[Does pre-incubation period affect detection of Pseudomonas aeruginosa and Acinetobacter baumannii species with automatized BACTEC 9120 blood culture system?].
In this study, the effect of the pre-incubation period on detection of non-fermentative species in blood culture system was investigated. Different concentrations of Pseudomonas aeruginosa and Acinetobacter strains were inoculated into BACTEC-9120 plus+Aerobic/F bottles and incubated for 0, 4, 8, 16 hours at 36 dgerees C and then were loaded to the system. Both P. aeruginosa and A.baumannii strains yielded positive signals within 24 hours after loading. In all preincubation periods, as the concentration of P. aeruginosa strains decreased, the detection time was increased. The higher the concentration of A.baumannii strains, is the longer the signalling time as the pre-incubation period is increased, whereas the lower the concentration of A. baumannii strains, is the shorter the signalling time as the preincubation period is increased. Our study indicated that the BACTEC-9120 blood culture system determined non-fermentative bacteria after a pre-incubation time of 16 hours.


Risk of hypotony after primary trabeculectomy with antifibrotic agents in a black west African population.
To evaluate the risk of hypotony and hypotony maculopathy following trabeculectomy with 5-fluorouracil (5-FU) and mitomycin C (MMC) in a black West African population. One hundred and one eyes of black Ghanaian patients with advanced primary open-angle glaucoma received intraoperative antifibrotic therapy with trabeculectomy as part of two randomized clinical trials. Overall, 57 patients received 5-FU (50.0 mg/ml for 5 minutes) and 44 received MMC (0.5 mg/ml for 3.5 minutes). All cases were performed by one of five surgeons at a single outpatient surgery center. Two of 101 eyes had a final intraocular pressure (IOP) of less than 5 mm Hg and were thus classified as having hypotony. No patient in either group was noted to develop hypotony-related maculopathy. Overall mean pre- and postoperative IOPs were 30.1 and 15.9 mm Hg, respectively. The patients receiving intraoperative MMC had a lower mean postoperative IOP (14.7 mm Hg) than those receiving 5-FU (first study, 17.1 mm Hg; second study, 16.7 mm Hg; p = 0.05). Mean overall follow-up was 17.7 months and did not differ significantly between the MMC and combined 5-FU groups. Hypotony following trabeculectomy supplemented with antifibrotic agents is a rare complication in this population. No eyes in either clinical trial developed hypotony maculopathy, suggesting that the prevalence of this condition is substantially lower in black West Africans than in whites.


Oncotargeting G proteins: The Hippo in the room.
The core components of the Hippo pathway are conserved from flies to mammals. In humans, these include a kinase cascade initiated by the Hippo kinase MST1/2 associated with the adaptor protein WW45/SAV1, and LATS1/2 in complex with MOB1, which in turn, phosphorylates and inhibits the mammalian transcription co-activator YAP and its related protein TAZ. YAP plays a critical role in organ size control during development, and its persistent nuclear localization and activation contributes to multiple human malignancies. The mechanisms driving YAP activation in most cancers, however, are often not clearly understood. In recent studies, we and Guan's team found that YAP activation represents a key molecular event contributing to uveal melanoma, the most frequent ocular malignancy in adults. Uveal melanoma growth is driven by gain-of-function mutations in GNAQ or GNA11 oncogenes, encoding persistently active G protein α subunits of the Gq family. As the signaling capacity of G proteins and their coupled receptors (GPCRs) has been extensively investigated, these findings provided an opportunity to identify cancer-associated mechanisms resulting in YAP activation, and to explore whether YAP represents a suitable oncotarget for cancer treatment.


Characteristics of light reflected from a dense ionization wave with a tunable velocity.
An optically dense ionization wave (IW) produced by two femtosecond (approximately 10/30 fs) laser pulses focused cylindrically and crossing each other may become an efficient coherent x-ray converter in accordance with the Semenova-Lampe theory. The resulting velocity of a quasiplane IW in the vicinity of pulse intersection changes with the angle between the pulses from the group velocity of ionizing pulses to infinity allowing a tuning of the wavelength of x rays and their bunching. The x-ray spectra after scattering of a lower frequency and long coherent light pulse change from the monochromatic to high order harmoniclike with the duration of the ionizing pulses.


[The own and the foreign. Philosophical and clinical aspects].
The own and the foreign are not actually philosophical basic concepts, but rather topoi, since they always relate to each other relationally and this always in relation to the perspective in which we experience something as foreign or own. Strangeness concerns us, irritates, unsettles, does not leave us alone, but at the same time, as strangeness, it eludes determination or cannot be determined, since it would then lose its strangeness. It has the character of a relapse, is paradoxically determined by presence in withdrawal, cannot be completely classified, is thus "extraordinary" and singular. It is incomparable and yet related to one's own. The article attempts a philosophical approach to the particularity of the foreign - also in ourselves - in order to clarify the theoretical considerations for the understanding of a concrete clinical case from a psychiatric-transcultural consultation. This case deals with the question of non-understanding in the face of a behavior of the patient that is alienating for the therapist as well as for the patient. This leads to the question whether and how this non-understanding could still be understandable.


The Effect of Various Mixing Techniques on the Push-Out Bond Strength of Calcium Enriched Mixture.
Correct proportioning and mixing are essential to ensure cements attain their optimum physical properties. The aim of this experimental study was to evaluate the influence of various mixing techniques including manual, mechanical mixing, and ultrasonic vibration on push-out bond strength of calcium enriched mixture (CEM). Ninety 2-mm-thick dentin disks were prepared from single-rooted human teeth and filled with CEM mixed with manual, trituration, or ultrasonic methods. Push-out bond strength values of the specimens were measured by a universal testing machine after 3 and 21 days. The samples were then examined under a stereomicroscope at 40× magnification to determine the nature of bond failure. Data were analyzed by Kruskal-Wallis and Mann-Whitney test. (p< 0.05). The highest (7.59 MPa) and lowest (4.01 MPa) bond strength values were recorded in conventional method (after 21 days) and trituration method (after 3 days), respectively. There was no statistically significant difference between the three techniques in 3 and 21 days. According to the results, various mixing techniques had no effect on the push-out bond strength of CEM cement.


Genome-wide polygenic risk score for type 2 diabetes in Indian population.
Genome-wide polygenic risk scores (PRS) for lifestyle disorders, like Type 2 Diabetes (T2D), are useful in identifying at-risk individuals early on in life, and to guide them towards healthier lifestyles. The current study was aimed at developing PRS for the Indian population using imputed genotype data from UK Biobank and testing the developed PRS on data from GenomegaDB of Indians living in India. 959 T2D cases and 2,818 controls were selected from Indian participants of UK Biobank to develop the PRS. Summary statistics available for South Asians, from the DIAMANTE consortium, were used to weigh genetic variants. LDpred2 algorithm was used to adjust the effect of linkage disequilibrium among the variants. The association of PRS with T2D, after adjusting for age, sex and top ten genetic principal components, was found to be very significant (AUC = 0.7953, OR = 2.9856 [95% CI: 2.7044-3.2961]). When participants were divided into four PRS quartile groups, the odds of developing T2D increased sequentially with the higher PRS groups. The highest PRS group (top 25%) showed 5.79 fold increased risk compared to the rest of the participants (75%). The PRS derived using the same set of variants was found to be significantly associated with T2D in the test dataset of 445 Indians (AUC = 0.7781, OR = 1.6656 [95%CI = 0.6127-4.5278]). Our study demonstrates a framework to derive Indian-specific PRS for T2D. The accuracy of the derived PRS shows it's potential to be used as a prognostic metric to stratify individuals, and to recommend personalized preventive strategies.


Microdosimetric analysis of 211At in thyroid models for man, rat and mouse.
The alpha particle emitter 211At is proposed for therapy of metastatic tumour disease. 211At is accumulated in the thyroid gland in a similar way as iodine. Dosimetric models of 211At in the thyroid are needed for radiation protection assessments for 1) patients receiving 211At-labelled pharmaceuticals where 211At may be released in vivo and 2) personnel working with 211At. Before clinical trials, preclinical studies are usually made in mice and rats. The aims of this study were to develop thyroid models for mouse, rat and man, and to compare microdosimetric properties between the models. A thyroid follicle model was constructed: a single layer of 6 to 10-μm thick follicle cells with centrally positioned 4 to 8 μm (diameter) spherical nuclei surrounded a 10 to 500 μm (diameter) spherical follicle lumen. Species-specific models were defined for mouse, rat and man. The source compartments for 211At were the follicle lumen, follicle cells and follicle cell nuclei. The target was the follicle cell nucleus. Simplified species-specific thyroid models were used to investigate the contribution from surrounding follicles. Monte Carlo simulations were performed using the general purpose radiation transport code MCNPX 2.6.0. When 211At was homogeneously distributed within the follicle lumen, the mean specific energies per decay, 〈z〉, to the follicle cell nucleus were 2.0, 1.1 and 0.17 mGy for mouse, rat and man, respectively. Corresponding values for the single-hit mean specific energy per decay, 〈z1〉, were 1.3, 0.61 and 0.37 Gy. Assuming a homogeneous 211At concentration in the follicle lumen, <0.5%, 7%, and 45% of the emitted alpha particles were fully stopped within the follicle lumen for the respective models. The results clearly show the influence of the follicle size, alpha particle range and 211At location within the thyroid follicle on the dosimetric parameters. Appropriate thyroid models are required for translation of dosimetric parameters between species.


[Increased occurrence of esophageal hypermotility disorders in patients with arterial hypertension].
It has been noted in previous manometric examinations of the oesophagus in patients with chest pain that abnormal motility was often associated with arterial hypertension. A systematic study of this relationship was therefore undertaken. In 40 patients with chest pain (18 women and 22 men, mean age 54.7 [24-70] years) and in 20 healthy volunteers (12 men, 8 women, mean age 50.8 [22-63] years) standardized oesophageal manometry and arterial blood pressure monitoring were performed over 24 hours. Coronary heart disease and gastrointestinal lesions had been excluded by angiography and endoscopy, respectively. 20 patients (group H) had hypertension (median 24-hour blood pressure > 135/85 mmHg), while 20 patients (group N) and the normal controls (group K) were normotensive. Oesophageal manometry data differed significantly between the three groups regarding distal pressure amplitude (in hPa [hectopascals]; group H: 62 hPa*,**, group N 44 hPa* and group K 36 hPa**; [*P < 0.0005]) and the proportion of simultaneous contractions (group H 23%, group N 22%**, group K 10%***; ***P < 0.001). The hypertensive patients had significantly more frequent motility abnormalities than normal controls (13/20 vs 4/20, P < 0.001); while normotensive patients had more frequent episodes of abnormal propulsion in the oesophagus (proportion of propulsive contractions in group H: 53%, in N: 44%, in K: 59%; P < 0.01). Oesophageal motility differed significantly in patients with chest pain from that in healthy controls. Patients with chest pain and hypertension more frequently had oesophageal hypermotility. This suggests a generalized abnormality of smooth muscle.


Edible/Biodegradable Packaging with the Addition of Spent Coffee Grounds Oil.
Following petroleum, coffee ranks as the second most extensively exchanged commodity worldwide. The definition of spent coffee ground (SCG) can be outlined as the waste generated after consuming coffee. The aims of the study are to produce edible/biodegradable packaging with the addition of spent coffee grounds (SCG) oil and to investigate how this fortification can affect chemical, textural, and solubility properties of experimentally produced films. The produced films were based on κ-carrageenan and pouring-drying techniques in petri dishes. Two types of emulsifiers were used: Tween 20 and Tween 80. The films were analyzed by antioxidant and textural analysis, and their solubility was also tested. Edible/biodegradable packaging samples produced with the addition of SCG oil showed higher (p < 0.05) antioxidant capacity in comparison with control samples produced without the addition of SCG oil. The results of the research showed that the fortification of edible/biodegradable packaging with the addition of SCG oil changed significantly (p < 0.05) both chemical and physical properties of the films. Based on the findings obtained, it was indicated that films manufactured utilizing SCG oil possess considerable potential to serve as an effective and promising material for active food packaging purposes.


Succinate dehydrogenase activity regulates PCB3-quinone-induced metabolic oxidative stress and toxicity in HaCaT human keratinocytes.
Polychlorinated biphenyls (PCBs) and their metabolites are environmental pollutants that are known to have adverse health effects. 1-(4-Chlorophenyl)-benzo-2,5-quinone (4-ClBQ), a quinone metabolite of 4-monochlorobiphenyl (PCB3, present in the environment and human blood) is toxic to human skin keratinocytes, and breast and prostate epithelial cells. This study investigates the hypothesis that 4-ClBQ-induced metabolic oxidative stress regulates toxicity in human keratinocytes. Results from Seahorse XF96 Analyzer showed that the 4-ClBQ treatment increased extracellular acidification rate, proton production rate, oxygen consumption rate and ATP content, indicative of metabolic oxidative stress. Results from a q-RT-PCR assay showed significant increases in the mRNA levels of hexokinase 2 (hk2), pyruvate kinase M2 (pkm2) and glucose-6-phosphate dehydrogenase (g6pd), and decreases in the mRNA levels of succinate dehydrogenase (complex II) subunit C and D (sdhc and sdhd). Pharmacological inhibition of G6PD-activity enhanced the toxicity of 4-ClBQ, suggesting that the protective function of the pentose phosphate pathway is functional in 4-ClBQ-treated cells. The decrease in sdhc and sdhd expression was associated with a significant decrease in complex II activity and increase in mitochondrial levels of ROS. Overexpression of sdhc and sdhd suppressed 4-ClBQ-induced inhibition of complex II activity, increase in mitochondrial levels of ROS, and toxicity. These results suggest that the 4-ClBQ treatment induces metabolic oxidative stress in HaCaT cells, and while the protective function of the pentose phosphate pathway is active, inhibition of complex II activity sensitizes HaCaT cells to 4-ClBQ-induced toxicity.


Are Biodegradable Osteosyntheses Still an Option for Midface Trauma? Longitudinal Evaluation of Three Different PLA-Based Materials.
The aim was to evaluate three different biodegradable polylactic acid- (PLA-) based osteosynthesis materials (OM). These OM (BioSorb, LactoSorb, and Delta) were used in 64 patients of whom 55 (85.9%) had fractures of the zygoma, five (7.8%) in the LeFort II level, two of the frontal bone (3.1%), and two of the maxillary sinus wall (3.1%). In addition to routine follow-up (FU) at 3, 6, and 12 months (m) (T1, T2, and T3) all patients were finally evaluated at a mean FU after 14.1 m for minor (e.g., nerve disturbances, swelling, and pain) and major (e.g., infections and occlusal disturbances) complications. Out of all 64 patients 38 presented with complications; of these 28 were minor (43.8%) and 10 major (15.6%) resulting in an overall rate of 59.4%. Differences in minor complications regarding sensibility disturbance at T1 and T3 were statistically significant (P = 0.04). Differences between the OM were not statistically significant. Apart from sufficient mechanical stability for clinical use of all tested OM complications mostly involved pain and swelling probably mainly related to the initial bulk reaction attributable to the drop of pH value during the degradation process. This paper includes a review of the current aspects of biodegradable OM.


Augmented surgery for esotropia associated with high hypermetropia.
Historically, surgical formulas for the management of accommodative esotropia have been based on the residual deviation with full hypermetropic correction. This "standard surgery" has resulted in a high incidence of undercorrection. In response to the large number of undercorrections with standard surgery, the authors have devised a formula for augmenting the amount of rectus recession based on the average of the near deviation with and without correction. In this study, we compare augmented surgery to standard surgery in patients who underwent bilateral medial rectus recessions for residual esotropia after prescribing full hypermetropic spectacle correction. Seventy patients with acquired esotropia after 6 months of age, and hypermetropia of +3.00 or more, were retrospectively studied. Thirty of these patients had undergone standard surgery, while 40 had augmented surgery. The follow up on each group was at least 1 year. Of the 30 patients in the nonaugmented group, 22 (74%) had postoperative deviations of 10 prism diopters or less with 8 (26%) showing a significant undercorrection. Of the 40 patients who received augmented surgery, 35 (88%) had postoperative deviations of 10 delta or less and 5 (12%) were exotropic while wearing full hypermetropic correction. Of the 5 patients with a consecutive exodeviation while wearing full hypermetropic correction, 2 corrected to orthotropia by reducing the spectacle correction by +1.50 diopters and +1.25 D (93% success), 2 were converted to orthotropia by removing +3.00 spectacle correction (97% success), and 1 continued to have an intermittent exodeviation even after removing spectacle correction. This brought the overall success rate for augmented surgery to 98%.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular cloning of CD1a (T6), a human epidermal dendritic cell marker related to class I MHC molecules.
To investigate the structure, function, and control of CD1a, we have cloned a 1.6-kbp cDNA which encodes the expressed CD1a protein and includes untranslated 5' and 3' sequences and the poly-A tail. As the protein recognized by the monoclonal antibody OKT6, CD1a is a useful marker for Langerhans cells (LC). CD1a is found on these cells and on thymocytes, suggesting an important immunologic role for this molecule. We constructed a cDNA library in lambda gt10 using mRNA from MOLT-4, a cell line that expresses the CD1a surface antigen. We then screened the library with an oligonucleotide synthesized according to a known partial sequence for CD1a, and subcloned the cDNA and its restriction fragments into pGEM for sequencing and probe production. Based on this sequence the CD1a protein is predicted to consist of three extracellular domains (alpha 1-3), a hydrophobic transmembrane region, and a cytoplasmic tail. DNA 5' to the alpha 1 region may undergo alternative exon splicing. There is high sequence identity between the beta-2 microglobulin binding region of MHC I molecules and CD1a. The secondary structure predicted for CD1a is very similar to the actual structure of HLA-A2, a classical MHC I molecule. The similarity includes the beta pleated sheets and alpha helices which form the antigen binding groove of the alpha-1 and alpha-2 domains. The homology predicted between CD1a and HLA-A2 in these regions appears to exist on the level of secondary structure despite low primary nucleotide and amino acid sequence identity. The structural data and probes we have developed should facilitate studies of the function of CD1a as well as novel investigations of LC.


Gender differences in cancer susceptibility: role of oxidative stress.
Cancer is a leading cause of death worldwide and environmental factors, including chemicals, have been suggested as major etiological incitements. Cancer statistics indicates that men get more cancer than women. However, differences in the known risk factors including life style or occupational exposure only offer partial explanation. Using a text mining tool, we have investigated the scientific literature concerning male- and female-specific rat carcinogens that induced tumors only in one gender in NTP 2-year cancer bioassay. Our evaluation shows that oxidative stress, although frequently reported for both male- and female-specific rat carcinogens, was mentioned significantly more in literature concerning male-specific rat carcinogens. Literature analysis of testosterone and estradiol showed the same pattern. Tox21 high-throughput assay results, although showing only weak association of oxidative stress-related processes for male- and female-specific rat carcinogens, provide additional support. We also analyzed the literature concerning 26 established human carcinogens (IARC group 1). Oxidative stress was more frequently reported for the majority of these carcinogens, and the Tox21 data resembled that of male-specific rat carcinogens. Thus, our data, based on about 600000 scientific abstracts and Tox21 screening assays, suggest a link between male-specific carcinogens, testosterone and oxidative stress. This implies that a different cellular response to oxidative stress in men and women may be a critical factor in explaining the greater cancer susceptibility observed in men. Although the IARC carcinogens are classified as human carcinogens, their classification largely based on epidemiological evidence from male cohorts, which raises the question whether carcinogen classifications should be gender specific.


Recent Developments of Systemic Chemotherapy for Gastric Cancer.
Gastric cancer (GC) is a molecularly heterogeneous disease. Its molecular background, epidemiology, and standard of care are quite different between Eastern and Western countries. Many efforts have been made in developing more effective surgeries and adjuvant chemotherapies for resectable GC in each region. Recently, an intensive combination of cytotoxic agents has been established as a new standard of adjuvant treatment. Meanwhile, palliative chemotherapy is a uniform standard treatment for unresectable GC worldwide. Recently, one of the most remarkable advances in therapy for unresectable GC has been the approval of immune checkpoint inhibitors (ICIs). The use of ICIs as frontline treatment is currently being investigated. In addition, novel combinations of ICIs and targeted drugs are being evaluated in clinical trials. Despite these advances, the complex biology of GC has resulted in the failure of targeted therapies, with the exceptions of HER2-targeted trastuzumab and VEGFR2-targeted ramucirumab. GC harbors many redundant oncogenic pathways, and small subsets of tumors are driven by different specific pathways. Therefore, a combination strategy simultaneously inhibiting several pathways and/or stricter patient selection for better response to targeted drugs are needed to improve clinical outcomes in this field.


Skin reflectance of lowland Bolivian youths of European ancestry.
The skin reflectances of 257 Bolivian youths of European ancestry (140 males, 117 females; 9.0-19.9 yr) residing in Santa Cruz, Bolivia (average altitude of 400 m) are described. Reflectances were measured at three wavelengths (425 nm, 545 nm, and 685 nm) on two different sites, the medial surface of the inner upper arm and the forehead. Males tended to be darker than females, significantly on the inner upper arm (P < .05). Males tended to darken significantly with age on both the upper arm and the forehead (P < .05), while females tended to lighten with age on the upper arm and darken with age on the forehead. However, with the exception of reflectances at 545 nm on the inner upper arm, the age changes in females were insignificant (P > .05). The results of comparisons between two groups based on maternal and paternal surnames (two Spanish surnames, at least one non-Spanish European surnames) were consistent with expectations, or with those with two Spanish surnames tending to be significantly darker than those with one or more non-Spanish European surname (P < .05). Finally, the results of a principal components analysis of reflectances were similar to those found in a previous study of highland Bolivians of Aymara ancestry. Am. J. Hum. Biol. 10:559-565, 1998. © 1998 Wiley-Liss, Inc.


Inhibition of the activity of cytotoxic murine T lymphocytes by antibodies to idiotypic determinants.
The nature of the receptors on the surface of cytotoxic T lymphocytes (CTL), which enable these cells to recognize antigens on allogeneic targets, is still a matter of controversy. In the present study various mouse alloantisera were tested for their capacity to inhibit, in the absence of complement, the cytotoxic activity of sensitized peritoneal T lymphocytes. The only antiserum which, even after heat inactivation, consistently inhibited cytotoxic T lymphocytes was an antiserum elicited in (C3H X C57B1/6)F1 mice by immunization with AKR/Cum thymus cells. The serum inhibited the cytotoxic reaction of either AKR/J or AKR/Cum CTL on EL-4 target cells but had no inhibitory activity on the cytotoxic reaction of AKR/J cells against P-815 target cells. Thus the inhibitory activity of the serum could not be attributed to antibodies against Ly-3 determinants present in the serum. This conclusion was strengthened by the finding that the inhibitory activity of the serum could be removed by absorption, not only with AKR/J thymus cells but also with AKR/J bone-marrow cells, a procedure which did not affect the titre of Ly-3 antibodies. The serum failed to exert any inhibition on cytotoxic T lymphocytes of BALB/c and C3H mice reacting against EL-4 target cells, indicating that the inhibitory activity of the antiserum did not result from contamination by antibodies against C57B1 antigenic determinants. It was concluded that the inhibitory activity of the antiserum resulted from the presence of antibodies against idiotypic determinants expressed on AKR/Cum thymus cells reacting against the hybrid hosts. It seems, therefore, that idiotypic determinants expressed on the surface of cytotoxic T lymphocytes may be directly involved in their cytotoxic activity.


Inhibition of adrenal cortical steroid formation by procaine is mediated by reduction of the cAMP-induced 3-hydroxy-3-methylglutaryl-coenzyme A reductase messenger ribonucleic acid levels.
Elevated glucocorticoid levels are associated with many diseases, including age-related depression, hypertension, Alzheimer's disease, and acquired immunodeficiency syndrome. Cortisol-lowering agents could provide useful complementary therapy for these disorders. We examined the effect of procaine and procaine in a pharmaceutical formulation on adrenal cortical steroid formation. Procaine inhibited dibutyryl cyclic AMP (dbcAMP)-induced corticosteroid synthesis by murine Y1 and human H295R adrenal cells in a dose-dependent manner without affecting basal steroid formation. Treatment of rats with the procaine-based formulation reduced circulating corticosterone levels. This steroidogenesis-inhibiting activity of procaine was not observed in Leydig cells, suggesting that the effect was specific to adrenocortical cells. In search of the mechanism underlying this inhibitory effect on cAMP-induced corticosteroidogenesis, procaine was found to affect neither the cAMP-dependent protein kinase activity nor key proteins involved in cholesterol transport into mitochondria, cytochrome P450 side chain cleavage enzyme expression, and enzymatic activities associated with cholesterol metabolism to final steroid products. However, procaine reduced in a dose-dependent manner the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity and the dbcAMP-induced HMG-CoA reductase mRNA levels by affecting mRNA stability. These data suggest that the inhibitory effect of procaine on cAMP-induced corticosteroid formation is due to the reduced synthesis of cholesterol. This modulatory effect of procaine on HMG-CoA reductase mRNA expression was also seen in dbcAMP-stimulated Hepa1-6 mouse liver hepatoma cells. Taken together, these results suggest that procaine may provide a pharmacological means for the control of hormone-induced HMG-CoA reductase mRNA expression and hypercortisolemia.


Whole globe enucleation versus in situ corneal excision: a study of tissue trauma and contamination.
Twenty-four pair of eyes donated to the Minnesota Lions Eye Bank were studied to determine the effect of corneal procurement methods on tissue quality. Eyes studied were ineligible for transplantation because of a preexisting medical condition other than sepsis or age of > 75 years. The procurement technique was randomized for each donor. One cornea was procured in situ (IS), whereas the fellow eye was enucleated and processed in the laboratory (EN). Procurement protocols were standard Eye Bank Association of America methods. Tissue characteristics were scored according to standard eye bank protocols. Cultures were performed at the time of tissue procurement and following storage for 7 days in Dexol media. With the exception of endothelial striae, no statistical difference was found between groups for any tissue characteristics. The average score for endothelial striae in the IS group was greater than twice that of the EN group. Initial cultures were positive in 10 of 24 in the IS group and four of 24 in the EN group. Each group had three positive end-storage cultures. These results demonstrate superior tissue decontamination after initial processing and less endothelial cell trauma with standard enucleation when compared to in situ corneal excisions.


Discovery of the spider wasp genus Sphictostethus Kohl, 1884 (Hymenoptera: Pompilidae: Pepsinae) in New Guinea, with description of two new species.
Two new species of the genus Sphictostethus Kohl, 1884 are described and illustrated from New Guinea (Indonesia: West Papua). Both species, S. papua Loktionov Lelej, sp. nov. and S. arfak Loktionov Lelej, sp. nov. differ from congeners by their peculiar head and clypeus shape, the presence of tubercles on the mesopleuron and propodeum, and the well-developed metasomal petiole. The genus Sphictostethus is newly recorded from New Guinea as a new northernmost border for their distribution within the Australian Region. An addition to the key of Australian species is given.


Some long-standing and emerging research lines in Africa.
Early research on child development in Africa was dominated by expatriates and was primarily addressed to the topics of testing the cross-cultural validity of theories developed "in the West," and the search for universals. After a brief review of the outcome of that research, we propose two additional types of motivation that seem important to us as African researchers begin to take the lead in articulating research agendas for the study of child development in Africa: articulating the contextual relevance and practical usefulness of developmental psychology in Africa; and making developmental psychology intelligible to local audiences. We highlight two major challenges for African societies in this era that call for attention by the emerging field of African child development research: linguistic hegemony and its effects on research and schooling; and the process of indigenization. We end with a preview of chapters in the rest of the volume.


B-lymphoma induction by reticuloendotheliosis virus: characterization of a mutated chicken syncytial virus provirus involved in c-myc activation.
Nondefective reticuloendotheliosis virus induces chicken bursal lymphoma in a manner similar to that of avian leukosis virus. The provirus integrates in the c-myc locus and uses a promoter insertion mechanism to activate c-myc expression. We cloned a provirus involved in c-myc activation from a B lymphoma. Detailed structural characterization of this clone, including sequence determination, revealed proviral insertion at 512 base pairs preceding the second c-myc exon. The provirus has a deletion of 80% of the viral genes but retains two intact long terminal repeats (LTRs). A segment of the viral env sequence is present in an inverted orientation. Elevated expression of c-myc, apparently directed by the 3' LTR, was detected. However, despite the presence of an intact 5' LTR, no viral transcripts were detected. Thus, the internal proviral rearrangement can affect 5' LTR transcription or stability of the message or both. This finding is in consonance with the view that proviral deletion plays an important role in the induction of bursal lymphomas by nonacute retroviruses.


Results From a Patient Experience Study in Pediatric Gastrointestinal Endoscopy.
Gastrointestinal endoscopy in children has become a standard diagnostic and therapeutic modality. The aim of our study was to characterize the most memorable elements of the patient experience from the parent's and patient's perspective and determine ways to improve the overall quality of their experience. Using a structured questionnaire, we conducted 47 phone interviews with families who had recently undergone gastrointestinal endoscopic procedures. Our study showed clear communication and mutual agreement on care decisions contributed to positive experiences. Inadequate communication of information regarding alternatives to the procedure and risk of complications during the informed consent discussion contributed to negative patient experiences. Standardization of postprocedure follow-up and timely communication of pathology findings also had potential for improvement. Our study revealed 2 areas for quality improvement interventions: The need to ensure that alternatives and complications are thoroughly discussed and the need for standardization of postprocedure follow-up.


Selection of Parameters for Optimized WAAM Structures for Civil Engineering Applications.
Using the CMT (Cold Metal Transfer, F. Fronius, Upper Austria) welding process, wire arc additive manufacturing (WAAM) enables companies to fabricate steel components in a resource-saving manner (additive vs. subtractive) by properly reinforcing existing steel components. Two fundamental questions are discussed in the current work. The first focus is on the general geometric possibilities offered by this process. The influence of various parameters, such as wire feed speed, travel speed, and torch inclination on the seam shape and build-up rate are presented. The microstructure of the manufactured components is evaluated through metallography and hardness testing. Based on the first results, print strategies are developed for different requirements. Moreover, suitable process parameter sets are recommended in terms of energy input per unit length, weld integrity and hardness distribution. The second focus is on testing and determining joint properties by analyzing the microhardness of the welded structures. The chosen parameter sets will be investigated, and steel quality equivalents according to ÖNORM EN ISO 18265 will be defined.


Photodynamic Therapy for Metastatic Melanoma Treatment: A Review.
This review article is based on specifically targeted nanoparticles that have been used in the treatment of melanoma. According to the Skin Cancer Foundation, within 2017 an estimated 9730 people will die due to invasive melanoma. Conventional treatments for nonmalignant melanoma include surgery, chemotherapy, and radiation. For the treatment of metastatic melanoma, 3 therapeutic agents have been approved by the Food and Drug Administration: dacarbazine, recombinant interferon α-2b, and high-dose interleukin 2. Photodynamic therapy is an alternative therapy that activates a photosensitizer at a specific wavelength forming reactive oxygen species which in turn induces cell death; it is noninvasive with far less side effects when compared to conventional treatments. Nanoparticles are generally conjugated to photosynthetic drugs, since they are biocompatible, stabile, and durable, as well as have a high loading capacity, which improve either passive or active photosensitizer drug delivery to targeted cells. Therefore, various photosynthetic drugs and nanoparticle drug delivery systems specifically targeted for melanoma were analyzed in this review article in relation to either their passive or their active cellular uptake mechanisms in order to deduce the efficacy of photodynamic therapy treatment for metastatic melanoma which currently remains ongoing. The overall findings from this review concluded that no current photodynamic therapy studies have been performed in relation to active nanoparticle platform photosensitizer drug carrier systems for the treatment of metastatic melanoma, and so this type of research requires further investigation into developing a more efficient active nano-photosensitizer carrier smart drug that can be conjugated to specific cell surface receptors and combinative monoclonal antibodies so that a further enhanced and more efficient form of targeted photodynamic therapy for the treatment of metastatic melanoma can be established.


Neonatal administration of tamoxifen causes disruption of myometrial development but not adenomyosis in the C57/BL6J mouse.
We previously demonstrated that in the CD-1 mouse, which exhibits a high incidence of age-related adenomyosis, neonatal exposure to tamoxifen induced premature uterine adenomyosis and was associated with abnormal development particularly of the inner myometrium. In the present study, we examined the effect of neonatal tamoxifen administration upon uterine development in the C57/BL6J mouse strain that is not known to develop uterine adenomyosis. Female C57/BL6J pups (n=20) were treated with oral tamoxifen (1 mg/kg) from age 1 to 5 days. Uteri from control and treated mice were obtained on days 5, 10, 15 and 42 of age. We examined sections histologically using image analysis and immunohistochemistry for alpha-smooth muscle actin (ACTA2, alpha-SMA), desmin, vimentin, laminin, fibronectin and oestrogen receptor-alpha (ESR1). Following tamoxifen exposure, all uteri showed inner myometrium thinning, lack of continuity, disorganisation and bundling. However, adenomyosis was not seen in any uterus. ACTA2 immunostaining was less in the circular muscle layer of treated mice. The temporal pattern of desmin immunostaining found in control mice was absent in tamoxifen-treated mice. There was no difference in the localisation of laminin or fibronectin between control and tamoxifen-treated groups. However, laminin immunostaining was reduced in the circular muscle layer of treated mice. Vimentin could not be detected in either group. In conclusion, our results demonstrate that the development of the inner myometrium is particularly sensitive to oestrogen antagonism, and is affected by steroid receptor modulation. Although tamoxifen induces inner myometrial changes including that of ACTA2, desmin, ESR1 and laminin expression in C57/BL6J neonatal mice similar to those induced in CD-1 mice, C57/BL6J mice did not develop premature adenomyosis. Thus, disruption of the development and differentiation of the inner myometrium cannot alone explain the development of tamoxifen-associated adenomyosis, and this must be dependent upon its interaction with strain-dependent factors.


Carcinosarcoma of the liver.
Herein we present a 73-year-old man with primary carcinosarcoma of the liver, a rare malignant tumor of the liver. The case was followed up due to HBV-related liver cirrhosis. Regular check-up by ultrasound demonstrated a hyperechoic tumor in the left lobe of the liver, and he was referred and admitted to our hospital. Dynamic CT studies revealed a mostly hypoenhancing hepatic mass with a peripheral ring enhancement. Surgical resection was performed, and the resected tumor was macroscopically a simple nodular type, 3 cm in diameter, with a dense fibrous capsule. Microscopically, undifferentiated cells were dominant in the tumor, while moderately differentiated hepatocellular carcinoma (HCC) were also observed. A transitional zone was noted between the undifferentiated tumor and HCC. Tumor tissue with adenocarcinoma, osteosarcoma and chondrosarcoma were also detected. Immunohistochemical studies demonstrated that tumor cells were HepPar 1 positive in hepatocellular carcinoma, and CK19 and partly CK7 positive in adenocarcinoma. Moreover, CD56, chromogranin A and c-kit were occasionally positive in undifferentiated tumor cells. The diagnosis of carcinosarcoma was made based on the concomitant presence of HCC and sarcomatous components, yet it is noteworthy that various types of tumor cells were observed.


Progress in the clinical development and utilization of vision prostheses: an update.
Vision prostheses, or "bionic eyes", are implantable medical bionic devices with the potential to restore rudimentary sight to people with profound vision loss or blindness. In the past two decades, this field has rapidly progressed, and there are now two commercially available retinal prostheses in the US and Europe, and a number of next-generation devices in development. This review provides an update on the development of these devices and a discussion on the future directions for the field.


Fixation-free assessment of the Hirschberg ratio.
To describe a novel methodology by which to measure the Hirschberg ratio (HR) in infants. The methodology does not require fixation on specific points, and measurements are made while infants look naturally at a display. The HR is calculated automatically from measurements of the direction of the optical axis, the position of the pupil center, and corneal reflexes in video images from an advanced two-camera eye-tracking system. The performance of the novel fixation-free procedure (FFP) was evaluated in 43 adults by measuring the average difference and the 95% limits of agreement with the standard fixation-based procedure (FBP). Repeatability of the HR measurements was evaluated by assessing the 95% limits of agreement between two independent measurements. Performance of the FFP was also evaluated in five infants. In adults, the average HR was 12.89 +/- 1.22 degrees/mm for FFP and 12.81 +/- 1.22 degrees/mm for FBP. FFP and FBP measurements were highly correlated (r = 0.95; P < 0.001). The 95% limits of agreement between FFP and FBP were +/-0.86 degrees/mm. The 95% limits of agreement of repeated measurements were +/-0.66 degrees/mm for FFP and +/-0.77 degrees/mm for FBP. In infants, the 95% limits of agreement of repeated measurements by FFP were +/-0.63 degrees/mm. In adults, the FFP provides accurate measurements of the HR that are in excellent agreement with measurements by FBP. In infants, measurements of HR by FFP show the same repeatability and consistency.


Immunogenicity of primary DPT vaccination.
Children have been given the diphtheria and tetanus toxoid and pertussis vaccine (DPT) in Taiwan for more than 30 years. Yet, the antibody responses to DPT have not been investigated in recent years. Two new antigens of Bordetella pertussis, pertussis toxin and filamentous hemagglutinin, were identified in B. pertussis several years ago and became the constituents of a new type of pertussis vaccine, acellular vaccine. This study was undertaken to test the antibody responses toward diphtheria, tetanus, and pertussis with conventional methods as well as new methods to detect antibodies against pertussis toxin and filamentous hemagglutinin. A total of 104 children, at ages between 12 and 23 months, who had received 3 doses of DPT vaccine were tested. Almost all (99%) of them possessed diphtheria and tetanus antitoxin concentrations above the protective level. With the criteria derived from an animal study, at least 85% of the vaccinees might have protective antibodies against pertussis. This serological study showed the effectiveness of the present DPT vaccine in Taiwan. If a new DPT vaccine is to be introduced into Taiwan, it should have at least the same immunogenicity as the present vaccine.


[Current methodologic approaches to the study of epidemiology extrapulmonary tuberculosis in the Russian Federation].
The study of the extrapulmonary tuberculosis epidemiological situation by using the routine methods leads to misinterpreted and subjective assessment of epidemiological parameters. The application of untraditional epidemiological analysis allows one to ascertain that in 1986-1990 the extrapulmonary tuberculosis epidemiological situation in the areas where the Saint-Petersburg Research Institute of Phthisiopulmonology is monitoring it is very similar to the average federation situation both in the incidence of active extrapulmonary tuberculosis and in the magnitude of changes in the rates of its incidence and prevalence. The lack of significant extrapulmonary tuberculosis shifts is the evidence that the existing measure system for detecting and treating patients in the areas (in the Far Eastern areas and autonomous districts of the Far North in particular) is far from perfect and it yields no adequate results in the prevention, treatment and diagnosis.


Comparison of maternal outcomes and clinical characteristics of prenatally vs nonprenatally diagnosed placenta accreta spectrum: a systematic review and meta-analysis.
This study aimed to compare maternal outcomes of prenatally and nonprenatally diagnosed placenta accreta spectrum. A systematic literature search was performed in PubMed, the Cochrane database, and Web of Science until November 28, 2022. Studies comparing the clinical presentation of prenatally and nonprenatally diagnosed placenta accreta spectrum were included. The primary outcomes were emergent cesarean delivery, hysterectomy, blood loss volume, number of transfused blood product units, urological injury, coagulopathy, reoperation, intensive care unit admission, and maternal death. In addition, the pooled mean values for blood loss volume and the number of transfused blood product units were calculated. The secondary outcomes included maternal age, gestational age at birth, nulliparity, previous cesarean delivery, previous uterine procedure, assisted reproductive technology, placenta increta and percreta, and placenta previa. Study screening was performed after duplicates were identified and removed. The quality of each study and the publication bias were assessed. Forest plots and I2 statistics were calculated for each study outcome for each group. The main analysis was a random-effects analysis. Overall, 415 abstracts and 157 full-text studies were evaluated. Moreover, 31 studies were analyzed. Prenatally diagnosed placenta accreta spectrum was associated with a significantly lower rate of emergency cesarean delivery (odds ratio, 0.37; 95% confidence interval, 0.21-0.67), higher hysterectomy rate (odds ratio, 1.98; 95% confidence interval, 1.02-3.83), lower blood loss volume (mean difference, -0.65; 95% confidence interval, -1.17 to -0.13), and lower number of transfused red blood cell units (mean difference, -1.96; 95% confidence interval, -3.25 to -0.68) compared with nonprenatally diagnosed placenta accreta spectrum. The pooled mean values for blood loss volume and the number of transfused blood product units tended to be lower in the prenatally diagnosed placenta accreta spectrum groups than in the nonprenatally diagnosed placenta accreta spectrum groups. Nulliparity (odds ratio, 0.14; 95% confidence interval, 0.10-0.20), previous cesarean delivery (odds ratio, 6.81; 95% confidence interval, 4.12-11.25), assisted reproductive technology (odds ratio, 0.19; 95% confidence interval, 0.06-0.61), placenta increta and percreta (odds ratio, 3.97; 95% confidence interval, 2.24-7.03), and placenta previa (odds ratio, 6.81; 95% confidence interval, 4.12-11.25) showed statistical significance. No significant difference was found for the other outcomes. Despite its severity, the positive effect of prenatally diagnosed placenta accreta spectrum on outcomes underscores the necessity of a prenatal diagnosis. In addition, the pooled mean values provide a preoperative preparation guideline.


Evaluating information for women referred for breast screening abnormalities.
To evaluate a plain-language guideline sent to women with abnormal screening results who attended the Manitoba Breast Screening Program (MBSP). A plain-language guideline was mailed with a result letter to 258 randomly chosen women who had abnormal mammograms and/or abnormal clinical breast examinations. Four weeks later, a satisfaction questionnaire was mailed to these women (cases) as well as to 254 randomly chosen women with abnormal results who were not sent a guideline (controls). All cases were interviewed by telephone three weeks after the questionnaire was mailed. A total of 345 patient satisfaction questionnaires (67%) were returned, and 47% of the cases completed the telephone interview. There was no difference in satisfaction between the women who received the guideline and those who did not. Most found the guideline easy to read (99%), and the majority (89%) felt that it clearly explained what happens if further tests are needed. However, a fourth thought the guideline made them anxious. A plain-language guideline was useful for most women who had abnormal screening results, although it did not alter the women's satisfaction with the MBSP. The guideline did increase anxiety for some women. These women may require other help to decrease their anxiety.


Quantifying protein measurands by peptide measurements: where do errors arise?
Clinically actionable quantification of protein biomarkers by mass spectrometry (MS) requires analytical performance in concordance with quality specifications for diagnostic tests. Laboratory-developed tests should, therefore, be validated in accordance with EN ISO 15189:2012 guidelines for medical laboratories to demonstrate competence and traceability along the entire workflow, including the selected standardization strategy and the phases before, during, and after proteolysis. In this study, bias and imprecision of a previously developed MS method for quantification of serum apolipoproteins A-I (Apo A-I) and B (Apo B) were thoroughly validated according to Clinical and Laboratory Standards Institute (CLSI) guidelines EP15-A2 and EP09-A3, using 100 patient sera and either stable-isotope labeled (SIL) peptides or SIL-Apo A-I as internal standard. The systematic overview of error components assigned sample preparation before the first 4 h of proteolysis as major source (∼85%) of within-sample imprecision without external calibration. No improvement in imprecision was observed with the use of SIL-Apo A-I instead of SIL-peptides. On the contrary, when the use of SIL-Apo A-I was combined with external calibration, imprecision improved significantly (from ∼9% to ∼6%) as a result of the normalization for matrix effects on linearity. A between-sample validation of bias in 100 patient sera further supported the presence of matrix effects on digestion completeness and additionally demonstrated specimen-specific biases associated with modified peptide sequences or alterations in protease activity. In conclusion, the presented overview of bias and imprecision components contributes to a better understanding of the sources of errors in MS-based protein quantification and provides valuable recommendations to assess and control analytical quality in concordance with the requirements for clinical use.


Gold nanoparticle/MXene for multiple and sensitive detection of oncomiRs based on synergetic signal amplification.
Multiple and sensitive detection of oncomiRs for accurate cancer diagnostics is still a challenge. Here, a synergetic amplification strategy was introduced by combining a MXene-based electrochemical signal amplification and a duplex-specific nuclease (DSN)-based amplification system for rapid, attomolar and concurrent quantification of multiple microRNAs on a single platform in total plasma. Synthesized MXene-Ti3C2Tx modified with 5 nm gold nanoparticles (AuNPs) was casted on a dual screen-printed gold electrode to host vast numbers of DNA probes identically co-immobilized on dedicated electrodes. Interestingly, presence of MXene provided biofouling resistance and enhanced the electrochemical signals by almost 4 folds of magnitude, attributed to its specious surface area and remarkable charge mobility. The 5 nm AuNPs were perfectly distributed within the whole flaky architect of the MXene to give rise to the electrochemical performance of MXene and provide the thiol-Au bonding feature. This synergetic strategy reduced the DSN-based biosensors' assay time to 80 min, provided multiplexability, antifouling activity, substantial sensitivity and specificity (single mutation recognition). The limit of detection of the proposed biosensor for microRNA-21 and microRNA-141 was respectively 204 aM and 138 aM with a wide linear range from 500 aM to 50 nM. As a proof of concept, this newly-developed strategy was coupled with a 96-well adaptive sensing device to successfully profile three cancer plasma samples based on their altered oncomiR abundances.


Reversible Cerebral Vasoconstriction Syndrome Associated With Oxybutynin Use; a Brief Review of Pathophysiology.
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by reversible vasospasm of the central nervous system vasculature. It usually presents as a classic thunderclap headache, but complications like a stroke, seizure, or intracranial hemorrhage may occur at the onset. Most cases are linked temporally to secondary agents. The most common suggested mechanism underlying the RCVS is vascular tone dysregulation. Our report describes the RCVS incidence associated with oxybutynin use in a young female. We aim to describe the potential pathophysiology linking oxybutynin use and RCVS.


Meckel's Diverticulum Enterolith: An Extremely Rare Cause of Intestinal Obstruction.
Meckel's diverticulum is usually asymptomatic but occasionally presents with complications. Formation of an enterolith inside a Meckel's diverticulum is very uncommon and dislodgement of such a stone causing obstruction is extremely rare. We herein present a case of a 48-year-old man who presented with small bowel obstruction. Preoperative radiologic studies revealed a stone-like lesion in the right lower quadrant. Upon laparotomy, an inflamed Meckel's diverticulum was found as well as a 2.5 cm stone obstructing the terminal ileum. The stone was removed and the diverticulum was excised. The differential diagnosis of acute intestinal obstruction should include this extremely rare clinical entity especially when the combination of small bowel obstruction with radiopaque stone-like finding on preoperative x-rays is present.


Pparα knockout in mice increases the Th17 development by facilitating the IKKα/RORγt and IKKα/Foxp3 complexes.
The helper CD4+ T cell-type 17 (Th17) cells and regulatory CD4+ T cells (Tregs) are balanced through numerous molecular regulators, particularly metabolic factors, and their alteration causes immune dysregulation. Herein, we report that peroxisome proliferator of activated receptor-alpha (Pparα), a lipid metabolism regulator, suppresses Th17 differentiation. We demonstrated that Pparα ablation improves Th17 and pro-Th17 factor HIF-1α by enhancing the expression and nuclear localization of NFκB-activator IκB kinase-alpha (IKKα). Unexpectedly, we found that IKKα directly interacts with RORγt and enhances the expression of Il17a gene. Meanwhile, IKKα also interacts with Foxp3, leading to the post-translational regulation of Foxp3 by elevating its proteasomal degradation, and influencing Th17 development. Pparα deficiency leads to enhanced Th17 development in vivo and is associated with enhanced pathology in a murine experimental autoimmune encephalomyelitis (EAE) model. Overall, our data indicate that Pparα may serve as a potential therapeutic target for autoimmune and inflammatory diseases.


Evaluation of the efficacy of octreotide LAR in the treatment of Crohn's disease associated refractory diarrhea.
Diarrhea is one of the main symptoms of Crohn's disease (CD). It is usually significantly improved with specific CD treatments, loperamide or cholestyramine. However, in some cases, diarrhea becomes refractory. The aim of this study was to assess the safety and efficacy of octreotide in this situation. Fifteen patients with CD refractory diarrhea defined by at least an average of five smooth or liquid stools per day despite an optimized CD treatment were included from three Belgian centers. Two patients were lost to follow-up. A subcutaneous injection of 100 μg octreotide was performed three times a day during three days. When the drug had been well tolerated, an intramuscular injection of 30 mg octreotide (Sandostatin® LAR 30) was realized. Evaluation was done at day 31. The primary endpoint was to assess the effect on the mean number of smooth or liquid stools per day. A significant reduction (p = 0.0001) of the average number of smooth or liquid stools over the last seven days was observed between baseline and day 31. The maximum number of smooth or liquid stools also significantly decreased (p = 0.0009). Four patients (26.7%) presented mild nonspecific adverse events but no serious one. We also observed a significant decrease (p = 0.0006) of the Harvey-Bradshaw Index (HBI) and a significant improvement (p = 0.0012) of the inflammatory bowel disease questionnaire (IBDQ). In this uncontrolled open-label study, octreotide appeared safe and effective in CD refractory diarrhea, in addition to CD treatments. It significantly improved the number of liquid or smooth stools, the HBI and the IBDQ.


Carbon molecules in space: from astrochemistry to astrobiology.
How complex carbonaceous molecules in space are, what their abundance is and on what timescales they form are crucial questions within cosmochemistry. Despite the large heterogeneity of galactic and interstellar regions the organic chemistry in the universe seems to follow common pathways. The largest fraction of carbon in the universe is incorporated into aromatic molecules (gaseous polycyclic aromatic hydrocarbon as well as solid macromolecular aromatic structures). Macromolecular carbon constitutes more than half of the interstellar carbon, approximately 80% of the carbon in meteorites, and is likely to be present in comets. Molecules of high astrobiological relevance such as N-heterocycles, amino acids and pre-sugars have all been identified in trace quantities (ppb) in extracts of carbonaceous meteorites. Their presence in inter- and circumstellar regions is either unknown or contentious. In any event such fragile species are easily destroyed by UV radiation, shocks and thermal processing and are unlikely to survive incorporation into Solar System material without some degradation. The more refractory material, in particular macromolecular carbon may retain an interstellar heritage more faithfully. We present laboratory measurements on the photostability of organic compounds and discuss their survival in regions with elevated UV radiation. We also show recent observations of diffuse interstellar bands indicating the presence of fullerenes. We investigate the link between the carbon chemistry in interstellar space and in the Solar System by analyzing the carbonaceous fraction of meteorites and by reviewing stable isotopic data. It also seems evident that both volatile and refractory material from carbonaceous meteoritic has been substantially altered owing to thermal and aqueous processing within the Solar System.


How to synthesise original findings back into the literature: a reintroduction to concurrent analysis.
All studies need to integrate their findings back into the literature to explain how the new knowledge changes understanding. This process can be anxiety-provoking, especially when new literature appears to threaten the originality of the study. To reintroduce 'concurrent analysis' (CA) - a method of synthesising relevant literature with primary data. CA treats all data as primary data. To illustrate the technique, the authors synthesise relevant literature with findings from a doctoral study of patients' experiences of vascular access devices. CA raised new questions that would otherwise have remained unasked. For example, it revealed cultural differences in the way patients react to suboptimal treatment. Nurse researchers are best placed to influence policy and practice when they can articulate the transferability of their findings. CA is a practical method of achieving this.


High molecular weight aspartic endopeptidase generates a coronaro-constrictory peptide from the beta-chain of hemoglobin.
Studying the influence of brain cathepsin D (EC 126.96.36.199) and high molecular weight (HMW) aspartic endopeptidase (EC 3.4.23.-) on the processing of hypothalamic calmodulin-binding coronaro-constrictory peptide factors from the beta-chain of globin it was found that only HMW aspartic endopeptidase generates the fragment 31-40 of the beta-chain of bovine hemoglobin (Hb) by cleavage of the Leu30-Leu31 and Phe40-Phe41 bonds. Digestion of the beta-chain of globin was performed at 37 degrees C at an enzyme/substrate ratio of 1:80 at pH 3.5 using different times of incubation (from 4 h to 10 h). The resulting peptides were separated by reversed-phase high-performance liquid chromatography (HPLC) and then identified by amino acid analysis and Edman degradation. The differences in specificity and activity of these two brain aspartic proteinases could be explained by their different structural features. Our finding provides evidence for a different biological function of these two enzymes. Data obtained give us reason to suppose that HMW aspartic proteinase probably can participate in the processing of the coronaro-constrictory peptide in vivo by limited proteolysis of Hb or Hb-like protein.


Transcriptomic profile of the porcine oviductal epithelial cells during the peri-conceptional period.
The optimal environment in the oviduct is created by adjusting its ultrastructure and secretory activity to serve the most suitable protection of gametes and to support embryo development. Through gametes/embryo's presence inside the oviduct, the oviductal transcriptomic profile may be altered, and these changes may be caused by DNA methylation. The results of the present study documented that in the epithelial cells of the ampulla and isthmus of the oviducts collected from pigs during the peri-conceptional period, the most differentially expressed genes (DEGs) were down-regulated. Identified DEGs were classified into gene ontology categories as well as annotated into different biological pathways. From evaluated DEGs, genes important for embryo development were selected and the level of DNA methylation was determined. It was documented CLDN18, MUC1, CYP19A3, SOCS1, and ESR1 methylation level have been altered. The presence of embryos in the oviduct changed the transcriptomic profile and the level of DNA methylation in the epithelial cells of ampulla and isthmus during the peri-conceptional period.


Cytokines, Transcription Factors, and the Initiation of T-Cell Development.
Multipotent blood progenitor cells migrate into the thymus and initiate the T-cell differentiation program. T-cell progenitor cells gradually acquire T-cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T-cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals. Together with Notch or pre-T-cell-receptor (TCR) signaling, cytokines always control proliferation, survival, and differentiation of early T cells, but little is known regarding their cross talk with transcription factors. However, recent results suggest ways that cytokines expressed in distinct intrathymic niches can specifically modulate key transcription factors. This review discusses how stage-specific roles of cytokines and transcription factors can jointly guide development of early T cells.


Evaluation of two socket healing procedures with and without mesenchymal stem cells: A comparative study.
Successful preservation of the edentulous ridge after extraction may eliminate or reduce the need for ridge augmentation procedures. It is proved that grafting of fresh extraction sockets with bone grafts promotes ridge preservation. An objective method of maintaining height and width of alveolar ridge using mesenchymal stem cells (MSCs) seeded on collagen membrane was implemented in this study. Ten bilaterally symmetrical extraction sockets scheduled for extraction were selected for this study. Involved teeth were extracted atraumatically and the sockets were curetted. MSCs seeded on collagen membrane were placed in the extracted socket on one side. On the other side, only collagen membrane was placed inside the socket. Both the sockets were closed primarily with nonresorbable sutures. Buccolingual and mesiodistal widths of the ridges at three different levels (2 mm below cementoenamel junction [CEJ], 5 mm below CEJ, and 8 mm below CEJ) were assessed immediately after extraction and postoperatively at 3 and 6 months. There was statistically significant observation in maintaining the alveolar ridge width in the grafted site when compared to the nongrafted site. Socket healing procedure using MSCs and collagen membrane was successful in maintaining width of alveolar socket.


Apical transportation: a comparative evaluation of three root canal instrumentation techniques with three different apical diameters.
This study conducted an in vitro analysis of the level of apical transportation in mesiobuccal roots of upper molars after manual instrumentation with stainless steel files, preparation with the K3 system, and with a reciprocating NSK handpiece. Sixty roots were mounted in muffles and then longitudinally sectioned. A digital image was acquired of the inner surface of one root half. After instrumentation, the inner surfaces of the same root halves were digitized with file sizes #30, #35, and #40. Each image obtained was superimposed over the corresponding preoperative image, and the apical transportation was measured. The Friedman and Wilcoxon tests were used to compare results for the file sizes, and comparison of the groups was made with the Kruskal-Wallis test, demonstrating statistically significant differences (P = .000). The stainless steel file sizes #35 and #40 caused significant apical transportation, and K3 system proved safe for apical preparation, with little deviation.


Apo-E genotypes and cardiovascular diseases: a sensitivity study using cross-validatory criteria.
The Apolipoprotein-E (Apo-E) gene, a gene that produces proteins which help to regulate lipid levels in the bloodstream, is of interest in the study of cardiovascular diseases. An approach to making inferences about the genetic effects of the Apo-E gene has been developed by Glickman and Gagnon (2002). The framework describes the role of genetic and risk factors on the onset ages of multiple diseases, and accounts for the possibility that an individual was censored for reasons related to the diseases of interest. The framework also allows for missing genetic information, so that subjects censored prior to genetic sampling, and therefore missing such information, may still be included in the analysis. We apply an extension to this framework to the original cohort of the Framingham Heart Study for measuring the effects of different Apo-E genotypes on the onset age of various cardiovascular disease events. In particular, we compare the fit of univariate versus multivariate onset age components to the model, whether to incorporate health covariates measured at baseline or at a point later in the study, and whether to assume a heritability model for Apo-E genotype frequencies. The results of the best fitting model are presented.


Encoding of whisker vibration by rat barrel cortex neurons: implications for texture discrimination.
Rats, using their whiskers, have excellent capabilities in texture discrimination. What is the representation of texture in rat somatosensory cortex? We hypothesize that as rats "whisk" over a surface, the spatial frequency of a grooved or pebbled texture is converted to a temporal frequency of whisker vibration. Surface features such as groove depth or grain size modulate the amplitude of this vibration. Validation of the hypothesis depends on showing that vibration parameters have distinct neuronal representations in cortex. To test this, we delivered sinusoidal vibrations to the whisker shaft and analyzed cortical neuronal activity. Seven amplitudes and seven frequencies were combined to construct 49 stimuli while recording activity through a 10 x 10 microelectrode array inserted into the middle layers of barrel cortex. We find that cortical neurons do not explicitly encode vibration frequency (f) or amplitude (A) by any coding measure (average spike counts over different time windows, spike timing patterns in the peristimulus time histograms or in autocorrelograms). Instead, neurons explicitly encode the product of frequency and amplitude, which is proportional to the mean speed of the vibration. The quantity Af is an invariant because neuronal response encodes this feature independently of the values of the individual terms A and f. This was true across a wide time scale of firing rate measurements, from 5 to 500 msec. We conclude that vibration kinetics are rapidly and reliably encoded in the firing rate of cortical ensembles. Therefore, the cortical representation of vibration speed could underlie texture discrimination.


Epstein-Barr virus and multiple sclerosis: association or causation?
Multiple sclerosis (MS) is a multifactorial disease in which both genetic and environmental factors and their interactions underlie causation. The current evidence base supports a strong association between Epstein-Barr virus (EBV) and MS, but potential causality remains strongly debated. It is not possible to exclude the possibility that an abnormal response to EBV infection is a consequence, rather than a cause, of the underlying pathophysiology of MS, or indeed that the association may be a reflection of a similar underlying disease mechanism. Substantial experimental progress is necessary to achieve consistency of molecular findings to complement the strong epidemiological association between EBV and MS, which cannot alone show causation. Collectively, the strength of the association between EBV and MS warrants careful development and trial of anti-EBV drugs to observe any effect on MS disease course.


Cation exchange on the surface of gold nanorods with a polymerizable surfactant: polymerization, stability, and toxicity evaluation.
Gold nanorods were synthesized using a seed-mediated wet chemical approach with a quaternary ammonium surfactant, cetyltrimethylammonium bromide (CTAB), that forms a bilayer on the surface of the nanorods. The CTAB molecules in the bilayer were exchanged with a similar polymerizable analog, 11-(acryloyloxy) undecyltrimethyl ammonium bromide (p-CTAB). Mass spectrometric analysis of the degree of exchange of CTAB for p-CTAB, after gold digestion, gave 77 +/- 3 and 23 +/- 1% for p-CTAB and CTAB, respectively. On-rod polymerization with a cationic free-radical initiator was confirmed by FTIR analysis and did not induce aggregation as judged by ultraviolet-visible spectroscopy, transmission electron microscopy, and dynamic light scattering measurements after polymerization. In contrast to the nanorods before polymerization, the nanorods with a polymerized bilayer showed improved stability against dialysis as well as enhanced biocompatibility as measured using a viability assay on cultured human cells. Our results indicate that (1) CTAB molecules on the surface of the gold nanorods are exchangeable with similar surfactants that have a positively charged headgroup and (2) surfactant polymerization on the surface of the gold nanorods enhances both the stability and biocompatibility of these nanomaterials, probably by decreasing the degree of surfactant desorption from the surface.


The challenges of determining metal-protein affinities.
A key property of metallo-proteins and -enzymes is the affinity of metal ion M for protein ligand P as defined by the dissociation constant KD = [M][P]/[MP]. Its accurate determination is essential for a quantitative understanding of metal selection and speciation. However, the surfaces of proteins are defined by the sidechains of amino acids and so abound in good metal ligands (e.g., imidazole of histidine,thiol of cysteine, carboxylate of aspartic and glutamic acids, etc.). Consequently, adventitious binding of metal ions to protein surfaces is common with KD values > or = 10(-6) M. On the other hand, transport proteins responsible for 'chaperoning' essential metals to their cellular destinations appear to bind the metal ions selectively (KD < 10(-7) M, both for speciation and to minimise the toxic effects of 'free' metal ions. These ions are normally bound with still higher affinities at their ultimate destinations (the active sites of metallo-proteins and -enzymes). This review surveys possible approaches to estimation of these dissociation constants and pinpoints the various problems associated with each approach.


Crimean-Congo hemorrhagic fever: aid of abdominal ultrasonography in prediction of severity.
Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection that involves multiple organs, and endothelium. We described abdominal sonographic findings of the patients infected with the Crimean-Congo hemorrhagic fever virus (CCHFV) in relation to the severity of the disease. This is a prospective study performed among hospitalized patients infected with CCHF between 2005 and 2011. A total of 210 hospitalized patients with confirmed CCHF infection were included in the study. The mean age was 47 and 49.5% of the patients were female. Patients were classified as mild, moderate, or severe disease according to their clinical and laboratory findings. The relationship between the clinical severity of CCHF and the abdominal sonographic findings was analyzed. Sonographic findings of abdomen included gallbladder wall thickening (GBWT) in 44 (21%), splenomegaly in 39 (19%), hepatomegaly in 52 (25%), decrease in echo of liver parenchyma in nine (4%), increase in echo liver parenchyma in 13 (6%), intra-abdominal fluid collection/ascites in 23 (11%), and enlarged periportal lymph nodes in seven (3%) cases. GBWT was detected in 3% of mild patients, 23% of moderate patients, and 61% of severe patients (p<0.001). In multivariate analysis to predict the severity, GBWT (odds ratio [OR] 5.4, confidence interval [CI] 1.76-16.49, p=0.003) and intra-abdominal fluid collection/ascites (OR 3.5, CI 1.07-12.61, p=0.049) were found to be significantly associated with disease severity. In conclusion, ultrasonography is a reliable, useful, and noninvasive diagnostic tool for evaluation of the abdominal findings of the patients with CCHFV infection. GBWT and intra-abdominal fluid collection/ascites were found to be predictors of severity.


[Epidemiological profile of tuberculosis in a health area of the Valencian Community (1998-2000)].
To find the epidemiological characteristics of cases of tuberculosis (TB) notified in Health Area 09 of the Valencian Community during 1998-2000.Design. Descriptive, observational, epidemiological study. Unit of epidemiology in the Public Health Centre of Alzira, Area 09 of the Valencian Community.Participants. Cases of TB that met the clinical or bacteriological definitions according to the protocols of the National Network of Epidemiology Protection. The epidemiological questionnaire for TB declaration in the Valencian Community was used. The variables included were: sex, age, town, risk factors, associated pathology, location, origin and study of contacts. A univariate statistical analysis was run, with the SPSS version 9.01. Cases numbered 118. The rate of annual occurrence ranged between 25.5 per 100 000 in 1999 and 43.5 per 100 000 in 1998, similar to that in the year 2000 (42.5 per 100 000). 64.4% were men and 26.3% were between 25 and 34 years old. 64.4% were admitted. There was a study of contacts in 73.7%. 78% of cases were declared by the referral hospital. TB in Area 09 was concentrated in young adults needing hospital admission. TB declaration was usually made from the hospital.


Rapid SNP allele frequency determination in genomic DNA pools by pyrosequencing.
Individual genotyping of single nucleotide polymorphisms (SNPs) remains expensive, especially for linkage disequilibrium mapping strategies involving high-throughput SNP genotyping. On one hand, current methods may suit scientific and laboratory needs in regard to accuracy, reproducibility/robustness, and large-scale application. On the other hand, a cheaper and less time-consuming alternative to individual genotyping is the use of SNP allelefrequencies determined in DNA pools. We have developed an accurate and reproducible protocol for allele frequency determination using Pyrosequencing technology in large genomic DNA pools (374 individuals). The measured correlation (R2) in large DNA pools was 0.980. In the context of disease-associated SNPs studies, we compared the allele frequencies between the disease (e.g., type 2 diabetes and obesity) and control groups detected by either individual genotyping or Pyrosequencing of DNA pools. In large pools, the variation between the two methods was 1.5 +/- 0.9%. It may be concluded that the allele frequency determination protocol could reliably detect over 4% differences between populations. The method is economical in regard to amounts of DNA, PCR, and primer extension reagents required. Furthermore, it allows the rapid determination of allelefrequency differences in case/control groups for association studies and susceptibility gene discovery in complex diseases.


Sleep and agitation in nursing home residents with and without dementia.
The prevalence of dementia in Australian nursing homes is high. A large proportion of residents express themselves through agitated behaviors, with substantial interpersonal and day-to-day variance. One factor that may increase agitation is poor sleep. The current study aimed to determine if sleep influences symptoms of agitation in nursing home residents, and whether this effect differed by dementia status. As benzodiazepines are used widely as hypnotic medication, their impact was also considered. Actigraph devices worn on residents' non-dominant wrists for three days were used to obtain objective measures of sleep. Symptoms of agitation were assessed using staff responses to two standardized questionnaires - the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory - nursing home version (NPI-NH). Presence of dementia and benzodiazepine use were obtained from resident medical charts. Forty-nine residents (mean age: 85.57 years) from four nursing homes in Tasmania were included in the study. Results indicated that residents were in bed for an average of 11.04 h and slept for 10.14 h per day. Significant relationships between sleep and verbal as well as non-aggressive agitation were found. No relationships between sleep and aggressive agitation were detected. A significant moderation effect of dementia was found, in which residents without dementia expressed verbal agitation when obtaining less sleep, but not residents with dementia. Benzodiazepine use did not result in significantly more sleep. These results suggest that sleep could play an important role in explaining agitation, but more research is needed to explore the relationship between sleep and benzodiazepines in nursing home residents.


Geometric Explanation of Anomalous Finite-Size Scaling in High Dimensions.
We give an intuitive geometric explanation for the apparent breakdown of standard finite-size scaling in systems with periodic boundaries above the upper critical dimension. The Ising model and self-avoiding walk are simulated on five-dimensional hypercubic lattices with free and periodic boundary conditions, by using geometric representations and recently introduced Markov-chain Monte Carlo algorithms. We show that previously observed anomalous behavior for correlation functions, measured on the standard Euclidean scale, can be removed by defining correlation functions on a scale which correctly accounts for windings.


Laboratory investigation and diagnosis of thrombotic thrombocytopenic purpura.
Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease for which rapid diagnosis is crucial for patient outcomes. Deficient activity (< 10%) of the liver enzyme, ADAMTS13, is the pathophysiological hallmark of TTP, and measurement of the enzyme activity can establish the diagnosis of TTP with high accuracy. Thus, along with the clinical history, appropriate laboratory assessment of a suspected case of TTP is essential for diagnosis and treatment. Here, we present a review of the available laboratory tests that can assist clinicians in establishing the diagnosis of TTP, with special focus on ADAMTS13 assays, including the measurement of the antigen and activity, and detection of autoantibodies to ADAMTS13.


Successful clinical use of an anti-HLA-DR monoclonal antibody for autologous bone marrow transplantation.
It has been widely assumed that anti-HLA-DR antibodies react with pluripotent stem cells and cannot be used in bone marrow purging. We report a case of non-Hodgkin's lymphoma in which an anti-HLA-DR antibody (AB4) was used for immunomagnetic purging and the subsequent autologous bone marrow transplantation resulted in rapid marrow engraftment with no serious complications. The results indicate that the AB4 antibody, which binds to an antigen encoded by the B3 gene of the DR region, can be safely used in the clinic in the purging of bone marrow from patients with AB4-positive tumors (non-T-cell acute lymphocytic leukemia, non-Hodgkin's lymphoma, and some cases of acute myelogenous leukemia.


Validation of liquid chromatography-electrospray ionization ion trap mass spectrometry method for the determination of mesocarb in human plasma and urine.
Mesocarb metabolism in humans is the target of this investigation. A high-performance liquid chromatographic (LC) method with electrospray ionization (ESI)-ion trap mass spectrometric (MS) detection ion trap "SL" for the simultaneous determination of mesocarb and its metabolites in plasma and urine is developed and validated. Ten metabolites and the parent drug are detected in human urine, and only four in human plasma, after the administration of a single oral dose of 10 mg of mesocarb (Sydnocarb, two 5-mg tablets). Seven of this metabolites have been found for the first time. The confirmation of the results and identification of all the metabolites except amphetamine is performed by LC-MS, LC-MS-MS, and LC-MS3. In the case of doping analysis, the reliable detection time for mesocarb (long-life dihydroxymesocarb metabolites of mesocarb) is approximately 10-11 days after the administration of the drug, which is a significant increase over the existing data. The detection of amphetamine in plasma and urine is made using simple flow-injection analysis without a chromatographic separation. The addition-calibration method is used with plasma and urine. The mean recoveries from plasma are 49.2% and 57.4% for mesocarb concentrations of 33.0 and 66.0 ng/mL, respectively, whereas the recoveries from human urine are 76.9% and 81.4% for concentrations of 1 and 2 ng/mL, respectively. Calibration curves (using an internal standard method) are linear (r2>0.9969) for concentrations 0.6 to 67 ng/mL and from 0.05 to 5 ng/mL in plasma and urine, respectively. Both intra- and interassay precision of plasma control samples at 3, 40, and 55 ng/mL are lower than 6.2%, and the concentrations do not deviate for more than -3.4% to 7.3% from their nominal values. In urine, intra- and interassay precision of control samples at 0.08, 1.5, and 3.0 ng/mL is lower than 14.1%, with concentrations not deviating for more than -11.3% to 13.7% from their nominal values. The plasma disappearance curve of the parent drug is obtained. The major pharmacokinetic parameters are calculated.


"Painless" spinal epidural hematoma during anticoagulant therapy.
Severe back or radicular pain has previously been considered as the earliest and most prominent symptom in spinal epidural hematoma. In the patient described here, a "painless" spinal epidural hematoma developed during anticoagulant therapy. The absence of pain delayed recognition of the lesion and institution of therapy. The absence of pain is distinctively rare, but should not delay appropriate diagnostic procedures when other signs suggest the presence of a spinal epidural hematoma.


Dynamics of coupled adaptive elements: bursting and intermittent oscillations generated by frustration in networks.
Adaptation to environmental change is a common property of biological systems. Cells initially respond to external changes in the environment, but after some time, they regain their original state. By considering an element consisting of two variables that show such adaptation dynamics, we studied a coupled dynamical system containing such elements to examine the diverse dynamics in the system and classified the behaviors on the basis of the network structure that determined the interaction among elements. For a system with two elements, two types of behaviors, perfect adaptation and simple oscillation, were observed. For a system with three elements, in addition to these two types of dynamics, rapid-burst-type oscillation and a slow cycle were discovered; depending on the initial conditions, these two types of dynamics coexisted. These behaviors are a result of the characteristic dynamics of each element, i.e., fast response and slow adaptation processes. The behaviors depend on the network structure (in specific, a combination of positive or negative feedback among elements). Cooperativity among elements due to a positive feedback loop leads to simple oscillation, whereas frustration involving alternating positive and negative interactions among elements leads to the coexistence of rapid bursting oscillation and a slow cycle. These behaviors are classified on the basis of the frustration indices defined by the network structure. The period of the slow cycle is much longer than the original adaptation time scale, while the burst-type oscillation is a continued response that does not involve any adaptation. We briefly discuss the universal applicability of our results to a network of a larger number of elements and their possible relevance to biological systems.


Binding of neomycin to the TAR element of HIV-1 RNA induces dissociation of Tat protein by an allosteric mechanism.
Neomycin inhibits the binding of Tat-derived peptides to the trans-activating region (TAR) of HIV-1 RNA. Kinetic studies reveal that neomycin acts as a noncompetitive inhibitor that can bind to the Tat-TAR complex and increase the rate constant (koff) for dissociation of the peptide from the RNA. Neomycin effects a conformational change in the structure of TAR that can be detected by circular dichroism spectroscopy. The increase in ellipticity measured at 265 nm upon binding of the aminoglycoside is opposite to the decrease seen when Tat peptides bind to the RNA. Thus, the structural transition induced by neomycin is apparently incompatible with the binding of Tat and underlies the inhibitory action of the antibiotic. The binding site for neomycin on TAR was identified in ribonuclease protection experiments and is located in the stem immediately below the three-nucleotide bulge that serves as the primary identity element for Tat. Apparent protection of residues in the bulge by neomycin may represent additional contacts to the aminoglycoside, but more likely result from changes in the structure of this region when the ligand binds to the RNA. Binding assays using variants of TAR in which inosine residues were substituted for guanosine residues support the results from the ribonuclease protection experiments. Inosine substitutions in the lower stem, but not the upper stem, decrease the binding constant for neomycin by approximately 100-fold. Neither of these variants affected the binding affinity of Tat peptide. In addition, these latter experiments suggest that the aminoglycoside may be located in the minor groove of the stem. This mode of association may be a critical aspect of neomycin's ability to bind to the Tat-TAR complex and could serve as a guide for the design of other drugs that bind to specific RNA targets as noncompetitive inhibitors.


Biocompatibility of mannuronic acid-rich alginates.
Highly purified algin preparations free of adverse contaminants with endotoxins and other mitogens recently became available by a new purification process (Klöck et al., Appl. Microbiol. Biotechnol., 1994, 40, 638-643). An advantage of this purification protocol is that it can be applied to alginates with various ratios of mannuronic acid to guluronic acid. High mannuronic acid alginate capsules are of particular practical interest for cell transplantation and for biohybrid organs, because mannuronate-rich alginates are usually less viscous, allowing one to make gels with a higher alginate content. This will increase their stability and reduce the diffusion permeability and could therefore protect immobilized cells more efficiently against the host immune system. Here we report the biocompatibility of purified, mannuronic acid-rich alginate (68% mannuronate residues) in a series of in vitro, as well as in vivo, assays. In contrast to raw alginate extracts, the purified product showed no mitogenic activity towards murine lymphocytes in vitro. Its endotoxin content was reduced to the level of the solvent. Animal studies with these new, purified algin formulations revealed the absence of a mitogen-induced foreign body reaction, even when the purified material (after cross-linking with Ba2+ ions) is implanted into animal models with elevated macrophage activity (diabetes-prone BB/OK rat). Thus, alginate capsules with high mannuronic acid content become available for applications such as implantation. In addition to the utilization as implantable cell reactors in therapy and biotechnology, these purified algins have broad application potential as ocular fillings, tissue replacements, microencapsulated growth factors and/or interleukins or slow-release dosage forms of antibodies, surface coatings of sensors and other invasive medical devices, and in encapsulation of genetically engineered cells for gene therapy.


Could legal requirements in nursing practice trigger actions that would change the rates of urinary tract infections? A case study in Brazil.
We evaluated the influence of a Brazilian resolution, published in 2013, that restricts the performing of urinary catheterization to nurses, as opposed to others from different nursing professional categories, on indicators of catheter-associated urinary tract infection in an intensive care unit. The resolution triggered actions such as the implementation of protocols and nursing staff training that led to behavior changes related to the reduction of catheter-associated urinary tract infection rates.


A new species of Sybistroma Meigen (Diptera: Dolichopodidae) from the Middle East with a key to West-Palaearctic species of the genus.
A new species, Sybistroma occidasiatica sp. nov., from the Middle East is described. It is close to S. inornata (Loew, 1857), but is distinguished by its long arista-like antennal stylus (longer than postpedicel) and short apicoventral epandrial lobe of the hypopygium (much shorter than cercus). The new species is peculiar in comprising two phenotypes, which can be distinguished by the length ratio of 1st and 2nd articles of the antennal stylus. The following recombination is also proposed: Sybistroma caudata (Loew, 1859), comb. nov. (transferred from Gymnopternus Loew, 1857). A checklist of the 26 West-Palaearctic species of the genus is compiled, as well as a key based mainly on male secondary sexual characters. The known distribution of Sybistroma Meigen, 1824, is discussed.


Dual Photo-/Electrochromic Pyromellitic Diimide-Based Coordination Polymer.
By the combination of N,N'-bis(carboxymethyl)-pyromellitic diimide (H2CMPMD, 1) and zinc ions, a novel PMD-based coordination polymer (CP), [Zn(CMPMD)(DMF)1.5]·0.5DMF (2) (DMF = N,N'-dimethylformamide), has been prepared and characterized. 1 and 2 exhibit completely different photochromic properties, which are mainly reflected in the photoresponsive rate (5 s for 1 vs 1 s for 2) and coloration contrast (from colorless to light green for 1 vs green for 2). This phenomenon should be attributed to the introduction of zinc ions and the consequent formation of the distinct interfacial contacts of electron donors (EDs) and electron acceptors (EAs) (dn-π = 3.404 and 3.448 Å for 1 vs dn-π = 3.343, 3.359, 3.398, and 3.495 Å for 2), suggesting a subtle modulating effect of metal ions on interfacial contacts, photoinduced intermolecular electron transfer (PIET) and photochromic behaviors. Interestingly, the photochromic performance of 2 can be enhanced after the removal of coordinated DMF, which might be ascribed to the decrease of the distance of EDs/EAs caused by lattice shrinkage, which further improves the efficiency of PIET. Meanwhile, 2 displays rapid electrochromic behavior with an obvious reversible color change from colorless to green, which can be used in an electrochromic device. This work develops a new type of EA for the construction of stimuli-responsive functional materials with excellent dual photo-/electrochromic properties.


Interleukin-1 and glucose homeostasis: an example of the biological relevance of immune-neuroendocrine interactions.
Interleukin-1 (IL-1), a cytokine mainly produced by monocytes-macrophages, plays a crucial role in immunological and inflammatory processes. We have recently demonstrated that IL-1 can also affect neuroendocrine mechanisms. In this paper, we refer to the capacity of IL-1 to affect glucose homeostasis. In normal mice, low doses of IL-1 induce a long-lasting hypoglycemia which is not dependent on possible insulin-secretagogue actions of this cytokine. The hypoglycemic effect of IL-1 is also observed in insulin-resistant diabetic mice. Furthermore, IL-1 seems to adjust the 'set point' for glucose regulation to a lower level. The effects of IL-1 on glucose homeostasis constitute a clear example of the biological relevance of immune-neuroendocrine interactions.


A Mysterious Recurrent Urticarial Rash and a Life-Altering Metal.
Allergic contact dermatitis is a common manifestation in individuals who have a contact hypersensitivity to nickel. Direct exposure to nickel triggers an adaptive immune response that mediates a localized inflammatory reaction of the skin, typically resulting in an erythematous and pruritic rash at the site of contact. We present a distinct case in which nickel was systemically introduced via a carotid stent into an individual with an unidentified allergy to nickel. This case emphasizes the potentially life-threatening risks associated with implantable hardware containing metals, such as nickel. Moreover, this case highlights the potential benefit that screening for metal allergies may have before surgically implanting permanent metal-based devices.


Genetic diversity in a world germplasm collection of tall fescue.
Festuca arundinacea Schreb., commonly known as tall fescue, is a major forage crop in temperate regions. Recently, a molecular analysis of different accessions of a world germplasm collection of tall fescue has demonstrated that it contains different species from the genus Festuca and allowed their rapid classification into the three major morphotypes (Continental, Mediterranean and Rhizomatous). In this study, we explored the genetic diversity of 161 accessions of Festuca species from 29 countries, including 28 accessions of INTA (Argentina), by analyzing 15 polymorphic SSR markers by capillary electrophoresis. These molecular markers allowed us to detect a total of 214 alleles. The number of alleles per locus varied between 5 and 24, and the values of polymorphic information content ranged from 0.627 to 0.840. In addition, the accessions analyzed by flow cytometry showed different ploidy levels (diploid, tetraploid, hexaploid and octaploid), placing in evidence that the world germplasm collection consisted of multiple species, as previously suggested. Interestingly, almost all accessions of INTA germplasm collection were true hexaploid tall fescue, belonging to two eco-geographic races (Continental and Mediterranean). Finally, the data presented revealed an ample genetic diversity of tall fescue showing the importance of preserving the INTA collection for future breeding programs.