One time nose-only inhalation of MWCNTs: Exploring the mechanism of toxicity by intermittent sacrifice in Wistar rats.
We have investigated the time-dependent effect of multi-walled carbon nanotubes (MWCNTs) in rats upon single inhalation exposure followed by intermittent sacrifice. The effects were monitored by analyzing the bronchoalveolar lavage fluid (BALF) and histopathological analysis. Cell count, neutrophils, lymphocytes, lactate dehydrogenase, alkaline phosphatase, protein and cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 4 (IL-4)) were significantly increased, while cell viability and alveolar macrophage count significantly decreased in the BALF of MWCNT-treated rats on day 1, day 7 and day 14 post-exposure, when compared to control rats. Histopathological analysis revealed inflammation, fibrosis and granuloma in the lungs of MWCNTs-treated rats on day 7 and day 14 post-exposure. We interpret that MWCNT induces inflammation, fibrosis and granuloma characterized by progressive elevation of TNF-α and IL-4. Histopathological studies further support our view and reveal the distribution of MWCNT in lungs and tracheobronchial lymph nodes (TBLN). We conclude that MWCNT-induced pulmonary toxicity is considerable even on single exposure.


[Effect of different food rations on nonspecific immunological reactivity indices in guinea pigs].
The highest activity of nonspecific immunity factors (phagocytic activity of the blood leucocytes, lysozyme and complementary activity of the blood sera) was defected in guinea pigs receiving food rations containing 19% of protein and 16% of roughage. These data jestify recommending to feed the test guinea pigs on granulated products, this being more convenient and suitable than using natural ones.


Adolescent age moderates genetic and environmental influences on parent-adolescent positivity and negativity: Implications for genotype-environment correlation.
We examined how genotype-environment correlation processes differ as a function of adolescent age. We tested whether adolescent age moderates genetic and environmental influences on positivity and negativity in mother-adolescent and father-adolescent relationships using parallel samples of twin parents from the Twin and Offspring Study in Sweden and twin/sibling adolescents from the Nonshared Environment in Adolescent Development Study. We inferred differences in the role of passive and nonpassive genotype-environment correlation based on biometric moderation findings. The findings indicated that nonpassive gene-environment correlation played a stronger role for positivity in mother- and father-adolescent relationships in families with older adolescents than in families with younger adolescents, and that passive gene-environment correlation played a stronger role for positivity in the mother-adolescent relationship in families with younger adolescents than in families with older adolescents. Implications of these findings for the timing and targeting of interventions on family relationships are discussed.


Vascular risk factors, apolipoprotein E, and hippocampal decline on magnetic resonance imaging over a 10-year follow-up.
Decline of hippocampal volume on magnetic resonance imaging (MRI) may be considered as a surrogate biomarker of accumulating Alzheimer disease (AD) pathology. Previously, we showed in the prospective population-based Rotterdam Scan Study that a higher rate of decline of hippocampal volume on MRI precedes clinical AD or memory decline. We studied potential risk factors for decline of hippocampal volume. At baseline (1995-1996), 518 nondemented elderly subjects were included, and the cohort was re-examined in 1999 and in 2006. At each examination, hippocampal volume was determined using an automated segmentation procedure. In all, 301 persons had at least two three-dimensional MRI scans to assess decline in hippocampal volume. Persons carrying the apolipoprotein E (APOE) ɛ4 allele had lower hippocampal volumes than persons with the ɛ3/ɛ3 genotype, but the rate of decline was not influenced by APOE genotype. In persons who did not use antihypertensive treatment, both a high (>90 mm Hg) and a low (<70 mm Hg) diastolic blood pressure were associated with a faster decline in hippocampal volume. Also, white matter lesions on baseline MRI were associated with a higher rate of decline in hippocampal volume. In a nondemented elderly population, persons with the APOE ɛ4 allele have a smaller hippocampal volume but not a higher rate of decline. Rate of decline of hippocampal volume was influenced by white matter lesions and diastolic blood pressure, supporting their hypothesized role in the pathogenesis of AD.


Influence of diet on iron, copper, and zinc status in children under 24 months of age.
The objective of the study was to determine whether iron and micronutrient status is improved with an increased amount of meat in the diet. To this end, a longitudinal prospective study with infants recruited at 4 mo and followed until 24 mo of age was undertaken. One hundred ninety-eight infants formed the original study cohort; 48 withdrew before the end of the study. Subjects were classified as nonmeat eaters or as mixed (red and white)-meat eaters subgrouped into tertiles depending on the meat content reported in diet diaries. Seven-day weighed food records were recorded at 4, 8, 12, 16, 20, and 24 mo. Blood samples taken at 4, 12, and 24 mo were analyzed for parameters of iron and micronutrient status. Iron intake increased during the first year, thereafter remaining constant. The percentages of subjects with hemoglobin values below 110 g/L were 34.1, 23.1, and 13.4 at 4, 12, and 24 mo, respectively. For parameters of iron status, the number of results below the reference range was determined for each diet group and a significant negative relationship between serum iron and meat intake at 12 mo of age was seen (p<0.023). There was a trend for hemoglobin concentrations to be inversely related to the meat intake, at the same age (p<0.068). No effects on zinc or copper status were seen. We conclude that a weak association between dietary meat and iron/Hb suggests a positive role for red meat. There was no disadvantage to the nonmeat-eating infants with respect to zinc or copper.


Possibility of re-screening intervals of more than one year in men with PSA levels of 4.0 ng/ml or less.
The optimal re-screening interval is one of the most important issues to evaluate the effectiveness of screening for prostate cancer. Between 1992 and 2000, 7,026 men aged 50-78 with baseline PSA levels of 4.0 ng/ml or lower underwent screening for prostate cancer twice or more. The risk of developing prostate cancer relative to elapsed years and baseline PSA levels were investigated. Prostate cancer was detected in a total of 127 cases (1.8%). The detection rate of prostate cancer was high between 1.6% and 5.5% at 1 year after baseline PSA measurements in men with baseline PSA levels of 2.1-4.0 ng/ml. In men with baseline PSA levels of 1.1- 2.0 ng/ml, the detection rate increased from 0.06% to 1.02% with passed years. The proportion of stage >/=T3 was high at 63% in prostate cancer cases detected between 3 and 4 years after baseline PSA levels being 1.1-2.0 ng/ml. In men with baseline PSA levels of 1.0 or lower, the cumulative detection rate of prostate cancer was low at 0.01% within 3 years, however, the detection rate increased to 0.34% after 5 or more years from baseline PSA measurements. The re-screening interval was recommended to be 1, 1-2, and 3-5 years for men with baseline PSA levels of 2.1-4.0 ng/ml, 1.1-2.0 ng/ml, and 1.0 ng/ml or lower, respectively.


Epidermal growth factor receptor variant type III markedly accelerates angiogenesis and tumor growth via inducing c-myc mediated angiopoietin-like 4 expression in malignant glioma.
Expression of the constitutively activated mutant EGFR variant III (EGFRvIII), the most common mutation in glioblastoma multiforme (GBMs), has been clinically correlated with tumor proliferation, invasion, and angiogenesis. In this study, we examined the role of EGFRvIII on the tumor microenvironment, especially on angiogenesis. To study the role of EGFRvIII in tumor angiogenesis, we prepared LN229 glioblastoma transfected with enhanced green fluorescent protein (EGFP), wild-type EGFR, or EGFRvIII (LN229-WT or -vIII), and examined tumor growth and microvessel density in the tumors. Additionally, the potential angiogenic factors were identified by real-time PCR analysis, and the functions in LN229-vIII cells were examined. LN229-vIII cells showed more aggressive tumor growth and higher vascularity as compared to LN229-WT cells in vivo, although there was no significant difference in the cell growth rates in vitro. We next investigated the expression of 60 angiogenesis-related factors to clarify the mechanisms underlying the difference in vascularity between tumor xenografts of LN229-vIII and LN229-WT. We found that the mRNA and protein expressions of angiopoietin-like 4 (Angptl4), a secreted protein involved in angiogenesis and metabolism regulation, were significantly induced by EGFRvIII overexpression, both in vitro and in vivo. Constitutive knockdown of Angptl4 in LN229-vIII using shRNA significantly decreased the microvessel density in the tumor xenografts and suppressed tumor growth. To clarify the regulatory mechanisms of Angptl4 by EGFRvIII, we analyzed the signaling pathways and transcription factors by pharmacological inhibition and RNA interference. U0126, an ERK signal inhibitor dramatically suppressed Angptl4 expression. The transcription factor c-Myc, which is regulated by ERK, was activated in the LN229-vIII cells and knockdown of c-Myc using siRNA also attenuated Angptl4 expression in the LN229-vIII cells. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed increased recruitment of c-Myc to the promoter region of Angptl4 in the LN229-vIII cells. In summary, we demonstrated that EGFRvIII induces Angptl4 expression through the ERK/c-Myc pathway and promotes tumor angiogenesis in malignant gliomas.


Delta component variations in human sleep electroencephalogram.
All night sleep was recorded polygraphically on 14 healthy adults, once for each person, and EEG was analyzed with bandpass filters. The integrated values during successive 10 second epochs were recorded consecutively at 1 mm intervals, separately for each frequency band. The variations of integrated values for long time span were clearly observed. The findings on 1-2 Hz component are reported exclusively in this report. (1) Four variation patterns were classified on the variations of integrated values of 1-2 Hz band component; long undulation, short undulation, irregular undulation and slight fluctuation. Short undulation was superimposed on long undulation. Long undulation had a gradually increasing slope, a plateau and steeply decreasing slope. Irregular undulation showed generally irregular fluctuations, without any definite variation patterns. During slight fluctuation the variations were small. Long undulation and irregular undulation corresponded to slow-wave sleep and slight fluctuation corresponded to REM sleep. The mean duration of each long undulation and irregular undulation was 31.2 and 11.9 minutes, respectively. In long undulations, 62.8% of the time was occupied by Stage 2 and the lesser ratio by Stages 3 and 4. In irregular undulation 89.1% of the time corresponded to Stage 2. (2) One sleep cycle was composed of the three sleep states which were accompanied with variation patterns, long undulation, irregular undulation and slight fluctuation. The sequence of the appearance of the former two patterns in one sleep cycle was classified into four types. About half of the sleep cycles in all records exhibited Type 1; the pattern started with long undulation, after one or several long undulations followed by irregular undulation and proceeded to slight fluctuation. The average number of long indulation in one sleep cycle was 1.58. (3) On all records, the highest long undulations appeared in the first cycle of all night sleep, in both frontal and central areas. In the occipital area, some of the highest crests appeared in the second cycle. When the highest of long undulations appeared, the height tended to decrease prior to wakening. The crest line of long undulation in frontal and central areas crossed in the latter period of all night sleep, in five controls. The mean voltage of long undulation in frontal, central and occipital areas was 52.4, 42.5 and 23.5 microvolts, respectively. The underlying physiological mechanism of delta waves in human sleep EEG and possible brain structures essential for long undulation and irregular undulation were discussed from both the clinical and experimental aspects.


MicroRNA-520a-3p suppresses epithelial-mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1-mediated JAK/STAT signaling pathway.
Papillary thyroid cancer (PTC) is a kind of thyroid cancer and frequently presents with epithelial-mesenchymal transition (EMT). MicroRNAs (miRNAs) were previously reported to be associated with PTC. Thus, this study aims to define the role of microRNA-520a-3p (miR-520a-3p) in PTC through the JAK/STAT signaling pathway by targeting JAK1. The PTC and normal thyroid tissues of 137 PTC patients were collected. First of all, the expression pattern of miR-520a-3p, JAK1, JAK2, STAT3, E-cadherin, and vimentin in PTC was identified. The relationship between miR-520a-3p and JAK1 was predicted and analyzed. And a series of miR-520a-3p mimic or inhibitor, or siRNA JAK1 introduced into PTC cells were applied to examine the effect of miR-520a-3p on PTC cell viability, migration, invasion, cell cycle, apoptosis, and EMT. Meanwhile, the regulatory effect of miR-520a-3p and JAK1 on the JAK/STAT signaling pathway was also determined. The expression of JAK1, JAK2, STAT3, and vimentin increased yet miR-520a-3p and E-cadherin decreased in PTC tissue. JAK1 was negatively regulated by miR-520a-3p. Functionally, EMT induction was prevented by miR-520a-3p upregulation through downregulating JAK1. When upregulating miR-520a-3p or silencing JAK1 in PTC cells, PTC cell viability, migration, and invasion were inhibited yet cell apoptosis promoted with cells arrested at G1 phase, indicating that miR-520a-3p prevented PTC progression by downregulating JAK1. Moreover, miR-520a-3p elevation or JAK1 inhibition inactivated the JAK/STAT signaling pathway. Collectively, miR-520a-3p prevents cancer progression through inactivating the JAK/STAT signaling pathway by downregulating JAK1 in PTC.


Reduced C9orf72 expression exacerbates polyGR toxicity in patient iPSC-derived motor neurons and a Type I protein arginine methyltransferase inhibitor reduces that toxicity.
Intronic repeat expansions in the C9orf72 gene are the most frequent known single genetic causes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These repeat expansions are believed to result in both loss-of-function and toxic gain-of-function. Gain-of-function results in the production of toxic arginine-rich dipeptide repeat proteins (DPRs), namely polyGR and polyPR. Small-molecule inhibition of Type I protein arginine methyltransferases (PRMTs) has been shown to protect against toxicity resulting from polyGR and polyPR challenge in NSC-34 cells and primary mouse-derived spinal neurons, but the effect in human motor neurons (MNs) has not yet been explored. To study this, we generated a panel of C9orf72 homozygous and hemizygous knockout iPSCs to examine the contribution of C9orf72 loss-of-function toward disease pathogenesis. We differentiated these iPSCs into spinal motor neurons (sMNs). We found that reduced levels of C9orf72 exacerbate polyGR15 toxicity in a dose-dependent manner. Type I PRMT inhibition was able to partially rescue polyGR15 toxicity in both wild-type and C9orf72-expanded sMNs. This study explores the interplay of loss-of-function and gain-of-function toxicity in C9orf72 ALS. It also implicates type I PRMT inhibitors as a possible modulator of polyGR toxicity.


Immunological similarity of epoxide hydrolase activity in the mitochondrial and cytosolic fractions of mouse liver.
The light and heavy mitochondrial fractions of mouse liver have relatively high levels of epoxide hydrolase (EH) activity when monitored with trans-stilbene oxide as substrate. Using double diffusion analysis and immunoprecipitation experiments it was shown that EH activity in the mitochondrial fractions is immunologically similar to cytosolic EH, but immunologically dissimilar from microsomal EH. The EHs in the mitochondrial and cytosolic fractions also have a similar pI.


Functional control of the binuclear metal site in the metallo-beta-lactamase-like fold by subtle amino acid replacements.
At present there are three protein families that share a common structural domain, the alphabeta/betaalpha fold of class B beta-lactamases: zinc beta-lactamases, glyoxalases II, and A-type flavoproteins. A detailed inspection of their superimposed structures was undertaken and showed that although these proteins contain binuclear metal sites in spatially equivalent positions, there are some subtle differences within the first ligand sphere that determine a distinct composition of metals. Although zinc beta-lactamases contain either a mono or a di-zinc center, the catalytically active form of glyoxalase II contains a mixed iron-zinc binuclear center, whereas A-type flavoproteins contain a di-iron site. These variations on the type of metal site found within a common fold are correlated with the subtle variations in the nature of the ligating amino acid residues and are discussed in terms of the different reactions catalyzed by each of the protein families. Correlation of these observations with sequence data results in the definition of a sequence motif that comprises the possible binuclear metal site ligands in this broad family. The evolution of the proteins sharing this common fold and factors modulating reactivity are also discussed.


Mathematical modeling on obligate mutualism: Interactions between leaf-cutter ants and their fungus garden.
We propose a simple mathematical model by applying Michaelis-Menton equations of enzyme kinetics to study the mutualistic interaction between the leaf cutter ant and its fungus garden at the early stage of colony expansion. We derive sufficient conditions on the extinction and coexistence of these two species. In addition, we give a region of initial condition that leads to the extinction of two species when the model has an interior attractor. Our global analysis indicates that the division of labor by worker ants and initial conditions are two important factors that determine whether leaf cutter ants' colonies and their fungus garden can survive and grow or not. We validate the model by comparing model simulations and data on fungal and ant colony growth rates under laboratory conditions. We perform sensitive analysis of the model based on the experimental data to gain more biological insights on ecological interactions between leaf-cutter ants and their fungus garden. Finally, we give conclusions and discuss potential future work.


Using a Modified Proximity Ligation Protocol to Study the Interaction Between Chaperones and Associated Proteins.
Molecular chaperones can interact with multiple proteins to form large networks. Understanding these interactions may shed light on the complexity of the chaperone functions. Here we developed a protocol for a modified proximity ligation-based methodology (PLA) for the detection of protein-protein interactions in order to understand how the Hsp70-Bag3 complex interacts with components of the Hippo signaling pathway. These experiments helped to elucidate the mechanisms of transmission of the proteotoxic stress signal to the Hippo pathway. The modified PLA technology has many advantages compared to co-immunoprecipitation protocols. It has higher sensitivity, is quantitative, and can be done in a 96-well format.


Comparison of vasculoprotective effects of benidipine and losartan in a rat model of metabolic syndrome.
Although antihypertensive drugs confer improvement in endothelial dysfunction and protection from atherogenesis in hypertension, different classes of antihypertensive drugs may elicit different degrees of vasculoprotective effects. We have investigated the effects of a long-acting calcium antagonist, benidipine, and an angiotensin AT(1) receptor antagonist, losartan, on the vascular damage observed in OLETF rats, an animal model of metabolic syndrome. At 34 weeks of age, OLETF rats were treated with either benidipine (3 mg/kg/day, per os) or losartan (25 mg/kg/day, per os) for 8 weeks. The extent of blood pressure reduction, restoration endothelium-dependent aortic relaxation, and elevation of serum nitrite/nitrate concentration did not differ significantly between benidipine- and losartan-treated OLETF rats. Benidipine and losartan also reduced the aortic expression of transforming growth factor-beta1 mRNA and thickening of the vascular wall to a similar extent. Increased cardiac fibrosis was also inhibited by both benidipine and losartan. These data suggest that, when used in an antihypertensive dose, benidipine is as effective as losartan in restoring vascular endothelial function and in suppressing of cardiovascular remodeling in an animal model of metabolic syndrome.


Mechanical thrombectomy in patients with proximal occlusions and low NIHSS: Results from a large prospective registry.
Mechanical thrombectomy is now standard of care for treatment of acute ischemic stroke secondary to large vessel occlusion in the setting of high NIHSS. We analysed a large nationwide registry focusing on patients with large vessel occlusion and low NIHSS on admission to evaluate the efficacy and safety of thrombectomy in this patient population METHODS: 2826 patients treated with mechanical thrombectomy were included in a multicentre registry from January 1, 2011 to December 31, 2015. We included patients with large vessel occlusion and NIHSS ≤ 6 on admission. Baseline characteristics, imaging, clinical outcome, procedure adverse events and positive and negative outcome predictors were analysed. 134 patients were included. 90/134 had an anterior circulation and 44 a posterior circulation stroke. One patient died before treatment. Successful revascularization (mTICI 2b-3) was achieved in 73.7% (98/133) of the patients. Intraprocedural adverse event was observed in 3% (4/133) of cases. Symptomatic intracranial haemorrhage rate was 5.3% (7/133). At three months, 70.9% (95/134) of the patients had mRS score 0-2, 15.7% (21/134) mRS 3-5 and 13.4% (18/134) mRS 6. Age and successful recanalization were significant predictors of a good clinical outcome on both univariate (p= 0.005 and p=0.007) and multivariable (p=0.0018 and p=0.009 [nat log]) analysis. Absence of vessel recanalization and symptomatic intracranial hemorrhage were independent predictors of poor outcome (p=0.021) . Our study suggests that patients with large vessel occlusion and low NIHSS score on admission can benefit from mechanical thrombectomy. Randomized trials are warranted.


Structural features of myofibrillar fish protein interacting with phosphatidylcholine liposomes.
The interactions between liposomes and fish myofibrillar protein (surimi ground salted protein, SURP) were evaluated. Liposomes prepared with ultrapure phosphatidylcholine (UPC) or partially purified phosphatidylcholine (PPC) were dispersed at different weight ratio on SURP. Changes in protein stability and structure were evaluated using FTIR, intrinsic fluorescence and free sulfhydryl groups, and changes in liposome properties were studied by dynamic light scattering and electron microscopy. PPC promoted denaturation and aggregation of SURP, reflected in secondary structure loss, exposure of tyrosine residues and increment of free sulfhydryl. UPC produced partial unfolding and changes in the secondary structure of SURP from α-helical to β-strand. Liposome size increased by about 40% and showed modified surface charge after SURP exposure, indicating the formation of protein corona. Surface charge and composition of liposomes influence SURP stability and could exert different effects on the myofibrillar protein network, which is important for liposome applications in surimi products.


Serum type III procollagen and basement membrane proteins as noninvasive markers of hepatic pathology in Indian childhood cirrhosis.
While serum concentrations of antigens of the aminopropeptide of type III procollagen have been considered as indicators of hepatic pathology in adults, the high concentrations normally found in children during growth may preclude their use in pediatric liver disease. To clarify this and to determine the role of other circulating connective tissue-related substances in children, we have measured serum concentrations of antigens related to aminopropeptide of type III procollagen, the 7S domain of type IV collagen and the P1 fragment of laminin in healthy subjects aged 1 month to 4 years and in children with Indian childhood cirrhosis, a particularly aggressive form of liver disease. In healthy subjects, there was a considerable age variation in serum aminopropeptide of type III procollagen but not in 7S collagen or laminin P1. In Indian childhood cirrhosis, all three serum antigens were increased (p less than 0.001) above the upper limit of normal for age. Both the serum 7S collagen and laminin P1 concentrations showed a significant correlation with the degree of intralobular fibrosis and also with the severity of necrosis and cellular infiltration, suggesting that these serum antigens may be a noninvasive means of assessing and monitoring events associated with hepatic fibrosis in Indian childhood cirrhosis. The raised serum aminopropeptide of type III procollagen in Indian childhood cirrhosis did not correlate with any histological parameter assessed. Gel filtration of serum showed that, in healthy subjects, the predominant antigenic form of aminopropeptide of type III procollagen was a degradation peptide smaller than authentic aminopropeptide of type III procollagen; while in Indian childhood cirrhosis the authentic peptide and a larger degradation peptide predominated.(ABSTRACT TRUNCATED AT 250 WORDS)


Removal of overextended gutta-percha root canal fillings in endodontic failure cases.
A procedure is proposed for the complete removal of an overextended root canal filling when associated with a root canal treatment failure. First, the gutta-percha is softened with xylene and removed to a distance of 2 to 3 mm short of the apex. Second, the remaining gutta-percha, which is preserved as solid as possible, is removed by a Hedstrom file. The file is extended 0.5 to 1.0 mm beyond the apex, firmly engages the gutta-percha and is slowly removed. In 17 of the 18 cases, this procedure successfully removed the overextended gutta-percha.


Impact of age on thromboembolic events in patients with non-valvular atrial fibrillation.
Age is a well-established risk factor for thromboembolic events in patients with atrial fibrillation (AF). However, the mechanism underlying the association between age and thromboembolic events in AF remains unknown. The prognostic value of age as a risk factor for thromboembolic events was analyzed using data from the Korean National Health Insurance Service (NHIS). In a large-scale single-center registry, cardiac hemodynamic parameters were examined to elucidate the cause of increased risk of thromboembolic events in older patients. NHIS sample cohort data including 5896 patients with AF revealed that the risk of thromboembolic complication differed significantly according to age despite equal CHA2 DS2 -VASc score. In the registry of 2801 patients, age showed significant correlations with left atrium (LA) diameter, LA volume, E/e', pulmonary artery pressure, and LA appendage flow velocity. Older patients had a significantly higher prevalence of spontaneous echocontrast (odds ratio [OR] = 1.030; P < .001). Age (OR = 1.031; P < .001), E/e' (OR = 1.065; P = .004), and LA appendage flow velocity (OR = .988; P = .009) were significant predictors for thromboembolic events in multivariate analyses. In data from the NHIS, CHA2 DS2 -VASc score did not outperform age to predict thromboembolic events. Age is a significant risk factor for thromboembolic events in patients with AF, and old age is associated with adverse cardiac hemodynamics. This study suggests that older patients with AF are at high risk of thromboembolic events regardless of CHA2 DS2 -VASc score.


Diprivan (ICI 35868, 2, 6, di-isoprophylphenol), a new intravenous anesthetic.
Diprivan is a new anesthetic agent that is being tested in the United States after preliminary trials in Europe. Characteristic features include rapid induction and recovery, with cardiovascular and respiratory changes that are insignificant at the recommended dose. Lack of excitatory and emetic complications, along with absence of any toxic effects to date, have contributed to its consideration as an auspicious new agent.


Characterization of Fusarium graminearum Mes1 reveals roles in cell-surface organization and virulence.
The surfaces of fungal hyphae are mosaics of carbohydrates and cell-surface proteins. Presently, very little is known about the role of these proteins and their organization at the cell surface. Here, we characterize two Fusarium graminearum genes implicated in cell-surface organization, mes1 (FGSG_06680) and pls1 (FGSG_08695). Mes1 is a homologue of mesA, which is required for the formation of stable polarity axes in Aspergillus nidulans. Pls1 encodes a tetraspanin, which belongs to a class of proteins that have been shown to aggregate in membrane rafts along with integrins and other signaling proteins. Our results indicate that Pls1 is dispensable for saprophytic growth and wheat head infection by F. graminearum (a pathogen that does not form appressoria). However, deletion of mes1 reduces sexual and asexual reproduction, severely perturbs the shape of macroconidia and hyphae, alters the pattern of cell wall deposition and the organization of sterol-rich rafts, and attenuates virulence on wheat heads. Our results provide a basis for identifying determinants of fungal virulence that may localize to specialized domains at the cell surface.


Stable and inheritable changes in genotype and phenotype of albino melanocytes induced by an RNA-DNA oligonucleotide.
Experimental strategies have been developed to correct point mutations using chimeric oligonucleotides composed of RNA and DNA. We used these RNA-DNA oligonucleotides to correct a point mutation in mouse tyrosinase, a key enzyme for melanin synthesis and pigmentation. Melanocytes derived from albino mice contain a homozygous point mutation (TGT-->TCT) in the tyrosinase gene, resulting in an amino acid change from Cys-->Ser. Correction of this point mutation results in the restoration of tyrosinase activity and melanin synthesis, thus changing the pigmentation of the cells. Upon transfection of the RNA-DNA oligonucleotide to albino melanocytes, we detected black-pigmented cells and isolated multiple single clones. All black-pigmented clones exhibited a correction of the point mutation in a single allele of the tyrosinase gene. A full-length tyrosinase was detected by an antityrosinase antibody, and the enzymatic activity was restored in all converted black-pigmented clones. Only degraded fragments were detected in albino cells due to proteolytic cleavage of mutant tyrosinase. The phenotype and genotype of converted black-pigmented clones was stable. These results demonstrate a permanent and stable gene correction by the RNA-DNA oligonucleotide at the level of genomic sequence, protein, and phenotypic change by clonal analysis.


Tryptic digestion of bovine secretory IgA at elevated temperature and in urea. Isolation of SC domain 1 which is covalently bound to IgA dimer and binds non-covalently to IgM.
1. Tryptic cleavage sites in bovine secretory component (SC) which become inaccessible when SC is bound to IgA dimer remained inaccessible at 60 degrees C and in 4 M urea at 37 degrees C. 2. This suggests the presence of strong interactions compatible with published affinity constants of ca 10(8) M-1. 3. In 5 M urea at 37 degrees C further cleavage of bound SC did occur to produce a fragment consisting of domain 1 which was disulphide bridged to the IgA dimer. 4. Binding studies on the isolated fragment showed that domain 1 did not account for all the binding by SC. 5. Cleavage of the isolated fragment with iodosobenzoic produced a smaller fragment consisting of the n-terminal third of domain 1 (residues 1-35). This N-terminal fragment showed significant binding.


Parallel forms of the Knowledge of Behavioral Principles as Applied to Children questionnaire: an independent, multi-centred, British replication.
The psychometric properties of the test entitled Knowledge of Behavioral Principles as Applied to Children and two shortened forms of this test were investigated in two samples of British subjects. The first consisted of 162 psychiatric nurses, psychiatrists, occupational therapists, physiotherapists and clinical psychologists attending behaviour modification courses. The second consisted of 49 teachers and nurses, all working with the mentally retarded, who completed the test by post. The whole test and the two sets of parallel forms all showed good internal consistency and sensitivity to change. Some shrinkage during replication was found. The 25-item forms showed evidence of the properties of parallel forms (equal means, standard deviations and standard errors) in both samples. The 10-item forms were also parallel in sample 1. However the 10-item forms did not remain parallel in sample 2 and so cannot always be recommended.


Duplication and remoulding of tRNA genes during the evolutionary rearrangement of mitochondrial genomes.
During the evolution of sea urchins, a transfer RNA gene lost its tRNA function and became part of a protein-coding gene. This functional loss of a tRNA with specificity for one group of leucine codons (CUN, where N is any base) was accompanied by the gain of a new tRNA with that specificity. The new tRNA gene for CUN codons appears to have evolved by duplication and divergence from a tRNA gene specific for another group of leucine codons (UUR, where R is a purine). These proposals account for (1) the strong sequence resemblance between the modern tRNA genes for CUN and UUR codons in Paracentrotus, (2) the altered location of the CUN gene in mitochondrial DNA of this urchin, and (3) the persistence of a 72-base pair sequence containing a trace of the old CUN gene at its original location. The old CUN gene now codes for an extra 24 amino acids at the amino end of subunit 5 in NADH dehydrogenase. Besides giving clues about the mechanisms by which tRNA genes move during mitochondrial DNA evolution, this finding leads us to propose a pathway relating the arrangements of other genes in mitochondrial DNAs from four animal phyla.


Gas-filled appendix with meniscus: outline of the appendicolith.
A meniscus was produced in a gas-filled appendix by the outline of the obstructing appendicolith. This meniscus appearance should be specific for appendicitis since it represents the obstructing stone. This sign can be elicited by oblique or other projections, perhaps with fluoroscopic control.


Identification, structure and function of a novel tetraspaninhomologue from Spirometra erinaceieuropaei.
To identify a full length c DNA sequence of a novel tetraspanin (TSP) homologue from Spirometra erinaceieuropaei and to predict the structure and function of its encoding protein using bioinformatics methods. Using the NCBI, EMBI, Expasy and other online sites, the open reading frame (ORF), conserved domain, physical and chemical parameters, signal peptide, transmembrane domain, epitope, topological structures of the protein sequences were predicted. And Vector NTI software was used for multiple sequence alignment and phylogenetic tree construction. The target sequence was 1132 bp length with a 681 bpbiggest ORF encoding 226 amino acids protein with typical TSP conserved domain. It was confirmed as full length c DNA of TSP16 from Spirometra erinaceieuropaei and named as SeTSP16 (GenBank accession number: JF728872). The predicted molecular weight and isoelectric point of the deduced protein were 24 750.5 Da and 7.88 Da, respectively. Compared with TSP16s from Schistosoma japonicum and Schistosoma mansoni, it showed similarity of 59% and 59%, respectively. SeTSP16 contained four transmembrane domains (TM1-4), intracellular N and C-termini, one short small extracellular loop and one large extracellular loop. Four major epitopes that were significant different from the corresponding epitope regions of TSP16 from Schistosoma mansoni and Schistosoma japonicum were predicted. The full length c DNA sequences of SeTSP16 are identified. It encodes a transmembrane protein which might be an ideal diagnosis antigen and target molecule for antiparasitic drugs.


Reversing the trend: reducing the prevalence of asthma.
We urgently need to take steps towards reducing the prevalence of asthma in countries where the prevalence has become unacceptably high in recent years. Because we do not have any good information about causes of the increased prevalence, we cannot act directly to reverse the trend. Therefore we need to take an indirect approach and use known information of etiologic factors to try to reduce asthma in the next generation, while acknowledging that we may be dealing with different factors from those responsible for the increased prevalence. Any successful strategies will also help to ensure that developing countries do not attain such high rates of asthma in their children in coming years. This article summarizes the roles of the risk factors that identify "high-risk" children, that provide insights into mechanisms, or that have potential for primary prevention. The factors with the most potential for primary prevention are allergen exposure, parental smoking, breast-feeding, and dietary fatty acids. In other health models, information about risk factors has been used in successful public health interventions. It is disappointing that the important risk factors for asthma are well documented but that there have been few trials of primary prevention and no changes in public health policies.


Synthesis and characterization of nanocatalyst Cu2+/mesoporous carbon for amidation reactions of alcohols.
In this research, mesoporous carbon (MC) with high efficiency (0.65 g yield from 1.0 g MCM-41 and 1.25 g sucrose) was successfully prepared by adding carbon precursor (sucrose) in a single step with ultrasonic waves, which reduces time and energy cost. Then, the Cu2+/Mesoporous carbon nanocatalyst (Cu2+/MC) was synthesized by adding Cu(NO3)2 in a single step and applied as a catalyst in amidation reactions of alcohols. Also, Cu2+/MC was characterized using different spectroscopic methods and techniques, including Fourier transform infrared spectroscopy (FT-IR), Field Emission Scanning Electron Microscopy (FE-SEM), N2 adsorption analysis (BET), X-ray diffraction analysis (XRD), Energy Dispersive X-ray (EDX), and Thermogravimetric Analysis (TGA). Moreover, to show the catalytic merits of Cu2+/MC, various primary and secondary amines and ammonium salts were applied in the amidation of alcohols. Easy synthesis method, recyclability, excellent yields (80-93%), and simple work-up are some noticeable strengths of using Cu2+/MC as a catalyst in this reaction.


Influence of recombinant alpha and gamma interferons on the in vitro proliferation of myeloid and leukemic progenitors.
We have compared the effect of alpha 2-C and gamma recombinant interferons (rIFNs) on normal myeloid progenitors (N-CFU-GM), chronic myeloid leukemia (CML) progenitors (CML-CFU-GM) and leukemic progenitors (L-CFU) of acute non-lymphoblastic leukemia (ANLL) patients. Within 14 days of continuous exposure in culture, a dose-dependent inhibition of CFU-GM was seen for most normal subjects. Resistance to rIFNs was frequent in leukemic patients and even more in acute leukemia than in CML. Stimulation of clonogenic cell growth was seen for a minority of leukemic patients. When only the sensitive cases were considered, no difference in sensitivity was noticed between normal, CML and ANLL patients. A good correlation was observed between the activity or the lack of activity of alpha and gamma rIFNs.


The rat clofibrate-inducible CYP4A gene subfamily. I. Complete intron and exon sequence of the CYP4A1 and CYP4A2 genes, unique exon organization, and identification of a conserved 19-bp upstream element.
The P450 CYP4A1 and CYP4A2 genes were isolated from a rat genomic library constructed in the vector lambda EMBL3 and their complete sequences were determined. The CYP4A1 and CYP4A2 genes spanned 14,144 and 10,576 bp and contained 13 and 12 exons, respectively. The CYP4A1 gene contained an additional intron that splits the exon corresponding to exon 12 of the CYP4A2 gene, resulting in a noncoding 13th exon in CYP4A1. The exon numbers of these genes were distinct among known P450 genes, and yet several intron-exon junctions along the P450 amino acid coding region were conserved with P450 genes in the CYP2, CYP11, and CYP21 gene families. On the basis of these data, the number of exons in the putative ancestral P450 gene was estimated. The evolutionary implications of this finding are discussed. No consensus TATA sequence was found upstream of either gene's transcription start site. Comparison of the CYP4A1 and CYP4A2 promoters with other genes that lack TATA boxes did not reveal any strong consensus sequence in their immediate upstream regions. However, a conserved 19-bp sequence was located at the positions of 42 and 48 bp upstream from the CYP4A1 and CYP4A2 genes' start sites, respectively. The CYP4A2 gene also contained two 378-bp direct repeats upstream from the start site; these repeats are derived from portions of the long interspersed middle repetitive element present in high copy numbers in the rat genome.


Stenting of the Brachiocephalic Vein Following Occlusion After Coronary Artery Bypass Surgery.
We describe a case of left arm swelling over nine months post coronary artery bypass grafting (CABG), due to occlusion of the left brachiocephalic vein. The patient's perioperative course, diagnosis, and management of this complication are presented. doi: 10.1111/jocs.12765 (J Card Surg 2016;31:432-434).


Human intracranial pulsatility during the cardiac cycle: a computational modelling framework.
Today's availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its environment feature a dynamic and complex interplay between the tissue, blood, cerebrospinal fluid (CSF) and interstitial fluid (ISF). Here, we design a computational platform for modelling and simulation of intracranial dynamics, and assess the models' validity in terms of clinically relevant indicators of brain pulsatility. Focusing on the dynamic interaction between tissue motion and ISF/CSF flow, we treat the pulsatile cerebral blood flow as a prescribed input of the model. We develop finite element models of cardiac-induced fully coupled pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI) and features a high level of detail including the brain tissue, the ventricular system, and the cranial subarachnoid space (SAS). We model the brain parenchyma at the organ-scale as an elastic medium permeated by an extracellular fluid network and describe flow of CSF in the SAS and ventricles as viscous fluid movement. Representing vascular expansion during the cardiac cycle, a prescribed pulsatile net blood flow distributed over the brain parenchyma acts as the driver of motion. Additionally, we investigate the effect of model variations on a set of clinically relevant quantities of interest. Our model predicts a complex interplay between the CSF-filled spaces and poroelastic parenchyma in terms of ICP, CSF flow, and parenchymal displacements. Variations in the ICP are dominated by their temporal amplitude, but with small spatial variations in both the CSF-filled spaces and the parenchyma. Induced by ICP differences, we find substantial ventricular and cranial-spinal CSF flow, some flow in the cranial SAS, and small pulsatile ISF velocities in the brain parenchyma. Moreover, the model predicts a funnel-shaped deformation of parenchymal tissue in dorsal direction at the beginning of the cardiac cycle. Our model accurately depicts the complex interplay of ICP, CSF flow and brain tissue movement and is well-aligned with clinical observations. It offers a qualitative and quantitative platform for detailed investigation of coupled intracranial dynamics and interplay, both under physiological and pathophysiological conditions.


Neospora caninum Suspects as One of the Most Important Causes of Abortion in Large Dairy Farms in Isfahan, Iran.
This study aimed to reveal the serological prevalence of Neospora caninum in large dairy farms in Isfahan Province, central Iran. Serum samples were collected from 1500 cattle living in four large dairy farms in Isfahan Province, Iran during 2014-2015 and examined for anti N. caninum IgG antibodies. Overall, 113 serum samples were also collected from the dogs living in these areas; suspecting to be risk factors for this infection. All the serum samples were investigated to find IgG antibodies by using ELISA. Dogs' sera were also analyzed by indirect fluorescent antibody test. Totally, 395 out of 1500 bovine samples (26.33%) were positive for N. caninum: 34%, 21.61%, 23.03% and 29.01% in four investigated clusters (farms). Infection rate was significantly more in cows with the history of abortion. The infection rate in dogs was 17.69%: (20 out of 113). The results show a high seroprevalence of the infection and possibly the role of the dogs in horizontal transmission of the infection.


Renal secondary hyperparathyroidism should be considered a differential diagnosis in forensic cases where animal abuse is suspected.
This case description reports an adult dog with multiple rib fractures that was initially suspected to be the victim of non-accidental trauma, but eventually was diagnosed with severe chronic interstitial nephritis and renal secondary hyperparathyroidism leading to fibrous osteodystrophy and multiple pathological fractures. The importance of the specific expertise of a dedicated expert panel on animal abuse is discussed. This case illustrates the significance of the identification of normal, pathological, and breed-related variations within an animal in addition to forensic expertise, emphasizing that the presence of multidisciplinary teams in an expert panel on animal abuse is crucial.


Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma.
Programmed cell death-1 (PD-1) inhibitor treatment can cause hyperprogressive disease (HPD), but the incidence, outcome, and predictive factors of HPD are unknown in patients with hepatocellular carcinoma (HCC). Herein, we assessed the existence and factors predictive of HPD in patients with advanced HCC treated with nivolumab. We enrolled 189 patients with advanced HCC treated with nivolumab. Occurrence of HPD was investigated using tumour growth dynamics based on tumour growth kinetics (TGK) and tumour growth rate (TGR) before and after treatment, or time to treatment failure. We additionally analysed patients treated with regorafenib (n = 95) or best supportive care (BSC)/placebo (n = 103) after progression on sorafenib to compare tumour growth dynamics. Flare-up of tumour growth was observed in a fraction of patients upon PD-1 blockade, indicating the occurrence of HPD. Based on distinct patterns of disease progression exclusively observed in the nivolumab-treated cohort, but not in the regorafenib- or BSC/placebo-treated cohorts, 4-fold increases in TGK and TGR ratios as well as a 40% increase in TGR were the cut-off values used to define HPD; 12.7% of the patients (24/189) treated with nivolumab met all these criteria. Patients with HPD had worse progression-free survival (hazard ratio [HR] 2.194; 95% CI 1.214-3.964) and overall survival (HR 2.238; 95% CI 1.233-4.062) compared to patients with progressive disease without HPD. More than 90% of patients with HPD missed the opportunity for subsequent treatment because of rapid clinical deterioration. An elevated neutrophil-to-lymphocyte ratio (>4.125) was associated with HPD and an inferior survival rate. HPD occurs in a fraction of patients with HCC who receive PD-1 inhibitor treatment. Analyses of the baseline immune profile and on-treatment tumour growth dynamics could enable optimal patient selection and earlier identification of HPD. Hyperprogressive disease is an unexpected response pattern observed in patients treated with an immune checkpoint inhibitor. This study revealed that hyperprogressive disease occurs in a fraction of patients with advanced hepatocellular carcinoma treated with an anti-PD-1 antibody, providing evidence to encourage careful monitoring of patients to prevent clinical deterioration induced by PD-1 blockade.


Galectin-3 and Epithelial MUC1 Mucin-Interactions Supporting Cancer Development.
Aberrant glycosylation of cell surface proteins is a very common feature of many cancers. One of the glycoproteins, which undergoes specific alterations in the glycosylation of tumor cells is epithelial MUC1 mucin, which is highly overexpressed in the malignant state. Such changes lead to the appearance of tumor associated carbohydrate antigens (TACAs) on MUC1, which are rarely seen in healthy cells. One of these structures is the Thomsen-Friedenreich disaccharide Galβ1-3GalNAc (T or TF antigen), which is typical for about 90% of cancers. It was revealed that increased expression of the T antigen has a big impact on promoting cancer progression and metastasis, among others, due to the interaction of this antigen with the β-galactose binding protein galectin-3 (Gal-3). In this review, we summarize current information about the interactions between the T antigen on MUC1 mucin and Gal-3, and their impact on cancer progression and metastasis.


Anesthetic state does not affect the map of the hand representation within area 3b somatosensory cortex in owl monkey.
Receptive fields defined for small clusters of neurons within the middle cortical layers of area 3b differed little in size or in the skin locations represented among: alert, nitrous oxide-anesthetized, deep sodium pentobarbital-anesthetized, and ketamine-anesthetized owl monkeys. Repeated recordings from nearly identical cortical loci yielded nearly identical multi-unit receptive fields under different conditions of anesthesia.


Rationalizing the environment-dependent photophysical behavior of a DNA luminescent probe by classical and non-adiabatic molecular dynamics simulations.
Environment-sensitive fluorescent nucleoside analogs are of utmost importance to investigate the structure of nucleic acids, their intrinsic flexibility, and sequence-specific DNA- and RNA-binding proteins. The latter play indeed a key role in transcription, translation as well as in the regulation of RNA stability, localization and turnover, and many other cellular processes. The sensitivity of the embedded fluorophore to polarity, hydration, and base stacking is clearly dependent on the specific excited-state relaxation mechanism and can be rationalized combining experimental and computational techniques. In this work, we elucidate the mechanisms leading to the population of the triplet state manifold for a versatile nucleobase surrogate, namely the 2-thienyl-3-hydroxychromone in gas phase, owing to non-adiabatic molecular dynamics simulations. Furthermore, we analyze its behavior in the B-DNA environment via classical molecular dynamics simulations, which evidence a rapid extrusion of the adenine facing the 2-thienyl-3-hydroxychromone nucleobase surrogate. Our simulations provide new insights into the dynamics of this family of chromophores, which could give rise to an integrated view and a fine tuning of their photochemistry, and namely the role of excited-state intramolecular proton transfer for the rational design of the next generation of fluorescent nucleoside analogs.


Hyaluronic acid and proteoglycan synthesis by lung fibroblasts in basal and activated states.
Most glycosaminoglycans (GAGs) formed by lung fibroblasts under both basal and stimulated conditions were secreted into the culture medium. High molecular weight (greater than 10(6) daltons) hyaluronic acid (HA) was the major GAG species formed. Most of the SO4-GAG synthesized by lung fibroblasts was of proteoglycan (PG) monomer size. Agents stimulating complex carbohydrate formation also exhibited some selectivity with respect to whether HA or PG was formed in incremental amounts. Hyaluronate synthesis was especially stimulated by endotoxins, SO4-GAG by beta-xylosides, and PG by CTAP-III.


Rethinking Prophylactic Laser Peripheral Iridotomy in Primary Angle-Closure Suspects: A Review.
To examine the generalizability, discuss limitations, and critically appraise recommendations on the management of primary angle-closure suspects (PACSs) that emerged as a result of recent randomized clinical trials challenging the widely accepted clinical practice of offering laser peripheral iridotomy (LPI) to PACS patients. To synthetize findings from these and other studies. Narrative review. Patients classified as PACS. The Zhongshan Angle-Closure Prevention (ZAP)-Trial and the Singapore Asymptomatic Narrow Angle Laser Iridotomy Study (ANA-LIS) along with accompanying publications were reviewed. Epidemiologic studies reporting on the prevalence of primary angle-closure glaucoma and other precursor forms of the disease were also analyzed along with publications reporting on the natural course of the disease or studies reporting on outcomes after prophylactic LPI. Incidence of progression to more severe forms of angle closure. Patients recruited in recent randomized clinical trials are asymptomatic, do not have cataracts, may be younger, and have, on average, deeper anterior chambers depth compared with patients treated with LPI in clinics. The ZAP-Trial and ANA-LIS clearly represent the best available data on PACS management, additional parameters however may need to be considered when physicians face patients in clinic. PACS patients encountered at tertiary referral centers may represent more advanced cases with respect to ocular biometric parameters and may be at higher risk for disease progression compared with those recruited through population-based screening. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Oncotyrol--Center for Personalized Cancer Medicine: Methods and Applications of Health Technology Assessment and Outcomes Research.
The Oncotyrol - Center for Personalized Cancer Medicine is an international and interdisciplinary alliance combining research and commercial competencies to accelerate the development, evaluation and translation of personalized healthcare strategies in cancer. The philosophy of Oncotyrol is to collaborate with relevant stakeholders and advance knowledge "from bench to bedside to population and back". Oncotyrol is funded through the COMET Excellence Program by the Austrian government via the national Austrian Research Promotion Agency (FFG). This article focuses on the role of health technology assessment (HTA) and outcomes research in personalized cancer medicine in the context of Oncotyrol. Oncotyrol, which currently comprises approximately 20 individual projects, has four research areas: Area 1: Biomarker and Drug Target Identification; Area 2: Assay Development and Drug Screening; Area 3: Innovative Therapies; Area 4: Health Technology Assessment and Bioinformatics. Area 4 translates the results from Areas 1 to 3 to populations and society and reports them back to Area 3 to inform clinical studies and guidelines, and to Areas 1 and 2 to guide further research and development. In a series of international expert workshops, the Oncotyrol International Expert Task Force for Personalized Cancer Medicine developed the Methodological Framework for Early Health Technology Assessment and Decision Modeling in Cancer and practical guidelines in this field. Further projects included applications in the fields of sequential treatment of patients with chronic myeloid leukemia (CML), benefit-harm and cost-effectiveness evaluation of prostate cancer screening, effectiveness and cost-effectiveness of multiple cervical cancer screening strategies, and benefits and cost-effectiveness of genomic test-based treatment strategies in breast cancer. An interdisciplinary setting as generated in Oncotyrol provides unique opportunities such as systematically coordinating lab and bench research, product development, clinical studies and decision science/HTA and transparent joint planning of research and development with a partnership of researchers, manufacturers and health policy decision makers. However, generating a joint research and legal framework with numerous partners from different sectors can be challenging, particularly in the starting period of such an endeavor. The journey to translational personalized medicine through multidisciplinary collaborations may still be long and difficult, but it is evident that it must be continued to turn vision into reality.


Inter-rater reliability of the Conversational Assessment of Neurocognitive Dysfunction.
Cognitive assessment through communication has been the focus of recent studies because the conventional cognitive tests are often considered invasive for older people. Although the Conversational Assessment of Neurocognitive Dysfunction is designed to assess cognitive function non-invasively, inter-rater reliability remains unclear. The current study investigated the Conversational Assessment of Neurocognitive Dysfunction's reliability. The Conversational Assessment of Neurocognitive Dysfunction was used by four clinical psychologists, who evaluated 38 older people with and without cognitive dysfunction. One clinical psychologist evaluated the assessment based on face-to-face communication with participants, while the other clinical psychologists evaluated it according to the audio data in the digital voice recorder. All clinical psychologists were blind to the results of other conventional cognitive tests and details surrounding participants' daily living activities. The univariate correlation scores of the Conversational Assessment of Neurocognitive Dysfunction among evaluators ranged from 0.61 to 0.79, all of which were significant (P < 0.001). The intraclass correlation coefficient was 0.64 (P < 0.001, 95% CI: 0.53-0.79 for agreement) and 0.67 (P < 0.001, 95% CI: 0.45-0.77 for consistency). The Conversational Assessment of Neurocognitive Dysfunction score of all evaluators was significantly associated with conventional cognitive tests like the Mini-Mental State Examination (P < 0.001). The findings suggested that the Conversational Assessment of Neurocognitive Dysfunction has moderate to good inter-rater reliability and high concurrent validity as a cognitive assessment tool, and it would be useful in clinical practice.


Dynamic contrast-enhanced MRI model selection for predicting tumor aggressiveness in papillary thyroid cancers.
The purpose of this study was to identify the optimal tracer kinetic model from T1 -weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data and evaluate whether parameters estimated from the optimal model predict tumor aggressiveness determined from histopathology in patients with papillary thyroid carcinoma (PTC) prior to surgery. In this prospective study, 18 PTC patients underwent pretreatment DCE-MRI on a 3 T MR scanner prior to thyroidectomy. This study was approved by the institutional review board and informed consent was obtained from all patients. The two-compartment exchange model, compartmental tissue uptake model, extended Tofts model (ETM) and standard Tofts model were compared on a voxel-wise basis to determine the optimal model using the corrected Akaike information criterion (AICc) for PTC. The optimal model is the one with the lowest AICc. Statistical analysis included paired and unpaired t-tests and a one-way analysis of variance. Bonferroni correction was applied for multiple comparisons. Receiver operating characteristic (ROC) curves were generated from the optimal model parameters to differentiate PTC with and without aggressive features, and AUCs were compared. ETM performed best with the lowest AICc and the highest Akaike weight (0.44) among the four models. ETM was preferred in 44% of all 3419 voxels. The ETM estimates of Ktrans in PTCs with the aggressive feature extrathyroidal extension (ETE) were significantly higher than those without ETE (0.78 ± 0.29 vs. 0.34 ± 0.18 min-1 , P = 0.005). From ROC analysis, cut-off values of Ktrans , ve and vp , which discriminated between PTCs with and without ETE, were determined at 0.45 min-1 , 0.28 and 0.014 respectively. The sensitivities and specificities were 86 and 82% (Ktrans ), 71 and 82% (ve ), and 86 and 55% (vp ), respectively. Their respective AUCs were 0.90, 0.71 and 0.71. We conclude that ETM Ktrans has shown potential to classify tumors with and without aggressive ETE in patients with PTC.


Revision shoulder arthroplasty with positive intraoperative cultures: the value of preoperative studies and intraoperative histology.
Currently, there are no reported results of patients without overt infection who had a positive intraoperative culture during revision shoulder arthroplasty. We therefore reviewed the intraoperative and preoperative investigations as well as the postoperative course of these patients who had positive intraoperative cultures. We reviewed the results of 75 shoulders without overt infection that underwent revision shoulder arthroplasty at our institution between January 1, 1974 and December 31, 2002 who had positive intraoperative cultures. Preoperatively, the results of 67 (93%) of 72 white-blood-cell counts were negative, 64 (91%) of 70 polymorphonuclear percentage distributions were negative, and 36 (86%) of 42 samples of erythrocyte sedimentation rate were negative. C-reactive protein concentration was measured in 16 patients, of which 12 (75%) had negative results. Results of intraoperative histologic evaluations were negative in 67 (92%) of 73 patients. The most common pathogen cultured was Propionibacterium acnes in 45 of 75, followed by Staphylococcus epidermidis in 10 of 75. Another operation was necessary in 10 (13%) of 75 shoulders to decrease pain or improve function. The mean time to re-revision was 2.5 years. The data from this study suggest that there are no good preoperative or intraoperative investigations to detect who will have a positive intraoperative culture at the time of revision shoulder arthroplasty.


Selective Hydrogenation of 5-Hydroxymethylfurfural to 1-Hydroxy-2,5-hexanedione by Biochar-Supported Ru Catalysts.
The development of sustainable and efficient catalysts -namely Ru supported on activated biochars- is carried out for the selective hydrogenation of 5-hydroxymethylfurfural (HMF) to 1-hydroxy-2,5-hexanedione (HHD). Activated biochars obtained from pyrolysis and steam-based physical activation of two different biomasses from animal (leather tannery waste; ALw ) and vegetal (hazelnut shells; AHSw ) origins show completely different chemical, textural, and morphological properties. Compared to ALw , after impregnation with 0.5 wt % Ru, AHSw , with inner micro-mesochannels and cavities and higher layer stacking disorder, leads to better trapping and anchoring of Ru nanoparticles on the catalyst and a suitable Ru single crystal dispersion. This leads to a highly active Ru/AHSw catalyst in the proposed reaction, giving more than 80 % selectivity to HHD and full HMF conversion at 100 °C with 30 bar H2 for 3 h. Ru/AHSw also shows promising performance compared to a commercial Ru/C catalyst.


Identification of olive (Olea europaea) seed and pulp proteins by nLC-MS/MS via combinatorial peptide ligand libraries.
Different types of extraction protocols are described for identifying proteins in seed and pulp of olive (Olea europea), by employing both conventional extraction methods and capture with ProteoMiner as well as with in house-made combinatorial peptide ligand libraries (HM-CPLLs) at pH 7.4 and at pH 2.2. Thanks to the use of CPLLs, able to dramatically amplify the signal of low-abundance species, a quite large number of compounds has been indeed identified: 61 in the seed (vs. only four reported in current literature) and 231 in the pulp (vs. 56 described so far), the deepest investigation up to the present of the olive proteome. In the seed, it highlights the presence of seed storage proteins, oleosins and histones. In the pulp, the allergenic thaumatin-like protein (Ole e 13) was confirmed, among the other 231, as the most abundant protein in the olive pulp. The present research has also been undertaken with the aim of identifying proteins in olive oil and ascertaining the relative contribution of seed and pulp proteins in their presence, if any, in oils.


Oocyst shedding in cats vaccinated by the nasal and rectal routes with crude rhoptry proteins of Toxoplasma gondii.
During this study, cats were immunized by the intranasal and rectal routes with crude rhoptry proteins of Toxoplasma gondii admixed with Quil-A. Twenty-five domestic short hair cats divided into five groups (n=5) were used during this evaluation: G1 and G3 cats received 200 μg of the rhoptry proteins with Quil-A (20 μg) by the intranasal and rectal routes, respectively; G2 and G4 cats received bovine serum albumin (BSA, 200 μg/dose) with Quil-A (20 μg); and G5 animals served as unvaccinated controls. All treatments were performed at days 0, 21, 42, and 63. The challenge was done with 800 cysts of the ME49 of T. gondii strain at day 70 (challenge day). The serum IgG, IgM, IgA, and fecal IgA antibody levels were evaluated by using the indirect enzyme-linked immunosorbent assay (ELISA). Some animals produced antibody levels beyond cut-off; however, two animals from G1 (OD(mean)=0.308, OD(cut-off)=0.200) and three from G3 (OD(mean)=0.254) demonstrated IgG levels on being challenged, with similar results occurring in two cats from G1 to IgM (OD(mean)=0.279, OD(cut-off)=0.200). Fecal IgA levels were detected in all G1 cats (OD(mean)=0.330, OD(cut-off)=0.065), and in one cat from G3 (OD(mean)=0.167). The serum and fecal humoral immune responses did not correlate with oocyst shedding. Oocyst shedding varied from 98.4% (G1), 87.5% (G2), 53.0% (G3), to 58% (G4), and was lower than that of G5 cats. The prepatent period of cats vaccinated intranasally (G1) was reduced from 6-9.6 to 2.8 days, suggesting protection of environmental contamination, considering cats as the primary source of contamination. The intranasally and rectally administered rhoptry vaccines were able to partially protect cats against T. gondii cysts on being challenged; however, the intranasal method of vaccination yielded better results relative to the rectal route.


Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells.
Diabetic nephropathy is characterised by mesangial extracellular matrix accumulation. Monocyte chemoattractant protein-1 (MCP-1), a chemokine promoting monocyte infiltration, is upregulated in the diabetic glomerulus. We performed in vitro and in vivo studies to examine whether MCP-1 may have prosclerotic actions in the setting of diabetes, presumably via its receptor, chemokine (C-C motif) receptor 2 (CCR2), which has been described in mesangial cells. Human mesangial cells were exposed to recombinant human (rh)-MCP-1 (100 ng/ml) for 12, 24 and 48 h and to rh-MCP-1 (10, 100 and 200 ng/ml) for 24 h. Fibronectin, collagen IV and transforming growth factor, beta 1 (TGF-beta1) protein levels were measured by ELISA and pericellular polymeric fibronectin levels by western blotting. The intracellular mechanisms were investigated using specific inhibitors for CCR2, nuclear factor kappa B (NF-kappaB), p38 mitogen-activated protein kinase and protein kinase C, and an anti-TGF-beta1 blocking antibody. In both non-diabetic and streptozotocin-induced diabetic mice that were deficient or not in MCP-1, glomerular fibronectin accumulation was examined by immunohistochemistry, while cortical Tgf-beta1 (also known as Tgfb1) and fibronectin mRNA and protein levels were examined by real-time PCR and western blotting. In mesangial cells, MCP-1 binding to CCR2 induced a 2.5-fold increase in fibronectin protein levels at 24 h followed by a rise in pericellular fibronectin, whereas no changes were seen in collagen IV production. MCP-1-induced fibronectin production was TGF-beta1- and NF-kappaB-dependent. In diabetic mice, loss of MCP-1 diminished glomerular fibronectin protein production and both renal cortical Tgf-beta1 and fibronectin mRNA and protein levels. Our in vitro and in vivo findings indicate a role for the MCP-1/CCR2 system in fibronectin deposition in the diabetic glomerulus, providing a new therapeutic target for diabetic nephropathy.


Concept analysis of uncertainty in people with mental disabilities.
This concept analysis clarified "uncertainty in people with mental disabilities". The research was conducted using Walker & Avant's conceptual analysis methodology. Uncertainty in people with mental disabilities showed the defining attributes of "ambiguity," "unpredictability," "distrust," and "lack of insight into illness," of which "distrust" and "lack of insight" were unique to people with mental disabilities. Accordingly, it was defined as a state in which it is difficult to determine the treatment's timing because (1) the disease process is often too ambiguous to make a decision; (2) abnormal behavior can recur at any time while the patients are under treatment and in recovery; and (3) patients struggle to accept the illness, tend to distrust healthcare professionals and family, and show lack of knowledge, making them miss their treatment's timing and even making the expectation for recovery vague. The attributes of uncertainty in people with mental disabilities identified in this study confirmed that mental health professionals should proactively intervene to treat patients at an appropriate time and continuously manage them to prevent recurrence. The study findings can be utilized in mental health research and in developing interventions to reduce uncertainty in people with mental disabilities, helping them recover and integrate into the community.


Demonstration of calcium-induced conformational change(s) in C-reactive protein by using monoclonal antibodies.
Three out of four anti-C-reactive protein monoclonal antibodies [HB3-2, (micro, k)], EA4-1 (gamma 2a, k) and FB2-1 (gamma 1, k) bind to C-reactive protein in the presence of 2.5 mM Ca2+ but not in the presence of 1.0 mM EDTA, indicating that the conformation of the antigenic determinant(s) recognized by these three antibodies is dependent upon Ca2+. This Ca2+-dependent binding can be inhibited by 1.0 mM phosphocholine, indicating that this antigenic determinant is at or near the phosphocholine-binding site of C-reactive protein. The binding of the fourth monoclonal antibody [HD2-4 (gamma 2-k)] is independent of the presence of Ca2+ and is not inhibited by phosphocholine. HB3-2 (micro, k) recognizes an antigenic determinant on the structurally related proteins, rabbit CRP and serum amyloid P.


Surfacing safety hazards using standardized operating room briefings and debriefings at a large regional medical center.
Briefings and debriefings, previously shown to be a practical and feasible strategy to improve interdisciplinary communication and teamwork in the operating room (OR), was then assessed as a strategy to prospectively surface clinical and operational defects in surgical care--and thereby prevent patient harm. A one-page, double-sided briefing and debriefing tool was used by surgical teams during cases at the William Beaumont Hospital Royal Oak (Royal Oak, Michigan) campus to surface clinical and operational defects during the study period (October 2006-May 2010). Defects were coded into six categories (with each category stratified by briefing or debriefing period) during the first six months, and refinement of coding resulted in expansion to 16 defect categories and no further stratification. A provider survey was used in January 2008 to interview a sample of 40 caregivers regarding the perceived effectiveness of the tool in surfacing defects. The teams identified a total of 6,202 defects--an average of 141 defects per month--during the entire study period. Of 2,760 defects identified during the six-defect coding period, 1,265 (46%) surfaced during briefings, and the remaining 1,495 (54%) during debriefings. Equipment (48%) and communication (31%) issues were most prominent. Of 3,442 defects identified during the 16-defect coding period, the most common were Central Processing Department (CPD) instrumentation (22%) and Communication/Safety (15%). Overall, 70 (87%) of the 80 responses were in agreement that briefings were effective for surfacing defects, as were 59 (76%) of the 78 responses for debriefings. Briefings and debriefings were a practical and effective strategy to surface potential surgical defects in the operating rooms of a large medical center.


Use of digirad 2020tc Imager, a multi-crystal scintillation camera with solid-state detectors in one case for the imaging of autografts of parathyroid glands.
99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy with Digirad 2020tc ImagerTM (2020tc), which was a multi-crystal scintillation camera with solid-state detectors was performed for patients with secondary hyperparathyroidism having autografts of parathyroid glands in the right arm. With the 2020tc camera, three abnormal accumulations were found in the right arm. The images obtained with this camera were superior in resolution to those obtained with a conventional NaI crystal gamma camera (ZLC7500, Siemens, Germany). The next day, resection of autografts of parathyroid glands was done. Four hyperplastic parathyroid glands were resected and all were hyperplastic in pathological findings.


Proneness to hypomania predicts EEG coherence between left motor cortex and left prefrontal cortex.
Previous research has demonstrated that hypomania is associated with approach motivation and activity in the left prefrontal cortex (PFC). Other research has linked left motor cortex excitability to approach motivation, suggesting the existence of connections between the motor cortex and PFC. The present research extends this work using unilateral hand contractions to manipulate contralateral cortical activity, and examining the relationship between motor cortex and PFC inter-electrode EEG coherence and hypomania. Within the right-hand contraction condition, hypomania related to greater connectivity between the left motor cortex and left PFC, relative to connectivity between the left motor cortex and right PFC. No relationships were found within the left-hand condition. The present research provides additional support for the role of the left PFC in bipolar disorder, as well as an important extension of research linking motor cortex excitability to emotion and approach motivation.


Immunochemical characterization of synthetic hexa-, octa- and decasaccharide conjugate vaccines for Vibrio cholerae O:1 serotype Ogawa with emphasis on antigenic density and chain length.
Cholera remains to be a global health problem without suitable vaccines for endemic control or outbreak relief. Here we describe a new parenteral vaccine based on neoglyco-conjugate of synthetic fragments of O-specific polysaccharide (O-SP) of Vibrio cholerae O1, serotype Ogawa. Hexa-, octa- and decasaccharides of the O-SP with carboxylic acid at the reducing end were chemically synthesized and conjugated to tetanus toxoid (TT). The conjugates prepared by a novel linking scheme consisted of 17-atom linker of hydrazide and alkyl bonds elicited robust serum IgG anti-LPS responses with vibriocidal activities in mice. There is a length dependence in immune response with decasaccharide conjugates elicited the highest anti-LPS IgG. There seems to be an indication that regardless of the carbohydrate chain length, a molar ratio of 230 ± 10 monosaccharide units per TT induced high antibody response. The conjugates also elicited cross-reactive antibodies to serotype Inaba. The formulation of the proposed cholera conjugate vaccine, similar to other licensed polysaccharide vaccine, is suitable for children immunization. A parenteral cholera vaccine could overcome the diminishing immunogenicity in most of oral vaccines due to the gastrointestinal complexity and environmental enteropathy in children living in impoverished environment and could be considered for global cholera immunization.


Psychological sequelae of medical and surgical abortion at 10-13 weeks gestation.
Although not much research comparing the emotional distress following medical and surgical abortion is available, few studies have compared psychological sequelae following both methods of abortion early in the first trimester of pregnancy. The aim of this review was to assess the psychological sequelae and emotional distress following medical and surgical abortion at 10-13 weeks gestation. Partially randomized patient preference trial in a Scottish Teaching Hospital was conducted. The hospital anxiety and depression scales were used to assess emotional distress. Anxiety levels were also assessed using visual analog scales while semantic differential rating scales were used to measure self-esteem. A total of 368 women were randomized, while 77 entered the preference cohort. There were no significant differences in hospital anxiety and depression scales scores for anxiety or depression between the groups. Visual analog scales showed higher anxiety levels in women randomized to surgery prior to abortion (P < 0.0001), while women randomized to surgical treatment were less anxious after abortion (P < 0.0001). Semantic differential rating scores showed a fall in self-esteem in the randomized medical group compared to those undergoing surgery (P = 0.02). Medical abortion at 10-13 weeks is effective and does not increase psychological morbidity compared to surgical vacuum aspiration and hence should be made available to all women undergoing abortion at these gestations.


Detecting clinically related content in online patient posts.
Patients with chronic health conditions use online health communities to seek support and information to help manage their condition. For clinically related topics, patients can benefit from getting opinions from clinical experts, and many are concerned about misinformation and biased information being spread online. However, a large volume of community posts makes it challenging for moderators and clinical experts, if there are any, to provide necessary information. Automatically identifying forum posts that need validated clinical resources can help online health communities efficiently manage content exchange. This automation can also assist patients in need of clinical expertise by getting proper help. We present our results on testing text classification models that efficiently and accurately identify community posts containing clinical topics. We annotated 1817 posts comprised of 4966 sentences of an existing online diabetes community. We found that our classifier performed the best (F-measure: 0.83, Precision: 0.79, Recall:0.86) when using Naïve Bayes algorithm, unigrams, bigrams, trigrams, and MetaMap Symantic Types. Training took 5 s. The classification process took a fraction of 1 s. We applied our classifier to another online diabetes community, and the results were: F-measure: 0.63, Precision: 0.57, Recall: 0.71. Our results show our model is feasible to scale to other forums on identifying posts containing clinical topic with common errors properly addressed.


An attempt to establish an Agrobacterium-mediated transient expression system in medicinal plants.
Genetic transformation has always been an important method for studying medical plant secondary metabolic regulation, among which stable transformation has a good reproducibility. However, it was time-consuming to obtain a stable transformed hairy root or transgenic plants, which was difficult to satisfy the great demand of researches on medical plant secondary metabolism-related genes. Moreover, Agrobacterium tumefaciens-mediated transient transformation has been extensively applied in studies of functional genes because of its simpleness, low cost, and short period. However, presently, researches on medical plant functional genes commonly used stable genetic transformation and some high-cost and high-difficulty transient transformation methods, such as gene gun and protoplast transformation. Thus, in this study, we selected the seedlings of Nicotiana benthamiana, Salvia miltiorrhiza, and Prunella vulgaris as the experimental material, with the methods of Agrobacterium tumefaciens injection, fast Agrobacterium-mediated seedling transformation (FAST), and FAST and mechanical damage. The results demonstrated that the injection transient transformation system of pCAMBIA1301 vector mediated by A. tumefaciens and the transient transformation of seedling system were not established in S. miltiorrhiza. In addition, the instantaneous transformation system of N. benthamiana and P. vulgaris seedlings was basically set up by FAST method. Besides, using the method of FAST and mechanical damage, the transient genetic transformation system of P. vulgaris seedlings was established for the first time. A. tumefaciens-mediated transient transformation of seedlings with pEAQ vectors provided an effective way and reference for the further study of functional genes of the medicinal plants N. benthamiana and P. vulgaris.


In vitro inhibition of HeLa cell nuclear ribonucleases by ADP-ribosylation.
Ribonuclease activity in HeLa cell nuclei is markedly inhibited by ADP-ribosylation following incubation of intact isolated nuclei with [14C]NAD. Time course experiments demonstrate that [14C] incorporation into proteins is accompanied by a 50% inhibition of ribonuclease activity on single-strand and double-strand polynucleotides. Inhibition does not occur when 3-aminobenzamide, a potent (ADP-ribose) polymerase inhibitor, is present. Two enzymatic activities that degrade double-strand polynucleotides have been purified and partially characterized. A relevant level of radioactivity resulting from [14C]NAD incubation of nuclei was associated to the purified enzyme. The RNase F1 component, which shows maximal activity on polyU-polyA is demonstrated to be the major ADP-ribose acceptor protein.


Neurokinin NK1- and NK3-immunoreactive neurons in serotonergic cell groups in the rat brain.
Interactions are known to occur in the brain between serotonin (5-HT) and substance P (SP). To investigate whether SP can directly influence serotonergic neurons, double immunohistochemical labelings were performed on rat brain sections with NK1 or NK3 affinity-purified antibodies and a 5-HT monoclonal antibody. It was found that the vast majority of serotonergic cell bodies do not colocalize NK1 or NK3 labeling. Only in the central linear nucleus and ventral part of the dorsal raphe nucleus were a few serotonergic neurons double-labeled for NK1 receptors (15 and 0.8% of serotonergic neurons, respectively). It is suggested that serotonergic neurons are not major direct targets for SP in the rat brain.


The role of regenerative therapy in the treatment of right ventricular failure: a literature review.
Right ventricular (RV) failure is a commonly encountered problem in patients with congenital heart disease but can also be a consequence of left ventricular disease, primary pulmonary hypertension, or RV-specific cardiomyopathies. Improved survival of the aforementioned pathologies has led to increasing numbers of patients suffering from RV dysfunction, making it a key contributor to morbidity and mortality in this population. Currently available therapies for heart failure were developed for the left ventricle (LV), and there is clear evidence that LV-specific strategies are insufficient or inadequate for the RV. New therapeutic strategies are needed to address this growing clinical problem, and stem cells show significant promise. However, to properly evaluate the prospects of a potential stem cell-based therapy for RV failure, one needs to understand the unique pathophysiology of RV dysfunction and carefully consider available data from animal models and human clinical trials. In this review, we provide a comprehensive overview of the molecular mechanisms involved in RV failure such as hypertrophy, fibrosis, inflammation, changes in energy metabolism, calcium handling, decreasing RV contractility, and apoptosis. We also summarize the available preclinical and clinical experience with RV-specific stem cell therapies, covering the broad spectrum of stem cell sources used to date. We describe two different scientific rationales for stem cell transplantation, one of which seeks to add contractile units to the failing myocardium, while the other aims to augment endogenous repair mechanisms and/or attenuate harmful remodeling. We emphasize the limitations and challenges of regenerative strategies, but also highlight the characteristics of the failing RV myocardium that make it a promising target for stem cell therapy.


Familial leukemia and inherited chromosomal aberration.
This communication contributes a family with 12 cases of cancer and two cases of leukemia. Chromosomal analysis was performed on three occasions, 9 months apart. In unaffected first-degree relatives, we have demonstrated high frequency of tetraradial figures: in parents, 1:243 mitoses, and in all first degree relatives, 1:328 mitoses. The rate of chromosomal breakage was moderately elevated in comparison with carefully matched controls, mainly in father (6.17), mother (4.01) and one sister (4.07). G-banded and C-banded karyotypes revealed no structural chromosomal abnormality in relatives of leukemic children. This family is one of five leukemic families investigated. Analogous methods of chromosomal analysis have been employed in all, but chromatid exchange figures and elevated chromosomal breakage were detected only in the presently reported pedigree. It has been postulated that in this family there exists a possible relation between increased incidence of chromatid exchange figures and increased tendency to leukemia.


Environmental noise degrades hippocampus-related learning and memory.
The neural mechanisms underlying the impacts of noise on nonauditory function, particularly learning and memory, remain largely unknown. Here, we demonstrate that rats exposed postnatally (between postnatal days 9 and 56) to structured noise delivered at a sound pressure level of ∼65 dB displayed significantly degraded hippocampus-related learning and memory abilities. Noise exposure also suppressed the induction of hippocampal long-term potentiation (LTP). In parallel, the total or phosphorylated levels of certain LTP-related key signaling molecules in the synapses of the hippocampus were down-regulated. However, no significant changes in stress-related processes were found for the noise-exposed rats. These results in a rodent model indicate that even moderate-level noise with little effect on stress status can substantially impair hippocampus-related learning and memory by altering the plasticity of synaptic transmission. They support the importance of more thoroughly defining the unappreciated hazards of moderately loud noise in modern human environments.


The role of cyclic 3',5'-AMP in the regulation of aminoacyl-tRNA synthetase activities in mouse uterus and liver following 17beta-oestradiol treatment. Activation of a phosphoaminoacyl-tRNA synthetase phosphatase by phosphorylation with cyclic 3',5'-AMP dependent protein kinase.
The changes in the activities of 17 aminoacyl-tRNA synthetases induced by phosphorylation [1] were reversed by the action of cyclic AMP in preparations from both uterus and liver. Cyclic AMP also inhibited the phosphorylation of aminoacyl-tRNA synthetase protein by endogenous non-cyclic AMP-dependent protein kinase and [gamma-32P]ATP. The effect was not due to a stimulation of phosphoaminoacyl-tRNA synthetase phosphatase or to an influence of cyclic AMP on aminoacyl-tRNA synthetases. The activity of phosphoaminoacyl-tRNA synthetase phosphatase was increased by treatment with endogenous cyclic AMP-dependent protein kinase, ATP and cyclic AMP. Affinity chromatography of the 32P-labeled phosphorylated phosphosynthetase phosphatase protein followed by gel electrophoresis showed that the activated phosphatase was phosphorylated. In the uterus, the changes in 17 aminoacyl-tRNA synthetase activities observed 5 min after dibutyryl cyclic AMP administration to ovariectomized mice were similar to those observed after 17beta-oestradiol treatment, whereas in the liver the changes in these activities were the opposite to those found after treatment with 17beta-oestradiol. A mechanism for the regulation of the 17 aminoacyl-tRNA synthetase activities is proposed, which suggests that the synthetase activities inhibited (group I) or stimulated (group II) by phosphorylation with a non-cyclic AMP-dependent aminoacyl-tRNA synthetase kinase are reactivated (group I) or inhibited (group II), respectively, by the action of a cyclic AMP-dependent phosphatase kinase through the increased activity of phosphorylated phosphoaminoacyl-tRNA synthetase phosphatase.


Sample preparation for gas chromatography with electron capture detection: determination of total and free thyroxin in serum.
Relatively clean gas chromatography with electron capture detection (GC-ECD) chromatograms are obtained for both total and free thyroxin (T4) in serum by improving sample preparation. This is based on establishing a sequence of steps that cumulatively overcome two classes of interference: those present in the initial sample and those introduced by the procedure. The main source for the latter contaminants is the derivatization step, a problem that was largely overcome by employing HPLC after this step. Also it is helpful to use ion-exchange columns early in the procedure under fast-flow conditions with intermediate flows of air to speed up and enhance their reliability. The work establishes some guidelines for future applications of GC-ECD to the determination of sub-nanogram analytes requiring derivatization, an area in which GC-ECD has been remiss in the past. As a side benefit, total T4 in serum is determined by HPLC for the first time with uv detection.


[Clinical efficacy of endoscopy in the treatment of lumbar disc herniation combined with posterior apophyseal ring separation].
To investigate the efficacy and safety of total spine endoscopy in the treatment of lumbar disc herniation combined with posterior apophyseal ring separation. From January 2015 to January 2018, a total of 21 patients with lumbar disc herniation complicated with posterior apophyseal ring separation were treated with total spine endoscopy via interlamina approach. There were 17 males and 4 females. The age ranged from 18 to 48 years old and the median age was 27 years old. All were single segment unilateral disc herniation, interlaminar approach was adopted, and the herniated disc was removed unilaterally at the symptomatic side under the microscope, and all or part of the broken bonewas removed. There were no complications such as incision infection, intervertebral space infection, intestinal injury, dural injury and cerebrospinal fluid leakage. The operation time ranged from 32 to 92 minutes and the median time was 57 minutes. Postoperative imaging examination showed that 2 patients had complete resection of osteotomy of posterior edge of vertebral body, 16 patients had partially resection and 3 patients had no resection. All intervertebral discs were completely removed. All 21 patients were followed up, and the duration ranged from 12 to 36 months, with a median of 15 months. The VAS of lumbago was 7.10±1.20 before surgery, 3.46±0.23 on the 3rd day after surgery, 2.36±0.19 on the 6th month after surgery; and the VAS of leg pain was 8.80±0.55 before surgery, 3.54±0.28 on the 3rd day after surgery, and 2.59±0.26 on the 6th month after surgery. The Oswestry Disability Index score was (69.71±9.37)% before surgery, (32.19±6.95)% on the 6th month after surgery, and (20.95± 6.16)% at the latest follow up. Onthe 1st year after operation, 16 patients got an excellent result, 4 good and 1 fair according to Macnab evaluation system. Total spine endoscopy via interlaminal approach can be used as an option in the treatment of lumbar disc herniation combined with vertebral posterior margin dissociation, which can reduce trauma and injury to the lumbar dorsal muscle and achieve similar decompression effect as open surgery. The long term efficacy needs to be further proved by prospective randomized controlled studies with larger sample size.


Hepatitis B surface antigen in urine of hemodialysis patients.
As part of an extensive epidemiological survey of chronic hemodialysis patients in Michigan, hepatitis B surface antigen (HBsAg) was identified in the sera of 79 of 701 (11%) patients. Of these patients, 59 were carriers of HBsAg for three or more months. Urine samples were collected from 36 of 39 HBsAg carriers having urinary output. Of these samples, 19 (52%) were positive for HBsAg by radioimmunoassay; this was confirmed by specific antibody neutralization. The HBsAg was not identified in the urine of seven hemodialysis patients who were lacking serum HBsAg or in urine samples from three HBsAg sero-carriers who had normal renal function. Patients undergoing maintenance hemodialysis appear to constitute a large reservoir of HBsAg chronic carriers. This study indicates that a minimum of 50% of persistent HBsAg carriers who are producing urine have detectable HBsAg in single, randomly timed, unconcentrated urine specimen. These data suggest that urine may represent a potential vehicle for transmission in nonparenterally acquired hepatitis B.


[Complications after stroke : Clinical challenges in stroke aftercare].
Besides the treatment of cardiovascular risk factors, the prevention and treatment of secondary complications is the main focus of outpatient poststroke care. The spectrum of noteworthy complications after a stroke changes during the course of the treatment and constitutes a specific challenge of outpatient poststroke care. This article provides references to the importance, management, diagnosis and treatment of the wide spectrum of nonvascular complications after stroke in the context of outpatient stroke aftercare. Poststroke depression (PSD), anxiety disorders and post-stroke fatigue are common complications after stroke, which require a timely diagnosis and treatment. Furthermore, the incidence of newly diagnosed dementia is 20% within the first 6 months after a stroke. Here too, therapeutic and preventive strategies especially in the early stage can delay the subsequent burden of the disease and the dependency on care. About half of every newly diagnosed epilepsy in patients older than 60 years is the result of a stroke. Falls and subsequent injuries are another important complication and a common reason for rehospitalization after a stroke. Although nearly 50% of patients suffer from chronic pain after a stroke this is often not sufficiently recognized. The wide spectrum of secondary complications after a stroke constitutes a complex, sustained and multidisciplinary challenge, which requires a cross-sectoral interaction of various and numerous actors in outpatient poststroke care.


Enhancement of tissue structure visualization in breast specimen radiography.
A simple technique is described for producing enhanced radiographs of excised breast specimens with clinical mammographic equipment. Radiographs of specimens immersed in water are compared to radiographs of the same specimen in air. Using this fluid-balancing technique, visualization of tissue structure is enhanced, particularly when negative-mode Xerox or film is used.


Comparison of duplex scanning and contrast arteriography: a community hospital experience.
In this study the results of ultrasonic scanning combined with spectral analysis (duplex scanning) are compared with contrast arteriograms. From an initial experience of more than 1000 duplex examinations 78 patients were identified who had independently interpreted carotid arteriograms within 1 month of their duplex study. Duplex and arteriogram reports were then compared on 156 individual carotid arteries. This study demonstrated that duplex scanning can identify hemodynamically significant carotid lesions with a high degree of accuracy. These lesions of greater than 50% diameter reduction were recognized with a sensitivity and specificity of 95%, compared with contrast radiography. We were also able to distinguish carotid occlusion with an accuracy of 93% (10 of 11). These results independently confirm the findings of other investigators and demonstrate the validity of duplex scanning in a community hospital as an accurate noninvasive examination in cerebral vascular disease.


Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis.
The stem cell pluripotency factor Oct4 serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment. Here, we show using Myh11-CreERT2 lineage-tracing with inducible SMC and pericyte (SMC-P) knockout of Oct4 that Oct4 regulates perivascular cell migration and recruitment during angiogenesis. Knockout of Oct4 in perivascular cells significantly impairs perivascular cell migration, increases perivascular cell death, delays endothelial cell migration, and promotes vascular leakage following corneal angiogenic stimulus. Knockout of Oct4 in perivascular cells also impairs perfusion recovery and decreases angiogenesis following hindlimb ischemia. Transcriptomic analyses demonstrate that expression of the migratory gene Slit3 is reduced following loss of Oct4 in cultured SMCs, and in Oct4-deficient perivascular cells in ischemic hindlimb muscle. Together, these results provide evidence that Oct4 plays an essential role within perivascular cells in injury- and hypoxia-induced angiogenesis.