Application of quantum-behaved particle swarm optimization to motor imagery EEG classification.
In this study, we propose a recognition system for single-trial analysis of motor imagery (MI) electroencephalogram (EEG) data. Applying event-related brain potential (ERP) data acquired from the sensorimotor cortices, the system chiefly consists of automatic artifact elimination, feature extraction, feature selection and classification. In addition to the use of independent component analysis, a similarity measure is proposed to further remove the electrooculographic (EOG) artifacts automatically. Several potential features, such as wavelet-fractal features, are then extracted for subsequent classification. Next, quantum-behaved particle swarm optimization (QPSO) is used to select features from the feature combination. Finally, selected sub-features are classified by support vector machine (SVM). Compared with without artifact elimination, feature selection using a genetic algorithm (GA) and feature classification with Fisher's linear discriminant (FLD) on MI data from two data sets for eight subjects, the results indicate that the proposed method is promising in brain-computer interface (BCI) applications.


Supercontinuum generation in strip/slot hybrid waveguide with flat and low dispersion.
A strip/slot hybrid waveguide with double horizontal silicon nanocrystals slots is proposed to achieve flat and low dispersion with four zero dispersion wavelengths. By tuning structural parameters of the waveguide, dispersion tailoring is fully characterized. The flat dispersion varying between -13 and 14 ps/(nm·km) is obtained over an 845 nm bandwidth. A broadband supercontinuum spectrum, spanning from 1.15 to 3.65 μm in the -15 dB level, was generated in this waveguide pumped by a femtosecond pulse at 1.86 μm. Results indicate that the waveguide has great potential in near- and mid-infrared nonlinear applications.


Outbreak of Multidrug-Resistant Tuberculosis - Kansas, 2021-2022.
An outbreak of multidrug-resistant (MDR) tuberculosis (TB) involved 13 persons in four households in a low-income, under-resourced urban Kansas community during November 2021-November 2022. A majority of the seven adults identified in the Kansas outbreak were born outside the United States in a country that had experienced an MDR TB outbreak with the same genotype during 2007-2009, whereas most of the six children in the Kansas outbreak were U.S.-born. Prompt identification, evaluation, and treatment of persons with MDR TB and their contacts is essential to limiting transmission.


Haemophilus influenzae type b disease in an Amish population: studies of the effects of genetic factors, immunization, and rifampin prophylaxis on the course of an outbreak.
In 1982, an outbreak of Haemophilus influenzae type b disease occurred in a 379-member Amish community. In an attempt to control the outbreak after the occurrence of the second case of disease, we investigated the combination of (1) rifampin chemoprophylaxis of all carriers of H influenzae type b and their household contacts from 1 month to 5 years of age and (2) H influenzae type b polysaccharide vaccine immunoprophylaxis of all community members 12 months of age and older. Despite our intervention, two additional cases of bacteremic H influenzae type b disease occurred in the ensuing 5 months, one in a 22-month-old infant who had been immunized at 19 months of age and the other in a child who had not been immunized because she was younger than 12 months of age. The outbreak ended following rifampin prophylaxis of all community members younger than 15 years of age. All of the children with disease were genetically related to one another, and three of the four were inbred. However, analysis of their coancestry revealed that neither the average level of kinship nor the average inbreeding level of the affected children differed significantly from those of the other children in the community. Furthermore, none of the four children with disease shared a human leukocyte antigen haplotype. Our observations suggest that inbreeding was not a risk factor in this community.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular cloning and analysis of the chromosomal region 26A of Drosophila melanogaster.
Region 26A of the second chromosome of Drosophila melanogaster has been extensively characterized at the genetic level. We report here the cloning of virtually the entire 26A region via a bidirectional chromosome walk. Deletion and translocation breakpoints in the 26A interval have been localized at the molecular level by both chromosomal in situ hybridization and Southern analysis. The locations of the genetically defined loci in this chromosomal region have also been correlated with transcriptional units mapped onto the DNA of the proximal region of the chromosomal walk. The position of the alpha-glycerophosphate dehydrogenase (alpha-Gpdh) gene in 26A5-7 has been confirmed and a putative transcriptional unit for the beta-galactosidase-1 (beta-Gal-1) gene has been identified in the 26A7-9 interval.


Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells.
(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.


Modulation of the mitochondrial permeability transition pore by pyridine nucleotides and dithiol oxidation at two separate sites.
After accumulation of a Ca2+ load, the addition of uncoupler to respiring rat liver mitochondria is followed by opening of the permeability transition pore (MTP), a voltage-dependent channel sensitive to cyclosporin A. The channel's voltage threshold is profoundly affected under conditions of oxidative stress, with a shift to more negative values that may cause MTP opening at physiological membrane potentials. In this paper we further clarify the mechanisms by which oxidative agents affect the apparent voltage dependence of the MTP. We show that two sites can be experimentally distinguished. (i) A first site is in apparent oxidation-reduction equilibrium with the pyridine nucleotide (PN) pool (NADH/NAD + NADPH/NADP); PN oxidation is matched by increased MTP open probability under conditions where the glutathione pool is kept in the fully reduced state; this site can be blocked by N-ethylmaleimide but not by monobromobimane, a thiol-selective reagent. (ii) A second site coincides with the oxidation-reduction-sensitive dithiol we have recently identified (Petronilli, V., Costantini, P., Scorrano, L., Colonna, R., Passamonti, S., and Bernardi, P. (1994) J. Biol. Chem. 269, 16638-16642); dithiol cross-linking at this site by arsenite or phenylarsine oxide is matched by increased MTP open probability under conditions where the PN pool is kept in the fully reduced state; at variance from the first, this site can be blocked by both N-ethylmaleimide and monobromobimane and is probably in equilibrium with the glutathione pool. Based on these findings, we reassess the mechanisms by which many oxidative agents affect the MTP and resolve conflicting reports on the relative role of PN and glutathione oxidation in the permeability transition within the framework of MTP (dys)regulation at two separate sites.


An angiogenic extract from skeletal muscle stimulates monocyte and endothelial cell chemotaxis in vitro.
The purpose of this study was to determine whether the extraction of skeletal muscle with a combination of ethanol and hydrochloric acid yields a product capable of stimulating angiogenesis. The resulting extract stimulated inflammation in the rabbit corneal assay, which was followed by capillary formation. In order to determine whether the observed angiogenesis was stimulated by a factor(s) acting directly on the endothelial cells versus a factor(s) recruiting macrophages that in turn release factors acting on endothelial cells, the muscle extract was tested for endothelial cell and monocyte chemotaxis activity in vitro. The muscle extract stimulated significant endothelial cell chemotaxis at concentrations between 94 and 750 micrograms of protein/ml and significant monocyte chemotaxis at concentrations between 8 and 75 micrograms of protein/ml. Polyacrylamide gel electrophoresis suggests that basic fibroblast growth factor and transforming growth factor-beta may be present in this acid/ethanol extract of skeletal muscle.


[Delays in wound healing due to drugs].
Many drugs may delay the cicatrization or healing of a wound. Cytotoxic drugs, inhibitors of vascular endothelial growth factor, epidermal growth factor receptor, and immunosuppressive drugs, may be responsible of these delays. When a wound does not heal, is not infected but there are constant blood or serum losses, it is reasonable to suspect that a drug may play a role.


Association of Early Adulthood 25-Year Blood Pressure Trajectories With Cerebral Lesions and Brain Structure in Midlife.
Midlife elevated blood pressure (BP) is an important risk factor associated with brain structure and function. Little is known about trajectories of BP that modulate this risk. To identify BP trajectory patterns from young adulthood to midlife that are associated with brain structure in midlife. This cohort study used data of US adults from Coronary Artery Risk Development in Young Adults (CARDIA), a prospective longitudinal study of Black and White men and women (baseline age 18 to 30 years) examined up to 8 times over 30 years (1985-1986 to 2015-2016). There were 885 participants who underwent brain magnetic resonance imaging (MRI) in the 25th or 30th year examinations. Analyses were conducted November 2019 to December 2020. Using group-based trajectory modeling, 5 25-year BP trajectories for 3 BP traits were identified in the total CARDIA cohort of participants with 3 or more BP measures, which were then applied to analyses of the subset of 853 participants in the Brain MRI substudy. Mean arterial pressure (MAP) was examined as an integrative measure of systolic and diastolic BP. With linear regression, the associations of the BP trajectories with brain structures were examined, adjusting sequentially for demographics, cardiovascular risk factors, and antihypertensive medication use. Brain MRI outcomes include total brain, total gray matter, normal-looking and abnormal white matter volumes, gray matter cerebral blood flow, and white matter fractional anisotropy. Brain MRI analyses were conducted on 853 participants (mean [SD] age, 50.3 [3.6] years; 399 [46.8%] men; 354 [41.5%] Black and 499 [58.5%] White individuals). The MAP trajectory distribution was 187 individuals (21.1%) with low-stable, 385 (43.5%) with moderate-gradual, 71 (8.0%) with moderate-increasing, 204 (23.1%) with elevated-stable, and 38 (4.3%) with elevated-increasing. Compared with the MAP low-stable trajectory group, individuals in the moderate-increasing and elevated-increasing groups were more likely to have higher abnormal white matter volume (moderate: β, 0.52; 95% CI, 0.23 to 0.82; elevated: β, 0.57; 95% CI, 0.19 to 0.95). Those in the MAP elevated-increasing group had lower gray matter cerebral blood flow (β, -0.42; 95% CI, -0.79 to -0.05) after adjusting for sociodemographics and cardiovascular risk factors. After adjustment for antihypertensive medication use, the difference was consistent for abnormal white matter volume, but results were no longer significant for gray matter cerebral blood flow. Among young adults with moderate to high levels of BP, a gradual increase in BP to middle-age may increase the risk in diffuse small vessel disease and lower brain perfusion.


Differential regulation of nitrate reductase induction in roots and shoots of cotton plants.
The induction of nitrate reductase activity in root tips of cotton (Gossypium hirsutum L.) was regulated by several amino acids and by ammonium. Glycine, glutamine, and asparagine strongly inhibited induction of activity by nitrate and also decreased growth of sterile-cultured roots on a nitrate medium. Methionine, serine, and alanine weakly inhibited induction, and 11 other amino acids had little or no effect. Ammonium also decreased induction in root tips, but was most effective only at pH 7 or higher. The optimum conditions for ammonium regulation of induction were identical to those for growth of sterile-cultured roots on ammonium as the sole nitrogen source. Aspartate and glutamate strongly stimulated induction, but several lines of evidence indicated that the mechanism of this response was different from that elicited by the other amino acids. The effects of amino acids on induction appeared to be independent of nitrate uptake.In green shoot tissues, all attempts to demonstrate regulation of induction by amino acids failed. The great difference in observed responses of root and shoot to amino acids suggests that their nitrate reductase activities are regulated differently. Differential regulation of this enzyme is consistent with the responses of root and shoot nitrate reductase activity to nitrate.


Direct Detection of Isolevuglandins in Tissues using a D11 scFv-Alkaline Phosphatase Fusion Protein and Immunofluorescence.
Isolevuglandins (IsoLGs) are highly reactive gamma ketoaldehydes formed from H2-isoprostanes through lipid peroxidation and crosslink proteins leading to inflammation and various diseases including hypertension. Detection of IsoLG accumulation in tissues is crucial in shedding light on their involvement in the disease processes. However, measurement of IsoLGs in tissues is extremely difficult, and currently available tools, including mass spectrometry analysis, are laborious and extremely expensive. Here we describe a novel method for in situ detection of IsoLGs in tissues using alkaline phosphatase-conjugated D11 ScFv and a recombinant phage-display antibody produced in E. coli by immunofluorescent microscopy. Four controls were used for validating the staining: (1) staining with and without D11, (2) staining with bacterial periplasmic extract with the alkaline phosphatase linker, (3) irrelevant scFV antibody staining, and (4) competitive control with IsoLG prior to the staining. We demonstrate the effectiveness of the alkaline phosphatase-conjugated D11 in both human and mouse tissues with or without hypertension. This method will likely serve as an important tool to study the role of IsoLGs in a wide variety of disease processes.


Utility of polyhistidine-tagged ubiquitin in the purification of ubiquitin-protein conjugates and as an affinity ligand for the purification of ubiquitin-specific hydrolases.
The purification and biochemical characterization of protein substrates of the ubiquitin-dependent pathway of proteolysis is made difficult in part by the low steady state levels of ubiquitin-protein conjugates. We report here on the use of a polyhistidine-tagged ubiquitin molecule (HisUb) for the purification of ubiquitin-protein conjugates by metal chelate chromatography. When Escherichia coli extracts containing expressed HisUb were passed through a nitrilotriacetic acid-agarose column containing immobilized Ni2+ ions (Ni-NTA column), HisUb was retained. After washing to remove unbound and nonspecifically bound proteins, a pH 4.5 wash was used to elute highly purified HisUb. Purified HisUb and wild-type ubiquitin were tested for their ability to form Ni(2+)-binding ubiquitin-protein conjugates in a wheat germ in vitro conjugation reaction. In some experiments, wheat germ extracts were preincubated with iodoacetamide to inhibit ubiquitin activating and conjugating enzymes. Only those conjugation assays containing HisUb and an ATP-regenerating system not pretreated with iodoacetamide produced significant levels of multiple Ni(2+)-binding ubiquitin-protein conjugates. We also examined the potential of HisUb as an affinity ligand for the purification of higher plant ubiquitin-specific hydrolases. As a test, a crude lysate of E. coli expressing a yeast ubiquitin-specific hydrolase (Yuh1) was passed through a Ni-NTA column containing bound HisUb. Yuh1 was retained on the column and was specifically eluted when the column was equilibrated with buffer containing wild-type ubiquitin.


Spidroins and Silk Fibers of Aquatic Spiders.
Spiders are commonly found in terrestrial environments and many rely heavily on their silks for fitness related tasks such as reproduction and dispersal. Although rare, a few species occupy aquatic or semi-aquatic habitats and for them, silk-related specializations are also essential to survive in aquatic environments. Most spider silks studied to date are from cob-web and orb-web weaving species, leaving the silks from many other terrestrial spiders as well as water-associated spiders largely undescribed. Here, we characterize silks from three Dictynoidea species: the aquatic spiders Argyroneta aquatica and Desis marina as well as the terrestrial Badumna longinqua. From silk gland RNA-Seq libraries, we report a total of 47 different homologs of the spidroin (spider fibroin) gene family. Some of these 47 spidroins correspond to known spidroin types (aciniform, ampullate, cribellar, pyriform, and tubuliform), while other spidroins represent novel branches of the spidroin gene family. We also report a hydrophobic amino acid motif (GV) that, to date, is found only in the spidroins of aquatic and semi-aquatic spiders. Comparison of spider silk sequences to the silks from other water-associated arthropods, shows that there is a diversity of strategies to function in aquatic environments.


Quality assessment of corneal storage media and their components.
To keep the loss of endothelial cell density in donor corneas to a minimum, a storage medium which is adjusted to their nutritional needs is necessary. Different media, used either serum-supplemented or serum-free, are available. The quality of medium- and serum-batches as well as support of endothelial cell viability by the medium are to be tested with a quality assured screening system that allows routine examination. A screening system was developed which is based on cell-culture tests with the well-established human corneal endothelial cell line HCEC-12, and therefore can be performed without the need for donor corneas. The cells are plated at a defined density in cell-culture dishes, and are cultured for a defined period of time in the test media. Evaluation is carried out by assaying cell count, activity of cell metabolism (resazurin conversion), and determining the number of apoptotic and necrotic cells (combined vital staining with YO-PRO®-1/propidium iodide and subsequent flow cytometry). Human corneal endothelial cells that are cultured in a medium which is adjusted to their nutritional needs achieve higher cell numbers and show a higher metabolic rate. Simultaneously, the percentage of apoptotic and necrotic cells is lower. The screening system developed in this study allows for easy and reliable detection of slightest differences between different media, different processing steps for same media, and different supplements, as well as different serum batches. The differentiated results show that the screening system is sensitive enough to show even minor quality differences. Therefore, it is more suitable than the hitherto commonly used growth assay with primary, mostly porcine, corneal endothelial cells.


Estrogens augment cell surface TLR4 expression on murine macrophages and regulate sepsis susceptibility in vivo.
Gender-based differences exist in infectious disease susceptibility. In general, females generate more robust and potentially protective humoral and cell-mediated immune responses after antigenic challenge than their male counterparts. Furthermore, evidence is accumulating that sex may also influence the early perception of microbial challenges and the generation of inflammatory immune responses such as sepsis. These differences have previously been attributed to the actions of reproductive hormones. Whereas androgens have been shown to suppress acute host immune responses to bacterial endotoxin challenge, estrogens have been found to promote increased resistance to bacterial infections. However, the mechanisms by which estrogens exert immunoprotective effects have not been established. In this study, we investigated the in vivo effects of 17beta-estradiol on endotoxin susceptibility in mice. Importantly, we have examined the actions of this female reproductive hormone on the expression of pattern recognition receptors that recognize bacterial endotoxin by key innate immune sentinel cells. We show that removal of endogenous estrogens decreases both pro- and antiinflammatory cytokine production, with a concomitant reduction in circulating levels of lipopolysaccharide-binding protein and cell surface expression of Toll-like receptor 4 on murine macrophages. Exogenous in vivo replacement of 17beta-estradiol, but not progesterone, significantly elevates sera lipopolysaccharide-binding protein levels and cell surface expression of Toll-like receptor 4 and CD14 on macrophages. Furthermore, this effect corresponds with significantly higher inflammatory cytokine levels after in vivo lipopolysaccharide challenge and a marked increase in endotoxin-associated morbidity. Taken together, these data provide a potential mechanism underlying the immunoenhancing effects of estrogens.


Assessment of working environment and personal dosimeter-wearing compliance of industrial radiographers based on chromosome aberration frequencies.
Industrial radiographers are exposed to relatively higher doses of radiation than other radiation-exposed workers in South Korea. The objective of our study was to investigate the impact of specific occupational conditions on chromosome aberration frequency and evaluate dosimeter-wearing compliance of industrial radiographers in Korea. We studied individual and occupational characteristics of 120 industrial radiographers working in South Korea and evaluated the frequency of dicentrics and translocations in chromosomes to estimate radiation exposure. The association between working conditions and chromosome aberration frequencies was assessed by Poisson regression analysis after adjusting for confounding factors. Legal personal dosimeter-wearing compliance among workers was investigated by correlation analysis between recorded dose and chromosome aberration frequency. Daily average number of radiographic films used in the last six months was associated with dicentrics frequency. Workers performing site radiography showed significantly higher translocation frequency than those working predominantly in shielded enclosures. The correlation between chromosome aberration frequency and recorded dose was higher in workers in the radiography occupation since 2012 (new workers) than other veteran workers. Our study found that site radiography could affect actual radiation exposure to workers. Controlling these working conditions and making an effort to improve personal dosimeter-wearing compliance among veteran workers as well as new workers may be necessary to reduce radiation exposure as much as possible in their workplace.


Ultraviolet-irradiated vaccinia virus recombinants, exposing HIV-envelope on their outer membrane, induce antibodies against this antigen in rabbits.
The construction and isolation of recombinants of vaccinia virus (IHD-J strain), bearing on their outer membrane a chimeric protein consisting of the cytoplasmic and transmembrane domains of vaccinia B5R protein and the external domain of HIV envelope, has been previously described by us. The present study aimed to investigate the potential use of such recombinants as a vaccine, following inactivation of their infectivity by ultraviolet (UV) irradiation. The minimal dose of UV irradiation, required for the complete inactivation of the infectivity of these recombinants, was determined. Injections of rabbits with the irradiated noninfectious recombinant viruses successfully induced specific antibodies against the HIV envelope antigen, in addition to those against the poxvirus.


United States National Library of Medicine Drug Information Portal.
The Drug Information Portal is a free Web resource from the National Library of Medicine (NLM) that provides a user-friendly gateway to current information for more than 15,000 drugs. The site guides users to related resources of NLM, the National Institutes of Health (NIH), and other government agencies. Current drug-related information regarding consumer health, clinical trials, AIDS, MeSH pharmacological actions, MEDLINE/PubMed biomedical literature, and physical properties and structure is easily retrieved by searching on a drug name. A varied selection of focused topics in medicine and drugs is also available from displayed subject headings. This column provides background information about the Drug Information Portal, as well as search basics.


Krill oil prevents lipopolysaccharide-evoked acute liver injury in mice through inhibition of oxidative stress and inflammation.
Acute liver injury is a life-threatening syndrome that often results from the actions of viruses, drugs and toxins. Herein, the protective effect and potential mechanism of krill oil (KO), a novel natural product rich in long-chain n-3 polyunsaturated fatty acids bound to phospholipids and astaxanthin, on lipopolysaccharide (LPS)-evoked acute liver injury in mice were investigated. Male C57BL/6J mice were administered intragastrically with 400 mg kg-1 KO or fish oil (FO) once per day for 28 consecutive days prior to LPS exposure (10 mg kg-1, intraperitoneally injected). The results revealed that KO pretreatment significantly ameliorated LPS-evoked hepatic dysfunction indicated by reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and attenuated hepatic histopathological damage. KO pretreatment also mitigated LPS-induced hepatic oxidative stress, as evidenced by decreased malondialdehyde (MDA) contents, elevated glutathione (GSH) levels, and elevated catalase (CAT) and superoxide dismutase (SOD) activities. Additionally, LPS-evoked overproduction of pro-inflammatory mediators in serum and the liver was inhibited by KO pretreatment. Furthermore, KO pretreatment suppressed LPS-induced activation of the hepatic toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway. Interestingly, the hepatoprotective effect of KO was superior to that of FO. Collectively, the current findings suggest that KO protects against LPS-evoked acute liver injury via inhibition of oxidative stress and inflammation.


[The natural history of of the antiretrovirals: the continuum of their evaluation].
Antiretroviral drugs have, as any medical therapy, their natural history. They are born by screening or designing of molecules with activity against HIV, their efficacy and safety is investigated by clinical trials, evaluated by regulatory bodies, used by clinical practice, and finally analyzed by quality of care, economic, social and ethical studies. This flow of information is dynamically accumulated, but it may stop if negative results are obtained. The described knowledge pathway implies that specific methods are needed to answer different questions. At the same time, many decisions have to be taken in order to keep the process flowing, including multiple agents, such as drug industries, government departments, clinicians, health care providers and health policy makers. This paper describes a comprehensive conceptual framework, including the "knowledge" on antiretroviral drugs, the "methodologies" needed to generate them, and the underlying processes of "decision making". It proposes the need for a continuum of assessment of these drugs.


Calcium hydroxide partial pulpotomy is an alternative to formocresol pulpotomy based on a 3-year randomized trial.
Considering formocresol's toxicity, Ca(OH)(2) partial pulpotomy (PP) was studied as a treatment alternative. To compare success rates of Ca(OH)(2) PP versus formocresol pulpotomy (FP) treatment of pulpally exposed lower primary molars. A total of 84 lower primary molars, which met study criteria, from 56 child patients were randomly assigned for each treatment. After treatment, blinded clinical and radiographic evaluation with 96.9% and 90% reliability was performed at 6-month intervals to determine treatment success/failure. Chi-squared test was used to compare success rates between the two treatments. The success rates from 6 to 36 months for PP ranged from 95.03% to 75%, whereas for FP, it was 92.7-74.2%. The success rates for the two treatments at each 6-month interval were not different (P ≥ 0.05). The most frequent failure was internal resorption, affecting five FP teeth and three PP teeth. The resorption was arrested in five of the teeth and was replaced by a radiopaque calcified tissue in one case. Considering the favourable clinical and radiographic success rate of PP and the potentially toxic effects of formocresol leads us to recommend the use of PP instead of FP in primary teeth with deep carious lesions.


[Development, adaptation and validation of silhouette scales for self-assessment of nutritional status: a systematic review].
Self-assessment of body image is a multidimensional construction by which individuals describe the internal representations of their body structure and physical appearance in relation to themselves and others. Silhouette scales have been used to for self-assessment of nutritional status, due to their low cost and ease of administration, especially in field surveys. This study aimed to identify the various silhouette scales that have been developed or adapted since 1983 and to conduct a systematic review of the validation of such scales against objective measures of nutritional status. A total of 33 publications were found and showed moderate to good correlation between nutritional status and both adapted (0.66 to 0.87) and developed silhouette scales (0.59 to 0.94) in adults, but much lower correlation in children and adolescents. Most of the studies used inappropriate statistical analysis. The data indicated that silhouette scales should be used with caution to predict nutritional status with or without anthropometric measures.


Regularly shaped, single-crystalline ZnO nanorods with Wurtzite structure.
A convenient route at ambient conditions was employed to prepare narrow-dispersed ZnO nanorods in terms of size and morphology. Transmission electron microscopy and X-ray diffraction were used to characterize the structurally uniform and well-proportioned products. The as-prepared specimen exhibits strong ultraviolet exciton emission at 385 nm and disappearance of visible defect emission.


Production of insulin-like growth factor-binding proteins by human central nervous system tumors.
Central nervous system (CNS) tumor cells possess specific receptors for insulin-like growth factors (IGFs) and respond to the growth-promoting effects of IGFs in cell culture. In the present study, we asked whether CNS tumors also produce IGF-binding proteins (BPs) which may modulate the effects of IGFs on CNS tumor cells. Primary cell cultures were established from 20 CNS tumors. Dot blot analysis with 125I-labeled recombinant human IGF-I revealed IGF-binding activity in serum-free conditioned medium from 5 of 7 meningiomas, 7 of 8 malignant gliomas, and 3 of 5 other CNS tumors. Specific IGF BPs in conditioned medium were characterized further by Western ligand and immunoblotting, affinity labeling, and precipitation with specific antibodies against human IGFBP-1, -2, and -3. All conditioned media tested contained an Mr 35,000 BP which was recognized by antiserum against IGFBP-2 and an Mr 24,000 BP that was not recognized by available antisera. Medium conditioned by meningiomas (and one glioma) also contained Mr 45,000 and 50,000 IGF BPs, similar in size and/or immunological properties to growth hormone-dependent BPs present in normal human serum (IGFBP-3). Ligand blotting also showed that meningiomas produce an Mr 29,000 BP; immunoblotting and immunoprecipitation of affinity-labeled IGF-BP complexes confirmed that this BP is recognized by antiserum against IGFBP-1. Immunohistochemistry with specific monoclonal antibodies demonstrated that IGFBP-1 is abundant in pathological specimens of meningiomas and that lower amounts also are detected in malignant gliomas. We conclude that human CNS tumor cells produce a variety of IGF BPs in cell culture, including several that are similar in size and immunological properties to previously characterized human IGF BPs. Immunohistochemistry with specific monoclonal antibodies against IGFBP-1 confirms that this BP is present in vivo, further supporting the concept that IGF BPs may contribute to the regulation of growth in human CNS tumors.


Survivors of Hodgkin's disease: prevention of sequelae.
Increasing numbers of patients are surviving Hodgkin's disease in their youth, creating an ever larger cohort who need careful attention to long-term preventive medicine in their older years. Vigilance is especially needed for those who received laparotomy, splenectomy, and irradiation for early stage I through stage III disease, the majority of whom are destined to be long-term survivors. With the frequent migration of the young, these patients often fall under the care of a physician other than their original oncologist. The diligent internist, oncologist, emergency room physician, and general practitioner can avoid several simple pitfalls in the long-term care of these young patients now entering middle age.


Solitary pulmonary nodule of benign metastasizing leiomyoma associated with primary lung cancer: a case report.
Benign metastasizing leiomyoma in the lung is a very rare disease characterized by the growth of uterine leiomyoma tissue. In most cases there is a previous history of hysterectomy for uterine leiomyoma. A 50-year-old Asian woman underwent a total abdominal hysterectomy for uterine leiomyoma at the age of 37 years old. She was referred to our hospital because of sudden anterior chest pain. A chest computed tomography scan revealed a ground-glass opacity in her left S10 lung segment and a solitary small nodule in her left bronchial segment, S4. We performed a left lower lobectomy and an upper lung partial resection in order to make a definitive diagnosis and to enable us to determine a further therapeutic strategy. The ground-glass opacity in her left S10 was a primary lung adenocarcinoma, while the small nodule in her left S4 was diagnosed as a benign metastasizing leiomyoma. No additional therapy was done and our patient was followed up with chest computed tomography. Up to date, repetitive evaluation by chest computed tomography has shown no sign of benign metastasizing leiomyoma or lung cancer recurrence. This is a very rare case of benign metastasizing leiomyoma of the lung associated with primary lung cancer. This comorbid association should be considered in the differential diagnosis when a solitary lung nodule is detected in a patient with a history of uterine leiomyoma.


Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice.
The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.


Complete Genome Sequence of the Acetylene-Fermenting Pelobacter sp. Strain SFB93.
Acetylene fermentation is a rare metabolism that was previously reported as being unique to Pelobacter acetylenicus Here, we report the genome sequence of Pelobacter sp. strain SFB93, an acetylene-fermenting bacterium isolated from sediments collected in San Francisco Bay, CA.


The surgical technique of vertical subcondylar osteotomy for correction of mandibular prognathism. A 10-year survey.
In the period 1975-1985 extraoral vertical, subcondylar osteotomies of the mandibular ramus (EVSO) were performed in 203 patients with mandibular prognathism at Haukeland University Hospital, Bergen. Refinements of this surgical technique are described. Clinical and surgical observations were analyzed as to preoperative orthodontic treatment, operation time, pre-/post-operative complications, and hospital stay. The findings confirm that the EVSO procedure is a safe technique, with minimal discomfort and morbidity for the patients. Even though intraoral procedures are the trend for surgical correction of mandibular prognathism at present, there are substantial indications for the use of EVSO.


Sex bias in immunization coverage in an urban area of U.P.
Two hundred and ten female and two hundred and ten male children aged 1-2 years were identified using 30 cluster random sampling technique in the Nagar Palika of Sitapur. The immunization status was determined to assess differences, if any, in the coverage in accordance with the sex of the child. Except for measles, a significantly higher vaccination coverage was observed for male children as compared to females for every vaccine, this being 65.2 and 60.9%, respectively for DPT III and OPV III for males as compared to 51.9 and 49.5%, respectively for girls. The drop out rates for DPT and OPV were also found to be higher (p greater than 0.05) in female children. However, no difference was observed in the reasons for non-immunization between the female and male children.


A putative flip-flop switch for control of REM sleep.
Rapid eye movement (REM) sleep consists of a dreaming state in which there is activation of the cortical and hippocampal electroencephalogram (EEG), rapid eye movements, and loss of muscle tone. Although REM sleep was discovered more than 50 years ago, the neuronal circuits responsible for switching between REM and non-REM (NREM) sleep remain poorly understood. Here we propose a brainstem flip-flop switch, consisting of mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum. Each side contains GABA (gamma-aminobutyric acid)-ergic neurons that heavily innervate the other. The REM-on area also contains two populations of glutamatergic neurons. One set projects to the basal forebrain and regulates EEG components of REM sleep, whereas the other projects to the medulla and spinal cord and regulates atonia during REM sleep. The mutually inhibitory interactions of the REM-on and REM-off areas may form a flip-flop switch that sharpens state transitions and makes them vulnerable to sudden, unwanted transitions-for example, in narcolepsy.


Genotypic Diversity of Ciprofloxacin Nonsusceptibility and Its Relationship with Minimum Inhibitory Concentrations in Nontyphoidal Salmonella Clinical Isolates in Taiwan.
This study analyzed the genetic diversity of ciprofloxacin (CIP) nonsusceptibility and the relationship between two major mechanisms and minimum inhibitory concentrations (MICs) of CIP in nontyphoidal Salmonella (NTS). Chromosomal mutations in quinolone resistance-determining regions (QRDRs) and plasmid-mediated quinolone resistance (PMQR) genes were searched from ResFinder, ARG-ANNOT, and PubMed for designing the sequencing regions in gyrA, gyrB, parC, and parE, and the 13 polymerase chain reactions for PMQR genes. We found that QRDR mutations were detected in gyrA (82.1%), parC (59.0%), and parE (20.5%) but not in gyrB among the 39 isolates. Five of the 13 PMQR genes were identified, including oqxA (28.2%), oqxB (28.2%), qnrS (18.0%), aac(6')-Ib-cr (10.3%), and qnrB (5.1%), which correlated with the MICs of CIP within 0.25-2 μg/mL, and it was found that oxqAB contributed more than qnr genes to increase the MICs. All the isolates contained either QRDR mutations (53.8%), PMQR genes (15.4%), or both (30.8%). QRDR mutations (84.6%) were more commonly detected than PMQR genes (46.2%). QRDR mutation numbers were significantly associated with MICs (p < 0.001). Double mutations in gyrA and parC determined high CIP resistance (MICs ≥ 4 μg/mL). PMQR genes contributed to intermediate to low CIP resistance (MICs 0.25-2 μg/mL), thus providing insights into mechanisms underlying CIP resistance.


The complete nucleotide sequence and genome organization of the M RNA segment of peanut bud necrosis tospovirus and comparison with other tospoviruses.
The M RNA of peanut bud necrosis virus (PBNV; synonym groundnut bud necrosis virus) is 4801 nucleotides in length. It comprised two ORFs in an ambisense organization and terminal inverted repeats. The 3' large ORF (3363 nucleotides in the virus-complementary strand) encoded a protein with a predicted size of 127.2 kDa which was identified as the glycoprotein precursor (GP) of the G1 and G2 glycoproteins. A comparison of the deduced amino acid sequence of GP revealed 37% identity and 58-59% similarity with that of tomato spotted wilt virus (TSWV, serogroup I) and impatiens necrotic spot virus (INSV, serogroup III), and 21-23% identity and 44-47% similarity with those of other members of the genus Bunyavirus. The 5' small ORF (924 nucleotides in the virussense strand) encoded a 34.2 kDa protein which was identified as the non-structural (NSm) protein based on 41-43% identity and 60-63% similarity with that of TSWV and INSV. Defective RNA molecules derived from the genomic M RNA were detected during continuous passage of the virus by sap inoculations.


The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant.
The p53-binding site of MDM2 holds great promise as a target for therapeutic intervention in MDM2-amplified p53 wild-type forms of cancer. Despite the extensive validation of this strategy, there are relatively few crystallographically determined co-complex structures for small-molecular inhibitors of the MDM2-p53 interaction available in the PDB. Here, a surface-entropy reduction mutant of the N-terminal domain of MDM2 that has been designed to enhance crystallogenesis is presented. This mutant has been validated by comparative ligand-binding studies using differential scanning fluorimetry and fluorescence polarization anisotropy and by cocrystallization with a peptide derived from p53. Using this mutant, the cocrystal structure of MDM2 with the benchmark inhibitor Nutlin-3a has been determined, revealing subtle differences from the previously described co-complex of MDM2 with Nutlin-2.


A stochastic HMM-based forecasting model for fuzzy time series.
Recently, fuzzy time series have attracted more academic attention than traditional time series due to their capability of dealing with the uncertainty and vagueness inherent in the data collected. The formulation of fuzzy relations is one of the key issues affecting forecasting results. Most of the present works adopt IF-THEN rules for relationship representation, which leads to higher computational overhead and rule redundancy. Sullivan and Woodall proposed a Markov-based formulation and a forecasting model to reduce computational overhead; however, its applicability is limited to handling one-factor problems. In this paper, we propose a novel forecasting model based on the hidden Markov model by enhancing Sullivan and Woodall's work to allow handling of two-factor forecasting problems. Moreover, in order to make the nature of conjecture and randomness of forecasting more realistic, the Monte Carlo method is adopted to estimate the outcome. To test the effectiveness of the resulting stochastic model, we conduct two experiments and compare the results with those from other models. The first experiment consists of forecasting the daily average temperature and cloud density in Taipei, Taiwan, and the second experiment is based on the Taiwan Weighted Stock Index by forecasting the exchange rate of the New Taiwan dollar against the U.S. dollar. In addition to improving forecasting accuracy, the proposed model adheres to the central limit theorem, and thus, the result statistically approximates to the real mean of the target value being forecast.


Hypothermia augments NF-kappaB activity and the production of IL-12 and IFN-gamma.
The differentiation of Th1 and Th2 is strictly regulated by humoral and cellular factors. The imbalance between Th1 and Th2 is considered to be the pathogenesis of allergic and autoimmune disorders. It is important to elucidate the effect of environmental factors, such as temperature, on the expression of cytokines of Th1 and Th2. We investigated the expression of IFN-gamma, IL-4, IL-5, IL-10 and IL-12 from LPS- or PHA-stimulated PBMCs at 30 degrees C or 37 degrees C using ELISA and Real-time PCR. We measured the change of NF-kappaB activity at 30 degrees C or 37 degrees C with LPS stimulation using the reporter gene assay. IFN-gamma production from LPS-stimulated PBMCs at 30 degrees C was up-regulated compared with 37 degrees C. IL-5 and IL-10 production from PHA-stimulated PBMCs at 30 degrees C were down-regulated compared with 37 degrees C. This augmented IFN-gamma production was caused by the up-regulation of IL-12 production from CD14+ blood monocytes. Both IL-12 mRNA and IL12 protein at 30 degrees C were up-regulated compared with 37 degrees C. NF-kappaB, the key molecule for the expression of IL-12, was also augmented at 30 degrees C compared with 37 degrees C. Hypothermia up-regulated the expression of IL-12 and IFN-gamma due to the augmented NF-kappaB activity. It is suggested that hypothermia modifies the pattern of cytokine gene expression.


First-principles insights into the electronic structure, optical and band alignment properties of earth-abundant Cu2SrSnS4 solar absorber.
Cu2SrSnS4 (CSTS) is a promising alternative candidate to Cu2ZnSnS4 (CZTS) for single- or multi-junction photovoltaics (PVs) owing to its efficient light-absorbing capability, earth-abundant, nontoxic constituents, and suitable defect properties. However, as a novel absorber material, several fundamental properties need to be characterized before further progress can be made in CSTS photovoltaics. In this letter, hybrid density functional theory (DFT) calculations have been used to comprehensively characterize for the first time, the electronic structure, band alignment, and optical properties of CSTS. It is demonstrated that CSTS possesses the ideal electronic structure (direct band gap of 1.98 eV and small photocarrier effective masses) and optical properties (high extinction coefficient and wide absorption) suitable for photovoltaic applications. Simulated X-ray photoelectron spectroscopy (XPS) valence band spectra using variable excitation energies show that Cu-3d electronic state dominates the valence band maximum of CSTS. Furthermore, the vacuum-aligned band diagram between CSTS and other common absorbers (CZTS, CIGS, CdTe) and the common n-type partner materials (CdS, ZnO) was constructed, which indicate staggered type-II band alignment at the CSTS/CdS and CSTS/ZnO interfaces. Based on these results, interface band offset engineering and alternative device architectures are suggested to improve charge carrier separation and power conversion efficiencies of CSTS.


A Censored Mixture Model for Modeling Risk Taking.
Risk behavior has substantial consequences for health, well-being, and general behavior. The association between real-world risk behavior and risk behavior on experimental tasks is well documented, but their modeling is challenging for several reasons. First, many experimental risk tasks may end prematurely leading to censored observations. Second, certain outcome values can be more attractive than others. Third, a priori unknown groups of participants can react differently to certain risk-levels. Here, we propose the censored mixture model which models risk taking while dealing with censoring, attractiveness to certain outcomes, and unobserved individual risk preferences, next to experimental conditions.


Variable effect of toxic shock toxins from different sources on neutrophil function in vitro.
Toxic shock syndrome toxins (TSST) are 23-30 kD proteins that have been isolated from incubation media of strains of Staphylococcus aureus cultured from patients with toxic shock syndrome (TSS). Injection of TSST into animals produces many of the symptoms that characterize TSS including shock, fever, and multiple organ failure. We found that addition of increasing concentrations of TSST-1-VP1035-16A, but not TSST-PEC, TSST-SEC, staphylococcal enterotoxin A or B, progressively decreased human neutrophil bactericidal activity against S. aureus, 502A in vitro. TSST-1-VP1035-16A, but not the other toxins, also decreased superoxide anion and hydrogen peroxide concentrations in mixtures containing neutrophils and phorbol myristate acetate (PMA) in vitro. The results indicate that various preparations of TSST have different effects on neutrophil function in vitro and, accordingly, may have different effects in other in vitro and in vivo models of TSS.


Evaluation of the clinical association between exfoliation syndrome and abdominal aortic aneurysm.
To assess the validity of the suggested association between intraocular exfoliation syndrome and aneurysm of the abdominal aorta. A total of 77 patients recently operated for abdominal aortic aneurysm underwent biomicroscopy under pupillary dilatation to detect the presence of manifest and suspect deposits of exfoliation material. The mean age of the 71 (92%) male and six female subjects was 73 years (range: 59-88 years). Manifest exfoliation was detected in 11 patients (14%; 95% CI 7-24), five of whom were aged 60-69 years and six of whom were aged 70-79 years. In addition, four patients (5%; 95% CI 1-13) had suspect exfoliation. The prevalence of exfoliation syndrome in patients operated for abdominal aortic aneurysm was similar to that in the general population of the same age in Finland. This finding does not support the proposed connection between exfoliation syndrome and abdominal aortic aneurysm.


An economical viable tokamak fusion reactor based on the ITER experience.
This is my personal vision and outlook towards a fusion reactor based on my extensive experience from being part of the ITER design, and now construction, as well as leading the largest fusion technology program worldwide (KIT-Karlsruhe Institute of Technology) for 7 years. In particular, I want to discuss how a fusion reactor can be economically viable without employing too advanced physics and technology. It certainly will be a pulsed machine (approx. 20 000 s pulses) with thermal energy storage (turbine is steady state). I also want to discuss the optimum machine size and toroidal field for such a machine and why I think that high field and smaller plasmas may not necessarily make a fusion reactor more competitive. When one extrapolates from today's knowledge on ITER construction, even considering that ITER can be built much cheaper, it is clear that a fusion power plant will cost more than 10 or more likely more than 15 billion Euros/Dollars (the first of a kind even approx. 30 billion). Therefore, in order to have an economically attractive fusion reactor, it needs to produce a large amount of power (on the order of 2.5 GW electric). The possible size (R ∼ 10 m) and reasonably conservative physics basis of such a machine will be briefly described in the presentation. If we are successful in achieving advanced physics in a burning plasma, e.g. in ITER, then we can make the machine slightly smaller but the principal arguments for a large machine will not change significantly. Key technologies and their status will be discussed with particular emphasis on a realistic blanket and divertor design and the size and issues of a tritium-plant (T-plant) for such a machine as well as the challenges which have to be overcome beyond what is needed for ITER. Finally, a simple economic consideration will be discussed to show that a large machine could be economically viable, even in today's environment, in particular, in competition with renewables. This article is part of a discussion meeting issue 'Fusion energy using tokamaks: can development be accelerated?'.


Prediction of the effects of soil-based countermeasures on soil solution chemistry of soils contaminated with radiocesium using the hydrogeochemical code PHREEQC.
For agriculturally used areas, which are contaminated by the debris from a nuclear accident, the use of chemical amendmends (e.g. potassium chloride and lime) is among the most common soil-based countermeasures. These countermeasures are intended to reduce the plant uptake of radionuclides (mainly 137Cs and 90Sr) by competitive inhibition by chemically similar ions. So far, the impacts of countermeasures on soil solution composition - and thus, their effectiveness - have almost exclusively been established experimentally, since they depend on mineral composition and chemical characteristics of the soil affected. In this study, which focuses on caesium contamination, the well-established code PHREEQC was used as a geochemical model to calculate the changes in the ionic compositions of soil solutions, which result from the application of potassium or ammonium in batch equilibrium experiments. The simple ion exchange model used by PHREEQC was improved by taking into account selective sorption of Cs+, NH4+ and K+ by clay minerals. Calculations were performed with three different initial soil solution compositions, corresponding to particular soil types (loam, sand, peat). For loamy and sandy soils, our calculational results agree well with experimental data reported by Nisbet (Effectiveness of soil-based countermeasures six months and one year after contamination of five diverse soil types with caesium-134 and strontium-90. Contract Report NRPB-M546, National Radiation Protection Board, Chilton, 1995.). For peat, discrepancies were found indicating that for organic soils a reliable set of exchange constants of the relevant cations still has to be determined experimentally. For cesium, however, these discrepancies almost disappeared if selective sites were assumed to be inaccessible. Additionally, results of sensitivity analyses are presented by which the influence of the main soil parameters on Cs+ concentrations in solution after soil treatment has been systematically studied. It is shown that calculating the impacts of soil-based chemical countermeasures on soil solution chemistry using geochemical codes such as PHREEQC offers an attractive alternative to establishing these impacts by often time-consuming and site-specific experiments.


Comorbidity and mixed anxiety-depressive disorders: is there epidemiologic evidence?
Recent epidemiologic studies (i.e., studies conducted since 1980) have consistently demonstrated, on the basis of standardized diagnostic assessments, that there is a substantial overlap between different types of anxiety and depressive disorders. The current literature, however, discusses this issue primarily within the concept of comorbidity and there are some controversies about the existence of a separate disorder of mixed anxiety-depression (MAD). MAD can be defined by the presence of mixed symptoms of depression and anxiety that are below the diagnostic threshold for either one of these diagnoses. Since MAD has not been included in any of the current official classification systems, its prevalence, risk factors, course, and outcome have not been studied specifically in any of the recent epidemiologic studies even though MAD is thought to be very important, especially in primary care settings. This paper reviews recent epidemiologic studies and presents data from the Munich Follow-Up Study, which has found a prevalence of about 1% for MAD as defined by the ICD-10. Despite the lack of clear diagnostic criteria for MAD, there are some indications that: (1) this disorder might be frequent in primary care settings, and (2) patients with MAD frequently demonstrate subjective suffering, show impairment in personal and occupational functioning, and have high health service utilization rates. Current empirical evidence is still insufficient for deciding a suitable classificatory solution for this problem.


The Study of EDLC Device with High Electrochemical Performance Fabricated from Proton Ion Conducting PVA-Based Polymer Composite Electrolytes Plasticized with Glycerol.
In the present work, a novel polymer composite electrolytes (PCEs) based on poly(vinyl alcohol) (PVA): ammonium thiocyanate (NH4SCN): Cd(II)-complex plasticized with glycerol (Gly) are prepared by solution cast technique. The film structure was examined by XRD and FTIR routes. The utmost ambient temperature DC ionic conductivity (σDC) of 2.01 × 10-3 S cm-1 is achieved. The film morphology was studied by field emission scanning electron microscopy (FESEM). The trend of σDC is further confirmed with investigation of dielectric properties. Transference numbers of ions (tion) and electrons (tel) are specified to be 0.96 and 0.04, respectively. Linear sweep voltammetry (LSV) displayed that the PCE potential window is 2.1 V. The desired mixture of activated carbon (AC) and carbon black was used to fabricate the electrodes of the EDLC. Cyclic voltammetry (CV) was carried out by sandwiching the PCEs between two carbon-based electrodes, and it revealed an almost rectangular shape. The EDLC exhibited specific capacitance, energy density, and equivalent series resistance with average of 160.07F/g, 18.01Wh/kg, and 51.05Ω, respectively, within 450 cycles. The EDLC demonstrated the initial power density as 4.065 × 103 W/Kg.


Stopover use of a large estuarine wetland by dunlins during spring and autumn migrations: Linking local refuelling conditions to migratory strategies.
Migratory strategies dictate stopover ecology, particularly concerning decisions of when, where and how long to stop, and what to do at stationary periods. In birds, individuals stop primarily to replenish energy stores, although the functions of stopover events vary among and within species, particularly between pre- and post-breeding seasons. Here, we combined plasma metabolite levels and haematological parameters to compare refuelling rates and physiological state within (early, mid, late) and between (spring, autumn) migratory periods, aiming to identify potentially different migratory strategies in a shorebird, the dunlin Calidris alpina, using a key stopover site in Iberia. Plasma triglycerides and β-hydroxybutyrate concentrations did not differ between seasons, and small differences were found in haematological profiles (higher haemoglobin and hematocrit levels in spring). Similar refuelling rates and physiological status suggests a single migratory strategy in spring and autumn. During both seasons, dunlins arrive at the Tagus estuary with medium-to-high fuel loads, indicating they do not engage in prolonged fuelling. This agrees with a skipping migratory strategy, where birds fly short-to-medium distances while fuelling at moderate rates along a network of sites. Although we may expect late spring migrants to experience stronger pressures to optimally schedule migratory events, we found no significant differences in physiological profiles among early, mid and late migrants. Unexpectedly, such differences were found in autumn: early birds showed the highest triglycerides and haemoglobin levels and lowest β-hydroxybutyrate concentrations. These results denote enhanced refuelling rates and blood oxygen-carrying capacity in early autumn migrants, which is typical of jumpers, i.e., birds travelling with larger fuel loads and performing fewer stops. Our study adds substantially to previous knowledge of stopover ecology in migratory shorebirds in the East Atlantic Flyway. Importantly, it indicates that the Tagus estuary is a high-quality stopover site for intermediate fuelling. Yet, understanding non-fuelling stopping functions is needed to ultimately inform conservation planning.


Natural Ingredients-Based Gummy Bear Composition Designed According to Texture Analysis and Sensory Evaluation In Vivo.
The increased interest in functional materials of natural origin has resulted in a higher market demand for preservative-free, "clean label", or natural ingredients-based products. The gummy bear food supplements are more acceptable to consumers and have fewer limitations compared to other dosage forms. The aim of our study was to produce natural ingredients-based gummy bear composition, and evaluate the influence of the selected ingredients on the product's textural properties, its acceptance in vivo, and the gummy bear's quality. The optimal base composition was determined using a surface response design: gelatin 4.3 g and agave syrup 6.3 g. The investigated sweeteners did not affect the textural properties (p > 0.05). However, further studies demonstrated that a 100% increase of agave results in up to 27% higher flexibility (p < 0.05). The addition of calcium and cholecalciferol reduced firmness by 59.59 ± 1.45% (p < 0.05). On the other hand, acai berry extract had no significant effect. The presence of calcium resulted in a decreased smell and taste; however, the data indicated that experimental texture analysis is a more accurate technique than in vivo evaluation. The acai berry extract did not improve all of the tested sensory properties. We can conclude that the suggested gummy bear base can be supplemented with various active ingredients and commercialized, though further studies are needed to investigate the other natural sources to mask the unpleasant taste of active ingredients and avoid water loss.


Side-effects of beta-adrenoceptor blocking drugs assessed by visual analogue scales.
A series of visual analogue scales (VAS) was used to examine the prevalence of side-effects among hypertensive patients taking beta-adrenoceptor blocking drugs. When compared to untreated non-hypertensive control subjects, patients taking beta-adrenoceptor blockers had a greater prevalence of tired legs (P less than 0.001), cold digits (P less than 0.01), insomnia (P less than 0.01) and loss of overall wellbeing (P less than 0.01). Side-effects did not differ significantly between patients taking atenolol (n = 30), oxprenolol (n = 16), propranolol (n = 15) or metoprolol (n = 10). If there is an important difference in the prevalence of side-effects between different beta-adrenoceptor blockers, a much larger study will be needed to demonstrate it.


A nanobody that recognizes a 14-residue peptide epitope in the E2 ubiquitin-conjugating enzyme UBC6e modulates its activity.
A substantial fraction of eukaryotic proteins is folded and modified in the endoplasmic reticulum (ER) prior to export and secretion. Proteins that enter the ER but fail to fold correctly must be degraded, mostly in a process termed ER-associated degradation (ERAD). Both protein folding in the ER and ERAD are essential for proper immune function. Several E2 and E3 enzymes localize to the ER and are essential for various aspects of ERAD, but their functions and regulation are incompletely understood. Here we identify and characterize single domain antibody fragments derived from the variable domain of alpaca heavy chain-only antibodies (VHHs or nanobodies) that bind to the ER-localized E2 UBC6e, an enzyme implicated in ERAD. One such VHH, VHH05 recognizes a 14 residue stretch and enhances the rate of E1-catalyzed ubiquitin E2 loading in vitroand interferes with phosphorylation of UBC6e in response to cell stress. Identification of the peptide epitope recognized by VHH05 places it outside the E2 catalytic core, close to the position of activation-induced phosphorylation on Ser184. Our data thus suggests a site involved in allosteric regulation of UBC6e's activity. This VHH should be useful not only to dissect the participation of UBC6e in ERAD and in response to cell stress, but also as a high affinity epitope tag-specific reagent of more general utility.


ALSUntangled No. 14: Mototab.
In conclusion, given the lack of demonstrated effectiveness, and the above-documented concerns about product safety and supplier identity and reliability, ALSUntangled does not support the use of mototab for amyotrophic lateral sclerosis or any other motor neuron disease. If Oslo Health Solutions ever contacts us with additional useful information on this product we will gladly publish an addendum to this investigation.


Laser-based spectroscopic technique for fast and reliable measurements of lifetimes of atomic metastable states in combustive situations.
A technique for a fast and reliable determination of the lifetime of atomic metastable states in combustive situations, based on the laser-enhanced ionization technique, is developed. The typical time required for a determination of the lifetime of an atomic metastable state in a given local position in a combustive situation ranges from some seconds to a minute (depending on the signal-to-noise ratio). The lifetime of the lowest metastable state in Au in an acetylene-air flame, which is used as the pilot metastable state in this paper, was found to vary over one order of magnitude (between 600 ns and 8.8 micros), depending on the local stoichiometric conditions in the probe volume (which, in turn, is a function of the probing position and the fuel-air ratio fed to the flame). It is demonstrated that the probing of the lifetime of atomic metastable states by this new technique can thus be used as a sensitive tool for mapping local stoichiometric conditions in a flame.


Discovery of a Tetrahydrobenzisoxazole Series of γ-Secretase Modulators.
The design and synthesis of a new series of tetrahydrobenzisoxazoles as modulators of γ-secretase activity and their structure-activity relationship (SAR) will be detailed. Several compounds are active γ-secretase modulators (GSMs) with good to excellent selectivity for the reduction of Aβ42 in the cellular assay. Compound 14a was tested in vivo in a nontransgenic rat model and was found to significantly reduce Aβ42 in the CNS compartment compared to vehicle-treated animals (up to 58% reduction of cerebrospinal fluid Aβ42 as measured 3 h after an acute oral dosing at 30 mg/kg).


Stepwise Motion in a Multivalent [2](3)Catenane.
The motions of biomolecular machines are usually multistep processes, and are involved in a series of conformational changes. In this paper, a novel triply interlocked [2](3)catenane composed of a tris(crown ether) host eTC and a circular ditopic guest with three dibenzyl ammonium (DBA) sites and three N-methyltriazolium (MTA) sites was reported. Due to the multivalency nature of the catenane, the acid-base triggered motion was performed by a stepwise manner. The coconformations of the four related stable states have been directly identified and quantified which confirmed the multistep process. In order to quantify the dynamics with environmental acidity changes, the values of the three levels of dissociation constant pKa have been determined. The special interlocked topology of the [2](3)catenane also endows the motion of each crown ether ring in the host with unexpected selectivity for the MTA sites. This study provides clues to comprehend the underlying motion mechanism of intricate biological molecular machines, and further design artificial molecular machine with excellent mechanochemistry properties.


Aberration-limited coupling efficiency from a plano-convex lens into an optical fiber.
Ray-tracing calculations of the coupling efficiency from a plano-convex lens of relatively low f/number ( approximately 2.35) into highly multimode step-index optical fibers have been performed for both orientations of the lens. The results of the calculations yield surprising discontinuities and asymmetries in the slope of the coupling efficiency versus longitudinal displacement. These features are explained in terms of the multiplicity of roots in the mapping of incident-ray heights onto the fiber core radius. In addition, it is found that the paraxial coupling efficiency result is in marked qualitative and quantitative disagreement with exact theoretical results, except at coupling efficiencies of less than a few percent. The relationship of these features to longitudinal spherical aberration, paraxial coupling, and the ray caustic is discussed.


Incidence estimation of thyroid cancer among Koreans.
The medical records of inpatients with diagnoses of either ICD-9 193(malignant neoplasm of the thyroid gland) or 226(benign neoplasm of the thyroid gland) in the claims sent in by medical care institutions throughout the country, to the Korea Medical Insurance Corporation (KMIC) during the period from January 1, 1986 to December 31, 1987 were abstracted. These records were abstracted in order to identify and confirm new cases of thyroid cancer among the beneficiaries of the KMIC. Using these data, the incidence rate of thyroid cancer among Koreans was estimated as of July 1, 1986 through June 30, 1987. The crude rates were estimated to be 0.76(95% Cl: 0.63-0.87) and 3.87(95% Cl: 3.60-4.14) per 100,000 in males and females, respectively, and the cumulative rates for the age spans 0-64 and 0-74 in males were 0.06% and 1.10%, respectively. In females, those were equally 0.35%. The age-adjusted rate for the world population was 0.93 per 100,000 in males, which is one of the lowest levels in the world. However, the adjusted rate in females was 3.96 per 100,000, which is an average level and very similar to that of the Chinese in Singapore and Shanghai. A similar tendency was shown in the case of the truncated rates for the age group of 35-64, which was 1.91 per 100,000 in males and 8.82 per 100,000 in females.


Evaluation of (-)[18F]fluoroethoxybenzovesamicol as a new PET tracer of cholinergic neurons of the heart.
18F-labeled (-)fluoroethoxybenzovesamicol [(-)FEOBV] is a novel PET tracer which binds to the vesicular acetylcholine transporter of cholinergic neurons. To evaluate the in vivo binding specificity and kinetic properties of (-)FEOBV, studies were performed in isolated working rat hearts. External gamma,gamma-coincidence monitoring of hearts indicated high extraction of radiotracer by the myocardium and rapid wash-out of unbound tracer (> 90% of maximal accumulation) within 5 min. Inclusion of (-)vesamicol (10 microM) throughout perfusion decreased the retention of (-)FEOBV by 71% (P < 0.005) and 76% (P < 0.005) in atria and ventricles, respectively. However, the initial uptake rate of the tracer was unaffected. Additional experiments showed the inactive stereoisomer, (+)FEOBV, to have a lower retention than the (-)FEOBV isomer in ventricles, indicating stereospecificity of the binding process that is consistent with structure-activity relationships of vesamicol congeners. The results indicate (-)FEOBV to be a moderately specific probe of vesamicol-sensitive binding in cholinergic neurons of the heart in experimental conditions that assure adequate washout of unbound tracer. However, the utility of the radiotracer for in vivo studies with PET is likely to be limited by the low rate of specific binding in myocardium consistent with the low density of cholinergic neurons in the heart.


Roles of the alternative complement pathway and C1q during innate immunity to Streptococcus pyogenes.
Complement is important for innate immunity to the common bacterial pathogen Streptococcus pyogenes, but the relative importance of the alternative and classical pathways has not been investigated. Using mice and human serum deficient in either C1q, the first component of the classical pathway, or factor B, an important component of the alternative pathway, we have investigated the role of both pathways for innate immunity to S. pyogenes. C3b deposition on four different strains of S. pyogenes was mainly dependent on factor B. As a consequence opsonophagocytosis of S. pyogenes was reduced in serum from factor B-deficient mice, and these mice were very susceptible to S. pyogenes infection. In contrast, C3b deposition was not dependent on C1q for two of the strains investigated, H372 and H305, yet opsonophagocytosis of all four S. pyogenes strains was impaired in serum deficient in C1q. Furthermore, infection in C1q-deficient mice with strain H372 resulted in a rapidly progressive disease associated with large numbers of bacteria in target organs. These results demonstrate the important role of the alternative pathway and C1q for innate immunity to S. pyogenes and suggest that C1q-mediated innate immunity to at least some strains of S. pyogenes may involve mechanisms that are independent of C3b on the bacteria.


Use of complete clearance for assessing treatment efficacy for 5-fluorouracil interventions in actinic keratoses: how baseline lesion count can impact this outcome.
Background: Many trials in actinic keratoses (AK) use complete clearance rate (100% reduction in number of lesions) as the primary endpoint. We explore limitations (predominantly baseline factors) associated with this outcome. Objective: This analysis assessed the effect of baseline lesion count on complete clearance rate using randomized controlled trials (RCTs) that evaluated 5-fluorouracil (5-FU) formulations, alone or with 10% salicylic acid solution, in patients with AK. Methodology: Correlation between baseline lesion count and complete clearance rate at week 8 was assessed using Pearson's coefficient. Results: Five RCTs assessing 5-FU (4%, 5%, or 0.5% in 10% salicylic acid solution) in 1,080 patients with AK were included. Mean lesion count at baseline ranged from 8.1 to 21.2 lesions per patient. Complete clearance rate was negatively associated with number of lesions at baseline. Correlation between mean number of lesions at baseline and complete clearance rate was strong (r2 = 0.94) and statistically significant (p < 0.001). Conclusion: This analysis showed that, in a homogenous set of trials, complete clearance rates achieved with 5-FU interventions are inversely related to number of lesions at baseline. These findings highlight the limits of restricting treatment evaluation to complete clearance rate and the relevance of alternative measures.


Fecal Calprotectin Is Highly Effective to Detect Endoscopic Ulcerations in Crohn's Disease Regardless of Disease Location.
As the reliability of fecal calprotectin (Fcal) remains debatable to detect endoscopic ulcerations in patients with pure ileal Crohn's disease (CD), we aimed to compare its performances with those observed in patients with colonic or ileocolonic location. Using a prospectively maintained database, we analyzed 123 CD patients with Fcal measurement and ileocolonoscopy performed within 1 month with no therapeutic intervention during this interval. Receiver operating characterstic curves (ROC) were used to determine the best Fcal threshold to detect endoscopic ulcerations, taking into account the clinical relevance and usual recommended indices. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were presented with 95% confidence intervals. The mean Fcal level was significantly higher in patients with endoscopic ulcerations in the L1 group (P = 0.025) and the L2-L3 group (P < 0.001). Using ROC curves, Fcal >200 µg/g and Fcal >250 µg/g were the best thresholds to detect endoscopic ulcerations in the L1 group (sensitivity = 75.0, 95% CI, 47.6-92.7; specificity = 87.5, 95% CI, 67.6-97.3; PPV = 80.0, 95% CI, 51.9-95.7; and NPV = 84.0; 95% CI, 63.9-95.5) and in the L2-L3 group (sensitivity = 84.1 95% CI, 69.9-93.4; specificity = 74.4, 95% CI, 57.9-87.0; PPV = 78.7, 95% CI, 64.3-89.3, and NPV = 80.6, 95% CI, 64.0-91.8), respectively. We compared the AUC between L1 and L2-L3 groups, and no difference was shown (0.89 vs 0.84, respectively, P = 0.46). We also compared 2-by-2 sensitivity, specificity, PPV, NPV, and accuracy and we did not observe any significant difference. Fecal calprotectin is highly effective to detect endoscopic ulcerations regardless of CD location but requires a lower cutoff value in patients with pure ileal involvement.


Fuchs' endothelial dystrophy: a fresh look at an aging disease.
The increasing number or corneal and intraocular surgeries performed together with longer life expectancy, elevates the risk for developing symptomatic Fuchs' endothelial dystrophy (FED). This article reviews the current understanding of FED, and, in addition, a case of early FED is presented clinically and histopathologically. Two FED corneas from one patient were examined histopathologically using an established histological protocol for light and electron microscopy. FED is an inherited autosomal dominant corneal endothelial disorder with incomplete penetrance that is up to 3 times less likely to develop in men. Treatment options are primarily palliative while surgical intervention routinely involves a penetrating keratoplasty. In this disease process the endothelium produces excessive amounts of basement membrane material of an abnormal composition resulting in the formation of a posterior collagenous layer. Extreme accumulations of this material created mushroom-like formations, guttae, projecting into the anterior chamber. The endothelial cells were extremely thinned over the guttae, to the point where the cells may provide little more than barrier function. Despite a presumably compromised endothelial pump the corneas appeared relatively free of edema clinically and histopathologically. However, some edematous pockets deep in the basal epithelial layer were present suggesting that epithelial involvement occurs at an early stage in the disease. An early diagnosis of FED will help patients and surgeons to better elect optimal surgical timing and procedures. The current trend is to intervene surgically before the patient reaches the painful end-stage. Interestingly, in the case examined, the endothelium presumably provided only a barrier function over large areas with an apparently reduced contribution from the endothelial fluid pump and yet the corneas remained relatively clear. Future research may confirm that decompensation occurs only when complete endothelial coverage is lost. If the endothelial barrier function is more important to corneal transparency than the endothelial pump function in FED, then the relative combination of these two functions in the normal cornea should also be reassessed.


Presence of previously undescribed bacterial taxa in non-axenic Chlorella cultures.
We determined the bacterial community profile in non-axenic cultures of Chlorella (Chlorophyceae, Chlorophyta) isolated from soil. The bacterial composition at the phylum level was different from that of whole soil bacteria, but it was similar to that reported for non-axenic cultures of marine microalgae such as diatoms (Bacillariophyceae, Heterokontophyta). Expected novel bacteria, i.e. those which do not have close relatives among described species, were maintained in the cultures, and these bacteria were chiefly composed of members of the phylum Bacteroidetes. They may have been 'as-yet-uncultured' but in practice unintentionally been cultured in microalgal cultures. They could serve as good bioresources in various fields of biological and ecological studies.


Radiotherapy in cT3 prostatic carcinoma: retrospective comparison between neoadjuvant and adjuvant hormonotherapy.
The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy. One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present. Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was recorded. In patients with cT3N0M0 prostate carcinoma, prolonged hormonotherapy was shown to be significantly correlated with biochemical failure-free survival and distant metastasis-free survival. Furthermore, tumor size had a significant impact on biochemical failure-free survival as well as on local control.


[Internal version maneuvers at the maternity hospital of Befelatanana--Antananarivo University Hospital Center (Madagascar): 177 cases].
Version by internal manipulations (VIM) cause high fetal and maternal morbidity and mortality rates. A retrospective study was carried out in 1998 at at the Maternity Hospital of Befelatanana, Antananarivo in order to assess VIM frequency, to specify their indications and technical difficulties by performing them. 177 VIM were registered for the period study: 85 on singleton pregnancies, 91 on the second twin and 1 on the third infant of a triplet pregnancy. VIM annual incidence was of 2.1 per cent. The average age of parturient women was 27 years old. Risk factors and determinative causes are gyneco-obstetrical history as abortion, preterm delivery, urogenital infections; high blood pressure; poor prenatal visits; poor cares during labor; untimely and inappropriate drug prescriptions; low standard of living. Maternal complications were hemorrhages of the afterbirth (73.0 per cent), uterine rupture (8.0 per cent), cervix tearing (5.0 per cent). 19 maternal deaths were noted. Infant perinatal mortality was of 68.0 per cent. The authors conclude that VIM is the only alternative to cesarotomy provided it is properly performed by a competent and experienced practitioner. VIM must be kept for the second twin in unengaged transverse lie.


Discovery of antimicrobials by massively parallelized growth assays (Mex).
The number of newly approved antimicrobial compounds has been steadily decreasing over the past 50 years emphasizing the need for novel antimicrobial substances. Here we present Mex, a method for the high-throughput discovery of novel antimicrobials, that relies on E. coli self-screening to determine the bioactivity of more than ten thousand naturally occurring peptides. Analysis of thousands of E. coli growth curves using next-generation sequencing enables the identification of more than 1000 previously unknown antimicrobial peptides. Additionally, by incorporating the kinetics of growth inhibition, a first indication of the mode of action is obtained, which has implications for the ultimate usefulness of the peptides in question. The most promising peptides of the screen are chemically synthesized and their activity is determined in standardized susceptibility assays. Ten out of 15 investigated peptides efficiently eradicate bacteria at a minimal inhibitory concentration in the lower µM or upper nM range. This work represents a step-change in the high-throughput discovery of functionally diverse antimicrobials.


Observations on carbapenem resistance by minimum inhibitory concentration in nosocomial isolates of Acinetobacter species: an experience at a tertiary care hospital in North India.
Acinetobacter species are emerging as an important nosocomial pathogen. Multidrug-resistant Acinetobacter spp. has limited the option for effective treatment. Although carbapenems are effective for the treatment of such infections, resistance to this drug has recently been reported. This study was undertaken to assess resistance to carbapenem in clinical isolates of Acinetobacter spp. from hospitalized patients by both disc-diffusion and minimum inhibitory concentration (MIC) methods. All clinical samples from suspected cases of nosocomial infections were processed, and 265 isolates were identified as Acinetobacter species. These isolates were tested for antibiotic resistance by the disc-diffusion method with 14 antimicrobials, including meropenem and imipenem. Thereafter, all Acinetobacter species were subjected to MIC for meropenem. More than 80% resistance to second- and third-generation cephalosporins, aminoglycosides, and quinolones was recorded. Thirty percent of the strains were resistant to cefoperazone/sulbactam. Resistance to meropenem was observed in 6.4% of Acinetobacter spp. while 8.3% of the isolates showed intermediate resistance detected by MIC. All carbapenem-resistant/intermediate strains were also resistant to other (>10) antibiotics tested by the disc-diffusion method. The rising trend of resistance to carbapenem poses an alarming threat to the treatment for such infections. Regular monitoring, judicious prescription, and early detection of resistance to carbapenem are necessary to check further dissemination of drug resistance in Acinetobacter spp.


Caval thrombolysis in neonates using low doses of recombinant human tissue-type plasminogen activator.
Four neonates suffered caval thrombosis secondary to indwelling central catheters. Dissolution of thrombus with recombinant tissue plasminogen activator (rt-PA) as a low-dose infusion (0.05 mg/kg/hr) directly into thrombus was successful in three patients. rt-PA was ceased after three days in the fourth patient because of catheter malposition. Thrombolysis was achieved between four and ten days. Rethrombosis occurred in one patient despite heparin prophylaxis. Plasminogen activator infusions were titrated to maintain fibrinogen levels above 100 mg/dl. One neonate suffered an intracranial haemorrhage. Regional rt-PA is an alternative to thrombectomy in critically ill neonates.


Predicting transcription factors in human alcoholic hepatitis from gene regulatory network.
Alcoholic hepatitis (AH) is a type of alcoholic liver disorder caused by overconsumption of alcohol. The involvement of several transcription factors (TF), as the main regulators of disease related gene expression has been documented previously. However, despite the importance of analysis of gene regulatory network for understanding the molecular basis in any disease, so far, there is no report on construction of such network for AH in human. Here, we used microarray analysis to construct a rather complete gene regulatory network and used it to predict TFs and pathways that affected by this disease. Ten TFs were shown to undergo significant alteration in AH. These TFs are AR, EGR1, MYC, TCF4, ATF3, JUN, FOXO3, STAT1, HIF1A and EOMES, where ATF3, TCF4 and MYC are the new TFs with a role in AH. Comparisons of gene expression profile of patients with those of healthy persons indicates 820 differentially expressed (DE) genes. Network analysis indicates that, these ten TFs regulate expression of 516 DE genes (out of 820 genes), by 1057 interactions. Furthermore, we report pathways that significantly affected by these ten TFs. These results may contribute to our limited understanding of the molecular basis of AH.


Molecular cloning, nucleotide sequencing, and expression of genes encoding alcohol dehydrogenases from the thermophile Thermoanaerobacter brockii and the mesophile Clostridium beijerinckii.
Proteins play a pivotal role in thermophily. Comparing the molecular properties of homologous proteins from thermophilic and mesophilic bacteria is important for understanding the mechanisms of microbial adaptation to extreme environments. The thermophile Thermoanaerobacter (Thermoanaerobium) brockii and the mesophile Clostridium beijerinckii contain an NADP(H)-linked, zinc-containing secondary alcohol dehydrogenase (TBADH and CBADH) showing a similarly broad substrate range. The structural genes encoding the TBADH and the CBADH were cloned, sequenced, and highly expressed in Escherichia coli. The coding sequences of the TB adh and the CB adh genes are, respectively, 1056 and 1053 nucleotides long. The TB adh gene encoded an amino acid sequence identical to that of the purified TBADH. Alignment of the deduced amino acid sequences of the TB and CB adh genes showed a 76% identity and a 86% similarity, and the two genes had a similar preference for codons with A or T in the third position. Multiple sequence alignment of ADHs from different sources revealed that two (Cys-46 and His-67) of the three ligands for the catalytic Zn atom of the horse-liver ADH are preserved in TBADH and CBADH. Both the TBADH and CBADH were homotetramers. The substrate specificities and thermostabilities of the TBADH and CBADH expressed inE. coli were identical to those of the enzymes isolated from T. brockii and C. beijerinckii, respectively. A comparison of the amino acid composition of the two ADHs suggests that the presence of eight additional proline residues in TBADH than in CBADH and the exchange of hydrophilic and large hydrophobic residues in CBADH for the small hydrophobic amino acids Pro, Ala, and Val in TBADH might contribute to the higher thermostability of the T. brockii enzyme.


Psychodynamic Therapist's Subjective Experiences With Remote Psychotherapy During the COVID-19-Pandemic-A Qualitative Study With Therapists Practicing Guided Affective Imagery, Hypnosis and Autogenous Relaxation.
The COVID-19-pandemic brought massive changes in the provision of psychotherapy. To contain the pandemic, many therapists switched from face-to-face sessions in personal contact to remote settings. This study focused on psychodynamic therapists practicing Guided Affective Imagery, Hypnosis and Autogenous Relaxation and their subjective experiences with psychotherapy via telephone and videoconferencing during the first COVID-19 related lockdown period in March 2020 in Austria. An online survey completed by 161 therapists produced both quantitative and qualitative data with the latter being subject to a qualitative content analysis. Our research suggests that telephone and videoconferencing are considered valuable treatment formats to deliver psychodynamic psychotherapy. However, therapists' experiences with remote psychotherapy are multifaceted and ambiguous. In particular, the findings raise questions concerning the maintenance of the therapeutic alliance, the development of the analytic process, the sensitivity to unconscious communication, and the indication for certain types of patients that still need further investigation. Our research indicates that the long-standing reticence toward remote treatments offers among psychodynamic therapists is becoming more differentiated and partially dissolves as therapists gain experiences in their use. Attitudes are becoming more open. At the same time, the way is being prepared to take a closer look at the specific processes and dynamics of remote psychotherapy and to examine them critically in future studies.


[Revisiting the therapeutic experience in a psychiatric day hospital six months after discharge: path and perceptions of people with mental disorders].
This article presents a qualitative study on the therapeutic experience in a psychiatric day hospital six months after discharge. The study explores the impact of this experience on the lives of people with mental disorders. A qualitative design using semi-structured individual interviews was completed with 18 participants six months after their discharge of a day hospital. Results showed that the day hospital experience was particularly helpful to improve symptoms and relationship with self. It activated a self-transformational process that continued afterwards. Termination created for many, an abrupt void. Issues at stake during the first six months were continuity of care, social support and maintaining skills and knowledge acquired.


Developmental Transition from Enzymatic to Acid Hydrolysis of Sucrose in Acid Limes (Citrus aurantifolia).
The sucrose breakdown mechanisms in juice sacs of acid lime (Citrus aurantifolia [Christm.] Swing.) were investigated throughout fruit development. All three enzymes of sucrose catabolism (sucrose synthase, acid, and alkaline invertase) are present during the initial stages. The activities of these enzymes declined rapidly and disappeared by stage 5 (80% development) but not before vacuolar pH had decreased to approximately 2.5. At this stage, sucrose breakdown occurs by acid hydrolysis. By attaining a vacuolar pH of 2.5 prior to enzyme disappearance, the cell maintains a continuous ability to break down sucrose throughout ontogeny. Thus, acid limes possess a unique and coordinated system for sucrose breakdown that involves both enzymatic and nonenzymatic pathways.


[Videofluoroscopic evaluation of the functional significance of the epiglottis in adults].
Our intention was to define the functional role of the epiglottis. Accordingly, we analysed its movements and correlation in 53 videofluroscopic exams: 26 were good health volunteers, 25 were patients with dysphagia and two were persons with pharyngeal diverticula. The exams register the rest phase, chewing, and the swallowing movements during the intake of the saliva, water, barium solution and different volumes of mass made with crumbled bread mixed with barium powder. We can see three sequential stages in epiglottic movement during swallowing. The first stage involves an upward epiglottic shift determined by hioepiglottic ligament, associated with a simultaneous bending caused by the tongue backward projection. The second stage is a posterior rotation of the epiglottis, limited by the adjustment of the epiglottic tubercle to the vestibular fold, determined by laryngeal upward shift against hyoid bone. The third stage in which occurs an eversion of the free extremity of the epiglottis beyond the horizontal plane can be absent in slow pressure swallowing. All stages of the epiglottic dynamics are passive. We have shown that the epiglottis has a protective action on the repiratory airways not limited to swallowing. It participates, during swallowing and regurgitation (vomica), through the passive adjustment of the intralaryngeal posterior surface of the epiglottis (epiglottic tubercle) to the vestibular folds. Both before and after swallowing, when frequently there are escapes of residues and small volumes out of the oral cavity, the epiglottis protects the repiratory airways, through its participation in the formation of the valleculae and as an insertion point for the aryepiglottic folds. In association with epiglottis participation there is a stretching of the aryepiglottic folds that allow a definition of the lateral channels. The upward and forward movements of the larynx associated with the opening of the pharyngoesophageal transition, that occurs synchronously with the ejection of the swallowed bolus, has been shown to be an important factor in the protective laringeal mechanism. The increase in the laryngeal resistance, in which the epiglottis takes part, is only efficient when there is wide and synchronous opening of the pharyngoesophageal transition. In this context the epiglottis is a secondary element in the protection of the respiratory airways.