Malignant pleural mesothelioma presenting as an acute surgical abdomen due to metastatic jejunal perforation.
A 52-year-old man was admitted to our hospital in June 2008 presenting abnormal tumor lesions along the left pleura on chest X-ray. The needle-biopsied specimen of the left pleura proved the biphasic type of malignant mesothelioma. However, he complained of acute abdominal pain 7 days after the diagnosis. Chest X-ray revealed free air below the right diaphragm. Emergency surgery revealed a 4-cm perforating jejunal tumor with peritonitis. Histopathology of the resected jejunum demonstrated a metastatic tumor of malignant pleural mesothelioma. This is the first reported case of malignant pleural mesothelioma presenting as an acute surgical abdomen due to jejunal metastasis with perforation.


Regulating private health insurance to serve the public interest: policy issues for developing countries.
Private health insurance plays a large and increasing role around the world. This paper reviews international experiences and shows that private health insurance is significant in countries with widely different income levels and health system structures. It contrasts trends in private health insurance expansion across regions and highlights countries with particularly important experiences of private coverage. It then discusses the regulatory approaches and policies that can structure private health insurance markets in ways that mobilize resources for health care, promote financial risk protection, protect consumers and reduce inequities. The paper argues that policy makers need to confront the role that private health insurance will play in their health systems and regulate the sector appropriately so that it serves public goals of universal coverage and equity.


Perioperative use of botulinum toxin for movement disorder-induced cervical spine disease.
Patients with cervical dystonia or tics of the nuchal muscles can develop serious cervical spine disease. We report a series of four patients who received botulinum toxin injections to control their movement disorders prior to their required surgery. One patient with cervical tic-induced radiculomyelopathy required botulinum toxin injection postoperatively to facilitate stabilization of the cervical fusion. Two patients with torticollis-induced cervical radiculomyelopathy, and one patient with dystonia-induced C5 fracture, had botulinum toxin injected preoperatively to facilitate postoperative recovery. Botulinum toxin appears to be a useful adjunct in the treatment of cervical movement disorders prior to or following surgery for associated cervical spine disease.


The endolysosomal cysteine cathepsins L and K are involved in macrophage-mediated clearance of Staphylococcus aureus and the concomitant cytokine induction.
Cysteine cathepsins are endolysosomal cysteine proteases highly expressed in macrophages; however, their individual contributions to the elimination of bacteria and bacteria-induced cytokine production by macrophages are unknown. We assessed the contribution of cysteine cathepsins to macrophage defense pathways against Staphylococcus aureus by using chemical inhibitors and by infecting primary bone marrow-derived macrophages deficient in 1 of 7 major macrophage-expressed endolysosomal cysteine proteases. We show that cysteine cathepsins are involved in the phagocytosis and killing of S. aureus. Cathepsin L was identified as an executor of nonoxidative killing. Moreover, microarray data revealed cysteine cathepsins to be important for the maximal induction of certain proinflammatory genes, such as IL6, in response to S. aureus. Cysteine cathepsin's contribution to IL6 production was dependent on phagocytosis, and cathepsin K was identified to be a critical protease in this process. Analysis of macrophages with impaired trafficking of endolysosomal Toll-like receptors (TLRs) to the acidic compartment revealed that they were not involved in cathepsin-dependent IL6 induction. Because IL6 production was completely dependent on the TLR-adaptor protein myeloid differentiation primary response gene 88 (MyD88), it appears that other TLRs are involved. In summary, lysosomal cysteine proteases are functionally linked to the complex bactericidal and inflammatory activities of macrophages.


Electron-transfer reactions and functionalization of cytochrome P450cam monooxygenase system in reverse micelles.
Enzyme-based electron-transfer reactions involved in the cytochrome P450 monooxygenase system were investigated in nanostructural reverse micelles. A bacterial flavoprotein, putidaredoxin reductase (PdR), was activated and shown to be capable of catalyzing the electron transport from NADH to electron-carrier proteins such as cytochrome b5 (tCyt-b5) and putidaredoxin (Pdx) in reverse micelles. Ferric tCyt-b5 in reverse micelles was effectively converted to its ferrous form by the exogenous addition of separately prepared reverse micellar solution harboring PdR and NADH. The fact that direct interactions of macromolecular proteins should be possible in the reverse micellar system encouraged us to functionalize a multicomponent monooxygenase system composed of the bacterial cytochrome P450cam (P450cam), putidaredoxin (Pdx), and PdR in reverse micelles. The successful camphor hydroxylation reaction catalyzed by P450cam was significantly dependent on the coexistence of Pdx, PdR, and NADH but not H2O2, suggesting that the oxygen-transfer reactions proceeded via a "monooxygenation" mechanism. This is the first report of a multicomponent cytochrome P450 system exhibiting enzymatic activity in organic media.


Is there a need for special antenatal clinic for women with a medical disorder?
A two year review of clinical practice in a medical antenatal clinic was performed. Forty-six per cent of the patients were diabetics and the other 54% were a mixture of endocrine, cardiac, vascular and other medical disorders. The referral rate was 1.5% of total deliveries during the time period and the perinatal mortality rate was 27/1000. The preterm delivery rate was 20%. The feasibility of this kind of clinic in a single hospital is discussed.


Post-natal management of antenatally detected, bilateral hydronephrosis.
26 children, with antenatally detected, isolated, bilateral hydronephrosis (thus consistent with pelvi-ureteric junction obstruction), were investigated for up to 7 years. The aim was to avoid operation. 34 kidneys were never operated on. Despite initially often severe hydronephrosis and poor isotope wash-out on the renogram, half of the kidneys improved or even normalized during follow-up. The final glomerular filtration rate (GFR) was always normal or almost normal. 18 kidneys came to surgery, because of poor filtration, symptoms or social reasons. At the end of the follow-up, GFR was normal in all but 2 kidneys. In a subgroup of the kidneys, with initially severe reduction in filtration, half were operated on and half were not; at the end, the GFR was normal in all of the non-operated kidneys (and in all but 1 of the operated kidneys). Total GFR was at the end normal or almost normal also in the children with persistingly filtration-reduced kidneys (always unilaterally), because of compensation by the contralateral, although hydronephrotic kidney. Thus, in this study the renographic parameters were not very helpful in predicting the prognosis. There was no consistent difference between operative and non-operative treatments on final filtration. Also hydronephrotic kidneys possessed a substantial capacity for contralateral compensation. It is concluded that the initial approach to bilateral, antenatally diagnosed hydronephrosis may safely be non-operative. This allows time for the clear expression of sustained impairment of renal filtration requiring surgical intervention.


Incremental clomiphene therapy: a new method for treating persistent anovulation.
Thirty anovulatory patients, previously unresponsive to clomiphene citrate in standard dosage, were treated with a new incremental method of clomiphene therapy. Clomiphene was given continuously with dosage increments every 5 days, up to a maximum dose of 3750 mg, and ovarian response was monitored with urinary estrogen estimation and with ultrasound. Twenty-one patients (70%) ovulated on this regimen and 8 (27%) conceived; 6 patients who ovulated but did not conceive had other infertility factors. Clomiphene response was associated with a progressive rise in follicle-stimulating hormone, luteinizing hormone, and estrogen excretion; these parameters were unchanged in nonresponders. Side effects of treatment were minimal and only 1 case of hyperstimulation occurred. Preliminary testing with estrogen-amplified gonadotropin-releasing hormone did not differentiate responders from nonresponders. Incremental clomiphene treatment appears to be a less complicated alternative for patients who would otherwise require exogenous gonadotropin therapy.


Ambulatory Assessment in the Research on Aging: Contemporary and Future Applications.
Older adults have surprisingly high levels of well-being, which has been referred to as a paradox in the past. Improved emotion regulation has been suggested to underlie these high levels of well-being. Later life is also a period with enhanced exposure to critical life events, and this comes with risks. During such times, and towards the end of life, emotional well-being may and eventually does decline. We suggest that ambulatory assessment (AA) is ideally suited for the investigation of the above phenomena and for intervention purposes. More precisely, AA can be used to thoroughly examine within-person processes of emotion regulation, including the multiple levels on which emotions occur (physiology, experience, behavior, context, and nonverbal expressions). It thereby provides a basis for understanding competent emotion regulation, the well-being paradox, and emotionally critical periods. Such insights can be utilized to detect person-specific critical periods and for designing immediate person-specific interventions. Although this is still a vision, the benefits of such an approach seem invaluable. The major part of this paper is organized around three general principles that we suggest to further tap the potential of AA in aging research, namely (1) identify within-subject processes and their relations to important life outcomes; (2) capitalize on the full scope of AA technology via multivariate assessments, and (3) combine real-time monitoring with real-time interventions.


Antiangiogenic agents: studies on fumagillin and curcumin analogs.
Cancer is a general term used to describe many disease states, each of which are characterized by abnormal cell proliferation. The causes which bring about this abnormal cellular behavior are specific to each type of cancer. The success of tumor-targeted therapy is limited by this diversity. One common denominator for all types of cancer is the requirement of a suitable blood supply. Therefore, tumor vasculature has emerged as a potential target for therapeutic intervention. New blood vessel growth from preexisting vasculature stimulated by biochemical signals is termed angiogenesis. Tumor masses require a constant supply of oxygen and nutrients, and a means of efficient waste removal to ensure sustained development. Diffusion from nearby capillaries can supply adequate nutrition for tumors less than 2 mm in size, but for continued growth the tumors must develop their own blood supply. Alteration of the delicate balance of angiogenic stimulating factors and angiogenic inhibitors results in the phenotypic change from quiescence to active endothelial proliferation. To date, this angiogenic switch is not completely understood. The goal of antiangiogenic therapy is to interfere with these mechanisms and prevent tumor cells from developing a viable blood supply. Fumagillin is a naturally occurring antifungal agent. Curcumin is a natural product isolated from the spice turmeric. Both compounds have been shown to have antiangiogenic properties in vitro and in vivo. This paper describes efforts to design and prepare fumagillin and curcumin analogs and evaluate their corresponding antiangiogenic activities.


[Imaging findings and transarterial therapy of primacy hepatic carcinoma fed by right renal capsular artery].
To evaluate the characteristics of primary hepatic carcinoma (PHC) teed by the right renal capsular artery(RRCA) and to assess the technical success rate,tumor response and complications in patients treated with transcatheter arterial chemoembolization (TACE) via the RRCA with or without other extrahepatic arteries and/or intrahepatic arteries. From July 2010 to February 2014,23 patients were treated by TACE via the RRCA. We evaluate the characteristics of tumor, the blood supply situation of RRCA and the technical success rate, complications and tumor response of TACE via the RRCA. Tumor size was 90.60+/-48.23 mm. Of the 23 rumors,3 were located in segment V, 11 in segment VI and 9 in segment VII.8 cases were found to have RRCA supply at the first TACE session. The technical success rate was 100%.No severe complication occurred in 23 patients. Among the 23 patients, CR, PR, SD and PD were achieved in 3(13.0%), 10(43.5%), 2(8.7%), 8(34.8%) respectively. The objective response rate was 56.5%. The overall cumulative 6 month, 1-3-and 5-year survival rates and the median survival time were 82.6%, 52.2%,21.7%, 17.4% and 16.8 months, respectively. RRCA can participate in tumor blood supply when it located in the right hepatic lobe and with a larger diameter, or it was small but located in the bare area.Superselective intubation of RRCA with microcatheter and precise TACE via right renal capsular artery is safe ,effective and feasible.


Novel immunotherapy for malignant melanoma with a monoclonal antibody that blocks CEACAM1 homophilic interactions.
CEACAM1 (biliary glycoprotein-1, CD66a) was reported as a strong clinical predictor of poor prognosis in melanoma. We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. Here, we present substantial evidence in vitro and in vivo that blocking of CEACAM1 function with a novel monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy. MRG1, a murine IgG1 monoclonal antibody, was raised against human CEACAM1. It recognizes the CEACAM1-specific N-domain with high affinity (K(D) ~ 2 nmol/L). Furthermore, MRG1 is a potent inhibitor of CEACAM1 homophilic binding and does not induce any agonistic effect. We show using cytotoxicity assays that MRG1 renders multiple melanoma cell lines more vulnerable to T cells in a dose-dependent manner, only following antigen-restricted recognition. Accordingly, MRG1 significantly enhances the antitumor effect of adoptively transferred, melanoma-reactive human lymphocytes using human melanoma xenograft models in severe combined immunodeficient/nonobese diabetic (SCID/NOD) mice. A significant antibody-dependent cell cytotoxicity response was excluded. It is shown that MRG1 reaches the tumor and is cleared within a week. Importantly, approximately 90% of melanoma specimens are CEACAM1(+), implying that the majority of patients with melanoma could be amenable to MRG1-based therapy. Normal human tissue microarray displays limited binding to luminal epithelial cells on some secretory ducts, which was weaker than the broad normal cell binding of other anticancer antibodies in clinical use. Importantly, MRG1 does not directly affect CEACAM1(+) cells. CEACAM1 blockade is different from other immunomodulatory approaches, as MRG1 targets inhibitory interactions between tumor cells and late effector lymphocytes, which is thus a more specific and compartmentalized immune stimulation with potentially superior safety profile.


Availability and properties of materials for the Fakse Landfill biocover.
Methane produced in landfills can be oxidized in landfill covers made of compost; often called biocovers. Compost materials originating from seven different sources were characterized to determine their methane-oxidizing capacity and suitability for use in a full-scale biocover at Fakse Landfill in Denmark. Methane oxidation rates were determined in batch incubations. Based on material availability, characteristics, and the results of batch incubations, five of the seven materials were selected for further testing in column incubations. Three of the best performing materials showed comparable average methane oxidation rates: screened garden waste compost, sewage sludge compost, and an unscreened 4-year old garden waste compost (120, 112, and 108 gm(-2)d(-1), respectively). On the basis of these results, material availability and cost, the unscreened garden waste compost was determined to be the optimal material for the biocover. Comparing the results to criteria given in the literature it was found that the C/N ratio was the best indicator of the methane oxidation capacity of compost materials. The results of this work indicate that batch incubations measuring methane oxidation rates offer a low-cost and effective method for comparing compost sources for suitability of use in landfill biocovers.


Comparison of proton pump inhibitor-based triple therapy with losec and the generic drug, Omepradex, for efficacy of Helicobacter pylori eradication.
Triple therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin is widely accepted in Israel for Helicobacter pylori eradication. Recently, a generic drug for omeprazole was introduced to the market, but its efficacy as a PPI was questioned. The aim of the study was to compare eradication efficacy of triple therapy-based regimens with Losec (Astra-Zeneca, Sweden) and the generic form, Omepradex (Dexxon, Israel). People belonging to Clalit Health Services (CHS), the biggest health insurance provider in Israel, and receiving omeprazole (Losec or Omepradex) for 7 days (assumed to be Helicobacter pylori eradication purposes), between 1.1.2001 and 31.12.2001, were retrieved from the CHS central computer. Of 450 patients (287 in the Losec group and 163 in the Omepradex group), 97 (21.6%) underwent 13C-urea breath test (13CUBT) for validation of Helicobacter pylori successful eradication and participated in the study. They were all treated with triple therapy with omeprazole, amoxicillin, and clarithromycin, and were stratified according to the PPI used: Group A, Losec; and Group B, Omepradex. Positivity of 13CUBT was computed. Sixty-one (21.25%) and 36 (22.08%) patients in Groups A and B, respectively, underwent 13 CUBT for validation of successful Helicobacter pylori eradication (NS). In Group A 41 of 61 patients (67.21%) had a negative 13CUBT, in comparison with 26 of 36 (72.22%) in Group B (NS). Using logistic regression analysis all confounding factors were found to be noncontributory to the discrimination between negative (successful eradication) and positive (failed eradication) 13CUBT. There is no statistically significant difference between Losec and the generic drug Omepradex as part of a PPI-based triple therapy for eradication efficacy of Helicobacter pylori.


Relationship Between Cortical Excitation and Inhibition and Task-Induced Activation and Deactivation: A Combined Magnetic Resonance Spectroscopy and Functional Magnetic Resonance Imaging Study at 7T in First-Episode Psychosis.
Schizophrenia is thought to be a disorder of brain dysconnectivity. An imbalance between cortical excitation/inhibition is also implicated, but the link between these abnormalities remains unclear. The present study used magnetic resonance spectroscopy and functional magnetic resonance imaging at 7T to investigate how measurements of glutamate and gamma-aminobutyric acid (GABA) relate to the blood oxygen level-dependent (BOLD) response during a cognitive task, and how these relationships are altered in schizophrenia. Usable functional magnetic resonance imaging data from 17 first-episode psychosis (FEP) patients (4 women, 13 men) and 21 matched healthy control subjects (HCs) (5 women, 16 men) were acquired during a Stroop task. Within- and between-group comparisons of the BOLD response were performed. Neurometabolite levels were measured in the dorsal anterior cingulate cortex. Two multiple regressions investigated how glutamate, glutamine, and GABA related to the BOLD response in HCs and FEP patients separately. A third investigated between-group differences in the relationships between the BOLD response and each of these neurometabolites. Compared with HCs, FEP patients showed an increased BOLD response within regions of the executive and default mode networks. In FEP patients, the relationship between anterior cingulate cortex glutamate levels and the BOLD response in regions of the posterior default mode network was opposite to that of HCs. In FEP patients but not HCs, anterior cingulate cortex GABA levels correlated with the local BOLD response and with the Stroop reaction time. These results suggest a mechanism whereby alterations in the relationship between cortical glutamate/GABA and BOLD response is disrupting the dynamic of major neural networks, possibly affecting cognition.


Clinical manifestations of benign prostatic hyperplasia.
The clinical diagnosis of BPH is usually established after completing the initial evaluation of patients who present with symptoms of prostatism. The steps recommended in the initial evaluation include a medical history, symptom assessment using a Symptom Score Index, a digital rectal examination, a focused neurological examination, urinalysis, measurement of serum creatinine, and an optional PSA measurement. Further examinations such as uroflowmetry and cystoscopy are indicated only if the diagnosis is uncertain, or to determine the feasibility of specific invasive therapies.


Pattern of pulses that maximize force output from single human thenar motor units.
We assessed the sequence of nerve impulses that maximize force output from individual human thenar motor units. When these motor units were stimulated intraneurally by a variable sequence of seven pulses, the pattern of pulses that elicited maximum force always started with a short (5-15 ms) interpulse interval termed a "doublet. " The twitch force summation caused by this "doublet" elicited, on average, 48 +/- 13% (SD) of the maximum tetanic force. The peak amplitude of "doublet" forces was 3.5 times that of the initial twitches, and twitch potentiation appeared to have little influence on twitch force summation elicited by the "doublets." For some units, the second optimal interpulse interval was also short. Peak forces elicited by the third to sixth interpulse intervals did not change substantially when the last interpulse interval was varied between 5 to 55 ms, so maximum force could not be attributed to any unique interpulse interval. Each successive pulse contributed a smaller force increment. When five to seven pulses were delivered in an optimal sequence, the evoked force was close to that recorded during maximal tetanic stimulation. In contrast, maximal force-time integral was evoked with one short interpulse interval (5-15 ms) then substantially longer interpulse intervals (>100 ms). Maximum force and force-time integrals were therefore elicited by different patterns of stimuli. We conclude that a brief initial interpulse interval (5-15 ms) is required to elicit maximum "doublet" force from human thenar motor units and that near-maximal tetanic forces can be elicited by only five or six additional post-"doublet" pulses if appropriately spaced in time. However, the rate at which these post-"doublet" stimuli must be provided is fairly uncritical. In contrast, maximum post-"doublet" force-time integrals were obtained at intervals corresponding to motoneuronal firing rates of approximately 7 Hz, rates close to that typically used to recruit motor units and to maintain weak voluntary contractions.


Screening for problem drinking among college freshmen.
This study identified predictors of older adolescents at risk for problem drinking. College freshmen (n = 492) completed a questionnaire that addressed drinking patterns, risk factors for problem drinking, the CAGE questions, the Perceived-Benefit-of-Drinking Scale (PBDS), and the Children of Alcoholics Screening Test (CAST). They also responded to questions regarding alcohol-related problems including blackouts; alcohol-related injury, illness, violence, or legal problems; driving under the influence; and missing class. 50% of students were male with a mean age of 17.9 years (SD = 0.5). Higher scores on the CAGE and PBDS, use of tobacco, best friend's drinking pattern, and younger age at first drinking were associated with higher scores on a quantity/frequency drinking index and with reports of significantly more alcohol-related problems. Regression models using these variables explained 40% to 51% of the variance in drinking habits and alcohol-related problems. A composite screening measure had significantly better sensitivity and specificity than either the CAGE or PBDS alone in identifying older adolescents at high risk for problem drinking.


Up-regulation of ectonucleotidase activity after cortical stab injury in rats.
The objective of this study was to examine the changes in the activity and expression of ectonucleotidase enzymes in the model of unilateral cortical stab injury (CSI) in rat. The activities of ecto-nucleoside triphosphate diphosphohydrolase 1 (NTPDase 1) and ecto 5'-nucleotidase were assessed by measuring the levels of ATP, ADP and AMP hydrolysis in the crude membrane preparations obtained from injured left cortex, right cortex, left and right caudate nucleus, whole hippocampus and cerebellum. Significant increase in NTPDase and ecto 5'-nucleotidase activities was observed in the injured cortex following CSI, whereas in other brain areas only an increase in ecto 5'-nucleotidase activity was seen. Immunohistochemical analysis performed using antibodies specific to NTPDase 1 and ecto 5'-nucleotidase demonstrated that CSI induced significant changes in enzyme expression around the injury site. Immunoreactivity patterns obtained for NTPDase 1 and ecto 5'-nucleotidase were compared with those obtained for glial fibrillary acidic protein, as a marker of astrocytes and complement receptor type 3 (OX42), as a marker of microglia. Results suggest that up-regulation of ectonucleotidase after CSI is catalyzed by cells that activate in response to injury, i.e. cells immunopositive for NTPDase 1 were predominantly microglial cells, whereas cells immunopositive for ecto 5'-nucleotidase were predominantly astrocytes.


Neutrality and evolvability of designed protein sequences.
The effect of foldability on protein's evolvability is analyzed by a two-prong approach consisting of a self-consistent mean-field theory and Monte Carlo simulations. Theory and simulation models representing protein sequences with binary patterning of amino acid residues compatible with a particular foldability criteria are used. This generalized foldability criterion is derived using the high temperature cumulant expansion approximating the free energy of folding. The effect of cumulative point mutations on these designed proteins is studied under neutral condition. The robustness, protein's ability to tolerate random point mutations is determined with a selective pressure of stability (ΔΔG) for the theory designed sequences, which are found to be more robust than that of Monte Carlo and mean-field-biased Monte Carlo generated sequences. The results show that this foldability criterion selects viable protein sequences more effectively compared to the Monte Carlo method, which has a marked effect on how the selective pressure shapes the evolutionary sequence space. These observations may impact de novo sequence design and its applications in protein engineering.


The acute porphyrias.
The porphyrias are a heterogeneous group of rare inborn errors of metabolism caused by inherited enzyme defects in the haem biosynthetic pathway, resulting in overproduction of porphyrins. The porphyrias can be distinguished biochemically but may be difficult to differentiate clinically. Considerable advances have been made in the understanding of the enzymology and molecular biology of the porphyrias. The acute attack of porphyria may be a life-threatening condition, and an understanding of its many precipitating factors, clinical features and management is of importance in a disease with a significant mortality.


Assembly of recombinant nucleosomes on nanofabricated DNA curtains for single-molecule imaging.
Eukaryotic chromosomes are highly packed into chromatin, the basic unit of which is the nucleosome. The presence of nucleosomes and the resulting organization of the genome into higher-order chromatin structures has profound consequences for virtually all aspects of DNA metabolism, including DNA transcription, repair, and chromosome segregation. We have developed novel approaches for nanofabricating "DNA curtains" for high-throughput single-molecule imaging, and we have begun adapting these new research tools in an effort to begin studying chromatin biology at the single-molecule level. In this protocol, we describe procedures for assembly and real-time single-molecule visualization of DNA curtains bound by reconstituted nucleosomes made from recombinant histones.


The sensilla of Aedes and Anopheles mosquitoes and their importance in repellency.
The aim of this study was to detect the role of some mosquito organs in their sensation of repellent materials. A total of 250 females (15 days old) of the target species Aedes aegypti and Anopheles stephensi were prepared and divided into five groups: group 1, without antenna; group 2, without maxillary bulbs; group 3, without proboscis; group 4, without frontal tarsus; and group 5, normal females as control. A mixture of five oils containing Litsea cubeba 1%, Melaleuca leucadendron 1%, Melaleuca quinquenervia 1%, Viola odorata 1%, and Nepeta cataria 1% was included in a complex solvent containing 20% genapol, 10% polyethylene glycol, 20% ethanol, and 50% water. Furthermore, Bayrepel was used in this experiment at a 20% concentration in the same solvent. Pure water was used as control in this study. The test was carried out by spreading 100 microl of the repellent material or water on a 30-cm2 exposure area of a human volunteer's arm. In A. aegypti, the biting and landing percentages increased significantly in those mosquito groups that lacked some organs (especially maxillary bulbs), while in A. stephensi, it became not clear which organ is responsible for perception of repellents.


Experimental study on allografts of amniotic epithelial cells in calcaneal tendon lesions of sheep.
An experimental protocol was designed to study the survival and behaviour of an allograft of amniotic epithelial cells (AECs) in an ovine model. The study was conducted on three healthy adult sheep. A core lesion was created in both calcaneal tendons under ultrasound (US) guidance by injecting 400 UI of Type 1A collagenase diluted in 0.6 ml saline. The AECs were obtained from a 60-80-day-old fetus and cultured under standard conditions. After 15 days of collagenase treatment, 2 x 10(6) AECs stained with a vital membrane fluorescent probe (PHK26) were injected under US guidance in 500 microl saline solution into the lesion of one limb. The contralateral untreated limb was used as a control. Animals were euthanatized 7 (1) and 30 (2) days later. Histological analyses performed on explanted tendons clearly demonstrate that AECs survived for at least 1 month inside the lesion without any adverse reactions. The damaged tissue of the treated tendons showed a high number of reparative cells in active proliferation that were accumulating collagen within the extracellular matrix. In addition, after 1 month, the neo-collagen began to be organized into parallel arrays of fibers oriented along the longitudinal axis of the tendon.


Erythroplasia of Queyrat of the glans penis on a background of Zoon's plasma cell balanitis.
Erythroplasia of Queyrat of the glans penis developed in a 79-year-old uncircumcised man on a background of biopsy proven Zoon's plasma cell balanitis affecting the same site on the glans. The Zoon's plasma cell balanitis had been treated with topical pimecrolimus for 1 month prior to the development of clinically evident erythroplasia of Queyrat. He was subsequently treated with topical 5-fluorouracil 5% for 2 weeks, which resulted in clinical clearance. He has since been circumcised.


Predictors of respiratory sickness absence: an international population-based study.
Respiratory tract-related occupational disability is common among adults of working age. We examined occupational vapors, gas, dust, or fume (VGDF) exposure as a predictor of disability, based on respiratory sickness absence among the actively employed, at an early point at which prevention may be most relevant. Currently employed European Community Respiratory Health Survey II participants (n = 6,988) were classified into three mutually exclusive, condition/symptom-based categories: physician-diagnosed asthma, self-reported rhinitis, and wheeze/breathlessness (n = 4,772). Logistic regression analysis estimated the odds of respiratory sickness absence (past 12 months) by VGDF exposure. In the condition/symptom groups, 327 (6.9%) reported respiratory sickness absence. Exposure to VGDF was associated with increased odds of respiratory sickness absence: asthma odds ratio [OR] 2.0 (95% confidence interval [CI] 1.1-3.6), wheeze/breathlessness OR 2.2 (95% CI 1.01-4.8); rhinitis OR 1.9 (95% CI 1.02-3.4). One in 15 currently employed with asthma, breathlessness, or rhinitis reported respiratory sickness absence. VGDF exposure doubled the odds of respiratory sickness absence, suggesting a focus for disability prevention.


Social environment, morbidity and use of health care among people with diabetes mellitus in Trinidad.
This study aimed to identify social characteristics associated with higher levels of morbidity from diabetes and their relationship to health care utilization. During a 6-month period 1149/1447 (79%) subjects admitted to Port of Spain Hospital, Trinidad with diabetes responded to a structured interview. Data collection included social factors, diabetes-related morbidity and health care utilization. Analyses were adjusted for age, sex, ethnic group and self-reported diabetes duration. Of 12 indicators of morbidity, nine were more frequent in subjects with no schooling compared with those with secondary education. At ages 15-59 years, nine morbidity indicators were less frequent among subjects in full-time jobs compared with those not in employment. The association of educational attainment was explained by confounding with age, sex, ethnic group and diabetes duration but five morbidity indicators were associated with employment status after adjusting for confounding. The type of water supply in the home was generally not associated with morbidity. Each of the indicators of lower socioeconomic status was associated with less use of private doctors and with more use of government health centres. Morbidity from diabetes was greater in groups with lower socioeconomic status. While morbidity associated with lower educational attainment was mostly explained by older age; the results suggested the possibility that diabetes may contribute to unemployment of those in the labour force. Private care was less accessible to social groups with higher levels of morbidity and the availability of government funded health services was important for reducing inequalities in health care utilization.


[Carotid MRI of initial and recurrent plaques in patients with restenosis after endarterectomy: three case reports].
Restenosis after carotid endarterectomy (CEA) is one of most significant complications. There is no previous report about MRI findings of restenotic lesions and preoperative plaques. The purpose of this study was to evaluate the initial and recurrent plaques in patients with restenosis after CEA by using black-blood MRI (BB-MRI). Three patients who underwent carotid artery stenting for restenosis after CEA were included in this study. The relative signal intensities (rSI) of the initial and recurrent plaques were calculated with reference to the sternocleidomastoid muscle on T1-weighted images (T1WI) and the submandibular gland on T2-weighted images (T2WI). This study investigated the rSI characteristics and morphology of the initial and recurrent plaques. All patients had restenosis within 1 year after CEA. The rSI values of the preoperative lesion were not high on T1WI and were high on T2WI in all cases (T1WI/T2WI: 0.63/2.43 in Case 1, 1.00/1.29 in Case 2, and 1.13/1.70 in Case 3). The morphology of the initial plaques was eccentric in 2 cases and concentric in 1 case. The rSI values of restenosis were high on T2WI in all cases (T1WI/T2WI: 1.09/1.20 in Case 1, 1.31/1.50 in Case 2, and 1.23/1.70 in Case 3). The morphology of restenotic lesions was concentric in all cases. The high rSI on T2WI and concentricity of the restenosis after CEA suggest early restenosis (intimal hyperplasia). The low-iso rSI on T1WI and high rSI on T2WI of the preoperative plaques are associated with restenosis after CEA. BB-MRI may be useful to evaluate and predict restenosis after CEA. (Received: May 7, 2012, Accepted: September 10, 2012).


Sequential treatment combining cladribine-based re-induction, myeloablative allogeneic HSCT, and prophylactic donor lymphocyte infusion: a promising treatment for refractory acute myeloid leukemia.
We describe the first multicenter prospective study to assess the efficacy, safety, and immune reconstitution of a novel sequential transplant approach in 24 patients with primary induction failure/relapsed acute myeloid leukemia (AML). The sequential regimen consisted of cladribine 5 mg/m2/day and cytarabine 2 g/m2/day for 5 days and mitoxantrone 7 mg/m2/day for 3 days, followed by myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) using intravenous busulfan (3.2 mg/kg/day) for 4 days and cyclophosphamide (60 mg/kg/day) for 2 days. Patients in CR without acute graft-versus-host disease at day + 90 received prophylactic donor lymphocyte infusion (pDLI). At the time of transplantation, a marrow blast infiltration > 20% or any level of circulating blasts was found in 62.5% of patients. The cumulative incidence of relapse at 2 years was 29.8%. Overall survival (OS) was 74.5% at 1 year and 56.5% at 2 years. Leukemia-free survival (LFS) at 1 and 2 years was 62.5 and 50.5%, respectively. Multivariate analysis demonstrated that haploidentical related donor, pDLI, and experiencing chronic graft-versus-host disease (cGVHD) were protective from relapse. Total T cells and T cell subsets in peripheral blood recovered at 3 months post-HSCT. The expressions of immune checkpoints (cytotoxic T lymphocyte antigen 4 and programmed death 1) were extremely low in T cells over the first 1 year post-transplantation.


Quality characteristics of wheat-bran chiffon cakes.
Wheat bran was substituted for cake flour in chiffon cakes at 10, 20, and 30 per cent levels. Bran incorporation significantly affected (P less than 0.05) the appearance, height, and grain of chiffon cakes. Cake height decreased and cell size and cell wall thickness increased with higher levels of bran. Tenderness decreased with higher levels of bran. Compressimeter readings were higher with bran substitution at the 10 and 20 per cent levels. Sensory evaluation indicated no significant differences (P less than 0.05) between the control and 10 per cent bran cakes for moistness, flavor, and overall acceptability. Panelists did note a significant (P less than 0.05) decrease in tenderness and softness and an increase in crumbliness with higher bran levels. All chiffon cakes, regardless of bran level, were termed acceptable.


Developmental changes in the effects of lidocaine and quinidine on the canine heart.
We studied the developmental changes that occur in the use-dependent effects of lidocaine and quinidine on the intact canine heart. At comparable intravenous dosages, adults showed higher total and free plasma lidocaine concentrations than young dogs, whereas for quinidine, the total and free levels were comparable. Lidocaine demonstrated a use-dependent depressant effect on intraventricular conduction in adults that was significantly greater than that in the young, and it significantly accelerated repolarization (QT interval) in the adult. In contrast, comparable effects of quinidine were seen on conduction in adult and young dogs, while repolarization was prolonged more in the young. These effects on conduction and repolarization in the adult and young hearts were explained by our earlier cellular electrophysiologic studies. Our findings indicate the following: (a) developmental changes in the cellular electrophysiologic effects of specific antiarrhythmic drugs are predictive of the effects in the in situ heart; (b) these effects are further modified by developmental differences in drug metabolism and protein binding; (c) developmental changes in the effects of one antiarrhythmic local anesthetic are not necessarily predictive of those for another; and (d) the effects of drugs on the adult heart may be, but are not necessarily, predictive of those in the young.


Parvalbumin in rat superior colliculus.
Parvalbumin-like immunoreactivity (PA-LI) has been studied in sections of the superior colliculus (SC) of the rat and its distribution compared to the patterns of acetylcholinesterase (AChE) and cytochrome oxidase (CO) staining. In the intermediate layers it was found that PA-LI is spatially associated with AChE only in the medial part of the SC, but assumes a complementary distribution further laterally. There was a positive correlation between PA-LI and CO. We conclude that the patterns of PA-LI and CO are not systematically related to collicular input known to be associated with the AChE-rich zones, but may reflect adherence to channel separation beyond the terminal fields of clustered afferents.


Dietary intakes of flavonols and flavones and coronary heart disease in US women.
Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990, 1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHD. However, a weak risk reduction for CHD death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk.


A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors.
A major obstacle for successful axon regeneration in the adult central nervous system (CNS) arises from inhibitory molecules in CNS myelin, which signal through a common receptor complex on neurons consisting of the ligand-binding Nogo-66 receptor (NgR) and two transmembrane coreceptors, p75 and LINGO-1. However, p75 expression is only detectable in subpopulations of mature neurons, raising the question of how these inhibitory signals are transduced in neurons lacking p75. In this study, we demonstrate that TROY (also known as TAJ), a TNF receptor family member selectively expressed in the adult nervous system, can form a functional receptor complex with NgR and LINGO-1 to mediate cellular responses to myelin inhibitors. Also, both overexpressing a dominant-negative TROY or presence of a soluble TROY protein can efficiently block neuronal response to myelin inhibitors. Our results implicate TROY in mediating myelin inhibition, offering new insights into the molecular mechanisms of regeneration failure in the adult nervous system.


Anal physiology testing in fecal incontinence: is it of any value?
The prognostic value of postoperative manometry in fecal incontinence is still controversial. The aims of this study were to establish if Fecal Incontinence Severity Index (FISI) and Fecal Incontinence Quality of Life Scale (FIQL) scores correlate with anal manometry and endoanal ultrasound findings and to define if there is any prognostic value in performing anal manometry after patients are surgically treated for fecal incontinence. Fifty-three patients, all women, were identified. All patients underwent a surgical procedure and were analyzed pre- and postoperatively. Fecal incontinence was assessed using the FISI and FIQL. Patients who did not have these score were excluded. Manometry and ultrasound findings before treatment and manometry findings after treatment were compared with surgical patient's incontinence scores. Anal canal length was noted, and its association with the pre- and postoperative manometry finding and incontinence scores were compared. No correlation of pre- and postoperative resting and squeeze pressures with incontinence scores was found. Ultrasound findings had no correlation with manometry results and incontinence scores. Anal canal length correlated with both pre- and postoperative manometry findings but not with incontinence scores. Preoperative anal manometry and endoanal ultrasound help in guiding treatment options in patients with fecal incontinence. A decrease in FISI and increase in FIQL scores after a sphincter repair quantifies improvement after incontinence surgery, while changes in anal manometry pressures readings do not.


[The effect of immune bovine whey on cell-associated glucosyltransferase activity of Streptococcus mutans].
To study the effect of immune bovine whey on cell-associated glucosyltransferase (GTF) activity of S. mutans MT8148. The immune milk was collected from cows immunized with cell-associated GTF overexpression strain B-29-33 of S. mutans MT8148. The control milk was from non-immunized cows. The immune absorbed whey was gotten from immune bovine whey which was absorbed with lyophilized Formalin-killed B-29 whole cells. Three kinds of whey were subdivided into three groups: 50 microliters, 70 microliters, 90 microliters. The content of insoluble glucan was estimated colorimetrically by anthrone method. The control bovine whey had an enhancing GTF activity (407.00%-485.62%). The immune absorbed whey inhibited partly the enhancing GTF activity (208.74%-273.00%). The immune whey inhibited significantly the GTF activity (70.24%-38.62%) and the inhibition showed a tendency to depend on doses. The immune bovine whey inhibits significantly the cell-associated GTF activity of S. mutans MT8148.


Characterization and phylogeny of bitter taste receptor genes (Tas2r) in Squamata.
The perception of bitter taste is linked to the detection of toxins. Therefore, it facilitates avoiding the consumption of potential toxins in the diet. At the molecular level, bitter taste is mediated by taste 2 receptors (Tas2rs). Studies on Tas2r have made major advances in recent years. However, little is known about Tas2rs in Squamata, the second largest order of extant vertebrates. To explore the repertoire and phylogenetic relationships among Tas2r genes in Squamata, we identified and characterized Tas2rs from genome assemblies of 15 Squamata species. We observed considerable Tas2r contraction and expansion in the suborders Serpentes and Lacertilia, respectively. Phylogenetic and reconciliation analysis suggested that lineage-specific gene gains and losses could have led to the Tas2r contraction and expansion in Squamata. Different Tas2r repertoires in Serpents and Lacertilia also reflect their oral anatomical features and taste behaviors. Our findings offer novel perspectives into the study of taste and dietary protection in Squamata species.


Agonist regulation of cellular G protein levels and distribution: mechanisms and functional implications.
Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to be dependent upon the level of receptor expression, and are generally restricted to the G protein(s) with which the receptor interacts. The mechanisms responsible, reviewed here by Graeme Milligan, vary with cell type and include both second messenger-dependent and -independent enhanced protein degradation. Agonist-induced reduction in cellular G protein levels can provide one mechanism for the development of sustained heterologous desensitization.


Land use impact on the water quality of large tropical river: Mun River Basin, Thailand.
Globally, rivers and streams are experiencing declining water quality. Anthropogenic activities largely contribute to surface water pollution. Understanding human-induced influence on river water quality remains a challenge owing to spatiotemporal variations. In this study, we assessed the influence of various land uses (LU) on 16 water quality parameters of the Mun River, a tributary of the Mekong River, at different scales. Water quality was statistically analyzed both spatially and temporally (1995-2010). Seasonal and annual effect of LU on water quality was evaluated at buffer zone scale and sub-basin scale (i.e., catchment scale) using multiple regression analysis. The result showed that urban LU extensively adds to the nutrient concentration [i.e., total phosphorus (TP), ammonia nitrogen (NH3-N)] followed by agriculture LU at the sub-basin scale. Site-specific variability of TP is explained by urban LU and biological oxygen demand (BOD) by agriculture LU at the 5-km buffer in Upper and Middle Mun whereas at Lower Mun, the 20-km buffer explains the variability of suspended solids (SS) and total suspended solids (TSS), suggesting a more localized effect on the parameters upstream. The high concentration of parameters was noted in the dry season whereas the opposite was true for fecal coliform bacteria (FCB), SS, and TP. The maximum parameter concentration of NH3-N, FCB, and total coliform bacteria exceeds the permissible surface water quality standards of the Pollution Control Department (PCD) of Thailand in all three sub-basins. The study suggests the need for multi-scale interventions and effective pollution control measures focusing on nutrient, pathogenic bacteria, and solids pollution to improve the river water quality of large river basin.


Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily.
cDNA clones encoding the human and murine interleukin-7 (IL-7) receptor were isolated and expressed in COS-7 cells. Binding of radiolabeled IL-7 to the recombinant IL-7 receptors produced curvilinear Scatchard plots containing high and low affinity classes. These binding properties, as well as the molecular size of the cloned receptor, were comparable to the native forms of the IL-7 receptor. In addition, several cDNA clones were isolated that encode a secreted form of the human IL-7 receptor capable of binding IL-7 in solution. Analysis of the sequence of the IL-7 receptor revealed significant homology in the extracellular domain to several recently cloned cytokine receptors, demonstrating that the IL-7 receptor is a member of a new receptor superfamily.


How Does the Display Luminance Level Affect Detectability of Breast Microcalcifications and Spiculated Lesions in Digital Breast Tomosynthesis (DBT) Images?
This study evaluates the influence of the calibrated luminance level of medical displays in the detectability of microcalcifications and spiculated lesions in digital breast tomosynthesis images. Four models of medical displays with calibrated maximum and minimum luminance, respectively, ranging from 500 to 1000 cd/m2 and from 0.5 to 1.0 cd/m2, were investigated. Forty-eight studies were selected by a senior radiologist: 16 with microcalcifications, 16 with spiculated lesions, and 16 without lesions. All images were anonymized and blindly evaluated by one senior and two junior radiologists. For each study, lesion presence or absence and localization statements, interpretative difficulty level, and overall quality were reported. Cohen's kappa statistic was computed between monitors and within or between radiologists to estimate the reproducibility in correctly identifying lesions; for multireader-multicase analysis, the weighted jackknife alternative free-response receiver operating characteristic statistical tool was applied. Intraradiologist reproducibility ranged from 0.75 to 1.00. Interreader as well as reader-truth agreement values were >0.80 and higher with the two 1000 cd/m2 luminance displays than with the lower luminance displays for each radiologist. Performances in the detectability of breast lesions were significantly greater with the 1000 cd/m2 luminance displays when compared to the display with the lowest luminance value (P value <0.001). Our findings highlight the role of display luminance level on the accuracy of detecting breast lesions.


The behavior of different carrageenans in pelletization by extrusion/spheronization.
kappa-Carrageenan is known as a novel pelletization aid in manufacturing of pellets by extrusion/spheronization. The implentation of kappa-carrageenan as a pelletization aid can overcome several disadvantages of commonly used microcrystalline cellulose (MCC) such as lacking disintegration and adsorption of several actives. The aim of this study was to compare different types of carrageenans from different suppliers: one iota-, five kappa-, and one lambda-carrageenan. The kappa-carrageenans had the best pelletization behavior. Four of the five tested kappa-carrageenans resulted in pellets with acceptable shapes, sizes, and size distributions using a high drug load of 80% hydrochlorothiazide. These pellets have similar properties over a wide range of water contents ranging from 90 to 105%. The filler, dicalcium phosphate, affected the pelletization process and the pellet properties of all investigated kappa-carrageenans.


[Si(SiMe(3))(3)](6)Ge(18)M (M = Cu, Ag, Au): metalloid cluster compounds as unusual building blocks for a supramolecular chemistry.
Very recently it was shown that the metalloid cluster compound {Ge(9)[Si(SiMe(3))(3)](3)}(-) can be used for subsequent reactions as the shielding of the cluster core is rather incomplete. Here further reactions of with M(+) sources of group 11 metals are described, leading to metalloid cluster compounds of the formula {MGe(18)[Si(SiMe(3))(3)](6)}(-) (M = Ag, Cu). These reactions can be seen as first steps into a supramolecular chemistry with metalloid cluster compounds. Beside this feature, the structural properties as well as the bonding situations in these cluster compounds are discussed.


FLT3 ligand can substitute for macrophage colony-stimulating factor in support of osteoclast differentiation and function.
Although bone resorption and osteoclast numbers are reduced in osteopetrotic (op/op) mice, osteoclasts are nevertheless present and functional, despite the absence of macrophage colony-stimulating factor (M-CSF). This suggests that alternative factors can partly compensate for the crucial actions of M-CSF in osteoclast induction. It was found that when nonadherent bone marrow cells were incubated in RANKL with Flt3 ligand (FL) without exogenous M-CSF, tartrate-resistance acid phosphatase (TRAP)-positive cells were formed, and bone resorption occurred. Without FL, only macrophagelike TRAP-negative cells were present. Granulocyte-macrophage CSF, stem cell factor, interleukin-3, and vascular endothelial growth factor could not similarly replace the need for M-CSF. TRAP-positive cell induction in FL was not due to synergy with M-CSF produced by the bone marrow cells themselves because FL also enabled their formation from the hemopoietic cells of op/op mice, which lack any M-CSF. FL appeared to substitute for M-CSF by supporting the differentiation of adherent cells that express mRNA for RANK and responsiveness to RANKL. To determine whether FL can account for the compensation for M-CSF deficiency that occurs in vivo, FL signaling was blockaded in op/op mice by the injection of soluble recombinant Flt3. It was found that the soluble receptor induced a substantial decrease in osteoclast number, strongly suggesting that FL is responsible for the partial compensation for M-CSF deficiency that occurs in these mice.


Effects of extraction conditions on the sensory and instrumental characteristics of fish gelatin gels.
Fish skin gelatin has recently been of interest as a product that eliminates religious concerns (Jewish and Muslim) and could be an alternative value-added product from fish waste. Recent research has shown that extraction conditions affect gelatin quality. In this study, gelatin from Asian silver carp skin and extracted under different conditions have been studied sensory properties using descriptive analysis and time intensity testing to determine how extraction conditions affect gelatin sensory properties. Three pairs of gelatin samples were selected based on their gel strength, viscosity, and melting temperature. The impacts of different extraction conditions on instrumental methods were examined. Some functionality measurements were also done to determine how sensory measurements correlate with instrumental measurements. The gel strength varied between 60 ± 10 g and 590 ± 30 g while the viscosity varied between 1.9 ± 0.0 cP and 7.4 ± 0.2 cP. The hardness, melting and gelling temperature of the samples were well correlated with the gel strength (r > 0.90). The results indicated that the strongest correlation among all the sensory attributes was between firmness and melting temperature, which was a negative correlation (-0.75) suggesting that the firmer the gel samples the slower they melt. The viscosity was found to be very discriminative between samples in terms of sensory properties. The functional measurements were found to be strongly correlated within themselves while the sensory measurements were less so, which might be due to the greater variability when using sensory panelists or sensory parameters simply might not be related. The firmness, melting rate, and aftertaste were those sensory attributes most successfully discriminated by the panelists.


Rapid recognition of aberrant dHPLC elution profiles using the Transgenomic Navigator software.
Despite the availability of numerous technologies for detecting mutations, only a few have been formatted for automated mutation calling. Here, we evaluate the utility of the Transgenomic Navigator software to facilitate automated detection of aberrant denaturing high performance liquid chromatography (dHPLC) elution profiles. We used dHPLC to identify germline variants in MSH6, NEIL2, NEIL3, and OGG1 in 172 patients with multiple colorectal adenomas. 3,747 dHPLC profiles were analysed with the Navigator software using three levels of analysis, each differing in the degree of operator input. 43.5% (60/138) and 98.3% (59/60) of products with profiles distinct from wild type ('outliers') harboured novel variants under Level 1 and Levels 2/3 analysis conditions, respectively. We also assessed the utility of the software to rapidly detect samples carrying common polymorphisms by analysing regions of the genes that harbour polymorphisms with minor allele frequencies between 8 and 40%, therein analysing 2,784 profiles. We showed that 1573/1612 (97.6%) and 1137/1172 (97.0%) of PCR products were correctly classified as wild-type and variant, respectively (Level 3 analysis conditions). Finally, we assessed the utility of the software to detect novel variants in fragments that also harboured common polymorphisms and showed that 59/61 (96.7%) of products with profiles outlying both the wild type and polymorphism groups harboured novel variants. We conclude that the Navigator software provides an excellent tool for rapid discrimination of aberrant dHPLC elution profiles that harbour sequence variants.


Separation of serum antibody activities by anion-exchange cellulose chromatography.
Mumps, Histoplasma capsulatum. thyroglobulin, and typhoid H antibodies were found in fraction 1, which contained only gamma globulins with ultracentrifugal sedimentation coefficients of 6.6 Svedberg units (S). Typhoid O antibodies and rheumatoid factor were only in fraction 5, composed principally of gamma macroglobulins with ultracentrifugal sedimentation coefficients of 18 S. In contrast isohemagglutinins, Rh antibodies, and anti-human liver nucleoprotein activities were found in two chromatogram fractions (1 and 5) with different physicochemical properties.


Foreign body removal assisted by an intraoral ultrasound probe.
Ultrasonography has recently been applied to the field of oral and maxillofacial surgery because of its noninvasiveness and ease of use. However, traditional transducers are not used in the intraoral area because of their large size. A novel intraoral transducer was introduced with size, volume, and axis modifications. This new transducer allows the surgeon to approach the intraoral region during dental procedures. This report describes a case of successful removal of a foreign body using the newly developed intraoral ultrasound probe. Precise localization and minimally invasive removal of the foreign body using the intraoral transducer were simultaneously conducted. Because of its many advantages, this intraoral ultrasound transducer has the potential to be applied in oral and maxillofacial surgery.


A methodical approach for the assessment of waste sorting plants.
A techno-economical evaluation of the processing result of waste sorting plants should at least provide a realistic assessment of the recovery yields of valuable materials and of the qualities of the obtained products. This practical data is generated by weighing all the output products and sampling these products. Due to the technological complexity of sorting plants, for example, lightweight packaging waste treatments plants and the high expenditures concerning time and costs of sampling with subsequent manual sorting for quality determination, usually only final products undergo such an investigation. Thereby, the transferability of the results depends decisively on the boundary conditions (extent, throughput of the plant, process parameterization). Given that the process is too complex, not all relevant information of the process steps can be determined by sampling. By model calculations and/or adjustment of reasonable assumptions, information concerning weak points in the process can be identified, which can be used for further plant optimization. For the example of the recovery of beverage cartons from co-collected and mechanically recovered mixtures of lightweight packaging waste, a methodical approach for the assessment of processing results will be presented.


Reduced functionality of PSE-like chicken breast meat batter resulting from alterations in protein conformation.
The objectives of this study were to evaluate protein thermal stability, water-protein interaction, microstructure, and protein conformation between PSE-like and normal chicken breast meat batters. Sixty pale, soft, and exudative (PSE)-like (L*>53, pH24 h<5.7) and 60 normal (46<L*<53, 5.7<pH24 h<6.1) chicken breast meats were selected from 3 different occasions in a major Chinese commercial plant. Two different meat batters were formulated to 14% meat protein and 2% salt, and they were analyzed for the protein changes and the microstructure using differential scanning calorimetry, low-field (LF)-NMR, SEM, and Raman spectroscopy. PSE-like meat batter had lower gel strength, water-holding capacity, and salt-soluble protein extraction (P<0.05). Heated PSE-like meat batter formed an aggregated gel matrix, while normal meat batter produced a compact gel network with fine, cross-linked strands by many protein filaments. LF-NMR revealed an increase in the water mobility in heated PSE-like meat batter with an increasing amount of loosely bound water (P<0.05). No significant changes were observed in the electrophoretic patterns of salt-soluble protein extracts by SDS-PAGE. However, differential scanning calorimetry showed that PSE-like meat had greater myosin and sarcoplasmic proteins/collagen denaturation (P<0.05). In PSE-like meat, actin denaturation was particular evident after salt addition (P<0.05) using differential scanning calorimetry. Moreover, Raman spectroscopy indicated that PSE-like meat batter had less unfolded α-helix and β-sheet structure formation, reduced exposure of hydrophobic and tyrosine residues (P<0.05), and changes in the microenvironment of aliphatic residues and tryptophan, which affected salt-soluble protein extraction, gel properties, and water-holding capacity. In conclusion, the inferior functional properties of PSE-like meat were attributed to not only myosin denaturation, but also actin denaturation after salt addition and different protein structural states.


Case of metastatic breast cancer from esophageal cancer.
Metastasis to the breast from extramammary malignancies is rare. This is the third case report of metastatic breast cancer from esophageal cancer. We report the clinical, radiographic, and pathologic findings of a 57-year-old woman who underwent esophagectomy for esophageal cancer and developed metastatic cancer 2 years later. Pathologic examination of a resected specimen of the breast revealed squamous cell carcinoma invading the mammary glands. Estrogen receptor and axillary lymph node metastasis were negative with immunostaining. She is alive 6 months after the modified radical mastectomy.


Regulatory T cells in a spectrum of HPV-induced cervical lesions: cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma.
Thriving of tumors amidst rich immune infiltrates is an unexplained paradox. Immune markers on lymphocytic infiltrates in HPV-positive cervicitis, cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (SCC) and normal cervices were characterized immunohistochemically. Regulatory T cells were enumerated and phenotypically characterized using antibodies to FOXP3. SCCs had higher numbers of CD4 and CD8 cells; infiltrates expressed more CD25, TGFbeta, and IL10 but had significantly lower IL2 compared with cervicitis and CIN III. Expression of CD25 and IL2 correlated well in cervicitis and CIN III but not in SCC. FOXP3 expression was also higher and ratios of CD4/FOXP3 and CD8/FOXP3 were lower in SCC. A fraction of cervicitis, CIN I, CIN II and CIN III had natural (n) regulatory T cells (Tregs); their lesional distribution was predominantly intraepithelial in cervicitis, while in CIN they were also present in the stroma. The proportion of FOXP3(+) CD25(+); FOXP3(+) CD25(-) and TGFbeta(+) CD25(+) in invasive tumors was 17; 19 and 22 respectively. Cervical tumors are marked by the presence of an immunoregulatory environment, and harbor equal proportions of 'inactive' n Tregs; activated n Tregs; and Tregs operating via TGFbeta. nTregs in cervicitis and CIN may be a potential marker of persistence.


Device for craniocervical isolation in rabbits.
To evaluate the craniocervical isolation collar, for use in rabbits, with regard to the following aspects: effectiveness of the craniocervical attachment for up to 120 hours; ease of handling; freedom of the animal to move about and ingest food; and the physical integrity of the animal during and after use of the device. Starting from an Elizabethan collar, a craniocervical collar was prepared for use in rabbits with the following modifications: a wide cut in the device in the shape of a half-moon, coinciding with the animal's mouth; inner division of the device into two compartments to individually isolate and immobilize the ears; multiple perforations in the upper compartment for better ventilation; adaptation of the cervical-thoracic band to attach the collar to the cervical region, keeping the fasteners on the animal's back. The device was used on 18 male New Zealand rabbits for up to 120 consecutive hours. The device was effective in the craniocervical isolation and separation of ears in rabbits without interfering with the animals' respiration, ability to swallow food, or causing physical trauma, while allowing the animals to move about freely and rest comfortably. Attaching and removing the device was easy and quick and it remained in place for up to 120 hours without the need to reposition it. The modified craniocervical isolation collar made it possible to conduct the experiment with isolation of the rabbits' ears, ease of handling, and without causing limitations in relation to the animals' ability to eat and move about freely.


After vs. priming effects of anodal transcranial direct current stimulation on upper extremity motor recovery in patients with subacute stroke.
Transcranial direct current stimulation (tDCS) of the motor cortex seems to be effective in improving motor performance in patients with chronic stroke, while some recent findings have reported conflicting results for the subacute phase. We aimed to verify whether upper extremity motor rehabilitation could be enhanced by treatment with tDCS administered before a rehabilitative session. Hand dexterity and force in 16 individuals with subacute stroke were assessed before (T0) and after anodal stimulation (T1) and after a successive session of motor rehabilitation (T2) in a double-blind, randomized, sham-controlled, crossover trial. To confirm the value of the device as a specific effector, behavioral tests were also administered. Anodal and sham stimulation plus rehabilitation significantly improved manual dexterity (repeated-measure Anova: A-tDCS: p = 0.005; S-tDCS: p = 0.042). Post hoc analysis revealed a significant stimulation effect only for A-tDCS (p = 0.013 between T0 and T1) and not for S-tDCS, whereas the rehabilitation effect (between T1 and T2) was not significant in either group. Hand force and behavioral features were unchanged. Anodal brain stimulation improves hand dexterity but does not increase the effectiveness of the rehabilitation directly. These results suggest the presence of aftereffects, not priming effects, of A-tDCS superimposed onto motor learning phenomena.


The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation.
The membrane attack complex of complement (MAC), apart from its classical role of lysing cells, can also trigger a range of non-lethal effects on cells, acting as a drive to inflammation. In the present study, we chose to investigate these non-lethal effects on inflammasome activation. We found that, following sublytic MAC attack, there is increased cytosolic Ca(2+) concentration, at least partly through Ca(2+) release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels. This increase in intracellular Ca(2+) concentration leads to Ca(2+) accumulation in the mitochondrial matrix via the 'mitochondrial calcium uniporter' (MCU), and loss of mitochondrial transmembrane potential, triggering NLRP3 inflammasome activation and IL-1β release. NLRP3 co-localises with the mitochondria, probably sensing the increase in calcium and the resultant mitochondrial dysfunction, leading to caspase activation and apoptosis. This is the first study that links non-lethal effects of sublytic MAC attack with inflammasome activation and provides a mechanism by which sublytic MAC can drive inflammation and apoptosis.


Differential linear scan voltammetry: analytical performance in comparison with pulsed voltammetry techniques.
We report here on differential linear scan voltammetry, DLSV, that combines the working principles of linear scan voltammetry, LSV, and the numerous existing pulsed voltammetry techniques. DLSV preserves the information from continuous interrogation in voltage and high accuracy that LSV provides about electrochemical processes, and the much better sensitivity of differential pulsed techniques. DLSV also minimizes the background current compared to both LSV and pulsed voltammetry. An early version of DLSV, derivative stationary electrode polarography, DSEP, had been proposed in the 1960s but soon abandoned in favor of the emerging differential pulsed techniques. Relative to DSEP, DLSV takes advantage of the flexibility of discrete smoothing differentiation that was not available to early investigators. Also, DSEP had been explored in pure solutions and with reversible electrochemical reactions. DLSV is tested in this work in more challenging experimental contexts: the measurement of oxygen with a carbon fiber microelectrode in buffer, and with a gold microdisc electrode exposed to a live biological preparation. This work compares the analytical performance of DLSV and square wave voltammetry, the most popular pulsed voltammetry technique.


Rational design, chemical synthesis and biological evaluation of novel biguanides exploring species-specificity responsiveness of TAAR1 agonists.
The design of novel chemical classes acting towards several G-protein-coupled receptors (GPCRs) represents a leading strategy in drug discovery, aimed at deriving effective and safe candidates for further assessment. During the last years, TAAR1 arose as a promising druggable target in medicinal chemistry, being of interest in the treatment of several pathologies, such as neuropsychiatric disorders, type 2 diabetes and obesity. Nevertheless, the limited number of known potent and selective ligands and the species-specificity responsiveness exhibited by those derivatives nowadays available make the discovery of novel compounds a challenging task. Herein, we discuss the development of two quantitative-structure activity relationship (QSAR) models around the agonism ability experienced by different chemo-types toward murine and human TAAR1 (m/hTAAR1) with the aim at deciphering some clues involved in their species-specificity responsiveness. Qualitatively, these information were evaluated guiding for the synthesis of novel ligands, which proved to feature selective agonism ability with respect to the mTAAR1 and hTAAR1 orthologues.


Preoperative prognostic factors in diabetic pars plana vitrectomy.
The postoperative, six-month visual acuities of 1056 diabetic vitrectomy cases were compared to the following preoperative findings: duration of decreased vision associated with detachments, pupillary responses, iris rubeosis, intraocular tensions, extent of neovascularization, macular status, the ability to recognize entoptic phenomena, bright-flash ERG, and ultrasonography. By comparing these findings to the postoperative visual results, several factors were detected that could be helpful in determining the preoperative prognosis for improved vision. However, major operative complications reduced the incidence of successful visual results from 53% to 22%.


Revisiting crowd-out update.
Crowd-out occurs when the existence of public insurance causes people to shift from private to public coverage, thus stretching scarce government resources to insure those who could access private plans. This update looks at the research published since the 2004 synthesis was released. Key findings include: Some level of crowd-out will always occur with public program expansions. There is a wide range of estimates of crowd-out with lower estimates for low-income children (0 to 15%) and higher rates for higher-income children and longer-term enrollees (35% to 50%). Recent studies confirm the most common anti-crowd-out measures--waiting periods and increased public-plan premiums--discourage both the uninsured and the privately insured from enrolling in public coverage. Crowd-out is more likely when eligibility is expanded to include higher-incomes and entire families. Crowd out can occur based on employers', as well as employees' behaviors, but it appear the recent decline in ESI is more a result of employee take-up rather than employers dropping health benefits. Finally, there is limited research that suggests children with public coverage are better off than those with private insurance.


Intravenous fentanyl increases natural killer cell cytotoxicity and circulating CD16(+) lymphocytes in humans.
Opioids, including fentanyl, are often administered to patients who may be at risk for the consequences of impaired immune function. We performed a clinical study to test the effects of the synthetic opioid fentanyl on human immune function. Participants received an IV fentanyl initial dose of 3 microg/kg followed by a 2-h IV infusion of 1.2 microg x kg(-1) x h(-1). Peripheral blood was drawn before and after fentanyl administration to test for neutrophil phagocytic function, neutrophil antibody-dependent cell cytotoxicity, natural killer cell cytotoxicity, percentage of lymphocyte populations, T-lymphocyte proliferative response, and in vivo antibody response to a pneumococcal vaccine inoculation given at the end of the fentanyl infusion. Fentanyl exposure under the conditions of this study caused a rapid and significant increase in natural killer cell cytotoxicity, which was coincident with an increase in the percentage of CD16(+) and CD8(+) cells in peripheral blood. Fentanyl did not significantly affect any of the other immune measurements. Many previous studies have suggested that opioid drugs can impair immune resistance in patients who may be at risk for infection. This study suggests that the opioid fentanyl, when given to healthy humans without coexisting diseases, does not suppress immune resistance. On the basis of these results, the use of fentanyl should not be restricted because of concerns that it may suppress immune function.


[The role of retinal-hypotalamic-pineal system in pro- and antioxidant processes in the gingival tissues of adult male albino rats].
The aim of this study is to evaluate the effects of pineal gland functional state on the prooxydant processes and antioxidant system in the gingival tissues. Male rats were assigned into one of the following groups in accordance with the duration of photoperiod: 1) control--natural daylight; 2) permanent darkness for 14 days; 3) permanent light for 14 days. The following parameters were measured in gingival tissues and the blood serum: 1) prooxidant factors (dieneconjugates--DC and malonic dialdehyde--MD); 2) antioxidant enzymes (superoxide dismutase--SOD and catalase). The present findings indicate that the gingival tissue of rats reacts to the changes in the duration of photoperiod by peroxidation and activity of antioxidant enzymes. The antioxidant-prooxidant index under dark conditions (high function of the pineal gland) was lower than under condition of permanent light ("physiological" pinealectomy). Different durations of photoperiod change the intensity of free radical oxidation and the activity of antioxidant enzymes at the systemic level (blood serum) and much more at the organ level (tissues of gingiva). Our data suggest that the gingival tissues possess rather powerful protective antioxidant system, which depends on the functional state of the pineal gland.


Dynamic cerebral autoregulation assessment using an ARX model: comparative study using step response and phase shift analysis.
Middle cerebral arterial blood velocity (MCAv) response to spontaneous and manipulated changes of arterial blood pressure (ABP) was studied in eight subjects using a linear autoregressive with exogenous input (ARX) model. ABP and MCAv were measured non-invasively by photoplethysmograph and transcranial Doppler ultrasound, respectively. Data were recorded at rest (spontaneous changes in ABP) and during thigh cuff (step-wise changes) and lower body negative pressure (sinusoidal changes of 1/12 Hz) tests in both normocapnia and hypercapnia (5% CO2). Since autoregulation is modulated by CO2, respiratory CO2 was simultaneously monitored to allow comparison of cerebral autoregulation status with different CO2 levels. ABP and MCAv were fitted by ARX models and dynamic cerebral autoregulation was estimated by analysing both the step responses and phase shift at the 1/12 Hz of the corresponding ARX models. The ARX model consistently modelled the phase lead of MCAv to ABP and it showed that the phase shift at 1/12 Hz of ARX model is consistent with the real phase shift of the data (p=0.59). Strong linear relationships between pCO2 and gradient of the step response (r=-0.58, p<0.0001) and between pCO2 and phase shift (r=-0.76, p<0.0001) were observed, which suggests that cerebral autoregulation can be assessed by step response or phase shift analysis of the ARX model fitted to ABP and MCAv data with spontaneous changes.


Convenient preparation of 1-amidoindenes.
Lewis acid-catalyzed alpha-amidoalkylation of enolizable aldehydes with N-(alpha-benzotriazolyl-alpha-arylalkyl)amides followed by intramolecular Friedel-Crafts cyclization provides a convenient route to 2-substituted 1-amidoindenes.


Autologous transplantation for CML using marrow treated ex vivo with recombinant human interferon gamma.
Six chronic and four advanced patients with Ph1 positive chronic myelogenous leukemia (CML) received autologous bone marrow transplantation (ABMT) using bone marrow treated ex vivo with recombinant human interferon gamma (rIFN gamma). In three cases 100% Ph1 negative bone marrow hematopoiesis was demonstrated 4 to 8 weeks after ABMT. In three additional cases, a maximum of 40-45% bone marrow metaphases were Ph1 negative 2 to 12 weeks following ABMT. In four cases, no or minimal evidence of Ph1 negative hematopoiesis could be demonstrated posttransplant. Seven patients survive in chronic phase at a median of 375 days (range 100-495 days). Five patients have not required therapy, while two patients receive low doses of rIFN alpha to control peripheral blood counts. Ex vivo treatment of CML bone marrow with rIFN gamma followed by ABMT in patients dependent upon or refractory to therapy prior to transplantation is associated with transient complete or partial Ph1 negative bone marrow hematopoiesis in the majority of patients post-transplant and with return of a chronic phase characterized by no need for therapy or by response to low doses of rIFN alpha. Modification of the ABMT procedure and efforts to maintain cytogenetic and hematologic remission following ABMT may lead to prolonged survival or cure.


Ultrastructural immunocytochemical localization of vitellogenin in the fat body of the blowfly, Calliphora vicina Rob.-Desv. (erythrocephala Meig.) by use of the unlabeled antibody-enzyme method.
The unlabeled antibody-enzyme method was used to demonstrate ultrastructurally the specific localization of vitellogenin in the fat body of Calliphora. In control flies the binding sites to vitellogenin were localized in secretory granules situated in the Golgi complex, and in larger bodies named composite secretory granules. These composite granules appear to be formed when a part of a Golgi complex containing secretory granules and a number of small vesicles become surrounded by a common membrane. Ovariectomized flies, which apparently do not produce secretory granules, exhibited no immunocytochemical staining. Ovariectomized flies in which the administration of ecdysterone induced formation of secretory granules, also revealed specific staining on these granules. This is the first ultrastructural evidence of: (a) the specific localization of vitellogenin in secretory granules of the fat body of an insect; (b) the relationship between the presence of the ovary, and of ecdysterone, and the synthesis of vitellogenin by the fat body.


Socioeconomic status in systemic lupus erythematosus.
Our understanding of the biological pathogenesis of systemic lupus erythematosus (SLE) is rapidly expanding. Although biologic research is vital, studies that address the importance of socioeconomic factors that contribute to the causation of the outcome of SLE are necessary to understand the full scope of the disease. Studies of social factors in SLE usually include ethnicity, gender and socioeconomic status (SES) as categorical variables. One hypothesis is that these variables exert their effect through a biologic or genetic factor. However, there is growing evidence to suggest a more direct psychological or sociological impact of these variables on disease. Although in research studies it may be difficult to tease out the biological and sociological impacts of these variables, the eventual understanding of these diverse roles will help in the design of eventual therapeutic interventions.


The influence of epidermal windows on the light environment within the leaves of six succulents.
An omni-directional fibre optic microprobe was used to measure the quantity and quality of light within the leaves of six succulents having epidermal windows, three species having a subterranean growth habit (Haworthia truncata, Lithops olivacea, and Opthalmophyllum longum) and three growing above ground (Peperomia dolabriformis, P. graveolens, and the sprawling vine Senecio rowleyanus). Although light levels at most locations inside the leaves of all species were high, near those incident on the window surfaces, light levels inside the leaves of the two species of Peperomia often greatly exceeded incident light levels, indicating considerable light scattering and focusing by the leaf tissue. The spectral quality of light inside the leaves of all taxa reflected the absorption properties of chlorophyll, with most of the photons in the green wavelengths. Light quality and quantity inside the leaves did not correlate with the growth habit of the plants, the size of the window (as a proportion of the total leaf area), or location inside the leaf, although light levels generally declined and wavelengths increased deeper in the leaves. Application of reflective tape to the windows reduced internal light levels in L. olivacea and S. rowleyanus, although reductions were not always statistically significant. Although light levels throughout the leaves of P. graveolens were substantially and significantly reduced as a result of the application of reflective tape to its windows, the light levels even at the basal chlorenchyma on the abaxial side of the leaf remained high. In all species investigated, the levels of near-infrared radiation inside the leaves were surprisingly high, yet also declined deeper inside the succulent leaves. This near-infrared radiation may add to the heat load of these plants. Furthermore, application of reflective tape to the windows also reduced the amount of near-infrared radiation inside the leaves of the three succulents examined. These results led to a novel, testable hypothesis that may help to explain previous findings that application of reflective tape to the windows of the leaves of these succulents did not effect a reduction in photosynthetic activity.


A comprehensive approach to die trimming.
Proper trimming of stone dies is an essential step in fixed prosthodontics. Die trimming requires meticulous technique and a thorough understanding of required elements in die design. By dividing the die into three zones, die contour requirements can be better understood, discussed, and demonstrated. A two-step technique provides optimal results, incorporating a logical plan with the use of proper magnification and illumination.


Detection of Borrelia burgdorferi DNA in tick feces provides evidence for organism shedding during vector feeding.
Borrelia burgdorferi, the bacterium that causes Lyme disease, is transmitted to a susceptible host by Ixodes spp. tick bites. However, there is uncertainty whether B. burgdorferi are shed from ticks by the fecal route. In this study, B. burgdorferi-infected ticks were fed on mice while confined to a certain area of the skin by a capsule. During and after feeding, tick feces were collected and placed in Barbour-Stoenner-Kelley (BSK)-II media for cultivation and in sterile water for polymerase chain reaction (PCR) analysis. Although none of the tested samples were culture positive for B. burgdorferi, all but one of the fecal DNA samples from infected ticks were PCR positive. These results indicated that B. burgdorferi were shed from feeding ticks during defecation and suggest that the spirochetes did not remain viable once exposed to the outside environment. This finding has important ramifications for investigators interpreting B. burgdorferi-specific PCR results when conducting tick transmission experiments.


Non-thermal internal energy distribution of ions observed in an electrospray source interfaced with a sector mass spectrometer.
The internal energy distribution P(E(int)) of ions emitted in an electrospray (ESI) source interfaced with a sector mass spectrometer is evaluated by using the experimental survival yield (SY) method including the kinetic shift. This method is based on the relationship between the degree of fragmentation of an ion and its amount of internal energy and uses benzylpyridinium cations due to their simple fragmentation scheme. Quantum chemical calculations are performed, namely at G3(MP2)//B3LYP and QCISD/MP2 levels of theory. The results show that the internal energy distribution of the ions emitted in the ESI source interfaced with a sector analyzer is very narrow. The MassKinetics software is used to confirm these observations. The P(E(int)) is the parameter that allows to fit the experimental SY of each substituted benzylpyridinium cation with theoretical mass spectra generated by the MassKinetics software. The resulting internal energy distributions are similar to the ones obtained with the experimental SY method. This indicates that in the present experimental conditions, P(E(int)) cannot be compared with a 'thermal-like' Boltzmann distribution. In addition, it appears that with the sector analyzer, increasing the collision energy in the first pumping stage of the ESI source does not correspond to a warm-up of the produced ions.


[The phenomenology of hysterical personality disorder].
Phenomena that are observable in the "classic" hysterical personality disorder are named, described and classified according to the basic functions of human experience and behavior. In this way, a psychopathological picture of the hysterical personality arises, which can facilitate the sometimes difficult task of diagnosis and differential diagnosis. It is shown that the phenomenon of dissociation is one essential characteristic of this disorder. The dissociation of the mental processes is demonstrated for the various basic functions. It implies a dissociation of contents and of parts of personality on the axis conscious-preconscious/unconscious. The dissociation ultimately becomes a prerequisite for living these not permitted and not integrated parts of personality in a partial and compromising way.


Clinical update: proteasome inhibitors in solid tumors.
The proteasome plays a critical role in regulating the cell cycle, neoplastic growth, and metastasis. Bortezomib (VELCADE; formerly PS-341, LDP-341, MLN341) is a novel dipeptide boronic acid that is the first proteasome inhibitor to have progressed to clinical trials. Preclinical research has shown that through the prevention of IkappaB degradation, bortezomib may block chemotherapy-induced NF-kappaB activation and augment the apoptotic response to chemotherapeutic agents. Bortezomib also appeared to increase the stabilization of p21 and p27, as well as transcription factor p53. In preclinical models of breast, lung, pancreatic, and ovarian tumor types, bortezomib inhibited tumor growth and demonstrated anti-angiogenic properties. Bortezomib exhibited the greatest activity when combined with standard chemotherapeutic agents, such as irinotecan, gemcitabine, and docetaxel, suggesting its potential additive/syngeristic role in overcoming resistance to conventional chemotherapy. Preliminary data from early clinical trials suggest that bortezomib can be given at pharmacologically active doses in combination with standard doses of chemotherapy with manageable toxicities. Responses have been seen and no evidence of additive toxicity has been exhibited in combination agent trials.


Analysis sans frontières: can we ever make economic evaluations generalisable across jurisdictions?
Over the last decade or so, a number of healthcare systems have used economic evaluations as a formal input into decisions about the coverage or reimbursement of new healthcare interventions. This change in the policy landscape has placed some important demands on the design and characteristics of economic evaluation and these are increasingly evident in studies being presented to decision makers. One challenge has been to make studies specific to the context in which the decision is being taken. This is because of the inevitable geographical variation in many of the parameters within an analysis. There has been a series of important contributions to the published literature in recent years on how to quantify geographical heterogeneity within economic analyses based on randomised controlled trials. However, there are good reasons for economic evaluation for decision making to be undertaken using methods of evidence synthesis and decision analytical modelling, but issues of geographical variation still need to be handled appropriately. The key requirements of economic evaluations for decision making within healthcare systems can be defined as follows: (i) a design that meets the objectives and constraints of the healthcare system; (ii) coherent and complete specification of the decision problem; (iii) inclusion of all relevant evidence; and (iv) recognition and appropriate handling of uncertainty. In satisfying these requirements, it is important to be aware of variation between jurisdictions, and this imposes some important analytical requirements on economic studies. While many agencies have produced guidelines on preferred methods for healthcare economic evaluation, these exhibit considerable variation. Some of this variation can be justified by genuine differences between systems in clinical practice, objectives and constraints, while some of the variation relates to differences of opinion about appropriate analysis given methodological uncertainty. However, some of the variation in guidance is difficult to justify and is inconsistent with the aims and objectives of the systems the analyses are seeking to inform. Decision makers and analysts need to work together to streamline and where possible harmonise guidelines on methods for economic evaluations, whilst recognising legitimate variation in the needs of different healthcare systems. Otherwise, there is the risk that scarce resources will be wasted in producing country-specific analyses in situations where these are not justified. Expected value of information analyses are also emerging as a tool that could be considered by decision makers to guide their policy on the acceptance or non-acceptance of data from other jurisdictions.


Function of the interarytenoid muscle in a canine laryngeal model.
The interarytenoid (IA) muscle has rarely been studied in the living larynx. In this work, the role of the IA muscle in phonation was studied in three dogs by means of an in vivo phonation model. The isolated action of the IA muscle was studied by sectioning and stimulating its nerve branch. As IA activity increased, subglottic pressure increased significantly until a plateau was reached. In the absence of superior laryngeal nerve stimulation, the fundamental frequency rose with increasing IA activity. In the presence of superior laryngeal nerve stimulation, however, no significant change in fundamental frequency was observed with increasing IA activity. Measurement of adductory force demonstrated that the IA muscle adducts primarily the posterior vocal fold. In this canine model, phonation was not possible without IA stimulation, owing to a large posterior glottic chink.


Cytokine profile of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during seasonal H1N1 infection.
Several studies support the role of viral infections in the pathogenesis of asthma exacerbation. However, several pediatricians believe that influenza virus infection does not exacerbate bronchial asthma, except for influenza A H1N1 2009 pandemic [A(H1N1)pdm09] virus infection. We previously reported that A(H1N1)pdm09 infection possibly induces severe pulmonary inflammation or severe asthmatic attack in a mouse model of bronchial asthma and in asthmatic children. However, the ability of seasonal H1N1 influenza (H1N1) infection to exacerbate asthmatic attacks in bronchial asthma patients has not been previously reported, and the differences in the pathogenicity profiles, such as cytokine profiles, remains unclear in bronchial asthma patients after A(H1N1)pdm09 and H1N1 infections. The cytokine levels and viral titers in the bronchoalveolar lavage (BAL) fluid from mice with and without asthma after H1N1 infection (A/Yamagata and A/Puerto Rico strains) were compared. The interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, IL-5, interferon (IFN)-α, IFN-β, and IFN-γ levels were significantly higher in the BAL fluids from the control/H1N1 mice than from the asthmatic/H1N1 mice. The viral titers in the BAL fluid were also significantly higher in the control/H1N1mice than in the asthmatic/H1N1 mice infected with either A/Yamagata or A/Puerto Rico. A(H1N1)pdm09 infection, but not H1N1 infection, can induce severe pulmonary inflammation through elevated cytokine levels in a mouse model of asthma.