A randomized clinical trial comparing enamel matrix derivative and membrane treatment of buccal class II furcation involvement in mandibular molars. Part II: secondary outcomes.
This multicenter, randomized trial compared enamel matrix derivative (EMD) with barrier membranes for the treatment of Class II mandibular furcations with regard to secondary outcomes. The influence of furcation morphology on the effectiveness of either treatment was also evaluated. Forty-eight patients (age range 28 to 73 years; 22 females, 26 males) with buccal Class II furcation involvements in both contralateral lower first or second molars were included. After initial periodontal treatment, defects were randomized to either EMD or bioabsorbable guided tissue regeneration (GTR) barrier. Study design and the results for the primary parameter were previously described. Results of the following secondary outcome variables are reported here: changes of the hard tissue boundaries describing the anatomical situation of the furcation defect and changes in the following clinical parameters between baseline and 14 months: plaque, level of gingival margin, probing depth, bleeding on probing, attachment level, and bone sounding at five sites/tooth at the buccal side. Descriptive statistics were applied for changes in clinical parameters and measurements of hard tissue boundaries. The differences observed under treatment with EMD or membrane were analyzed by means of the Wilcoxon two-sample test. The difference between the effect of the EMD and membrane treatment was estimated by means of the Hodges-Lehmann estimator. Overall, similar healing results were observed for both treatments. However, there was slightly more recession in the mid-furcation site following membrane treatment (P = 0.04). Additionally, different treatment effects could be detected for the distances from the stent or cemento-enamel junction (CEJ) to the buccal bone crest, mid-distal root (Pstent = 0.01; PCEJ = 0.07) and for the distance from the stent or CEJ to the buccal bone crest, mid-mesial root (Pstent = 0.01; PCEJ = 0.01). There was no measurable bone resorption in EMD sites, whereas a slight resorption occurred with membrane treatment. Furcation morphology at the time of surgery was not associated with clinical outcome, irrespective of the treatment. With regard to secondary outcome parameters, enamel matrix derivative treatment led to a similar regenerative result as the membrane procedure.


Pectin-fermenting bacteria isolated from the bovine rumen.
Thirty-two strains of pectin-fermenting rumen bacteria were isolated from bovine rumen contents in a rumen fluid medium which contained pectin as the only added energy source. Based on differences in morphology and the Gram stain, 10 of these strains were selected for characterization. Two strains were identified as Lachnospira multiparus, four strains were identified as Butyrivbrio fibrisolvens, and three strains were identified as Bacteroides ruminicola. Characteristics of the remaining strain did not correspond with any previously described species. It was a gram-positive anaerobic coccus, 1.0 to 1.2 mum in diameter, and occurred primarily as single cells or diplococci. The strain fermented pectin rapidly but showed little or no growth on any other energy sources tested. The only detectable end products were acetic acid and gas, a portion of which was identified as hydrogen. Although the physiological characteristics of this organism differ markedly from other described species, it has been placed in the genus Peptostreptococcus on the basis of morphology, Gram stain, relations to oxygen, and the occurrence of cell division in only one plane. End products of fermentation are somewhat similar to those of the cellulolytic ruminococci. Eight previously characterized strains of cellulolytic bacteria isolated in nonselective media were unable to ferment pectin, whereas ten strains of hemicellulolytic rumen bacteria, eight of which were isolated with a xylan medium, showed considerable variation in this characteristic.


Successful Pregnancy Outcomes After Laparoscopic Management of Pheochromocytoma.
Background: Pheochromocytoma is a rare cause of hypertension in pregnancy, which is often overlooked; especially in late pregnancy because of more prevalent pre-eclampsia. It has been associated with significant morbidity and mortality rates in both mother and fetus, if not diagnosed and treated in time. Minimally invasive surgery has been infrequently used for surgical management of pheochromocytoma in pregnancy, with <20 reported cases in English literature. Case Presentation: A 26-year-old pregnant woman presented at 9 weeks of gestation with complaints of palpitations, sweating, and headache; with past history of first trimester spontaneous abortion caused by accelerated hypertension. She was found to have hypertension and diabetes, but no pedal edema, weight gain, or proteinuria. Ultrasonogram and MRI of abdomen revealed a left adrenal mass and 24 hours urinary catecholamines levels were increased, suggesting a pheochromocytoma. After preoperative optimization in consultations with obstetricians, endocrinologists, and anesthetists, she underwent laparoscopic left adrenalectomy during 15th week of gestation. Perioperative hospital course was uneventful for both mother and the fetus. After adrenalectomy, her diabetes was cured and hypertension was controlled with single antihypertensive. She was readmitted at 31 weeks of gestation with accelerated hypertension and underwent emergency caesarean for impending eclampsia at 32 weeks, and delivered a healthy female baby. 131I-meta-iodobenzylguanidine (MIBG) scan and 68Ga-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-octreotide positron emission tomography-CT (68Ga-DOTANOC PET-CT) scan was obtained in postpartum period to rule out any extra-adrenal pheochromocytoma, both of which did not reveal any abnormality. At 1 year follow-up, she is normoglycemic and hypertension controlled on single antihypertensive. Conclusion: Pheochromocytoma in pregnancy is a rare but potentially lethal condition, and high index of suspicion is required for early diagnosis. Multidisciplinary coordination is required for effective management of this rare condition. Laparoscopic adrenalectomy is safe in second trimester of pregnancy for both mother and fetus.


Hypothalamic superfusion with histamine agonists and antagonists modifies the pressor response to hypothalamic stimulation.
The posterior hypothalamus of anaesthetized cats were superfused with CSF through a push-pull cannula and electrically stimulated with its tip. Hypothalamic stimulation elicited a pressor response. Superfusion of the hypothalamus with histamine-containing CSF elicited a concentration-dependent enhancement of the pressor response. The enhancing effect of histamine was abolished, when the hypothalamus was pre-superfused with metiamide, whereas pre-superfusion with mepyramine only slightly inhibited the effect of histamine. Hypothalamic superfusion with dimaprit caused a concentration-dependent increase in the pressor response. The effect of dimaprit was abolished by pre-superfusion of the hypothalamus with metiamide, but it was not affected by pre-superfusion with mepyramine. Superfusion of the hypothalamus with 2-methylhistamine did not affect the pressor response. It is concluded that histamine increases the pressor response to hypothalamic stimulation. The enhancing effect of histamine is mainly due to its action on H2-receptors of the posterior hypothalamus.


Zn(II)-PEG 300 globules as soft template for the synthesis of hexagonal ZnO micronuts by the hydrothermal reaction method.
Hexagonal ZnO micronuts (HZMNs) have been successfully synthesized with the assistance of poly(ethylene glycol) (PEG) 300 via a hydrothermal method. The structure and morphology of the HZMNs were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). An individual ZnO micronut is revealed as twinned crystals. Time-dependent investigation shows that the growth of HZMNs involves a dissolution-recrystallization process followed by Ostwald ripening, in which is the first formed solid ZnO particles dissolve and transform to HZMNs with hollow structure. PEG 300 has been found to play a crucial role in the growth of this unique hollow structure. TEM observations show that the PEG chains aggregate to globules in water, which then have interaction with the dissolved zinc species to form the globules in a coiled state under hydrothermal conditions. These Zn(II)-PEG 300 globules act as soft template for the growth of HZMNs, and the possible growth mechanism is proposed. The room-temperature photoluminescence (PL) spectrum shows red emission around 612 nm with a full width at half-maximum (fwhm) only about 13 nm.


A tetrazol-5-yl analogue of glycine, 5-ammoniomethyl-1H-tetrazolide, and its copper(II) complex.
A nonclassical tetrazole isostere of glycine, viz. zwitterionic 5-ammoniomethyl-1H-tetrazolide, C(2)H(5)N(5), (I), crystallizes in the chiral P3(1) space group, similar to gamma-glycine. The crystal packing of (I) is determined by a set of classical hydrogen bonds, forming a three-dimensional network that is practically the same as that in gamma-glycine. The Cu(II) complex of (I), poly[[bis(mu(2)-5-aminomethyl-1H-tetrazolido-kappa(3)N(1),N(5):N(4))copper(II)] dihydrate], {[Cu(C(2)H(4)N(5))(2)].2H(2)O}(n), (II), is a layered coordination polymer formed as a result of tetrazole ring bridges. The Cu(II) cations lie on inversion centres, are surrounded by four anions and adopt elongated octahedral coordination. Water molecules are located in the interlayer space and connect the layers into a three-dimensional network via a system of hydrogen bonds.


[Value of cytapheresis in the treatment of loaiasis with high blood microfilaria levels. Results in 7 cases].
Seven patients infected with the filarial worm Loa loa received a treatment by cytapheresis in an attempt to lower the microfilaraemia. Microfilarial levels of between 6,000 and 38,500 ml, before extraction, were reduced, according to the case, by between 47 and 97% (mean 76%). The diethylcarbamazine chemotherapy which followed in 6 of 7 patients showed no sign of any of the serious side-effects which often occur in these type of cases. Due to its practicality and the fact that it is well tolerated, both clinically and biologically, cytapheresis would seem to represent the best method for initially treating loaiasis with high microfilaremia.


Large scale near-duplicate celebrity web images retrieval using visual and textual features.
Near-duplicate image retrieval is a classical research problem in computer vision toward many applications such as image annotation and content-based image retrieval. On the web, near-duplication is more prevalent in queries for celebrities and historical figures which are of particular interest to the end users. Existing methods such as bag-of-visual-words (BoVW) solve this problem mainly by exploiting purely visual features. To overcome this limitation, this paper proposes a novel text-based data-driven reranking framework, which utilizes textual features and is combined with state-of-art BoVW schemes. Under this framework, the input of the retrieval procedure is still only a query image. To verify the proposed approach, a dataset of 2 million images of 1089 different celebrities together with their accompanying texts is constructed. In addition, we comprehensively analyze the different categories of near duplication observed in our constructed dataset. Experimental results on this dataset show that the proposed framework can achieve higher mean average precision (mAP) with an improvement of 21% on average in comparison with the approaches based only on visual features, while does not notably prolong the retrieval time.


Prenatal health of immigrant women in Norway - an exploratory literature review.
Immigrant women are a vulnerable group within Norwegian prenatal care and have an increased risk of adverse pregnancy outcomes. The purpose of this exploratory literature review was to compile an overview of the available knowledge on the prenatal health of immigrant women in Norway. The literature review covers 44 peer-reviewed articles on the prenatal health of immigrant women in Norway. The articles reflect a variety of study designs and were published in the period 2000-2019. Searches were conducted in MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO, Maternity & Infant Care Database and SveMed+. Frequently studied topics included gestational diabetes, obesity, hyperemesis gravidarum, preeclampsia and folate use. We found a considerable variation in the disease risk for different sub-groups of immigrants. Little research has been conducted on especially vulnerable immigrant groups, such as new arrivals, undocumented immigrants and refugees. We recommend that future studies consider using a qualitative research design that sheds light on the experiences of immigrant families, as well as intervention studies that test the effectiveness of measures for improving prenatal care.


Elevated potassium enhances glutamate vulnerability of dopaminergic neurons developing in mesencephalic cell cultures.
This study examines the effects of high K+ concentration on the growth and development of mesencephalic cells and their glutamate vulnerability. Mesencephalic cell cultures obtained from Wistar rat embryos on the 14th gestational day were maintained for 14 days in medium with either normal (4.2 mM) or elevated (24.2 mM) potassium concentration. There was no significant difference due to various K+ concentration in cell growth and survival up to day in vitro (DIV) 13-14. In order to test the glutamate (Glu) vulnerability, cultures were treated with 100 mu M Glu for 15 min in salt solution on the DIV 3,6,8 and 13. Glu-induced neuronal damage was estimated 24 h later by measuring the neuron-specific enolase (NSE) content in the culture medium and by counting the number of tyrosine hydroxylase-immunoreactive (TH-IR) neurons. Glu had no damaging effect on the cells on DIV 3, but became pronounced beyond DIV 6. Elevated potassium concentration 24.2 mM) in the culture medium during development significantly increased neuronal vulnerability to Glu treatment, indicated by a higher increase of NSE content in the medium and by a more pronounced Glu-induced decrease of the number of TH-IR cells. The Glu-induced decrease of the number of TH-IR cells and of NSE-IR cells let us conclude that dopaminergic neurons are more vulnerable to glutamate than other neurons from mesencephalic culture.


Protein-protein interactions involving T4 phage-coded deoxycytidylate deaminase and thymidylate synthase.
The enzymes deoxycytidylate deaminase (EC) and thymidylate synthase (EC) are functionally associated with one another, since they catalyze sequential reactions. In T4 coliphage infection the two enzymes are found in dNTP synthetase, a multienzyme complex for deoxyribonucleotide biosynthesis. Protein-protein interactions involving the phage-coded forms of these two enzymes have been explored in three experiments that use the respective purified protein as an affinity ligand. First, an extract of radiolabeled T4 proteins was passed through a column of immobilized enzyme (either dTMP synthase or dCMP deaminase), and the specifically bound proteins were identified. Second, two mutant form of dCMP deaminase (H90N and H94N), altered in presumed zinc-binding sites, were analyzed similarly, with the results suggesting that some, but not all, interactions require normal structure near the catalytic site. Third, affinity chromatography using either enzyme as the immobilized ligand, revealed interactions between the two purified enzymes in the absence of other proteins. In these experiments we noted a significant effect of dCTP, an allosteric modifier of dCMP deaminase, upon the interactions.


Antibiofilm and anticancer activities of unripe and ripe Azadirachta indica (neem) seed extracts.
Antibiotic resistances of pathogens and breast cancer warrant the search for new alternative strategies. Phytoextracts can eradicate microbe-borne diseases as well as cancer with lower side effects compared to conventional antibiotics. Unripe and ripe Azadirachta indica (neem) seed extracts were explored as potential antibiofilm and anticancer agents in combating multidrug-resistant infectious bacteria as well as anticancer agents against the MDR breast cancer cell lines. Shed-dried neem seeds (both unripe and ripe) were pulverized and extracted using methanol. The chemical components were identified with FTIR and gas chromatography - mass spectrometry. Antibiofilm activity of neem seed extracts were assessed in terms of minimum biofilm inhibitory concentration (MBIC), minimum biofilm eradication concentration (MBEC), and fluorescence microscopic studies on Staphylococcus aureus and Vibrio cholerae. Bacterial cells were studied by fluorescence microscopy using acridine orange/ethidium bromide as the staining agents. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were evaluated to observe the antibacterial activities. Cytotoxicity of the extracts against human blood lymphocytes and the anticancer activity against drug-resistant breast cancer cell lines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and fluorescence-activated cell sorting (FACS) studies. 4-Ethyl-2-hydroxy-2-cyclopentene-1-one, phthalic acid, and 2-hexyl-tetrahydro thiophane were the major compounds in unripe neem seed, whereas 3,5-dihydroxy-6-methyl-2,3-dihydro-4-H-pyran-4-one and 4-ethylbenzamide were predominant in ripe neem seed. Triazine derivatives were also common for both the extracts. MBIC values of unripe and ripe neem seed extracts for S. aureus are 75 and 100 µg/mL, respectively, and for V. cholerae, they are 100 and 300 µg/mL, respectively. MBEC values of unripe and ripe seed extracts are 500 and 300 µg/mL, respectively for S. aureus and for V. cholerae the values are 700 and 500 µg/mL, respectively. Fluorescence microscopic studies at 16 and 24 h, after bacterial culture, demonstrate enhanced antibiofilm activity for the ripe seed extract than that of the unripe seeds for both the bacteria. MTT assay reveals lower cytotoxicity of both the extracts towards normal blood lymphocytes, and anticancer activity against breast cancer cell line (MDA-MB-231) with superior activity of ripe seed extract. FACS studies further supported higher anticancer activity for ripe seed extract. Methanolic extract of neem seeds could substantially inhibit and eradicate biofilm along with their potent antibacterial and anticancer activities. Both the extracts showed higher antibiofilm and antibacterial activity against S. aureus (gram-positive) than V. cholerae (gram-negative). Moreover, ripe seed extract showed higher antibiofilm and anticancer activity than unripe extracts.


[AOAC/EURACHEM symposium "Development in chemical analysis of environmental samples at the edge of the 21st century"].
Information on the International Symposium on "Development in Chemical Analysis of Environmental Samples at the Edge of 21st Century" which was organized in Warsaw (21-22 Nov. 1996) by the AOAC International Central Europe Subsection in cooperation with National Section of Eurachem-Pl/Pollab-Chem was provided. The following national organizations/institutions also participated in the organization of the conference: the Committee of Analytical Chemistry Polish Academy of Sciences, Meat and Fat Research Institute, Institute of Agricultural and Food Biotechnology, National Institute of Hygiene and Central Chemical Laboratory "Polcargo". It was the third Symposium organized annually by this AOAC Subsection since it was established. The first meeting was in Smolenice, Slovakia (1994), the second in Budapest, Hungary (1995), the third one in Warsaw, Poland (1996). In the Symposium attended the representatives from AOAC Int. (L. Kurtyka (USA), M. Lauwaars (The Netherlands) and from Eurachem-M. Walsh (Ireland) and also invited speakers from universities, research and testing institutes as well as from government authorities who presented the best knowledge coming from their experience. During two days of Symposium 11 plenary lectures and 4 short communications were presented. There were two main topic related groups of the lectures: (1) Analytical quality assurance with regard to the problems of accreditation, certification and quality control. (2) New methods and their applicability for the instrumental analysis and monitoring. In the opinion of the participants, the lectures and the following discussion provided many useful and updated information on development in analytical chemistry. The participants pointed out the need of the organisation of similar meetings aimed at the exchange of the views on the particular aspects of the chemical analysis and quality assurance in the laboratory.


The extracellular domain of the TSH receptor has an immunogenic epitope reactive with Graves' IgG but unrelated to receptor function as well as determinants having different roles for high affinity TSH binding and the activity of thyroid-stimulating autoantibodies.
The possibility that thyroid-stimulating antibodies (TSAbs) might interact with receptor determinants different from those important for high affinity TSH binding has been evaluated. Deletion mutants of the extracellular domain of the rat TSH receptor as well as point mutations of potential N-linked glycosylation sites were created. TSH binding and the ability of TSH or a TSAb to increase cAMP levels after transfection in Cos-7 cells were then measured. Mutation of two glycosylation sites (residues 77 and 198) was shown to significantly decrease high affinity TSH binding but not the activity of a TSAb. A third glycosylation site mutant (residue 302) was identified that enhanced TSAb activity but had no effect on high affinity TSH binding, and a deletion mutant (residues 308-410) lost TSAb activity but preserved TSH binding. The last two mutations are within a region having low homology with gonadotropin receptors. This same region has, in addition, a determinant that is not important for receptor activity, yet is reactive with Graves' IgG. Thus, a deletion of residues 339-367 has no effect on TSH binding or TSH/TSAb activity, yet contains a peptide (residues 352-367) reactive in ELISA assays with IgG from greater than 80% of Graves' patients but not with IgG from normal individuals, patients with nonautoimmune thyroid disease, or patients with autoimmune disease not related to the thyroid. We, therefore, identify different receptor determinants for TSAb and high affinity TSH binding, consistent with predictions from TSH receptor monoclonal antibody studies. In addition, we identify a receptor peptide that is reactive with TSH receptor antibodies in Graves' patients, despite its having no determinants important for TSH or autoantibody activity in functional assays.


A comparison of the temporal weighting of annoyance and loudness.
The influence of single temporal portions of a sound on global annoyance and loudness judgments was measured using perceptual weight analysis. The stimuli were 900-ms noise samples randomly changing in level every 100 ms. For loudness judgments, Pedersen and Ellermeier [J. Acoust. Soc. Am. 123, 963-972 (2008)] found that listeners attach greater weight to the beginning and ending than to the middle of a stimulus. Qualitatively similar weights were expected for annoyance. Annoyance and loudness judgments were obtained from 12 listeners in a two-interval forced-choice task. The results demonstrated a primacy effect for the temporal weighting of both annoyance and loudness. However, a significant recency effect was observed only for annoyance. Potential explanations of these weighting patterns are discussed. Goodness-of-fit analysis showed that the prediction of annoyance and loudness can be improved by allowing a non-uniform weighting of single temporal portions of the signal, rather than assuming a uniform weighting as in measures like the energy-equivalent level (L(eq)). A second experiment confirmed that the listeners were capable of separating annoyance and loudness of the stimuli. Noises with the same L(eq) but different amplitude modulation depths were judged to differ in annoyance but not in loudness.


Chemoarchitectonic subdivisions of the visual pulvinar in monkeys and their connectional relations with the middle temporal and rostral dorsolateral visual areas, MT and DLr.
The organization of the inferior pulvinar complex (PI) in squirrel monkeys was studied with histochemical localization of the calcium binding proteins calbindin-D28k and parvalbumin, and of cytochrome oxidase. With each of these markers, the inferior pulvinar complex can be subdivided into four distinct regions. Calbindin-D28k immunoreactivity is densely distributed in cells and neuropil within PI, except for a distinct centromedially located gap. This calbindin-poor zone, termed the medial division of the inferior pulvinar (PIM), corresponds precisely to a region that contains elevated cytochrome oxidase activity and parvalbumin immunostaining. The PIM extends slightly above and behind the classically defined limit of the inferior pulvinar, the corticotectal tract. Regions of inferior pulvinar with intense immunostaining for calbindin-D28k were the posterior division of the inferior pulvinar (PIP, medial to PIM) and the central division (PIC, lateral to PIM). A newly recognized lateral region, PIL, adjoins the lateral geniculate nucleus and stains more lightly for calbindin and parvalbumin immunoreactivity and for cytochrome oxidase. Staining patterns for calbindin, parvalbumin, and cytochrome oxidase in the pulvinar of rhesus monkeys closely resemble those shown in squirrel monkey inferior pulvinar, suggesting that a common organization exists in all primates. In order to examine cortical connection patterns of the histochemically defined compartments in the inferior pulvinar, injections of up to five neuroanatomical tracers (wheat germ agglutinin conjugated to horseradish peroxidase and fluorescent retrograde tracers) were placed in the same cerebral hemisphere. Single injection sites were in the middle temporal area (MT), and several separate injections were placed in a strip corresponding to the rostral subdivision of the dorsolateral area (DLr). Injections that involved only DLr and not MT labeled principally the PIC, and more sparsely PIP and PIL. DLr connections occupied a "shell" region dorsal to PIM that extended from PIC into the lateral and medial divisions of the pulvinar, PL and PM. Injection sites that included MT or were largely restricted to MT produced dense label in PIM and moderate label in PIC and PIL. The retinotopic organization within the inferior pulvinar was inferred from patterns of connections. Connections with cortex related most closely to central vision were found posteriorly in PIM and in adjacent portions of PIC as it wraps around the caudal pole of PIM. Cortex related to more peripheral locations in the lower visual field connected with more rostral PIM and PIC. Patterns of label within the portions of PL and PM that were immediately adjacent to PIM roughly paralleled those in PIM and PIC.(ABSTRACT TRUNCATED AT 400 WORDS)


Potential vaccine hesitancy regarding COVID-19 vaccines in Kashmiri population.
India is all set to begin vaccination against COVID-19. A good number of people are falling prey to anti-vaccination campaigns, and therefore, some amount of vaccine hesitancy must have developed. The primary objective of the study was to find the level of potential COVID-19 vaccine hesitancy in Kashmiri population. This was a cross-sectional study conducted in the valley of Kashmir. A predesigned questionnaire was shared online. The participation of respondents was voluntary. Exclusions were made on account of residence outside Kashmir valley, duplicate forms, and wrong information. The data were entered into Microsoft Excel 2010 and analyzed using SPSS version 23. A total of 487 respondents were included. About 67% of the participants were in the age group of ≤30 years, 55% female, 54% rural, and 16% had ever been COVID-19 positive. About 14% of the participants were completely hesitant about receiving the COVID-19 vaccine, whereas 40% were unsure if they will accept the vaccination. The main reason for the total nonacceptance of the vaccine was the doubts about the safety of COVID-19 vaccines (67%). Urban people were more likely to be hesitant to the vaccine than rural people (odds ratio [OR] 1.845, confidence interval CI 1.022 to 3.333). Those who were ever COVID-19 positive were 3.3 times more likely to say "no" to COVID-19 vaccination than those who were never positive. Strategic steps must be taken to minimize the vaccine hesitancy associated with COVID-19 vaccination. Authorities should direct efforts toward vaccine education, creating awareness among people about the importance of COVID-19 vaccination.


Genomic expression analysis reveals strategies of Burkholderia cenocepacia to adapt to cystic fibrosis patients' airways and antimicrobial therapy.
Pulmonary colonization of cystic fibrosis (CF) patients with Burkholderia cenocepacia or other bacteria of the Burkholderia cepacia complex (Bcc) is associated with worse prognosis and increased risk of death. During colonization, the bacteria may evolve under the stressing selection pressures exerted in the CF lung, in particular, those resulting from challenges of the host immune defenses, antimicrobial therapy, nutrient availability and oxygen limitation. Understanding the adaptive mechanisms that promote successful colonization and long-term survival of B. cenocepacia in the CF lung is essential for an improved therapeutic outcome of chronic infections. To get mechanistic insights into these adaptive strategies a transcriptomic analysis, based on DNA microarrays, was explored in this study. The genomic expression levels in two clonal variants isolated during long-term colonization of a CF patient who died from the cepacia syndrome were compared. One of the isolates examined, IST439, is the first B. cenocepacia isolate retrieved from the patient and the other isolate, IST4113, was obtained three years later and is more resistant to different classes of antimicrobials. Approximately 1000 genes were found to be differently expressed in the two clonal variants reflecting a marked reprogramming of genomic expression. The up-regulated genes in IST4113 include those involved in translation, iron uptake (in particular, in ornibactin biosynthesis), efflux of drugs and in adhesion to epithelial lung tissue and to mucin. Alterations related with adaptation to the nutritional environment of the CF lung and to an oxygen-limited environment are also suggested to be a key feature of transcriptional reprogramming occurring during long-term colonization, antibiotic therapy and the progression of the disease.


The association of cardiovascular disease and metabolic syndrome with nephrolithiasis.
This review describes the relationship between nephrolithiasis, vascular disease and metabolic syndrome. There is increasing evidence that kidney stone formation is associated with a number of systemic problems including cardiovascular disease, metabolic syndrome and its components. Some of these associations are bidirectional. The reasons for these associations are not totally clear, but potential factors include metabolic responses associated with these disorders that promote a stone forming milieu in urine, environmental factors such as diet, oxidative stress and inflammation and molecular changes impacting the transport of certain analytes in urine. Urologists need to be cognizant of these associations as they may be able to contribute to an early diagnosis of a significant medical problem, or provide counseling to patients to prevent their occurrence.


Mathematical modeling of a Nafion membrane based optode incorporating 1-(2'-pyridylazo)-2-naphthol under flow injection conditions.
A general mathematical model of a flow-through optical chemical sensor prepared by the immobilization of 1-(2'-pyridylazo)-2-naphthol (PAN) into a commercial Nafion membrane was developed. The model takes into account the preparation of the optode membrane and in our opinion the most important chemical and physical processes involved in the generation of the analytical signal. The following model parameters were determined separately from the experimental verification of the model: aqueous diffusion coefficient of CuSO(4) - 8.75 x 10(-10)m(2)s(-1); membrane self-diffusion coefficient of the Cu(2+)-PAN complex and Cu(2+) - 1.87 x 10(-16) and 6.00 x 10(-15)m(2)s(-1), respectively; Nafion/water ion-exchange equilibrium constants for the Cu(2+)-PAN complex and Cu(2+) - 109.2 and 3.65 x 10(-3), respectively. Very good agreement was obtained between the experimental optode response and the model predictions thus showing that the model developed could be used successfully for the mathematical description and optimization of the PAN/Nafion optode as well as of other ion-exchange membrane based optodes having a similar response mechanism.


Diagnosis and management of non-criteria obstetric antiphospholipid syndrome.
Accurate diagnosis of obstetric antiphospholipid syndrome (APS) is a prerequisite for optimal clinical management. The international consensus (revised Sapporo) criteria for obstetric APS do not include low positive anticardiolipin (aCL) and anti β2 glycoprotein I (aβ2GPI) antibodies (< 99th centile) and/or certain clinical criteria such as two unexplained miscarriages, three non-consecutive miscarriages, late pre-eclampsia, placental abruption, late premature birth, or two or more unexplained in vitro fertilisation failures. In this review we examine the available evidence to address the question of whether patients who exhibit non-criteria clinical and/or laboratory manifestations should be included within the spectrum of obstetric APS. Prospective and retrospective cohort studies of women with pregnancy morbidity, particularly recurrent pregnancy loss, suggest that elimination of aCL and/or IgM aβ2GPI, or low positive positive aCL or aβ2GPI from APS laboratory diagnostic criteria may result in missing the diagnosis in a sizeable number of women who could be regarded to have obstetric APS. Such prospective and retrospective studies also suggest that women with non-criteria obstetric APS may benefit from standard treatment for obstetric APS with low-molecular-weight heparin plus low-dose aspirin, with good pregnancy outcomes. Thus, non-criteria manifestations of obstetric APS may be clinically relevant, and merit investigation of therapeutic approaches. Women with obstetric APS appear to be at a higher risk than other women of pre-eclampsia, placenta-mediated complications and neonatal mortality, and also at increased long-term risk of thrombotic events. The applicability of these observations to outcomes in women with non-criteria obstetric APS remains to be determined.


Chemically active filaments: analysis and extensions of slender phoretic theory.
Autophoretic microswimmers self-propel via surface interactions with a surrounding solute fuel. Chemically-active filaments are an exciting new microswimmer design that augments traditional autophoretic microswimmers, such as spherical Janus particles, with extra functionality inherent to their slender filament geometry. Slender Phoretic Theory (SPT) was developed by Katsamba et al. to analyse the dynamics of chemically-active filaments with arbitrary three-dimensional shape and chemical patterning. SPT provides a line integral solution for the solute concentration field and slip velocity on the filament surface. In this work, we exploit the generality of SPT to calculate a number of new, non-trivial analytical solutions for slender autophoretic microswimmers, including a general series solution for phoretic filaments with arbitrary geometry and surface chemistry, a universal solution for filaments with a straight centreline, and explicit solutions for some canonical shapes useful for practical applications and benchmarking numerical code. Many common autophoretic particle designs include discrete jumps in surface chemistry; here we extend our SPT to handle such discontinuities, showing that they are regularised by a boundary layer around the jump. Since our underlying framework is linear, combinations of our results provide a library of analytic solutions that will allow researchers to probe the interplay of activity patterning and shape.


The Moderating Role of Attention Biases in understanding the link between Behavioral Inhibition and Anxiety.
The current study aimed to extend the results of White et al. (2015) by examining the moderating role of attention biases at age 5 on the relations between Behavioral Inhibition (BI) during toddlerhood and anxiety symptoms at age 10. Children's BI at 2 and 3 years of age was measured using laboratory assessments, and attention bias towards threat was assessed using a dot-probe task at age 5. Latent Class Analysis (LCA) was used to identify the probability for children's membership in an anxiety class, which reflected primary anxiety at age 10 that was not comorbid with symptoms of inattention. Maternal and self-report measures of children's mental health, collected via questionnaires and semi-structured diagnostic interviews, were used as indicators for the LCA. The results revealed that threat-related attention biases moderated the relation between BI and anxiety, such that BI positively predicted the probability of being in the anxiety class only when children had an attention bias towards threat. BI was unrelated to anxiety when children had no attention bias or an attention bias away from threat. These results indicated that attention biases during preschool may differentiate between inhibited children who are at heightened risk for anxiety later in childhood from those who are not. The results are discussed in a framework detailing the role of attention biases in increasing the sensitivity for anxiety-related problems in children who display high levels of BI during early childhood.


Kinetics of phase separation in thin films: lattice versus continuum models for solid binary mixtures.
A description of phase separation kinetics for solid binary (A,B) mixtures in thin film geometry based on the Kawasaki spin-exchange kinetic Ising model is presented in a discrete lattice molecular field formulation. It is shown that the model describes the interplay of wetting layer formation and lateral phase separation, which leads to a characteristic domain size l(t) in the directions parallel to the confining walls that grows according to the Lifshitz-Slyozov t;{13} law with time t after the quench. Near the critical point of the model, the description is shown to be equivalent to the standard treatments based on Ginzburg-Landau models. Unlike the latter, the present treatment is reliable also at temperatures far below criticality, where the correlation length in the bulk is only of the order of a lattice spacing, and steep concentration variations may occur near the walls, invalidating the gradient square approximation. A further merit is that the relation to the interaction parameters in the bulk and at the walls is always transparent, and the correct free energy at low temperatures is consistent with the time evolution by construction.


Effects of salicylic acid derivatives on red blood cell membranes.
Salicylamide, sodium salicylate and acetylsalicylic acid are salicylic acid derivates. They differ in their substitution on the benzene ring and may have different effects on membranes. Red blood cells were used as a prototypical cellular system regarding drug mediated plasma bilayer effects. Established photometric methods sensing tiny changes of red blood cell morphology at rest (red blood cell shape) and at very low shear forces (red blood cell stiffness, red blood cell relaxation time) were applied. The derivative induced effects were detected in a time- and dose-dependent manner. Salicylamide induced a most pronounced echinocytic shape at 5 mM. The shape effect was smaller above as well as below 5 mM. Sodium salicylate induced echinocytes with increasing concentrations showing a saturation above 10 mM. In contrast, the shape was not affected by acetylsalicylic acid. All shape changes occurred within 2 min, and were reversible. The above tendencies were in parallel to a slight red blood cell stiffening. The relaxation time continuously increased with increasing concentrations in both salicylamide and sodium salicylate, with salicylamide always acting stronger. Acetylsalicylic acid again showed no effect. We hypothesize that the observed effects of sodium salicylate and salicylamide are due to their phenolic character mediating a molecular hydrophobicity. According to the bilayer couple hypothesis this would lead to an insertion into the red blood cells outer plasma bilayer leaflet. The extension induced here would cause a positive membrane bending leading to echinocytic shapes and the observed loss of red blood cell fluidity. In contrast, the hydrophilic aspirin would penetrate and thus not affect the red blood cell plasma membrane.


Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients.
We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients. We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement. 54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23-4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log10 increase, 2.05 [0.91-4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log10 increase, 1.39 (1.01-1.91), P = 0.043; and OR (95% CI) per 1 log10 increase, 1.46 (1.07-1.99), P = 0.014, respectively, when adjustment included F2-IsoPs and MDA. Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation.


Optimization of the Detection Method for Phosphorylated α-Synuclein in Parkinson Disease by Skin Biopsy.
Background: Recent studies have found deposition of phosphorylated α-synuclein (p-syn) in Parkinson disease (PD) patients' skin, indicating p-syn may be a potential biomarker of PD. However, the sensitivity of the p-syn detection varied largely from 5. 3 to 100%, this influenced the clinical use of this detection method to some extent. Objective: This study aimed to optimize the skin biopsy method for detecting p-syn deposition in patients with PD. Methods: Ninety PD patients and 30 healthy controls underwent skin biopsies at 2-3 of the following sites: the distal leg, thigh, cervical region, or forearm. Skin biopsy samples were cut to 50- and 15-μm thickness sections. Deposition of p-syn were detected by using double immunofluorescence labeling of protein gene production 9.5 (PGP9.5) /p-syn. Statistical data analysis was performed using SPSS 25.0 software. Results: Deposition of p-syn were found in 75/90 PD patients but not in healthy controls (p < 0.001). The positive deposition rate of p-syn in the single cervical site was significantly higher than that in the distal leg, thigh, and forearm site. Two samples from the cervical region had a higher p-syn positive rate compared to single cervical site (90.5 vs. 66.7%, p = 0.037). There was no significant difference between the p-syn positive rate of samples from the distal leg/cervical sites and 2 samples from cervical region (80 vs. 90.5%, p = 0.261). Next, the p-syn positive deposition rate of 2-biopsy samples including distal leg/cervical sites and double samples in the cervical site were comparable to the 3-biopsy samples. The 50-μm section had a significantly higher p-syn positive rate than the 15-μm section (p = 0.049). Conclusions: Two biopsy sites (cervical/distal leg) or 2 samples from the cervical site were considered to be priority biopsy sites for detecting p-syn in PD patients. Thick sections may provide a higher p-syn positive rate than thin sections for skin biopsies. These findings provide an optimized p-syn detection method, indicate the valuable pathology biomarker of PD and will promote the clinical use of skin biopsy in the future.


Intracellular retention and subsequent release of bovine milk lactoferrin taken up by human enterocyte-like cell lines, Caco-2, C2BBe1 and HT-29.
Lactoferrin (LF) is an iron-binding glycoprotein contained in milk and other exocrine fluids, and is believed to have multiple biological functions. We investigated the intracellular dynamics of LF taken up by three lines of human enterocytes and the subsequent release of internalized LF by using two-site ELISA and confocal microscopy. LF taken up by Caco-2 cells was kept partially intact within the cells and subsequently released to the medium as degraded fragments of 30-50 kDa. The retention and subsequent release of LF by Caco-2 cells were much more abundant than those of ovalbumin, ovomucoid and lysozyme. Such results characteristic of LF were also similarly observed in C2BBe1 and HT29 cells more markedly. LF was detected as punctate signals and partially colocalized with the lactoferrin receptor, intelectin-1, in the respective cytoplasm and nuclei of Caco-2 and C2BBe1 cells. In contrast, LF within the HT-29 cells was detected as much smaller punctate signals scattered in the cytoplasm.


Synthesis and biological activity of 2-cyanoacrylamide derivatives tethered to imidazopyridine as TAK1 inhibitors.
The importance of transforming growth factor beta-activated kinase 1 (TAK1) to cell survival has been demonstrated in many studies. TAK1 regulates signalling cascades, the NF-κB pathway and the mitogen-activated protein kinase (MAPK) pathway. TAK1 inhibitors can induce the apoptosis of cancerous cells, and irreversible inhibitors such as (5Z)-7-oxozeaenol are highly potent. However, they can react non-specifically with cysteine residues in proteins, which may have serious adverse effects. Reversible covalent inhibitors have been suggested as alternatives. We synthesised imidazopyridine derivatives as novel TAK1 inhibitors, which have 2-cyanoacrylamide moiety that can form reversible covalent bonding. A derivative with 2-cyano-3-(6-methylpyridin-2-yl)acrylamide (13h) exhibited potent TAK1 inhibitory activity with an IC50 of 27 nM. It showed a reversible reaction with β-mercaptoethanol, which supports its potential as a reversible covalent inhibitor.


[Therapeutic advances in breast cancer].
The treatment of breast cancer has made significant improvements during the past ten years. For early breast cancer with a clinically negative axilla sentinel node biopsy has become the preferred approach. For endocrine therapy of postmenopausal patients the selective aromatase inhibitors have become standard in metastatic as well as in early breast cancer. Trastuzumab (Herceptin) plays an important role in the treatment of HER2-positive breast cancer in the metastatic and since 2005 also in the adjuvant setting. When chemotherapy is used to treat metastatic breast cancer drug combinations are superior to monotherapy only in terms of response rates. By contrast, in the adjuvant setting combination drug therapy is the standard. New methods of tissue analysis including expression patterns of mRNA and proteins are promising research strategies to further advance the field.


Reinforced PEI/PVdF Multicore-Shell Structure Composite Membranes by Phase Prediction on a Ternary Solution.
To construct a polyetherimide (PEI)-reinforced polyvinylidene fluoride (PVdF) composite membrane with multicore-shell structure, a ternary solution was prepared and electrospun by single-nozzle electrospinning. A theoretical prediction was made for the feasibility of complete distinction of two phases. The diameters of the membrane fibers and the PEI multi-core fibrils varied with the PEI ratio and the spinning time, respectively. The tensile strength and modulus were improved to 48 MPa and 1.5 GPa, respectively. The shrinkage of the membrane was only 6.6% at 180 °C, at which temperature the commercial PE separator melted down. The reinforcement in mechanical and thermal properties is associated with multiple PEI nanofibrils oriented along the fiber axis. Indeed, the unique morphology of self-assembled multicore-shell fibers plays an important role in their properties. All in all, PEI/PVdF membranes are appropriate for a lithium-ion battery application due to their high mechanical strength, excellent thermal stability, and controllable textural properties.


Forms of Damage of Bricks Subjected to Cyclic Freezing and Thawing in Actual Conditions.
The paper presents the characteristics of damage of bricks in masonry structures of significant historical value as a result of cyclic freezing and thawing. Based on extensive investigation, which included macroscopic description, determination of compressive strength and tensile strength, determination of the mineral composition, scanning microscopy observation and determination of the porosity structure of bricks, three forms of frost damage were distinguished, termed as powdering, flaking and cracking. Bricks were collected from existing historical buildings 70 years after their construction. It was observed that the particular form of frost damage of bricks is highly correlated with the structure of porosity. Additional factors affecting the form of frost destruction are the strength of the material, its mineral composition and the spatial arrangement of the texture elements. Taking the above into account, it is possible to evaluate frost resistance of bricks and specify the form of damage. Predicting frost resistance and forms of damage based on low-destructive methods using small samples is the expected solution in the case of heritage facilities.


Optomechanically Actuated Microcilia for Locally Reconfigurable Surfaces.
Artificial microcilia structures have shown potential to incorporate actuators in various applications such as microfluidic devices and biomimetic microrobots. Among the multiple possibilities to achieve cilia actuation, magnetic fields present an opportunity given their quick response and wireless operation, despite the difficulty in achieving localized actuation because of their continuous distribution. In this work, a high-aspect-ratio (>8), elastomeric, magnetically responsive microcilia array is presented that allows for wireless, localized actuation through the combined use of light and magnetic fields. The microcilia array can move in response to an external magnetic field and can be locally actuated by targeted illumination of specific areas. The periodic pattern of the microcilia also diffracts light with varying diffraction efficiency as a function of the applied magnetic field, showing potential for wirelessly controlled adaptive optical elements.


Electrokinetic microscopy: a technique for imaging three-dimensional surface topography and heterogeneity of surface material.
In the present study, we introduce the concept of an electrokinetic microscope (EKM), a non-contact type probe microscope that can simultaneously provide a test specimen's three-dimensional surface topography and heterogeneity of surface material. In the EKM, the flow impedance and the streaming potential are measured during the scanning process to reproduce the topography and the heterogeneity, respectively. The working principle of the EKM is experimentally demonstrated by measuring specimens whose surfaces consist of thin layers of various materials and topographical differences. Experimental results also show that the EKM can be used regardless of the electrical conductivity of test specimens.


Hyperamylasaemia & related enzyme factors in renal failure associated with benign & malignant conditions.
Total serum amylase activity, its isoenzymes and pancreatic to salivary amylase (P/S) ratio were studied in 40 normal subjects and 47 patients with renal failure, 32 with benign and 15 with malignant conditions. Amylase to creatinine clearance (Cam/Ccr) was studied in 17 normals and 14 patients with renal failure, 10 benign and 4 with malignant diseases. Total amylase activity, and pancreatic and salivary fractions were found to be increased by about 3.4 times the normal in both benign and malignant conditions producing renal failure though the P/S ratio was within the normal range. However, the increase in the urea and creatinine levels in patients could not be related to the increase in serum total amylase. Besides the Cam/Ccr ratio was elevated in patients with both benign and malignant conditions producing renal insufficiency whereas the Cam and Ccr were individually found to be decreased. Why patients with chronic renal failure in both conditions without clinical evidence of pancreatitis should have elevated Cam/Ccr ratio is not clear.


[The impact of different comprehensive treatment models on patients with adenocarcinoma of esophagogastric junction based on propensity score matching: a single center cohort study].
Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ2 test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ2 test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ2=6.971, P=0.008) and nCRT group (6.9% (2/29), χ2=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ2=10.881, P=0.001; χ2=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ2=6.740, P=0.009) and nCRT group (31.0% (9/29), χ2=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ2=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ2=4.976, P=0.083) and progression-free survival (χ2=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.


Introducing a Virtual Reality Experience in Anatomic Pathology Education.
A proper examination of surgical specimens is fundamental in anatomic pathology (AP) education. However, the resources available to residents may not always be suitable for efficient skill acquisition. We propose a method to enhance AP education by introducing high-definition videos featuring methods for appropriate specimen handling, viewable on two-dimensional (2D) and stereoscopic three-dimensional (3D) platforms. A stereo camera system recorded the gross processing of commonly encountered specimens. Three edited videos, with instructional audio voiceovers, were experienced by nine junior residents in a crossover study to assess the effects of the exposure (2D vs 3D movie views) on self-reported physiologic symptoms. A questionnaire was used to analyze viewer acceptance. All surveyed residents found the videos beneficial in preparation to examine a new specimen type. Viewer data suggest an improvement in specimen handling confidence and knowledge and enthusiasm toward 3D technology. None of the participants encountered significant motion sickness. Our novel method provides the foundation to create a robust teaching library. AP is inherently a visual discipline, and by building on the strengths of traditional teaching methods, our dynamic approach allows viewers to appreciate the procedural actions involved in specimen processing.


A neural substrate of hyperactivity in borna disease: changes in brain dopamine receptors.
Rats experimentally infected with the neurotropic RNA virus, Borna disease virus, have a hyperactive movement disorder. Because locomotor activity is modulated by the nucleus accumbens (N. Acc.) dopamine (DA) system, high-affinity DA uptake, DA D1, D2, and D3 receptor binding sites were examined in N. Acc. subregions of normal and infected rats by quantitative receptor autoradiography. The N. Acc. of infected rats had decreased mazindol and D2 and D3 radioligand binding in the core and decreased D3 radioligand binding in rostral subregions. The abnormalities observed in the N. Acc. DA system of infected rats may offer insights into the potential viral pathogenesis of psychiatric conditions with a dopaminergic substrate such as schizophrenia and affective disorders.


[A comparative study of fibrinogenolysis of adult and cord vein fibrinogen (author's transl)].
The streptokinase induced fibrinogenolysis of cord vein fibrinogen follows a slower degradation rate than adult fibrinogen prepared from plasma in the same manner. However, no difference in the degradation rate could be observed when plasmin was used. It is suggested that the lower plasminogen content in the preparation of the cord vein fibrinogen is responsible for the slower degradation rate observed after streptokinase induction.


Distribution of cerebral lesions in acquired hepatocerebral degeneration.
The brain lesions of our patients with chronic portal-systemic venous shunts were much the same regardless of the presence or absence of primary liver disease. Alzheimer's type 2 abnormality of astrocytes and demarcated areas of spongy degeneration were found, mainly in the grey matter, with more severe involvement of the basal ganglia and the deeper layers of the frontal, parietal and occipital cortex. The spongy degeneration showed an especially close correlation with the arterial blood supply, being greatest in borderland areas that fall between the regions usually supplied by one or other of the major cerebral arteries. Previous investigations have not been primarily concerned with selective vulnerability so that comparisons are difficult, but on review, there is evidence that this pattern of involvement is a feature of both Wilson's disease and acquired hepatocerebral degeneration. The toxic effect of the portal blood is greatest in the grey matter, probably because of the greater metabolic activity there, and the distribution of lesions within this area of greater vulnerability appears to be further influenced by circulatory factors.


Dynamic intracellular distribution of Eaf2 and its potential involvement in UV-Induced DNA damage response.
Eaf2 encodes a tumor suppressor that plays multiple functions in transcriptional activation, apoptosis, and embryonic development. In this study, we utilized GFP-EAF2 fusion protein to describe the dynamic subcellular movement of Eaf2. GFP-EAF2 is preferentially localized to the nucleus, and in the presence of ELL, it accumulates in nuclear speckles. However, Eaf2 is an unstable nuclear protein whose stability is affected by serum. Further, we provided first evidence that nuclear distribution of Eaf2 is responsive to DNA damage. Following UV irradiation, Eaf2 is relocalized to the nucleolus, suggesting a possible functional involvement of Eaf2 in DNA damage response.


Voltage-dependent anion channel (VDAC) as mitochondrial governator--thinking outside the box.
Despite a detailed understanding of their metabolism, mitochondria often behave anomalously. In particular, global suppression of mitochondrial metabolism and metabolite exchange occurs in apoptosis, ischemia and anoxia, cytopathic hypoxia of sepsis and multiple organ failure, alcoholic liver disease, aerobic glycolysis in cancer cells (Warburg effect) and unstimulated pancreatic beta cells. Here, we propose that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane accounts for global mitochondrial suppression. In anoxia, cytopathic hypoxia and ethanol treatment, reactive oxygen and nitrogen species, cytokines, kinase cascades and increased NADH act to inhibit VDAC conductance and promote selective oxidation of membrane-permeable respiratory substrates like short chain fatty acids and acetaldehyde. In cancer cells, highly expressed hexokinase binds to and inhibits VDAC to suppress mitochondrial function while stimulating glycolysis, but an escape mechanism intervenes when glucose-6-phosphate accumulates and dissociates hexokinase from VDAC. Similarly, glucokinase binds mitochondria of insulin-secreting beta cells, possibly blocking VDAC and suppressing mitochondrial function. We propose that glucose metabolism leads to glucose-6-phosphate-dependent unbinding of glucokinase, relief of VDAC inhibition, release of ATP from mitochondria and ATP-dependent insulin release. In support of the overall proposal, ethanol treatment of isolated rat hepatocytes inhibited mitochondrial respiration and accessibility to adenylate kinase in the intermembrane space, effects that were overcome by digitonin permeabilization of the outer membrane. Overall, these considerations suggest that VDAC is a dynamic regulator, or governator, of global mitochondrial function both in health and disease.


[Two-dimensional gel electrophoresis map of serum proteins in patients with chronic Keshan disease].
To identify the different serum proteins expressed in patients with Keshan disease (KD). Two-dimensional gel electrophoresis (2-DE) was performed with serum samples from the patients with chronic KD and healthy controls to separate serum proteins. The gels were stained by sliver and scanned by Umax scanner. The data were analyzed by ImageMaster 2D software. KD related proteins were identified through searching the ExPASy SWISS-2DPAGE database. Stable two-dimensional gel electrophoresis maps were established for serum samples of KD patients and healthy controls. A total of 808 and 814 protein spots were observed in KD patients and healthy controls, respectively. The two maps had 96.5475% identical protein spots and 44 differentially expressed protein spots. Eleven protein spots were expressed exclusively in KD patients and 12 protein spots only appeared in healthy controls. About 21 proteins were expressed in both groups but varied in quantities (14 proteins were over-expressed by more than 3 times and 7 proteins were under-expressed by more than 3 times in KD patients, P < 0.01). Among the 353 protein spots matched with the ExPASy-SWISS-2DPAGE databank, No. 1177 protein appeared in the KD patient was found to have the closest match with P02774 2-D0004T6 known as vitamin D binding protein (VDBP). There is a significant difference in serum protein expression between KD patients and normal people. VDBP might play a role in cardiac muscle damage via inflammatory immune reactions.


Transferable crosslinked chitosan membranes for human melanocyte culture.
Development of transferable biocompatible membranes, which can be used for melanocyte culture and transplantation, is considered a feasible approach to increase the success rate for vitiliginous treatment. In this study, a crosslinked chitosan membrane (CCM) was produced via physical crosslinking of chitosan with sodium sulfate. The physical and mechanical properties as well as growth and phenotype expression of melanocytes on the CCM were investigated. The CCM supported growth and proliferation of melanocytes with the existence of melanin granules in the cytoplasm. The melanocytes remained active after transplantation. The CCM absorbed water approximately doubled from its original weight and permitted ∼2400 g/m² per day of water vapor transmission, suggesting that the CCM can function as an efficient wound dressing. Dynamic mechanical and tensile measurement results showed that the CCM possessed favorable wet strength for cell culture, separation, transfer, and transplantation application. This transferable CCM has the potential to be applied for vitiligo treatment.


Pancreatic cancer in an 18-year-old boy.
We report a case of histopathologically proven pancreatic cancer in an 18-year-old boy. Complete blood picture revealed moderate normochromic normocytic anaemia with anisocytosis. Other laboratory results including liver function tests, renal functions tests, serum amylase, fasting blood sugar level and serum electrolytes were all of normal values. Abdominal US showed a focal mass of the pancreatic body and tail with involvement of the spleen and the transverse colon. Laparotomy confirmed the sonographic findings and demonstrated adhesions of the transverse colon to the mass at the splenic hilum. Histology of the mass showed a well differentiated adenocarcinona of the body and tail of the pancreas. This highlights the differentiation of pancreatic cancer from autoimmune pancreatitis and, to a lesser extent, other forms of pancreatitis and benign pancreatic lesions.


Kinetics of citrate-induced activation and polymerization of chick liver acetyl-CoA carboxylase.
The kinetic time course of citrate-induced activation and polymerization (into filaments) of the protomeric form of acetyl-CoA carboxylase were compared to assess the concertedness of the two processes. Rapid-quench techniques were employed to measure the kinetics of activation of the carboxylase-catalyzed reaction by citrate. When enzyme was preincubated with citrate prior to initiating the steady state turnover reaction with acetyl-CoA in the rapid-quench device, the observed rate of carboxylation of acetyl-CoA was apparently linear from the moment of mixing. However, when enzyme was mixed with citrate to initiate the reaction, a lag (t1/2 = 0.7 s) occurred in the approach to steady state carboxylation rate. This lag was independent of enzyme concentration over a 230-fold range and was marginally dependent upon citrate concentration. Over the same range of enzyme concentration, polymerization of carboxylase protomers, as determined by right angle light scattering, was enzyme concentration-dependent in a manner predicted by a single protomer activation step, followed by a rate-limiting dimerization of active protomer and subsequent polymerization. Polymerization is a second order process, with a second order rate constant of 597,000 M-1 s-1. There appear to be two steps that limit polymerization of the inactive carboxylase protomer: a rapid citrate-induced conformational change, which is independent of enzyme concentration and leads to an active protomeric form of the enzyme and the dimerization of the active protomer, which constitutes the first step of polymerization and is enzyme concentration-dependent. Dimerization is the rate-limiting step of acetyl-CoA carboxylase polymerization. On the basis these results, it is concluded that activation of catalysis and the polymerization of carboxylase protomers are not concerted. Furthermore, activation of carboxylation leading to the formation of an active protomer was faster than polymerization under all conditions, and therefore precedes polymerization. It was also shown that the activation constant (Kact) for citrate is altered in a predictable manner by the accumulation of the reaction product, malonyl-CoA, the Kact increasing with malonyl-CoA concentration. Depolymerization of fully polymerized acetyl-CoA carboxylase is caused by malonyl-CoA or ATP.Mg (and HCO3-). Both malonyl-CoA and ATP.Mg (and HCO3-) compete with citrate in the maintenance of a given state of the protomer-polymer equilibrium apparently by carboxylating the enzyme to form enzyme-biotin CO2- which destabilizes the polymeric form.


Extrahepatic manifestations of Hepatitis C Virus infection: a general overview and guidelines for a clinical approach.
Hepatitis C Virus is associated with a wide series of extrahepatic manifestations. Based on available data the link between the virus and some of these extrahepatic diseases is only suggested and needs further confirmation. Hepatitis C Virus-related lymphoproliferative disorders, whose prototype is mixed cryoglobulinaemia, represent the most closely related extrahepatic manifestations of Hepatitis C Virus. Other Hepatitis C Virus-associated disorders include nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, porphyria cutanea tarda, lichen planus, diabetes, chronic polyarthritis, cardiopathy and atherosclerosis. A pathogenetic link between Hepatitis C Virus and some extrahepatic manifestations was confirmed by their responsiveness to antiviral therapy, which is now deemed the first therapeutic option to consider. By contrast, there are diseases where treatment with interferon was ineffective or dangerous. The aim of the present paper is to outline the most recent evidence concerning extrahepatic disorders that are possibly associated with Hepatitis C Virus infection. Special emphasis will be given to discussion of the most appropriate clinical approaches to be adopted in order to diagnose, treat (possibly prevent) and follow-up extrahepathic diseases in patients with Hepatitis C Virus infection.


Comprehensive Characterization of Linalool-HP-β-Cyclodextrin Inclusion Complexes.
The objective of the present study is to obtain linalool- cyclodextrin (CDs) solid complexes for possible applications in the food industry. For this purpose, a detailed study of linalool complexation was carried out at different pH values, to optimize the type of CDs and reaction medium that support the highest quantity of encapsulated linalool. Once demonstrated the ability of hydroxypropyl-β-cyclodextrin (HP-β-CDs), to form inclusion complexes with linalool (KC = 921 ± 21 L mol-1) and given their greater complexation efficacy (6.788) at neutral pH, HP-β-CDs were selected to produce solid inclusion complexes by using two different energy sources, ultrasounds and microwave irradiation, subsequently spraying the solutions obtained in the Spray Dryer. To provide scientific solidity to the experimental results, the complexes obtained were characterized by using different instrumental techniques in order to confirm the inclusion of linalool in the HP-β-CDs hydrophobic cavity. The linalool solid complexes obtained were characterized by using 1H nuclear magnetic resonance (1H-NMR) and 2D nuclear magnetic resonance (ROSEY), differential scanning calorimetry, thermogravimetry and Fourier transform infrared spectrometry. Moreover, the structure of the complex obtained were also characterized by molecular modeling.


Bone mineral density accrual determines energy expenditure with refeeding in anorexia nervosa and supersedes return of menses.
Osteopenia and osteoporosis are major complications of anorexia nervosa (AN). Since bone is a tissue requiring large amounts of energy, we examined the disproportionate increase in resting energy expenditure (REE) that occurs with refeeding of AN patients to determine if it was related to bone accretion. Thirty-seven AN patients aged 23.4 ± 4.8 years underwent a behavioral weight-gain protocol lasting a median of 66 days; 27 remained amenorrheic, and 10 regained menses. Sixteen controls aged 25.1 ± 4.7 years were age- and % IBW matched with patients. REE was measured using a respiratory chamber-indirect calorimeter. Significant correlations were found between REE and changes in spine (r = 0.48, P < 0.02) and leg (r = 0.43, P < 0.05) BMDs in AN patients. Further subgroup analysis of the amenorrheics revealed significant correlation between REE and change in spine BMD (r = 0.59, P < 0.02) and higher IGF-1 after weight gain compared to controls. Amenorrheics also had lower BMDs. These findings were absent in the regained menses group. The increase in REE seen in women with AN during nutritional rehabilitation may be related to active bone formation, which is not as prominent when menses have returned.


Technique for transmission and immunoelectron microscopy of the human endolymphatic sac and vestibular epithelia.
A surgical technique is presented to obtain the entire vestibular aqueduct, containing the endolymphatic duct and sac as well as the vestibular epithelia, from the maculae and cristae during labyrinthectomy. The inner ear tissue was fixed in 3% glutaraldehyde, decalcified in 0.1 mol/L Na-EDTA, and routinely processed for transmission electron microscopy, including post-fixation with osmium tetroxide. Postembedding protein A-colloidal gold immunoelectron microscopy was performed after exposure of cellular antigenic sites by sodium metaperiodate. To validate this technique, thin sections from the crista ampullaris and the endolymphatic sac were incubated with antibodies raised against S-100, a protein present in specific types of neural tissue. Specific immunoreactivity was observed in the crista ampullaris, but not in the endolymphatic sac. The surgical biopsy technique described provides a means for the neuro-otologist to collect inner ear tissue from surgical patients that can be used for pathological studies using immunohistochemistry and electron microscopy.


Variability of protein content in calcium oxalate monohydrate stones.
Urinary stones are heterogeneous in their fragility to lithotripter shockwaves. As a first step in gaining a better understanding of the role of matrix in stone fragility, we measured extractible protein in calcium oxalate monohydrate (COM) stones that were extensively characterized by micro-computed tomography (micro CT). Stones were scanned using micro CT (Scanco mCT20, 34 microm). They were ground, and the protein extracted using four methods: 0.25M EDTA, 2% SDS reducing buffer, 9M urea buffer, and 10% acetic acid. Protein was measured using NanoOrange. The SDS extracts were also examined using polyacrylamide electrophoresis (PAGE). Extracted protein was highest with the SDS or urea methods (0.28% +/- 0.13% and 0.24% +/- 0.11%, respectively) and lower using the EDTA method (0.17% +/- 0.05%; P < 0.02). Acetic acid extracted little protein (0.006 +/- 0.002%; P < 0.001). Individual stones were significantly different in extractability of protein by the different methods, and SDS-PAGE revealed different protein patterns for individual stones. Extracted protein did not correlate with X-ray-lucent void percentage, which ranged from 0.06% to 2.8% of stone volume, or with apatite content. Extractible stone-matrix protein differs for individual COM stones, and yield is dependent on the extraction method. The presence of X-ray-lucent voids or minor amounts of apatite in stones did not correlate with protein content. The amounts of protein recovered were much lower than reported by Boyce, showing that these methods extracted only a fraction of the protein bound up in the stones. The results suggest that none of the methods tested will be useful for helping to answer the question of whether matrix content differs among stones of differing fragility to lithotripter shockwaves.


Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: II. Modulation of the transient and resting cytosolic free calcium alters progesterone secretion.
A previous study demonstrated that prostaglandin F2 alpha (PGF2 alpha) stimulates a transient increase in cytosolic free Ca2+ levels [( Ca2+]i) in ovine large luteal cells. In the present study, the magnitude of the PGF2 alpha (0.5 microM)-induced calcium transient in Hanks' medium (87 +/- 2 nM increase above resting levels) was reduced (P less than 0.05) but not completely eliminated in fura-2 loaded large luteal cells incubated in Ca2(+)-free or phosphate- and carbonate-free medium (10 +/- 1 nM, 32 +/- 6 nM, above resting levels; respectively). Preincubation for 2 min with 1 mM LaCl3 (calcium antagonist) eliminated the PGF2 alpha-induced calcium transient. The inhibitory effect of PGF2 alpha on secretion of progesterone was reduced in Ca2(+)-free medium or medium plus LaCl3. Resting [Ca2+]i levels and basal secretion of progesterone were both reduced (P less than 0.05) in large cells incubated in Ca2(+)-free medium (27 +/- 4 nM; 70 +/- 6% control, respectively) or with 5 microM 5,5'-dimethyl bis-(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (40 +/- 2 nM; 49 +/- 1% control; respectively). In addition, secretion of progesterone was inhibited (P less than 0.05) by conditions that increased (P less than 0.05) [Ca2+]i; that is LaCl3 ([Ca2+]i, 120 +/- 17 nM; progesterone, 82 +/- 8% control) and PGF2 alpha ([Ca2+]i, 102 +/- 10 nM; progesterone, 82 +/- 3% control). In small luteal cells, resting [Ca2+]i levels and secretion of progesterone were reduced by incubation in Ca2(+)-free Hanks ([Ca2+]i, 28 +/- 2 nM; progesterone, 71 +/- 6% control), however, neither LaCl3 nor PGF2 alpha increased [Ca2+]i levels or inhibited secretion of progesterone. The findings presented here provide evidence that extracellular as well as intracellular calcium contribute to the PGF2 alpha-induced [Ca2+]i transient in large cells. Furthermore, whereas an adequate level of [Ca2+]i is required to support progesterone production in both small and large cells, optimal progesterone production in large cells depends upon an appropriate window of [Ca2+]i.


Exploring Autism, Culture, and Immigrant Experiences: Lessons from Sri Lankan Tamil Mothers.
Background: Canada is home to a mosaic of cultures with immigrant communities from a wide range of countries, but there are significant variations in how autism spectrum disorder (ASD) may be understood across different immigrant groups, including Sri Lankan Tamils. Such gaps in knowledge may present challenges for immigrant families that are trying to access appropriate care for their child, including occupational therapy services. Purpose: This descriptive qualitative study aimed to better understand the experiences of immigrant Sri Lankan Tamil parents of children diagnosed with ASD in Southern Ontario, Canada. Method: Interviews were analyzed using an in-depth content analysis. Findings: Results demonstrated parents' perceived supports and barriers towards ASD intervention planning, and indicated that parents were generally satisfied by the level of cultural competence in current ASD systems. However, families may still experience significant immigrant-related barriers that are not fully addressed. Implications: Recommendations to improve cultural awareness among occupational therapists utilizing ASD interventions are suggested.


Unification of hierarchical reference theory and self-consistent Ornstein-Zernike approximation: analysis of the critical region for fluids and lattice gases.
The hierarchical reference theory (HRT) and the self-consistent Ornstein-Zernike approximation (SCOZA) are two liquid state theories that both yield a largely satisfactory description of the critical region as well as the phase coexistence and equation of state in general. In two previous works, unification of these theories has been considered and general equations were established. Further it was shown that the solution of the mean spherical model and a generalized version of it can be obtained in this way. In the present work, analysis of the critical region for fluids and lattice gases is performed. A key result of our HRT-SCOZA approximation is that for the standard three-dimensional fluid, lattice gas, or Ising model, the critical index for the critical isotherm is delta=5 and for the curve of coexistence it is beta=13 provided full scaling is assumed. More generally we find beta=2(delta+1) .


High Yielding, One-Pot Synthesis of Bis(1H-indazol-1-yl)methane Catalyzed by 3d-Metal Salts.
Synthetic access to poly(indazolyl)methanes has limited their study despite their structural similarity to the highly investigated chelating poly(pyrazolyl)methanes and their potentially important indazole moiety. Herein is presented a high yielding, one-pot synthesis for the 3d-metal catalyzed formation of bis(1H-indazol-1-yl)methane from 1H-indazole utilizing dimethylsulfoxide as the methylene source. Complete characterization of bis(1H-indazol-1-yl)methane is given with 1H and 13C NMR, UV/Vis, FTIR, high resolution mass spectrometry and for the first time, single crystal X-ray diffraction. This simple, inexpensive pathway to yield exclusively bis(1H-indazol-1-yl)methane provides synthetic access to further investigate the coordination and potential applications of the family of bis(indazolyl)methanes.


French-Canadian version of the Chronic Respiratory and St George's Respiratory questionnaires: an assessment of their psychometric properties in patients with chronic obstructive pulmonary disease.
French versions of the Chronic Respiratory Questionnaire (CRQ) and the St George's Respiratory Questionnaire (SGRQ) have largely been used in Canada, although the process by which they were translated remains unknown and the psychometric properties of these translated versions have not been assessed in a properly designed study. To translate and evaluate the psychometric properties of the French-Canadian versions of the CRQ and the SGRQ. The questionnaires were translated according to standardized guidelines for cross-cultural adaptation. Measurements were made at baseline and again after two weeks in 27 chronic obstructive pulmonary disease (COPD) patients known to have stable disease. Measurements were also taken pre- and post-treatment in patients with acute exacerbation of COPD (33 patients) or in pulmonary rehabilitation (32 patients). The CRQ showed high test-retest reliability (the majority above 0.70), although it was slightly lower for the dyspnea dimension (0.58 to 0.65). The SGRQ also showed high test-retest reliability (above 0.80), although it was lower for the symptoms dimension (0.54 to 0.58). The internal consistency reliability coefficients ranged from 0.73 to 0.90 for the CRQ and above 0.80 for the SGRQ, except for the symptoms dimension. The Pearson's correlation coefficients were low (less than 0.30) between most of the translated questionnaire dimension scores and forced expiratory volume in 1 s, 6 min walking test and dyspnea measures. The correlation was generally high (greater than 0.50) between the two questionnaires and the 36-item short form health survey, and for those domains that measured the same construct. The changes in the total and subscale scores of the CRQ and the SGRQ (except for the symptoms domain) were all largely above the variability of the score in the stable disease group. The present study confirms that the French-Canadian translated versions of the CRQ and the SGRQ perform well with respect to their psychometric properties. They are both suitable for their intended purpose, ie, to detect change in health status in patients with COPD when assessing if a treatment is beneficial. However, the symptoms domain of the SGRQ cannot be used to assess acute change with respect to a given therapy.


Developing Effective Case Scenarios for Interprofessional Electronic Health Record Research.
In the last decade, there have been numerous calls for research in interprofessional communication and documentation. Some of the limitations of research in this area have been proprietary user interfaces that may not be generalizable and impact varying adoption rates of electronic documentation among different health disciplines. In order to address these concerns, researchers need to create standardized case scenarios as research instruments. This paper outlines the process for developing a case scenario instrument for use in interprofessional electronic documentation research.


Mandibular advancement using an intra-oral osteogenic distraction technique: a report of three clinical cases.
Osteogenic distraction has been used for decades to lengthen limbs and now attention is focused upon its use within the craniofacial skeleton. This paper addresses distraction of the mandible. It is proposed that mandibular osteogenic distraction could be a possible adjunct to the orthodontic treatment of those adult patients with skeletal anomalies, who would benefit from combined orthodontic/orthognathic treatment. Three consecutive cases from one unit are presented, where adult patients with severe Class II division 1 malocclusions have undergone orthodontic treatment combined with mandibular osteogenic distraction, instead of conventional bilateral sagittal split osteotomies.


[Repair and regeneration of the airway epithelium].
Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions, through several mechanisms including basal cell spreading and migration, followed by proliferation and differentiation of epithelial cells. The cellular and molecular factors involved in wound repair and epithelial regeneration are closely interacting and imply extracellular matrix proteins, matrix metalloproteinases (MMPs) and their inhibitors as well as cytokines and growth factors secreted by airway epithelial and mesenchymal cells. The development of in vitro and in vivo models of airway epithelium wound repair allowed the study of the spatio-temporal modulation of these factors during the different steps of epithelial repair and regeneration. In this context, several studies have demonstrated that the matrix and secretory environment are markedly involved in these mechanisms and that their dysregulation may induce remodelling of the airway mucosa. A better knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to regenerative therapeutics allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.


Discovery of a 25-cm asteroid clast in the giant Morokweng impact crater, South Africa.
Meteorites provide a sample of Solar System bodies and so constrain the types of objects that have collided with Earth over time. Meteorites analysed to date, however, are unlikely to be representative of the entire population and it is also possible that changes in their nature have occurred with time. Large objects are widely believed to be completely melted or vaporized during high-angle impact with the Earth. Consequently, identification of large impactors relies on indirect chemical tracers, notably the platinum-group elements. Here we report the discovery of a large (25-cm), unaltered, fossil meteorite, and several smaller fragments within the impact melt of the giant (> 70 km diameter), 145-Myr-old Morokweng crater, South Africa. The large fragment (clast) resembles an LL6 chondrite breccia, but contains anomalously iron-rich silicates, Fe-Ni sulphides, and no troilite or metal. It has chondritic chromium isotope ratios and identical platinum-group element ratios to the bulk impact melt. These features allow the unambiguous characterization of an impactor at a large crater. Furthermore, the unusual composition of the meteorite suggests that the Morokweng asteroid incorporated part of the LL chondrite parent body not represented by objects at present reaching the Earth.


Increased erythrocyte C4D is associated with known alloantibody and autoantibody markers of antibody-mediated rejection in human lung transplant recipients.
Immune responses to mismatched donor human leukocyte antigens (HLA) are important in the pathogenesis of chronic rejection. This study evaluated whether erythrocyte-bound C4d (E-C4d) is associated with known alloimmune and autoimmune markers of antibody-mediated rejection after human lung transplantation (LTx). Flow cytometry was used to analyze 22 LTx recipients and 15 healthy individuals for E-C4d. Development of antibodies to donor-mismatched HLA (donor-specific antibody [DSA]) and antibodies to HLA were determined using the solid-phase method by Luminex. Development of antibodies to self-antigens, K-alpha-1-tubulin (KA1T) and collagen V (Col-V), were measured by enzyme-linked immunosorbent assay. C3d deposition in lung biopsy specimens was determined by immunohistochemical staining. Percent E-C4d (%E-C4d) levels were 19.9% in LTx patients vs 3.7% in healthy individuals (p = 0.02). DSA+ patients had higher E-C4d levels than DSA- patients (34.1% vs 16.7%, p = 0.02). In 5 patients with preformed anti-HLA, E-C4d levels were not significantly different vs 13 patients without detectable anti-HLA (p = 0.1). E-C4d levels were higher in patients who developed antibodies to KA1T (p = 0.02) and Col-V (p = 0.03). Recipients with C3d-positive tissue deposition had higher E-C4d levels than patients with C3d-negative biopsy results (p = 0.01). Increased %E-C4d levels are found in patients with positive DSA, high antibody titers to KA1T and Col-V, and have C3d+ lung biopsy findings. Therefore, %E-C4d can serve as a potential marker for antibody-mediated rejection after LTx.


[Involvement of the intraabdominal lymph nodes in a case of subacute necrotizing lymphadenitis].
A 40-year-old woman was admitted to our hospital because of fever, polyposia and polyuria in October 1990. The fasting blood sugar level was 471mg/dl and abdominal CT showed enlargement of the liver, kidneys, and intraabdominal lymph nodes. Although severe diabetes mellitus was controlled with insulin, intraabdominal lymph node swelling continued. Lymph node biopsy was performed under laparotomy. Four from intraabdominal lymph nodes, in addition to one from the left axillary lymph nodes. Four showed findings of non specific lymphadenitis, but one specimen obtained from near the right kidney demonstrated focal necrosis and invasion of macrophages and immunoblasts, which were compatible with the features of subacute necrotizing lymphadenitis (SANL). In SANL, lymphadenopathy is usually observed in the cervical region of young female and the involvement of intraabdominal lymph nodes is quite rare. This patient is the second case of SANL involving an intraabdominal lymph node reported in Japan, and it is suggested that SANL should be considered as a causative disorder of intraabdominal lymphadenopathy.


The cracked container, the containing crack: chronic illness--its effect on the therapist and the therapeutic process.
In this paper, we have tried to examine the complex dynamics of the therapist's physical chronic illness. Little attention has been paid to physical non-functioning, especially during chronic illness, and its psychotherapeutic corollaries. A crucial theme is the extent of damage to the capacity to contain. It is our claim that, when sufficiently worked through, the 'cracked therapeutic container' may serve as a facilitator of better understanding and enhance empathy. The impact of chronic illness on the therapeutic setting, contract, process and language is discussed as well as some salient features of chronicity.


Auditory Hallucinations as Translational Psychiatry: Evidence from Magnetic Resonance Imaging.
In this invited review article, I present a translational perspective and overview of our research on auditory hallucinations in schizophrenia at the University of Bergen, Norway, with a focus on the neuronal mechanisms underlying the phenomenology of experiencing "hearing voices". An auditory verbal hallucination (i.e. hearing a voice) is defined as a sensory experience in the absence of a corresponding external sensory source that could explain the phenomenological experience. I suggest a general frame or scheme for the study of auditory verbal hallucinations, called Levels of Explanation. Using a Levels of Explanation approach, mental phenomena can be described and explained at different levels (cultural, clinical, cognitive, brain-imaging, cellular and molecular). Another way of saying this is that, to advance knowledge in a research field, it is not only necessary to replicate findings, but also to show how evidence obtained with one method, and at one level of explanation, converges with evidence obtained with another method at another level. To achieve breakthroughs in our understanding of auditory verbal hallucinations, we have to advance vertically through the various levels, rather than the more common approach of staying at our favourite level and advancing horizontally (e.g., more advanced techniques and data acquisition analyses). The horizontal expansion will, however, not advance a deeper understanding of how an auditory verbal hallucination spontaneously starts and stops. Finally, I present data from the clinical, cognitive, brain-imaging, and cellular levels, where data from one level validate and support data at another level, called converging of evidence. Using a translational approach, the current status of auditory verbal hallucinations is that they implicate speech perception areas in the left temporal lobe, impairing perception of and attention to external sounds. Preliminary results also show that amygdala is implicated in the emotional «colouring» of the voices and that excitatory neurotransmitters might be involved. What we do not know is why hallucinatory episodes occur spontaneously, why they fluctuate over time, and what makes them spontaneously stop. Moreover, is voice hearing a category or dimension in its own right, independent of diagnosis, and why is the auditory modality predominantly implicated in psychotic disorders, while the visual modality dominates in, for example, neurological diseases?


Filtrate of fermented mycelia from Antrodia camphorata reduces liver fibrosis induced by carbon tetrachloride in rats.
To investigate the effects of filtrate of fermented mycelia from Antrodia camphorata (FMAC) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats. Forty Wistar rats were divided randomly into control group and model group. All model rats were given 200 mL/L CCl(4) (2 mL/Kg, po) twice a week for 8 wk. Four weeks after CCl(4) treatment, thirty model rats were further divided randomly into 3 subgroups: CCl(4) and two FMAC subgroups. Rats in CCl(4) and 2 FMAC subgroups were treated with FMAC 0, 0.5 and 1.0 g/kg, daily via gastrogavage beginning at the fifth week and the end of the eighth week. Spleen weight, blood synthetic markers (albumin and prothrombin time) and hepatic malondialdehyde (MDA) and hydroxyproline (HP) concentrations were determined. Expression of collagen I, tissue inhibitor of metalloproteinases (TIMP)-1 and transforming growth factor beta1 (TGF-beta1) mRNA were detected by RT-PCR. Histochemical staining of Masson's trichrome was performed. CCl(4) caused liver fibrosis, featuring increased prothrombin time, hepatic MDA and HP contents, and spleen weight and decreased plasma albumin level. Compared with CCl(4) subgroup, FMAC subgroup (1 g/kg) significantly decreased the prothrombin time (36.7+/-7.2 and 25.1+/-10.2 in CCl(4) and FMAC groups, respectively, P<0.05) and increased plasma albumin concentration (22.7+/-1.0 and 30.7+/-2.5 in CCl(4) and FMAC groups, respectively, P<0.05). Spleen weight was significantly lower in rats treated with CCl(4) and FMAC (1 g/kg) compared to CCl(4) treated rats only (2.7+/-0.1 and 2.4+/-0.2 in CCl(4) and FMAC groups, respectively, P<0.05). The amounts of hepatic MDA and HP in CCl(4)+FAMC (1 g/kg) subgroup were also lower than those in CCl(4) subgroup (MDA: 3.9+/-0.1 and 2.4+/-0.6 in CCl(4) and CCl(4)+FMAC groups, respectively, P<0.01; HP: 1730.7+/-258.0 and 1311.5+/-238.8 in CCl(4) and CCl(4)+FMAC groups, respectively, P<0.01). Histologic examinations showed that CCl(4)+FMAC subgroups had thinner or less fibrotic septa than CCl(4) group. RT-PCR analysis indicated that FMAC (1 g/kg) reduced mRNA levels of collagen I, TIMP-1 and TGF-beta1 (collagen I: 5.63+/-2.08 and 1.78+/-0.48 in CCl(4) and CCl(4)+FMAC groups, respectively, P<0.01; TIMP-1: 1.70+/-0.82 and 0.34+/-0.02 in CCl(4) and CCl(4)+FMAC groups, respectively, P<0.01; TGF-beta1:38.03+/-11.9 and 4.26+/-2.17 in CCl(4) and CCl(4)+FMAC groups, respectively, P<0.01) in the CCl(4)-treated liver. It demonstrates that FMAC can retard the progression of liver fibrosis induced by CCl(4) in rats.