Can the Bio-Transfx pin fail during initial ACL graft insertion?
The Bio-Transfix pin is a biodegradable device used for femoral tunnel anterior cruciate ligament (ACL) graft fixation. Recent clinical studies have suggested the possibility of the pin's postoperative failure. This investigation evaluates the initial strength of several Bio-Transfix pin ACL fixations in a simulated femoral tunnel model. The forces generated by five surgeons during simulated ACL graft tensioning were also measured. Average strengths of the pins ranged from 1075 to 2160 N for 10 and 8 mm tunnels, respectively, whereas the maximum surgeon-generated forces were 535 N. These results imply that initial fracture of the pin itself is unlikely; however, failure of the supporting bone or a decrease in pin strength due to biodegradation could account for early loss of the fixation.


Lessons learned in adopting endovascular techniques for treating abdominal aortic aneurysm.
Endovascular exclusion of abdominal aortic and common iliac aneurysms can be performed safely, and in the short term represents a feasible alternative to traditional, open aneurysm repair. Forty-one patients were treated with endovascular grafts for 39 abdominal aortic and 2 common iliac artery aneurysms. All devices were successfully deployed. The size of the abdominal aortic aneurysms varied from 4.9 to 11.9 cm (average, 6.13 cm). The median procedure time was 195 minutes. There was one iliac artery rupture, which required celiotomy for repair. The hospital stay varied from 2 to 39 days (average, 6.7 days). The perioperative mortality rate was 2.4%. Sixteen patients (39%) had groin wound complications. Ten patients (24%) had evidence of contrast (endoleak) within the aneurysm sac on completion of the procedure. There were no obvious direct leaks from either the point of proximal or distal fixation. Seven of these endoleaks have resolved spontaneously. Two patients required additional procedures in the postoperative period to treat endoleak. The final patient has evidence of persistent endoleak on 3-month surveillance computed tomography scan. Major late problems occurred in 3 patients. Patients with large abdominal aortic aneurysms and considerable cardiac comorbidity can safely undergo endovascular aneurysm repair. Femoral groin wound complications resulting in prolonged hospitalization remain the major cause of perioperative morbidity. In contradistinction to open aneurysm repair, long-term surveillance is essential to detect migration of the device and identify flow within the residual aneurysm sac-complications that could lead to aneurysm rupture following endovascular repair.


Comparison of arterial and arterialized venous concentrations of propofol during infusion of propofol.
Seven patients received a series of low-dose propofol infusions designed to produce three successive pseudo-steady states of arterial blood concentration: 0.06, 0.17 and 0.43 micrograms ml-1. Arterial and arterialized venous blood samples were obtained simultaneously at the end of each infusion. The results indicate that 95% of the arterialized venous concentrations may be expected to lie within 1 +/- 43% of the corresponding arterial concentration, or -5 +/- 35% if one set of measurements with poor agreement between duplicate aliquots is omitted.


Growth factors promote meiosis in mouse fetal ovaries in vitro.
Mouse fetal ovaries were cultured to investigate germ cell development in the presence of a combination of the growth factors (GFs) stem cell factor, insulin-like growth factor-1 and leukaemia inhibitory factor. Ovaries were isolated from fetal mice at 13 and 14 days post-coitum (dpc) and cultured to the equivalent of 17 dpc. Culture conditions comprised minimal essential medium-alpha plus 5% fetal calf serum, with or without GFs. Oocytes were assessed using immunofluorescence to illustrate synaptonemal complexes and recombination foci. The proportions of pachytene cells in freshly isolated 13, 14 and 17 dpc ovaries were 0, 8 and 74% respectively. There was a significant (P < 0.0001) increase in the number of pachytene cells after 4 days culture with GFs, with 24% of germ cells from 13 dpc ovaries reaching pachytene. In contrast, no pachytene cells were detected in cultures of 13 dpc ovaries without GFs. After 3 days in culture with GFs, 38% of germ cells from 14 dpc ovaries were at pachytene compared with 19% without GFs. In conclusion, we have demonstrated positive effects of GFs upon oocyte formation by meiosis in vitro. The observed results could be explained by an increased survival of premeiotic oogonia entering meiosis, or by effects on oocytes already in early meiosis.


GABA(A) receptor signaling in the lateral septum regulates maternal aggression in mice.
Maternal aggression (maternal defense) is a fierce aggression produced by lactating females toward intruders that plays an important role in protection of vulnerable offspring. Enhancement of GABA(A) receptor signaling by benzodiazepines increases maternal aggression, and we recently found indirect evidence that lateral septum (LS) could be a key site where benzodiazepines elevate aggression. In this study, we directly tested the hypothesis that activation of GABA(A) receptors in LS would promote maternal aggression while inhibition of this receptor would decrease aggression. Site-directed injections to LS were made using the GABA(A) receptor antagonist, bicuculline (3-30 ng), or the GABA(A) receptor agonists, chlordiazepoxide, a benzodiazepine (2.5-5 microg), and muscimol (0.05-5 ng). Maternal aggression and other behavioral measures were then evaluated in lactating mice. Neither GABA(A) receptor agonist elevated aggression, which could reflect a ceiling effect. However, 7 ng of the GABA(A) receptor antagonist, bicuculline, in LS significantly decreased maternal aggression without altering other maternal behaviors or light-dark box performance, suggesting some GABA(A) receptor signaling in LS is required for full maternal aggression expression. Together, these results confirm a role for GABA(A) receptor signaling in LS in the regulation of maternal aggression.


Memory improvement tapes: How effective for elderly adults?
The effectiveness of two commercially available audiocassette memory improvement programs was evaluated in a sample of 32 healthy, community-living elderly adults. Participants were given a set of either Syber Vision's Neuropsychology of Memory Power tapes (Bornstein, 1989) or Nightingale-Conant's Mega Memory tapes (Trudeau, 1992), and a portable cassette player, and instructed to complete the programs within 10 weeks. All participants received a comprehensive battery of memory tests prior to and immediately following the memory improvement programs. Participants completing the memory improvement programs showed no greater gains in memory test performance than no-treatment control participants, but did report greater confidence in their memory abilities. Participants completing the Mega Memory program thought they were less likely to develop Alzheimer's disease after having completed it compared with participants in the other two conditions. Participants reported finding both tape programs acceptable and potentially useful for improving memory; those who completed the Memory Power program reported somewhat greater satisfaction than those completing the Mega Memory program. the claims about rapid, dramatic memory improvement with use of these products were not substantiated in this group of elderly adults and appear to be grossly exaggerated.


Control of Salmonella and Pathogenic E. coli Contamination of Animal Feed Using Alternatives to Formaldehyde-Based Treatments.
This study compared a novel non-formaldehyde combination product developed for pathogen control in animal feed Finio (A), with a panel of three commonly used organic acid feed additive products: Fysal (B), SalCURB K2 (C) and Salgard (D). Products were evaluated for their ability to reduce Salmonella Typhimurium DT104 and avian pathogenic Escherichia coli in poultry feed. A commercial layer-hen mash was treated with each product and then mixed with feed previously contaminated (via inoculated meat and bone meal) with either Salmonella or E. coli. After 24 hours at room temperature, 10 replicate samples were taken from each preparation and plate counts were performed using a selective agar. All concentrations of product A (0.5, 1.0, 1.5, 2.0 and 2.5 kg per metric tonne (MT)) plus the higher concentration of products B and D (6.0 kg MT-1) significantly reduced Salmonella counts compared with those in the untreated control group (p < 0.05). Product C did not significantly reduce levels of Salmonella under these conditions. Because of the poor recovery of E. coli, statistical comparisons for this organism were limited in scope, but only product A at the highest concentration appeared to have eliminated it.


Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation.
Platelet activation is a complex balance of positive and negative signaling pathways. The protein kinase C (PKC) family is a major regulator of platelet granule secretion, integrin activation, aggregation, spreading and procoagulant activity. As broad-spectrum PKC inhibitors reduce secretion and aggregation, the PKC family is generally considered to be a positive regulator of platelet activation. However, the individual members of the PKC family that are expressed in platelets are regulated in different ways, and an increasing body of evidence indicates that they have distinct, and often opposing, roles. Many of the recent advances in understanding the contributions of individual PKC isoforms have come from mouse gene knockout studies. PKCalpha, a classic isoform, is an essential positive regulator of granule secretion and thrombus formation, both in vitro and in vivo. Mice lacking PKCalpha show much reduced thrombus formation in vivo but do not have a bleeding defect, suggesting that PKCalpha could be an attractive antithrombotic target. Important, apparently non-redundant, roles, both positive and negative, for the novel PKC isoforms delta, theta and epsilon in granule secretion have also been proposed, indicating highly complex regulation of this essential process. Similarly, PKCbeta, PKCdelta and PKCtheta have non-redundant roles in platelet spreading, as absence of either PKCbeta or PKCtheta reduces spreading, whereas PKCdelta negatively regulates filopodial formation. This negative signaling by PKCdelta may reduce platelet aggregation and so restrict thrombus formation. In this review, we discuss the current understanding of the regulation and functions of individual PKC isoforms in platelet activation and thrombus formation.


Estimation of vehicle speed using wayside sound pressure onset rate.
Transportation-related environmental noise studies, particularly those associated with rail traffic, often require long term measurements near existing rights of way. In addition to the sound produced by passing vehicles, it is also useful to know their speed. Previously, speed measurements have generally required an additional piece of instrumentation, such as a second microphone, video camera, or a radar gun--resulting in added measurement cost and complexity. The present study shows how estimations of vehicle speed can be obtained using a single wayside microphone. The method is based on the rate of pressure rise as the vehicle approaches, specifically the maximum onset rate. This paper shows how the maximum onset rate depends only on the vehicle speed, the microphone distance, and the speed of sound. In order to demonstrate the feasibility of the approach field test data are presented for train passages ranging in speed from 33.5 to 55.6 m/s, as measured by a microphone located 28.65 m from the tracks. Speed estimates derived from the onset rate were generally accurate to within 8% of the independently measured speed of the train.


Trunk bradykinesia and foveation delays during whole-body turns in spasmodic torticollis.
We have investigated how the abnormal head posture and motility in spasmodic torticollis interferes with ecological movements such as combined eye-to-foot whole-body reorientations to visual targets. Eight mildly affected patients and 10 controls voluntarily rotated eyes and body in response to illuminated targets of eccentricities up to ± 180°. The experimental protocol allowed separate evaluation of the effects of target location, visibility and predictability on movement parameters. Patients' latencies of eye, head, trunk and foot motion were prolonged but showed a normal modification pattern when target location was predictable. Peak head-on-trunk displacement and velocity were reduced both ipsi- and contralaterally with respect to the direction of torticollis. Surprisingly, peak trunk velocity was also reduced, even more than in previously studied patients with Parkinson's disease. As a consequence, patients made short, hypometric gaze saccades and only exceptionally foveated initially nonvisible targets with a single large gaze shift (4 % of predictable trials as opposed to 30 % in controls). Foveation of distant targets was massively delayed by more than half a second on average. Spontaneous dystonic head movements did not interfere with the execution of voluntary gaze shifts. The results show that neck dystonia does not arise from gaze (head-eye) motor centres but the eye-to-foot turning synergy is seriously compromised. For the first time we identify significant 'secondary' complications of torticollis such as trunk bradykinesia and foveation delays, likely to cause additional disability in patients. Eye movements per se are intact and compensate for the reduced head/trunk performance in an adaptive manner.


Genome-wide polymorphisms show unexpected targets of natural selection.
Natural selection can act on all the expressed genes of an individual, leaving signatures of genetic differentiation or diversity at many loci across the genome. New power to assay these genome-wide effects of selection comes from associating multi-locus patterns of polymorphism with gene expression and function. Here, we performed one of the first genome-wide surveys in a marine species, comparing purple sea urchins, Strongylocentrotus purpuratus, from two distant locations along the species' wide latitudinal range. We examined 9112 polymorphic loci from upstream non-coding and coding regions of genes for signatures of selection with respect to gene function and tissue- and ontogenetic gene expression. We found that genetic differentiation (F(ST)) varied significantly across functional gene classes. The strongest enrichment occurred in the upstream regions of E3 ligase genes, enzymes known to regulate protein abundance during development and environmental stress. We found enrichment for high heterozygosity in genes directly involved in immune response, particularly NALP genes, which mediate pro-inflammatory signals during bacterial infection. We also found higher heterozygosity in immune genes in the southern population, where disease incidence and pathogen diversity are greater. Similar to the major histocompatibility complex in mammals, balancing selection may enhance genetic diversity in the innate immune system genes of this invertebrate. Overall, our results show that how genome-wide polymorphism data coupled with growing databases on gene function and expression can combine to detect otherwise hidden signals of selection in natural populations.


[Enlarged translabyrinthine resection of recurrent acoustic neuroma after suboccipital resection].
To evaluate the technique and the outcome of enlarged translabyrinthine removal of recurrent acoustic neuromas after a suboccipital resection. Five patients were proved to have recurrent acoustic neuromas after previous suboccipital removal procedures. Revision surgery was accomplished in these patients using the enlarged translabyrinthine approach by sufficiently removing petrous temporal bone to enlarge exposed sight during the operation. The sizes of the recurrent tumors ranged from 2.5 to 4.0 cm. Total removal was achieved in all patients, with no death and other major complications such as intracranial infection and cerebrospinal fluid leakage. The facial nerve function was the same as pre-operative condition. There was no residual tumor showed in CT scans and MRI examinations after operation. The cerebel and brainstem resumed to normal position in each patient. No second recurrences had occurred to date at follow-up of 6 months to 2 years and 7 months. All patients recuperated and came back to work. Acoustic neuroma recurs frequently after the suboccipital surgery because there is a residual tumor inside the internal acoustic canal (IAC). The enlarged translabyrinthine approach is the most direct access to acoustic neuroma and the brainstem by which recurrent tumor can be removed is avoided during the second operation. Moreover, it is praisable that there are several advantages such as slight invasion and convenience of facial nerve orientation so as to excellent outcome of facial nerve preservation in the enlarged translabyrinthine surgery.


[Subperiostal orbital hemorrhage induced by effort for vomiting].
Subperiostal orbital hemorrhage is a rare condition. It usually occurs as a result of trauma or because of a vascular disorder. We present a case of subperiostal orbital hemorrhage induced by effort for vomiting. A 41-year-old pregnant patient (30 weeks of amenorrhea), with no prior history, was referred to the ENT emergency by her gynecologist for unilateral ptosis and proptosis secondary to efforts for vomiting. Clinical examination and CT scanner showed a subperiostal hematoma of the orbital roof. The hematoma resolved in ten days without sequels, under simple surveillance. Non-traumatic subperiostal orbital hemorrhage remains rare. Clinical examination and orbital CT scan allow making the diagnosis. If the optic nerve is not compressed, clinical surveillance during hematoma resorption is sufficient.


Verbascoside isolated from Lepechinia speciosa has inhibitory activity against HSV-1 and HSV-2 in vitro.
Verbascoside has been isolated form L. speciosa after several different chromatographic methods. After its purification, the structure has been unequivocally established using modern spectroscopic techniques. As for the antiviral activity, the maximum non toxic concentration has been established and this concentration has been used in the anti herpes assay, in vitro. Mechanism of action for this molecule regarding the anti-herpes activity has been studied encompassing the following assays: virucidal activity, cellular receptor assay, penetration assay and intracellular assay, in order to understand the activity for this natural product.


Factors affecting the self-rated health of elderly individuals living alone: a cross-sectional study.
In Japan, the number of elderly individuals living alone is continuing to increase as society ages. Although studies have considered quality of life, life expectancy, and gender differences in elderly individuals living alone, only a few have considered the health and lifestyle of these individuals. Therefore, we aimed to investigate the factors that affect the self-rated health of elderly individuals living alone to understand this group and how best to offer them support. We include 113 individuals. There was a significant difference (P < 0.05) in some characteristics (e.g., age, chronic illness, frequency of hospital visits in 1 month, and caregivers), activities of daily living (e.g., motor tasks), and instrumental activities of daily living (e.g., household affairs, heavy housework, outdoor household, and outdoor activities).


Nutrient digestibilities of soft winter wheat, improved triticale cultivars, and pearl millet for finishing pigs.
A replicated 4 x 4 Latin square digestion trial was conducted to determine apparent nutrient digestibilities and N and energy balances for soft red winter wheat, Beagle 82 triticale, Florico triticale, and pearl millet using finishing pigs fitted with ileal T-cannulas. Fortified experimental diets contained 97.5% of each respective grain. Nitrogen and amino acid digestibilities of soft winter wheat and triticale were similar (P greater than .13) when measured near the end of the small intestine and over the total digestive tract. Ileal digestibilities of alanine, isoleucine, leucine, threonine, tryptophan, and valine were higher (P less than .05) for pearl millet than for the other grains. Total tract N and amino acid digestibilities were all higher than ileal digestibilities. Gross energy and DM digestibilities determined at the small intestine were higher (P less than .05) for wheat and pearl millet than for Beagle 82 triticale, with the Florico variety being intermediate in energy digestibility. Total tract digestible and ME concentrations followed essentially the same pattern as ileal GE digestibility and were 2 to 3% higher (P less than .05) for wheat and pearl millet than Beagle 82 triticale. Florico triticale had similar (P greater than .05) DE but was 1.3% lower (P less than .05) in ME content than wheat.


Antimicrobial Activities of Starch-Based Biopolymers and Biocomposites Incorporated with Plant Essential Oils: A Review.
Recently, many scientists and polymer engineers have been working on eco-friendly materials for starch-based food packaging purposes, which are based on biopolymers, due to the health and environmental issues caused by the non-biodegradable food packaging. However, to maintain food freshness and quality, it is necessary to choose the correct materials and packaging technologies. On the other hand, the starch-based film's biggest flaws are high permeability to water vapor transfer and the ease of spoilage by bacteria and fungi. One of the several possibilities that are being extensively studied is the incorporation of essential oils (EOs) into the packaging material. The EOs used in food packaging films actively prevent inhibition of bacteria and fungi and have a positive effect on food storage. This work intended to present their mechanical and barrier properties, as well as the antimicrobial activity of anti-microbacterial agent reinforced starch composites for extending product shelf life. A better inhibition of zone of antimicrobial activity was observed with higher content of essential oil. Besides that, the mechanical properties of starch-based polymer was slightly decreased for tensile strength as the increasing of essential oil while elongation at break was increased. The increasing of essential oil would cause the reduction of the cohesion forces of polymer chain, creating heterogeneous matrix and subsequently lowering the tensile strength and increasing the elongation (E%) of the films. The present review demonstrated that the use of essential oil represents an interesting alternative for the production of active packaging and for the development of eco-friendly technologies.


Long-Term Retention of an Intraorbital Metallic Foreign Body Adjacent to the Optic Nerve.
We report the case of an asymptomatic 47 year-old male patient who suffered a penetrating wound from a metallic foreign body that became embedded adjacent to the optic nerve for over thirty years, as well as the associated examination, imaging, and fundus photography. Intraorbital metallic foreign bodies can be well tolerated and may not require surgical intervention despite proximity to important structures.


Induction of single chain tetracycline repressor requires the binding of two inducers.
In this article we report the in vivo and in vitro characterization of single chain tetracycline repressor (scTetR) variants in Escherichia coli. ScTetR is genetically and proteolytically stable and exhibits the same regulatory properties as dimeric TetR in E.coli. Urea-dependent denaturation of scTetR is independent of the protein concentration and follows the two-state model with a monophasic transition. Contrary to dimeric TetR, scTetR allows the construction of scTetR mutants, in which one subunit contains a defective inducer binding site while the other is functional. We have used this approach to establish that scTetR needs occupation of both inducer binding sites for in vivo and in vitro induction. Single mutations causing loss of induction in dimeric TetR lead to non-inducible scTetR when inserted into one half-side. The construction of scTetR H64K S135L S138I (scTetR(i2)) in which one half-side is specific for 4-dedimethylamino-anhydrotetracycline (4-ddma-atc) and the other for tetracycline (tc) leads to a protein which is only inducible by the mixture of tc and 4-ddma-atc. Fluorescence titration of scTetR(i2) with both inducers revealed distinct occupancy with each of these inducers yielding roughly a 1:1 stoichiometry of each inducer per scTetR(i2). The properties of this gain of function mutant clearly demonstrate that scTetR requires the binding of two inducers for induction of transcription.


Comparison of radiographic changes in the alveolar crest after extraction of fully and partially erupted premolars during orthodontic treatment: A retrospective analytical study.
Background. The alveolar process plays an essential role in providing dental support and gradually disappears with tooth loss. Space deficiency can cause one premolar to remain semi-erupted adjacent to a fully-erupted premolar. During orthodontic treatment, each of these premolars can be extracted. This retrospective study aimed to compare radiographic changes of the alveolar crest due to orthodontic movements of fully-erupted and semi-erupted premolars into the extraction sites before and after treatment. Methods. The patients were divided into the fully-erupted premolar extraction (first) group and the semi-erupted premolar extraction (second) group. The distance between the cementoenamel junction (CEJ) and the alveolar crest, from the distal aspect of the canine to the mesial aspect of the first molar, was measured on panoramic radiographs of 78 patients (39 from each group) before and after treatment with a digital caliper. Changes in the alveolar crest were compared between the two groups. Finally, the height differences of the alveolar crest in mesial and distal aspects of the remaining premolars in both groups were calculated at the end of treatment. Descriptive statistical analyses and paired and independent t tests were used in the study. Results. The distance from the CEJ to the alveolar crest at mesial and distal aspects in the first group and the distal aspect of the extraction site in the second group increased significantly. However, changes at the mesial aspect were not significant in the second group. Comparing the alveolar crest height between the two groups and between the mesial and distal aspects of the remaining premolar tooth indicated no significant differences. Conclusion. No significant difference was observed between the extraction of a fully-erupted or semi-erupted premolar to obtain greater alveolar height.


Desmoplastic Fibroma of the Mandible: Usefulness of CT and MR Imaging in Diagnosis and Treatment. A Case Report.
Desmoplastic fibroma (DF) is a rare non-metastasizing benign neoplasm of the bone characterized by aggressive local infiltration, also known as desmoid tumour. Desmoplastic fibroma of the mandible may recur locally when incompletely excised. In particular it can occur adjacent to and display contiguous extension along the mandibular nerve. This case report describes the imaging findings of a histopathologically proven desmoplastic fibroma involving the right mandibular region in a three-year-old Italian girl. We also discuss the usefulness of different imaging modalities (CT and MRI) in DF diagnosis and treatment.


The path to fusion power.
The promise, status and challenges of developing fusion power are outlined. The key physics and engineering principles are described and recent progress quantified. As the successful demonstration of 16 MW of fusion in 1997 in the Joint European Torus showed, fusion works. The central issue is therefore to make it work reliably and economically on the scale of a power station. We argue that to meet this challenge in 30 years we must follow the aggressive programme known as the 'Fast Track to Fusion'. This programme is described in some detail.


Proteomic and bioinformatic analysis on endocrine organs of domesticated silkworm, Bombyx mori L. for a comprehensive understanding of their roles and relations.
Three organs of silkworm larva endocrine system, including brain (Br), subesophageal ganglion (SG) and prothoracic glands (PG), were studied employing shotgun LC-MS/MS combined with bioinformatic analysis to comprehensively understand their roles and relations. Totally, 3430, 2683, and 3395 proteins were identified including 1885 common and 652, 253, and 790 organ-specific ones in Br, SG, and PG, respectively. Identified common-expressed proteins indicated the existence of intrinsic complex interactions among these parts of endocrine system. Most of the reputed organs-specific proteins were identified by this approach. KEGG pathway analysis showed 162 same pathways among the 169, 164, and 171 relating Br, SG, and PG. This analysis revealed functional similarities with exceptional resemblance in their metabolism and signaling pathways of the three organs. On the other hand, 70, 57, and 114 organ-specific enzymes related pathways were detected for Br, SG, and PG confirming their functional differences. These results reveal a cooperative mechanism among the three endocrine organs in regulating various physiological and developmental events, and also suggest that the organ-specific proteins might be the fundamental factors responsible for the functional differentiation of these organs.


O-GlcNAc modifications regulate cell survival and epiboly during zebrafish development.
The post-translational addition of the monosaccharide O-linked beta-N-acetylglucosamine (O-GlcNAc) regulates the activity of a wide variety of nuclear and cytoplasmic proteins. The enzymes O-GlcNAc Transferase (Ogt) and O-GlcNAcase (Oga) catalyze, respectively, the attachment and removal of O-GlcNAc to target proteins. In adult mice, Ogt and Oga attenuate the response to insulin by modifying several components of the signal transduction pathway. Complete loss of ogt function, however, is lethal to mouse embryonic stem cells, suggesting that the enzyme has additional, unstudied roles in development. We have utilized zebrafish as a model to determine role of O-GlcNAc modifications in development. Zebrafish has two ogt genes, encoding six different enzymatic isoforms that are expressed maternally and zygotically. We manipulated O-GlcNAc levels in zebrafish embryos by overexpressing zebrafish ogt, human oga or by injecting morpholinos against ogt transcripts. Each of these treatments results in embryos with shortened body axes and reduced brains at 24 hpf. The embryos had 23% fewer cells than controls, and displayed increased rates of cell death as early as the mid-gastrula stages. An extensive marker analysis indicates that derivatives of three germ layers are reduced to variable extents, and the embryos are severely disorganized after gastrulation. Overexpression of Ogt and Oga delayed epiboly and caused a severe disorganization of the microtubule and actin based cytoskeleton in the extra-embryonic yolk syncytial layer (YSL). The cytoskeletal defects resemble those previously reported for embryos lacking function of the Pou5f1/Oct4 transcription factor spiel ohne grenzen. Consistent with this, Pou5f1/Oct4 is modified by O-GlcNAc in human embryonic stem cells. We conclude that O-GlcNAc modifications control the activity of proteins that regulate apoptosis and epiboly movements, but do not seem to regulate germ layer specification. O-GlcNAc modifies the transcription factor Spiel ohne grenzen/Pou5f1 and may regulate its activity.


Low-Cost Clamp-On Photometers (ClampOD) and Tube Photometers (TubeOD) for Online Cell Density Determination.
Optical density (OD) measurement is the gold standard to estimate microbial cell density in aqueous systems. Recording microbial growth curves is essential to assess substrate utilization, gauge sensitivity to inhibitors or toxins, or determine the perfect sampling point. Manual sampling for cuvette-photometer-based measurements can cause disturbances and impact growth, especially for strictly anaerobic or thermophilic microbes. For slow growing microbes, manual sampling can cause data gaps that complicate analysis. Online OD measurement systems provide a solution, but are often expensive and ill-suited for applications such as monitoring microbial growth in custom or larger anaerobic vessels. Furthermore, growth measurements of thermophilic cultures are limited by the heat sensitivity of complex electronics. Here, we present two simple, low-cost, self-assembled photometers-a "TubeOD" for online measurement of anaerobic and thermophilic cultures in Hungate tubes and a "ClampOD" that can be attached to virtually any transparent growth vessel. Both OD-meters can be calibrated in minutes. We detail the manufacturing and calibration procedure and demonstrate continuous acquisition of high quality cell density data of a variety of microbes, including strict anaerobes, a thermophile, and gas-utilizing strains in various glassware. When calibrated and operated within their detection limits (ca. 0.3-90% of the photosensor voltage range), these self-build OD-meters can be used for continuous measurement of microbial growth in a variety of applications, thereby, simplifying and enhancing everyday lab operations.


[Synthesis and anti-inflammatory, antipyretic and analgesics properties of 5-(1,2-benzisothiazolyl)tetrazoles].
Tetrazole analogs of a series of known 1,2-benzisothiazolalkanoic acids were synthesized and tested for anti-inflammatory, antipyretic and analgesic activities in comparison with their corresponding carboxylic acids. The benzisothiazoliltetrazoles showed high antipyretic activity and each tetrazole, except one, was appreciably more potent than the corresponding acid. The examined tetrazoles are generally inactive as anti-inflammatory agents and weakly active in the mouse writhing test, with effect comparable with those of the corresponding carboxylic acids.


Fetal growth and sex related to placenta praevia.
A retrospective study investigating all cases given a diagnosis of placenta praevia at the Birmingham Women's Hospital Trust, January 1993 to June 1997, was undertaken to investigate any neonatal sex or weight differences compared with the general singleton pregnancies. Mothers with placenta praevia were at increased risk of preterm delivery, fetal malpresentation and having a caesarean section as the mode of delivery. No differences were found in the fetal sex ratio or incidence of small for gestational age (SGA) infants and indeed male infants overall were larger for dates in the placenta praevia group when compared with their gestational equivalents in the control population. Although ultrasound assessment of pregnancies complicated by placenta praevia may be useful in checking the resolution of the condition by 'placental migration', there is no indication for its use in monitoring growth restriction.


Measurement of x-ray pulse widths by intensity interferometry.
The pulse width of hard undulator radiation (32 ps width, energy 14 keV) was determined by intensity interferometry. The method, in combination with various x-ray monochromators, enables measurements to be taken over a wide range of time frames, from ns to fs. The applicable target includes measurements of ultrafast x-ray pulse widths from fourth generation synchrotron light sources.


Suicidal thinking, depression, and religiosity in a freedom-deprived population.
to analyze the influence of sociodemographic variables, prison context, religiosity, and symptoms of depression on the presence of suicidal thinking in a population deprived of liberty. a cross-sectional study with a quantitative approach, conducted with 228 participants, based on a sociodemographic questionnaire, on the prison context, and on the presence of suicidal thinking, from the Duke Religiosity Scale and the Depression, Anxiety and Stress Scale (DASS-21). the variables that showed a statistically significant correlation were the following: female gender, not having a partner, working inside the penitentiary, being a primary defendant and using controlled medication, and females are 7.2 times more likely to present suicidal thinking, for each point more in the depression score, increases by 21% in the chances and not having a partner increases the chances of thinking about suicide by three times. Although the scores of religiosity were high, they did not present a statistically significant correlation with the presence of suicidal thinking. the prison context is complex and contains peculiarities that cause the involvement of mental health problems, as well as self-harming thoughts. Considering the relevance of the subject at issue, this work stands out in view of the scarce scientific production on the subject.


Behavioral changes in mice caused by Toxoplasma gondii invasion of brain.
Toxoplasma gondii, a protozoan parasite, is capable of infecting a broad range of intermediate warm-blooded hosts including humans. The parasite undergoes sexual reproduction resulting in genetic variability only in the intestine of the definitive host (a member of the cat family). The parasite seems to be capable of altering the natural behavior of the host to favor its transmission in the environment. The aim of this study was to evaluate the number of parasite cysts formed in the hippocampus and amygdala of experimentally infected mice as these regions are involved in defense behaviors control and emotion processing, and to assess the influence of the infection on mice behavior. The obtained results revealed the presence of parasite cysts both in the hippocampus and the amygdala of infected mice; however, no clear region-dependent distribution was observed. Furthermore, infected mice showed significantly diminished exploratory activity described by climbing and rearing, smaller preference for the central, more exposed part of the OF arena and engaged in less grooming behavior compared to uninfected controls.


Comparison of Transverse and Coronal Plane Stability at the First Tarsal-Metatarsal Joint With Multiple Screw Orientations.
Intercuneiform instability has been recognized as a potential cause of hallux valgus recurrence following tarsal-metatarsal joint (TMTJ) fusion. Recommendations have been made for additional screw placement between the metatarsals and/or the cuneiforms to improve stability. The screw orientation that provides the best stability has not been documented. Twelve cadavers with the first TMTJ fixated were used for testing. Using a consistent force application of 15 pounds in both the transverse and coronal planes, we measured the change in intermetatarsal angle on radiographs. Force testing was repeated with screws deployed individually in the following orientations: first to second cuneiform (CC), first to second metatarsal (MM), and first metatarsal to middle cuneiform (MC). Our results indicate that stability of the first ray in the transverse and coronal planes is not improved with TMTJ fixation alone or with an additional CC screw. The MM screw consistently reduced first metatarsal instability in both planes. The MC screw had intermediate results. These findings strengthen the notion that first ray instability is complex and involves the tarsal and metatarsal articulations at multiple levels outside of the TMTJ alone. Diagnostic and Therapeutic, Level IV: Cadaveric Study.


Development of the binary vector pTACAtg1 for stable gene expression in plant: Reduction of gene silencing in transgenic plants carrying the target gene with long flanking sequences.
Genetic modification in plants helps us to understand molecular mechanisms underlying on plant fitness and to improve profitable crops. However, in transgenic plants, the value of gene expression often varies among plant populations of distinct lines and among generations of identical individuals. This variation is caused by several reasons, such as differences in the chromosome position, repeated sequences, and copy number of the inserted transgene. Developing a state-of-art technology to avoid the variation of gene expression levels including gene silencing has been awaited. Here, we developed a novel binary plasmid (pTACAtg1) that is based on a transformation-competent artificial chromosome (TAC) vector, harboring long genomic DNA fragments on both sides of the cloning sites. As a case study, we cloned the cauliflower mosaic virus 35S promoter:β-glucuronidase (35S:GUS) gene cassettes into the pTACAtg1, and introduced it with long flanking sequences on the pTACAtg1 into the plants. In isolated transgenic plants, the copy number was reduced and the GUS expressions were detected more stably than those in the control plants carrying the insert without flanking regions. In our result, the reduced copy number of a transgene suppressed variation and silencing of its gene expression. The pTACAtg1 vector will be suitable for the production of stable transformants and for expression analyses of a transgene.


Contrast enhanced phototrichogram (CE-PTG): an improved non-invasive technique for measurement of scalp hair dynamics in androgenetic alopecia--validation study with histology after transverse sectioning of scalp biopsies.
Global changes of scalp hair represent the cumulative end result of discrete changes of individual hair follicle structure and/or function. Monitoring of such changes requires an accurate non-invasive method. The phototrichogram (PTG) appears to be an appropriate choice to do so. However, a known weakness of the method is the lack of detection of less pigmented or thinning hair. Balding scalp of male subjects with androgenetic alopecia (AGA) was analysed with our previously published PTG method and with contrast enhanced (CE-)PTG followed by biopsy and transverse section examination with the light microscope. As compared with PTG, the CE-PTG method significantly improved detection not only of thin but also of thick hair. Equal numbers of thick (diameter > 40 mm) hair were detected with CE-PTG and with histology. CE-PTG was also able to detect the severely miniaturised hair fiber (down to 8 mm diameter) and was comparable to scalp biopsy analysis. The latter could identify hair fibres, which did not reach the scalp surface, a measure that is considered as not clinically significant. All growth stages - anagen, catagen and telogen - as well as the empty follicle stage could clearly be observed with CE-PTG. Staging of the more severely affected hair follicles was not always possible neither with CE-PTG nor histology - even with serial sectioning. The finding of such technological advantages makes the CE-PTG a first choice method for detailed analysis of hair cycling in androgenetic alopecia - a scalp disorder characterised by extreme hair follicle miniaturisation, decreased hair pigmentation and hair thinning.


(2E)-1-(2,5-Dimethyl-thio-phen-3-yl)-3-(3-nitro-phen-yl)prop-2-en-1-one.
In the title compound, C(15)H(13)NO(3)S, the benzene ring and the five-membered heterocyclic ring are oriented at a dihedral angle of 12.00 (6)°. In the crystal, C-H⋯O inter-actions generate two types of cyclic motifs, R(2) (2)(14) and R(2) (2)(26), connecting the mol-ecules into tapes extending along [101]. In addition, there are π-π stacking inter-actions between the benzene and thio-phene rings with centroid-centroid distances of 3.7263 (14) and 3.7487 (14) Å.


Hirudin attenuates puromycin aminonucleoside-induced glomerular podocyte injury by inhibiting MAPK-mediated endoplasmic reticulum stress.
Damage to podocytes is an important determinant of renal pathology. The puromycin aminonucleoside (PAN) mice nephropathy model is commonly used in the study of renal disease with podocyte injury. Hirudin has a broad nephroprotective effect and has been shown to treat renal interstitial fibrosis in previous studies. Mice were given PAN by gavage to prepare animal models, and MPC5 cells were incubated with PAN in vitro. Twenty-four hours urine was collected for analysis of urinary protein levels. Renal pathological changes were observed by hematoxylin and eosin staining. Immunofluorescence detection of nephrin in kidney tissues and cells. Apoptosis was analyzed with over TUNEL. Cytoskeleton, endoplasmic reticulum stress (ERS), p38 MAPK signaling, and apoptosis-related proteins were assessed by western blot analysis. The data suggested that hirudin attenuated reduced renal injury and increased urine protein in PAN mice. Hirudin also attenuated cytoskeletal protein (synaptopodin, nephrin, and podocin) disruption, ERS activation, and apoptosis in PAN mice and PAN-induced podocytes. In addition, hirudin inhibited the expression of p38 MAPK signaling key proteins upregulated by PAN, thereby suppressing ERS. The p38 MAPK agonist was able to partially antagonize the inhibition of p38 MAPK signaling by hirudin in PAN-induced podocytes, thereby reactivating the ERS inhibited by hirudin, promoting cytoskeletal protein degradation and increasing the level of apoptosis. In conclusion, hirudin could decrease podocyte injury by inhibiting p38 MAPK signaling-mediated ERS, resulting in the protection of the kidney from PAN damage. These findings may provide an experimental basis for hirudin treatment of podocyte injury diseases.


Hydroxylation of the triterpenoid dipterocarpol with CYP106A2 from Bacillus megaterium.
The bacterial steroid-hydroxylase CYP106A2 from Bacillus megaterium ATCC 13368 hydroxylates a variety of 3-oxo-Δ-4-steroids and has recently been shown to catalyse regioselective hydroxylation of the diterpene abietic acid, as well as the pentacyclic triterpene 11-keto-β-boswellic acid. The broad substrate spectrum of this enzyme makes it an excellent candidate for biotechnological application. Because the natural substrate of this enzyme is not known, we assumed that the whole substrate spectrum might not yet be fully discovered. The difference spectroscopy method was used to screen a natural product library of 502 compounds. Screening of the library resulted in the identification of twelve hits, among them eight potential and four known substrates for CYP106A2. Interestingly, when testing the potential substrates, product formation was obtained only with triterpenes, namely dipterocarpol and betulin. Dipterocarpol is the most promising compound for biotechnological application because it is a dammarane-type triterpenoid, as are the major bioactive compounds of ginseng. The dipterocarpol hydroxylation products were analysed by NMR and identified as 7β-hydroxydipterocarpol and 7β,11α-dihydroxydipterocarpol. To investigate the putative bioactive properties of these novel compounds, in vitro cytotoxicity assays with HeLa and COS-1 cells were performed. The substrate dipterocarpol and the dihydroxylated product did not show cytotoxic activity in our study. By contrast, the 7β-hydroxylated product was found to be cytotoxic to both tested cell lines. This study highlights the potency of CYP106A2 as a versatile biocatalyst for the bioconversion of natural products into pharmaceutically relevant bioactive products.


New diagnostic inroads in hypertension and atherosclerosis.
In the past two to three decades, the practice among hypertension specialists has been to lower blood pressure with the strong assumption that morbidity and mortality would be reduced. This was largely based on large clinical trials done in the 1960s and 1970s that did not include angiotensin-converting enzyme inhibitors or calcium-channel blockers. Performing large clinical trials is expensive and the results often do not apply to individual patients. Until recently, noninvasive methods to monitor end-organ effects of elevated blood pressure and other cardiovascular risk factors were limited. The development of high-resolution ultrasound and evolving magnetic resonance technology will allow early detection of heart and blood vessel changes and will make monitoring of the progression and regression of disease possible. This will allow better selection of treatment programs for each patient.


Pharmacokinetics and initial distribution of a new neuroleptic agent picobenzide (M-14012-4).
The pharmacokinetics of picobenzide was studied in 14 adult patients undergoing neuroleptoanalgesic sessions. The dose of picobenzide administered was 10 mg/kg by i.v. injection. The pharmacokinetic parameters obtained revealed a good distribution capacity with an average value of the apparent distribution volume at steady state of 28.29 +/- 4.98 1. The drug was also seen to be eliminated rapidly from the organism with an average value of the serum half-life of 2.05 +/- 0.42 h. The determination of the initial distribution kinetics of picobenzide shows that the use of a conventional kinetic model induces an overestimation of the initial distribution volume in turn caused by an underestimation of the initial serum concentration.


The Influence of Some Axial Ligands on Ruthenium-Phthalocyanine Complexes: Chemical, Photochemical, and Photobiological Properties.
This work presents a new procedure to synthesize ruthenium-phthalocyanine complexes and uses diverse spectroscopic techniques to characterize trans-[RuCl(Pc)DMSO] (I) (Pc = phthalocyanine) and trans-[Ru(Pc)(4-ampy)2] (II) (4-ampy = 4-aminopyridine). The triplet excited-state lifetimes of (I) measured by nanosecond transient absorption showed that two processes occurred, one around 15 ns and the other around 3.8 μs. Axial ligands seemed to affect the singlet oxygen quantum yield. Yields of 0.62 and 0.14 were achieved for (I) and (II), respectively. The lower value obtained for (II) probably resulted from secondary reactions of singlet oxygen in the presence of the ruthenium complex. We also investigate how axial ligands in the ruthenium-phthalocyanine complexes affect their photo-bioactivity in B16F10 murine melanoma cells. In the case of (I) at 1 μmol/L, photosensitization with 5.95 J/cm2 provided B16F10 cell viability of 6%, showing that (I) was more active than (II) at the same concentration. Furthermore, (II) was detected intracellularly in B16F10 cell extracts. The behavior of the evaluated ruthenium-phthalocyanine complexes point to the potential use of (I) as a metal-based drug in clinical therapy. Changes in axial ligands can modulate the photosensitizer activity of the ruthenium phthalocyanine complexes.


Cognitive, academic, and attitudinal predictors of the grade point averages of college students with learning disabilities.
This study examined cognitive, academic, and attitudinal predictors of college grade point average (GPA) among college students with learning disabilities (LD). The study population included 84 youth who attended a large private university in the midwestern United States. Measures of cognitive and academic functioning, along with a self-report measure of study habits and study attitudes, were used to predict college GPA. The results indicated that Full Scale IQ and one factor on the self-reported study habits scale accounted for a significant amount of variance in students' college GPA. These findings suggest that variables other than traditional cognitive and academic skills are important for determining the performance of youth with LD during college. The implications of these findings for future research efforts and practice are discussed.


Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.
The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.


Reducing Depressive Symptoms in Nursing Home Residents: Evaluation of the Pennsylvania Depression Collaborative Quality Improvement Program.
Depression reduces quality of life for nursing home (NH) residents and places them at greater risk for disability, medical morbidity, and mortality. However, accumulating evidence suggests that interventions for early detection and treatment can mitigate symptoms of clinical and subclinical levels of depression. The Promoting Positive Well-Being (PPW) program is a quality improvement (QI) intervention that features tools and strategies to assist NHs in early identification, assessment, treatment, and monitoring of residents with depressive symptoms. The PPW was evaluated in 40 NHs through an 8-month QI collaborative that provided participants with tools, webinar training, and technical support. Results showed a significant group by time interaction effect with facility quality rating as a covariate; the active group (n = 18 NHs) outperformed the waitlist control group (n = 19 NHs). In all, there was a 58% relative reduction in the percentage of residents with self-reported moderate-to-severe depressive symptoms. Most NHs reported that they were satisfied with the collaborative (97%) and would recommend it to others (86%); only 15% reported significant challenges. The rate of webinar attendance and data submission compliance was 92%. Results suggest that PPW is a promising approach that should be further evaluated in larger NH initiatives and other settings.


Cardiorespiratory coupling of sympathetic outflow in humans: a comparison of respiratory and cardiac modulation of sympathetic nerve activity to skin and muscle.
What is the central question of this study?Muscle sympathetic nerve activity (MSNA) is well known to be modulated by the arterial baroreceptors and respiration, but what are the magnitudes of cardiac and respiratory modulation of skin sympathetic nerve activity (SSNA), which primarily subserves thermoregulation?What is the main finding and what is its importance?Using direct microelectrode recordings of MSNA and SSNA in awake humans, we show that the magnitude of respiratory modulation of SSNA is identical to that of MSNA, the primary difference between the two sources of sympathetic outflow being the greater cardiac modulation of MSNA. This emphasises the role of the baroreceptors in entraining sympathetic outflow to muscle. It is well known that microelectrode recordings of skin sympathetic nerve activity (SSNA) in awake human subjects reveal spontaneous bursts of activity with no overt modulation by changes in blood pressure or respiration, in contrast to the clear cardiac and respiratory modulation of muscle sympathetic nerve activity (MSNA). However, cross-correlation analysis has revealed that, like individual muscle vasoconstrictor neurones, the firing of individual cutaneous vasoconstrictor neurones is temporally coupled to both the cardiac and respiratory rhythms during cold-induced cutaneous vasoconstriction, and the same is true of single sudomotor neurones during heat-induced sweating. Here, we used cross-correlation analysis to determine whether SSNA exhibits cardiac and respiratory modulation in thermoneutral conditions and to compare respiratory and cardiac modulation of SSNA with that of MSNA. Oligounitary recordings of spontaneous SSNA (n = 20) and MSNA (n = 18) were obtained during quiet, unrestrained breathing. Respiration was recorded by a strain-gauge transducer around the chest and ECG recorded by surface electrodes. Respiratory and cardiac modulation of SSNA and MSNA were quantified by fitting polynomial equations to the cross-correlation histograms constructed between the sympathetic spikes and respiration or ECG. The amplitude of the respiratory modulation (52.5 ± 3.4%) of SSNA was not significantly different from the amplitude of the cardiac modulation (46.6 ± 3.2%). Both were comparable to the respiratory modulation of MSNA (47.7 ± 4.2%), while cardiac modulation of MSNA was significantly higher (89.8 ± 1.5%). We conclude that SSNA and MSNA share similar levels of respiratory modulation, the primary difference between the two sources of sympathetic outflow being the marked cardiac modulation of MSNA provided by the baroreceptors.


Full-Thickness Skin Graft as an Independent or Adjunctive Technique for Repair of Cicatricial Lower Eyelid Ectropion Secondary to Actinic Skin Changes.
To retrospectively review and describe full-thickness skin graft repair of lower eyelid cicatricial ectropion secondary to actinic skin. A retrospective, noncomparative chart review of all patients who underwent lower eyelid ectropion repair with placement of a full-thickness skin graft between June 2004 and March 2014 was conducted with IRB approval. The etiology of lower eyelid ectropion, demographics including age, gender, ethnicity, laterality, graft donor site, additional surgical procedures, graft viability, surgical success rate, complications, and clinical exam findings were summarized. Twenty-nine eyelids in 24 patients underwent skin grafting for repair of cicatricial ectropion secondary to actinic skin changes. Ninety six percent of patients were male and 96% were Caucasian. Donor sites for skin grafts included upper eyelid (9, 31%), supraclavicular skin (9, 31%), postauricular skin (7, 24%), inner brachial skin (2, 7%), axilla (1, 3.5%), and preauricular skin (1, 3.5%). Twenty-four of 29 eyelids in the series underwent 1 or more additional procedures at the time of full-thickness skin grafting, including lateral tarsal strip (9 eyelids, 37.5%), punctoplasty (8, 33%), canthoplasty (7, 29%), excision of keratinized conjunctiva (2, 8%), transverse tarsotomy (1, 4%), ipsilateral external dacryocystorhinostomy (3, 12.5%), and lesion removal (1, 4%). There was 100% viability of the skin grafts. Overall surgical success rate was 76%, with asymptomatic recurrence rate of 17% and symptomatic recurrence rate of 7%. Repair of cicatricial lower eyelid ectropion secondary to actinic skin changes may be accomplished with full-thickness skin grafting, and is often performed in conjunction with additional procedures to fully address anatomic abnormalities.


NY-ESO-1 and CTp11 expression may correlate with stage of progression in melanoma.
As tumor cells spread beyond their primary site they undergo changes in their gene expression that may be detectable and useful for microstaging. The cancer/testis (CT) antigens are a family of proteins that include MAGE 1-3, NY-ESO-1, SSX 1-5, and others that are potential markers for microstaging melanoma. CT antigens are produced by many tumor types but few normal tissues other than testis. One CT antigen, CTp11, was shown to be expressed by metastasizing melanoma cell lines but not by nonmetastasizing variants. We tested this finding by studying the expression of CTp11 and NY-ESO-1 by melanoma samples from different stages of progression. We collected 20 primary, 22 locoregional, and 10 distant metastatic melanoma samples. We extracted total RNA, and reverse transcription yielded cDNA, which was PCR-amplified using primers to detect beta-actin, tyrosinase, MART-1, NY-ESO-1, and CTp11. The PCR products were separated on ethidium bromide-stained agarose gels and visualized by UV transillumination. All samples were positive for beta-actin and MART-1 and all but two were positive for tyrosinase, confirming RNA integrity and the presence of melanoma. Twenty-seven samples were positive for NY-ESO-1, CTp11, or both. CTp11 tended to be expressed by primary melanomas and NY-ESO-1 by metastatic samples (P < 0.02). There is a statistically significant difference in the distribution of the expression of CTp11 and NY-ESO-1 in melanoma from different stages of progression. NY-ESO-1 may be a marker of more advanced disease and CTp11 of less advanced disease.


Does the apodized diffractive intraocular lens Acrysof ReSTOR Natural interfere with FDT Matrix perimetry results?
To compare the effect of an apodized diffractive intraocular lens (IOL) (Acrysof ReSTOR Natural) and its yellow counterpart (Natural IQ) on frequency doubling technology (FDT) perimetry results. This study included 37 eyes from 22 patients at the 'Centro Oftalmológico Tranjan' who had undergone uncomplicated phacoemulsification and intraocular lens implantation (17 Acrysof ReSTOR Natural, 20 Natural IQ) performed by the same surgeon, at least three months prior to the study. Patients were subject to frequency doubling technology Matrix Perimeter testing. The patients were between 41 to 79 years old (mean, 70.78 +/- 9.83) in the Natural IQ and 49 to 81 years old (mean, 67.11+/- 11.48) in the Acrysof ReSTOR Natural group, and the mean IOP was 13.64 +/- 2.02 mmHg in the Natural IQ 12.94 +/- 1.39 mmHg in the Acrysof ReSTOR Natural group. The mean pupillary diameter under scotopic conditions was 6.63 +/- 1.16 mm in the Natural IQ group and 7.20 +/- 1.8 mm in the Acrysof ReSTOR Natural group (p=0.20). The mean deviation was -1.83 +/- 3.46 dB in the Natural IQ group and -1.77 +/- 3.94 dB in the Acrysof ReSTOR Natural group (p=0.28). The pattern standard deviation was 3.49 +/- 0.79 dB in the Natural IQ group and 3.20 +/- 0.86 dB in the Acrysof ReSTOR Natural group (p=0.27). There was no difference in the results of FDT Matrix perimetry in eyes that received apodized diffractive IOLs implant or eyes that received monofocal intraocular lens implant.


60-nt DNA Direct Detection without Pretreatment by Surface-Enhanced Raman Scattering with Polycationic Modified Ag Microcrystal Derived from AgCl Cube.
Direct detection of long-strand DNA by surface-enhanced Raman scattering (SERS) is a valuable method for diagnosis of hereditary diseases, but it is currently limited to less than 25-nt DNA strand in pure water, which makes this approach unsuitable for many real-life applications. Here, we report a 60-nt DNA label-free detection strategy without pretreatment by SERS with polyquaternium-modified Ag microcrystals derived from an AgCl cube. Through the reduction-induced decomposition, the size of the about 3 × 3 × 3 μm3 AgCl cube is reduced to Ag, and the surface is distributed with the uniform size of 63 nm silver nanoparticles, providing a large area of a robust and highly electromagnetic enhancement region. The modified polycationic molecule enhances the non-specific electrostatic interaction with the phosphate group, thereby anchoring DNA strands firmly to the SERS enhanced region intactly. As a result, the single-base recognition ability of this strategy reaches 60-nt and is successfully applied to detect thalassemia-related mutation genes.


Ventilation and neurochemical changes during µ-opioid receptor activation or blockade of excitatory receptors in the hypoglossal motor nucleus of goats.
Neuromodulator interdependence posits that changes in one or more neuromodulators are compensated by changes in other modulators to maintain stability in the respiratory control network. Herein, we studied compensatory neuromodulation in the hypoglossal motor nucleus (HMN) after chronic implantation of microtubules unilaterally ( n = 5) or bilaterally ( n = 5) into the HMN. After recovery, receptor agonists or antagonists in mock cerebrospinal fluid (mCSF) were dialyzed during the awake and non-rapid eye movement (NREM) sleep states. During day studies, dialysis of the µ-opioid inhibitory receptor agonist [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO; 100 µM) decreased pulmonary ventilation (V̇i), breathing frequency ( f), and genioglossus (GG) muscle activity but did not alter neuromodulators measured in the effluent mCSF. However, neither unilateral dialysis of a broad spectrum muscarinic receptor antagonist (atropine; 50 mM) nor unilateral or bilateral dialysis of a mixture of excitatory receptor antagonists altered V̇i or GG activity, but all of these did increase HMN serotonin (5-HT) levels. Finally, during night studies, DAMGO and excitatory receptor antagonist decreased ventilatory variables during NREM sleep but not during wakefulness. These findings contrast with previous dialysis studies in the ventral respiratory column (VRC) where unilateral DAMGO or atropine dialysis had no effects on breathing and bilateral DAMGO or unilateral atropine increased V̇i and f and decreased GABA or increased 5-HT, respectively. Thus we conclude that the mechanisms of compensatory neuromodulation are less robust in the HMN than in the VRC under physiological conditions in adult goats, possibly because of site differences in the underlying mechanisms governing neuromodulator release and consequently neuronal activity, and/or responsiveness of receptors to compensatory neuromodulators. NEW & NOTEWORTHY Activation of inhibitory µ-opioid receptors in the hypoglossal motor nucleus decreased ventilation under physiological conditions and did not affect neurochemicals in effluent dialyzed mock cerebral spinal fluid. These findings contrast with studies in the ventral respiratory column where unilateral [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO) had no effects on ventilation and bilateral DAMGO or unilateral atropine increased ventilation and decreased GABA or increased serotonin, respectively. Our data support the hypothesis that mechanisms that govern local compensatory neuromodulation within the brain stem are site specific under physiological conditions.


[EMTALA: what it is, its origins, and how it functions in Puerto Rico].
EMTALA (Emergency Medical Treatment and Active Labor Act) is a law born during the mid-eighties as an anti-discrimination law. Initially, its intention was to protect the uninsured population from being denied medical care due to inability to pay medical bills. Presently, EMTALA helps assure that patients get a screening evaluation about their medical condition, that they are stabilized or transferred to an appropriate medical facility, and that hospitals are obliged to accept patient's in transfer if they offer the medical services needed and have the capacity to manage the patient's condition. EMTALA is a Federal Law that has been interpreted and adapted for its use in Puerto Rico. It is the intention of this article to describe the events that led to the Law's creation, explains how it is applied in our hospitals, and describes the implications of EMTALA in our daily practice.


Molecular features of the viral and cellular Src kinases involved in interactions with the GTPase-activating protein.
GTPase-activating protein (GAP) enhances the rate of GTP hydrolysis by cellular Ras proteins and is implicated in mitogenic signal transduction. GAP is phosphorylated on tyrosine in cells transformed by Rous sarcoma virus and serves as an in vitro substrate of the viral Src (v-Src) kinase. Our previous studies showed that GAP complexes stably with normal cellular Src (c-Src), although its association with v-Src is less stable. To further investigate the molecular basis for interactions between GAP and the Src kinases, we examined GAP association with and phosphorylation by a series of c-Src and v-Src mutants. Analysis of GAP association with c-Src/v-Src chimeric proteins demonstrates that GAP associates stably with Src proteins possessing low kinase activity and poorly with activated Src kinases, especially those that lack the carboxy-terminal segment of c-Src containing the regulatory amino acid Tyr-527. Phosphorylated Tyr-527 is a major determinant of c-Src association with GAP, as demonstrated by c-Src point mutants in which Tyr-527 is changed to Phe. While the isolated amino-terminal half of the c-Src protein is insufficient for stable GAP association, analysis of point substitutions of highly conserved amino acid residues in the c-Src SH2 region indicate that this region also influences Src-GAP complex formation. Therefore, our results suggest that both Tyr-527 phosphorylation and the SH2 region contribute to stable association of c-Src with GAP. Analysis of in vivo phosphorylation of GAP by v-Src mutants containing deletions encompassing the SH2, SH3, and unique regions suggests that the kinase domain of v-Src contains sufficient substrate specificity for GAP phosphorylation. Even though tyrosine phosphorylation of GAP correlates to certain extent with the transforming ability of various c-Src and v-Src mutants, our data suggest that other GAP-associated proteins may also have roles in Src-mediated oncogenic transformation. These findings provide additional evidence for the specificity of Src interactions with GAP and support the hypothesis that these interactions contribute to the biological functions of the Scr kinases.


The role of personality beliefs and "small talk" in strategic behaviour.
Humans are predisposed to forming "first impressions" about the people we encounter including impressions about their personality traits. While the relationship between personality and strategic decision-making has been widely explored, we examine the role of personality impressions in predicting strategic behaviour and devising behavioural responses. In a laboratory setting, after only 4-minutes of "small talk", subjects developed a sense of the personality of their partners, particularly extraversion, which consequently changed their behaviour in future interactions. Subjects cooperated more in public goods games when they believed their partner to be extraverted and found it more difficult to out-guess opponents they perceived as similar to themselves in a level-k reasoning task, having engaged in conversation with them. We trace how language can generate these effects using text analysis, showing that talking more makes individuals appear extraverted and pro-social which in turn engenders pro-social behaviour in others.


Gold deposited on a Ge(0 0 1) surface: DFT calculations.
The atomic geometry, stability and electronic properties of self-organized Au induced nanowires on a Ge(0 0 1) surface are investigated based on the density-functional theory in the generalized gradient approximation and the stoichiometry of Au. According to the formation energy and the simulated STM image, the Ge atoms substituted by the Au atoms have been confirmed as occurring at a Au coverage lower than 0.25 Ml. The STM image with single and double dimer vacancies looks like the Au atoms have penetrated the subsurface. The energetically favorable dimer-row arrayed structures at 0.50 Ml and 0.75 Ml Au coverages have a 4 × 1, 4 × 2 or c(8 × 2) transition symmetry, which comprise a flat Au-Au homodimer row and an alternating various buckling phase Ge-Ge or Au-Ge dimer row. The c(8 × 2) zigzag-shaped protruding chains of shallow-groove STM images are highly consistent with the observations, but a long-range order dimer-row arrayed structure formation requires sufficient mobile energy to complete mass transport of the substituted Ge atoms in order to avoid the re-adsorption of these atoms; otherwise a deep-groove structure reconstruction is sequentially formed. A quasi-1D electron-like energy trough aligns in the direction perpendicular to the nanowire of the dimer-row arrayed structure in the c(8 × 2) phase on a 0.75 Ml Au/Ge(0 0 1) surface, which is contributed by the Au-Ge dimer rows and the subsurface Ge atoms below them. The bottom energy of the energy trough is consistent with angle-resolved photo-emission spectroscopy studies (Schäfer et al 2008 Phys. Rev. Lett. 101 236802, Meyer et al 2011 Phys. Rev. B 83 121411(R)).


Education and the risk factors of ischaemic heart disease.
Screening for the risk factors of ischaemic heart disease among the male residents of the district of Prague 4 aged 40--49 years was undertaken under the "National multifactorial primary preventive study of myocardial infarction and stroke". Of the 11 091 men invited, 5395 met the defined criteria and were admitted to the study. 58% of them were included in the risk group. The level of attained school education was ascertained at the initial examination. The lowest percentage of persons with hypercholesterolaemia, overweight, elevated blood pressure and smokers was found among university graduates. The results are compared with data of other studies and possible causes of the findings are discussed.


Heightened Negative Affects Associated With Neurotic Personality in Behavioral Addiction.
Although studies have demonstrated that negative affects are critical attributes of drug addiction, this has remained less clear in behavioral addiction. In this preliminary study with a relatively small number of samples, we investigated negative affects in patients diagnosed with behavioral addiction, particularly paraphilia and kleptomania. Negative affects were examined using self-rating questionnaire and further evaluated by objective assessments in behavioral addicts and normal subjects. Explicit, self-referential negative affects, such as anxiety, stress, and depression, were higher in behavioral addicts than control subjects. Such self-referential negative affects were, although not entirely, consistent with objective evaluations by others and blood stress hormone concentrations. Further investigation of personality traits in behavioral addicts unveiled that heightened negative affects were associated with stronger neurotic personality in behavioral addicts than normal subjects. These results suggest that behavioral addiction, such as paraphilia and kleptomania, may be characterized by heightened negative affects attributable to stronger neurotic personality.


Laparoscopic pelvic lymphadenectomy for malignant melanoma.
Therapeutic laparoscopic techniques are well accepted in many areas of general surgery. The use of laparoscopy for the staging of malignancy, in a diagnostic role, is not used widely. Urologists use pelvic lymph node dissection (LPLND) to define those patients who are suitable for curative local therapy in carcinoma of the prostate. We present a case of a patient with metastatic malignant melanoma in whom LPLND was employed as a minimally invasive way of staging and treating her disease.


[Definitive assumption of heart function by the artificial heart].
Reproducing the function of the natural heart with an artificial heart requires a multi-disciplinary approach. Problems to be solved are anatomical, physiological, biological and technical ones. Moreover, clinical use of the artificial heart on a large scale in the near future may involve economical, ethical and legal issues. These several aspects are reviewed, and the State of the Art in 1981 is established.


Increased total Renin levels but not Angiotensin-converting enzyme activity in obese patients with polycystic ovary syndrome.
To investigate the renin-angiotensin-aldosterone system and angiotensin-converting enzyme (ACE) activity in patients with polycystic ovarian syndrome (PCOS). In this case-control study, 41 obese (PCOS) women and 29 healthy controls, matched for age and body mass index, were enrolled. Anthropometric, metabolic, and hormonal patterns, including plasma aldosterone, plasma renin, and ACE activity, were measured in each subject. Plasma renin levels were significantly higher in PCOS patients (19.7 ± 14.5 µg/ml) compared with controls (12.9 ± 9.0 µg/ml, p < 0.05). ACE activity and aldosterone levels did not significantly differ between both groups (p = 0.15 and p = 0.18, respectively). Analysis of PCOS patients showed a significant correlation of fasting insulin levels with levels of renin (r = 0.305, p < 0.01) and free testosterone (r = 0.384, p = 0.001). Similarly, homeostasis model assessment index was positively correlated with total renin concentrations (r = 0.366, p < 0.01) and free testosterone (r = 0.352, p < 0.01). Obese PCOS women had higher total renin levels, but not ACE activity and aldosterone levels, related to insulin resistance compared with controls.


Antigen presentation by human dermal fibroblasts: activation of resting T lymphocytes.
We have shown that human dermal fibroblasts, exposed to interferon-gamma (IFN-gamma) to induce surface class II major histocompatibility complex (MHC) antigens, were capable of presenting tetanus toxoid (TT) antigen to human TT-specific T cell clones. Antigen presentation by fibroblasts was antigen dependent, required HLA-DR expression by fibroblasts, and was MHC restricted. In contrast, we now report that IFN-gamma-treated fibroblasts are unable to present TT antigen to purified resting T cells obtained from the peripheral blood of TT-immune donors. In addition, although IFN-gamma-treated fibroblasts were able to stimulate alloreactive T cell clones, they were unable by themselves to stimulate primary allogeneic responses in resting T cells. The failure of fibroblasts to stimulate resting T cells was not due to suppressor effects by fibroblasts, because induction of TT and alloantigen responses in resting T cells by monocytes was not inhibited by the presence of fibroblasts. On the contrary, IFN-treated fibroblasts were synergistic with small numbers of monocytes in activating resting T cells. In addition, the failure of antigen presentation by fibroblasts to resting T cells was reversed by the addition of recombinant human interleukin 2 (rIL 2) to cultures, but not of purified human interleukin 1 (IL 1). These results emphasize that the requirements for activation of resting T cells differ from those of T cell clones. Although fibroblasts can efficiently present antigen to T cell clones, antigen presentation by fibroblasts to resting T cells requires the addition of exogenous IL 2. It is postulated that fibroblasts differ from classical antigen-presenting cells in that fibroblasts are incapable of stimulating the production of IL 2 in resting T cells.


Komagataeibacter intermedius V-05: An Acetic Acid Bacterium Isolated from Vinegar Industry, with High Capacity for Bacterial Cellulose Production in Soybean Molasses Medium.
Despite the great properties of bacterial cellulose, its manufacture is still limited due to difficulties in large-scale production. These problems are mainly related to low production yields and high overall costs of the conventional culture media normally used. To surpass these problems, it is necessary to identify new cheap and sustainable carbon sources. Thus, this work aims to isolate and select a high cellulose-producing Komagataeibacter strain from vinegar industry, and study its potential for bacterial cellulose synthesis in an industrial soybean co-product, known as soybean molasses, used as fermentation medium. One isolated strain was able to produce high amount of cellulose in the standard Hestrin-Schramm medium, so we tested its ability to produce this biopolymer in a soybean molasses medium. The characteristics and properties of the produced bacterial cellulose membranes were analyzed by thermogravimetric analysis, X-ray diffraction, infrared spectroscopy, water-holding capacity and rehydration ratio. Genetic analysis of the selected strain served to determine its genus and species. An isolated strain that produced the highest amount of cellulose in Hestrin-Schramm medium (3.7 g/L) was genetically identified as Komagataeibacter intermedius V-05. This strain produced 10.0 g/L of cellulose in soybean molasses medium. Membranes from both substrates had similar chemical structure, crystallinity and thermal degradation. Soybean molasses proved to be a suitable alternative medium for biosynthesis of cellulose in comparison with the standard medium. In addition to providing higher production yield, the membranes showed great structural characteristics, similar to those obtained from standard medium. In this research, we have isolated and identified a Komagataeibacter strain which exhibits a high capacity for cellulose production in soybean molasses. The isolation and selection of strains with high capacity for microbial metabolite production is important for decreasing bioprocess costs. Furthermore, as there is a necessity today to find cheaper carbon sources to obtain microbial products at a lower cost, soybean molasses represents an interesting alternative medium to produce bacterial cellulose for its industrial application.


Learning as doing: common goals and interests across management and education.
The aim of the present study was to evaluate approaches to learning of healthcare professionals in a postgraduate management programme. The study was carried out in a higher education institution. An evaluation research study of an inter-professional healthcare group was carried out with students (insider stakeholders), their lecturers and an external examiner (external stakeholders). All three perspectives are presented here. Data were collected by interview, document analysis and reflection. The present study focused on the domain of learning as doing, as a major theme of the study, drawing variances between nurses and other healthcare professionals. The study highlights the importance of exploring approaches to learning from a pluralistic stance. There is a risk of adopting a narrow approach to education if management programmes are overly influenced by the immediate needs of application of knowledge to practice. Education is influenced by the needs of the students themselves in coming to the programme to acquire knowledge and skills for application to practice. Nurses undertaking management programmes need to be facilitated to cope with the conflicting demands of completing tasks on the job, engaging deeply with learning from these demands and becoming empowered to develop professionally and personally.


Adhesion molecules in the pathogenesis of asthma.
Using a primate antigen inhalation model the mechanisms involved in the induction of airway hyperresponsiveness were studied. Antigen inhalation induced a prolonged airway eosinophilia. Chronic airway eosinophilia, intratracheal instillation of eosinophil major basic protein, repeated antigen inhalation, and airway epithelial desquamation induced, or were associated with, an increase in airway responsiveness. Using monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1), the contributions of these cell adhesion molecules to antigen-induced airway hyperresponsiveness were studied. ICAM-1 partially mediated eosinophil adhesion to endothelium in vitro, was upregulated on inflamed endothelium and epithelium in vitro and in vivo, and contributed to repeated antigen-induced airway eosinophilia and hyperresponsiveness. ELAM-1 was upregulated on inflamed endothelium (but not epithelium) in vitro and in vivo, but did not contribute to the repeated antigen-induced airway eosinophilia and hyperresponsiveness. These results indicate that antagonism of ICAM-1, but not ELAM-1, may provide a novel therapeutic approach to reducing the airway inflammation and hyperresponsiveness commonly found in asthmatics.


Emerging microfluidic technologies for microbiome research.
The importance of the microbiome is increasingly prominent. For example, the human microbiome has been proven to be strongly associated with health conditions, while the environmental microbiome is recognized to have a profound influence on agriculture and even the global climate. Furthermore, the microbiome can serve as a fascinating reservoir of genes that encode tremendously valuable compounds for industrial and medical applications. In the past decades, various technologies have been developed to better understand and exploit the microbiome. In particular, microfluidics has demonstrated its strength and prominence in the microbiome research. By taking advantage of microfluidic technologies, inherited shortcomings of traditional methods such as low throughput, labor-consuming, and high-cost are being compensated or bypassed. In this review, we will summarize a broad spectrum of microfluidic technologies that have addressed various needs in the field of microbiome research, as well as the achievements that were enabled by the microfluidics (or technological advances). Finally, how microfluidics overcomes the limitations of conventional methods by technology integration will also be discussed.


Pharmacological characterization of metabotropic glutamate receptors coupled to phospholipase D in the rat hippocampus.
1. Phospholipase D (PLD) is the key enzyme in a signal transduction pathway leading to the formation of the second messengers phosphatidic acid and diacylglycerol. In order to define the pharmacological profile of PLD-coupled metabotropic glutamate receptors (mGluRs), PLD activity was measured in slices of adult rat brain in the presence of mGluR agonists or antagonists. Activation of the phospholipase C (PLC) pathway by the same agents was also examined. 2. The mGluR-selective agonist (1S,3R)-l-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] induced a concentration-dependent (10-300 microM) activation of PLD in the hippocampus, neocortex, and striatum, but not in the cerebellum. The effect was particularly evident in hippocampal slices, which were thus used for all subsequent experiments. 3. The rank order of potencies for agonists stimulating the PLD response was: quisqualate > ibotenate > (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine > (1S,3R)-ACPD > L-cysteine sulphinic acid > L-aspartate > L-glutamate. L-(+)-2-Amino-4-phosphonobutyric acid and the ionotropic glutamate receptor agonists N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate failed to activate PLD. (RS)-3,5-dihydroxyphenylglycine (100300 microM), an agonist of mGluRs of the first group, stimulated PLC but inhibited the PLD response elicited by 100 microM (1S,3R)-ACPD. 4. (+)-alpha-Methyl-4-carboxyphenylglycine (0.1-1 mM), a competitive antagonist of mGluRs of the first and second group, elicited a significant PLD response. L-(+)-2-Amino-3-phosphonopropionic acid (1 mM), an antagonist of mGluRs of the first group, inhibited the 100 microM (1S,3R)-ACPD-induced PLC response but produced a robust stimulation of PLD. 5. 12-O-Tetradecanoylphorbol 13-acetic acid and phorbol 12,13-dibutyrate (PDBu), activators of protein kinase C, at 1 microM had a stimulatory effect on mGluRs linked to PLD but depressed (1S,3R)-ACPD-induced phosphoinositide hydrolysis. The protein kinase C inhibitor, staurosporine (1 and 10 microM) reduced PLD activation induced by 1 microM PDBu but not by 100 microM (1S,3R)-ACPD. 6. Our results suggest that PLD-linked mGluRs in rat hippocampus may be distinct from any known mGluR subtype coupled to PLC or adenylyl cyclase. Moreover, they indicate that independent mGluRs coupled to the PLC and PLD pathways exist and that mGluR agonists can stimulate PLD through a PKC-independent mechanism.


Linear conjugated polymer photocatalysts with various linker units for photocatalytic hydrogen evolution from water.
Polymer photocatalysts have shown potential for light-driven hydrogen evolution from water. Here we studied the relative importance of the linker type in two series of conjugated polymers based on dibenzo[b,d]thiophene sulfone and dimethyl-9H-fluorene. The alkenyl-linked polymers were found to be more active photocatalysts than their alkyl and alkyne-linked counterparts. The co-polymer of dibenzo[b,d]thiophene sulfone and 1,2-diphenylethene has a hydrogen evolution rate of 3334 μmol g-1 h-1 and an external quantum efficiency of 5.6% at 420 nm.


Solid papillary carcinoma of the breast: report of two cases.
Two cases of solid papillary carcinoma of the breast were pathologically studied. Subjects included two female patients: a 76-year-old (Case 1) and a 43-year-old (Case 2). Both cases showed solid and papillary proliferation of spindle cells in expanded ducts, perivascular pseudorosettes, eosinophilic fine granules in an abundant cytoplasm, intracellular mucin production, and positivity for chromogranin A. Case 1 showed an aggregation form involving multiple ducts, admixture of signet-ring like cells, mucin pools, and small and large electron-dense granules and flocculent granules in electron microscopy. Case 2 showed a solitary and compact form in a dilated duct and an interlacing bundle pattern.


Cerebral mast cells mediate blood-brain barrier disruption in acute experimental ischemic stroke through perivascular gelatinase activation.
Perivascularly positioned cerebral mast cells (MC) have been shown to participate in acute blood-brain barrier disruption and expansive brain edema following experimental transient cerebral ischemia. However, the underlying molecular mechanisms remain unknown. Because proteolytic gelatinase enzymes, matrix metalloproteinases (MMP)-2 and MMP-9, are thought to have a central role in compromising the integrity of the blood-brain barrier following ischemia, we examined whether cerebral MCs influence gelatinase activity in ischemic cerebral microvasculature. Rats underwent 60 minutes of middle cerebral artery occlusion followed by 3-hour reperfusion, and were treated with a MC-stabilizing (cromoglycate), or MC-degranulating (compound 48/80) agent, or vehicle. Genetically manipulated, MC-deficient WsRc(Ws/Ws) rats and their wild-type littermates (WT) underwent the same procedures. Cerebral edema and extravasation of Evans blue albumin were measured. Gelatinase activity was visualized by in situ zymography and was quantified with computerized high-throughput image and data analysis. Activated MCs showed secretion of gelatinase-positive granules. Genetic MC deficiency decreased global gelatinase-active area (-69%, compared with WT; P<0.001) and the mean gelatinase activity of the ischemic microvasculature (-57% compared with WT; P=0.002). MC stabilization with cromoglycate decreased the percentage of microvessels with high gelatinase activity (-36% compared with saline; P<0.05). Compound 48/80 showed increased area of in situ zymography activity in the ischemic lesion (+55% compared with saline; P<0.001). Microvascular gelatinase activity correlated with brain swelling (r=0.84; P<0.001; and r=0.61; P=0.02). Our data demonstrate that cerebral MCs participate in regulation of acute microvascular gelatinase activation and consequent blood-brain barrier disruption following transient cerebral ischemia.


[Maternal and fetal metabolic parameters in acute and chronic fetal malnutrition].
The respiratory pathophysiology of placental insufficiency is well understood, whereas the metabolic effects of chronical or acute malnutrition still need further evaluation. In a comprehensive study of 20 deliveries respiratory parameters and substrates of carbohydrate- and lipid-metabolism were analysed simultaneously from maternal blood at 4 cm dilatation, at cord clamping immediately delivery and 2 hours post partum as well as from arterial and venous umbical blood samples. Normal deliveries were compared with cases of fetal retardation and moderate acute fetal acidosis. For glucose, insulin, c-peptide and pyruvate a strong rise in maternal blood during labour was observed as well as for the non-esterified fatty acids (NEFA), which have a high materno-fetal gradient. Arterio-venous differences of concentrations were found in the umbilical cord blood for glucose, pyruvate and NEFA. In cases of chronical insufficiency of the placenta especially elevated lactate levels were measured, whereas a moderate fetal acidosis obviously leads to an additional feto-maternal pyruvate transfer. The results lead to the conclusion that the fetal metabolism has considerable means of adaptation during delivery even under chronical or moderate acute stress conditions.


[Seroepidemiologic studies].
Serological studies allow us to study diseases distribution by an indirect way, trough serological detection of infection and immunity markers. These studies are applied in public health research, in studies to infections, to evaluate control and immunization programs and to evaluate historical background when a new microorganism is found. In the vaccines field, epidemiological studies present two main objectives: The study of the epidemiology of the infection and the study of the protective immunity in vaccinable or immuno preventable diseases, and planning and evaluation of vaccine programs. For the good quality of epidemiological studies is important to use serum samples which are representative of the total population under study, and to take into account that the serological tests used have to show a high sensitivity.


Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease.
Beta-secretase (BACE1), an enzyme responsible for the production of amyloid beta-peptide (Abeta), is increased by oxidative stress and is elevated in the brains of patients with sporadic Alzheimer's disease (AD). Here, we show that oxidative stress fails to induce BACE1 expression in presenilin-1 (gamma-secretase)-deficient cells and in normal cells treated with gamma-secretase inhibitors. Oxidative stress-induced beta-secretase activity and sAPPbeta levels were suppressed by gamma-secretase inhibitors. Levels of gamma- and beta-secretase activities were greater in brain tissue samples from AD patients compared to non-demented control subjects, and the elevated BACE1 level in the brains of 3xTgAD mice was reduced by treatment with a gamma-secretase inhibitor. Our findings suggest that gamma-secretase mediates oxidative stress-induced expression of BACE1 resulting in excessive Abeta production in AD.


The acoustic bases of human voice identity processing in dogs.
Speech carries identity-diagnostic acoustic cues that help individuals recognize each other during vocal-social interactions. In humans, fundamental frequency, formant dispersion and harmonics-to-noise ratio serve as characteristics along which speakers can be reliably separated. The ability to infer a speaker's identity is also adaptive for members of other species (like companion animals) for whom humans (as owners) are relevant. The acoustic bases of speaker recognition in non-humans are unknown. Here, we tested whether dogs can recognize their owner's voice and whether they rely on the same acoustic parameters for such recognition as humans use to discriminate speakers. Stimuli were pre-recorded sentences spoken by the owner and control persons, played through loudspeakers placed behind two non-transparent screens (with each screen hiding a person). We investigated the association between acoustic distance of speakers (examined along several dimensions relevant in intraspecific voice identification) and dogs' behavior. Dogs chose their owner's voice more often than that of control persons', suggesting that they can identify it. Choosing success and time spent looking in the direction of the owner's voice were positively associated, showing that looking time is an index of the ease of choice. Acoustic distance of speakers in mean fundamental frequency and jitter were positively associated with looking time, indicating that the shorter the acoustic distance between speakers with regard to these parameters, the harder the decision. So, dogs use these cues to discriminate their owner's voice from unfamiliar voices. These findings reveal that dogs use some but probably not all acoustic parameters that humans use to identify speakers. Although dogs can detect fine changes in speech, their perceptual system may not be fully attuned to identity-diagnostic cues in the human voice.


The effect of isotonic multiple electrolyte infusions during anesthesia on blood gas and enzymatic values in horses.
General equine anesthesia is accompanied by the risk of complications and even death. The majority of general anesthetics used in veterinary practice lead to arterial hypotension, decreased capillary perfusion and ventilatory depression leading to pathological changes referred to as postanesthetic myopathy. In this study an attempt was made to analyze changes in the perioperative and postoperative acid-base equilibrium and blood enzymatic activity in horses, subject to the intensity of the applied fluid therapy. The horses were divided into two groups: I--administered Ringer's solution during surgery at a dose of 6-10 ml/kg BW/h, II--Ringer's solution administered at a dose of 12-15 ml/kg BW/h. The results of the study indicate that use of hydrating fluid infusions during general anesthesia, including infusions without hypertensive substances, minimizes the risk of myocyte damage due to disturbances in local and general blood circulation.


Calpain 2 is required for glioblastoma cell invasion: regulation of matrix metalloproteinase 2.
Invasion of glioblastoma cells significantly reduces the effectiveness of current treatments, highlighting the importance of understanding dispersal mechanisms and characteristics of the invasive population. Induction of calcium fluxes into glioblastoma cells by autocrine glutamate is critical for invasion. However, the target(s) by which calcium acts to stimulate the dispersal of glioblastoma cells is not clear. In this study, we tested the hypothesis that the calcium-activated protease calpain 2 is required for glioblastoma cell invasion. Knockdown of calpain 2 expression using shRNA or chemical inhibition of calpain activity reduced glioblastoma cell invasion by 90%. Interestingly, decreased expression of calpain 2 did not influence morphology or migration, suggesting regulation of invasion specific mechanisms. Consistent with this idea, 39% less extracellular MMP2 was measured from knockdown cells identifying one mechanism by which calpain 2 mediates glioblastoma cell invasion. This is the first report demonstrating that calpain 2 is required for glioblastoma cell invasion.