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Taxonomic diversity and structure of benthic macroinvertebrates in Aby Lagoon (Ivory Coast, West Africa). The benthic macroinvertebrates of Aby lagoon (West Africa: Ivory coast) was studied during four seasons (high dry season, high rainy season, low dry season and low rainy season, respectively) from June 2006 to March 2007. The distribution of the benthic macroinvertebrates species was recorded at 13 stations on the whole of the lagoon. A total of 62 taxa of benthic macroinvertebrates belonging to 28 families and 10 orders were listed. The molluscs and crustaceans dominate qualitatively by adding up 51 and 24%, respectively of the total number of organisms. Five taxa (Corbula trigona (20%), Pachymelania aurita (12%), Clibernhardius cooki (7%), Oligochaeta (7%) and Crassostrea gasar (6%) accounted for 52% of total abundance. Classification analysis used to perform the characterisation of the lagoon on the basis of benthic macroinvertebrates showed the existence of four main clusters in which the seasonal pattern in benthic macroinvertebrates were very similar in the four seasons. In contrast the species richness and diversity indices were significantly different. Furthermore these indices where higher in the stations closer to the sea and surrounded by mangrove trees (southern area) compared to the inland ones.

The effect of retention on the relapse of Class II Division 1 cases. Sixty cases of Class II Division 1 malocclusion were studied; 30 of them had been retained after the completion of orthodontic treatment, the other 30 had not and acted as a control group. Using measurements from lateral skull radiographs and statistical analysis, the two groups were compared in respect of skeletal pattern, soft tissue, overjet, overbite and interincisal angle. Both the retained and the non-retained group showed a tendency to relapse after the completion of active treatment; a tendency to relapse even while in retention was observed. The relapse in overjet was found to be more significant than the relapse in overbite. In both groups the relapse in overjet was found to be associated with the size of the original overjet, the overbite at the end of active treatment and the interincisal angle at the end of active treatment. In both groups the relapse in overbite was found to be associated with the size of the original overbite, the change in maxillary-mandibular planes angle and the interincisal angle at the end of active treatment.

Acute hazard of biocides for the aquatic environmental compartment from a life-cycle perspective. One of the aims of the European project LIFE-COMBASE is to build a computational tool to predict the acute toxicity for aquatic organisms of biocidal active substances and its environmental degradation products. A database was implemented compiling toxicity data for these substances in organisms of the freshwater/marine and sewage treatment plant compartments. The goal of this study is to analyze the compiled data to identify the possible hazard of these compounds for the aquatic compartments. Several official and scientific databases were consulted. Data from 196 biocidal substances and 206 environmental metabolites were collected for the taxonomic groups, including fish, invertebrates, algae and sewage treatment plant (STP) microorganisms. Substances were categorized for their toxicity in four groups, considering values of L(E)C50, according to EU Regulation (EC) No 1272/2008. >50% of the parent were located in category 1 (L(E)C50 ≤ 1 mg/L) for fish, invertebrates and algae, indicating a high toxicity for the freshwater/marine compartments. However >60% were not toxic for STP microorganisms. Metabolites were mainly less toxic than the parent compounds, but 22-36% presented the same toxicity and ~6% were more toxic. No toxicological information was found for ~50% of the metabolites for fish, invertebrates and algae, reaching the 96% for the microorganisms. In addition, information on toxicity to the STP microorganisms was only found for 40% of the parent compounds. The high percentage of toxic metabolites and the scarcity of data for these compounds indicate the need to further study their impact in the aquatic compartments.

Prospective evaluation of aortic valve replacement in young adults and middle-aged patients: mechanical prosthesis versus pulmonary autograft. The best option for aortic valve replacement (AVR) in young adults and middle-aged patients remains controversial. A longitudinal comparison between the Ross procedure (RP) and mechanical prosthesis (MP) was conducted in this group of patients. Between January 1997 and January 2003, 125 consecutive patients (age range: 20-50 years) were submitted for AVR; 62 patients (mean age 37.73+/-7.28 years) were included in the MP group, and 63 (mean age 35.33+/-7.63 years) in the RP group. Gender, etiology, NYHA functional class and other preoperative data were comparable between the two groups. The operative mortality was four (6.5%) in the MP group, and one (1.6%) in the RP group (p = NS). The postoperative complication rate was similar in both groups. Two RO patients required early autograft replacement due to severe regurgitation. There were no late deaths during the follow up period. In the MP group, three patients (4.8%) suffered major bleeding, three (4.8%) were diagnosed with prosthetic endocarditis (one required reoperation), and three (4.8%) suffered valve- or coumarin-related thromboembolic complications. All RP patients were free from bleeding, thromboembolic, or infectious complications, but three suffered severe pulmonary homograft stenosis (one re-replacement, one Palmaz stent, and one under clinical surveillance). The combined freedom from death or major complications was 64.72+/-4.3% in the MP group, and 87.92+/-9.65% in the RP group (p = 0.068). Intraoperative and early postoperative morbidity and mortality rates were similar among RP and MP patients, despite a steep learning curve during the early RP cases. Although the follow up was limited, and homograft-related morbidity was seen in the RP group, the overall five-year major complication rate supported use of the pulmonary autograft for AVR in patients aged between 20 and 50 years.

Arterial spin-labeling MR imaging in moyamoya disease compared with SPECT imaging. Arterial spin-labeling (ASL) is a noninvasive magnetic resonance (MR) imaging method used to obtain brain perfusion information on various cerebrovascular diseases. We retrospectively compared the use of ASL-MRI and single-photon emission CT (SPECT) imaging to determine absolute cerebral blood flow (CBF) in moyamoya disease. CBF examinations using ASL-MRI on 3-T MRI and SPECT imagings with iodine-123-N-isopropyl-p-iodoamphetamine at resting (rest-IMP) and after acetazolamide challenge (ACZ-IMP) were performed on 12 patients with moyamoya disease (men, 5; women, 7; age range/average (year), 7-66/35.0). The CBF values determined by ASL-MRI (ASL-value), rest-IMP (rest-IMP-value), and ACZ-IMP (ACZ-IMP-value) of cerebral hemispheres (24 sides) were measured with normalized CBF maps created from data of those 3 perfusion imaging methods. Cerebrovascular reactivity (CVR) was calculated as follows: {(ACZ-IMP-value)-(rest-IMP-value)}/(rest-IMP-value)×100 (%). The ASL-value was compared with the rest-IMP-value, ACZ-IMP-value, and CVR. The ASL-value, rest-IMP-value, ACZ-IMP-value, and CVR (average±standard deviation) were 26.6±14.8 (mL/100 g/min), 27.5±6.4 (mL/100 g/min), 37.1±13.2 (mL/100 g/min), and 35.9±44.3 (%), respectively. Significant relationships between the ASL-value versus (vs.) the rest-IMP-value (rs=0.500, p<0.05), the ASL-value vs. the ACZ-IMP-value (rs=0.863, p<0.01), and the ASL-value vs. the CVR (rs=0.699, p<0.01) were observed. Although the ASL-value was lower than the rest-IMP-value, the significant relationship between the ASL-value and the rest-IMP-value may suggest that perfusion imaging by ASL-MRI could be used to recognize the condition of brain perfusion. In particular, the stronger correlation coefficient between the ASL-value and ACZ-IMP-value might suggest that perfusion imaging by ASL-MRI could show the potentially dangerous zone for ischemia.

Substance P, a neuropeptide, inhibits measles virus replication in cell culture. Substance P, a neuropeptide of the tachykinin group, inhibits measles virus replication in cell culture and partially blocks viral fusion activity assayed in the haemolysis system. The ID50 for the inhibition of measles virus single-cycle replication is 0.6 mumol/l, and the effect is fully reversible. The antiviral activity of substance P corresponds to that of previously described synthetic tri-to heptapeptides. Tachykinins and these oligopeptides share a short homology with the N-terminus of paramyxovirus fusion proteins.

Elution characteristics of gentamicin-PMMA beads after implantation in humans. Seventeen patients had gentamicin-PMMA beads implanted for treatment of orthopedic infections. The authors found that beads implanted in patients for 3 to 36 weeks were capable of eluting high levels of antibiotic after retrieval. Beads that were implanted in patients for less than 10 weeks eluted significantly higher antibiotic levels than beads were implanted for more than 14 weeks. This study supports the local use of these beads in the treatment of musculoskeletal infections.

Proteolytic cleavage sites of band 3 protein in alkali-treated membranes: fidelity of hydropathy prediction for band 3 protein. To assess the fidelity of hydropathy prediction for band 3 protein, we determined the cleavage sites of the protein and the portions of the protein tightly bound to the membrane lipid bilayer by means of in situ proteolytic digestion. For the removal of all anticipated hydrophilic connector loops from membranes, we had to denature the band 3 protein molecule in situ by alkali treatment. When the alkali-treated membranes were digested with trypsin, chymotrypsin, and pepsin, the majority of the anticipated transmembrane portions remained in the membrane fraction. However, five anticipated transmembrane portions were released into the supernatant fraction. Thus, the first, second, third, sixth and tenth anticipated transmembrane portions, in accordance with the hydropathy prediction, were released into the supernatant with the proteolytic digestion method. This indicates that these anticipated transmembrane portions are not bound with the boundary lipids although the hydrophobicity of these portions is comparable to that of the portions experimentally remaining in the membrane fraction. It is conceivable that the membrane peptide portions of band 3 protein could be classified into at least two categories, i.e. one bound to the boundary lipids and the other free from the boundary lipids. Approximately 90% of the transmembrane domain of the band 3 protein are recovered in either the supernatant fraction or the membrane fraction. The fidelity of hydropathy prediction for polytopic membrane proteins and the nature of the membrane embedded peptide portions are discussed.

Recovery of the immune system with antiretroviral therapy: the end of opportunism? Clinical care of people infected with human immunodeficiency virus (HIV) has been substantially affected by the introduction of potent antiretroviral therapy. Changes in the immune system after such therapy and the clinical consequences are important issues for clinicians treating patients with HIV. A systematic review of MEDLINE, 1993 to January 1998, of peer-reviewed publications, abstracts from national and international conferences, and product registration information through January 1998. Criteria used to select studies include relevance to immune reconstitution with potent antiretroviral therapy and having been published in the English language. Assessment of data quality and validity included consideration of venue of the publication and relevance to practice. Suppression of viral replication after administration of potent antiretroviral therapy that includes inhibitors of the HIV-1 protease is associated with quantitative and qualitative changes in the immune system. In patients with relatively advanced disease, there is a first-phase rise (during the initial 3 months) in both naive and memory CD4+ and CD8+ T lymphocytes and B lymphocytes. This is followed by a slower second-phase increase (after 3 months) in cells primarily of the naive CD4+ and CD8+ phenotypes. These quantitative changes are associated with qualitative improvements in host immune responses, best characterized by dramatically reduced risk of opportunistic infection. Restoration of the immune system during the first year of potent antiretroviral therapy is partial at best. Potent antiretroviral therapy has become the standard of care for people with HIV infection, and its use has led to significant reductions in the incidence of the acquired immunodeficiency syndrome (AIDS) and in mortality from HIV infection. Although incomplete, considerable immune recovery occurs, sufficient, in most cases, to provide adequate protection against most AIDS-associated opportunistic infections.

Emotional Symptoms and Dietary Patterns in Early Adolescence: A School-Based Follow-up Study. To examine the relationship between early emotional symptoms and dietary patterns over 3 years in a school-based sample. Three-year longitudinal prospective study. Thirteen schools in Reus, Spain. From a sample of 562 preadolescents with and without emotional symptoms, 165 were observed and were classified as either showing (n = 100) or not showing emotional symptoms (n = 65). Emotional symptoms were assessed at baseline and after 1 and 3 years. In the third year, data were collected on food consumption, adherence to the Mediterranean diet (MD), and physical activity. Dietary patterns were created by principal component analysis. Multivariate logistic regression was conducted with P < .05 considered significant. Girls with emotional symptoms scored significantly lower in assessments for MD (score of 5.41 ± 2.19) and physical activity (score of 4.97 ± 2.05) than did girls who had no emotional symptoms (scores: MD, 6.19 ± 1.67; physical activity: 5.86 ± 1.94). Approximately 39.68% of girls with emotional symptoms showed high adherence to a sweet and fatty food pattern. After adjusted logistic regression, girls with emotional symptoms were 4 times as likely to have high adherence to a sweet and fatty food pattern (odds ratio, 4.79; 95% confidence interval, 1.55-15.10). No differences were observed among boys. Girls with emotional symptoms during early adolescence have high adherence to a pattern rich in sweet and fat foods and low adherence to MD, and engage in low levels of physical activity. These findings highlight the importance of managing emotional distress to prevent it from having a negative effect on eating behavior.

Isolation, characterization and investigation of Cordia dichotoma fruit polysaccharide as a herbal excipient. The objective of the present research work was to isolate, purify and characterize Cordia dichotoma gum and investigate its disintegration property in oral tablets. The isolated gum was tested for physicochemical characteristics such as solubility, pH (1% w/w in water), swelling index, loss on drying, ash value, bulk and tapped density, Carr's index, Hausner's ratio and angle of repose. The Orodispersible tablets of valsartan were prepared by direct compression method and evaluated for average weight (mg), drug content (%), thickness (mm), hardness (kg/cm(2)), friability (%), wetting time (sec), water absorption ratio (%) and disintegration time (sec). FTIR studies revealed that there was no interaction between drug, gum and other excipients used in the study. The F4 batch with disintegration time 26.34 ± 0.78 s and in vitro release 99.64 ± 0.43% was selected as optimized formulation. This formulation was compared with conventional marketed formulation and was found superior. Batch F4 was subjected to stability studies for three months and was tested for its disintegration time, drug contents and dissolution behaviour. Batch F4 was found stable for three months at accelerated temperature.

New aspects of the glucose activation of the H(+)-ATPase in the yeast Saccharomyces cerevisiae. The glucose-induced activation of plasma membrane ATPase from Saccharomyces cerevisiae was first described by Serrano in 1983. Many aspects of this signal transduction pathway are still obscure. In this paper, evidence is presented for the involvement of Snf3p as the glucose sensor related to this activation process. It is shown that, in addition to glucose detection by Snf3p, sugar transport is also necessary for activation of the ATPase. The participation of the G protein, Gpa2p, in transducing the internal signal (phosphorylated sugars) is also demonstrated. Moreover, the involvement of protein kinase C in the regulation of ATPase activity is confirmed. Finally, a model pathway is presented for sensing and transmission of the glucose activation signal of the yeast H(+)-ATPase.

[Clinical characteristics and genetic analysis of three pediatric patients with idiopathic restrictive cardiomyopathy]. Restrictive cardiomyopathy (RCM) is rare in children, and little is known about the molecular basis of RCM. The aim of this study was to investigate the clinical and myopathological characteristics and to detect mutations on cardiac sarcomere protein genes in three idiopathic pediatric RCMs. Detailed clinical characteristics and familiar history were obtained in three idiopathic pediatric RCMs. One hundred healthy pediatric individuals were recruited as controls. Histological evaluation was performed with heart tissue retrieved at catheterization in case-1 and case-2. The entire coding sequences of four cardiac sarcomere protein genes, including cardiac troponin T (TNNT2), cardiac troponin I(TNNI3), β-myosin heavy chain (MYH7), and α-actin (ACTC)were screened for mutations. Sequence variants were then tested in the family as well as in 100 healthy control DNAs. All three index cases were diagnosed as primary RCMs without family history, and their clinical conditions deteriorated rapidly. Case-1 was in combination with ventricular septal defect. Case-2 was in combination with mid- and inferoseptal hypertrophy. In case-1, myocardial biopsies displayed extensive an isomorphism and disarray of cardiomyocytes; electron microscopy showed large stacks of severely dysmorphic megamitochondria and focal Z-disc streaming. In case-2, endomyocardial biopsy revealed moderate myocyte hypertrophy with mild interstitial fibrosis; transmission electron microscopy showed misalignment of Z-bands and unequal Z-Z band distances. Genetic analysis identified two heterozygous missense mutations in TNNI3, with R204H in case-1 and R192H in case-3 respectively. A de novo heterozygous deletion in TNNT2 (p. Asn100_Glu101del) was identified in case-2. Sequence analysis shows that all three mutations are located in a position highly conserved across many species. The three mutations were negative for their parents and controls. The clinical conditions in all three index cases are deteriorated rapidly after diagnosed as primary RCM. Three heterozygous mutations including two in TNNI3 and one in TNNT2 gene are identified in the three RCMs respectively, which are considered as causative mutations. These findings provide new insights into the molecular etiology responsible for pediatric RCM.

Radiological evaluation of bone growth in neonates born at gestational ages between 26 and 41 weeks: cross-sectional study. The length of the ossified part of the long bones of the upper (humerus) and lower limb (femur) as well as the axial length (that is, height) of the vertebral body of L1 were measured on a plain supine radiograph in 347 newborn babies (228 males, 119 females) with the gestational age (GA) from 26 to 41 weeks. All were admitted to the neonatal intensive care unit. Reasons for admission included hyaline membrane disease, meconium aspiration syndrome, neonatal asphyxia or transient tachypnea of the newborn. Patients with abnormal growth, gross anomalies, or who were the products of multiple births were excluded. The average weekly increment in the height of L1 for male infants born at GA varying from 26 to 41 weeks was 0.23 mm, for the humerus 1.82 mm and for the femur 2.35 mm. The corresponding data for females was 0.20 mm, 1.54 mm and 2.30 mm. The ratio of the height of L1 to body length progressively increased between 26 to 41 weeks. A growth spurt in L1 was noted for both sexes at 34 weeks of GA. Long bone growth was similar in male and female infants born before 36 weeks. However, the ratio of femur to body length in males increased after 36 weeks. The ratio of humerus to body length remained constant over the entire range of GA.

Not throwing out the baby with the bathwater: lessons from the Fibromyalgia Impact Questionnaire. The Fibromyalgia Impact Questionnaire (FIQ) is the most frequently used questionnaire in patients with fibromyalgia in the last 20 years. Recently, a revised version of the FIQ has been published. In this study, we examined the factor structure of the original version using explorative and confirmative factor analyses in a representative group of about 500 Dutch and Belgian patients with fibromyalgia, in which the work-related item was excluded. The FIQ consisting of a three-factor structure with a functional domain (ten items), physical symptom domain (six items), and mental symptom domain (two items), which is the most accurate. From the data presented, it is concluded that the FIQ is a solid, worldwide-used questionnaire with a history of 20 years consisting of three domains. When constructing a revised FIQ, the results of this study can be incorporated.

Platynosomum fastosum in ex-captive orangutans from Indonesia. The liver fluke Platynosomum fastosum was identified upon necropsy of three ex-captive orangutans (Pongo pygmaeus) which had been part of a rehabilitation program for reintroduction to the wild. This trematode has not been reported in orangutans previously and is commonly found in cats in Southeast Asia. Cross infection from cats via intermediate hosts, to orangutans kept in captivity as pets, could explain their presence in the latter. Although P. fastosum caused intrahepatic and bile duct damage, death of the hosts could not be attributed solely to the presence of the liver fluke infection.

Magnetic and seizure thresholds before and after six electroconvulsive treatments. Electroconvulsive therapy (ECT) is a well-established treatment in psychiatry. It has been reported that in patients with nondelusional major depression, transcranial magnetic stimulation (TMS) may substitute for ECT. To explore whether ECT and TMS share mechanisms of action, we studied the effects of ECT on both seizure threshold (ST) and magnetic motor threshold (MT). We measured ST and MT in 10 patients referred for ECT. MT was defined as the minimal power of the TMS equipment at which a motor evoked potential (MEP) response could be detected 50% of the time. ST was defined as the minimal intensity of electrical stimulation needed to elicit an adequate seizure. ECT was performed following the methods recommended by the American Psychiatric Association. All subjects signed an informed consent for participation in the research. We measured MT and ST in 10 patients before and after 6 ECT treatments. No changes in MT were detected from the treatment (paired t-test: t = 1.05, SD = 4.78, p = 0.25). ST, on the other hand, increased significantly with treatment (paired t-test: t = 2.99, SD = 190.20, p < 0.001). ECT and TMS do not share a common mechanism at least with regard to MT and ST.

Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias. Leukemic blasts from patients with acute phase chronic myeloid leukemic and refractory acute myeloid leukemia are highly resistant to a number of cytotoxic drugs. To overcome multi-drug resistance, we engineered a diphtheria fusion protein by fusing human interleukin-3 (IL3) to a truncated form of diphtheria toxin (DT) with a (G4S)2 linker (L), expressed and purified the recombinant protein, and tested the cytotoxicity of the DTLIL3 molecule on human leukemias and normal progenitors. The DTLIL3 construct was more cytotoxic to interleukin-3 receptor (IL3R) bearing human myeloid leukemia cell lines than receptor-negative cell lines based on assays of cytotoxicity using thymidine incorporation, growth in semi-solid medium and induction of apoptosis. Exposure of mononuclear cells to 680 pM DTLIL3 for 48 h in culture reduced the number of cells capable of forming colonies in semi-solid medium (colony-forming units leukemia) > or =10-fold in 4/11 (36%) patients with myeloid acute phase chronic myeloid leukemia (CML) and 3/9 (33%) patients with acute myeloid leukemia (AML). Normal myeloid progenitors (colony-forming unit granulocyte-macrophage) from five different donors treated and assayed under identical conditions showed intermediate sensitivity with three- to five-fold reductions in colonies. The sensitivity to DTLIL3 of leukemic progenitors from a number of acute phase CML patients suggests that this agent could have therapeutic potential for some patients with this disease.

Methylphenidate in children with ADHD with or without learning disability. To explore treatment response to Osmotic Release Oral System(®) (OROS) methylphenidate in children with ADHD with and without comorbid learning disability (LD). Data were analyzed from two 6-week, double-blind, randomized, placebo-controlled, crossover studies evaluating individually determined doses of OROS methylphenidate versus placebo in 135 children (ages 9 to 12 years) with ADHD with or without an LD in reading, math, or both. The sample was demographically diverse, with 31% females and more than 40% minority, predominantly African American and Hispanic. On two laboratory school days, participants received either OROS methylphenidate or placebo and were given a battery of cognitive and behavioral tests. Treatment with OROS methylphenidate led to improvement in ADHD Rating Scale scores for participants with or without comorbid LD. Both groups performed better during treatment with OROS methylphenidate than placebo on measures of cognitive skills (i.e., Test of Variables of Attention, Finger Windows Backwards), academically related tasks (i.e., Dynamic Indicators of Basic Early Literacy Skills, Test of Handwriting Skills-Revised, Permanent Product Math Test), and observed classroom behavior (i.e., Swanson, Kotkin, Alger, M-Flynn, and Pelham Scale). In children with ADHD with or without comorbid LD, behavior and performance improved during treatment with OROS methylphenidate.

Distance geometry approach to rationalizing binding data. A new method is presented for calculating a type of quantitative structure-activity relationship, given experimental data on the binding affinity of a series of ligands to a receptor site on a protein. All ligands are presumed to have known chemical structure but may be conformationally flexible, and all are presumed to bind to the same, single, fairly rigid site of the (pure) receptor protein molecule. Given the experimentally determined free energies of binding of the ligand molecules, possible binding sites are deduced in terms of geometry and the chemical character of the various parts of the site. A test of the method is given for a series of chymotrypsin inhibitors and for a series of dihydrofolate reductase inhibitors. The proposed dihydrofolate reductase site suggests that a quinazoline inhibitor may rock between two different binding nodes depending on the pK of the ring N(1).

Elevated blood pressure and personality: a meta-analytic review. A meta-analysis of 295 relevant effect sizes obtained from 25,469 participants confirmed expectations that elevated blood pressure (BP) and essential hypertension (EH) would be associated with lower affect expression but with more negative affectivity and defensiveness. The strongest associations occurred for defensiveness and measures of anger and affect expression linked to an interpersonal context(s). However, a number of other factors also were found to moderate associations of BP with personality measures, including awareness of BP status, gender, occupation, and diastolic versus systolic BP assessment. Given these moderators, the authors conclude that a traditional view of personality causing EH is untenable and that, not incorporating multifactorial, synergistic approaches is likely to obscure associations of personality-behavior with EH.

Immunohistochemical studies in lymphocytic infiltration of the skin (Jessner) and discoid lupus erythematosus. A comparative study. Differentiation between Jessner's lymphocytic infiltration of the skin (LIS) and discoid lupus erythematosus (DLE) may be extremely difficult. Therefore, skin biopsy specimens from eight patients with LIS and eight with DLE were studied immunohistochemically with monoclonal antibodies against T cell differentiating antigens, Ia-like (HLA-DR) antigens, and antigens present on Langerhans and/or related cells (OKT6), B cells, and monocytes (OKM1). In all patients studied the majority of the infiltrating cells reacted with the pan-T cell antisera Leu-1 and Leu-4, whereas B cells were few or absent. However, whereas OKT6+ Langerhans cells and HLA-DR+ (activated) T cells were present in most patients with DLE, these cells were never observed in the perivascular infiltrates of patients with LIS. These different staining patterns for OKT6 and anti-HLA-DR antisera may not only be of help in differentiating between LIS and DLE, but may also reflect differences in the pathogenetic mechanisms involved, which argues against a possible relationship between these conditions.

[The basics of catecholamine therapy. 2. A guide to clinical use]. Myocardial function is determined by preload, afterload, contractility and heart rate. Pathologic changes of these variables may result in decrease of blood pressure, acute heart failure or cardiogenic shock. Hyperdynamic septic shock is associated with systemic hypotension despite increased cardiac output. Mediators of sepsis induce both myocardial depression and pulmonary arterial hypertension. Moreover, sepsis is characterized by microcirculatory disturbances and dysbalance in regional oxygen delivery and consumption. Severe systemic hypotension is a symptom often requiring catecholamine therapy to restore systemic circulation and to avoid organ damage. As the use of catecholamines is not a causal therapy administration should be limited to an initial measure until correction of the underlying abnormalities can be achieved. Different etiologies of shock as well as diseases requiring specific interventions as pulmonary embolectomy, systemic lysis or coronary angioplasty have to be considered. First line intervention consists of optimizing preload by fluid resuscitation as appropriate and use of dopamine (4-12 micrograms/kg.min) as primary catecholamine to increase contractility and blood pressure. In acute left heart failure inotropic support with dobutamine (4-12 micrograms/kg.min) or epinephrine (0.05-1 microgram/kg.min) may be necessary, frequently combined with a vasodilator (sodium nitroprusside 0.2-5 micrograms/kg.min or nitroglycerine 0.5-2.5 micrograms/kg.min) or phosphodiesterase-III-inhibitor (milrinone 0.3-0.8 microgram/kg.min). In right heart failure norepinephrine is preferred to increase coronary perfusion pressure. Hyperdynamic septic shock with decreased vascular resistance is treated with norepinephrine to restore mean arterial pressure and to improve right ventricular dysfunction induced by pulmonary hypertension.

[A case of coronary artery bypass surgery using left internal thoracic artery and right gastroepiploic artery for a patient with essential thrombocythemia]. The 78-year-old male underwent coronary angiography because of angina pectoris. He was revealed to have essential thrombocythemia with a platelet count of over 1,000,000/mm3. Essential thrombocythemia belongs to the group of chronic myeloproliferative disorders. It displays both thrombogenic and bleeding tendency due to the increased platelet count, as well as to dysfunction. CABG was performed using the left internal thoracic artery and the right gastroepiploic artery. Hydroxycarbamide was taken to regulate the platelet count before surgery. There was no difficulty with hemostasis during surgery. Warfarin and hydroxycarbamide were used as anticoagulant therapies after surgery. Postoperative CAG demonstrated both grafts to be patients. The patient remained in good condition until he died suddenly on the 159th postoperative day. The cause of death was not clear because no autopsy was carried out. The death may have been associated with a thromboembolism, acute graft thrombosis or cerebral infarction, or pulmonary embolism. This patient did not take antiplatelet drugs because the platelet count and prothrombin time was well controlled. Nonetheless, an antiplatelet agent might reduce the risk of thromboembolism in such patients. It is suggested that meticulous anticoagulation therapy must be important for a patient with essential thrombocythemia, especially in the postoperative period.

Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs. Adult hematopoietic stem cells (HSCs) with serially transplantable activity comprise two subtypes. One shows a balanced output of mature lymphoid and myeloid cells; the other appears selectively lymphoid deficient. We now show that both of these HSC subtypes are present in the fetal liver (at a 1:10 ratio) with the rarer, lymphoid-deficient HSCs immediately gaining an increased representation in the fetal bone marrow, suggesting that the marrow niche plays a key role in regulating their ensuing preferential amplification. Clonal analysis of HSC expansion posttransplant showed that both subtypes display an extensive but variable self-renewal activity with occasional interconversion. Clonal analysis of their differentiation programs demonstrated functional and molecular as well as quantitative HSC subtype-specific differences in the lymphoid progenitors they generate but an indistinguishable production of multipotent and myeloid-restricted progenitors. These findings establish a level of heterogeneity in HSC differentiation and expansion control that may have relevance to stem cell populations in other hierarchically organized tissues.

Test-retest reliability of the profile of hearing aid performance. This study was designed to replicate the test-retest reliability and critical difference components of the Profile of Hearing Aid Performance (PHAP) as established by Cox and Gilmore (1990). Subjects were 18 experienced hearing aid users ranging in age from 62 to 74 years old. The initial and retest administrations of the PHAP were conducted with no rehabilitative treatment pertaining to hearing loss or amplification provided during the intervening period. The interval between the first and second administrations of the profile was 4-5 months. The mean test-retest difference scores obtained in this investigation were small, not unlike those reported by Cox and Gilmore (1990). Critical difference (CD) values closely approximated those of the previous study except for the Background Noise subscale and the Environment C scale. A pooled estimate of each standard deviation of test-retest differences was computed using data from both investigations. This resulted in critical differences considered to be more precise than the CD values derived from either study alone. Findings strongly support the utility of the PHAP as an effective tool for generating reliable information regarding self-perceived hearing aid performance.

[Computer-assisted evaluation of mammography images. Initial clinical experiences]. Preceding studies have shown that a second independent reviewer of conventional mammographies increases the detection rate of features typical for malignancy by up to 15%. In order to test a computer-aided diagnostic (CAD) system (ImageChecker, R2 Technology, USA) for the detection of pathologic criteria in conventional mammography, 96 mammographies were retrospectively evaluated using ImageChecker. Thirty-five of these mammographies had been diagnosed as not showing pathologies, and 61 had depicted histologically confirmed malignancy. Detecting 41 of 61 breast malignancies, ImageChecker showed a diagnostic sensitivity of 70.5%. All malignancies accompanied by microcalcifications were identified by ImageChecker, whereas 18 cases characterized by parenchymal opacity without microcalcifications were not marked. On the average, 1.95 markers per image were set, giving a total of 187 markers in this study. 63% of all markers showed normal tissue and were thus false positive. Pathologic parenchymal opacities in mammography are a well-known problem for all CAD systems in use. Despite this major drawback, even now ImageChecker can provide tremendous support in routine interpretation of conventional mammographies.

The role of therapeutic endoscopic ultrasound now and for the future. Therapeutic endoscopic ultrasound (EUS) became possible after the advent of the linear echoendoscope and the EUS guided fine needle aspiration. Over the past two decades, the indications for therapeutic EUS have expanded and evidence regarding its utility has been steadily accumulating. Randomized studies have shown EUS to be effective for cancer pain relief (celiac plexus neurolysis), pancreatic fluid collection drainage, and biliary drainage. Prospective studies have shown EUS-guided biliary drainage to be safe and effective in patients with failed ERCP. There is evidence to suggest that EUS is effective for pancreatic duct drainage, gallbladder drainage, and drainage of pelvic collections. EUS may also be useful for targeted cancer treatment via brachytherapy, radiofrequency ablation, or injection therapy. Therapeutic EUS is likely to play an increasingly important role in endoscopic therapy of gastrointestinal diseases in the near future.

Software for the automatic correction of recorded eye fixation locations in reading experiments. Because the recorded location of an eyetracking fixation is not a perfect measure of the actual fixated location, the recorded fixation locations must be adjusted before analysis. Fixations are typically corrected manually. Making such changes, however, is time-consuming and necessarily involves a subjective component. The goal of this article is to introduce software to automate parts of the correction process. The initial focus is on the correction of vertical locations and the removal of outliers and ambiguous fixations in reading experiments. The basic idea behind the algorithm is to use linear regression to assign each fixation to a text line and to identify outliers. The freely available software is implemented as a function, , written in R.

Extension of the clomiphene citrate stair-step protocol to gonadotropin treatment in women with clomiphene resistant polycystic ovarian syndrome. Our objective was to evaluate the safety and efficacy of direct initiation of gonadotropin ovarian stimulation without prior withdrawal bleeding in anovulatory clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS) patients. Eighteen PCOS patients underwent ovulation induction with CC using a stair-step regimen. Patients who failed to respond to the maximal dose of CC initiated gonadotropin stimulation without inducing withdrawal bleeding, using the chronic low dose regimen. The primary outcome measure was the time to ovulation from the beginning of CC treatment until the day of ovulatory trigger. This was compared with the time to ovulation calculated according to the traditional approach, which includes inducing progesterone withdrawal bleeding between each CC dose increment and before gonadotropin therapy. The time to ovulation in the study group was 67.0 ± 6.8 days. The estimated time to ovulation according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence the live birth rate was 38.9% (7/18). Direct initiation of gonadotropin therapy without prior induction of withdrawal bleeding in clomiphene resistant PCOS patients results in considerable reduction of the time to ovulation and is both safe and efficacious.

Basketball injuries. Basketball injuries are most prevalent in the lower extremity, especially at the ankle and knee. Most basketball injuries are orthopedic in nature and commonly include ligament sprains, musculotendinous strains, and overuse injuries including stress fractures. By virtue of its excellent contrast resolution and depiction of the soft tissues and trabecular bone, magnetic resonance imaging has become the principal modality for evaluating many basketball injuries. In this article, commonly encountered basketball injuries and their imaging appearances are described. The epidemiology of basketball injuries across various age groups and levels of competition and between genders are reviewed.

A Redox-Active Binder for Electrochemical Capacitor Electrodes. A promising strategy for increasing the performance of supercapacitors is proposed. Until now, a popular strategy for increasing the specific capacity of the electrode consists of grafting redox molecules onto a high surface area carbon structure to add a faradaic contribution to the charge storage. Unfortunately, the grafting of molecules to the carbon surface leads to a dramatic decrease of the electrochemical performances of the composite material. Herein, we used the organic binder as an active material in the charge/discharge process. Redox molecules were attached onto its polymeric skeleton to obtain a redox binder with the dual functionalities of both the binder and the active material. In this way, the electrochemical performance was improved without detrimentally affecting the properties of the porous carbon. Results showed that the use of a redox binder is promising for enhancing both energy and power densities.

[HCG-producing intrahepatic cholangiocarcinoma]. The serum level of human chorionic gonadotropin (hCG) in a 60-year-old man with intrahepatic cholangiocarcinoma was found to be abnormal (44.6 mIU/ml) at the diagnosis. The patient underwent right hemihepatectomy, and the high serum hCG returned to normal 28 days postoperatively. Six months after the operation, the cholangiocarcinoma recurred in the remnant liver and the hCG level was again elevated to 268 mIU/ml. The patient died of liver failure eight months after the operation. Immunohistochemical studies of the resected tumor showed hCG-positive cells in the cancer nest. In this case, it is (believed) that the intrahepatic cholangiocarcinoma produced hCG and secreted it to the serum.

T-cell acute lymphoblastic leukemia in infants has distinct genetic and epigenetic features compared to childhood cases. For reasons not yet understood, nearly all infants with acute lymphoblastic leukemia (ALL) are diagnosed with the B-cell type, with T-ALL in infancy representing a very rare exception. Clinical and molecular knowledge about infant T-ALL is still nearly completely lacking and it is also still unclear whether it represents a distinct disease compared to childhood T-ALL. To address this, we performed exome sequencing of three infant cases, which enabled the detection of mutations in NOTCH2, NOTCH3, PTEN, and KRAS. When analyzing the transcriptomes and miRNomes of the three infant and an additional six childhood T-ALL samples, we found 760 differentially expressed mRNAs and 58 differentially expressed miRNAs between these two cohorts. Correlation analysis for differentially expressed miRNA-mRNA target pairs revealed 47 miRNA-mRNA pairs, with many of them previously described to be aberrantly expressed in leukemia and cancer. Pathway analysis revealed differentially expressed pathways and upstream regulators related to the immune system or cancerogenesis such as the ERK5 pathway, which was activated in infant T-ALL. In summary, there are distinct molecular features in infant compared to childhood T-ALL on a transcriptomic and epigenetic level, which potentially have an impact on the development and course of the disease. © 2016 Wiley Periodicals, Inc.

Eulerian field-theoretic closure formalisms for fluid turbulence. The formalisms of Wyld [Ann. Phys. 14, 143 (1961)] and Martin, Siggia, and Rose (MSR) [Phys. Rev. A 8, 423 (1973)] address the closure problem of a statistical treatment of homogeneous isotropic turbulence (HIT) based on techniques primarily developed for quantum field theory. In the Wyld formalism, there is a well-known double-counting problem, for which an ad hoc solution was suggested by Lee [Ann. Phys. 32, 292 (1965)]. We show how to implement this correction in a more natural way from the basic equations of the formalism. This leads to what we call the Improved Wyld-Lee Renormalized Perturbation Theory. MSR had noted that their formalism had more vertex functions than Wyld's formalism and based on this felt Wyld's formalism was incorrect. However a careful comparison of both formalisms here shows that the Wyld formalism follows a different procedure to that of the MSR formalism and so the treatment of vertex corrections appears in different ways in the two formalisms. Taking that into account, along with clarifications made to both formalisms, we find that they are equivalent and we demonstrate this up to fourth order.

Children with acute rheumatic fever and acute poststreptococcal glomerulonephritis and their families in a subtropical zone: a three-year prospective comparative epidemiological study. Over a period of three years (December 1980 through November 1983) the incidence and epidemiological features of acute rheumatic fever (ARF) and acute poststreptococcal glomerulonephritis (AGN) were studied prospectively in two regional hospitals in Kuwait serving a childhood population of 225,000. The study included 146 children with ARF and 256 family members and 125 children with AGN and 199 family members. The annual incidence of ARF and AGN were 19.6 and 17.8 respectively per 100,000 childhood population (7.3 and 6.7 respectively per 100,000 total population). Both diseases occurred sporadically throughout the year with a similar peak in winter. The clinical profile of ARF was essentially similar to that reported from temperate climates, and AGN followed mainly throat infections. Microscopic haematuria was detected in ten ARF family members (4%) and in 20 AGN family members (10%). Haematuria and low C3 were found in two (0.8%) and in seven (3.5%) ARF and AGN family members respectively. Of the nine family members with subclinical nephritis the group C streptococcus was isolated from three (33%). The geometric mean titre (GMT) of antistreptolysin O (ASO) and of antihyaluronidase (AH) in ARF and AGN patients were markedly elevated. Although the median age of ARF and AGN family members were 13 and 15 years respectively, yet the GMT of ASO and AH in the family members were slightly higher than those of the normal childhood population.

[Endoscopic treatment and recanalization with a needle-knife in the total stenosis of the esophago-jejunal anastomosis]. This is to report on a 44-year old female patient diagnosed with gastric cancer who was surgically treated with a total D-2 radical gastrectomy, block splenectomy and a lateral esophagus-jejunal anastomosis. A month after surgery and various post-surgery complications, a total stenosis of the esophagus-jejunal anastomosis was detected which was endoscopically solved with a needle-knife type obtaining an adequate recanalization of the lumen, which is the subject of this report.

Protein content and number of nucleolar organizer regions are enhanced during phorbol ester-induced differentiation of cultured human megakaryocytic cells. In order to investigate the protein synthesis in megakaryocyte polyploidization, phorbol myristate acetate (PMA, 5 x 10(-9) M), a differentiation marker known to induce megakaryocyte polyploidization, was added to human megakaryocytic cell lines (DAMI, HEL and K562) and the expression of platelet/megakaryocytic integrins, the numbers of nucleolar organizer regions (AgNORs) and the total protein content were estimated. Following exposure of PMA, the expression of the platelet membrane glycoprotein GPIIIa and thrombospondin and transferrin receptors was augmented in the three cell lines. The number of AgNORs shifted from 16.4 +/- 4.3, 24.4 +/- 2.5 and 13.6 +/- 3.1 for unstimulated cells to 20.0 +/- 5.3, 38.7 +/- 7.9 and 16.8 +/- 2.3 for PMA-treated DAMI, HEL and K562 cells, respectively. Furthermore, after treatment with PMA, the numbers of AgNORs clusters or nucleoles increased significantly to 179%, 238% and 154% of controls in DAMI, HEL and K562 cell lines, respectively. Finally, addition of PMA culture for four days, significantly increased the protein contents to 153%, 171% and 254% of controls for DAMI, HEL and K562 cell lines, respectively (p < 0.05 by t-test). In conclusion, the increase in the total protein content and in the number of AgNORs by PMA, suggests that PMA-induced-megakaryocyte polyploidization occurs by enhanced protein production.

Two new steroids with cytotoxicity from the marine sponge Dactylospongia elegans collected from the South China Sea. A new steroid, (3S,5R,9R,10S,13R,17R,20R,24S,22E)-ergosta-6,8,22-triene-3,25-diol (1), and its sulfonated analogue (2) together with a known one, 5α,8α-epidioxy-cholest-6-en-3β-ol (3) were isolated from the marine sponge Dactylospongia elegans collected from the South China Sea. The new structures including absolute configurations were established by the HRESIMS and 1D and 2D NMR analysis coupled with the X-ray crystal analysis. Both of 1 and 2 exhibited cytotoxicity against cancer cell line MCF-7 with IC50 values of 9.7 and 8.5 μM, respectively.

Synthesis and anticancer activity of oxindole derived imidazo[1,5-a]pyrazines. A series of oxindole derivatives of imidazo[1,5-a]pyrazines were prepared and confirmed by 1H NMR, mass and HRMS data. These compounds were evaluated for their anticancer activity against a panel of 52 human tumor cell lines derived from nine different cancer types: leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate and breast. Among them compound 7l showed significant anticancer activity with GI50 values ranging from 1.54 to 13.0 μM. Cell cycle arrest was observed in G0/G1 phase upon treatment of A549 cells with 6.5 μM (IC50) concentration of compound 7l and induced apoptosis. This was confirmed by Annexin V-FITC as well as DNA fragmentation analysis and interestingly this compound (7l) did not affect the normal cells.

Noise and neuronal populations conspire to encode simple waveforms reliably. Sensory systems rely on populations of neurons to encode information transduced at the periphery into meaningful patterns of neuronal population activity. This transduction occurs in the presence of intrinsic neuronal noise. This is fortunate. The presence of noise allows more reliable encoding of the temporal structure present in the stimulus than would be possible in a noise-free environment. Simulations with a parallel model of signal processing at the auditory periphery have been used to explore the effects of noise and a neuronal population on the encoding of signal information. The results show that, for a given set of neuronal modeling parameters and stimulus amplitude, there is an optimal amount of noise for stimulus encoding with maximum fidelity.

Two-field surface pattern control via marginally stable magnetorheological elastomers. The stability and post-bifurcation of a non-linear magnetoelastic film/substrate block is experimentally exploited to obtain active control of surface roughness. The non-intuitive interplay between magnetic field and elastic deformation owes to material and geometry selection, namely a ferromagnetic particle composite film bonded on a compliant passive foundation. Cooperation of the two otherwise independent loading mechanisms-mechanical pre-compression and magnetic field-allows one to bring the structure near a marginally stable state and then destabilize it with either magnetic or mechanical fields. We demonstrate for the first time that the critical magnetic field is a decreasing function of pre-compression and vice versa. The experimental results are then probed successfully with full-field finite element simulations at large strains and magnetic fields. The magnetoelastic coupling allows for reversible on/off control of surface wrinkling under adjustable critical magnetic and mechanical fields, thus this study constitutes a first step towards realistic active haptic and morphing devices.

Picrotoxin enhances latent extinction of conditioned fear. Male CD1 mice received 20 pairings of tone and footshock (FS) or tone alone in an arm of a Y-maze on Day 1. On Day 2 either extinction (tone alone) or no extinction was followed immediately by saline or picrotoxin (0.5 or 1.0 mg/kg ip). Nonextinguished groups received only saline or picrotoxin (1.0 mg/kg ip) on Day 2. Other groups received saline or picrotoxin (1.0 mg/kg) 2 hr after extinction. On Day 3 all mice were placed in the Y-maze (with doors to all 3 alleys open), and total alley entries during a 2-min test session were recorded. Day 1 FS training resulted in reduced alley entries during the test session. Day 2 extinction session significantly attenuated the effects of the FS training. Day 3 performance of mice given picrotoxin (1.0 but not 0.5 mg/kg) immediately postextinction was comparable to that of mice not given FS on Day 1. The findings suggest that picrotoxin enhanced extinction of conditioned fear.

Report of 24 cases of Listeria monocytogenes infection at the University of Miami Medical Center. To examine the epidemiological spectrum of human listeriosis at a large municipal hospital in Miami, we reviewed the cases of Listeria monocytogenes infection seen at the University of Miami Medical Center over a nine-year period (1986-94). Twenty-four patients (13 adults, 11 neonates) with bacteriologically proven Listeria monocytogenes infections were identified. The annual rate of listeriosis for the entire period 1986-1994 was 0.042 cases/1,000 hospital admissions. The rates of listeriosis during the first half of the study period (0.0628/1,000 admissions) were three times higher than the rates observed during the second half of the study (0.0214/1,000 admissions). Four (57%) of the 7 adult cases of listeriosis seen after 1987 occurred in HIV-seropositive patients. Compared with the hospital population, the annual rates of listeriosis were several fold higher in patients post-renal transplant (4.65 cases/1,000 renal transplant-related admissions) and patients with HIV/AIDS (0.27 cases/1,000 HIV-related admissions). No deaths were recorded. The decline in the annual rate of listeriosis noted in our study parallels national trends recently reported by the Centers for Disease Control and Prevention.

A self-assembled CdSe QD-organogel hybrid: photophysical and thermoresponsive properties. A luminescent hybrid gel was prepared by incorporating organic ligand capped CdSe quantum dots (QDs) into a steroid-dimer derived organogel. Photophysical measurements and electron microscopy studies allowed us to understand the nature of the hybrid. Detailed analysis of the excited state dynamics of the hybrid was carried out using a kinetic decay model. The luminescence of the QDs in the hybrid was unaltered by taking it through a gel-sol-gel cycle induced by thermal stimuli. We believe that the results obtained herein provide a route to develop a thermoresponsive device for practical applications, because of the spatial assembly between soft organic scaffolds and colloidal QDs.

Pregnancy rates for grade 2 embryos following administration of synthetic GnRH at the time of transfer in embryo-recipient cattle. To succeed with pregnancy a bovine embryo must overcome the luteolytic mechanism and achieve recognition of pregnancy. It is understood that well developed embryos are more successful in achieving recognition of pregnancy than poorly developed ones. Attempts have been made to assist this recognition of pregnancy by utilising a number of hormonal supplements with varying levels of success. A study was undertaken to test the hypothesis that supplementation with synthetic GnRH at the time of transfer of Grade 2 embryos will enhance pregnancy rates in recipients receiving this category of embryo. Pairs of fresh and frozen Grade 2 embryos (n = 38) from 34 donor animals were allocated to the trial. Thirty eight pairs of recipients were used and one of each pair was randomly assigned to receive treatment on the day of embryo transfer (Day 7) with 5 ml of gonadorelin, containing a synthetic gonadotrophin releasing hormone, 0.1 mg/ml. Pregnancy diagnosis was carried out from 42 days post-transfer by either palpation per rectum or ultrasound scanning. Treatment, embryo processing, side of transfer, parity of recipient, breed of recipient and breed of donor dam showed no statistically significant effect on pregnancy rate. The overall pregnancy rate in this study was within commercially accepted limits for Grade 2 embryos at 38.2%. The pregnancy rates were 34.2 and 42.1% for the GnRH-treated and control groups, respectively and were not significantly different at P < 0.05. The failure of this treatment to improve pregnancy rates could be due to its effect being transitory therefore allowing subsequent pregnancy loss. The timing of the treatment post-transfer, treatment dose and potency of the GnRH analogue may also play a role in this. Further study is required to determine the hormonal or follicular status of prospective candidates for treatment before applying this as a whole herd regime.

Memory impairments following lesions to the mammillary region of the rat. The contribution of the mammillary region to learning and memory was investigated. It was demonstrated that lesions of this region impair performance on tasks that require memory for spatial information but that the deficit depends both on the amount of damage within the region and the difficulty of the task. A dissociation in the effect of such lesions on performance of comparable spatial and non-spatial memory tasks was shown. In contrast to the deficits observed on spatial memory tasks, the acquisition and retention of a complex non-spatial memory task was not impaired after extensive damage to the mammillary region. Such lesions also did not impair performance in a conditioned taste aversion task. These experiments suggest that the mammillary region may be selectively involved in spatial learning and memory.

Multiresolution local contrast enhancement of x-ray images for poultry meat inspection. A multiresolution-analysis-based local contrast transform is proposed to enhance local structures in x-ray images. The local contrast is defined as a ratio of the local intensity variation to the local mean. With wavelet multiresolution decomposition, the detail coefficients and approximation coefficients are interpreted, respectively, as local variations and local averages in virtue of the localization property of wavelet transform. Based on the local contrast transform, an algorithm is developed to modify coefficients before wavelet synthesis. An across-scale local contrast is obtained when the scale associated with the local variation is different from that of the local mean. The nonlinearity and local adaptiveness properties of local contrast transform result in structural enhancement in local dark regions in the reconstructed images. We applied this technique to deboned poultry inspection using x-ray images. Because of its high x-ray absorption, a foreign inclusion appears as a low-intensity object in an x-ray image, thus resulting in contrast enhancement in the reconstructed multiresolution images.

Immunohistochemical characterization of the cutaneous cellular infiltrate in different areas of chronic leg ulcers. Current understanding of the immunological mechanisms involved in the pathogenesis of venous leg ulcers is insufficient. In this study the cellular composition of skin biopsies taken from the center, the edge, and 2 cm distant from the edge of venous leg ulcers was characterized quantitatively by immunohistochemical staining. In the epidermis the mean numbers of Langerhans cells (CD1a+) were four times lower at the edge of the ulcer compared to clinically intact epidermis 2 cm distant from the edge. In the dermis a statistically significant increase in the mean numbers of macrophages (CD68+) and neutrophils (NP57+) from the distant area towards the center of the ulcer was observed. No significant differences were observed in the distribution of T cells nor in the ratio of CD4+/CD8+ T-cell subsets between the different regions of the ulcer. About 30% of T lymphocytes were CD8+ in all microenvironments. The center and the edge of the ulcer were dominated by macrophages comprising 63% and 53% of the cells respectively, while T lymphocytes dominated the distant area. The area 2 cm distant from the edge was also heavily infiltrated by macrophages and neutrophils. B cells (CD22+) and NK cells (CD56+) were relatively rare in all areas, comprising less than 3% of the dermal infiltrate. In conclusion, local microenvironments each with a different cellular composition can be defined within venous leg ulcers.

Adriamycin-induced myocardial dysfunction in vitro is mediated by free radicals. The role of free radicals in adriamycin (Adr)-induced acute myocardial changes was examined by using different antioxidants. Exposure of papillary muscles to Adr (100 microM) in a tissue bath for 60 min reduced developed force by 42%, increased lipid peroxidation by 200%, and resulted in characteristic ultrastructural changes. Catalase (4 x 10(4) U/l), an enzyme effective in the hydrolysis of hydrogen peroxide (H2O2), was more effective in maintaining the developed force than mannitol (20 mM), a hydroxyl radical scavenger. A small protection of developed force seen with superoxide dismutase (1.2 x 10(5) U/l), a quencher of superoxide radical, was evident for the first 15 min only. Only catalase and mannitol showed significant protection against Adr-induced increase in lipid peroxidation. Ultrastructural changes due to Adr alone included mitochondrial swelling, intramitochondrial granules, vacuolization, and disruption of sarcomeres. All of these changes were reduced in the presence of both catalase and mannitol, whereas superoxide dismutase was without any effect. Complete structural or functional protection was not seen with any of the antioxidants used in the study. Although both H2O2 and hydroxyl radical appear to be involved in Adr-induced deleterious effects, data on developed force also indicate that H2O2 may have a major role in mediating the acute effects of Adr in vitro.

Investigating the impacts of DNA binding mode and sequence on thermodynamic quantities and water exchange values for two small molecule drugs. Doxorubicin and nogalamycin are antitumor antibiotics that interact with DNA via intercalation and threading mechanisms, respectively. Because the importance of water, particularly its impact on entropy changes, has been established in other biological processes, we investigated the role of water in these two drug-DNA binding events. We used the osmotic stress method to calculate the number of water molecules exchanged (Δnwater), and isothermal titration calorimetry to measure Kbinding, ΔH, and ΔS for two synthetic DNAs, poly(dA·dT) and poly(dG·dC), and calf thymus DNA (CT DNA). For nogalamycin, Δnwater<0 for CT DNA and poly(dG·dC). For doxorubicin, Δnwater>0 for CT DNA and Δnwater<0 for poly(dG·dC). For poly(dA·dT), Δnwater~0 with both drugs. Net enthalpy changes were always negative, but net entropy changes depended on the drug. The effect of water exchange on the overall sign of entropy change appears to be smaller than other contributions.

Cutaneous ciliated cysts. We studied 11 patients with a cutaneous cyst lined by a simple columnar ciliated epithelium. All of the patients were women in the second or third decade of life. Each had only a single lesion, located on the lower extremity. Clinical examination showed a cyst without specific identifying characteristics. The cyst is considered benign, because of the high degree of differentiation and lack of cellular atypia. The origin of the cyst is unknown. We favor the theory of sequestration and migration over that of transplantation or metaplasia.

Carboxyhemoglobin, cotinine, and thiocyanate assay compared for distinguishing smokers from non-smokers. We compared cotinine, carboxyhemoglobin, and thiocyanate concentrations in blood sampled from 187 cigarette smokers and 181 non-smokers. All three differed significantly between smokers and non-smokers. Cotinine performed best as a test for assessing smoking status, with a sensitivity of 98% as compared with 94% for carboxyhemoglobin and 80% for thiocyanate, all at a specificity of 95%. These differences were statistically significant. Results by none of these three methods correlated well with number of cigarettes smoked per day.

Design and fabrication of a bending rotation fatigue test rig for in situ electrochemical analysis during fatigue testing of NiTi shape memory alloy wires. The current investigation proposes a novel method for simultaneous assessment of the electrochemical and structural fatigue properties of nickel-titanium shape memory alloy (NiTi SMA) wires. The design and layout of an in situ electrochemical cell in a custom-made bending rotation fatigue (BRF) test rig is presented. This newly designed test rig allows performing a wide spectrum of experiments for studying the influence of fatigue on corrosion and vice versa. This can be achieved by performing ex situ and∕or in situ measurements. The versatility of the combined electrochemical∕mechanical test rig is demonstrated by studying the electrochemical behavior of NiTi SMA wires in 0.9% NaCl electrolyte under load. The ex situ measurements allow addressing various issues, for example, the influence of pre-fatigue on the localized corrosion resistance, or the influence of hydrogen on fatigue life. Ex situ experiments showed that a pre-fatigued wire is more susceptible to localized corrosion. The synergetic effect can be concluded from the polarization studies and specifically from an in situ study of the open circuit potential (OCP) transients, which sensitively react to the elementary repassivation events related to the local failure of the oxide layer. It can also be used as an indicator for identifying the onset of the fatigue failure.

Phase I evaluation of therapy with four schedules of 5-fluorouracil by continuous infusion combined with recombinant interferon alpha. The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of 5-fluorouracil (5-FU) when administered concurrently with recombinant IFN-alpha using four continuous infusion (CI) dosing schedules of 5-FU. Forty-five patients with advanced or refractory cancers were treated with 5-FU by CI, plus IFN during the infusion only, by one of four schedules: schedule A: 24-h 5-FU infusion repeated weekly, 9 x 10(6) units IFN x 2 doses weekly; schedule B: 48-h 5-FU infusion repeated weekly, 9 x 10(6) units IFN x 4 doses weekly; schedule C: 5-day 5-FU infusion repeated every 3 weeks, 9 x 10(6) units IFN three times weekly; and schedule D: 21-day 5-FU infusion, repeated after 7 days off therapy, 9 x 10(6) units IFN three times weekly. At least three patients were treated at all dose levels. Doses of 5-FU were escalated to the next level if less than one half of the patients at a given level developed grades 2-4 toxicity. The maximum tolerated dose for 5-FU was 2150 mg/m2/week for schedule A (24-h CI), 2350 mg/m2/week for schedule B (48-h CI), 750 mg/m2/day for schedule C (5-day CI), and 175 mg/m2/day for schedule D (21-day CI). Median delivered dose intensities at these levels were 1788 mg/m2/week for schedule A, 2192 mg/m2/week for schedule B, 1250 mg/m2/week for schedule C, and 593 mg/m2/week for schedule D. The dose-limiting toxicities were hematological and gastrointestinal (stomatitis, diarrhea, nausea, anorexia) for schedules A and B and gastrointestinal (mostly stomatitis) for schedules C and D. Severe fatigue due to IFN was rare. Responses correlated with toxicity >/= grade 2, but not with increased dose intensity. Responses were noted in several tumor types on schedules A, B, and D. 5-FU can be combined with IFN using 24- and 48-h high-dose and long-term low-dose CI schedules, with large differences in dose intensity at maximum tolerated dose. Shorter infusions produce less mucosal and more hematological toxicity. Tumor responses were seen on both short- and long-term CI schedules. Future studies can establish the efficacies of these new schedules of 5-FU/IFN administration in specific tumor types.

Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome. We have investigated the involvement of the MAPK signaling pathway in increased androgen biosynthesis and CYP17 gene expression in women with polycystic ovary syndrome (PCOS). A comparison of MAPK kinase (MEK1/2) and ERK1/2 phosphorylation in propagated normal and PCOS theca cells, revealed that MEK1/2 phosphorylation was decreased more than 70%, and ERK1/2 phosphorylation was reduced 50% in PCOS cells as compared with normal cells. Infection with dominant-negative MEK1 increased CYP17 mRNA and dehydroepiandrosterone (DHEA) abundance, whereas constitutively active MEK1 reduced DHEA production and CYP17 mRNA abundance. Similarly, the MEK inhibitor, PD98059, increased CYP17 mRNA accumulation and CYP17 promoter activity to levels observed in PCOS cells. Remarkably, in theca cells maintained in the complete absence of insulin, ERK1/2 phosphorylation was decreased in PCOS theca cells as compared with normal theca cells, and CYP17 mRNA and DHEA synthesis were increased in PCOS theca cells. These studies demonstrate that in PCOS cells reduced levels of activated MEK1/2 and ERK1/2 are correlated with increased androgen production, irrespective of the insulin concentration. These findings implicate alterations in the MAPK pathway in the pathogenesis of excessive ovarian androgen production in PCOS.

Implementation of laparoscopy surgery training via simulation in a low-income country. The objective of this study was to evaluate laparoscopy training using pelvitrainers for gynaecological surgeons in a low-income country. The study was carried out in Madagascar from April 2016 to January 2017. The participants were gynaecological surgeons who had not previously performed laparoscopy. Each surgeon was timed to evaluate the execution times of four proposed exercises, based on the fundamentals of laparoscopic surgery (FLS) programme's skills manual, as follows: exercise 1, involving a simple object transfer; exercises 2 and 3, comprising complex object transfers; and exercise 4, a precision cutting exercise. The 8-month training and evaluation programme was divided into different stages, and the four following evaluations were compared: a pretest (T0), assessment at the end of the first training (T1) and auto-evaluation at 2 months (T2) and 8 months (T3). Eight participants were included. The median time was significantly reduced (P<0.05) at each evaluation for exercises 1, 2 and 4 compared to the pretest. For exercise 3, there was no difference between T0 and T1 (P=0.07). After 8 months of training, all participants progressed in all exercises. Our study showed that it is possible and beneficial to develop a programme for teaching laparoscopic surgery in low-income countries before providing the necessary equipment.

[Effectiveness of the use of momensin for cattle fattening]. Two groups of fattened bulls (125 bulls in each group) were investigated for the effect of monensin (125-175 mg per head/day) on live weight gains and for the effectiveness of monensin administration. After 160 days of fattening, the average daily weight gain was 713 g in the control group and 800 g in the monensin-treated group (an increase by 12.2%). After 11 months of fattening the daily weight gain was 702 g in the control group and 768 g in the monensin-treated group (an increase by 9.4%). Besides the control and experimental groups, monensin was administered to 1500 head of fattened cattle on the whole. Greater differences in the daily live weight gains (higher gains in the monensin-treated animals) were recorded mainly in the period when the feed ration contained high-quality bulk feeds. When the bulls were given feeds of lower quality (mainly late in winter), the differences in the average daily live weight gains decrease and the effect of monensin treatment is not so great. Throughout the fattening period, monensin had a favourable influence on the live weight gains and its use was economically advantageous.

The role of business process reengineering in health care. Business process reengineering (BPR) is a management philosophy capturing attention in health care. It combines some new, old, and recycled management philosophies, and, more often than not, is yielding positive results. BPR's emphasis is on the streamlining of cross-functional processes to significantly reduce time and/or cost, increase revenue, improve quality and service, and reduce risk. Therefore, it has many applications in health care. This article provides an introduction to the concept of BPR, including the definition of BPR, its origin, its champions, and factors for its success.

Marfan Syndrome: A Clinical Update. Marfan syndrome is a connective tissue disorder that can affect many organ systems. Affected patients present with orthopaedic manifestations of the syndrome during all phases of life. Pain caused by musculoskeletal abnormalities often requires definitive orthopaedic treatment. Orthopaedic surgeons must understand the phenotypes of Marfan syndrome so they can recognize when screening is warranted and can appropriately address the skeletal manifestations. Through medical advancements, patients with Marfan syndrome are living longer and more active lives. Knowledge of the latest diagnostic criteria for the disorder, as well as of advances in understanding the skeletal phenotype, clinical trials of medication therapy, and lifestyle considerations is important for orthopaedic surgeons who treat these patients because these clinicians often are the first to suspect Marfan syndrome and recommend screening.

New perspectives on mechanisms of sound generation in songbirds. The physical mechanisms of sound generation in the vocal organ, the syrinx, of songbirds have been investigated mostly with indirect methods. Recent direct endoscopic observation identified vibrations of the labia as the principal sound source. This model suggests sound generation in a pulse-tone mechanism similar to human phonation with the labia forming a pneumatic valve. The classical avian model proposed that vibrations of the thin medial tympaniform membranes are the primary sound generating mechanism. As a direct test of these two hypotheses we ablated the medial tympaniform membranes in two species (cardinal and zebra finch) and found that both were still able to phonate and sing without functional membranes. Small changes in song structure (harmonic emphasis, frequency control) occurred after medial tympaniform membrane ablation and suggest that the medial tympaniform membranes play a role in adjusting tension on the labia. Such a role is consistent with the fact that the medial tympaniform membranes are directly attached to the medial labia. There is no experimental support for a third hypothesis, proposing an aerodynamic model for generation of tonal sounds. Indirect tests (song in heliox atmosphere) as well as direct (labial vibration during tonal sound) measurements of syringeal vibrations support a vibration-based sound-generating mechanism even for tonal sounds.

Pectin modifications: a review. In recent years, the interest in studying modification of pectin has increased. A number of hydroxyl and carboxyl groups distributed along the backbone as well as a certain amount of neutral sugars presented as side chains make pectin capable of preparing a broad spectrum of derivatives. By forming pectin derivatives, their properties may be modified and some other new functional properties may be created. This article attempts to review the information about various methods used for pectin modification, including substitution (alkylation, amidation, quaternization, thiolation, sulfation, oxidation, etc.), chain elongation (cross-linking and grafting) and depolymerization (chemical, physical, and enzymatic degradation). Characteristics and applications of some pectin derivatives are also presented. In addition, the safety and regulatory status of pectin and its derivatives were reviewed.

The mechanism of facial sweating and cutaneous vascular responses to painful stimulation of the eye. The vascular response in the forehead and cheeks to irritating the eye with soapy water was measured in 15 normal subjects. Electrodermal activity, which reflects sweating, was also measured from both sides of the forehead. The mechanism of the response was studied in 15 patients with a unilateral lesion of the facial nerve blocking parasympathetic outflow. Pulse amplitude usually increased briefly on both sides of the forehead after the soap was placed in the eye; the response persisted for several minutes on the ipsilateral side after the soap had been washed from the eye. A facial nerve lesion blocked the vascular response on the lesioned side to stimulation of either eye. No consistent change in pulse amplitude was recorded from the cheeks, although a response was observed in a few subjects. Electrodermal responses to ocular irritation were generally larger on the ipsilateral than contralateral side of the forehead; in patients with facial palsy, electrodermal responses were greater on the normally innervated side than on the lesioned side. The findings suggest that irritating the eye induces a trigeminal-parasympathetic vasodilator reflex and local sweating. The restricted distribution of the response indicates that separate parasympathetic vasodilator reflexes might operate for each division of the trigeminal nerve.

Effects of phospholipase A2 and its hydrolytic products on alveolar epithelial permeability and elastase-induced emphysema. To cause emphysema, proteases that are instilled into the air spaces must first be transported across the alveolar epithelium, a barrier that is normally quite impermeable to macromolecules. It was postulated that phospholipase A2 (PLA2) exposure would potentiate porcine pancreatic elastase (PPE)-induced epithelial solute permeability in a manner similar to that which was previously shown with lysophosphatidylcholine (lysoPC), a naturally occurring, membrane-perturbing agent that is formed principally through the hydrolysis of phosphatidylcholine by PLA2. Groups of hamsters were given intratracheal injections of PLA2 (0.3 units) or one of the expected hydrolytic products of PLA2 in equimolar concentrations, lysoPC (135 micrograms), arachidonic acid (AA) (100 micrograms), or palmitic acid (PA) (70 micrograms) with or without PPE (4 units). Epithelial permeability surface area products (PS) of the alveolar epithelium to [14C]sucrose and 125I-labeled neutral dextran (MW, 70,000) were measured in isolated perfused lungs 30 min after instillation, and emphysema severity was assessed at 3 wk by pressure-volume relationships and by mean linear intercepts. Additionally, the effects of lysoPC, PA, and AA on the functions of PPE and alpha 1-antiprotease (alpha 1 PI) in vitro were evaluated. Sucrose and dextran 70 PS differed significantly from controls only in those groups of hamsters that received PLA2 of lysoPC (p less than 0.05). LysoPC and PLA2 also potentiated the severity of PPE-induced emphysema to a similar degree (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Segmental enhancement on breast MR images: differential diagnosis and diagnostic strategy. The histopathological variations of segmental enhancement on breast magnetic resonance imaging (MRI) were investigated, with the aim of identifying imaging characteristic clues to their differential diagnosis. We reviewed 70 breast MRI examinations demonstrating segmental enhancement, classified them based on their histopathology, and assessed their MRI findings as follows: (1) confluent or not confluent, (2) late enhancement pattern, and the absence or presence of (3) clustered ring enhancements and (4) surrounding high signal intensity (SI) on T2-weighted imaging. Thirteen lesions (18.5%) were benign, eight (11.5%) were high risk, 25 (36%) were ductal carcinoma in situ (DCIS) and 24 (34%) were infiltrating mammary carcinomas (IMC). Clustered ring enhancements were demonstrated in 74% of malignancies (high risk, DCIS and IMC) but no benign lesions (P=0.0001). The surrounding high SI on T2-weighted imaging was seen in four of five IMC with marked lymphatic involvement. Clustered ring enhancement was not demonstrated in six of seven IMC of tubular and/or lobular types. Segmental enhancement was seen in not only DCIS but also IMC, high-risk and benign lesions. Clustered ring enhancement and surrounding high SI on T2-weighted imaging were clues to their differential diagnosis and helpful to decide their diagnostic strategy.

Dual-axis joint-Fourier-transform correlator. Theory and experimental results of a dual-axis joint-Fourier-transform (JFT) optical correlator are reported. The correlator is capable of recording large-carrier-frequency holograms of signals with a large space-bandwidth product. Experimental demonstration is carried out using the thermoplastic device as the JFT hologram-recording medium.

Role of the supplementary motor area in auditory sensory attenuation. Self-generated tones elicit smaller brain responses as compared to externally generated tones. This phenomenon known as sensory attenuation has been explained in terms of an internal forward model in which the brain predicts the upcoming events and thereby attenuates the sensory processing. Such prediction processes have been suggested to occur via an efference copy of the motor command that is sent from the motor system to the lower order sensory cortex. However, little is known about how the prediction is implemented in the brain's network organization. Because the supplementary motor area (SMA) is a primary brain structure of the motor system, we attributed the implementation of the prediction to the SMA. To address this question, we examined generative network models for auditory ERPs. ERPs were evoked by either a self-generated or externally generated tone, while subjects were paying attention to their motor action or to the tone. The tone itself was the same throughout all conditions. The network models consisted of three subsets embedding alternative hypotheses of the hierarchical structures: (1) auditory fields of the temporal lobe, (2) adding connections to the SMA, and (3) adding prediction signal to the SMA. The model comparison revealed that all ERP responses were mediated by the network connections across the auditory cortex and the SMA. Importantly, the prediction signal to the SMA was required when the tone was self-generated irrespective of the attention factor, whereas the externally generated tone did not require the prediction. We discussed these results in the context of the predictive coding framework.

Luminescent properties of BaAl12O19:Tb, Dy phosphors prepared by sol-gel method. BaAl12O19:Tb, Dy phosphor was prepared by the sol-gel technique using citric acid as a complextant. XRD was used to characterize the relevant crystallization behavior of the phosphor. The luminescence properties and energy transfer between Tb3+ and Dy3+ were investigated. The results revealed that energy transfer exists between Dy3+ and Tb3+ at appropriate Tb3+ concentrations. The emission intensity of Tb3+ increases and energy transfer happens from Dy3+ to Tb3+ ions at the higher content of Tb3+ when Tb3+ and Dy3+ ions were co-doped. BaAl12O19 phosphors doped with Tb3+ or Dy3+ ions only were studied to compared with BaAl12O19:Tb, Dy phosphors. The results showed that the maximum excitation peak of BaAl12O19:Tb is 240 nm and the emission spectrum consists of four peaks at 490, 545, 590, and 625 nm, originating from 5D4 --> 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ ion, respectively. The excitation peaks of BaAl12O19:Dy are at 291, 324 nm and the emissions of Dy3+ are at 370, 447 and 578 nm, originating from 4F9/2 --> 6P5/2, 4F9/2 --> 6H15/2 and 4F9/2 --> 6H13/2 transitions of Dy3+ ion, respectively.

The difference between children and adults in the onset of post-traumatic epilepsy. In order to clarify the difference between children and adults in the onset of post-traumatic epilepsy, 96 outpatients of our clinic were investigated statistically. The subjects comprising 40 children and 56 adults were followed up for more than three years. The latency of the children i.e., the interval between a head injury and the onset of epilepsy, was longer than that of the adults. The 95%-confidential interval classified by age group indicated that the upper limits of latency of the group under the age of two, those between three and 14 and those aged more than 15 were about 13, six and three years, respectively. We concluded that children with a severe head injury should be followed up until age 20 and adults for about three years.

ADAM33 protein expression and the mechanics of airway smooth muscle cells are highly correlated in ovalbumin-sensitized rats. A disintegrin and metalloproteinase 33 (ADAM33) has been identified as an asthma susceptibility gene; however, the role of ADAM33 in the pathogenesis and progression of asthma remains to be elucidated. As ADAM33 is predominantly expressed in airway smooth muscle cells (ASMCs), it is feasible to investigate whether ADAM33 protein expression is correlated with ASMC mechanics that are ultimately responsible for airway hyperresponsiveness in asthma. To determine this, Sprague Dawley rats were sensitized with ovalbumin (OVA) for up to 12 weeks to simulate asthma symptoms. Subsequently, ASMCs were isolated from the rats and cultured in vitro. The protein expression of ADAM33 and cytoskeletal proteins (including F‑actin and vinculin), cell stiffness and contractility, as well as traction force were measured. The results demonstrated that compared with the non‑sensitized rats, the protein expression of ADAM33 in ASMCs from the OVA‑sensitized rats increased in a time‑dependent manner, reaching a maximum level at 4 weeks of sensitization and gradually subsiding as OVA sensitization continued (P<0.001). The cell stiffness, traction force and expression of vinculin and F‑actin changed similarly, resulting in a positive correlation with ADAM33 protein expression (Pearson's correlation coefficient, 0.864, 0.716, 0.774 and 0.662, respectively; P=0.1‑0.3). The in vivo results of OVA‑induced ADAM33 protein expression and its association with the mechanics of ASMCs suggested that ADAM33 is a mediator of ASMC dysfunction in asthma, and may provide a rationale for the therapeutic targeting of ADAM33 in the treatment of asthma.

Increased beat-to-beat variability during uterine contractions: a common association in uncomplicated labor. A computerized system was used during labor to provide a quantitative and objective analysis of fetal heart rate, beat-to-beat variability, and uterine contractions. Twenty-nine healthy pregnant women at term participated in this study. Each woman was studied for a 40-minute period during the active phase of spontaneous labor. The results indicate that beat-to-beat variability rises from a value of 4.62 +/- 1.11 (mean +/- SD) between contractions to 6.86 +/- 1.53 during contractions. This rise is significant (p less than 0.01). At the same time, changes in fetal heart rate are small, inconsistent, and not significant. We conclude that an increased beat-to-beat variability is commonly associated with uterine contractions in normal fetuses. This increase is probably due to mild hypoxia caused by decreased perfusion of the placenta and to increased vagal tone caused by fetal head compression.

Inflammation and infection in clinical stroke. Stroke has enormous clinical, social, and economic implications, and demands a significant effort from both basic and clinical science in the search for successful therapies. Atherosclerosis, the pathologic process underlying most coronary artery disease and the majority of ischemic stroke in humans, is an inflammatory process. Complex interactions occur between the classic risk factors for atherosclerosis and its clinical consequences. These interactions appear to involve inflammatory mechanisms both in the periphery and in the CNS. Central nervous system inflammation is important in the pathophysiologic processes occurring after the onset of cerebral ischemia in ischemic stroke, subarachnoid hemorrhage, and head injury. In addition, inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia. Peripheral infection and inflammatory processes are likely to be important in this respect. Thus, it appears that inflammation may be important both before, in predisposing to a stroke, and afterwards, where it is important in the mechanisms of cerebral injury and repair. Inflammation is mediated by both molecular components, including cytokines, and cellular components, such as leukocytes and microglia, many of which possess pro- and/or antiinflammatory properties, with harmful or beneficial effects. Classic acute-phase reactants and body temperature are also modified in stroke, and may be useful in the prediction of events, outcome, and as therapeutic targets. New imaging techniques are important clinically because they facilitate dynamic evaluation of tissue damage in relation to outcome. Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory. Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems. Considerable opportunities therefore exist for the development of novel therapies. It seems likely that drugs currently used in the treatment of stroke, such as aspirin, statins, and modulators of the renin-angiotensin-aldosterone system, act at least partly via antiinflammatory mechanisms. Newer approaches have included antimicrobial and antileukocyte strategies. One of the most promising avenues may be the use of cytokine antagonism, for example, interleukin-1 receptor antagonist.

Nanoparticle-tuned self-organization of a bulk heterojunction hybrid solar cell with enhanced performance. We demonstrate here that the nanostructure of poly(3-hexylthiophene) and [6,6]-phenyl-C61-butyric acid methyl ester (P3HT/PCBM) bulk heterojunction (BHJ) can be tuned by inorganic nanoparticles (INPs) for enhanced solar cell performance. The self-organized nanostructural evolution of P3HT/PCBM/INPs thin films was investigated by using simultaneous grazing-incidence small-angle X-ray scattering (GISAXS) and grazing-incidence wide-angle X-ray scattering (GIWAXS) technique. Including INPs into P3HT/PCBM leads to (1) diffusion of PCBM molecules into aggregated PCBM clusters and (2) formation of interpenetrating networks that contain INPs which interact with amorphous P3HT polymer chains that are intercalated with PCBM molecules. Both of the nanostructures provide efficient pathways for free electron transport. The distinctive INP-tuned nanostructures are thermally stable and exhibit significantly enhanced electron mobility, external quantum efficiency, and photovoltaic device performance. These gains over conventional P3HT/PCBM directly result from newly demonstrated nanostructure. This work provides an attractive strategy for manipulating the phase-separated BHJ layers and also increases insight into nanostructural evolution when INPs are incorporated into BHJs.

Current CML therapy: progress and dilemma. Rarely has progress in treatment of leukemia been as dramatic and convincing as with the BCR-ABL tyrosine kinase inhibitor imatinib.(1) Imatinib induces remissions of CML as fast as hydroxyurea, achieves rates of cytogenetic remissions that by far exceed those induced by interferon alpha and has a toxicity profile as favourable as that of hydroxyurea and much superior to that of interferon alpha.(2) In addition, the causal approach of this new drug, which may well serve as a model for new treatment modalities in other neoplasias is reassuring.

Breakdown in the temporal and spatial organization of spontaneous brain activity during general anesthesia. Which temporal features that can characterize different brain states (i.e., consciousness or unconsciousness) is a fundamental question in the neuroscience of consciousness. Using resting-state functional magnetic resonance imaging (rs-fMRI), we investigated the spatial patterns of two temporal features: the long-range temporal correlations (LRTCs), measured by power-law exponent (PLE), and temporal variability, measured by standard deviation (SD) during wakefulness and anesthetic-induced unconsciousness. We found that both PLE and SD showed global reductions across the whole brain during anesthetic state comparing to wakefulness. Importantly, the relationship between PLE and SD was altered in anesthetic state, in terms of a spatial "decoupling." This decoupling was mainly driven by a spatial pattern alteration of the PLE, rather than the SD, in the anesthetic state. Our results suggest differential physiological grounds of PLE and SD and highlight the functional importance of the topographical organization of LRTCs in maintaining an optimal spatiotemporal configuration of the neural dynamics during normal level of consciousness. The central role of the spatial distribution of LRTCs, reflecting temporo-spatial nestedness, may support the recently introduced temporo-spatial theory of consciousness (TTC).

The Scientific Illusion of Victor Burq (1822-1884). Victor Burq (1822-1884) is closely associated with a therapy named "burquism" by Jean-Martin Charcot, which was used in treating hysteria, especially hysteric anesthesia and paralysis, by applying metals, mainly copper, to affected zones. In 1876, Charcot, Luys, and Dumontpallier, commissioned by the Société de Biologie, issued 2 opinions validating the results obtained by Burq during the 25 years he dedicated to his research. From that point forward, the careers of these 3 famous physicians were lastingly reoriented toward the practice of hypnosis. This neo-mesmeric resurgence at the end of the nineteenth century can be considered the cause of an epistemological change that gave rise to "psychological medicine." During the repeated cholera epidemics in the mid-nineteenth century, Burq recommended preventive and corrective ingestion of copper, after observing that smelter workers were unaffected by the disease. The mechanisms of copper's anti-bacterial action have since been elucidated and legitimize Burq's anti-cholera campaign. Burq also advocated the ingestion of copper sulphate to treat diabetes. Current-day findings on intestinal microbiota and how these organisms influence blood sugar regulation support Burq's claims, considered far-fetched for many years.

Clinical reasoning and population health: decision making for an emerging paradigm of health care. Chronic conditions now provide the major disease and disability burden facing humanity. This development has necessitated a reorientation in the practice skills of health care professions away from hospital-based inpatient and outpatient care toward community-based management of patients with chronic conditions. Part of this reorientation toward community-based management of chronic conditions involves practitioners' understanding and adoption of a concept of population health management based on appropriate theoretical models of health care. Drawing on recent studies of expertise in physiotherapy, this article proposes a clinical reasoning and decision-making framework to meet these challenges. The challenge of population and community-based management of chronic conditions also provides an opportunity for physiotherapists to further clarify a professional epistemology of practice that embraces the kinds of knowledge and clinical reasoning processes used in physiotherapy practice. Three case studies related to the management of chronic musculoskeletal pain in different populations are used to exemplify the range of epistemological perspectives that underpin community-based practice. They illustrate the link between conceptualizations of practice problems and knowledge sources that are used as a basis for clinical reasoning and decision making as practitioners are increasingly required to move between the clinic and the community.

T wave morphology changes during hemodialysis. Risk stratification for sudden cardiac death in hemodialysis (HD) patients is an unmet clinical need. Non invasive electrophysiological testing is challenging in these patients due to their oscillating cardiovascular and electrolyte status induced by the intermittent HD treatment. We hypothesized that continuous electrocardiographic monitoring during their regular HD session can provide reproducible repolarisation profiles. Continuous 12-lead digital electrocardiographs (ECGs) were recorded during dialysis in stable patients and were repeated at two-week intervals for 5 times. QRS-to-T angle (TCRT), principal component analysis (PCA) ratio and T wave morphology dispersion (TMD) were calculated every 5s in overlapping 10-s ECG segments. Serum electrolytes and plasma parathyroid hormone (PTH) levels were measured prior to the first recording. There were 319 acceptable recordings from 76 hemodialysed patients. Repeated Measures Anova showed intra-subject reproducibility of all descriptors. Mean PCA ratio and TMD values increased through dialysis and their intradialytic change correlated with heart rate changes (r = 0.305, p = 0.007 and r = 0.287, p = 0.012, respectively). TCRT showed a variable response to HD and the intradialytic change correlated positively with PTH levels (r = 0.284, p = 0.023). Repolarisation descriptors demonstrate subject-specific dynamic profiles during HD. PTH has a role in dynamics of myocardial repolarisation. The potential clinical utility of continuous intradialytic ECGs for risk stratification purposes should be prospectively evaluated.

VEGF signalling: integration and multi-tasking in endothelial cell biology. The central role of VEGF (vascular endothelial growth factor A) in angiogenesis is dependent upon its ability to co-ordinately regulate multiple endothelial functions. The multifunctionality of VEGF at the cellular level results from its ability to initiate a diverse, complex and integrated network of signalling pathways via its major receptor, kinase-insert-domain-containing receptor (KDR). Activation of phospholipase C-gamma, protein kinase C, Ca(2+), ERK (extracellular-signal-regulated protein kinase), Akt, Src, focal adhesion kinase and calcineurin pathways has been implicated in mediating multiple VEGF functions, including survival, proliferation, migration, vascular permeability, tubulogenesis, NO and prostanoid synthesis, and gene expression. NO and prostanoids in turn play paracrine and autocrine roles in linking post-receptor signalling to biological functions. Integration between biologically important signalling cascades occurs at several points. Akt and ERK, for example, are key junction points linking together signal transduction involved in survival and NO generation, and proliferation and prostanoid biosynthesis. Together, the multiplicity, functional versatility and integration of VEGF signalling provide a useful framework for understanding the mechanisms underlying the endothelial biological response to this key factor.

Energetics of target peptide recognition by calmodulin: a calorimetric study. Calmodulin is a small protein involved in the regulation of a wide variety of intracellular processes. The cooperative binding of Ca2+ to calmodulin's two Ca2+ binding domains induces conformational changes which allow calmodulin to activate specific target enzymes. The association of calmodulin with a peptide corresponding to the calmodulin binding site of rabbit smooth muscle myosin light chain kinase (smMLCKp) was studied using isothermal titration microcalorimetry. The dependence of the binding energetics on temperature, pH, Ca2+ concentration, and NaCl concentration were determined. It is found that the binding of calmodulin to smMLCKp proceeds with negative changes in enthalpy (deltaH), heat capacity (deltaCp), and entropy (deltaS) near room temperature, indicating that it is an enthalpically driven process that is entropically unfavorable. From these results it is concluded that the hydrophobic effect, an entropic effect which favors the removal of non-polar protein groups from water, is not a major driving force in calmodulin-smMLCKp recognition. Although a large number of non-polar side-chains are buried upon binding, these stabilize the complex primarily by forming tightly packed van der Waals interactions with one another. Binding at acidic pH was studied in order to assess the contribution of electrostatic interactions to binding. It is found that moving to acidic pH results in a large decrease in the Gibbs free energy of binding but no change in the enthalpy, indicating that electrostatic interactions contribute only entropically to the binding energetics. The accessible surface area and atomic packing density of the calmodulin-smMLCKp crystal structure are analyzed, and the results discussed in relation to the experimental data.

The course of fibrinolytic proteins in children with malignant bone tumours. To evaluate the role of fibrinolytic and proteolytic proteins in children and adolescents suffering from Ewing sarcoma or osteosarcoma with respect to postoperative complications and late outcome, a prospective two-arm two-centre study was conducted. Plasminogen, plasminogen activator inhibitor (PAI)-1, tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) were investigated in the pre-surgical period and in the postoperative follow-up period in children suffering from Ewing sarcoma (ES; n = 36) or osteosarcoma (OS; n = 39). In addition, the factor V mutation (FV) Q506, protein C, protein S, antithrombin and lipoprotein (a) were determined. All children received LMWH (EnoxaparinR) 1 mg/kg s.c. once daily over a period of 6 weeks to 3 months. Besides a short-lasting increase of PAI-1 in patients with OS on day 1 and in children with Es on day 14, a small and significant but clinically irrelevant difference was found on days 7-10 for plasminogen, t-PA and u-PA. No thromboembolic complications occurred in patients treated with LMWH and having a prothrombotic genetic risk factor. Within one year of surgery 7 out of 36 patients with ES and 5 out of 39 children with OS showed a relapse of their disease. Prior to the first local tumour therapy, 5 out of 7 children with ES and relapse had elevated u-PA concentrations compared with 2 out of 5 children in the OS group. No such differences were found for PAI-1- or t-PA antigen. The role of u-PA as a possible follow-up marker for a poorer outcome in children with ES should be evaluated in a prospective multicentre study.

FhuF, part of a siderophore-reductase system. FhuF is a cytoplasmic 2Fe-2S protein of Escherichia coli loosely associated with the cytoplasmic membrane. E. coli fhuF mutants showed reduced growth on plates with ferrioxamine B as the sole iron source, although siderophore uptake was not defective in transport experiments. Removal of iron from coprogen, ferrichrome, and ferrioxamine B was significantly lower in fhuF mutants compared to the corresponding parental strains, which suggested that FhuF is involved in iron removal from these hydroxamate-type siderophores. A redox potential E(1/2) of -310 +/- 25 mV relative to the normal hydrogen electrode was determined for FhuF by EPR redox titration; this redox potential is sufficient to reduce the siderophores coprogen and ferrichrome. Mössbauer spectra revealed that FhuF in its [Fe(2+)-Fe(3+)] state is also capable of direct reduction of ferrioxamine B-bound ferric iron, thus proving its reductase function. This is the first report on a bacterial siderophore-iron reductase which in vivo seems to be specific for a certain group of hydroxamates.

Regional bone loss following femoral neck fracture: A comparison between cemented and cementless hemiarthroplasty. The aim of this prospective, randomised study was to measure and evaluate regional bone mineral changes and clinical results following the use of cemented and cementless hemiarthroplasty (HA) for treatment of femoral neck fracture in elderly patients. The study comprised 60 patients, 30 with cemented HA (group A) and 30 with cementless HA (group B). All patients underwent osteodensitometry of the contralateral hip, lumbar spine and bilateral distal femur. Dual-energy x-ray absorptiometry (DEXA) was scheduled at 1 month, 6 months and 1 year after surgery. Harris Hip Score (HHS) was used for functional assessment. Overall mortality rate was 20.3% within 1 year after surgery. There were no significant differences in morbidity, mortality and hospital stay between the two groups of patients. The implantation of cemented prosthesis took statistically significantly longer than that of cementless prosthesis (79.03±3.59 vs 68.02±5.97min; p=0.00). Functional score in patients treated with cemented HA was significantly higher compared with those with cementless HA. There was a trend of less intensive reduction of bone mineral density (BMD) in regions of interest of the lumbar spine and ipsilateral distal femur in patients with cemented HA (group A), whereas bone loss was less pronounced for the contralateral hip and distal femur in patients treated with cementless HA (group B). Management of displaced femoral neck fractures in elderly patients with cemented and cementless HA provides a comparable outcome with regard to morbidity and mortality; however, functional outcome of patients treated with cementless HA tends to be lower. There is less intensive BMD reduction in lumbar spine and ipsilateral distal femur in patients treated with cemented HA, whereas BMD reduction in patients treated with cementless HA is more likely to be less intensive in contralateral hip and distal femur.

A methylene blue-mediated enzyme electrode for the determination of trace mercury(II), mercury(I), methylmercury, and mercury-glutathione complex. A methylene blue-mediated enzyme biosensor has been developed for the detection of inhibitors including mercury(II), mercury(I), methylmercury, and mercury-glutathione complex. The inhibition to horseradish peroxidase was apparently reversible and noncompetitive in the presence of HgCl2 in less than 8 s and irreversibly inactivated when incubated with different concentrations of HgCl2 for 1-8 min. The binding site of horseradish peroxidase with HgCl2 probably was a cysteine residue SH. Mercury compounds can be assayed amperometrically with the detection limits 0.1 ng ml(-1) Hg for HgCl2 and methylmercury, 0.2 ng ml(-1) Hg for Hg2(NO3)2 and 1.7 ng ml(-1) Hg for mercury glutathione complex. Inactivation of the immobilized horseradish peroxidase was displayed in the AFM images of the enzyme membranes.

Response criteria for the prostate of the USA National Prostatic Cancer Project. Response criteria developed by the national Prostatic Cancer Project to evaluate chemotherapy for advanced disease and as an adjuvant in early disease are described. Subjective and objective procedures and tests are used to compare pre- and post-treatment disease activity in advanced disease. These patients enter trials in demonstrated progression; hence stabilization of activity was considered a category of objective response. Other response categories include the rare complete response and less rare partial regression, with progression for non-responders. In adjuvant studies response indicators are the incidence of recurring disease and length of disease-free-interval.

Kinetics of the reductive dissolution of lead(IV) oxide by iodide. Lead(IV) oxide (PbO(2)) is a corrosion product found in lead service lines used to convey drinking water. The presence of reductants can accelerate PbO(2) dissolution and enhance lead release to drinking water. The dissolution rate rather than the equilibrium solubility of PbO(2) can control the dissolved lead concentrations in water distributed through pipes containing PbO(2). Iodide, a known reductant for PbO(2), was selected as a model reductant for investigating the kinetics and mechanisms of the reductive dissolution of PbO(2). The dissolution rate of plattnerite (β-PbO(2)) was determined as a function of pH, iodide concentration, and dissolved inorganic carbon (DIC) concentration using continuously stirred tank reactors. The dissolution rate of plattnerite increased with decreasing pH and increasing iodide concentrations. The presence of 10 mg C/L DIC accelerated plattnerite dissolution, but further increases in DIC concentration did not affect the dissolution rate. The reductive dissolution of PbO(2) can be interpreted as a coupled process involving chemical reduction of Pb(IV) to Pb(II) at the PbO(2) surface followed by detachment of Pb(II) to solution. The data suggest that chemical reduction is the rate-limiting step for PbO(2) dissolution in the presence of iodide.

The effect of early treatment at the initial stage 3 moderate phase of retinopathy of prematurity on severe retinal changes. To compare the outcome of early treatment at the initial stage 3 moderate phase of retinopathy of prematurity (ROP) with that at prethreshold ROP. The outcome of treatment of 117 very-low-birth-weight infants was reviewed. Sixty-eight infants underwent their first treatment at prethreshold ROP (group A). The other 49 infants underwent their first treatment at the initial stage 3 moderate phase of ROP (pre-prethreshold ROP) (group B). The first treatment was performed by laser photocoagulation or cryotherapy. Eleven clinical variables were included in the evaluation of the two groups. The outcome of treatment of the two groups was compared as favorable or unfavorable. Logistic regression analysis was performed to assess the relation between each independent variable and an unfavorable outcome. The extent of contiguous stage 3 moderate ROP and that of cumulative stage 3 moderate ROP were significantly smaller in group B. There were nine unfavorable outcomes in group A, but none in group B. Logistic regression analysis showed that the extent of cumulative stage 3 moderate ROP and the presence of zone 1 retinopathy were major predictive factors for unfavorable outcome in the treatment of very-low-birth-weight infants. Early treatment at the initial stage 3 moderate phase of ROP decreases the occurrence of severe retinal changes.

Using fractal analysis to characterize cerebral blood flow and immunohistopathology for ischemic stroke research. This paper presents an application of fractal analysis to characterization of global cerebral blood flow and immunohistopathology for ischemic stroke research on animal experiments. A brain's vasculature has features of a branching tree and can be modeled as a fractal system. Fractal analysis can be then employed to assess cerebral blood flow and immuno-positives on a whole brain section. Fractal analysis on experimental data from three imaging modalities under ischemic and control status is presented in this paper. Statistic analysis and correlative study prove the effectiveness of fractal analysis. An analytical description of fractal parameters for experimental ischemic stroke has been achieved.

Renal crystal-storing histiocytosis involving glomeruli - A comprehensive clinicopathologic analysis. Crystal-storing histiocytosis (CSH) is a rare manifestation of monoclonal gammopathy in which histiocytes containing monoclonal proteins in their cytoplasm are found in various organs of the body including the kidney. Within the kidney, these monoclonal crystal-laden histiocytes have been described to occur in the interstitium (most commonly) or in the glomerular mesangium. CSH within glomerular capillary loops has rarely been reported. We describe three cases of CSH primarily affecting the glomerular capillaries and review the literature of CSH in general. Twenty cases of CSH involving the kidney are present in the literature; three describe CSH in glomeruli, only one of which showed histiocytes predominantly in glomerular capillary loops, while 15 had predominantly or solely interstitial CSH. Most cases involve IgG kappa crystals with only one case involving lambda light chain. Patients with CSH predominantly involving the glomerular capillaries showed a trend toward lower serum creatinine and proteinuria at presentation, and several patients with CSH lacked a definitive diagnosis of a monoclonal gammopathy at the time of diagnosis, emphasizing the role that kidney biopsy and particularly electron microscopy play in diagnosis of this entity.

Differences in regional capillary distribution and myocyte sizes in normal and hypertrophic rat hearts. Data are reported which show significant regional capillary differences in left ventricular endocardium and epicardium of normal rats and of rats with hyperthyroid-induced cardiac hypertrophy. The epicardial region of control rats has 38% more capillaries than the endocardial region. Control endocardial myocytes are 62% larger in cross-sectional area than epicardial myocytes. Hypertrophic hearts exhibit regional differences in capillary density similar to those in the normal hearts, but there is an overall reduction of 12 and 17.5% in capillary density in both regions. The average cross-sectional area of myocytes increases 34.5% in the epicardium and 22.5% in the endocardium.

Exploring The Impact Of The US Measles Outbreak On Parental Awareness Of And Support For Vaccination. Despite consensus among health officials that childhood immunizations are a safe and effective means of protecting people from disease, some parents remain hesitant about vaccinating their children. This hesitancy has been linked to a lack of confidence in recommended vaccinations as well as a desire to delay or further space out scheduled vaccinations but also outright refusal of vaccines. Using two national surveys of parents of children ages five and younger, collected immediately prior to and in the weeks following the 2014-15 US measles outbreak, this study examined the awareness of this vaccine-preventable disease outbreak among parents and whether awareness of the outbreak affected their beliefs about childhood vaccination, confidence, and intentions. The study found that while most parents were aware of the outbreak, many were not, and the level of familiarity mattered, particularly on measures of confidence in vaccines and support for mandates requiring childhood vaccination. Increases in vaccine-related concerns were found as well, indicating that disease outbreaks foster not just awareness of vaccines and their potential to prevent disease but a range of parental responses.

Validity of four models for predicting outcome in critically ill acute renal failure patients. Several mathematical models are used to predict the survival of patients in renal failure and have become standards. Few of these models have been sufficiently validated, however, and their applicability at other institutions has been established. We attempted to validate four models used to predict mortality in the setting of acute renal failure (Lohr, Bullock, Cioffi, APACHE II) with a registry of 512 ICU patients who received acute dialysis at our institution between 1988 and 1992. Using mortality as an endpoint, we applied each model as described by the original authors and compared the predicted results against the actual outcomes recorded in the registry. The Lohr Model is based on five risk factors thought to predict mortality or survival. Although we found these five factors were strongly associated with mortality (p < 0.001), more than 20% of the highest-risk group survived. The Bullock Model predicted only 20% of the mortality of our data. For the Cioffi Model, the original study found a clear discrimination score (survivors: 1.76, non-survivors: -0.423); however, we found no significant difference in the score discriminating survivors and non-survivors (survivors: 0.70, non-survivors: 0.71, p = 0.96). APACHE II is a risk model consisting of a premorbid assessment of chronic health and 12 physiologic variables taken during ICU admission. We applied APACHE II to both our cardiac and non-cardiac patients, and found that this score did not discriminate between survivors and non-survivors (p values ranged from 0.37 to 0.62) in acute renal failure in either case: the original APACHE II system was not applied to cardiac surgery patients. We conclude that models with good performance in their institutions of origin may not be valid in other institutions. Before using a predictive model, validity testing at the specific institution should be undertaken.

Perioperative morbidity of laparoscopic cryoablation of small renal masses with ultrathin probes: a European multicentre experience. Low morbidity has been advocated for cryoablation of small renal masses. To assess negative perioperative outcomes of laparoscopic renal cryoablation (LRC) with ultrathin cryoprobes and patient, tumour, and operative risk factors for their development. Prospective collection of data on LRC in five centres. LRC. Preoperative morbidity was assessed clinically and the American Society of Anaesthesiologists (ASA) score was assigned prospectively. Charlson Comorbidity Index (CCI) and Charlson-Age Comorbidity Index (CACI) scores were retrospectively assigned. Negative outcomes were prospectively recorded and defined as any undesired event during the perioperative period, including complications, with the latter classed according to the Clavien system. Patient, tumour, and operative variables were tested in univariate analysis as risk factors for occurrence of negative outcomes. Significant variables (p<0.05) were entered in a step-forward multivariate logistic regression model to identify independent risk factors for one or more perioperative negative outcomes. The confidence interval was settled at 95%. There were 148 procedures in 144 patients. Median age and tumour size were 70.5 yr (range: 32-87) and 2.6 cm (range: 1.0-5.6), respectively. A laparoscopic approach was used in 145 cases (98%). Median ASA, CCI, and CACI scores were 2 (range: 1-3), 2 (range: 0-7), and 4 (range: 0-11), respectively. Comorbidities were present in 79% of patients. Thirty negative outcomes and 28 complications occurred in 25 (17%) and 23 (15.5%) cases, respectively. Only 20% of all complications were Clavien grade > or = 3. Multivariate analysis showed that tumour size in centimetres, the presence of cardiac conditions, and female gender were independent predictors of negative perioperative outcomes occurrence. Receiver operator characteristic curve confirmed the tumour size cut-off of 3.4 cm as an adequate predictor of negative outcomes. Perioperative negative outcomes and complications occur in 17% and 15.5%, respectively, of cases treated by LRC with multiple ultrathin needles. Most of the complications are Clavien grade 1 or 2. The presence of cardiac conditions, female gender, and tumour size are independent prognostic factors for the occurrence of a perioperative negative outcome.

A case of hyponatremia after cervical spinal cord injury. Hyponatremia is known as a complication of neurosurgical conditions or brain. The prevalence of hyponatremia in acute spinal cord injury has been known to be much higher than in the general medical or surgical patient population. We report here a case of hyponatremia, which occurred 10 days after cervical spinal cord injury. The data on sodium levels were improved under the tapered infusion volume and water intake restriction. Treatment for this case is the same as that for syndrome of inappropriate antidiuretic hormone, which have suggested that reduced extracellular volume is important to improve the hyponatremia after traumatic spinal cord injury. Uncontrolled hyponatremia may lead to lethargy, seizures, coma, cardiac arrhythmia and death. Therefore, the complication of hyponatremia should be paid attention after cervical spinal cord injury. A careful monitoring of sodium levels after the injury is required in the cases of cervical spinal cord injury.

Growth hormone binding protein and maternal body mass index in relation to placental growth hormone and insulin requirements during pregnancy in type 1 diabetic women. In pregnancy, the growth hormone axis is shifted from pituitary growth hormone (GH) to placental growth hormone (PGH). Their common binding protein, GH binding protein (GHBP), displays peak serum levels at mid-gestation in normal individuals. In the non-pregnant state, diabetes is known to be associated with elevated levels of GH and decreased levels of insulin-like growth factors (IGFs) and GHBP. Diabetes in pregnancy may therefore as well be associated with disturbances in the growth hormone axis. In the present study, we aimed at investigating the impact of GHBP and maternal body mass index (BMI) on levels of PGH, thereby enabling estimation of any association between free PGH and weight adjusted insulin requirements. In 51 type 1 diabetic women, blood samples were collected in gestational week 10+, 16+, 22+, 28+ and 34+, and analysed for their serum content of GHBP, PGH, and GH. Serum GHBP increased from the first weeks of pregnancy to median 2.07 nmol/l (range 1.17-4.26) in week 22+, then declined to median 1.29 nmol/l (range 0.77-2.35) in week 34+ (ANOVA P < 0.001). Serum PGH levels were highest in week 34+ at median 21.3 microg/l (range 5.1-165.4) (P < 0.001), whereas a steady decrease in GH values was observed throughout pregnancy to a median 0.17 microg/l (range 0-5.53). The fraction of calculated free PGH to total PGH increased from mid-gestation onwards to 55.2% (37.0-87.1) in week 34+ at a median level of free PGH of 10.4 microg/l (range 1.9-144.0) (P < 0.001). Similarly, the molar ratio of total PGH to GHBP increased to a maximum of 0.68 (0.12-6.62) in week 34+. As in normal pregnancies, the correlation between BMI and GHBP was lost in late pregnancy. The newborns birth weight z-score correlated with total PGH and derivatives here-of in week 34+. Neither total nor weight adjusted insulin requirements correlated to total PGH, calculated free PGH, nor GHBP. In conclusion, PGH and GHBP display a similar course during pregnancy in type 1 diabetic women as described in normal women. The well-known association between GHBP and BMI was lost in late pregnancy. Calculated levels of free PGH were positively associated to fetal growth, but not to maternal insulin requirements.

Hepatic microvascular pressure during anaphylactic shock in anesthetized rats. Hepatic venoconstriction plays a significant role in anaphylactic hypotension in anesthetized rats. The purpose of this study is to determine whether the primary site of anaphylactic venoconstriction in the liver venous circulation occurs prior to or distal to the sinusoidal capillaries. We also determined whether the hepatic blood volume is increased during anaphylactic hypotension. We measured, using a servo-null micropipette pressure-measuring system, the hepatic venular transmural pressure (P micro hv) at the liver surface of anesthetized rats sensitized with the antigen of ovalbumin (1 mg). We also measured the liver lobe thickness, using the ultrasonic crystal dimension measuring system. Anaphylactic hypotension was induced by an intravenous injection of 0.6 mg ovalbumin. When the antigen was injected, the systemic arterial pressure decreased profoundly from 118+/-9 to 45+/-4 mm Hg, which was accompanied by an increase in Ppv and P micro hv: P micro hv only transiently increased from 3.1+/-0.9 to 8.8+/-1.5 cm H(2)O at 1 min and then rapidly returned to the baseline within 2 min, when Ppv continued to increase and reached the peak of 36+/-7 cm H(2)O at 3.5 min after antigen. This greater increase in Ppv-to-P micro hv gradient than that in P micro hv-to-Pcv gradient after antigen indicated that the constriction of the portal veins and the sinusoids much predominates over that of the hepatic veins. Along with this hepatic pre- and sinusoidal constriction, the liver lobe thickness significantly decreased by 4% after antigen. Pre-sinusoidal constriction during anaphylactic shock in anaesthetized rats increased the portal venous pressure while the hepatic venular pressure only increased slightly and transiently. This predominant pre-sinusoidal constriction is accompanied by a decrease in liver volume.

Novel Approach to Generate a Self-Deliverable Ru(II)-Based Anticancer Agent in the Self-Reacting Confined Gel Space. Finding the most effective method for cancer treatment is one of the thought-provoking tasks. Drug delivery by collapsing of metallogel to the cancer cell is an appealing way out. Cancer cells have an acidic environment due to excessive accumulation of lactic acid. In this work, the novel G5 gelator with a strategically free carboxylic acid arm has been designed and fabricated and characterized by several spectroscopic and microscopic techniques. These experiments suggest the formation of an ordered supramolecular gel with clover-leaf-like morphology. Mechanical properties from rheological measurements suggest the viscoelastic nature of the gel. Furthermore, we have obtained crystals of G5 from the pure dimethyl sulfoxide solution, whereas gelation gets induced by addition of water. This G5 gelator loses its gelation capability once the carboxylate is esterified by layering with methanol, which furnished the crystals of Me-G5' (G5' = G5-H). Further, the G5 gelator is used for the formation of ruthenium metallogel. Interestingly, we obtained the monomeric species [Ru(G5')(η6-p-cymene)Cl] [Ru(II)G5] only in confined gel space upon addition of a [Ru2(η6-p-cymene)2Cl4] dimer to G5. The Ru(II)G5 metallogel has an inherent anticancer property with an IC50 value of 10.53 μM for the A549 cancer cell line. Treatment of the Ru(II)G5 metallogel by lactic acid for mimicking the acidic environment of the malignant cell results in collapsing of the gel by releasing the ruthenium metal ion. This released ruthenium ion binds with the lactic acid derivative making the gelator G5 free and producing a new compound Ru(II)L, which has also shown the anticancer property. The molecular docking study revealed that the released G5 could interact with a monocarboxylate transporter to disrupt the lactate transport chain, which might induce apoptosis.

The enhancement of interstitial transport of a doxorubicin-lactosaminated albumin conjugate by imatinib: in rat hepatocellular carcinoma it is not preferentially higher than that in liver and bone marrow. The finding that imatinib enhances the drug transport from bloodstream to neoplastic cells suggested a possible role of this drug as an adjuvant to the chemotherapeutics given in the treatment of solid malignancies.The present experiments aimed to verify whether imatinib can selectively increase the penetration of a doxorubicin-lactosaminated human albumin conjugate (L-HSA-DOXO) in chemically induced rat hepatocellular carcinomas (HCCs). We observed that imatinib increased the uptake of L-HSA-DOXOby HCCs but at the same time caused a similar enhanced penetration of the conjugate in liver and bone marrow. To our knowledge, this is the first demonstration that the enhancing effect of imatinib on interstitial drug transport is not restricted to the tumors, but can be also displayed in normal tissues. This observation casts some doubts about the possibility that the value of anticancer agents with toxic side effects on liver and bone marrow can be improved by imatinib.

[Therapeutic penetrating keratoplasty: indications and results in Tunisia]. To report the experience of the Tunis Institute of Ophthalmology (Tunisia) in therapeutic penetrating keratoplasty. We retrospectively analyzed 35 patients after therapeutic penetrating keratoplasty over a period of 6 years (between September 2002 and September 2008). The mean patient age was 49.3 years. Men outnumbered women by a ratio of 2.5 to 1. The mean follow-up was 13.5 months. Corneal diseases within a therapeutic penetrating keratoplasty were divided into infectious keratitis (21 eyes) and noninfectious diseases (14 eyes). Herpetic keratitis was the most common etiology (11 eyes). The anatomical success rate was 92.4%, with infection eradicated in 80% of cases. The graft clarity at the end of follow-up was 54.2%. Rejection was the leading cause of graft opacification (50%). Final visual acuity was better than 1/10 in 25.7% of patients. Recovery of useful vision was observed in 45.7% of patients. Therapeutic penetrating keratoplasty is a surgical technique that has proved its effectiveness in maintaining the integrity of the eyeball. The prognosis for this intervention would probably be better if it could be postponed.

Transport and dynamics of toxic pollutants in the natural environment and their effect on human health: research gaps and challenge. The source-pathway-receptor (SPR) approach to human exposure and risk assessment contains considerable uncertainty when using the refined modelling approaches to pollutant transport and dispersal, not least in how compounds of concern might be prioritized, proxy or indicator substances identified and the basic environmental and toxicological data collected. The impact of external environmental variables, urban systems and lifestyle is still poorly understood. This determines exposure of individuals and there are a number of methods being developed to provide more reliable spatial assessments. Within the human body, the dynamics of pollutants and effects on target organs from diffuse, transient sources of exposure sets ambitious challenges for traditional risk assessment approaches. Considerable potential exists in the application of, e.g. physiologically based pharmacokinetic (PBPK) models. The reduction in uncertainties associated with the effects of contaminants on humans, transport and dynamics influencing exposure, implications of adult versus child exposure and lifestyle and the development of realistic toxicological and exposure data are all highlighted as urgent research needs. The potential to integrate environmental with toxicological models provides the next phase of research opportunity and should be used to drive empirical and model assessments.