Morphogenesis and differentiation of the avian endocrine pancreas, with particular reference to experimental studies on the chick embryo.
The avian pancreas has three or four lobes and develops from a dorsal and two ventral buds. The cells that will contribute to formation of the dorsal bud are at first located in the mid-dorsal endoderm, those of the ventral buds in the floor of the foregut. The determination of endoderm to form dorsal and ventral bud derivatives occurs before formation of the buds. The highest concentration of endocrine tissue is in the splenic lobe. The lobes contain A and B islets in which glucagon and insulin cells, respectively, predominate. Islets contain somatostatin and pancreatic polypeptide (PP) cells, both of which also occur scattered in the exocrine parenchyma. Pancreatic endocrine cells arise from endoderm: glucagon, insulin, and somatostatin cells differentiate early, PP cells later. To establish culture conditions suitable for avian insulin cells, the epithelial component of dorsal buds of 5-day chick embryos was cultured under various conditions. At the end of 7 days the proportion of insulin cells was determined. In raising the proportion of insulin cells, Matrigel was superior to collagen gel and a serum-free medium (incorporating insulin, transferrin, and selenium) was superior to a serum-containing medium. Modifications to the serum-free medium were tested. Raising the level of glucose or of glucose and essential amino acids increased the proportion of insulin cells. This proportion was also increased by replacement of insulin by insulin-like growth factor-I, whereas addition of transforming growth factor beta1 reduced the proportion. Transfer of explants from poor to favourable culture conditions showed that the improved conditions stimulated quiescent insulin progenitor cells to develop.


Desaturase mutants reveal that membrane rigidification acts as a cold perception mechanism upstream of the diacylglycerol kinase pathway in Arabidopsis cells.
Membrane rigidification could be the first step of cold perception in poikilotherms. We have investigated its implication in diacylglycerol kinase (DAGK) activation by cold stress in suspension cells from Arabidopsis mutants altered in desaturase activities. By lateral diffusion assay, we showed that plasma membrane rigidification with temperature decrease was steeper in cells deficient in oleate desaturase than in wild type cells and in cells overexpressing linoleate desaturase. The threshold for the activation of the DAGK pathway in each type of cells correlated with this order of rigidification rate, suggesting that cold induced-membrane rigidification is upstream of DAGK pathway activation.


Sample-centred shimming enables independent parallel NMR detection.
Two major technical challenges facing parallel nuclear magnetic resonance (NMR) spectroscopy, at the onset, include the need to achieve exceptional [Formula: see text] homogeneity, and good inter-detector radiofrequency signal decoupling, and have remained as technical obstacles that limit high throughput compound screening via NMR. In this contribution, we consider a compact detector system, consisting of two NMR 'unit cell' resonators that implement parallel [Formula: see text] shimming with parallel radiofrequency detection, as a prototype NMR environment, pointing the way towards achieving accelerated NMR analysis. The utility of our approach is established by achieving local field correction within the bore of a 1.05T permanent magnet MRI. Our forerunner platform suppresses signal cross-coupling in the range of [Formula: see text] dB to [Formula: see text] dB, under a geometrically decoupled scheme, leading to a halving of the necessary inter-coil separation. In this permanent magnet environment, two decoupled parallel NMR detector sites simultaneously achieve narrow spectral linewidth, overcoming the spatial inhomogeneity of the magnet from 400 to 28 Hz.


Enhancement of long-term potentiation at CA1-subiculum synapses in MK-801-treated rats.
The subiculum plays a key role in processing neuronal information from the hippocampus to different cortical and subcortical brain regions. The subicular projections to the nucleus accumbens and the prefrontal cortex have received increasing attention, as alterations of their activity seem to be involved in schizophrenia. Phencyclidine and other non-competitive antagonists of NMDA receptors (such as ketamine and MK-801) induce psychotic effects in humans that closely resemble the positive, negative and cognitive symptoms of schizophrenia. Using the MK-801 model of psychosis, we investigated the time course of alterations of synaptic transmission and plasticity at CA1-subiculum synapses of hippocampal brain slices 4 h, 24 h and 4 weeks after MK-801 treatment. We report here that systemic application of MK-801 causes a facilitation of LTP at CA1-subiculum synapses 24 h after treatment as compared with control LTP. Four weeks after MK-801 treatment, the magnitude of LTP reversed to control values. The priming of LTP 24 h after systemic application of MK-801 suggest a new form of metaplasticity that sheds light on the delayed facilitating effect of this drug on synaptic efficacy.


Outcomes of 25-gauge vitrectomy for proliferative diabetic retinopathy.
To evaluate the efficacy and safety of 25-gauge transconjunctival sutureless vitrectomy (25-G TSV) in the management of vitreoretinal complications of proliferative diabetic retinopathy (PDR). A retrospective review of a noncomparative interventional case series including 200 eyes of 164 consecutive patients who underwent 25-G TSV for the management of PDR was performed. The main outcome measures were preoperative and postoperative visual acuity and intraocular pressure (IOP), the surgical success rate, and intraoperative and postoperative complications. All cases had a follow-up period of at least 6 months. The mean logarithm of the minimum angle of resolution (LogMAR) visual acuity was significantly improved from 1.55 preoperatively to 0.72 at the final visit. No intraoperative complications related to the 25-G TSV procedure were recorded. Transient hypotony was recorded in 18 eyes (9%) on postoperative day 1 and 15 eyes (7.5%) on postoperative day 5. Two of these eyes (1%) had choroidal detachment on postoperative day 5. One case showed bacterial endophthalmitis after the second surgery. The single operation and final surgical success rates were 81.5% and 98% respectively. These outcomes of 25-G TSV showed its safety and efficacy in the management of PDR.


EMOCOV: Machine learning for emotion detection, analysis and visualization using COVID-19 tweets.
The adversarial impact of the Covid-19 pandemic has created a health crisis globally all over the world. This unprecedented crisis forced people to lockdown and changed almost every aspect of the regular activities of the people. Thus, the pandemic is also impacting everyone physically, mentally, and economically, and it, therefore, is paramount to analyze and understand emotional responses during the crisis affecting mental health. Negative emotional responses at fine-grained labels like anger and fear during the crisis might also lead to irreversible socio-economic damages. In this work, we develop a neural network model and train it using manually labeled data to detect various emotions at fine-grained labels in the Covid-19 tweets automatically. We present a manually labeled tweets dataset on COVID-19 emotional responses along with regular tweets data. We created a custom Q&A roBERTa model to extract phrases from the tweets that are primarily responsible for the corresponding emotions. None of the existing datasets and work currently provide the selected words or phrases denoting the reason for the corresponding emotions. Our classification model outperforms other systems and achieves a Jaccard score of 0.6475 with an accuracy of 0.8951. The custom RoBERTa Q&A model outperforms other models by achieving a Jaccard score of 0.7865. Further, we present a historical emotion analysis using COVID-19 tweets over the USA including each state level analysis.


Allogenic sternal transplant after sternectomy for metastasis of ovarian carcinoma.
Sternal metastasis from ovarian carcinoma is extremely rare. We report a case of a young woman in whom a single metastasis at the level of the upper portion of the sternum developed. Surgical excision of the sternum was performed with replacement by a sternal allograft stabilized by titanium plates and transosseous high-tension sutures. With this simple and reproducible technique, we obtained a stable and dynamic reconstruction of the sternoclavicular joints and shoulder girdle. The use of a sternal allograft provides excellent functional and cosmetic results. The implantation technique is simple and reproducible.


Erectile dysfunction: prevalence and associated variables in patients with chronic renal failure.
Patients with chronic renal failure (CRF) experience a significant decrease in quality of life, due both to the limitations imposed by the disease as well as the demands of the treatment that they receive. Some side effects of both illness and treatment contribute to increase the morbidity of these patients. Among them, erectile dysfunction (ED) is notable. One hundred and nineteen patients received clinical and laboratory evaluation. The following clinical data were observed: age, education, income, race, period of dialysis, period of complaints of ED, etiology of ED, use of erythropoietin, presence of arterial hypertension and/or diabetes mellitus, use of antihypertensive drugs, use of cigarettes, and psycho-emotional state of the patients. Assessment of complaints of ED was achieved using the International Index of Erectile Function (IIEF). The following laboratory data were analyzed: hemoglobin, hematocrit, free testosterone, gonadotrophin levels (FSH and LH), HDL-cholesterol, total cholesterol, prolactin, and parathyroid hormone. Statistical analysis of the means of continuous variables was performed through use of the Student's t-test. Analysis of significance of category variables was performed using the chi(2) test. Descriptive analysis was obtained through use of the clinical and socio-demographic data. A multivariate model was created and the odds ratio calculated. The average age of the patients was 47.3+/-15.9 y. The mean duration of erectile dysfunction complaints was 4 y. The average duration of dialysis was 66.2+/-58.9 months. Prevalence of erectile dysfunction in this population was 57.9%. The main known etiology of chronic renal failure was glomerulonephritis. The main variables associated with erectile dysfunction were age, psycho-emotional state, and levels of HDL-cholesterol. This study showed a high prevalence of erectile dysfunction in the group of patients examined. Factors such as age, anxiety and depressive complaints, and dyslipidemy seem to play an important role in the origin of erectile dysfunction in such patients.


Tips and Tricks: Preconceptional Laparoscopic Cervical Cerclage Made Easier and Safer With the Titiz Uterovaginal Manipulator.
To demonstrate safe and easy surgical steps to facilitate preconceptional laparoscopic cervical cerclage with the Titiz uterovaginal manipulator. Narrated step-by-step video demonstration of preconceptional laparoscopic cervical cerclage under the guidance of the Titiz uterovaginal manipulator. Cervical incompetence or cervical insufficiency is 1 of the causes of preterm birth. Incidence is 0.1% to 1% of all pregnancies. Traditionally, cervical cerclage is placed vaginally, but sometimes it is not possible to perform this procedure vaginally. When this occurs, cerclage needs to be inserted abdominally either by laparotomy or by laparoscopy. Laparoscopic cervical cerclage is indicated when vaginal cerclage has failed or is not possible due to a deficient or a short cervix caused by previous cervical surgery. Although laparoscopic cervical cerclage has a good success rate (90%-100% live births), there is a risk of injury to the bladder, sigmoid colon, and the uterine vessels. It is also important to put the suture in the right place, which is at the internal cervical os (cervico-isthmic junction) and medial to the uterine vessels. Therefore, it can be a challenging operation, especially when the uterus is bulky and more vascular due to adenomyosis or fibroids. A 32-year-old woman, G0P0, with the surgical history of cone biopsy presented with a history of infertility. On vaginal examination, there was no vaginal portion of the anterior cervix, and there was only 0.5 cm of the vaginal portion of the posterior cervix. After extensive counseling, the decision was made to perform a preconceptional laparoscopic abdominal cerclage. This video demonstrates the Titiz uterovaginal manipulator components and how to insert the manipulator. It also shows tips and tricks on laparoscopic cervical cerclage: (1) how to determine the anatomic relationships among the bladder, uterine vessels, cervico-vaginal junction and cervico-isthmic part of uterus; (2) how the Titiz uterovaginal manipulator helps to dissect the bladder and uterine arteries and veins safely; and (3) how to determine where and how to pass the sutures. The patient was discharged the same day and did not have any postoperative complications. The patient had transvaginal ultrasound 1 week after the operation. Tape was shown to be at the internal cervical os level. The Titiz uterovaginal manipulator can make preconceptional laparoscopic abdominal cerclage safer and easier.


Detection of ischemic changes on baseline multimodal computed tomography: expert reading vs. Brainomix and RAPID software.
The aim of the study was to compare the assessment of ischemic changes by expert reading and available automated software for non-contrast CT (NCCT) and CT perfusion on baseline multimodal imaging and demonstrate the accuracy for the final infarct prediction. Early ischemic changes were measured by ASPECTS on the baseline neuroimaging of consecutive patients with anterior circulation ischemic stroke. The presence of early ischemic changes was assessed a) on NCCT by two experienced raters, b) on NCCT by e-ASPECTS, and c) visually on derived CT perfusion maps (CBF<30%, Tmax>10s). Accuracy was calculated by comparing presence of final ischemic changes on 24-hour follow-up for each ASPECTS region and expressed as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The subanalysis for patients with successful recanalization was conducted. Of 263 patients, 81 fulfilled inclusion criteria. Median baseline ASPECTS was 9 for all tested modalities. Accuracy was 0.76 for e-ASPECTS, 0.79 for consensus, 0.82 for CBF<30%, 0.80 for Tmax>10s. e-ASPECTS, consensus, CBF<30%, and Tmax>10s had sensitivity 0.41, 0.46, 0.49, 0.57, respectively; specificity 0.91, 0.93, 0.95, 0.91, respectively; PPV 0.66, 0.75, 0.82, 0.73, respectively; NPV 0.78, 0.80, 0.82, 0.83, respectively. Results did not differ in patients with and without successful recanalization. This study demonstrated high accuracy for the assessment of ischemic changes by different CT modalities with the best accuracy for CBF<30% and Tmax>10s. The use of automated software has a potential to improve the detection of ischemic changes.


Determinants and patterns of renin-angiotensin system inhibitors' prescription in the first year following kidney transplantation.
The benefit of prescribing angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor antagonists (ARB) to kidney transplant recipients remains controversial. We investigated determinants and prescribing patterns of ACEi/ARB during the first year following kidney transplantation. All recipients of a first kidney transplant performed at the university hospital of Nancy (France) between January 1997 and June 2004 were included. Determinants of ACEi/ARB prescription were identified by Cox models among various recipient characteristics (at transplantation and during follow-up), donor characteristics and transplant parameters. Of 491 patients, 28.9% started using ACEi/ARB during the year after transplantation, and 26.9% were taking them at one yr. Recipient determinants of ACEi/ARB use were male sex (HR: 1.82, p = 0.003), pre-transplant hypertension (HR: 2.27, p = 0.0002) and ACEi/ARB administration (HR: 1.85, p = 0.002), post-transplant proteinuria (HR: 1.62, p < 0.0001) and anemia (HR: 4.08, p < 0.0001). Glomerular filtration rate level was not associated with ACEi/ARB use. Post-transplant hypercholesterolemia (HR: 0.42, p = 0.013) and higher donor age (HR: 0.98, p = 0.015) were associated with a lower likelihood of ACEi/ARB use. Fewer HLA mismatches (HR: 1.16, p = 0.029) and shorter cold ischemia duration (HR: 1.02, p = 0.045) were also independent predictors of ACEi/ARB use. Regardless of recipient characteristics, nephrologists were more likely to prescribe ACEi/ARB after kidney transplantation when the transplant parameters were favorable.


In-hospital mortality in heart failure in Germany during the Covid-19 pandemic.
The Covid-19 pandemic affects care for cardiovascular conditions, but data on heart failure (HF) are scarce. This study aims to analyse HF care and in-hospital outcomes during the pandemic in Germany. A total of 9452 HF admissions were studied using claims data of 65 Helios hospitals; 1979 in the study period (13 March 30 April 2020) and 4691 and 2782 in two control periods (13 March to 30 April 2019 and 1 January to 12 March 2020). HF admissions declined compared with both control periods by 29-38%. Cardiac resynchronization therapy was implanted in 0.55% during the study period, 0.32% [odds ratio (OR) 1.66, 95% confidence interval (CI) 0.68-4.04, P = 0.27] in the previous year and 0.43% (OR 1.35, 95% CI 0.64-2.84, P = 0.43) in the same year control. Intensive care treatment was 6.22% during the study period, 4.49% in the previous year (OR 1.46, 95% CI 1.13-1.89, P < 0.01), and 5.27% in the same year control (OR 1.19, 95% CI 0.96-1.49, P = 0.12). Length of hospital stay was 7.0 ± 5.0 days in the study and 7.8 ± 5.6 (P < 0.01) and 7.3 ± 5.1 days (P = 0.07) in the control periods. In-hospital mortality was 7.0% in the study and 5.5% in both control periods (P < 0.05). During the early phase of the Covid-19 pandemic in Germany, HF treatment pathways seem not to be affected, but hospital stay shortened and in-hospital mortality increased. As the pandemic continues, this early signal demands close monitoring and further investigation of potential causes.


[Double ricochet marks].
When bullets are flying stably and ricochet on a surface, only one mark is produced. In contrast yawing bullets can produce a double mark if the angle of incidence is sufficiently small (less than or equal to 5 degrees). Distances up to 15 cm were seen between the two marks.


[Effect of aggregation inhibitors on thrombocyte enzymatic activity].
Experiments on rabbits proved that amidopyrin, sulphatizonicotinoilamine-guanidine, chlorpromazine, triphthazine, euphylline and tedamine inhibit aggregation of thrombocytes and unidirectionally have an effect on the carbohydrate metabolism enzymes in these cells, both in vitro and in vivo following their single and coursewise introduction. They also activate the lactate- and glyceraldehide-3-phosphate-dehydrogenase and reduce the activity of glucose-6-phosphate-dehydrogenase.


Selective activation of adenosine A3 receptors with N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA) provides cardioprotection via KATP channel activation.
The aim of this study was to characterize the adenosine A3 receptor agonist, N6-(3-chlorobenzyl)-5'-N-methylcarboxamidoadenosine (CB-MECA), evaluate its ability to reduce myocardial ischemia/reperfusion injury and determine the role of KATP-channel activation in A3 receptor-mediated cardioprotection. Binding affinities and adenylate cyclase inhibition were examined in CHO cells expressing rabbit recombinant adenosine A1 or A3 receptors. Infarct size (normalized for area-at-risk; % IA/AAR) was measured in buffer-perfused rabbit hearts exposed to 30-min regional ischemia and 120 min of reperfusion. CB-MECA was 100-fold selective for A3 vs. A1 receptors (A3 Ki: 1 nM; A1 Ki: 105 nM). Five-min perfusion with CB-MECA before ischemia/reperfusion elicited a concentration-dependent reduction in infarct size (EC50: 0.3 nM). The CB-MECA-dependent cardioprotection (control: 58 +/- 2; CB-MECA: 21 +/- 3% IA/AAR) was unchanged by an A1-selective concentration of the antagonist, BWA1433, but was completely prevented (P < 0.05) by a nonselective (A1/A3) concentration (55 +/- 6% IA/AAR). The KATP channel inhibitors, glibenclamide and 5-HD, had no effect on control infarct size, yet significantly (P < 0.05) blunted the CB-MECA-dependent cardioprotection (glibenclamide: 49 +/- 6; 5-HD: 58 +/- 4% IA/AAR). CB-MECA is a novel 100-fold A3 receptor-selective agonist which should prove useful for elucidating A3-dependent mechanisms in the rabbit heart. Selective stimulation of adenosine A3 receptors with CB-MECA reduces myocardial ischemia/reperfusion injury via a mechanism which involves activation of KATP channels.


Identification of latent procathepsins B and L in microsomal lumen: characterization of enzymatic activation and proteolytic processing in vitro.
Procathepsins B and L in the hepatic endoplasmic lumen were identified as having a molecular weight of 39,000 by immunoblot analysis. The proenzymes were then purified to remove the mature enzymes by concanavalin A-Sepharose chromatography. The concanavalin A-adsorbed fractions containing the proenzymes showed no appreciable activities of cathepsins B and L. When those fractions were incubated at pH 3.0, the enzymatic activities markedly increased: the activities of cathepsins B and L after 36 h incubation were 60 and 210 times those of the controls, respectively. Immunoblot analysis showed that after 36 h incubation the proenzymes disappeared and the mature enzymes increased. Thus the proenzymes were processed to the mature enzymes under acidic conditions of pH 3.0. The marked increases of enzymatic activities and the conversion of the proenzymes to the mature forms were completely blocked with pepstatin, which is a potent inhibitor of aspartic proteases. The results strongly suggested that a processing protease for procathepsins B and L might be cathepsin D, a major lysosomal aspartic protease. Indeed, lysosomal cathepsin D could convert microsomal procathepsin B to the mature enzyme in vitro. Therefore, procathepsins B and L seem first to be synthesized as enzymatically inactive forms in endoplasmic reticulum and successively may be converted into active forms by cathepsin D in lysosomal compartments.


Treatment of resistant severe psoriasis with systemic cyclosporine.
Four patients with severe psoriasis have been treated with oral cyclosporine for 6 months. Two had generalized erythroderma and two had extensive plaque-type psoriasis; all had either become unresponsive to or were unable to use other accepted treatments. All four patients responded rapidly and were completely clear of psoriasis within 3 weeks of beginning therapy. Initial doses ranged from 7.5 to 8.5 mg/kg/day. Mild reversible nephrotoxicity occurred in the one patient whose cyclosporine trough level briefly exceeded 200 ng/ml. Cyclosporine may offer an alternative therapeutic modality in the management of erythrodermic or severe resistant plaque-type psoriasis. The effectiveness of cyclosporine in psoriasis underscores the putative role of cell-mediated immune factors in the pathogenesis of psoriasis.


Metabolic fate of N1-methyladenine in yeast auxotrophic to adenine.
The metabolic fate of N1-methyladenine in yeast with respect to its incorporation into RNA has been studied. Chromatographic analysis of the PCA-soluble and -insoluble fractions of cells grown in the combined presence of adenine and 3H-labeled N1-methyladenine show that (a) N1-methyladenine can enter the cells, (b) however, it is very poorly utilized by the salvage pathway for nucleic acid synthesis and (c) the inhibition occurs probably at the first stage of conversion of the methylated base to the corresponding nucleotide.


NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells.
A major group of murine NK T (NKT) cells express an invariant Valpha14Jalpha18 TCR alpha-chain specific for glycolipid Ags presented by CD1d. Murine Valpha14Jalpha18(+) account for 30-50% of hepatic T cells and have potent antitumor activities. We have enumerated and characterized their human counterparts, Valpha24Vbeta11(+) NKT cells, freshly isolated from histologically normal and tumor-bearing livers. In contrast to mice, human NKT cells are found in small numbers in healthy liver (0.5% of CD3(+) cells) and blood (0.02%). In contrast to those in blood, most hepatic Valpha24(+) NKT cells express the Vbeta11 chain. They include CD4(+), CD8(+), and CD4(-)CD8(-) cells, and many express the NK cell markers CD56, CD161, and/or CD69. Importantly, human hepatic Valpha24(+) T cells are potent producers of IFN-gamma and TNF-alpha, but not IL-2 or IL-4, when stimulated pharmacologically or with the NKT cell ligand, alpha-galactosylceramide. Valpha24(+)Vbeta11(+) cell numbers are reduced in tumor-bearing compared with healthy liver (0.1 vs 0.5%; p < 0.04). However, hepatic cells from cancer patients and healthy donors release similar amounts of IFN-gamma in response to alpha-galactosylceramide. These data indicate that hepatic NKT cell repertoires are phenotypically and functionally distinct in humans and mice. Depletions of hepatic NKT cell subpopulations may underlie the susceptibility to metastatic liver disease.


Infantile myopathy with type 1 fibre specific hypertrophy.
Two children are described whose clinical and muscle biopsy findings suggested a previously unrecognised variant of congenital fibre-type disproportion myopathy, characterised by selective hypertrophy of type 1 fibres.


The role of disturbance in the evolution of life history strategies in the intertidal mussels Mytilus edulis and Mytilus californianus.
The intertidal mussels Mytilus edulis and M. californianus compete for space on the west coast of North America. An analysis of differences in size, growth rate, age at first reproduction, life span, mode of reproduction, niche and habitats between these two species demonstrates that their life history strategies are different in several important ways. M. californianus is a larger, sturdier, slower growing mussel which has effective predator-deterring mechanisms and is an overall superior competitor for space in the intertidal. Its reproductive strategy is based on continually spawning at a very low level throughout a yearly cycle. M. edulis is a classic fugitive species which rarely attains a large size but matures early and is characterized by a single massive reproductive output each year. The differences noted in their life history strategies are very likely the result of either a) a "pre-adaptation" for coexistence, or b) a competitively-induced regional evolutionary divergence.In Washington a band of small M. edulis (removed from most predation and competition) exists in a high intertidal spatial refuge, and contributes relatively little to the gene pool. Larger individuals exist in disturbed areas lower in the intertidal zone. These lower zones represent a relatively high risk, and usually only temporary, habitat for M. edulis because of mortality due to competition and predation. Individuals, however, colonizing these two intertidal patches contribute 43 times as much as their high intertidal counterparts in terms of reproductive fitness (calculated on a populationwide basis).


From black water to flushing water: potential applications of chlorine-mediated indirect electrooxidation for ammonia removal.
Removing ammonia from black water is one of the most urgent issues before it can be recycled as flushing water. In this study, an electrochemical oxidation (EO) process with commercial Ti/IrO2-RuO2 anodes to treat black water could remove 100% of different concentrations of ammonia by adjusting the dosage of chloride. Through the relationship between ammonia, chloride, and corresponding the pseudo-first-order degradation rate constant (Kobs), we could determine the chloride dosage and predict the kinetics of ammonia oxidation based on initial ammonia concentration in black water. The optimal N/Cl molar ratio was 1:1.8. The difference between black water and the model solution in terms of ammonia removal efficiency and oxidation products was explored. A higher chloride dosage was beneficial for removing ammonia and shortening the treatment cycle, but it also led to the generation of toxic by-products. Especially HClO and ClO3- generated in black water were 1.2 and 1.5 times more than the synthesized model solution under 40 mA cm-2. Through SEM characterization of electrodes and repeated experiments, the electrodes always maintained a high treatment efficiency. These results demonstrated the potential of the electrochemical process as a treatment method for black water.


Determination of cannabinoids in biological samples using a new solid phase micro-extraction membrane and liquid chromatography-mass spectrometry.
A simple, rapid and relatively solventless method for extraction of objective compounds would be useful for forensic, judicial and clinical purposes. Solid phase micro-extraction membrane (SPMEM) is one such extraction technique that integrates sampling, extraction and concentration into a single step, and combines the advantages of both the solid phase micro-extraction (SPME) and membrane separation. In this study, a new kind of membrane was prepared using polyamide and Tenax compounds, and applied to solid phase micro-extraction. Characteristics of the membrane such as adsorption capacity were tested. Extraction conditions such as adsorption time, desorption solvents, desorption time and assisted desorption treatment methods were studied and optimized. Tetrahydrocannabinol (THC) and cannabidiol (CBD) in blood and brain of the injected male mice, and in spiked human urine were extracted using this solid phase micro-extraction membrane method. The extracted THC and CBD were further determined with LC-MS using APCI. Ions analyzed in single ion monitoring mode were 315 for THC and CBD, and 318 for the deuterated THC internal standard.


Inhibitory receptors signal activation.
Natural killer cell inhibitory receptors block effector responses by recruiting phosphatases that dephosphorylate molecules involved in activation. However, in this issue of Immunity, Peterson and Long show that inhibitory receptors also signal tyrosine phosphorylation, an event usually indicating cellular activation.


Rapid determination of immunoglobulin G concentration in cold ethanol precipitation process of raw plasma with near-infrared spectroscopy.
Near-infrared spectroscopy (NIRS) is known to be a powerful analytical tool in process monitoring. The feasibility of NIRS was investigated for determination of immunoglobulin G (IgG) in raw plasma cold ethanol precipitation process. Partial least squares (PLS) was used to develop regression model for 63 samples between spectra and reference data measured with a UV spectrophotometer. Three different variable selection methods, including correlation coefficient method, interval partial least squares (iPLS) and successive projection algorithm (SPA), were performed and compared with models based on all the variables. The values of Rc and root mean square error of cross validation (RMSECV) produced by the best model for the calibration set were 0.9599 and 0.6135 g/L, respectively. While for the validation set, the values of Rp and root mean square error of prediction (RMSEP) were 0.9577 and 0.4913 g/L, respectively. The results of this paper demonstrated that NIRS could be a feasible alternative approach for rapid determination of IgG in the cold ethanol precipitation process and can be used as a PAT tool in the future.


Longitudinal surveillance of serum titanium ion levels in patients with indigenous 3D printed total temporomandibular joint replacement.
The purpose of this longitudinal study was to surveil the serum titanium ion levels at various time intervals in patients with indigenous 3D-printed total temporomandibular joint replacement (TMJ TJR). The study was conducted on 11 patients (male: 8; female: 3) who had undergone unilateral or bilateral TMJ TJR. Blood samples were drawn preoperatively (T0), 3 months (T1), 6 months (T2), and 1 year (T3) postoperatively. Data were analyzed and a p value of < 0.05 was considered statistically significant. The mean serum titanium ion levels at T0, T1, T2, and T3 was 9.34 ± 8.70 µg/L (mcg/L), 35.97 ± 20.27 mcg/L, 31.68 ± 17.03 mcg/L, and 47.91 ± 15.47 mcg/L respectively. The mean serum titanium ion levels increased significantly at T1 (p = 0.009), T2 (p = 0.032), and T3 (p = 0.00) interval. There was no significant difference between unilateral and bilateral groups. Serum titanium ion continued to show increased levels till the last follow-up of 1 year. These initial serum titanium ion levels increase is due to the initial wear phase of the prosthesis which manifests over 1 year. Further studies with large sample sizes and long-term follow-ups are required to see the deleterious effect if any on the TMJ TJR.


Histone H2A ubiquitination in transcriptional regulation and DNA damage repair.
The precise molecular strategies that coordinate patterns of transcriptional response to specific signals is central for understanding normal development and disease. Precise control of transcriptional programs underlying metazoan development is modulated by enzymatically active coregulatory complexes, coupled with epigenetic strategies. Epigenetic modifications, particularly DNA methylation and covalent histone modifications, for instance acetylation, methylation, phosphorylation and ubiquitination, play an essential role in transcription regulation, chromatin remodeling, genome instability and X chromosome inactivation. Recently, the ubiquitinases and deubiquitinases responsible for histone H2A ubiquitination and deubiquitination have been identified and characterized. These studies suggest that histone H2A ubiquitination play important roles in many cellular events, such as transcription initiation and elongation, silencing, and DNA repair. Alteration of histone H2A ubiquitination modifications may contribute human diseases, such as cancer. In this review, we discuss enzymes involved in H2A ubiquitination/deubiquitination and that possible molecular mechanisms underlying histone H2A ubiquitination/deubiquitination in transcriptional regulation and DNA damage repair.


Roles of airway basal stem cells in lung homeostasis and regenerative medicine.
Airway basal stem cells (BSCs) in the proximal airways are recognized as resident stem cells capable of self-renewing and differentiating to virtually every pseudostratified epithelium cell type under steady-state and after acute injury. In homeostasis, BSCs typically maintain a quiescent state. However, when exposed to acute injuries by either physical insults, chemical damage, or pathogen infection, the remaining BSCs increase their proliferation rate apace within the first 24 h and differentiate to restore lung homeostasis. Given the progenitor property of airway BSCs, it is attractive to research their biological characteristics and how they maintain homeostatic airway structure and respond to injury. In this review, we focus on the roles of BSCs in lung homeostasis and regeneration, detail the research progress in the characteristics of airway BSCs, the cellular and molecular signaling communications involved in BSCs-related airway repair and regeneration, and further discuss the in vitro models for airway BSC propagation and their applications in lung regenerative medicine therapy.


Malignant duodenocolic fistulas.
Five cases of malignant duodenocolic fistula seen at the Massachusetts General Hospital in the past thirty years are reviewed. Rarely encountered, these lesions are characterized by diarrhea, weight loss, abdominal pain, anemia, and sometimes feculent vomiting. Barium enemas are more likely to demonstrate the fistula tract than upper gastrointestinal series. Nutritional deficiencies may be profound, and the use of preoperative hyperalimentation is encouraged. Operations that accomplish only bypass of the fistula are of minimal palliative value, and the fistula should be divided or resected if possible. When feasible, wide resection is the procedure of choice, and a fourteen year survival is reported after this operation.


The relative bioavailability of temafloxacin administered through a nasogastric tube with and without enteral feeding.
The relative bioavailability of a single oral dose of temafloxacin given with and without enteral feeding was determined in 18 healthy male volunteers in a randomised crossover study. Subjects were administered 600mg of temafloxacin orally as an intact tablet, or a crushed tablet suspended in water administered through a nasogastric tube with or without an enteral feeding solution [Osmolite (Ross) 100 ml/h started 2h before administration of temafloxacin and continued for 4h postdose]. Plasma samples were analysed by a high performance liquid chromatographic technique. Mean peak plasma concentrations (Cmax) for the oral tablet, crushed tablet, and crushed tablet with enteral feeding solution were 3.95 +/- 1.02, 4.85 +/- 0.69, and 4.69 +/- 0.61 mg/L/70kg, respectively, and mean calculated area under the concentration-time curve from time 0 to 48h (AUC(0-48h)) values were 48.1 +/- 11.0, 54.5 +/- 6.52, and 49.7 +/- 5.89 mg/L.h/70kg, respectively. In terms of AUC(0-48h) and Cmax, the relative bioavailability of temafloxacin after nasogastric delivery of crushed temafloxacin given with and without an enteral feeding solution was equivalent to the reference oral regimen.


The chemical pesticide, imidacloprid (IMI) has long-lasting effectiveness against Hemiptera. IMI is commonly used to control the brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae). Some chemical pesticides, however, can induce the susceptibility of rice to BPH, which has indirectly led to the resurgence of BPH. The mechanism of the chemical induction of the susceptibility of rice to BPH was not previously understood. Here, a 44 K Agilent Rice Expression Microarray was used to identify changes in gene expression that accompany IMI-induced rice susceptibility to BPH. The results showed that 225 genes were differentially expressed, of which 117 were upregulated, and 108 were downregulated. Gene ontology annotation and pathway analysis revealed that differentially expressed genes were mainly classified into the eight functional groups: oxidation reduction, regulation of cellular process, response to stress, electron carrier activity, metabolic process, transport, signal transducer, and organismal development. The genes encoding plant lipid transfer protein, lignin peroxidase, and flavonol-3-O-methyltransferenase may be important responses to the IMI-induced susceptibility of rice to BPH. The reliability of the microarray data was verified by performing quantitative real-time PCR and the data provide valuable information for further study of the molecular mechanism of IMI-induced susceptibility of rice.


Quality service delivery in cardiac rehabilitation: cross-cultural challenges in an Australian setting.
Cardiac rehabilitation is an evidence-based health service model for providing secondary prevention strategies following an acute cardiac event. In spite of the benefits of cardiac rehabilitation, there are striking cultural and ethnic disparities with regard to access to and usage of these programmes. To investigate the challenges in providing cardiac rehabilitation to culturally diverse populations in Australia to inform culturally competent care. This was a qualitative study using interviews with 25 health professionals from diverse professional and language backgrounds working in cardiac rehabilitation and participant observation of educational and counselling sessions in four cardiac rehabilitation programmes in metropolitan Sydney, Australia. Providing cardiac rehabilitation to patients from culturally and linguistically diverse backgrounds presented greater challenges than did provision to the mainstream population. These challenges resulted from the interaction of multiple and complex factors such as patients, providers, structural and organisational characteristics within the treatment setting. Communication issues, reconciling health messages with culturally specific issues such as diet, social and family structure and implementation of self-management strategies are significant challenges. Strategies are needed to overcome cross-cultural challenges and ensure effective and equitable cardiac rehabilitation service delivery.


Effect of sweet grass extract against oxidative stress in rat liver and serum.
Ethanol metabolism is accompanied by generation of free radicals which can damage the cell components. However, sweet grass is a source of coumarin and its derivatives have emerged as a promising group of antioxidant compounds. The aim of this study has been to investigate the influence of sweet grass on oxidative stress formation in the liver and serum of rats intoxicated with ethanol. Alcohol intoxication led to a decrease in the superoxide dismutase, catalase, glutathione peroxidase and reductase activity in the blood serum as well as in the liver, but not in the glutathione reductase activity. The decrease in the antioxidant abilities of the examined tissues after ethanol intoxication resulted in enhanced lipid peroxidation measured as malondialdehyde and 4-hydroxynonenal levels. The metabolic consequence of oxidative modifications of lipids was damage of the liver cells membrane and an increase in its permeability appeared as a leakage of alanine aminotransferase and aspartate aminotransferase into the blood. Administration of sweet grass to the ethanol-intoxicated rats remarkably prevented the significant increase in concentrations of all measured lipid peroxidation products as well as the damage of the liver cell membrane. These results indicate beneficial antioxidant effect of the sweet grass on the liver of rats intoxicated with ethanol.


Aberrant expression of PAX6 gene associated with classical aniridia: identification and functional characterization of novel noncoding mutations.
The PAX6 is essential for ocular morphogenesis and is known to be highly sensitive to changes in gene expression, where neither over- nor under-expression ensures normal ocular development. Two unrelated probands with classical aniridia who were previously considered "PAX6-negative", were studied by whole-genome sequencing. Through the use of multiple in silico deep learning-based algorithms, we identified two novel putative causal mutations, c.-133_-132del in the 5' untranslated region (5'-UTR) and c.-52 + 5G>A in an intron upstream of the PAX6 gene. The luciferase activity was significantly increased and VAX2 binding was disrupted with the former 5'-UTR variant compared with wild-type sequence, which resulted in a striking overexpression of PAX6. The minigene assay showed that the c.-52 + 5G>A mutation caused defective splicing, which resulted in the formation of truncated transcripts.


Management of cerebellar infarction with associated occlusive hydrocephalus.
We review here 10 cases of cerebellar infarction and associated occlusive hydrocephalus. Surgical therapy consisted of placement of a permanent shunt in 4, and a temporary external ventricular drainage in 6 individuals. This treatment regimen was effective in 9 cases and remained without adequate response in only 1 patient with multiple supra- and infratentorial infarctions. These results and similar reports from the literature suggest that treatment of the hydrocephalus alone might be sufficient in most cases and should therefore constitute the primary treatment of choice in patients presenting with cerebellar infarction and obstruction of cerebrospinal fluid (CSF) pathways.


Thermal behavior, specific heat capacity and adiabatic time-to-explosion of G(FOX-7).
[H(2)N=C(NH(2))(2)](+)(FOX-7)(-)-G(FOX-7) was prepared by mixing FOX-7 and guanidinium chloride solution in potassium hydroxide solution. Its thermal decomposition was studied under the non-isothermal conditions with DSC and TG/DTG methods. The apparent activation energy (E) and pre-exponential constant (A) of the two exothermic decomposition stages were obtained by Kissinger's method and Ozawa's method, respectively. The critical temperature of thermal explosion (T(b)) was obtained as 201.72 degrees C. The specific heat capacity of G(FOX-7) was determined with Micro-DSC method and theoretical calculation method and the standard molar specific heat capacity is 282.025 J mol(-1) K(-1) at 298.15 K. Adiabatic time-to-explosion of G(FOX-7) was also calculated to be a certain value between 13.95 and 15.66 s.


A randomized trial of topical 5% 5-fluorouracil (Efudix cream) in the treatment of actinic keratoses comparing daily with weekly treatment.
Topical 5-fluorouracil (5-FU) cream is widely used in the treatment of actinic keratoses (AKs) but the optimum treatment regimen that provides efficacy while minimizing side-effects remains unclear. A randomized trial to compare the efficacy and side-effects of daily vs. weekly application of 5% 5-FU in the treatment of AKs of the scalp and face. Twenty patients were recruited and randomized to two groups. Group 1 (13 patients) applied 5% 5-FU twice daily for 3 weeks, group 2 (seven patients) applied 5% 5-FU twice daily for 1 day per week for 12 weeks. Patients were reviewed at weeks 3, 12, 24 and 52. At each review a lesion count and lesion map were completed and patients were asked to score efficacy and inflammation. At week 0 the median lesion count was the same in both groups, 17.5 lesions. At 12 weeks the median lesion count in group 1 had fallen to 0 where it remained for the duration of follow-up. In group 2 the median lesion count fell to 6 at 12 weeks, 5.5 at 24 weeks and was 3 at 52 weeks. The difference in the lesion count was significant at all time points after week 0: P < 0.05 at weeks 12 and 52, and P < 0.01 at week 24. The mean inflammation score was higher in patients clear of AKs at 12 weeks compared with those who had not cleared, 3.8 compared with 1.9. This difference was statistically significant (P < 0.05) suggesting that inflammation is necessary for efficacy. We conclude that daily application of 5% 5-FU cream is more effective than weekly application at clearing AKs from the scalp and face. Our results also suggest that inflammation is likely to be required to achieve a therapeutic effect.


Light-independent biosynthesis and assembly of the photosystem II complex in the diatom Chaetoceros gracilis.
Diatoms can survive for long periods in the dark. However, how biosynthesis of photosynthetic proteins contributes to survival in the dark is poorly understood. Using a radiolabeling technique, we examined whether de novo biosynthesis and assembly of photosynthetic proteins differs in light-adapted vs. dark-adapted marine diatoms (Chaetoceros gracilis). In light-adapted cells, D1 protein was heavily radiolabeled owing to rapid turnover of photosystem II (PSII). In dark-adapted cells (>24 h), the radiolabeling patterns of PSII components changed, but the PSII dimer still formed. Therefore, diatoms may regulate the biosynthesis of photosynthetic proteins for long-term survival in the dark.


Are there reliable predictors of postoperative pain?
The purpose of this study was to identify the preoperative determinants of severe postoperative pain. Potential predictors were assessed using a questionnaire submitted on the day before surgery. Pain at rest, and pain during coughing/mobilization, were measured using visual analog scales on the day of surgery and on the following 2 days. The type of postoperative pain management was not standardized and was prescribed by the anesthesiologist in charge. Multivariate logistic regression models explaining postoperative pain were developed in Group I, comprising 304 consecutive patients undergoing orthopedic or intraperitoneal surgery, and validated in Group II, comprising 145 independent patients. Of the 62 variables examined by univariate analysis, only five were found to increase the risk of severe postoperative pain in Group I at rest and six factors during cough/mobilization. In the multivariate model for pain at rest, general anesthesia, expectation of postoperative pain, and chronic sleeping difficulties increased the risk of severe postoperative pain. In Group II, only chronic sleeping difficulties remained (OR: 3.97, 95% Cl: 1.69-9.29). In the multivariate model during cough/mobilization, intraperitoneal surgery, fear of postoperative pain, and having a relative with a history of pain increased the risk of severe postoperative pain in Group I. Intraperitoneal surgery OR 2.45 (95% Cl = 1.01-4.50) and having a relative with a history of pain OR 2.06 (95% Cl = 1.005-4.50) remained in Group II. Of the many factors that may influence postoperative pain, chronic sleeping difficulties emerge in this population of patients as the strongest determinant of pain at rest. Intraperitoneal surgery and having a relative with a history of pain are the strongest determinants of pain during cough/mobilization. These findings make physiological sense and deserve more attention by anesthesiologists.


Organizational impact of governmental audit of blood transfusion services in Norway: A qualitative study.
Little is known about the organizational impact of supervisory activities in blood banks. We did a study with the aim to explore health professional's experiences with the external audit of blood transfusion services in Norway. The audit and supervision brought attention to deficiencies in systems and practices, and had been a catalyst for quality improvement. We identify facilitators and barriers to change. While audits can bring attention to known deficiencies, and trigger improvement processes which previously have not been prioritized, involvement of senior management is important to secure change across departments.


Fast pyrolysis char - Assessment of alternative uses within the bioliq® concept.
Experiments with a process development unit for fast pyrolysis of biomass residues of 10kgh(-1) have been performed to quantify the impact of two different product recovery options. Wheat straw, miscanthus and scrap wood have been used as feedstock. A separate recovery of char increases the organic oil yield as compared to a combined recovery of char and organic condensate (OC). Furthermore, it allows for an alternative use of the byproduct char which represents an important product fraction for the high ash biomass residues under consideration. The char produced shows little advantage over its biomass precursor when considered as energy carrier due to its high ash content. Significant value can be added by demineralizing and activating the char. The potential to increase the economic feasibility of fast pyrolysis is shown by an assessment of the bioliq® process chain.


Influence of gentamicin and tobramycin on binary biofilm formation by co-cultures of Burkholderia cepacia and Pseudomonas aeruginosa.
The aim of this study was to investigate the stability and dynamics of binary culture biofilm formation following antibiotic treatment. Pseudo steady-state biofilm cultures of clinical strains of P. aeruginosa and B. cepacia concurrently isolated from a single CF patient were established in separate Constant Depth Film Fermenters (CDFFs). Pans, containing established biofilms, were swapped between CDFFs. Biofilms were treated either for 5 days with tobramycin (0.3 mg/ml) prior to pan-swapping, or with gentamicin (1 mg/ml) immediately following pan-swapping. In both instances stable binary biofilms were formed. In addition, fresh un-colonised surfaces added at the time of pan-swapping and exposed simultaneously to biofilm derived P. aeruginosa and B. cepacia and subjected to antibiotic challenge also established stable binary communities. Treatment of P. aeruginosa and B. cepacia with tobramycin or gentamicin, either prior to or immediately after surface colonisation had little effect on the establishment of stable binary biofilms. Such treatment also had little effect on the immigration of one organism into an established biofilm of a second organism.


Relation between previous lipid-lowering therapy and infarct size (creatine kinase-MB level) in patients presenting with acute myocardial infarction.
Animal experimental data have shown that lipid-lowering agents reduce myocardial infarct size. This association has not been well studied in humans. We compared infarct size in 10,548 patients in the GUSTO IIb and PURSUIT trials who were (n = 1,028) or were not (n = 9,520) on lipid-lowering therapy before an enrolling myocardial infarction (MI). Patients using lipid-lowering agents before their index MI had smaller infarcts than those who were not using these agents (median peak creatine kinase [CK]-MB 4.2 vs 5.2 times the upper limit of normal [ULN]; p <0.0001). Similarly, in an unadjusted model, patients on previous lipid-lowering therapy were less likely to have a peak CK-MB >3 times the ULN (620 of 1,028 [60.3%] vs 6,486 of 9,520 patients [68.1%]; p <0.001; relative risk 0.88, 95% confidence interval 0.84 to 0.93, p <0.0001). In a covariate- and propensity-adjusted multivariable model, the association between pretreatment with lipid-lowering agents and smaller infarct size persisted (relative risk for CK-MB >3 times the ULN 0.94, 95% confidence interval 0.88 to 0.99, p = 0.04). In conclusion, patients on lipid-lowering agents before an MI had significantly smaller infarcts. These findings suggest that lipid-lowering therapy may exert additional salutary effects in the setting of acute coronary syndromes.


Heparin-like anticoagulant activity of sulphonated poly(ethylene oxide) and sulphonated poly(ethylene oxide)-grafted polyurethane.
Sulphonated poly(ethylene oxide) (PEO-SO3) and PEO-SO3-grafted polyurethane (PU-PEO-SO3) were prepared by bulk modification and their anticoagulant and heparin-like activities were investigated. Anticoagulant activity measured by activated partial thromboplastin time of PU-PEO-SO3 displayed 2%, whereas that of PEO-SO3 itself reached 14% as compared to free heparin. In addition, the anticoagulant effects of these sulphonated polymers were not due to factor Xa inhibition but mainly thrombin inhibition. From the clotting time measurements using reptilase instead of thrombin and antithrombin III (AT III), PEO-SO3 and PU-PEO-SO3 indicated heparin-like activity which represents both prolonged thrombin time (TT) and normal reptilase time and increased TT in the presence of AT III. Thrombin was also neutralized by sulphonated polymers to a great extent. Therefore, the anticoagulant and heparin-like activities of PEO-SO3 and PU-PEO-SO3 seem to contribute to their improved blood compatibility.


Toxicity evaluation of reactive dyestuffs, auxiliaries and selected effluents in textile finishing industry to luminescent bacteria Vibrio fischeri.
The toxicity of 17 selected process effluents, 11 reactive dyestuffs and 8 auxiliaries from a textile dyeing and finishing mill in Ayazaga, Istanbul, Turkey was evaluated by bioluminescence test using bacteria Vibrio fischeri in LUMIStox 300. The EC20 and EC50 for auxiliaries, the EC20 for dyestuffs were determined. For selected process effluents GL-values, the dilution level at which a wastewater sample causes less than 20% inhibition, were examined. Our results demonstrate that the toxicity assessment with luminescent bacteria is effective and of practical use for chemicals applied in textile finishing industry with the limitation of the deep dark-colored dye bath samples and for the related effluents. Inhibition effects of numerous dyestuffs as well as auxiliaries to luminescent bacteria differed considerably with a range 5-600 mg l(-1) for EC20 and 9-6930 mg l(-1) for EC50, respectively. Among 17 effluents, I sample exhibited high toxicity (GL = 100), 7 showed moderate toxicity (GL = 12-32), and 9 had a GL-value <10 indicating a low or no toxicity.


Single-drug parenteral estrogen treatment in prostatic cancer: a study of two maintenance-dose regimens.
Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol-17 beta (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels, increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses less than or equal to 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.


The cognitive tenacity of self-directed ageism.
Ageism refers to prejudice or discrimination based on a person's age. When ageism is directed at older people, it is unique in two ways: it is socially condoned in a manner that other types of prejudice are not, and the animus is eventually self-directed. Of central interest here is why ageism becomes self-directed in late adulthood, despite its potentially harmful personal costs. We present a cognitive model in which negative ageist beliefs become increasingly accessible and difficult to eliminate owing to broader developmental shifts in mentation. Given that these effects are contingent on our social environment, systemic changes in societal conceptions of age and aging are needed if we are to reduce vulnerability to self-directed ageism.


Proteomic Profiles of the Longissimus Muscles of Entire Male and Castrated Pigs as Related to Meat Quality.
There are indications of reduced meat quality in entire male pigs (EMs) in comparison to surgically castrated pigs (SCs); however, the differences are not strongly confirmed, and the etiology is not clarified. In the present study, samples of the longissimus dorsi, pars lumborum muscle (LL) from EMs (n = 12) and SCs (n = 12) of the same age and weight were evaluated at the physico-chemical and proteomic level. EMs exhibited lower intramuscular fat content, higher collagen content with higher solubility, a higher level of protein carbonyl groups (indicating higher protein oxidation), lower water holding capacity, and tougher meat than SCs. Proteomic analysis revealed differences in heat shock proteins expression, while a greater abundance of several other identified proteins (malate dehydrogenase, Na/K-transporting adenosintriphosphatase (ATP-ase) subunit alpha-1, and blood plasma proteins) indicates that EMs have a more oxidative metabolic profile than that of SCs. More abundant protein fragments (mainly actin and myosin heavy chain) suggest a higher degree of proteolysis in EMs, which was not followed by lower meat toughness.


Development and First Use of the Patient's Qualitative Assessment of Treatment (PQAT) Questionnaire in Type 2 Diabetes Mellitus to Explore Individualised Benefit-Harm of Drugs Received During Clinical Studies.
Individualised benefit-harm assessments can help identify patient-perceived benefits and harms of a treatment, and associated trade-offs that may influence patients' willingness to use a treatment. This research presents the first use of a patient-reported outcome measure designed to assess patient-perceived benefits and disadvantages of drugs received during clinical studies. The Patient's Qualitative Assessment of Treatment (PQAT) was developed in English and cognitively tested with US (n = 4) and Canadian (n = 3) patients with type 1 and type 2 diabetes mellitus (T2DM). The revised version of the PQAT comprises three qualitative open-ended questions focused on the benefits and disadvantages of treatment and reasons why patients would choose to continue/discontinue treatment. A final quantitative question asks patients to evaluate the balance between benefits and disadvantages using a 7-point scale. The revised version of the questionnaire was administered as an exploratory endpoint in a phase II clinical trial for a new injectable treatment for T2DM. Qualitative data were analysed using thematic analysis, and relationships between qualitative and quantitative data were identified. Patient-reported benefits of treatment administered during the clinical trial included clinical markers of efficacy and subjective markers. Disadvantages reported by patients were mainly related to drug adverse effects or to the mode of administration. Of the 57 patients completing the PQAT, 70.2% reported being willing to continue treatment, with 59.6% reporting that the benefits outweighed the disadvantages. The reported benefits of feeling better and improved energy levels were more likely to be associated with a more positive ratio (70% and 71.4%, respectively), while the disadvantages of fatigue, headaches, and stomach pain were associated with a negative ratio and patients not being willing to continue the treatment. The PQAT is a unique patient-reported outcome tool designed to aid understanding patients' real experience of benefits and disadvantages of a treatment. It combines the richness of qualitative data with quantitative data-information valuable for various stakeholders to make well-informed treatment decisions. ClinicalTrials.gov identifier: NCT02973321.


Using MTBindingSim as a tool for experimental planning and interpretation.
MTBindingSim is a program that enables users to simulate experiments in which proteins or other ligands (e.g., drugs) bind to microtubules or other polymers under various binding models. The purpose of MTBindingSim is to help researchers and students gain an intuitive understanding of binding behavior and design experiments to distinguish between different binding mechanisms. MTBindingSim is open-source, freely available software and can be found at bindingtutor.org/mtbindingsim. This chapter first describes the capabilities of MTBindingSim, including the experimental designs and protein-binding models that it simulates, and then discusses two examples in which MTBindingSim is utilized in an experimental context. In the first, MTBindingSim is used to investigate potential explanations for unusual behavior observed in the binding of the neuronal protein Tau to microtubules, demonstrating that some potential explanations are incompatible with the experimental data. In the second example, MTBindingSim is used to design experiments to examine the question of whether the plus-end tracking protein EB1 binds preferentially to the microtubule seam.


Complications and deaths after operations for esophageal carcinoma.
In a series of 908 patients with squamous cell carcinoma of the esophagus, 512 operations were performed on 503 of the patients. Postoperative mortality was the highest after bypass operations, being 41.5%. After palliative resection, mortality was 22.7% and after curative resection, 12.8%. Overall resection in 283 patients resulted in a 17% mortality. The postoperative mortality for all resections for carcinoma at the three levels was as follows: cervical and thoracic inlet, 17.6%; upper thoracic, 16.9%; and lower thoracic, 16.9%. The most frequent causes of death were anastomotic leak and pulmonary complications. Nonfatal complications occurred in 13.3% of the 512 operations.


Transport of anti-IL-6 antigen binding fragments into cartilage and the effects of injury.
The efficacy of biological therapeutics against cartilage degradation in osteoarthritis is restricted by the limited transport of macromolecules through the dense, avascular extracellular matrix. The availability of biologics to cell surface and matrix targets is limited by steric hindrance of the matrix, and the microstructure of matrix itself can be dramatically altered by joint injury and the subsequent inflammatory response. We studied the transport into cartilage of a 48 kDa anti-IL-6 antigen binding fragment (Fab) using an in vitro model of joint injury to quantify the transport of Fab fragments into normal and mechanically injured cartilage. The anti-IL-6 Fab was able to diffuse throughout the depth of the tissue, suggesting that Fab fragments can have the desired property of achieving local delivery to targets within cartilage, unlike full-sized antibodies which are too large to penetrate beyond the cartilage surface. Uptake of the anti-IL-6 Fab was significantly increased following mechanical injury, and an additional increase in uptake was observed in response to combined treatment with TNFα and mechanical injury, a model used to mimic the inflammatory response following joint injury. These results suggest that joint trauma leading to cartilage degradation can further alter the transport of such therapeutics and similar-sized macromolecules.


Real-time polymerase chain reaction for the qualitative and quantitative detection of Mycoplasma gallisepticum.
The aim of this study was to evaluate the sensitivity and the detection limit of a real-time polymerase chain reaction (Q-PCR) developed for the qualitative and quantitative detection of Mycoplasma gallisepticum. No cross-reactivity was observed with DNA from other important avian mycoplasmas, including Mycoplasma synoviae and Mycoplasma meleagridis. However, the Q-PCR could not distinguish between M. gallisepticum and Mycoplasma imitans. The Q-PCR had detection limits 10 to 1000 times lower than a conventional commercial PCR method and than culture. The Q-PCR was used quantitatively by incorporating a set of external M. gallisepticum DNA standards, derived from a M. gallisepticum log-phase culture of a known concentration. The number of colony-forming unit equivalents per millilitre in tracheal swabs from experimentally infected birds could be determined from a single sample. The method had good reproducibility and correlated well with standard counting techniques using culture. It can be concluded that the Q-PCR described is suitable for qualitative and quantitative detection of M. gallisepticum in clinical samples.


"Me and 'that' machine": the lived experiences of people with neuromuscular disorders using non-invasive ventilation.
Neuromuscular disorders (NMD) encompasses a wide range of conditions, with respiratory weakness a common feature. Respiratory care can involve non-invasive ventilation (NIV) resulting in fewer hospital admissions, a lower mortality rate and improved quality of life. The aim of this study was to explore the 'lived experience' of NIV by people with NMD. Interpretive Phenomenological Analysis (IPA) with semi-structured, face to face interviews with 11 people with NMD, using bi-level positive airway pressure for NIV for more than 12 months. Three themes were interpreted: (i) Alive, with a life; (ii) Me and 'that' machine; and (iii) Precariousness of this life. NIV enabled hope, independence and the opportunity to explore previously perceived unattainable life experiences. Yet, participants felt dependent on the machine. Furthermore, practical considerations and fear of NIV failure created a sense of precariousness to life and a reframing of personal identity. The findings highlight the broad ranging positive and negative effects that may occur for people with NMD when using this important therapy. Ongoing non-judgemental support and empathy are required from health professionals as the use of NIV challenged concepts such as 'living life well' for people with NMD. IMPLICATIONS FOR REHABILITATIONNeuromuscular disorders may result in respiratory weakness requiring non-invasive ventilation (NIV).When prescribed early, NIV can results in fewer hospital admissions, a lower mortality rate and improved quality of life.The relationship of people with NMD with their NIV machine is complex and impacts on and requires adjustment to their identity.NIV users acknowledged that NIV provided hope but simultaneously recognised the precariousness of NIV on their life.In order to better support people with NMD healthcare professionals need to better understand how the physical, psychological and social implications of NIV affect an individual's life.


Enzyme induction by estrogen.
The injection of estrogen into an immature or ovariectomized rat results in an increase in the specific activities of many uterine enzymes which can be detected, usually, within hours to days. The recent identification of the "estrogen-induced protein" as the brain type isozyme of creatine kinase (CKBB), provided an easily measurable enzyme marker, the mRNA of which doubles 1 h after estrogen injection. The increase in synthesis of CKBB from a high constitutive rate to a several-fold higher induced rate may be a more general response to hormonal stimulation in a mammalian system than the "all or none" induction exemplified by bacterial systems. This rapid estrogen-induced increase in the rate of CKBB synthesis is now reported in several rat reproductive organs; ovary, uterus, vagina and estrogen receptor-rich regions of the hypothalamus (anterior hypothalamus and median basal eminence) and preoptic areas, as well as in normal human breast tissue and in human breast tumors. The rapidity of CKBB induction makes it a favorable candidate marker for developing a cell-free induction system to study the interaction of the estrogen-receptor complex with specific loci in chromatin. For this purpose, molecular cloning of cDNA for CKBB is now under way.


HIV-associated PML presenting as epilepsia partialis continua.
Two patients with human immunodeficiency virus (HIV) type 1 infection presented new-onset epilepsia partialis continua (EPC) as an early manifestation of progressive multifocal leukoencephalopathy (PML). EPC occurred with no other seizures and was associated with negative radiographic and electrophysiological findings for several weeks. PML represents an increasingly recognized cause of new-onset seizures in both seropositive and seronegative patients, with no report of EPC as a presenting complaint.


Rapid genomic convergent evolution in experimental populations of Trinidadian guppies (Poecilia reticulata).
Although rapid phenotypic evolution has been documented often, the genomic basis of rapid adaptation to natural environments is largely unknown in multicellular organisms. Population genomic studies of experimental populations of Trinidadian guppies (Poecilia reticulata) provide a unique opportunity to study this phenomenon. Guppy populations that were transplanted from high-predation (HP) to low-predation (LP) environments have been shown to evolve toward the phenotypes of naturally colonized LP populations in as few as eight generations. These changes persist in common garden experiments, indicating that they have a genetic basis. Here, we report results of whole genome variation in four experimental populations colonizing LP sites along with the corresponding HP source population. We examined genome-wide patterns of genetic variation to estimate past demography and used a combination of genome scans, forward simulations, and a novel analysis of allele frequency change vectors to uncover the signature of selection. We detected clear signals of population growth and bottlenecks at the genome-wide level that matched the known history of population numbers. We found a region on chromosome 15 under strong selection in three of the four populations and with our multivariate approach revealing subtle parallel changes in allele frequency in all four populations across this region. Investigating patterns of genome-wide selection in this uniquely replicated experiment offers remarkable insight into the mechanisms underlying rapid adaptation, providing a basis for comparison with other species and populations experiencing rapidly changing environments.


Characterization of the complete mitochondrial genome of Plagiorchis multiglandularis (Digenea, Plagiorchiidae): Comparison with the members of Xiphidiatan species and phylogenetic implications.
Plagiorchis multiglandularis Semenov, 1927 is a common fluke of birds and mammals, with significant impacts on animals and also human health. However, the systematics of Plagiorchiidae remain ambiguous. In the present study, the complete mitochondrial (mt) genome of P. multiglandularis cercariae was sequenced and compared with other digeneans in the order Xiphidiata. The complete circular mt genome of P. multiglandularis was 14,228 bp in length. The mitogenome contains 12 protein-coding genes and 22 transfer RNA genes. The 3' end of nad4L overlaps the 5' end of nad4 by 40 bp, while the atp8 gene is absent. Twenty-one transfer RNA genes transcribe products with conventional cloverleaf structures, while one transfer RNA gene has unpaired D-arms. Comparative analysis with related digenean trematodes revealed that A + T content of mt genome of P. multiglandularis was significantly higher among all the xiphidiatan trematodes. Phylogenetic analyses demonstrated that Plagiorchiidae formed a monophyletic branch, in which Plagiorchiidae are more closely related to Paragonimidae than Prosthogonimidae. Our data enhanced the Plagiorchis mt genome database and provides molecular resources for further studies of Plagiorchiidae taxonomy, population genetics and systematics.


X-ray investigation of lateral hetero-structures of inversion domains in LiNbO3, KTiOPO4 and KTiOAsO4.
In this paper periodically domain-inverted (PDI) ferroelectric crystals are studied using high-resolution X-ray diffraction. Rocking curves and reciprocal-space maps of the principal symmetric Bragg reflections in LiNbO3 (LN) (Λ = 5 µm), KTiOPO4 (KTP) (Λ = 9 µm) and KTiOAsO4 (KTA) (Λ = 39 µm) are presented. For all the samples strong satellite reflections were observed as a consequence of the PDI structure. Analysis of the satellites showed that they were caused by a combination of coherent and incoherent scattering between the adjacent domains. Whilst the satellites contained phase information regarding the structure of the domain wall, this information could not be rigorously extracted without a priori knowledge of the twinning mechanism. Analysis of the profiles reveals strain distributions of Δd/d = 1.6 × 10(-4) and 2.0 × 10(-4) perpendicular to domain walls in KTP and LN samples, respectively, and lateral correlation lengths of 63 µm (KTP), 194 µm (KTA) and 10 µm (LN). The decay of crystal truncation rods in LN and KTP was found to support the occurrence of surface corrugations.


Effect of sodium stibogluconate and pentamidine on in vitro multiplication of Leishmania donovani in peritoneal macrophages from infected and drug-treated BALB/c mice.
The in vitro antileishmanial activity of sodium stibogluconate (SSG) and pentamidine in peritoneal macrophages from three different groups of animals (i.e. normal, Leishmania donovani-infected and drug-treated BALB/c mice) is reported. Peritoneal macrophages were extracted from all these animals and infected in vitro with L. donovani promastigotes. After 24 h, the infected macrophages (with amastigotes) were exposed to various concentrations of SSG (10-90 micrograms/mL) and pentamidine (0.1-5.0 micrograms/mL). The in vitro infection could be cured readily with 80 micrograms/mL of SSG and 4 micrograms/mL of pentamidine in macrophages from normal animals. But even higher dosages of these drugs added in vitro could not reduce the amastigote loads in macrophages from infected animals. In contrast, incubation in vitro of infected macrophages with very low dosages of these drugs (40 micrograms/mL of SSG and 1.0 mu/mL of pentamidine) could eliminate the parasites present within macrophages obtained from drug-treated animals. This was probably because the macrophages from drug-treated animals tackled the parasites themselves by their microbicidal mechanisms and the in vitro infection was tackled by the drug in vitro. This implies that a well-developed specific immunity in leishmaniasis helps in the antileishmanial activity of these drugs.


Evaluation of vanillic acid as inhibitor of carbonic anhydrase isozyme III by using a modified Hummel-Dreyer method: approach for drug discovery.
α-3 carbonic anhydrase isozyme (CAIII) is the most abundant protein in adipocytes and considered insensitive to sulfonamide inhibitors. It was reported recently that the knock-down of CAIII is attributed with controlling lipogenesis. Thus inhibition of this target may lead to the discovery of new therapies against obesity and insulin resistance. Vanillic acid as a small molecule with coordinating groups and has a potential to bind zinc atoms in CA binding sites. Inhibition of CAIII by vanillic acid was evaluated by Hummel-Dreyer chromatography because it provides free interaction between ligand and macromolecule and introduces solution for faulty results obtained by current colorimetric assays. HPLC system of vanillic acid produces vacancy (negative) peak representing the amount of attached vanillic acid with CAIII. It was found that vanillic acid is able to bind with CAIII through two equilibria, one at equimolar ratio and another at 2:1 (vanillic acid-CAIII) ratio. The affinity constant of equimolar binding between CAIII and vanillic acid was found to be 14,400 m(-1) . It was found that vanillic acid binding with CAIII is much stronger than phenol and acetazolamide (positive controls).


"Frustrated Exocytosis"--a novel phenomenon: membrane fusion without contents release, followed by detachment and reattachment of dense core vesicles in Paramecium cells.
The lipophilic fluorescent dye, FM1-43, as now frequently used to stain cell membranes and to monitor exo-endocytosis and membrane recycling, induces a cortical [Ca(2+)](i) transient and exocytosis of dense core vesicles ("trichocysts") in Paramecium cells, when applied at usual concentrations (</=10 microm) in presence of extracellular Ca(2+) ([Ca(2+)](o) = 50 microm). When [Ca(2+)](o) is kept at 30 nm (<[Ca(2+)](rest)(i)), in about one third of the population of extrudable trichocysts docked at the cell membrane, FM1-43 induces membrane fusion, visible by FM1-43 fluorescence of the vesicle membrane. However, in this system extrusion of secretory contents cannot occur in absence of any sufficient Ca(2+)(o). Upon readdition of Ca(2+)(o) or some other appropriate Me(2+)(o) at 90 microm, secretory contents can be released (complete exocytosis). Resulting ghosts formed in presence of Ca(2+), Sr(2+) or Mn(2+) are vesicular, but when formed in presence of Mg(2+), for reasons to be elucidated, they are tubular, though both types are endocytosed and lose their FM1-43 stain. In contrast, in presence of [Mg(2+)](o) = 3 mm (which inhibits contents release), the exocytotic openings reseal and intact trichocysts with labeled membranes and with still condensed contents are detached from the cell surface ("frustrated exocytosis") within approximately 15 min. They undergo cytoplasmic streaming and saltatory redocking, with a half-time of approximately 35 min. During this time, the population of redocked trichocysts amenable to exocytosis upon a second stimulus increases with a half-time of approximately 35 min. Therefore, acquirement of competence for exocytotic membrane fusion may occur with only a small delay after docking, and this maturation process may last only a short time. A similar number of trichocysts can be detached by merely increasing [Mg(2+)](o) to 3 mm, or by application of the anti-calmodulin drug, R24517 (calmidazolium). Essentially we show (i) requirement of calmodulin and appropriate [Me(2+)] to maintain docking sites in a functional state, (ii) requirement of Ca(2+)(o) or of some other Me(2+)(o) to drive membrane resealing during exo-endocytosis, (iii) requirement of an "empty" signal to go to the regular endocytotic pathway (with fading fluorescence), and (iv) occurrence of a "filled" signal for trichocysts to undergo detachment and redocking (with fluorescence) after "frustrated exocytosis".


Biological pretreatment with a cellobiose dehydrogenase-deficient strain of Trametes versicolor enhances the biofuel potential of canola straw.
The use of Trametes versicolor as a biological pretreatment for canola straw was explored in the context of biofuel production. Specifically, the effects on the straw of a wild-type strain (52J) and a cellobiose dehydrogenase (CDH)-deficient strain (m4D) were investigated. The xylose and glucose contents of the straw treated with 52J were significantly reduced, while only the xylose content was reduced with m4D treatment. Lignin extractability was greatly improved with fungal treatments compared to untreated straw. Saccharification of the residue of the m4D-treated straw led to a significant increase in proportional glucose yield, which was partially attributed to the lack of cellulose catabolism by m4D. Overall, the results of this study indicate that CDH facilitates cellulose access by T. versicolor. Furthermore, treatment of lignocellulosic material with m4D offers improvements in lignin extractability and saccharification efficacy compared to untreated biomass without loss of substrate due to fungal catabolism.


The effect of device use after sequential bilateral cochlear implantation in children: An electrophysiological approach.
In many studies evaluating the effect of sequential bilateral cochlear implantation in congenitally deaf children, device use is not taken into account. In this study, however, device use was analyzed in relation to auditory brainstem maturation and speech recognition, which were measured in children with early-onset deafness, 5-6 years after bilateral cochlear implantation. We hypothesized that auditory brainstem maturation is mostly functionally driven by auditory stimulation and is therefore influenced by device use and not mainly by inter-implant delay. Twenty-one children participated and had inter-implant delays between 1.2 and 7.2 years. The electrically-evoked auditory brainstem response was measured for both implants separately. The difference in interaural wave V latency and speech recognition between both implants were used in the analyses. Device use was measured with a Likert scale. Results showed that the less the second device is used, the larger the difference in interaural wave V latencies is, which consequently leads to larger differences in interaural speech recognition. In children with early-onset deafness, after various periods of unilateral deprivation, full-time device use can lead to similar auditory brainstem responses and speech recognition between both ears. Therefore, device use should be considered as a relevant factor contributing to outcomes after sequential bilateral cochlear implantation. These results are indicative for a longer window between implantations in children with early-onset deafness to obtain symmetrical auditory pathway maturation than is mentioned in the literature. Results, however, must be interpreted as preliminary findings as actual device use with data logging was not yet available at the time of the study.


The yield of continuous EEG monitoring in the intensive care unit at a tertiary care hospital in Saudi Arabia: A retrospective study.
Background: The practice of continuous EEG monitoring (CEEG) in the intensive care unit (ICU) has been spreading over the past decade. Building an effective ICU CEEG program with sufficient quality demands adequate EEG equipment and significant human resources. While this is available in large tertiary care centers where the practice of CEEG has developed, it may not be available in developing healthcare systems. This study sought to provide data generated from a CEEG program in the adult ICU at a tertiary healthcare center in Saudi Arabia, shedding light on the real-life utility of CEEG in a developing healthcare system. Methods: This is a retrospective review of CEEG findings, along with mortality and duration of hospitalization of patients who had CEEG during a 12-month period at the adult ICU at the King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Results: A total of 202 CEEG records were identified. A total of 52 patients had non-convulsive seizures (NCS); 10 clearly fulfilled criteria for non-convulsive status epilepticus. There were 120 patients that had clinical seizures upon presentation. Among them, 36 (30%) had NCS on EEG. The proportion of patients who were deceased at 60 days was higher in patients who had NCS (42%) than those who didn't (26%, χ 2 (2, n=200)= 4.4, p=0.03). The duration of hospital stay was longer for those who had periodic or rhythmic CEEG patterns (χ 2 (2, n=200)= 7.6, p=0.02) but there was no significant relationship with mortality at 60 days. Conclusion: This study demonstrates a real-world experience from a tertiary care center in Saudi Arabia, a developing healthcare system. Findings are consistent with prior experience with ICU CEEG, demonstrating that finding ictal, rhythmic or periodic patterns is associated with morbidity and mortality. Further studies are needed to demonstrate how the practice of CEEG may alter patient outcomes.


Secondary reactive oxygen species production after PDT during pulmonary tumor growth in sera of nude mice.
Photodynamic therapy (PDT), mediated by a sensitizer exposed to light to produce singlet oxygen ((1)O2), induces tumor responses varying from one person to another. Cancer growth induces oxidative stress at any step of its development from induction to treatment, which could also modify response to PDT. After the initial amount of (1)O2 delivered, secondary oxidative species (SOS) are also generated inducing additional damages. Using an in vitro assay we saw variations among mice strains concerning their serum capability to generate SOS after (1)O2 production. Nude mice had a higher capability to generate SOS as compared to the non mutated strain. Capability to generate SOS evolved during growth of orthotopically-grafted pulmonary cancers (A549), with either values corrected for hemolysis or not. Immediately after graft SOS production decreased, then increased again, reaching a plateau phase after 10 days which lasted for 20 days and finally increased steeply during the last phase of tumor growth, preceding cachexia and death. This profile differed profoundly from the one observed after heterotopic tumor grafts for which hemolysis induced artifacts masking important variations in SOS production. Our results demonstrate experimentally a relationship between the general health status of an individual, cancer progression and serum capability to generate SOS during PDT. These findings could explain some PDT failures as well as some unexpected successes on large tumors and should be taken into account when determining treatment parameters. They may also explain why different effects are observed on different experimental models with similar sensitizers.


A hypothesis on the action of chromosomal genes.
According to the analysis of the chromosomal genes which act in development, we advance a model of gene action in development. In this model, the development is regarded as the programming action of different gene groups. The action of each and every gene group will activate the next gene group and make a self-inhibition. Therefore, the activation and inhibition of genes is a chain reaction during development; it is unlikely that the action of genes is entirely from inhibition to respective activation (Morgan model, 1934) or entirely from activation to respective inhibition (Caplan-Ordhal model, 1978). We use this model to explain some biological problems, such as development and differentiation, senescence and the cancer. According to our model, development and differentiation are not the same thing, senescence is the self-inhibition of the last gene group in somatic cells and the oncogene is the connexion gene in the programming action of gene groups.


Calcium regulation of inositol 1,4,5-trisphosphate receptors.
Ca2+ exerts both a stimulatory and inhibitory effect on type-I IP3R channel activity. However, the structural determinants of Ca2+ sensing in IP3Rs are not fully understood. Previous studies by others have identified eight domains of the type-I IP3R that bind 45Ca2+ when expressed as GST-fusion proteins. We have mutated six highly conserved acidic residues within the second of these domains (aa378-450) in the full-length IP3R and measured the Ca2+ regulation of IP3-mediated Ca2+ release in COS-7 cells. 45Ca2+ flux assays measured with a maximal [IP3] (1 microM) indicate that one of the mutants retained a Ca2+ sensitivity that was not significantly different from control (E411Q), three of the mutants show an enhanced Ca2+ inhibition (D426N, E428Q and E439Q) and two of the mutants were relatively insensitive to Ca2+ inhibition (D442N and D444N). IP3 dose-response relationships indicated that the sensitivity to Ca2+ inhibition and affinity for IP3 were correlated for three of the constructs. Other mutants with enhanced IP3 sensitivity (e.g. R441Q and a type-II/I IP3R chimera) were also less sensitive to Ca2+ inhibition. We conclude that the acidic residues within the aa378-450 segment are unlikely to represent a single functional Ca2+ binding domain and do not contribute to Ca2+ activation of the receptor. The different effects of the mutations may be related to their location within two clusters of acidic residues identified in the crystal structure of the ligand-binding domain [I. Bosanac, J.R. Alattia, T.K. Mal, et al., Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand, Nature 420 (2002) 696-700]. The data support the view that all IP3R isoforms may display a range of Ca2+ sensitivities that are determined by multiple sites within the protein and markedly influenced by the affinity of the receptor for IP3.


Hypertrophic cardiomyopathy and systemic lupus erythematosus.
We report the case of a 45 year-old woman with systemic lupus erythematosus (SLE), who developed clinical and echocardiographic signs of hypertrophic cardiomyopathy. Neither a family history of cardiomyopathy or sudden death nor a personal history of hypertension or valvular lesions were present. The association of SLE with hypertrophic cardiomyopathy has been previously described in only 2 patients.


Label-free multiphoton imaging of β-amyloid plaques in Alzheimer's disease mouse models.
β -Amyloid ( A β ) plaque, representing the progressive accumulation of the protein that mainly consists of A β , is one of the prominent pathological hallmarks of Alzheimer's disease (AD). Label-free imaging of A β plaques holds the potential to be a histological examination tool for diagnosing AD. We applied label-free multiphoton microscopy to identify extracellular A β plaque as well as intracellular A β accumulation for the first time from AD mouse models. We showed that a two-photon-excited fluorescence signal is a sensitive optical marker for revealing the spatial-temporal progression and the surrounding morphological changes of A β deposition, which demonstrated that both extracellular and intracellular A β accumulations play an important role in the progression of AD. Moreover, combined with a custom-developed image-processing program, we established a rapid method to visualize different degrees of A β deposition by color coding. These results provide an approach for investigating pathophysiology of AD that can complement traditional biomedical procedures.


Unusual case of papillary thyroid carcinoma mimicking paraganglioma in a 16-year-old girl.
Papillary thyroid carcinoma is a common neoplasm arising from follicular cells of the thyroid. Differentiating the neck mass between thyroid paraganglioma and papillary thyroid carcinoma is often difficult. We report a 16-year-old girl with painless neck mass. Physiological goiter was suspected initially but we found papillary thyroid carcinoma. CT neck revealed hyper vascular lesions in bilateral lobes of thyroid. DSA imaging was done for further evaluation which showed high flow fistulous type of lesion supplying from superior thyroidal artery raising suspicion of paraganglioma. Postoperative biopsy ultimately revealed papillary carcinoma of thyroid in the background of hashimotos' thyroiditis with metastatic deposits in neck lymph nodes. Thyroid paraganglioma is a rare type of tumor, it arises from inferior laryngeal paraganglioma within thyroid capsule and is as thus difficult to distinguish from thyroid carcinomas. A biopsy is the best diagnostic choice but immunohistochemistry is the only investigation which is considered as the gold standard for distinguishing between these two diseases.


Multiple myeloma masquerading as mandibular medication-related osteonecrosis of the jaw: a case report.
This is a unique case report of a 67-year-old female diagnosed with multiple myeloma and extensive use of intravenous bisphosphonate, whose clinical and radiographic presentation of an oral lesion made it challenging to confirm its definitive diagnosis. This patient was referred to the dental service for a suspected medication-related osteonecrosis of the jaw (MRONJ). Clinically, the lesion was located underneath a fixed partial denture in the left posterior mandible. There was a purulent swelling on the lingual side of the fixed partial denture, and a hyperplastic exophytic lesion on the buccal side of the bridge. Panoramic radiograph showed a well circumscribed radiolucent lesion in the left mandible. A biopsy of the gingival lesion on the buccal aspect was inconclusive. As the positron emission tomography scan showed lytic lesions, oral manifestation of multiple myeloma could not be ruled out. A computed tomography-guided biopsy of the left mandible showed plasma cell neoplasm in the histological analysis. Upon confirmed diagnosis, the patient was treated with 20Gy to the left mandible and subsequent debridement of the loose necrotic bone. Following treatment, this gingival lesion resolved completely, and the tumour has remained stable till date.


Validation and analysis of prognostic scoring systems for critically ill patients with cirrhosis admitted to ICU.
The number of patients admitted to ICU who have liver cirrhosis is rising. Current prognostic scoring tools to predict ICU mortality have performed poorly in this group. In previous research from a single centre, a novel scoring tool which modifies the Child-Turcotte Pugh score by adding Lactate concentration, the CTP + L score, is strongly associated with mortality. This study aims to validate the use of the CTP + L scoring tool for predicting ICU mortality in patients admitted to a general ICU with cirrhosis, and to determine significant predictive factors for mortality with this group of patients. This study will also explore the use of the Royal Free Hospital (RFH) score in this cohort. A total of 84 patients admitted to the Glasgow Royal Infirmary ICU between June 2012 and Dec 2013 with cirrhosis were included. An additional cohort of 115 patients was obtained from two ICUs in London (St George's and St Thomas') collected between October 2007 and July 2009. Liver specific and general ICU scoring tools were calculated for both cohorts, and compared using area under the receiver operating characteristic (ROC) curves. Independent predictors of ICU mortality were identified by univariate analysis. Multivariate analysis was utilised to determine the most predictive factors affecting mortality within these patient groups. Within the Glasgow cohort, independent predictors of ICU mortality were identified as Lactate (p < 0.001), Bilirubin (p = 0.0048), PaO2/FiO2 Ratio (p = 0.032) and PT ratio (p = 0.012). Within the London cohort, independent predictors of ICU mortality were Lactate (p < 0.001), PT ratio (p < 0.001), Bilirubin (p = 0.027), PaO2/FiO2 Ratio (p = 0.0011) and Ascites (p = 0.023). The CTP + L and RFH scoring tools had the highest ROC value in both cohorts examined. The CTP + L and RFH scoring tool are validated prognostic scoring tools for predicting ICU mortality in patients admitted to a general ICU with cirrhosis.


Ischemic stroke accompanied by anti-PR3 antibody-related cerebral vasculitis and hepatitis C virus infection.
Hepatitis C virus (HCV) infection has been found to be strikingly associated with autoimmune phenomena. Autoantibodies are commonly found in patients with HCV infection. The aim of the present study was to investigate the presence of anti-neutrophil cytoplasmic antibody (ANCA) in patients with ischemic stroke and HCV infection. ANCA were determined in sera from 36 patients with ischemic stroke and HCV infection (18 females, 18 males, mean age 75+/-10 years) and 44 healthy controls. Assays employed were indirect immunofluorescence for detection of ANCA and ELISA for anti-proteinase 3 (anti-PR3-ANCA). No one of the patients studied received IFN-alpha treatment before blood collection. ANCA were positive in 21 out of 36 (58 %) patients with ischemic stroke and HCV infection. All sera with ANCA showed cANCA patterns and contained anti-PR3 specificity. HCV patients with ANCA showed a higher prevalence of cerebral vasculitis. HCV may be regarded as a possible causative factor in ANCA-related vasculitis.


Application of topological methods in enzyme kinetics.
A criticism [Cornish-Bowden (1976) Biochem. J. 159, 167] of an algebraic method for deriving steady-state rate equations [Indge & Childs (1976) Biochem. J. 155, 567-570] is theoretically founded.