An oligoarray for the detection of human papillomavirus type 16 variants.
On the basis of human papillomavirus (HPV) E6 gene mutations, there are more than five variants of HPV 16. We applied a sensitive and specific stacking hybridization assay using an oligoarray for the detection of Asian-American (AA) and European (E) (E350G) HPV 16 variants. A simple glass slide was coated with capture probes consisting of short oligonucleotide DNA sequences (7-9 mers) specific for AA and E variants. Two different regions of the E6 HPV 16 gene were amplified with a set of two primers, which were used as target DNA. These targets were preannealed with auxiliary labeled oligonucleotides and hybridized to the oligoarray in the presence of specific and complementary capture probes. Our designed array based on shorter capture probes successfully discriminated between HPV 16 AA and E variants. The present DNA oligoarray system could be useful as a reliable technique for HPV 16 detection and does not require specialized equipment; nevertheless, further intra- and interlaboratory studies are needed.


F-actin clustering and cell dysmotility induced by the pathological W148R missense mutation of filamin B at the actin-binding domain.
Filamin B (FLNB) is a dimeric actin-binding protein that orchestrates the reorganization of the actin cytoskeleton. Congenital mutations of FLNB at the actin-binding domain (ABD) are known to cause abnormalities of skeletal development, such as atelosteogenesis types I and III and Larsen's syndrome, although the underlying mechanisms are poorly understood. Here, using fluorescence microscopy, we characterized the reorganization of the actin cytoskeleton in cells expressing each of six pathological FLNB mutants that have been linked to skeletal abnormalities. The subfractionation assay showed a greater accumulation of the FLNB ABD mutants W148R and E227K than the wild-type protein to the cytoskeleton. Ectopic expression of FLNB-W148R and, to a lesser extent, FLNB-E227K induced prominent F-actin accumulations and the consequent rearrangement of focal adhesions, myosin II, and septin filaments and results in a delayed directional migration of the cells. The W148R protein-induced cytoskeletal rearrangement was partially attenuated by the inhibition of myosin II, p21-activated protein kinase, or Rho-associated protein kinase. The expression of a single-head ABD fragment with the mutations partially mimicked the rearrangement induced by the dimer. The F-actin clustering through the interaction with the mutant FLNB ABD may limit the cytoskeletal reorganization, preventing normal skeletal development.


[Problems with radiation protection for adjuvant radiotherapy of thyroid cancer].
Ablative treatment of thyroid cancer with 131I is associated with the exposure to ionizing radiation of not only the target cells but also other cells and organs in the patient's body. Thermoluminescent dosimetry showed that the mean dose equivalent in ovaries equaled to several dozen mSv when the mean therapeutic dose was 2.8 GBq of 131I. In the treated young women the performed ovulation tests revealed no dysfunction of the ovaries. The highest dose equivalent in the clinic staff would not exceed 20 mSv per year. Accordingly, the dose equivalents to the public would not exceed the threshold limit of 1 mSv per year. In order to fulfill the requirements of regulations for disposal of radioactive waste and the necessity to store the waste for as long as 80 days it is obligatory to utilize setting tanks of very large capacity.


Assessing the potential of enhanced primary clarification to manage fats, oils and grease (FOG) at wastewater treatment works.
Daily, sewage treatment works (STWs) receive large volumes of fats, oils and greases (FOG), by-products of food preparation. To increase FOG removal at STW, conventional primary sedimentation tanks (PSTs) can be enhanced using chemical coagulant or through dissolved air flotation (DAF) techniques. This work aimed to assess the potential benefits of enhanced primary treatment for FOG removal through an energy and costs analysis. To achieve this, a five-year sampling programme was conducted monthly at 15 STWs measuring FOG concentrations in crude and settled sewage (i.e. after primary treatment). In addition, two DAF pilot systems were trialled for four months and their performance, in terms of FOG removal, was assessed and compared to that of a control primary clarifier. Across the 15 STWs, influent FOG concentrations were found at 57 ± 11 mg.L-1. Chemical coagulants dosed prior to PSTs increased FOG removal rates on average to 71% whilst traditional sedimentation only achieved 50% removal. Effluent FOG concentrations were found between 12-22 mg.L-1 and 19-36 mg.L-1 respectively. By contrast, DAF achieved FOG effluent concentrations on average at 10 ± 4 mg.L-1 corresponding to 74% removal from a relatively low influent concentration of 40 ± 30 mg.L-1. Thus, enhanced primary treatments have the potential to reduce organic load to secondary treatment and increase energy generation through anaerobic digestion. The overall net energy balance was estimated at 2269 MWh.year-1 for the DAF compared to 3445 MWh.year-1 for the chemically-enhanced PST making it a less financially attractive alternative. Yet, in the case where the works require upgrading to accommodate flow or load increases, DAF appeared as a sensible option over sedimentation offering significantly lower capital costs and footprint. In relation to FOG management, upgrading all STWs is not realistic and will require understanding where the benefits would be the highest.


Epidemiological study of mental morbidity in an urban slum community in India for the development of a community mental health programme.
A crossectional field study was carried out in an urban slum in order to assess the prevalence and nature of mental morbidity and identify stressors in the community. A face to face interview was conducted with the help of a questionnaire. The interview consisted of three sections as follows: Data identifying the informant by age, sex, marital status, education, occupation, age at marriage, number of members, children and monthly income. General Health Questionnaire (GHQ) 5- item version used as a screening instrument to assess the present mental health status of the informant and data of past illnesses in self or family and questions framed to elicit perceptions regarding mental illness, alcoholism, their causation and treatment. The subjects who scored above 2 ie 3,4,and 5 in the GHQ were requested to follow up at the Mental Health OPD and subjected to a standardized psychiatric interview by a Psychiatrist. The Diagnostic and Statistical Manual Third Revised (DSM 3 R) criteria were used for diagnosis. After the interview and examination, the appropriate treatment was instituted. A total of 443 individuals were screened. The overall prevalence rate of mental illness in the community was 61 per thousand. It is estimated that the case rate ranges from 38 to 84 per thousand within 95% confidence limits. The overall severity ranged from mild to severe morbidity. The prevalence of severe mental morbidity which includes psychosis, depressive illness, mental retardation was 22.5 per thousand. Neurosis (63.31%) especially Major Depression and Adjustment disorder, Psychosis (10.00%), Somatization disorder (6.66%) and Psychiatric symptoms secondary to physical illness were the major groups of illness. Women were found to have more mental health problems than men. The morbidity pattern also differs significantly with the gender. Neurosis was seen more among the female subjects. There was a significant association of mental health problems with low educational status, unemployment and large family size. Financial problems, marital conflicts, interpersonal conflicts and housing problems were the major stressors as perceived by the respondents. There exists significant mental health problems in the community which can be due to deleterious sociocultural factors and we recommend the integration of mental health care with general health care.


Use of follow-on fingolimod for multiple sclerosis: Analysis of effectiveness and patient reported outcomes in a real-world clinical setting.
Follow-on disease modifying therapies (FO-DMTs) do not always require Phase III studies. There are concerns that cheaper FO-DMTs are only used to reduce healthcare costs. However, the well-being of people with MS (pwMS) should be a priority. We aimed to evaluate the efficacy, safety and treatment satisfaction of one of the FO- Fingolimod (FTY) used in Turkey with the approval of Turkish Ministry of Health. PwMS under FTY were recruited from 13 centers and real-world data and answers of satisfaction and adherence statements of pwMS on FTY treatment were analyzed. Data of 239 pwMS were obtained. The duration of FTY treatment was 2.5 ± 0.8 (1-4) years in pwMS who were included in the study and whose treatment continued for at least one year. Significant decreases in annual relapse rate (p < 0.001), Expanded Disability Status Scale (p < 0.001) and neuroimaging findings (p < 0.001) were observed. While 64% of the patients were satisfied and 71.5% were found to adherent with this FO-FTY. This multicenter retrospective study found that the efficacy, safety and treatment adherence of a prescribed FO-FTY were consistent with the results of real-world studies. Studies including real-world data may provide guidance to address issues related to FO-FTY use.


Differential myeloma cell responsiveness to interferon-alpha correlates with differential induction of p19(INK4d) and cyclin D2 expression.
Interferon-alpha (IFN-alpha) has been used as therapy for the treatment of a variety of viral diseases and malignancies including multiple myeloma. The effectiveness of interferon-alpha in treating multiple myeloma, however, has been somewhat variable, and the mechanism(s) accounting for this is not well understood. As a means to examine the basis for the differential effectiveness of this cytokine, we have analyzed IFN-alpha-mediated modulation of the cell cycle in two human myeloma cell lines. These two cell lines, ANBL-6 and KAS-6/1, display dramatically different outcomes in response to this cytokine. Although IFN-alpha inhibited the growth of ANBL-6 cells by blocking cell cycle progression from G0/G1 to S phase, IFN-alpha stimulated cell cycle progression in KAS-6/1 cells. Moreover, the effects of IFN-alpha on cell cycle progression correlated with the phosphorylation status of the retinoblastoma protein. Of interest, IFN-alpha increased cyclin D2 expression and cyclin-dependent kinase activity in the KAS-6/1 cells but not in the ANBL-6 cells. To determine whether the differential effects of IFN-alpha on myeloma cell cycle progression could also result from differences in the expression of cyclin-dependent kinase inhibitors, we examined the effects of IFN-alpha on the induction of cyclin-dependent kinase inhibitors with broad regulatory function (p21 and p27) and those with specificity for G1-associated cyclin-cyclin-dependent kinase complexes (p15, p16, p18, and p19). Although we failed to detect an effect of IFN-alpha on expression levels of p21, p15, p16, or p18, IFN-alpha treatment of the ANBL-6 cell line resulted in induction of p19 expression, whereas it was without effect on the KAS-6/1 cell line. These results suggest that heterogeneity in IFN-alpha-mediated growth effects in myeloma cells correlates with differential induction of cyclin D2 and p19(INK4d) expression.


Complete Genome Sequence of Bacillus cereus Group Phage TsarBomba.
The Bacillus cereus group bacteriophage TsarBomba, a double-stranded DNA Myoviridae, was isolated from soil collected in Saratov, Russia. TsarBomba was found to be similar to Bacillus phages BCP78 and BCU4, and to have a wide host range among Bacillus cereus group species.


Cytomegalovirus appendicitis after hematopoietic stem cell transplantation.
We present the case of a young man with acute lymphoblastic leukemia who developed cytomegalovirus (CMV) appendicitis after receiving alemtuzumab for acute refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT). CMV appendicitis is a rare complication; and we are reporting the first case to our knowledge of CMV appendicitis following HSCT. Our case highlights the importance of recognition of CMV viral reactivation following the use of alemtuzumab. Using a preemptive strategy of checking CMV PCR, with initiation of early effective treatment on detection of CMV replication, may be appropriate following use of alemtuzumab in hematologic malignancies in patients after HSCT.


The variable discharge of cortical neurons: implications for connectivity, computation, and information coding.
Cortical neurons exhibit tremendous variability in the number and temporal distribution of spikes in their discharge patterns. Furthermore, this variability appears to be conserved over large regions of the cerebral cortex, suggesting that it is neither reduced nor expanded from stage to stage within a processing pathway. To investigate the principles underlying such statistical homogeneity, we have analyzed a model of synaptic integration incorporating a highly simplified integrate and fire mechanism with decay. We analyzed a "high-input regime" in which neurons receive hundreds of excitatory synaptic inputs during each interspike interval. To produce a graded response in this regime, the neuron must balance excitation with inhibition. We find that a simple integrate and fire mechanism with balanced excitation and inhibition produces a highly variable interspike interval, consistent with experimental data. Detailed information about the temporal pattern of synaptic inputs cannot be recovered from the pattern of output spikes, and we infer that cortical neurons are unlikely to transmit information in the temporal pattern of spike discharge. Rather, we suggest that quantities are represented as rate codes in ensembles of 50-100 neurons. These column-like ensembles tolerate large fractions of common synaptic input and yet covary only weakly in their spike discharge. We find that an ensemble of 100 neurons provides a reliable estimate of rate in just one interspike interval (10-50 msec). Finally, we derived an expression for the variance of the neural spike count that leads to a stable propagation of signal and noise in networks of neurons-that is, conditions that do not impose an accumulation or diminution of noise. The solution implies that single neurons perform simple algebra resembling averaging, and that more sophisticated computations arise by virtue of the anatomical convergence of novel combinations of inputs to the cortical column from external sources.


Prolyl oligopeptidase attenuates hepatic stellate cell activation through induction of Smad7 and PPAR-γ.
Prolyl oligopeptidase (POP) is a serine endopeptidase widely distributed in vivo with high activity in the liver. However, its biological functions in the liver have remained largely elusive. A previous study by our group has shown that POP produced N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) and thereby exerted an anti-fibrogenic effect on hepatic stellate cells (HSCs) in vitro. It was therefore hypothesized that POP may affect the activation state of HSCs and has an important role in liver fibrosis. The HSC-T6 immortalized rat liver stellate cell line was treated with the POP inhibitor S17092 or transfected with recombinant lentivirus to overexpress POP. Cell proliferation and apoptosis were determined using a Cell Counting Kit-8 and flow cytometry, respectively. The activation status of HSCs was determined by examination of the expression of α-smooth muscle actin (α-SMA), collagen I, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF)-β-Smad signaling and peroxisome proliferator activated receptor-γ (PPAR-γ). Inhibition by S17092 decreased, whereas lentiviral expression increased the activity of POP and cell proliferation, while neither of the treatments affected cell apoptosis. Of note, S17092 significantly increased, whereas POP overexpression decreased the expression of α-SMA and MCP-1 without affecting the expression of collagen I and TGF-β1. Furthermore, S17092 caused a reduction, whereas POP overexpression caused an upregulation of Smad7 protein and PPAR-γ, but not phosphorylated-Smad2/3 expression. In conclusion, POP attenuated the activation of HSCs through inhibition of TGF-β signaling and induction of PPAR-γ, which may have therapeutic potential in liver fibrosis.


cpsA regulates mycotoxin production, morphogenesis and cell wall biosynthesis in the fungus Aspergillus nidulans.
The model fungus Aspergillus nidulans synthesizes numerous secondary metabolites, including sterigmatocystin (ST). The production of this toxin is positively controlled by the global regulator veA. In the absence of veA (ΔveA), ST biosynthesis is blocked. Previously, we performed random mutagenesis in a ΔveA strain and identified revertant mutants able to synthesize ST, among them RM1. Complementation of RM1 with a genomic library revealed that the mutation occurred in a gene designated as cpsA. While in the ΔveA genetic background cpsA deletion restores ST production, in a veA wild-type background absence of cpsA reduces and delays ST biosynthesis decreasing the expression of ST genes. Furthermore, cpsA is also necessary for the production of other secondary metabolites, including penicillin, affecting the expression of PN genes. In addition, cpsA is necessary for normal asexual and sexual development. Chemical and microscopy analyses revealed that CpsA is found in cytoplasmic vesicles and it is required for normal cell wall composition and integrity, affecting adhesion capacity and oxidative stress sensitivity. The conservation of cpsA in Ascomycetes suggests that cpsA homologs might have similar roles in other fungal species.


Structural evolution and the control of defects in atomic layer deposited HfO2-Al2O3 stacked films on GaAs.
The structural characteristics and interfacial reactions of bilayered dielectric stacks of 3 nm HfO2/2 nm Al2O3 and 3 nm Al2O3/2 nm HfO2 on GaAs, prepared by atomic layer deposition (ALD), were examined during film growth and the postannealing process. During the postdeposition annealing (PDA) of the Al2O3/HfO2/GaAs structures at 700 °C, large amounts of Ga oxides were generated between the Al2O3 and HfO2 films as the result of interfacial reactions between interdiffused oxygen impurities and out-diffused atomic Ga. However, in the case of the HfO2/Al2O3/GaAs structures, the presence of an Al2O3 buffer layer effectively blocked the out-diffusion of atomic Ga, thus suppressing the formation of Ga oxide. Microstructural analyses showed that HfO2 films that were deposited on Al2O3/GaAs had completely crystallized during the PDA process, even at 700 °C, because of the Al2O3 diffusion barrier. Capacitance-voltage measurements showed a relatively large frequency dispersion of the Al2O3/HfO2/GaAs structure in accumulation capacitance compared to the HfO2/Al2O3/GaAs structure due to a higher interface state density. Conductance results revealed that the Al2O3 buffer layer on GaAs resulted in a significant reduction in gap states in GaAs. The induced gap state in the Al2O3/HfO2/GaAs structure originated from the out-diffusion of atomic Ga into the HfO2 film. Density functional theory calculations supported this conclusion.


[Dengue outbreaks in the French West-Indies in a context of arbovirosis emergence and reemergence].
In the French West Indies (Martinique, Guadeloupe and French Guyana), dengue represents a model of a reemerging arbovirosis, with hyperendemicity and more severe cases and deaths than previously observed Co-circulation of the four serotypes, the increasing number of cases during interepidemic periods, and the increase in severe forms (particularly hemorrhagic forms), are signs of forthcoming hyperendemicity. DEN-2 is the viral subtype most frequently associated with severe forms. Other arboviroses, like West Nile disease and chikungunya, overflowing from their usual geographical areas and with the potential to cause hemorrhagic syndromes and encephalitis, have emerged or reemerged in tropical zones of Africa, Asia, America and the Indian Ocean, but also in temperate areas of northern America and southern Europe. The risk of imported arboviroses, particularly dengue and chikungunya, is a real threat in temperate countries, including southern France, where Aedes albopictus, a vector mosquito, is present.


Evaluation of Probably Benign Adnexal Masses in Postmenopausal Women.
Background Preoperatively identification of malignancy potential of a postmenopausal adnexal masses is important. Aim To evaluate the effectiveness of the Risk of Malignancy Index-2 in presumably benign adnexal masses in postmenopausal women. Study Design Retrospective, observational study. Methods 119 women with postmenopausal adnexal masses with a preliminary diagnosis of benign tumors according to the Risk of Malignancy Index-2 were included. Age, duration of menopause, ultrasonographic findings, and serum CA-125 levels were recorded preoperatively. The definitive diagnosis was based on postoperative histopathological examination. Results Of 119 adnexal mass, 10 were malignant and 109 were benign. There was no statistically significant difference with regard to age and tumor size between the groups. The two significant ultrasonographic parameter between groups were the presence of solid area in the mass and bilaterality. Moreover, if the cut off point for serum CA-125 was adjusted to 14.75 IU/mL according to ROC curve, a sensitivity value of 80% and a specificity value of 72% could be achieved to discriminate benign and malign cysts. Conclusion In the differential diagnosis of benign and malignant adnexal masses in postmenopausal women, the presence of a solid component, bilaterallity based on ultrasonography and high CA-125 values may be used as discriminative criteria. There is no direct relation between the size of the adnexal mass and malignancy potential. Therefore, in the malignancy indexes of postmenopausal women, we recommend lower cut-off values of CA-125 to increase the sensitivity of preoperative evaluation tests without having a great impact on negative predictive values.


Alternate monolayers of CdSe nanocrystals and perylene tetracarboxylate: quantum dot hypersensitization for dye-sensitized solar cells.
Mono- and multilayers from CdSe nanocrystal dispersion and perylene tetracarboxylate solution are reported for the first time. The layers were investigated by UV-visible spectroscopy, cyclic voltammetry, photoconductivity, and photoelectrochemical techniques. The n-type organic semiconductor gives enhanced photoconductivity to the CdSe-NC multilayer structure. The photoactive perylene monolayer acts also as hypersensitizer of CdSe-NC structures. The perylene-modified CdSe-NC monolayer on indium tin oxide (ITO) electrode in a three-electrode photoelectrochemical cell upon illumination in the presence of oxygen generates an intense steady photocurrent as high as 10-20 times that expected from the individual contributions of perylene and CdSe-NCs. The hypersensitization mechanism is discussed on the basis of the energy level diagram of the components.


Evaluation of physicochemical and antioxidant properties of peanut protein hydrolysate.
Peanut protein and its hydrolysate were compared with a view to their use as food additives. The effects of pH, temperature and protein concentration on some of their key physicochemical properties were investigated. Compared with peanut protein, peanut peptides exhibited a significantly higher solubility and significantly lower turbidity at pH values 2-12 and temperature between 30 and 80°C. Peanut peptide showed better emulsifying capacity, foam capacity and foam stability, but had lower water holding and fat adsorption capacities over a wide range of protein concentrations (2-5 g/100 ml) than peanut protein isolate. In addition, peanut peptide exhibited in vitro antioxidant properties measured in terms of reducing power, scavenging of hydroxyl radical, and scavenging of DPPH radical. These results suggest that peanut peptide appeared to have better functional and antioxidant properties and hence has a good potential as a food additive.


Hemoglobin stability: observations on the denaturation of normal and abnormal hemoglobins by oxidant dyes, heat, and alkali.
Several unstable mutant hemoglobins have alterations which affect areas of the molecule involved in the attachment of heme to globin. Loss of heme from globin has been demonstrated during the denaturation of some of these unstable mutants. The importance of heme ligands for the stability of hemoglobin was illustrated in the present experiments on the denaturation of several hemoglobins and hemoglobin derivatives by heat, oxidative dyes, and alkali. Heating of normal hemolysates diluted to 4 g of hemoglobin per 100 ml at 50 degrees C for 20 hr in 0.05 M sodium phosphate, pH 7.4, caused precipitation of 23-54% of the hemoglobin. Dialysis against water or dilution of the sample decreased denaturation to 12-20%. Precipitation was decreased to less than 3.5% by the presence of 0.015 M potassium cyanide. Increasing the ionic strength of the medium increased precipitation. Cyanide prevented the formation of inclusion bodies when red cells containing unstable hemoglobin Philly, beta35 tyr --> phe, were incubated with the redox dye new methylene blue. Conversion to methemoglobin increased the rate of alkali denaturation of hemoglobin but the presence of potassium cyanide returned the denaturation rate to that of ferrohemoglobin. The ability of cyanide to decrease heat precipitation of hemoglobin may depend on a dimeric or tetrameric state of the hemoglobin molecule. Purified beta-chains, which exist as tetramers, were stabilized but purified monomeric alpha-chains were not rendered more heat resistant by the ligand. Stabilization of hemoglobin by cyanide required binding of the ligand to only one heme of an alphabeta-dimer. Hemoglobin Gun Hill, an unstable molecule with heme groups present only on the alpha-chains was quite heat stable in the presence of cyanide. The binding of cyanide to the iron atom in methemoglobin is thought to be associated with increased planarity of the heme group and increased stability of the heme-globin complex. The stabilizing effect of cyanide in the above experiments suggests that Heinz body formation, heat precipitation of hemoglobin, and the increased alkali denaturation of methemoglobin depend on changes of heme-globin binding.


Study of FABP's interactome and detecting new molecular targets in clear cell renal cell carcinoma.
Fatty acids (FAs) play a crucial role in the development of clear cell renal cell carcinoma (ccRCC), FAs function requires the participation of fatty-acid-binding protein (FABP). Current studies have shown that different members of the FABP's family play different roles in the tumorigenesis of ccRCC. Therefore, the systematic analysis of FABPs will be of great significance. However, the diverse expression patterns and prognostic values of nine FABPs have yet to be elucidated. In this study, through multiple analysis and verification of multiple databases, such as ONCOMINE, The Human Protein Atlas, UALCAN, Gene Expression Profiling Interactive Analysis, and cBioPortal, we found that the expression of FABP1 was significantly downregulated and the expression of FABP5/6/7 was significantly upregulated in ccRCC compared with renal tissues, and the patients with high messenger RNA (mRNA) levels of the FABP5/6/7 or low mRNA levels of FABP1 were predicted to have a lower overall survival or disease-free survival. Further analysis by the protein-protein interaction (PPI), Gene Ontology pathway, and Kyoto Encyclopedia of Genes and Genomes pathway showed that FABPs were mainly involved in the peroxisome proliferator-activated receptor (PPAR) pathway. In coexpression analysis, we found that FABP1/5/6/7 was coexpressed with transforming growth factor-β1 (TGF-β1), PPARA, and LPL. This study implied that FABP1/5/6/7 could act as an important tumor biomarker of ccRCC; the role of FABPs may be related to PPAR or TGF-β pathway.


Retrospective analysis of patients clinical manifestations before and after pheochromocytoma surgery.
A retrospective analysis of presurgical clinical picture and blood pressures of 34 patients with histologically verified pheochromocytoma. Assessment of clinical state, blood pressure and prognosis in the course of patients control hospitalizations from 2001 to 2002. The study was designed as a synoptic one, based on a retrospective analysis of 34 patients records with histologically verified pheochromocytoma (26 women and 8 men). Our assessments of clinical symptomatology, maximum paroxysmal hypertension values, average blood pressure values in patients with persistent arterial hypertension, arterial hypertension grade and circadian index were based on patients records. Patients epinephrectomies were followed during their control hospitalizations to assess their clinical state. Their blood pressures were evaluated by means of their circadian monitoring. From the 34 patients, 21 were diagnosed with solitary pheochromocytomas. The circadian index persistence analysis prior to the surgery was associated with circadian blood pressure monitoring in 21 patients. It was lost in 57% of patients. During their control hospitalization as many as 82% of patients preserved their circadian blood pressure variability with a more than 10% decrease in the night time, 5 patients did not preserve their circadian blood pressure variability. Seven from the original 34 patients died: Three of them died from their primary disease, one 63-year old man died from shock following tumour extirpation. The death of other 3 patients was not associated with their primary disease. Long-lasting survival of patients with pheochromocytoma after surgical treatment--except for those with malignant disease--was demonstrated. Although our assessment of the resulting treatment effects was positive, a long-term follow-up is inevitable because of a difficult pathologic-anatomical verification of the malignant nature of the disease as well as of the risk of tumour relapse assessment. (Tab. 1, Fig. 5, Ref 36.)


Oxygen-induced enzyme release after irreversible myocardial injury. Effects of cyanide in perfused rat hearts.
The effects of 5 mM potassium cyanide (KCN) on creatine phosphokinase (CPK) release and cellular morphology were studied. Rat hearts were perfused with substrate-deficient media gassed with O2 or N2 (O2 medium, N2 medium) at 37 C, and effluent was collected for creatine phosphokinase analysis. Tissue fixation was with glutaraldehyde for light and electron microscopy. Experiments included the following: a) continuous perfusion with O2- or N2-medium in the presence of KCN; b) 45 or 60 minutes of perfusion with N2-medium followed by O2-medium for 15 or 180 minutes, respectively; c) 45 minutes of perfusion with N2-medium with KCN added 15 minutes before reoxygenation with O2-medium plus KCN; (4) 60 minutes of N2-medium plus KCN followed by O2-medium plus KCN for 180 minutes; d) as a control for irreversible injury, 21 minutes of perfusion with calcium-free O2-medium followed by 2.5 mM calcium-O2-medium ("calcium paradox"). The following results were seen: a) Initial CPK release occurred about 30 minutes later from hearts perfused with O2-medium plus KCN than from hearts perfused with N2-medium plus KCN. b) Upon reoxygenation after either 45 or 60 minutes of anoxia, hearts had a sudden peak of oxygen-induced CPK release. Most irreversibly injured cells were massively swollen and had sarcolemmal defects and contraction bands. Reversibly injured cells in the same hearts resembled normal myocardium. A previously unrecognized third population of cells is described. These cells were characterized by contraction bands but were not swollen, had intact sarcolemma, and contained both normal and damaged mitochondria with intramatrical calcium accumulation granules. It could not be determined if these cells were reversibly injured or in an early stage of irreversible injury. c) KCN added 15 minutes before reoxygenation of hearts after 45 minutes of anoxia inhibited the sudden peak of oxygen-induced CPK release but not a slow sustained release. Small to moderate numbers of cells in these hearts contained contraction bands. d) After 60 minutes, KCN completely inhibited both oxygen-induced CPK release and contraction band formation. e) Addition of calcium to calcium-free hearts caused both massive CPK release and contraction band formation. It is concluded that: the beginning of CPK release from oxygenated KCN-inhibited hearts requires about 30 minutes longer than from anoxic hearts; KCN can inhibit both oxygen-induced CPK release and contraction bands in irreversibly injured rat myocardial cells; sudden contracture of myocardial cells as occurs in the calcium paradox can result in massive CPK release; contraction bands occur in nonswollen cells, hence contraction bands can occur independently of massive cell swelling or membrane rupture. It is postulated that there may be two stages of irreversible myocardial injury; a) loss of control of contraction and b) progressive loss of mitochondrial and membrane integrity.


Barriers to prescribing oral anticoagulants to inpatients aged 80 years and older with nonvalvular atrial fibrillation: a cross-sectional study.
To investigate the temporal trend of the prevalence of underprescription of anticoagulation treatment and explore the factors associated with underprescription of oral anticoagulants (OACs) among inpatients aged ≥ 80 years with nonvalvular atrial fibrillation (NVAF). We retrospectively reviewed the medical records of inpatients with a discharge diagnosis of NVAF from a medical database. We used the Pearson chi-square or Fisher's exact test to compare categorical variables between patients with and without OAC prescriptions during hospitalization. Logistic regression analysis was used to assess the association between risk factors and underprescription of OACs. A total of 4375 patients aged ≥ 80 years with AF were assessed in the largest academic hospital in China from August 1, 2016, to July 31, 2020, and 3165 NVAF patients were included. The prevalence of underprescription of OACs was 79.1% in 2017, 71.3% in 2018, 64.4% in 2019, and 56.1% in 2020. Of all participants, 2138 (67.6%) were not prescribed OACs; 66.3% and 68.2% of patients with and without prior stroke did not receive OACs, respectively. Age (85-89 vs 80-84, OR = 1.48, 95% CI (1.25-1.74); 90 + vs 80-84, OR = 2.66, 95% CI: 2.09-3.42), clinical department where patients were discharged (Reference = Cardiology, Geriatrics: OR = 2.97, 95% CI: 2.45- 3.61; neurology: OR = 1.25, 95% CI: 0.96, 1.63; others: OR = 4.23, 95% CI: 3.43- 5.24), use of antiplatelets (OR = 1.69, 95% CI: 1.45- 1.97), and history of stroke (OR = 0.83, 95% CI: 0.71- 0.98 adjusted age), and dementia (OR = 2.16, 95% CI: 1.60- 2.96) were significantly associated with not prescribing OACs. The prevalence of underprescription of OACs has decreased over the past several years. The rate of underprescription of OACs was higher among NVAF patients who were older, prescribed antiplatelets, discharged from nondepartmental cardiology, and suffered from comorbidities. This study found iatrogenic factors affecting the underprescription of OACs in inpatients aged ≥ 80 years, providing clues and a basis for the standardized use of OACs in inpatients.


TFCP2 Genetic Polymorphism Is Associated with Predisposition to and Transplant Prognosis of Hepatocellular Carcinoma.
TFCP2 is an oncogene and plays crucial roles in the incidence and progression of hepatocellular carcinoma (HCC). However, no reports are available on the impact of TFCP2 genetic polymorphism on the susceptibility to and the transplant prognosis of HCC. Here, we genotyped 7 SNPs of TFCP2 in a case-control study of 119 patients with HCC and 200 patients with chronic liver disease. Of the 7 SNPs in TFCP2, rs7959378 distributed differentially between patients with versus patients without HCC. The patients with the CA (OR = 0.58, 95% CI = 0.35-0.96), the CC (OR = 0.39, 95% CI = 0.20-0.76), and the CA/CC (OR = 0.52, 95% CI = 0.32-0.83) genotypes had significantly decreased risk for HCC compared with those carrying the rs7959378 AA genotype. After adjusting for confounding factors, rs7959378 still conferred significant risk for HCC. Furthermore, the patients who carried rs7959378 AC/CC had a higher overall survival and lower relapse-free survival than those with the rs7959378 AA genotype. Similar results were found in the multivariate analysis adjusted by AFP, tumor size and tumor number, and differentiation. These findings indicate that rs7959378 is associated with the risk of HCC in patient with chronic liver disease and prognosis of HCC patients after liver transplantation.


Small molecular amine mediated synthesis of hydrophilic CdS nanorods and their photoelectrochemical water splitting performance.
Photoelectrochemical (PEC) water splitting is a promising route for solar energy harvesting and storage, but it has been highly limited by the performance of the semiconductor photoelectrodes. Herein, we report a small molecular amine-mediated solvothermal method for synthesizing CdS nanorods. The obtained CdS nanorods are hydrophilic and can be easily dispersed in water. Furthermore, the small molecular amine, activating elemental sulfur and mediating the growth of CdS, all play a role similar to that of long-chain surfactant molecules in "non-aqueous" systems. Thus, the obtained CdS nanorods show uniform shape with monodispersed size, the length of which can be tuned by the sulfur dosage. In addition, the CdS nanorods show a broader light absorption than CdS nanoparticles. Their photoelectrochemical water splitting performances were then tested. Under light irradiation of λ > 200 nm, the photocurrent density of CdS nanorods at -0.2 V bias potential (vs. Ag/AgCl) is found to be 25 times of that obtained with CdS nanoparticles. The present finding demonstrates that small amine molecules could be efficient mediators for the synthesis of hydrophilic sulfides with high quality. The simple synthesis method and the good photoelectrochemical properties illustrate the hydrophilic CdS nanorods are potential candidate for photoelectrochemical applications.


Primary cutaneous non-Hodgkin's lymphoma with aggressive histology: inferior outcome is associated with peripheral T-cell type and elevated lactate dehydrogenase, but not extent of cutaneous involvement.
The aim of this study was to explore the association between extent of cutaneous involvement, presenting features and progression-free survival (PFS) in patients with primary cutaneous non-Hodgkin's lymphoma (PCNHL) of aggressive histology. Previously untreated patients with localized or extensive PCNHL of aggressive histology, treated with combination chemotherapy, but excluding lymphoblastic lymphoma and mycosis fungoides and its variants, were reviewed retrospectively. We identified 53 patients, of whom 52 (35 males, 17 females) were treated with doxorubicin-based regimens. Median age was 52 years (range 25-81 years), and disease was localized and extensive in 37 and 16 patients, respectively. Twenty-four patients had diffuse large B-cell lymphoma, nine had grade 3 follicular lymphoma, 13 had peripheral T-cell lymphoma (PTCL; not otherwise specified) and seven had anaplastic large cell lymphoma (WHO classification). With a median follow-up of 101 months (range 2-237 months) for survivors, the 10-year PFS was 65 +/- 7% and overall survival was 72 +/- 8%. The first failure involved the skin in 33% of B-cell and 91% of relapsing T-cell lymphomas. Univariate analysis revealed that PTCL (P = 0.005), lymphopenia (P = 0.01) and high serum levels of beta(2)-microglobulin (P = 0.0006) and LDH (P = 0.002), but not extent of skin involvement, were associated with inferior PFS. Multivariate analysis revealed that only PTCL and high serum lactate dehydrogenase (LDH) were independently associated with inferior PFS. PTCL and elevated serum LDH level, but not extent of cutaneous involvement are associated with inferior PFS in aggressive PCNHL treated with combination chemotherapy.


Comparative anatomy of arterial vascularization of the rhinencephalon in man, cat and sheep.
The aim of this study was anatomical and comparative examination of arterial vascularization of the rhinencephalon in man and in macrosmatic mammals. The studies were performed by the own injection method on 27 human brains and 27 animal ones. The cerebral arteries were injected with synthetic colored latex and then prepared in an operating microscope. It was found, that the structure, topography and vascular areas of arteries supplying the rhinencephalon in man and animals are different. Contrary to the human rhinencephalon, strongly developed rhinencephalon in cat and sheep possess its own separate arterial pattern composed of special arteries for each regions of paleocortex, supplying the olfactory bulb and lobe. In the cat and sheep brains, the region corresponding to the human anterior perforated substance comprises the greater rhinencephalon surface. It includes the olfactory tubercle and sulcus between the olfactory and pyriform lobes. Extracerebral segments of the internal arterioles of the anterior and middle cerebral arteries in man and animals have different topography and courses. In the human brain, the studied arterioles originate from the maternal arteries with singular trunks or vascular pedicles and then enter directly the anterior perforated substance. In the cat and sheep brain they derive in two forms: as trunks divided into cortical branches of the olfactory lobe running on the olfactory tubercle surface and penetrating it, as well as singular trunks that enter the brain just over the maternal arteries. In contrary to the extracerebral segments of the anterior perforating arteries in man, analogical arterioles in the cat and sheep brains form numerous anastomoses. Thus, they create anatomical conditions for collateral circulation.


Response to an unusual outbreak in a high-risk situation.
In 2010, a series of lead poisoning outbreaks linked to artisanal gold processing killed at least 400 young children in Zamfara State in northwestern Nigeria. There were several efforts to respond to the outbreaks as they occurred. Subsequent recurrence of lead poisoning outbreaks within Zamfara and beyond suggested that there were no efforts to mitigate the outbreaks as recommended for disaster management. This case study, to be completed within 3 hours, is suitable for senior level public health officials and those training for such positions. It enables participants to review and apply epidemiological principles for managing disasters and suggest steps toward development of policy recommendations based on the context of environmental lead exposure. It will serve as a generic training module for managers/responders of other natural (floods, heat stroke) and man-made disasters (civil strife, conflict, insurgency) based on the general/standard principle of the complete disaster management cycle.


Development of Untargeted Metabolomics Methods for the Rapid Detection of Pathogenic Naegleria fowleri.
Despite comparatively low levels of infection, primary amoebic meningoencephalitis (PAM) induced by Naegleria fowleri is extremely lethal, with mortality rates above 95%. As a thermophile, this organism is often found in moderate-to-warm climates and has the potential to colonize drinking water distribution systems (DWDSs). Current detection approaches require days to obtain results, whereas swift corrective action can maximize the benefit of public health. Presently, there is little information regarding the underlying in situ metabolism for this amoeba but the potential exists to exploit differentially expressed metabolic signatures as a rapid detection technique. This research outlines the biochemical profiles of selected pathogenic and nonpathogenic Naegleria in vitro using an untargeted metabolomics approach to identify a panel of diagnostically meaningful compounds that may enable rapid detection of viable pathogenic N. fowleri and augment results from traditional monitoring approaches.


A new species of Espeletiopsis (Millerieae, Asteraceae) from Colombia.
A new species of Espeletiopsis was found in two small páramos of Norte de Santander, Colombia. The species is named Espeletiopsis diazii honoring the contributions of Santiago Díaz-Piedrahita in recognition of his vast knowledge of the Compositae in Colombia. This is a very distinctive species, markedly different from most of the Espeletiopsis present in Colombia. The new species is closely related to Espeletiopsis caldasii and Espeletiopsis santanderensis, but differs in having (1-)4-6(-7) capitula, with very short peduncles, and capitula arranged in a compact or densely glomerate cyme. With a total distribution area of less than 75 km(2), this species is probably critically endangered or imperiled.


Prorenin receptor blockers: effects on cardiovascular complications of diabetes and hypertension.
When the 'handle region' of the prorenin prosegment interacts with the (pro)renin receptor, the prorenin molecule partially changes the conformation to an enzymatically active state. On the other hand, the receptor triggers its own intracellular signalling pathways independent of the renin-angiotensin system (RAS). The 'handle region' peptide competitively binds to the receptor as a decoy peptide and inhibits both the non-proteolytic activation of prorenin and the RAS-independent intracellular signals. Therefore, prorenin receptor blockers including the decoy peptide may have superior benefits on end-organ damage in diabetes and hypertension compared with conventional RAS inhibitors.


Preformed Ω-profile closure and kiss-and-run mediate endocytosis and diverse endocytic modes in neuroendocrine chromaffin cells.
Transformation of flat membrane into round vesicles is generally thought to underlie endocytosis and produce speed-, amount-, and vesicle-size-specific endocytic modes. Visualizing depolarization-induced exocytic and endocytic membrane transformation in live neuroendocrine chromaffin cells, we found that flat membrane is transformed into Λ-shaped, Ω-shaped, and O-shaped vesicles via invagination, Λ-base constriction, and Ω-pore constriction, respectively. Surprisingly, endocytic vesicle formation is predominantly from not flat-membrane-to-round-vesicle transformation but calcium-triggered and dynamin-mediated closure of (1) Ω profiles formed before depolarization and (2) fusion pores (called kiss-and-run). Varying calcium influxes control the speed, number, and vesicle size of these pore closures, resulting in speed-specific slow (more than ∼6 s), fast (less than ∼6 s), or ultrafast (<0.6 s) endocytosis, amount-specific compensatory endocytosis (endocytosis = exocytosis) or overshoot endocytosis (endocytosis > exocytosis), and size-specific bulk endocytosis. These findings reveal major membrane transformation mechanisms underlying endocytosis, diverse endocytic modes, and exocytosis-endocytosis coupling, calling for correction of the half-a-century concept that the flat-to-round transformation predominantly mediates endocytosis after physiological stimulation.


Gp91phox NADPH oxidase modulates litter size by regulating mucin1 in the uterus of mice.
Active oxygen derived from gp91phox is critical for gestation. However, no reports have evaluated the relationship between reactive oxygen species (ROS) and the number of births in a given pregnancy. In this study, we examined the influence of ROS produced by gp91phox activity on the number of births using C57BL/6j (control) and gp91phox-knockout (gp91phox-/-) mice. The number of births in gp91phox-/- mice was found to be lower than that in control mice. We observed sequential increases in gp91phox, ROS, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-18 (IL-18), followed by increased expression of mucin1 (MUC1), in control mice. However, none of these markers were upregulated in gp91phox-/- mice. In addition, in control mice administered IL-18 or MUC1 inhibitors, the number of births decreased to a number similar to that of gp91phox-/- mice. These results suggest that ROS derived from gp91phox activity altered the inflammatory system and produced IL-18, which subsequently increased the expression of MUC1, thereby modulating fetal development. IL-1 β: interleukin-1β; IL-18: interleukin-18; NLRP3: nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; IgA: immunoglobulin A; MUC1: mucin1.


Renal Medullary Carcinoma; A Rare Entity.
Renal medullary carcinoma (RMC) is an uncommon aggressive neoplasm of the kidney. RMC is biologically aggressive with a very poor prognosis, and metastasis is seen in up to 95% of the patients at diagnosis or shortly thereafter. The common sites of metastasis are respectively lymph nodes, lungs, livers, and adrenal glands in order of frequency. The presence of poorly differentiated eosinophilic cells in a characteristic fibro-inflammatory stroma is seen in histological examination. The origin and pathogenesis of RMC are unclear. The radiographical and pathological findings suggest that RMC probably originates in the calyceal epithelium in or near the renal papillae, which could be the result of chronic ischemic damage in the renal papillae epithelium by sickled erythrocytes. Positivity of VEGF and HIF-1α supports the chronic hypoxia that may be caused in the pathogenesis of RMC. Other factors such as genetic or environmental factors are important. Although hemoglobinopathy is very common, RMC is very rare. An understanding of the molecular and genetic factors of this rare disease is important for its prevention and treatment. We herein describe an adult Turkish patient, who presented with hematuria. The diagnosis was RMC after pathological examination.


History of plastid DNA insertions reveals weak deletion and at mutation biases in angiosperm mitochondrial genomes.
Angiosperm mitochondrial genomes exhibit many unusual properties, including heterogeneous nucleotide composition and exceptionally large and variable genome sizes. Determining the role of nonadaptive mechanisms such as mutation bias in shaping the molecular evolution of these unique genomes has proven challenging because their dynamic structures generally prevent identification of homologous intergenic sequences for comparative analyses. Here, we report an analysis of angiosperm mitochondrial DNA sequences that are derived from inserted plastid DNA (mtpts). The availability of numerous completely sequenced plastid genomes allows us to infer the evolutionary history of these insertions, including the specific nucleotide substitutions and indels that have occurred because their incorporation into the mitochondrial genome. Our analysis confirmed that many mtpts have a complex history, including frequent gene conversion and multiple examples of horizontal transfer between divergent angiosperm lineages. Nevertheless, it is clear that the majority of extant mtpt sequence in angiosperms is the product of recent transfer (or gene conversion) and is subject to rapid loss/deterioration, suggesting that most mtpts are evolving relatively free from functional constraint. The evolution of mtpt sequences reveals a pattern of biased mutational input in angiosperm mitochondrial genomes, including an excess of small deletions over insertions and a skew toward nucleotide substitutions that increase AT content. However, these mutation biases are far weaker than have been observed in many other cellular genomes, providing insight into some of the notable features of angiosperm mitochondrial architecture, including the retention of large intergenic regions and the relatively neutral GC content found in these regions.


[Seroprevalence of Leptospira spp in population groups of Villavicencio, Colombia].
Determining Leptospira spp . antibody seroprevalence in an apparently healthy population and in groups at risk plus their associated factors in the town of Villavicencio in the Meta department of Colombia A cross-sectional epidemiological model was used (subjects being selected by convenience sampling). Blood-samples were obtained by cubital puncture from (n: 503) people, consisting of 230 first semester students from different programmes at the Universidad de los Llanos and 273 people corresponding to 8 groups at risk. Information regarding risk factor was obtained from interviewing the 503 people. A commercial indirect ELISA kit (Pambio) was used for determining IgM antibodies. Seroprevalence was 5,2 % in the low risk group. There was 19 % seroprevalence for groups at risk, 7 % for the group of people working in slaughterhouses, 17 % for vets and small animal clinic assistants, 17 % for students in their last year of Veterinary Medicine and Zootechnia, 21 % for people milking cows on dual-purpose farms, 23 % for people working in rice-fields, 35 % for people working on pig-farms and 48 % for those working on fish-farms. Three factors were found to be associated: rural social level, having a pet dog and coming into contact with rodents in the workplace. A high seroprevalence for Leptospira spp was found in the groups at risk, people working on pig-farms and fish-farms being those most affected. There was a 1,86 relative risk in both groups indicated as having a greater risk of contagion amongst the population suffering occupational exposure.


Clinical significance of quantitative analysis of plasma epstein- barr virus DNA in patients of Xinjiang Uygur nationality with Hodgkin's Lymphoma.
To investigate the relationship between plasma EBV-DNA concentration and clinicopathologic features of Hodgkin's lymphoma cases. At first, the positive rate of plasma EBV-DNA was determined with a nested-PCR method using 45 specimens from Uygur HL patients, as well as 110 healthy people sampled as normal controls. Secondly, using fluorescent quantitative nested-PCR, EBV viral load was assessed in the EBV-DNA positive plasma samples. Then, relationships between plasma EBV viral load and clinicopathologic features of HL patients were analyzed. The positive rate of plasma EBV-DNA of HL patients was significantly higher than that of normal controls (53.3%vs26.4%, P=0.001). There was no significant difference about plasma EBV viral load between EBV-associated HL and EBV-DNA positive normal people (P=0.490). Looking at patients' characteristics, plasma EBV viral load in 10-20 years EBV-associated HL was higher than in EBV cases which were less than 10 years or more than 35 years (P=0.025). Furthermore, in EBV-associated HL, concentration of plasma EBV-DNA was significantly higher in advanced stage disease (stages III-IV; P=0.013), and with B-symptoms (P=0.020). EBV-DNA levels were associated with part of clinicopathologic features of cases. It was of practical use to screen HL. Further etiological studies appear warranted.


Prevention and treatment of nutritional rickets.
Nutritional rickets continues to be a significant health problem for children worldwide with recent evidence of increasing incidence in many developed countries. It is due to vitamin D deficiency and/or inadequate dietary calcium intake with variation in the relative contributions of each of these dependant on environmental factors such a dietary intake and sunlight exposure. Key to the prevention of rickets is ensuring that pregnant women and their infants receive vitamin D supplementation with good evidence from randomised controlled trials that infants who receive 400iu daily can achieve levels of 25 hydroxyvitamin D of >50nmol/l. However, public health implementation of daily supplementation is more challenging with a need to revisit food fortification strategies to ensure optimal vitamin D status of the population. Treatment of nutritional rickets has traditionally been with vitamin D2 or D3, often given as a daily oral dose for several weeks until biochemical and radiological evidence of healing. However, other treatment regimes with single or intermittent high doses have also proved to be effective. It is now recognised that oral calcium either as dietary intake or supplements should be routinely used in conjunction with vitamin D for treatment.


Caretta - A multiple protein structure alignment and feature extraction suite.
The vast number of protein structures currently available opens exciting opportunities for machine learning on proteins, aimed at predicting and understanding functional properties. In particular, in combination with homology modelling, it is now possible to not only use sequence features as input for machine learning, but also structure features. However, in order to do so, robust multiple structure alignments are imperative. Here we present Caretta, a multiple structure alignment suite meant for homologous but sequentially divergent protein families which consistently returns accurate alignments with a higher coverage than current state-of-the-art tools. Caretta is available as a GUI and command-line application and additionally outputs an aligned structure feature matrix for a given set of input structures, which can readily be used in downstream steps for supervised or unsupervised machine learning. We show Caretta's performance on two benchmark datasets, and present an example application of Caretta in predicting the conformational state of cyclin-dependent kinases.


Coding region prediction based on a universal DNA sequence representation method.
Graphical representation of DNA sequences provides a simple and intuitive way of viewing, anchoring, and comparing various gene structures, so a simple and non-degenerate method is attractive to both biologists and computational biologists. In this study, a universal graphical representation method for DNA sequences based on S.S.-T. Yau's method is presented. The method adopts a trigonometric function to represent the four nucleotides A, G, C, and T. Some interesting characteristics of the universal representation are introduced. We exploit frequency analysis with our representation method on DNA sequences, demonstrating possible applications in coding region prediction, and sequence analysis. Based on the statistically experimental results from this frequency analysis, a simple coding region predictor and an optimized one are presented. An experiment on the broadly accepted ROSETTA data set demonstrates that the performance of the optimized predictor is comparable to that of other popular methods.


Elevation of cellular BPDE uptake by human cells: a possible factor contributing to co-carcinogenicity by arsenite.
Arsenite (iAsIII) can promote mutagenicity and carcinogenicity of other carcinogens. Considerable attention has focused on interference with DNA repair by inorganic arsenic, especially the nucleotide excision repair (NER) pathway, whereas less is known about the effect of arsenic on the induction of DNA damage by other agents. We examined how arsenic modulates DNA damage by other chemicals. We used an NER-deficient cell line to dissect DNA damage induction from DNA repair and to examine the effects of iAsIII on the formation of benzo[a]pyrene diol epoxide (BPDE)-DNA adducts. We found that pretreatment with iAsIII at subtoxic concentrations (10 microM) led to enhanced formation of BPDE-DNA adducts. Reduced glutathione levels, glutathione S-transferase activity and chromatin accessibility were also measured after iAsIII treatment, but none of these factors appeared to account for the enhanced formation of DNA adducts. However, we found that pretreatment with iAsIII increased the cellular uptake of BPDE in a dose-dependent manner. Our results suggest that iAsIII enhanced the formation of BPDE-DNA adducts by increasing the cellular uptake of BPDE. Therefore, the ability of arsenic to increase the bioavailability of other carcinogens may contribute to arsenic co-carcinogenicity.


Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review.
Human immunodeficiency virus type I (HIV-1) is associated with a spectrum of neurological disorders. At the time of primary HIV-1 infection, an acute aseptic meningitis or encephalitis indicates central nervous system invasion. Evidence of HIV-1 infection is found in the CSF of most asymptomatic seropositive individuals, suggesting viral persistence in the nervous system. After a long incubation period, viral activation is signaled by expression of HIV-1 antigen in the CSF, which correlates with a profound dementia in adults or with an analogous progressive encephalopathy in children. The neuropathological substrate of this dementing process consists of multinucleated giant cells and diffuse white matter pallor. Immunocytochemical and in situ hybridization studies demonstrate that antigen presenting cells, including blood derived macrophages and resident brain microglia, are directly infected by HIV-1, and participate in the formation of the syncytial giant cells. Astrocytes and endothelial cells may also be infected, but evidence for infection of oligodendroglia and neurons is lacking. Studies of lentiviral encephalitides in ungulates and non-human primates emphasize the importance of specific viral antigenic stimulation and the role of inflammatory cells as direct or indirect mediators of tissue damage. The disorders of the peripheral nervous system described in patients with HIV-1 infection have not been convincingly linked to direct viral infection. At least two of the neuromuscular complications, the inflammatory motor neuropathy and polymyositis are likely to have an autoimmune pathogenesis.


Detrimental effect of electromagnetic pulse exposure on permeability of in vitro blood-brain-barrier model.
To study the effect of electromagnetic pulse (EMP) exposure on permeability of in vitro blood-brain-barrier (BBB) model. An in vitro BBB model, established by co-culturing brain microvascular endothelial cells (BMVEC) and astroglial cells (AC) isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance (TEER) and the horseradish peroxidase (HRP) transmission at different time points. Levels of BBB tight junction-related proteins were measured at 0, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting. The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure. EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability.


Clinical usefulness of ambulatory blood pressure monitoring.
During the last decade, ambulatory blood pressure monitoring (ABPM) made a transition from a method reserved for clinical investigators to a technique considered useful by practicing physicians in assessing certain problems in hypertension. Recent recommendations of the National High Blood Pressure Education Program (NHBPEP) Working Group on Ambulatory Blood Pressure Monitoring suggested using ABPM for a number of clinical problems, including borderline hypertension without target organ damage, evaluation of drug resistance, and white-coat hypertension. We evaluated the clinical indications for ordering ABPM by Connecticut physicians both in hospital and community-based practices. Through specific questionnaires, the clinical indications used by referring physicians to order ABPM and their inclinations for future use of the methodology were assessed. Forty-seven of 70 physicians (65%) responded to the questionnaire, basing their answers on 237 patients. The majority of physicians were internists (57%) or cardiologists (25%). Leading indications for patient referral for ABPM included borderline hypertension (27%), assessment of drug therapy/BP control (25%), and possible white-coat hypertension (22%). Far fewer referrals were observed for severe hypertension or as a routine test for the diagnosis of hypertension. These data suggest that practicing physicians have become aware of the usefulness of ambulatory blood pressure recordings and are following the NHBPEP guidelines on referral for the study.


Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells.
Dendrite morphology of neurons provides a structural basis for their physiological characteristics, and is precisely regulated in a cell type-dependent manner. Using a unique transposon-mediated gene transfer system that enables conditional and cell-type specific expression of exogenous genes, we investigated the role of cadherin on dendritic morphogenesis of horizontal cells in the developing chicken retina. We first visualized single horizontal cells by overexpressing membrane-targeted EGFP, and confirmed that there were three subtypes of horizontal cells, the dendritic terminals of which projected to distinct synaptic sites in the outer plexiform layer. Expression of a dominant-negative cadherin decreased the dendritic field size, and perturbed the termination of dendritic processes onto the photoreceptor cells. The cadherin blockade also impaired the accumulation of GluR4, a postsynaptic marker, at the cone pedicles. We thus provide in vivo evidence that cadherin is required for dendrite morphogenesis of horizontal cells and subsequent synapse formation with photoreceptor cells in the vertebrate retina.


Dacryocystitis caused by community-onset methicillin-resistant Staphylococcus aureus.
To describe the occurrence of community-onset methicillin-resistant Staphylococcus aureus (MRSA) infections of the lacrimal system and their treatment. This cases series consisted of data obtained from seven clinical cases of acute or subacute MRSA dacryocystitis, with or without concurrent conjunctivitis, occurring in nonhospitalized individuals presenting between December 2001 and July 2003. Clinical presentations, microbial culture results, treatment modalities, and outcomes were retrospectively reviewed. Three patients were successfully treated with antibiotics and lacrimal surgery with no recurrence of symptoms after surgery for 6 months or longer. Four patients had temporary relief of symptoms with antibiotic therapy, but surgery was not performed for non-ophthalmologic reasons, and recurrence occurred. The treatment of MRSA dacryocystitis can be challenging. Microbiologic cultures should be performed in all patients with dacryocystitis that is unresponsive to conventional first-line antibiotic treatment and in patients at risk for acquisition of MRSA. Appropriate antibiotic therapy in combination with dacryocystorhinostomy appears to be the optimal treatment.


Effects of the histone deacetylase inhibitor, trichostatin A, in a chronic allergic airways disease model in mice.
There is a need for new asthma therapies that can concurrently address airway remodeling, airway hyperresponsiveness and progressive irreversible loss of lung function, in addition to inhibiting inflammation. Histone deacetylase inhibitors (HDACi) alter gene expression by interfering with the removal of acetyl groups from histones. The HDACi trichostatin A (TSA) has pleiotropic effects targeting key pathological processes in asthma including inflammation, proliferation, angiogenesis and fibrosis. The aim was to evaluate the effects of TSA treatment in a mouse model of chronic allergic airways disease (AAD). Wild-type BALB/c mice with AAD were treated intraperitoneally with 5 mg/kg TSA or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid (BALF) cell counts and histological examination of lung tissue sections. Remodeling was assessed by morphometric analysis and airway hyperresponsiveness was assessed by invasive plethysmography. TSA-treated mice had a reduced number of total inflammatory cells and eosinophils within the BALF as compared to vehicle-treated mice (both p < 0.05). Furthermore, airway remodeling changes were significantly reduced with TSA compared to vehicle-treated mice, with fewer goblet cells (p < 0.05), less subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness at the highest methacholine dose. These findings demonstrate that treatment with an HDACi can concurrently reduce structural airway remodeling changes and airway hyperresponsiveness, in addition to attenuating airway inflammation in a chronic AAD model. This has important implications for the development of novel treatments for severe asthma.


Early puberty in adopted children.
Early puberty is frequently observed in adopted children. In various studies, early puberty has been associated with decreased final height. In Europe, studies were undertaken to treat early puberty in adopted children with GnRH agonist. This article reviews the current understanding of early puberty in adopted children, including prevalence, background and treatment options. Data from the European studies are briefly described. Besides auxological aspects, psychological items are addressed as well. Studies on the psychological effect of early puberty in adopted children are reported. Future issues include further study in the mechanism of early puberty in adopted children, evaluation of final height results of the growth studies and quality of life assessments in this specific group of children.


Karyotypes of Elymus scabrifolius (Poaceae: Triticeae) from South America studied by banding techniques and in situ hybridization.
Karyotypes of 4 accessions of Elymus scabrifolius (2n = 4x = 28) were investigated by Giemsa C- and N-banding, GAA-banding (one accession), AgNO3-staining and in situ hybridization with the rDNA probe pTa71. Two additional accessions were studied in less detail. The chromosomes were large (9-14 microns). The complements included 11 pairs of metacentrics, one with conspicuous satellites on the short arms, and 3 pairs of submetacentrics. Two of 4 accessions from Eastern Argentina and Uruguay had minute or small satellites on a submetacentric pair. No such satellites were observed in the other two accessions. In two accessions from the Cordoba province, a non-homologous submetacentric pair had very long satellites. AgNO3-staining established the presence of 4 nucleoli, two larger and two small ones, in 5 accessions. The C-banding patterns comprised from one to 12 conspicuous bands per chromosome at no preferential positions. The amount of constitutive heterochromatin (19-21%) was the highest hitherto established in the Triticeae. Similarities in banding patterns and chromosome morphology identified homologous and discriminated between non-homologous chromosomes within and, except for two chromosomes, between plants. Heteromorphic chromosome pairs were identified in satellite-carrying chromosomes only. N-banding produced conspicuous bands overall at the same positions as C-banding. GAA-banding patterns were similar to N-banding patterns. The rDNA probe hybridized to chromosome segments at nucleolar constrictions only. The production of C- and N-banding patterns in both genomes of E. scabrifolius suggests the presence of two H genomes and the absence of the pivotal St genome of Elymus. On account of the uncertain identity of one genome, and the overall similar gross morphology of E. scabrifolius and other tetraploid South American species referred to Elymus, E. scabrifolius is retained in Elymus.


The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage.
A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species. We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013. These duck viruses have genetic background distinct from the zoonotic H7N9 lineage. We found that the introduction of PB2 mutation with K at 627 but not K at 591 or N at 701 to the duck H7N9 virus led to increased pathogenicity in mice. We also found that the induction of pro-inflammatory cytokines including TNF-α, IP-10, MCP-1 and MIP-1α were associated with increased severity of infection. We conclude that introduction of the mammalian adaptation mutations into the PB2 gene of duck H7N9 viruses, which are genetically unrelated to the zoonotic H7N9 lineage, can also enhance pathogenicity in mice.


Transfer of the horizontal patient: the effect of a friction reducing assistive device on low back mechanics.
Recognizing that the transfer of bedridden patients is associated with a high rate of low back injuries, various devices have been developed to assist with sparing the patient handlers. The purpose of this study was to quantify the friction-reducing ability of three different 'sliding' patient transfer devices together with the subsequent consequences on the low back loads of people performing the transfers. Coefficients of friction of the devices were determined by 'transferring' a standard object and a 'patient' over several surfaces common to a hospital setting. Then three participants performed controlled transfers with the various devices. Electromyography to measure muscle activation levels together with external forces and kinematic positional data were collected during push, pull and twist transfers. Spine loads were estimated with a three-dimensional biomechanical static link-segment model of the human body. Simply sliding a patient on a cotton sheet (control condition) produced a coefficient of friction of 0.45. The assistive devices substantially reduced friction by well over one-half (coefficients of 0.18 - 0.21). However, when using the devices the subjects adopted a variety of postures and techniques, such that there were no consistent influences on trunk inclination, low back compression or muscle activation profiles. Direct measurement of reduced friction between the bed and the patient with a friction-reducing device together with measurement of the back loads when actually transferring a patient formed a proof of principle. Specifically, while the device lowers friction, the transfer technique adopted by the lifter must be proper to reduce low back loading and any subsequent risks of back troubles associated with patient transfers. The direction of hand forces and torso position remains important.


Failure of multiple-site intradermal postexposure rabies vaccination in patients with human immunodeficiency virus with low CD4+ T lymphocyte counts.
Human immunodeficiency virus (HIV)-infected patients with low CD4(+) T lymphocyte counts had a poor neutralizing antibody response to pre- and postexposure rabies vaccination. This study of HIV-infected patients with CD4(+) T lymphocyte counts < 200/microL indicated that patients had a poor response after 4-site intradermal vaccinations (4-4-4-0-2-2, doubling the intradermal doses of cell-culture rabies vaccine).


Highly Er(3+)-doped ZrF4-based fluoride glasses for 2.7 μm laser materials.
A new type of fluoride glasses with high erbium-doping concentration (up to 6 mol. % Er(3+)) is investigated. The intensive 2.7 μm fluorescence is demonstrated with minimized concentration quenching. The intensity parameters and radiative properties are determined from the absorption spectrum based on the Judd-Ofelt theory. The prepared Er(3+)-doped ZBYA glass possesses high predicted spontaneous-transition probability (28.92 s(-1)) and large calculated emission cross section (9.8×10(-21) cm(2)). All these results indicate that this Er(3+)-doped ZrF(4)-based fluoride glass has potential applications in 2.7 μm laser materials.


Prosthetic rehabilitation of a patient with mandibular resection prosthesis using mini dental implants (MDIs)--case report.
Physical disfigurement and functional impairments associated with facial trauma are a challenge to a prosthodontist, because even novel sophisticated surgical reconstructive techniques fail to provide adequate support for dental resection prosthesis. Therefore, different endosseous implants are often used as prosthesis-supporting elements. Manufacturers of dental implants have recently presented mini dental implants (MDIs) with diameter of only 1.8-2.4 mm. These implants allow very suitable prosthetic solutions within the range of their indications due to good osseointegration success rates, simple surgical technique, and immediate loading possibility. In this report, a case was presented for prosthetic rehabilitation including implantation of two Sendax type (IMTEC, Ardmore, Oklahoma, USA) MDIs in mental region, to obtain better retention and stability of the mandibular resection prosthesis and to improve function, phonation and aesthetics. The use of these implants, among aforementioned preferences, is also very cost-effective, so this implantation possibility should be taken into consideration during prosthetic treatment planning.


Morphology of the tibialis anterior muscle and its implications in minimally invasive plate osteosynthesis of tibial fractures.
We examined the variation in the origin of the tibialis anterior muscle from the lateral aspect of the tibial shaft and interosseous membrane as well as the variation in the morphology of its musculotendinous junction. Forty cadaveric lower leg specimens (20 right and 20 left) were dissected to reveal the anterior compartment. The origin of the tibialis anterior muscle and its relation to the lateral tibial shaft and interosseous membrane were determined. The position of the musculotendinous junction relative to the medial malleolus was also measured. Tibial length ranged from 29.5 to 45 cm (mean, 36.5+/-3.1 cm). The distal limit of the muscle origin was 5.9 to 20.5 cm (mean, 12.1+/-3.3 cm) from the tip of the medial malleolus. The distance between the musculotendinous junction and the medial malleolus ranged from 1.4 to 10.8 cm (mean, 6.1+/-1.9 cm). The attachment of the muscle belly ends between 15.3 and 31.8 cm (mean, 24.4+/-4.1 cm) distally from the joint line at the knee. There was no statistical correlation between tibial length and muscle morphology.This variation warrants consideration in the percutaneous insertion of screws in the distal end of long plates, as the neurovascular bundle may be injured in patients with a shorter muscle belly. We advocate an open distal approach to protect the neurovascular bundle during insertion of the plate and distal screws.


[High-sensitivity troponin in patients with stable coronary artery disease].
With the introduction of more sensitive markers of myocardial necrosis, it was shown that the diagnosis of (acute) myocardial infarction could be improved. However, many patients without myocardial infarction have elevated troponin levels (low sensitivity), resulting in additional diagnostic testing and longer admission times to find the cause of the troponin rise. Elevated troponin levels in these patients were found to have limited diagnostic but strong prognostic value. This led to studies assessing the value of high-sensitivity troponin in patients with stable disease, e.g. coronary artery disease, or even in patients without apparent (clinical) disease. These studies consistently showed a strong association with long-term (cardiac) mortality. What is the value for the general physician in daily practice? Although troponin levels may help in finding (healthy?) patients at higher risk, it remains unclear whether interventions (medication, lifestyle) are more (cost-)effective in this high-risk subgroup. The role of troponin levels as a prognostic marker in stable patients therefore remains to be determined.


Drug-induced hair loss.
Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.


Vessel-on-a-chip with Hydrogel-based Microfluidics.
Hydrogel structures equipped with internal microchannels offer more in vivo-relevant models for construction of tissues and organs in vitro. However, currently used microfabrication methods of constructing microfluidic devices are not suitable for the handling of hydrogel. This study presents a novel method of fabricating hydrogel-based microfluidic chips by combining the casting and bonding processes. A twice cross-linking strategy is designed to obtain a bonding interface that has the same strength with the hydrogel bulk, which can be applied to arbitrary combinations of hydrogels. It is convenient to achieve the construction of hydrogel structures with channels in branched, spiral, serpentine, and multilayer forms. The experimental results show that the combination of gelatin and gelatin methacrylate (GelMA) owns the best biocompatibility and can promote cell functionalization. Based on these, a vessel-on-a-chip system with vascular function in both physiological and pathological situations is established, providing a promising model for further investigations such as vascularization, vascular inflammation, tissue engineering, and drug development. Taken together, a facile and cytocompatible approach is developed for engineering a user-defined hydrogel-based chip that can be potentially useful in developing vascularized tissue or organ models.


Design Rules for Graphene and Carbon Nanotube Solvents and Dispersants.
The constantly widening industrial applications of carbon-based nanomaterials puts into sharp perspective the lack of true solvents in which the materials spontaneously exfoliate to individual molecules. This work shows that the different geometry of graphene compared to that of carbon nanotubes can change the potency of a molecule to act as a solvent or dispersant. Through analysis of the structure/function relationships, we derive a number of design rules that will aid the identification of the best solvent or dispersant candidates.


Mechanical properties of viscoelastic media by local frequency estimation of divergence-free wave fields.
Magnetic resonance elastography (MRE) is an imaging modality with which mechanical properties can be noninvasively measured in living tissue. Magnetic resonance elastography relies on the fact that the elastic shear modulus determines the phase velocity and, hence the wavelength, of shear waves which are visualized by motion-sensitive MR imaging. Local frequency estimation (LFE) has been used to extract the local wavenumber from displacement wave fields recorded by MRE. LFE -based inversion is attractive because it allows material parameters to be estimated without explicitly invoking the equations governing wave propagation, thus obviating the need to numerically compute the Laplacian. Nevertheless, studies using LFE have not explicitly addressed three important issues: (1) tissue viscoelasticity; (2) the effects of longitudinal waves and rigid body motion on estimates of shear modulus; and (3) mechanical anisotropy. In the current study we extend the LFE technique to (1) estimate the (complex) viscoelastic shear modulus in lossy media; (2) eliminate the effects of longitudinal waves and rigid body motion; and (3) determine two distinct shear moduli in anisotropic media. The extended LFE approach is demonstrated by analyzing experimental data from a previously-characterized, isotropic, viscoelastic, gelatin phantom and simulated data from a computer model of anisotropic (transversely isotropic) soft material.


Hibiscus sabdariffa L. polyphenolic-rich extract promotes muscle glucose uptake and inhibits intestinal glucose absorption with concomitant amelioration of Fe2+ -induced hepatic oxidative injury.
In this current study, the antidiabetic effectiveness of Hibiscus sabdariffa and its protective function against Fe2+ -induced oxidative hepatic injury were elucidated using in vitro, in silico, and ex vivo studies. The oxidative damage was induced in hepatic tissue by incubation with 0.1 mMolar ferrous sulfate (FeSO4) and then treated with different concentrations of crude extracts (ethyl acetate, ethanol, and aqueous) of H. sabdariffa flowers for 30 min at 37°C. When compared to ethyl acetate and aqueous extracts, the ethanolic extract displayed the most potent scavenging activity in ferric-reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and nitric oxide (NO) assays, with IC50 values of 2.8 μl/ml, 3.3 μl/ml, and 9.2 μl/ml, respectively. The extracts significantly suppressed α-glucosidase and α-amylase activities (p < .05), with the ethanolic extract demonstrating the highest activity. H. sabdariffa significantly (p < .05) raised reduced glutathione (GSH) levels while simultaneously decreasing malondihaldehyde (MDA) and NO levels and increasing superoxide dismutase (SOD) and catalase activity in Fe2+ induced oxidative hepatic injury. The extract of the plant inhibited intestinal glucose absorption and increased muscular glucose uptake. The extract revealed the presence of several phenolic compounds when submitted to gas chromatography-mass Spectroscopy (GC-MS) screening, which was docked with α-glucosidase and α- amylase. The molecular docking displayed the compound 4-(3,5-Di-tert-butyl-4-hydroxyphenyl)butyl acrylate strongly interacted with α-glucosidase and α-amylase and had the lowest free binding energy compared to other compounds and acarbose. These results suggest that H. sabdariffa has promising antioxidant and antidiabetic activity. PRACTICAL APPLICATIONS: In recent years, there has been increased concern about the side effects of synthetic anti-diabetic drugs, as well as their expensive cost, especially in impoverished nations. This has instigated a radical shift towards the use of traditional plants, which are rich in phytochemicals many years ago. Among these plants, H. sabdariffa has been used to treat diabetes in traditional medicine. In this present study, H. sabdariffa extracts demonstrated the ability to inhibit carbohydrate digesting enzymes, facilitate muscle glucose uptake and attenuate oxidative stress in oxidative hepatic injury. Hence, demonstrating H. sabdariffa's potential to protect against oxidative damage and the complications associated with diabetes. Consumption of Hibiscus tea or juice may be a potential source for developing an anti-diabetic drug.


A new acylated flavonoid glycoside from the flowers of Camellia nitidissima and its effect on the induction of apoptosis in human lymphoma U937 cells.
From the EtOH extract of the flowers of Camellia nitidissima Chi, a new acylated flavonoid glycoside, quercetin 7-O-(6"-O-E-caffeoyl)-β-D-glucopyranoside (1), has been isolated, together with three known flavonoids: quercetin (2), quercetin 3-O-β-D-glucopyranoside (3), and quercetin 7-O-β-D-glucopyranoside (4). Their structures were elucidated on the basis of spectroscopic analysis. Compound 1 was shown to inhibit proliferation and to induce apoptosis of human lymphoma U937 cells.


CT-guided percutaneous ethanol injection therapy for ultrasonically invisible hepatocellular carcinoma.
We report the case of a 75-year-old woman with hepatitis C virus-related cirrhosis and recurrent hepatocellular carcinoma located just beneath the diaphragm. Computed tomography-guided percutaneous ethanol injection therapy was performed, because images of the tumor were hard to obtain on ultrasonography. The angle and depth of needle insertion were determined by using the geometric relationship between the target lesion and the skin insertion site on computed tomography scans. A 22-gauge needle was inserted through the right 6th intercostal space under local anesthesia. Computed tomography scanning was repeated to verify the needle position. After entry of the needle into the target lesion was confirmed, 10 mL of absolute ethanol was injected. This procedure caused transient mild pain, but there were no serious adverse effects such as pneumothorax or hemothorax. Three months after treatment, the lesion was not enhanced on dynamic computed tomography scanning, suggesting complete tumor ablation. At present, the patient is doing well. In conclusion, computed tomography-guided percutaneous ethanol injection therapy was safe and accurately achieved the desired tumoricidal effect in a patient with ultrasonically invisible hepatocellular carcinoma.


Greater circadian disadvantage during evening games for the National Basketball Association (NBA), National Hockey League (NHL) and National Football League (NFL) teams travelling westward.
We investigated the effects of a circadian disadvantage (i.e. playing in a different time zone) on the winning percentages in three major sport leagues in North America: the National Basketball Association, the National Hockey League and the National Football League. We reviewed 5 years of regular season games in the National Basketball Association, National Hockey League and National Football League, and noted the winning percentage of the visiting team depending on the direction of travel (west, east, and same time zone) and game time (day and evening games). T-tests and analysis of variance were performed to evaluate the effects of the circadian disadvantage, its direction, the number of time zones travelled, and the game time on winning percentages in each major league. The results showed an association between the winning percentages and the number of time zones traveled for the away evening games, with a clear disadvantage for the teams travelling westward. There was a significant difference in the teams' winning percentages depending on the travelling direction in the National Basketball Association (F2,5908 = 16.12, P < 0.0001) and the National Hockey League (F2,5639 = 4.48, P = 0.011), and a trend was found in the National Football League (F2,1279 = 2.86, P = 0.058). The effect of the circadian disadvantage transcends the type of sport and needs to be addressed for greater equity among the western and eastern teams in professional sports. These results also highlight the importance of circadian rhythms in sport performance and athletic competitions.


Orphanin FQ/nociceptin not only blocks but also reverses behavioral adaptive changes induced by repeated cocaine in mice.
Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL1) receptor, blocks cocaine sensitization in rats. In this study, we tested whether OFQ/N would block sensitization to the motor stimulatory and conditioned rewarding actions of cocaine in mice. We also examined whether OFQ/N, given to cocaine-sensitized mice, would reverse the sensitized response and whether it would prevent the amplified sensitized response induced by a second cocaine-sensitizing regimen in sensitized mice. ORL1 knockout and wild-type mice were treated with saline or OFQ/N before saline or cocaine on Days 1-3 and tested for sensitization on Day 8. Additionally, wild-type mice were treated similarly but tested for the conditioned rewarding action of cocaine, in which mice were tested for place preference before and after single conditioning with cocaine. Furthermore, mice were rendered sensitized, treated with saline or OFQ/N before saline or cocaine on Days 13-15, and received cocaine on Day 20 to test whether OFQ/N would reverse sensitization or block the amplified sensitized response induced by a second cocaine-sensitizing regimen in sensitized mice. OFQ/N blocked cocaine-induced psychomotor sensitization in wild-type but not knockout mice. It also blocked sensitization to the conditioned rewarding action of cocaine and reversed a preexisting locomotor sensitized response. Furthermore, OFQ/N prevented the amplified sensitized response that developed following a second cocaine sensitizing regimen given to sensitized mice. These results illustrate that OFQ/N not only blocks but also reverses maladaptive behavioral changes induced by repeated cocaine treatment in mice.


Fibrosing alveolitis associated with primary antiphospholipid syndrome.
The spectrum of the primary antiphospholipid syndrome has expanded in recent years. It has been associated with a number of non-thrombotic syndromes such as pulmonary hypertension, adrenal insufficiency, chorea and avascular necrosis of bone. Yet, it has not been described in association with inflammatory pulmonary disease. We describe a young male with definite primary antiphospholipid syndrome who developed insidious diffuse pulmonary infiltrates. The histopathologic examination of the involved lung demonstrated alveolitis and fibrosis. We suggest that this pulmonary involvement may represent another manifestation of the primary antiphospholipid syndrome.


Perceived Characteristics of Intervention Scale: Development and Psychometric Properties.
The Perceived Characteristics of Intervention Scale (PCIS), a 20-item assessment measure, was developed to assess health care providers' views of interventions. Two hundred and fifteen Department of Veterans Affairs' residential treatment providers from 38 programs across the United States completed an online survey that included the PCIS as well as self-reported use of two evidence-based treatments. The PCIS was anchored to ask about two evidence-based psychotherapies for posttraumatic stress disorder, prolonged exposure, and cognitive processing therapy. The PCIS is a reliable measure of perceived characteristics of interventions, with some preliminary support for its validity. Consideration of providers' perceptions of particular evidence-based treatments may serve as an aid to improve their dissemination, implementation, and sustained use.


Metabolic profiling of Alzheimer's disease: Untargeted metabolomics analysis of plasma samples.
Alzheimer's disease (AD) is often not recognized or is diagnosed very late, which significantly reduces the effectiveness of available pharmacological treatments. Metabolomic analyzes have great potential for improving existing knowledge about the pathogenesis and etiology of AD and represent a novel approach towards discovering biomarkers that could be used for diagnosis, prognosis, and therapy monitoring. In this study, we applied the untargeted metabolomic approach to investigate the changes in biochemical pathways related to AD pathology. We used gas chromatography and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively) to identify metabolites whose levels have changed in subjects with AD diagnosis (N = 40) compared to healthy controls (N = 40) and individuals with mild cognitive impairment (MCI, N = 40). The GC-MS identified significant differences between groups in levels of metabolites belonging to the classes of benzene and substituted derivatives, carboxylic acids and derivatives, fatty acyls, hydroxy acids and derivatives, keto acids and derivatives, and organooxygen compounds. Most of the compounds identified by the LC-MS were various fatty acyls, glycerolipids and glycerophospholipids. All of these compounds were decreased in AD patients and in subjects with MCI compared to healthy controls. The results of the study indicate disturbed metabolism of lipids and amino acids and an imbalance of metabolites involved in energy metabolism in individuals diagnosed with AD, compared to healthy controls and MCI subjects.


Bronchial arteriography in patients with pulmonary embolism.
At various times after clinical embolism, bronchial arteriography was performed in 23 patients with documented pulmonary embolism. In 17 patients with no radiologic infiltrates, chronic stage bronchial arteriograms demonstrated bronchial-to-pulmonary arterial collaterals with antegrade filling of distal pulmonary arteries. No collateral circulation was detected at the acute stage. In one case of massive pulmonary embolism with well-developed bronchial-to-pulmonary arterial collaterals and antegrade filling of distal pulmonary arteries, brisk back-bleeding occurred at surgery, and an excellent therapeutic result following thromboembolectomy was gained. By contrast, in six patients with radiologic infiltrates, only one patient (subacute stage) showed bronchial-to-pulmonary arterial collaterals; these were peripheral and associated with retrograde, not antegrade, filling of distal pulmonary arteries. Bronchial arteriography has provided information about the development of collateral circulation in pulmonary embolism, and might be useful when thromboembolectomy is planned.