Effect of argon-beam coagulation on the integrity of suture material.
To evaluate the effect of argon-beam coagulator (ABC) energy on suture materials. Six absorbable and nonabsorbable suture materials (polyglactin, chromic catgut, polydioxanone, silk, poliglecaprone, and Gore-Tex) were placed under tension and exposed to ABC energy to determine breaking times. Subsequently, all suture materials were exposed to limited ABC energy, and tensiometry was used to determine decreases in breaking strengths. Among the suture materials tested, Gore-Tex was the most resistant to ABC energy. Although absorbable suture materials were less resistant than nonabsorbable suture materials, 2-0 polyglactin manifested the greatest resiliance to deterioration with ABC energy exposure. The ABC has differential effects on suture materials. Larger-gauge suture materials are more resistant to ABC than smaller materials. Similarly, nonabsorbable sutures are generally more resilient to ABC energy than absorbable materials. Among the suture materials evaluated in our in vitro model, 2-0 Gore-Tex was best suited for vascular ligation, and 2-0 polyglactin is optimal for renal collecting system closure if ABC is anticipated as an adjunct for hemostasis.


Influence of chewing rate on salivary stress hormone levels.
The purpose of this study was to clarify the effect of different chewing rates on salivary cortisol levels as a stress indicator. The subject group consisted of 16 healthy males. They were required to rest for 30 min, and then given arithmetic calculations to perform for 30 min as stress loading. Immediately after, the first set of saliva specimens (S1) was collected over a period of 1 min to measure cortisol levels. Next, they were asked to chew a tasteless gum base for 10 min, and the second set of saliva specimens (S2) was collected in the same manner. They were then required to rest for 10 min, after which the third set of saliva specimens (S3) was collected. Chewing rates were set to slow, habitual, and fast in time with a metronome. Salivary cortisol levels were analyzed by radioimmunoassay. Changes in salivary cortisol levels comparing S1 with S2, and S1 with S3 were determined. Changes in salivary cortisol levels between S1 and S2 showed a reduction of 4.7%, 14.6%, and 16.2% with slow, habitual, and fast chewing, respectively. A significant difference was observed between slow and fast chewing. Changes in salivary cortisol levels between S1 and S3 showed a reduction of 14.4%, 22.2%, and 25.8% with slow, habitual, and fast chewing, respectively. A significant difference was observed between slow and fast chewing. This study showed that differences in chewing rate affected salivary cortisol levels as a stress indicator, and suggested that the effect on stress release with fast chewing is greater than that with slow chewing.


Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes.
Mesenchymal stem cells (MSCs) are pluripotent stromal cells that have the potential to give rise to cells of diverse lineages. Interestingly, MSCs can be found in virtually all postnatal tissues. The main criteria currently used to characterize and identify these cells are the capacity for self-renewal and differentiation into tissues of mesodermal origin, combined with a lack in expression of certain hematopoietic molecules. Because of their developmental plasticity, the notion of MSC-based therapeutic intervention has become an emerging strategy for the replacement of injured tissues. MSCs have also been noted to possess the ability to impart profound immunomodulatory effects in vivo. Indeed, some of the initial observations regarding MSC protection from tissue injury once thought mediated by tissue regeneration may, in reality, result from immunomodulation. Whereas the exact mechanisms underlying the immunomodulatory functions of MSC remain largely unknown, these cells have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. This article focuses on recent advances that have broadened our understanding of the immunomodulatory properties of MSC and provides insight as to their potential for clinical use as a cell-based therapy for immune-mediated disorders and, in particular, type 1 diabetes.


On the value and costs of protective actions in a nuclear emergency.
This paper reviews the current orthodoxy for the prompt application of shelter and evacuation advice in the event of a nuclear emergency in the light of the reassessment of the perceived costs and benefits of these protective actions that followed the Fukushima event. In particular, it discusses the mechanisms and criteria for the withdrawal of protective action advice or their continuation for more than a few hours and their impact on public perception. It suggests that lack of thought given to this area may lead to protective actions being kept in place for longer than necessary leading to more harm than good. It also considers the language used to recommend protective actions and to modify them as the event unfolds. Would over strong language used at the start of the event to encourage compliance contribute to public concerns later? Finally, the report poses some discussion points.


A review of legal and policy issues in legislating compensation for victims of toxic substance pollution.
Despite the actual and potential effects of toxic substance pollution upon human health, the United States Congress has never enacted a comprehensive victim compensation system. The approach of the Congress, to date, has been limited by a concern about legislating on a topic fraught with scientific uncertainty--the actual causation of injury or death by toxic substance pollution. Individuals who believe they have been injured by toxic substances often bring their claims in state courts, where they face the difficult task of proving causation. Industry is principally concerned with the high cost of a compensation system, not the public health issue of scientific causation. From a policy standpoint, legislation is needed that produces information and standards on causation which assist both victims and industry. Congress has the opportunity to craft legislation that will deal rationally with an epic problem. To do so, however, the Congress must recognize scientific uncertainty as an omnipresent element of causation in cases of toxic substance pollution. This starting point, a comprehensive system of compensating victims of toxic substance pollution, can be drafted to address the values of data collection, data interpretation, prevention, conservation of economic resources, and fairness.


Resin characterization by electro-acoustic measurements.
The electro-acoustic effects, namely the ion vibration potential (IVP) and the colloidal vibration current (CVI), colloidal vibration potential (CVP) first described by P. Debye [P. Debye, J. Chem. Phys. 1 (1933) 13], are a result of charge separation of bound or free ions at different degrees by ultrasonic waves. Today commercial instruments are available to investigate liquid homogeneous and heterogeneous systems. In the present paper the application of this technique for the characterization of salts, protein solutions and resins for biochromatography is shown and valuable information about resins can be derived in a short time. Various resins were investigated with the following results: (1) the CVI magnitude is dependent of several parameters (such as particle size distribution, volume fraction, density difference); (2) the CVI is influenced by the surface modification of the resins. Polymeric modifications decrease the value of CVI. The CVI is generally lower for high capacity resins; (3) the measurement of the electro-acoustic effects can be used to detect small changes in resins. The CVI is dependent of the amount of adsorbed protein in "native" and denatured state.


Persistent homology for the quantitative prediction of fullerene stability.
Persistent homology is a relatively new tool often used for qualitative analysis of intrinsic topological features in images and data originated from scientific and engineering applications. In this article, we report novel quantitative predictions of the energy and stability of fullerene molecules, the very first attempt in using persistent homology in this context. The ground-state structures of a series of small fullerene molecules are first investigated with the standard Vietoris-Rips complex. We decipher all the barcodes, including both short-lived local bars and long-lived global bars arising from topological invariants, and associate them with fullerene structural details. Using accumulated bar lengths, we build quantitative models to correlate local and global Betti-2 bars, respectively with the heat of formation and total curvature energies of fullerenes. It is found that the heat of formation energy is related to the local hexagonal cavities of small fullerenes, while the total curvature energies of fullerene isomers are associated with their sphericities, which are measured by the lengths of their long-lived Betti-2 bars. Excellent correlation coefficients (>0.94) between persistent homology predictions and those of quantum or curvature analysis have been observed. A correlation matrix based filtration is introduced to further verify our findings.


Flexor carpi ulnaris muscle flap for soft tissue reconstruction after total elbow arthroplasty.
The soft tissue at the tip of the olecranon is very thin, leading to the frequent occurrence of wound complications after total elbow arthroplasty. To cover a soft tissue defect of the elbow, the flexor carpi ulnaris muscle flap is thought to be appropriate for reconstruction of the elbow with regard to its size, location, and blood supply. We got positive clinical results, so we report our experiences of using a flexor carpi ulnaris muscle flap for soft tissue reconstruction after total elbow arthroplasty.


Chronobiological regulation of psychosocial and physiological outcomes in multiple sclerosis.
There is mounting scientific evidence showing the importance of innate biological rhythms on disease onset and progression. Perhaps the most important of these is the circadian rhythm, a cycle of oscillations lasting approximately 24 h. Recent work has shown that circadian rhythms are intrinsically linked to the immune system in a bidirectional fashion, and that disruption of these cycles can contribute to changes in pathology and quality of life (including fatigue, mood, and disability). This is particularly true in diseases of the nervous and immune systems. We review here the current preclinical and clinical literature to highlight interactions between circadian rhythms and multiple sclerosis, as well as its animal model, experimental autoimmune encephalomyelitis. We highlight potential benefits of chronotherapy (the temporal administration of immunomodulatory drugs) in an effort to increase treatment efficacy and reduce the negative side-effects of the drugs that often burden those suffering from the disease.


Haemorrhagic cholecystitis treated with endovascular embolization.
Haemorrhagic cholecystitis is a rare complication of acute cholecystitis. Traditionally, treatment has been with emergency cholecystectomy. Endovascular management of haemorrhage allows the patient to be optimized for surgery at a later date. Our case presents a 52-year-old woman with haemorrhagic cholecystitis who underwent endovascular coil embolization of the cystic artery in interventional radiology. Further complications later ensued including a haematoma in the gallbladder fossa and a bile leak into the peritoneal cavity. As a result, the patient had an endoscopic retrograde cholangiopancreatography (ERCP) with placement of a covered stent into the extrahepatic bile ducts. The patient later developed abscess formation in the gallbladder fossa, which was managed with a percutaneous pigtail drain. Following clinical and radiological improvement, the patient was discharged with the gallbladder fossa drain and biliary stent in situ to await elective cholecystectomy. Endovascular embolization is a useful alternative, in the acute setting, to emergency surgical cholecystectomy.


Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies.
Keratoconus is a bilateral noninflammatory progressive corneal disorder with complex genetic inheritance and a common cause for cornea transplantation in young adults. A genomewide linkage scan in keratoconus families identified a locus at 5q23.2, overlapping the gene coding for the lysyl oxidase (LOX). LOX encodes an enzyme responsible for collagen cross-linking in a variety of tissues including the cornea. Corneal collagen cross-linking with long-wave ultraviolet light and riboflavin is a promising new treatment for keratoconus. To determine whether LOX is a genetic determinant of the pathogenesis of keratoconus, we analyzed association results of LOX polymorphisms in two independent case-control samples and in keratoconus families. Association results were analyzed of single-nucleotide polymorphisms (SNPs) in the LOX gene from a Genome-Wide Association Study (GWAS) investigation in two independent panels of patients with keratoconus and controls and in keratoconus families. Evidence of association was found at SNPs rs10519694 and rs2956540 located in intron 4 of LOX in the GWAS discovery case-control panel with P values of 2.3×10(-3) and 7×10(-3), respectively. The same two SNPs were found to be associated with keratoconus by family-based association testing with P values of 2.7×10(-3) and 7.7×10(-4), respectively. Meta P values of 4.0×10(-5) and 4.0×10(-7) were calculated for SNPs rs10519694 and rs2956540 by analyzing case-control and family samples simultaneously. Sequencing of LOX exons in a subset of keratoconus patients identified two polymorphisms, rs1800449 and rs2288393, located in LOX transcripts I and II, associated with keratoconus in case-control and family samples with a meta P value of 0.02. Results provided strong genetic evidence that LOX variants lead to increased susceptibility to developing of keratoconus.


[Small interfering RNA targeting C-erbB-2 gene increases the radiosensitivity of lung adenocarcinoma cells in vitro].
To investigate the effect of small interfering RNA (siRNA) targeting C-erbb-2 oncogene on the radiosensitivity of C-erbb-2-overexpressing lung adenocarcinoma cell line. Four pairs of siRNA targeting the coding sequence of C-erbb-2 mRNA were synthesized and their interference effects were evaluated using quantitative real-time fluorescence PCR. The siRNA with the best interference effects was transfected into Calu-3 cells, which were then exposed to 2 or 5 Gy irradiation, with the cells with transfection or irradiation alone as the control groups. The cell apoptosis after the treatment was detected using annexin V-FITC Kit. The apoptosis rate of the Calu cells was 7.767-/+0.551 in the blank group, 14.400-/+1.114 in the interference group, 11.867-/+0.737 in 2 Gy irradition group, 23.000-/+1.664 in 2 Gy irradiation + interference group, 16.100-/+0.624 in 5 Gy irradiation group, and 27.900-/+1.709 in 5 Gy irradiation+interference group. The siRNA targeting C-erbb-2 gene can enhance the radiosensitivity of Calu-3 cells to gamma-ray and increase their apoptosis rate following gamma-ray exposure in vitro.


Enantioselective Palladium-Catalyzed Oxidative β,β-Fluoroarylation of α,β-Unsaturated Carbonyl Derivatives.
The site-selective palladium-catalyzed three-component coupling of deactivated alkenes, arylboronic acids, and N-fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step-economical approach to the stereoselective β-fluorination of α,β-unsaturated systems.


Influences of Partial Destruction of Ti-MOFs on Photo(electro)catalytic H2 Evolution by Dominating Role of Charge Carrier Trapping over Surface Area.
The design of water-stable photo and electrocatalysts of metal-organic frameworks (MOFs) for its promising catalytic applications at long-term irradiations or persisted current loads is extremely necessary but still remains as challenging. A limited number of reports on Ti-MOF-based catalysts for water splitting are only available to explain and understand the correlation between the nature of materials and MOFs array. Herein, spherical Ti-MOFs and corresponding partially annealed hollow core-shell Ti-MOFs (Ti-MOF/D) are designed and the correlation with their photo(electro)catalytic water splitting performance is evaluated. The switchable valence state of Ti for the Ti-MOF as a function of molecular bonding is the possible reason behind the observed photocatalytic hydrogen generation and light-harvesting ability of the system. Besides, the defect state, solid core-shell mesoporous structure, and active sites of Ti-MOF help to trap the charge carriers and the reduction of the recombination process. This phenomenon is absent for hollow core-shells Ti-MOF/D spheres due to the rigid TiO2 outer surface although there is a contradiction in surface area with Ti-MOF. Considering the diversity of Ti-MOF and Ti-MOF/D, further novel research can be designed using this way to manipulate their properties as per the requirements.


Redundant down-regulation pathways for p53.
The aim of this review is to underline the redundancy of down-regulation pathways for p53, at the light of the two more important degradative systems: calpains and ubiquitin-dependent pathways. The MDM2 feed-back loop is also illustrated, as well as the phosphorylative/dephosphorylative regulation of the latent and active p53 isoforms. The mechanisms prolonging p53 half life, following irradiation, are also discussed.


Behavior systems and reinforcement: an integrative approach.
Most traditional conceptions of reinforcement are based on a simple causal model in which responding is strengthened by the presentation of a reinforcer. I argue that reinforcement is better viewed as the outcome of constraint of a functioning causal system comprised of multiple interrelated causal sequences, complex linkages between causes and effects, and a set of initial conditions. Using a simplified system conception of the reinforcement situation, I review the similarities and drawbacks of traditional reinforcement models and analyze the recent contributions of cognitive, regulatory, and ecological approaches. Finally, I show how the concept of behavior systems can begin to incorporate both traditional and recent conceptions of reinforcement in an integrative approach.


Alcohol consumption, drinking patterns, and cognitive function in older Eastern European adults.
To investigate associations of frequency, quantity, binge, and problem drinking with cognitive function in older Eastern European adults. The investigation included 14,575 participants, aged 47 to 78 years at cognitive assessment in 2006-2008 from Novosibirsk (Russia), Krakow (Poland), and 6 Czech towns participating in the HAPIEE (Health, Alcohol, and Psychosocial Factors in Eastern Europe) prospective cohort study. Average response rates were 59% at baseline (2002-2005) and 63% in 2006-2008. Alcohol consumption was assessed at baseline and in 2006-2008. Cognitive tests included immediate and delayed word recall, semantic fluency (animal naming), and letter cancellation. Associations between alcohol indices and cognitive scores were analyzed cross-sectionally (all measures from 2006 to 2008) and prospectively (alcohol and covariates from 2002 to 2005 and cognition from 2006 to 2008). In cross-sectional analyses, nondrinkers had lower cognitive scores and female moderate drinkers had better cognitive performance than light drinkers. Heavy, binge, and problem drinking were not consistently associated with cognitive function. Few associations were replicated in prospective analyses. Participants who stopped drinking during follow-up had worse cognition than stable drinkers; in men, regression coefficients (95% confidence interval) ranged from -0.26 (-0.36, -0.16) for immediate recall to -0.14 (-0.24, -0.04) for fluency. Regular and episodic heavy drinking were not consistently associated with cognitive function. Worse cognition in participants who stopped drinking during follow-up suggests that inclusion of less healthy ex-drinkers may partly explain poorer cognition in nondrinkers.


Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion for the diagnosis of colorectal polyp and cancer.
Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) is useful for the diagnosis of cancer as it presents a clear contrast between cancerous and non-cancerous tissue. The present study investigated the limitations and advantages of DWIBS/T2 with regards to the diagnosis of colorectal polyp (CP) or cancer (CRC). The current study included patients diagnosed with CP or CRC following colonoscopy, who were subjected to DWIBS/T2 between July 2012 and March 2015. Patient records were analyzed retrospectively. Patients were subjected to DWIBS/T2 when they presented with abdominal cancers or inflammation. Colonoscopy was performed as part of screening, or if patients had suspected colon cancer or inflammatory bowel disease. A total of 8 male and 7 female patients were enrolled in the present study. All patients, with the exception of one who had been diagnosed with CRC following colonoscopy, had positive results and all patients diagnosed with CP following a colonoscopy, with the exception of one, had negative results on DWIBS/T2. Thus, CRC was detected by DWIBS/T2, while CP was not (P=0.0028). The diameter of CRC lesions was significantly larger than that of CP (P<0.0001) and that of lesions positive on DWIBS/T2 was significantly larger than that of negative lesions (P=0.0004). The depth of invasion tended to be greater for lesions positive on DWIBS/T2 compared with that of negative ones. This indicated that DWIBS/T2 may be suitable for the detection of CRC but not for detection of CP. The results of DWIBS/T2 may also be affected by lesion diameter and depth of invasion.


Prognosis and Predictors of Symptomatic Intracranial Hemorrhage After Endovascular Treatment of Large Vessel Occlusion Stroke.
Symptomatic intracranial hemorrhage (sICH) is a devastating complication of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) and is associated with high risk of disability and mortality. This study intended to evaluate the predictors of sICH after EVT in patients with large vessel occlusion (LVO)-induced AIS. We conducted a retrospective review on consecutive AIS patients who underwent EVT in our University hospital between January 2019 and August 2020. The patients were classified into two groups based upon the occurrence of sICH. The main outcomes were the occurrence of sICH using the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristics (ROC) curves were used to identify independent predictors of sICH after EVT. Three hundred and 69 patients were enrolled in the study, of which 16.8% (n = 62) developed sICH. Favorable neurological outcome was lower in patients with sICH than in patients without sICH (6.5 vs. 43.3%; P < 0.001), with the overall mortality being 112 (30.4%) at 90 days post- EVT. Results from univariate analysis showed significant differences between the two groups in the prevalence of diabetes, initial Alberta Stroke Program Early CT Score (ASPECTS) score, National Institutes of Health Stroke Scale (NIHSS) score after operation, the levels of fasting blood glucose (FBG), neutrophil to lymphocyte ratio (NLR), platelets (PLT), and thrombin time (TT) at admission. Multivariate logistic regression analysis showed that FBG ≥ 7.54 mmol/L (OR: 2.765; 95% confidence interval [CI]: 1.513-5.054), NLR ≥ 5.48 (OR: 2.711; 95% CI: 1.433-5.128), TT at admission ≥ 16.25 s (OR: 2.022; 95% CI: 1.115-3.667), and NIHSS score within 24 h after the operation ≥ 10 (OR: 3.728; 95% CI: 1.516-9.170) were independent predictors of sICH. The combination of NLR ≥ 5.48, FBG ≥ 7.54 mmol/L, TT at admission ≥ 16.25 s, and NIHSS score within 24 h after the operation ≥ 10 generated an optimal prediction model (AUC: 0.723). Higher levels of FDG, NLR, TT at admission, and NIHSS score after operation were associated with sICH after EVT in patients with LVO-induced AIS.


Pediatric coccidioidomycosis in central California: a retrospective case series.
Coccidioidomycosis, an endemic fungal infection seen throughout the southwestern United States, is not well described in children. We performed a retrospective observational study of all children admitted to Children's Hospital Central California with coccidioidomycosis from 1 January 2010 to 1 September 2011. Thirty-three children, aged 6 months to 17 years, were hospitalized during the study period. These included patients with pneumonia (n = 28), pleural effusion (n = 13), pleural empyema (n = 4), lung abscess (n = 7), pericarditis (n = 2), osteomyelitis (n = 5), meningitis/cerebritis (n = 2), and vocal cord infection (n = 1). Mediastinitis, with radiographic evidence of purulence and necrotic/abscessed lymph nodes in the mediastinum, was present in 7 patients (21%) and tended to occur more often in younger children (median age, 3 years [range, 0.5-11 years] vs 7 years [range, 0.6-17 years] for non-mediastinitis patients; P = .10). Seven patients were admitted to the intensive care unit and 10 required surgical intervention. One patient died of meningitis. Hospitalizations were longer for patients with mediastinitis (median, 130 days [range, 58-200 days] vs 43 days [range, 3-273 days for non-mediastinitis patients]; P < .01) and those with maximum coccidioidal complement fixing antibody titers ≥1:128 (median, 174 days [range, 53-273 days] vs 33 days [range, 3-200 days] for those with maximum titers <1:128; P < .01). Coccidioidomycosis causes a substantial disease burden in the children of central California. Mediastinitis is common and tends to occur in younger children. Patients with mediastinitis or elevated coccidioidal complement fixation titers require longer hospitalizations. Further research is needed on the prevention and treatment of this disease.


On component-wise dissimilarity measures and metric properties in pattern recognition.
In many real-world applications concerning pattern recognition techniques, it is of utmost importance the automatic learning of the most appropriate dissimilarity measure to be used in object comparison. Real-world objects are often complex entities and need a specific representation grounded on a composition of different heterogeneous features, leading to a non-metric starting space where Machine Learning algorithms operate. However, in the so-called unconventional spaces a family of dissimilarity measures can be still exploited, that is, the set of component-wise dissimilarity measures, in which each component is treated with a specific sub-dissimilarity that depends on the nature of the data at hand. These dissimilarities are likely to be non-Euclidean, hence the underlying dissimilarity matrix is not isometrically embeddable in a standard Euclidean space because it may not be structurally rich enough. On the other hand, in many metric learning problems, a component-wise dissimilarity measure can be defined as a weighted linear convex combination and weights can be suitably learned. This article, after introducing some hints on the relation between distances and the metric learning paradigm, provides a discussion along with some experiments on how weights, intended as mathematical operators, interact with the Euclidean behavior of dissimilarity matrices.


Markers of pancreatic function in the breath.
Exhaled breath analysis is able to identify biomarkers of respiratory and systemic diseases. It was hypothesized that markers of pancreatic function would be identified in the breath of those with diabetes mellitus and cystic fibrosis. Children aged 6-18 years old with diabetes mellitus (DM), cystic fibrosis (CF), cystic fibrosis related diabetes (CFRD) and healthy controls (C) contributed exhaled breath condensate (EBC), with concurrent blood glucose measurements taken from a subset. EBC C-peptide, glucose, sodium concentrations and conductivity were subsequently measured.A total of 104 children were recruited (DM = 56, CF = 26, CFRD = 5, C = 17). C-peptide was detected in EBC: CF 19.6 ± 11.7 pmol L(-1); DM: 9.66 ± 8.27 pmol L(-1); CFRD: 11.9 ± 9.23 pmol L(-1) which was significantly higher than in the control group (0.987 ± 2.26 pmol L(-1)) (p < 0.0001). No statistically significant difference was seen between the three groups for glucose, conductivity or sodium concentration.Glucose was not reliably found in EBC, but C-peptide was found to be higher in CF EBC. This may represent inflammation and a change in airway integrity, rather than increased secretion of this peptide.


Transcriptome Analysis of Carbohydrate Metabolism Genes and Molecular Regulation of Sucrose Transport Gene LoSUT on the Flowering Process of Developing Oriental Hybrid Lily 'Sorbonne' Bulb.
The quality of Lily cut flower was determined by the quality of bulbs. During the process of vernalization and flower bud differentiation, sugar massively accumulated in the bulb, which influenced the bulb development. However, the details of sugar genes' regulation mechanism for these processes were not fully understood. Here, morphological physiology, transcriptomes and gene engineering technology were used to explore this physiological change. Seventy-two genes of 25 kinds of sugar metabolism-related genes were annotated after re-analyzing transcriptome data of Oriental hybrid lily 'Sorbonne' bulbs, which were generated on Hiseq Illumina 2000. The results showed that these genes were closely related to lily bulb vernalization and development. Combining gene expression pattern with gene co-expression network, five genes (Contig5669, Contig13319, Contig7715, Contig1420 and Contig87292) were considered to be the most potential signals, and the sucrose transporter gene (SUT) was the focus of this study. Carbohydrate transport pathway and genes' regulation mechanism were inferred through a physiological and molecular test. SUT seemed to be the sugar sensor that could sense and regulate sugar concentration, which might have effects on other genes, such as FT, LFY and so on. LoSUT2 and LoSUT4 genes were cloned from Oriental hybrid lily 'Sorbonne' by RACE, which was the first time for these genes in Oriental hybrid lily 'Sorbonne'. The physiological properties of these proteins were analyzed such as hydrophobicity and phosphorylation. In addition, secondary and tertiary structures of proteins were predicted, which indicated the two proteins were membrane proteins. Their cellular locations were verified through positioning the experiment of the fluorescent vector. They were highly expressed in cells around phloem, which illustrated the key role of these genes in sugar transport. Furthermore, transient expression assays showed that overexpressed LoSUT2 and LoSUT4 in Arabidopsis thaliana bloomed significantly earlier than the wild type and the expression of FT, SOC1 and LFY were also affected by LoSUT2 and LoSUT4, which indicated that LoSUT2 and LoSUT4 may regulate plants flowering time.


Expression and Regulation Network of HDAC3 in Acute Myeloid Leukemia and the Implication for Targeted Therapy Based on Multidataset Data Mining.
Histone deacetylase 3 (HDAC3) plays an important role in the development and progression of a variety of cancers, but its regulatory mechanism in acute myeloid leukemia (LAML) is not entirely understood. We analyzed the expression of HDAC3 in normal and cancerous tissues using Oncomine, UALCAN, and GEO databases. Changes of the HDAC3 gene were analyzed by cBioPortal. The genes coexpressed with HDAC3 were analyzed by WebGestalt, and the predicted signaling pathways in KEGG were discussed. We discovered that the expression of HDAC3 was elevated in some types of acute myeloid leukemia. The HDAC3 gene has a strong positive correlation with SLC25A5, NDUFA2, Cox4I1, and EIF3K, which regulate cell growth and development. HDAC3 transcription is higher in patients with FLT3 mutation than in healthy people. HDAC3 can be directly involved in regulating the thyroid hormone signaling pathway. MEF2D is directly involved in the cGMP-PKG signaling pathway, and the HDAC3 gene has a strong synergistic relationship with MEF2D. HDAC3 is indirectly involved in the cGMP-PKG signaling pathway, thereby indirectly regulating the expression levels of p53 and p21 genes in patients with LAML. Genomics of Drug Sensitivity in Cancer (GDSC) database analysis revealed that the application of the HDAC3 inhibitor can inhibit the proliferation of leukemia cells. Therefore, our data suggest that HDAC3 may be a possible therapeutic target for acute myeloid leukemia.


The Kleinian expansion of Freud's metapsychology.
This lecture, delivered extemporaneously, recorded and edited, is a précis of the book, The Kleinian Development (1989) which consists of three sets of lectures, delivered over a period of years at the Tavistock Clinic. These were devoted to the clinical aspects of the work of Freud, Melanie Klein and Wilfred Bion. Although this lecture has been oriented towards the philosophical problem of meaning, to meet the requirements of the audience at University College, London, its basic undertaking is to trace the implicit and explicit models of the mind utilized in clinical work by these three masters. The central thesis is that the three models of the mind, the neurophysiological one of Freud, the quasi-theological one of Melanie Klein and the epistemological one of Bion, can be superimposed upon one another to form a continuous line of development. This line develops an apparatus for mental life which embraces meaning and emotion within the framework of a structural concept of mental apparatus, allowing for a limitless area of discourse concerning an infinitely variable non-causal system with a capability for growth beyond the scope of Darwinian evolutionary modes.


Frequency of renal stone disease in patients with urinary tract infection.
To determine incidence of renal stone disease in patients with urinary tract infection, this cross sectional study was conducted at Surgical Unit of District Head Quarters Hospital, Charsadda over a period of one year from January to December 2005. One hundred consecutive patients were enrolled in this study. All those patients who presented with urinary symptoms were included. While patients with lower urinary tract stones, upper urinary tract stones with renal failure, renal tumours and previous history of renal stones disease were excluded. The data was obtained and analyzed by filling a specially designed proforma for each patient. All 100 patients were between age ranges of 15-60 years (Mean age 37.5 years). Infection was present in 79% of cases. The commonest organisms isolated according to culture report were E. Coli (30%), Proteus (19%), Klebsiella (11%), Pseudomonas (7%), Staphylococcus aureus (3%) etc. The frequency of renal stone disease in patients with urinary tract infection was 18.98%. (12.6% in male and 6.3% in female). Mean age of patients with renal stones was 31.26 years and male to female ratio was 1.5:1. Renal stone disease makes an important group among urinary stone diseases. Urinary tract infection with certain bacteria plays an important role in the synthesis of renal stones. A high incidence can be prevented by adopting a variety of simple conservative measures.


Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction.
It is recognized that airway inflammation has a central role in the pathogenesis of asthma, but how it relates to exercise-induced bronchoconstriction (EIB) is not completely understood. The aim of our study was to investigate the relationship between EIB and baseline concentrations of cysteinyl leukotrienes (Cys-LTs) and other inflammatory markers in exhaled breath condensate (EBC). EBC was collected, and the fraction of exhaled nitric oxide (FE NO ) was measured in a group of 19 asthmatic children, after which they performed a treadmill exercise test. Fourteen healthy children were enrolled as control subjects. The asthmatic children were divided into the EIB group (decrease in FEV 1 , > or =12%) and the non-EIB group. The EBC was analyzed for the presence of Cys-LTs, leukotriene B 4 , and ammonia. Asthmatic patients with EIB (mean FEV 1 decrease, 23% +/- 3%) had higher Cys-LT concentrations than either asthmatic patients without EIB or control subjects (42.2 pg/mL [median] vs 11.7 pg/mL and 5.8 pg/mL; P < .05 and P < .001, respectively). Ammonia concentrations were lower in both the EIB and non-EIB groups than in control subjects (253.2 microM and 334.6 microM vs 798.4 microM; P < .01 and P < .05, respectively). No difference in EBC leukotriene B 4 levels was found among the 3 groups. Both asthmatic groups had higher FE NO levels than control subjects ( P < .001). EBC Cys-LT ( P < .01; r = 0.7) and FE NO ( P < .05; r = 0.5) values both correlated significantly with the postexercise FEV 1 decrease. this study shows that EBC Cys-LT values are higher in asthmatic children with EIB and correlate with the decrease in FEV 1 after exercise. These findings suggest that the pathways of both Cys-LT and nitric oxide are involved in the pathogenesis of EIB.


Multifunctional Photonic Nanomaterials for Diagnostic, Therapeutic, and Theranostic Applications.
The last decade has seen dramatic progress in the principle, design, and fabrication of photonic nanomaterials with various optical properties and functionalities. Light-emitting and light-responsive nanomaterials, such as semiconductor quantum dots, plasmonic metal nanoparticles, organic carbon, and polymeric nanomaterials, offer promising approaches to low-cost and effective diagnostic, therapeutic, and theranostic applications. Reasonable endeavors have begun to translate some of the promising photonic nanomaterials to the clinic. Here, current research on the state-of-the-art and emerging photonic nanomaterials for diverse biomedical applications is reviewed, and the remaining challenges and future perspectives are discussed.


[The adult patient after surgical repair of tetralogy of Fallot: the never-ending story].
Tetralogy of Fallot is a common complex congenital heart disease, nowadays amenable to safe surgical repair with good early and long-term outcomes. Notwithstanding this, surgical repair is not a definite treatment, and the heart of patients with tetralogy of Fallot remains anatomically, physiologically and electrically abnormal. Indeed, long-term survival of patients with repaired tetralogy of Fallot differs from that of the general population. Major long-term complications include supraventricular and ventricular arrhythmias, with risk of sudden cardiac death, and chronic pulmonary regurgitation, which gradually leads to right ventricular dilation and dysfunction. Thus, the primary aims of clinical follow-up for adult patients with repaired tetralogy of Fallot should be to assess ventricular morphology and function, to stratify the arrhythmic risk and to define the optimal surgical or interventional timing.


A model of neurovascular coupling and its application to cortical spreading depolarization.
Cortical spreading depolarization (CSD) is a neuropathological condition involving propagating waves of neuronal silence, and is related to multiple diseases, such as migraine aura, traumatic brain injury (TBI), stroke, and cardiac arrest, as well as poor outcome of patients. While CSDs of different severity share similar roots on the ion exchange level, they can lead to different vascular responses (namely spreading hyperemia and spreading ischemia). In this paper, we propose a mathematical model relating neuronal activities to predict vascular changes as measured with near-infrared spectroscopy (NIRS) and fMRI recordings, and apply it to the extreme case of CSD, where sustained near-complete neuronal depolarization is seen. We utilize three serially connected models (namely, ion exchange, neurovascular coupling, and hemodynamic model) which are described by differential equations. Propagating waves of ion concentrations, as well as the associated vasodynamics and hemodynamics, are simulated by solving these equations. Our proposed model predicts vasodynamics and hemodynamics that agree both qualitatively and quantitatively with experimental literature. Mathematical modeling and simulation offer a powerful tool to help understand the underlying mechanisms of CSD and help interpret the data. In addition, it helps develop novel monitoring techniques prior to data collection. Our simulated results strongly suggest that fMRI is unable to reliably distinguish between spreading hyperemia and spreading ischemia, while NIRS signals are substantially distinct in the two cases.


Enantiomeric separation of glycidyl tosylate by CE: application to the study of catalytic asymmetric epoxidation of allyl alcohol.
A CE method using CDs as chiral selectors was developed and validated to achieve the separation of glycidyl tosylate enantiomers originated by in situ derivatization of glycidol enantiomers obtained in asymmetric epoxidation of allyl alcohol with chiral titanium-tartrate complexes as catalysts. The effects of the nature, pH and concentration of the buffer, the nature and concentration of chiral selector, the addition of SDS, methanol, ethanol or 2-propanol, the capillary temperature, the effective capillary length and the applied voltage on the chiral resolution of glycidyl tosylate enantiomers were investigated. The best separation conditions were achieved using a Tris-borate buffer mixture (50 and 25 mM, respectively) at pH=9.3 with a dual CD system consisting of 2.5% succinyl-beta-CD and 1.0% beta-CD w/v at 15 degrees C. A baseline separation (resolution approximately 2.0) of the glycidyl tosylate enantiomers was obtained in a relatively short time (less than 12 min). Satisfactory results were obtained in terms of linearity (r>0.99) and intermediate precision (RSD below 8.5%). The LOD and LOQ were 3.0 and 10.0 mg/L, respectively, and the recoveries ranged from 99.8 to 108.8%. Finally, the method was applied to the determination of the enantiomeric excess and the yield obtained in the asymmetric epoxidation of allyl alcohol employing chiral titanium-tartrate complexes as catalysts after an in situ derivatization of glycidol enantiomers to glycidyl tosylate.


Comparative studies of transcriptional regulation mechanisms in a group of eight gamma-proteobacterial genomes.
Experimental data on the Escherichia coli transcriptional regulation has enabled the construction of statistical models to predict new regulatory elements within its genome. Far less is known about the transcriptional regulatory elements in other gamma-proteobacteria with sequenced genomes, so it is of great interest to conduct comparative genomic studies oriented to extracting biologically relevant information about transcriptional regulation in these less studied organisms using the knowledge from E. coli. In this work, we use the information stored in the TRACTOR_DB database to conduct a comparative study on the mechanisms of transcriptional regulation in eight gamma-proteobacteria and 38 regulons. We assess the conservation of transcription factors binding specificity across all the eight genomes and show a correlation between the conservation of a regulatory site and the structure of the transcription unit it regulates. We also find a marked conservation of site-promoter distances across the eight organisms and a correspondence of the statistical significance of co-occurrence of pairs of transcription factor binding sites in the regulatory regions, which is probably related to a conserved architecture of higher-order regulatory complexes in the organisms studied. The results obtained in this study using the information on transcriptional regulation in E. coli enable us to conclude that not only transcription factor-binding sites are conserved across related species but also several of the transcriptional regulatory mechanisms previously identified in E. coli.


Novel bioemulsomes for baicalin oral lymphatic targeting: development, optimization and pharmacokinetics.
Aim: The aim of this study was to elaborate on 'bioemulsomes,' novel biocompatible lipoprotein analogs for effective lymphatic transport of baicalin (BCL). Methods: BCL bioemulsomes were developed and optimized and in vitro physicochemical characterization performed. The bioavailability of BCL bioemulsomes compared with free BCL was investigated using in vivo pharmacokinetics studies. Finally, BCL lymphatic transport was assessed via cycloheximide blockade assay. Results: Optimized BCL-loaded nanoemulsomes showed promising in vitro characteristics that favor lymphatic targeting. In vivo pharmacokinetics showed a significant improvement in bioavailability over free BCL. A significant decrease in BCL emulsome absorption (33%) was exhibited after chemical blockage of the lymphatic pathway, confirming the lymphatic transport potential. Conclusion: Bioemulsomes could be a promising tool for bypassing BCL oral delivery hurdles as well as lymphatic transport, paving the way for potential treatment of lymphoma.


Successful Outcome of Twin Gestation with Partial Mole and Co-Existing Live Fetus: A Case Report.
Sad fetus syndrome comprising of a live twin gestation with a hydatidiform mole is a rare entity. The condition is even rarer when the co-existing live fetus is associated with a partial mole than a complete mole. We report the case of a 24-year-old G2P1L1 at 28 weeks gestation who presented to our casualty in the second stage of labour. She had a previous ultrasound scan at 13 weeks which showed a live fetus with a focal area of multicystic placenta. She delivered an alive preterm male fetus weighing 1.32 kg vaginally. Following expulsion of normal placenta of the live fetus, partial mole was expelled. The fetus was admitted to neonatal ICU and discharged after two weeks. Soon after delivery, β-hCG (human chorionic gonadotropin) was 1,21,993 mIU/ml which decreased to 30mIU/ml within two weeks. The patient was discharged with advice of regular follow up of β-hCG reports.


Improved PRF-based MR thermometry using k-space energy spectrum analysis.
Proton resonance frequency (PRF) thermometry encodes information in the phase of MRI signals. A multiplicative factor converts phase changes into temperature changes, and this factor includes the TE. However, phase variations caused by B0 and/or B1 inhomogeneities can effectively change TE in ways that vary from pixel to pixel. This work presents how spatial phase variations affect temperature maps and how to correct for corresponding errors. A method called "k-space energy spectrum analysis" was used to map regions in the object domain to regions in the k-space domain. Focused ultrasound heating experiments were performed in tissue-mimicking gel phantoms under two scenarios: with and without proper shimming. The second scenario, with deliberately de-adjusted shimming, was meant to emulate B0 inhomogeneities in a controlled manner. The TE errors were mapped and compensated for using k-space energy spectrum analysis, and corrected results were compared with reference results. Furthermore, a volunteer was recruited to help evaluate the magnitude of the errors being corrected. The in vivo abdominal results showed that the TE and heating errors being corrected can readily exceed 10%. In phantom results, a linear regression between reference and corrected temperatures results provided a slope of 0.971 and R2 of 0.9964. Analysis based on the Bland-Altman method provided a bias of -0.0977°C and 95% limits of agreement that were 0.75°C apart. Spatially varying TE errors, such as caused by B0 and/or B1 inhomogeneities, can be detected and corrected using the k-space energy spectrum analysis method, for increased accuracy in proton resonance frequency thermometry.


[Normal and abnormal height and weight development in children and adolescents in Krakow--changes and trends in the last thirty years].
The aim of this study is to determine the frequency of height and weight disharmony in children and adolescents in Krakow, i.e. both overweight and underweight in relation to height and the trends in last thirty years. 4532 individuals -- a random sample of children and adolescents (2416 boys and 2107 girls) were examined in 2000. The results of the examination were compared with data obtain in 1971 (random sample of 4090 individuals) and with results from 1983 (random sample of 6536 individuals). Percentile position of height and weight were compared: the difference of two or more percentiles channels classified the results as overweight or underweight depending on height. Of the research prove that the frequency of occurrence of dis-harmonious body built increases with age, both with regard to overweight and underweight related to height and this phenomenon is more frequent in girls. In last thirty years a progressive increase of frequency of overweight was observed, but in girls it was noticeable and statistically significant only in 1971 -- 1983.


Reasons for non-compliance among patients treated under Revised National Tuberculosis Control Programme (RNTCP), Tiruvallur district, south India.
To elicit reasons for treatment default from a cohort of TB patients under RNTCP and their DOT providers. A total of 186 defaulters among the 938 patients registered during 3rd and 4th quarters of 1999 and 2001 in one Tuberculosis Unit (TU) of Tiruvallur district, Tamil Nadu and their DOT providers were included in the study. They were interviewed using a semi-structured interview schedule. Sixteen (9%) had completed treatment, 25 (13%) died after defaulting, and 4 (2%) could not be traced. Main reasons given by the remaining 141 patients and their DOT providers were: drug related problems (42%, 34%), migration (29%, 31%), relief from symptoms (20%, 16%), work related (15%, 10%), alcohol consumption (15%, 21%), treatment from other centers (13%, 4%), respectively. Risk factors for default were alcoholism (P<0.001), category of treatment (P<0.001), smear status (P<0.001), type of disease (P<0.001) and inconvenience for DOT (P<0.01). This study has identified group of patients vulnerable to default such as males, alcoholics, smear positive cases, and DOT being inconvenient. Intensifying motivation and counselling of this group of cases are likely to improve patient compliance and reduce default.


Growth, growth factors and diabetes.
Type 1 diabetes mellitus (T1DM) and other chronic diseases in children are well known to adversely affect linear growth and pubertal development. In the years immediately following the introduction of insulin therapy, short stature was consistently reported in children with T1DM. However, over the past 50 years significant improvement in the prognosis for growth and final height in children with diabetes has been achieved. Although pre-pubertal and post-pubertal growth are important phases in growth, puberty and its related hormonal changes represent a critical phase for growth gain and final height particularly in patients with T1DM. Growth impairment reported in diabetic patients is dependent on abnormalities in physiological bone growth and corresponds to abnormalities of the growth hormone-insulin-like growth-I (GH-IGF-I) axis. These alterations seem to be related to appropriate insulin levels and thereby to glycaemic control as judged by haemoglobin levels. Modern diabetes care, particularly intensified insulin regimens, might improve metabolic control in patients with T1DM, therefore preventing abnormalities of the GH-IGF-I axis and leading to normal growth and final height similar to that of their unaffected peers.


Inactivation of Mycobacterium avium with monochloramine.
Batch experiments were performed to study the inactivation kinetics of Mycobacterium avium in the presence of monochloramine at 5-30 degrees C, pH 6-10, and 0.30-42.3 mg Cl2/ L. For each temperature and pH investigated, limiting high and low inactivation rates were observed for high and low disinfectant concentrations, respectively, within the range investigated. The rate of inactivation transitioned from high to low over a relatively narrow range of intermediate monochloramine concentrations. The observed temperature dependence of inactivation was consistent with an Arrhenius expression with activation energies of 58.0 and 71.7 kJ/mol for the high and low concentration ranges, respectively. The rate of inactivation increased with decreasing pH, consistent with trends reported for the reaction of monochloramine with protein thiols. Experiments performed at pH approximately 3.5 showed that dichloramine was a weaker disinfectant than monochloramine, and that its contribution to the overall inactivation of M. avium with combined chlorine was negligible at pH 6-10. A kinetic model incorporating disinfectant concentration, temperature, and pH effects was used to illustrate that monochloramine efficiency to inactivate M. avium in water could vary broadly from adequate (e.g., 99.9% inactivation efficiency in 32 min at 5 mg Cl2/L, pH 6, 30 degrees C) to impractical (e.g., 99.9% inactivation efficiency in 9 d at 1 mg Cl2/L, pH 9, 5 degrees C).


[Role of vascular calcium-activated potassium channels in the regulation of human peripheral conduit artery diameter].
The role of an endothelium-derived hyperpolarizing factor (EDHF), acting through the opening of vascular calcium-activated potassium (K(Ca)) channels, in the regulation of the basal diameter of human peripheral conduit arteries has never been investigated in vivo. We measured in 7 healthy subjects the effect of the local infusion of an inhibitor of K(Ca) channels, tetraethylammonium chloride (TEA, 9 micromol/min, 8 min), on radial artery diameter (echotracking) and flow (Doppler). Endothelium-independent dilatation was assessed before and after TEA using sodium nitroprusside (SNP: 5, 10 and 15 nmol/min, 3 min each). TEA induced a decrease in radial artery diameter (2.65 +/- 0.09 to 2.52 +/- 0.09 mm: p < 0.05) and flow (9.4 +/- 1.2 to 7.4 +/- 1.1 ml/min; p < 0.01) without modification in the radial artery dilatation in response to SNP (NS). The decrease in radial artery diameter was still significant even when the decrease in flow was taken as covariate into analysis (p < 0.05). These results demonstrate the role of vascular K(Ca) channels in the regulation of basal peripheral conduit artery diameter and arteriolar tone in human strongly suggesting the involvement of an EDHF a these two levels.


Genomic determinants of epidermal appendage patterning and structure in domestic birds.
Variation in regional identity, patterning, and structure of epidermal appendages contributes to skin diversity among many vertebrate groups, and is perhaps most striking in birds. In pioneering work on epidermal appendage patterning, John Saunders and his contemporaries took advantage of epidermal appendage diversity within and among domestic chicken breeds to establish the importance of mesoderm-ectoderm signaling in determining skin patterning. Diversity in chickens and other domestic birds, including pigeons, is driving a new wave of research to dissect the molecular genetic basis of epidermal appendage patterning. Domestic birds are not only outstanding models for embryonic manipulations, as Saunders recognized, but they are also ideal genetic models for discovering the specific genes that control normal development and the mutations that contribute to skin diversity. Here, we review recent genetic and genomic approaches to uncover the basis of epidermal macropatterning, micropatterning, and structural variation. We also present new results that confirm expression changes in two limb identity genes in feather-footed pigeons, a case of variation in appendage structure and identity.


Mechanical role of the spatial patterns of contractile cells in invagination of growing epithelial tissue.
Epithelial invagination is one of the fundamental deformation modes during morphogenesis, and is essential for deriving the three-dimensional shapes of organs from a flat epithelial sheet. Invagination occurs in an orderly manner according to the spatial pattern of the contractile cells; however, it remains elusive how tissue deformation can be caused by cellular activity in the patterned region. In this study, we investigated the mechanical role of the spatial patterns of the contractile cells in invagination of growing tissue using multicellular dynamics simulations. We found that cell proliferation and apical constriction were responsible for expanding the degree of tissue deformation and determining the location of the deformation, respectively. The direction of invagination depended on the spatial pattern of the contractile cells. Further, comparing the simulation results of surface and line contractions as possible modes of apical constriction, we found that the direction of invagination differed between these two modes even if the spatial pattern was the same. These results indicate that the buckling of the epithelial cell sheet caused by cell proliferation causes the invagination, with the direction and location determined by the configuration of the wedge-shaped cells given by the spatial pattern of the contractile cells.


Spino-pelvic alignment, balance, and functional disability in patients with low-grade degenerative lumbar spondylolisthesis.
To evaluate the relationships among spino-pelvic parameters, trunk balance and functional disability in patients with degenerative lumbar spondylolisthesis. Cross-sectional study. Forty-five patients with degenerative lumbar spondylolisthesis and 32 patients without degenerative lumbar spondylolisthesis. Spino-pelvic parameters (pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis) and pain severity were evaluated. Biodex balance tests (postural stability, limits of stability, modified clinical test of sensory interaction and balance, fall risk) and Quebec Back Pain Disability Scale (QBDS) scores were measured. Intergroup differences were found in age, low back pain, limits of stability, pelvic incidence, pelvic tilt and some subscales of QBDS. Correlations were found: (i) in the degenerative lumbar spondylolisthesis group: between pelvic incidence and sacral slope/pelvic tilt/lumbar lordosis/height/limits of stability; sacral slope and lumbar lordosis/height/limits of stability/modified clinical test of sensory interaction and balance (eyes closed on foam); lumbar lordosis and body mass index/QBDS/postural stability/modified clinical test of sensory interaction and balance (eyes open and eyes closed on foam); (ii) in the non-degenerative lumbar spondylolisthesis group: between pelvic incidence and pelvic tilt; pelvic tilt and sacral slope/lumbar lordosis; sacral slope and lumbar lordosis/fall risk. All spino-pelvic parameters in the degenerative lumbar spondylolisthesis group and pelvic tilt in the non-degenerative lumbar spondylolisthesis group correlated with QBDS. Pelvic tilt was the major compensating factor in both groups (patients with and without degenerative lumbar spondylolisthesis). Sacral slope and lumbar lordosis contributed to partial compensation in the degenerative lumbar spondylolisthesis group. Lumbar lordosis correlated with body mass index. Sacral slope could be an indicator of fall risk in the non-degenerative lumbar spondylolisthesis group.


Subgingival delivery of therapeutic agents in the treatment of periodontal diseases.
This article reviews the current status of controlled local delivery of antibacterial agents in the treatment of periodontitis. The principle of local intrapocket delivery of antibacterial agents and their delivery are discussed. The dosage forms include fibers, film/slabs, and injectable systems, some of which are degradable, while others are not and need to be removed at the termination of the treatment. The antibacterial agents used cover a range of antibiotics as well as antiseptics, and the composition of the delivery systems, their reported use, and the clinical results are summarized. The use of these systems in clinical practice is relatively recent, and therefore their application and integration into the dental office are not yet clearly defined. Clinical applications that have been tested are critically reviewed, and clinical situations in which controlled delivery of antibacterial agents may prove to be clinically useful are suggested for scientific evaluation.


High-throughput development of a hybrid-type fluorescent glutamate sensor for analysis of synaptic transmission.
Fluorescent sensors are powerful tools for visualizing cellular molecular dynamics. We present a high-throughput screening system, designated hybrid-type fluorescence indicator development (HyFInD), to identify optimal position-specific fluorophore labeling in hybrid-type sensors consisting of combinations of ligand-binding protein mutants with small molecular fluorophores. We screened sensors for glutamate among hybrid molecules obtained by the reaction of four cysteine-reactive fluorescence probes with a set of cysteine-scanning mutants of the 274 amino acid S1S2 domain of AMPA-type glutamate receptor GluA2 subunit. HyFInD identified a glutamate-responsive probe (enhanced glutamate optical sensor: eEOS) with a dynamic range >2400 %, good photostability, and high selectivity. When eEOS was specifically tethered to neuronal surfaces, it reliably visualized the spatiotemporal dynamics of glutamate release at single synapses, revealing synapse-to-synapse heterogeneity of short-term plasticity.


Oxygen poisoning in Drosophila.
Fruit flies live longer at the partial pressure of oxygen found in air than at either larger or smaller partial pressures. Flies exposed to 1 atm of oxygen for 8 hr every day do not recover completely in the remaining 16 hr. In general, intermittent exposures to 1 atm of oxygen are better tolerated than continuous exposure to the same average oxygen concentration per day, but exposures to higher pressures of 2-5 atm of oxygen for as little as a half hour every two days markedly shorten the life-span. Older flies consume more oxygen per minute and are more sensitive to oxygen poisoning than young flies, and the rate of dying in 6 atm of O(2), or the reciprocal of the survival time, is a linear function of the age. The oxygen pressure-time curve can be well expressed by the general empirical equation (P(OO2))(2) x time = 120 where P is in atmosphere and survival time in hours. The progress of oxygen poisoning appears to be linear with time rather than exponential.


Preschool children's health and its association with parental education and individual living conditions in East and West Germany.
Social inequalities in health exist globally and are a major public health concern. This study focus on a systematic investigation into the associations between health indicators, living conditions and parental educational level as indicator of the social status of 6-year-old children living in West and East Germany in the decade after re-unification. Explanations of observed associations between parental education and health indicators were examined. All boys and girls entering elementary school and living in predefined areas of East and West Germany were invited to participate in a series of cross-sectional surveys conducted between 1991 and 2000. Data of 28,888 German children with information on parental education were included in the analysis. Information about educational level of the parents, individual living conditions, symptoms and diagnoses of infectious diseases and allergies were taken from questionnaire. At the day of investigation, atopic eczema was diagnosed by dermatologists, blood was taken for the determination of allergen-specific immuno-globulin E, height and weight was measured and lung function tests were done in subgroups. Regression analysis was applied to investigate the associations between the health indicators and parental educational level as well as the child's living conditions. Gender, urban/rural residency and year of survey were used to control for confounding. Average response was 83% in East Germany and 71% in West Germany. Strong associations between health indicators and parental education were observed. Higher educated parents reported more diagnoses and symptoms than less educated. Children of higher educated parents were also more often sensitized against grass pollen or house dust mites, but had higher birth weights, lower airway resistance and were less overweight at the age of six. Furthermore, most of the health indicators were significantly associated with one or more living conditions such as living as a single child, unfavourable indoor air, damp housing condition, maternal smoking during pregnancy or living near a busy road. The total lung capacity and the prevalence of an atopic eczema at the day of investigation were the only health indicators those did not show associations with any of the predictor variables. Despite large differences in living conditions and evidence that some poor health outcomes were directly associated with poor living conditions, only few indicators demonstrated poorer health in social disadvantaged children. These were in both parts of Germany increased levels of overweight, higher airway resistance and, in East Germany only, reduced height in children with lower educated parents compared to those of higher education. In both East and West Germany, higher prevalence of airway symptoms was associated with a damp housing condition, and lower birth weight, reduced height and increased airway resistance at the age of six were associated with maternal smoking during pregnancy. The latter explained to a large extent the difference in birth weight and airway resistance between the educational groups.


Perimortem caesarean delivery (PMCD).
When a woman in late pregnancy has cardiac arrest and resuscitation fails, should an attempt be made to deliver the baby by Caesarean section? Many obstetricians would hesitate to operate in these circumstances for fear of delivery a baby who survives but shows profound neurological handicap. Obstetricians need to have a clear view on whether and when to operate in such cases. Here we report two cases of PMCD.


Down-Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide-Induced Glioma Cells Growth Inhibition and Invasion Impairment.
Glioma is the most common and lethal central nervous system tumors. Temozolomide (TMZ) is an effective drug for malignant glioma, however, the intracellular and molecular mechanisms behind this anti-cancer effect have yet to be fully understood. The aim of the present study was to determine whether TMZ inhibits proliferation, invasion of glioma cells in vitro and whether these effects can be mediated through modulation of aquaporin 4 (AQP4) and phosphorylation of the MAPK pathway. The viability of U87 and U251 human glioma cells was evaluated using MTT assay. The cell cycle distribution was detected with flow cytometry. Migration ability and invasion ability were tested by scratch assays and transwell assays, respectively. The levels of AQP4 and MAPK were measured using immunoblot analyses. Our results showed that TMZ inhibited proliferation, migration and invasion, and induced G2/M arrest in U87 and U251 glioma cell lines. These changes were associated with a decrease in the levels of AQP4 expression as well as activation phosphorylated level of p38. Treatment with a p38 chemical activator (anisomycin) resulted in similar effects as TMZ treatment on glioma cells. And p38 chemical inhibitor (SB203580) could block these effects in glioma treated with TMZ, suggesting a direct up-regulation of the p38 signaling pathway. Therefore, we identified that TMZ might have therapeutic potential for controlling proliferation, invasion of malignant glioma by inhibiting AQP4 expression through activation of p38 signal transduction pathway. J. Cell. Biochem. 118: 4905-4913, 2017. © 2017 Wiley Periodicals, Inc.


Breast cancer response to paclitaxel in vivo.
Clinical trials using neoadjuvant (primary, preoperative) chemotherapy demonstrate that breast cancer reduction relates to survival. To date, no pre-treatment pathologic, phenotypic, or genotypic tumor characteristics predict a patient's likely benefit from paclitaxel. This has led to pilot clinical studies that have attempted to identify whether early cellular responses in vivo can be used to predict the effectiveness of chemotherapy. A potential benefit of such predictive studies will be the ability to tailor specific therapeutic approaches to individual patients. Important issues surrounding this field include how to accurately measure and/or categorize the extent of tumor reduction, and how and when to assess breast cancer cellular responses in vivo. Preliminary data indicate that initial apoptotic responses are critical to tumor reduction, and that the timing of tumor samples for assessment of response is important. Although inherent complete resistance of breast cancer to paclitaxel occurs in a minority of patients, mechanisms of acquired or partial resistance require further study. However, the initial apoptotic response to paclitaxel has been shown to transiently reduce both cell density and intratumoral pressure, providing a window of time when there can be improved penetration of paclitaxel into the tumor. Thus a strong initial apoptotic response can set up a compounding benefit from subsequent treatments. Knowledge of breast cancer response to paclitaxel in vivo could lead to therapeutic strategies that enhance the apoptotic response and optimize the dosing schedule, to improve the tumor reduction for most patients.


Acetylated histone H4 is preferentially associated with template-active chromatin.
Chromatin from trout testis at an early stage of development was digested with DNase II (deoxyribonucleate 3'-oligonucleotidohydrolase; EC 22.214.171.124), and the solubilized products were fractionated into Mg2+-soluble and -insoluble components. An examination of the histones from these fractions by one- and two-dimensional polyacrylamide gels showed that the highly acetylated species of histone H4 (di-, tri-, and tetra-acetylated) were associated mainly with the Mg2+-soluble material. Digestion of this chromatin fraction with pancreatic ribonuclease converted more than half of it to an insoluble state, and the acetylated H4 remained associated with the precipitated fraction. No changes in the other histones were noted, but two other basic proteins were also found to be associated with the Mg2+-soluble fraction. Since this fraction is enriched in transcribing gene sequences, it is concluded that the histone H4 of active genes is present in a highly acetylated state.


A never-ending succession of epidemics? Mortality in early-modern York.
Early-modern cities are often perceived to be centres of high mortality and under constant siege from a barrage of epidemics. However, few urban mortality rates have been calculated and by employing parish register evidence from the regional capital of York, the thesis that the city was subjected to continual sudden increases in mortality can be firmly rejected. Infant mortality was high but remained virtually constant between 1561 and 1700. About a quarter of all infants did not survive to reach their first birthday and neonatal mortality was especially severe. From the mid-seventeenth century a series of epidemics increased child mortality although overall levels of mortality were not significantly affected. Relatively little can be said about adult mortality and apart from two periods of 'crisis' mortality there is little to suggest that adults were greatly affected by epidemics. Indeed, for many adults the urban environment appears to have posed no great threat to health and most could look forward to a relatively long life in the city. York's mortality regime was very similar to that of the smaller market town of Gainsborough where high levels of mortality remained stable throughout much of the early-modern period.


A storage-based model of heterocyst commitment and patterning in cyanobacteria.
When deprived of fixed nitrogen (fN), certain filamentous cyanobacteria differentiate nitrogen-fixing heterocysts. There is a large and dynamic fraction of stored fN in cyanobacterial cells, but its role in directing heterocyst commitment has not been identified. We present an integrated computational model of fN transport, cellular growth, and heterocyst commitment for filamentous cyanobacteria. By including fN storage proportional to cell length, but without any explicit cell-cycle effect, we are able to recover a broad and late range of heterocyst commitment times and we observe a strong indirect cell-cycle effect. We propose that fN storage is an important component of heterocyst commitment and patterning in filamentous cyanobacteria. The model allows us to explore both initial and steady-state heterocyst patterns. The developmental model is hierarchical after initial commitment: our only source of stochasticity is observed growth rate variability. Explicit lateral inhibition allows us to examine ΔpatS, ΔhetN, and ΔpatN phenotypes. We find that ΔpatS leads to adjacent heterocysts of the same generation, while ΔhetN leads to adjacent heterocysts only of different generations. With a shortened inhibition range, heterocyst spacing distributions are similar to those in experimental ΔpatN systems. Step-down to non-zero external fN concentrations is also investigated.


Bilateral Internal Carotid Artery Agenesis in a Patient With a Family History of Intracranial Pathology.
Background: Agenesis of the internal carotid artery (ICA) is a rare congenital malformation that is often asymptomatic until the fourth or fifth decade. ICA agenesis is associated with several intracranial pathologies, the most reported being intracranial aneurysms, thought to be attributable to the increased flow in the collateral vessels supplying the anterior circulation. The cause of ICA agenesis is largely unknown and has not been consistently associated with any genetic mutations or syndromes. Case Report: We present the case of a 37-year-old female who was incidentally found to have bilateral agenesis of the ICA system. Patient history revealed that the patient's father and 12 of his 14 siblings died from either ruptured brain aneurysms or cerebrovascular accidents before the age of 50 years. Presenting symptoms included right eye pain radiating to her right posterior neck, a 2-month history of diplopia, and associated nausea and vomiting. Differential diagnoses included immunoglobulin G4-related disease, sarcoidosis, lymphoma, and vasculitis. Absent internal carotids were attributed to congenital agenesis vs hypoplasia. The patient was seen by neurology and initiated on prednisone 80 mg by mouth once daily with a 2-week taper to treat systemic inflammation. The patient was deemed stable for discharge after a 2-day hospital admission and was scheduled for follow-up appointments with genetics, neurology, rheumatology, and ophthalmology. Conclusion: Bilateral ICA agenesis is a rare occurrence, with only 33 cases documented in a case report and literature review published in 2016. Because of the otherwise normal anatomy of the patient and the pervasive intracranial pathology seen in late adulthood in her family, we propose the likelihood of an inheritable form of bilateral ICA agenesis vs vascular disease or familial aneurysms.


Cyano-Rich g-C3 N4 in Photochemistry: Design, Applications, and Prospects.
Cyano-rich g-C3 N4 materials are widely used in various fields of photochemistry due to the very powerful electron-absorbing ability and electron storage function of cyano, as well as its advantages in improving light absorption, adjusting the energy band structure, increasing the polarization rate and electron density in the structure, active site concentration, and promoting oxygen activation ability. Notwithstanding, there is yet a huge knowledge break in the design, preparation, detection, application, and prospect of cyano-rich g-C3 N4 . Accordingly, an overall review is arranged to substantially comprehend the research progress and position of cyano-rich g-C3 N4 materials. An overall overview of the current research position in the synthesis, characterization (determination of their location and quantity), application, and reaction mechanism analysis of cyano-rich g-C3 N4 materials to provide a quantity of novel suggestions for cyano-modified carbon nitride materials' construction is provided. In view of the prevailing challenges and outlooks of cyano-rich g-C3 N4 materials, this paper will purify the growth direction of cyano-rich g-C3 N4 , to achieve a more in-depth exploration and broaden the applications of cyano-rich g-C3 N4 .


Multimodal non-invasive assessment of intracranial hypertension: an observational study.
Although placement of an intra-cerebral catheter remains the gold standard method for measuring intracranial pressure (ICP), several non-invasive techniques can provide useful estimates. The aim of this study was to compare the accuracy of four non-invasive methods to assess intracranial hypertension. We reviewed prospectively collected data on adult intensive care unit (ICU) patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH) in whom invasive ICP monitoring had been initiated and estimates had been simultaneously collected from the following non-invasive indices: optic nerve sheath diameter (ONSD), pulsatility index (PI), estimated ICP (eICP) using transcranial Doppler, and the neurological pupil index (NPI) measured using automated pupillometry. Intracranial hypertension was defined as an invasively measured ICP > 20 mmHg. We studied 100 patients (TBI = 30; SAH = 47; ICH = 23) with a median age of 52 years. The median invasively measured ICP was 17 [12-25] mmHg and intracranial hypertension was present in 37 patients. Median values from the non-invasive techniques were ONSD 5.2 [4.8-5.8] mm, PI 1.1 [0.9-1.4], eICP 21 [14-29] mmHg, and NPI 4.2 [3.8-4.6]. There was a significant correlation between all the non-invasive techniques and invasive ICP (ONSD, r = 0.54; PI, r = 0.50; eICP, r = 0.61; NPI, r = - 0.41-p < 0.001 for all). The area under the curve (AUC) to estimate intracranial hypertension was 0.78 [CIs = 0.68-0.88] for ONSD, 0.85 [95% CIs 0.77-0.93] for PI, 0.86 [95% CIs 0.77-0.93] for eICP, and 0.71 [95% CIs 0.60-0.82] for NPI. When the various techniques were combined, the highest AUC (0.91 [0.84-0.97]) was obtained with the combination of ONSD with eICP. Non-invasive techniques are correlated with ICP and have an acceptable accuracy to estimate intracranial hypertension. The multimodal combination of ONSD and eICP may increase the accuracy to estimate the occurrence of intracranial hypertension.


A Conceptual Framework for Understanding the Role of Adverse Childhood Experiences in Pediatric Chronic Pain.
This review outlines a conceptual framework adapted from the biopsychosocial model of pain to examine the relationship between adverse childhood experiences (ACEs) and chronic pain in youth to highlight the state of current research and guide future efforts. A review of the literature was performed in the areas of ACEs and health outcomes with general adult and pediatric populations in addition to studies within the pain literature. Potential relationships between ACEs, chronic pain, and its impact in youth are outlined and discussed. The literature suggests an association between adverse outcomes of ACEs and chronic pain in children and adolescents although causal links have not been confirmed. However, ACEs are associated with multiple risk factors identified in the biopsychosocial model of pain, and may serve to exacerbate or confer heightened risk for pain and poor outcomes. Adverse experiences in childhood may be associated with greater risk for the development/maintenance of chronic pain in youth. More research is needed on ACEs and how they uniquely affect the biopsychosocial mechanisms underlying chronic pain in children throughout the lifespan.


The analysis of pyridylamino-dextran sulfate oligomers by high-performance liquid chromatography and a novel detection system for sulfated polysaccharides.
Dextran sulfate sodium (DSS) is a strong negatively charged heparin-like polysaccharide and has anti-immunodeficiency virus, anti-carcinogenesis, or occasionally tumor-promotion effects. The biological metabolism of DSS, however, remains unclear. In a previous study, we reported a novel method for the separation and quantification of DSS, using fluorometric labeling with 2-aminopyridine and a combination of size-exclusion and reverse phase high-performance liquid chromatography. In the present study, we have applied this method for analyses of in vitro chemical or enzymatic depolymerization of pyridylamino-DSS (PA-DSS). PA-DSS was depolymerized by specific enzymes such as alpha-amylase and alpha-glycosidase, but not by dextranase or heparinase. Unknown enzymes derived from cultured intestinal cells also strongly depolymerized PA-DSS as did alkaline substances. On the other hand, we have established a novel detection system using a post-column reaction. This method utilizes the spectrophotometrically metachromatic reaction of toluidine blue solution with DSS. This novel detection system may be specific and may potentially provide useful information in the analyses of sulfated polysaccharides, which are present in environmental and biological materials.


Absolute asymmetric synthesis of enantiopure organozinc reagents, followed by highly enantioselective chlorination.
We report the absolute asymmetric synthesis (AAS) of indenylzinc reagents by using total spontaneous resolution followed by enantiospecific conversion into 1-chloroindene. The chiral complex [Zn(dcp)(ind)(tmeda)] (dcp = 2,6-dichlorophenoxy and tmeda = N,N,N',N'-tetramethylethylenediamine) (3) was prepared from the achiral starting materials indene, potassium, zinc chloride, TMEDA, and 2,6-dichlorophenol. The reagent resolved spontaneously on crystallization, and single crystals of 3 react with N-chlorosuccinimide in the presence of benzoquinone in 2-propanol to give 1-chloroindene in >98 % enantiomeric excess. It was found that (R)-3 gave (R)-1-chloroindene upon reaction, indicating an SE 2'-mechanism. Since bulk samples of 3 gave optically active product upon chlorination, total spontaneous resolution must have occurred. This demonstrates that enantiopure products can be obtained through the absolute asymmetric synthesis of organometallic reagents starting from achiral materials. The general absolute asymmetric synthesis (AAS) method offers easy access to both enantiomers and an almost limitless variation in the design of the product.


Changes in growth hormone (GH), GH receptor, and GH signal transduction in hippocampus of congenital hypothyroid rats.
Recent studies have shown that, like thyroid hormone (TH), growth hormone (GH) plays a critical role in development of the brain. However, it is still unclear whether the functions of the two hormones are locally orchestrated in the brain or whether TH has a permissive effect on GH in the central nervous system as it does in the periphery. To address this question, the present study investigated the changes in local expression of GH and GH receptor (GHR) and the activity of GH signaling molecules in the hippocampus of congenitally hypothyroid (CHT) rats. As demonstrated by morphometric measurements and the Y-maze test, CHT rats had decreased neurons and weaker Nissl staining in the stratum pyramidal/granule in the hippocampus and a reduced acquisition of safe place recognition memory. Analyses of QPCR and Western blot revealed a substantially decreased hippocampal expression of GH and GHR, accompanied by a corresponding decrease in phosphorylation of JAK2 and STAT5 in the CHT rats. These changes were, at least in part, corrected by systemic supplement of T3. The findings provide the first direct evidence suggesting that the functional autocrine and paracrine regulation of GH in the CNS is orchestrated by TH.


Comparison of methods for extraction, storage, and silylation of pentafluorobenzyl derivatives of carbonyl compounds and multi-functional carbonyl compounds.
The employment of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) derivatization along with bis-(trimethylsilyl)trifluoroacetamide (BSTFA) or N, N-( tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) derivatization is a popular method for measurement of oxygenated organics in environmental and biological samples. Most notably, the derivatization method enables the measurement of atmospheric photooxidation products not detected by using other methods. PFBHA derivatization is often conducted in an aqueous solution. Accordingly, experiments were performed to compare the efficiency of hexane, methyl- tert-butyl ether (MTBE), and dichloromethane (CH(2)Cl(2)) for extraction of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) derivatives of carbonyl compounds from water. Further, the stability of these compounds when stored at 4 degrees C in CH(2)Cl(2) was determined, and commonly used methods for silylation of -OH and -COOH groups on the PFBHA derivatives were compared. Overall, CH(2)Cl(2)was the most efficient solvent for extraction of PFBHA derivatives of hydroxycarbonyl compounds, dicarbonyl compounds, and keto-acids from water. Derivatives of carbonyl compounds that do not have secondary functional groups were extracted with approximately equal efficiency by each of the three solvents examined. The PFBHA derivatives of aromatic and saturated aliphatic carbonyl compounds and hydroxycarbonyl compounds were stable in CH(2)Cl(2) at 4 degrees C for > or = 66 days whereas the derivatives of keto-acids and unsaturated aliphatic aldehydes begin to degrade after approximately 38 days. Comparison of four procedures for bis-(trimethylsilyl)trifluoroacetamide (BSTFA) derivatization of -OH and -COOH groups on PFBHA derivatives revealed that primary -OH groups react efficiently in 20-100% BSTFA in CH(2)Cl(2), and do not require a catalyst. Secondary -OH groups also react efficiently in 20-100% BSTFA, but the reaction yield improves slightly when trimethylchlorosilane (TMCS) is added as a catalyst. Reaction of tertiary -OH groups with BSTFA was very inefficient, but improved with addition of 10% TMCS to the BSTFA solution. Finally, -COOH groups seemed to react most efficiently and consistently in 100% BSTFA, without catalyst.


[Radio-frequency ablation of T1a renal cell carcinoma].
We report the efficacy of radio-frequency ablation (RFA) for T1a renal cell carcinoma (RCC). RFA was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in seven patients with Tla RCC, who were at significant operative or anesthetic risk for invasive surgery. At a median follow-up of 17.5 months, 6 (86%) of the seven patients showed no tumor enhancement in follow-up CT scans or magnetic resonance images. Temporary macroscopic hematuria was observed in one case. RFA is an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.


Visual statistical learning based on the perceptual and semantic information of objects.
Five experiments examined what is learned based on the perceptual and semantic information of objects in visual statistical learning (VSL). In the familiarization phase, participants viewed a sequence of line drawings and detected repetitions of various objects. In a subsequent test phase, they watched 2 test sequences (statistically related triplets vs. unrelated foils) and decided whether the first or second sequence was more familiar based on the familiarization phase. In Experiment 1A, the test sequences comprised line drawings; in Experiment 1B, they comprised word stimuli representing each line drawing. The results showed that performance for statistically related triplets was greater than chance. In Experiments 2 and 3 containing the forward ABC and backward CBA triplets in the test, the results showed the importance of temporal order, especially in line drawings. In Experiment 4, in which the forward triplets were pitted against the backward triplets, we showed that temporal order is still important for the expression of VSL with word stimuli. Finally, in Experiment 5, we replicated the results of Experiments 2 and 3 even with the images of visual objects. These results suggest the parallel processes on the visual features and semantic information of objects in VSL.


Hospital-Based Surveillance for Infectious Etiologies Among Patients with Acute Febrile Illness in Georgia, 2008-2011.
Information on the infectious causes of undifferentiated acute febrile illness (AFI) in Georgia is essential for effective treatment and prevention. In May 2008, a hospital-based AFI surveillance was initiated at six hospitals in Georgia. Patients aged ≥ 4 years with fever ≥ 38°C for ≥ 48 hours were eligible for surveillance. Blood culture and serologic testing were conducted for Leptospira spp., Brucella spp., West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus, Coxiella burnetii, tick-borne encephalitis virus (TBEV), hantavirus, Salmonella enterica serovar Typhi (S. Typhi), and Rickettsia typhi. Of 537 subjects enrolled, 70% were outpatients, 54% were males, and the mean age was 37 years. Patients reported having fatigue (89%), rigors (87%), sweating (83%), pain in joints (49%), and sleep disturbances (42%). Thirty-nine (7%) patients were seropositive for R. typhi, 37 (7%) for Brucella spp., 36 (7%) for TBEV, 12 (2%) for Leptospira spp., 10 (2%) for C. burnetii, and three (0.6%) for S. Typhi. None of the febrile patients tested positive for WNV antibodies. Of the patients, 73% were negative for all pathogens. Our results indicate that most of the targeted pathogens are present in Georgia, and highlight the importance of enhancing laboratory capacity for these infectious diseases.


Propane-d6 Heterogeneously Hyperpolarized by Parahydrogen.
Long-lived spin states of hyperpolarized propane-d6 gas were demonstrated following pairwise addition of parahydrogen gas to propene-d6 using heterogeneous parahydrogen-induced polarization (HET-PHIP). Hyperpolarized molecules were synthesized using Rh/TiO2 solid catalyst with 1.6 nm Rh nanoparticles. Hyperpolarized (PH ∼ 1%) propane-d6 was detected at high magnetic field (9.4 T) spectroscopically and by high-resolution 3D gradient-echo MRI (4.7 T) as the gas flowed through the radiofrequency coil with a spatial and temporal resolution of 0.5 × 0.5 × 0.5 mm3 and 17.7 s, respectively. Stopped-flow hyperpolarized propane-d6 gas was also detected at 0.0475 T with an observed nuclear spin polarization of PH ∼ 0.1% and a relatively long lifetime with T1,eff = 6.0 ± 0.3 s. Importantly, it was shown that the hyperpolarized protons of the deuterated product obtained via pairwise parahydrogen addition could be detected directly at low magnetic field. Importantly, the relatively long low-field T1,eff of HP propane-d6 gas is not susceptible to paramagnetic impurities as tested by exposure to ∼0.2 atm oxygen. This long lifetime and nontoxic nature of propane gas could be useful for bioimaging applications including potentially pulmonary low-field MRI. The feasibility of high-resolution low-field 2D gradient-echo MRI was demonstrated with 0.88 × 0.88 mm2 spatial and ∼0.7 s temporal resolution, respectively, at 0.0475 T.


Novel SLA-DR alleles of three Chinese pig strains and the related function in human T cell response.
To elucidate the structures of SLA-DR (swine leukocyte antigen DR) genes of three Chinese pig strains (Gz, Bm and Yn), the SLA-DRA and SLA-DRB cDNA were amplified by RT-PCR and subjected to determine the sequences. The whole structures of SLA-DRA alleles are identical among three strains, consisting of 759 nucleotides including an open reading frame (ORF), and are shared with those reported from NIH minipigs SLA-DRA(c) and SLA-DRA(d). The same length of the ORF-containing SLA-DRB genes of three Chinese pig strains was also identified. They are composed of 801 nucleotides encoding a xenogeneic antigen molecule of 266 amino acid residues. The nucleotide sequences of the SLA-DRB genes, however, are different when compared either among the three strains or with the published data of SLA-DRB sequences, which allowed our novel SLA-DRB alleles receiving their accession numbers AY102479, AY102480 and AY102481 from the GenBank. This study further reveals that the phylogenic homologies of MHC DR or DR-like genes in structures of nucleotides and deduced amino acids between Chinese pigs (SLA) and human (HLA-DRB1*0901) are better than those between pigs and mice (H-2(b)Ebeta). High similarities were also found for DRalpha-DRbeta heterodimers between Chinese pigs and human in terms of amino acids sequences critical for binding with human CD4 coreceptor molecule, which are better than those between SLA-DR and H-2 I-E molecules. A functional test indicated that, by cotransfection with Bm-DRA and Bm-DRB genes, the Bm-DR molecule-expressed L929 cells could stimulate human T cells quite well in a xenogeneic reaction in presence of human APCs.


The global burden of urinary bladder cancer.
Statistics on the incidence of bladder cancer are particularly hard to interpret, because of changing classification, variations in counting of multiple cancers in the same individual and, most importantly, the variable inclusion of non-invasive cancers in different data sets. Mortality statistics are almost certainly more comparable, but as indirect estimators of disease risk, require some cautious interpretation, because of differing survival between populations, and over time. Cancer of the bladder is estimated to be the ninth most common cause of cancer worldwide (357 000 cases in 2002) and the 13th most numerous cause of death from cancer (145 000 deaths). Rates in males are three to four times those in females. Incidence rates are high in many southern and eastern European countries, in parts of Africa and the Middle East, and in North America. The highest estimated mortality is in Egypt, where rates are more than three times greater than the highest rates in Europe and eight times those in the USA. In the USA, the incidence in whites is higher than in blacks. In general, in Western countries, incidence rates have been rising, but the increase has slowed or stopped in many. Mortality rates are, for the most part, decreasing. Trends are more variable in developing countries. To some extent, the geography and time trends are related to prevalence of known risk factors, especially exposure to tobacco (responsible for almost one-third of bladder cancer deaths) and, in some specific areas, schistosomiasis.


N-acetylcysteine alleviates phenylephrine-induced cardiomyocyte dysfunction via engaging PI3K/AKT signaling pathway.
Increased ROS and oxidative stress response lead to cardiomyocyte hypertrophy and apoptosis, which play crucial roles in the pathogenesis of heart failure. The purpose of current research was to explore the role of antioxidant N-acetylcysteine (NAC) on cardiomyocyte dysfunction and the underlying molecular mechanisms. Compared with control group without NAC treatment, NAC dramatically inhibited the cell size of primary cultured neonatal rat cardiomyocytes (NRCMs) tested by immunofluorescence staining and reduced the expression of representative markers associated with hypertrophic, fibrosis and apoptosis subjected to phenylephrine (PE) administration examined by RT-PCR and western blot. Moreover, enhanced ROS expression was attenuated, whereas activities of makers related to oxidative stress response examined by individual assay Kits, including total anti-oxidation capacity (T-AOC), glutathione peroxidase (GSH-Px) and primary antioxidant enzyme SOD were induced by NAC treatment in NRCMs previously treated with phenylephrine. Mechanistically, we noticed that the protein expression levels of phosphorylated PI3K and AKT were increased by NAC stimulation. More importantly, we identified that the negative regulation of NAC in cardiomyocyte dysfunction was contributed by PI3K/AKT signaling pathway through further utilization of PI3K/AKT inhibitor (LY294002) or agonist (SC79). Collected, NAC could attenuate cardiomyocyte dysfunction subjected to phenylephrine, partially by regulating the ROS-induced PI3K/AKT dependent signaling pathway.


GTP binding by Arabidopsis extra-large G protein 2 is not essential for its functions.
The extra-large guanosine-5'-triphosphate (GTP)-binding protein 2, XLG2, is an unconventional Gα subunit of the Arabidopsis (Arabidopsis thaliana) heterotrimeric GTP-binding protein complex with a major role in plant defense. In vitro biochemical analyses and molecular dynamic simulations show that affinity of XLG2 for GTP is two orders of magnitude lower than that of the conventional Gα, AtGPA1. Here we tested the physiological relevance of GTP binding by XLG2. We generated an XLG2(T476N) variant with abolished GTP binding, as confirmed by in vitro GTPγS binding assay. Yeast three-hybrid, bimolecular fluorescence complementation, and split firefly-luciferase complementation assays revealed that the nucleotide-depleted XLG2(T476N) retained wild-type XLG2-like interactions with the Gβγ dimer and defense-related receptor-like kinases. Both wild-type and nucleotide-depleted XLG2(T476N) restored the defense responses against Fusarium oxysporum and Pseudomonas syringae compromised in the xlg2 xlg3 double mutant. Additionally, XLG2(T476N) was fully functional restoring stomatal density, root growth, and sensitivity to NaCl, but failed to complement impaired germination and vernalization-induced flowering. We conclude that XLG2 is able to function in a GTP-independent manner and discuss its possible mechanisms of action.


BRAF Mutation Status Concordance Between Primary Cutaneous Melanomas and Corresponding Metastases: A Review of the Latest Evidence.
The identification of B-Raf proto-oncongene (BRAF) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.