In vitro digestion of spermidine and amino acids in fresh and processed Agaricus bisporus mushroom.
Mushrooms are significant sources of amino acids and bioactive amines; however, their bioaccessibility can be affected by processing and during in vitro digestion. Fresh Agaricus bisporus mushroom was submitted to cooking and canning and samples were submitted to in vitro gastric and gastric-intestinal digestions. An UHPLC method was used for the simultaneous determination of 18 free amino acids, 10 biogenic amines and ammonia in the samples. Fresh mushroom contained 14 free amino acids, with predominance of alanine and glutamic acid; spermidine was the only amine detected; and ammonia was also detected. Spermidine levels were not affected by cooking, but there was a significant loss (14%) after canning. Spermidine levels were not affected by the in vitro gastric and intestinal digestion, suggesting full bioaccessibility. There was a significant decrease on total amino acids levels after cooking and canning, with higher losses for aspartic and glutamic acids in cooked and for aspartic acid and valine in canned mushrooms. After the in vitro gastric and intestinal digestions, the total levels of amino acids increased and two additional amino acids (arginine and methionine) were detected. During in vitro digestion many of the amino acids were released mainly in the intestinal phase. After in vitro digestion, amino acids per gram of protein of mushrooms are adequate for most FAO amino acid pattern for adults. Multivariate analysis confirmed that protein hydrolysis in processed mushrooms is higher in intestinal phase. Bioaccessibility data for spermidine in A. bisporus is a novelty and increase the value of this food.


Infection-related vasculitis.
Infection-related vasculitis constitutes the most common cause of secondary vasculitis. A great variety of microorganisms can induce directly or indirectly inflammatory vascular damage resulting in vascular occlusion, tissue ischemia, and necrosis. In the developed world hepatitis B and C-related vasculitis remain the most common clinical syndromes, while HIV-associated vasculitis remains a concern in developing countries.


The pairing of light and heavy chains of isomeric anti-lactose antibodies.
Sets of polyclonal isomeric anti-carbohydrate antibodies are present in sera of rabbits immunized with vaccines of non-viable streptococcal cells containing antigenic glycans. Anti-lactose antibodies have been purified by affinity chromatography and have been subjected to dissociation, electrophoretic and agar diffusion analyses. The anti-lactose antibody preparation was found to be composed of 16 isomeric proteins which yield 16 heavy chains and 16 light chains.


An exploratory study of the relation between psychoticism and certain aspects of auditory hallucinations in schizophrenics.
30 schizophrenics who met the criteria of Feighner et al. and were having verbal auditory hallucination with or without hallucinations of other varieties were chosen for the study. Psychoticism was measured with the help of Eysenck's Personality Questionnaire. The relation of psychoticism scores to different aspects of auditory hallucinations was examined. High psychoticism scores seemed to be associated with a greater number of languages of the voice, known living 'speakers' and less fear and passive listening during the voice.


Impulse control and criminal responsibility: lessons from neuroscience.
Almost all of the world's legal systems recognize the "M'Naghten" exception to criminal responsibility: the inability to appreciate the wrongfulness of action. This exception rests on the assumption that punishment is morally justified only if the defendant was able to choose whether to do wrong. Jurists and jurisdictions differ, however, on whether to extend M'Naghten's logic to cases where the defendant understood the wrongfulness of an act but was incapable of resisting an impulse to commit it. In this article I ask whether contemporary neuroscience can help lawmakers to decide whether to adopt or retain this defense, known variously as the "irresistible impulse" defense or the "control" or "volitional" test for insanity. More specifically, I ask firstly, whether it is empirically true that a person can understand the wrongfulness of an act yet be powerless to refrain from committing it; and second (assuming an affirmative answer to the first), whether the law of criminal responsibility can practically accommodate this phenomenon? After canvassing the relevant neuroscientific literature, I conclude that the answer to the first question is "yes." After examining the varied treatment of the defense in the United States and other nations, I also give an affirmative answer to the second question, but only in limited circumstances. In short, the defense of irresistible impulse should be recognized, but only when it can be shown that the defendant experienced a total incapacity to control his or her conduct in the circumstances.


Development of safe and efficient novel nonviral gene transfer using ultrasound: enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle.
Although clinical trials of stimulation of angiogenesis by transfection of angiogenic growth factors using naked plasmid DNA or adenoviral vector have been successful, there are still unresolved problems for human gene therapy such as low transfection efficiency and safety. From this viewpoint, it is necessary to develop safe and efficient novel nonviral gene transfer methods. As therapeutic ultrasound induces cell membrane permeabilization, ultrasound irradiation might increase the transfection efficiency of naked plasmid DNA into skeletal muscle. Thus, we examined the transfection efficiency of naked plasmid DNA using ultrasound irradiation with echo contrast microbubble (Optison) in vitro and in vivo experiments. First, we examined the feasibility of ultrasound-mediated transfection of naked plasmid DNA into skeletal muscle cells. Luciferase plasmid mixed with or without Optison was transfected into cultured human skeletal muscle cells using ultrasound (1 MHz; 0.4 W(2)) for 30 s. Interestingly, luciferase activity was markedly increased in cells treated with Optison, while little luciferase activity could be detected without Optison (P < 0.01). Electron microscopy demonstrated the transient formation of holes (less than 5 microM) in the cell surface, which could possibly explain the rapid migration of the transgene into the cells. Next, we studied the in vivo transfection efficiency of naked plasmid DNA using ultrasound with Optison into skeletal muscle. Two days after transfection, luciferase activity in skeletal muscle transfected with Optison using ultrasound was significantly increased about 10-fold as compared with plasmid alone. Successful transfection was also confirmed by beta-galactosidase staining. Finally, we examined the feasibility of therapeutic angiogenesis using naked hepatocyte growth factor (HGF) plasmid in a rabbit ischemia model using the ultrasound-Optison method. Five weeks after transfection, the angiographic score and the number of capillary density in rabbits transfected with Optison using ultrasound was significantly increased as compared with HGF plasmid alone (P < 0.01), accompanied by a significant increase in blood flow and blood pressure ratio (P < 0.01). Overall, the ultrasound transfection method with Optison enhanced the transfection efficiency of naked plasmid DNA in vivo as well as in vitro. Transfection of HGF plasmid by the ultrasound-Optison method could be useful for safe clinical gene therapy to treat peripheral arterial disease without a viral vector system.


Estimates of carbon stored in harvested wood products from the United States forest service northern region, 1906-2010.
Global forests capture and store significant amounts of CO2 through photosynthesis. When carbon is removed from forests through harvest, a portion of the harvested carbon is stored in wood products, often for many decades. The United States Forest Service (USFS) and other agencies are interested in accurately accounting for carbon flux associated with harvested wood products (HWP) to meet greenhouse gas monitoring commitments and climate change adaptation and mitigation objectives. This paper uses the Intergovernmental Panel on Climate Change (IPCC) production accounting approach and the California Forest Project Protocol (CFPP) to estimate HWP carbon storage from 1906 to 2010 for the USFS Northern Region, which includes forests in northern Idaho, Montana, South Dakota, and eastern Washington. Based on the IPCC approach, carbon stocks in the HWP pool were increasing at one million megagrams of carbon (MgC) per year in the mid 1960s, with peak cumulative storage of 28 million MgC occurring in 1995. Net positive flux into the HWP pool over this period is primarily attributable to high harvest levels in the mid twentieth century. Harvest levels declined after 1970, resulting in less carbon entering the HWP pool. Since 1995, emissions from HWP at solid waste disposal sites have exceeded additions from harvesting, resulting in a decline in the total amount of carbon stored in the HWP pool. The CFPP approach shows a similar trend, with 100-year average carbon storage for each annual Northern Region harvest peaking in 1969 at 937,900 MgC, and fluctuating between 84,000 and 150,000 MgC over the last decade. The Northern Region HWP pool is now in a period of negative net annual stock change because the decay of products harvested between 1906 and 2010 exceeds additions of carbon to the HWP pool through harvest. However, total forest carbon includes both HWP and ecosystem carbon, which may have increased over the study period. Though our emphasis is on the Northern Region, we provide a framework by which the IPCC and CFPP methods can be applied broadly at sub-national scales to other regions, land management units, or firms.


Pre-diagnostic circulating p53 autoantibodies and subsequent lung cancer risk in low-income African and European Americans.
Mutations of the TP53 gene lead to the production of autoantibodies against p53, a major tumor suppressor protein. Although studies have indicated the association of p53 autoantibodies with human cancers, epidemiologic evidence on lung cancer is still lacking. In this nested case-control study conducted within the Southern Community Cohort Study, we investigated the association of circulating p53 autoantibodies with the subsequent risk of developing lung cancer. Using blood samples collected prior to any cancer diagnosis from 295 cases and their individually matched controls, seroreactivity to p53 was assessed by fluorescent bead-based multiplex serology. Conditional logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for lung cancer risk associated with p53 autoantibodies. After adjustment for potential confounders, p53 seropositivity was significantly associated with an increased risk of lung cancer (OR=2.98, 95 % CI: 1.10-8.06) among African Americans, but not among European Americans (OR=1.21, 95 % CI: 0.24-6.15). The positive associations were restricted to men (OR=4.59, 95 % CI: 1.30-16.16) and participants with a short interval (≤ 4 years) from blood collection to diagnosis (OR=4.30, 95 % CI: 1.33-13.89). Our findings add to the evidence supporting p53 autoantibodies as a biomarker of lung cancer.


Accuracy of intraoperative frozen section analysis of nasopharyngeal carcinoma resection margins.
Frozen section analysis (FSA) is frequently used in salvage surgery for recurrent or residual nasopharyngeal carcinoma (rNPC) after radiotherapy to ensure adequate tumor removal. However, the diagnostic accuracy of FSA in rNPC has never been clearly established. We believe that this is the first study to specifically address these issues. Patients with rNPC who underwent nasopharyngectomy in Queen Mary Hospital from 2006 to 2011 were identified. Clinical data, FSA results, and permanent histological results were analyzed. In the tissue-based analysis, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 70.6%, 100%, 100%, 95.2%, and 95.7%, respectively. Only 37% of inconclusive FSA turned out negative on permanent histology. Presence of inconclusive (p = .000) or positive (p = .000) FSA results in the same operation significantly lowered the NPV of FSA. FSA is useful in ensuring clear resection margins for rNPC. Further resection is advisable in cases of inconclusive FSA results.


Polymer architectures via mass spectrometry and hyphenated techniques: A review.
This review covers the application of mass spectrometry (MS) and its hyphenated techniques to synthetic polymers of varying architectural complexities. The synthetic polymers are discussed as according to their architectural complexity from linear homopolymers and copolymers to stars, dendrimers, cyclic copolymers and other polymers. MS and tandem MS (MS/MS) has been extensively used for the analysis of synthetic polymers. However, the increase in structural or architectural complexity can result in analytical challenges that MS or MS/MS cannot overcome alone. Hyphenation to MS with different chromatographic techniques (2D × LC, SEC, HPLC etc.), utilization of other ionization methods (APCI, DESI etc.) and various mass analyzers (FT-ICR, quadrupole, time-of-flight, ion trap etc.) are applied to overcome these challenges and achieve more detailed structural characterizations of complex polymeric systems. In addition, computational methods (software: MassChrom2D, COCONUT, 2D maps etc.) have also reached polymer science to facilitate and accelerate data interpretation. Developments in technology and the comprehension of different polymer classes with diverse architectures have significantly improved, which allow for smart polymer designs to be examined and advanced. We present specific examples covering diverse analytical aspects as well as forthcoming prospects in polymer science.


Separation of calcium-48 isotope by crown ether chromatography using ethanol/hydrochloric acid mixed solvent.
Benzo-18-crown-6 ether resin embedded in porous silica beads was synthesized and used as the packing material for chromatographic separation of (48)Ca isotope. The aim of the present work is to develop efficient isotope enrichment process for double β decay nuclide (48)Ca. To this end, ethanol/HCl mixed solvent was selected as the medium for the chromatographic separation. Adsorption of calcium on the resin was studied at different HCl concentrations and different ethanol mixing ratios in batch-wise experiments. A very interesting phenomenon was observed; Ca adsorption is controlled not by the overall HCl concentration of the mixed solvent, but by the initial concentration of added HCl solution. Calcium break-through chromatography experiments were conducted by using 75v/v% ethanol/25v/v% 8M HCl mixed solvent at different flow rates. The isotope separation coefficient between (48)Ca and (40)Ca was determined as 3.8×10(-3), which is larger than that of pure HCl solution system. Discussion is extended to the chromatographic HETP, height equivalent to a theoretical plate.


Alpha cell receptor for advanced glycation end products associate with glucagon expression in type 1 diabetes.
Hypoglycemia in type 1 diabetes associates with changes in the pancreatic islet α cells, where the receptor for advanced glycation end products (RAGE) is highly expressed. This study compared islet RAGE expression in donors without diabetes, those at risk of, and those with type 1 diabetes. Laser-dissected islets were subject to RNA bioinformatics and adjacent pancreatic tissue were assessed by confocal microscopy. We found that islets from type 1 diabetes donors had differential expression of the RAGE gene (AGER) and its correlated genes, based on glucagon expression. Random forest machine learning revealed that AGER was the most important predictor for islet glucagon levels. Conversely, a generalized linear model identified that glucagon expression could be predicted by expression of RAGE signaling molecules, its ligands and enzymes that create or clear RAGE ligands. Confocal imaging co-localized RAGE, its ligands and signaling molecules to the α cells. Half of the type 1 diabetes cohort comprised of adolescents and a patient with history of hypoglycemia-all showed an inverse relationship between glucagon and RAGE. These data confirm an association between glucagon and islet RAGE, its ligands and signaling pathways in type 1 diabetes, which warrants functional investigation into a role for RAGE in hypoglycemia.


Nuclear magnetic resonance imaging of the heart.
NMR imaging is a noninvasive technique that has been shown to provide high-quality images of the heart. Due to the signal characteristics of flowing blood, inherent contrast between blood pool and myocardium is achieved without the use of contrast media. This paper briefly describes technical aspects of NMR imaging of the heart, normal cardiovascular anatomy, applications of the technique in patients with ischemic heart disease, and the potential of NMR imaging for functional studies in various forms of heart disease.


Buckling procedures for retinal detachment caused by retrolental fibroplasia in premature babies.
Three premature babies with advanced stages of retrolental fibroplasia underwent retinal surgery by buckling procedures, with satisfactory results. The indications and surgical technical problems are discussed.


Emergency nurses' experience of providing care to patients who self-harm.
Individuals who self-harm may present to emergency departments (EDs) for medical care. As first responders, emergency nurses can have a significant impact on the health outcomes of people who self-harm. This research explored emergency nurses' experiences of working with patients who self-harm. Data were collected using semi-structured interviews and analysed using Elo and Kyngäs' inductive content analysis. Researcher checks ensured consensus of identified categories. Adherence to the research method and inclusion of participant citations added to the trustworthiness of findings. Eighteen emergency nurses from across Australia participated in the research. The category "Nurses' level of preparedness to work with people who self-harm" emerged during data analysis with four sub-categories: (1) Nurses' level of comfort to work with people who self-harm; (2) Nursing role; (3) Barriers and facilitators to providing quality care; and (4) Education and training. The ED is a challenging environment to provide care to people who present with self-harm. Nurses' level of comfort and attitudes towards caring for people who self-harm improved with knowledge, support and experience. Education and training in the area were important.


Sensory information processing in patients with nonalcoholic cirrhosis. Short-latency visual, auditory, and somatosensory event-related potentials.
Visual, auditory and brainstem event-related potentials were obtained from patients with hepatocellular and cholestatic disease and a control group of normal subjects. The results did not reveal systematic neurophysiologic disturbances in persons with well compensated cirrhosis. It is concluded that short-latency event-related potentials are rather insensitive for detecting subclinical hepatic encephalopathy.


Apparent affinity and potency of BIBP3226, a non-peptide neuropeptide Y receptor antagonist, on purported neuropeptide Y Y1, Y2 and Y3 receptors.
The newly developed, purported non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 was evaluated for its potential effect on the recently characterized Y3 receptor subtype and for its apparent affinity in rat and human brain membrane binding assays using highly selective neuropeptide Y Y1 and Y2 radioligands. BIBP3226 potently blocked (pA2 = 7.36) the contractile effect of neuropeptide Y in the rabbit saphenous vein, a Y1 receptor bioassay and demonstrated nM affinity for Y1/[125I][Leu31,Pro34]peptide YY binding sites. In contrast, it failed to antagonize the biological effects of neuropeptide Y in the rat vas deferens (Y2) and rat colon (Y3) and did not significantly competed for Y2/[125I]peptide YY-(3-36) binding sites in rat and human brain homogenates. Taken together, the results demonstrate further the high potency and selectivity of BIBP3226 for the neuropeptide Y Y1 receptor by establishing its lack of antagonist activity on the Y3 subtype.


Glatiramer acetate: evidence for a dual mechanism of action.
Glatiramer acetate is a disease-modifying drug approved for the treatment of relapsing-remitting multiple sclerosis. Since its discovery almost four decades ago, and in particular since the observation of its beneficial clinical effects in the late 1980s and early 1990s, numerous data have been generated and contribute pieces of a puzzle to help explain the mechanism of action of glatiramer acetate. Two major themes have emerged, namely (i) the induction of glatiramer acetate-reactive TH2 immunoregulatory cells, and (ii) the stimulation of neurotrophin secretion in the central nervous system that may promote neuronal repair.


Meiosis in Plasmodium: how does it work?
Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites appears to diverge from the process with respect to the molecular mechanisms involved; the biology of Plasmodium meiosis, and its regulation by means of post-translational modification, are largely unexplored. Here, we discuss the impact of technological advances in cell biology, evolutionary bioinformatics, and genome-wide functional studies on our understanding of meiosis in the Apicomplexa. These parasites, including Plasmodium falciparum, Toxoplasma gondii, and Eimeria spp., have significant socioeconomic impact on human and animal health. Understanding this key stage during the parasite's life cycle may well reveal attractive targets for therapeutic intervention.


Maternal, placental and fetal exposure to bisphenol A in women with and without preeclampsia.
We aimed to investigate potential association between the exposure of bisphenol A (BPA) and preeclampsia. Concentrations of BPA were assessed in 58 pregnancies including 35 normotensive and 23 preeclamptic women, using a highly sensitive gas chromatography-mass spectrometry (GC-MS) method. BPA was detected in maternal blood, fetal blood and placental tissue; and actual concentrations of BPA were determined. Interestingly, significant accumulation of BPA in the placentas of women with preeclampsia compared to normotensive women has been shown. This is the first study to highlight a significant correlation between preeclampsia and a high accumulation of BPA in the placenta.


Cellular heterogeneity in normal human urothelium: quantitative studies of lectin binding.
A panel of 10 FITC-labelled lectins (MPA, PNA, ConA, DBA, SBA, RCA-120, WGA, UEA, GS-I, GS-II+) was applied to cryosections of seven specimens of normal urothelium. Seven of the lectins (MPA, ConA, RCA, WGA, UEA, GS-I and GS-II) showed a pattern of increasing fluorescence intensity from basal to superficial cells of the urothelium whereas PNA, DBA and SBA showed more uniform binding throughout the urothelium. Urothelial cell suspensions labelled with FITC-lectins were studied by flow cytometry to quantify the variation in binding to different cells types. Three cellular subpopulations were identified in normal urothelium on the basis of their optical properties. Fluorescence intensity due to specific lectin binding was then measured separately for each subpopulation. Although there was some variation among individual cases, a general pattern emerged in this small series. WGA, RCA, and GS-II bind in large quantities to all urothelial cells while PNA, SBA, ConA and DBA show little binding. MPA, RCA, UEA and GS-I showed the most marked increase in fluorescence intensity from basal to superficial cells as observed microscopically and quantified by flow cytometry.


Investigation on the biodegradability of mycotoxins nivalenol (NIV) and deoxynivalenol (DON) in a rusitec fermentor and their monitoring by HPLC/MS.
Biodegradation of two B-trichothecenes nivalenol (NIV) and deoxynivalenol (DON) have been studied in a RUSITEC (rumen simulation technique) system. The fermentation studies were carried out in vessels containing the rumen fluid. To reach steady state an adaptation period of one week was carried out. The mycotoxin standards were then added into the fermentor in a concentration of 1ppm NIV and 2ppm DON. The kinetics of NIV and DON biodegradability during the fermentation process were monitored by using a rapid HPLC method combined with a mass spectrometer and an atmospheric pressure chemical ionisation (APCI(-)) interface. Also the effect of mycotoxin addition on different parameters such as ammonia production, pH, gas production and volatile fatty acids have been studied.


The effects of choline on body temperature in conscious rats.
Choline (75-300 microg) produced dose-dependent hypothermia when injected intracerebroventricularly (i.c.v.). Pre-treatment with the muscarinic receptor antagonist, atropine (10 microg, i.c.v.), blocked the hypothermic effect of choline (150 microg), but the response was only partially attenuated by pre-treatment with the nicotinic receptor antagonist, mecamylamine (20 microg, i.c.v.). Pirenzepine (25 microg), a muscarinic M1 receptor antagonist, or hexahydro-siladifenidol (HHSD) (100 microg), a muscarinic M3 receptor antagonist, also blocked choline-induced hypothermia when injected centrally. Unlike the other muscarinic receptor antagonists, M2-selective 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyri do[2,3-b][1,4]benzodiazepin-6-one (AF-DX116) (10 microg), did not affect choline-induced hypothermia. We also found that choline-induced hypothermia was very sensitive to the ambient temperature. Similar to its effect at room temperature, choline produced dose-dependent hypothermia at 4 degrees C, but this effect was abolished at 32 degrees C. These data suggest that choline produces hypothermia and this effect is mediated by muscarinic receptors.


Generation of radio waves in pulsars.
Pulsars generate radio waves by an unknown process which gives the highest volume emissivity known in astrophysics. The radiation forms a beam the width and polarization of which are independent of frequency. This article assembles the observational facts which any theory of emission must explain.


Enhanced striatal glutamate release after the administration of rimonabant to 6-hydroxydopamine-lesioned rats.
While recent studies have shown that the blockade of cannabinoid CB(1) receptors might be beneficial to alleviate the motor inhibition typical of Parkinson's disease (PD), the neurochemical substrates for this effect remain elusive. Here we have carried out microdialysis experiments to determine whether the effects of rimonabant, a selective antagonist of CB(1) receptors, might be associated with changes in striatal glutamate release in a rat model of PD generated by intracerebroventricular injection of 6-hydroxydopamine. Our data demonstrate that the treatment with rimonabant slightly increased striatal glutamate release in control rats, although this effect was only evident with the highest dose of rimonabant tested (1mg/kg). However, the increase in glutamate release was much more marked in the parkinsonian rats where similar changes were observed at a dose of 1 and 0.1mg/kg, exactly the same dose that relieved motor inhibition in previous behavioral studies. In summary, the potential of rimonabant to act as a possible antihypokinetic agent in parkinsonian rats seems to be related to enhanced glutamate release from excitatory afferents to the striatum. This observation is of potential clinical interest, particularly for those parkinsonian patients that exhibit a poor response to classic levodopa treatment.


Poly[tetra-aqua-(5-hy-droxy-pyridin-1-ium-3-carboxyl-ato-κO (3))tris-(μ-oxalato-κ(4) O (1),O (2):O (1'),O (2'))dieuropium(III)].
In the title compound, [Eu2(C6H5NO3)2(C2O4)3(H2O)4] n , the Eu(III) atom is bonded to one O atom from a monodentate 5-hy-droxy-pyridin-1-ium-3-carboxyl-ate ligand, six O atoms from three oxalate ligands and two water mol-ecules, exhibiting a highly distorted tricapped trigonal geometry. Three independent oxalate ligands, each lying on an inversion center, bridge the Eu(III) atoms, forming a brickwall-like layer parallel to (001), which is stabilized by intra-layer O-H⋯O hydrogen bonds. The layers are further linked through inter-layer O-H⋯O and N-H⋯O hydrogen bonds and π-π inter-actions between the pyridine rings [centroid-centroid distance = 3.5741 (14) Å] into a three-dimensional supra-molecular network.


Is the time from the onset to the treatment a prognostic indicator for hearing recovery in idiopathic sudden sensorineural hearing loss?
This study aims to investigate whether the time from the onset of symptoms to the start of treatment is a prognostic indicator in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). In this study, 96 patients (58 males, 38 females; mean age 37.8±2.5 years; range 16 to 67 years) who were diagnosed with ISSNHL in our clinic between January 1992 and April 2010 were retrospectively analyzed. All patients were treated with dextran 40 (rheomacrodex), pentoxifyllin, vitamin B complex and vitamin C regimen over 10 days with hospitalization and bed rest. The patients were tested by pure-tone audiometry. Audiograms were obtained on alternate days and at the end of the treatment. There was a complete recovery in 45 (60%) of 75 patients whose treatment was started in the first seven days, while a partial recovery was observed in 17 (22.66%) and no recovery was observed in 13 (17.33%). There was a complete recovery in two (9.52%) of 21 patients whose treatment was started after the eighth day, while a partial recovery was observed in seven (33.33%) and no recovery was observed in 12 (57.14%). Our study results suggest that treatment outcomes are better in the patients presenting to hospital at an early stage of loss of hearing.


The actions of 3-aminopropanephosphinic acid at GABAB receptors in rat hippocampus.
The actions of 3-aminopropanephosphinic acid (APPA) were examined using whole-cell patch-clamp recording in rat hippocampal slice. In recordings from neurons in subfield CA1 of slices from young (2-4 weeks) and adult (greater than 2 month) rats, APPA (0.5-50 microM) produced membrane hyperpolarization and outward current under voltage-clamp. APPA also inhibited excitatory postsynaptic potentials with an IC50 of 2.3 microM, and reduced inhibitory postsynaptic potentials at concentrations from 0.1 to 1 microM. The hyperpolarizing and synaptic depressant effects of APPA were reduced by 2-OH-saclofen an antagonist at the B-type receptor for the neurotransmitter gamma-aminobutyric acid (GABA). In this preparation APPA exhibited potencies similar to those previously reported for the GABAB receptor agonist baclofen. APPA was much less effective in inhibiting synaptic transmission measured using field potential recordings. The observations made with whole-cell patch-clamp recording indicate that in hippocampus APPA acts as a potent agonist at presynaptic GABAB receptors associated with both excitatory and inhibitory synapses, and also activates postsynaptic GABAB receptors.


Systemic Diseases and Conditions Affecting Jaws.
This article discusses the radiographic manifestation of jaw lesions whose etiology may be traced to underlying systemic disease. Some changes may be related to hematologic or metabolic disorders. A group of bone changes may be associated with disorders of the endocrine system. It is imperative for the clinician to compare the constantly changing and dynamic maxillofacial skeleton to the observed radiographic pathology as revealed on intraoral and extraoral imagery.


Decreased phosphoribosylpyrophosphate as the basis for decreased purine synthesis during amino acid starvation of human lymphoblasts.
Rates of de novo and salvage purine synthesis decrease by approximately 80 and 60%, respectively, when normal human lymphoblasts are starved 3 h for an essential amino acid (Boss, G. R., and Erbe, R. W. (1982) J. Biol. Chem. 257, 4242-4247). Amino acid starvation decreased the intracellular phosphoribosylpyrophosphate (PP-Rib-P) and ribose 5-phosphate concentrations by approximately 40%, but neither the specific activities of PP-Rib-P synthetase and glutamine amidophosphoribosyltransferase nor the intracellular concentrations of purine nucleotides and inorganic phosphate changed significantly. In mutant cells with either an increased capacity to generate PP-Rib-P (superactive PP-Rib-P synthetase), or an increased PP-Rib-P concentration (inosinate-guanylate:pyrophosphate phosphoribosyltransferase deficiency), the intracellular PP-Rib-P concentration decreased by less than 15% during amino acid starvation and de novo purine synthesis decreased significantly less than in normal cells. When normal cells were treated with drugs that simultaneously decreased feed-back inhibition by purine nucleotides and increased the intracellular concentration of ribose 5-phosphate and PP-Rib-P rates of de novo purine synthesis were stimulated 3-fold in nonstarved cells and more than 8-fold in starved cells. This greater stimulation in the starved cells appeared to be from the increased PP-Rib-P production; moreover, in starved cells in which the increase of the PP-Rib-P concentration by the drugs was impaired because of purine nucleoside phosphorylase deficiency, rates of de novo purine synthesis increased only 3.5-fold. The data suggest that amino acid starvation decreases purine synthesis by decreasing the generation of PP-Rib-P from glucose.


Thyroid hormone (fT4) reduces lipoprotein(a) plasma levels.
To study the influence of thyroid hormone on Lp(a) plasma concentration we measured Lp(a), total cholesterol, LDL-C, HDL-C, triglycerides and fT4 levels and determined apo(a) phenotypes in 26 patients with hyperthyroidism in a follow-up study before and after thyreostatic treatment. The pretreatment values of total cholesterol (TC), LDL-C, and Lp(a) were significantly reduced as compared with those of healthy controls. The reduced mean Lp(a) concentrations could not be explained by a difference of apo(a) 'size allele' frequencies between patients and controls. During thyreostatic treatment mean concentrations of TC, LDL-C, and HDL-C increased significantly. The mean Lp(a) value was not changed after 4 weeks of treatment. The individual changes of Lp(a), however, correlated significantly with those of LDL-C levels (R = 0.40, P = 0.04). Eighty-one per cent of the patients showed an increase of Lp(a) or no change of the Lp(a) level and 19% reacted with a decrease upon thyreostatic treatment. The observed lipid and lipoprotein changes were not different in patients with Graves disease or multifocal toxic goiter. The results indicate that Lp(a) plasma levels are decreased in the hyperthyroid state irrespective of the pathogenic mechanism.


Effects of wheat germ agglutinin and concanavalin A on parameters of highly purified sodium-potassium adenosine triphosphatases from Squalus acanthias and Electrophorus electricus.
The effects of two lectins, wheat germ agglutinin and concanavalin A, were studied on a variety of parameters of two highly purified (Na+ + K+)-ATPases (ATP phosphohydrolase, EC 184.108.40.206), from the rectal salt gland of Squalus acanthias and from the electroplax of Electrophorus electricus. Both lectins agglutinated the rectal gland enzyme equally, but wheat germ agglutinin inhibited (Na+ + K+)-ATPase activity much more. The electroplax enzyme was only marginally agglutinated and inhibited by the lectins. Neuraminidase treatment of the rectal gland (Na+ + K+)-ATPase had no effect on germ agglutinin inhibition. The inhibition of the rectal gland (Na+ + K+)-ATPase by wheat germ agglutinin could be reversed by N,N'-diacetylchitobiose, which has a high affinity for wheat germ agglutinin. Neither ouabain inhibition nor ouabain binding to the rectal gland enzyme was affected by wheat germ agglutinin. The p-nitrophenylphosphatase activity of the rectal gland enzyme was not inhibited by wheat germ agglutinin. Na+-ATPase activity, which reflects ATP binding and phosphorylation at the substrate site was inhibited by wheat germ agglutinin and this inhibition was reversed by potassium. Evidence is cited (Pennington, J. and Hokin, L.E., in preparation) that the inhibition of the (Na+ + K+)-ATPase by wheat germ agglutinin is due to binding to the glycoprotein subunit.


Strength-interval relation for ventricular functional refractoriness.
Successful initiation and termination of presumed reentrant ventricular tachycardia frequently depends on the ability to deliver closely coupled impulses to the region of the tachycardia origin. To evaluate systematically the relative influence of local latency and large-scale conduction delay in limiting the delivery of closely coupled impulses, the strength-interval relation of the effective refractory period (RP), and the local and remote functional RP in 35 patients at paced cycle length of 500 ms were measured. The pacing threshold was less than or equal to 0.25 mA in all patients. The drive-train (S1) and the extrastimulus (S2) were applied from the same site, the right ventricular (RV) apex, in 25 patients, and from separate sites (RV apex and RV outflow tract) in 10 patients. The effect of procainamide (plasma concentration 10.1 +/- 2.3 micrograms/ml) on the strength-interval relations in 10 patients was also assessed. Although effective RP decreased significantly with each successive increase in current strength (p less than 0.001), local functional RP decreased only up to current strength of 4 mA, and remote functional RP decreased only up to 2 mA. Procainamide shifted the effective RP and local and remote functional RP strength-interval curves uniformly to the right without altering their relation. These data indicate that large-scale conduction delay provides the principal limitation for using increasing current strengths of a single extrastimulus to initiate or terminate ventricular tachycardia.


Decrease in incidence of hepatitis A infections in Germany.
The hypothesis of a decline in the incidence of hepatitis A infections in Germany in recent decades was confirmed by determining the prevalence of hepatitis A antibody (anti-HAV) in sera collected in 1965 and in 1975 under the same conditions in North Germany. The prevalence of anti-HAV correlated with the year of birth and was independent of the time of serum sampling. The force of infection fell from 0.04 in 1945 to 0.005 in 1965 as judged from a catalytic epidemic model with a sigmoidal decrease.


Modulation of Neuroimmune and Epithelial Dysregulation in Patients With Moderate to Severe Prurigo Nodularis Treated With Nemolizumab.
Prurigo nodularis (PN) is a debilitating skin disease characterized by intense pruritus and hyperkeratotic skin nodules. Nemolizumab, a monoclonal antibody targeting interleukin 31 receptor α, is a promising novel therapy for the treatment of moderate to severe PN. The biological mechanisms by which nemolizumab promotes improvement of itch and skin lesions in PN are unknown. To characterize changes in plasma protein biomarkers associated with clinical response to nemolizumab in patients with PN. This multicenter cohort study included patients recruited from Austria, France, Germany, Poland, and the US from a phase 2 clinical trial. Adults diagnosed with moderate to severe PN with severe pruritus for at least 6 months were included in the original trial. Patients in the nemolizumab group were included in the present study if they achieved at least a 4-point decrease in the Peak Pruritus Numerical Rating Scale (PP-NRS) from baseline to week 12 during nemolizumab treatment. Placebo controls did not experience a 4-point decrease in PP-NRS. Mass spectrometry with tandem mass tags to enrich skin-specific protein detection was used to characterize changes in plasma protein expression in nemolizumab and placebo groups. Data were collected from November 2, 2017, to September 26, 2018, and analyzed from December 6, 2019, to April 8, 2022. As part of the clinical trial, patients were treated with 3 doses of nemolizumab or placebo at 0, 4, and 8 weeks. Changes in plasma and epidermal protein expression in nemolizumab-treated patients compared with the placebo group at 0, 4, and 12 weeks. Among the 38 patients included in the analysis (22 women and 16 men; mean [SD] age, 55.8 [15.8] years), enrichment analysis of canonical pathways, biological functions, and upstream regulators showed downregulation of terms involving inflammation (IL-6, acute-phase response, signal transducer and activator of transcription 3, and interferon γ), neural processes (synaptogenesis signaling and neuritogenesis), tissue remodeling and fibrosis (transforming growth factor β1 and endothelin-1), and epidermal differentiation (epithelial mesenchymal transition) in the plasma of nemolizumab group. In this cohort study, differences between nemolizumab and placebo groups included modulation of inflammatory signaling, neural development, and epithelial differentiation, suggesting a promising potential approach for clinical management of PN.


Mass cultivation of Dunaliella salina in a flat plate photobioreactor and its effective harvesting.
Mass cultivation of Dunaliella salina was standardized in a flat plate photobioreactor followed by a vertical flat plate photobioreactor. Maximum biomass productivity (14.95 ± 0.43 mgL-1d-1 dry cell weight) was achieved in the latter at inoculum concentration of OD680nm = 0.1, 100 µmolm-2s-1 light illumination and 1.0 L min-1 aeration. Semicontinuous operation with varying KNO3 and NaHCO3 concentrations resulted highest biomass productivity (17.85 ± 0.55 mgL-1d-1) at 0.50 mM NaHCO3 and 15 mM KNO3. However, maximum lipid (16.36 ± 1.18% dry cell weight) was achieved at 0.75 mM NaHCO3 and 10 mM KNO3. Flocculation studies employing potash alum, FeCl3·6H2O or pH showed harvesting efficiencies exceeding 90% in 0.75 mM potash alum or FeCl3·6H2O or pH 11, but they yielded low concentration factor (<5) and were detrimental (Fv/Fm < 0.50). A combination of 0.50 mM FeCl3·6H2O and pH 9 was found as most suitable flocculating strategy with maximum concentration factor (>14) and least damaging (Fv/Fm > 0.54).


Induction and suppression of renal and hepatic cytochrome P450-dependent monooxygenases by acute and chronic streptozotocin diabetes in hamsters.
The acute and chronic effects of streptozotocin diabetes on kidney and liver microsomal monooxygenases were studied using hamsters 2 days and 6 weeks following treatment with the diabetogen, respectively. Acute diabetes increased aniline hydroxylation and N-nitrosodimethylamine demethylation, decreased pentoxyresorufin O-dealkylation, without affecting benzo(a)pyrene hydroxylation and 7-ethoxycoumarin O-deethylation in kidney and liver microsomes. The effects of chronic diabetes on the microsomal monooxygenases were similar to the effects of acute diabetes, except that the chronic diabetic condition markedly decreased benzo(a)pyrene and 7-ethoxycoumarin oxidations in kidney microsomes. Total cytochrome P450 content and NADPH-cytochrome P450 reductase activity in kidney and liver microsomes of the diabetic hamsters were similar to the controls. Gel electrophoresis of microsomes from control and streptozoptocin treated hamster tissues revealed that diabetes enhanced the intensity of protein band(s) in the P450 molecular weight region. Immunoblotting of microsomal proteins showed that acute and chronic streptozotocin diabetes induced proteins immunorelated to P450s 2E1 and 1A in kidney and liver. In marked contrast, the acute and chronic diabetic conditions decreased the level of a P450 2B-immunorelated protein(s) in kidney and liver. The present study demonstrates that acute and chronic streptozotocin diabetes has the ability to induce P450 2E1 and 1A and suppress P450 2B in hamster kidney and liver and that the hamster monooxygenase responds to diabetes differently from the rat enzyme.


Exploring Attitudes of Children 12-17 Years of Age Toward Electronic Cigarettes.
The purpose of this study is to explore electronic cigarettes (EC) use among youth. Focus group sessions with youth (aged 12-17) were held to explore their knowledge and attitudes about EC use. Content analysis techniques were used. There has been an increase in the visibility and accessibility of EC in the past few years among youth. Compared with conventional cigarettes (CC), youth indicated that they would be more willing to use EC under their peer influence. This was motivated by the perception that EC were less harmful. Among youth EC are perceived as less harmful, easier to access and use than CC. Youth do not appear to have received much education about EC. However, they were not convinced that EC were risk free. Clear and unambiguous education about the risk of engaging in any form of smoking/vaping and enforcement of access restrictions appear to be required.


Comparing anti-hyperglycemic activity and acute oral toxicity of three different trivalent chromium complexes in mice.
Three different ligands (rutin, folate and stachyose) of chromium(III) complexes were compared to examine whether they have similar effect on anti-hyperglycemic activity as well as the acute toxicity status. Anti-hyperglycemic activities of chromium rutin complex (CrRC), chromium folate complex (CrFC) and chromium stachyose complex (CrSC) were examined in alloxan-induced diabetic mice with daily oral gavage for a period of 2 weeks at the dose of 0.5-3.0 mg Cr/kg. Acute toxicities of CrRC and CrFC were tested using ICR mice at the dose of 1.0-5.0 g/kg with a single oral gavage and observed for a period of 2 weeks. Biological activities results indicated that only CrRC and CrFC could decrease blood glucose level, reduce the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and increase liver glycogen level. In acute toxicity study, LD(50) values for both CrRC and CrFC were above 5.0 g/kg. The minimum lethal dose for CrFC was above 5.0 g/kg, while that for CrRC was 1.0 g/kg. Anti-diabetic activity of those chromium complexes was not similar and their acute toxicities were also different. CrFC represent an optimal chromium supplement among those chromium complexes with potential therapeutic value to control blood glucose in diabetes and non-toxicity in acute toxicity.


Acquisition of fluorescence and reflectance spectra during routine bronchoscopy examinations using the ClearVu Elite device: pilot study.
Fluorescence flexible bronchoscopy (FFB) has proved to be very useful for detecting carcinoma in situ (CIS) and pre-cancerous lesions of the lung that are generally occult to white light reflectance bronchoscopy (WLRB). However, the increased sensitivity has caused a significant decrease of specificity, resulting in a large number of false positive signals that lead to a significant number of unnecessary biopsies. We have been planning to test a hypothesis that reflectance spectra and fluorescence spectra could be used to distinguish the true positive lesions from the false positive ones. To properly test such hypothesis, several thousand patients will need to be examined to obtain sufficient data from different lung lesions. Towards this goal, we have developed and have been testing a special system (ClearVu Elite ) that facilitates acquisition of both WLRB and FFB spectra during routine bronchoscopy examinations. In this pilot study we examined (1) if such could be used in a practical, routine clinical conditions without affecting commonly used bronchoscopy procedures; (2) if the spectral data obtained from the images are identical to those obtained with fiber-optic probes; and (3) if the few malignant and early neoplastic lesions available for this pilot study show any differences from normal lung tissue. The study population consisted of 63 patients that were suspicious for presence of lung cancer (19 female and 44 male, smokers and non-smokers). All were examined by diagnostic bronchoscopy using ClearVu Elite during a period of 8 weeks. The experimental system provides excellent real time WLRB and FFB that can be switched from one to another mode instantaneously. Acquisition of both white light reflectance spectra and fluorescence spectra is acquired in real time through the images and does not prolong the routine WLRB and FFB procedures. The experimental bronchoscopy procedure is as simple as conventional bronchoscopy, adding on average less than 5 min to the 20 min procedure. The acquired spectra are identical to those obtained by fiber-optic probes. In all of the limited number of malignant and early neoplastic lesions, there were differences found which are sufficiently pronounced to warrant initiation of a large, multicenter study for development of differentiating algorithms of statistical validity.


The finasteride prostate cancer prevention trial (PCPT)--what have we learned?
In 2003, the first of two large NCI-sponsored prostate cancer chemoprevention trials was reported. The prostate cancer prevention trial (PCPT) demonstrated a 24.8% reduction in the prevalence of prostate cancer in men taking finasteride 5mg/d for 7 years. However, despite the overall reduced risk of prostate cancer, men in the finasteride-treated arm of the study were more likely to develop high-grade disease. This article examines some of the controversies aroused by the PCPT and evaluates some of the arguments that have been advanced in an attempt to explain some of the unexpected outcomes of the study. In addition, some of the recent studies assessing the potential impact of an effective chemopreventive strategy on population mortality are reviewed. To conclude, there is some discussion of factors, which need to be openly discussed with male patients who might be considered for finasteride therapy.


Administration of mylotarg 4 days after beginning of a chemotherapy including intermediate-dose aracytin and mitoxantrone (MIDAM regimen) produces a high rate of complete hematologic remission in patients with CD33+ primary resistant or relapsed acute myeloid leukemia.
We have used the dose of 9 mg/m(2) of mylotarg 4 days after the beginning of a chemotherapy including intermediate-dose aracytin and mitoxantrone (MIDAM) in 17 patients with refractory (n=4) or relapsed (n=13) AML. Thirteen patients (76%) achieved CR (n=12) or partial CR (n=1). All four refractory patients and all four patients with poor risk cytogenetic achieved CR or CRp. Although the dose of mylotarg given in combination with chemotherapy was not reduced, the toxicity profile was acceptable (1VOD/17 patients). The MIDAM protocol appears to be highly effective especially in patients with poor risk cytogenetic and/or refractory disease.


Neutrophil-lymphocyte ratio as a predictive marker for postoperative infectious complications: A systematic review and meta-analysis.
Postoperative infection is a common but costly complication. The neutrophil-lymphocyte ratio is a promising marker for the identification of postsurgical infectious events. We aimed to perform this meta-analysis to assessed the accuracy of the neutrophil-lymphocyte ratio for the prediction of postsurgical infection. We searched PubMed, Embase, Web of Science, and Cochrane Library without language restriction from their inceptions to April 2022, and checked reference lists of included studies. Studies were included if they assessed predictive accuracy of neutrophil-lymphocyte ratio for postsurgical infection. We estimated its predictive value and explored the source of heterogeneity. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess methodological quality and the Deeks' test to evaluate publication bias. The bivariate model and hierarchical summary receiver operating characteristic (HSROC) curve were used for meta-analysis and generated a summary receiver operating characteristic space (ROC) curve. Our search returned 379 reports, of which 12 fulfilled the inclusion criteria, accounting for 4375 cases. The bivariate analysis yielded a pooled sensitivity of 0.77 (95%C.I.: 0.65-0.85) and specificity of 0.78 (95%C.I.: 0.67-0.86). Pooled positive LR and negative LR were 3.48 (95%C.I.: 2.26-5.36) and 0.30 (95%C.I.: 0.20-0.46), respectively. A negative LR of 0.30 reduces the post-test probability to 2% for a negative test result. The area under of receiver operating characteristic curve was 0.84 (95%C.I.: 0.80-0.87). Subgroups comparisons revealed difference by study design, surgical site, presentence of implant, time of sampling, type of infection event and prevalence of infection. The Deeks' test showed no publication bias. The sensitivity analysis showed no study affected the robustness of combined results. Low-certainty evidence suggests that the neutrophil-lymphocyte ratio is a helpful marker for predicting postoperative infectious complication. The negative predictive value of the neutrophil-lymphocyte ratio enables for reliable exclusion of postoperative infection.Trial registrationPROSPERO registration number CRD42022321197. Registered on 27 April 2022.


[Postcoital bleeding: 68 case-reports and review of the literature].
Consensual or imposed sexual act can cause traumas. Post coital bleeding is a common gynecological symptom. It can reveal serious problems. The aim of our study is to analyze the epidemiological, diagnostic and therapeutic profile as well as preventive measures in case of post coital tear. This is a prospective study, over two years, conducted in the Department of Obstetrics and Gynecology at the Center Hospital University Mohammad VI (CHU) in Marrakech. We collected 68 patients. The average age was 27 years. Most of the patients were nulliparous (89.7% of the cases). Half of the patients had traditional wedding. Sexual intercourse was consensual in 74% of the cases. Vaginal bleeding was the most frequent reason for consultation (98% of the cases). Hymenal lesions were found in 39% of the cases and the lesion involved the posterior fornix of the vagina in 35% of the cases. Therapeutic management consisted of a surgical suture in 97% of the cases, associated with blood transfusion in two patients and sexual abstinence of all patients for at least two weeks. The social context as well as the lack of sex education were often highlighted, hence the importance of psychological support to prevent both the impact of traumas on sexuality and the recurrences.


Combining prehabilitation with enhanced recovery programs in gynecological surgery.
Prehabilitation is a multimodal approach to preoperative care based on physical exercise, dietary/nutritional interventions, smoking and alcohol cessation, and psychological care. The goal is to reduce stress and apprehension, encourage general well-being, and thus optimize the patient's state of health before surgery. Prehabilitation encompasses all the actions undertaken between the diagnosis of the disease and the initiation of surgery to reduce the morbidity attributable to the latter. Although there are few literature data on prehabilitation in gynecological surgery, the management of moderate-to-severe undernutrition prior to gynecological oncology surgery reduces the risk of postoperative complications and increases the overall survival rate.


Thermoluminescence properties and identification of irradiated cocoa beans during long-term storage.
This work reports on the thermoluminescence (TL) properties and detection of contaminating minerals isolated from Mexican cocoa beans irradiated with gamma radiation and stored for 4 years. Contaminating minerals isolated from cocoa beans consisting of quartz, diopside, plagioclase, albite, and iron oxide with irregular and rectangular grains and average length of 135 μm. Cocoa beans are detected as irradiated even after 4 years of storage using the shape and maximum temperature of the TL glow curve of contaminating minerals. The TL properties of dose-response, and fading of minerals were also analysed. The TL dose-response is linear from 5 to 100 Gy, supra-linear between 250 and 1000 Gy, and sub-linear above 1500 Gy. Based on the TL1/TL2 ratio the minerals are identified as irradiated from 250 Gy to 4500 Gy in the dose-response test and after different storage times in the darkness at room temperature. A continuum trap distribution can be associated with the TL glow curve of minerals using the Tm-Tstop method. First order kinetic peaks were used in the Glow Curve Deconvolution of natural and irradiated (1 and 10 kGy) TL curves.


Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced gastric mucosal lesions in rats.
We previously demonstrated the circadian variation of water-immersion restraint stress (WRS)-induced gastric mucosal lesions in rats. To investigate the roles of melatonin and prostaglandin in the gastric mucosa in circadian modulation of WRS. Fasted rats were subjected to 4-h WRS during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2 (PGE2) and mucosal gene expressions of cyclooxygenase (COX)-1 and -2 were evaluated. Lesion area after 4-h stress during the dark phase was significantly smaller than that in light-phase controls. Serum melatonin concentration in control rats during the light phase was significantly increased 4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in intact mucosa before stress. In the dark phase, melatonin concentration after 4-h WRS was significantly depressed as compared with the control level at the corresponding time. PGE2 concentrations after 4-h WRS in the dark phase were not decreased compared with the control level at the corresponding time, although PGE2 level was significantly lower than that in light-phase controls. Expression of COX-1 and COX-2 mRNA was detected after exposure to stress in both the light and dark phases. These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats. The circadian rhythm of melatonin responses and PGE2 generation may contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between day and night.


The anatomy and complications of "T" versus vertical closure of the hypopharynx after laryngectomy.
The early postoperative hypopharyngeal anatomy of 37 consecutive patients undergoing total laryngectomy at the Boston Veteran's Administration Hospital between July 1977 and April 1980 was studied by barium swallow radiographs and correlated with the technique of closure. The "pseudoepiglottis," a structure radiographically resembling a normal epiglottis, was seen arising from the anterior hypopharynx near the base of the tongue in 21 of 28 evaluable patients. It occurred in all patients with vertical closures vs. 67% of patients with a "T" shaped closure. The average length in the "T" closure group was 9.6 mm (range 0-35) vs. 18.4 mm (6-40) in the vertical group, a statistically significant difference (p less than 0.05). Radiologic strictures occurred in 39% of all patients, dysphagia in 29%, fistulae in 18%, and sinus tracts in 14%. All complications occurred more frequently in the vertical closure group. Patients who received preoperative cis-platinum bleomycin chemotherapy and postoperative irradiation had 50% dysphagia and 67% stricture rates. The average ratio of the width of the retropharyngeal space to that of C4 was 0.48 in stricture patients vs. 0.29 in non-stricture patients (statistically significant at the p less than 0.01 level). This ratio taken in the early postoperative period may help predict which patients will develop strictures.


Quantitation of LH subunits released by rat anterior pituitary cells in primary culture.
Immunoreactive rLH, rLH alpha, rLH beta and rFSH in the cell extracts and medium of rat anterior pituitary cell cultures were measured after gel filtration on Sephadex G-100 Superfine. Cell extracts contained uncombined rLH alpha and rLH beta present as approximately 40% and 4%, respectively, of native rLH on a molar basis. Unstimulated cultures appeared to release a large excess of rLH alpha (approximately 2560% of rLH on a molar basis) as well as a minimum of uncombined rLH beta. Stimulation of cultures with physiological (LHRH) or non-physiological agents (A23187, elevated K+) increased the absolute but not the relative quantities of uncombined subunits released relative to those present intracellularly. Thus, rat anterior pituitary cell cultures appear to produce and release an excess of free alpha subunit as well as a minimum of uncombined rLH beta. However, one cannot be certain whether the uncombined rLH beta represents a pool of 'free' rLH beta or simply results from the dissociation of rLH.


Daytime driving simulation performance and sleepiness in obstructive sleep apnoea patients.
Sleepiness related car accidents are common in obstructive sleep apnoea syndrome (OSAS) patients. The objective measurements of sleepiness used in clinical setting quantify the tendency to fall asleep in quiet situations that are completely different from driving. We studied 30 OSAS patients with subjective (subjective sleepiness scales) and objective (multiple sleep latency test, MSLT) sleepiness measurements, associated with driving simulation test (DST), previously validated in young healthy subjects. The results of subjective and objective sleepiness tests were compared with simulated driving performance in order to evaluate the suitability of our DST for measuring alertness. Subjective and objective sleepiness measurements were significantly correlated with driving performance on the simulator. The most significant correlates of sleepiness were the measures of the primary vehicle control task on the simulator: lane position variability and crash data. The comparison of DST and MSLT results suggested our driving simulated approach could be used to evaluate daytime sleepiness in the clinical setting of OSAS patients. Our DST is a suitable objective tool to detect sleepiness in OSAS patients, and could be useful in the clinical setting of sleep medicine and research.


Pitfalls to avoid: spasm in ulcerative colitis masquerading as carcinoma.
A barium enema on a patient with chronic ulcerative colitis demonstrated a stricture with the radiographic characteristics of an annular carcinoma. The "lesion" disappeared following administration of glucagon.


Cerebrospinal fluid ferritin in glioblastoma: evidence for tumor synthesis.
Ferritin concentrations in cerebrospinal fluid (CSF) of 16 patients with glioblastoma were found to be very high (mean, 103.0 ng/mL) relative to 29 patients with viral meningitis and 20 patients with headache (mean concentrations, 5.4 and 4.3 ng/mL respectively). Simultaneous measurement of ferritin in CSF and serum revealed CSF concentrations exceeding those in serum in 11 of 16 patients with glioblastoma (CSF vs. serum ratio, 132.6%), contrasting with very low ratios in patients with meningitis (7.9%) or headache (4.9%). Ferritin was detected immunocytochemically in tumor cell cytoplasm in a resected glioblastoma. Thus, ferritin in CSF appears to be produced by glioblastoma cells, with a biologic significance requiring further investigation.


Warfarin enantiomer disposition: determination by stereoselective radioimmunoassay.
Immunoassay techniques offer promise for the selective analysis of enantiomeric substances without prior separation. In a demonstrationof this selective analysis, radioimmunoassays were developed for R- and S-warfarin. The 4'-carboxyethyl analog of R,S-warfarin was resolved and the enantiomeric acids were coupled to bovine serum albumin. Immunization of rabbits with the conjugates led to formation of antisera which selectively bound the predicted enantiomer. Cross-reactions with various metabolites of warfarin were low (0.1--4%) except for 4'-hydroxywarfarin, as were cross-reactions with the opposite enantiomer (0.3--3%). Assays were developed and used to determine enantiomer half-lives in rats dosed with racemic warfarin. Results were consistent with those found previously by administration of individual enantiomers, thus indicating the utility of the radioimmunoassay method.


Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein.
Acute lymphoblastic leukemia (ALLs) expressing MLL-AF4, the fusion product of t(4;11)(q21;q23), show marked leucocytosis and extramedullary disease in multiple organs, respond poorly to chemotherapy and have poor prognosis. In vitro, leukemic cells with the t(4;11) show resistance to serum deprivation-induced or interferon gamma-regulated CD95-mediated apoptosis. In addition, t(4;11) cells have prolonged doubling time and lower percentage of cells in cycle compared to non-t(4;11) B lineage cell lines. In this study, we examine the time- and level-dependent effects of MLL-AF4 conditional expression on cell cycle and differentiation of myelomonocytic leukemia cell line U937. By varying the concentration of tetracycline in growth media, we found that increasing levels of MLL-AF4 expression result in a progressive decrease in growth rate and fraction of S phase cells, paralleled by an increase in percentage of cells expressing CD11b. Our results demonstrate a dosage-dependent effect of MLL-AF4 fusion oncoprotein on cell cycle progression, with increasing expression levels resulting in the accumulation in G1, prolonged doubling time, both findings that might be responsible for the increased resistance to etoposide-mediated cytotoxicity. We propose the cell cycle control exerted by MLL-AF4 may be responsible of resistance to cell-death promoting stimuli in leukemia carrying the t(4;11) translocation.


5-hydroxytryptamine1A (5-HT1A) receptor agonists: A decade of empirical evidence supports their use as an efficacious therapeutic strategy for brain trauma.
Traumatic brain injury (TBI) is a significant and enduring health care issue with limited treatment options. While several pre-clinical therapeutic approaches have led to enhanced motor and/or cognitive performance, the benefits of these treatments have not translated to the clinic. One plausible explanation is that the therapies may not have been rigorously evaluated, thus rendering the bench-to-bedside leap premature and subsequently unsuccessful. An approach that has undergone considerable empirical research after TBI is pharmacological targeting of 5-HT1A receptors with agonists such as repinotan HCl, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and buspirone. The goal of this review is to integrate and interpret the findings from a series of studies that evaluated the efficacy of 5-HT1A receptor agonists on functional, histological, and molecular outcome after acquired brain injury. The overwhelming consensus of this exhaustive review is that a decade of empirical evidence supports their use as an efficacious therapeutic strategy for brain trauma. This article is part of a Special Issue entitled SI:Brain injury and recovery.


COVID-19 pandemic in Japan.
The disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus Disease-2019 (COVID-19), is a global emergency. The first case of COVID-19 was confirmed in Japan in January 2020, a second outbreak of infection occurred in mid-March and a third peak at the beginning of August. The COVID-19 phenotype was milder in Japan than in other countries, although the restrictive measures applied in the country have not been as strict as in other places. Factors related to a possible reduced susceptibility to the pulmonary manifestations of SARS-CoV-2 may have contributed to better outcomes and lower mortality in Japan.


[High lactose content of the Lundh test meal adversely affects the reliability of the ALTAB test].
The exocrine pancreatic function was examined in 20 patient without any detectable gastrointestinal disorder. We used 1 g 4(N-acetyl-L-thyrosil) aminobenzoic acid (ALTAB) an Lundh's test meal containing 25 g lactose, and the test was repeated with 3 g lactase (Galantase). The urine was collected for 6 hours to check PABA excretion in urine. Lactose intolerance was diagnosed in 10 patients on the basis of an increase of H2 in the breath at least 15 ppm after Lundh's test meal and/or diarrhoea after test in two hours if this diarrhoea could be prevented by giving Galantase orally. We measured PABA excretion in patients with and without lactose intolerance after Lundh's test meal: 17.8% (SD = 6.7) and 47% (SD = 13) respectively (p less than 0.001), and after Lundh's test meal with Galantase: 34.3% (SD = 12.7) and 43.6% (SD = 10.9) respectively. The increase after Galantase in the group with lactose intolerance was significant (p less than 0.01). 1. Lactose content of Lundh's test meal causes a considerable lactose load in patients with lactose intolerance. 2. Oral lactase enzyme usually normalises the result of ALTAB test. 3. It is necessary to detect lactose intolerance before use of Lundh's test meal.


Nitrogen requirements in severely injured patients.
The study was designed to evaluate nitrogen needs in severely injured patients during the first week after trauma. Thirty-nine patients aged from 18 to 65 years with a burn or fractures of more than two long bones were studied. Energy requirements were given parenterally as fat and glucose in isocaloric amounts. The patients were randomized into five groups receiving different amounts of nitrogen from zero to 0.3 g kg body-weight-1 24 h-1. Daily and cumulative nitrogen balance, urinary 3-methylhistidine excretion and nitrogen retention were calculated on days 2-8 after trauma. With no nitrogen, the mean(s.e.m.) daily nitrogen balance after the trauma was -13.8(0.5) gN. The balance improved markedly in groups with a nitrogen intake of up to 0.2 g kg body-weight-1 (P less than 0.001) compared with the no-nitrogen group. The 3-methylhistidine excretion increased because of the trauma in all groups with no statistically significant difference between the groups. Nitrogen retention decreased with increase in nitrogen supply and with time after injury. It is suggested that a nitrogen supply of 0.20 kg bodyweight-1 24 h-1 is optimal for severely injured patients during the first week after trauma.


The effectiveness of biomechanical taping and Kinesiotaping on shoulder pain, active range of motion and function of participants with Trapezius Myalgia: A randomized controlled trial.
Trapezius Myalgia (TM) is characterized by shoulder pain and dysfunction. Kinesio Taping is commonly used in symptom management of TM. Biomechanical Taping (BMT), a novel intervention, may provide equally effective management. This paper reports on the effectiveness of Biomechanical Taping compared with Kinesio Taping in improving shoulder pain, active range of motion (AROM), and function. Two groups of participants with TM were recruited through simple random sampling of participants from nine call centers and purposively-sampled participants from one fast-food chain and one community based rehabilitation center in Manila, Philippines. Participants were randomly allocated to either Kinesio Taping or biomechanical taping group in a double-blind clinical trial. Irrespective of the type of taping, participants performed gentle passive stretching of upper trapezius for six times each held for 30 s on Days 1, 3, and 5. On Days 2 and 4, participants performed gentle passive stretch of upper trapezius three times a day. Pre- and post-intervention measures were taken of Visual Analogue Scale for pain intensity, AROM for shoulder movement, and Disability of Arm, Shoulder, and Hand for function. Of 68 participants, 62 had shoulder symptoms secondary to TM. Similar significant within group improvements were found for Visual Analogue Scale scores, and Disability of Arm, Shoulder and Hand for biomechanical taping and Kinesio Taping interventions when comparing between group results (p < 0.05). Biomechanical Taping appears to be as effective as Kinesio Taping in the short term in decreasing pain and improving function of individuals with TM. Both taping techniques did not restrict shoulder AROM of included participants. Athletic Tape, Myalgia, Pain Measurements, Shoulder Pain NON-MESH TERMS: Biomechanical Taping Technique.


Haemodynamic stability after paracervical block: A randomized, controlled, double-blind study comparing bupivacaine-adrenaline with bupivacaine.
Paracervical block is widely used in gynaecological interventions on cervix and uterus. Many surgeons add adrenaline 100 μg or pitressin 3-5 IU in a total volume of 10-20 mL to reduce total blood loss. We wanted to examine haemodynamic stability in healthy patients given bupivacaine with and without adrenaline. In this randomised, double-blinded, controlled study, 30 healthy women scheduled for cervical conisation got a paracervical block using bupivacaine 50 mg with adrenaline 100 μg (BA-group, n = 14) or without adrenaline (B-group, n = 16) after induction of general anaesthesia. LiDCOplus was used for minimally invasive haemodynamic monitoring. Changes in cardiac output (CO) and systolic blood pressure (SBP) were the primary outcome. Changes in heart rate (HR), stroke volume (SV), and systemic vascular resistance (SVR) were secondary outcome variables. Area under the curve (AUC) ratios and change from baseline to maximal values were used as effect measures comparing the two groups. The AUC-ratio for CO and SBP was 2.50 (P < 0.001) and 1.70 (P = 0.03), respectively. For HR, SV, and SVR the AUC-ratio was 1.59 (P < 0.01), 1.52 (P < 0.001), and 0.90 (P = 0.14), respectively. CO increased 68% (standard deviation (SD) 42%, P < 0.001), HR increased 41% (SD 26%, P < 0.001), and SV increased 26% (SD 17%, P < 0.001) from baseline to maximal values after 70-90 seconds in the BA-group. Paracervical block with bupivacaine 50 mg and adrenaline 100 μg may give haemodynamic instability in healthy females and is not recommended if haemodynamic side effects are to be avoided.


Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer.
Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells. We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP) -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients' chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor. Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells. Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.


Differential patterns of glial fibrillary acidic protein-immunolabeling in the brain of adult lizards.
The present study describes by means of immunohistochemistry the comparative distribution of glial fibrillary acidic protein (GFAP)-positive cells in the forebrain and midbrain of three species of lizards: Eumeces algeriensis, Scincoidae; Agama impalearis, Agamidae; Tarentola mauritanica, Gekkonidae. In the species studied, the different types and proportions of glial cells expressing GFAP showed considerable variation. These cells include radial glia, oval cells, tanycytes, ependymocytes, glia limitans, and astrocytes. In Eumeces, astrocytes are particularly abundant and their processes form numerous perivascular end-feet; in addition well-differentiated ependymal cells and glia limitans express GFAP. These mature glial features are concordant with the relatively advanced phylogenetic level of Eumeces. In Tarentola, relatively few GFAP-expressing glial cells are observed, consisting mainly of radial glia and tanycytes. These features indicate a relatively immature state of the glial cell populations in this species. In Agama, GFAP-immunostained cells are confined to the periventricular and subpial brain areas; the ventricular lining contains numerous GFAP-immunopositive tanycytes and well-differentiated glia limitans. This pattern indicates that the glial cell profile in Agama exhibits characteristics intermediate between Eumeces and Tarentola, a feature which is discordant with the relatively primitive phylogenetic level of Agamidae compared to Gekkonidae. Together, the results of the present study provide novel data on the characterization of GFAP-expressing cell populations in different species of lizards. We suggest that the different glial patterns observed in the lizard brain correlates with developmental and functional aspects.


Dynamics of Mycoplasma bovis in Dutch dairy herds during acute clinical outbreaks.
Mycoplasma bovis (M. bovis) can cause serious illness in cattle, presenting as arthritis and mastitis in dairy cows and pneumonia, arthritis and otitis media in calves. This study aimed to provide insight into the dynamics of M. bovis within dairy herds, experiencing an acute outbreak in dairy cows. Twenty farms were followed with laboratory testing of suspected dairy cows. Each outbreak farm was sampled five times, at 2-3 week intervals, sampling blood and milk and conjunctival fluid from clinically suspected dairy cows and healthy animals from three different age groups: dairy cows, young stock (7-24 months) and calves (1-6 months). Additionally, bulk tank milk was sampled every visit and environmental samples were taken on the first and last visits. The presence of M. bovis was tested by evaluating antibody titres in blood, bacterial DNA in conjunctival fluid and environmental samples and viable bacteria in milk samples. All data were analysed using logistic regression models, corrected for repeated sampling and within-herd correlation. Sixty percent (12/20) of the herds showed a combination of arthritis and mastitis, while other herds experienced only clinically mastitis (3/20) or arthritis (5/20). From the time an outbreak was confirmed, M. bovis infection was not only present in dairy cows, but also in young stock and calves (80% of the farms). Laboratory tests also confirmed the presence of M. bovis in healthy animals. The M. bovis PCR levels of calves and young stock were highly correlated at all visits (rtotal = 0.81, P < 0.01). Furthermore, M. bovis was present in the environment of the animals. At the end of the 3-month study period, none of the 20 clinical outbreak farms were M. bovis-'negative', based on laboratory testing, although hardly any clinical cases were observed at that time.


The radiology of the neurological complications of the reticuloses.
The application of radiology to the diagnosis of reticulosis involving the nervous system is briefly reviewed, and the pathogenesis of spinal extradural block is discussed. Six cases are added to the existing literature.


[The metabolic regulation of the retinal blood flow and the role of prostaglandins (author's transl)].
The microioptophoretic injection of PGE1 close to the retinal arterioles procedures a segmental vasodilatation of 40%. The inhibition of prostaglandin synthesis with indomethacin or aspirin blocks the vasodilatatory effect of hypercapnia and, to a lesser extent, of hypoxia. These results suggest that prostaglandins play a role in the regulation of retinal vasomotor activity.


Efficient algorithms for reconciling gene trees and species networks via duplication and loss events.
Reconciliation methods explain topology differences between a species tree and a gene tree by evolutionary events other than speciations. However, not all phylogenies are trees: hybridization can occur and create new species and this results into reticulate phylogenies. Here, we consider the problem of reconciling a gene tree with a species network via duplication and loss events. Two variants are proposed and solved with effcient algorithms: the first one finds the best tree in the network with which to reconcile the gene tree, and the second one finds the best reconciliation between the gene tree and the whole network.


Is the community radiation oncologist ready for clinical hyperthermia?
The author, in assessing this "new" therapeutic modality, clearly identifies the many problems associated with it and emphasizes its still experimental nature.


Mortality at ages 75 and older in the Cancer Prevention Study (CPS I).
In the fall of 1959 the American Cancer Society began a comprehensive epidemiologic investigation of more than one million men and women drawn mainly from the middle-class population. The study reported here presents a portion of the investigation relating to the mortality among 49,469 subjects who attained age 75 years and older during the course of the study. Both men and women who at entry into this study (1960) were judged to be in good health registered distinctly lower mortality than those judged to be in poor health. Men and women with some college education had significantly lower death rates than those with lesser schooling. Men and women who reported a good family history of longevity showed consistently lower death rates in each five-year age group than those with average or poor family history of longevity. Persons with an average family history of longevity generally had lower death rates than those with a poor family history of longevity. Analysis of mortality by cause indicated that at ages 75 and older nearly half the deaths were attributed to all forms of heart disease. Coronary heart disease accounted for about 35 percent of all deaths, with the proportion decreasing with age. Deaths from stroke rose from 15 to about 20 percent with increase in age. Deaths from all sites of cancer declined with advancing age in both sexes, from about 16 percent of all deaths at ages 75 to 79 to about six percent at ages 90 to 99. Among men, cancer of the prostate accounted for 3.5 percent of deaths at ages 75 to 84, decreasing to about one half this proportion in the early-90s age group. Colorectal cancer decreased from about three percent of total deaths at ages 75 to 84 to about 1.5 percent in the early 90s. Lung cancer and stomach cancer remained at the same level at these ages.


Longitudinal trends in using physical interventions to manage aggression and self-harm in mental health services.
Repetitive aggression by a patient receiving mental health inpatient care is likely to elicit various patterns of response from care staff over time. This study sought to examine patterns of coercive physical intervention in relation to repeated episodes of aggression by particular patients. A data set of 9,945 aggression and self-harm incidents over a five-year period in one mental health service in England was constructed. Incidents by a specific individual were categorized according to their position in a sequence (first, second, and so on) and by the use of physical intervention by staff to manage the incident. Trends in the use of physical intervention varied across settings. There was a significant tendency in general (nonforensic) services for use of physical intervention to increase in response to physical aggression (physical intervention in first versus subsequent incidents: odds ratio [OR]=.69, 95% confidence interval [CI]=.54-.90) and to decrease in response to threats (physical intervention in first threat versus subsequent threats: OR=1.62, CI=1.09-2.39). There were significant trends over time in the use of physical intervention to manage violence and self-harm. However, the dynamics behind this finding will remain unclear without further research.


Immune responses triggering colitis and colitis-associated carcinoma.
Inflammatory bowel diseases compromise of two forms of chronic intestinal inflammatory disorders: Crohn's disease and ulcerative colitis. Both forms of inflammatory bowel disease result from inappropriate inflammatory responses to the intestinal microbiota, but have different underlying immune responses. The connection between inflammation and cancer has long been established and longstanding inflammatory bowel diseases are an important risk factor for developing colorectal cancer. Colitis-associated colorectal cancer pathogenesis is highly influenced by specific inflammatory processes during inflammatory bowel disease. This article reviews the immunological responses affecting Crohn's disease and ulcerative colitis as well as the linkage of inflammatory bowel disease to the development of colitis-associated cancer. Finally, we discuss the prospects of using new research efforts to devise new immunotherapeutic approaches.


Enhanced selenium effect on growth arrest by BiP/GRP78 knockdown in p53-null human prostate cancer cells.
Redox modification of thiol/disulfide interchange in proteins by selenium could lead to protein unfolding. When this occurs in the endoplasmic reticulum (ER), a process known as unfolded protein response (UPR) is orchestrated for survival through activation of PERK-eIF2alpha (PERK: double-stranded RNA-activated protein kinase-like ER kinase; eIF2alpha: eucaryotic initiation factor 2alpha), ATFalpha (ATFalpha: activating transcription factor 6) and inositol requiring 1 (IRE1)-x-box-binding protein 1 (XBP1) signalings. All three UPR transducer pathways were upregulated very rapidly when PC-3 cells were exposed to selenium. These changes were accompanied by increased expression of UPR target genes, including immunoglobulin heavy chain-binding protein/glucose-regulated protein, 78 kDa and CCAAT/enhancer binding protein-homologous protein/growth arrest- and DNA damage-inducible gene (CHOP/GADD153). Induction of BiP/GRP78, an ER-resident chaperone, is part of the damage control mechanism, while CHOP/GADD153 is a transcription factor associated with growth arrest and apoptosis in the event of prolonged ER stress. Knocking down BiP/GRP78 induction by small interference RNA produced a differential response of the three transducers to selenium, suggesting that the signaling intensity of each transducer could be fine-tuned depending on BiP/GRP78 availability. In the presence of selenium, CHOP/GADD153 expression was raised even higher by BiP/GRP78 knockdown. Under this condition, the selenium effect on wild-type p53-activated fragment p21 (p21(WAF)), cyclin-dependent kinase (CDK)1 and CDK2 was also magnified in a manner consistent with enhanced cell growth arrest. Additional experiments with CHOP/GADD153 siRNA knockdown strongly suggested that CHOP/GADD153 may play a positive role in upregulating the expression of p21(WAF) in a p53-independent manner (PC-3 cells are p53 null). Collectively, the above findings support the idea that UPR could be an important mechanism in mediating the anticancer activity of selenium.


High-voltage and short-time dielectric barrier discharge plasma treatment affects structural and digestive properties of Tartary buckwheat starch.
To systematically explore the effects of high-voltage and short-time (HV-ST) dielectric barrier discharge (DBD) plasma treatment on Tartary buckwheat starch (TBS), TBS was treated at 15 and 20 kV for 20 and 40 s. Compared to native starch, more corrosions and holes were observed on the surfaces of plasma-modified TBS observed by SEM. Increased crystallinity and short-range structure order in plasma-modified TBS were determined using XRD and FT-IR respectively, while the average chain length and amylose content decreased, with lowest values (13.5 and 6.9%) in sample 20-40. Meanwhile, the solubility and paste clarity of plasma-modified TBS increased, whereas the viscosities decreased, enhancing in vitro digestibility with highest value (79.5%) in sample 20-40. These changes of TBS properties positively correlated with the treatment voltage and time length. Therefore, HV-ST DBD plasma treatment served as an effective tool for altering the properties of TBS. It is favorable for the applications of starch ingredients with low viscosity and high paste clarity, as well as accelerating starch hydrolyzation processes, such as brewing and food fermentation.


Mapping the distribution and tree canopy cover of Jacaranda mimosifolia and Platanus × acerifolia in Johannesburg's urban forest.
This study investigated the distribution and the tree canopy cover (TCC) of the two most prominent street trees (Jacaranda mimosifolia and Platanus × acerifolia) in Johannesburg, using the multispectral SPOT 6 satellite data and field survey GPS points. The importance of the spectral bands (Blue, Green, Red and NIR) and the NDVI index in discriminating between the tree species was quantified using five separability indices (Divergence, Bhattacharyya, Transformed Divergence, Jeffries-Matusita and M-statistic). The visual comparison of the Blue band and the NDVI histograms between the two species and other vegetation type showed the lowest feature overlap, suggesting the highest separability between paired classes. This was further supported by the highest Divergence value for the Blue band (3.68) and NDVI index (2.48) followed by the M-statistic (0.8 and 0.73, respectively) indicating good to moderate separability between the two species, respectively. The results were also consistent with the RF classification where the Blue band and NDVI index were the most important variables for the discrimination between the two species with an overall accuracy of 88% (kappa = 8). The TCC of J. mimosifolia and P. × acerifolia constituted 38% of the total vegetation cover in the city. These findings not only would help prioritize the increase of targeted vegetation cover in low cover areas, but will also provide a valuable information for assessment and protection of vulnerable species such as P. × acerifolia from the threat of the polyphagous shot hole borer, Euwallacea fornicatus in Johannesburg.


Amplification of ST50 gene using dry-reagent-based polymerase chain reaction for the detection of Salmonella typhi.
Conventional polymerase chain reaction (PCR) testing requires many pipetting steps and has to be transported and stored in cold chain. To overcome these limitations, we designed a ready-to-use PCR test for Salmonella typhi using PCR reagents, primers against the ST50 gene of S. typhi, a built-in internal amplification control (IAC), and gel loading dye mixed and freeze-dried in a single tube. The 2-step dry-reagent-based assay was used to amplify a 1238-bp target gene and an 810-bp IAC gene from 73 BACTEC blood culture broths (33 true positives for S. typhi and 40 true negatives for non-S. typhi). The sensitivity, specificity, positive predictive value, and negative predictive value of the PCR assay were 87.9%, 100%, 100%, and 90.9%, respectively. We suggest that this rapid 2-step PCR test could be used for the rapid diagnosis of typhoid fever.


Unraveling the Biology of Auditory Learning: A Cognitive-Sensorimotor-Reward Framework.
The auditory system is stunning in its capacity for change: a single neuron can modulate its tuning in minutes. Here we articulate a conceptual framework to understand the biology of auditory learning where an animal must engage cognitive, sensorimotor, and reward systems to spark neural remodeling. Central to our framework is a consideration of the auditory system as an integrated whole that interacts with other circuits to guide and refine life in sound. Despite our emphasis on the auditory system, these principles may apply across the nervous system. Understanding neuroplastic changes in both normal and impaired sensory systems guides strategies to improve everyday communication.


A single residual replacement improves the folding and stability of recombinant cassava hydroxynitrile lyase in E. coil.
Substitution of Ser113 for Gly113 in the cap domain of hydroxynitrile lyase from Manihot esculenta (MeHNL) was performed by site-directed mutagenesis to improve its self-generated folding and stability under denaturation conditions. The yield of the recombinant mutant HNL1 (mut-HNL1), which had higher specific activity than the wild type HNL0 (wt-HNL0), was increased by 2 to 3-fold. Thermostability of MeHNL was also enhanced, probably due to an increase in content of the beta-strand secondary structure according to CD analysis. Our data in this report suggest that Ser113 significantly contributes to the in vivo folding and stability of MeHNL and demonstrates an economic advantage of mut-HNL1 over the wt-HNL0.


Spatially dissociated flow-metabolism coupling in brain activation.
The relationships among cerebral blood flow (CBF), oxygen consumption (CMRO(2)) and glucose use (CMR(glc)) constitute the basis of functional brain-imaging. Here we report spatially dissociated changes of CMRO(2) and CBF during motor activity that lead us to propose a revision of conventional CBF-CMRO(2) coupling models. In the left primary and supplementary motor cortices, CBF and CMRO(2) rose significantly during finger-thumb tapping. However, in the right putamen CBF did not rise, despite a significant increase in CMRO(2). We explain these observations by invoking a central command mechanism that regulates CBF in the putamen in anticipation of movement. By this mechanism, CBF rose in the putamen before the measurements of CBF and CMRO(2) while CMRO(2) rose when actual motion commenced.


Wear versus thickness and other features of 5-Mrad crosslinked UHMWPE acetabular liners.
The low wear rates of crosslinked polyethylenes provide the potential to use larger diameters to resist dislocation. However, this requires the use of thinner liners in the acetabular component, with concern that higher contact stresses will increase wear, offsetting the benefits of the crosslinking. We asked the following questions: Is the wear of conventional and crosslinked polyethylene liners affected by ball diameter, rigidity of backing, and liner thickness? Are the stresses in the liner affected by thickness? Wear rates were measured in a hip simulator and stresses were calculated using finite element modeling. Without crosslinking, the wear rate was 4% to 10% greater with a 36-mm diameter than a 28-mm diameter. With crosslinking, wear was 9% lower with a 36-mm diameter without metal backing and 4% greater with metal backing. Reducing the thickness from 6 mm to 3 mm increased the contact stress by 46%, but the wear rate decreased by 19%. The reduction in wear with 5 Mrad of crosslinking was not offset by increasing the diameter from 28 mm to 36 mm or by using a liner as thin as 3 mm. The results indicate, for a properly positioned 5-Mrad crosslinked acetabular component and within the range of dimensions evaluated, neither wear nor stresses in the polyethylene are limiting factors in the use of larger-diameter, thinner cups to resist dislocation.


Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1.
Myelin-associated glycoprotein (MAG) is a quantitatively minor component in both peripheral and central myelin sheaths that is thought to have a role in cell-cell interactions within the nervous system. We show here that a mouse monoclonal antibody, HNK-1, which is directed against human natural killer cells also recognizes an antigenic determinant of human central and peripheral nervous system white matter by immunoperoxidase staining of tissue sections. Immunoblot analysis of myelin proteins and purified extracted MAG indicates that the antigen recognized is MAG.


Overexpression of ThSAP30BP from Tamarix hispida improves salt tolerance.
Histone deacetylases (HDACs) play an important regulatory role in plant response to biotic and abiotic stresses. They improve plant stress resistance by increasing the degree of histone acetylation associated with stress-responsive genes. SAP30BP, a human transcriptional regulatory protein, can increase histone deacetylase activity by regulating the deacetylation levels of lysines 9 and 14 in histone H3. In this study, a ThSAP30BP gene was cloned and characterized from Tamarix hispida (a kind of woody halophyte). The expression patterns of ThSAP30BP under different abiotic stresses and hormone treatments were detected by qRT-PCR. The results showed that ThSAP30BP was significantly upregulated at most time points under various stress treatments, suggesting that ThSAP30BP may be related to the abiotic stress response of T. hispida. To further analyze the salt stress resistance function of the ThSAP30BP gene, the plant overexpression vector pROKII-ThSAP30BP was instantaneously constructed and transformed into T. hispida. Meanwhile, the empty vector pROKII was also transformed as a control. The activities of SOD and POD, the contents of H2O2 and MDA, the relative conductance and the staining of NBT, DAB and Evans blue were analyzed and compared under salt stress. The results showed that the overexpression of ThSAP30BP in T. hispida reduced the accumulation of ROS in plants and the cell death rate under salt stress. These results suggested that ThSAP30BP may play an important physiological role in salt tolerance of T. hispida.