muscles lead to IDD and LBP, or pain leads to reduced CSA and functions of core muscles in patients with symptomatic IDD. Therefore, this study aimed to compare the CSA and functions of core muscles between asymptomatic participants with and without IDD in magnetic resonance imaging (MRI). METHODS: Twenty asymptomatic participants (12 men and 8 women) participated in this study. Ten participants had asymptomatic IDD at L4-5. The others were healthy controls (without IDD at all levels of lumbar spine). The CSA of core muscles was measured using MRI. Maximal isometric trunk flexor strength and side bridge strength were measured by a Smart KEMA strength sensor. Trunk flexor endurance test, side bridge endurance test and plank endurance test were used to measure core endurance. Double legs loading test was used to measure core stability. Mann-Whitney U test was used to compare the differences between two groups. RESULTS: There were no significant differences in core muscle functions between the two groups (p > 0.05). Moreover, there was no significant difference in CSA between the two groups (p > 0.05). CONCLUSIONS: There was no significant difference in CSA and core muscle functions between asymptomatic participants with and without IDD. These findings indicate that a degenerative or bulging disc in asymptomatic individuals has little effect on CSA and functions of core muscles, especially in young age. Therefore, the general core endurance test or strength test could not differentiate asymptomatic people with and without IDD of lumbar spine. TRIAL REGISTRATION NUMBER: Clinical Research information Service. KCT0004061. Registered 13 June 2019. retrospectively registered.

Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling.

Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient's daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation-induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.

Collagen VI-related myopathy: Expanding the clinical and genetic spectrum.

INTRODUCTION: We aimed to analyze the clinical and genetic characteristics of collagen VI-related myopathy. METHODS: We analyzed the clinical course and mutation spectrum in patients with collagen VI gene mutations among our congenital muscular dystrophy cohort. RESULTS: Among 24 patients with mutations in collagen VI coding genes, 13 (54.2%) were categorized as Ullrich type, and 11 (45.8%) as non-Ullrich type. Congenital orthopedic problems were similarly observed in both types, yet multiple joint contractures were found only in the Ullrich type. Clinical courses and pathology findings varied between patients. Mutations in COL6A1, COL6A2, and COL6A3 were found in 15 (65%), 3 (13%), and 5 (22%) patients, respectively, without genotype-phenotype association. Five novel variants were detected. DISCUSSION: We verified clinical heterogeneity of collagen VI-related myopathy, which emphasizes the importance of genetic testing. Genotype-phenotype association or early predictors for progression were not identified. Multiple joint contractures predict rapid deterioration. Muscle Nerve 58: 381-388, 2018.

Comparative toxicity of silver nanoparticles and silver ions to Escherichia coli.

With the increase in silver (Ag)-based products in our lives, it is essential to test the potential toxicity of silver nanoparticles (AgNPs) and silver ions (Ag ions) on living organisms under various conditions. Here, we investigated the toxicity of AgNPs with Ag ions to Escherichia coli K-12 strain under various conditions. We observed that both AgNPs and Ag ions display antibacterial activities, and that Ag ions had higher toxicity to E. coli K-12 strain than AgNPs under the same concentrations. To understand the toxicity of AgNPs at a cellular level, reactive oxygen species (ROS) enzymes were detected for use as antioxidant enzymatic biomarkers. We have also studied the toxicity of AgNPs and Ag ions under various coexistence conditions including: fixed total concentration, with a varied the ratio of AgNPs to Ag ions; fixed the AgNPs concentration and then increased the Ag ions concentration; fixed Ag ions concentration and then increasing the AgNPs concentration. Exposure to AgNPs and Ag ions clearly had synergistic toxicity; however, decreased toxicity (for a fixed AgNPs concentration of 5mg/L, after increasing the Ag ions concentration) to E. coli K-12 strain. AgNPs and Ag ions in the presence of L-cysteine accelerated the bacterial cell growth rate, thereby reducing the bioavailability of Ag ions released from AgNPs under the single and coexistence conditions. Further works are needed to consider this potential for AgNPs and Ag ions toxicity across a range of environmental conditions. ENVIRONMENTAL SIGNIFICANCE STATEMENT: As silver nanoparticles (AgNPs)-based products are being broadly used in commercial industries, an ecotoxicological understanding of the AgNPs being released into the environment should be further considered. Here, we investigate the comparative toxicity of AgNPs and silver ions (Ag ions) to Escherichia coli K-12 strain, a representative ecotoxicological bioreporter. This study showed that toxicities of AgNPs and Ag ions to E. coli K-12 strain display different relationships when existing individually or when coexisting, and in the presence of L-cysteine materials. These findings suggest that the toxicology research of nanomaterials should consider conditions when NPs coexist with and without their bioavailable ions.

PAX6 aniridia syndrome: clinics, genetics, and therapeutics.

PURPOSE OF REVIEW: Aniridia is a rare and panocular disorder affecting most of the ocular structures which may have significant impact on vision. The purpose of this review is to describe the clinical features, genetics, and therapeutic options for this disease and to provide an update of current knowledge and latest research findings. RECENT FINDINGS: Aside from the ocular features, a variety of associated systemic abnormalities, including hormonal, metabolic, gastrointestinal, genitourinary, and neurologic pathologies have been reported in children with aniridia. Although mutations in PAX6 are a major cause of aniridia, genetic defects in nearby genes, such as TRIM44 or ELP4, have also been reported to cause aniridia. Recent improvement in genetic testing technique will help more rapid and precise diagnosis for aniridia. A promising therapeutic approach called nonsense suppression therapy has been introduced and successfully used in an animal model. SUMMARY: Aniridia is a challenging disease. The progressive nature of this condition and its potential complications require continuous and life-long ophthalmologic care. Genetic diagnosis for aniridia is important for establishing definitive molecular characterization as well as identifying individuals at high risk for Wilms tumor. Recent advancement in understanding the genetic pathogenesis of this disease offers promise for the approaches to treatment.