The effect of hypochlorite on human erythrocytes pretreated with X-radiation.
Both hypochlorite and ionizing radiation induce oxidation processes of biomolecules. The effects are dependent to a large degree on the dose of the oxidizing agent. Previously we observed that split doses of gamma radiation caused lower hemolysis than the same but single doses. The critical factors influencing the occurrence of this effect were: the value of the first dose and the time between the doses. In this work we examined the effect of gamma radiation (40-400 Gy) on hemolysis of human erythrocytes induced by hypochlorite. Erythrocytes in PBS, hematocrit 2 %, were irradiated with doses of 40, 200 or 400 Gy. The dose-rate was 23.8 Gy/min. Cell suspensions were stirred during irradiation. After irradiation the erythrocytes were incubated for 1, 3 or 4 hours at room temperature and then hypochlorite was added to a 250 microM concentration. Control samples were erythrocytes treated only with NaOCl. The level of hemolysis was determined after NaOCl addition. Hemolysis of erythrocytes preirradiated with the dose of 400 Gy was lower than hemolysis of erythrocytes treated only with NaOCl. The effect was dependent on the time between the end of irradiation and the addition of NaOCl. In contrast, slightly higher hemolysis was observed for erythrocytes preirradiated with lower (40 or 200 Gy) doses of radiation. The observed effect is similar to that obtained for radiation-induced hemolysis. It suggests that ionizing radiation may induce structural and/or functional changes in erythrocytes, which make the cell more resistant to further oxidative damage.


Characteristics of chronic wounds that itch.
This study was designed to explore characteristics of chronic wounds that present with wound-related itch. Although wound-related itch is recognized clinically, little is known about the phenomenon. Recent scientific advances have enabled the study of itch physiology, yet the clinical problem is not well described in the literature. The study was observational, descriptive. Persons (N = 200) with wounds being followed up at a hospital-affiliated wound care center were interviewed and assessed. Instruments included a health history tool, Paul-Pieper Itching Questionnaire, Bates-Jensen Wound Assessment Tool, and 10-g monofilament for assessment of sensation in the area of the wound. Participants were aged 21 to 98 years (mean, 66.82 [SD, 14.02] years); 56% of the participants were men, and 85% were white. One-fourth (56/200) of the participants reported wound-related itch. Wounds that itched were generally larger (t77.74 = -3.27; P = .002; d = 0.63; 95% confidence interval [CI], -1.01 to -0.25), had more tissue edema (t88.38 = -2.19; P = .031; 95% CI, -0.93 to -0.47), and demonstrated more granulation tissue in the wound base (t98.71 = 2.03; P = .045; 95% CI, 0.01-0.87), compared with wounds without itch. Greater itch was associated with wounds that had a moderate amount of exudate (P = .02) or necrotic tissue in the base. Wound itch was present in more severe wounds as evidenced by larger size, more tissue edema, and necrotic tissue. Understanding wound itch could promote wound healing and improve quality of life for persons with chronic wounds.


A novel apoptotic pathway of 3'-Ethynylcytidine(ECyd) involving the inhibition of RNA synthesis--the possibility of RNase L activated pathway as a target of ECyd.
RNase L functions as a tumor suppressor protein due to its role in apoptosis during viral infections and various agents treatment. RNase L-mediated apoptosis is accompanied by cytochrome c release from mitochondria and requires caspase-3 activity. It was reported that RNase L is involved in JNK activation during viral infections, and that JNK is essential for apoptosis in response to RNase L activation. However, the proximal signals of RNase L that trigger JNK activation have not as yet been identified, and it is possible that the interactions between RNase L and other proteins play an important role in the RNase L-JNK apoptotic signal pathway. To investigate this hypothesis, we attempted to identify the proteins associated with RNase L using coimmunoprecipitation. In this study, we found that RNase L was associated with other proteins. Here we identified the protein X by LC-MS/MS analysis. We demonstrated that this association was increased in the presence of activated RNase L. Moreover, Protein X was phosphorylated during the activation of RNase L by treatment with cytotoxic agent, ECyd, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine and 2-5A. To reveal the role of protein X in RNase L-mediated apoptosis, we decreased the level of protein X by a small interfering RNA (siRNA). As a result, protein X deficient cells became resistant to the apoptosis mediated by RNase L, suggesting that protein X is related to RNase L-mediated apoptosis following JNK activation. Therefore, in this study, we report the identification of a novel protein, protein X that transduces between RNase L and JNK signals.


Effect of daylight on regrowth of bacteria in anaerobically digested sludge.
This study investigated the regrowth of total coliform, Salmonella, and Clostridium perfringens in anaerobically digested sludge after centrifuge dewatering in the presence and absence of daylight. Sludge cake and centrate samples were collected from a treatment plant, and half of the samples was stored in daylight and the other half was stored in dark for three weeks. The bacteria levels in the cake and centrate samples were measured periodically throughout the storage period, and all three bacteria showed substantial regrowth. Presence of daylight increased the regrowth of Salmonella both in sludge cake and centrate, and increased the regrowth of total coliform in centrate. Salmonella exhibited the highest regrowth rate in cake among the three bacteria tested both in the presence and absence of light. Daylight did not appear to have a significant impact on the regrowth of Clostridium perfringens in cake and centrate, and on the regrowth of total coliform in cake. This might, however, be caused by the masking effect of the higher initial numbers of these bacteria in the samples. There is need for more research to thoroughly understand the effect of daylight on the regrowth of sludge bacteria.


The anticancer activity of 3- and 10-bromofascaplysins is mediated by caspase-8, -9, -3-dependent apoptosis.
3- and 10-Bromofascaplysins was previously found to possess cytotoxic activity. In this study, we investigated their cancer preventive and proapoptotic properties. These effects were tested on mouse skin epidermal JB6 P(+) Cl41 cell line, its stable transfectants, and human tumor HL-60, THP-1, SNU-C4, SK-MEL-28, DLD-1, MDA-MB-231, and HeLa cells using a variety of assessments, including a cell viability (MTS) assay, flow cytometry, anchorage-independent soft agar assay, luciferase assay, mitochondrial permeability assay, and Western blotting. 3- and 10-Bromofascaplysins were effective at submicromolar concentrations as the anticancer agents, which exerted their action, at least in part, through the induction of caspase-8, -9, -3-dependent apoptosis.


Optimization of DHEA Extraction from Sweet Potato Pomace by Ultrasonic-Microwave Synergistic Employing Response Surface Methodology.
Background: A lot of sweet potato residues (SPR) were discarded and wasted. Objective: To make full use of the SPR. Methods: Ultrasonic microwave synergistic (UMS) extraction method was used to extract dehydroepiandrosterone (DHEA) in SPR. The extraction conditions were optimized by response surface methodology based on single factors. Results: The optimum extraction conditions were 1:25 (solid-liquid ratio), 300 W (microwave power), 30 min (extraction time), and 30°C (extraction temperature). The extraction yield of DHEA from SPR reached 117.25 μg/100 g. Conclusions: The advantage of UMS extraction technology is to make full use of the synergistic effect of ultrasound and microwave to improve extraction efficiency. Highlights: The technology provides an effective way to improve the DHEA extraction yield from the SPR in industrial production.


Pollen Serum Specific IgE Sensitization in Respiratory Allergic Patients in Jakarta, Indonesia.
pollens from trees or grasses in Indonesia have a perennial distribution due to the tropical climate. However, pollen allergy has not been well studied. This study aimed to evaluate the profile of pollen IgE sensitization in respiratory allergic patients in Jakarta. this was a cross-sectional study in patients with a history of respiratory allergy in Jakarta, Indonesia between September and December 2016. Adult asthmatic patients aged 19-60 years were invited to undergo serum specific IgE testing at the Allergy and Immunology Clinic, Cipto Mangunkusumo Hospital, Jakarta. Patients were included if they showed at least one positive skin prick test with environmental allergens. Quantitative determination of specific IgE in serum was carried out by multiple allergosorbent (MAST) assays (Polycheck Allergy®, Biocheck GmbH, Munster, Germany). Serum specific IgE levels of more than 0.35 kU/L or Class 1 was considered positive. a total of 106 cases were eligible for analysis; 81 (76.4%) were women. Patients' mean age was 38.8+12.1 (range 19-59) years old. 59.4% of patients have both asthma and allergic rhinitis. There are 9 (8.5%) patients positive for IgE-pollen sensitization; 8 among them showed sensitization to at least 2 pollens. Sensitivity to goosefoot pollen is the highest (5.7%), followed by rye pollen (4.7%), plantain pollen (4.7%), wall pellitory pollen (4.7%), and Bermuda grass pollen (3.8%). although most pollens tested are not originated from native plants to Indonesia, a small number of patients showed specific IgE-sensitizations. Allergic persons planning to travel to the endemic areas of the relevant pollen should be advised. A panel of pollen allergens from local plants is highly desired.


The cation-controlled and hydrogen bond-mediated shear-thickening behaviour of a tree-fern isolated polysaccharide.
The shear-thickening rheological behaviour (between 5 and 20s(-1)) of a 5% (w/w) viscoelastic gum extracted from the fronds of the native New Zealand black tree fern or mamaku in Māori was further explored by manipulating the salt content. The freeze-dried mamaku gum contained a high mineral content and sugars which upon removal via dialysis, resulted in the loss of shear thickening. However, this loss was reversible by the addition of salts to the dialysed dispersion. The mechanism of shear-thickening behaviour was therefore hypothesised to be due to shear-induced transition of intra- to intermolecular hydrogen bonding, promoted by the screening effect of cations. Mono-, di- and trivalent salts, i.e. Na(+), K(+), N(CH3)4(+), Ca(2+), Mg(2+), Al(3+) and La(3+) at concentrations between 0.001 and 1.0M were tested to support the hypothesis as well as to demonstrate the sensitivity of the biopolymer to cation valency and concentrations. The cation valency and concentration were crucial factors in determining: (i) zero-shear viscosity, (ii) critical shear rate, γ˙c (or shear rate at the onset of shear-thickening) and (iii) the extent of shear-thickening of the solution. For mono- and divalent cations these parameters were similar at equivalent ionic strengths and fairly independent of the cation type. Trivalent cations (La(3+)) however caused precipitation of the gum in the concentration range of 0.005-0.05 M but clear dispersions were obtained above 0.05 M.


Derivation of dendritic cells from myeloid and lymphoid precursors.
The antigen presenting dendritic cells (DC) found in mouse and human lymphoid tissues are heterogeneous. Several subsets of mature DC have been described and these may correspond to distinct lineages. In this review, we present evidence obtained from a series of studies on the lineage origin of DC. This evidence points to the existence of at least three pathways for DC development, namely one from myeloid progenitors, a second from lymphoid progenitors and the third for Langerhans cells from precursors whose relationship to myeloid or lymphoid cell types is not yet clearly defined.


Transient elastography with a new probe for obese patients for non-invasive staging of non-alcoholic steatohepatitis.
Transient elastography (TE) has shown promising results for the staging of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) with the limitation that 25% of obese patients cannot be examined with the standard TE probe. The aim of this study was to evaluate a new XL probe for obese patients for the staging of liver fibrosis in NAFLD/NASH. Fifty patients with NAFLD/NASH and histological assessment of liver fibrosis were included in the study. All patients received TE with the standard probe (M probe) and the new XL probe, and the results were compared with liver histology. The diagnostic accuracy expressed as the area under the ROC curve for TE measurements with the M probe and the XL probe was 0.80 and 0.82 for the diagnosis of significant fibrosis, and 0.91 and 0.95 for the diagnosis of liver cirrhosis, respectively. Eighty-three percent of the patients who could not be measured with the M probe could be measured using the XL probe. Transient elastography using the XL probe for obese patients can be performed with comparable diagnostic accuracy to the standard probe and enables the examination of significantly more obese patients.


Palladium-catalyzed denitrogenation reaction of 1,2,3-benzotriazin-4(3H)-ones incorporating isocyanides.
1,2,3-Benzotriazin-4(3H)-ones and 1,2,3,4-benzothiatriazine 1,1(2H)-dioxide reacted with isocyanides in the presence of a palladium catalyst to give 3-(imino)isoindolin-1-ones and 3-(imino)thiaisoindoline 1,1-dioxides, respectively, in high yield. An intermediate azapalladacycle was generated through denitrogenation of the triazine moiety, and an isocyanide was incorporated therein.


Radiation-induced mammary carcinogenesis in rodent models: what's different from chemical carcinogenesis?
Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models.JRRS Incentive Award in 2009.


Survival Trends of Patients With Surgically Resected Gastric Cardia Cancer From 1988 to 2015: A Population-based Study in the United States.
The incidence of gastric cardia cancer (GCC) patients has been increasing, while the survival trends of GCC patients over time remains unclear. Thus, the aim of our study was to determine the survival trends of GCC patients over time using a population-based data in the United States. A total of 9044 surgically resected GCC patients during 1988 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were identified. The survival probabilities were calculated by Kaplan-Meier method and the different survival probabilities between groups were examined by log-rank test. The median overall survival time was 27 (interquartile range, 12 to 99) months, and the median disease-specific survival time was 32 (interquartile range, 13 to 320) months for GCC patients. There was a statistically significant increase in median overall survival time (17 to 46 mo; P<0.001) and disease-specific survival time (19 to 67 mo; P<0.001) from 1988 to 1997 to 2008 to 2015. More GCC patients were diagnosed at an early stage in recent years. Meanwhile, adequate lymph nodes examined (eLNs) were obtained in more GCC patients during surgery. Also, the proportion of GCC patients who received chemoradiotherapy increased significantly. Moreover, early diagnosis, adequate eLNs, and chemoradiotherapy were associated with mortality. The survival rates of surgically resected GCC patients had a significant improvement from 1988 to 1997 to 2008 to 2015 in the United States, which might relate to the early discovery of GCC, greater utilization of adequate eLNs, and chemoradiotherapy.


Racist organ donors and saving lives.
This paper considers what should be done about offers of organs for transplant that come with racist strings attached. Saving lives or improving their quality seem powerful reasons to accept the offer. Fairness, justice, and rejecting racism seem like powerful reasons against. This paper argues that conditional allocation should occur when it would provide access to organs for at least one person without costing others their access to organs. The bulk of the paper concentrates on defending this claim against these objections: (i) that the good that might come about through conditional allocation does so through wrongful complicity in the racist's wrongdoing; (ii) that conditional allocation symbolizes support for racism; and (iii) that conditional allocation is unjust or unfair and is, for that reason, impermissible. The final section, on conditional allocation as a policy, considers the speculative possibility that conditional allocation would reduce access to organs for some, but it argues that, even then, conditional allocation could be justified.


The Hierarchical Organization of Cognitive Abilities: Restoring General Intelligence Through the Use of Linear Structural Relations (LISREL).
While considerable support has been obtained for the distinction, due to Cattell and Horn, between the broad factors fluid intelligence (Gf) and crystallized intelligence (Gc), there is also some evidence that Gf is equivalent to the factor of general intelligence (g). This hypothesis is investigated by using LISREL to specify higher-order models in reanalyses of three sets of psychometric data from subjects 11, 13, and 15 years old, respectively. The three studies unanimously showed Gf to be equivalent with a general factor. The discussion is centered upon the use of LISREL and the differences in results between the exploratory and confirmatory approaches to factor analysis.


[Sirenomelia. Review of nosology and a case report].
We report a case of sirenomelus observed at 21 weeks amenorrhoea with oligoamnios. This syndrome results from an anomaly during the fourth week of gestation perturbing development of the lower limbs and the pelvis. Normal differentiation of the sexual organs, urinary tract and terminal intestine is interrupted. Recent progress in embryopathology has led to identification of a caudal regression syndrome but the aetiology remains unknown as is the nature of the relationship with VATER association.


The influence of the sympathetic impulse pattern on contractile responses of rat mesenteric arteries and veins.
Contractile responses to electrical field stimulation of excised small mesenteric arteries and veins of the rat were compared when stimuli were delivered in irregular bursts or at regular intervals. Spontaneously occurring skin vasoconstrictor impulses in a few-unit median nerve recording in man were stored on tape and used to trigger a stimulator. Two irregular stimulation sequences at average frequencies of 1.6 and 1.8 Hz, respectively, were used. In the arteries, average contractile responses were significantly greater at an irregular than at an even stimulation frequency, but in the veins, similar degrees of contraction were obtained with the two modes of stimulation. The frequency-response relationships to continuous regular stimulation showed the artery to respond less than the vein at low frequencies. This apparently explains the differences in behaviour between the vessels to irregular stimulation. The results show that not only the number of impulses, but also their pattern of occurrence, may influence the degree of vasoconstriction. Thus, the normal irregular sympathetic discharge pattern in itself has a bearing on the physiology of neuro-effector control mechanisms.


Relationship between histology and aetiological factors in primary liver cancer.
A review of 205 primary hepatic cancers from different geographic areas reveals that HCC which forms the vast majority (86%) of these, commonly presents as the trabecular variety (76%). The compact and pseudoglandular forms are rare (18% and 6%). Relatively fewer cases of undifferentiated cancer, hepatoblastoma and cholangiocarcinoma are encountered. HCC is often associated with the presence of hepatitis B virus surface antigen (HBsAg) in the liver. This is particularly true of the trabecular variety (81%). A proportion of the compact variety as well as undifferentiated cancers do not appear to be related to HBV infection. Cholangio carcinomas are considered to be related to infection by liver flukes. Hepatoblastomas occur in infancy and childhood and show no known aetiologic association. Aflatoxin may be aetiologically related to same cases of HCC. Continued use of oral contraceptives can occasionally induce HCC.


Flow cytometric DNA analysis of wheat-rye addition lines.
The nuclear DNA content of the 7 wheat-rye chromosome addition lines were determined by flow cytometry. The nuclear DNA content of each line was compared to the original wheat parental line. From this information, the amount of DNA per rye chromosome was calculated. The DNA per chromosome ranged from 0.8 picograms (pg) in chromosome 3R to 1.4 pg in chromosome 7R. Flow cytometry was proven to be a rapid and reliable technique for the evaluation of aneuploid plant populations. Flow cytometry has the potential to allow for more rapid screening of aneuploid and euploid cytological stocks than conventional cytogenetic techniques.


EGF receptor targeted lipo-oligocation polyplexes for antitumoral siRNA and miRNA delivery.
Antitumoral siRNA and miRNA delivery was demonstrated by epidermal growth factor receptor (EGFR) targeted oligoaminoamide polyplexes. For this purpose, the T-shaped lipo-oligomer 454 was used to complex RNA into a core polyplex, which was subsequently functionalized with the targeting peptide ligand GE11 via a polyethylene glycol (PEG) linker. To this end, free cysteines on the surface of 454 polyplex were coupled with a maleimide-PEG-GE11 reagent (Mal-GE11). Resulting particles with sizes of 120-150 nm showed receptor-mediated uptake into EGFR-positive T24 bladder cancer cells, MDA-MB 231 breast cancer cells and Huh7 liver cancer cells. Furthermore, these formulations led to ligand-dependent gene silencing. RNA interference (RNAi) triggered antitumoral effects were observed for two different therapeutic RNAs, a miRNA-200c mimic or EG5 siRNA. Using polyplexes modified with a ratio of 0.8 molar equivalents of Mal-GE11, treatment of T24 or MDA-MB 231 cancer cells with miR-200c led to the expected decreased proliferation and migration, changes in cell cycle and enhanced sensitivity towards doxorubicin. Delivery of EG5 siRNA into Huh7 cells resulted in antitumoral activity with G2/M arrest, triggered by loss of mitotic spindle separation and formation of mono-astral spindles. These findings demonstrate the potential of GE11 ligand-containing RNAi polyplexes for cancer treatment.


Magnetic resonance imaging of muscle tears.
Magnetic resonance scans were obtained on 17 patients with acute, subacute, or chronic muscle tears. These patients presented with complaints of persistent pain or a palpable mass. Magnetic resonance findings were characterized according to alterations in muscle shape and the presence of abnormal high signal within the injured muscle. These areas of high signal were noted on both T1-weighted and T2-weighted scans and were presumed to represent areas of intramuscular hemorrhage.


Biomarker strategies to predict need for renal replacement therapy in acute kidney injury.
The early detection and diagnosis of acute kidney injury (AKI) with the standardization of novel kidney-injury-specific biomarkers is one of the highest research priorities in nephrology. Accordingly, the majority of studies of novel AKI biomarkers have focused on the early diagnosis of AKI using serum creatinine-based definitions as the gold standard. However, another potential application of kidney-injury-specific biomarkers is for guiding decisions on when to initiate renal replacement therapy (RRT). The purpose of this review is to summarize recent findings concerning some of the more promising AKI biomarkers on their capacity, either alone or integrated with traditional surrogate measures of kidney injury, for early prediction of whether patients will develop severe AKI requiring RRT. Some studies that have examined neutrophil gelatinase-associated lipocalin, cystatin-C, N-acetyl-β-d-glucosaminidase, kidney injury molecule-1, and α(1)-microglobulin, among others, have suggested that these novel biomarkers have the potential to distinguish patients in whom RRT will be needed. This would imply that these biomarkers may be integrated into clinical decision algorithms and could synergistically improve our current ability to predict worsening AKI and need for RRT. However, published studies have many recognized limitations, which preclude our ability to adapt their findings into clinical practice today. While currently available data are not sufficient to conclude that biomarkers should be used routinely for clinical decision making for RRT initiation, additional data may in the future significantly modify the clinical variability for initiation of RRT, and potentially translate into improved outcomes and cost-effectiveness. Finally, we propose a potential approach to future biomarker strategies for RRT initiation, integrating these biomarkers with "traditional" clinical factors.


BAP1 facilitates diagnostic objectivity, classification, and prognostication in malignant pleural mesothelioma.
BRCA-associated protein 1 (BAP1) has emerged as a promising biomarker for malignant pleural mesothelioma (MPM). Loss of BAP1 expression can occur by a variety of mechanisms, but reports on incidence are variable and the clinical significance is unclear. In order to investigate the diagnostic and prognostic significance of BAP1, we constructed a tissue microarray consisting of 111 MPM cases and performed BAP1 immunohistochemistry. BAP1 was lost in 77% of epithelioid cases (n=58) but was retained in all sarcomatoid cases (n=10); 49% of biphasic cases showed loss (n=43), and BAP1-negative cases demonstrated loss of staining in both the epithelioid and sarcomatoid components. All non-neoplastic mesothelial tissues (n=20) retained BAP1, resulting in a sensitivity, specificity, positive predictive value, and negative predictive value of 61%, 100%, 100%, and 32%, respectively. Moreover, BAP1 expression in spindled mesothelium enabled discrimination of reactive and malignant cells, thus providing a more objective means of distinguishing epithelioid from biphasic morphology compared to histology alone. Nonetheless, BAP1 staining was patchy in some benign mesothelial neoplasms, which raises concern for using BAP1 in small biopsies. Kaplan-Meier analysis demonstrated a significant improvement in overall survival with BAP1 loss, but this did not reach significance in multivariate analysis accounting for histologic subtype. When only epithelioid cases were analyzed there was a trend toward increased survival, but it did not reach significance. We conclude that BAP1 loss is frequent in epithelioid MPM, which is in turn associated with improved survival, and that it can have additional clinical significance by facilitating histologic classification.


Spatial clustering in childhood diabetes: evidence of an environmental cause.
If environmental factors are important in the aetiology of insulin-dependent (Type 1) diabetes mellitus, primary schooling would be more likely to be shared by cases in an epidemic year compared with controls. We have examined a case control study, comparing primary schools attended. Cases were identified from an established register with known accurate ascertainment and compared with controls taken from a central register of all children and date of birth, sex, and race matched. Parents were asked to complete a structured questionnaire which included questions relating to the child's schooling. There were 187 cases with at least a first matched control. Thirty-two of the cases attended the same nursery or primary school as another case, 18 in the same academic year, compared with 12 controls attending the same school as another control (99% confidence interval (CI) for the difference between proportions 0.0572 - 0.107). Of these cases diagnosed in 1986, 9 attended the same school as another case. Spatial clustering occurs in Type 1 diabetes. This is further evidence of an environmental factor contributing to the genesis of the disease.


Design and synthesis of a series of 6-substituted-2-pyridinylmethylamine derivatives as novel, high-affinity, selective agonists at 5-HT1A receptors.
A search for novel, selective agonists with high intrinsic activity at the 5-HT1A subtype of serotonin (5-HT) receptors was undertaken. Mechanistic and thermodynamic considerations led to the design of 6-substituted-2-pyridinylmethylamine as a potential 5-HT1A pharmacophore. Various adducts derived from the 6-substituted-2-pyridinylmethylamine moiety were tested for their affinity at 5-HT1A, alpha1-adrenergic, and D2-dopaminergic receptors. Compounds with high affinity for 5-HT1A receptors (pKi >/= 8) were examined for agonist properties by measuring their ability to inhibit forskolin-stimulated cAMP production in HA7 cells (i.e., HeLa cells permanently transfected with the h5-HT1A receptor gene and expressing the h5-HT1A receptor protein). Several compounds of the type aryl¿4-[(6-substituted-pyridin-2-ylmethylamino)methyl]piperidin -1-yl¿ methanone had nanomolar affinity for 5-HT1A binding sites and were more than 500-fold selective with respect to alpha1 and D2 sites. Importantly, their 5-HT1A agonist properties were demonstrated in HA7 cells where they behaved as potent inhibitors of cAMP accumulation. In particular, (3, 4-dichlorophenyl)¿4-[(6-oxazol-5-ylpyridin-2-ylmethylamin o)methyl]pip eridin-1-yl¿methanone (70) and (3, 4-dichlorophenyl)¿4-[(6-azetidinopyridin-2-ylmethylamino)met hyl]piper idin-1-yl¿methanone (36) appeared to be more potent than, and at least as efficacious as, the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT. SAR studies revealed that the pyridine nitrogen atom and the nature and the position of the substituents on the pyridine ring were critically involved in the ability of the compounds to recognize and activate 5-HT1A receptors. Structural modifications of the nonpharmacophoric part of the molecule showed, however, that the entire structure was required for affinity at 5-HT1A binding sites.


Interaction of Na+ and K+ transport with aerobic energy metabolism in slices of Morris hepatoma 3924A.
Addition of increasing concentrations of glucose to slices of Morris hepatoma 3924A greatly stimulated aerobic lactate production and reduced respiration by 20%. Neither the adenine nucleotide content of the slices nor the calculated rate of adenosine 5'-triphosphate synthesis was altered. Ouabain reduced the rate of O2 uptake (by 20 to 25%) and of aerobic lactate production (by 25 to 50%) without affecting adenine nucleotide contents. The reduction by ouabain of the calculated rate of adenosine 5'-triphosphate synthesis was similar whether the slices were utilizing only endogenous substrate or exogenous glucose also. Raising the medium K+ concentration (and correspondingly reducing Na+) partially overcame the inhibition of ion transport by ouabain and partially restored the rates of respiration and aerobic lactate production toward control levels. Electron microscopic observations of mitochondria within the slices incubated under different conditions showed variations in configuration between "orthodox," "condensed" and degenerating forms. Slices preincubated at 1 degrees showed mitochondria in the condensed form: they were restored to the orthodox configuration during incubation at 38 degrees in oxygenated medium. Oligomycin and glucose enhanced the transition, but ouabain reduced the number of mitochondria undergoing the change. The results suggest that in hepatoma 3924A utilization of adenosine 5'-triphosphate by ion transport exerts a simultaneous control of both respiration and aerobic glycolysis, which is presumably mediated by alterations in the availability of adenosine 5-diphosphate. The mitochondria undergo conformational transitions under conditions likely to affect local availability of adenosine 5'-diphosphate within cell compartments, but the transitions are not all externally added adenosine diphosphate on isolated mitochondria.


[Development of anti-Alzheimer's disease drug based on beta-amyloid hypothesis].
Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. However, these drugs do not cure Alzheimer's, but are only symptomatic treatments. Therefore, a cure for Alzheimer's disease is truly needed. Alzheimer's disease is a progressive neurodegenerative disease characterized by cognitive deficits. The cause of the disease is not well understood, but research indicates that the aggregation of beta-amyloid is the fundamental cause. This theory suggests that beta-amyloid aggregation causes neurotoxicity. Therefore, development of the next anti-Alzheimer's disease drug is based on the beta-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.


Trends in cardiac catheterization laboratories in the United States.
The Society for Cardiac Angiography and Interventions has periodically published a Directory of Cardiac Catheterization Laboratories in the United States. All known catheterization laboratories are surveyed and certain operational characteristics are queried. These surveys, in 1983, 1987, 1993, 1995 and 1998, have demonstrated a 2.5 fold increase in cardiac catheterization laboratories since 1983, corresponding increases in numbers of physicians that perform procedures, and in the numbers of procedures performed, reflecting advances in cardiovascular medicine and technology. These surveys have also documented the evolution of interventional techniques, and a shift away from film based imaging, to digitally based methods. These data provide a substrate for consideration of national cardiovascular objectives and planning of future resource allocation by cardiovascular physicians and their colleagues.


[A rare variant of enterocele entrapment in the abdominal cavity of a woman].
Abdominal enterocele is a result of entering abdominal organs into peritoneal pockets and folds through the holes in mesenterium or into the adjoining cavities through defects in their walls. Enteroceles are localized at the sites where one segment of the gastrointestinal tract passes into another, in a pocket behind the cecum and sigmoid, between mesenteric layers of small intestine and colon, in the holes of mesenterium of vermiform appendage, gastrocolic and falciform ligaments, pockets and holes of broad ligament of the uterine, omental foramen, rectouterine excavation, and diaphragmal defects. We observed a 26 year old woman with enterocele entrapment in the abdominal cavity complicated by necrosis of part of the small intestine.


Lithocarpus polystachyus Rehd. leaves aqueous extract protects against hydrogen peroxide‑induced SH-SY5Y cells injury through activation of Sirt3 signaling pathway.
Lithocarpus polystachyus Rehd. (sweet tea; ST) leaves is a type of Chinese folkloric medicine from southern China. The purpose of the present study was to explore the neuroprotective effect of ST, and to explore its underlying mechanisms in hydrogen peroxide (H2O2)‑induced neuronal cell injury in cultured human neuroblastoma. H2O2 was used as oxidant inducer and human SH‑SY5Y neuroblastoma cells were treated with various concentrations of ST. Cell viability and cell death were detected using MTT and LDH assays, respectively. Additionally, the production of intracellular and mitochondrial reactive oxygen species (ROS) were determined by 2',7'‑dichlorodihydrofluorescein diacetate (DCFH‑DA) and MitoSOX Red, respectively. The production of malondialdehyde (MDA), reduced glutathione (GSH) level, glutathione peroxidase (GSH‑Px), superoxide dismutase (SOD) activities, and NAD+/NADH ratio were confirmed using relevant kits. The expression of adenosine monophosphate‑activated protein kinase (AMPK), peroxisome proliferator‑activated receptor coactivator (PGC)‑1α, Sirt3, isocitrate dehydrogenase (IDH)2, forkhead boxO3a (Foxo3a), and SOD2 were analyzed by western blot analysis. It was demonstrated that pre‑treatment with ST enhanced cell viability and repressed cell death, and it also reduced intracellular and mitochondrial ROS accumulation. Additionally, ST attenuated MDA production and enhanced GSH level, GSH‑Px and SOD activities. Furthermore, ST not only increased NAD+/NADH ratio, but also inhibited the decrease of AMPK, PGC‑1α, Sirt3, IDH2, Foxo3a, and SOD2. The present study revealed that ST exerts protective effects against oxidative stress‑induced SH‑SY5Y cells injury, and the underlying mechanisms are, at least partly, associated with its antioxidant capacity and function through mitochondrial Sirt3 signaling pathway.


Total, ultrafiltrable, dialysable and ionised calcium measurements in randomly selected samples compared with clinical diagnoses.
Total, ultrafiltrable (Worthington 'Ultrafree'), dialysable and ionised (Orion SS-20) calcium levels were measured in 110 serum samples selected randomly from patients for whom total calcium was ordered as a routine test. The available medical records were used to categorize most of the 86 patients as a guide to determining if the calcium results were appropriate to the diagnosis. Total calcium measurement was precise and reliable but was affected by the albumin level. Dialysable calcium measurement was good for diagnostic purposes and was not affected by albumin. Of 25 patients with apparently normal calcium metabolism, six had elevated ultrafiltrable calcium results. Ionised calcium measurement required the most time and sample and offered few, if any, clear advantages in diagnosis over the other free calcium tests. Further improvements in ionised calcium measurements appear to be needed.


Sperm quality as reflected through morphology in salmon alternative life histories.
Male salmon exhibit alternative mating strategies, as both older anadromous adults and precocious juveniles (parr) participate in the spawning of a single female. This study tested the following hypotheses: 1) different intensities of sperm competition may reflect different sperm tail optima; 2) long spermatozoa are superior to short ones, with an associated cost on sperm longevity; and 3) a disfavored role in sperm competition selects for parr investing more in sperm quality. Comparisons included sperm morphological traits, whereas sperm quality was investigated by motility duration observations, measurement of the sperm adenylate system, and fertilization experiments. No evidence of different adaptive sperm dimensions between the male types was found. Positive association between spermatocrit and energy charge was, however, detected. Sperm length parameters correlated positively with ATP, energy charge, and fertilization success, whereas no evidence for an effect of sperm morphology on longevity was found. Male parr had greater spermatocrit than adults and fertilized equal proportions of eggs as adults despite a pronounced numerical subordinance in the fertilization experiments. It is concluded that a long sperm tail and midpiece may be selected to optimize energetic demands under conditions of increased sperm competition intensity.


[Spatial mortality disparities in the metropolitan region of Montreal, 1984-1988: an ecological analysis of the role of social, economic, and cultural factors].
Geographic differentials in mortality and life expectancy in the region surrounding Montreal, Canada, are compared. The author notes that "despite a marked drop of mortality in the Montreal region, there are still important geographic disparities at the end of the [1980s]....A multiple regression analysis shows that the proportion of poor and the percentage of immigrants account for more than 80% in the geographic disparities of life expectancy in the Montreal region." (SUMMARY IN ENG AND SPA)


Persistent and/or late complications of combined radiation therapy and hyperthermia.
Persistent and/or late complications were analysed in 64 patients (183 fields) that were treated with combined hyperthermia and radiation therapy for advanced, recurrent or metastatic cancer. The incidence and type of complications were evaluated over a minimum follow-up period of 2 years from the onset of treatment (mean 38.7 months; range 24-82.5 months). The primary malignancies included: breast (39), melanomas (6), adenoid cystic carcinomas of salivary glands (4), prostate (4), soft tissue sarcomas (3), squamous cell carcinoma of head and neck (3), lymphomas (3), transitional cell carcinoma of bladder (1) and basal cell carcinoma of the skin (1). The persistent complications noted included induration and fibrosis (39 hyperthermia fields, 22 patients), ulceration at the site of prior tumour (three patients, three fields), and ulceration in normal tissue (one patient, one field). Brachial plexopathy developed in one patient treated for recurrent breast cancer, but she had active disease at that time. A squamous cell carcinoma of the skin developed within the treatment field in a breast cancer patient. Radionecrosis of the mandible was seen in one patient treated for a floor of the mouth cancer, and osteomyelitis with septic arthritis developed in one patient treated for a soft tissue sarcoma of the thigh. Univariate logistic regression analyses of pretreatment and radiation-hyperthermia treatment parameters revealed that maximal tumour temperature had a borderline significant correlation with the development of complications (p = 0.07). Multivariate analyses of the pretreatment and treatment parameters revealed the best-two-covariate model to predict complications included mean maximal tumour temperature and tumour type (macroscopic tumours had greater incidence of complications than for microscopic residual disease). The rate and type of persistent and/or late complications seen following combined radiation and hyperthermia did not appear to dramatically differ from those that would be anticipated from irradiation alone in this patient population, with the exception of an increased incidence of areas of induration and tumour necrosis.


Demographic and work-related correlates of job burnout in professional eating disorder treatment providers.
Patients with eating disorders present unique challenges to treatment providers that may contribute to job burnout. This study examined demographic and work-related correlates of three primary components of burnout (i.e., emotional exhaustion, cynicism, and lack of personal accomplishment) in a sample of 296 professional eating disorder treatment providers. Participants completed the Maslach Burnout Inventory-Human Services Survey (MBI-HSS; Maslach, Jackson, & Leiter, 1996), demographics, and a questionnaire developed by the authors measuring eating disorder-specific factors theorized to be relevant to burnout. Overall, participants reported comparable levels of emotional exhaustion but significantly less cynicism and lack of personal accomplishment relative to established norms for mental health care providers on the MBI-HSS. Analyses of variance and backward regression analyses suggested that higher levels of burnout were associated with being younger, female, and overweight; working longer hours; having less experience; and experiencing a patient's death. Conversely, working in a private practice setting, having children, and having a personal history of an eating disorder were associated with lower burnout levels. Furthermore, over 45% of participants reported that treatment resistance, ego-syntonicity, high relapse rates, worry about patient survival, emotional drain, lack of appropriate financial reimbursement, and extra hours spent working contributed to feelings burned out somewhat to very much. Overall, these data suggest that emotional exhaustion is the most common aspect of burnout experienced by eating disorder treatment providers and highlight some of the key correlates of burnout for this population, which can be used to inform prevention and intervention efforts.


Mortality and recruitment of trees in a secondary montane rain forest in southeastern Brazil.
Mortality and recruitment rates were obtained for tree species over a 5.6 year period in a 1-ha fragment of secondary montane rain forest in Southeastern Brazil. All plants with a diameter at breast height (dbh) > or = 8 cm were sampled in 1989-1990 and 1995. There was an increase from 90 to 96 species, and 669 ind./ha to 749 ind./ha over the period. The mortality rate of 1.67%/yr was similar to findings for other forests, while recruitment of 3.46%/yr was the highest rate reported. Both mortality and recruitment were significantly higher in the smaller dbh classes. Recruitment was higher among rare species, and the relatively slow-growing species had significantly higher mortality rates. Differences between species dynamics were marked. Species with high values of lambda were mainly early successional and understorey trees but some understorey species also suffered a marked population decline. The classification system of species in response to light which divides understorey species into "partial shade-bearers" and "shade-bearers" groups showed to be the most suitable to the obtained results. The results suggest that this forest is undergoing a process of recovery from past disturbance.


Mild copper-catalyzed fluorination of alkyl triflates with potassium fluoride.
A chemoselective catalytic fluorination of alkyl triflates is described using potassium fluoride as a fluoride source. Excellent yields of the desired alkyl fluorides are obtained after one hour at 45 °C using 2 mol% of the copper catalyst. With 10 mol% of the catalyst, full conversion can be achieved in less than 10 minutes at 45 °C, and thus makes this procedure potentially suited for the preparation of (18) F-labeled PET probes. As a result of the mild reaction conditions, only the substitution products are observed with no evidence of common side reactions, such as elimination. Reported is a preliminary study of the reaction scope, which demonstrates that the fluorination can be performed in the presence of a wide range of functional groups. Evidence suggests an unusual role of the [IPrCuOTf] catalyst as a phase-transfer catalyst and points to [IPrCuF] as the active fluorinating reagent (IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene).


Enhancing Antigen Cross-Presentation in Human Monocyte-Derived Dendritic Cells by Recruiting the Intracellular Fc Receptor TRIM21.
Suboptimal immune responses to pathogens contribute to chronic infections. One way to improve immune responses is to boost Ag presentation. In this study, we investigate the potential of the tripartite motif-containing 21 (TRIM21) pathway. TRIM21 is a ubiquitously expressed cytosolic protein that recognizes the Fc region of Abs. When Abs that are bound to pathogens enter the cell as immune complexes, binding of TRIM21 to Fc initiates downstream inflammatory signaling and targets the immune complexes for proteasomal degradation. In APCs, peptides generated by proteasomes are loaded onto MHC class I molecules to stimulate CD8 T cell responses, which are crucial for effective immunity to pathogens. We hypothesized that increasing the affinity between immune complexes and TRIM21 might markedly improve CD8 T cell responses to Ags processed by the TRIM21 pathway. Using phage display technology, we engineered the human IgG1 Fc to increase its affinity for TRIM21 by 100-fold. Adenovirus immune complexes with the engineered Fc induced greater maturation of human dendritic cells (DC) than immune complexes with unmodified Fc and stimulated increased Ag-specific CD8 T cell proliferation and IFN-γ release in cocultures of DC-PBMC. Thus, by increasing the affinity between Fc and TRIM21, Ags from immune complexes undergo enhanced cross-presentation on DC, leading to greater CD8 T cell responses. Our study reveals an approach that could potentially be used in vaccines to increase cytotoxic T cell responses against Ags that are targeted or delivered by Fc-modified Abs.


Successful endovascular treatment of ruptured bronchial artery aneurysm.
Rupture of a bronchial artery aneurysm occurs rarely and may mimic aortic dissection. A 78-year-old-man was admitted with sudden chest pain. Chest radiography showed widening of the mediastinum, suggestive of aortic dissection, but contrast-enhanced computed tomography revealed hemomediastinum and bronchial artery aneurysm. Although open surgery has been the first choice for ruptured bronchial artery aneurysm, this case was successfully treated by an endovascular procedure with the combined use of coils and a gelatin sponge.


Purification of human erythrocyte glucose 6-phosphate dehydrogenase and glutathione reductase enzymes using 2',5'-ADP Sepharose 4B affinity column material in single chromatographic step.
The enzymes of glucose 6-phosphate dehydrogenase and glutathione reductase were purified from human erythrocytes in one chromatographic step consisting of the use of the commercially available resin 2',5'-ADP Sepharose 4B by using different washing buffers. Ammonium sulfate (30-70%) precipitation was performed on the hemolysate before applying to the affinity column. Using this procedure, G6PG, having the specific activity of 22.9 EU/mg proteins, was purified with a yield of 43% and 9150-fold; GR, having the specific activity of 20.7 EU/mg proteins, was purified with a yield of 26% and 8600-fold. The purity of the enzymes was checked on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and each purified enzyme showed a single band on the gel. This procedure has advantages of preventing of enzyme denaturation, short experimental duration, and use of less chemical materials for purification of the enzymes.


[Treatment of calcaneal fractures by fixation of Kirschner needle and thread cancellous bone screw through sinus tarsi interstice].
To explore the effect of fixation of Kirschner needle and thread cancellous bone screw through the sinus tarsi interstice for the treatment of calcaneal fractures. From January 2009 to December 2012,20 patients with calcaneal fracture were treated by minimally invasive Kirschner wire and threaded cancellous bone screw fixation and bone graft,including 12 males and 8 females with an average age of 39 years old ranging from 21 to 65. Among them, 8 cases were left foot, 12 were right foot. According to Sanders's classification, 8 cases were type II, 10 cases were type III, 2 cases were type IV. All patients were followed up from 6 to 16 months with an average of 12 months. The incision were healed. Böhler angle were increased from preoperative (17.75 +/- 4.22) degrees to postoperative (26.85 +/- 7.37) degrees (t = 4.308, P = 0.000). Gissane angle were reduced from preoperative (137.05 +/- 24.91) degrees to postoperative (113.75 +/- 13.17) degrees (t = 7.083, P = 0.000). At 3 months after operation, the scores of AOFAS were 85.50 +/- 7.99; the results were excellent in 5 feet and good in 11 feet, fair in 3 feet, and poor in 1 foot. Minimally invasive fixation of Kirschner needle and thread cancellous bone screw fixation is a simple operation, it can get reliable fixation, easy to remove, low cost, less postoperative complications, and it is a good treatment of calcaneal fracture.


Effects of enamel matrix derivative and transforming growth factor-β1 on connective tissue growth factor in human periodontal ligament fibroblasts.
Enamel matrix derivative (EMD) is suggested to stimulate transforming growth factor-β (TGF-β) production. Connective tissue growth factor (CTGF) is a downstream mediator of TGF-β. This study explores the effects of EMD and TGF-β1 on CTGF in periodontal ligament (PDL) fibroblasts and their interactions in PDL proliferation and development. Human PDL cells were stimulated with EMD. To explore the effects of EMD and TGF-β1 on CTGF expression, cells were treated with and without TGF-β inhibitor, and CTGF protein levels were assayed by Western blot analysis. To study the role of CTGF in PDL development, cells were treated with CTGF inhibitor. DNA synthesis was analyzed by bromodeoxyuridine enzyme-linked immunosorbent assay. Reverse-transcription polymerase chain reaction was performed to examine messenger RNA expression of PDL osteoblastic differentiation markers: type I collagen, alkaline phosphatase, and osteocalcin. EMD induced a concentration-dependent increase of CTGF protein expression in PDL cells. EMD- and TGF-β1-stimulated CTGF expression was significantly reduced in the presence of TGF-β inhibitor. CTGF inhibition downregulated both EMD- and TGF-β1-induced DNA synthesis. The effect of CTGF and EMD on osteoblastic mRNA expression in PDL cells is not obvious. EMD stimulates CTGF expression in human PDL cells, a process modulated by the TGF-β pathway. CTGF can affect EMD- and TGF-β1-induced PDL cell proliferation, but its effects on PDL with regard to osteoblastic differentiation remain inconclusive. The results provide novel insights into EMD-CTGF interaction in PDL cells.


Surface Aesthetics and Analysis.
Surface aesthetics of an attractive nose result from certain lines, shadows, and highlights with specific proportions and breakpoints. Analysis emphasizes geometric polygons as aesthetic subunits. Evaluation of the complete nasal surface aesthetics is achieved using geometric polygons to define the existing deformity and aesthetic goals. The relationship between the dome triangles, interdomal triangle, facet polygons, and infralobular polygon are integrated to form the "diamond shape" light reflection on the nasal tip. The principles of geometric polygons allow the surgeon to analyze the deformities of the nose, define an operative plan to achieve specific goals, and select the appropriate operative technique.


Epidermal growth factor impairs the cytochrome C/caspase-3 apoptotic pathway induced by transforming growth factor beta in rat fetal hepatocytes via a phosphoinositide 3-kinase-dependent pathway.
Transforming growth factor beta (TGF-beta)-mediated apoptosis is one of the major death processes in the liver. We have previously shown that epidermal growth factor (EGF) is an important survival signal for TGF-beta-induced apoptosis in fetal hepatocytes (Fabregat et al., FEBS Lett 1996;384:14-18). In this work we have studied the intracellular signaling implicated in the protective effect of EGF. We show here that EGF activates p42 and p44 mitogen-activated protein kinases (MAPK). However, mitogen extracellular kinase (MEK) inhibitors do not block the survival effect of EGF. EGF also activates phosphoinositide 3-kinase (PI 3-kinase) and protein kinase B (PKB/AKT) in these cells. The presence of PI 3-kinase inhibitors blocks the protective effect of EGF on cell viability, DNA fragmentation, and caspase-3 activity. We have found that TGF-beta disrupts the mitochondrial transmembrane potential (DeltaPsi(m))( )and activates the release of cytochrome c, this effect being blocked by EGF, via a PI 3-kinase-dependent pathway. A detailed study on bcl-2 superfamily gene expression shows that TGF-beta produces a decrease in the messenger RNA (mRNA) and protein levels of bcl-x(L), an antiapoptotic member of this family, capable of preventing cytochrome c release. EGF is able to maintain bcl-x(L) levels even in the presence of TGF-beta. PI 3-kinase inhibitors completely block the protective effect of EGF on TGF-beta-induced bcl-x(L )down-regulation. We conclude that PI 3-kinase mediates the survival effect of EGF on TGF-beta-induced death by acting upstream from the mitochondrial changes, i.e., preventing bcl-x(L) down-regulation, cytochrome c release, and activation of caspase-3.


[Clinical comparative studies on multiphase lipectomy and one-phase lipectomy with skin graft transplantation in skin flap contouring].
To discuss the advantages of two flap contouring methods and to explore the best choice for the flap contouring. From March 2002 to March 2006, 59 patients were admitted for a flap-contouring operation. Of the 59 patients, 40 (32 males, 8 females; average age, 34 years) underwent the multiphase lipectomy (the multiphase lipectomy group). The original flaps included the abdominal flap in 19 patients, the groin flap in 10, the thoracic flap in 4, the free anteriolateral thigh flap in 6, and the cross leg flap in 1. The flaps ranged in size from 6 cmX 4 cm to 32 cm x 17 cm. However, the remaining 19 patients (16 males, 3 females; average age, 28 years) underwent the one-phase lipectomy with skin graft transplantation(the one-phase lipectomy group). The original flaps included the abdominal flap in 4 patients, the groin flap in 6, the thoracic flap in 3, and the free anteriolateral thigh flap in 6. The flaps ranged in size from 4 cm x 3 cm to 17 cm x 8 cm. The results were analyzed and compared. In the multiphase lipectomy group, partial flap necrosis developed in 4 patients but the other flaps survived. The followed-up of 27 patients for 3 months to 2 years revealed that the flaps had a good appearance and texture, having no adhesion with the deep tissues. However, the flaps became fattened in 22 patients with their body weight gaining. The patients who had a flap >5 cm x 5 cm in area had their sensation functions recovering more slowly; only part of the sensations to pain and heat recovered. The two point discrimination did not recover. In the one-phase lipectomy group, total graft necrosis developed in 1 patient but the healing was achieved with additional skin graft transplantation; partial graft necrosis developed in 2 patients but the wounds were healed after the dressing changes; the remaining flaps survived completely. The follow-up of the 16 patients for 3 months to 3 years revealed that all the 16 patients had a good sensation recovery, 12 patients had the two point discrimination <15 mm, with no recurrence of the fattening of the flaps; however, the grafted skin had a more severe pigmentation, and no sliding movement developed between the skin and the tissue basement. The multiphase lipectomy and the one-phase lipectomy with skin graft transplantation are two skin flap contouring methods, which have their own advantages and disadvantages. Which method is taken should be based on the repair location of the skin flap and the condition of the skin flap.


Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates. II. Comparison of fixed amplitude with amplitude modulated stimuli.
We have previously shown that acute electrical stimulation of the auditory nerve using charge-balanced biphasic current pulses presented continuously can lead to a prolonged decrement in auditory nerve excitability (Tykocinski et al., Hear. Res. 88 (1995), 124-142). This work also demonstrated a reduction in electrically evoked auditory brainstem response (EABR) amplitude decrement when using an otherwise equivalent pulse train with a 50% duty cycle. In the present study we have extended this work in order to compare the effects of electrical stimulation using both fixed amplitude electrical pulse trains and amplitude modulated (AM) pulse trains that more accurately model the dynamic stimulus paradigms used in cochlear implants. EABRs were recorded from guinea pigs following acute stimulation using AM trains of charge-balanced biphasic current pulses. The extent of stimulus-induced reductions in the EABR were compared with our previous results using either fixed amplitude continuous, or 50% duty cycle pulse trains operating at 0.34 microC/phase (2 mA, 170 micros/phase) at 400 or 1000 pulses/s (Tykocinski et al., Hear. Res. 88 (1995) 124-142). The AM pulse train, operating at the same rates, was based on a 1-s sequence of the most extensively activated electrode of a Nucleus Mini-22 cochlear implant using the SPEAK speech processing strategy exposed to 4-talker babble, and delivered the same total charge as the fixed amplitude 50% duty cycle pulse train. Two hours of continuous stimulation induced a significant, rate-dependent reduction in auditory nerve excitability, and showed only a slight post-stimulus recovery for monitoring periods of up to 6 hours. Following 2 or 4 h of stimulation using an otherwise equivalent pulse train with a 50% duty cycle or the AM pulse train, significantly less reduction in the EABR was observed, and recovery to pre-stimulus levels was generally rapid and complete. These differences in the extent of the recovery between the continuous waveform and both the 50% duty cycle and AM waveforms were statistically significant for both 400 and 1000 pulses/s stimuli. Consistent with our previous results, the stimulus changes observed using AM pulse trains were rate dependent, with higher rate stimuli evoking more extensive stimulus-induced changes. The present findings show that while stimulus-induced reductions in neural excitability are dependent on the extent of stimulus-induced neuronal activity, the use of an AM stimulus paradigm further reduces post-stimulus neural fatigue.


Intimate partner violence incidence and continuation in a primary care screening program.
There are few longitudinal estimates of intimate partner violence (IPV) incidence and continuation. This report provides estimates of IPV incidence and continuation in women receiving health care in clinics participating in an IPV assessment and services intervention study. The Women's Experience with Battering Scale was used in combination with questions addressing physical and sexual assault to annually screen women for IPV. Between April 2002 and August 2005, 657 women in rural South Carolina consented and were screened at least twice. Among those with a current partner (n = 530), the majority (86.2%) had never experienced IPV. Among prevalent victims, IPV continued over time for 37%. IPV continuation rates were higher among older women and those who considered abuse as a problem in their relationship. Of those women who were IPV negative at time 1, IPV incidence at time 2 was 4.2%. A higher score on the Women's Experience with Battering Scale at time 1, a marker of psychological abuse, was a strong predictor of physical IPV incidence (p(trend) = 0.0001). These data suggest that the incidence of IPV over a short follow-up period is relatively low and that the majority of IPV desists over this short follow-up period.


Resolving fiber crossing using advanced fast marching tractography based on diffusion tensor imaging.
Magnetic resonance diffusion tensor tractography is a powerful tool for the non-invasive depiction of the white matter architecture in the human brain. However, due to limitations in the underlying tensor model, the technique is often unable to reconstruct correct trajectories in heterogeneous fiber arrangements, such as axonal crossings. A novel tractography method based on fast marching (FM) is proposed which is capable of resolving fiber crossings and also permits trajectories to branch. It detects heterogeneous fiber arrangements by incorporating information from the entire diffusion tensor. The FM speed function is adapted to the local tensor characteristics, allowing in particular to maintain the front evolution direction in crossing situations. In addition, the FM's discretization error is reduced by increasing the number of considered possible front evolution directions. The performance of the technique is demonstrated in artificial data and in the healthy human brain. Comparisons with standard FM tractography and conventional line propagation algorithms show that, in the presence of interfering structures, the proposed method is more accurate in reconstructing trajectories. The in vivo results illustrate that the elucidated major white matter pathways are consistent with known anatomy and that multiple crossings and tract branching are handled correctly.


[HOX genes in embryo- and phylogenesis].
This review is concerned with the structure and function of the protein products and homeobox genes of the HOX complex. We also trace a relationship between morphological evolution and the evolution of the homeotic complex.


A developmental approach to the risk of a first recurrence in child protective services.
The objective of this study is to estimate the risk of a first recurrence over a five-year period following initial child protective services (CPS) intervention and identify the characteristics associated with the risk of recurrence for three different age groups. Recurrence is defined as the first substantiated report within the observation period after initial services have ended. The study involved a cohort of 25,897 Quebec children who received postinvestigation services for the first time and whose cases were closed between 2005 and 2009. Survival analysis was used to estimate the five-year risk of recurrence and Cox regression to model the risk of recurrence for three age groups. The covariates introduced into the regression analyses were characteristics of the child and initial services. The risk of recurrence in the five years following termination of initial CPS services was 36% for the entire cohort and varied depending on the child's age at the time of case closure. Children aged 6-11 when their cases were closed had the highest risk of recurrence. Although Aboriginal descent and prior CPS investigations have a consistent effect on the risk of recurrence in all three age groups, the effects of other covariates, such as out-of-home placement and court involvement, vary or are even reversed, depending on the child's age. These findings highlight the need to adopt a differential approach that takes into account the child's age, both in the provision of protective services and in research involving the population receiving such services.


Superstimulation of ovarian follicular development in beef cattle with a single intramuscular injection of Folltropin-V.
The need to inject FSH twice daily for superstimulation of ovarian follicular development in cattle necessitates frequent attention by farm-personnel and increases the possibility of failures due to mishandling and errors in administration of treatments. A series of three experiments were designed to evaluate the feasibility of superstimulation in beef cattle with a single intramuscular (IM) injection of Folltropin-V diluted in a hyaluronan-based slow-release formulation (SRF). In Experiment 1, cows were assigned to one of three treatment groups to compare two methods of injection as compared to the twice daily IM injection protocol. Superovulatory response of cows (n=6) treated with twice daily IM injections over 4 days (Control) was greater than of cows treated with a single subcutaneous (SC) injection in SRF (n=6), while superovulatory response of cows treated with a single IM injection in SRF (n=6) was intermediate. Experiment 2 was designed to compare two concentrations of SRF (20mg/mL hyaluronan, 100% compared to 10mg/mL hyaluronan, 50%) in a single IM injection protocol. The mean number of corpora lutea (CL) were not significantly different (P≥0.05), but the numbers of total ova/embryos (P<0.05), fertilized ova (P<0.01) and transferable embryos (P<0.001) were greater in cows treated with FSH in 100% SRF (n=20) than cows treated with FSH in 50% SRF (n=20). Experiment 3 was designed to compare superovulatory response in Red Angus donor cows treated with a single IM injection of Folltropin-V diluted in 100% solution of SRF with those treated with the traditional twice-daily IM injection protocol over 4 days. Mean (±SEM) numbers of CL (13.7±1.2 compared to 13.8±1.2), total ova/embryos (12.3±1.5 compared to 13.7±2.1), fertilized ova (7.2±1.1 compared to 8.4±1.4) and transferable embryos (4.9±0.8 compared to 6.4±1.3) were not significantly different between Control (n=29) and Single injection (n=29) groups, respectively. In summary, superstimulation of beef donor cows with a single IM injection of Folltropin-V diluted in 100% solution of SRF resulted in a comparable superovulatory response to the traditional twice-daily IM administration of Folltropin-V diluted in saline over 4 days.


Imaging the hidden modes of ultrathin plasmonic strip antennas by cathodoluminescence.
We perform spectrally resolved cathodoluminescence (CL) imaging nanoscopy using a 30 keV electron beam to identify the resonant modes of an ultrathin (20 nm), laterally tapered plasmonic Ag nanostrip antenna. We resolve with deep-subwavelength resolution four antenna resonances (resonance orders m = 2-5) that are ascribed to surface plasmon polariton standing waves that are confined on the strip. We map the local density of states on the strip surface and show that it has contributions from symmetric and antisymmetric surface plasmon polariton modes, each with a very different mode index. This work illustrates the power of CL experiments that can visualize hidden modes that for symmetry reasons have been elusive in optical light scattering experiments.


Diagnosis of urinary incontinence in dogs: role of the urethral pressure profile.
Nine cases of urinary incontinence in dogs were evaluated by various diagnostic methods, including the urethral pressure profile (UPP). The UPP was derived from a need to study th dynamics of the urethra in patients with urinary tract obstruction or incompetence of the urethral sphincteric mechanism and was obtained in dogs with similar problems. The method involved slowly withdrawing a fluid-filled catheter through the urethra while a chart recorder graphed the pressure changes within the urethral lumen. The graphs obtained from clinical cases were compared with normal values established for the UPP in dogs. The UPP proved to be a simple and reliable means by which to determine intraurethral events and aided in establishing the cause of urinary incontinence in several dogs. The profile provided a graphic description of intraurethral resistance in each case and was valuable in localizing areas of increased urethral resistance or obstructions and decreased urethral resistance or incompetence. Frequently, specific therapy for the urinary incontinence was instituted on the basis of the UPP.


[FTIR spectroscopic study on carcinoma cells].
The aim of this research is to establish the cell basis for the carcinoma tissue diagnosis by exploring a method to obtain the FTIR (Fourier transform infrared) spectra of the cultured carcinoma cells with FTIR spectroscopy and investigating the special spectral features of the carcinoma cells compared with the carcinoma tissues. In the present paper, the gastric carcinoma tissues confirmed by histology were measured using a Nicolet Magna750-II FTIR spectrometer and the corresponding FTIR spectra were obtained. The cultured gastric carcinoma cells (SGC7901) were centrifuged to provide a small pellet of cells for FTIR analysis. The cell pellet was then placed on a specially designed salt plate made of BaF2. Then the infrared spectra were recorded by the same equipment. Based on the previously established criteria, a comparative study was subsequently carried out between the spectra of the cultured carcinoma cells (SGC7901) and that of the corresponding gastric tissues. Several infrared spectral features of the carcinoma cells were obtained: the different bands between cells and tissues locate in the range of 3 000-3 600 cm(-1) and 1 640 cm(-1) which are the range of the hydroxy stretching and blending bands of H2O. There are more H2O out of carcinoma cells in carcinoma tissues, so the strong bands of H2O cover the distinctive bands of carcinoma cells in carcinoma tissues. Although the carcinoma tissue is more complicated, which might originate from the intrinsic complexity of the tissue, the results suggest that the spectral features of the carcinoma cells can be well reflected by that of the carcinoma tissue. This study shows that the diagnosis of carcinoma tissue by FTIR method exhibits sufficient cell basis.


Animate models of human head injury.
A review of animal models of nonpenetrating head injury caused by mechanical energy is presented that focuses on the ability of various categories of models and their relationships to the types of head injury seen in humans. Basic hypotheses of animal modeling of human disease and outcome measures are addressed. Current models are reviewed and compared for their differences and similarities regarding behavioral, pathologic, physiologic, and biochemical fidelity to human head injury.


Rapid gas chromatographic procedure for the determination of topiramate in serum.
A rapid gas chromatographic method for the routine determination in serum of the new anticonvulsant drug topiramate (Topamax) (TOP) is described. The method involves extracting 0.50 mL of sample, previously adjusted to pH 9.5 with saturated borate buffer with ethyl acetate. One-microliter aliquots of the extract were injected into a 10-m x 0.53-mm i.d. x 0.5-microm 100% methyl silicone megabore capillary column connected to a nitrogen-phosphorus detector. The column temperature was initially at 170 degrees C for 0.1 min, then programmed at 10 degrees C/min to 240 degrees C, then 20 degrees C/min to 280 degrees C for 0.5 min. Under these conditions of the assay, the retention times of TOP and mepivicaine, internal standard, were 4.0 and 3.4 min, respectively. Quantitative determinations were performed with peak-height ratios of TOP to the internal standard. Calibration curves were linear from 2.5 to 150 mg/L TOP. The assay had a limit of quantitation of 2.5 mg/L. The overall within-run precision of the method yielded coefficients of variation (CV) of 3.9% at 10 mg/L (n = 10) and 3.1% at 100 mg/L (n = 10). The overall between-run precision calculated by three determinations on a single day for a week yielded CVs of 7.3% at 23 mg/L (n = 12) and 7.8% at 85 mg/L (n = 12). Common anticonvulsant and basic/neutral extractable drugs were found not to interfere with the assay. At present, no correlation has been demonstrated between trough plasma TOP concentrations and clinical efficacy. However, TOP values observed in our laboratory in serums from patients receiving adjunctive treatment for seizure disorders ranged from 2.5 to 35 mg/L.


Remifentanil Ameliorates Liver Ischemia-Reperfusion Injury Through Inhibition of Interleukin-18 Signaling.
Hepatic injury induced by ischemia-reperfusion (I/R) after transplantation or lobectomy is a major clinical problem. The potential benefit of remifentanil in these hepatic surgeries remains unknown. The current study investigated whether remifentanil protects the liver against I/R injury in a rat model and whether the underlying mechanism involves the modulation of interleukin (IL)-18 signaling. Male Sprague-Dawley rats were subjected to 45 minutes of partial hepatic ischemia followed by 6 hours of reperfusion. Then, they received an intravenous saline or remifentanil (0.4, 2, or 10 μg/kg per minute) infusion from 30 minutes before ischemia until the end of ischemia with or without previous administration of naloxone, a nonselective opioid receptor antagonist. Serum aminotransferase, hepatic morphology, and hepatic neutrophil infiltration were analyzed. The expression of hepatic IL-18; IL-18-binding protein (BP); and key cytokines downstream of IL-18 signaling were measured. Remifentanil significantly decreased serum aminotransferase levels and profoundly attenuated the liver histologic damages. Liver I/R injury increased the expression of both hepatic IL-18 and IL-18BP. Although remifentanil pretreatment significantly decreased I/R-induced IL-18 expression, it further upregulated IL-18BP levels in liver tissues. The I/R-induced increases of hepatic interferon-γ, tumor necrosis factor-α and IL-1β expression, and neutrophil infiltration were also significantly reduced by remifentanil. Naloxone inhibited the remifentanil-induced downregulation of IL-18, but not the elevation of IL-18BP, and significantly attenuated its protective effects on liver I/R injury. Remifentanil protects the liver against I/R injury. Modulating the hepatic IL-18/IL-18BP balance and inhibiting IL-18 signaling mediate, at least in part, the hepatoprotective effects of remifentanil.


Impact of Early Postnatal NSAID Treatment on Nephrogenesis in Wistar Rats.
Prematurely born children with patent ductus arteriosus are treated with ibuprofen or indomethacin, which may inhibit kidney development. We determined whether clinical doses affected kidney development and function, with or without extrauterine growth retardation. Wistar rats were cross-fostered in normal food (NF) or food restricted (FR) litters at postnatal day (PND) 2. On PND 3 to 4, three doses of 0.9% NaCl, 0.1 mg/kg indomethacin, or 10 mg/kg ibuprofen were administered via intraperitoneal injection with 12-hr intervals. Kidneys were evaluated for apoptosis, proliferation, and gene expression at PND 8; stereological assessment of nephron number at PND 35; and clinical pathology and neutrophil gelatinase-associated lipocalin at 4 and 9 months. Blood pressure was measured at the ages of 4, 6, and 9 months. NF and FR bodyweight differed from PND 3 onwards, ranging from 16.5 g at weaning (p < 0.001) to 39 g at necropsy (p = 0.019). Kidney proliferation/apoptosis ratios were 7:1 and 3:1 (p = 0.001), respectively and different expression of Wnt4 (0.7x), Oat1 (1.3x), Nphs1 (1.7x), and Aqp4 (1.3x) was noted (but its biological relevance doubted). Nephron numbers were decreased by 12% (p = 0.109) in the ibuprofen-NF group and 7.5% (p = 0.237) in FR groups. This coincided with a tendency to increased neutrophil gelatinase-associated lipocalin at 9 months. No differences were noted in electrolytes, creatinine, or urea clearance. No valid blood pressure results could be obtained. A clinical Ibuprofen dose showed potential to inhibit kidney development in neonatal rats. FR did not modulate these effects.


Sorting nexin 10 induces giant vacuoles in mammalian cells.
Eukaryotic cells maintain a sophisticated network of intracellular membranous system to ensure the proper distribution and compartmentalization of cellular proteins critical for diverse functions such as cell division or cell-cell communication. Yet, little is known about the mechanism that regulates the homeostasis of this system. While analyzing the impact of sorting nexins on the trafficking of membrane type matrix metalloproteinases, we unexpectedly discovered that the expression of SNX10 induced the formation of giant vacuoles in mammalian cells. This vacuolizing activity is sensitive to mutations at the putative phosphoinositide 3-phosphate binding residue Arg(53). Domain-swap experiments with SNX3 demonstrate that the PX domain of SNX10 alone is insufficient to generate vacuoles and the downstream C-terminal domain is required for vacuolization. Brefeldin A, a chemical known to block the endoplasmic reticulum to Golgi transport, inhibited the vacuolization process. Together, these results suggest that SNX10 activity may be involved in the regulation of endosome homeostasis.


Serum concentrations of myoglobin vs human heart-type cytoplasmic fatty acid-binding protein in early detection of acute myocardial infarction.
We compared the diagnostic utility of serum concentrations of human heart-type cytoplasmic fatty acid-binding protein (H-FABPc), myoglobin, and their ratio for the early diagnosis of acute myocardial infarction (AMI) in 104 healthy volunteers and 165 patients at admission within 6 h of the onset of chest pain. The ROC curves of the H-FABPc [0.946, 95% confidence interval (CI) = 0.913-0.979] and myoglobin (0.895, 95% CI = 0.846-0.944) between patients with AMI and healthy volunteers were significantly greater than the area under the ratio of myoglobin to H-FABPc (0.823, 95% CI = 0.765-0.881). In 165 patients, the sensitivity (81.8%, 95% CI = 74.2-89.4%), specificity (86.4%, 95% CI = 78.1-94.6%), and predictive accuracy (83.6%, 95% CI = 78.0-89.3%) of H-FABPc > 12 micrograms/L in diagnosing AMI were significantly higher than those of myoglobin, and were similar to those of the combination of H-FABPc > 12 micrograms/L and the ratio < or = 14. We conclude that H-FABPc is a more sensitive and specific marker than myoglobin for the early diagnosis of AMI, and that their ratio cannot give a clear advantage over the measurement of H-FABPc alone.


The experience of reducing antibiotics used in animal production in the Nordic countries.
The Nordic countries (Denmark, Finland, Norway and Sweden) have a long tradition of infectious disease control in animal production. Special attention has also been paid to the use of antibiotics. This has resulted in a relatively low use of antibiotics and also relatively favourable status of antibiotic resistance. The current situation, interventions and achievements are summarised with special reference to Sweden which was probably the first country where stringent control and prudent use of antibiotics was put into practice. The use of antibiotics for growth-promoting purposes is highlighted.


Clustering of concordant and discordant cancer types in Swedish couples is rare.
Spouses are exposed to common environmental cancer risk factors during adulthood. Investigating the aggregation of cancer in couples might provide valuable insights into cancer development. The 2008 update of the Swedish Family-Cancer Database includes over 2 million couples with at least one child in common with one single partner. We quantified the contribution of shared adulthood environment by standardised incidence ratios (SIRs) and population attributable fractions (PAFs). Estimated SIRs were used to build an etiological map reflecting the similarity of cancers by adult environmental exposures. Increased risks of concordant types amongst spouses were found for lung, upper aerodigestive tract and skin cancers (SIRs from 1.24 to 1.97),which are probably related to shared exposure to smoking and UV radiation. PAFs were low with the highest value of 1.46% for uterus cancer in wives of men affected by prostate cancer. Further analysis, based on all non-sex-specific concordant and discordant types, revealed a clustering of lung, stomach, pancreas and bladder cancers sharing smoking as a risk factor. This aggregation was used as a cut-point to identify further "novel" clusters. Shared lifestyles including smoking and drinking habits as well as human papilloma virus infection (HPV) might be associated with an excess of cancer incidence amongst spouses. We observed significantly an increased risk for smoking-related cancers such as lung, upper aerodigestive tract and oesophageal cancers. The present population-based study confirms that the lifestyle shared by spouses plays a minor role in cancer causation. Only strong environmental risk factors such as smoking seem to influence cancer development in adulthood. The proposed etiological map based on 24 cancer types identifies novel clusters--for example, non-Hodgkin lymphoma and leukaemia, bone cancer and myeloma--that are not completely explained by established risk factors. Some of the identified clusters relied on reproduced associations between cancer risks amongst husband and wives; however, the role of chance cannot be excluded.


[Productions analyses and pH dynamics during rice straw degradation by the lignocellulose degradation bacteria system WSC-6].
To detect the metabolic characteristic of rice straw degradation by composite microbial system WSC-6, we cultured WSC-6 in the media used rice straw as the limiting carbon source. The rice straw was added in the style of different quantity once or the same quantity at the different time intervals during 90 days culture. The systems were cultivated under static condition at 50 degrees C. The degradation ratio, absolute degradation quantity,products from degradation and dynamics of pH value of fermentation system were all investigated. The results showed: when 1% rice straw was added once, the pH of fermentation system decreased from initial 7.8 to 6.0 within the first three days inoculation, and after six-day cultivation, it increased to 8.0 and was stable. For dissolved oxygen concentration (DO), the value was maintained at range of 0.01 to 0.12 mg x L(-1) of microaerobic condition. During the rice straw degradation, more than ten kinds of products including ethanol, acetic acid, lactic acid and glycerol and so on were detected using GC-MS. Especially, the highest concentration of lactic acid among all products was 7.381 g x L(-1) at 24 h after inoculation. During 90-day cultivation, for the addition treatments of the different quantity once, the more rice straw added, the quicker and lower the pH decreased, and the longer time intervals returned the pHs were. Especially for 5.0% addition, when 5.0% of rice straw was added once, pH did not increase again after it decreased. Among the addition of the same quantity at the different time intervals, the trend of decrease-increase in pH at 12-day and 15-day intervals could be repeated and high degradation activity well maintained. After 90-day of inoculation, the highest degradation ratio occurred in the treatment at 15-day interval, which was 86.7%. The highest absolute quantity occurred in the treatment at 6-day interval, which was 32.4 g. The trend of pH changes can indicate the activity of lignocellulose degradation and degradation process of the WSC-6.


Molecular targets of the oncogenic transcription factor jun.
The Jun oncoprotein is a major component of the transcription factor complex AP-1, which regulates the expression of multiple genes essential for cell proliferation, differentiation and apoptosis. Constitutive activation of endogenous AP-1 is required for tumor formation in avian and mammalian cell transformation systems, and also occurs in distinct human tumor cells suggesting that AP-1 plays an important role in human oncogenesis. The highly oncogenic v-jun allele capable of inducing neoplastic transformation in avian fibroblasts and fibrosarcomas in chicken as a single oncogenic event, was generated by mutation of the cellular c-jun gene during retroviral transduction. Hence, avian cells represent an excellent model system to investigate molecular mechanisms underlying jun-induced cell transformation. Approaches aimed at the identification of genes specifically deregulated in jun-transformed fibroblasts have led to the identification of several genes targeted by oncogenic Jun. Some of the activated genes represent direct transcriptional targets of Jun encoding proteins, which are presumably involved in cell growth and differentiation. Genes suppressed in v-jun-transformed cells include several extracellular proteins like components of the extracellular matrix or proteins involved in extracellular signalling. Due to aberrant regulation of multiple genes by the Jun oncoprotein, it is assumed that only the combined differential expression of Jun target genes or of a subset thereof contributes to the conversion of a normal fibroblast into a tumor cell displaying a phenotype typical of jun-induced cell transformation. It has already been shown that distinct activated targets exhibit partial transforming activity upon over-expression in avian fibroblasts. Also, distinct target genes silenced by v-Jun inhibit tumor formation when re-expressed in v-jun-transformed cells. The protein products of these transformation-relevant genes may thus represent potential drug targets for interference with jun-induced tumorigenesis.


Increased aortic stiffness and attenuated lysyl oxidase activity in obesity.
One potential mechanism through which obesity exerts adverse effects on the vascular system is by increasing aortic stiffness, a change known to be predictive of increased cardiovascular mortality. The aim of this study was to investigate the pathophysiology that links obesity to aortic stiffening. Obese (ob/ob) mice were used to examine physical, morphological, and molecular changes in the aorta in response to obesity. ob/ob mice had increased aortic pulse wave velocity and tissue rigidity. ob/ob aorta exhibited decreases of lysyl oxidase (LOX) activity and cross-linked elastin, and increases of elastin fragmentation and elastolytic activity. The aortas of ob/ob mice were surrounded by a significant amount of proinflammatory and pro-oxidative perivascular adipose tissue. In vitro studies revealed that the conditioned medium from differentiated adipocytes or the perivascular adipose tissue of ob/ob mice attenuated LOX activity. Furthermore, inhibition of LOX in wild-type lean mice caused elastin fragmentation and induced a significant increase in pulse wave velocity. Finally, we found that obese humans had stiffer arteries and lower serum LOX levels than do normal-weight humans. Our results demonstrated that obesity resulted in aortic stiffening in both humans and mice, and established a causal relationship between LOX downregulation and aortic stiffening in obesity.


Patterns of hearing aid usage predict hearing aid use amount (data logged and self-reported) and overreport.
Previous studies found that, on average, users overreport their daily amount of hearing aid use compared to objective measures such as data logging. However, the reasons for this are unclear. This study assessed data-logged and self-reported amount of hearing aid use in a clinical sample of hearing aid users. It identified predictors of data-logged hearing aid use, self-reported hearing aid use, and hearing aid use overreport. This observational study recruited adult hearing aid users from 22 private dispensers in the Netherlands and in Denmark. The sample consisted of 228 hearing aid users. Typical participants were over the age of 65 and retired, were fitted binaurally, and had financially contributed to the cost of their hearing aids. Participants had on average a mild-to-severe sloping bilateral hearing impairment. Participants completed a purposefully designed questionnaire regarding hearing aid usage and the International Outcome Inventory-Hearing Aids. Dispensers collected audiometric results and data logging. Multiple linear regression identified predictors of data-logged hearing aid use, self-reported hearing aid use, and hearing aid use overreport when controlling for covariates. Data logging showed on average 10.5 hr of hearing aid use (n = 184), while participants reported on average 11.8 hr of daily hearing aid use (n = 206). In participants for which both data-logged and self-reported hearing aid use data were available (n = 166), the average absolute overreport of daily hearing aid use was 1.2 (1 hr and 11 min). Relative overreport was expressed as a rate of absolute overreport divided by data-logged hearing aid use. A positive rate denotes hearing aid use overreport: the average overreport rate was .38. Cluster analysis identified two data-logged patterns: "Regular," where hearing aids are typically switched on for between 12 and 20 hr before their user powers them off (57% of the sample), and "On-off," where hearing aids are typically switched on for shorter periods of time before being powered off (43% of the sample). In terms of self-report, 77% of the sample described their hearing aid use to be the same every day, while 23% of the sample described their hearing aid use to be different from day to day. Participants for whom data logging showed an On-off pattern or who reported their hearing aid use to be different from day to day had significantly fewer data-logged and self-reported hours of hearing aid use. Having an On-off data-logging pattern or describing hearing aid use as the same every day was associated with a significantly greater hearing aid use overreport. Data-logged and self-reported usage patterns significantly predicted data-logged hearing aid use, self-reported hearing aid use, and overreport when controlling for covariates. The results point to patterns of hearing aid usage as being at least as important a concept as amount of hearing aid use. Dispensers should discuss not only the "how much", but also the "how" of hearing aid usage with their clients.


Completion pneumonectomy: experience with 47 cases.
From 1982 through March 1994, fourty-seven patients underwent completion pneumonectomy for a reappearing lung cancer, lung metastases, late complications, benign lung diseases, and early complication of bronchial or pulmonary artery sleeve resections. Intraoperative bleeding was higher than in standard pneumonectomy; there was one intraoperative mortality (2.3%). Operative mortality was 14.9% overall but was 3.6% in completion pneumonectomy for lung cancer, 20% for late complications and benign disease, and 57% for the treatment of early complications of sleeve resections. Three and five-year survival in patients with lung cancer who survived the operation was 43.8% and 28.7% according to the Kaplan-Meier method; no significant difference in long-term survival was present between patients with a second primary lung cancer or recurrence. Completion pneumonectomy is indicated in reappearing lung cancer and should be considered in benign disease when a less invasive procedure is not available. Completion pneumonectomy for the treatment of early complications of bronchial or pulmonary artery sleeve resections has a very high mortality but no alternative is available.


[Cholera in Benin (epidemic of 1991)].
Authors report on epidemiologic, bacteriology and therapeutic data related to 1991 cholera outbreak in Benin in the general context of the 7th world pandemic. 7474 cases were notified from all over the country. Vibrio cholerae 01, El Tor biotype, was identified in many patients stools and in the surroundings. Control measures implemented in this situation are described: early parenteral and mainly oral rehydration, antibiotic treatments for patients and contacts, systematic home control around cases, wells disinfection and general hygiene promotion, mobilization of the Civil Service Authorities and population education. Authors conclude that strict epidemiologic monitoring is necessary in epidemic circumstances as well as during endemo-sporadic period.


Connecting environmental exposure and neurodegeneration using cheminformatics and high resolution mass spectrometry: potential and challenges.
Connecting chemical exposures over a lifetime to complex chronic diseases with multifactorial causes such as neurodegenerative diseases is an immense challenge requiring a long-term, interdisciplinary approach. Rapid developments in analytical and data technologies, such as non-target high resolution mass spectrometry (NT-HR-MS), have opened up new possibilities to accomplish this, inconceivable 20 years ago. While NT-HR-MS is being applied to increasingly complex research questions, there are still many unidentified chemicals and uncertainties in linking exposures to human health outcomes and environmental impacts. In this perspective, we explore the possibilities and challenges involved in using cheminformatics and NT-HR-MS to answer complex questions that cross many scientific disciplines, taking the identification of potential (small molecule) neurotoxicants in environmental or biological matrices as a case study. We explore capturing literature knowledge and patient exposure information in a form amenable to high-throughput data mining, and the related cheminformatic challenges. We then briefly cover which sample matrices are available, which method(s) could potentially be used to detect these chemicals in various matrices and what remains beyond the reach of NT-HR-MS. We touch on the potential for biological validation systems to contribute to mechanistic understanding of observations and explore which sampling and data archiving strategies may be required to form an accurate, sustained picture of small molecule signatures on extensive cohorts of patients with chronic neurodegenerative disorders. Finally, we reflect on how NT-HR-MS can support unravelling the contribution of the environment to complex diseases.