A Case Report on Mid-Dermal Elastolysis: A Distinctive Presentation on the Neck.
Mid-dermal elastolysis (MDE) is a very rare and acquired skin condition. MDE has a variety of clinical manifestations that can be presented with a reticular erythematous patch with telangiectasis, perifollicular popular protrusions, or finely wrinkled skin. A biopsy is always necessary to rule out other potential elastic fiber disorders. In this case study, a 33-year-old female with an odd MDE presentation in her neck area is examined. No contributing factors, apart from exposure to sunlight, could be gleaned from the patient's history. The patient didn't benefit from the application of various types of topical agents or any other therapies to lessen the size and advancement of the lesion. In this distinct case, we discuss clinical and histological findings and the treatment plan offered, as well as include a concise review of specific past literature.


Detection and survival of Toxoplasma gondii in milk and cheese from experimentally infected goats.
The consumption of unpasteurized goat cheese and goat's milk has been suggested as a risk factor for toxoplasmosis in humans. In the present study, detection and survival of Toxoplasma gondii in milk and cheese was studied by bioassay in mice (milk) and in cats (cheese). Eight goats were inoculated orally with 300 to 10,000 oocysts of T. gondii strain TgGoatUS26. Milk samples were collected daily up to 30 days postinoculation and bioassayed in mice and cats. For mouse bioassay, 50 ml of milk samples were centrifuged, and the sediment was inoculated subcutaneously into mice. Mice were tested for T. gondii infection by seroconversion and by the demonstration of parasites. By mouse bioassay, T. gondii was detected in milk from all eight goats. The T. gondii excretion in milk was intermittent. For cat bioassay, 400 ml (100 ml or more from each goat) of milk from four goats from 6 to 27 days postinoculation were pooled daily, and cheese was made using rennin. Ten grams of cheese was fed daily to four cats, and cat feces were examined for oocyst shedding. One cat fed cheese shed oocysts 7 to 11 days after consuming cheese. Attempts were made to detect T. gondii DNA in milk of four goats; T. gondii was detected by PCR more consistently, but there was no correlation between detection of viable T. gondii by bioassay in mice and T. gondii DNA by PCR. Results indicate that T. gondii can be excreted in goat's milk and can survive in fresh cheese made by cold-enzyme treatment. To prevent transmission to humans or animals, milk should not be consumed raw. Raw fresh goat cheese made by cold-enzyme treatment of unpasteurized milk also should not be consumed.


Transient, high-grade atrioventricular block from high-dose cyclophosphamide.
Cyclophosphamide, an alkylation agent, is widely used in stem cell transplantation for its antineoplastic and myeloablative properties. Congestive heart failure, pericarditis, and arrhythmias are well-known cardiac sequelae of high-dose cyclophosphamide therapy; however, high-grade atrioventricular block has rarely been reported. We present the case of a 71-year-old man who developed a high degree of atrioventricular block several hours after therapy with high-dose cyclophosphamide. After treatment with a temporary pacemaker and cessation of cyclophosphamide, the patient experienced no more events. Before administering cyclophosphamide, evaluating patients for underlying conduction abnormalities is advisable. Agents other than cyclophosphamide are available.


Influence of soil moisture regimes on growth, photosynthetic capacity, leaf biochemistry and reproductive capabilities of the invasive agronomic weed; Lactuca serriola.
Global temperatures are predicted to increase by 1.5-5.9°C during this century, and this change is likely to impact average rainfall, with predictions that water deficit will perhaps be the most severe threat to sustainable agriculture. In this respect, invasive weeds, which have traits better adapted to drought stress than crops, add to concerns regarding crop sustainability. Lactuca serriola, an aggressive agronomic weed is thought to be a successful weed because of its ability to maintain high water use efficiency under drought conditions. In this study, experiments were conducted to examine the influence of different soil moisture regimes (100%, 75%, 50% and 25% water holding capacity (WHC)) on growth, photosynthetic capacity, leaf biochemistry and reproduction of this species. Soil moisture significantly affected plant's height, stem diameter, number of leaves and biomass. The highest plant height (115.14 cm ± 11.64), shoot diameter (9.4 mm ± 0.18), leaf area (1206.5 mm2 ± 73.29), plant fresh weight (83.1 ± 3.98) and dry weight (22.38 ± 1.24) were recorded at 75% soil moisture content. A fundamental adaptation to drought was observed as plants in the 25% WHC treatment had the highest root: shoot ratio. Soluble sugars and total phenolic content were highest in the 25% WHC treatment and significantly different to 100% WHC which was a response to soil moisture stress to ameliorate the damaging effects of reactive oxygen species produced under stress conditions. Results also indicate that L. serriola can survive and produce seeds under water stress as more than 6000 seeds were produced per plant in all WHC treatments. In this study, there was no significant difference in the seed weight, number of seeds produced and their germination ability. This can have a huge impact on agricultural systems as the species can survive both under low and high soil moisture conditions. We therefore suggest that the demonstrated ability of L. serriola to complete its life cycle and produce biomass and seeds under water stressed conditions leads to the introduction of strategies that minimize weed survival while maximizing irrigation efficiency for the crop. A clear understanding of the ecological and biological characteristics of this weed will help land managers take appropriate control measures to mitigate the effect of this species on economic crop productivity.


[Accidental tetanus in the State of Ceará, between 2002 and 2005].
The demographic and clinical characteristics of individuals with accidental tetanus in Ceará are described. This was retrospective analysis of 131 cases of accidental tetanus notified in a state referral hospital between 2002 and 2005. Most of these cases (84.8%) occurred among men and among people living in the urban zone (93.2%). The age group with highest incidence was between 35 and 49 years old (35.2%). A complete vaccination history was reported in four (3%) cases. Puncturing/cutting wounds were the cause most commonly observed and the legs were the area most affected. Trismus (lockjaw) was reported in 86.2% of the cases, followed by muscle contractions (54.1%). Among the notified cases, 95.5% were confirmed and 33 patients (26.4%) died. We conclude that accidental tetanus in Ceará significantly affects the population, in spite of being a disease that is preventable by immunization. The health authorities and health administration entities are urged to program strategies that aim towards changes in public policies concerning the vaccination coverage for susceptible individuals, particularly adults.


Role of optical coherence tomography in managing patients with ST elevation myocardial infarction.
Stenting the culprit lesion in patients presenting with acute coronary syndrome (ACS) is the standard of care. Although plaque rupture on an atheromatous lesion is the most common underlying pathology, other mechanisms can also result in ACS presentation; some of which can be managed without stenting. Here we describe a case that was managed conservatively, after evaluating plaque erosion as the underlying mechanism and lack of obstructive lesion. This case highlights the importance of intracoronary imaging to assess the underlying mechanism in patients presenting with acute coronary syndrome.


Enhanced expression and activation of major matrix metalloproteinases in distinct topographic areas of invasive breast carcinomas.
Matrix metalloproteinases (MMPs) play a key role in events related to tumor cell invasion and growth. Therefore, we examined tumor tissue samples from 12 individuals with invasive breast cancer for the expression and localization of MMP-1, -2, -3 and -9. These were detected by immunohistochemistry. Simultaneously in this material the matrix-degrading enzyme activity was tested by in situ zymography. Additionally, we used a spheroid model of two breast cancer cell lines (MCF-7 and MDA-MB-435) for MMP-expression and activity by immunohistochemistry and in situ zymography. Semi-quantitative investigation of various MMPs by immunohistochemistry in tissue samples revealed higher expression levels at the tumor periphery where tumor cells grow less compact when compared to compact tumor cell complexes as in the center of the tumors. In situ gelatinolytic activity paralleled these observations showing pronounced activity at the tumor periphery when compared to tumor centers. Similarly, tumor cell spheroids of two cell lines had higher gelatinolytic activity in less densely growing tumor cell groups than in the more densely growing ones. Our study provides considerable evidence that expression and activation of major MMPs is dependent on tumor cell density. This has a major impact on the biological behavior of tumor cells such as invasion and metastasis.


Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release.
Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant "burst release" of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.


Knowing before doing: discrimination by rats of a brief interruption of a tone.
Eight rats' lever presses were reinforced after an interruption in a tone, provided the lever had not been pressed before the tone interruption. After a few sessions, long before the animals reliably refrained from lever pressing before the interruption, the latencies of postinterruption presses (time from the termination of the interruption to the moment of the lever press) dissociated into two classes: short ones for to-be-rewarded presses, and long ones for presses in the other trials, which contained no reward because one or more lever presses had occurred before the interruption. Thus discrimination of impending reinforcement in the current trial occurred before there was evidence of sensitivity to reinforcement in the reinforcement-producing aspect of behavior. This finding is related to Shimp's (1981) contention that the temporal properties of recent behavior are reinforceable, if remembered. The present finding shows that learning to discriminate whether one's behavior has met a contingency, and learning to carry out this behavior, need not go together, implying that memory of temporal properties is probably a necessary but not a sufficient condition for learning the latter.


Self-construal, affective valence of the encounter, and quality of social interactions: Within and cross-culture examination.
In two samples, one from Greece and another from Germany, we examined relationships between self-construal, emotional experience, and the quality of social interactions. In Greece, a more collectivistic culture, the negative affect people experienced in social interactions was more weakly related to the quality of social interactions for those higher in interdependent self-construal than it was for those lower in interdependent self-construal. In Germany, a more independent culture, a contrasting pattern was observed such that the positive affect people experienced in social interaction was more strongly related to the quality of social interactions for those higher in independent self-construal than it was for those lower in independent self-construal. These findings suggest that positive and negative affect in social encounters can have different effects for persons with independent and interdependent cultural orientations within different cultural settings.


Simulated atmospheric processing of iron oxyhydroxide minerals at low pH: roles of particle size and acid anion in iron dissolution.
A number of recent studies have shown that iron dissolution in Fe-containing dust aerosol can be linked to source material (mineral or anthropogenic), mineralogy, and iron speciation. All of these factors need to be incorporated into atmospheric chemistry models if these models are to accurately predict the impact of Fe-containing dusts into open ocean waters. In this report, we combine dissolution measurements along with spectroscopy and microscopy to focus on nanoscale size effects in the dissolution of Fe-containing minerals in low-pH environments and the importance of acid type, including HNO(3), H(2)SO(4), and HCl, on dissolution. All of these acids are present in the atmosphere, and dust particles have been shown to be associated with nitrate, sulfate, and/or chloride. These measurements are done under light and dark conditions so as to simulate and distinguish between daytime and nighttime atmospheric chemical processing. Both size (nano- versus micron-sized particles) and anion (nitrate, sulfate, and chloride) are found to play significant roles in the dissolution of alpha-FeOOH under both light and dark conditions. The current study highlights these important, yet unconsidered, factors in the atmospheric processing of iron-containing mineral dust aerosol.


A Systematic Study of PLLA Aligned Nanofiber-Induced Differentiation of PC12 Cells Using mRNA-microRNAProtein Biomics Integrated Analyses.
This study aimed to explore the regulatory molecular mechanism of microRNA (miRNA) in poly(L-lactic acid) (PLLA) nanofiber-induced PC12 cell differentiation by combining transcriptomics, proteomics and miRNA sequencing technology. Primarily, PLLA random/aligned nanofibers were fabricated by electrospinning, and their morphology, chemical composition and mechanical properties were measured. Next, PC12 cells were planted on the PLLA film (control), PLLA random nanofibers (RF) and PLLA aligned nanofibers (AFs), and the morphology and synapse length of the PC12 cells were observed. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-labeled proteomics qualification technologies were applied to identify protein expression information of PC12 cells, and differentially expressed proteins were determined. To elucidate the regulatory relationship among mRNA, miRNA and protein, bioinformatics methods were adopted to analyze the proteomics data using early mRNA profile data and miRNA sequencing data, from which collective gene ontologies, biological pathways and the matched miRNA mRNA/protein target pairs were filtered. The experiment yielded the following results: 1. PLLA random/aligned nanofibers were composed of PLLA, and all the materials were uniform. 2. The modulus elasticity of PLLA aligned nanofibers was dramatically higher than that of PLLA random nanofibers. 3. PC12 cells were in good condition in all three groups. 4. Cells were nearly round in the control group and extended synapses in the RF and AF groups, yet they had shorter and randomly oriented synapses in the RF group. However, the length of the synapses was significantly increased in the AF group compared with that of the control and RF groups. More specifically, there were 235 and 281 differentially expressed proteins in the RF and AF groups, respectively, compared with the control group. Comparing the integrated analysis of the proteomics experimental data with the miRNA and mRNA profiles, collective differentially expressed data were involved in 2 and 5 gene ontologies and 4 and 7 biological pathways in the RF and AF groups, respectively, which were related to cell differentiation. Through data comparison, 0 and 5 matched miRNA genes/proteins pairs were filtered in the RF and AF groups, respectively. Further discussion revealed that PLLA aligned nanofibers could regulate 5 mRNA/protein target pairs (Dnajb12, Rhob, Wbp11, Hmgcs1 and Hmgn2) by 8 miRNAs (miR-24, miR-25, miR-92a, miR-19b, miR-183, miR-29a, miR-29c and miR-23b) and further regulate 'focal adhesion' pathways and many functions (e.g., cell adhesion, transport, gene transcription, biosynthesis, and DNA assembly), which could finally influence the migration and differentiation of PC12 cells. The results showed that the focal adhesion pathway, integrin-mediated cell adhesion pathway, MAPK pathway and TGF-β pathway play key functions in the process of PLLA-aligned, nanofiber-induced PC12 cell differentiation.


Hemodynamic efficacy of the new resolution clip device in comparison with high-volume injection therapy in spurting bleeding: a prospective experimental trial using the compactEASIE simulator.
Peptic ulcers are the most frequent cause of gastrointestinal bleeding. The use of hemoclips has become established as an effective form of treatment in addition to injection therapy. However, hemoclips have not previously been compared with injection therapy in an experimental setting using objective parameters. In a prospective, randomized, and controlled trial, the disposable Resolution hemoclip device (Boston Scientific, n = 40) was compared with conventional injection therapy (n = 40) in an experimental setting, using the compactEASIE simulator equipped with an upper gastrointestinal organ package to simulate bleeding. Four investigators with different levels of endoscopic experience participated in the study. On a randomized basis, each investigator treated 20 bleeding sites either by applying one clip (n = 10) or by carrying out high-volume four-quadrant injection (4 x 10 ml saline) of a spurting vessel. The efficacy of the hemostasis was assessed by continuous measurement of pressure within the afferent vessel before and after clip application or injection therapy and calculating the relative reduction in the vessel's diameter with each treatment method. The system pressure was recorded 1 min before and 1 min after treatment. The ease of application of each method was rated by the endoscopist and by the assisting nurse using a visual analogue scale (0 - 100, with 100 being best). All of the 40 hemoclipping and injection treatments were carried out successfully. Both methods led to a significant increase in peak pressure (Resolution clip 71.8 +/- 66.8 mm Hg, P < 0.001; injection 71.9 +/- 53.8 mm Hg, P < 0.001), representing a significant relative reduction in the vessel diameter. There were no significant differences in peak pressure between the two treatments ( P = 0.995). The mean increase in pressure during the first minute after the intervention (clip 49.3 +/- 67.0 mm Hg vs. injection 19.9 +/- 41.6 mm Hg) was significantly greater with the hemoclipping procedure ( P = 0.021). More experienced investigators achieved a greater increase in system pressure, but the difference was not significant. The assessments of the ease of application by the assistants (84 +/- 13) and endoscopists (86 +/- 16) did not show any significant differences ( P = 0.402) for the clipping device. No significant differences between the two treatment methods were detected with regard to the immediate efficacy of hemostasis. However, long-term hemostasis was better with hemoclipping. The endoscopist's level of experience also appears to play a role, particularly when hemoclips are used.


Responsiveness to Tocilizumab in Anti-Acetylcholine Receptor-Positive Generalized Myasthenia Gravis.
Tocilizumab, a humanized IL-6R monoclonal antibody, has been used in autoimmune diseases closely related to humoral immunity. This report aims to evaluate the efficacy and safety in patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG). We performed a prospective, open-label, single-arm study in patients with gMG in a 48-week follow-up. All patients were AChR+ and were given tocilizumab by intravenous infusion at a dose of 8 mg/kg at intervals of 4 weeks. The primary endpoint was mean change from baseline in quantitative MG (QMG) score at week 12. The secondary endpoints were mean changes from baseline in MG activities of daily living (MG-ADL) score, AChR-ab titers, and the dosage of oral prednisone at week 12. At week 48, QMG, MG-ADL, and the use of prednisone were also evaluated. Fourteen gMG patients were enrolled and all of them completed the study. Tocilizumab treatment started 8 (4-192) months after the onset of gMG. During tocilizumab treatment, the QMG score was significantly decreased from 15.5 (interqualile range, 9-26) at baseline to 4 (0-9) at week 12 (p > 0.001). The change of ADL was decreased from 14.5(11-19) at baseline to 4 (0-19) at week 12 (p > 0.001) and the change of AChR-ab titers from 15 (7.5-19) at baseline to 6.8 (11.6-4.3) at week 12 (p > 0.001). The dosage of prednisone decreased from baseline 60 (20-65) mg/d to 30 (30-50) mg/d at week 12 (p > 0.001). By the end of the study, the QMG score was 2 (0-7) and MG-ADL score was 1.5 (0-6). 12 (85.7%) patients achieved minimal manifestations. 4 (28.6%) patients were able to discontinue prednisone. No patients experienced exacerbation at the end of the study. No serious adverse events were observed during follow-up. Tocilizumab treatment was associated with a good clinical response and safety over a 48-week observation period, as evidenced by significant improvements in QMG and MG-ADL.


Synthesis of nanocrystalline Ce(0.8)Gd(0.2)O(2-delta) electrolyte materials for IT-SOFC.
We successfully synthesized nano-sized Ce(0.8)Gd(0.2)O(2-delta) powders by combustion method, using gelatin as fuel. The calcined powders showed high-quality characteristics, i.e., nano-scale size (14-35 nm) and narrow size distribution. The structural, morphological, and electrical characteristics of the sintered Ce(0.8)Gd(0.2)O(2-delta) were studied systematically, depending on sintering temperature. The crystal structure of the Ce(0.8)Gd(0.2)O(2-delta) belonged to the cubic fluorite structure. The gelatin-assisted combustion synthesized Ce(0.8)Gd(0.2)O(2-delta) powders allowed to sinter well at low temperature for dense and ultra-fine Ce(0.8)Gd(0.2)O(2-delta) electrolyte with good electrical conductivity. The sintering temperature of the Ce(0.8)Gd(0.2)O2 powder was approximately 300 degrees C lower than that of conventional solid-state synthesized powder. The nanopowder produced was sintered into pellets with relative densities over 99.1% of the theoretical value even at 1400 degrees C. The Ce(0.8)Gd(0.2)O(2-delta) sintered at 1400 degrees C exhibited a conductivity of 0.101 S/cm at 800 degrees C in air.


An attempt to locate the non-helical and permissively helical sequences of proteins: application to the variable regions of immunoglobulin light and heavy chains.
From a consideration of (varphi, Psi) values of the amino acids of myoglobin, lysozyme, the alpha and beta chains of horse oxyhemoglobin, tosyl-alpha-chymotrypsin, and carboxypeptidase A, an empirical procedure of predicting whether amino-acid residues in proteins are in a non-helical or may be in a helical conformation has been developed. The conformation of an amino acid at any position n is considered to be influenced by its nearest neighbors (the amino acids at positions n + 1 and n - 1), and the (varphi, Psi) values of the middle amino acid n for the various tripeptide sequences in the known proteins are tabulated. If helical, the (varphi, Psi) values are plotted to define a helical (varphi, Psi) domain. A 20 x 20 table for all tripeptides (n - 1)-(n)-(n + 1) taken sequentially for the entire chain was constructed; it lists the number of instances in which helical and non-helical conformations for the amino acids at position n were found. Certain sequences are found to be associated exclusively with non-helical and others exclusively with helical conformations, whereas many sequences may be either helical or non-helical. The distribution of non-helical residues serves to limit stretches of permissively helical regions; these are then further examined by the helical wheel method. As applied to cytochrome c from 18 species, the only permissively helical segment found was the stretch 91-101 near the C-terminus. For the variable regions of three light and three heavy chains of immunoglobulins, upper limits of 12 and 17% alpha-helix, respectively, were obtained.


Imaging in the diagnosis of juvenile nasopharyngeal angiofibroma.
Juvenile nasopharyngeal angiofibroma (JNA) is a rare, benign, highly vascular, and locally aggressive tumor that predominantly occurs in adolescent males. Usually, the presenting symptom is a painless nasal obstruction or epistaxis; however, other symptoms may develop depending on the size and extent of the tumor mass. Owing to the vascularity of the tumor, incisional biopsy is not attempted. The diagnosis is dependent on multiplanar imaging modalities like Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Angiography. These imaging modalities help in assessing the tumor mass, pre-operative embolization of the feeder vessel, and treatment planning. Usually, patients with JNA are diagnosed by otorhinolaryngologists, but here, we present a rare case of JNA reporting to the dental hospital due to a tender palatal swelling.


Strain and Vibration in Mesenchymal Stem Cells.
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into any mesenchymal tissue, including bone, cartilage, muscle, and fat. MSC differentiation can be influenced by a variety of stimuli, including environmental and mechanical stimulation, scaffold physical properties, or applied loads. Numerous studies have evaluated the effects of vibration or cyclic tensile strain on MSCs towards developing a mechanically based method of differentiation, but there is no consensus between studies and each investigation uses different culture conditions, which also influence MSC fate. Here we present an overview of the response of MSCs to vibration and cyclic tension, focusing on the effect of various culture conditions and strain or vibration parameters. Our review reveals that scaffold type (e.g., natural versus synthetic; 2D versus 3D) can influence cell response to vibration and strain to the same degree as loading parameters. Hence, in the efforts to use mechanical loading as a reliable method to differentiate cells, scaffold selection is as important as method of loading.


Concepts of function of peripheral non-chromatin and endosome in Entamoeba histolytica.
The distribution of RNA (to a lesser extent DNA) in the nucleus of E. histolytica appeared to be the opposite of what one found in other eukaryotic cells (originally stated by Pan and Geiman in 1955). Autoradiographs of amebae labelled with 3H-thymidine revealed primarily randomly distributed DNA-3H (probably euchromatin) in interphase cells. This DNA was so low in amount in individual cells that it usually did not stain with the Feulgen procedure. A small amount of DNA-3H was also detected by autoradiography in the peripheral chromatin (= rDNA?; occasionally it was abundant) and endosome. Clumps of DNA-3H were also observed around the endosomal area in some amebae. This labelling pattern was not observed in 3H-uridine (for RNA) incorporation experiments. These data were consistent with the possibility that the endosome, which was sometimes Feulgen +, was a site of condensation of DNA prior to nuclear division. As detected by light and electron microscopy autoradiographic analysis of 3H-uridine incorporation, RNA was synthesized (or accumulated) primarily in the peripheral chromatin; lesser amounts were evenly distributed. Most of the peripherally located amebal nuclear RNA was probably rRNA and/or precursor rRNA. If this is the case, it is probable that the peripheral chromatin, although structurally unlike nucleoli, may be "functionally" comparable to nucleoli of eukaryotes.


DOCK 8 Deficiency, EBV+ Lymphomatoid Granulomatosis, and Intrafamilial Variation in Presentation.
Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive, combined immunodeficiency within the spectrum of hyper-IgE syndromes. Epstein-Barr virus-positive lymphomatoid granulomatosis (LYG) (EBV + LYG) is a rare diagnosis and a previously unreported presentation of DOCK8 deficiency. A 10-year-old girl was initially evaluated for mild eczema and recurrent sinopulmonary infections. She had normal immunoglobulins with elevated IgE, poor polysaccharide response with low switched memory B cells, low CD4 count, and normal mitogen and antigen responses. Despite clinical improvement following immunoglobulin replacement, a prolonged cough prompted a CT scan, which showed nodules. Biopsy identified a Grade 2 EBV + LYG. Due to an inadequate response with chemotherapy, further workup for primary immunodeficiency was performed. With her symptoms of eczema and IgE elevation, along with her brother's history of recurrent sinopulmonary infections and warts, targeted sequencing of DOCK8 was performed revealing compound heterozygous mutations for the two siblings. Both patients were successfully transplanted with resolution of the LYG and warts, respectively. This is the first reported case of LYG in DOCK8 deficiency. The EBV-driven lymphoproliferative disease along with the infection history in the brother led to the diagnosis of DOCK8 deficiency and curative hematopoietic stem cell transplants.


Role of macrophage-derived histamine in atherosclerosis-- chronic participation in the inflammatory response --.
The atherosclerotic intimal lesion contains endothelial cells, smooth muscle cells, monocytes/macrophages and T lymphocytes, which constitute a histamine-cytokine network that participates in chronic inflammatory responses. Monocytes/macrophages and T lymphocytes express the histamine-producing enzyme histidine decarboxylase (HDC), and specific histamine receptors (HHR), which are switched from HH2R to HHR1 during macrophage differentiation. Endothelial and smooth muscle cells also express HHR in response to histamine. The effects of histamine on these cells include a regulation of atherosclerosis-related events such as cell proliferation, expression of matrix metalloproteinase, adhesion molecules and cytokines. Furthermore, recent studies have indicated that histamine and the activation of its specific receptors modulate the Th1/Th2 balance in inflammatory lesions through the regulation of cytokine production from inflammatory cells. The histamine-cytokine network in the atherosclerotic intima could regulate inflammatory and immune responses, including Th1/Th2 balance, and contribute to atherogenesis.


Biological Activity of Bacillus thuringiensis (Bacillales: Bacillaceae) in Anastrepha fraterculus (Diptera: Tephritidae).
Anastrepha fraterculus (Wiedemann) (Diptera: Tephritidae) is considered to be one of the major pest insects in fruit orchards worldwide. Bacillus thuringiensis Berliner (Bacillales: Bacillaceae) strains are widely used as biological control agents and show high biological activity against different insect species. The objective of this study was to evaluate the biological activity of different strains of B. thuringiensis against A. fraterculus larvae and adults. Bioassays were performed using suspensions of bacterial spores/crystals of B. thuringiensis var. israelensis (Bti), kurstaki (Btk), and oswaldocruzi (Bto) strains at three concentrations [2 × 107, 2 × 108, and 2 × 109 colony-forming units per ml (CFU ml-1)]. At a concentration of 2 × 109 CFU ml-1, a significant larval effect (mortality 60%) was observed when compared with the control treatment. Larvae that ingested spore/crystal suspensions of Bti, Btk, or Bto bacterial strains exhibited significant larval and pupal deformations, leading to a significant decrease (~50%) in the completion of the insects' biological cycle (egg to adult). The B. thuringiensis strains (Bti, Btk, or Bto) at a concentration of 2 × 109 CFU ml-1 in combination with one food attractant (BioAnastrepha 3% or CeraTrap 1.5%) in formulations of toxic baits provided high mortality (mortality > 85%) of A. fraterculus adults 7 d after treatment. However, the Btk strain in combination with CeraTrap 1.5% caused mortality of 40%. On the basis of these results, the native bacterial strains Bti, Btk, and Bto were considered to be promising candidates as biological control agents against A. fraterculus.


Assessment of collateral circulation to the hand prior to radial artery harvest.
Assessment of collateral circulation to the hand is required prior to invasive procedures or harvesting of the radial artery (RA). A modified Allen's test (MAT) is commonly used to assess palmar arch collaterals. A variety of non-invasive methods including digital pressures, plethysmography, pulse oximetry and duplex ultrasonography are available to supplement physical examination. However, no consensus exists about the proper role of the MAT and the most appropriate non-invasive test (NIT) in this situation. Interpretation of the MAT and NIT findings are also controversial. This paper reviews the anatomy and the physiologic basis for the MAT and various NITs, the pros and cons of various NITs and recommendations for the assessment of collateral circulation to the hand prior to interventions directed at the RA.


A single mycobacterial protein (hsp 65) expressed by a transgenic antigen-presenting cell vaccinates mice against tuberculosis.
We used a retroviral shuttle vector [pZIPNeoSV(X)] to transfect a monocyte-like murine tumour cell line (J774.G8) with the Mycobacterium leprae gene encoding heat-shock protein (hsp) 65. The antigen was expressed and presented on the surface of the transfected cell in association with major histocompatibility complex (MHC) class I and class II for recognition by T cells from specifically sensitized mice. We show here that when these transfected cells were used as a vaccine and introduced parentally into syngeneic (BALB/c) mice they conferred a remarkably high degree of protective immunity against subsequent challenge with either M. bovis bacillus Calmette-Guérin (BCG) or M. tuberculosis H37Rv.


Malunion after midshaft clavicle fractures in adults.
This is an overview of the current literature on malunion after midshaft clavicle fracture. Anatomy, trauma mechanism, classification, incidence, symptoms, prevention, and treatment options are all discussed. The conclusion is that clavicle malunion is a distinct clinical entity that can be treated successfully.


The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen.
Repeated hyperbaric oxygen (HBO) exposure prior to ischemia has been reported to provide neuroprotection against ischemic brain injury. The present study examined the time course of neuroprotection of HBO (3.5 atmosphere absolute, 100% oxygen, 1 h for 5 consecutive days) and the changes of gene/protein expression in rats. First, at 6 h, 12 h, 24 h, and 72 h after HBO sessions, rats were subjected to forebrain ischemia (8 min). Histopathological examination of hippocampal CA1 neurons was done 7 days after ischemia. Second, temporal genomic responses and protein expression were examined at the same time points after HBO sessions without subjecting animals to ischemia. HBO significantly reduced loss of hippocampal CA1 neurons that normally follows transient forebrain ischemia when the last HBO session was 6 h, 12 h, or 24 h before ischemia (survived neurons 55%, 75%, and 53%, respectively), whereas if there was a 72-h delay before the ischemic insult, HBO was not protective (survived neurons only 6%). Statistical analysis on microarray data showed significant upregulation in 60 probe sets including 7 annotated genes (p75NTR, C/EBPdelta, CD74, Edg2, Trip10, Nrp1, and Igf2), whose time course expressions corresponded to HBO-induced neuroprotection. The protein levels of p75NTR, C/EBPdelta, and CD74 were significantly increased (maximum fold changes 2.9, 2.0, and 7.9, respectively). The results suggest that HBO-induced neuroprotection against ischemic injury has time window, protective at 6 h, 12 h and 24 h but not protective at 72 h. Although the precise interaction is to be determined, the genes/proteins relevant to neurotrophin and inflammatory-immune system may be involved in HBO-induced neuroprotection.


[MOBILE TECHNOLOGY AS A POTENTIAL TOOL IN RESEARCH ON STIGMA ASSOCIATED WITH HIV/AIDS AMONG MEDICAL STUDENTS].
The identification and reduction of manifestations of stigma associated with HIV/ AIDS among health professionals continues facing significant challenges. Some of these are the measurement of stigma in complex setting such as clinical scenarios. However, with the emergence of mobile technology in recent years, such as smartphones and tablets, possibilities for exploration and reduction of stigma manifestations are enhanced. This article aims to reflect on the ability of the iPad to help assess manifestations of stigma associated with HIV/AIDS within a controlled clinical setting with medical students. It is based on a research experience that was carried out to measure behavioral manifestations of stigma associated with HIV/AIDS among medical students in Puerto Rico. The study integrated the use of iPad in the data's collection, storage and analysis. This article highlights the use of existing applications (Apps) for iPad for the implementation of digital tools to measure stigma towards HIV/AIDS. In discussing the experience of researchers, the iPad's potential and it applications for research on stigma are highlighted. Also, implications for the use of mobile technology in social research are discussed.


miR-424 protects PC-12 cells from OGD-induced injury by negatively regulating MKP-1.
It's of great significance to investigate the novel targets of drugs for the treatment of stroke. In this study, we explored the neuroprotective role of miR-424 in oxygen glucose deprivation (OGD)-induced injuries in PC-12 cells. PC-12 cells were subjected to OGD stimulation to mimic ischemic injury. The expressions of miR-424 and mitogen-activated protein kinase phosphatase-1 (MKP-1) were altered by transient transfection with miR-424 mimic, miR-424 inhibitor, pEX-MKP-1, or sh-MKP-1. Cell counting kit-8 (CCK-8) assay, flow cytometry, and quantitative reverse transcription polymerase chain reaction (qRT-PCR), were conducted to respectively detect cell viability, apoptotic cells, and the expression of miR-424 and MKP-1. The protein expressions of several factors were determined by Western blot. Meanwhile, relative luciferase activity assay was done to verify the predicted targets association. OGD induced injury in PC-12 cells by suppressing cell viability and inducing apoptosis. OGD also induced the expression of miR-424 in PC-12 cells. Overexpression of miR-424 protected PC-12 cells from OGD-induced injury by increasing cell viability and decreasing apoptosis. MKP-1 was a direct target of miR-424, and its expression was negatively regulated by miR-424. Up-regulation of expression of MKP-1 aggravated OGD-induced cell injury by inhibiting the expression of hypoxia-inducible factor 1α (HIF-1α), thus inhibiting the PI3K/AKT/mTOR pathways. miR-424 protected PC-12 cells from OGD-induced injury through direct suppression of MKP-1 expression, as MKP-1 promoted OGD-induced cell injury by inhibiting the expression of HIF-1α and PI3K/AKT/mTOR pathways.


Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malaria parasites contain similar sequence motifs.
Properdin is a plasma glycoprotein which stabilizes the C3bnBb enzyme complex of the alternative pathway of the complement system. Unlike the classical pathway, which is initiated by interaction of C1q with the Fc regions of IgG or IgM antibodies in immune complexes, the alternative pathway can be directly activated via binding of C3b to surfaces of foreign organisms. The stabilized C3bnBbP complex activates components C3 and C5 resulting in opsonization of foreign material (via C3b) and assembly of the membrane attack complex (via C5b) on target cells. Therefore properdin greatly enhances complement-mediated clearance and inactivation mechanisms in both natural and acquired resistance to infection. This paper shows that the primary amino acid sequence of properdin is composed mainly of six repeating motifs, each of approximately 60 amino acids, and that similar sequences are found in thrombospondin, the circumsporozoite protein of malaria parasites and regions of the membrane-attack components of complement. These similarities may provide insight into the mechanisms by which parasites avoid host defences mediated by complement.


Regulation of protoxin synthesis in Bacillus thuringiensis.
A derivative of Bacillus thuringiensis subsp. kurstaki (HD-1) formed parasporal inclusions at 25 degrees C, but not at 32 degrees C. This strain differed from the parent only in the loss of a 110-megadalton (Md) plasmid, but plasmid and chromosomal copies of protoxin genes were present in both strains. On the basis of temperature shift experiments, the sensitive period appeared to be during midexponential growth, long before the time of protoxin synthesis at 3 to 4 h after the end of exponential growth. The conditional phenotype could be transferred by cell mating to naturally acrystalliferous Bacillus cereus. In all such cases, a 29-Md protoxin -encoding plasmid was transferred, but this plasmid alone was barely sufficient for protoxin synthesis. Protoxin production increased to detectable levels, but well below those of the parental donor strain, by simultaneous transfer of a 44-Md protoxin -encoding plasmid. Transfer of a 5-Md plasmid with the two larger protoxin -coding plasmids resulted in a protoxin synthesis level approaching that of the donor strain. A role for some of the cryptic plasmids of kurstaki in parasporal body formation was implied. In contrast, a closely related B. thuringiensis strain, HD73 , produced crystals at both 25 and 32 degrees C even when the capacity was transferred on a 50-Md plasmid to B. cereus. The amount of protoxin produced in these B. cereus transcipients , however, was somewhat less than that produced in the parental strain HD73 , implying that catabolic differences, gene dosage, or the presence of a chromosomal gene (or a combination of these) may be necessary for maximum production. A regulatory component of the 29-Md plasmid appeared to be trans-acting and dominant since B. cereus transcipients containing the 29-Md plasmid from kurstaki and the 50-Md plasmid from HD73 produced more protoxin at 25 degrees C than at 30 degrees C. Similar results were obtained when protoxin synthetic capacity was transferred from B. thuringiensis subsp. israelensis to the conditional B. thuringiensis subsp. kurstaki strain.


Immune responses in human necatoriasis: association between interleukin-5 responses and resistance to reinfection.
Cytokine and proliferative responses to Necator americanus infection were measured in a treatment-reinfection study of infected subjects from an area of Papua New Guinea where N. americanus is highly endemic. Before treatment, most subjects produced detectable interleukin (IL)-4 (97%), IL-5 (86%), and interferon (IFN)- gamma (64%) in response to adult N. americanus antigen. Pretreatment IFN- gamma responses were negatively associated with hookworm burden, decreasing by 18 pg/mL for each increase of 1000 eggs/gram (epg) (n=75; P<.01). Mean IFN- gamma responses increased significantly after anthelmintic treatment, from 166 to 322 pg/mL (n=42; P<.01). The intensity of reinfection was significantly negatively correlated with pretreatment IL-5 responses, decreasing by 551 epg for each 100 pg/mL increase in production of IL-5 (n=51; P<.01). These data indicate that there is a mixed cytokine response in necatoriasis, with worm burden-associated suppression of IFN- gamma responses to adult N. americanus antigen. Resistance to reinfection is associated with the parasite-specific IL-5 response.


Ultradian rhythms in hydromineral hormones.
The maintenance of hydromineral homeostasis depends on the coordinated action of arginine vasopressin (AVP), atrial natriuretic peptide (ANP), the renin-angiotensin-aldosterone system and other recently identified endocrine or paracrine hormones. Several reports have pointed out the changes in urinary excretion and osmolality during the sleep-wake cycle and the rapid eye movement (REM)-non(N)REM sleep cycles. No such changes occur for ANP levels which have a flat profile over 24 h. The pulsatile fluctuations of AVP are described as random. The ultradian rhythm of plasma renin activity (PRA) depends on the regularity of the REM-NREM sleep cycles and the nocturnal curves reflect all disturbances in the internal sleep structure. A study with a shift in the normal sleep time clearly demonstrated that both PRA and aldosterone oscillations are sleep-stage dependent. These hormones could account for the ultradian variations in renal function. The nocturnal oscillations in sympathovagal balance may play an additional role. It is suggested that a central generator synchronizes endocrine, renal, autonomic and sleep processes.


Content Based Image Retrieval by Using Color Descriptor and Discrete Wavelet Transform.
Due to recent development in technology, the complexity of multimedia is significantly increased and the retrieval of similar multimedia content is a open research problem. Content-Based Image Retrieval (CBIR) is a process that provides a framework for image search and low-level visual features are commonly used to retrieve the images from the image database. The basic requirement in any image retrieval process is to sort the images with a close similarity in term of visually appearance. The color, shape and texture are the examples of low-level image features. The feature plays a significant role in image processing. The powerful representation of an image is known as feature vector and feature extraction techniques are applied to get features that will be useful in classifying and recognition of images. As features define the behavior of an image, they show its place in terms of storage taken, efficiency in classification and obviously in time consumption also. In this paper, we are going to discuss various types of features, feature extraction techniques and explaining in what scenario, which features extraction technique will be better. The effectiveness of the CBIR approach is fundamentally based on feature extraction. In image processing errands like object recognition and image retrieval feature descriptor is an immense among the most essential step. The main idea of CBIR is that it can search related images to an image passed as query from a dataset got by using distance metrics. The proposed method is explained for image retrieval constructed on YCbCr color with canny edge histogram and discrete wavelet transform. The combination of edge of histogram and discrete wavelet transform increase the performance of image retrieval framework for content based search. The execution of different wavelets is additionally contrasted with discover the suitability of specific wavelet work for image retrieval. The proposed algorithm is prepared and tried to implement for Wang image database. For Image Retrieval Purpose, Artificial Neural Networks (ANN) is used and applied on standard dataset in CBIR domain. The execution of the recommended descriptors is assessed by computing both Precision and Recall values and compared with different other proposed methods with demonstrate the predominance of our method. The efficiency and effectiveness of the proposed approach outperforms the existing research in term of average precision and recall values.


Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer.
Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients' outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.


The role of colonoscopy in the diagnosis of tuberculosis.
The value of colonoscopy in the diagnosis of ileocolonic tuberculosis at Groote Schuur Hospital was assessed and the published world experience reviewed. During a 4-year period, abdominal tuberculosis was diagnosed in 94 patients, of whom 18 manifested involvement of the ileocecal area and/or colon. Colonoscopy, performed in 10 of these, provided diagnostic information in 7. Since the endoscopic appearance of diseased mucosa is nonspecific, adequate bacteriological and histological assessment of biopsied tissue is essential to differentiate tuberculosis from other disorders that may simulate it. We stress the importance of microscopy and culture for Mycobacterium tuberculosis.


Cataract surgery in patients taking alpha-1 antagonists: know the risks, avoid the complications.
The growing use of alpha-1 receptor antagonists in the treatment of benign prostatic hyperplasia (BPH) has created a new problem in ophthalmic surgery, the so-called intraoperative floppy iris syndrome (IFIS). This consists of a billowing iris, insufficient pupillary dilation with progressive intraoperative miosis, and protrusion of iris tissue through the tunnel and side port incision that are made for access to the anterior chamber during surgery. IFIS presents particular difficulties in cataract surgery which is carried out through the pupil with manipulations in the immediate vicinity of the iris. The complications range from poor visibility of the operative field to iris damage with the surgical instruments and to rupture of the posterior capsule, with loss of lens material into the vitreous body. Selective literature review. Alpha-blockers have a direct effect on the alpha-receptors of the iris but also induce ultrastructural changes in the iridial stroma, leading to IFIS. The most important factor in avoiding complications of IFIS seems to be the ophthalmic surgeon's knowledge that the patient is taking an alpha-1 receptor antagonist. A thorough medical history and an optimized information flow among all physicians treating the patient-the urologist, the family physician, and the ophthalmic surgeon-are essential for safe cataract surgery.


Total Syntheses of Norrisolide-Type Spongian Diterpenes Cheloviolene C, Seconorrisolide B, and Seconorrisolide C.
The first total syntheses of three unusual norrisolide-type rearranged spongian diterpenes, cheloviolene C, seconorrisolide B, and seconorrisolide C, have been accomplished via a common intermediate through late-stage ring-scissoring. The synthesis features a Wolff ring contraction for the synthesis of the trans-hydrindane system, and a crucial retro Diels-Alder reaction/intramolecular ene cyclization for the rapid stereoselective construction of the furo[2,3-b]furan system, which is commonly seen in rearranged spongian diterpenes.


Mapping the accessibility of the disulfide crosslink network in the wool fiber cortex.
The disulfide bond network within the cortex of mammalian hair has a critical influence on the physical and mechanical characteristics of the fiber. The location, pattern, and accessibility of free and crosslinked cysteines underpin the properties of this network, but have been very difficult to map and understand, because traditional protein extraction techniques require the disruption of these disulfide bonds. Cysteine accessibility in both trichocyte keratins and keratin associated proteins (KAPs) of wool was investigated using staged labeling, where reductants and chaotropic agents were used to expose cysteines in a stepwise fashion according to their accessibility. Cysteines thus exposed were labeled with distinguishable alkylation agents. Proteomic profiling was used to map peptide modifications and thereby explore the role of KAPs in crosslinking keratins. Labeled cysteines from KAPs were detected when wool was extracted with reductant only. Among them were sequences from the end domains of KAPs, indicating that those cysteines were easily accessible in the fiber and could be involved in forming interdisulfide linkages with keratins or with other KAPs. Some of the identified peptides were from the rod domains of Types I and II keratins, with their cysteines positioned on the exposed surface of the α-helix. Peptides were also identified from keratin head and tail domains, demonstrating that they are not buried within the filament structure and, hence, have a possible role in forming disulfide linkages. From this study, a deeper understanding of the accessibility and potential reactivity of cysteine residues in the wool fiber cortex was obtained.


The role of Toll-like receptor 4 on inflammation and Aβ formation in cortex astrocytes.
To investigate the role and possible molecular mechanism of astrocytes in inflammation and amyloid β-protein (Aβ) formation, in this research, by using LPS to stimulate cultured rat astrocytes in vitro with or without anti-Toll-like receptor 4 (TLR4) antibody pretreatment, we first detected the TLR4, TNF-α, IL-1β, β-amyloid precursor protein (β-APP) and β-site APP clearing enzyme 1 (BACE1) mRNA with real-time PCR, and TLR4, NF-κB/P65 protein in cultured astrocytes by Western blot, and then further probed the translocation of NF-κB/P65 using immunofluorescence and the contents of TNF-α, IL-1β and Aβ in culture supernatant through ELISA. We found that all of these indexes increased at different degrees after LPS-stimulation. However, if pretreatment with anti- TLR4 antibody, such stimulating effects of LPS on the nuclear translocation of NF-κB/P65 and TNF-α, IL-1β, Aβ contents in astrocytic culture supernatant were reduced significantly or disappeared in comparison with the group with only LPS-administration. Our results suggest that TLR4 in astrocytes might play an important role in the inflammation and Aβ formation through the TLR4/NF-κB signaling pathway, thus providing new knowledge and understanding of the inflammatory hypothesis of AD pathogenesis.


Erikson's concept of ego identity reconsidered.
This paper explores and attempts to explain the paradox that Erik Erikson--after Freud, undoubtedly the psychoanalyst best known, most deeply esteemed, and most widely influential in the sociohistorical surround of world culture--has at the same time never been properly integrated into the psychoanalytic mainstream, but has instead been marginalized, consigned to a persisting psychoanalytic limbo. Two successive contexts within the historical unfolding of psychoanalysis in America, the milieu in which Erikson worked, would seem to account for this neglect. First, Erikson's monumental contributions to our understanding of the psychosocial developmental process, of the epigenesis of the ego, of the phase-specific developmental tasks across the eight postulated stages of the life cycle, and of the intergenerational cogwheeling of the life cycles were made during the 1950s and 1960s and could not easily be integrated into the ego psychology metapsychological paradigm then monolithically regnant within American psychoanalysis. And, second, as a major paradigm shift took place in America, beginning in the 1970s, toward a more relational, interpersonal, and intersubjective framework, Erikson's contributions, couched as they were in the structural language of the ego psychology of his time, were overlooked and went unremarked as seminal precursors of the newly emerging emphases. The clear relationship of Erikson's concepts of (ego) identity to emerging conceptions of self in relation to objects was simply not noticed, and his work continues to this day to be neglected and unintegrated within psychoanalysis.


Interstage Home Monitoring After Newborn First-Stage Palliation for Hypoplastic Left Heart Syndrome: Family Education Strategies.
Children born with hypoplastic left heart syndrome are at high risk for serious morbidity, growth failure, and mortality during the interstage period, which is the time from discharge home after first-stage hypoplastic left heart syndrome palliation until the second-stage surgical intervention. The single-ventricle circulatory physiology is complex, fragile, and potentially unstable. Multicenter initiatives have been successfully implemented to improve outcomes and optimize growth and survival during the interstage period. A crucial focus of care is the comprehensive family training in the use of home surveillance monitoring of oxygen saturation, enteral intake, weight, and the early recognition of "red flag" symptoms indicating potential cardiopulmonary or nutritional decompensation. Beginning with admission to the intensive care unit of the newborn with hypoplastic left heart syndrome, nurses provide critical care and education to prepare the family for interstage home care. This article presents detailed nursing guidelines for educating families on the home care of their medically fragile infant with single-ventricle circulation.


Chromaffin cell catecholamine secretion: bisindolylmaleimide compounds exhibit novel and potent antagonist effects at the nicotinic cholinergic receptor in pheochromocytoma cells.
Activation of protein kinase C (PKC) stimulates nicotine-induced catecholamine secretion. PKC down-regulation by prolonged pretreatment with phorbol 12-myristate 13-acetate diminished nicotine-induced catecholamine secretion only slightly (approximately 16%), suggesting substantial PKC independence of nicotinic receptor activation. However, we found that bisindolylmaleimide compounds (which are also putative PKC chemical inhibitors) dramatically inhibited nicotine-induced catecholamine secretion (IC(50) values of approximately 24-37 nM). This inhibition was specific for the nicotinic cholinergic receptor. Catecholamine secretion induced by other nicotinic agonists (such as epibatidine, anatoxin, or cytisine) was also powerfully antagonized by bisindolylmaleimide II (IC(50) values of approximately 60-90 nM). Even high-dose nicotinic agonists failed to overcome the inhibition by bisindolylmaleimide II, suggesting noncompetitive nicotinic antagonism by this class of compounds. Nicotinic inhibition by bisindolylmaleimide seemed not to be readily reversible. Structure-activity studies of bisindolylmaleimide compounds revealed that bisindolylmaleimides I through III are the most potent nicotinic antagonists at the nicotinic cholinergic receptor in PC-12 cells (IC(50) < or =37 nM), whereas bisindolylmaleimide IV and V have far less nicotinic antagonist activity (IC(50) >1 microM); the active compounds I through III have cationic tails at an indole nitrogen, whereas the least potent compounds IV and V do not. By contrast, a free NH within the maleimide ring is crucial for PKC inhibition by this class of compounds. We conclude that bisindolylmaleimides I through III are some of the most potent noncompetitive neuronal nicotinic antagonists, indeed the most potent such antagonists we have observed in PC-12 cells. Nicotinic antagonism of these compounds seems to be independent of PKC inhibition.


Simultaneous use of camera and probe diagnostics to unambiguously identify and study the dynamics of multiple underlying instabilities during the route to plasma turbulence.
We use multiple-tip Langmuir probes and fast imaging to unambiguously identify and study the dynamics of underlying instabilities during the controlled route to fully-developed plasma turbulence in a linear magnetized helicon plasma device. Langmuir probes measure radial profiles of electron temperature, plasma density and potential; from which we compute linear growth rates of instabilities, cross-phase between density and potential fluctuations, Reynold's stress, particle flux, vorticity, time-delay estimated velocity, etc. Fast imaging complements the 1D probe measurements by providing temporally and spatially resolved 2D details of plasma structures associated with the instabilities. We find that three radially separated plasma instabilities exist simultaneously. Density gradient driven resistive drift waves propagating in the electron diamagnetic drift direction separate the plasma into an edge region dominated by strong, velocity shear driven Kelvin-Helmholtz instabilities and a central core region which shows coherent Rayleigh-Taylor modes propagating in the ion diamagnetic drift direction. The simultaneous, complementary use of both probes and camera was crucial to identify the instabilities and understand the details of the very rich plasma dynamics.


The Isiokpo oil-pipeline leakage: total organic carbon/organic matter contents of affected soils.
The environmental impact of the 1997 leakage of the high-pressure crude-oil pipeline at Isiokpo in the Niger Delta in the southeast of Nigeria was evaluated, with particular reference to total-organic-carbon (TOC) and total-organic-matter (TOM) contents of soils within the vicinity of the oil spillage. The soils, taken from depths of 0-15 cm (surface) and 15-30 cm (subsurface), were found to be more acidic (pH 4.2-5.6) than the unpolluted soils, with a high average moisture content of 6.8%. The extractable hydrocarbon content ranged from 2.71-3.48 mg/kg, indicating hydrocarbon contamination. However, contrary to expectation, the TOC and TOM contents of the polluted soils did not show any significant increase in concentration, supposedly due to natural rehabilitation of the affected mat layer of soils. Thus, notwithstanding the possible proliferation of heterotrophic organisms by the presence of the added petroleum hydrocarbons, environmental conditions such as weathering and climatic predispositions, as well as physico-chemical parameters such as pH, moisture content, and temperature must have encumbered the carbon-mineralizing capacity of the heterotrophs, thereby reducing the turnover of carbon and the decomposition of organic matter. The restrictions by high moisture content might not come directly from H(2)O itself, but are probably a consequence of hindered soil ventilation, which reduces O(2) supply and gaseous diffusion, conditions that might have been substantially aggravated by the added petroleum hydrocarbons.


[Dynamics of the cytoplasmic RNA content in the sympathetic neurons in a synaptic block].
Cytophotometry of RNA was carried out in the neurons of the superior cervical sympathetic ganglion of the adult rabbits under the effect of various doses of the ganglion blocking agent dimecolin. Marked oscillations in the RNA content were observed in the neuronal cytoplasm after administration of the preparation. Dynamics of revealed shifts significantly differed depending on the dose of the preparation, and it was similar in the mono- and binucleated neurons. On the basis of the analysis of the character of variations revealed it is suggested that the synaptic processes have an important role in the development of quantitative RNA shifts in postsynaptic neurones. The results obtained indicate that the functional activity in some ganglioid neurones increases after administration of various doses of dimecolin during the blockade and after its termination.


Temperature-Responsive Pickering Double Emulsions Stabilized by Binary Microgels.
Microgels are excellent emulsifiers that can self-assemble to reduce interfacial tension and form a steric barrier at an oil-water interface. Herein, we report a two-step emulsification approach to prepare oil-in-water-in-oil (O/W/O) Pickering double emulsions through the dispersion of microgels in two immiscible phases. The stabilization mechanism depends on the uneven distribution and adsorption of hydrophilic water-swollen microgels and hydrophobic octanol-swollen microgels on either outer water droplets or inner oil droplets. Our results reveal that binary microgels outperformed single microgels in terms of interfacial tension reduction and emulsion stabilization. Notably, the binary microgel-stabilized Pickering double emulsions show excellent temperature responsiveness owing to the intrinsic thermal sensitivity of microgels. Consequently, the selective and rapid release of encapsulated substances in different phases can be achieved through the adjustment of the ambient temperature.


Anatomy of the knee joint of the cat.
Based on dissection of 20 adult specimens the anatomy of the knee joint of the cat is described. An attempt is made to include all functionally relevant structures such as bones, ligaments, menisci, joint capsule and capsular reinforcements. A comparison with the human knee joint is made. There is a high resemblance in construction with the main differences occurring in the proportions of the constituent elements. A comparison of the semimembranosus and biceps femoris receives particular attention. These descriptions lead to functional considerations in relation to the stability and force transmission of the knee joint in the cat.


[Trends in Google searches on complementary and alternative medicine].
The aim of this article is to evaluate the interest in complementary and alternative medicine (CAM) therapies using Google Trends in spanish-speaking countries. An observational study was conducted using GoogleTrends. The search volume of 34 CAM therapies in spanish were evaluated globally and in 21 spanish-speaking countries. Also, the relationship between the median of the most popular searches and the gross domestic product (GDP) per capita in each of the countries was evaluated using Spearman's test. A decreased trend in search volume was observed in homeopathy, herbal medicine, acupunctureand sensory therapies; and an increasing trend in chiropraxy. A direct association was observed between the GDP per capita and the median between the most popular CAM therapies, this relationship was no significant (p = 0.432). The interest in CAM therapies shows temporal and geographic variations that must be studied in depth. These results can be used for the establishment of an international monitoring for the use of CAM therapies.


Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial.
The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2. Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18-80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids). Efficacy endpoints included respiratory failure-free (RFF) days through day 28 as the primary endpoint. Secondary endpoints included safety and change from baseline oxygen saturation (SaO2)/fraction of inspired oxygen (FiO2) ratio on day 7, and 28-day mortality rate was a prespecified exploratory endpoint. Between June 2020 and April 2021, 205 patients were treated (nezulcitinib, 103; placebo, 102). There was no statistically significant difference between nezulcitinib versus placebo in the primary endpoint (RFF days; median, 21.0 vs 21.0; p=0.6137) or secondary efficacy endpoints. Nezulcitinib was generally well tolerated with a favourable safety profile. Although the prespecified primary, secondary and exploratory efficacy endpoints, including RFF through day 28, change from baseline SaO2/FiO2 ratio on day 7, and 28-day mortality rate, were not met, nezulcitinib was generally well tolerated and had a favourable safety profile. Further studies are required to determine if treatment with nezulcitinib confers clinical benefit in specific inflammatory biomarker-defined populations of patients with COVID-19.


Myricetin protects Galleria mellonella against Staphylococcus aureus infection and inhibits multiple virulence factors.
Staphylococcus aureus is an opportunistic pathogen related to a variety of life-threatening infections but for which antimicrobial resistance is liming the treatment options. We report here that myricetin, but not its glycosylated form, can remarkably decrease the production of several S. aureus virulence factors, including adhesion, biofilm formation, hemolysis and staphyloxanthin production, without interfering with growth. Myricetin affects both surface proteins and secreted proteins which indicate that its action is unrelated to inhibition of the agr quorum sensing system. Analysis of virulence related gene expression and computational simulations of pivotal proteins involved in pathogenesis demonstrate that myricetin downregulates the saeR global regulator and interacts with sortase A and α-hemolysin. Furthermore, Myr confers a significant degree of protection against staphylococcal infection in the Galleria mellonella model. The present findings reveal the potential of Myr as an alternative multi-target antivirulence candidate to control S. aureus pathogenicity.


Quantitative Detection of Oxidative Burst upon Activation of Plant Receptor Kinases.
The oxidative burst or the production of reactive oxygen species (ROS) is a typical cellular response of both plants and animals to diverse abiotic and biotic stresses. Mainly, the (re-)active oxygen species include the superoxide anion (O2-), hydrogen peroxide (H2O2), and the hydroxyl radical (OH•). Here, we outline the detection of extracellularly produced ROS in plant leaf pieces using a chemiluminescence-based bioassay with the luminol L-012 as a substrate being oxidized in the presence of ROS. Since this type of assay is in use in many laboratories, e.g., as a readout for activation of plant receptor kinases, we include a discussion on the interpretation of results and points addressing problems with the buffers at suboptimal pH values that negatively influence the chemiluminescence production.


New assays for parathyroid hormone (PTH) and the relevance of PTH fragments in renal failure.
Immunometric assays for parathyroid hormone (PTH) are used extensively to assess bone and mineral metabolism in patients with end-stage renal disease (ESRD) who are treated with dialysis. Results generally correspond to bone histology as documented by bone biopsy, and they are useful in monitoring disease progression. Recent work has shown, however, that older, first-generation immunometric PTH assays detect not only full-length PTH(1-84), but also other amino-terminally-truncated PTH fragments (ntPTH) that may have inhibitory effects on bone cell metabolism and/or contribute to the development of adynamic renal osteodystrophy. New second-generation immunometric PTH assays, by contrast, detect PTH(1-84) exclusively. The diagnostic value of plasma PTH determinations using second-generation immunometric PTH assays and the utility of estimates of the concentration of ntPTH in plasma in patients with ESRD has been assessed only recently. Results were reviewed from three published studies that examined the relationship between bone histology and plasma PTH levels as measured both by first- and by second-generation immunometric PTH assays in patients with ESRD. In all three studies, the concentration of ntPTH was estimated from the numerical difference between the results obtained with each assay and a ratio of PTH(1-84)/ntPTH was calculated. In one report, all patients with adynamic renal osteodystrophy had PTH(1-84)/ntPTH ratio values <1.0, although some patients with high-turnover skeletal lesions also had values <1.0. Estimates of the ratio of PTH(1-84)/ntPTH were found to be a better predictor of adynamic bone than PTH values measured by either assay. By contrast, two other studies failed to confirm these observations. One made use of the same second-generation immunometric PTH assay employed in the original report, whereas the other used a different assay with similar specificity for PTH(1-84). Plasma PTH levels obtained by first- and second-generation assays were highly correlated in these two independent reports. Plasma PTH levels, as determined by first-generation and second-generation immunometric assays, are highly correlated and have similar diagnostic value for the non-invasive assessment of renal osteodystrophy. The contention that ntPTH estimates and values for the PTH(1-84)/ntPTH ratio are useful in the diagnostic assessment of renal osteodystrophy has yet to be confirmed.


Immune response-related genes associated to blocking midgut dengue virus infection in Aedes aegypti strains that differ in susceptibility.
Aedes (Stegomyia) aegypti, the principal global vector of dengue viruses, has differences in its susceptibility to dengue virus infection. We compared the global expression of genes in the midguts of Colombian Ae. aegypti dengue-susceptible (Cali-S) and dengue-refractory (Cali-MIB) field derived strains after ingesting either a sugarmeal, a bloodmeal, or a bloodmeal containing dengue virus serotype 2 (DENV-2). Microarray-based transcriptome analysis among treatments indicated a total of 4725 transcripts with differential expression between the two strains. Eleven genes were selected from different functional groups based on their significant up or down expression levels as well as reports in the literature suggesting they are associated with dengue virus elimination. We measured mRNA abundance of these 11 genes at 0, 8, 24, and 36 h postinfection using quantitative real time PCR (qPCR) to confirm the microarray results and assess any temporal patterns. Four genes were selected (Gram-negative binding protein-GNBP [AAEL009176], Niemann Pick Type-C2-NPC2 [AAEL015136], Keratinocyte lectin [AAEL009842], and Cathepsin-b [AAEL007585]) for knockdown experiments using RNA interference (RNAi) methodology to determine the phenotype (DENV-2 susceptible or refractory). Silencing GNBP, Cathepsin-b and Keratinocyte lectin reduced the percentage of mosquitoes with disseminated virus in the Cali-S strain to 8%, 20%, and 12% respectively compared with 96% in the controls. Silencing of NPC2 increased the percentage of mosquitos with disseminated virus infections in Cali-MIB to 66% compared with 35% in the controls. This study provides insight into genes that may contribute to the Cali-S susceptible and Cali-MIB refractory phenotypes in Ae. aegypti.


Reduced susceptibility to eccentric exercise-induced muscle damage in resistance-trained men is not linked to resistance training-related neural adaptations.
The purpose of this study was to examine the acute effects of maximal concentric vs. eccentric exercise on the isometric strength of the elbow flexor, as well as the biceps brachii muscle electromyographic (EMG) responses in resistance-trained (RT) vs. untrained (UT) men. Thirteen RT men (age: 24 ± 4 years; height: 180.2 ± 7.7 cm; body weight: 92.2 ± 16.9 kg) and twelve UT men (age: 23 ± 4 years; height: 179.2 ± 5.0 cm; body weight: 81.5 ± 8.6 kg) performed six sets of ten maximal concentric isokinetic (CON) or eccentric isokinetic (ECC) elbow flexion exercise in two separate visits. Before and after the exercise interventions, maximal voluntary contractions (MVCs) were performed for testing isometric strength. In addition, bipolar surface EMG signals were detected from the biceps brachii muscle during the strength testing. Both CON and ECC caused isometric strength to decrease, regardless of the training status. However, ECC caused greater isometric strength decline than CON did for the UT group (p = 0.006), but not for the RT group. Both EMG amplitude and mean frequency significantly decreased and increased, respectively, regardless of the training status and exercise intervention. Resistance-trained men are less susceptible to eccentric exercise-induced muscle damage, but this advantage is not likely linked to the chronic resistance training-induced neural adaptations.


Tridentate NacNac Stabilized Tin and Nickel Complexes: Access to a Monomeric Nickel Hydride and Its Catalytic Application.
The transmetalation reaction of picolyl-supported tridentate nacnac germylene monochloride [2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)]GeCl (1) (py = pyridine) with SnCl2 results in an analogous stannylene chloride (2). The three-coordinated stannylenium cation [{2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)}Sn]+ with SnCl3- as a counteranion (3) has been generated through the abstraction of chloride ligand from 2 using an additional equivalent of SnCl2. Instead of forming a donor-acceptor complex, 2 undergoes a facile redox transmetalation reaction with Ni(COD)2 (COD = cyclooctadiene) and CuCl to afford analogous nickel and copper complexes [2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)]MCl [M = Ni (4) and Cu (5)]. The reactions of 4 with potassium tri-sec-butylborohydride (commonly known as K-selectride) and AgSbF6 provide access to monomeric Ni(II) hydride, [2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)]NiH (6) and a Ni(II) cation, [{2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)}Ni][SbF6] (7), respectively. 6 was found to be an effective catalyst for the hydroboration of amides.


Modulatory Effect of Protein and Carotene Dietary Levels on Pig gut Microbiota.
In this study we investigated the impact of dietary protein and carotene levels on microbial functions and composition during the last month of purebred fattening Duroc pigs. Fecal microbiota was characterized using 16S ribosomal RNA sequencing at two points of live, 165 (T1) and 195 (T2) days. From 70 to 165 days of age, 32 pigs were divided into two groups fed either a standard-protein (SP) or a low-protein (LP) diet. In the last month (165-195 days), all pigs received a LP diet, either carotene-enriched (CE) or not (NC). Significant differences were observed between T1 and T2 at Amplicon Sequences Variants (ASVs), phylum and genus levels. In T1 group, Prevotella, Faecalibacterium and Treponema were the genera most influenced by dietary protein, together with predicted functions related with the degradation of protein. In contrast, the CE diet did not impact the microbiome diversity, although 160 ASVs were differentially abundant between CE and NC groups at T2. Weak stability of enterotype clusters across time-points was observed as consequence of medium-term dietary interventions. Our results suggest that during the last month of fattening, dietary protein have a stronger effect than carotenes on the modulation of the compositional and functional structure of the pig microbiota.


Genetic variants of FZD4 and LRP5 genes in patients with advanced retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a complex disease with a genetic predisposition, but little is known about its genetic background. It has a clinical resemblance to familial exudative vitreoretinopathy (FEVR), a hereditary disease characterized by defects in the development of retinal vessels. Several studies have suggested that mutations in the causative genes for FEVR may account for a proportion of advanced ROP, but conflicting data have also been reported for some variants. To address the possibility of genetic involvement of FEVR genes in ROP, we performed comprehensive sequence analyses of 53 Japanese patients with advanced ROP for the FEVR-causing genes. Peripheral blood DNA was obtained from 53 patients referred to our hospitals for retinal surgery. Polymerase chain reaction followed by direct sequencing of the coding regions of the known FEVR-causing genes (FZD4, LRP5, TSPAN12, and NDP) and a noncoding exon of the NDP gene was performed. Possible pathogenicity of the sequence changes were analyzed by orthologous protein sequence alignment and by computational predictions. We identified six different nonsynonymous DNA variants in the coding region of either the FZD4 gene (p.H69Y, p.R127H, and p.Y211H) or the LRP5 gene (p.R1219H, p.H1383P, and p.T1540M) in seven patients. The corresponding codons of these changes were highly conserved among species, and these changes were predicted to be pathogenic by at least two of four computational prediction programs. No such changes were found in the TSPAN12 and NDP genes. Six possibly pathogenic variants of FZD4 or LRP5 were found in seven advanced ROP patients. Although these variants do not yet provide definitive evidence that they are causal, the results imply a role of the FZD4 and LRP5 genes in the development of advanced ROP.


Pancreatitis following spinal cord injury.
Six cases of pancreatitis following spinal cord injury are presented. No single, etiologically accepted mechanism already postulated to cause pancreatitis can account for all the cases reported. The authors hypothesize that spinal cord disruption may produce pacreatitis by sympathetic-parasympathetic nervous system imbalance resulting in over-stimulation of the sphincter of Oddi. This may lead to stasis of secretions with absorption of amylase into the systemic circulation, and structural pancreatic damage. Pancreatitis in those with cord injuries is easily overlooked because abdominal pain is usually absent and fever is usually attributed to more frequently occurring pulmonary or urinary tract infections. Recognition of this complication is important in order to decrease the morbidity and mortality that follows spinal cord damage.


Transplantation and microsurgical anastomosis of free omental grafts: experimental animal model of a new operative technique in dogs.
Our objective was the elaboration of a new animal model for the free transplantation of an omental flap and the examination of its viability in dogs. The cooled omental flap from the abdomen was freely transplanted to the lateral cervical region, and its blood supply was established with microsurgical anastomoses. The technique was developed in 5 dogs, and short-term survival examinations were later carried out in 3 cases by means of this method. Postoperative viability was assessed by angiography, methylene blue testing, and histology. Of the 3 transplanted grafts, 2 still survived 1 week after the operation. For technical reasons, 1 flap thrombotized. For determination of the viability of the transplanted graft, histology proved best. Vital reactions, including granulation tissue and angiogenesis, were present on the histological slides. The short-term survival of an omental flap can be ensured with microsurgical transplantation in dogs.


Non-Electrocardiogram-Triggered 70-kVp High-Pitch Computed Tomography Angiography of the Whole Aorta With Iterative Reconstruction: Initial Results.
To evaluate the feasibility of non-electrocardiogram (ECG)-triggered 70-kVp high-pitch aortic computed tomography angiography (CTA) with iterative reconstruction (IR) and reduced contrast agent using second-generation dual-source CT (DSCT). Seventy-seven patients were examined: group A (n = 21), 70-kVp high-pitch (3.2) CTA, 60 mL contrast agent and IR on second-generation DSCT; group B (n = 29), standard-pitch (1.2) CTA, automatic tube voltage selection, filtered back projection and 80 mL contrast agent on second-generation DSCT; group C (n = 27), 120-kVp standard-pitch (1.2) CTA, filtered back projection, and 80 mL contrast agent on first-generation DSCT. Computed tomography values, noise, signal-to-noise ratio, contrast-to-noise ratio, and subjective image quality were compared. Computed tomography values and noise of all aortic segments in group A were increased compared with groups B and C (P < 0.05). Group B showed the highest signal-to-noise ratio and contrast-to-noise ratio for all aortic segments (P < 0.05), whereas no significant differences were found between groups A and C (P > 0.05). Mean effective dose was 0.88 ± 0.08 mSv for group A, reduced by 93% compared to group C and by 90% compared to group B. Non-ECG-triggered 70-kVp high-pitch aortic CTA with IR provides equivalent diagnostic image quality with 90% reduction of radiation dose and 25% reduction of contrast volume compared with standard 120-kVp CTA.


Oral HIV-associated Kaposi sarcoma.
Kaposi sarcoma (KS), an AIDS defining condition, remains one of the most commonly HIV-associated neoplasms. While the use of highly active antiretroviral therapy (HAART) has brought about a dramatic decrease in the prevalence and incidence of AIDS-KS worldwide, this has not been the case in resource-poor sub-Saharan African countries, where HIV has reached epidemic proportions and human herpesvirus-8 infection is endemic. Oral involvement is a common manifestation of AIDS-associated KS and may be an early presenting finding of HIV infection. The clinical manifestation of oral KS can vary and may have an unpredictable course ranging from mild to fulminant. Rapidly progressive facial lymphoedema associated with extensive advanced oral KS portends a poor prognosis. Oral KS may regress with antiretroviral therapy or may flare up as part of the immune reconstitution inflammatory syndrome. The oral lesions of AIDS-KS are best managed with HAART together with systemic chemotherapy. This article provides a review of contemporary knowledge of the biology, pathology, clinical features and management of oral AIDS-KS.


Exposure to hydrogen peroxide induces cell death via apoptosis in cultured rat cortical neurons.
To investigate whether direct oxidative damage may induce neuronal death via an apoptotic cell suicide pathway, we exposed cultured cortical neurons to the prooxidant hydrogen peroxide. Our experiments demonstrate that brief exposures to low concentrations of hydrogen peroxide can induce neuronal cell death via apoptosis as demonstrated by toxicity assays, specific DNA staining, and the appearance of DNA laddering on agarose gels. These results suggest that direct oxidative injury may serve as a general trigger for apoptosis in the CNS, and that other apoptotic stimuli, such as exposure to amyloid-beta peptides, may also involve oxidative injury. Peroxide-induced apoptosis may serve as a valuable model for further studies of apoptosis in neurons.


Changes in acute hospital costs after employing clinical facilitators to improve stroke care in Victoria, Australia.
Hospital costs for stroke are increasing and variability in care quality creates inefficiencies. In 2007, the Victorian Government (Australia) employed clinical facilitators for three years in eight public hospitals to improve stroke care. Literature on the cost implications of such roles is rare. We report changes in the costs of acute stroke care following implementation of this program. Observational controlled before-and-after cohort design. Standardised hospital costing data were compared pre-program (financial year 2006-07) and post-program (2010-11) for all admitted episodes of stroke or transient ischaemic attack (TIA) using ICD-10 discharge codes. Costs in Australian dollars (AUD) were adjusted to a common year 2010. Generalised linear regression models were used for adjusted comparisons. A 20% increase in stroke and TIA episodes was observed: 2624 pre-program (age > 75 years: 53%) and 3142 post-program (age > 75 years: 51%); largely explained by more TIA admissions (up from 785 to 1072). Average length of stay reduced by 22% (pre-program 7.3 days to post-program 5.7 days, p < 0.001). Six hospitals provided cost data. Average per-episode costs decreased by 10% (pre-program AUD7888 to post-program AUD7115). After adjusting for age, sex, stroke type, and hospital, average per-episode costs decreased by 6.1% from pre to post program (p = 0.025). When length of stay was additionally adjusted for, these costs increased by 10.8%, indicating a greater mean cost per day (p < 0.001). Cost containment of acute inpatient episodes was observed after the implementation of stroke clinical facilitators, likely associated with the shorter lengths of stay.


A cross-sectional observation of burnout in a sample of Irish junior doctors.
Stress and burnout are common among doctors. Excess levels of stress have been shown to have detrimental personal and professional effects as well as a negative influence on patient care. The aim of our pilot study was to assess the levels of burnout among a cohort of interns. A voluntary written self-assessment of burnout levels was distributed to interns in two teaching hospitals. The Maslach Burnout inventory is a 22-question survey assessing the three components of the burnout syndrome-emotional exhaustion (EE), depersonalisation (DP) and personal achievement (PA). Twenty-seven surveys were distributed to interns in two hospitals with a 96.3 % (n = 26) response rate. The mean age was 25.1 years (range 24-31 years). 14 were medical interns, 12 were surgical interns at the time of completion. Overall, the mean EE score was 23.4 (range 11-29), representing moderate levels of EE. The mean DP score was 9.4 (range 4-14), representing moderate levels of DP. The mean PA score was 18.9 (range 12-29), representing high levels of PA. There were no significant differences noted between levels of EE, DP or PA among male or female interns, medical or surgical interns or those who worked in a peripheral or university hospital. Burnout is reported among interns in our pilot study. Measures need to be taken to heighten awareness of burnout among doctors and to educate physicians regarding self-awareness and personal health.


The yield of microscopic varicocelectomy in men with severe oligospermia.
Varicocele is detected in 35%-50% of men with primary infertility and up to 81% with secondary infertility. Various studies have shown that varicocele is related to testicular hypotrophy and impaired spermatogenesis. The effect of varicocelectomy in mild-to-moderate male factor infertility has been well reported. However, only a few studies addressed the impact of varicocelectomy in severe oligospermia. We included 45 patients with severe oligospermia (<5 million/mL) who underwent microsurgical varicocelectomy between May 2014 and November 2017. Results of semen analysis taken at 6 months after varicocelectomy were compared and patients were divided into responders and nonresponders. Chi-square was used to compare the preoperative and postoperative sperm count, motility, and volume. After 6 months only one patient was found to be a responder with a pre- to post-operative motility of 45%-74% and a sperm concentration of 1 million/mL to 28.1 million/mL. There was a significant improvement in the mean sperm concentration after varicocelectomy which improved from 1.31 million/mL to 5.32 million/mL. However, a significant decrease in sperm motility was noted which decreased from 35.62% to 28.64% postoperatively. Postoperative semen volume increased from 2.56 mL to 3.19 mL, but this difference was not found to be statistically significant (P > 0.05). Four patients (8.9%) were found to have azoospermia after a 6-month follow-up. In these four patients who turned azoospermic had count <50,000 sperm/mL, two of them had a history of cryptospermia before varicocelectomy. Ejaculate sperm returned in two of these four patients in long-term follow-up (>6 months). The magnitude of improvement after microsurgical varicocelectomy for severely oligospermic patients is less profound than reported in mild male factor infertility.


Serotonin modulates voltage-dependent calcium current in Necturus taste cells.
Necturus taste buds contain two primary cell types: taste receptor cells and basal cells. Merkel-like basal cells are a subset of basal cells that form chemical synapses with taste receptor cells and with innervating nerve fibers. Although Merkel-like basal cells cannot interact directly with taste stimuli, recent studies have shown that Merkel-like basal cells contain serotonin (5-HT), which may be released onto taste receptor cells in response to taste stimulation. With the use of whole cell voltage clamp, we examined whether focal applications of 5-HT to isolated taste receptor cells affected voltage-activated calcium current (I(Ca)). Two different effects were observed. 5-HT at 100 microM increased I(Ca) in 33% of taste receptor cells, whereas it decreased I(Ca) in 67%. Both responses used a 5-HT receptor subtype with a pharmacological profile similar to that of the 5-HT1A receptor, but the potentiation and inhibition of I(Ca) by 5-HT were mediated by two different second-messenger cascades. The results indicate that functional subtypes of taste receptor cells, earlier defined only by their sensitivity to taste stimuli, may also be defined by their response to the neurotransmitter 5-HT and suggest that 5-HT released by Merkel-like basal cells could modulate taste receptor function.


Comparative study of the anticonvulsive activity of N-aminomethylpiperazine-3,3-diethyl 2,4-pyridinedione with the activity of known antiepileptic agents.
N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione (DKMP) is a newly synthesized compound with a marked anticonvulsive effect in various epileptic models. The aim of the present work is to compare its anticonvulsive effect in corazol convulsions (100 mg/kg corazol, s.c.) with known anticonvulsants applied in clinical practice. The compounds tested were applied subcutaneously in equitoxic doses (1/20 and 1/30 of their respective LD50). Some undesirable side effects of the antiepileptic agents tested were also studied. With the experimental model used, DKMP was found to have a better anticonvulsive effect compared with diphenylhydantoin, depakin, suxilep and phenobarbital. Diazepam completely inhibited the convulsions, but it has an undesirable strong myorelaxing effect. In a subchronical experiment it was found that no tolerance developed toward DKMP, while the anticonvulsant effect of diazepam significantly decreased on the 15th day, compared with a single administration. Using the rota-rod test it was found that the agents studied had a stronger neurotoxic action compared with DKMP. These results outline DKMP as a promising compound with good antiepileptic activity, comparable to that of the known anticonvulsants.


Early Initiation of Tocilizumab in Clinically Isolated Aortitis.
Clinically isolated aortitis can arise from infectious or inflammatory etiologies. Glucocorticoids are the first-line therapy for inflammatory causes of aortitis such as large-vessel vasculitis. However, prolonged steroids use is associated with numerous side effects. We present a case of a 60-year-old woman with clinically isolated aortitis who received early treatment with tocilizumab to avoid prolonged steroid use.


Vanadium toxicity in the thymic development.
The purpose of this study was to define the toxic effects of vanadium on thymic development in broilers fed on diets supplemented with 0, 5, 15, 30, 45 and 60 mg/kg of vanadium for 42 days. We examined the changes of relative weigh, cell cycle phase, apoptotic cells, and protein expression of Bcl-2, Bax, and caspase-3 in the thymus by the methods of flow cytometry, TUNEL (terminal-deoxynucleotidyl transferase mediated nick end labeling) and immunohistochemistry. The results showed that dietary high vanadium (30 mg/kg, 45 mg/kg and 60 mg/kg) caused the toxic effects on thymic development, which was characterized by decreasing relative weigh, increasing G0/G1 phase (a prolonged nondividing state), reducing S phase (DNA replication) and proliferating index (PI), and increasing percentages of apoptotic thymocytes. Concurrently, the protein expression levels of Bax and caspase-3 were increased, and protein expression levels of Bcl-2 were decreased. The thymic development suppression caused by dietary high vanadium further leads to inhibitive effects on T lymphocyte maturity and activity, and cellular immune function. The above-mentioned results provide new evidences for further understanding the vanadium immunotoxicity. In contrast, dietary 5 mg/kg vanadium promoted the thymic development by increasing relative weigh, decreasing G0/G1 phase, increasing S phase and PI, and reducing percentages of apoptotic thymocytes when compared to the control group and high vanadium groups.