Underwater target classification in changing environments using an adaptive feature mapping.
A new adaptive underwater target classification system to cope with environmental changes in acoustic backscattered data from targets and nontargets is introduced. The core of the system is the adaptive feature mapping that minimizes the classification error rate of the classifier. The goal is to map the feature vector in such a way that the mapped version remains invariant to the environmental changes. A K-nearest neighbor (K-NN) system is used as a memory to provide the closest matches of an unknown pattern in the feature space. The classification decision is done by a backpropagation neural network (BPNN). Two different cost functions for adaptation are defined. These two cost functions are then combined together to improve the classification performance. The test results on a 40-kHz linear FM acoustic backscattered data set collected from six different objects are presented. These results demonstrate the effectiveness of the adaptive system versus nonadaptive system when the signal-to-reverberation ratio (SRR) in the environment is varying.


Overrepresentation of extreme events in decision making reflects rational use of cognitive resources.
People's decisions and judgments are disproportionately swayed by improbable but extreme eventualities, such as terrorism, that come to mind easily. This article explores whether such availability biases can be reconciled with rational information processing by taking into account the fact that decision makers value their time and have limited cognitive resources. Our analysis suggests that to make optimal use of their finite time decision makers should overrepresent the most important potential consequences relative to less important, put potentially more probable, outcomes. To evaluate this account, we derive and test a model we call utility-weighted sampling. Utility-weighted sampling estimates the expected utility of potential actions by simulating their outcomes. Critically, outcomes with more extreme utilities have a higher probability of being simulated. We demonstrate that this model can explain not only people's availability bias in judging the frequency of extreme events but also a wide range of cognitive biases in decisions from experience, decisions from description, and memory recall. (PsycINFO Database Record


Peptides increase anion conductance of canine trachea: an effect on tight junctions.
The ionic basis for the rapid reduction in potential difference (dip) produced on luminal addition of substance P and related peptides was analysed by altering the electromotive force and chemical gradients across the isolated, canine tracheal epithelium. The dip could be exaggerated, minimised or reversed by increasing, decreasing or reversing the basal potential difference, and the intercept of the line relating the two was close to zero when the Cl- compositions of the two bathing solutions were identical. Luminal Cl- replacement by a non-permeant anion (isethionate) attenuated the dip which was, however, exaggerated by a permeant anion (nitrate). Replacement of serosal Na+ or luminal HCO3- had no significant effect on the magnitude of the dip. The tachykinins exhibited cross-tachyphylaxis with each other, indicating a common receptor. Bradykinin, a structurally unrelated peptide, also produced dips upon luminal addition, but showed no cross-tachyphylaxis with the tachykinins. Again, a linear relation between basal potential difference and the dip elicited by bradykinin was observed. Based on current awareness of the bioelectric properties of the canine tracheal epithelium, we suggest that these peptides modulate paracellular anion permeabilities.


A novel ATM-dependent X-ray-inducible gene is essential for both plant meiosis and gametogenesis.
DNA damage in Arabidopsis thaliana seedlings results in upregulation of hundreds of genes. One of the earliest and highest levels of induction is displayed by a previously uncharacterized gene that we have termed X-ray induced 1 (XRI1). Analysis of plants carrying a null xri1 allele revealed two distinct requirements for this gene in plant fertility. XRI1 was important for the post-meiotic stages of pollen development, leading to inviability of xri(-) pollen and abnormal segregation of the mutant allele in heterozygous xri1(+/-) plants. In addition, XRI1 was essential for male and female meiosis, as indicated by the complete sterility of homozygous xri1 mutants due to extensive chromosome fragmentation visible in meiocytes. Abolition of programmed DNA double-strand breaks in a spo11-1 mutant background failed to rescue the DNA fragmentation of xri1 mutants, suggesting that XRI1 functions at an earlier stage than SPO11-1 does. Yeast two-hybrid studies identified an interaction between XRI1 and a novel component of the Arabidopsis MND1/AHP2 complex, indicating possible requirements for XRI1 in meiotic DNA repair.


Increased expression of cytoplasmic tail-containing form of gp600/megalin in active Heymann nephritis.
Active Heymann nephritis of rat, an autoimmune glomerular disease, is a model of human membranous glomerulonephropathy. The major target autoantigen of this disease is a 600 kD renal glycoprotein, variously named gp600/gp330/megalin/LRP2. It has been shown previously that there is a marked increase in the gp600/megalin mRNA level in glomeruli of rats with this disease. A rabbit antibody was prepared against a peptide located at the very end of the cytoplasmic tail of rat gp600/megalin. Affinity purified anti-peptide antibody was monospecific and reacted only with gp600/megalin on the immunoblots of total kidney proteins. Immunofluorescence microscopy on frozen kidney sections probed with this antibody revealed the presence of the cytoplasmic tail-containing form of gp600/megalin in both proximal tubules and glomeruli. Expression in glomeruli of normal kidneys was less than in tubules but was clearly detectable. In active Heymann nephritis kidneys, expression of this form was increased most remarkably in glomeruli. These results, showing increased expression of the cytoplasmic tail-containing form in active Heymann nephritis glomeruli, contradict previous reports of its absence. This is the first study to show that there is increased expression of the cytoplasmic tail-containing form of gp600/megalin in the glomeruli of rats with this disease and its role in active Heymann nephritis is discussed.


Prevalence of multidrug-resistant gram-negative bacteria among nursing home residents: A systematic review and meta-analysis.
Multidrug-resistant gram-negative bacteria (MDR-GNB) are associated with an increasing proportion of infections among nursing home (NH) residents. The objective of this systematic review and meta-analysis was to critically review evidence of the prevalence of MDR-GNB among NH residents. Following Meta-Analysis of Observational Studies in Epidemiology guidelines, a systematic review of literature for the years 2005-2016 using multiple databases was conducted. Study quality, appraised by 2 reviewers, used Downs and Black risk of bias criteria. Studies reporting prevalence of MDR-GNB colonization were pooled using a random effects meta-analysis model. Heterogeneity was assessed using Cochran Q and I2 statistics. Of 327 articles, 12 met the criteria for review; of these, 8 met the criteria for meta-analysis. Escherichia coli accounted for the largest proportion of isolates. Reported MDR-GNB colonization prevalence ranged from 11.2%-59.1%. Pooled prevalence for MDR-GNB colonization, representing data from 2,720 NH residents, was 27% (95% confidence interval, 15.2%-44.1%) with heterogeneity (Q = 405.6; P = .01; I2 = 98.3). Two studies reported MDR-GNB infection rates of 10.9% and 62.7%. Our findings suggest a high prevalence of MDR-GNB colonization among NH residents, emphasizing the need to enhance policies for infection control and prevention (ICP) in NHs.


Effect of ketamine on dendritic arbor development and survival of immature GABAergic neurons in vitro.
Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors, was reported to induce neuronal cell death when administered to produce anesthesia in young rodents and monkeys. Subanesthetic doses of ketamine, as adjuvant to postoperative sedation and pain control, are also frequently administered to young children. However, the effects of these low concentrations of ketamine on neuronal development remain unknown. The present study was designed to evaluate the effects of increasing concentrations (0.01-40 microg/ml) and durations (1-96 h) of ketamine exposure on the differentiation and survival of immature gamma-aminobutyric acidergic (GABAergic) interneurons in culture. In line with previous studies (Scallet et al., 2004), we found that a 1-h-long exposure to ketamine at concentrations > or = 10 microg/ml was sufficient to trigger cell death. At lower concentrations of ketamine, cell loss was only observed when this drug was chronically (> 48 h) present in the culture medium. Most importantly, we found that a single episode of 4-h-long treatment with 5 microg/ml ketamine induced long-term alterations in dendritic growth, including a significant (p < 0.05) reduction in total dendritic length and in the number of branching points compared to control groups. Finally, long-term exposure (> 24 h) of neurons to ketamine at concentrations as low as 0.01 microg/ml also severely impaired dendritic arbor development. These results suggest that, in addition to its dose-dependent ability to induce cell death, even very low concentrations of ketamine could interfere with dendritic arbor development of immature GABAergic neurons and thus could potentially interfere with the development neural networks.


Are mortality rates for respiratory diseases in the RSA affected by climate?
Age-standardized and age-specific mortality rates (MRs)/100 000 of whites for the pneumonias and chronic respiratory diseases averaged over the 3-year period 1979-1981 for four highveld cities, Johannesburg, Bloemfontein, Pretoria and Germiston, were compared with those for four coastal cities, Cape Town, Durban, Port Elizabeth and East London--Durban being in the subtropics. The highveld cities have cold winter climates with air temperatures falling to freezing point in June and July, whereas the winters are mild in the coastal cities. In Durban, for example, the mean minimum monthly air temperature rarely falls below 10 degrees C in winter. Age-standardized MRs for the pneumonias were negatively associated with the average mean monthly minimum air temperatures in June-July. These rates were much higher in the highveld cities (varying from 63,9/100 000 to 71,4/100 000) than in the coastal cities (varying from 29,8/100 000 to 40,7/100 000). Age-specific MRs in the over-75-year age group in highveld cities were twice as high as the MRs of this age group in the coastal cities. Age-standardized MRs for chronic respiratory diseases, on the other hand, were not associated with winter air temperatures in these eight cities. Age-specific MRs for the over-75-year age group were also not related to the winter air temperatures in the eight cities. This lack of association between MRs for chronic respiratory diseases and winter air temperatures might be due to the confounding effect of air pollution.


Modality-specific outcomes of patients undergoing carotid revascularization in the setting of recent myocardial infarction.
Recent myocardial infarction (MI) represents a real challenge in patients requiring any vascular procedure. There is currently a lack of data on the effect of preoperative MI on the outcomes of carotid revascularization methodology (carotid enterectomy [CEA], transfemoral carotid artery stenting [TFCAS], or transcarotid artery revascularization [TCAR]). This study looks to identify modality-specific outcomes for patients with recent MI undergoing carotid revascularization. Data was collected from the Vascular Quality Initiative (2016-2022) for patients with carotid stenosis in the United States and Canada with recent MI (<6 months) undergoing CEA, TFCAS, or TCAR. In-hospital outcomes after TFCAS vs CEA and TCAR vs CEA were compared. TCAR vs TFCAS were compared in a secondary analysis. We used logistic regression models to compare the outcomes of these three procedures in patients with recent MI, adjusting for potential confounders. Primary outcomes included 30-day in-hospital rates of stroke, death, and MI. Secondary outcomes included stroke/death, stroke/death/MI, postoperative hypertension, postoperative hypotension, prolonged length of stay (>2 days), and 30-day mortality. The final cohort included 1217 CEA (54.2%), 445 TFCAS (19.8%), and 584 TCAR (26.0%) cases. Patients undergoing CEA were more likely to have prior coronary artery bypass graft/percutaneous coronary intervention and to use anticoagulant. Patients undergoing TFCAS were more likely to be symptomatic, have prior congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and undergo urgent operations. Patients undergoing TCAR were more likely to have higher rates of American Society of Anesthesiologists class IV to V, P2Y12 inhibitor, and protamine use. In the univariate analysis, CEA was associated with a lower rate of ipsilateral stroke (P = .079), death (P = .002), and 30-day mortality (P = .007). After adjusting for confounders, TFCAS was associated with increased risk of stroke/death (adjusted odds ratio [aOR], 2.69; 95% confidence interval [CI], 1.36-5.35; P = .005) and stroke/death/MI (aOR, 1.67; 95% CI, 1.07-2.60; P = .025) compared with CEA. However, TCAR had similar outcomes compared with CEA. Both TFCAS and TCAR were associated with increased risk of postoperative hypotension (aOR, 1.62; 95% CI, 1.18-2.23; P = .003 and aOR, 1.74; 95% CI, 1.31-2.32; P ≤ .001, respectively) and decreased risk of postoperative hypertension (aOR, 0.59; 95% CI, 0.36-0.95; P = .029 and aOR, 0.50; 95% CI, 0.36-0.71; P ≤ .001, respectively) compared with CEA. Although recent MI has been established as a high-risk criterion for CEA and an approved indication for TFCAS, this study showed that CEA is safer in this population with lower risk of stroke/death and stroke/death/MI compared with TFCAS. TCAR had similar stroke/death/MI outcomes in comparison to CEA in patients with recent MI. Further prospective studies are needed to confirm our findings.


[Hypertension in patients with diabetes].
The documentation for the beneficial effects of antihypertensive treatment in patients with diabetes is overwhelming. Most patients will require three or four antihypertensive drugs to achieve blood pressure (BP) goals. The regime should include an agent that blocks the renin angiotensin aldosterone system. Reduction in albuminuria during antihypertensive treatment is indicative of renal and cardiovascular protection. Thus, if the level of albuminuria remains high, the treatment should be intensified, even in the light of achieved BP goals. Options for intensification are dual blockade, supramaximal doses of ACE-I or ARB, or addition of aldosterone or renin-blocking agents. Long-term data are awaited regarding the optimal strategy for combination therapy. Patients on intensive antihypertensive treatment should be monitored regularly.


Prevalence of soil-transmitted helminth infestations among children attending Integrated Child Development Service centers in a tea garden area in Darjeeling.
Helminths infestations are common in children in the tea garden areas of Darjeeling, which present unique social, cultural, and environmental conditions. The present study was conducted to determine the proportion of soil-transmitted helminth (STH) infestations and association of STH to sociodemographic variables among children attending Integrated Child Development Services centers of a tea garden area in Darjeeling. A cross-sectional descriptive study was conducted at Kiran Chandra Tea Estate, a tea garden in Naxalbari, Darjeeling, between August and September 2016. Stool samples were collected from children attending ICDS centers in the area and examined using the direct and concentration methods. A pretested and predesigned questionnaire was used to collect data on the sociodemographic profile of the children's families. Stool samples could be collected from 52 (45%) of the 115 eligible children. The children were predominantly male (61.5%), from families with an income between Rs. 2000 and 4000 per month, had mothers with no formal education (75.0%) and came from households with no sanitary toilets (33.5). The proportion of children with STHs was 9.6%; with Ascaris found in 7.7% and Trichuris in 1.9%. No statistically significant differences were found in selected variables between the worm-positive and worm-negative children. The proportion of STH infestation is low among children <6 years of age attending ICDS in the study area probably because of the mass de-worming strategy of the government of India. Some differences in infestations among groups might suggest a clustering effect.


Clinicopathological Characteristics, Treatment and Outcome of 123 Patients with Synchronous or Metachronous Bilateral Breast Cancer in a Swiss Institutional Retrospective Series.
To evaluate the prognosis, the patient and tumor characteristics, and the treatment of bilateral breast cancer (BBC) and to compare synchronous (sBBC) and metachronous BBC (mBBC). For this retrospective study, data from 123 consecutive BBC patients (56 sBBC and 67 mBBC) that were presented at the Sion Hospital tumor board between 2007 and 2018 were collected retrospectively. Mean follow-up was 85 months. 2nd tumors in both groups were more often diagnosed radiologically. Mean time interval between mBBC was 115 months. A shorter interval was positively correlated with a negative hormonal receptor (HR) status and higher grade for the 2nd tumor. There was no difference in overall survival (OS) and relapse-free survival (RFS) between sBBC and mBBC. OS was longer if both tumors were hormonal receptor (HR) positive. mBBC exhibited a higher local recurrence rate than sBBC (p=0.03). sBBC and mBBC patients did not show any difference in OS or RFS, although mBBC patients were more prone to local relapses.


The crystallization age of eucrite zircon.
Eucrites are a group of meteorites that represent the first planetary igneous activity following metal-silicate differentiation on an early planetesimal, similar to Asteroid 4 Vesta, and, thus, help date geophysical processes occurring on such bodies in the early solar system. Using the short-lived radionuclide (182)Hf as a relative chronometer, we demonstrate that eucrite zircon crystallized quickly within 6.8 million years of metal-silicate differentiation. This implies that mantle differentiation on the eucrite parent body occurred during a period when internal heat from the decay of (26)Al and (60)Fe was still available. Later metamorphism of eucrites took place at least 8.9 million years after the zircons crystallized and was likely caused by heating from impacts, or by burial under hot material excavated by impacts, rather than from lava flows. Thus, the timing of eucrite formation and of mantle differentiation is constrained.


Prevalence of hepatitis D virus among HBsAg-positive individuals, 2015-2016: Azar cohort study.
Background: Hepatitis D virus (HDV) is a defective RNA pathogen that requires the presence of the hepatitis B virus (HBV) for infection. Middle East countries are endemic areas for HDV infection. So, it is important to estimate the prevalence of HDV in these countries. This study aimed to estimate the prevalence of HDV in HBsAg positive patients participated in Azar cohort study, North-west of Iran. Methods: In this cross-sectional study, out of 4949 participants of the Azar cohort study, 51 HBsAg positive patients were selected. Five participants did not consent to HDV testing. The presence of anti-HDV IgG was checked in 46 patients (13 chronic hepatitis B and 33 inactive chronic hepatitis B) using enzyme-linked immunosorbent assay (ELISA) kit. The serum level of liver enzymes was measured and a questionnaire about risk factors was completed. Results: In this study, the mean age of HBsAg positive patients was 50.06 (SD 9.14) years and 41.3% were female. Only one out of 46 patients was positive for HDV infection. Thus, the prevalence of HDV infection among hepatitis B virus surface antigen (HBsAg) positive patients was 2.17% (95% CI: 0.1-11.5). The positive anti-HDV patient was in the inactive chronic hepatitis B state and she had a history of hospitalization and dental procedures. Conclusion: The results showed that the prevalence of HDV infection in HBsAg positive patients was 2.1% that was lower than the reported prevalence in many other regions of Iran. Health policymakers and healthcare providers should design coherent and orderly epidemiological studies for planning and monitoring HDV infection.


Is targeting angiotensin-converting enzyme 2 (ACE2) a prophylactic strategy against COVID-19?
Prophylaxis against COVID-19 is greatly needed for vulnerable populations who have a higher risk of developing severe disease. Vaccines and neutralizing antibodies against SARS-CoV-2 are currently the main approaches to preventing the virus infection. However, the constant mutation of SARS-CoV-2 poses a huge challenge to the effectiveness of these prophylactic strategies. A recent study suggested that downregulation of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2 entry into human cells, can decrease susceptibility to viral infection in vitro, in vivo, and in human lungs and livers perfused ex situ. These findings indicate the potential to use agents to reduce ACE2 expression to prevent COVID-19, but the efficacy and safety should be verified in clinical trials. Considering ACE2 performs physiological functions, risks due to its downregulation and benefits from prophylaxis against SARS-CoV-2 infection should be carefully weighed. In the future, updating vaccines against variants of SARS-CoV-2 might still be an important strategy for prophylaxis against COVID-19. Soluble recombinant human ACE2 that acts as a decoy receptor might be an option to overcome the mutation of SARS-CoV-2.


Rapid and Accurate Molecular Identification of the Emerging Multidrug-Resistant Pathogen Candida auris.
Candida auris is an emerging multidrug-resistant fungal pathogen causing nosocomial and invasive infections associated with high mortality. C. auris is commonly misidentified as several different yeast species by commercially available phenotypic identification platforms. Thus, there is an urgent need for a reliable diagnostic method. In this paper, we present fast, robust, easy-to-perform and interpret PCR and real-time PCR assays to identify C. auris and related species: Candida duobushaemulonii, Candida haemulonii, and Candida lusitaniae Targeting rDNA region nucleotide sequences, primers specific for C. auris only or C. auris and related species were designed. A panel of 140 clinical fungal isolates was used in both PCR and real-time PCR assays followed by electrophoresis or melting temperature analysis, respectively. The identification results from the assays were 100% concordant with DNA sequencing results. These molecular assays overcome the deficiencies of existing phenotypic tests to identify C. auris and related species.


Treatment of the common cold.
Common colds are usually treated by the patients themselves with over-the-counter (OTC) cold medications. Many cough and cold remedies are available and sold freely without prescription. The authors conducted a study to compare the efficacy, adverse effects, the quality of life (QOL) and the patient's opinion and appreciation on the drugs (POD) between Dayquil/Nyquil and Actifed DM plus paracetamol syrup. In this prospective, investigator-blinded clinical trial, 120 patients, aged between 15 and 60 years old, with common colds within 72 hours, who accepted the trial and gave informed written consent, were randomized into two treatment groups. One patient was excluded due to evidence of bacterial infection. Fifty-nine patients were treated with Dayquil/Nyquil (D/N group), while the other 60 patients had Actifed DM plus paracetamol (ADM/P group) for three days. On day 1 the patient's demographic data (sex, age, body weight, blood pressure, co-existing diseases/conditions, drug use, and allergy to any drugs), the most prominent symptoms and its duration were recorded. All patients were screened for bacterial infection by physical examination, complete blood count and sinus radiographs. The symptoms (nasal obstruction, rhinorrhea, sneezing, cough, sore throat, fever and headache) and signs (injected nasal mucosa, nasal discharge and pharyngeal discharge) were scored, based on 4-point scale (0 to 3), on days 1 and 4. Changing of the symptoms and QOL were recorded on the diary card. The patient's opinion and appreciation on the drugs (POD) was assessed on day 4. The effectiveness (the ability to lessen the symptoms and signs), QOL and POD between two treatments were compared. The demographic data between the two groups were similar. The four most common prominent symptoms of common colds in our series were cough (47.9%), sore throat (26.17%), rhinorrhea (8.4%) and headache (8.4%). However, both treatments were equally effective in lessening the symptoms (P = 0.426) and signs (P = 0.716) of common cold from days 1 to 4. The adverse effects were significantly higher in ADM/P group than in D/N group (p = 0.006). In contrast, QOL in terms of alertness, freshness and sound sleep improved from day 1 to day 3 in both treatments, but the overall day-3 score was significantly higher in the D/N group than the ADM/P group (1.85 +/- 1.83; 1.25 +/- 1.94: p = 0.024). POD in terms of convenience, flavour of drug, effectiveness of the drug and a need to repeat the drug assessed on day 4, was also significantly higher in the D/N group than the ADM/P group (10.68 +/- 2.56; 8.92 +/- 2.27: p < 0.001). Dayquil/Nyquil are as effective as Actifed DM plus paracetamol in controlling the symptoms and signs of the common cold, but have fewer adverse effects. The quality of life assessed during the use of the drugs was significantly higher in the Dayquil/Nyquil group, and according to the patients, they prefered Dayquil/Nyquil more than Actifed DM plus paracetamol.


Rho GTPases of the RhoBTB subfamily and tumorigenesis.
RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases). Their most salient feature is their domain architecture: a GTPase domain (in most cases, non-functional) is followed by a prolinerich region, a tandem of 2 broadcomplex, tramtrack, bric a brac (BTB) domains, and a conserved Cterminal region. In humans, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi. Interest in RhoBTB arose when RHOBTB2 was identified as the gene homozygously deleted in breast cancer samples and was proposed as a candidate tumor suppressor gene, a property that has been extended to RHOBTB1. The functions of RhoBTB proteins have not been defined yet, but may be related to the roles of BTB domains in the recruitment of cullin3, a component of a family of ubiquitin ligases. A model emerges in which RhoBTB proteins are required to maintain constant levels of putative substrates involved in cell cycle regulation or vesicle transport through targeting for degradation in the 26S proteasome. RhoBTB proteins are engrossing the list of Rho GTPases involved in tumorigenesis. Unlike typical Rho GTPases (usually overexpressed or hyperactive), RhoBTB proteins appear to play a part in the carcinogenic process through a mechanism that involves the decreased or abolished expression of the corresponding genes, or more rarely, mutations that result in impaired functioning of the protein, presumably leading to the accumulation of RhoBTB substrates and alterations of the cellular homeostasis.


Association between Estrogen, Vitamin D and Microrna17 Gene Polymorphisms and Periapical Lesions.
This study evaluated the association between polymorphisms in genes encoding estrogen receptors 1 (ESR1) and 2 (ESR2), vitamin D receptor (VDR) and in microRNA17 (which binds to ESR1 and VDR) with persistent apical periodontitis (PAP) after the endodontic treatment. We included 162 patients who completed endodontic treatment at least one year ago and presented apical periodontitis at the beginning of the root canal therapy. Clinical and radiographic exams were performed to evaluate the presence of PAP or healthy periradicular tissues (healed). Saliva samples were collected as a genomic DNA. The genotyping of ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938), VDR (rs739837 and rs2228570) and miRNA17 (rs4284505) were performed by real-time PCR. Chi-square test was used to the distribution of genotype and allele frequencies. Haplotype analysis was also performed. Eighty-nine patients were included in the "healed" group and 73 in the "PAP" group. No association was found between the allelic and genotypic polymorphisms studied and PAP (p>0.05). Haplotype analysis also did not demonstrated an association (p>0.05). In conclusion, the genetic polymorphisms in ESR1, ESR2, VDR and miRNA17 are not associated with PAP.


Pregnancy and parturition in rats after sympathetic denervation of the ovary, oviduct and utero-tubal junction.
The ovarian vascular pedicle and ovarian suspensory ligament were briefly frozen to destroy the nerves. Examination of sections from the ovary, oviduct and utero-tubal junction by fluorescence histochemistry showed that they were usually devoid of adrenergic nerves. Measurement of noradrenaline in segments of the uterine horn by high-performance liquid chromatography showed that the transmitter was eliminated from the upper third but not the middle or lower thirds of the uterine horn. Unilateral or bilateral denervations at metoestrus in cyclic rats did not affect either the number of ovulations or the numbers or spacing of conceptuses at Day 7 of pregnancy. Bilateral denervations on Days 4, 7 or 11 of pregnancy did not affect ovarian weights or numbers of conceptuses observed 1 week later. Plasma progesterone concentrations were at least as high in the denervated groups as in the sham-operated control groups. After unilateral or bilateral denervations at Day 15, pregnancy continued normally and birth of normal young occurred, without apparent problems, at the same time as for sham-operated rats. The mothers tended their young and allowed them to suck. It is concluded that the adrenergic innervation of the ovary in the rat is not required for its normal function during pregnancy; that of the oviduct and mesosalpinx is not required for ovum pick-up or for transport of oocytes, spermatozoa or early embryos; and that of the utero-tubal junction is not required for uterine motility involved in embryo spacing and parturition.


The effect of amblyopia on fine motor skills in children.
In an investigation of the functional impact of amblyopia in children, the fine motor skills of amblyopes and age-matched control subjects were compared. The influence of visual factors that might predict any decrement in fine motor skills was also explored. Vision and fine motor skills were tested in a group of children (n = 82; mean age, 8.2 +/- 1.7 [SD] years) with amblyopia of different causes (infantile esotropia, n = 17; acquired strabismus, n = 28; anisometropia, n = 15; mixed, n = 13; and deprivation n = 9), and age-matched control children (n = 37; age 8.3 +/- 1.3 years). Visual motor control (VMC) and upper limb speed and dexterity (ULSD) items of the Bruininks-Oseretsky Test of Motor Proficiency were assessed, and logMAR visual acuity (VA) and Randot stereopsis were measured. Multiple regression models were used to identify the visual determinants of fine motor skills performance. Amblyopes performed significantly poorer than control subjects on 9 of 16 fine motor skills subitems and for the overall age-standardized scores for both VMC and ULSD items (P < 0.05). The effects were most evident on timed tasks. The etiology of amblyopia and level of binocular function significantly affected fine motor skill performance on both items; however, when examined in a multiple regression model that took into account the intercorrelation between visual characteristics, poorer fine motor skills performance was associated with strabismus (F(1,75) = 5.428; P = 0.022), but not with the level of binocular function, refractive error, or visual acuity in either eye. Fine motor skills were reduced in children with amblyopia, particularly those with strabismus, compared with control subjects. The deficits in motor performance were greatest on manual dexterity tasks requiring speed and accuracy.


Laparoscopic repair of inferior vena caval injury using a chitosan-based hemostatic dressing.
Vena caval injury is a rare but serious complication of laparoscopic surgery, and often requires conversion to an open procedure. The current study investigated whether a vena caval injury could be repaired with a chitosan dressing laparoscopically. Six domestic swine were studied. A 4- to 5-mm circumferential incision was created in the inferior vena cava (IVC) and repaired laparoscopically with a chitosan dressing. Neither suture nor additional hemostatic techniques were used. The animals were killed at 30 minutes (n = 2) and at 1 week (n = 4) postoperatively for histopathological analysis. All IVC injuries were successfully repaired laparoscopically using a single chitosan dressing application without recurrent hemorrhaging. Mean operative time was 6 minutes and the blood loss was approximately 55 mL. There was no evidence of clot formation in the repaired vessels. Histology showed that the chitosan dressing had partially degenerated into small particles with moderate chronic inflammatory response 1 week after repair. Use of the chitosan-based hemostatic dressing is a simple and reliable technique to control serious hemorrhage from IVC injury during laparoscopic surgery.


Interleukin-18 activates NF-kappaB in murine T helper type 1 cells.
Interleukin-18 (IL-18) activated T helper type 1 (Th1) cells, OVA#4, and induced production of interleukin-2 (IL-2) in costimulation with anti-CD3 antibody. Upon stimulation with IL-18, IkappaB disappeared from cytoplasm and subsequently nuclear factor-kappaB (NF-kappaB) (p65) accumulated in the nucleus. Corresponding with that, DNA binding activity of NF-kappaB (p65 homodimer or p65/p50 heterodimer) was detected in the nucleus. In the transfection experiments, an IL-2 promoter-driven reporter construct showed the similar responsiveness against IL-18 to that of the intrinsic IL-2 gene, and a construct lacking kappaB site failed to respond to IL-18. These results suggest that IL-18 activates NF-kappaB and it is important for enhancement of IL-2 gene expression by Th1 cells stimulated with IL-18.


Effect of vaccination with selective bacterins on conventional pigs infected with type 2 porcine circovirus.
The objective of this study was to determine whether vaccination with bacterins commonly used in the USA, when administered at a time typical of US protocol, enhances porcine circovirus type 2 (PCV2) replication and the incidence and severity of clinical signs and lesions characteristic of postweaning multisystemic wasting syndrome (PMWS) in conventional pigs. Sixty-one pigs free of PCV2 were randomly assigned to four groups. Groups 1 (n = 15) and 2 (n = 15) pigs served as sham-inoculated negative controls. Groups 3 (n = 14) and 4 (n = 17) pigs were inoculated intralymphoid with PCV2 field isolate ISU-40895. Pigs in groups 2 and 4 were vaccinated with Actinobacillus pleuropneumoniae (APP) and Mycoplasma hyopneumoniae (M. hyopneumoniae) bacterins 21 days before and again 1 day before inoculation with PCV2. Mild transient respiratory disease and diarrhea were observed from 13 to 34 days postinoculation (DPI) in pigs in groups 3 and 4. Half the pigs from each group were necropsied at 22 and 34 DPI, respectively. Moderately enlarged, tan-colored lymph nodes were observed in the majority of pigs in groups 3 and 4. There was a significantly (P < 0.05) longer length of viremia (2.14 +/- 0.26 versus 4.44 +/- 0.23 weeks), a higher copy number of the PCV2 genome in serum, a wider range of tissue distribution of PCV2 antigen, and an increased severity of lymphoid depletion in pigs vaccinated with commercial APP and M. hyopneumoniae vaccines and inoculated with PCV2 compared with PCV2-inoculated unvaccinated pigs. Swine producers and veterinarians may need to consider changes in vaccination protocols in herds with recurrent PCV2-associated PMWS.


Automatic gait recognition via statistical approaches for extended template features.
A gait recognition system using extended template features is presented. A proposed statistical approach is applied for feature extraction from spatial and temporal templates. This method can be used to reduce data dimensionality and to optimize the class separability of different gait sequences simultaneously. Dimensionality reduction is achieved by template extraction followed by principal component analysis. Gait recognition is achieved in the canonical space using a measure of accumulated distance as the metric. By incorporating spatial and temporal information into an extended feature, gait recognition becomes more robust and accurate than using spatial or temporal features alone.


Trends and hotspots in research of traumatic brain injury from 2000 to 2022: A bibliometric study.
Traumatic brain injury (TBI) is a major health concern globally, which is characterized by high morbidity and mortality rates. Since the 21st century, TBI has received increasing attention and the number of publications is growing rapidly. This study aimed to characterize the volume and quality of scholarly output on TBI and identify the most impactful literature, research trends, and hotspots from the year 2000-2022. We searched publications on TBI through the Web of Science Core Collection-Science Citation Index Expanded database which were published from 2000 to 2022. Basic information of each paper, including publication year, countries, authors, affiliations, journal, fundings, subject areas, and keywords were collected for further analysis by using Microsoft Excel, VOSviewer, and CiteSpace software. A total of 47231 TBI-related publications were identified through database retrieval. The annual number of publications on TBI has increased steadily over the past twenty years and the number in the year 2022 is sevenfold higher than that in 2000. The United States of America (USA) was the leading country in both numbers of publications and citations, which is consistent with the finding that it had the most funding agencies. Menon DK was the author with the highest influence and the University of California System was the most productive affiliation. Moreover, keywords analysis suggested that the research topics can be mainly divided into six categories: management, rehabilitation, mechanisms, concussion, neuroimaging, and neuroendocrine. This study visualized the trends and focuses of scientific research related to TBI, both quantitatively and qualitatively. The USA had a relatively high academic impact owing to its productive experts and institutions in this field. Neuroinflammation, machine learning, tranexamic acid, and extracellular vesicles are currently hot topics in the field of TBI.


Carcinoma ex microcystic adenoma of the pancreas: a report of a novel form of malignancy in serous neoplasms.
Serous cystic neoplasms of the pancreas are generally considered benign lesions. Malignant counterparts have been occasionally described, and the diagnosis of malignancy is based solely on the presence of synchronous or metachronous metastases to the lymph nodes or liver, direct tumor invasion into adjacent organs, or vascular invasion. However, these malignant serous cystic tumors are lined by benign-appearing glycogen-rich cuboidal cells, which have been morphologically indistinguishable from benign microcystic serous cystadenoma in all the cases reported so far. We report a unique case of microcystic serous cystadenoma giving rise to carcinoma with distinctive histologic features including signet ring-like cells and solid nests. We believe that this case represents the first case of a cytologically malignant neoplasm arising from a benign serous cystadenoma (carcinoma ex microcystic serous cystadenoma).


Measuring Histone Deacetylase Inhibition in the Brain.
Histone deacetylases (HDACs) represent a family of enzymes that are targets for epigenetic modulation of genomic activity and may be beneficial in the treatment of many diseases, including cancer and central nervous system disorders. In animal models, HDAC inhibitors have neuroprotective, antiepileptogenic, and antidepressant effects. Assaying HDAC activity provides a robust method for identifying HDAC inhibitors and for assessing their effects under various physiological conditions or after pathological insults. In this unit, a simple and sensitive assay for measuring HDAC activity is described. HDAC activity in tissue lysates can be assessed fluorometrically using a Boc-Lys(Ac) HDAC activity kit. HDACs catalyze the deacetylation of the substrate Boc-Lys(Ac)-AMC. Addition of a trypsin-containing developer converts the deacetylated product to a quantifiable fluorophore that can be used both as a screening method to identify putative HDAC inhibitors and to assess the effects of these inhibitors on tissue and animal epigenetic-modulated phenotypes. © 2018 by John Wiley & Sons, Inc.


Asymptomatic Periprosthetic Joint Infection of the Hip with High-Virulence Pathogens: Report of Two Cases.
Periprosthetic joint infection (PJI) may be a life-threatening condition, particularly when caused by pathogens with high virulence, capable of developing secondary bloodstream infection. We report two cases of chronic PJI of the hip, one with Staphylococcus aureus in a 27-year-old female with severe anorexia, the other one with Staphylococcus lugdunensis in a 74-year-old female suffering from morbid obesity. Both infections did not cause relevant symptoms over time despite the absence of suppressive antibiotic treatment. To our knowledge, there are no similar cases described in the literature. While it remains difficult to recommend postponing treatment in such cases, this option may be an alternative to suppressive antibiotic therapy.


Bio-inspired materials for defluoridation of water: A review.
The polluted water sources pose a serious issue concerning the various health hazards they bring along. Due to various uncontrolled anthropogenic and industrial activities, a great number of pollutants have gained entry into the water systems. Among all the emerging contaminants, anionic species such as fluoride cause a major role in polluting the water bodies because of its high reactivity with other elements. The need for water remediation has led the research community to come up with several physicochemical and electrochemical methods to remove fluoride contamination. Among the existing methods, biosorption using bio and modified biomaterials has been extensively studied for defluoridation, as they are cheap, easily available and effectively recyclable when compared to other methods for defluoridation. Adding on, these materials are non-toxic and are safe to use compared to many other synthetic materials that are toxic and require high-cost design requirements. This review focuses on the recent developments made in the defluoridation techniques by biosorption using bio and modified biomaterials and defines the current perspectives of fluoride removal specifically using biomaterials.


[EEG and bispectral analysis during inhalational anesthesia in children].
Bispectral index (BIS) is a parameter of the depth of anesthesia, but the use of it in children remains discussable. The study was carried out to compare EEG and BIS considering the age of patients during anesthesia with halotane, sevoflurane and consequent combination of sevoflurane and isoflurane. 60 children 3 to 17 years of age, who underwent urological surgeries, were divided into 3 groups (20 patients in each): 1st--halothane group, 2nd--sevoflurane group and 3rd--consequent combination of sevodlurane and isoflurane group. The oxygen: nitrous oxide 1:1 mixture was used in all the mentioned groups. EEG recording (6 channel computerised encephalograph) and BIS monitoring (XP version) was carried out through the whole duration of anesthesia. In the 1st group the gradual reduction of main rhythm was registered on EEG, with slow activity and restoration during awakening. The BIS index values changed from 95-98 to 39-47 with rise to 77-85 during awakening. In the 2nd and 3rd group where sevoflurane was used for anesthesia induction sharpened alpha rhythms, amplitude enlargement and rhythm synchronization were registered on EEG. BIS values changed from 96-99 to 13-38. During the maintenance of anesthesia in the 2nd group BIS values were 30-40 and 72-77 during awakening. In the stage of isoflurane anesthesia in the 3rd group EEG pattern changed towards the rhythm synchronization and slow oscillations in all the leads. The BIS index was 30-39 during maintenance and 70-76 during awakening. The parameters of EEG and BIS in all the investigated groups were proportional to the clinical stage and depth of anesthesia. Based on the clinical data and its comparison to EEG and BIS values it is determined that BIS index can be used for monitoring depth of anesthesia in children.


An intracellular loop 2 amino acid residue determines differential binding of arrestin to the dopamine D2 and D3 receptors.
Dopamine D(2) and D(3) receptors are similar subtypes with distinct interactions with arrestins; the D(3) receptor mediates less agonist-induced translocation of arrestins than the D(2) receptor. The goals of this study were to compare nonphosphorylated arrestin-binding determinants in the second intracellular domain (IC2) of the D(2) and D(3) receptors to identify residues that contribute to the differential binding of arrestin to the subtypes. Arrestin 3 bound to glutathione transferase (GST) fusion proteins of the D(2) receptor IC2 more avidly than to the D(3) receptor IC2. Mutagenesis of the fusion proteins identified a residue at the C terminus of IC2, Lys149, that was important for the preferential binding of arrestin 3 to D(2)-IC2; arrestin binding to D(2)-IC2-K149C was greatly decreased compared with wild-type D(2)-IC2, whereas binding to the reciprocal mutant D(3)-IC2-C147K was enhanced compared with wild-type D(3)-IC2. Mutating this lysine in the full-length D(2) receptor to cysteine decreased the ability of the D(2) receptor to mediate agonist-induced arrestin 3 translocation to the membrane and decreased agonist-induced receptor internalization in human embryonic kidney 293 cells. The reciprocal mutation in the D(3) receptor increased receptor-mediated translocation of arrestin 3 without affecting agonist-induced receptor internalization. G protein-coupled receptor crystal structures suggest that Lys149, at the junction of IC2 and the fourth membrane-spanning helix, has intramolecular interactions that contribute to maintaining an inactive receptor state. It is suggested that the preferential agonist-induced binding of arrestin3 to the D(2) receptor over the D(3) receptor is due in part to Lys149, which could be exposed as a result of receptor activation.


Primary mucinous eccrine adenocarcinoma - a rare malignant cutaneous adnexal neoplasm at an unconventional site.
Primary mucinous eccrine adenocarcinoma, a rare malignant neoplasm of the skin adnexa usually occurs in the head and neck region. The most common sites for its occurrence are the eyelid, the peri-orbital region and the scalp. We report the rare occurrence of primary mucinous eccrine adenocarcinoma of the inguinal region which has been reported in only 1% of cases according to literature search. Since the differentiation from metastatic mucinous carcinomas is difficult, a careful search for primary in the breast, gastrointestinal tract and prostate is mandatory. This case report highlights the importance of precise diagnosis and accurate histological typing of mucinous carcinomas with an emphasis on their role in appropriate patient management along with a brief review of literature.


MHCI negatively regulates synapse density during the establishment of cortical connections.
Major histocompatibility complex class I (MHCI) molecules modulate activity-dependent refinement and plasticity. We found that MHCI also negatively regulates the density and function of cortical synapses during their initial establishment both in vitro and in vivo. MHCI molecules are expressed on cortical neurons before and during synaptogenesis. In vitro, decreasing surface MHCI (sMHCI) on neurons increased glutamatergic and GABAergic synapse density, whereas overexpression decreased it. In vivo, synapse density was higher throughout development in β2m(-/-) mice. MHCI also negatively regulated the strength of excitatory, but not inhibitory, synapses and controlled the balance of excitation and inhibition onto cortical neurons. sMHCI levels were modulated by activity and were necessary for activity to negatively regulate glutamatergic synapse density. Finally, acute changes in sMHCI and activity altered synapse density exclusively during early postnatal development. These results identify a previously unknown function for immune proteins in the negative regulation of the initial establishment and function of cortical connections.


Miniature fiber-optic high-intensity focused ultrasound device using a candle soot nanoparticles-polydimethylsiloxane composites-coated photoacoustic lens.
We present a miniature fiber-optic ultrasound transmitter for generating high-intensity focused ultrasound (HIFU) based on photoacoustic transduction. The HIFU device consists of a fiber and a photoacoustic lens. We develop a simple fabrication procedure for making the photoacoustic lens, which is coated with candle soot nanoparticles-polydimethylsiloxane composites. The fiber is used to deliver pulsed laser for photoacoustic excitation, which facilitates the use of the HIFU device by eliminating the need of free-space optical alignment. The HIFU device (6.5 mm in diameter) produces focused acoustic pressures up to >30 MPa in peak positive with a tight -6-dB focal volume of ~100 μm and ~500 μm in the lateral and axial directions, respectively. Acoustic cavitation induced by the HIFU device is demonstrated. The miniature HIFU device facilitates handheld operation. It holds promise for clinical applications in intraoperative high-precision HIFU therapy. It can even be used for intracavitary therapy with further miniaturization.


Sustainability and scalability of a volunteer-based primary care intervention (Health TAPESTRY): a mixed-methods analysis.
Chronic diseases are a significant public health concern, particularly in older adults. To address the delivery of health care services to optimally meet the needs of older adults with multiple chronic diseases, Health TAPESTRY (Teams Advancing Patient Experience: Strengthening Quality) uses a novel approach that involves patient home visits by trained volunteers to collect and transmit relevant health information using e-health technology to inform appropriate care from an inter-professional healthcare team. Health TAPESTRY was implemented, pilot tested, and evaluated in a randomized controlled trial (analysis underway). Knowledge translation (KT) interventions such as Health TAPESTRY should involve an investigation of their sustainability and scalability determinants to inform further implementation. However, this is seldom considered in research or considered early enough, so the objectives of this study were to assess the sustainability and scalability potential of Health TAPESTRY from the perspective of the team who developed and pilot-tested it. Our objectives were addressed using a sequential mixed-methods approach involving the administration of a validated, sustainability survey developed by the National Health Service (NHS) to all members of the Health TAPESTRY team who were actively involved in the development, implementation and pilot evaluation of the intervention (Phase 1: n = 38). Mean sustainability scores were calculated to identify the best potential for improvement across sustainability factors. Phase 2 was a qualitative study of interviews with purposively selected Health TAPESTRY team members to gain a more in-depth understanding of the factors that influence the sustainability and scalability Health TAPESTRY. Two independent reviewers coded transcribed interviews and completed a multi-step thematic analysis. Outcomes were participant perceptions of the determinants influencing the sustainability and scalability of Health TAPESTRY. Twenty Health TAPESTRY team members (53% response rate) completed the NHS sustainability survey. The overall mean sustainability score was 64.6 (range 22.8-96.8). Important opportunities for improving sustainability were better staff involvement and training, clinical leadership engagement, and infrastructure for sustainability. Interviews with 25 participants (response rate 60%) showed that factors influencing the sustainability and scalability of Health TAPESTRY emerged across two dimensions: I) Health TAPESTRY operations (development and implementation activities undertaken by the central team); and II) the Health TAPESTRY intervention (factors specific to the intervention and its elements). Resource capacity appears to be an important factor to consider for Health TAPESTRY operations as it was identified across both sustainability and scalability factors; and perceived lack of interprofessional team and volunteer resource capacity and the need for stakeholder buy-in are important considerations for the Health TAPESTRY intervention. We used these findings to create actionable recommendations to initiate dialogue among Health TAPESTRY team members to improve the intervention. Our study identified sustainability and scalability determinants of the Health TAPESTRY intervention that can be used to optimize its potential for impact. Next steps will involve using findings to inform a guide to facilitate sustainability and scalability of Health TAPESTRY in other jurisdictions considering its adoption. Our findings build on the limited current knowledge of sustainability, and advances KT science related to the sustainability and scalability of KT interventions.


Faster clonal turnover in high-infection habitats provides evidence for parasite-mediated selection.
According to the Red Queen hypothesis for sex, parasite-mediated selection against common clones counterbalances the reproductive advantage of asexual lineages, which would otherwise outcompete sexual conspecifics. Such selection on the clonal population is expected to lead to a faster clonal turnover in habitats where selection by parasites is stronger. We tested this prediction by comparing the genetic structure of clonal and sexual populations of freshwater snail Potamopyrgus antipodarum between years 2003 and 2007 in three depth-specific habitats in Lake Alexandrina (South Island, New Zealand). These habitats differ in the risk of infection by castrating trematodes and in the relative proportion of sexual individuals. As predicted, we found that the clonal structure changed significantly in shallow and mid-water habitats, where prevalence of infection was high, but not in the deep habitat, where parasite prevalence was low. Additionally, we found that both clonal diversity and evenness of the asexual population declined in the shallow habitat. In contrast, the genetic structure (based on F-statistics) of the coexisting sexual population did not change, which suggests that the change in the clonal structure cannot be related to genetic changes in the sexual population. Finally, the frequency of sexuals had no effect on the diversity of the sympatric clonal population. Taken together, our results show a more rapid clonal turnover in high-infection habitats, which gives support for the Red Queen hypothesis for sex.


[Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Bone manifestations].
This is a benign disease from the group of histiocytoses with a slow progressive course. Bone manifestations are extranodal disease manifestations. 3 cases of the disease in females of 21, 42 and 49 years old with involvement of ilial, tibia and femur bones, respectively, are described. Lymph node changes in one patient arose 9 years after the bone involvement. Microscopic bone picture was similar to that in the lymph node. 2 patients received radiation therapy on the affected bone and were discharged from the hospital with the improvement and 1 patient was treated surgically.


Role of the quaternary ammonium ion determinants in allergy to muscle relaxants.
Anaphylaxis to muscle relaxants appears to be a very useful model to study the IgE-dependent mechanisms of mediator release in humans. The serum IgE binding sites of the drugs appeared to be the ammonium ion determinants. In patients allergic to suxamethonium, one of the most frequently used muscle relaxants for general anesthesia, significant histamine release could be obtained in each case with simple diammonium salts. The length of the chain linking the ammonium groups appears to play an important role. In fact, when the length was less than or equal to 4 A, no significant histamine release could be obtained, whereas the optimal length for histamine release appeared to be greater than or equal to 6 A. Furthermore, muscle relaxants with a rigid backbone between the ammonium determinants (such as pancuronium) are less active than flexible molecules (such as suxamethonium) in initiating mediator release. This study suggests that small divalent molecules can induce anaphylactic shock in sensitized patients and that the length and the flexibility of the chain bearing the haptenic determinants appear to be important factors in the elicitation of mediator release.


Fluorenyl hexa-peri-hexabenzocoronene-dendritic oligothiophene hybrid materials: synthesis, photophysical properties, self-association behaviour and device performance.
Apart from molecular properties, intermolecular forces play a vital role in defining the performance of organic electronic devices. This is particularly relevant in bulk heterojunction (BHJ) solar cells in which the arrangement of electron-donor and -acceptor materials into distinct crystalline phases of ideal size and distribution can lead to better power conversion efficiencies. In this study, a series of fluorenyl hexa-peri-hexabenzocoronenes (FHBC) decorated with thiophene dendrons (DOT) of variable size was obtained by using a convergent synthetic approach. With such variety of molecular sizes and shapes in hand, the objective of this study is to highlight the relationships between molecular properties, bulk properties and device performance. Correlations between π-π stacking ability and dendrimer generation were established from self-organisation studies in solution and solid state. The synergistic combination of molecular organisation at the nanoscale and photophysical characteristics derived from the FHBC and DOT moieties leads to a notable improvement of the photovoltaic performance.


A systematic method for DNA fragment amplification and sequencing based on DNA indexing technology. Protocol and technical considerations.
DNA indexing is based on a presynthesized library of oligonucleotide adaptors (256 in total), named indexers, and type-IIS restriction endonucleases. It enables amplification and direct analysis of large DNA fragments with low overall redundancy and without subcloning. Here, we describe a detailed protocol for PCR-based amplification of DNA fragments followed by DNA sequencing by indexer walking and provide helpful hints on its practical use. The proposed protocol can be applied to the sequencing of plasmids, cDNA clones, and longer DNA fragments. It can also be used for gap filling at the final stage of genome sequencing projects.


Klebsiella pneumoniae pathogenicity in silk moth larvae infection model.
The emergence of antibiotic resistant bacteria is a major health concern worldwide in recent years. The objective of this study is to establish the larvae of the silk moth (commonly known as silkworm), Bombyx mori as an infection model to study antibacterial effect of antibiotics against Klebsiella pneumoniae. In this study, the pathogenicity of a K. pneumoniae strain isolated from food to silkworm larvae was examined. Within 72 h of bacterial injection, all silkworm larvae were killed in a dose-dependent manner with their body color turning into black due to increased melanization. Bacterial numbers in the larval hemolymph (blood) significantly increased after 9 h of infection with a decrease in viable circulatory hemocytes in hemolymph. When presented with bacteria laden leaves, larvae did not eat but injection of bacteria directly into the midgut killed larvae within 12 h with a higher load required in comparison to that required for the killing by hemolymph injection. Administration of four different antibiotics into larval hemolymph showed therapeutic effect at different doses with varying efficacies against hemolymph-injected K. pneumoniae. These results indicate that the silkworm larvae can be used as an infection model not only to study the pathogenicity of K. pneumoniae but also to perform rapid screening for the identification of antibiotics effective against multidrug-resistant strains of K. pneumoniae.


Decline of acute myocardial infarction death rates not due to cause of death coding.
The recent decline in coronary heart disease (CHD) mortality has been attributed to reduction in risk factors, improved management and the possibility of statistical artifacts. The purpose of this study is to assess the impact of geographic and time variation in the coding of cause of death from death certificates into ICD codes upon CHD mortality rates in Canada. Equal samples of death certificates were recoded for Nova Scotia and Saskatchewan for each of the years 1970 and 1984: 1) a first set of 1,600 death certificates originally coded as acute myocardial infarction (AMI) and 2) a second set of 800 death certificates from all causes of death. The coding error rates increased with age and with the number of contributing and underlying causes of death reported on the death certificates. The net effect of false positive and false negative AMI codes on death certificates did not vary significantly by province or year. Thus, variation of death certificate coding over time and geographic regions do not contribute toward the explanation of the AMI mortality rate decline.


Use of pulmonary function tests in the assessment and treatment of patients with airway hyperreactivity.
Simple spirometry at each office visit (and if feasible, determination of lung volume) along with regular assessment of peak flow by the patient are important determinations that facilitate assessment of the progress of the disorder, as well as the impact of therapy. When there is a trend towards falling air flow rates, determination of the arterial blood gas tensions and calculation of the P(A-a)O2 will foster early recognition of the development of increased flow resistance in the peripheral lung units, so that intervention can be instituted. In the early stages of peripheral airway obstruction, the arterial PO2 and the P(A-a)O2 are sensitive indicators of the severity of the disturbance, whereas changes in FEV1 may be minimal. If intervention is not instituted early enough, the work of breathing may increase significantly and reach a stage where hypoxemia is associated with a rising PaCO2, which is indicative of serious deterioration.


A new non-covalent complex of semisynthetically modified tryptic fragments of cytochrome c.
We have prepared a semisynthetic analogue of fully acetimidylated horse cytochrome c, a complex in which the peptide bond between residues glycine-37 and arginine-38 is lacking. In contrast with the complex that we have previously described [Harris & Offord (1977) Biochem. J. 161, 12-25], in which the break in continuity is between residues arginine-38 and lysine-39, the new analogue has a nearly normal redox potential, and can more fully restore succinate oxidation to mitochondria depleted of cytochrome c. Studies of this and other analogues lead us to propose an explanation for the low biological activity of complex (1-38)-(39-104) and a role for the invariance of arginine-38.


Fibroepithelial polyp of the lower urinary tract in adults.
Fibroepithelial polyps of the urinary tract are rare with most cases reported in children. We report the clinicopathologic features of 12 fibroepithelial polyps of the lower urinary tract in adults. There were 9 males, 2 females, and 1 patient where the gender was unknown (median age, 44 years; range, 17-70 years). Chief clinical symptoms were hematuria, urinary urgency, and hesitancy. Five patients were asymptomatic, where the lesions were discovered incidentally. Most lesions were located near the verumontanum or the bladder neck. Ten patients were treated by transurethral resection. Of the 10 patients with follow-up information, none showed recurrence (mean, 20 months; median, 17 months). Histologically, all of the fibroepithelial polyps were lined by normal-appearing urothelium, with in one lesion the additional finding of a columnar epithelial lining. There were three overall architectural patterns seen within fibroepithelial polyps. The most common pattern (Pattern 1) seen in 5 cases consisted of a polypoid mass with club-like projections resembling a cloverleaf with florid cystitis cystica et glandularis of the nonintestinal type in the stalk. The second pattern (Pattern 2) seen in 4 cases consisted of a papillary tumor composed of numerous small, rounded fibrovascular cores containing dense fibrous tissue. The last morphologic pattern (Pattern 3) consisted of a polypoid lesion with secondary tall finger-like projections, which was seen in 3 cases. All lesions lacked prominent edema and inflammation seen in polypoid cystitis. Fibroepithelial polyps contained broader stalks with dense fibrous tissue, in contrast to the thin delicate loose fibroconnective tissue seen in the stalk of papillomas. One lesion contained atypical degenerative-appearing stromal cells. Although fibroepithelial polyps have been considered to be congenital, we think that some of these polyps could develop after birth because all of our patients first showed clinical symptoms in adulthood. Because fibroepithelial polyps in adults are rare, some of these cases can be misdiagnosed as urothelial neoplasms or reactive conditions. Recognition of the precise histologic features of fibroepithelial polyp can facilitate its correct diagnosis.


Astragaloside IV suppresses transforming growth factor-β1-induced epithelial-mesenchymal transition through inhibition of Wnt/β-catenin pathway in glioma U251 cells.
Astragaloside IV (AS#IV) has previously demonstrated antitumoractivity. We investigated the effect and mechanisms of AS#IV in relation to epithelial-mesenchymal transition (EMT), viainterference with the Wnt/β-catenin signaling pathway in gliomaU251 cells. Induction of glioma U251 cells by transforming growthfactor (TGF)#β1 activated EMT, including switching E#cadherin toN-cadherin and altering the expression of Wnt/β-catenin signalingpathway components such as vimentin, β-catenin, and cyclin-D1.AS-IV inhibited the viability, invasion, and migration of TGF-β1-induced glioma U251 cells. AS-IV also interfered with the TGF#β1-induced Wnt/β-catenin signaling pathway in glioma U251 cells.These findings indicate that AS#IV prohibits TGF#β1-induced EMTby disrupting the Wnt/β-catenin pathway in glioma U251 cells. AS#IV may thus be a potential candidate agent for treating glioma andother central nervous system tumors.


Wnt signaling in castration-resistant prostate cancer: implications for therapy.
Increasing evidence has indicated that Wnt signaling plays complex roles in castration resistant prostate cancer (CRPC). Although not all data were consistent, β-catenin nuclear localization and its co-localization with androgen receptor (AR) were more frequently observed in CRPC compared to hormone naïve prostate cancer. This direct interaction between AR and β-catenin seemed to elicit a specific expression of a set of target genes in low androgen conditions in CRPC. Paracrine Wnt signaling also was shown to aid resistance to chemotherapy and androgen deprivation therapy. Results from the next generation sequencing studies (i.e. RNA-seq and whole exosome sequcing) of CRPC specimens have identified the Wnt pathway as one of the top signaling pathways with significant genomic alterations in CRPC, whereas, Wnt pathway alterations were virtually absent in hormone naïve primary prostate cancer. Furthermore, Wnt signaling has been suggested to play an important role in cancer stem cell functions in prostate cancer recurrence and resistance to androgen deprivation therapy. Therefore, in this review we have summarized existing knowledge regarding potential roles of Wnt signaling in CRPC and underline Wnt signaling as a potential therapeutic target for CRPC. Further understanding of Wnt signaling in castration resistance may eventually contribute new insights into possible treatment options for this incurable disease.


Thyroid cancer in dogs: an update based on 638 cases (1995-2005).
The goal of this study was to update the descriptive statistics of thyroid cancer by using data from multiple institutions collected through the Veterinary Medical Database (VMDB). Information was collected and reported from cases of canine thyroid cancer submitted to the VMDB between January 1, 1995 and December 31, 2005. Odds ratio (OR) analysis was performed on breeds that had > or =3% of the total number of dogs with thyroid cancer; ORs for each age category were also determined. Thyroid cancer represented 1.1% of all neoplasms during the time period of interest. Golden retrievers, beagles, and Siberian huskies all had significantly increased ORs for developing thyroid cancer. No sex predisposition was evident, but dogs between 10 and 15 years of age had a significantly increased chance of developing thyroid disease. Carcinomas and adenocarcinomas represented 90% of thyroid cancers, while adenomas represented 9.3%. Thyroid carcinoma and adenocarcinoma continue to be uncommon in our canine population. Older dogs are still more commonly affected, and this study is in agreement with previous studies that golden retrievers and beagles are overrepresented. A new finding is that Siberian huskies are also overrepresented. Carcinomas represent a much higher proportion of thyroid cancers than previously reported, and adenomas are likely incidental findings on necropsy. Thyroid cancer should be high on the list of differentials for a neck mass in older, large-breed dogs, as they make up 1.1% of the cancer cases reported. The overwhelming majority of thyroid cancers are carcinomas, and they are most common in golden retrievers, beagles, and Siberian huskies.


Clinical manifestations of mousepox in an experimental animal holding room.
A study of the clinical aspects of mousepox was conducted during the 1979-80 outbreak at the National Institutes of Health. The disease was detected serologically in a room located adjacent to the index room. The index room received animals prior to this outbreak from a noncommercial colony which later was found to be infected with mousepox. The infection was present in the room for at least 6 weeks prior to the completion of the study. The paucity of clinical signs and low mortality were striking when compared to previous descriptions of mousepox in the United States. Only 27 of the 939 mice in the room were infected, and only one of these had typical skin lesions. A few of the mice had non-specific signs such as ruffled hair coat and hunched appearance. Minimal spread of the disease was evidenced by clustering of infected cages on one of five animal racks in the room.


Public health significance of four cardiovascular risk factors assessed 25 years ago in a low prevalence country.
The individual and combined effect of cardiovascular disease (CVD) risk factors (RFs) on CVD mortality varies between populations. Our aim was to examine this association and its public health impact in Switzerland, a country with comparably low CVD mortality. We included 9853 men and women aged 25-74 years who participated in the Swiss MONICA (MONItoring of trends and determinants in CArdiovascular disease) study (1983-1992) and were followed up for survival until 2008. Adjusted Cox regression was used to calculate CVD mortality hazard ratios (HR). CVD-RFs were obesity (body mass index ≥ 30 kg/m(2)), smoking (≥ 1 cig/d), high blood pressure (≥ 140 or ≥ 90 mmHg), and total: high-density lipoprotein cholesterol ratio (≥ 5.0). Besides age and sex, models were adjusted for diet, physical activity, educational class, marital status, and the respective other CVD-RFs. After adjustment for age and sex, the HR of CVD death was for obesity 1.86 (95% CI 1.50-2.31), for smoking 1.63 (95% CI 1.32-2.01), for high blood pressure 1.42 (95% CI 1.16-1.73), and for high cholesterol ratio 1.30 (95% CI 1.06-1.60). Adjustment for other covariates moderately attenuated estimates. CVD-RFs had an independent and synergistic effect and accounted for 43.0% of population attributable risk. The presence of all four compared to zero CVD-RFs was associated with a 9.6 years shorter expected survival for a man aged 50. Most CVD deaths could be avoided by prevention of four traditional CVD-RFs. Reduction of smoking prevalence and avoidance of weight gain in the population are the most effective measures. Particular attention should be dedicated to persons with multiple CVD-RFs.


Growth and characterisation of primary bovine colon epithelial cells in vitro.
Epithelial crypts from the bovine colon were obtained by using a combined mechanical and enzymatic isolation method, followed by differential D-sorbitol gradient centrifugation. By using this isolation technique, a pure fraction of epithelial crypts with minimal mesenchymal contamination was obtained. The crypts were seeded in collagen-coated plastic flasks. The attached epithelial cells proliferated and formed a confluent monolayer after 6 days in culture. Under low-serum culture conditions (1% fetal calf serum), the cells had a population doubling time of 21-22 hours. During the culture period, the colonocytes were characterised morphologically and enzymatically. The morphology of the cultured cells was confirmed by scanning electron microscopy and transmission electron microscopy. The presence of microvilli, tight junctions and desmosomes demonstrated the ability of the cultured cells to restore an epithelial-like cell monolayer. The epithelial origin of the cells was demonstrated by labelling the cells with antibodies against epithelial-specific cytokeratins 7 and 13. The functional integrity of the cells was evaluated by measuring various marker enzymes (gamma-glutamyltranspeptidase, acid phosphatase, alkaline phosphatase, NADH-dehydrogenase) and membrane-associated Na+-K+-ATPase activity. Membrane integrity was determined by measuring the leakage of lactate dehydrogenase into the culture medium. This new culture system for bovine colon epithelial cells could be used as an in vitro model of the colon epithelium in physiological and toxicological studies.


The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites.
Malaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin (ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance. Here, we evaluate the in vitro drug sensitivity profile of normally-developing P. falciparum ring stages and DHA-pretreated dormant rings (DP-rings) using a panel of antimalarial drugs, including the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691. We report that while KDU691 shows no activity against rings, it is highly inhibitory against DP-rings; a drug effect opposite to that of ART. Moreover, we provide evidence that KDU691 also kills DP-rings of P. falciparum ART-resistant strains expressing mutant K13.


Genetic structure and differentiation in cultivated grape, Vitis vinifera L.
222 cultivated (Vitis vinifera) and 22 wild (V. vinifera ssp. sylvestris) grape accessions were analysed for genetic diversity and differentiation at eight microsatellite loci. A total of 94 alleles were detected, with extensive polymorphism among the accessions. Multivariate relationships among accessions revealed 16 genetic groups structured into three clusters, supporting the classical eco-geographic grouping of grape cultivars: occidentalis, pontica and orientalis. French cultivars appeared to be distinct and showed close affinity to the wild progenitor, ssp. sylvestris from south-western France (Pyrenees) and Tunisia, probably reflecting the origin and domestication history of many of the old wine cultivars from France. There was appreciable level of differentiation between table and wine grape cultivars, and the Muscat types were somewhat distinct within the wine grapes. Contingency chi2 analysis indicated significant heterogeneity in allele frequencies among groups at all loci. The observed heterozygosities for different groups ranged from 0.625 to 0.9 with an overall average of 0.771. Genetic relationships among groups suggested hierarchical differentiation within cultivated grape. The gene diversity analysis indicated narrow divergence among groups and that most variation was found within groups (approximately 85%). Partitioning of diversity suggested that the remaining variation is somewhat structured hierarchically at different levels of differentiation. The overall organization of genetic diversity suggests that the germplasm of cultivated grape represents a single complex gene pool and that its structure is determined by strong artificial selection and a vegetative mode of reproduction.


[Advances in the diagnosis of epilepsy].
INTRODUCTION. Over the past ten years, evaluation of epilepsy has changed drastically thanks to the development of diagnostic procedures which have transformed understanding of the neurophysiological basis of the development of convulsive seizures. In the USA alone 2 million people are affected by this disease. Of these approximately 20% continued to have seizures in spite of receiving medical treatment. This means that the condition is of a priority for public health attention in any country. Technology used in many areas of diagnosis has allowed the patient with epilepsy to be managed in a much more integrated manner, and therefore to have better possibilities regarding quality of life . DEVELOPMENT. We define these technological advances in three areas in which progress has fortunately been outstanding. Firstly, obtention of better anatomical and functional images permit correlation of the pathology with a specific type of epileptogenic activity. Secondly, understanding the electro clinical semiology resulting from the generation of abnormal cortical activity with subsequent activation of different areas of the cerebral cortex, has made it possible to treat epilepsy surgically. Finally the discovery of genes affecting the presentation of a particular epilepsy syndrome defines the diagnosis and give orientation as to treatment and prognosis in particular cases.


Nurses experiences in palliative care of terminally-ill HIV patients in a level 1 district hospital.
Whilst the discourse of palliative care in HIV management is largely documented and regarded as being an essential component, various authors have further argued that within the context of HIV care in sub-Saharan Africa, palliative care and exploration of the dimensions thereof is largely lacking. This article presents the lived experiences of nurses involved in palliative care, thus providing the perspective of nurses and the multi-faceted dimensions of the nature of caring inherent. This study explored the respondents' understanding of the concepts 'caring' and 'terminal patient' and described the experiences of nurses caring for terminally-ill patients with HIV and how these experiences influence the nature of care rendered. Qualitative research using Husserl's approach of phenomenology design underpinned the study and Giorgi's steps of analysis were used to make meaning of the data. The concept 'caring' was experienced by the nurses as transforming the patients' quality of life through supportive care and hope for life. Palliative care made the nurses conscious of their own mortality, enabling them to be more sensitive, compassionate and dedicated to caring for their patients. The findings described the social networking that enabled nurses to collaborate with colleagues in the interdisciplinary teams and shared knowledge, skills and support within the palliative care team in order to optimise patient outcomes. Nurses with prolonged involvement in caring for terminally-ill patients with HIV experienced helplessness and emotional stress. Recommendations based on the results are that training in psychological and holistic care of the patient, professional counselling and stress management services are needed to support the nurse in this context.


Delayed administration of a single dose of lithium promotes recovery from AKI.
Evidence suggests that glycogen synthase kinase 3β (GSK3β) contributes to AKI; however, its role in post-AKI kidney repair remains uncertain. Here, delayed treatment with a single dose of lithium, a selective inhibitor of GSK3β and a US Food and Drug Administration-approved mood stabilizer, accelerated recovery of renal function, promoted repopulation of renal tubular epithelia, and improved kidney repair in murine models of cisplatin- and ischemia/reperfusion-induced AKI. These effects associated with reduced GSK3β activity and elevated expression of proproliferative molecules, including cyclin D1, c-Myc, and hypoxia-inducible factor 1α (HIF-1α), in renal tubular epithelia. In cultured renal tubular cells, cisplatin exposure led to transient repression of GSK3β activity followed by a prolonged upregulation of activity. Rescue treatment with lithium inhibited GSK3β activity, enhanced nuclear expression of cyclin D1, c-Myc, and HIF-1α, and boosted cellular proliferation. Similarly, ectopic expression of a kinase-dead mutant of GSK3β enhanced the expression of cyclin D1, c-Myc, and HIF-1α and amplified cellular proliferation after cisplatin injury, whereas forced expression of a constitutively active mutant of GSK3β abrogated the effects of lithium. Mechanistically, GSK3β colocalized and physically interacted with cyclin D1, c-Myc, and HIF-1α in tubular cells. In silico analysis revealed that cyclin D1, c-Myc, and HIF-1α harbor putative GSK3β consensus phosphorylation motifs, implying GSK3β-directed phosphorylation and subsequent degradation of these molecules. Notably, cotreatment with lithium enhanced the proapoptotic effects of cisplatin in cultured colon cancer cells. Collectively, our findings suggest that pharmacologic targeting of GSK3β by lithium may be a novel therapeutic strategy to improve renal salvage after AKI.


[The use of cluster analysis in clinico-neurophysiological study].
Neurophysiological characteristic--an amplitude of P300 auditory evoked potentials (EP) wave registered in 12 and 5 EEG leads--was studied in 22 patients with endogenous psychoses. Using cluster analysis, it was shown that the differences between the EP amplitudes before and after treatment split into clusters thus indicating a fine structure of the data, reflecting an objective changes in the patient's state during the treatment. The results obtained correlated with an evaluation of patient' clinical state by the PANSS, namely with scores on general psychopathological and positive symptoms subscales.


The negative effects of prejudice on interpersonal relationships within adolescent peer groups.
Social development theories highlight the centrality of peer groups during adolescence and their role in socializing attitudes and behaviors. In this longitudinal study, we tested the effects of group-level prejudice on ensuing positive and negative interpersonal interactions among peers over a 7-month period. We used social network analysis to identify peer groups based on sociometric nominations, followed by multilevel modeling of the effects of sexual prejudice at the group level on interpersonal interactions among individuals in these groups. As hypothesized, the interpersonal interactions in peer groups with stronger group-level sexual prejudice were distinct from and poorer than those in groups with weaker group-level sexual prejudice. Moreover, longitudinal models indicated that adolescents in groups with stronger initial sexual prejudice reported worse interpersonal interactions with their peers seven months later. These findings provide a contextual understanding of prejudice and its negative effects on how adolescents come to relate with one another over time.


Print-Pause-Print Fabrication of Tailored Electrochemical Microfluidic Devices.
Three-dimensional (3D) printing technology has emerged as a powerful technology for the fabrication of low-cost microfluidics. Nevertheless, the fabrication of microfluidic devices integrating high-performance electrochemical sensors in practical applications is still an open challenge. Although automatic fabrication of the microfluidic device and the electrodes can be successfully carried out using a one-step multimaterial fused filament fabrication (FFF) approach, the as-printed electrochemical performance of these electrodes is not good enough for chemical (bio)sensing and their surface modification is challenging because after closing the channel there is no physical access to the electrode. Thus, here a pause-print-pause (PPP) microfabrication approach was implemented. The fabrication was paused before printing the microfluidics, and the filament-based electrodes were directly modified on the printing bed via stencil printing, drop casting, and electrodeposition. To exemplify this versatile workflow, the design of a microfluidic glucose sensor was proposed. To this end, first, the working and counter electrodes were stencil printed with graphite ink while the reference electrode was stencil printed with Ag|AgCl ink. Then, Prussian blue was formed on the working electrode either by drop casting or by electrodeposition, and glucose oxidase was drop cast on top. At this point, the microfabrication process was resumed, and the microfluidics were printed on top of the modified electrodes to complete the construction of hybrid electrochemical fluidic fused filament fabricated devices (h-eF4Ds). This print-pause-print approach is not limited to ink-based electrodes or glucose oxidase, and we envisage these results will pave the way for the effective integration of electrodes in microfluidic devices in a simple and clean-room-free approach, allowing the development of highly customized eF4Ds for a plethora of analytes with high significance.


Broader curve criteria for selective thoracic fusion.
Retrospective radiographic review. To evaluate the outcome of selective thoracic fusion (STF) by using cantilever bending technique (CBT) and the direct vertebral rotation (DVR) technique for major thoracic-compensatory lumbar (MTCL) curves selected by new curve criteria, which are broader than Lenke curve criteria for STF. Surgical treatment of MTCL curves aims to maximize the number of MTCL curves that can be treated with STF and optimize instrumented thoracic and spontaneous lumbar correction. Comparing current guidelines for STF shows that the surgical technique utilized for STF may affect the curve criteria for MTCL curves for successful STF and thoracic and lumbar correction. Seventy-eight consecutive idiopathic scoliosis patients with major thoracic-compensatory "C" modifier lumbar curves who met the following three criteria: (1) main thoracic curve (MT) to compensatory lumbar curve (CL) ratios of Cobb magnitude and apical vertebral translation (AVT) greater than one; (2) MT/CL ratio of flexibility less than one; (3) Cobb magnitude of lumbar curve less than 35° on side bending, were treated with STF by using CBT and DVR. Radiographs were analyzed before surgery, immediately after surgery, and at the most recent follow-up (range, 2-5 years). All 78 MTCL curves were successfully treated with STF by using CBT and DVR. A mean 61% thoracic correction was matched by 55% lumbar correction at the most recent follow-up. Spontaneous correction of lumbar AVT occurred in all patients. Global coronal imbalance was common before surgery (mean, 14 mm) and remained so after surgery (mean, 12 mm). There were 49 MTCL curves that did not meet Lenke curve criteria for STF. All were successfully treated with STF by using CBT and DVR. Among these 49 MTCL curves, there were 14 Lenke 1C and 18 Lenke 2C curves with one or two, or all of MT/CL ratios of Cobb magnitude, AVT, and apical vertebral rotation of 1.2 or less, and 6 Lenke 3C and 11 Lenke 4C curves with the Cobb magnitude of residual lumbar curve on side bending between 25° and 35°. CBT and DVR can broaden the current curve criteria of MTCL curves for STF to have more MTCL curves treatable with STF and optimize instrumented thoracic and spontaneous lumbar correction. A more effective surgical technique can not only improve instrumented thoracic and spontaneous lumbar correction but also can broaden the MTCL curve criteria for STF to have more MTCL curves treatable with STF.


Extraoccipital photoparoxysmal response in a case of focal encephalitis.
Photoparoxysmal response (PPR) is commonly associated with idiopathic generalised epilepsies. Most of the focal events induced by intermittent photic stimulation (IPS) are reported to be of occipital origin. Only six temporal lobe epilepsy patients have been reported in the literature with focal PPR at extraoccipital sites. We report a four-year-old girl with possible encephalitis who presented initially with epilepsia partialis continua of limbs on the right side. Interictally, she had left centro-parietal periodic lateralized epileptiform discharges (PLEDs). She responded to medical treatment and was free of seizures and motor and cognitive deficits at six months follow-up. Repeat EEG at follow-up showed left centro-parietal spikes accentuated by IPS. This is the first report of an extraoccipital, extratemporal focus showing PPR. The possible mechanism of PPR from this fronto-parietal epileptogenic focus is discussed.


Intracellular Ca(2+) release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal.
Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca(2+)-activated Cl(-) channels. We investigated the hypothesis that the Ca(2+) responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca(2+) stores. ICC, obtained from the small intestine of Kit(+/copGFP) mice, were studied under voltage and current clamp to determine the effects of blocking Ca(2+) uptake into stores and release of Ca(2+) via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca(2+) concentration, suggesting that pacemaker activity depends on Ca(2+) dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca(2+) from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC.


Antisera to bovine oligodendroglia raised in guinea pigs bind to surface of rat oligodendroglia and Schwann cells.
Antisera against bulk isolated bovine oligodendrocytes was raised in 2 guinea pigs (GPaBO). The sera bound only to surface of rat oligodendrocytes in dissociated rat corpus callosum and cerebellar cultures and only to surface of Schwann cells in primary and secondary sciatic nerve and dorsal root ganglia cultures as determined by indirect immunofluorescence. No cells in muscle or retinal cultures bound the guinea pig antisera. The shared antigen does not seem to be either galactocerebroside (GalC) or a myelin basic protein. GPaBO can serve as a useful marker in double-label experiments to identify oligodendrocytes and Schwann cells in dissociated cultures.


Effects of glutamate and aspartate on myocardial substrate oxidation during potassium arrest.
A recent report (J Clin Invest 1993;92:831-9) found no effect of glutamate plus aspartate on metabolic pathways in the heart, but the experimental conditions did not model clinical cardioplegia. The purpose of this study was to determine the effects of glutamate and aspartate on metabolic pathways feeding the citric acid cycle during cardioplegic arrest in the presence of physiologic substrates. Isolated rat hearts were supplied with fatty acids, lactate, pyruvate, glucose, and acetoacetate in physiologic concentrations. These substrates were enriched with 13C, which allowed a complete analysis of substrate oxidation by 13C-nuclear magnetic resonance spectroscopy in one experiment. Three groups of hearts were studied: arrest with potassium cardioplegic solution, arrest with cardioplegic solution supplemented with glutamate and aspartate (both in concentrations of 13 mmol/L), and a control group without cardioplegic arrest. In potassium-arrested hearts, the contributions of fatty acids and lactate to acetyl coenzyme A were reduced, and acetoacetate was the preferred substrate for oxidation in the citric acid cycle. The addition of aspartate and glutamate in the presence of cardioplegic arrest did not further alter patterns of substrate utilization substantially, although acetoacetate use was somewhat lower than with simple cardioplegic arrest. When [U-13C]glutamate (13 mmol/L) and [U-13C]aspartate (13 mmol/L) were supplied as the only compounds labeled with 13C, little enrichment in citric acid cycle intermediates could be detected. Glutamate and aspartate when added to potassium cardioplegic solutions have relatively minor effects on citric acid cycle metabolism.


Significant downregulation of the major swine xenoantigen by N-acetylglucosaminyltransferase III gene transfection.
Introduction of the beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene into swine endothelial cells (SEC) reduced their susceptibility to normal human serum (NHS) in complement-mediated cell lysis and also suppressed the antigenicity to human natural antibodies as evidenced by flow cytometric analysis, as well as Griffonia simplicifolia 1 isolectin (1B4 lectin) binding to the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (the alpha-galactosyl epitope). Western blot analysis indicated that proteins smaller than 66 kDa had diminished reactivity to NHS and 1B4 lectin. GnT-III, a key enzyme involved in branch formation of N-linked sugars, was found to downregulate the expression of xenoantigen, suggesting that this approach may be of value in clinical xenotransplantation in the future.


Hydroxyl radical and hypochlorous acid scavenging activity of small centaury (Centaurium erythraea) infusion. A comparative study with green tea (Camellia sinensis).
Small centaury (Centaurium erythraea Rafin.) is a herbal species with a long use in traditional medicine due to its digestive, stomachic, tonic, depurative, sedative and antipyretic properties. This species is reported to contain considerable amounts of polyphenolic compounds, namely xanthones and phenolic acids as the main constituents. Although the antiradicalar activity of some pure polyphenolic compounds is already known, it remains unclear how a complex mixture obtained from plant extracts functions against reactive oxygen species. Thus, the ability of small centaury infusion to act as a scavenger of the reactive oxygen species hydroxyl radical and hypochlorous acid was studied and compared with that of green tea (Camellia sinensis L.). Hydroxyl radical was generated in the presence of Fe3+-EDTA, ascorbate and H2O2 (Fenton system) and monitored by evaluating hydroxyl radical-induced deoxyribose degradation. The reactivity towards hypochlorous acid was determined by measuring the inhibition of hypochlorous acid-induced 5-thio-2-nitrobenzoic acid oxidation to 5,5'-dithiobis(2-nitrobenzoic acid). The obtained results demonstrate that small centaury infusion exhibits interesting antioxidant properties, expressed both by its capacity to effectively scavenge hydroxyl radical and hypochlorous acid, although with a lower activity against the second than that observed for green tea. Green tea exhibited a dual effect at the hydroxyl radical scavenging assay, stimulating deoxyribose degradation at lower dosages.