Structural and functional characterization of rabbit and human L-gulonate 3-dehydrogenase.
L-Gulonate 3-dehydrogenase (GDH) catalyzes the NAD(+)-linked dehydrogenation of L-gulonate into dehydro-L-gulonate in the uronate cycle. In this study, we isolated the enzyme and its cDNA from rabbit liver, and found that the cDNA is identical to that for rabbit lens lambda-crystallin except for lacking a codon for Glu(309). The same cDNA species, but not the lambda-crystallin cDNA with the codon for Glu(309), was detected in the lens, which showed the highest GDH activity among rabbit tissues. In addition, recombinant human lambda-crystallin that lacks Glu(309) displays enzymatic properties similar to rabbit GDH. These data indicate that GDH is recruited as lambda-crystallin without gene duplication. An outstanding feature of GDH is modulation of its activity by low concentrations of P(i), which decreases the catalytic efficiency in a dose dependent manner. P(i) also protects the enzyme against both thermal and urea denaturation. Kinetic analysis suggests that P(i) binds to both the free enzyme and its NAD(H)-complex in the sequential ordered mechanism. Furthermore, we examined the roles of Asp(36), Ser(124), His(145), Glu(157 )and Asn(196) in the catalytic function of rabbit GDH by site-directed mutagenesis. The D36R mutation leads to a switch in favor of NADP(H) specificity, suggesting an important role of Asp(36) in the coenzyme specificity. The S124A mutation decreases the catalytic efficiency 500-fold, and the H145Q, N196Q and N195D mutations result in inactive enzyme forms, although the E157Q mutation produces no large kinetic alteration. Thus, Ser(124), His(145) and Asn(196) may be critical for the catalytic function of GDH.


Cannabinoid hyperemesis syndrome: case report of a paradoxical reaction with heavy marijuana use.
Cannabinoid hyperemesis syndrome (CHS) is a rare constellation of clinical findings that includes a history of chronic heavy marijuana use, severe abdominal pain, unrelenting nausea, and intractable vomiting. A striking component of this history includes the use of hot showers or long baths that help to alleviate these symptoms. This is an underrecognized syndrome that can lead to expensive and unrevealing workups and can leave patients self-medicating their nausea and vomiting with the very substance that is causing their symptoms. Long-term treatment of CHS is abstinence from marijuana use-but the acute symptomatic treatment of CHS has been a struggle for many clinicians. Many standard medications used for the symptomatic treatment of CHS (including ondansetron, promethazine, and morphine) have repeatedly been shown to be ineffective. Here we present the use of lorazepam as an agent that successfully and safely treats the tenacious symptoms of CHS. Additionally, we build upon existing hypotheses for the pathogenesis of CHS to try to explain why a substance that has been used for thousands of years is only now beginning to cause this paradoxical hyperemesis syndrome.


Fat induced hypertension in rabbits: the effects of dietary linoleic and linolenic acid.
It has been suggested that dietary linoleic and gamma-linolenic acid may be hypotensive. Fat enriched diets increase blood pressure, and the effects of linoleic and linolenic acids on this increase have been investigated. After a control period on a low fat diet, rabbits were given four fat enriched diets containing different proportions of linoleic, gamma-linolenic and alpha-linolenic acids for 8 weeks, and returned to the low fat control diet for 3 weeks. Blood pressures were measured non-invasively every day. Blood pressures increased from the 4th week of fat feeding. The blood pressure increase at 8 weeks was 10%, 13%, 15% and 14% respectively for primrose, starflower, safflower and olive oils (all P less than 0.001). Return to the low fat control diet for 3 weeks restored blood pressures to near control values. These results do not support the suggestion that either linoleic or gamma-linolenic acids are effective antihypertensive agents.


Differences in patient-reported hormone therapy use for menopause symptoms by provider specialty.
Hormone therapy (HT) is an effective treatment for menopause symptoms in select women. This study aimed to determine whether there is different prevalence of HT use based on patient report by women who see different provider specialties. This study was a cross-sectional analysis of published data from the Survey of Midlife in the United States (MIDUS), a telephone or self-administered questionnaire of 3294 participants aged 39-90 years. Postmenopausal women were included. Self-reported HT use and provider specialty seen were each assessed by one question. Univariate logistic regression assessed factors possibly related to HT use. Variables with p < 0.1 were entered into a multivariable logistic regression model. Of the 938 postmenopausal respondents, 720 (76%) saw a gynecologist for care. One-hundred and thirty-one (13%) women used HT for menopausal symptoms. Of women using HT, 72 (55%) saw a gynecologist. When controlling for other factors, women who saw a gynecologist had three times higher odds of using HT. The most frequently seen provider specialty was not associated with use. Women who ever see a gynecologist are more likely to use HT for menopausal symptoms, but fewer women see gynecologists as they age. Generalists are the most seen provider specialty, positioning them to counsel patients about HT.


Structural measurements and vessel density of spectral-domain optic coherence tomography in early, moderate, and severe primary angle-closure glaucoma.
To compare the macular ganglion cell-inner plexiform layer (GCIPL) thickness, retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) parameters, and retinal vessel density (VD) measured by spectral-domain optical coherence tomography (SD-OCT) and analyze the correlations between them in the early, moderate, severe primary angle-closure glaucoma (PACG) and normal eyes. Totally 70 PACG eyes and 20 normal eyes were recruited for this retrospective analysis. PACG eyes were further separated into early, moderate, or severe PACG eyes using the Enhanced Glaucoma Staging System (GSS2). The GCIPL thickness, RNFL thickness, ONH parameters, and retinal VD were measured by SD-OCT, differences among the groups and correlations within the same group were calculated. The inferior and superotemporal sectors of the GCIPL thickness, rim area of ONH, average and inferior sector of the retinal VD were significantly reduced (all P<0.05) in the early PACG eyes compared to the normal and the optic disc area, cup to disc ratio (C/D), and cup volume were significantly higher (all P<0.05); but the RNFL was not significant changes in early and moderate PACG. In severe group, the GCIPL and RNFL thickness were obvious thinning with retinal VD were decreasing as well as C/D and cup volume increasing than other three groups (all P<0.01). In the early PACG subgroup, there were significant positive correlations between retinal VD and GCIPL thickness (except superonasal and inferonasal sectors, r=0.573 to 0.641, all P<0.05), superior sectors of RNFL thickness (r=0.055, P=0.049). More obvious significant positive correlations were existed in moderate PACG eyes between retinal VD and superior sectors of RNFL thickness (r=0.650, P=0.022), and temporal sectors of RNFL thickness (r=0.740, P=0.006). In the severe PACG eyes, neither GCIPL nor RNFL thickness was associated with retinal VD. The ONH damage and retinal VD loss appears earlier than RNFL thickness loss in PACG eyes. As the PACG disease progressed from the early to the moderate stage, the correlations between the retinal VD and RNFL thickness increases.


Voice gains following thyroplasty may improve over time.
Type I thyroplasty for unilateral vocal fold paralysis restores voice. The purpose of this study was to evaluate measures of voice before thyroplasty, and at 3 months and 1 year after surgery. Of interest was whether vocal improvement in the first weeks after surgery was maintained or even enhanced over time. A total of 40 patients with unilateral paralysis underwent type I thyroplasty with or without arytenoid adduction. Perceptual, acoustic and aerodynamic measures of voice were studied. Perceptual analysis determined that optimal postoperative voice quality evolved over the first year. Acoustic indices of perturbation demonstrated progressive improvement over 12 months, whereas pitch and intensity ranges were increasingly extended. Postoperative glottal flow rates were normalized and phonation times were significantly longer, with benefits maintained over time. All perceptual, aerodynamic and acoustic measures of voice were improved 3 months after thyroplasty, with many measures further improved at 1 year. Such findings provide evidence that voice outcome progressively evolves over the first 12 months after surgery.


Differential expression of ten-eleven translocation genes in endometrial cancers.
Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC. The prognostic significance of TETs expression for overall survival was established. We found that TET1 and TET2 messenger RNA expression was lower and TET3 was higher in cancers compared to normal tissues. Positive correlation between 5-hmC and the relative expression of TET1 and TET2 was found, but no correlation was observed in the case of TET3. Decreased expression of TET1 and TET2 was significantly associated with increased lymph node metastasis and International Federation of Gynecology and Obstetrics stage. Kaplan-Meier analysis indicated that low TET1 expression predicted poor overall survival (p = 0.038). Multivariate analysis identified the TET1 expression in endometrial cancer as an independent prognostic factor. Our results suggest that decreased expression of TET1 correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.


Comparison of intravenous buprenorphine and methadone self-administration by recently detoxified heroin-dependent individuals.
Although buprenorphine is used worldwide as a safe and effective maintenance medication for opioid dependence, some countries have reported a growing incidence of abuse of this medication. Buprenorphine is considered to have lower abuse potential because of its partial agonist profile, but no studies have directly compared the reinforcing effects of buprenorphine with those of full mu opioid agonists in humans. The present double-blind, placebo-controlled inpatient study compared the reinforcing and subjective effects of intravenously administered buprenorphine (0.5, 2, and 8 mg) and methadone (5, 10, and 20 mg). Participants (n = 6) were detoxified from heroin during the first 1 to 2 weeks after admission. During subsequent weeks, participants received a sample drug dose and $20 on Monday, and they could self-administer either the sampled dose or $20 during one choice session per day on Thursday and Friday. Participants responded under a modified progressive ratio schedule during each choice session. All active doses maintained higher progressive ratio break points (largest completed ratio) than placebo. There were no significant differences in break point values between buprenorphine and methadone or among the different doses of drug. However, several subjective ratings, including "good drug effect", "high", and "liking" dose-dependently increased after administration of buprenorphine and methadone. The peak ratings for these effects did not significantly differ for the two drugs. These results demonstrate that under these experimental conditions, buprenorphine and methadone were equally effective in producing reinforcing and subjective effects.


Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle.
McArdle's disease is caused by genetic defects of the muscle-specific isozyme of glycogen phosphorylase, which block ATP formation from glycogen in skeletal muscle. Creatine supplementation and ketogenic diet have been tested as potential supplements for muscle energy metabolism which may improve muscle symptomatic. Outcome measures were clinical scores describing muscle symptomatic and parameters derived from 31P-MRS examinations on working muscle. In two placebo controlled cross-over studies low dose creatine showed beneficial effects on muscle symptoms and performance whereas high dose creatine distinctly worsened muscle symptomatic in patients. In both studies, however, the absence of an elevation in phosphocreatine indicated the absence of a creatine uptake by the muscle fibre. The effects of creatine on muscle symptomatic may be independent from energy metabolism in muscle. In a case study, ketogenic diet improved muscle symptomatic and performance. However, these effects again did not result in 31P-MRS visible changes in muscle energy metabolism.


A novel role of HSP90 in regulating osteoclastogenesis by abrogating Rab11b-driven transport.
Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that plays a pivotal role in folding, activating and assembling a variety of client proteins. In addition, HSP90 has recently emerged as a crucial regulator of vesicular transport of cellular proteins. In our previous study, we revealed Rab11b negatively regulated osteoclastogenesis by promoting the lysosomal proteolysis of c-fms and RANK surface receptors via the axis of early endosome-late endosome-lysosomes. In this study, using an in vitro model of osteoclasts differentiated from murine macrophage-like RAW-D cells, we revealed that Rab11b interacted with both HSP90 isoforms, HSP90 alpha (HSP90α) and HSP90 beta (HSP90β), suggesting that Rab11b is an HSP90 client. Using at specific blocker for HSP90 ATPase activity, 17-allylamino-demethoxygeldanamycin (17-AAG), we found that the HSP90 ATPase domain is indispensable for maintaining the interaction between HSP90 and Rab11b in osteoclasts. Nonetheless, its ATPase activity is not required for regulating the turnover of endogenous Rab11b. Interestingly, blocking the interaction between HSP90 and Rab11b by either HSP90-targeting small interfering RNA (siHSP90) or 17-AAG abrogated the inhibitory effects of Rab11b on osteoclastogenesis by suppressing the Rab11b-mediated transport of c-fms and RANK surface receptors to lysosomes via the axis of early endosome-late endosome-lysosomes, alleviating the Rab11b-mediated proteolysis of these surface receptors in osteoclasts. Based on our observations, we propose a HSP90/Rab11b-mediated regulatory mechanism for osteoclastogenesis by directly modulating the c-fms and RANK surface receptors in osteoclasts, thereby contributing to the maintenance of bone homeostasis.


Impact of hypothermia on implementation of CPAP for neonatal respiratory distress syndrome in a low-resource setting.
Neonatal hypothermia is widely associated with increased risks of morbidity and mortality, but remains a pervasive global problem. No studies have examined the impact of hypothermia on outcomes for preterm infants treated with CPAP for respiratory distress syndrome (RDS). This retrospective analysis assessed the impact of hypothermia on outcomes of 65 neonates diagnosed with RDS and treated with either nasal oxygen (N = 17) or CPAP (N = 48) in a low-resource setting. A classification tree approach was used to develop a model predicting survival for subjects diagnosed with RDS. Survival to discharge was accurately predicted based on three variables: mean temperature, treatment modality, and mean respiratory rate. None of the 23 neonates with a mean temperature during treatment below 35.8°C survived to discharge, regardless of treatment modality. Among neonates with a mean temperature exceeding 35.8°C, the survival rate was 100% for the 31 neonates treated with CPAP and 36.4% for the 11 neonates treated with nasal oxygen (p<0.001). For neonates treated with CPAP, outcomes were poor if more than 50% of measured temperatures indicated hypothermia (5.6% survival). In contrast, all 30 neonates treated with CPAP and with more than 50% of temperature measurements above 35.8°C survived to discharge, regardless of initial temperature. The results of our study suggest that successful implementation of CPAP to treat RDS in low-resource settings will require aggressive action to prevent persistent hypothermia. However, our results show that even babies who are initially cold can do well on CPAP with proper management of hypothermia.


OxyR is involved in the expression of thioredoxin reductase TrxB in Pseudomonas putida.
OxyR regulates the expression of a peroxiredoxin (AhpC) and two catalases (KatA and KatB), which play roles in peroxide protection, at the transcription level in Pseudomonas putida KT2442. Proteome analysis indicated significantly increased amounts of the enzymes AhpC, KatA, KatB, and a peroxiredoxin reductase (AhpF) in the oxyR1 mutant cells; these increases reflected the upregulation of the expression of the genes encoding these enzymes. Additionally, although the effect of oxyR1 mutation on the trxB transcript level was not clearly evident, it increased the amount of thioredoxin reductase (TrxB) by fivefold. Primer extension analysis revealed that trxB was constitutively transcribed from the P1 site; however, hydrogen peroxide treatment lowered the transcription of trxB from P1 but induced its transcription from P2. Adjacent to the -35 base of the P2 initiation site, sequences similar to those involved in the proposed OxyR binding in Escherichia coli were found in a region to which OxyR was shown to bind. These observations suggest that in P. putida, OxyR regulates TrxB expression by promoting trxB transcription from the P2 site when oxidative stresses lowered the transcription from the constitutive P1 site.


Bernard Soulier Syndrome: 10 years' experience at a tertiary care hospital.
To determine clinical manifestations and laboratory findings in patients with BSS diagnosed through platelet aggregometry followed in a tertiary care hospital in Lahore, Pakistan. The retrospective study comprised patients who presented in Hematology and Transfusion Medicine Department of The Children Hospital & Institute of Child Health, Lahore with the relevant diagnosis from 2006 to 2013. The result of all the patients were collected on a predesigned proforma. Medical data was scrutinized to collect age, gender, clinical findings along with results of complete blood count, bleeding time and platelet aggregation studies for the diagnosis of Bernard Soulier Syndrome. Among 49 patients, 26 patients were females and 23 males. The mean age of the patients was 5±2.5 years. 81% had a family history of consanguinity. The most common presenting symptom included epistaxis seen in 73.4% patients. Complete blood count demonstrated decreased platelets in 85.7% of patients ranging from 20 X 109/L to 130 X 109/L. Anemia was seen in 67.3% and 93.8% had prolonged bleeding time. Peripheral blood smears demonstrated giant platelets in all patients. The majority of patients 65.3% had mild bleeding episodes. Platelet aggregation studies showed normal aggregation with ADP, Collagen and Epinephrine in 100% of our patients whereas all showed no response of aggregation with Ristocetin. Our data is consistent with other reports regarding clinical presentation of BSS, but we report large number of BSS patients from our area, emphasizing significance to provide diagnostic services in Pakistan to find out exact magnitude of disease.


Unexplored potentials of epigenetic mechanisms of plants and animals-theoretical considerations.
Morphological and functional changes of cells are important for adapting to environmental changes and associated with continuous regulation of gene expressions. Genes are regulated-in part-by epigenetic mechanisms resulting in alternating patterns of gene expressions throughout life. Epigenetic changes responding to the environmental and intercellular signals can turn on/off specific genes, but do not modify the DNA sequence. Most epigenetic mechanisms are evolutionary conserved in eukaryotic organisms, and several homologs of epigenetic factors are present in plants and animals. Moreover, in vitro studies suggest that the plant cytoplasm is able to induce a nuclear reassembly of the animal cell, whereas others suggest that the ooplasm is able to induce condensation of plant chromatin. Here, we provide an overview of the main epigenetic mechanisms regulating gene expression and discuss fundamental epigenetic mechanisms and factors functioning in both plants and animals. Finally, we hypothesize that animal genome can be reprogrammed by epigenetic factors from the plant protoplast.


[Inflammatory myofibroblastic tumor of the bladder: a case report].
A 15-year-old girl presented to a clinic with an asymptomatic macrohematuria. Cystoscopy revealed a bladder tumor. The next day she was admitted to our hospital because of preshock status with macrohematuria. Abdominal computed tomography (CT) revealed a solid tumor in the left anterior to lateral wall. Urinary cytology was negative. She received a transfusion and transurethral resection of bladder tumor as an emergent operation. Histopathological examination revealed inflammatory myofibroblastic tumor. Anaplastic lymphoma kinase immunohistopathological studies revealed cytoplasmic staining of the myofibroblasts. To our knowledge, this is the 35th reported case of inflammatory myofibroblastic tumor of the bladder in Japan. She has been followed up for 13 months without any evidence of local recurrence.


Interactions between growth factors and gap junctional communication in developing systems.
In the vertebrate limb bud fibroblast growth factor (FGF) 4 secreted by cells of the posterior apical ectodermal ridge controls digit pattern, which is directed by polarizing cells in the posterior mesenchyme at the tip of the bud. FGF4 also controls the expression of gap junctions in the limb. Both chick and mouse limb bud mesenchyme express connexin 32 (Cx32; beta 1) and Cx43 (alpha 1), although not in the same gap junction plaques. Quantitative analysis reveals two gradients of gap junctions: from posterior to anterior in the subapical mesenchyme and from distal to proximal along the bud. The highest gap junction density is associated with the polarizing region. Micromass cultures of chick and mouse posterior and anterior mesenchyme cells were used to assess the ability of FGF4 to modulate gap junctional communication. Posterior mesenchyme (polarizing region) cells express a population of gap junctions that are highly sensitive to FGF4, whereas gap junctions between anterior mesenchyme cells are completely insensitive to FGF4. FGF4 doubles gap junction density, intercellular communication and the polarizing capacity of posterior mesenchyme cells, restoring polarizing capacity to in vivo levels. We conclude that gap junctional communication and polarizing capacity are intimately linked. Interactions between signalling molecules and junctional communication may play an important role in controlling development.


[Septic arthritis in systemic lupus erythematosus: a retrospective analysis of 6 cases].
Base on the clinical characteristics of septic arthritis in a group of systemic lupus erythematosus patients, this study has found out that high systemic lupus erythematosus disease activity index, leucopenia, high cumulative dose of glucocorticoid, methylprednisolone intravenous pulse therapy and joint cavity puncture were closely correlated with septic arthritis. Once septic arthritis is suspected, culture specimens should be collected and appropriate antibiotics are suggested immediately. Also, surgical drainage is a very useful approach.


Effects of oxicam inhibitors of cyclooxygenase on oxidative stress generation in rat gastric mucosa. A comparative study.
The aim of this study was to compare the effects of two nonsteroidal anti-inflammatory drugs (NSAID), members of the same family with a different cyclooxygenase (COX) inhibition selectivity, meloxicam, preferent COX-2 inhibitor, and piroxicam, preferent COX-1 inhibitor, on oxygen radical generation in rat gastric mucosa. Therefore, the activity of oxidative stress-related enzymes such as xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione (GSH) homeostasis were studied in rats. Gastric prostaglandins (PG) were also assessed as a measure of COX-1 inhibition. Both oxicams produced a similar extent of the gastric mucosal damage and a significant decrease in PGE2 synthesis, however only piroxicam induced an increase of both myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-alpha content in the gastric mucosa, indicating that neutrophil-derived free radicals were involved in gastric injury. Furthermore, both compounds reduced SOD activity and increased XO activity in gastric mucosa. Our results also revealed modifications in GSH metabolism: although glutathione peroxidase (GSH-px) activity was unaffected by meloxicam or piroxicam administration, both glutathione reductase (GSSG-rd) activity and total GSH content were significantly decreased after dosing. These results suggest that under our experimental conditions, meloxicam, preferential COX-2 inhibitor causes rates of gastric lesion in rats comparable to those seen with the traditional NSAID piroxicam, preferential COX-1 inhibitor. In addition to suppression of systemic COX activity, oxygen radicals, probably derived via the XO, and neutrophils play an important role in the production of damage induced by both oxicams. Moreover, the decrease in SOD activity and changes in glutathione homeostasis in gastric mucosa may also contribute to pathogenesis of meloxicam- or piroxicam-induced gastropathy.


Radiographic Blind Test of Curvature of the Posterior Border of the Mandibular Ramus as a Morphological Indicator of Gender.
Curvature of the posterior border of the mandibular ramus at the occlusal plane has been described as a morphological trait for males. Controversy over the accuracy of this method remains among researchers; studies employing similar methods report accuracy rates for successful gender identification ranging from 59% to 99%. This blind study assessed evaluators' ability to determine gender based on the presence or absence of curvature of the posterior margin of the mandibular ramus through panoramic radiographs. Randomly selected panoramic radiographs were obtained from The Ohio State University College of Dentistry for 413 adult male (M) and female (F) subjects. Two evaluators separately assigned ratings using a similar method to the Loth and Henenberg methodology to each subject on the right and left sides of mandibular rami. The ratings were based upon three criteria: (1) presence of curvature at the occlusal plane (M), (2) presence of curvature but not at the occlusal plane (F), and (3) lack of curvature (F). Pearson exact chi-squared test was used to evaluate the statistical strength of the ratings. The evaluators were only in agreement for both the right and left rami in roughly two-thirds (66.8%) of cases when there was no excessive tooth loss (ETL); however, the inter-observer agreement improved to 82.1% for those rami associated with ETL. Inter-observer agreement occurred in 72.9% of female rami and in only 64.4% of male rami. The results of this study indicated that assessment of posterior border curvature of mandibular rami through panoramic radiographs was not a reliable indicator of gender and was further plagued by unacceptably high levels of inter-observer disagreement.


Effect of diuretics on oxidative phosphorylation of dog kidney mitochondria.
An effect of diuretics on cellular metabolism has been shown. In order to examine further the direct effect of diuretics on renal mitochondria, their effect on isolated cortical (C) and outer medullary (OM) mitochondrial respiration was examined. Oxygen consumption rate (QO2) was measured in a Gilson oxygraph utilizing either glutamate-malate or succinate as substrate. QO2, expressed in nanoatoms of O2 per milligram of protein per minute, was always higher in C than OM: 140.7 +/- 2.8 VS. 121.2 +/- 2.4 (P less than 0.001) with glutamate-malate and 181.1 +/- 6.3 vs. 129.7 +/- 5.2 (P less than 0.001) with succinate. A dose-response curve was constructed for each of the following: sodium ethacrynate, furosemide, chlorothiazide, acetazolamide and chlormerodrin. All diuretics inhibited C and OM equally. The 50% inhibitory molar concentration for EA was 6.2 times 10(-4); for furosemide 1.5 times 10(-3); for chlorothiazide 8.1 times 10(-3); for acetazolamide 10.8 times 10(-3); and for chlomerodrin 3.1 times 10(-5). Neither cysteine nor dithiothreitol inhibited the effect of EA. The effect of chlormerodrin was abolished by cysteine. These results demonstrate that while a difference exists between C and OM mitochondria during control studies, each of the diuretics examined exerted an equal inhibitory effect on mitochondrial respiration from both C and OM. Mercurials are the most potent inhibitors and presumably exert their effect by reacting with sulfhydryl groups. They are followed in potency by ethacrynic acid, furosemide, chlorothiazide and acetazolamide.


Hollow Cobalt Phosphide with N-Doped Carbon Skeleton as Bifunctional Electrocatalyst for Overall Water Splitting.
The development of cost-effective, high-performance, and robust bifunctional electrocatalysts for overall water splitting remains highly desirable yet quite challenging. Here, by selecting appreciate precursors of dopamine and a Co-containing metal-organic framework of ZIF-67, we subtly couple their reaction processes to develop a facile approach for the synthesis of a hollow CoP nanostructure with N-doped carbon skeleton (H-CoP@NC). Benefiting from the highly porous nanostructure and conductive carbon skeleton, H-CoP@NC is capable of working as highly active and durable bifunctional electrocatalyst for both hydrogen and oxygen evolution reaction. When further used as the electrocatalyst for overall water splitting, H-CoP@NC delivers excellent activity (cell voltage of 1.72 V at a current density of 10 mA cm-2), close to that of the noble-metal-based benchmark catalyst couple of Pt/C||RuO2. Our work thus provides new insights into the development of transitional metal phosphides based hollow hybrid nanostructures, particularly those with multiple functionalities in sustainable energy conversion technologies and systems.


Genomewide association study of ionomic traits on diverse soybean populations from germplasm collections.
The elemental content of a soybean seed is a determined by both genetic and environmental factors and is an important component of its nutritional value. The elemental content is chemically stable, making the samples stored in germplasm repositories an intriguing source of experimental material. To test the efficacy of using samples from germplasm banks for gene discovery, we analyzed the elemental profile of seeds from 1,653 lines in the USDA Soybean Germplasm Collection. We observed large differences in the elemental profiles based on where the lines were grown, which lead us to break up the genetic analysis into multiple small experiments. Despite these challenges, we were able to identify candidate single nucleotide polymorphisms (SNPs) controlling elemental accumulation as well as lines with extreme elemental accumulation phenotypes. Our results suggest that elemental analysis of germplasm samples can identify SNPs in linkage disequilibrium to genes, which can be leveraged to assist in crop improvement efforts.


From Isolated Anions to Polymer Structures through Linking with I2: Synthesis, Structure, and Properties of Two Complex Bismuth(III) Iodine Iodides.
We report the synthesis, crystal structures, and optical properties of two new compounds, K18Bi8I42(I2)0.5·14H2O (1) and (NH4)7Bi3I16(I2)0.5·4.5H2O (2), as well as the electronic structure of the latter. They crystallize in tetragonal space group P4/ mmm with the unit cell parameters a = 12.974(1) and c = 20.821(3) Å for 1 and a = 13.061(3) and c = 15.162(7) Å for 2. Though 1 and 2 are not isomorphous, their crystal structures display the same structural organization; namely, the BiI6 octahedra are linked by I2 units to form disordered layers in 1 and perfectly ordered chains in 2. The I-I bond distances in the thus formed I-I-I-I linear links are not uniform; the central bond is only slightly longer than in a standalone I2 molecule, whereas the peripheral bonds are significantly shorter than longer bonds typical for various polyiodides, which is confirmed by Raman spectroscopy. The analysis of the electronic structure shows that the atoms forming the I-I-I-I subunits transfer electron density from their occupied 5p orbitals onto their vacant states as well as onto 6s orbitals of bismuth atoms that center the BiI6 octahedra. This leads to low direct band gaps that were found to be 1.57 and 1.27 eV for 1 and 2, respectively, by optical absorption spectroscopy. Luminescent radiative relaxation was observed in the near-IR region with emission maxima of 1.39 and 1.24 eV for 1 and 2, respectively, in good agreement with the band structure, despite the strong quenching propensity of I2 moieties.


Accurate reconstructions of pelvic defects and discontinuities using statistical shape models.
Treatment of large acetabular defects and discontinuities remains challenging and relies on the accurate restoration of the native anatomy of the patient. This study introduces and validates a statistical shape model for the reconstruction of acetabular discontinuities with severe bone loss through a two-sided Markov Chain Monte Carlo reconstruction method. The performance of the reconstruction algorithm was evaluated using leave-one-out cross-validation in three defect types with varying severity as well as severe defects with discontinuities. The two-sided reconstruction method was compared to a one-sided methodology. Although, reconstruction errors increased with defect size and this increase was most pronounced for pelvic discontinuities, the two-sided reconstruction method was able to reconstruct the native anatomy with higher accuracy than the one-sided reconstruction method. These findings can improve the preoperative planning and custom implant design in patients with large pelvic defects, both with and without discontinuities.


Preparation and characterization of a human scFv against the Clostridium perfringens type A alpha-toxin.
Alpha-toxin produced by Clostridium perfringens is an important virulence factor, causing food poisoning and gas gangrene in humans. As such, it is considered a potential bioterrorism threat. To date, there is still no human effective therapeutic drug against alpha-toxin. In this study, a human single chain antibody against alpha-toxin was produced from synthetic (Tomlinson I + J) naive phage display libraries, and its preventive and therapeutic efficacy in mice was examined. To prove the neutralizing potential of the scFv, alpha-toxin was preincubated with scFv and subsequently tested for its lecithinase and hemolytic activity, as well as its lethal effect in mice following intravenous administration. The equilibrium association constant between scFv and CPA was 2.02 × 1010 (1/M), as analyzed by SPR. The scFv could inhibit lecithinase and hemolytic activity, and provided effective protection against alpha-toxin when mice were challenged 1-h post scFv injection. In addition, the survival rate reached 80% for mice treated with scFv within 30 min of being challenged with a 2 × LD50 dose of alpha-toxin. These results confirmed that we successfully prepared a human scFv against C. perfringens type A alpha-toxin, which can be used in the prevention and treatment of alpha-toxin-related illness.


Lesbian, Gay, and Heterosexual Adoptive Parents' Experiences in Preschool Environments.
Little research has examined the school experiences of lesbian/gay (LG) parent families or adoptive parent families. The current exploratory study examined the experiences of 79 lesbian, 75 gay male, and 112 heterosexual adoptive parents of preschool-age children with respect to their (a) level of disclosure regarding their LG parent and adoptive family status at their children's schools; (b) perceived challenges in navigating the preschool environment and advocating on behalf of their children and families; and (c) recommendations to teachers and schools about how to create affirming school environments with respect to family structure, adoption, and race/ethnicity. Findings revealed that the majority of parents were open about their LG and adoptive family status, and had not encountered challenges related to family diversity. Those parents who did experience challenges tended to describe implicit forms of marginalization, such as insensitive language and school assignments. Recommendations for teachers included discussing and reading books about diverse families, tailoring assignments to meet the needs of diverse families, and offering school community-building activities and events to help bridge differences across families.


Triptolide enhances the tumoricidal activity of TRAIL against renal cell carcinoma.
Renal cell carcinoma (RCC) is resistant to traditional cancer therapies, and metastatic RCC (mRCC) is incurable. The shortcomings in current therapeutic options for patients with mRCC provide the rationale for the development of novel treatment protocols. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has proven to be a potent inducer of tumor cell death in vitro and in vivo, and a number of TRAIL death receptor agonists (recombinant TRAIL or TRAIL death receptor-specific mAb) have been developed and tested clinically. Unfortunately the clinical efficacy of TRAIL has been underwhelming and is likely due to a number of possible mechanisms that render tumors resistant to TRAIL, prompting the search for drugs that increase tumor cell susceptibility to TRAIL. The objective of this study was to determine the effectiveness of combining the diterpene triepoxide triptolide, or its water-soluble prodrug, Minnelide, with TRAIL receptor agonists against RCC in vitro or in vivo, respectively. TRAIL-induced apoptotic death of human RCC cells was increased in the presence of triptolide. The triptolide-induced sensitization was accompanied by increased TRAIL-R2 (DR5) and decreased heat shock protein 70 expression. In vivo treatment of mice bearing orthotopic RCC (Renca) tumors showed the combination of Minnelide and agonistic anti-DR5 mAb significantly decreased tumor burden and increased animal survival compared to either therapy alone. Our data suggest triptolide/Minnelide sensitizes RCC cells to TRAIL-induced apoptosis through altered TRAIL death receptor and heat shock protein expression.


An Auditory Nerve Stimulation Chip with Integrated AFE, Sound Processing, and Power Management for Fully Implantable Cochlear Implants.
This paper presents a system on chip for a fully implantable cochlear implant. It includes acoustic sensor front-end, 4-channel digital sound processing and auditory nerve stimulation circuitry. It also features a digital, switched mode, single inductor dual output power supply that generates two regulated voltages; 0.4 V used to supply on-chip digital blocks and 0.9 V to supply analog blocks and charge the battery when an external RF source is detected. All passives are integrated on-chip including the inductor. The system was implemented in 14nm CMOS and validated with post layout simulations.


Transcriptional regulation of comC: evidence for a competence-specific transcription factor in Bacillus subtilis.
comC specifies a protein product that is required for genetic competence in Bacillus subtilis. The probable transcriptional start site of comC has been localized by high-resolution primer extension analysis and shown to be preceded by an appropriately positioned sequence that resembles the consensus promoter for the sigma A form of RNA polymerase. Low-resolution S1 nuclease transcription mapping was used to identify the comC terminator, which is located near a palindromic element recognizable in the DNA sequence. Deletion analysis of the sequence upstream from the likely promoter identified a region required in cis for the expression of comC. An overlapping, and possibly identical, sequence was shown to inhibit the expression of competence and of several late competence genes, when present in multiple copies. This was interpreted as due to the titration of a positively acting competence transcription factor (CTF) by multiple copies of the promoter-bearing fragment. In crude lysates of B. subtilis grown to competence, a DNA-binding activity that appeared to be specific for the comC promoter fragment was detected by gel retardation assays. This activity, postulated to be due to CTF, was detected only following growth in competence medium, only in the stationary phase of growth, and was dependent on the expression of ComA, a known competence-regulatory factor. In the presence of the mecA42 mutation, the ComA requirement for CTF activity was bypassed, and CTF activity could be detected in lysates prepared from a strain grown in complex medium. This behavior suggested that either the expression or the activation of CTF was regulated in a competence-specific manner. Comparison of the putative CTF-binding site defined by deletion analysis with a similarly positioned sequence upstream from the start site of the late competence gene comG revealed that both sequences contained palindromes, with 5 of 6 identical base pairs in each arm. It is suggested that these palindromic sequences comprise recognition elements for CTF binding and that CTF binding must occur for the appropriate expression of late competence genes.


Growth of Escherichia coli in whole and skim milk from endotoxin-induced mastitic quarters: in vitro effects of deferoxamine, zinc, and iron supplementation.
A marked growth inhibition of Escherichia coli 0101 K99 F41 was observed in whole and skim milk collected from inflamed quarters 18 and 36 h after intramammary administration of .1 mg E. coli lipopolysaccharide. Individual cow variation in the ability of milk from endotoxin-infused quarters to inhibit growth of E. coli was found. Growth inhibition of E. coli was observed in milk from endotoxin-infused quarters and was most pronounced in skim milk sampled at postinfusion h 18, and incubated at 38 degrees C. The mechanism by which bacterial growth was depressed was probably of noncellular origin. Addition of Fe (45.5 micrograms/ml) and Zn (2.7 micrograms/ml) to whole and skim milk sampled from inflamed quarters at 18 h after endotoxin infusion resulted in a growth-promoting effect. Addition of deferoxamine (6 mg/ml) depressed bacterial growth. Effects of Fe, Zn, and deferoxamine on bacterial growth did not differ in whole and skim milk. No clear relationship was observed between reduction in Zn concentrations in skim milk from inflamed quarters at 18 h after endotoxin infusion and growth inhibition of E. coli in the same samples.


Moral development at the crossroads: new trends and possible futures.
This article introduces a special section on moral development. We claim that the field is now undergoing a resurgence of theoretical and methodological innovation after the eclipse of paradigmatic moral stage theory. Although research on prosocial development, moral emotions, and social domain theory has sustained interest in moral development, recent additional trends have contributed to its resurgence. This includes research in neuroscience, sociobiology, and social psychology; broad interest in moral-character education and virtues; and the appearance of recent handbooks and special journal issues. We review 3 broad possible future themes (early development, self and personality, and culture) of moral development research and introduce a set of new contributions in this special section as examples.


Expectancy-Value Motivation and Physical Activity- and Health-Related Outcomes among At-Risk Children and Adolescents.
Despite a large amount of research having been done to examine and promote physical activity and health among adolescents and children, relatively little attention has been paid attention to underrepresented populations. In this study, we investigated the relationships between expectancy-value motivation and physical activity- and health-related outcomes among a group of at-risk boys at a summer sports camp. The total participants included 107 boys (Mage = 11.78 years, SD = 1.20). The boys' perceived expectancy beliefs (EXP), importance (IMP), interest (INT), usefulness (USE), effort (EFT), and intention for future participation (IFP) were assessed using established questions on a five-point Likert scale, and a PACER test was performed to estimate their cardiovascular fitness (CVF). Through a path analysis, we found that EXP positively predicted CVF (β = 0.19, p < 0.01), IMP positively predicted EFT (β = 0.26, p < 0.01), and INT positively predicted both EFT (β = 0.34, p < 0.01) and IFP (β = 0.28, p < 0.01), while USE had no statistically significant effect on either EFT, IFP, or CVF. We discussed the limitations and implications of the present study. We recommend including a diverse sample and employing the expectancy-value model in future research, and advocating expectancy beliefs and task values, especially importance and interest, among participants during physical activity promotion.


Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins.
The susceptibility of colistin-resistant clinical isolates of Klebsiella pneumoniae to ceragenins and antimicrobial peptides (AMPs) suggests that there is little to no cross-resistance between colistin and ceragenins/AMPs and that lipid A modifications are found in bacteria with modest changes in susceptibility to ceragenins and with high levels of resistance to colistin. These results suggest that there are differences in the resistance mechanisms to colistin and ceragenins/AMPs.


Analysis of biodegradation of copolymer dermis substitutes in the dorsal skinfold chamber of balb/c mice.
PEGT/PBT-block-copolymer dermis substitutes were inserted into dorsal skinfold chambers of balb/c mice (n=36). Scaffolding matrices with 3 different pore diameters (pore diameter: <75 micro m, 75-212 micro m and 250-300 micro m) were analyzed on days 7, 14, and 21 post implantation by scanning electron and light microscopy. The quantification of matrix fragmentation was performed using image-analytical software analySIS(R). The fragmentation rate in scaffolding matrices with a pore size of < 75 micro m was observed to be higher than in matrices of larger pore sizes. Image-analytical evaluation over 21 days revealed a reduction of the copolymer matrix by approximately 32% for the <75 micro m matrices, 23% for the 75-212 micro m matrices and 18% for the matrices, where pore size ranged between 250 micro m and 300 micro m. Twenty-one days after implantation, the matrix pores of 75-212 micro m and 250-300 micro m scaffolds were totally filled by vascularized fibrous tissue. Contrarily, an increased formation of foreign-body giant cells was observed in matrices with pore size <75 micro m. The pore size of the scaffolding PEGT/PBT dermis substitutes affects their degradative behaviour in vivo.


Primate Lentiviruses Modulate NF-κB Activity by Multiple Mechanisms to Fine-Tune Viral and Cellular Gene Expression.
The transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) plays a complex role during the replication of primate lentiviruses. On the one hand, NF-κB is essential for induction of efficient proviral gene expression. On the other hand, this transcription factor contributes to the innate immune response and induces expression of numerous cellular antiviral genes. Recent data suggest that primate lentiviruses cope with this challenge by boosting NF-κB activity early during the replication cycle to initiate Tat-driven viral transcription and suppressing it at later stages to minimize antiviral gene expression. Human and simian immunodeficiency viruses (HIV and SIV, respectively) initially exploit their accessory Nef protein to increase the responsiveness of infected CD4+ T cells to stimulation. Increased NF-κB activity initiates Tat expression and productive replication. These events happen quickly after infection since Nef is rapidly expressed at high levels. Later during infection, Nef proteins of HIV-2 and most SIVs exert a very different effect: by down-modulating the CD3 receptor, an essential factor for T cell receptor (TCR) signaling, they prevent stimulation of CD4+ T cells via antigen-presenting cells and hence suppress further induction of NF-κB and an effective antiviral immune response. Efficient LTR-driven viral transcription is maintained because it is largely independent of NF-κB in the presence of Tat. In contrast, human immunodeficiency virus type 1 (HIV-1) and its simian precursors have lost the CD3 down-modulation function of Nef and use the late viral protein U (Vpu) to inhibit NF-κB activity by suppressing its nuclear translocation. In this review, we discuss how HIV-1 and other primate lentiviruses might balance viral and antiviral gene expression through a tight temporal regulation of NF-κB activity throughout their replication cycle.


Psychiatric issues in palliative care: assessing mental capacity.
Issues surrounding capacity to consent to or refuse treatment are increasingly receiving clinical and legal attention. Through the use of 3 case vignettes that involve different aspects of mental health care in palliative care settings, mental capacity issues are discussed. The vignettes tackle capacity in a patient with newly developed mental illness consequent to physical illness, capacity in a patient with mental illness but without delirium and capacity in a patient with known impairment of the mind. These discussions give credence to best practice position where physicians act in the best interests of their patients at all times. It is important to emphasize that capacity decisions have to be made on a case by case basis, within the remit of legal protection. This is a fundamental requirement of the Mental Capacity Act 2005, England & Wales (MCA). The later is used as the legal basis for these discussions. The psychiatric liaison service is a useful resource to provide consultation, advice and or joint assessment to clinicians encountering complex dilemmas involving decision-making capacity.


Renal malacoplakia reappraised.
Renal malacoplakia is an unusual form of chronic tubulointerstitial nephritis with a predilection for patients with recurrent urinary tract infections and an immunocompromised state. Its characteristic feature is the parenchymal infiltration by macrophages with ample cytoplasm containing abundant periodic acid-Schiff-positive granules, known as von Hansemann cells, and the presence of diagnostic extracytoplasmic or intracytoplasmic calcospherites, known as Michaelis-Gutmann bodies. Renal malacoplakia is more common in women (female to male ratio 3:1), in whom the lesions develop in a younger age group (third to fifth decade) than in men (over 50 years). Enlarged kidneys in the presence of persistent urinary infection should lead to the consideration of this entity. The diagnosis can only be established by pathologic examination of renal tissue. Renal biopsy early in the course of the disease is essential since in an increasing number of cases medical therapy has resulted in resolution of the disease process and preservation of renal function.


Right heart-pulmonary circulation unit and cardiac resynchronization therapy.
Clinical response to cardiac resynchronization therapy (CRT) has been known for years to be highly variable, with a spectrum of responses from no change or even deterioration of cardiac function to spectacular improvements. In the plethora of clinical, echocardiographic, biohumoral, and electrophysiological predictors of response to CRT and postimplant issues besides patient selection, the role of right ventricular (RV) function has been largely overlooked. In reviewing current evidence, we noticed conflicting results between observational studies and randomized trials not only concerning the impact of baseline RV function on CRT efficacy but also on the effects of CRT on RV size and function. Hence, we aimed to provide a critical reappraisal of current knowledge and unresolved issues on the reciprocal interactions between RV function and CRT, shifting the spotlight on the concept of right heart pulmonary circulation unit and on the clinical and prognostic significance of impaired ventricular-arterial coupling reserve. In this viewpoint, we propose that (1) CRT should not be denied to potential candidate because of "isolated" RV dysfunction and (2) assessment of baseline right heart pulmonary circulation unit and its dynamic response to pharmacological stress should be considered in future studies, as well as in the preimplant evaluation of individual candidates among other clinical factors.


Telemonitoring in Chronic Obstructive Pulmonary Disease (CHROMED). A Randomized Clinical Trial.
Early detection of chronic obstructive pulmonary disease (COPD) exacerbations using telemonitoring of physiological variables might reduce the frequency of hospitalization. To evaluate the efficacy of home monitoring of lung mechanics by the forced oscillation technique and cardiac parameters in older patients with COPD and comorbidities. This multicenter, randomized clinical trial recruited 312 patients with Global Initiative for Chronic Obstructive Lung Disease grades II to IV COPD (median age, 71 yr [interquartile range, 66-76 yr]; 49.6% grade II, 50.4% grades III-IV), with a history of exacerbation in the previous year and at least one nonpulmonary comorbidity. Patients were randomized to usual care (n = 158) or telemonitoring (n = 154) and followed for 9 months. All telemonitoring patients self-assessed lung mechanics daily, and in a subgroup with congestive heart failure (n = 37) cardiac parameters were also monitored. An algorithm identified deterioration, triggering a telephone contact to determine appropriate interventions. Primary outcomes were time to first hospitalization (TTFH) and change in the EuroQoL EQ-5D utility index score. Secondary outcomes included: rate of antibiotic/corticosteroid prescription; hospitalization; the COPD Assessment Tool, Patient Health Questionnaire-9, and Minnesota Living with Heart Failure questionnaire scores; quality-adjusted life years; and healthcare costs. Telemonitoring did not affect TTFH, EQ-5D utility index score, antibiotic prescriptions, hospitalization rate, or questionnaire scores. In an exploratory analysis, telemedicine was associated with fewer repeat hospitalizations (-54%; P = 0.017). In older patients with COPD and comorbidities, remote monitoring of lung function by forced oscillation technique and cardiac parameters did not change TTFH and EQ-5D. Clinical trial registered with www.clinicaltrials.gov (NCT 01960907).


Transmembrane prostatic acid phosphatase (TMPAP) delays cells in G1 phase of the cell cycle.
Prostate adenocarcinoma is the most common form of prostate cancer. We have previously shown in a murine model that prostatic acid phosphatase (PAP) deficiency leads to increased cell proliferation and development of prostate adenocarcinoma. The association between PAP and prostate cancer has been reported. Indeed, high PAP enzymatic activity is detected in the serum of patients with metastatic disease while its expression is reduced in prostate cancer tissue. However, the molecular mechanisms behind the onset of the disease remains poorly understood. We previously identified a novel transmembrane prostatic acid phosphatase (TMPAP) isoform, which interacts with snapin. TMPAP is expressed on the plasma membrane, as well as endosomal/lysosomal and exosomal membrane vesicles by means of a tyrosine-based lysosomal targeting motif (Yxxϕ). We used stable overexpression of the secreted isoform (SPAP) and TMPAP in LNCaP cells, live cell imaging, microarray and qRT-PCR analyses, and fluid phase uptake of HRP and transferrin. Our results indicate that the stable overexpression of TMPAP, but not SPAP in LNCaP cells reduces cell growth while increasing endo/exocytosis and cell size. Specifically, cells overexpressing TMPAP accumulate in the G1 phase of the cell cycle, and show altered gene expression profile. Our data suggests that TMPAP may function as a non-canonical tumor suppressor by delaying cell growth in G1 phase of the cell cycle.


Illness-related factors, stress and coping strategies in relation to psychological distress in HIV-infected persons in Hong Kong.
This study examined the relationships among illness-related factors, stress, coping strategies and psychological distress in HIV-infected persons in Hong Kong (N=118). Multiple regression analyses were used to examine the models of psychological distress as a function of demographic factors, illness-related factors, psychosocial stressors and coping. Results showed that positive thinking was inversely related to psychological distress and avoidance was associated with higher level of anxiety. However, the use of problem solving was found to be inversely related to anxiety. Results are discussed in the context of Chinese culture and the service in Hong Kong.


Modulating risky decision-making in Parkinson's disease by transcranial direct current stimulation.
Performance on gambling tasks in Parkinson's disease (PD) is of particular interest, as pathological gambling is often associated with dopamine replacement therapy in these patients. We aimed to evaluate the effects of transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) in modulating gambling behaviour in PD. We assessed the effects of cathodal tDCS over the right DLPFC during the Iowa Gambling Task in 20 patients with PD, compared with sham stimulation. We then conducted a second experimental design, assessing the effects of anodal tDCS over the right DLPFC. We observed that cathodal tDCS over the right DLPFC increased Iowa Gambling Task scores compared with sham stimulation. In the second experimental design, we did not find significant differences between anodal and sham tDCS. Cathodal tDCS over the right DLPFC possibly reduces the pathological overdrive in frontostriatal networks in patients with PD on dopaminergic medication, thus modulating impulsive and risky decision-making.


Reduction the contamination of patulin during the brewing of apple cider and its characteristics.
Patulin is one of the most significant food safety problems in fruit and derived products. The reduction of patulin contamination in food processing has always been the focus of research. In this study, nine yeast strains were applied for the brewing of apple cider and the fate of patulin was determined. In this process, the patulin contamination can be decreased by adsorption onto and degradation of yeast cells in the main fermentation (20.8-49.1%), as well as the adsorption removal during clarification (18.7-58%), inverted cans (21.3-31.4%) and aging (1.0-5.8%). Saccharomyces cerevisiae (1027) was selected to reveal the elimination mechanism of patulin in main fermentation. The decrease of patulin content was mainly due to degradation and the intracellular enzymes played a more important role than extracellular ones. In addition, the synthesis of enzymes was related to the induction of patulin. Furthermore, the degradation product of patulin in the main fermentation was identified as E-ascladiol, which is less toxic than patulin. Based on the representative strain of S. cerevisiae 1027, patulin contamination can be effectively eliminated during apple cider brewing. This study provides a new insight into eliminating patulin contamination in the brewing of apple cider.


Case report and literature review: PET/CT in the evaluation of response to treatment of liver metastasis from colorectal cancer with DEBIRI-TACE.
Irinotecan-loaded drug-eluting beads transarterial chemoembolization (DEBIRI-TACE) is a safe and effective therapeutic option for unresectable colorectal liver metastases (CRLM). The evaluation of treatment response after DEBIRI-TACE is very important for assessing the patient's condition. At present, the Response Evaluation Criteria in Solid Tumors (RECIST) with the tumor size obtained by CT and/or MRI and PET Response Criteria in Solid Tumors (PERCIST) based on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) are used for evaluating the response to therapy of solid tumors; however, their value in the assessment of treatment response after DEBIRI-TACE remains unclear. A 52-year-old male with unresectable simultaneous CRLM was treated in the Affiliated Hospital of Yanbian University with DEBIRI-TACE combined with systemic chemotherapy and targeted therapy. Carcinoembryonic antigen levels decreased by 82.50% after 27 days of treatment. At 6 weeks post-surgery, FDG-PET/CT showed that the maximum standardized uptake value (SUVmax) of intrahepatic lesions was reduced to 62.14%. Abdominal MRI revealed that the sum of target lesion diameters was less than 30% that at baseline. PERCIST indicated partial metabolic response, whereas RECIST suggested stable disease. FDG PET/CT-based PERCIST may be accurate in determining treatment response and evaluating patient prognosis after DEBIRI-TACE in unresectable CRLM.


A pan-HER-targeted approach for recurrent or late-stage cervical cancer therapy: mechanisms, recent advances, and clinical prospects.
Over-expression of the epidermal growth factor receptor (EGFR) protein, along with gene amplification, is closely associated with recurrent cervical cancer and the disease's advanced stages. Additionally, it can have a direct impact on the disease's prognosis. The following are the members of the HER family: (i) EGFR/HER1; (ii) HER2; (iii) HER3; and (iv) HER4. Figure 1 shows its signalling pathway. The synergy between the members facilitates immune escape by tumour cells, which can lead to tolerance to HER inhibitors. A broad HER inhibitor, a pan-HER inhibitor, can irreversibly inhibit a cell membrane's HER receptors to their ligands, thereby blocking downstream signal-transduction cascades, inhibiting tumour growth, adhesion, invasion, differentiation, and metastasis. As such, pan-HER inhibitors may be an area of interest in treating recurrent or late-stage cervical cancer. Through a review of HER-family receptors and their molecular mechanism, we can conclude that pan-HER inhibitors do indeed have a positive impact on therapy for recurrent or late-stage cervical cancer patients. This paper reviews the molecular mechanism that underlies receptors within the HER family, current developments in HER inhibitors, and the potential clinical impacts of pan-HER inhibitors in treating recurrent or late-stage cervical cancer. Pan-HER inhibitors have been shown to improve prognoses for recurrent or late-stage cervical cancer patients. Preclinical studies show promising results, as well as the potential to improve results for recurrent or late-stage cervical cancer patients. Pan-HER inhibitors have also shown synergistic results in clinical and pre-clinical settings when combined with chemotherapy. However, long-term study is required regarding the combination of pan-HER inhibitors with radiotherapy and other targeted inhibitors. The question of whether or not these inhibitors have a more potent effect across the blood-brain barrier when compared to single HER-targeting agents may be an area of interest for future research. This idea will be explored in clinical cervical cancer trials.


[Mechanism of troponin and CK-MB release after percutaneous coronary interventions].
Cardiac troponins are highly sensitive and specific markers of early detection of myocardial injury. The incidence of cardiac troponin increase is of 5-40% after percutaneous coronary interventions and is significantly higher in patients undergoing stenting than in patients with balloon angioplasty only. Four mechanisms are responsible for myocardial necrosis during coronary angioplasty: 1) distal embolization of small fragments of the atherosclerotic plaque; 2) side branch occlusion; 3) intimal dissection, and 4) temporary vessel occlusion. The multiple and/or complex lesions, the diabetic status and plaque instability increase the probability of troponin elevation during coronary angioplasty. Moreover, the long time needed for interventional as well as atherectomy procedures may induce myocardial necrosis. In conclusion, after successful percutaneous coronary interventions, minor elevation of troponin may occur. In this setting cardiac troponin I is a highly specific marker of myocardial injury.


The influence of π-conjugation on competitive pathways: charge transfer or electron transfer in new D-π-A and D-π-Si-π-A dyads.
In order to elucidate the influence of π-conjugation on photoinduced electron transfer (PET) and intramolecular charge transfer processes, donor-π-acceptor dyads (D-π-A (1) and D-π-Si-π-A (2)) were newly synthesized. In these dyads, carbazole and triazine moieties acted as the electron donor and acceptor, respectively. The fluorescence of dyad 1 red-shifted as the solvent polarity was increased. The electron charge distribution of the excited state of dyad 1 was delocalized in the acceptor moiety, forming the charge transfer D(δ+)-π-A(δ-) dyad in the excited state. In the excited state of dyad 1, the π-conjugation acted as the linker for charge transfer between the donor and acceptor moieties. A large dipole moment change (Δμ = 45.6 D) between the ground and excited states was determined using the Lippert-Mataga plot. Furthermore, the fluorescence of dyad 1 was observed upon two-photon excitation. In contrast, dyad 2, in which the π-conjugation is disconnected by a Si-atom in the linker, displayed weak dual-emission: a short-wavelength emission at around 350 nm arising from the monomeric species and a long-wavelength one assigned to the emission from an intramolecular exciplex between the donor and acceptor moieties. The weak emission of dyad 2 indicates that the D(+)˙-π-Si-π-A(-)˙ species was generated through a PET process in the excited state. The cationic radical species of the carbazole and the anionic radical species of the triazine, which show transient absorption (TA) bands at around 780 and 530 nm, respectively, were characterized using the femtosecond TA method.


Segmental kinematics and adjacent level degeneration following disc replacement versus fusion: RCT with three years of follow-up.
Prospective, randomized and controlled clinical and radiological study. The aim of this study was to assess the segmental kinematics and clinical outcome of disc replacement with ProDisc C versus anterior cervical discectomy and fusion (ACDF) for monosegmental disease 3 years after surgery. Anterior cervical discectomy and fusion (ACDF), including plate fixation, is an accepted technique for treatment of symptomatic degenerative disc disease (DDD). However, various studies could show that fusion of a relative mobile spinal segment leads to heightens of stresses on the discs below and above fusion, which is manifested as adjacent level degeneration. Intervertebral disc replacement has been attempted to restore intervertebral disc height and to maintain segmental motion, which may be thought to avoid the accelerated degeneration to the adjacent level. In earlier studies, we could show that ProDisc C could maintain segmental motion for 1 year after surgery. 49 patients with cervical disc herniation underwent arthroplasty of a single level using ProDisc C disc prosthesis or received fusion using a cage and anterior titanium plate fixation. Clinical outcome was assessed using the visual analogue scale (VAS) and the neck disability index (NDI). Radiostereometry was performed immediately postoperative and then after 1, 2, and 3 years after surgery to quantify the segmental kinematics. The range of motion of the treated segment with prosthesis remained unchanged 3 years after surgery in comparison to the 1-year result. The prosthesis shows a significant segmental motion in contrast to the fusion group at each RSA examination time (p < 0.05). After both procedures, a significant pain reduction in neck and arm was observed, without significant differences between both groups. During the course of the 3 years follow-up, no patients of the prosthesis group required further surgical intervention.


Dynamic changes in microtubules and early development of reconstructed embryos after somatic cell nuclear transfer in a non-human primate.
In order to improve somatic cell nuclear transfer (SCNT) efficiency and to understand cellular changes in SCNT, the dynamic changes in microtubules/DNA and early development of SCNT embryos with single or multiple pronuclei were investigated, along with activation timing on efficiency of SCNT, were studied in the Cynomolgus monkey. The confocal images showed that microtubules assembled around condensed DNA at 1h after cell injection; normal or abnormal reconstructed spindle formed at 2 h after cell injection; and reconstructed spindle separated at 2 h after activation. The results of nuclear formation showed that 61.3% of the reconstructed embryos did not form pronuclei; 19.3% formed a single nucleus, and 11.9% and 7.5% formed two and more than two reconstructed pronuclei, respectively. The cleavage and 8-cell development rates of SCNT embryos with pronuclei were significantly higher than those without pronuclei, but there was no difference in development rates among NT embryos with single, two and more then two pronuclei. Activation at 2 h after cell injection yielded more embryos with pronuclei and yielded 8-cell NT embryos more reliably than did activation at 3-4 h. In conclusion, microtubules assembled around condensed DNA at 1-2 h after cell injection, and formed a spindle at 2 h after SCNT, which separated at 2 h after activation; early development was affected by activation time, but no different between single and multiple pronuclei.


Molecular genetic analysis of TGF-beta1 in ovarian neoplasia.
Malignant ovarian tumours have been associated with a loss of autocrine growth inhibition by transforming growth factor-beta. This study aimed to detect abnormalities in the gene structure, expression and localization of TGF-beta1, in paraffin-embedded samples from 31 ovarian neoplasias (21 malignant, 5 borderline and 5 benign). Gene mutations in the region coding for the active protein were detected by PCR-SSCP analysis of exons 5, 6 and 7. mRNA expression and localization was studied by nonisotopic in situ hybridization (NISH) using cDNA probes generated by the reverse transcriptase polymerase chain reaction (RT-PCR), and immunohistochemistry, using antibodies against both intracellular and extracellular (matrix-associated) forms of TGF-beta1. Four mutations were found: one in exon 6 (serous adenocarcinoma), one in exon 7 (Mullerian tumor), and two in exons 5 and 6 from a serous cystoadenoma. TGF-beta1 mRNA was expressed in 87% and proteins in 90% of ovarian tumours. Most tumours expressing large amounts of TGF-beta1 mRNA, also contained a large number of protein binding sites. In malignant tumors, TGF beta1 was more strongly expressed in high-grade ovarian carcinomas with a cystic-papillary pattern than in tumours with a solid growth pattern. Normal ovarian tissue (follicles, granulosa cells) adjacent to tumor showed weak epithelial labeling and staining. Gene mutation did not correlate with histological type of tumor, mRNA or protein expression. TGF-beta1 mutation and abnormalities in its expression seem to occur in benign and malignant ovarian tumors, and could be involved in their pathogenesis. TGF beta1 gene mutations may act in multistage ovarian neoplasia, by reducing epithelial cell responsiveness to TGF-beta1 negative growth control.


Leptomeningeal metastases from solid malignancy: a review.
Leptomeningeal metastases (LMM) consist of diffuse involvement of the leptomeninges by infiltrating cancer cells. In solid tumors, the most frequent primary sites are lung and breast cancers, two tumors where the incidence of LMM is apparently increasing. Careful neurological examination is required to demonstrate multifocal involvement of the central nervous system (CNS), cranial nerves, and spinal roots, which constitute the clinical hallmark of the disease. Cerebro-spinal fluid (CSF) analysis is almost always abnormal but only a positive cytology or demonstration of intrathecal synthesis of tumor markers is diagnostic. T1-weighted gadolinium-enhanced sequence of the entire neuraxis (brain and spine) plays an important role in supporting the diagnosis, demonstrating the involved sites and guiding treatment. Radionuclide CSF flow studies detect CSF compartmentalization and are useful for treatment planning. Standard therapy relies mainly on focal irradiation and intrathecal or systemic chemotherapy. Studies using other therapeutic approaches such as new biological or cytotoxic compounds are ongoing. The overall prognosis remains grim and quality of life should remain the priority when deciding which treatment option to apply. However, a sub-group of patients, tentatively defined here, may benefit from an aggressive treatment.


Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor.
Cytotoxic lymphocyte maturation factor (CLMF) is a disulfide-bonded heterodimeric lymphokine that (i) acts as a growth factor for activated T cells independent of interleukin 2 and (ii) synergizes with suboptimal concentrations of interleukin 2 to induce lymphokine-activated killer cells. We now report the cloning and expression of both human CLMF subunit cDNAs from a lymphoblastoid B-cell line, NC-37. The two subunits represent two distinct and unrelated gene products whose mRNAs are coordinately induced upon activation of NC-37 cells. Coexpression of the two subunit cDNAs in COS cells is necessary for the secretion of biologically active CLMF; COS cells transfected with either subunit cDNA alone do not secrete bioactive CLMF. Recombinant CLMF expressed in mammalian cells displays biologic activities essentially identical to natural CLMF, and its activities can be neutralized by monoclonal antibodies prepared against natural CLMF. Since this heterodimeric protein displays the properties of an interleukin, we propose that CLMF be given the designation interleukin 12.


BADGE SIZE, PHENOTYPIC QUALITY, AND REPRODUCTIVE SUCCESS IN THE HOUSE SPARROW: A STUDY ON HONEST ADVERTISEMENT.
Honest signaling theory suggests that advertising traits must be costly to their bearer; thus, only individuals of high phenotypic quality can exhibit maximal expression of these traits. Males of the sexually dichromatic house sparrow, Passer domesticus, have a black throat patch that functions as a badge of status. I investigated whether badge size honestly shows phenotypic quality. Badge size increases with age and decreases with advancing fledging date in yearling males; thus, badge size was larger in older individuals even though age differences were small. Badge size also increased with physical condition independent of age. These results indicate that badge size functions as an honest signal, possibly because there are costs involved in its production. I also found that males with enlarged badges acquired more nest sites than either control males or males with reduced badges. However, males with enlarged badges possessing a nest site raised fewer fledglings per year than did males with reduced badges, suggesting that cheating has no selective benefit. Further studies that accurately measure the energy expenditure allocated to badge production and that quantify additional fitness components are needed to clarify how reliable badges are maintained.


Effect of graduated compression stockings on venous blood velocity in supine resting hospitalized patients.
The effects of graduated compression stockings (GCSs) on venous blood velocity were measured in 26 hospitalized medical patients while supine at rest. Peak blood velocity in the right femoral vein was 21.6 cm/s without GCS and 23.0 cm/s with GCS [not significant (NS)]. Peak blood velocity in the right popliteal vein was 12.5 cm/s without GCS and 15.0 cm/s with GCS (NS). Mean blood velocity in the right femoral vein did not increase significantly with GCS, but mean blood velocity in the right popliteal vein increased marginally from 5.0 cm/s to 5.8 cm/s (P = .05). Among 11 patients with venous insufficiency (refilling time ≤19 s), neither peak nor mean blood velocity in the femoral or popliteal veins increased significantly with GCS. In conclusion, thigh-length GCS in hospitalized patients had little or no effect on popliteal or femoral vein blood velocity while supine at rest, irrespective of whether the patients had venous insufficiency.


Transport of proteins into chloroplasts. Organization, orientation, and lateral distribution of the plastocyanin processing peptidase in the thylakoid network.
Plastocyanin is synthesized in the cytoplasm as a larger precursor and transported into the thylakoid lumen of the chloroplast. Maturation of preplastocyanin involves successive cleavages by a stromal peptidase and a distinct thylakoidal peptidase. In this report we have analyzed the precise location and orientation of the thylakoidal peptidase with respect to the thylakoid membrane. Experiments involving differential centrifugation of thylakoid extracts and sonication of isolated vesicles indicate that the peptidase is tightly bound to the thylakoid membrane but not intimately associated with any of the major thylakoid protein complexes. Analysis of the lateral distribution of the peptidase has shown that the enzyme is exclusively located in the non-appressed lamellae of the thylakoid network. The active site of the peptidase is on the lumenal face of the thylakoid membrane.


The evaluation of protein Z levels of children with acute lymphoblastic leukaemia during induction therapy.
The objective of this study was to evaluate the protein Z levels of children with acute lymphoblastic leukaemia (ALL) during induction therapy. Although several studies investigated the association between steroid and L-asparaginase (L-ASP) administration and levels of coagulation proteins such as protein C, protein S and antithrombin in children with ALL, protein Z levels have not been examined in any study yet. Peripheral blood was drawn from the study group before chemotherapy (PZ0) at diagnosis, at 12th day (PZ1), 15th day (PZ2), 18th day (PZ3) and 21st day (PZ4) of treatment wherein L-ASP treatment is given along with steroid administration according to ALL BFM-1995 chemotherapy protocol. Plasma protein Z levels were measured by enzyme immunoassay method. Mean protein Z level at PZ0 was 1.628 ± 0.485 μg/ml in the study group and 1.672 ± 0.662 μg/ml in the control group. No statistical difference was observed. In the study group, there was a slight increase in protein Z levels between the PZ0 and PZ1 periods in which only steroid therapy was administered. Statistically significant decrease was observed between protein Z levels in PZ0-PZ4, PZ1-PZ2, PZ1-PZ3, PZ1-PZ4 and PZ3-PZ4 periods. During the induction treatment, symptomatic haemorrhage or thrombosis was not followed up in any patients. We demonstrated that children with ALL have similar protein Z values to those of the control group at diagnosis. A significant decrease occurs at the end of the induction treatment with steroid and L-ASP administration. However, this deficiency does not result in development of symptomatic thrombosis or bleeding in these patients.


Micellar Brønsted Acid Mediated Synthesis of DNA-Tagged Heterocycles.
The translation of well-established molecular biology methods such as genetic coding, selection, and DNA sequencing to combinatorial organic chemistry and compound identification has made extremely large compound collections, termed DNA-encoded libraries, accessible for drug screening. However, the reactivity of the DNA imposes limitations on the choice of chemical methods for encoded library synthesis. For example, strongly acidic reaction conditions must be avoided because they damage the DNA by depurination, i.e. the cleavage of purine bases from the oligomer. Application of micellar catalysis holds much promise for encoded chemistry. Aqueous micellar dispersions enabled compound synthesis under often appealingly mild conditions. Amphiphilic block copolymers covalently functionalized with sulfonic acid moieties in the lipophilic portion assemble in water and locate the Brønsted catalyst in micelles. These acid nanoreactors enabled the reaction of DNA-conjugated aldehydes to diverse substituted tetrahydroquinolines and aminoimidazopyridines by Povarov and Groebke-Blackburn-Bienaymé reactions, respectively, and the cleavage of tBoc protective groups from amines. The polymer micelle design was successfully translated to the Cu/Bipyridine/TEMPO system mediating the oxidation of DNA-coupled alcohols to the corresponding aldehydes. These results suggest a potentially broad applicability of polymer micelles for encoded chemistry.


Identifying fungal-host associations in an amphibian host system.
Host-associated microbes can interact with macro-organisms in a number of ways that affect host health. Few studies of host-associated microbiomes, however, focus on fungi. In addition, it is difficult to discern whether a fungal organism found in or on an ectotherm host is associating with it in a durable, symbiotic interaction versus a transient one, and to what extent the habitat and host share microbes. We seek to identify these host-microbe interactions on an amphibian, the Colorado boreal toad (Anaxyrus boreas boreas). We sequenced the ITS1 region of the fungal community on the skin of wild toads (n = 124) from four sites in the Colorado Rocky Mountains, across its physiologically dynamic developmental life stages. We also sampled the common habitats used by boreal toads: water from their natal wetland and aquatic pond sediment. We then examined diversity patterns within different life stages, between host and habitat, and identified fungal taxa that could be putatively host-associated with toads by using an indicator species analysis on toad versus environmental samples. Host and habitat were strikingly similar, with the exception of toad eggs. Post-hatching toad life stages were distinct in their various fungal diversity measures. We identified eight fungal taxa that were significantly associated with eggs, but no other fungal taxa were associated with other toad life stages compared with their environmental habitat. This suggests that although pre- and post-metamorphic toad life stages differ from each other, the habitat and host fungal communities are so similar that identifying obligate host symbionts is difficult with the techniques used here. This approach does, however, leverage sequence data from host and habitat samples to predict which microbial taxa are host-associated versus transient microbes, thereby condensing a large set of sequence data into a smaller list of potential targets for further consideration.


Corneal ulcer caused by Nocardia asteroides in a patient with leprosy.
Nocardia asteroides is a rare cause of keratitis usually associated with trauma. We report a case of corneal ulceration caused by N. asteroides in a patient with leprosy. This is the first case report of nocardial keratitis from Southeast Asia. The diminished corneal sensation in a patient with leprosy could be a predisposing factor for development or exacerbation of corneal ulceration.


Response independent habituation of territorial aggression in the three-spined stickleback (gasterosteus aculeatus).
Territorial sticklebacks were habituated to a male conspecific confined to a clear glass tube in a two stage experiment. In the first stage, one group was allowed complete access to a stimulus tube containing a live, male conspecific and the number of bites directed at the stimulus was recorded. A second group was prevented from biting at the stimulus fish by placing a glass barrier between the territorial resident and stimulus tube. A third group was treated the same as the second but without a stimulus fish present. During the second stage of the experiment, which followed a 15 min rest, all groups were allowed access to the stimulus tube and confined conspecific. A typical habituation curve resulted across both sessions for the first group. The second group, which was characterized by very infrequent attempts to bite during state 1, showed behavior during stage 2 identical to that of group 1. During the second stage, the third group demonstrated typical initial habituation behavior (parallel to that of group 1 during the first stage). These results are interpreted as evidence that habituation proceeds as a function of exposure to a stimulus and is independent of whether or not a response is made.


Pituitary apoplexy presenting as a peripheral rim enhancing parasellar mass lesion with dural enhancement along the tentorium.
Pituitary apoplexy is a potentially life-threatening clinical condition caused by rapid enlargement of a pituitary adenoma because of haemorrhage or infarction. The clinical features are typically acute in onset. We report an interesting case of 25-year-old man with complaints of sudden onset of headache and ophthalmoplegia in the right eye one month previously. He had ptosis and complete ophthalmoplegia in the right eye with visual acuity 6/24 and 6/12. Imaging showed a peripheral rim-enhancing mass lesion in the right parasellar and cavernous sinus with a dural tail. He underwent craniotomy and subtotal excision of the lesion. Histopathology was reported as pituitary apoplexy. Hormonal analysis was within normal limits. At two years of follow-up he had complete resolution of ophthalmoplegia and improvement in his vision. It is very uncommon to see pituitary apoplexy evolved in right parasellar region presenting as peripheral rim-enhancing mass lesion.


The catalytic subunit of Drosophila glutamate-cysteine ligase is a nucleocytoplasmic shuttling protein.
GSH concentration is considerably lower in the nucleus than in the cytoplasm; however, it is significantly elevated during active cell proliferation. The main purpose of this study was to understand the mechanism underlying these variations in nuclear/cytoplasmic distribution of GSH. The rate-limiting step in the de novo GSH biosynthesis pathway is catalyzed by glutamate cysteine ligase (GCL), a heterodimer, composed of a catalytic subunit (GCLc) and a modulatory subunit (GCLm). In Drosophila, GCLc, but not GCLm, contains a nuclear localization signal (NLS). Drosophila S2 cells, constitutively expressing regular GCLc protein or expressing GCLc protein with a mutated NLS motif, were generated by transfection. In quiescent S2 cells, GCLc is aggregated in the perinuclear cytosol and the nucleus, whereas GLCm resides solely in the cytosol. In actively proliferating S2 cells, expressing the normal NLS motif, GCLc migrates from the perinuclear cytoplasm into the nucleus, and the nuclear GSH level becomes elevated; in contrast, in proliferating cells, expressing the mutated NLS motif, neither does the GCLc migrate into the nucleus nor does the nuclear GSH amount rise. In S2 cells expressing wild type GCLc, perturbation of cellular redox state by exposure to cadmium resulted in the migration of GCLc into the nucleus but not in cells expressing GCLc with the mutated NLS motif. Overall, results indicated that GSH biosynthesis in the nucleus is associated with migration of only the GCLc subunit from the cytoplasm into the nucleus, and this migration requires the presence of an intact NLS.


Validity of MAST-CLA for diagnosis of arthropod allergy using receiver operating characteristic (ROC) analysis.
Many allergists are currently focusing on the development of new diagnostic tools, and are attempting to improve both the sensitivity and specificity. A multiple allergen simultaneous test-chemiluminescent assay (MASTCLA) is one of the most popular diagnostic tools used in the Republic of Korea. However, there remains controversy among allergists with regard to the cut-off point for a positive result. The present study was conducted in order to determine the validity of MAST-CLA as compared with that of the skin prick test, with particular emphasis on arthropod allergens, on the basis of percentage agreement rates and kappa-values, and also to suggest the optimal positive cutoff points using receiver operating characteristic (ROC) curves. The study was conducted with 97 subjects (54 men, 43 women). Optimal individual cut-off points were calculated as follows; class II for Dermatophagoides farinae, class I for Dermatophagoides pteronyssinus, and trace for a cockroach mix. These findings suggest that attempting to apply optimal individual cut-off points will be a good way of improving diagnostic tests, particularly MAST-CLA.


Particle size dependent chemistry from laser ablation of brass.
The proportion of zinc and copper in particles formed by laser ablation of brass was found to vary with the particle diameter. Energy-dispersive X-ray analysis showed that smaller particles were zinc enhanced while larger particles were composed mostly of copper. A model based on condensation of vapor onto large droplets ejected from a melted liquid layer is proposed to describe the change in particle composition versus size.


Critical action to redress systemic oppression: a person-centered approach.
In 2020, public outcry against police brutality prompted many social media users to post black squares and use the hashtag #BlackLivesMatter (BLM). Many of the people who posted these squares were engaging in performative action in the sense that they failed to engage with BLM's history and core principles. Drawing from a critical action framework, the current research seeks to more deeply understand what drives people to engage in more versus less impactful forms of action to resist systemic oppression. We employed a mixed-methods and person-centered methodological approach with the goal of providing nuanced information about factors that distinguish among individuals who engage in different forms of action. Participants were 359 undergraduates who reported that they engaged in some form of action to support BLM. Latent profile analysis identified three subgroups (i.e., latent classes) in the larger sample, which we labeled (1) intentional action, (2) intermediate action, and (3) passive action. Participants in each latent class differed from one another in their sociopolitical attitudes, sociodemographic background, and level of action to support BLM. Through the qualitative coding process, the research team unearthed three overarching themes and a range of subthemes that help to explain why the members of each class engaged in different forms of action. We conclude by proposing a flexible intervention that may motivate individuals to engage in critical action to support BLM.


Self-enucleation in a young schizophrenic patient--a case report.
Self-enucleation represents an extreme but fortunately rare form of deliberate self-harm. Case reports of patients who self-enucleate reveal some common features. A case of auto-enucleation in a young schizophrenic patient and a short discussion on deliberate self-harm are presented.


Comparison and efficacy of low-dose and standard-dose tamsulosin and alfuzosin in medical expulsive therapy for lower ureteral calculi: prospective, randomized, comparative study.
Typically in Korea, for a standard dose (0.4 mg) of tamsulosin, two low doses (0.2 mg) are administered. The aim of this study was to evaluate and compare the efficacy of tamsulosin (0.2 mg and 0.4 mg) and alfuzosin (10 mg) in the treatment of lower ureteral stones. A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were randomly assigned to 4 groups. Patients in group 1 (n=41) and group 2 (n=30) received an oral dose of 0.2 mg tamsulosin once and twice daily, respectively, and patients in group 3 (n=36) received a daily oral dose of 10 mg alfuzosin. Patients in group 4 (n=34) received trospium chloride only. The spontaneous passage of stones, the stone expulsion time, and adverse effects were evaluated. There were no significant differences in patient background, including age, sex, BMI, stone size, stone side, and symptom duration. The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1, 2, and 3 than in group 4. There were no statistically different changes in groups 1, 2, and 3. The adverse effects observed in all groups were comparable and were mild. Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin (10 mg) proved to be safe and effective. A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone.


An additional facet of the incest taboo: a protection of the mating-strategy template.
It is suggested that sexual intercourse between adult males and girls tends to distort an inherent mating-strategy template: female choice of mating partner. The distortion seems to have long-range consequences in the form of myriad psychopathologies, which, in turn, reduce the afflicted individuals' chances for normative marriage and parenting profiles. In addition, a similar dynamic would hypothetically result from adult-male to boy incest. It is suggested that to minimize the chances of adult-child sexual intercourse, incest taboos have historically been reinforced and extended to nonparental adults, especially men, beyond the immediate nuclear family.


Urinary excretion of zinc, copper and iron in the streptozotocin-diabetic rat.
The influence of the chemically diabetic condition on urinary excretion of zinc, copper and iron was investigated. Male Sprague-Dawley rats were injected with streptozotocin to induce insulin-dependent diabetes (day 0) and 24-hour urinary collections taken 1, 4, 7, 10 and 14 days later. Onset of the diabetic condition was correlated with a rapid and persistent increase in the amounts of the three trace metals excreted daily in the urine. Diabetic rats excreted 3.4-, 5.0- and 4.9-fold more zinc, copper and iron, respectively, than controls in the urine on day 14. Insulin treatment of diabetic rats significantly reduced the quantities of the micronutrients excreted in urine, suggesting that altered hormonal status was the primary cause of increased urinary losses. Enhanced urinary output of the metals was not associated with reduction in the plasma, liver and kidney contents of zinc, copper and iron. Urinary trace metal excretion was correlated with food ingestion and urinary volume with greater amounts lost during the dark period for control and diabetic animals. The influence of endocrine status on urinary excretion of trace metals is discussed.


Investigation of Aneusomy of Chromosome 21 in the Micronuclei of 13 Patients with Early Onset Alzheimer's Disease Using Fluorescence in Situ Hybridization: A Pilot Study.
Alzheimer's disease is one of the most common neurodegenerative and dementia disorders in people between the ages of 30 and 65. When symptoms appear in this age group, the disease is referred to as early-onset Alzheimer's disease (EOAD). Unfortunately, the symptoms are progressive and no current treatments are effective. In this research, 13 patients, aged 37 to 65 years with symptoms of early-onset Alzheimer's disease, were studied. First, patient lymphocytes were isolated and cultured in RPMI 1640 medium using a special micronucleus (MN) culture method. Next, the lymphocytes were harvested and prepared on slides. The slides were then examined by fluorescent microscopy using a unique FISH protocol specific for MNs. The patients were divided into groups aged 30-39, 40-49, and 50-65. We found that 19.76% of the MNs from our EOAD patients originated in chromosome 21. Micronuclei originated in chromosome 21 in 21.20 and 16.52% of patients without and with family histories of Alzheimer's, respectively. This difference was not significant. Also, the percentage of micronuclei originating in chromosome 21 was not dependent on the patient age at the time of the study, or symptom onset age or duration. This study shows that the rate of micronuclei with the origin of chromosome 21 is high in these patients. However, the micronucleus increased has no significant relationship with age and duration of disease or family history of it.


[The terminase complex, a relevant target for the treatment of HCMV infection].
Human cytomegalovirus (HCMV) is an important ubiquitous opportunistic pathogen that belongs to the betaherpesviridae. Primary HCMV infection is generally asymptomatic in immunocompetent individuals. In contrast, HCMV infection causes serious disease in immunocompromised patients and is the leading cause of congenital viral infection. Although they are effective, the use of conventional molecules is limited by the emergence of resistance and by their toxicity. New antivirals targeting other replication steps and inducing fewer adverse effects are therefore needed. During HCMV replication, DNA packaging is performed by the terminase complex, which cleaves DNA to package the virus genome into the capsid. With no counterpart in mammalian cells, these terminase proteins are ideal targets for highly specific antivirals. A new terminase inhibitor, letermovir, recently proved effective against HCMV in phase III clinical trials. However, its mechanism of action is unclear and it has no significant activity against other herpesvirus or non-human CMV.