Phenyl-substituted analogues of oxotremorine as muscarinic antagonists.
A series of phenyl-substituted analogues of the muscarinic agent oxotremorine (1) have been prepared. The new compounds (3b-11b and 9c) were assayed for antimuscarinic activity on the isolated guinea pig ileum and in intact mice. They were also evaluated for ability to inhibit the binding of the muscarinic antagonist (-)-[3H]-N-methylscopolamine to homogenates of the rat cerebral cortex. The phenyl-substituted derivatives were devoid of intrinsic muscarinic activity. Instead, they behaved as competitive muscarinic antagonists in these assays with similar or lower affinity for muscarinic receptors than the corresponding methyl-substituted analogues. The succinimide (8b) and the pyrrolidone (3b) derivatives of 1 substituted with a phenyl group at position 1 of the butynyl chain showed the highest antimuscarinic potency with dissociation constants (KD) of 0.10 and 0.20 microM, respectively, in the ileum assay. The phenyl-substituted analogues showed an approximately 10-fold lower in vivo antimuscarinic potency than their corresponding methyl-substituted positional isomers. A correlation was observed between in vitro and in vivo potency within subsets consisting of methyl- and phenyl-substituted derivatives.


One of the duplicated matrix metalloproteinase-9 genes is expressed in regressing tail during anuran metamorphosis.
The drastic morphological changes of the tadpole are induced during the climax of anuran metamorphosis, when the concentration of endogenous thyroid hormone is maximal. The tadpole tail, which is twice as long as the body, shortens rapidly and disappears completely in several days. We isolated a cDNA clone, designated as Xl MMP-9TH, similar to the previously reported Xenopus laevis MMP-9 gene, and showed that their Xenopus tropicalis counterparts are located tandemly about 9 kb apart from each other in the genome. The Xenopus MMP-9TH gene was expressed in the regressing tail and gills and the remodeling intestine and central nervous system, and induced in thyroid hormone-treated tail-derived myoblastic cultured cells, while MMP-9 mRNA was detected in embryos. Three thyroid hormone response elements in the distal promoter and the first intron were involved in the upregulation of the Xl MMP-9TH gene by thyroid hormone in transient expression assays, and their relative positions are conserved between X. laevis and X. tropicalis promoters. These data strongly suggest that the MMP-9 gene was duplicated, and differentiated into two genes, one of which was specialized in a common ancestor of X. laevis and X. tropicalis to be expressed in degenerating and remodeling organs as a response to thyroid hormone during metamorphosis.


Fanconi anemia pathway regulates convergent transcription-induced cell death at trinucleotide repeats in human cells.
Almost 20 incurable neurodegenerative disorders are caused by trinucleotide repeat (TNR) expansion beyond a certain threshold, with disease time of onset and severity positively correlating with repeat length. Typically, long TNRs display a bias toward further expansion and repeats continue to expand not only during germline transmissions from parents to offspring, but also remain highly unstable in somatic tissues of patients. Hence, understanding TNR instability mechanisms sheds light on underlying disease pathology. Recently, we showed that activated ATR is the major signal for convergent-transcription-induced cell death at CAG repeats and is regulated by the mismatch repair (MMR) pathway. Additionally, components of other DNA repair pathways such as transcription-coupled nucleotide excision repair (TC-NER) and R-loop resolution by RNaseH reduce cell death. Because activated ATR signals the Fanconi anemia (FA) pathway of interstrand crosslink DNA repair, we asked whether the FA pathway also modulates convergent-transcription-induced cell death at expanded CAG repeats. We show here that siRNA knockdown of FA components-FANCI, FANCJ, FANCM, FANCA, and FANCD2-decreases cell death, suggesting that FA proteins, like MMR proteins, are activators of cell death during convergent transcription.


[Otoneurological symptoms and their changes after removal of pineal tumors].
The authors analyze otoneurological symptoms in 120 patients with pineal tumors. A marked cochleovestibular syndrome was found characterized by bilateral neurosensory hypoacusis with vocal-tonal dissociation, head noises, vertigo, multiple spontaneous nystagmus including a converging one, impaired optokinetic nystagmus, enhanced vestibulovegetative reactions. 39 cases are reported with pineal tumors removed microsurgically. Otoneurological symptoms were followed up in 32 patients early after surgery (within 20 postoperative days) and in 6 patients 1 to 5 years after radiotherapy. As evident from otoneurological examination, electronystagmography, tonal and speech audiometry, positive postoperative changes in auditory and vestibular functions occurred in most of the patients. The response persisted long in 5 patients.


Nursing management of umbilical cord prolapse.
Advances in the management of umbilical cord prolapse hold promise for reducing perinatal morbidity and mortality. This article reviews traditional nursing management of umbilical cord prolapse and introduces the use of real-time ultrasound and bladder filling as additional methods of nursing management. A case report is provided.


St. John's Wort extract: efficacy for menopausal symptoms of psychological origin.
Herbal remedies such as St. John's Wort preparations can be used successfully to relieve the psychological and vegetative symptoms of menopause. This drug-monitoring study investigated 12 weeks of treatment with St. John's Wort, one tablet three times daily (900 mg Hypericum, Kira), in 111 women from a general medical practice. The patients, who were between 43 and 65 years old, had climacteric symptoms characteristic of the pre- and postmenopausal state. Treatment outcome was evaluated by the Menopause Rating Scale, a self-designed questionnaire for assessing sexuality, and the Clinical Global Impression scale. The incidence and severity of typical psychological, psychosomatic, and vasomotor symptoms were recorded at baseline and after 5, 8, and 12 weeks of treatment. Substantial improvement in psychological and psychosomatic symptoms was observed. Climacteric complaints diminished or disappeared completely in the majority of women (76.4% by patient evaluation and 79.2% by physician evaluation). Of note, sexual well-being also improved after treatment with St. John's Wort extract.


Structure and ionic interactions of organic-inorganic composite polymer electrolytes studied by solid-state NMR and Raman spectroscopy.
Solid-state NMR studies of composite polymer electrolytes are reported. The materials consist of polyethylene oxide and an organic inorganic composite, together with a lithium salt, and are candidates for electrolytes in solid-state lithium ion batteries. Silicon and aluminum MAS and multiple quantum MAS are used to characterize the network character of the organic-inorganic composite, and spin diffusion measurements are used to determine the nanostructure of the polymer/composite blending. Multiple quantum spin counting is used to measure the ion aggregation. The NMR results are supported by Raman spectra, calorimetry, and impedance spectroscopy. From these experiments it is concluded that the composite suppresses polymer crystallization without suppressing its local mobility, and also suppresses the tendency for the ions to aggregate. This polymer composite thus appears very promising for application in lithium ion batteries.


Green fluorescent protein (GFP) as a marker during pollen development.
The transient expression of three mutant forms of green fluorescent protein (GFP) genes, GFP4, GFP5ER, and GFP4S65C, under several constitutive and pollen-specific promoters throughout pollen development in Nicotiana tabacum, Arabidopsis thaliana and Antirrhinum majus is described. Immature pollen of tobacco, Arabidopsis and snapdragon, isolated at different developmental stages, were bombarded with plasmids containing the GFP and cultured in vitro for several days until maturity. The expression of GFP was monitored every day during in vitro maturation, germination and pollination, as well as after in situ pollination. The expression pattern of each GFP construct was compared in parallel experiments to that of beta-glucuronidase (GUS) constructs expressed by the same promoters. The results show that the expression level of all three GFP mutant forms was dependent on the strength of the promoter used. The strongest promoter was the DC3 promoter, and no notable differences in the intensity and brightness of all three versions of GFP were observed. GFP-expressing pollen from tobacco and snapdragon developed in vitro for several days until maturity and germinated in vitro as well as on the surface of stigmata, strongly suggesting that all three GFPs are not toxic for the development of functional pollen. Furthermore, stably transformed tobacco plants expressing GFP under the control of the strong pollen-expressed DC3 and LAT52 promoters were not impaired in reproductive function, confirming that GFP can be used as a non-destructive marker for plant reproductive biology and development.


Dissolution Effect of Alteplase on Arterial Blood Clot Model of Hypertensive Intracerebral Hemorrhage Patients in vitro.
To explore the dissolution effect of alteplase (rt-PA) on arterial blood clots of patients with hypertensive cerebral hemorrhage in vitro and analyze the optimal concentration and action time of rt-PA for intracranial hematomas. The arterial blood of 35 patients with confirmed hypertensive cerebral hemorrhage were collected, centrifuged, and the serum was aspirated to prepare the blood clot model. The 0.125, 0.25, 0.5, 1, 2, and 3 mg t-PA, 20,000 U, and 40,000 U urokinase (u-PA) were taken for the corresponding blood clot for dissolution test. The blood clot volume and dissolution volume was measured at 0, 30, 60, 90, 120, and 150 min. Without intervention, the blood clot volume of men was higher than that of women at 0, 30, 60, and 90 min (P < 0.05). Without intervention, hematocrit (HCT) was correlated with blood clot volume and the correlation decreased with time. The 30, 60, and 90 min dissolution curves of each group showed an upward trend (P < 0.05), and the dissolution curves tended to be flat at 120 min and 150 min. The dissolution volume of.125 mg/3 ml, 0.25 mg/3 ml, 0.5 mg/3 ml rt-PA, 20,000 U, 40,000 U u-PA was higher than that of 1, 2, 3 mg/ml rt-PA (P < 0.05). The dissolution volume of.125 mg/3 ml, 0.25 mg/3 ml, 0.5 mg/3 ml rt-PA was not significantly different from 20,000 and 40,000 U u-PA (P > 0.05). Gender differences did not affect the effects of the above drugs. In vitro, low-concentration rt-PA has a better dissolution effect, and it shows a time-dependent effect, reaching the highest effect in 90 min.


[Effects of ibotenic acid lesions to rat's hippocampus CA1 on place and cue learning in Morris water maze].
It is known that the multiple injections of ibotenic acid to the hippocampal CA1 (Cornu Ammonis 1) field of a rat cause cell loss and spatial learning impairment in the place task of Morris water maze. However, no study seems to have been conducted concerning the cue task of the maze. This study examined (1) whether cell loss in the CA1 field produced learning deficits in both the place and cue tasks; (2) whether training could remedy the deficit in spatial learning; and (3) whether the order of place training and cue training could change the performance outcome. Thirty-seven rats of Wistar strain were divided into Place-Cue (PC) group that received place training first and then cue training, and Cue-Place (CP) group that received training in the reverse order. Half rats in each group were damaged in the CA1 field by ibotenic acid injections. Results indicated that damage to CA1 pyramidal cells led to performance deficits only in the place task throughout training, regardless of the sequence of training. The results also indicated that training in the prior task affected learning in the succeeding task, only at the beginning of training, and the effect is transient.


Hydrazinocurcumin, a novel synthetic curcumin derivative, is a potent inhibitor of endothelial cell proliferation.
Curcumin and some of its derivatives were known as in vivo inhibitors of angiogenesis. In present study, a novel curcumin derivative, named hydrazinocurcumin (HC) was synthesized and examined for its biological activities. HC potently inhibited the proliferation of bovine aortic endothelial cells (BAECs) at a nanomolar concentration (IC(50)=520 nM) without cytotoxicity. In vivo and in vitro angiogenesis experiments showed HC as a new candidate for anti-angiogenic agent.


Electroconvulsive therapy and the chronic use of pseudocholinesterase-inhibitor (echothiophate iodide) eye drops for glaucoma. A case report.
A case is presented in which a patient who required treatment with electroconvulsive therapy had a history of being treated with pseudocholinesterase-inhibitor eye drops (echothiophate iodide) for glaucoma. As treatment with this antiglaucoma agent contraindicated the use of succinylcholine for a minimum of 10-14 days, the short-acting nondepolarizing agent atracurium was employed instead. The anesthetic management of this patient is described as a guide for clinicians facing similar clinical situations.


Characterization of gibberellin biosynthetic gene cluster from Fusarium proliferatum.
Gibberellins (GAs) are a group of phytohormones that control many developmental processes in higher plants. We report the cloning and expression pattern of gibberellin biosynthesis genes from a new GA-producing fungus, Fusarium proliferatum (strain KGL0401). These genes sequences are deposited in the National Center for Biotechnology Information (NCBI) under accession numbers EF119831, EF119832, DQ313173, DQ313174, DQ313175, DQ313176, and DQ313177. The expression level of these genes was maximal at a 0.5 M : 0.17 M carbon : nitrogen ratio, and minimal at a 0.25 M : 0.47 M carbon : nitrogen ratio.


Practice and barriers toward breast self-examination among young Malaysian women.
The etiology of breast cancer is still unknown and adequate primary prevention strategies or interventions are still not possible. Therefore, early detection remains the first priority and regular practice of breast self-examination (BSE) influences treatment, quality of life, survival, and prognosis of breast cancer patients. The objective of this study was to determine the practices and barriers towards breast self-examination among young Malaysian women. Cross-sectional study was conducted among 251 female students at the Management and Science University, Shah Alam, Selangor, Malaysia. Questionnaires were distributed at gathering places such as the university cafeteria, the university plaza, the Islamic center, and at the library. In addition, questionnaires were distributed in the lecture halls. The proposal of this study was approved by the Ethics and Research Committee of Management and Science University. Data was analysis using SPSS version 13, t-test was used to analyze the associated factors toward the practice of BSE. A total number of 251 students participated in this study. The majority of them were older than 20 years old,of Malay racial origin, single and from urban areas (66.5%; 63.7%; 96%; 70.9% respectively). Regarding their lifestyle practices, the majority of participants do exercise, are non-smokers and do not drink alcohol (71.3%; 98.4%; 94.4% respectively). More than half of the study participants mentioned that they have practiced BSE (55.4%). Regarding the sources of information about BSE, the majority mentioned that radio and TV were their main sources of information (38.2%). Age, exercise and family history of cancer significantly influenced the practice of BSE (p = 0.045; p=0.002; p=0.017 respectively). Regarding the barriers to BSE, the majority who never practiced BSE mentioned that lack of knowledge, not having any symptoms, and being afraid of being diagnosed with breast cancer were the main barriers to practicing BSE (20.3%; 14.3%; 4.4% respectively). More than half of the participants practiced BSE. Age, exercise and family history of cancer significantly influenced the practice of the BSE. Lack of knowledge, not having any symptoms and being afraid of being diagnosed with breast cancer were the main barriers to practicing BSE. There is an urgent need to develop a continuous awareness campaign among university students on the importance of performing BSE.


Comprehensive analysis of organophosphorus flame retardant-induced mitochondrial abnormalities: Potential role in lipid accumulation.
Organophosphorus flame retardants (OPFRs), a group of new emerging endocrine disruption chemicals, have been reported to cause metabolic disturbance. Currently, mitochondrial abnormality is a new paradigm for evaluating chemical-mediated metabolic disruption. However, a comprehensive correlation between these two aspects of OPFR remains elusive. In the work reported here, 3 markers for morphological abnormality, and 7 markers of mitochondrial dysfunction were detected after treatment with two aryl-OPFRs (TCP and TPhP) and three chlorinated-OPFRs (TDCPP, TCPP, and TCEP) on hepatocyte. The two aryl-OPFRs and TDCPP can cause intracellular lipid accumulation at non-cytotoxic concentrations (<10 μM), while the other two chlorinated-OPFRs only caused lipid deposition at 10 μM. Furthermore, at the tested concentrations, all of them reduced mitochondrial (mito)-network numbers, enlarged mito-area/cells, and skewed mitoATP/glycoATP. Excluding TCEP, the other four chemicals induced mito-ROS and depleted mitochondrial membrane potential (MMP). Notably, only TCP, TPhP and TDCPP impeded mitoATP generation rate and mito-respiratory rate. Based on potency estimates, the capacity for lipid accumulation was significantly correlated with mito-network numbers (R2 = 0.6481, p < 0.01), mitoATP/glycoATP (R2 = 0.5197, p < 0.01), mitoROS (R2 = 0.7197, p < 0.01), and MMP (R2 = 0.7715, p < 0.01). Remarkably, the mito-respiratory rate (R2 = 0.8753, p < 0.01) exhibited the highest correlation. Thus, the more potent lipid inducers TPhP, TCP and TDCPP could be identified. The results of this study demonstrate that aryl-OPFRs are more potent in metabolic disruption than other esters examined. Metabolic disruption should be examined further for chemicals that have the capacity to counteract the aforementioned functions of mitochondrial.


Association between polymorphisms of the BRCA2 gene and clinical parameters in breast cancer.
A C/T transition - rs4987117 (the Thr1915Met polymorphism) and an A/G transition - rs11571653 (the Met784Val polymorphism) in the BRCA2 gene were linked to breast cancer risk in Polish and Japanese populations, respectively. To study the association between polymorphisms of the BRCA2 gene and clinical parameters in breast cancer. Both polymorphisms were evaluated by RFLP - PCR in blood samples obtained from 117 women with sporadic breast cancer. Patients were stratified by genotype, Bloom - Richardson grade, TNM stage, estrogene and progesterone receptors (PR) status and the linkages of each genotype with each stratum were calculated by logistic regression. Variant genotypes and alleles of both polymorphisms of the BRCA2 gene were inversely related to hormone receptor status for a group of patients with at least one positive receptor status as compared to a group with both receptors negative status (OR 0.27, 95% CI 0.07 - 0.95, p = 0.043 and OR 0.39, 95% CI 0.19 - 0.82, p = 0.013 for Met1915Met homozygote and 1915Met allele, respectively and OR 0.02, 95% CI 0.00 - 0.13, p = 0.0005 and OR 0.43, 95% CI 0.21 - 0.88, p = 0.021, for Val784Val homozygote and the 784Val allele. No association was found between both polymorphisms and Bloom - Richardson grading and TNM staging. Our results suggest that variant genotypes of the Thr1915Met and Met784Val polymorphisms of the BRCA2 gene may be indicative factors in therapy of ductal breast cancer.


Bone marrow processing for transplantation using the COBE spectra cell separator.
BM processing, volume reduction, and granulocyte and erythrocyte depletion are important considerations for minimizing the side effects of graft administration and bypassing ABO incompatibility in allogeneic BMT. We used the COBE Spectra cell separator for BM processing in 33 patients suffering from hematologic malignancy and solid tumor (median age 39 years). We processed 42 BM harvests with the aim of maximizing recovery of mononuclear cells (MNC). BM was collected from the posterior iliac crest under general anesthesia. The mean volume of collected BM before filtration was 1,303 ml, and the mean number of collected total nucleated cells (TNC) was 2.61 x 10(8)/kg. The BM processing resulted in a mean recovery of 35.8% (10.1%-78.3%) TNC, 22.3% (1.1%-75.7%) of granulocytes, 78.8% (34.3%-135.2%) of MNC, 77.2% (8.3%-260.0%) of CD34+ cells, and 153.3% (32.9%-464.0%) of colony-forming units (CFU-GM) in the final product. A mean of 98.2% (94.5%-99.5%) of RBC was removed, with a mean of 13.3 ml (5.1-26.2 ml) of RBC in the final product. BM processing using the COBE Spectra cell separator proved to be fast, safe, and effective. However, the reasons for the very wide range of recovery of harvested CD34+ cells and CFU-GM need to be further investigated.


[TSH determination in central hypothyroidism].
Central hypothyroidism is one of the limitations of the use of sensitive TSH assays as first line screen in evaluating thyroid function. Studies on this subject are however scarce. The aim of the present study is to evaluate the usefulness of TSH assay before and after TRH on a large series of patients with central hypothyroidism. Fifty two patients presenting with post-partum hypopituitarism (Sheehan's Syndrome), 32 hypothyroids and 20 euthyroids were studied, as well as 21 normal females. There was no difference in TSH basal levels (TSH0) between the hypothyroid (1.43 +/- 0.98 mU/l), the euthyroid patients (1.45 +/- 0.83 mU/l) and the controls (1.32 +/- 0.58 mU/l). Delta TSH (TSH 30 mn after TRH-TSH0) was higher (p < 0.001) in the control group (8.48 +/- 3.76 mU/l) than in the euthyroid group (2.63 +/- 2.22 mU/l) that had a better (p < 0.001) response than the hypothyroid group (0.93 +/- 1.11 mU/l). Ten euthyroid patients had impaired response to TRH, while 6 hypothyroids had a normal test. This test has no advantage over basal TSH in central hypothyroidism diagnosis. TRH test gives many misleading results and have an elevated cost/benefit ratio as compared with the characteristic combination of low thyroxinemia and non elevated TSH0.


The underrecognition and undertreatment of depression: what is the breadth and depth of the problem?
Currently, 1 in 6 of the population will, at some point during their lives, suffer from major depression. By the year 2020, it has been estimated that major depression will be the second most important cause of disability worldwide. Major depression is associated not only with significant morbidity, but with comorbid chronic illnesses and lost productivity because of excess mortality and morbidity. The most important reason for the recognition and adequate treatment of depression is that symptoms can be effectively controlled. Despite this, patients are frequently neither recognized nor treated adequately. Underdiagnosis and undertreatment of major depression can be associated with factors relating to patients, their physicians, and the health care systems that provide their care. The treatment of depressed patients with appropriate agents, at appropriate doses, for appropriate periods of time, and incorporating appropriate nonpharmacologic strategies, is cost-effective. Since much of the management of depression occurs in primary care, approaches aimed at improving the overall management of the condition have a major role to play in lessening the burden of the disease.


Pituitary growth hormone from human cadavers: neurologic disease in ten recipients.
Creutzfeldt-Jakob disease (CJD) has been reported in three US patients previously treated with human growth hormone derived from large pools of human cadaver pituitary glands (pit-hGH). Neurologic disorders other than CJD occurred in 10 growth hormone-deficient patients treated with pit-hGH. These 10 cases could have been chance events or true syndromes; some cases may have been caused by transmissible agents contained in the pooled growth hormone product.


Profound molecular changes following hippocampal slice preparation: loss of AMPA receptor subunits and uncoupled mRNA/protein expression.
The acute hippocampal slice preparation is a convenient, in vitro model widely used to study the biological basis of synaptic plasticity. Although slices may preserve their electrophysiological properties for several hours, profound molecular changes in response to the injury caused by the slicing procedure are likely to occur. To determine the magnitude and duration of these changes we examined the post-slicing expression kinetics of three classes of genes known to be implicated in long-term synaptic plasticity: glutamate AMPA receptors (GluR), transcription factors and neurotrophins. Slicing resulted in a striking loss of GluR1 and GluR3, but not of GluR2 proteins suggesting that rapid changes in the composition of major neurotransmitter receptors may occur. Slicing caused a significant induction of the transcription factors c-fos, zif268, CCAAT enhancer binding protein (C/EBP ) beta and delta mRNAs and of the neurotrophin brain-derived neurothophic factor (BDNF ) mRNA. In contrast, there was no augmentation, and sometimes a decline, in the levels of the corresponding proteins. These data reveal that significant discrepancies exist between the slice preparation and the intact hippocampus in terms of the metabolism of molecular components known to be involved in synaptic plasticity.


Long-Term Transcriptional Consequences of Drug Exposure as Cues to Understand Vulnerability to Relapse: Advances and Perspectives.
Quitting drug abuse represents a true challenge for addicted individuals because of the highly persistent vulnerability to relapse. Identifying long-lasting, drug-induced alterations in the brain-including at the transcriptome level-that underlie such vulnerability appears invaluable to improve relapse prevention. Despite substantial technological developments and research effort, however, the picture of drug-induced adaptations provided by high-throughput transcriptomics remains frustratingly partial, notably because of methodological issues. Major advances were made, however, regarding the time course and specificity of long-term transcriptional consequences of drug exposure as well as the recruitment of small, noncoding mRNAs (or miRNAs [microRNAs]) that were previously undetectable. Most importantly, high-throughput studies have benefited from systems biology approaches and shifted their interest toward regulations within functional gene networks rather than individual changes. Such network-based gene discovery approaches have proven informative to delineate the physiological processes, cellular signaling pathways, and neuronal populations altered by drug exposure. Provided the high-throughput effort will be pursued, together with the development of adapted bioinformatics tools, addiction transcriptomics should progressively integrate data across multiple scales (from epigenome to protein), allowing a better understanding of the genetics of drug abuse and opening novel therapeutic trails.


Rib cartilage characterization in patients affected by pectus excavatum.
Pectus excavatum (PE) is the most frequent anterior chest deformity which may be frequently associated with connective tissue disorders. We performed microscopic analyses to better understand cartilage behavior and obtain clues on its pathogenesis. In 37 PE patients, none with Marfan syndrome, we analyzed costal cartilage by light microscopy, immunohistochemistry and transmission electron microscopy. Control tissue specimens were harvested from four patients without any connective tissue disease. In both control and PE patients, chondrocytes were on the average <15 µm in diameter and occupied <10% of tissue volume; in most cases the extracellular matrix was stained by alcian blue, instead of safranin; no difference between PE and control samples was significant. All samples showed an uneven collagen type II immunolabeling both within the cells and pericellular matrix, and occasionally of the territorial matrix. In all cases numerous cells underwent apoptosis accompanied by matrix condensation as shown by electron microscopy. Our results suggest that matrix composition and the cell number and size of costal cartilage are dependent on the subject and not on the disease; the microscopic organization of cartilage is correlated with the stabilization of the defective shape rather than with the onset of the deformity.


New prognostic biomarker CMTM3 in low grade glioma and its immune infiltration.
The CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3) is differentially expressed in a variety of tumors and closely related to tumor occurrence and progression. The expression of CMTM3 was significantly elevated in glioma compared with normal brain tissue, to explore the potential function of CMTM3 in the prognosis and immune infiltration of glioma has certain clinical significance. The tumor data in this study were derived from the sequencing data of various tumors in The Cancer Genome Atlas (TCGA) database. Low-grade glioma (LGG) data in the TCGA database include sequencing and clinical data. Clinical data mainly include survival time, survival outcome, age, WHO classification and other information. Sequencing data for normal tissues were obtained from the Genotype Tissue Expression (GTEx) database. Statistical analyses were mainly performed using bioinformatics tools and the corresponding R software (version 3.6.3). The Mann-Whitney U test (Wilcoxon rank sum test) was used to compare the expression differences between the tumor group and the normal group. Survival analysis was conducted using log-rank test to compare whether the overall survival (OS) time was statistically different between the CMTM3 high and low expression groups. The Tumor Immunity Estimation Resource (TIMER) database was used for immune infiltration analysis. The results showed that the expression of CMTM3 in World Health Organization (WHO) II and WHO III gliomas was significantly higher than that of normal tissues (P<0.05). Glioma with high CMTM3 expression showed a lower overall survival (OS) (P<0.05). Gene enrichment analysis showed that CMTM3 was significantly enriched in 4 pathways (FDR <0.25, P<0.05). A high correlation was detected between CMTM3 and a variety of immune cells. CMTM3 is highly correlated with macrophages (r=0.536, P=1.31e-36), dendritic cells (r=0.546, P=2.85e-38), CD4+ T cells (r=0.517, P=6.17e-34). The CMTM3 gene can be used as a potential prognostic marker for WHO grade II and WHO grade III glioma, is related to the immune infiltration in glioma microenvironment, and may became a new immunotherapy target.


Dysphagia in the setting of left ventricular assist device hemolysis.
A 69-year-old man with advanced heart failure treated with a continuous-flow left ventricular assist device presented for evaluation of dark urine and severe dysphagia. Because of evidence of ongoing intravascular hemolysis with device dysfunction, there was a clinical suspicion for pump thrombosis. He had progressive end-organ dysfunction and was therefore treated with tissue plasminogen activator with prompt resolution in hemolysis and dysphagia. Although symptoms of smooth muscle dystonia could represent worsening heart failure in the setting of device failure, the observation may also be related to intravascular hemolysis as described in the prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria.


Reasons for Suicide Attempts in South India during the COVID-19 Pandemic.
Objective: By increasing the risk of isolation, fear, stigma, abuse, and economic fallout, COVID-19 has led to an increase in the risk of psychiatric disorders, chronic trauma, and stress. These factors eventually increase suicidality and suicidal behavior. This study intends to evaluate the reasons for suicide attempts due to the COVID-19 pandemic in the south Indian population.Design: Cross-sectional studySetting: The study was conducted in R. L. Jalappa Hospital and Research Centre, Kolar.Participants: This study was conducted on 91 patients admitted to the general medicine department for a suicide attempt because of the COVID 19 pandemic.Methods: A single examiner conducted a structured interview with a pretested questionnaire with each participant. Participants were asked to indicate the primary reason or motivation for their suicide attempt. Patients answered a set of questions regarding personal and family concerns (marginalization, fear and uncertainty, domestic abuse, loneliness, grief over loss of loved one) and work-related concerns (economic fallout, high-risk environment, shortage of personnel and personal protective equipment [PPE]). We employed mean and standard deviation to descriptively analyze quantitative variables. Categorical variables were expressed in terms of frequency and proportion. For non-normally-distributed quantitative parameters, medians and interquartile range (IQR) were compared across study groups using the Kruskal-Wallis test (> 2 groups). Data was analyzed using coGuide software, V.1.03.Results: The mean age of participants was 29.47±11.06 years, the majority (43.63%) of which were aged between 21 to 40 years of age. The majority (72.53%) of participants reported personal and family concerns as reasons/motivation for suicide, whereas only 17.58% reported work-related concerns. There was a statistically significant difference across reason or motivation for suicide with age (in years) and gender (P value < 0.001).Conclusion: The study concluded that more than half of the patients indicated personal and family concerns as the major reason for suicide attempts during the pandemic. It is vital to emphasize the mental health well-being of the population and take proactive steps to minimize its detrimental effects during the COVID-19 pandemic.


Band 3 missense mutations and stomatocytosis: insight into the molecular mechanism responsible for monovalent cation leak.
Missense mutations in the erythroid band 3 protein (Anion Exchanger 1) have been associated with hereditary stomatocytosis. Features of cation leaky red cells combined with functional expression of the mutated protein led to the conclusion that the AE1 point mutations were responsible for Na(+) and K(+) leak through a conductive mechanism. A molecular mechanism explaining mutated AE1-linked stomatocytosis involves changes in AE1 transport properties that become leaky to Na(+) and K(+). However, another explanation suggests that point-mutated AE1 could regulate a cation leak through other transporters. This short paper intends to discuss these two alternatives.


Physical activity assessment in children and adolescents.
Chronic disease risk factors, including a sedentary lifestyle, may be present even in young children, suggesting that early prevention programmes may be critical to reducing the rates of chronic disease. Accurate assessment of physical activity in children is necessary to identify current levels of activity and to assess the effectiveness of intervention programmes designed to increase physical activity. This article summarises the strengths and limitations of the methods used to evaluate physical activity in children and adolescents. MEDLINE searches and journal article citations were used to locate 59 articles that validated physical activity measurement methods in children and adolescents. Only those methods that were validated against a more stringent measure were included in the review. Based on the definition of physical activity as any bodily movement resulting in energy expenditure (EE), direct observation of the individual's movement should be used as the gold standard for physical activity research. The doubly labelled water technique and indirect calorimetry can also be considered criterion measures for physical activity research, because they measure EE, a physiologic consequence closely associated with physical activity. Devices such as heart rate monitors, pedometers and accelerometers have become increasingly popular as measurement tools for physical activity. These devices reduce the subjectivity inherent in survey methods and can be used with large groups of individuals. Heart rate monitoring is sufficiently valid to use in creating broad physical activity categories (e.g. highly active, somewhat active, sedentary) but lacks the specificity needed to estimate physical activity in individuals. Laboratory and field validations of pedometers and accelerometers yield relatively high correlations using oxygen consumption (r = 0.62 to 0.93) or direct observation (r = 0.80 to 0.97) as criterion measures, although, they may not be able to capture all physical activity. Physical activity has traditionally been measured with surveys and recall instruments. These techniques must be used cautiously in a paediatric population that has difficulty recalling such information. Still, some studies have reported 73.4% to 86.3% agreement between these instruments and direct observation. Future investigations of physical activity instruments should validate the novel instrument against a higher standard. Additional studies are needed to investigate the possibility of improving the accuracy of measurement by combining 2 or more techniques. The accurate measurement of physical activity is critical for determining current levels of physical activity, monitoring compliance with physical activity guidelines, understanding the dose-response relationship between physical activity and health and determining the effectiveness of intervention programmes designed to improve physical activity.


Photo-conversion of self-assembled structures into continuous covalent structures via [2 + 2]-cycloaddition reactions.
In this study, the conversion of self-assembled structures into continuous polymeric structures by linking the self-assembled molecules using the [2 + 2]-cycloaddition reaction was investigated. Synthesized bio-inspired thymine-based bolaamphiphilic molecules were designed to force the interactions between two molecules to engage two thymines in their self-assembled structure to undergo a cycloaddition reaction. Thymine-based bolaamphiphilic molecules were designed and synthesized using different phenylene spacers based on aromatic substituents (ortho-) (meta-) (para-). The formed self-assembled structures from these molecules were characterized and compared using molecular mechanical simulations. Simulations were performed to discuss the relationship between the inter- and intramolecular cycloaddition sensitivity to different substituents. This study provides a strategy for creating higher molecular weight linear polymers by controlling the photocyclization sites within the self-assembly by spacers between thymines. An intermolecular [2 + 2] cycloaddition reaction of thymine-based bolaamphiphilic molecules proceeded within the self-assembled nano-ribbon-like structure to form the continuous covalent structure.


Ewing sarcoma of the acetabulum in children: a "growth plate-based" surgical strategy.
Surgical strategy for Ewing sarcoma (ES) of the pelvis relies on Enneking classification. In adults, in case the acetabulum is involved, excision of the entire acetabulum is needed and often leads to loss of function. In children, the surgeon may adopt a strategy, such as in metaphyseal tumors of long bones where an unaffected growth plate allows a transepiphyseal resection, therefore sparing the joint. We present a "triradiate cartilage strategy" for the excision of ES of the pubic component of the acetabulum, which allows a wide resection while preserving most of the socket. The approach is ilioinguinal. Osteotomies of the iliopubic and ischio pubicrami are performed, followed by hip arthrotomy and anterior dislocation. Transacetabular resection is achieved using osteotomes, under image intensifier guidance, with no further reconstruction. Cases are presented for 2 boys aged 6.5 and 9.5 years, treated with chemotherapy and transacetabular resection. Resections were all rated R0. Patient #1 remained asymptomatic, including during sport activities, and had normal hip range of motion at 12-year follow-up. Radiograph demonstrated mild protrusio acetabuli. Patient #2 had no complain at 3-year follow-up with normal hip range of motion, although he presented with an equinus gait. Radiographs demonstrated a well-covered femoral head without medial shift. A "growth plate-based" surgical strategy can be adapted to malignant pelvic tumors in skeletally immature children. This technique leaves intact the ilio ischiatic component of the triradiate cartilage, which, according to Ponseti, contributes the most to the growth of the acetabulum. Joint sparing improves the functional result and decreases the risk of complication. IV.


The comparative molecular surface analysis (COMSA)--a nongrid 3D QSAR method by a coupled neural network and PLS system: predicting pK(a) values of benzoic and alkanoic acids.
A self-organizing neural network was used to design a novel method capable of the quantitative prediction of molecular properties. The method is based on the comparison of molecular surfaces performed by the coupled neural network and PLS system. Unlike CoMFA and related methods it does not compare the properties describing a discrete set of points but the average property values calculated for a certain area of the molecular surface. It has been found that the results of the PLS analysis of the series of the comparative matrices of the molecular electrostatic potential (MEP) are quite stable. Also the results only slightly depend on such parameters as the number of points sampled at the molecular surface (D) or a winning distance (MD) of the self-organizing neurons. The influence of these parameters for modeling the effects limited by steric and electronic effects was determined and the pK(a) values of the ortho-, meta-, and para- (o-, m-, p-) analogues of benzoic acid and selected alkanoic acids were predicted. We generally found that for the series analyzed CoMSA gave better models than CoMFA.


Kinesiology taping and the world wide web: a quality and content analysis of internet-based information.
Due to limited regulation of websites, the quality and content of online health-related information has been questioned as prior studies have shown that websites often misrepresent orthopaedic conditions and treatments. Kinesio tape has gained popularity among athletes and the general public despite limited evidence supporting its efficacy. The primary objective of this study was to assess the quality and content of Internet-based information on Kinesio taping. An Internet search using the terms "Kinesio tape" and "kinesiology tape" was performed using the Google search engine. Websites returned within the first two pages of results, as well as hyperlinks embedded within these sites, were included in the study. These sites were subsequently classified by type. The quality of the website was determined by the Health On the Net (HON) score, an objective metric based upon recommendations from the United Nations for the ethical representation of health information. A content analysis was performed by noting specific misleading versus balanced features in each website. A total of 31 unique websites were identified. The majority of the websites (71%) were commercial. Out of a total possible 16 points, the mean HON score among the websites was 8.9 points (SD 2.2 points). The number of misleading features was significantly higher than the balanced features (p < 0.001). Fifty-eight percent of sites used anecdotal testimonials to promote the product. Only small percentages of websites discussed complications, alternatives, or provided accurate medical outcomes. Overall, commercial sites had a greater number of misleading features compared to non-commercial sites (p = 0.01). Websites discussing Kinesio tape are predominantly of poor quality and present misleading, imbalanced information. It is of ever-increasing importance that healthcare providers work to ensure that reliable, balanced, and accurate information be available to Internet users. IV.


Classical to quantum optical network link for orbital angular momentum-carrying light.
Using orbital angular momentum (OAM) conservation in second-order nonlinear interaction processes, we create a classical to quantum optical network link in the OAM degrees of freedom of light via sum frequency generation, followed by spontaneous parametric down-conversion. Coherent OAM-carrying beams at 1550 nm are up-converted to 525.5-nm OAM-carrying beams in the first crystal, and are used to pump a second crystal to generate non-degenerate OAM entangled photon pairs at 795 nm and 1550 nm. By switching the OAM carried by the classical part, OAM correlation in the quantum part is shifted. High-level OAM entanglements in two-dimensional subspaces are verified.


Award for Distinguished Scientific Applications of Psychology: James H. Sidanius.
The Award for Distinguished Scientific Applications of Psychology is presented to a person who, in the opinion of the Committee on Scientific Awards, has made distinguished theoretical or empirical advances leading to the understanding or amelioration of important practical problems. The 2021 recipients of the APA Scientific Contribution Awards were recognized by the 2020 Board of Scientific Affairs and selected by the 2020 Committee on Scientific Awards. For profound contributions to social, personality, and political psychology. Crossing levels of analysis from social science to evolutionary biology, James H. Sidanius's work is exemplary on theoretical,methodological, and empirical grounds and is widely regarded for its societal significance. He used sophisticated statistical techniques to analyze the cognitive-motivational basis of political ideology and the role of racial resentment in public opinion. He was an early advocate and practitioner of collecting data from different societies and cultures. The development of social dominance theory represents a milestone in the scientific understanding of intergroup dynamics, social hierarchy, and the psychology of oppression. His work was often provocative and controversial, and he played a key role in important debates concerning racism, sexism, and world politics. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Intraventricular infusion of apolipoprotein E ameliorates acute neuronal damage after global cerebral ischemia in mice.
The ability of intraventricular infusion of apolipoprotein E (apoE) to reduce neuronal damage after global cerebral ischemia was investigated in apoE-deficient and wild-type mice. ApoE (5 microg/mL lipid-conjugated derived from human plasma; 1 microL/h, continuous infusion) significantly reduced neuronal damage in the caudate nucleus and CA2 pyramidal cell layer by approximately 50% in apoE-deficient mice after global ischemia compared to vehicle infusion. In wild-type mice infused with apoE, there was a trend for ischemic neuronal damage to be reduced. ApoE-infused mice had a marked reduction in 4-hydroxynonenal immunoreactivity, as a marker of lipid peroxidation. The results show that the presence of apoE at or after the time of injury can be neuroprotective, possibly via an anti-oxidant mechanism.


Human platelet acetylcholinesterase inhibition by cyclophosphamide: a combined experimental and computational approach.
Acetylcholinesterase (AChE)-inhibition is an area of priority research as various roles have been attributed to AChE in neurodegenerative disorders and cancer as well. In the present study, a comparative multiple 4 dimensional (4D)-approach was applied to analyze human platelet AChE-inhibition by cyclophosphamide (CP). AChE activity was assessed by measuring the hydrolysis of acetylthiocholine iodide (ASChI). The different perspective of analysis was based on two classical (Lineweaver-Burk as well as Dixon) plots, built-in equations of GOSA and a recently introduced graphical approach. Thus, various kinetic constants such as KI, Ks, Km, ksl, Vmao, Ki, ksli, Slmax, �Ks, K1/2, kcat and ksp were estimated. Previous findings of AChE (from different sources) inhibition by CP were also compared. This study extends the elucidation of the kinetic approach of analysis and quantifying enzyme-substrate and enzyme-inhibitor interactions, which is crucial to bringing any drug from bench to bedside. The acyl pocket of human AChE was found to interact with CP through the amino acid residues Y70, Y121, W233, F288, F290, Y334, F408 and Y442, while the anionic sub-site of catalytic site (CAS) interacted with the ligand through residues W84, N85, G116, G117, Y121, S122, G123, L127, Y130, E198, Y334, H443 and G444. CP displayed variable docking poses with the peripheral anionic site (PAS) of human AChE. The findings of kinetic analysis were reinforced by the results of docking experiments. Both the applied approaches strongly indicate partial mixed type of inhibition pattern for the study enzyme (AChE) and its inhibitor (CP).


Injectable iodine-125 labeled tissue marker for radioactive localization of non-palpable breast lesions.
We have developed a 125I-radiolabeled injectable fiducial tissue marker with the potential to replace current methods used for surgical guidance of non-palpable breast tumors. Methods in routine clinical use today such as radioactive seed localization, radio-guided occult lesion localization and wire-guided localization suffers from limitations that this injectable fiducial tissue marker offers solutions to. The developed 125I-radiolabeled injectable fiducial tissue marker is based on highly viscous sucrose acetate isobutyrate. The marker was readily inserted in NMRI mice and proved to be spatially well-defined and stable over a seven day period with excellent CT contrast (>1500 HU), enabling fluoroscopic visualization of the marker during placement. The radioactivity remains strongly associated with the marker during the implantation period, which limits exposure to healthy tissue. Biodistribution studies show that there is negligible radioactivity in all non-tumor tissues sampled, with the exception of the thyroid gland, where limited accumulation was observed (0.06% of injected dose after 7 days). Based on the excellent performance of the marker and the fact that it can be delivered through thin hypodermic needles (≥27G), the marker holds great promise for clinical application, since patient discomfort is reduced significantly compared to current methods. A new type of tissue marker for local administration to non-palpable breast tumors has been developed. The surgical guidance marker is based on derivatives of the biomaterial sucrose acetate isobutyrate and unlike currently used markers it is injectable in the tissue using thin needles, reducing the discomfort to the patients significantly. The marker confers CT contrast and has radioactive properties, meaning it also could find use in brachytherapy. The design of the iodine-125 labeled fiducial tissue marker enables control of dosimetry as well as a choice of iodine isotope used. The marker is anticipated to be clinical applicable due to its contrast performance in mice and its potential for enhanced flexibility in surgical procedures, compared to current methods.


Translational Science for Energy and Beyond.
A clear challenge for the coming decades is decreasing the carbon intensity of the global energy supply while simultaneously accommodating a rapid worldwide increase in power demand. Meeting this challenge of providing abundant, clean energy undoubtedly requires synergistic efforts between basic and applied researchers in the chemical sciences to develop and deploy new technologies. Among the available options, solar energy is one of the promising targets because of the high abundance of solar photons over much of the globe. Similarly, decarbonization of the global energy supply will require clean sources of hydrogen to use as reducing equivalents for fuel and chemical feedstocks. In this report, we discuss the importance of translational research-defined as work that explicitly targets basic discovery as well as technology development-in the context of photovoltaics and solar fuels. We focus on three representative research programs encompassing translational research in government, industry, and academia. We then discuss more broadly the benefits and challenges of translational research models and offer recommendations for research programs that address societal challenges in the energy sector and beyond.


Phase extraction algorithm considering high-order harmonics in fringe image processing.
A phase calculation method using discrete Fourier series (DFS) is proposed to eliminate the effects of nonsinusoidal characteristics. In this method, the fundamental coefficients are extracted from continuous N samples in one cycle by DFS, with which four images with π/2 intervals are reconstructed, and then more accurate phase distribution can be further obtained. This method is applicable for improving the precision of the traditional phase-shifting algorithm. Its effectiveness and accuracy are verified by computer simulations and moiré fringe and projecting fringe experiments with about 85% of the phase error reduced compared with a four-step phase-shifting algorithm, about 70% reduction compared with a 16-step phase-shifting algorithm.


Ill health and retirement in Britain: a panel data-based analysis.
We examine the effect of ill health on retirement decisions in Britain, using the British Household Panel Survey (1991-1998). As self-reported health status is likely to be endogenous to the retirement decision, we instrument self-reported health by a constructed 'health stock' measure using a set of health indicator variables and personal characteristics, as suggested by Bound et al. (Bound, J., Schoenbaum, M., Stinebrickner, T.M., Waidmann, M., 1999. The dynamic effects of health on the labor force transitions of older workers. Labour Economics 6, 179-202). Using a range of econometric techniques, we show that adverse shocks to individual health stocks predict individual retirement behaviour among workers aged from 50 until state pension age. We compare responses of economic activity to constructed health measures with that arising using direct indicators of functional limitations and specific health problems. We also examine the dynamics of health shocks and whether adverse and positive health shocks have symmetric effects on transitions in and out of economic activity.


Laparoscopic peritoneal drainage of symptomatic lymphoceles after pelvic lymph node dissection using methylene blue instillation.
Lymphoceles are frequent complications of pelvic lymph node dissection. While small lymphoceles often remain undetected, larger ones can cause complications and require further treatment, e.g. percutaneous tube drainage alone or in combination with sclerotherapy. However, recurrence rates are considerable, and long-lasting drainage may lead to infection, prolonged hospitalization, and as a consequence, increased overall costs. We report the results of a simplified laparoscopic approach to drain lymphoceles after radical prostatectomy plus pelvic lymphadenectomy using methylene blue instillation. 13 patients with large symptomatic pelvic/retroperitoneal lymphoceles refractory to percutaneous tube drainage and doxycycline sclerotherapy received a laparoscopic transperitoneal marsupialization following instillation of a sterile diluted methylene blue solution into the drained cavity to refill and mark the lymphocele. All lymphoceles were sterile and ranged in size from 7 x 6 x 4 to 15 x 12 x 6 cm. Clinical symptoms included lower abdominal swelling, tenderness in the iliac fossa, ipsilateral lymphedema, deep venous thrombosis, wound fistula, and hydronephrosis due to ureteral obstruction. After methylene blue instillation, the lymphoceles were easily identified and opened. Median total operative time was 50 (range 25-70) min; blood loss was negligible. There was one complication in the form of a metachronous infection in the operating field and no relapses. Patients were discharged 1-5 (median 3) days after the surgical procedure. Laparoscopic peritoneal drainage requires greater operative skill than percutaneous approaches. However, the instillation of a methylene blue solution simplifies this procedure as the extent and location of the lymphoceles can be precisely identified during laparoscopy. We recommend early application of laparoscopic peritoneal drainage following methylene blue instillation for patients with sterile lymphoceles after pelvic lymph node dissection in whom temporary percutaneous drainage and sclerotherapy failed to resolve the lymph fluid collection.


Febuxostat (Teijin/Ipsen/TAP).
Febuxostat (TEI-6720; TMX-67), an oral non-purine, selective inhibitor of xanthine oxidase (NP-SIXO), is being developed by Teijin, with licensees Ipsen and TAP Holdings, for the potential treatment of gout. In February 2005, it was reported that launch in Japan was expected to be delayed for several years due to the need for additional clinical trials; in May 2005, an EU filing was expected by the end of 2005.


A comprehensive approach to the treatment of uterine leiomyomata.
Leiomyomas (fibroids) are the most common tumors in women, with a prevalence between 30% and 50%. They affect women primarily during their reproductive years, spontaneously regressing after menopause in most women. They may cause significant symptoms of pain, dysmenorrhea, abnormal uterine bleeding, and infertility. Because leiomyomas are so common, treatment should be reserved for those patients with symptoms. Treatment options have recently expanded beyond hysterectomy. Medical therapies, including gonadotropin-releasing hormone agonists and progesterone modulators, have become more widely used. Less invasive options such as uterine fibroid embolization, magnetic resonance imaging-guided focused ultrasound, and radiofrequency ablation are being used to avoid more invasive surgery. Because of limited and negative information regarding these alternatives to surgery, they are not recommended for women desiring future fertility. If surgery is desired or required, often less invasive approaches via hysteroscopy for intracavitary lesions or robot-assisted laparoscopy for patients with a small number of myomas have become preferred options. Treatment should be tailored to the patient.


Zinc Protects against MDMA-Induced Apoptosis of Sertoli Cells in Mouse via Attenuation of Caspase-3.
3,4-Methylenedioxymethamphetamine (MDMA) disrupts function of the endocrine system and different organs such as heart, blood vessels, kidney, liver and nervous systems. This revision was conducted to evaluate impact of MDMA on apoptosis and Zinc in the MDMA-induced apoptosis of cultured Sertoli cells by measuring Caspase-3 gene expression. In this experimental study, Sertoli cells were incubated with MDMA (0, 0.5, 1, 3 and 5 mM), Zinc (0, 8, 16, 32, 64 μM) and Zinc (8 μM) prior to adding MDMA (5 mM) for 24 and 48 hours. MTT assay was used for evaluating impacts of these conditions on the viability of Sertoli cells. Caspase-3 gene expression level was detected using quantitative reverse transcription PCR (qRT-PCR) in all of the tested groups. Finding showed that cellular viability was decreased and level of Caspase-3 mRNA was increased in MDMA treated cells. Additionally, pre-treatment with Zinc (8 μM) attenuated MDMA-induced apoptosis and down-regulated caspase-3. The mean of caspase-3 mRNA level (fold change ± SE) was 3.98 ± 1.18, 0.31 ± 0.28, and 1.72 ± 0.28 in respectively MDMA (5 mM), Zinc (8 μM), and Zinc+MDMA groups vs. control group. The mean of Caspase-3 mRNA (fold change) was not statistically different in the tested groups (P>0.05), unless MDMA (5 mM) group (P=0.008). We suggest that MDMA toxicity could be involved in apoptosis of Sertoli cells. In addition, Zinc could reduce MDMA-induced apoptosis by down-regulation of Caspase-3 mRNA levels.


Gut hormones profile after an Ivor Lewis gastro-esophagectomy and its relationship to delayed gastric emptying.
Delayed gastric emptying (DGE) is common after an Ivor Lewis gastro-esophagectomy (ILGO). The risk of a dilated conduit is the much-feared anastomotic leak. Therefore, prompt management of DGE is required. However, the pathophysiology of DGE is unclear. We proposed that post-ILGO patients with/without DGE have different gut hormone profiles (GHP). Consecutive patients undergoing an ILGO from 1 December 2017 to 31 November 2019 were recruited. Blood sampling was conducted on either day 4, 5, or 6 with baseline sample taken prior to a 193-kcal meal and after every 30 minutes for 2 hours. If patients received pyloric dilatation, a repeat profile was performed post-dilatation and were designated as had DGE. Analyses were conducted on the following groups: patient without dilatation (non-dilated) versus dilatation (dilated); and pre-dilatation versus post-dilatation. Gut hormone profiles analyzed were glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) using radioimmunoassay. Of 65 patients, 24 (36.9%) had dilatation and 41 (63.1%) did not. For the non-dilated and dilated groups, there were no differences in day 4, 5, or 6 GLP-1 (P = 0.499) (95% confidence interval for non-dilated [2822.64, 4416.40] and dilated [2519.91, 3162.32]). However, PYY levels were raised in the non-dilated group (P = 0.021) (95% confidence interval for non-dilated [1620.38, 3005.75] and dilated [821.53, 1606.18]). Additionally, after pyloric dilatation, paired analysis showed no differences in GLP-1, but PYY levels were different at all time points and had an exaggerated post-prandial response. We conclude that DGE is associated with an obtunded PYY response. However, the exact nature of the association is not yet established.


Attenuation of systolic blood pressure and pulse transit time hysteresis during exercise and recovery in cardiovascular patients.
Pulse transit time (PTT) is a cardiovascular parameter of emerging interest due to its potential to estimate blood pressure (BP) continuously and without a cuff. Both linear and nonlinear equations have been used in the estimation of BP based on PTT. This study, however, demonstrates that there is a hysteresis phenomenon between BP and PTT during and after dynamic exercise. A total of 46 subjects including 16 healthy subjects, 13 subjects with one or more cardiovascular risk factors, and 17 patients with cardiovascular disease underwent graded exercise stress test. PTT was measured from electrocardiogram and photoplethysmogram of the left index finger of the subject, i.e., a pathway that includes predominately aorta, brachial, and radial arteries. The results of this study showed that, for the same systolic BP (SBP), PTT measured during exercise was significantly larger than PTT measured during recovery for all subject groups. This hysteresis was further quantified as both normalized area bounded by the SBP-PTT relationship (AreaN) and SBP difference at PTT during peak exercise plus 20 ms (ΔSBP20). Significant attenuation of both AreaN (p <; 0.05) and ΔSBP20 (p <; 0.01) is observed in cardiovascular patients compared with healthy subjects, independent of resting BP. Since the SBP-PTT relationship are determined by the mechanical properties of arterial wall, which is predominately mediated by the sympathetic nervous system through altered vascular smooth muscle (VSM) tone during exercise, results of this study are consistent with the previous findings of autonomic nervous dysfunction in cardiovascular patients. We further conclude that VSM tone has a nonnegligible influence on the BP-PTT relationship and thus should be considered in the PTT-based BP estimation.


Cardiac stress testing of hemiparetic patients with a supine bicycle ergometer: preliminary study.
Ten hemiparetic subjects underwent functional cardiac stress testing on a supine bicycle ergometer. Their heart rate (HR), blood pressure (BP), and rate pressure product (RPP) were determined at rest and at incremental workloads. Three subjects with no previous history of coronary artery disease (CAD) had positive test results diagnostic or suggestive of CAD. None of the three subjects with a history of myocardial infarction displayed any ECG abnormalities during the exercise. The RPPs obtained during testing were compared to those recorded during various rehabilitation activities. As some difficulties arose in the performance and interpretation of the stress test in patients receiving beta-blocking medication and others with arthritis, spasticity, and orthopedic problems, procedures for handling these problems needed review. The supine bicycle proved to be an appropriate device for cardiac stress testing in a hemiparetic population.


Update: stability of allergen extracts to establish expiration dating.
The article reviews studies pertaining to US manufactured allergen extract stability that contribute to guidance for expiration dating for bulk concentrates, diluted patient testing and treatment vials, and adjustments following elevated temperature excursions. Studies on allergen stability were completed to satisfy the Food and Drug Administration requirements supporting labeled expiration dating for standardized short ragweed, dust mites, cat, grass, and venom extracts and are not published. These studies demonstrated the stability enhancing parameters of 50% glycerin and support the Food and Drug Administration mandated expiration of nonstandardized extracts allowing glycerin extracts twice the dating of nonglycerin aqueous extracts. Patient vials are commonly given 6-12 months dating. There is adequate evidence that human serum albumin stabilizes low protein diluted vials. High protease allergens such as molds and insects compromised potency of pollens when mixed. Subsequent work continued to define the effects of diluents on extract dilutions, temperature excursions that occasionally occur with shipping or refrigerator malfunctions, and allergen compatibility. Potency has been determined for allergen dilutions with diluents typically used for allergen immunotherapy. These studies along with changes of potency under various storage conditions and mixing designed to improve our guidance on expiration dating of allergen extracts will be discussed.


Apical hypertrophic cardiomyopathy and arrhythmia in military pilots.
Apical hypertrophic cardiomyopathy (ApHCM), a subtype of hypertrophic cardiomyopathy, may be found incidentally in healthy young adults. Arrhythmias are poor prognostic signs, and are the most frequent cause of sudden cardiac death. We present two cases of military aviators with ApHCM. One was a high-performance jet weapon system operator, who had asymptomatic non-sustained ventricular tachycardia (NSVT) and subsequently a symptomatic episode of paroxysmal atrial fibrillation. The second was a helicopter pilot, who had asymptomatic NSVT. Both aviators continue their aviation duties without exposure to +Gz under a regime of regular thorough cardiac assessment.


Intrauterine application of progestins in hormone replacement therapy: a review.
The intrauterine application of progestins as endometrial protection against hyperstimulation by estrogen replacement therapy has been investigated in clinical trials since the early 1990s and one product has become available for this indication. This review considers the available published and presented reports on intrauterine use of progestin to date. Reports of 19 studies were reviewed. These studies included both peri- and postmenopausal women (826 in total), treated with different types of estrogens administered via various routes. Progesterone was used in two small studies, while all other studies used different doses of levonorgestrel for periods ranging from 6 months to more than 5 years. Endometrial effects, bleeding profiles, systemic effects (symptoms and metabolic), as well as clinical experience, were considered and were comparable to other forms of continuous combined hormone replacement therapy (HRT). It is concluded that the current evidence supports complete endometrial protection and a good safety profile. The observed bleeding profiles appear favorable but have not yet been directly compared with other forms of continuous combined HRT. A favorable effect on serum lipids has been observed and also awaits direct comparative confirmation. Progestin-attributable side-effects, effects on bone and breast tissues and other systemic effects have not yet been studied. Acceptance by patients has been good, while insertion did not present undue problems for the investigating physicians. Retention of the studied intrauterine systems has been very good. Intrauterine use of progestins, especially levonorgestrel, by purpose-designed systems as part of combined HRT, is a new way of administration and carries good benefits, while some aspects require more clinical evidence.


Retinol-binding protein 4 and its potential roles in hypercholesterolemia revealed by proteomics.
Effects of hypercholesterolemia on alterations of serum proteins have not been fully elucidated. Herein, using two-dimensional gel electrophoresis (2-DE) in conjunction with LC-MS searching has successfully been carried out to investigate the change of protein expression profiles as consequences of raised blood cholesterol at different levels (normal group: total cholesterol 200 mg/dL; borderline high group: total cholesterol 200-239 mg/dL; and high group: total cholesterol ≥ 240 mg/dL) (n = 45). Results revealed that down-regulation of retinol-binding protein 4 (RBP4) (-2.26 fold), transthyretin (-1.25 fold) and gelsolin (-1.47 fold) was observed in the high group. Meanwhile, the other proteins such as haptoglobin, complement factor B and CD5 antigen-like protein were up-regulated upto +3.24, +1.96 and +2.04 fold, respectively. Confirmation by Western blotting revealed a significant reduction of RBP4 (approximately 50 %) in individual samples derived from the high group. Presumptive conclusion can be drawn that down-regulation of RBP4 might be attributable to the inflammation of adipocytes caused by the release of proinflammatory cytokines (e.g. tumor necrosis factor α and interleukin-1β) from adipose tissues. Moreover, the decrease of transthyretin might also be taken into accounts since it is known that the transthyretin usually forms complex with RBP4 to prevent glomerular filtration and excretion through the kidney. The suppressing effect on RBP4 should be potentiated by the increase of complement factor B and CD5 antigen-like protein, which rendered the adipose tissues to overwhelm the liberation of RBP4 to blood circulation by metabolic and inflammatory processes. Such inflammation could further modulate the induction of cytokine release (e.g. IL-6 and IL-1β), resulting in the synthesis of acute phase protein, in particular, haptoglobin and C-reactive proteins from hepatocytes. However, the mechanism of gelsolin reduction remains unclear. Among these differentially expressed proteins, the RBP4 has been proposed as a major linkage between hypercholesterolemia, adipose tissues, liver and kidney, which is believed to be a potential biomarker for metabolic and cardiovascular disorders associated with dyslipidemia in the future.


Study of the frequency and the features of supranumerary teeth found in one Portuguese population.
The present study was performed on a population of subjects assisted at the dental clinic of Instituto Superior de Ciências da Saúde-Norte. The aims of the study were: (1) to analyse the prevalence of supernumerary teeth, (2) to characterise its gender distribution, and (3) to investigate the repercussions of supernumerary teeth over neighbouring teeth and tissues. From the records of all the patients received from 1993 to 2000, 16771 clinical files contained panoramic X-ray plates (8712 females and 8059 males) and were selected. A total of 151 supernumerary teeth were found in 127 patients (72 males and 55 females, aged from 5 to 63 years), corresponding to a prevalence of 0.76%. Other designed important issues were one supernumerary teeth for individual; the mesiodens type (followed by the 4th molar); conical morphology; the maxilla (namely on the maxillary medial line): location as predominant findings. Evolutionary state, 47 (31.1%) were erupted and 104 (68.9%) unerupted. In most cases 108 (71.5%), the radiological images didn't suggest alterations on adjacent teeth and/or tissues. The repercussions found, potentially associated to supernumerary teeth were: 12 (7.9%) displacement of adjacent teeth, nine (6%) delayed eruption of permanent teeth, and eight cases (5.3%) diastema formation.


Notable coordination effects of 2-pyridinesulfonamides leading to efficient aziridination and selective aziridine ring opening.
[reaction: see text] We have developed, on the basis of a chelation-strategy, an efficient copper-catalyzed aziridination protocol with the use of 5-methyl-2-pyridinesulfonamide and PhI(OAc)(2). The reaction proceeds smoothly under mild conditions to give aziridines in moderate to good yields in the absence of external ligands or bases. The coordination-assisted approach offers the additional benefits that efficient deprotection of the N-substituent and selective aziridine ring-opening are effectively achieved.


A stereoselective switch: enantiodivergent approach to the synthesis of isoflavanones.
A modular six-step asymmetric synthesis of two naturally occurring and three non-natural isoflavanones containing tertiary α-aryl carbonyls is reported. This synthetic route, utilising a Pd-catalyzed decarboxylative asymmetric protonation, produces isoflavanones in excellent enantioselectivities from 76-97 %. A switch in the sense of stereoinduction was observed when different H(+) sources were employed, showing the first example of dual stereocontrol in an asymmetric protonation reaction. The first enantioselective synthesis of the naturally occurring isoflavanones sativanone and 3-o-methylviolanone has been accomplished.


The Hypersensitive Reaction of Tobacco to Pseudomonas syringae pv. pisi: Activation of a Plasmalemma K/H Exchange Mechanism.
Net electrolyte efflux from suspension-cultured tobacco cells undergoing the hypersensitive reaction to Pseudomonas syringae pv. pisi resulted from a specific efflux of K(+) which was accompanied by an equimolar net influx of H(+). These fluxes began 60 to 90 minutes after inoculation of tobacco cells with bacteria, reached maximum rates of 6 to 9 micromoles per gram fresh weight tobacco cells per hour within 2.5 to 3 hours, and dropped below 4 micromoles per gram per hour within 5 hours. Tobacco cells lost approximately 35% of total K(+) during this period, and average cellular pH declined by approximately 0.75 pH unit. These events were accompanied by a 30% decrease in cellular ATP. K(+) and H(+) fluxes were inhibited by the protonophore (p-trifluoromethoxy)carbonyl cyanide phenylhydrazone and by increasing the K(+) concentration of the external solution. Tobacco leaf discs inoculated with the bacterium also exhibited a specific net K(+) efflux and H(+) influx. These results suggest that induction of the hypersensitive reaction in tobacco proceeds through the activation of a passive plasmalemma K(+)/H(+) exchange mechanism. It is hypothesized that activation of this exchange is a major contributing factor in hypersensitive plant cell death.


Conglomerate crystallization on self-assembled monolayers.
In this communication, we demonstrate that chiral self-assembled monolayers can be used for polymorphism control of chiral crystals. We studied the crystallization of DL-glutamic acid on chiral self-assembled monolayers and showed that crystallization of DL-glutamic acid on the chiral SAMs resulted in stabilization of the metastable conglomerate form.


[Surveillance on the etiology and molecular epidemiology of Shigella sonnei isolated in Henan province from 2011 to 2014].
To detect and analyze the distribution of virulence factors, antimicrobial resistance and pulsed field gel electrophoresis (PFGE) patterns of Shigella sonnei, isolated in Henan province from 2011 to 2014. Samples of diarrhea patients were collected and isolated with SS selective culture medium in 37 ℃ for 18-24 hours. All strains were identified under the Kligler iron agar/motility-indol-urea biochemical action and API20E biochemical system. Serological typing and prepared DNA template were carried out with thermal cracking method and multiplex PCR, to detect the virulence genes of Shigella sonnei. According to the molecular typing method and K-B drug susceptibility testing method published by the international PulseNet bacterial infectious disease monitoring network and USA clinical and Laboratory Standards Institute, antimicrobial susceptibility tests and PFGE molecular characteristics of these positive strains isolated from sentinel hospitals patients stool samples were analyzed. Among the 98 strains of Sonnei type Ⅰ and 118 strains of Sonnei type Ⅱ, all the strains carried carry different virulence genes including SHET-1B, SHET-2, ial, ipaH genes, with 4 kinds of virulence gene combination types. All the 216 strains of Shigella sonnei belonged to the multi-drug resistant strains, including 34 isolates resistant to 2-4 kinds of antibiotics(15.7%), 147 isolates to 5-8 kinds of antibiotics (68.1%), 24 to 9-10 kinds of antibiotics (11.1%), 7 to 11 kinds of antibiotics (3.2%), and 4 to 13 kinds of antibiotics (1.9%). A total of 100 strains of Shigella sonnei were divided into 31 molecular patterns, digested by XbaⅠ and PFGE. Each pattern contained 1-13 strains with similarities ranged from 68.6%-100.0%. All the Shigella sonnei strains carried virulence pathogenic factors, presenting serious status on drug resistance. PFGE fingerprinting patterns showed high polymorphism and dominant characteristics. PFGE patterns of partial strains and corresponding antidrug spectrum presented certain relevance and with same aggregation relationship.


Self-catalyzed insertion of proteins into phospholipid membranes.
We present evidence that the mitochondrial channel, VDAC, when reconstituted into a phospholipid membrane, can catalyze the insertion of other VDAC channels. This property called "auto-directed insertion" was first proposed by Zizi et al. (1995) to explain observations on asymmetric VDAC channels. We found that 2 urea or guanidinium chloride (GdmCl) caused a burst of insertions of VDAC channels when added to the same side as VDAC addition. More strikingly, when added to the opposite side they caused a 10-60-fold sustained yet reversible increase in insertion rate. Protein stabilization by sarcosine eliminated the effect of urea and GdmCl on VDAC insertion. Control experiments showed that water flow, ionic strength, osmotic force, phospholipid type, and membrane potential were not involved. Therefore, although both urea and GdmCl affect the properties of phospholipid membranes, it is more likely that these agents act either by changing the structure of the pre-inserted channels, allowing them to be more effective catalysts for VDAC insertion, or by flowing through the channels and acting on nearby VDAC channels inducing them to insert. Either way, insertion must be occurring next to pre-inserted channels. Urea and GdmCl may mimic chaperones by partially unfolding VDAC and keeping it in an insertion-competent state. "Auto-directed insertion" may ensure both correct targeting and orientation of nascent proteins in vivo.


Psoriatic arthritis treated by anti-TNFs: a monocentric trial of 102 cases in Auvergne, France.
While several registries have already evaluated the retention of anti-TNF therapy in psoriatic arthritis (PsA), they sometimes reach divergent conclusions. Our study therefore sought to assess therapeutic retention rates and predictive factors of response in a patient cohort from Auvergne, France, followed up in routine clinical practice. Medical records of all PsA patients treated from 2002 to May 2015 were analysed. PsA diagnosis was established based on the CASPAR criteria. In total, 102 patients were analysed, comprising 62 men (44.6±12.6 years) and 40 women (37.8±13.4). Mean PsA evolution was 2.7 years (0.8-11.2). The most common forms were peripheral (47/102, 45.1%) and mixed (46/102, 46.1%) PsA. The anti-TNF treatment initiated was etanercept in 47 cases (45.2%), adalimumab in 29 (27.9%), infliximab in 20 (19.2%), and golimumab in six [5.8%]. In 28 cases (27.4%), anti-TNF was associated with methotrexate (MTX). Overall, the median duration of anti-TNF retention was 76.5 months. The hazard ratios (HR) for treatment cessation did not significantly differ between the etanercept and monoclonal antibody groups (HR=1.35[0.96-1.93], p=0.08). After 5 years, approximately 30.8% of etanercept patients and 68.8% of monoclonal antibody patients (adalimumab 71.2%; infliximab 67.2%) were still being treated. Combining with MTX did not prolong the overall retention rate (HR=0.85[0.37-1.96], p=0.71). Tobacco use was predictive of discontinuation (p=0.03). Our study demonstrates good anti-TNF treatment retention in PsA patients, as well as confirming the deleterious effect of smoking while providing no argument in favour of combined treatment with MTX to improve maintenance.


A new approach to acute renal failure.
The phrase pre-renal failure does not capture the subtleties of hemodynamic changes that result in low-normal blood pressure or volume and increased serum creatinine. Clarifying terms, normotensive ischemic acute renal failure and prerenal success, are reviewed.


Differential role of cation and anion exchange in lymphocyte pH regulation.
In lymphocytes, the Na+/H+ antiport is well suited to function in cytoplasmic pH (pHi) regulation. It is activated by departures from the physiological pHi and is thermodynamically poised to compensate for the tendency of the cells to become acidic. The driving force for H+ (equivalent) efflux is indirectly provided by the Na+ pump. Lymphocytes also possess a cation-independent anion (Cl-/HCO3-) exchange system, which, under the appropriate conditions, tends to restore pHi after an alkali load. Unlike the cation antiport, the source of energy driving the anion exchanger, i.e. the factors that determine the transmembrane Cl- distribution, is not well understood. The contribution of conductive pathways appears to be minimal, resulting in a marked difference between the membrane potential and ECl-. Instead, ECl- is very similar to EH+. Moreover, changes in the distribution of Cl- lead to alterations in the transmembrane delta pH and vice versa, suggesting a relationship between these parameters. Evidence is presented which suggests that the transmembrane distribution of HCO3-, dictated by delta pH, is a major determinant of the intracellular Cl- concentration, a process mediated by the anion exchanger. Thus, if Cl- is driven by the gradient of HCO3-, the cation-independent anion exchanger cannot play an active role in determining pHi. Instead, Cl-/HCO3- exchange may simply stabilize pHi by increasing the dynamic buffering power of the cells. Cation-independent Cl-/HCO3- exchange could be involved in pHi regulation only if coupled to a separate mechanism of intracellular Cl- accumulation, such as Na+-K+-2Cl- co-transport or an inward Cl- pump, which have not been detected in lymphoid cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Reliability and Validity of the Functional Gait Assessment in Incomplete Spinal Cord Injury.
There are limited psychometrically sound measures to assess higher level balance in individuals with incomplete spinal cord injury (iSCI). To evaluate interrater and intrarater reliability and convergent validity of the Functional Gait Assessment (FGA) in individuals with iSCI. Twelve participants (11 male, 1 female) 32 to 73 years old with chronic motor iSCI, American Spinal Injury Association Impairment Scale C (n = 2) or D (n = 10), were included. Participants completed five outcome measures during a single test session including lower extremity motor scores from the International Standards for the Neurological Classification of Spinal Cord Injury, FGA, 10-Meter Walk Test (10MWT), Walking Index for Spinal Cord Injury (WISCI-II), and the Spinal Cord Injury Functional Ambulation Profile (SCI-FAP). Inter- and intrarater reliability for the FGA were excellent. Interrater reliability was excellent with intraclass correlation coefficient (ICC) scores greater than 0.92 (p < .001). Interrater reliability against an expert was also excellent for all raters, with an ICC greater than or equal to 0.92 (p < .01). Intrarater reliability was excellent with an ICC score of greater than 0.91 (p < .002) for all raters. Validity of the FGA with 10MWT was -0.90 (p = .000), FGA with WISCI-II was 0.74 (p = .006), and FGA with SCI-FAP was -0.83 (p = .001). The FGA is a reliable and valid outcome measure to use when assessing gait and balance in individuals with motor iSCI. The FGA provides clinicians with a single tool to utilize across a variety of neurologic diagnoses.


Metabolism of Specifically Labeled Glucose, Glucose 1-Phosphate, and Glucose 6-Phosphate via the Oxidative Pentose Phosphate Cycle in a Reconstituted Spinach Chloroplast System in Darkness and in the Light.
Using isolated spinach (hybrid 424) chloroplasts deprived of their envelopes (reconstituted chloroplast system), the metabolism of glucose, glucose 1-phosphate, and glucose 6-phosphate via the oxidative pentose phosphate cycle was analyzed. The activity of oxidative pentose phosphate cycle was monitored by continuous sampling of the CO(2) released during the decarboxylation process of 6-phosphogluconate.The rate of CO(2) released in the dark from [C-1-(14)C]glucose 6-phosphate was 4 to 6 micromoles per milligram chlorophyll per hour. A CO(2) release from the C-6 position of [C-6-(14)C]glucose 6-phosphate was hardly measurable within 60 minutes of incubation. Glucose 1-phosphate was readily converted to glucose 6-phosphate without externally added glucose bisphosphate and was metabolized via the oxidative pentose phosphate cycle. The phosphorylation of glucose to glucose 6-phosphate was mediated by hexokinase present in the reconstituted system. This step was rate-limiting for the over-all reaction of the oxidative pentose phosphate cycle with glucose being the substrate (0.5 micromoles per milligram chlorophyll per hour). Addition of hexokinase increased the rate of CO(2) release to 5 micromoles per milligram chlorophyll per hour.The flow of carbon through the oxidative pentose phosphate cycle was greatly reduced upon the addition of NADPH and ATP. Whereas NADPH inhibited the metabolism of [C-1-(14)C]glucose 6-phosphate via the oxidative pentose phosphate cycle, ATP stimulated carbon flow into the 3-phosphoglycerate, dihydroxyacetone phosphate, and bisphosphates pools via the glycolytic pathway mediated by phosphofructokinase. This regulatory phenomenon could also be demonstrated with the reconstituted system undergoing a dark-light-dark transition. Data are presented indicating the conditions under which glucose 6-phosphate or glucose 1-phosphate are metabolized via the oxidative pentose phosphate cycle and the glycolytic pathway.


Fractionating the multi-character processing deficit in developmental dyslexia: Evidence from two case studies.
While there is growing evidence that some dyslexic children suffer from a deficit in simultaneously processing multiple visually displayed elements, the precise nature of the deficit remains largely unclear. The aim of the present study is to investigate possible cognitive impairments at the source of this deficit in dyslexic children. The visual processing of simultaneously presented letters was thus thoroughly assessed in two dyslexic children by means of a task that requires the report of briefly presented multi-letters arrays. A computational model of the attentional involvement in multi-object recognition (Bundesen, 1990, 1998) served as framework for analysing the data. By combining psychophysical measurements with computational modelling, we demonstrated that the visual processing deficit of simultaneously displayed letters, observed in the two dyslexic individuals reported in the current study, stems from at least two distinct cognitive sources: a reduction of the rate of-letter-information uptake, and a limitation of the maximal number of elements extracted from a brief visual display and stored in visual short-term memory. Possible relations between these impairments and learning to read proficiently are discussed.


Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.
Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.


Renormalization Group Flows on Line Defects.
We consider line defects in d-dimensional conformal field theories (CFTs). The ambient CFT places nontrivial constraints on renormalization group (RG) flows on such line defects. We show that the flow on line defects is consequently irreversible and furthermore a canonical decreasing entropy function exists. This construction generalizes the g theorem to line defects in arbitrary dimensions. We demonstrate our results in a flow between Wilson loops in four dimensions.


Attomolar detection of protein biomarkers using biofunctionalized gold nanorods with surface plasmon resonance.
This paper describes an ultrasensitive surface plasmon resonance (SPR) detection method using biofunctionalized gold nanorods for the direct detection of protein biomarkers. Immunoglobulin E (IgE), which has separate antibody and DNA aptamer binding sites, was chosen as a model protein for which a sandwich assay platform was designed. Detection was achieved via the specific adsorption of unlabelled IgE proteins onto the surface immobilized aptamer followed by the specific adsorption of anti-IgE coated gold nanorods (Au-NRs). Using the biofunctionalized nanorods in conjunction with SPR, we were able to directly measure IgE proteins at attomolar concentrations. This is a remarkable 10(8) enhancement compared to conventional SPR measurements of the same surface sandwich assay format 'anti-IgE/IgE/surface bound IgE-aptamer' in the absence of gold nanorod signal amplification.


Antioxidant vitamin-cardiovascular disease hypothesis is still promising, but still unproven: the need for randomized trials.
The hypothesis that antioxidant vitamins might decrease the risk of cardiovascular disease (CVD) is a promising area of research. At present, however, it is far from certain whether antioxidant vitamins confer protection against CVD. Evidence for the antioxidant vitamin-cardiovascular disease hypothesis has accumulated from several lines of research. Laboratory research has identified biochemical properties of antioxidant vitamins that could explain their possible role in inhibiting and delaying coronary atherosclerosis. Epidemiologic studies have provided support for the hypothesis by showing that people who consume high amounts of antioxidant vitamins through diet or supplements, or those with high concentrations of these nutrients in their blood, tend to have lower risks of CVD. In the case of the former, however, laboratory findings may not have relevance to free-living humans. Observational epidemiologic studies cannot exclude the possibility that people who consume antioxidant-rich diets or who take vitamin supplements also share other lifestyle or dietary practices that actually account for their lower disease rates. Because of these uncertainties, the only way to determine reliably whether antioxidants play any role in reducing the risk of CVD is to conduct large-scale, randomized trials of these agents, in which adequate doses of antioxidant vitamins are tested for a sufficient duration to allow for any benefits to emerge. Several large-scale trials are now ongoing in both primary and secondary prevention. The results of these trials over the next several years should provide reliable evidence for this promising, but as yet unproven, hypothesis.


Host Materials Transformable in Tumor Microenvironment for Homing Theranostics.
A pathology-adaptive nanosystem, in which nest-like hosts are built based on nanofibers that are transformed from i.v. injected nanoparticles under the acidic tumor microenvironment. The solid tumor is artificially modified by nest-like hosts readily and firmly, resulting in highly efficient accumulation and stabilization of guest theranostics. This strategy shows great potential for the theranostics delivery to tumors.


Artificial extracellular matrix for biomedical applications: biocompatible and biodegradable poly (tetramethylene ether) glycol/poly (ε-caprolactone diol)-based polyurethanes.
The cells as a tissue component need to viscoelastic, biocompatible, biodegradable, and wettable extracellular matrix for their biological activity. In this study, in order to prepare biomedical polyurethane elastomers with good mechanical behavior and biodegradability, a series of novel polyester-polyether- based polyurethanes (PUs) were synthesized using a two-step bulk reaction by melting pre-polymer method, taking 1,4-Butanediol (BDO) as chain extender, hexamethylene diisocyanate as the hard segment, and poly (tetramethylene ether) glycol (PTMEG) and poly (ε-caprolactone diol) (PCL-Diol) as the soft segment without a catalyst. The soft to the hard segment ratio was kept constant in all samples. Polyurethane characteristics such as thermal and mechanical properties, wettability and water adsorption, biodegradability, and cellular behavior were changed by changing the ratio of polyether diol to polyester diol composition in the soft segment. Our present work provides a new procedure for the preparation of engineered polyurethanes in surface properties and biodegradability, which could be a good candidate for bone, cartilage, and skin tissue engineering.


Patient satisfaction and oral health-related quality of life after treatment with traditional and simplified protocols for complete denture construction.
The objective of this randomised controlled clinical trial study was to compare the effectiveness of a traditional and a simplified protocol for construction of conventional CD. The replacement of conventional dentures can result in potential functional and aesthetic benefits to the patient. Previous studies suggest that simplified procedures for complete dentures (CD) construction achieve results similar to the traditional methods. Fifty patients were randomly divided into two equal groups, traditional protocol (T group) and simplified protocol (S group). Treatment outcomes were assessed before the insertion of the new dentures and 30 days and 6 months after the last adjustment. It included measurements of quality of life related to oral conditions measured by the Brazilian version of OHIP-Edentulous scale and patients' satisfaction with the upper and lower dentures using a visual analogue scale (VAS), which combines the patient's perception in relation to overall satisfaction with the comfort, stability, ability to chew, ability to talk and aesthetics. The results showed significant reduction in negative impacts of oral conditions on quality of life and improved satisfaction with the upper and lower dentures (p < 0.001) at the 30-day and 6-month follow-up. Quality of life improvement occurred in all dimensions of the OHIP-Edentulous (p < 0.001). Despite the significant reduction in quality of life impacts and significant increase in patients' satisfaction with the dentures, there were no differences between the traditional and simplified protocols (p > 0.05). It was concluded that the simplified protocol results in patent's perception of treatment outcomes similar to the traditional protocol.


Favorable outcome with hemoperfusion of polymyxin B-immobilized fiber column for rapidly progressive interstitial pneumonia associated with clinically amyopathic dermatomyositis: report of three cases.
We present 3 cases of rapidly progressive interstitial pneumonia (RPIP) associated with clinically amyopathic dermatomyositis (C-ADM) that were treated with two courses of direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). Despite initial treatment with high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine, the lung disease and hypoxemia deteriorated in all the patients. After PMX-DHP treatment, the PaO2/FiO2 ratio and serum LDH and KL-6 were improved, the abnormal shadows in chest high-resolution computed tomography (HRCT) scans gradually decreased, and, finally, all patients survived. These findings indicate that PMX-DHP treatment could be effective in the management of RPIP in patients with C-ADM in combination with conventional therapy.