Home-based telehealth service for swallowing and nutrition management following head and neck cancer treatment.
Introduction Following (chemo)radiotherapy (C/RT) for head and neck cancer (HNC), patients return to hospital for regular outpatient reviews with speech pathology (SP) and nutrition and dietetics (ND) for acute symptom monitoring, nutritional management, and swallowing and communication rehabilitation. The aim of the current study was to determine the feasibility of a home-based telehealth model for delivering SP and ND reviews, to provide patients with more convenient access to these appointments. Methods Service outcomes, costs, and consumer satisfaction were examined across 30 matched participants: 15 supported via the standard model of care (SMOC), and 15 via the home-based telehealth model of care (TMOC). Results All patients were successfully managed via telehealth. The TMOC was more efficient, with a reduced number ( p < 0.003) and duration ( p < 0.01) of appointments required until discharge. Significant patient cost savings ( p = 0.002) were reported for the TMOC due to decreased travel requirements. While staff costs were reduced, additional telehealth equipment levies resulted in a lower but non-significant overall cost difference to the health service when using the TMOC. High satisfaction was reported by all participants attending the TMOC. Discussion The findings support the feasibility of a home-based telehealth model for conducting SP and ND reviews post C/RT for HNC.


In vitro T lymphopoiesis of human and rhesus CD34+ progenitor cells.
Differentiation of hematopoietic progenitor cells into T lymphocytes generally occurs in the unique environment of the thymus, a feature that has hindered efforts to model this process in the laboratory. We now report that thymic stromal cultures from rhesus macaques can support T-cell differentiation of human or rhesus CD34+ progenitor cells. Culture of rhesus or human CD34+ bone marrow-derived cells depleted of CD34+ lymphocytes on rhesus thymic stromal monolayers yielded CD3+CD4+CD8+, CD3+CD4+CD8-, and CD3+CD4-CD8+ cells after 10 to 14 days. In addition to classical T lymphocytes, a discrete population of CD3+CD8loCD16+CD56+ cells was detected after 14 days in cultures inoculated with rhesus CD34+ cells. CD3+ T cells arising from these cultures were not derived from contaminating T cells present in the CD34+ cells used to inoculate thymic stromal monolayers or from the thymic monolayers, as shown by labeling of cells with the lipophilic membrane dye PKH26. Expression of the recombinase activation gene RAG-2, which is selectively expressed in developing lymphocytes, was detectable in thymic cultures inoculated with CD34+ cells but not in CD34+ cells before thymic culture or in thymic stromal monolayers alone. Reverse transcriptase-polymerase chain reaction analysis of T cells derived from thymic stromal cultures of rhesus and human CD34+ cells showed a polyclonal T-cell receptor repertoire. T-cell progeny derived from rhesus CD34+ cells cultured on thymic stroma supported vigorous simian immunodeficiency virus replication in the absence of exogenous mitogenic stimuli. Rhesus thymic stromal cultures provide a convenient means to analyze T-cell differentiation in vitro and may be useful as a model of hematopoietic stem cell therapy for diseases of T cells, including acquired immunodeficiency syndrome.


Effect of Ca2+, Ba2+, and Sr2+ on alginate microbeads.
Microcapsules of alginate cross-linked with divalent ions are the most common system for cell immobilization. In this study, we wanted to characterize the effect of different alginates and cross-linking ions on important microcapsule properties. The dimensional stability and gel strength increased for high-G alginate gels when exchanging the traditional Ca2+ ions with Ba2+. The use of Ba2+ decreased the size of alginate beads and reduced the permeability to immunoglobulin G. Strontium gave gels with characteristics lying between calcium and barium. Interestingly, high-M alginate showed an opposite behavior in combination with barium and strontium as these beads were larger than beads of calcium-alginate and tended to swell more, also resulting in increased permeability. Binding studies revealed that different block structures in the alginate bind the ions to a different extent. More specifically, Ca2+ was found to bind to G- and MG-blocks, Ba2+ to G- and M-blocks, and Sr2+ to G-blocks solely.


[Drug residues in food fish].
The present paper reviews different possibilities of pharmacolegal residues in fish. Sometimes the treatment of fish with registered drugs in therapeutical dosage is provable in spite of keeping the withdrawal time. To that experiences of the persistence and values of Chloramphenicol, Chlortetracycline and Furazolidone proved after therapeutical treatment in fish correlated to the water temperature are compared with results of experiments documented in literature. Investigations on the residues of Enrofloxacin after application of different doses to rainbow trout were carried out. Sometimes the proof of drug residues in fish can be done without an advanced treatment. The recontamination of fish with drugs or their metabolites in environment is discussed as a possibility for drug residues. The carry-over-effect of drug during the animal food production can be also the reason for residues in fish. Experiments with Chloramphenicol contaminated feed in rainbow trout show residues in muscle of fish higher than 10 ppb during the feeding period. Finally the results of residues different drug used in fish--given in literature--are collected in two tables.


Hydration-responsive folding and unfolding in graphene oxide liquid crystal phases.
Graphene oxide is promising as a plate-like giant molecular building block for the assembly of new carbon materials. Its water dispersibility, liquid crystallinity, and ease of reduction offer advantages over other carbon precursors if its fundamental assembly rules can be identified. This article shows that graphene oxide sheets of known lateral dimension form nematic liquid crystal phases with transition points in agreement with the Onsager hard-plate theory. The liquid crystal phases can be systematically ordered into defined supramolecular patterns using surface anchoring, complex fluid flow, and microconfinement. Graphene oxide is seen to exhibit homeotropic surface anchoring at interfaces driven by excluded volume entropy and by adsorption enthalpy associated with its partially hydrophobic basal planes. Surprisingly, some of the surface-ordered graphene oxide phases dry into graphene oxide solids that undergo a dramatic anisotropic swelling upon rehydration to recover their initial size and shape. This behavior is shown to be a unique hydration-responsive folding and unfolding transition. During drying, surface tension forces acting parallel to the layer planes cause a buckling instability that stores elastic energy in accordion-folded structures in the dry solid. Subsequent water infiltration reduces interlayer frictional forces and triggers release of the stored elastic energy in the form of dramatic unidirectional expansion. We explain the folding/unfolding phenomena by quantitative nanomechanics and introduce the potential of liquid crystal-derived graphene oxide phases as new stimuli-response materials.


LASOR: Learning Accurate 3D Human Pose and Shape via Synthetic Occlusion-Aware Data and Neural Mesh Rendering.
A key challenge in the task of human pose and shape estimation is occlusion, including self-occlusions, object-human occlusions, and inter-person occlusions. The lack of diverse and accurate pose and shape training data becomes a major bottleneck, especially for scenes with occlusions in the wild. In this paper, we focus on the estimation of human pose and shape in the case of inter-person occlusions, while also handling object-human occlusions and self-occlusion. We propose a novel framework that synthesizes occlusion-aware silhouette and 2D keypoints data and directly regress to the SMPL pose and shape parameters. A neural 3D mesh renderer is exploited to enable silhouette supervision on the fly, which contributes to great improvements in shape estimation. In addition, keypoints-and-silhouette-driven training data in panoramic viewpoints are synthesized to compensate for the lack of viewpoint diversity in any existing dataset. Experimental results show that we are among the state-of-the-art on the 3DPW and 3DPW-Crowd datasets in terms of pose estimation accuracy. The proposed method evidently outperforms Mesh Transformer, 3DCrowdNet and ROMP in terms of shape estimation. Top performance is also achieved on SSP-3D in terms of shape prediction accuracy. Demo and code will be available at https://igame-lab.github.io/LASOR/.


[Bevacizumab and Ranibizumab for macular edema due to retinal vein occlusions].
The effect of Bevacizumab (BE) (Avastin®) or Ranibizumab (RA) (Lucentis®) on the visual acuity (VA) and on the central foveal thickness (CFT) was evaluated in macular edema due to retinal vein occlusion. Eyes with a macular edema due to a central retinal vein occlusion or to a branch retinal vein occlusion were considered if at least 3 intravitreal injections of Bevacizumab (1.25 mg) or Ranibizumab (0.5 mg) had been performed. The visual acuity with ETDRS and the central foveal thickness with spectral optical coherence tomography (OCT) were measured. The 3-months follow-up and, if further injections were necessary, the 6-months follow-up were evaluated. After 3 months a significant improvement of the visual acuity was measured in both groups (p < 0.001) while during the same period the mean central foveal thickness diminished significantly (p < 0.001). At the 3-months follow-up there were no significant differences between the two groups for the mean visual acuity and for the mean central foveal thickness. The treatment was continued in 36 eyes and the visual acuity and the central foveal thickness were compared between the 3-months and the 6-months follow-up. No further improvements of the visual acuity or of the central foveal thickness were measured in both groups. A relapse of the macular edema was diagnosed in 30 eyes without a significant difference in the Bevacizumab group compared to the Ranibizumab group. Intravitreal injections of Bevacizumab and Ranibizumab improved the visual acuity and the central foveal thickness in macular edema due to retinal vein occlusion at 3 months. A further improvement was not measured if the treatment was prolonged to 6 months. There were no significant differences measured between Bevacizumab and Ranibizumab. The ratio of relapses is important to note.


Use of zoledronic acid in antiosteoporosis treatment is associated with a decreased blood lipid level in postmenopausal women with osteoporosis: a cohort study in China.
This cohort study aimed to evaluate the protective effects of zoledronic acid (ZA) in lipidemia in postmenopausal women with osteoporosis. A total of 668 postmenopausal women with osteoporosis were regularly followed up for 12 months between January 2018 and August 2021 in the department of endocrinology and the health examination center of the hospital. They were divided into group I and group II depending on lipid metabolism disorder; Group II received atorvastatin 20 mg/d orally. Groups I and II were divided into experimental group (ZA exposure) and control group (ZA nonexposure). In group I, which was the ZA exposure group, the level of low-density lipoprotein cholesterol (LDL-C) was significantly lower than that before ZA treatment (P = 0.017); in the ZA nonexposure group, the levels of LDL-C, total cholesterol (TC), and triglycerides (TG) significantly increased after 12 months of follow-up (P = 0.005, P < 0.001, and P = 0.001). At the baseline, no significant difference was found in blood lipid indicators between the ZA exposure and nonexposure groups (P > 0.05), but the levels of LDL-C and TC in the exposed group significantly decreased after 12 months of follow-up (P = 0.008 and P = 0.027). In group II, which was the ZA exposure group, the levels of LDL-C and TC were significantly lower than those before ZA treatment (P < 0.001 and P < 0.001). At the baseline, the ZA exposure and nonexposure groups had no significant difference in blood lipid indicators (P > 0.05), but the levels of LDL-C and TC significantly decreased in the exposed group after 12 months of follow-up (P < 0.001 and P = 0.003). This cohort study found that ZA might exert a protective effect on lipid metabolism in postmenopausal women with osteoporosis. In postmenopausal women with lipid disorders suffering from osteoporosis, the treatment with ZA combined with atorvastatin significantly reduced the level of blood lipid compared with atorvastatin alone.


Wildfires, complexity, and highly optimized tolerance.
Recent, large fires in the western United States have rekindled debates about fire management and the role of natural fire regimes in the resilience of terrestrial ecosystems. This real-world experience parallels debates involving abstract models of forest fires, a central metaphor in complex systems theory. Both real and modeled fire-prone landscapes exhibit roughly power law statistics in fire size versus frequency. Here, we examine historical fire catalogs and a detailed fire simulation model; both are in agreement with a highly optimized tolerance model. Highly optimized tolerance suggests robustness tradeoffs underlie resilience in different fire-prone ecosystems. Understanding these mechanisms may provide new insights into the structure of ecological systems and be key in evaluating fire management strategies and sensitivities to climate change.


[Vertebral canal abscess as a complication of congenital sacral sinus in a two year old girl].
Vertebral canal abscess is rather an uncommon disease. Since 1830, when the first report that spinal of abscess was published. Till to 2000, no more than 20 cases as a result of dermal sinus infection were reported. Dermal sinus results from an incomplete separation of the cutaneus ectoderm from the neural ectoderm between the 4 and 6 weeks of fetal development. Surgical excision of the sinus is the treatment of choice for prevention of infection. The authors describes a 2-year-old girl with that abscess secondary to dorsal dermal sinus in sacral region. The patient presented with fever, since two weeks, flaccid paraparesis mainly in the right lower extremity, urinary and bowel incontinence. The child was initially treated conservatively, and after limitation of inflammatory process the dermal sinus and dermoid cyst containing a large quantity of pus were excised. The authors reviewed the literature of spinal cord abscesses secondary to congenital dermal sinus. The diagnostic and therapeutic methods presented in the literature are discussed in comparison with our case.


SDHI Fungicide Toxicity and Associated Adverse Outcome Pathways: What Can Zebrafish Tell Us?
Succinate dehydrogenase inhibitor (SDHI) fungicides are increasingly used in agriculture to combat molds and fungi, two major threats to both food supply and public health. However, the essential requirement for the succinate dehydrogenase (SDH) complex-the molecular target of SDHIs-in energy metabolism for almost all extant eukaryotes and the lack of species specificity of these fungicides raise concerns about their toxicity toward off-target organisms and, more generally, toward the environment. Herein we review the current knowledge on the toxicity toward zebrafish (Brachydanio rerio) of nine commonly used SDHI fungicides: bixafen, boscalid, fluxapyroxad, flutolanil, isoflucypram, isopyrazam, penthiopyrad, sedaxane, and thifluzamide. The results indicate that these SDHIs cause multiple adverse effects in embryos, larvae/juveniles, and/or adults, sometimes at developmentally relevant concentrations. Adverse effects include developmental toxicity, cardiovascular abnormalities, liver and kidney damage, oxidative stress, energy deficits, changes in metabolism, microcephaly, axon growth defects, apoptosis, and transcriptome changes, suggesting that glycometabolism deficit, oxidative stress, and apoptosis are critical in the toxicity of most of these SDHIs. However, other adverse outcome pathways, possibly involving unsuspected molecular targets, are also suggested. Lastly, we note that because of their recent arrival on the market, the number of studies addressing the toxicity of these compounds is still scant, emphasizing the need to further investigate the toxicity of all SDHIs currently used and to identify their adverse effects and associated modes of action, both alone and in combination with other pesticides.


Role of Y(2) receptors in the regulation of gastric tone in rats.
We set out to determine the effect of peptide YY(3-36) (PYY(3-36)) on the gastric muscle tone in conscious rats by measuring intragastric pressure (IGP) during intragastric nutrient drink infusion. After an overnight fast, a chronically implanted gastric fistula was connected to a custom-made nutrient drink infusion system and a catheter to measure IGP. IGP was measured before and during the infusion of a nutrient drink (Nutridrink; 0.5 ml/min) until 10 ml was infused. Rats were treated with PYY(3-36) (0, 33, and 100 pmol·kg(-1)·min(-1)) in combination with a subcutaneous injection of the Y(2) receptor antagonists JNJ31020028 (10 mg/kg) or BIIE0246 (2 mg/kg). Experiments were also performed after subdiaphragmatic vagotomy and after pretreatment with 3 ml of nutrient drink (to mimic a fed state). IGP was compared as the average IGP during nutrient infusion, represented as means ± SE and compared using ANOVA. PYY(3-36) dose dependently increased the IGP during nutrient infusion (4.7 ± 0.3, 5.7 ± 0.5 and 7.3 ± 0.7 mmHg; P < 0.01) while JNJ31020028 and BIIE0246 could block this increase [4.4 ± 0.5 (P < 0.001) and 4.8 ± 0.4 (P < 0.05) mmHg, respectively]. Also in vagotomized rats, PYY(3-36) was able to significantly increase the IGP during, an effect attenuated by JNJ31020028. BIIE0246 and JNJ31020028 were not able to decrease the IGP when no PYY(3-36) was administered. PYY(3-36) increased gastric tone through an Y(2) receptor-mediated mechanism that does not involve the vagus nerve. Y(2) receptor antagonists were not able to decrease gastric tone without exogenous administration of PYY(3-36), indicating that Y(2) receptors do not play a crucial role in the determination of gastric tone in physiological conditions.


Ovarian transforming growth factor-alpha gene expression: immunohistochemical localization to the theca-interstitial cells.
Rat ovaries were examined for the presence of transforming growth factor-alpha (TGF-alpha). Immature diethylstilbestrol-primed rats were treated for 3 days prior to sacrifice with or without FSH. Their ovaries were either fixed in formaldehyde for immunohistochemistry or the RNA was extracted for northern blot analysis. Hybridization with a rat TGF-alpha cDNA probe revealed a 4.5 kilobase mRNA whose abundance was markedly stimulated in the rats treated with FSH. Immunohistochemical staining, using a sequence specific monoclonal antibody to TGF-alpha, MF9, detected immunoreactive TGF-alpha only in the interstitial and theca cells. FSH treatment resulted in no appreciable change in the immunostaining. These results suggest that TGF-alpha is synthesized in the ovary, perhaps in the theca-interstitial compartment.


Caries diagnosis: agreement between WHO and ICDAS II criteria in epidemiological surveys.
The aim of this study was to ascertain the equivalence between WHO caries diagnosis criteria and the ICDAS II caries classification scale for comparisons in epidemiological studies. Two intraoral examinations, one using the ICDAS II caries codes and the other the WHO caries assessment method, were performed in a random sample of 101 children (29 aged 5-6 years, 32 aged 12 and 40 aged 15). Both examinations were performed not more than one month apart by two calibrated examiners (one for ICDAS II criteria, Kappa=0.86, and the other for WHO criteria, Kappa=0.91). The DMFT/dft, DMFS/dfs and caries prevalence (DMFT or dfs>0) indices were obtained in accordance with WHO assessment criteria and by applying 5 cut-off points on the ICDAS II scale. The differences between means were analysed with the Wilcoxon test and those between proportions with the McNemar test. Agreement was determined by the intraclass correlation index and the Kappa statistic. The least differences between the WHO and ICDAS 11 criteria were found at cut-off point 3 (ICDAS 11 codes 3 to 6). The greatest agreement was found at the same cut-off point. While the equivalence between both methods used in epidemiological studies does not appear to be clear, possible errors could be reduced by locating this equivalence at cut-off point 3 and not at cut-off point 4.


Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system (CNS) induced in rodents by activated CD4+ T cells specific for various myelin proteins such as myelin basic protein and proteolipid protein. The disease is characterized by breach of the blood-brain barrier, perivascular infiltration of leukocytes into the CNS, local inflammation and demyelination in the form of plaques. In this study, we evaluated the effect of administration of antibodies to two members of the beta 2 integrin sub-family of adhesion molecules, CD11a and CD11b, on the onset and progression of EAE. CD11a and CD11b are involved in cell-cell interactions leading to T cell and macrophage extravasation to inflammatory sites and T cell activation. Our results show that anti-CD11a antibodies could completely block the induction of EAE and anti-CD11b antibodies significantly delayed the onset and diminished the severity of clinical signs of EAE even when injections were initiated at the first appearance of clinical signs.


R-flurbiprofen improves tau, but not Aß pathology in a triple transgenic model of Alzheimer's disease.
We have previously reported that chronic ibuprofen treatment improves cognition and decreases intracellular Aß and phosphorylated-tau levels in 3xTg-AD mice. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that independently of its anti-inflammatory effects has anti-amyloidogenic activity as a gamma-secretase modulator (GSM) and both activities have the potential to decrease Aß pathology. To further understand the effects of NSAIDs in 3xTg-AD mice, we treated 3xTg-AD mice with R-flurbiprofen, an enantiomer of the NSAID flurbiprofen that maintains the GSM activity but has greatly reduced anti-inflammatory activity, and analyzed its effect on cognition, Aß, tau, and the neurochemical profile of the hippocampus. Treatment with R-flurbiprofen from 5 to 7 months of age resulted in improved cognition on the radial arm water maze (RAWM) test and decreased the level of hyperphosphorylated tau immunostained with AT8 and PHF-1 antibodies. No significant changes in the level of Aß (using 6E10 and NU-1 antibodies) were detected. Using magnetic resonance spectroscopy (MRS) we found that R-flurbiprofen treatment decreased the elevated level of glutamine in 3xTg-AD mice down to the level detected in non-transgenic mice. Glutamine levels correlated with PHF-1 immunostained hyperphosphorylated tau. We also found an inverse correlation between the concentration of glutamate and learning across all the mice in the study. Glutamine and glutamate, neurochemicals that shuttles between neurons and astrocytes to maintain glutamate homeostasis in the synapses, deserve further attention as MR markers of cognitive function.


In vivo studies on the effects of memantine on dopamine metabolism in the striatum and n. accumbens of the rat.
The action of the amantadine derivative memantine on the dopamine metabolism in the striatum and the n. accumbens of the rat was studied in vivo with different voltammetrical techniques. It was shown by differential pulse voltammetry that memantine enhanced extracellular levels of dopamine (DA) in the striatum of the anaesthetized rat, whereas an increase of 3,4 dihydroxyphenylacetic acid (DOPAC) could be observed only under freely moving conditions using square wave voltammetry. Under chloral hydrate anaesthesia the effect of memantine on extracellular DOPAC levels in the striatum and the n. accumbens was compared with MK-801, a well-known non-competitive NMDA-antagonist. Memantine did not affect striatal DOPAC concentrations under these conditions whereas MK-801 reduced the DOPAC signal. In the n. accumbens memantine enhanced the levels of extracellular DOPAC, while after MK-801 the signal was only slightly different from control. These findings suggest that in addition to its NMDA receptor antagonism, memantine affects dopaminergic transmission also by other mechanisms.


A minima hopping study of all-atom protein folding and structure prediction.
The minima hopping algorithm (MHOP) to find global minima on potential energy surfaces is used for protein structure prediction. The energy surface of the protein is represented with an all-atom OPLS force field and an implicit free energy solvation term. The system we studied here is the small 10-residue beta-hairpin mini-protein, chignolin. Starting from a completely extended structure, we found minima with <0.5 A rms coordinate deviation from the geometry-optimized native experimental conformation. A few lowest-energy conformations were used for the calculation of NMR-restraint violations and chemical shifts, and the local minima found during each run leading to the global minimum were connected to trace out a search pathway of the folding process.


Sclerochoroidal calcification: clinical manifestations and systemic associations.
Sclerochoroidal calcification is an unusual ocular condition that is believed to be idiopathic in most cases. To describe the clinical manifestations of sclerochoroidal calcification and to investigate its possible systemic associations. This noncomparative consecutive case series included patients diagnosed as having sclerochoroidal calcification based on clinical characteristics and diagnostic test findings. We analyzed the demographic, systemic, and ocular features of 27 such patients. Systemic evaluation included tests for calcium-phosphorus metabolism in 19 patients and renal tubular hypokalemic metabolic alkalosis syndromes (Bartter or Gitelman syndrome) in 13. All the patients were asymptomatic older (mean age, 70 years) white individuals, incidentally noted as having a choroidal lesion on routine examination. Among 38 eyes, the main referral diagnoses were choroidal metastasis in 10 eyes (26%), choroidal melanoma in 8 (21%), and choroidal nevus in 4 (11%). Sixteen patients (59%) had unilateral clinical findings, while 11 (41%) had bilateral. The Snellen visual acuity was 20/50 or better in 37 eyes (97%). Cogan scleral plaque was visible anterior to the insertion of horizontal rectus muscles in 10 eyes (26%). Among 77 foci, there were a mean of 2 foci of sclerochoroidal calcification in each eye, 41 yellow (53%), 32 yellow-white (42%), 2 white (3%), and 2 orange (3%), measuring a mean 2.6 mm in diameter and 1.1 mm in thickness. The most common locations were postequatorial in 45 (58%), along the temporal vascular arcades in 30 (39%), and in the superotemporal quadrant in 43 (56%). A-scan and B-scan ultrasonography revealed dense echoes compatible with calcium, with orbital shadowing. All the lesions remained stable in size and configuration during a mean follow-up of 38 months. One patient developed a choroidal neovascular membrane over the area of sclerochoroidal calcification. Investigations for abnormal calcium-phosphorus metabolism in 19 patients revealed primary hyperparathyroidism in 1 patient (5%). Clinical and biochemical evaluation of 13 patients demonstrated hypomagnesemia in 6 (46%). Four patients (31%) met the criteria for the diagnosis of Gitelman syndrome. Sclerochoroidal calcification usually manifests as multiple discrete yellow placoid lesions in the midperipheral fundus of asymptomatic older white individuals. Although most cases may be idiopathic in nature, some patients may have underlying systemic disorders involving abnormal calcium-phosphorus metabolism or renal tubular hypokalemic metabolic alkalosis syndromes. All patients with sclerochoroidal calcification should be tested for these treatable systemic associations.


The case for the listening region.
A recent study of maternity services in London highlighted big discrepancies between the planning methods adopted by different RHAs. This article carries forward that theme, and examines the last round of strategic plans drawn up by a number of English regions. Using maternity services as an example, it calls for a more open, thoughtful and analytical approach as new plans are developed.


Listening to the patient: a flexible approach to the use of antimuscarinic agents in overactive bladder syndrome.
Several studies with modern antimuscarinics have used a flexible-dosing strategy. We reviewed data from several studies with solifenacin, darifenacin and oxybutynin extended-release that evaluated the impact of dose flexibility on clinical management. A strategy based on patient-requested dose increases was found to be consistently effective in improving the symptoms of overactive bladder. Patients requesting a dose increase often had more severe symptoms at baseline than those who did not request a dose increase, and these patients derived most benefit from the increased dose. Specialists and family doctors should encourage open discussion with their patients about requesting dose titration so as to meet patients' individual needs.


Evaluation of the risk factors associated with lipodystrophy development in a cohort of HIV-positive patients.
The prevalence of lipodystrophy in an HIV-infected population and the risk factors associated with body shape changes were analysed in this study. Five hundred and four subjects were included. Among these, 201 (39.9%) had features of lipodystrophy syndrome (cases); 303 (60.1%) constituted the control group. Compared with the control group, the lipodystrophy subjects were different in age (P = 0.01); duration of antiretroviral therapy (P < 0.001); length of exposure to nucleoside reverse transcriptase inhibitors (NRTIs) (P < 0.001) and to protease inhibitors (P < 0.001); nadir of CD4 cell count (P < 0.001); and value of plasma HIV-RNA before antiretroviral therapy (P = 0.008). In a multivariate analysis, length of therapy and a nadir CD4 cell count below 250 cell/microl were associated with an increased risk of lipodystrophy. Among patients with lipodystrophy, isolated fat loss was observed in 46 (23%); isolated fat accumulation in 40 (20%); mixed (loss and accumulation) syndrome in 50 (25%); and isolated metabolic changes in 65 (32%). Subjects with morphological alterations displayed a greater cumulative time of exposure to NRTIs and to protease inhibitors than patients with isolated metabolic alterations. Patients with lipoatrophy had had a greater exposure to stavudine.


Regeneration of Tumor-Antigen-Specific Cytotoxic T Lymphocytes from iPSCs Transduced with Exogenous TCR Genes.
In the current adoptive T cell therapy, T cells from a patient are given back to that patient after ex vivo activation, expansion, or genetic manipulation. However, such strategy depends on the quality of the patient's T cells, sometimes leading to treatment failure. It would therefore be ideal to use allogeneic T cells as "off-the-shelf" T cells. To this aim, we have been developing a strategy where potent tumor-antigen-specific cytotoxic T lymphocytes (CTLs) are regenerated from T-cell-derived induced pluripotent stem cells (T-iPSCs). However, certain issues still remain that make it difficult to establish highly potent T-iPSCs: poor reprogramming efficiency of T cells into iPSCs and high variability in the differentiation capability of each T-iPSC clone. To expand the versatility of this approach, we thought of a method to produce iPSCs equivalent to T-iPSCs, namely, iPSCs transduced with exogenous T cell receptor (TCR) genes (TCR-iPSCs). To test this idea, we first cloned TCR genes from WT1-specific CTLs regenerated from T-iPSCs and then established WT1-TCR-iPSCs. We show that the regenerated CTLs from TCR-iPSCs exerted cytotoxic activity comparable to those from T-iPSCs against WT1 peptide-loaded cell line in in vitro model. These results collectively demonstrate the feasibility of the TCR-iPSC strategy.


Occult Bone Metastases From Hepatocellular Carcinoma Detected on 68Ga-PMSA PET/CT.
68Ga-PSMA is an excellent radiotracer for both staging and detection of recurrence in prostate cancer, but it can also be useful in other solid tumors due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of an 82-year-old man with hepatocellular carcinoma who presented with rising tumor marker but stable CT findings 6 months after transarterial chemoembolization. 68Ga-PSMA PET/CT showed high PSMA-expressing hyperneovascular hepatic lesions (primary tumor), additional multifocal hepatic lesions, and with unexpected multiple bone metastases. 68Ga-PSMA expression in hepatocellular carcinoma can influence patient management and potentially guide radionuclide legend therapy.


Effects of a fructose-enriched diet on plasma insulin and triglyceride concentration in SHR and WKY rats.
Significant increases (P less than 0.001) in plasma insulin and triglyceride concentrations and in blood pressure were seen when SHR and WKY rats ate a fructose-enriched diet for 14 days. However, all of the changes were significantly accentuated (P less than 0.02-0.001) in SHR rats. Specifically the increment in plasma insulin concentration following the fructose-enriched diet was 42 +/- 4 microU/ml in SHR as compared to 25 +/- 4 microU/ml in WKY rats (P less than 0.001). Plasma triglyceride concentrations also increased to a greater degree in response to fructose in SHR rats (260 +/- 24 vs. 136 +/- 20 mg/dl, P less than 0.001). Finally, the fructose-induced increase in blood pressure of 29 +/- 4 mm of Hg in SHR rats was greater (P less than 0.02) than that seen in WKY rats (19 +/- 2 mm of Hg). There was no change in plasma glucose concentration in response to the fructose diet. WKY rats gained more weight than did the SHR rats. Thus, although plasma triglyceride and insulin concentration and blood pressure increased when either WKY or SHR rats consumed a fructose enriched diet, the magnitude of these changes was greater in SHR rats.


Cancer incidence and risk estimation among medical x-ray workers in China, 1950-1995.
Cancer incidence (1950-1995) among 27,011 medical diagnostic x-ray workers was compared by means of O/E system with that of 25,782 other medical specialists employed between 1950 and 1980 to provide evidence of human malignant tumors produced by protracted and fractionated exposure to ionizing radiation and to assess resultant cancer risk. Significant cancer risk was seen among diagnostic x-ray workers (RR = 1.2, 95% CI: 1.1-1.3). Significantly elevated risks were found for leukemia and cancers of skin, female breast, lung, liver, bladder, and esophagus; the RRs were 2.2, 4.1, 1.3, 1.2, 1.2, 1.8, and 2.7, respectively. The patterns of risk associated with years since beginning x-ray work and with age and calendar year of initial employment suggest that the excesses of leukemia, skin cancer, and female breast cancer-and possibly thyroid cancer-were related to occupational exposure to x rays. Because of a lack of individual dosimetry for Chinese medical x-ray workers (CMXW) before 1985, the dose was reconstructed by physical and biological retrospective dosimetry methods. The cancer risk of CMXW was estimated based on the reconstructed dose. The average cumulative dose for the earlier cohort (employed before 1970) was 551 mGy, and for the later cohort (employed from 1970 to 1980) it was 82 mGy. The RRs of leukemia and solid cancer were significantly high for the earlier cohort: 2.4 for leukemia, 1.2 for solid cancer. But no significant increase of RR was evident for the later cohort. The RR of leukemia was 1.7 and 1.1 for solid cancer. This means a significant cancer risk can be induced by long term fractionated exposure to ionizing radiation when the cumulative dose reaches a certain level.


Effects of Chronic Dietary Exposure to Phytoestrogen Genistein on Uterine Morphology in Mice.
Genistein is naturally occurring in plants and binds to estrogen receptors. Humans are mainly exposed through diet, but the use of supplements is increasing as genistein is claimed to promote health and alleviate menopausal symptoms. We analyzed diverse uterine features in adult mice chronically fed genistein for different times. The luminal epithelium height was increased in females treated with 500 and 1000 ppm at PND 95, and the width of the outer myometrium was increased in females treated with 1000 ppm at PND 65 compared to that in controls. An increase in proliferation was noted in the inner myometrium layer of animals exposed to 300 ppm genistein at PND 185 compared to that in controls. Luminal hyperplasia was greater in the 1000 ppm group at PND 65, 95, and 185, although not statistically different from control. These results indicate that genistein may exert estrogenic activity in the uterus, without persistent harm to the organ.


Energy-Efficient Monitoring of Fine Particulate Matter with Tiny Aerosol Conditioner.
Fine particulate matter (PM) is associated with an increased risk of respiratory and cardiovascular diseases. Fine PM absorbs water molecules at high relative humidity, and then their size grows. Such hygroscopic growth causes a large error when monitoring PM concentrations. To lower the relative humidity, monitors use an indirect heating device, which is large and consumes large amounts of power. The problem with conventional particle separators is that their efficiency depends on temperature and humidity, and their traditional structure, which lets air flow downward. As such, this paper addresses these problems and presents a PM monitor with a new type of dryer that is free from these problems. The proposed monitor requires less energy and has an efficient dehumidifier and a new structure in which air flows upward. The presented experiments were conducted to compare the proposed device with a reference monitor managed by a governmental institute, and to evaluate the effect of the dehumidifier, the relative precision of the proposed devices, and the correlation with the reference monitor. The experimental results showed that the proposed monitor satisfies the U.S. EPA indicators for class III monitors.


Docetaxel induced gene expression patterns in head and neck squamous cell carcinoma using cDNA microarray and PowerBlot.
The purpose is to identify gene expression patterns induced by docetaxelin head and neck squamous carcinoma (HNSCC) cells using high throughput techniques. HNSCC cells were treated with docetaxel or solvent. After mRNA extraction, cDNA fluorescent (Cy3 or Cy5)-labeled probes were synthesized. Then, Cy3 and Cy5-labeled samples were hybridized onto a microarray slide. The fluorescent images were scanned and analyzed for quantification. PowerBlot immunoblotting technique was used to measure protein expression level. Using this dual approach, we focused on genes in established pathways (cell cycle, apoptosis, angiogenesis, and signal transduction) of tumorigenesis and confirmed these results with conventional techniques. Using cDNA microarray, we found that docetaxel altered the expression of >100 genes in HNSCC cells. A total of 153 of 1191 genes was found to have altered expression in either HN12 (n = 102), HN30 (n = 72), or both (n = 21) by docetaxel. For the PowerBlot analysis, a subset of genes (n = 46) in the cDNA microarray analysis and an additional 98 genes in the cell cycle, apoptosis, angiogenesis, and signal transduction pathways were chosen. We found that PowerBlot data agreed with cDNA microarray in 65% of genes examined. The expression of a cell cycle inhibitor (p19) and promoters (cyclin A, cyclin B1, and cyclin E2F) were increased and decreased, respectively. Apoptosis induced by docetaxel was independent of p53 and, in part, related to increased Fas expression. Both vascular endothelial growth factor secretion and basic fibroblast growth factor expression were inhibited by docetaxel, whereas thrombospondin-1 expression was increased by docetaxel. Epidermal growth factor receptor, activated epidermal growth factor receptor, and activated c-Jun NH(2)-terminal kinase expression was lowered by docetaxel. Activated extracellular signal-regulated kinase was elevated by docetaxel, but not total extracellular signal-regulated kinase levels. The identification of altered gene expression induced by docetaxel demonstrates additional biological activity in HNSCC cells, and the altered expression of these genes may serve as potential biomarkers to both predict clinical activity and provide information regarding potential efficacy of adding novel agents.


Quality of life in unipolar and bipolar depression: are there significant differences?
In the present investigation, we compared the impact of illness on quality of life (QOL) in adult outpatients with unipolar (N = 89) and bipolar (N = 25) depression. While attending a university hospital in southern Brazil, patients completed the WHO's QOL Instrument-Short Version and the Beck Depression Inventory. After analyses, patients with bipolar depression reported significantly lower scores on the psychological QOL domain (p = .013) than patients with unipolar depression. There were no significant differences between the study groups in terms of social and demographic variables, in the other QOL domains assessed (i.e., physical health, social relationships, and environmental), and in the severity of depressive symptoms. In conclusion, our findings suggest that patients with bipolar and unipolar depressions have different QOL profiles, and that this difference is probably independent of the severity of the mood disturbance and might be related to the higher rates of suicide observed in the bipolar population.


Increased bcl-2 Protein Levels in Rat Primary Astrocyte Culture Following Chronic Lithium Treatment.
B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has been implicated in lithium's neuroprotective effect. However, most studies have focused on assessing the effects of lithium in neurons, ignoring examination of bcl-2 in astrocytes, which also influence neuronal survival and are affected in bipolar disorder. The aim of this study was to evaluate whether chronic lithium treatment also elevates bcl-2 expression in astrocytes compared with neuronal and mixed neuron-astrocyte cultures. Rat primary astrocyte, neuronal, and mixed neuron-astrocyte cultures were prepared from the cerebral cortices of 18-day embryos. The cell cultures were treated with lithium (1 mM) or vehicle for 24 h or 7 days. Thereafter, bcl-2 mRNA and protein levels were determined by RT-PCR and ELISA, respectively. Chronic, but not acute, lithium treatment significantly increased bcl-2 protein levels in the astrocyte cultures compared with the vehicle-treated cultures. While lithium treatment increased bcl-2 protein levels in both neuronal and mixed neuron-astrocyte cultures, the elevations fell short of statistical significance compared with the respective vehicle-treated cultures. However, neither acute nor chronic lithium treatment affected bcl-2 mRNA levels in any of the three cell types studied. Increased bcl-2 levels in rat primary astrocyte cultures following chronic lithium treatment suggest astrocytes are also a target of lithium's action. In light of the evidence showing decreased numbers of glial cells in the post-mortem brain of patients bipolar disorder with and increased glial numbers following lithium treatment, the findings of this study indicate that lithium's action on astrocytes may account, at least in part, for its therapeutic effects in bipolar disorder.


Short communication: The lag response of daily milk yield to heat stress in dairy cows.
Previous studies suggest that there exists a lag relationship between daily milk yield and heat stress. The values of heat stress indicators (e.g., temperature-humidity index and ambient temperature) before test day have a simple correlation with daily milk yield on test day. However, the simple correlation might not be the best description because daily milk yield and heat stress indicators have a nature of time series in common, and their correlations are cross correlations that could be affected by autocorrelations. We hope to give a more reliable estimation on the lag relationship of daily milk yield via excluding autocorrelations with transfer function modeling. In this study, we found a lag relationship between daily milk yield and heat stress indicators based on transfer function modeling. Heat stress indicators included ambient temperature and temperature-humidity index. The daily milk yield data from 123 cows were obtained during a consecutive 63-d period (July 10-September 10, 2016). The mean daily milk yield (MY) and the maximum daily ambient temperature (TA_max) satisfied the stationary hypothesis, and the cross correlation between them was calculated. Before excluding autocorrelation, MY at 0 to 4 d after test day had significant cross correlations with TA_max on test day. After excluding the influence of autocorrelations, MY at 1 to 3 d after the test day had significant cross correlations with TA_max on test day. This result suggested that MY would respond to TA_max 1 d after the test day. In addition, the strength of cross correlations between MY and TA_max decreased from 1 to 3 d in sequence, implying a declining lag response of MY that would last for 3 d. The transfer function model for MY and TA_max is written as: MYt = 16.90 + 0.74MYt- 1 - 0.25TA_maxt- 1 + Nt, where Nt is white noise. This model can be used to track and predict the dynamic response of MY to TA_max.


Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds: Caulerpa racemosa and Caulerpa lentillifera.
Seaweeds are gaining a considerable amount of attention for their antioxidant and antibacterial properties. Caulerpa racemosa and Caulerpa lentillifera, also known as 'sea grapes', are green seaweeds commonly found in different parts of the world, but the antioxidant and antibacterial potentials of Malaysian C. racemosa and C. lentillifera have not been thoroughly explored. In this study, crude extracts of the seaweeds were prepared using chloroform, methanol, and water. Total phenolic content (TPC) and total flavonoid content (TFC) were measured, followed by in vitro antioxidant activity determination using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Antibacterial activities of these extracts were tested against Methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Liquid chromatography-mass spectrometry (LCMS) analysis was then used to determine the possible compounds present in the extract with the most potent antioxidant and antibacterial activity. Results showed that C. racemosa chloroform extract had the highest TPC (13.41 ± 0.86 mg GAE/g), antioxidant effect (EC50 at 0.65 ± 0.03 mg/mL), and the strongest antibacterial effect (97.7 ± 0.30%) against MRSA. LCMS analysis proposed that the chloroform extracts of C. racemosa are mainly polyunsaturated and monounsaturated fatty acids, terpenes, and alkaloids. In conclusion, C. racemosa can be a great source of novel antioxidant and antibacterial agents, but isolation and purification of the bioactive compounds are needed to study their mechanism of action.


Comparing Tapering Strategy to Standard Dosing Regimen of Tumor Necrosis Factor Inhibitors in Patients with Spondyloarthritis in Low Disease Activity.
To compare clinical outcomes, incidence of flares, and administered drug reduction between patients with spondyloarthritis (SpA) under TNF inhibitor (TNFi) tapering strategy with patients receiving a standard regimen. In this retrospective study, 74 patients with SpA from Spain on tapering strategy (tapering group; TG) were compared with 43 patients from the Netherlands receiving a standard regimen (control group; CG). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at visit 0 (prior to starting the TNFi), visit 1 (prior to starting tapering strategy in TG and at least 6 months with BASDAI < 4 after starting the TNFi in the TG and CG), visit 2 (6 mos after visit 1), visit 3 (1 year after visit 1), and visit 4 (the last visit available after visit 1). An overall reduction of the administered drug was seen at visit 4 in the TG [dose reduction of 22% for infliximab (IFX) and an interval elongation of 28.7% for IFX, 45.2% for adalimumab, and 51.5% for etanercept] without significant differences in the BASDAI between the groups at visit 4 (2.15 ± 1.55 in TG vs 2.11 ± 1.31 in CG, p = 0.883). The number of patients with flares was similar in both groups [22/74 (30%) in the TG vs 8/43 (19%) in the CG, p = 0.184]. The tapering strategy in SpA results in an important reduction of the drug administered, and the disease control remains similar to that of the patients with SpA receiving the standard regimen.


Additive and/or synergistic action (downregulation) of androgens and thyroid hormones on the cellular distribution and localization of a true tissue kallikrein, mK1, in the mouse submandibular gland.
We investigated the effects of 5alpha-dihydrotestosterone (DHT), 3,5,3'-triiodo-l-thyronine (T(3)), and dexamethasone (Dex) on the expression of mK1 in the granular convoluted tubule (GCT) cells of the submandibular gland (SMG) of hypophysectomized (Hypox) male mice by indirect enzyme-labeled antibody and immunogold antibody methods for light and electron microscopy. Hypox resulted in considerable atrophy of the GCT cells, which were always immunoreactive for mK1, and the cells were characterized by apical small dense secretory granules labeled with gold particles suggesting the presence of mK1, small Golgi apparatus, sparse rough endoplasmic reticulum (RER), and developed basal infoldings. Each of the hormones, DHT, T(3), and Dex, enhanced the GCT phenotype to various degrees in Hypox male mice. Both DHT alone and T(3) alone moderately inhibited mK1 synthesis by increasing the number of mK1-immunonegative GCT cells in Hypox males, but Dex alone had no inhibitory effect on mK1 synthesis. A significant trophic effect on GCT cells was induced by combined injection of DHT and T(3) or of all three hormones, and was reflected in the appearance of abundant large secretory granules, well-developed Golgi apparatus and RER, and reduced basal infoldings. Only a few such GCT cells were immunopositive for mK1, and the pattern of immunopositive and immunonegative cells very closely resembled the mosaic pattern seen in normal male GCTs. These findings suggested that the sexual dimorphism of mK1 expression and the morphological appearance of GCT cells can be induced by treatment with two hormones, DHT and T(3), but not by either of them alone. T(3) appears to have a permissive effect on committed GCT cells that results in downregulation of mK1 expression in these cells.


PSPS: A Step toward Tamper Resistance against Physical Computer Intrusion.
Cyberattacks are increasing in both number and severity for private, corporate, and governmental bodies. To prevent these attacks, many intrusion detection systems and intrusion prevention systems provide computer security by monitoring network packets and auditing system records. However, most of these systems only monitor network packets rather than the computer itself, so physical intrusion is also an important security issue. Furthermore, with the rapid progress of the Internet of Things (IoT) technology, security problems of IoT devices are also increasing. Many IoT devices can be disassembled for decompilation, resulting in the theft of sensitive data. To prevent this, physical intrusion detection systems of the IoT should be considered. We here propose a physical security system that can protect data from unauthorized access when the computer chassis is opened or tampered with. Sensor switches monitor the chassis status at all times and upload event logs to a cloud server for remote monitoring. If the system finds that the computer has an abnormal condition, it takes protective measures and notifies the administrator. This system can be extended to IoT devices to protect their data from theft.


Experience with somatostatin receptor scintigraphy in the management of pulmonary carcinoid tumors.
Somatostatin receptor scintigraphy has been used widely for the evaluation of neuroendocrine tumors in the gastrointestinal tract. Its use for detecting and staging thoracic carcinoids is only sporadically reported. To evaluate the possible roles of SRS in the management of proven or suspected pulmonary carcinoids. We conducted a retrospective study of all patients undergoing SRS for known or suspected pulmonary carcinoids in a tertiary referral center during a 10 year period. During this period 89 patients underwent resection of pulmonary carcinoids and SRS was used for detection, staging or localization purposes in 8 of them (9%). Scans were labeled true positive, true negative, false positive, or false negative in comparison with histologic or follow-up results. SRS was true positive in 6/6 lung locations; true positive in 2/8, true negative in 4/8 and false positive in 2/8 lymph node locations; and true positive in 1/8, true negative in 6/8 and false negative in 1/8 distant locations. The sensitivity, specificity, positive and negative predictive values and accuracy were 90%, 83%, 83%, 91% and 87% respectively. The scans were strongly positive in the tumors and involved lymph nodes. SRS correctly localized an occult secreting pulmonary carcinoid. Granulomatous and reactive lymph nodes showed increased uptake. SRS was accurate in ruling out distant metastases. SRS is effective for visualizing and localizing pulmonary carcinoids. It assists in the staging of these tumors by detecting lymph node involvement and confirming or ruling out distant metastases. Inflammatory areas in the lung or lymph nodes may be falsely positive.


A pictographic method for teaching spelling to Greek dyslexic children.
In the Greek orthography every letter consistently represents the same sound, but the same sound can be represented by different letters or pairs of letters. This makes spelling more difficult than reading. Two methods of teaching spelling to Greek dyslexic children are compared. The first involved pictograms (specially drawn pictures) for use when alternative spellings are possible. This is referred to as the 'PICTO' method. The second was in effect a combination of two traditional methods: the first involved the teaching of letter-sound correspondences in a multisensory way; the second involved the use of concepts derived from linguistics, the children being taught the derivations of words and shown how the same root morphemes, derivative morphemes, etc., were cosistently represented by the same spelling pattern. This combination of methods is referred to as 'TRAD', signifying 'traditional'. There were 72 subjects in the study, aged between 9 and 11 years. Four different teachers, each using both PICTO and TRAD, took part in the teaching sessions. The PICTO method proved considerably more effective; and possible reasons are suggested as to why this might be so.


Molecular system bioenergics of the heart: experimental studies of metabolic compartmentation and energy fluxes versus computer modeling.
In this review we analyze the recent important and remarkable advancements in studies of compartmentation of adenine nucleotides in muscle cells due to their binding to macromolecular complexes and cellular structures, which results in non-equilibrium steady state of the creatine kinase reaction. We discuss the problems of measuring the energy fluxes between different cellular compartments and their simulation by using different computer models. Energy flux determinations by (18)O transfer method have shown that in heart about 80% of energy is carried out of mitochondrial intermembrane space into cytoplasm by phosphocreatine fluxes generated by mitochondrial creatine kinase from adenosine triphosphate (ATP), produced by ATP Synthasome. We have applied the mathematical model of compartmentalized energy transfer for analysis of experimental data on the dependence of oxygen consumption rate on heart workload in isolated working heart reported by Williamson et al. The analysis of these data show that even at the maximal workloads and respiration rates, equal to 174 μmol O(2) per min per g dry weight, phosphocreatine flux, and not ATP, carries about 80-85% percent of energy needed out of mitochondria into the cytosol. We analyze also the reasons of failures of several computer models published in the literature to correctly describe the experimental data.


Field and laboratory studies on water conditions affecting the potency of VectoBac (Bacillus thuringiensis serotype H-14) against larvae of the blackfly, Simulium damnosum.
River water conditions that might influence the efficacy of VectoBac, a formulation of the microbial insecticide Bacillus thuringiensis H-14 Berliner against Simulium damnosum sensu lato Theobald (Diptera: Simuliidae) larvae were investigated. A standard formulation was assayed 130 times over 15 months using a mini-gutter system at a field station beside the River Pra in Ghana. The lethal concentration (LC) values, river temperature, conductivity, turbidity and pH were analysed using univariate and multivariate statistics to identify which of these parameters influenced its performance. River temperature, conductivity and turbidity (in that order) were identified as having direct effects on the potency of VectoBac. Water temperature and conductivity were negatively correlated, whereas turbidity and pH were positively correlated with LC values. Analyses of river water samples revealed that despite observed differences in total solids, sodium and potassium cations and chloride concentrations, all the parameters measured did not differ significantly between wet and dry seasons. A simple method for rearing S. damnosum s.l. in the laboratory was then adopted to study the effect of conductivity on potency of VectoBac under controlled conditions. Increasing the conductivity of the water medium up to 3,000 microS enhanced potency by about 42%, whereas increasing that of the insecticide alone raised it by 37%. The results obtained suggest that for effective use of VectoBac for blackfly control in West Africa, river temperature, conductivity and turbidity should be taken into consideration, perhaps by only selecting rivers with optimal conditions for treatment. The laboratory-based system developed for assaying the product overcomes the vagaries associated with field conditions and also the demand for huge logistic requirements of the mini-gutter system, which has to be sited near rivers.


ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin.
ADAM15 belongs to the family of proteins containing disintegrin and metalloprotease domains (ADAM) that have been implicated in cell adhesion via integrin binding and shedding of cell surface molecules. Here we provide the first report on the localization of an ADAM in adherens junctions. We show that ADAM15 colocalizes with a cell adhesion molecule, vascular endothelial (VE)-cadherin, which mediates endothelial cell adherens junction formation. In contrast, the distribution of ADAM15 correlates poorly with the localization in cell contacts of one of its proposed ligands, the beta1-integrin. Furthermore, ADAM15 accumulation in cell-cell contacts is preceded by VE-cadherin-mediated adherens junction formation. To investigate the dependence of ADAM15 surface expression on adherens junction formation, we coexpressed VE-cadherin with ADAM15 and an ADAM15 green fluorescence protein (GFP) fusion protein in Chinese hamster ovary cells. VE-cadherin coexpression results in the translocation of ADAM15-GFP to the cell periphery. Analysis of cell surface levels of ADAM15 and ADAM15-GFP, with or without VE-cadherin coexpression, clearly demonstrates that VE-cadherin can drive surface expression of ADAM15. Our data suggest that ADAM15 may be a novel component of adherens junctions and thus could play a role in endothelial functions that are mediated by these cell contacts.


A Fungal Promiscuous UbiA Prenyltransferase Expands the Structural Diversity of Chrodrimanin-Type Meroterpenoids.
Prenyltransferases play important roles in the diversification of natural products and the improvement of biological activities. A UbiA-type prenyltransferase CdnC with substrate promiscuity was identified as the pivotal builder of the noncanonical chrodrimanin skeletons, which carry a benzo-cyclohexanone structure as the nonterpene part. In vitro and heterologous expression studies with CdnC led to the production of a series of novel chrodrimanin-like structures. The discovery of CdnC offers a referable strategy for the biosynthesis and structural diversification of farnesyl-derived meroterpenoids.


Approach to Chronic Lymphocytic Meningitis.
Chronic meningitis is a common clinical problem. Early diagnosis and appropriate therapy is important in improving the overall outcome and to prevent long-lasting sequels. As many etiological agents lead to the development of chronic lymphocytic meningitis, it is important to develop a systematic approach to the diagnosis; taking clues from history, examination and laboratory tests, to make an accurate diagnosis and institute appropriate therapy. This review focuses on the diagnostic approach towards the commonly encountered situation of chronic lymphocytic meningitis. Chronic meningitis is defined as meningeal inflammation that persists for more than 4 weeks. Chronic meningitis accounts for less than 10% of all the cases of meningitis.1 Causes of chronic lymphocytic meningitis are mainly divided into infectious and non-infectious listed in Table 1.2 Due to advancement in investigations, diseases causing chronic meningitis may be diagnosed earlier than 4 weeks and hence the definition should be considered as a rough guideline.


A comparative study on the reliability of an automated system for the evaluation of cell-based indirect immunofluorescence.
Automated interpretations systems for anti-nuclear antibody (ANA), anti-double stranded DNA antibody (dsDNAab), and anti-neutrophil cytoplasmic antibody (ANCA) assessment by indirect immunofluorescence (IIF) have been recently introduced. The aim of this study was to compare the diagnostic performance of the automated IIF reading system AKLIDES with both traditional visual interpretation of IIF by laboratory experts and confirmatory tests. Visual and automated autoantibody interpretations of IIF findings using AKLIDES pattern recognition algorithms were performed for ANA on HEp-2 cells (n=182), dsDNAab on Crithidia luciliae (n=44) and ANCA on human neutrophils (n=46). All serum samples tested by IIF for ANCA and dsDNAab were also assessed with the corresponding enzyme-linked immunosorbent assays (ELISAs). Out of the 182 sera tested for ANA by IIF, 116 were also assessed for antibodies to extractable nuclear antigens (ENA) by ELISA and dot immunoassay (DIA). ANA testing showed an excellent agreement between visual and AKLIDES reading (98.9%). The overall agreement of dsDNAab testing on C. luciliae substrate slides was 91.0%, whereas ANCA showed a concordance of 89.1%. There was a remarkable agreement of AKLIDES findings for dsDNAab with confirmatory tests. Visual and automated interpretations of IIF findings for ANA, ANCA, and dsDNAab demonstrated a good agreement when assessing patients with suspected autoimmune diseases. Automated interpretation systems such AKLIDES may improve laboratory efficiency and support standardization of IIF in clinical laboratories.


Autoradiographic localization of dopamine D1 receptors in the human kidney.
The pharmacological profile and the anatomical localization of the selective D1-receptor antagonist [3H][R]-(+)-8-chloro-2,3,4,5-tetrahydro-5-phenyl-1H-3-benzazepin-7 -al- hemimaleate ([3H]SCH 23390) were studied in frozen sections of human kidney by using combined in vitro radioreceptor binding and autoradiographic techniques. [3H]SCH 23390 was bound by sections of human kidney in a manner consistent with the labeling of D1 sites, with a Kd value of 3.87 nM and with a Bmax value of 143 fmol/mg protein. Light microscope autoradiography revealed the highest density of [3H]SCH 23390 binding sites within the macula densa and the proximal tubules followed in descending order by the ascending limb of the loop of Henle, the distal tubules and the descending limb of the loop of Henle. No specific binding was noticeable within the glomeruli or within the epithelium of collecting tubules. [3H]SCH 23390 binding sites were also observed within the medial layer of intrarenal artery branches. These findings show that dopamine D1 receptor sites in the human kidney have a localization similar to that described in laboratory mammals with a higher density of tubular than of vascular receptors. The above data account for the vascular, diuretic and natriuretic effects elicited by D1 receptor stimulation in man.


Effect of light and glucose on the induction of nitrate reductase and on the distribution of nitrate in etiolated barley leaves.
Barley seedlings grown in the dark with 10 mm KNO(3) have low levels of nitrate reductase activity even though large amounts of No(3) (-) accumulate in the leaves. When the leaves are excised and transferred to the light, there is an increase in nitrate reductase activity both in the presence and absence of exogenous NO(3) (-). When the leaves are transferred to a glucose solution (0.05 m) but kept in the dark, induction of nitrate reductase activity occurs only when fresh NO(3) (-) is added to the system.In dark-grown leaves, there are small traces of NO(3) (-) in a "metabolic pool." Addition of glucose does not alter this distribution. Light, on the other hand, results in an appreciable accumulation of NO(3) (-) in the metabolic pool. There is a linear correlation between nitrate reductase activity and the size of the metabolic NO(3) (-) pool. Our results thus suggest that NO(3) (-) accumulates in a storage pool when seedlings are grown in continuous darkness. The transfer of this NO(3) (-) to an active metabolic pool is mediated by light but not by glucose. We believe that this transfer of NO(3) (-) leads to the induction of nitrate reductase. When NO(3) (-) is included in the medium, both light and glucose increase its incorporation into the metabolic pool. The results suggest two mechanisms for regulating the metabolic NO(3) (-) pool: (a) a transfer from the storage pool which requires light; and (b) a transfer from the external medium which requires either glucose or light.


Influence of the filling fluid on frequency-dependent velocity and attenuation in cancellous bones between 0.35 and 2.5 MHz.
The paper is focused on experiments on human cancellous bones filled with different fluids with the goal of evaluating their contribution to velocity dispersion, absorption, and scattering mechanisms. The specimens were measured first filled with marrow and subsequently, after marrow removal, with water and alcohol. No significant influence of the fluids was evidenced on the attenuation coefficient. Given the absence of impact of viscosity of the saturating fluid, the authors hypothesized that the source of attenuation is associated with viscoelastic absorption in the solid trabeculae and with scattering. Alteration of scattering obtained by changing the acoustic impedance mismatch between the fluid (alcohol vs water) and the trabeculae was reflected neither in the attenuation nor in its slope. This led the authors to suggest that longitudinal-to-shear scattering together with absorption in the solid phase are candidates as main sources for the attenuation. The differences in velocity values indicate that the elastic properties of the fluid are main determinants of the phase velocity. This finding is particularly significant in the context of /in vivo/ measurements, because it demonstrates that the subject-dependent properties of marrow may partly explain the inter-subject variability of speed of sound values.


The economic returns of ending the AIDS epidemic as a public health threat.
In 2016, countries agreed on a Fast-Track strategy to "end the AIDS epidemic by 2030". The treatment and prevention components of the Fast-Track strategy aim to markedly reduce new HIV infections, AIDS-related deaths and HIV-related discrimination. This study assesses the economic returns of this ambitious strategy. We estimated the incremental costs, benefits and economic returns of the Fast-Track scenario in low- and middle-income countries, compared to a counterfactual defined as maintaining coverage of HIV-related services at 2015 levels. The benefits are calculated using the full-income approach, which values both the changes in income and in mortality, and the productivity approach. The incremental costs of the Fast-Track scenario over the constant scenario for 2017-2030 represent US$86 billion or US$13.69 per capita. The full-income valuation of the incremental benefits of the decrease in mortality amounts to US$88.14 per capita, representing 6.44 times the resources invested for all countries. These returns on investment vary by region, with the largest return in the Asia-Pacific region, followed by Eastern and Southern Africa. Returns using the productivity approach are smaller but ranked similarly across regions. In all regions, the economic and social value of the additional life-years saved by the Fast-Track approach exceeds its incremental costs, implying that this strategy for ending the AIDS epidemic is a sound economic investment.


Species-specific engagement of human nucleotide oligomerization domain 2 (NOD)2 and Toll-like receptor (TLR) signalling upon intracellular bacterial infection: role of Crohn's associated NOD2 gene variants.
Recognition of bacterial peptidoglycan-derived muramyl-dipeptide (MDP) by nucleotide oligomerization domain 2 (NOD2) induces crucial innate immune responses. Most bacteria carry the N-acetylated form of MDP (A-MDP) in their cell membranes, whereas N-glycolyl MDP (G-MDP) is typical for mycobacteria. Experimental murine studies have reported G-MDP to have a greater NOD2-stimulating capacity than A-MDP. As NOD2 polymorphisms are associated with Crohn's disease (CD), a link has been suggested between mycobacterial infections and CD. Thus, the aim was to investigate if NOD2 responses are dependent upon type of MDP and further to determine the role of NOD2 gene variants for the bacterial recognition in CD. The response pattern to A-MDP, G-MDP, Mycobacterium segmatis (expressing mainly G-MDP) and M. segmatisΔnamH (expressing A-MDP), Listeria monocytogenes (LM) (an A-MDP-containing bacteria) and M. avium paratuberculosis (MAP) (a G-MDP-containing bacteria associated with CD) was investigated in human peripheral blood mononuclear cells (PBMCs). A-MDP and M. segmatisΔnamH induced significantly higher tumour necrosis factor (TNF)-α protein levels in healthy wild-type NOD2 PBMCs compared with G-MDP and M. segmatis. NOD2 mutations resulted in a low tumour necrosis factor (TNF)-α protein secretion following stimulation with LM. Contrary to this, TNF-α levels were unchanged upon MAP stimulation regardless of NOD2 genotype and MAP solely activated NOD2- and Toll-like receptor (TLRs)-pathway with an enhanced production of interleukin (IL)-1β and IL-10. In conclusion, the results indicate that CD-associated NOD2 deficiencies might affect the response towards a broader array of commensal and pathogenic bacteria expressing A-MDP, whereas they attenuate the role of mycobacteria in the pathogenesis of CD.


Reporting the Presence of Coronary Artery Calcium in the Final Impression of Non-gated CT Chest Scans Increases the Appropriate Utilization of Statins.
Background Coronary artery calcium (CAC) scoring based on gated non-contrast cardiac computed tomography (CT) is a validated risk marker of major adverse cardiovascular events (MACE). Reporting of CAC on non-gated CT chest (NGCT) scans and the impact on medical therapy is not well studied. Methods A retrospective cohort of 5,043 NGCT scans was reviewed for the presence of CAC. The radiology report was reviewed to determine whether CAC was mentioned in either the body of the report or the final impression. Electronic medical records (EMR) were abstracted for baseline demographics, cardiovascular (CV) risk factors, lipid-lowering agents, and aspirin (ASA) prior to and after NGCT. Results CAC was present in 63.0% of NGCT scans. Of these scans, CAC was mentioned in the body of the report in 81.6% of studies. Conversely, CAC was mentioned in the final impressions in only 15.1% of these scans. Amongst patients with CAC, initiation of a statin in treatment-naive patients was more common when CAC was mentioned in the final impression versus the body only (12.3% vs. 4.9%, p=0.001) despite the fact that baseline utilization of statins in this cohort was higher (71.1% vs. 64.1%, p=0.005). Initiation of a statin in treatment-naive patients had a trend towards significance when CAC was mentioned in the body of the report versus not reported (4.9% vs. 2.62%, p=0.142). Reporting of CAC in the final impression significantly increased the initiation of ASA in treatment-naive patients (9.52% vs. 4.33%, p=0.033). Reporting of CAC in either the final impression or the body of the report did not affect the initiation of non-statin lipid-lowering therapies in patients with CAC. Conclusion The inclusion of CAC in the final impression of NGCT radiology reports positively impacts the appropriate initiation of statin and aspirin therapy in treatment-naive patients. Universal adherence to a standardized reporting system for the presence of CAC on NGCT should be considered to improve the initiation of guideline-directed medical therapy.


Changes in expression of the neuropeptide Y Y1 receptor gene in the medial amygdala of transgenic mice during pregnancy and after delivery.
Long-term administration of progesterone or allopregnanolone was previously shown to increase Y1 receptor gene expression in the medial amygdala of Y1R/LacZ transgenic mice, which harbor a construct comprising the murine Y1 receptor gene promoter and a lacZ reporter. We have now investigated the effects of physiological fluctuations in the cerebrocortical concentrations of neuroactive steroids during pregnancy on Y1R/LacZ transgene expression by quantitative histochemical analysis of beta-galactosidase activity. Cerebrocortical concentrations of progesterone and its metabolites allopregnanolone and allotetrahydrodeoxycorticosterone were increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Transgene expression in the medial amygdala was also increased on day 18 of pregnancy and had returned to control values 2 days after delivery. Similar results were obtained after analysis of Y1R mRNA levels in the medial amygdala of pregnant mice by in situ hybridization. Administration of the 5alpha-reductase inhibitor finasteride to pregnant mice prevented both the increase in the cerebrocortical concentrations of neuroactive steroids as well as the increase in transgene expression. These data suggest that fluctuations in the brain concentrations of endogenous neuroactive steroids during pregnancy are associated with changes in Y1 receptor gene expression in the medial amygdala, further supporting a functional interaction between the GABAergic and NPY-Y1 receptor systems.


Effects of mirogabalin, a novel ligand for the α₂δ subunit of voltage-gated calcium channels, on N-type calcium channel currents of rat dorsal root ganglion culture neurons.
Mirogabalin, which is a novel ligand for the α₂δ subunit of voltage-gated calcium channels, is being developed for treating neuropathic pain including diabetic peripheral neuropathy and postherpetic neuralgia. Mirogabalin possesses unique α₂δ subunit binding characteristics and has potent and long-lasting analgesic effects in neuropathic pain models. In the present study, we investigated the effects of mirogabalin on N-type calcium channel currents of the rat dorsal root ganglion (DRG) culture neurons using the whole-cell patch clamp technique. Small or medium DRG neurons were isolated from Sprague-Dawley rats and were incubated for 20 to 24 h with mirogabalin or pregabalin. The DRG neurons were depolarised from a holding potential of -40 mV to +40 mV in steps of 10 mV for 220 ms, and elicited N-type calcium channel currents were recorded. The N-type calcium channel currents were verified by sensitivity to ω-conotoxin GVIA, a selective N-type calcium channel blocker. Mirogabalin inhibited the calcium channel currents of rat DRG neurons at 50 μM, and pregabalin inhibited them at 200 μM. Mirogabalin and pregabalin showed significant differences in the peak current densities at depolarisation to -20 and -10 mV when compared with that shown by the vehicle control. In conclusion, mirogabalin inhibits N-type calcium channel currents in rat DRG culture neurons. The potent and long-lasting analgesic effects of mirogabalin are thought to be associated with its potent and selective binding to α₂δ-1 subunits and following functional inhibition of calcium channel currents.


C reactive protein concentrations in neonates: determination by a latex enhanced immunoassay.
A latex enhanced immunoassay on a centrifugal fast analyser was used to compare serum C reactive protein concentrations in maternal and neonatal blood. In the neonate the C reactive protein concentration at birth was less than 1.0 mg/l; the concentration rose slightly during the first two weeks of life. There was no correlation between C reactive protein concentrations in maternal and neonatal sera. No significant difference was found between the C reactive protein concentrations in blood obtained by either heel prick or venepuncture.


Art promoting mental health literacy and a positive attitude towards people with experience of mental illness.
Exhibitions of art by people with experience of mental illness are increasingly being staged to improve awareness of mental health issues in the general community and to counter the stigma of mental illness. However, few exhibitions have incorporated research to ascertain their actual effectiveness. This paper reports the results of a study that considered the responses of 10,000 people after they viewed exhibitions of art produced by people with experience of mental illness. These works were selected from the Cunningham Dax Collection, one of the world's most extensive collection of artworks by people with experience of mental illness and/or psychological trauma. More than 90% of respondents agreed with three propositions that the exhibitions helped them: (1) gain a better understanding of mental illness; (2) gain a more sympathetic understanding of the suffering of people with mental illness; and (3) appreciate the ability and creativity of people with mental illness. The results suggest that exhibitions can successfully promote mental health literacy and contribute to positive attitudes towards people with experience of mental illness. This paper explores these findings and raises questions about how the presentation of artworks in an exhibition influences their effectiveness in mental health promotion.


Community neonatal nursing work.
A neonatal community nursing service may help families to cope with the early transfer of small, vulnerable infants to home. The previous literature has relied on self-reports to explore this kind of work. This paper reports a study exploring the work of a community neonatal nursing team in order to describe the strategies and interventions used to support families of preterm infants. A qualitative case study design was adopted. Data were collected using fieldwork observations, semi-structured interviews and documentary analysis with a team of four community neonatal nurses. A nursing model of transition was explored as a possible framework for practice. Thematic data analysis yielded two broad themes: Working with Mothers and Working with Others. Subcategories of Working with Mothers consisted of Baby Well; Mum Happy; Keeping in Touch and One of the Family. Working with Others focussed on multidisciplinary liaison activities. The complexity of nursing work was interdependent with maternal caregiving and dependent upon effective liaison with other health care professionals. The nursing model of transition requires further development to offer a sufficiently coherent practice model to direct neonatal nursing care delivery.


[Clinical evaluation of calculating carboplatin doses using modification of diet in renal disease (MDRD) estimate and adverse events].
A modified diet in renal disease (MDRD), a formula to estimate glomerular filtration rate (GFR), was proposed by Levey in 2006. In this study, we compared the dosage of carboplatin (CBDCA) calculated using MDRD with that calculated by conservative creatinine clearance (Ccr), and investigated the actual dosage given and the incidence of its adverse effects. In the 101 patients undergoing chemotherapy including CBDCA, the dosage calculated from the estimated GFR was 16% lower than that based on the estimated Ccr. This difference was greater in those under 65 years, women and those with a body mass index (BMI) > or =25. The most prominent incidence of adverse effects was thrombocytopenia in patients with lung cancer. In men, a serum creatinine level of > or =0. 6 mg/dL, GFR of <50 mL/min/1. 73 m(2) and a combined use of gemcitabine were cited as the factors responsible for the development of thrombocytopenia. It was concluded that the MDRD formula is an effective tool for evaluating patients with impaired renal function. It was suggested, on the other hand, that the dosage for medication should be decided by giving due consideration to factors other than renal functions.


A critical role of VMP1 in lipoprotein secretion.
Lipoproteins are lipid-protein complexes that are primarily generated and secreted from the intestine, liver, and visceral endoderm and delivered to peripheral tissues. Lipoproteins, which are assembled in the endoplasmic reticulum (ER) membrane, are released into the ER lumen for secretion, but its mechanism remains largely unknown. Here, we show that the release of lipoproteins from the ER membrane requires VMP1, an ER transmembrane protein essential for autophagy and certain types of secretion. Loss of vmp1, but not other autophagy-related genes, in zebrafish causes lipoprotein accumulation in the intestine and liver. Vmp1 deficiency in mice also leads to lipid accumulation in the visceral endoderm and intestine. In VMP1-depleted cells, neutral lipids accumulate within lipid bilayers of the ER membrane, thus affecting lipoprotein secretion. These results suggest that VMP1 is important for the release of lipoproteins from the ER membrane to the ER lumen in addition to its previously known functions.


"It's a place to feel like part of the community": Counterspace, inclusion, and empowerment in a drop-in center for homeless and marginalized women.
In the context of rising inequality and eroding safety nets for marginalized communities, research is needed to demonstrate the ways in which settings can facilitate community, agency, and capabilities for low-income women. The purpose of this study is to examine if and how an organizational setting designed to support homeless, low-income, and other marginalized women can facilitate empowering changes and increased wellbeing among the women who participate. A thematic analysis of interviews conducted with 22 participants who attend a women's day center identified three ways in which the organizational setting impacted women's lived experiences: (a) increasing a sense of agency through acceptance, active and participatory roles, and ownership over the physical environment, (b) promoting a sense of community through rituals of care and attentiveness, alleviated social isolation, and mutual relationships, and (c) improving life circumstances by offering a safe environment, access to basic resources such as housing, and support for health and wellbeing. Findings highlight the setting features and psychosocial processes that foster flourishing and resist patterns of exclusion and devaluation imposed on marginalized women by dominant neoliberal values, institutions, and policies.


Cyclin-dependent kinases phosphorylate the adenovirus E1A protein, enhancing its ability to bind pRb and disrupt pRb-E2F complexes.
The adenovirus E1A protein of 243 amino acids has been shown to affect a variety of cellular functions, most notably the immortalization of primary cells and the promotion of quiescent cells into S phase. The activity of E1A is derived, in part, from its association with various cellular proteins, many of which play important roles in regulating cell cycle progression. E1A is known to have multiple sites of phosphorylation. It has been suggested that cell cycle-dependent phosphorylation may also control some of E1A's functions. We find now that immune complexes of cyclin-dependent kinases such as cdk4, cdk2, and cdc2 are all capable of phosphorylating E1A in vitro. Additionally, the sites on E1A phosphorylated by these kinases in vitro are similar to the E1A sites phosphorylated in vivo. We have also found that a phosphorylated E1A is far more efficient than an unphosphorylated E1A in associating with pRB and in disrupting E2F/DP-pRB complexes as well. On the basis of our findings and the differences in timing and expression levels of the various cyclins regulating cdks, we suggest that E1A functions at different control points in the cell cycle and that phosphorylation controls, to some extent, its biological functions.


Changes in Taiwanese nursing student values during the educational experience.
Professional values are standards for action and provide a framework for evaluating behavior. This study examined changes in the professional values of nursing students between their entrance to and graduation from an undergraduate nursing program. A pre- and post-test design was employed. A convenience sample of 94 students from a university in Taiwan was surveyed. Data were collected from students during the sophomore and senior years. Total scores obtained for the revised Nurses Professional Values Scale during the senior year of the nursing program were significantly higher than upon program entry. The 'caring' subscale was scored highest at both program entry and graduation, but the pre- and post-test scores were not significantly different from each other. The students scored significantly higher on the 'professionalism' and 'activism' subscales at post-test than they did at pre-test. Professional values changed in a positive direction between the beginning of the student nurses' educational experience and their graduation. The results supported the premise that education had a positive effect on these students' professional values but causality could not be assumed.


Oral brush biopsy technique instruction outcomes for senior dental students.
Computerized oral brush biopsy became commercially available in 1999. The objectives of this study were to provide senior dental students with the clinical competency to perform oral brush biopsy and to evaluate the extent to which students used this technique and the outcomes of their biopsy techniques. During the 2004-05 academic year, 114 senior dental students at The Ohio State University College of Dentistry participated in a brush biopsy instructional program. Brush biopsy training was part of their outreach and engagement experience. Technique instruction included 1) completion of thirteen interactive online educational modules, 2) discussion of a written protocol including clinical photographs and an oral pathology position paper, and 3) performance of a trial demonstration brush biopsy on each other. Eighty-one students submitted brush biopsies on clinical patients. Lesions were found in approximately one out of every twenty patients. Seventy-four biopsy results (91 percent) were diagnostic although seventeen (21 percent) were limited by suboptimal cellular representation and seven (9 percent) were inadequate. The high percentage (71 percent) of students who actually applied their training in a true clinical setting indicates that the program was successful in providing dental students the information necessary to perform this procedure on their own. However, the number of incomplete specimens suggests the need for technique refinement and additional clinical experience.


Analyses of CYP2C in porcine microsomes.
The cytochrome P450 2C (CYP2C) subfamily in human beings includes four different isoenzymes that metabolize different substrates although with some cross reactivity. Some of these substrates (e.g. diclofenac and tolbutamide), have been investigated in porcine microsomes, but without identifying the specific CYP catalysing the reactions. The objective of this study was therefore to test some CYP2C substrates and identify the porcine CYP2C responsible for the reaction. Three substrates, paclitaxel, tolbutamide and omeprazole, were chosen, as they are metabolized by three different CYP2C isoenzymes in human beings. Microsomes, isolated from 20 different pigs, 12 conventional, and 8 minipigs, were incubated with these compounds, and correlations between the metabolism rates of these three substrates were found indicating that the reactions are catalysed by the same enzyme. Male minipigs tend to have higher average activity than female minipigs, which is in contrast to the gender-dependent expression seen for other CYP isoenzymes. The metabolic activities correlated with the protein level determined in Western blotting, using anti-human CYP2C9, indicating that this enzyme is responsible for the reaction. The expression of the CYP2C enzymes was analysed by real-time polymerase chain reaction, using a primer set that could amplify CYP2C8, CYP2C9 and CYP2C19. The melting curves (peaks) revealed that all three genes were present, showing very different expression levels in the various types of pigs. The area of one of the peaks, however, correlated with the CYP2C9-like enzyme concentration, suggesting that this peak represents CYP2C9. Among paclitaxel, tolbutamide and omeprazole, omeprazole is the best probe of CYP2C9-like enzyme in the pig.


Activation of leukemic pro-suppressor cells to become suppressor-effector cells. Influence of cooperating normal T cells.
We studied the suppressor activity and surface-membrane antigens of immunoregulatory neoplastic T cells from a child with acute lymphoblastic leukemia and hypogammaglobulinemia. The neoplastic T cells were potent inhibitors of immunoglobulin production by pokeweed-mitogen-stimulated normal B cells when radiosensitive cooperative normal T cells were present. Preculturing the leukemic cells with normal T cells or soluble factors allowed them to mediate suppression without the need for cooperating T cells. While acquiring new functional capabilities, approximately 95 per cent of the leukemic cells displayed an antigen (OKT-3) that is found on mature normal T cells; 77 per cent displayed an antigen (Tac) that is found on normal activated immunoregulatory effector cells but not on thymocytes or circulating T cells that are precursors of these effector cells. The results suggest that a population of leukemic prosuppressor cells can be induced to undergo both functional and antigenic differentiation by the influence of normal T cells.


Prevalence and Associations of Posterior Segment Manifestations in a Cohort of Egyptian Patients with Pathological Myopia.
Purpose: To determine the prevalence of posterior segment manifestations among consecutive patients with pathological myopia attending our University Hospital general ophthalmology clinic and their association with age, refractive error, axial length and each other. Methods: Patients diagnosed with pathological myopia underwent full ophthalmological examination, optical coherence tomography, fluorescein angiography, and ocular ultrasonography. Manifestations detected were recorded for each eye and their prevalence and association with age, refractive error, axial length and each other was determined. Results: A total of 127 eyes of 77 patients with pathological myopia were examined. The most prevalent manifestation was peripheral retinal lesions, found in 63.8% of examined eyes, followed by tigroid fundus, found in 59.1%. Peripheral lesions were significantly associated with more myopia (P = .02) and longer axial length (P = .046). The commonest peripheral lesion was white without pressure, found in 37.8% of eyes. Lattice degeneration was found in 11.8% and snail track degeneration in 4.7% and was not associated with degree of myopia or axial length. Diffuse chorioretinal atrophy was present in 40.9% of eyes, while patchy atrophy was present in 18.9%. Macular holes were present in 4.7% of eyes and were significantly associated with foveoschisis (P = .035) and retinal detachment (P = .003), while foveoschisis was present in 5.5% and was significantly associated with older age (P = .012), longer axial length (P = .010) and patchy chorioretinal atrophy (P = .024). Retinal detachment was found in 6.3% of eyes and retinal breaks in 4.7%. Posterior staphyloma was detected in 33.1% and lacquer cracks and choroidal neovascular membranes in 6.3% of eyes. Conclusions: The prevalence of pathological myopia manifestations may differ between different populations. This may be due to the multiple genetic and environmental factors involved which may result in a variable natural history of the condition among different populations.


Pulmonary perfusion after endovascular stenting of pulmonary artery stenosis.
Pulmonary artery stenosis is a well-known condition after surgical correction of tetralogy of Fallot. Endovascular stenting of the stenosis is a new technique for correction without surgical intervention. Objective evaluation of the procedure, however, is often hampered by moderate or severe pulmonary valve insufficiency. This disadvantage does not apply to 99mTc-macroaggregates of albumin (MAA) scintigraphy of the lungs. Moreover, quantification can be performed relatively easy. Seven patients with surgically corrected tetralogy of Fallot (4 men, 3 women, mean age 15.7 yr, range 5-24 yr) were studied. The mean diameter decrement of a pulmonary artery was 69% +/- 8.7%. Before and after stenting, relative uptake in the left and right lung was assessed after injection of 37-55 MBq 99mTc-MAA. Three patients were studied twice after stenting. In all patients, perfusion of the affected lung increased significantly: before 22.7% +/- 10.8%, after 38.6% +/- 12.3% (p < 0.0001). All patients claimed clinical improvement of their condition after stenting. The perfusion gain did not correlate with the prestenting diameter decrement or with the pressure gradient over the stenosis. Lung uptake in the patients studied twice after stenting was similar between the initial and poststenting study (< or = 2% difference). Quantitative 99mTc-MAA lung imaging is a noninvasive technique without patient discomfort that objectively measures the effect of stenting pulmonary artery stenosis. The final outcome of stenting with regard to increment of pulmonary blood flow is not predicted by the severity of the stenosis or the pressure gradient over the stenosis.


Inhibitory neurons in the human epileptogenic temporal neocortex. An immunocytochemical study.
Immunocytochemical methods were used to study alterations in inhibitory neuronal circuits in human neocortex resected during surgical treatment of intractable temporal epilepsy associated or not with brain tumours. The epileptogenic cortex was characterized and divided into spiking or non-spiking zones by intraoperative electrocorticography (ECOG). The resected cortex was cut into blocks, sectioned and stained immunocytochemically for visualization of glutamic acid decarboxylase (GAD), the calcium-binding protein, parvalbumin (PV) and glial fibrillary acidic protein (GFAP). A variety of alterations in cortical neuronal circuits as revealed by immunocytochemical and histological methods were found. Similar alterations in inhibitory neuronal circuits appear to occur independently of the primary epileptogenic site and pathology associated with epilepsy, which suggests that there is possibly a common basic underlying mechanism that leads to seizure activity. These changes were apparently unrelated to ECOG findings at surgery, which bring into question the value of the use of interictal epileptic discharges recorded by ECOG to guide cortical resections. The most conspicuous and common change was the loss of chandelier cells. The finding that these cells are among the most vulnerable types of GABAergic interneurons in the epileptogenic temporal cortex indicates that they might be of great functional importance, since the axon terminals of chandelier cells are likely to exert powerful regulation of impulse generation in cortical pyramidal cells. Therefore, these cells might represent a key component in the aetiology of human epilepsy.