Modified T-maze training demonstrates dissociated memory loss in rats with ischemic hippocampal injury.
Rats were trained for 20 days on a modified T-maze which required discrimination of a stem choice that was invariant and a goal choice that alternated. Animals were then exposed to 30 min of transient severe forebrain ischemia (postischemic, PI animals), 30 min of less severe ischemia (non-criterion ischemic, NCI animals), or sham operations (controls). After 30 postoperative days, all animals were returned to the maze for an additional 30 trials. PI rats demonstrated a dissociated performance on stem and goal choice. Specifically, the PI animals were significantly impaired on discrimination of a goal choice, yet performed comparably to controls on discrimination of a stem choice. Impaired goal choice for PI animals was not due to differential run times, proactive interference, or interaction between goal and stem choice. Histopathologic analysis of PI animals revealed bilateral destruction of the pyramidal neurons in the dorsal CA 1 region of the hippocampus and lesser damage in the anterodorsal subiculum and the dorsolateral caudate. NCI animals had patchy variable ischemic neuronal damage. These data suggest that ischemic-induced bilateral CA 1 pyramidal neuron loss is sufficient to cause dissociated performance in trained animals on a T-maze, but that less severe ischemia does not cause reproducible hippocampal neuron damage or functional deficits. Further, the data extends the development of reliable behavioral measures for an animal model of the amnesic syndrome that may occur in humans after cardiac arrest.


Dealing with uncertainty and pursuing superior technology options in risk management--the inherency risk analysis.
Current regulatory systems focus on the state of scientific evidence as the predominant factor for how to handle risks to human health and the environment. However, production and assessment of risk information are costly and time-consuming, and firms have an intrinsic disincentive to produce and distribute information about risks of their products as this could endanger their production opportunities and sales. An emphasis on more or better science may result in insufficient thought and attention going into the exploration of technology alternatives, and that risk management policies miss out on the possible achievement of a more favorable set of consequences. In this article, a method is proposed that combines risk assessment with the search for alternative technological options as a part of the risk management procedure. The method proposed is the inherency risk analysis where the first stage focuses on the original agent subject to investigation, the second stage focuses on identifying technological options whereas the third stage reviews the different alternatives, searching for the most attractive tradeoffs between costs and inherent safety. This is then used as a fundament for deciding which technology option to pursue. This method aims at providing a solution-focused, systematic technology-based approach for addressing and setting priorities for environmental problems. By combining risk assessment with a structured approach to identify superior technology options within a risk management system, the result could very well be a win-win situation for both company and the environment.


The Mannheim interview on social support psychometric characteristics of a Spanish version.
This study analysed the psychometric characteristics of a Spanish version of the Mannheim Interview on Social Support (MISS) with 82 mental health care centre outpatients. Moderate and high correlation coefficients were obtained on test-retest reliability for a 6 week interval. In addition, correlations with the Revised UCLA Loneliness Scale and the Perceived Social Support scale confirmed an acceptable concurrent validity.


Evaluation of acute toxicity of essential oil of garlic (Allium sativum) and its selected major constituent compounds against overwintering Cacopsylla chinensis (Hemiptera: Psyllidae).
In our screening program for insecticidal activity of the essential oils/extracts derived from some Chinese medicinal herbs and spices, garlic (Allium sativum L.) essential oil was found to possess strong insecticidal activity against overwintering adults of Cacopsylla chinensis Yang et Li (Hemiptera: Psyllidae). The commercial essential oil of A. sativum was analyzed by gas chromatography-mass spectrometry. Sixteen compounds, accounting for 97.44% of the total oil, were identified, and the main components of the essential oil of A. sativum were diallyl trisulfide (50.43%), diallyl disulfide (25.30%), diallyl sulfide (6.25%), diallyl tetrasulfide (4.03%), 1,2-dithiolane (3.12%), allyl methyl disulfide (3.07%), 1,3-dithiane (2.12%), and allyl methyl trisulfide (2.08%). The essential oil of A. sativum possessed contact toxicity against overwintering C. chinensis, with an LC50 value of 1.42 microg per adult. The two main constituent compounds, diallyl trisulfide and diallyl disulfide, exhibited strong acute toxicity against the overwintering C. chinensis, with LC50 values of 0.64 and 11.04 /g per adult, respectively.


Treatment of spinal deformity associated with myelomeningocele in young children with the use of the four-rib construct.
Surgery for myelomeningocele spinal deformity is accompanied by a high rate of complications. These include infection, pathological skin breakage, instrumentation failure, and neurological deterioration. The four-rib construct associated with the percutaneous technique in immature children with myelomeningocele and spinal deformity is introduced. The four-rib construct serves to correct for deformity and to allow for growth, with minimal complications. The study was small and retrospective, a level four case series. The results of four patients who underwent the four-rib construct surgery in 2008 and 2009 was revised. All four were nonambulatory, skeletally immature children, not previously corrected by bracing, with the progressive spinal deformity associated with myelomeningocele affecting their sitting position. Furthermore, the research protocol was approved by our institutional review board. Three patients were females and one was male. Two cases of kyphoscoliosis, one of kyphosis, and one of scoliosis. Age at the time of the initial procedure ranged between 64 and 82 months, with a mean age of 70 months. Follow-up time after surgery ranged from 24 to 39 months, with a mean of 31 months. Preoperatively, deformity angles were severe, averaging 55° for thoracic scoliosis, 67° for thoracolumbar scoliosis, and 85° for thoracolumbar kyphosis. Surgery mitigated the deformities markedly. Postoperative angles measured were 42° for thoracic scoliosis, 21° for thoracolumbar scoliosis, and 45° for thoracolumbar kyphosis. These observations indicate significant reductions in spinal deformity, by 24, 69, and 48%, respectively. In total, 14 procedures were performed: four initial implants and 10 lengthening and exchange procedures. There were no intraoperative complications. The postoperative complications that did arise consisted of two instances of skin breakage, one distal iliac screw dislodgement, and one shunt displacement. Significantly, no proximal fixation dislodgement, deep-seated infection, or damage in the pathological skin were detected. The four-rib construct technique can be considered as a potential surgical option in (powered by Editorial Manager and Preprint Manager; Aries Systems Corporation) treating spinal deformity associated with myelomeningocele, but still more patients with long term follow-up are needed to prove the efficacy of this procedure. The four-rib construct is simple, minimally invasive, and does not exclude alternative treatment. Moreover, the incidence of complications associated with the four-rib construct compares favorably with other growth techniques.


Electron-phonon coupling and intervalley splitting determine the linewidth of single-electron transport through PbSe nanocrystals.
The linewidth of the resonances in the single-electron tunneling spectra has been investigated for PbSe semiconductor nanocrystals (NCs) with scanning tunneling spectroscopy at low temperature. The linewidth of the resonances corresponding to tunneling through the first conduction and valence levels is found to increase with decreasing size of the NCs. Based on theoretical calculations, this broadening is mainly induced by the coupling between the tunneling electrons and the longitudinal optical phonon mode of the NC, and by the splitting of the degenerate electronic levels between the different L-valleys in the Brillouin zone. For the smallest sizes, it is shown that the intervalley splitting is the major source of broadening.


[Controversy on platelet-inhibiting drugs].
The only well established, clinically useful platelet inhibiting drug is aspirin, though the optimal dose is unknown. Experimental findings, the virtual absence of side effects and, so far, four clinical studies favour a dose of 100-300 mg per day. The majority of clinical studies, however, and particularly those involving patients with cerebrovascular diseases, have employed doses of aspirin of 1000-1200 mg per day. Aspirin reduces mortality and infarction rates in patients who have already had myocardial infarction by 0-30%. The efficacy of additional dipyridamol or of sulfinpyrazone is not proven either. So far the effects of aspirin in patients with unstable angina and in patients after aortocoronary bypass surgery are more favourable. The best evidenced indication for aspirin treatment is transient ischemic attacks and status post stroke. The beneficial effect of aspirin in these conditions may also extend to women. Additional dipyridamol is also useless in this condition.


[Determinants of exclusive breastfeeding in low birthweight infants under six months of age].
The study aimed to assess factors associated with exclusive breastfeeding in low birthweight infants under six months of age in 64 Brazilian municipalities. This cross-sectional study included the 2,745 low birth weight infants under six months of age in the Survey on Prevalence of Breastfeeding (2008) in Brazilian municipalities. The outcome was exclusive breastfeeding. Individual determinants included socioeconomic characteristics (infants' age and sex), maternal characteristics (age bracket, work status, and parity), and characteristics of health services (birth in a Child-Friendly Hospital; place of outpatient follow-up; type of delivery). Two contextual determinants were also included: "number of Human Milk Banks per municipality per 10,000 live births" and "municipal human development index". The individualized effect of the study factor on the outcome was assessed by multilevel Poisson regression with level of significance under 5%. Exclusive Breastfeeding was more prevalent in low birth weight infants whose mothers were 20-35 years of age, who were not working away from home or were on maternity leave, who had given birth in a Child-Friendly Hospital, and who lived in municipalities with more human milk banks per 10,000 live births. The result of the positive and independent effect of strategies that were already part of the National Breastfeeding Policy (birth in a Child-Friendly Hospital, living in a municipality with more human milk banks, and adopting laws that guarantee maternity leave) on exclusive breastfeeding in low birth weight infants points to the need to expand the coverage of these measures in order to meet the breastfeeding targets proposed by the World Health Organization.


Efficacy of the Combination of Pinaverium Bromide 100 mg Plus Simethicone 300 mg in Abdominal Pain and Bloating in Irritable Bowel Syndrome: A Randomized, Placebo-controlled Trial.
We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS). IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials. IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, double-blind, placebo-controlled study of PB+S versus placebo, bid. The primary endpoint was overall symptom improvement, evaluated weekly by the patient (Likert Scale). Secondary endpoints included the weekly improvement in the severity of abdominal pain and bloating assessed both by patients (10-cm Visual Analogue Scale) and investigators (Likert Scale); frequency of Bristol Scale stool types (consistency) evaluated by patients and the IBS Quality of Life scores. A total of 285 patients (female: 83%; 36.5±8.9 y old) received at least 1 dose of PB+S (n=140) or placebo (n=145). No difference was observed in overall symptom improvement between the groups (P=0.13). However, PB+S was superior in abdominal pain (effect size: 31%, P=0.038) and bloating (33%, P=0.019). Patients with IBS-C and IBS-M showed the best improvement in the frequency of stool types with PB+S. No differences were observed in IBS Quality of Life scores and adverse events. PB+S was superior to placebo in improving abdominal pain and bloating in patients with active IBS. The effect on the frequency of stool consistency was particularly significant in IBS-C and IBS-M.


In Vivo Gold Complex Catalysis within Live Mice.
Metal complex catalysis within biological systems is largely limited to cell and bacterial systems. In this work, a glycoalbumin-AuIII complex was designed and developed that enables organ-specific, localized propargyl ester amidation with nearby proteins within live mice. The targeted reactivity can be imaged through the use of Cy7.5- and TAMRA-linked propargyl ester based fluorescent probes. This targeting system could enable the exploitation of other metal catalysis strategies for biomedical and clinical applications.


[Long-term results of porcine bioprosthetic valves].
Between November 1977 and October 1980, 54 patients underwent valve replacements with porcine bioprostheses at Hyogo Kenritsu Amagasaki Hospital. The late complications and the long term durability of 53 porcine bioprostheses were documented in 48 patients after discharge (34 mitral, 7 aortic, 2 tricuspid, and 5 multiple, consisting of 38 Hancock, 15 Carpentier-Edwards prostheses). Cumulative duration of follow-up is 420 patient-years. The valve related late mortality was 0.52%/patient-years. There were 6 thromboembolic events (1.6% patient-years), only 1 episode of endocarditis (0.26%/patient-years). Valve dysfunction is defined as stenosis or regurgitation by echocardiogram or cardiac catheterization. There were 21 instances of porcine bioprosthetic dysfunction (6.6% patient-years). Freedom from valve dysfunction at 12 years was 24.4%. There were 17 valves of mitral bioprosthetic dysfunction (6.4% patient-years). The incidences of mitral stenosis (MS), mitral regurgitation (MR), and paravalvular leakage were 4.5, 3.6, and 0.7%/patient-years respectively. Freedom from MR was higher than MS at 8 years. The 14 patients were needed reoperation due to valve dysfunction (3.6%/patient-years). We concluded that the porcine bioprostheses showed a high incidence of valve dysfunction at 7 to 8 years after operation, we presently choose mechanical valve in most cases.


A tool for scoring of acneiform skin eruptions induced by EGF receptor inhibition.
Acneiform skin eruptions are the most common side effect of epidermal growth factor receptor (EGFR) inhibitors. The National Cancer Institute Common Toxicity Criteria allow for quick severity estimation of a patient, but are not suitable for monitoring the severity of the skin lesions over time, as needed for treatment studies. Here we present our scoring tool for acneiform skin eruptions, which is calculated from body involvement, facial involvement and clinical grading of the skin items erythema, papulation, pustulation and scaling/crusts. The final score is a number between 0 and 100.


A non-linear optimization programming model for air quality planning including co-benefits for GHG emissions.
This paper introduces the MAQ (Multi-dimensional Air Quality) model aimed at defining cost-effective air quality plans at different scales (urban to national) and assessing the co-benefits for GHG emissions. The model implements and solves a non-linear multi-objective, multi-pollutant decision problem where the decision variables are the application levels of emission abatement measures allowing the reduction of energy consumption, end-of pipe technologies and fuel switch options. The objectives of the decision problem are the minimization of tropospheric secondary pollution exposure and of internal costs. The model assesses CO2 equivalent emissions in order to support decision makers in the selection of win-win policies. The methodology is tested on Lombardy region, a heavily polluted area in northern Italy.


Response of maize biomass and soil water fluxes on elevated CO2 and drought-From field experiments to process-based simulations.
The rising concentration of atmospheric carbon dioxide (CO2 ) is known to increase the total aboveground biomass of several C3 crops, whereas C4 crops are reported to be hardly affected when water supply is sufficient. However, a free-air carbon enrichment (FACE) experiment in Braunschweig, Germany, in 2007 and 2008 resulted in a 25% increased biomass of the C4 crop maize under restricted water conditions and elevated CO2 (550 ppm). To project future yields of maize under climate change, an accurate representation of the effects of eCO2 and drought on biomass and soil water conditions is essential. Current crop growth models reveal limitations in simulations of maize biomass under eCO2 and limited water supply. We use the coupled process-based hydrological-plant growth model Catchment Modeling Framework-Plant growth Modeling Framework to overcome this limitation. We apply the coupled model to the maize-based FACE experiment in Braunschweig that provides robust data for the investigation of combined CO2 and drought effects. We approve hypothesis I that CO2 enrichment has a small direct-fertilizing effect with regard to the total aboveground biomass of maize and hypothesis II that CO2 enrichment decreases water stress and leads to higher yields of maize under restricted water conditions. Hypothesis III could partly be approved showing that CO2 enrichment decreases the transpiration of maize, but does not raise soil moisture, while increasing evaporation. We emphasize the importance of plant-specific CO2 response factors derived by use of comprehensive FACE data. By now, only one FACE experiment on maize is accomplished applying different water levels. For the rigorous testing of plant growth models and their applicability in climate change studies, we call for datasets that go beyond single criteria (only yield response) and single effects (only elevated CO2 ).


[Parkinson's disease and psychoses].
Psychotic symptoms are common in Parkinson's disease (PD) and are associated with increased disability, worsened quality of life, and poor long-term prognosis. In this article, clinical features, hypotheses on pathogenesis, and current treatment strategies for Parkinson's disease psychosis (PDP) are reviewed. According to epidemiological studies, the prevalence of PDP is between 20 to 40 %. Complex visual hallucinations are the most common psychotic symptoms and are present in 17-72 % of the patients. Other sensory disturbances encompass tactile hallucinations and minor hallucinatory phenomena, such as sense of presence and visual illusions. Hallucinations are often accompanied by delusions, whose most frequent themes are persecution and jealousy. The pathophysiology of PDP remains unclear. Different factors have been implicated, including Levo-dopa and dopaminergic medications, neurotransmitter imbalances, neuroanatomic alterations, abnormal visuospatial processes, and genetic predisposition. The first-line strategy in the treatment of persistent and problematic PDP is represented by reduction in anti-PD medications. Second-generation antipsychotics are the treatment of choice, with clozapine being demonstrated as the most effective and tolerable drug for PD patients.


[Taxonomic analysis of Pseudomonas strains with uncertain taxonomic status].
Pseudomonas strains isolated from soil and rhizosphere and designated as "Pseudomonas rathonis", Pseudomonas sp. B and Pseudomonas sp. C have been characterized by 113 phenotypic properties and studied by methods of molecular-genetic analysis. The 5'-terminal hypervariable 16S rRNA regions, containing from 208 to 344 nucleotides have been amplified and sequenced. The comparative analysis of sequence results gave evidence about phylogenetic relatedness of studied bacteria (98-100% of 16S rRNA sequences identity) to some saprophytic and plant-pathogenic Pseudomonas species. The latter substantially differed from studied strains in phenotypic characteristics. The DNA-DNA hybridization results have shown the low (0-36%) level of chromosomic DNA homology of "Pseudomonas rathonis", Pseudomonas sp. B, Pseudomonas sp. C strains with the type strains of P. fluorescens, P. putida, P. mendocina, P. pseudoalcaligenes. Obtained data give evidence that these strains belong to some novel Pseudomonas species.


Curative-intent Surgery for Perihilar Cholangiocarcinoma with and without Portal Vein Resection - A Comparative Analysis of Early and Late Outcomes.
Introduction: The safety of portal vein resection (PVR) during surgery for perihilar cholangiocarcinoma (PHC) has been demonstrated in Asia, America, and Western Europe. However, no data about this topic are reported from Eastern Europe. The aim of the present study is to comparatively assess the early and long-term outcomes after resection for PHC with and without PVR. The data of 21 patients with PVR were compared with those of 102 patients with a curative-intent surgery for PHC without PVR. The appropriate statistical tests were used to compare different variables between the groups. Results: A PVR was performed in 17% of the patients. In the PVR group, significantly more right trisectionectomies (p=0.031) and caudate lobectomies (0.049) were performed and, as expected, both the operative time (p=0.015) and blood loss (p=0.002) were significantly higher. No differences between the groups were observed regarding the severe postoperative morbidity and mortality rates, and completion of adjuvant therapy. However, in the PVR group the postoperative clinicallyrelevant liver failure rate was significantly higher (p=0.001). No differences between the groups were observed for the median overall survival times (34 vs. 26 months, p = 0.566). A histological proof of the venous tumor invasion was observed in 52% of the patients with a PVR and was associated with significantly worse survival (p=0.027). A PVR can be safely performed during resection for PHC, without significant added severe morbidity or mortality rates. However, clinically-relevant liver failure rates are significantly higher when a PVR is performed. Furthermore, increased operative times and blood loss should be expected when a PVR is performed. Histological tumor invasion of the portal vein is associated with significantly worse survival.


Association of common variants in KIF21B and ankylosing spondylitis in a Chinese Han population: a replication study.
KIF21B polymorphisms were found associated with susceptibility to multiple sclerosis and ankylosing spondylitis (AS) in populations of white European ancestry. We aimed to replicate the association of polymorphisms around KIF21B and AS in a Chinese Han population. This case-control study included 665 patients with AS and 1,042 healthy controls genotyped for seven single nucleotide polymorphisms (SNPs) of KIF21B--rs12118246, rs4915464, rs502658, rs10494829, rs12089839, rs6687260, and rs957957--by TaqMan genotyping assay; statistical analyses involved the use of PLINK. We also estimated the linkage disequilibrium and haplotypes of these SNPs. Two SNPs--rs502658 (allelic p = 0.0002, odds ratio [OR] 0.60, 95 % confidence interval [95 % CI] 0.47-0.76) and rs10494829 (allelic p = 0.003, OR 1.30, 95 % CI 1.12-1.52)--were significantly associated with AS in the Chinese Han population. In addition, a linear regression test showed that they have independent contribution to disease susceptibility. For both SNPs, haplotype AT was strongly associated with AS and increased the risk of the disease (p = 0.045, OR 1.183, 95 % CI 1.004-1.395), and the genotype GC reduced the risk (p = 0.011, OR 0.715, 95 % CI 0.55-0.928). This work identified a significant association of two SNPs in KIF21B and AS in the Chinese Han population. KIF21B may play an important role in the pathogenesis of AS in the Chinese population and might be a new therapeutic target for AS.


Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.
In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.


Effect of angiotensin II antagonist, alpha-receptor blockage, and denervation on blood flow reduction in experimental, chronic hydronephrosis.
We studied the mechanism of elevated vascular resistance in 34 dogs with unilateral hydronephrotic kidneys. Neither an alpha-receptor blocking agent nor angiotensin II-antagonist reversed renal blood flow reduction 7 hr, 1, 2, and 3 weeks after complete unilateral ureteral ligation. We conclude that blood flow reduction is the same in the denervated hydronephrotic kidney as in the innervated obstructed kidney.


WD40 repeat-containing 62 overexpression as a novel indicator of poor prognosis for human gastric cancer.
WD40 repeat-containing 62 (WDR62) is a centrosome-associated gene involved in cell cycling and proliferation. However, the role of WDR62 in human malignancies remains unknown. The present study aimed to identify the role, if any, of WDR62 in the pathogenesis of human gastric cancer (GC). WDR62 expression in 372 cases of human GC and eight GC cell lines was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blotting. Correlations between WDR62 expression and clinicopathological characteristics, as well as GC prognosis were determined. WDR62 regulation of GC cell proliferation, invasion, migration and cell cycle distribution were studied both in vitro and in vivo. WDR62 expression was significantly increased in GC tissues and cell lines and was associated with poor differentiation and prognosis of GC. WDR62 expression was elevated in GC multidrug resistant cells. Suppressing WDR62 significantly decreased cell proliferation and induced G2/M phase arrest of GC cells. Consistently, WDR62 knockdown inhibited gastric carcinogenesis in nude mice. Regulation of Akt/p38-mitogen-activated protein kinase (MAPK)/multidrug resistance gene 1 (MDR1) expression and activation by WDR62 contributed to the chemoresistance of GC cells. WDR62 overexpresses in GC and the suppression of WDR62 inhibits GC cell growth by inducing G2/M cell cycle arrest. WDR62 may be a novel prognostic marker and a potential chemotherapy target for GC.


Left Main coronary angioplasty of a 9-year-old child with bioresorbable vascular scaffold [corrected].
Familial hypercholesterolemia is an autosomal dominant disorder due to mutations in the low-density lipoprotein receptor gene, characterized by skin and tendon xanthomas, xanthelasmas, and increased risk of premature coronary artery disease. Here, we report a case of 9-year-old girl who presented with angina and dyspnoea on exertion with xanthomas and an elevated serum cholesterol and triglyceride. She had severe stenosis of the left main coronary artery (LMCA) requiring angioplasty and placement of Bioresorbable vascular scaffold (BVS). This is the first case report in literature of the use of BVS for LMCA stenosis in a 9-year-old child. © 2017 Wiley Periodicals, Inc.


Polymerase chain reaction detection of bacterial 16S rRNA gene in human blood.
Bacterial 16S ribosomal RNA genes (rDNA) were detected in blood samples from two healthy individuals by PCR under conditions involving 30 cycles that did not produce any visible products from negative control saline. Even from control samples, PCR involving 35-40 cycles yielded visible bands. Major clones detected in the blood samples, but not in control, were the Aquabacterium subgroup, Stenotrophomonas subgroup, Budvicia subgroup, Serratia subgroup, Bacillus subgroup and Flavobacteria subgroup. No clone was located within the bacteroides-clostridium-lactobacillus cluster, which is indigenous to gastrointestinal flora.


Conjugational transfer system to shuttle giant DNA cloned by Bacillus subtilis genome (BGM) vector.
The Bacillus subtilis GenoMe (BGM) vector was designed as a versatile vector for the cloning of giant DNA segments. Cloned DNA in the BGM can be retrieved to a plasmid using our Bacillus recombinational transfer (BReT) method that takes advantage of competent cell transformation. However, delivery of the plasmid to a different B. subtilis strain by the normal transformation method is hampered by DNA size-related inefficiency. Therefore, we designed a novel method, conjugational plasmid-mediated DNA retrieval and transfer (CReT) from the BGM vector, and investigated conjugational transmission to traverse DNA between cells to circumvent the transformation-induced size limitation. pLS20, a 65-kb plasmid capable of conjugational transfer between B. subtilis strains, was modified to retrieve DNA cloned in the BGM vector by homologous recombination during normal culture. As the plasmid copy number was estimated to be 3, the retrieval plasmid was selected using increased numbers of marker genes derived from the retrieved DNA. We applied this method to retrieve Synechocystis genome segments up to 90 kb in length. We observed retrieved plasmid transfers between B. subtilis strains by conjugation in the absence of structural alterations in the DNA fragment. Our observations extend DNA transfer protocols over previously exploited size ranges.


Porins limit the intracellular persistence of Mycobacterium smegmatis.
The genus Mycobacterium comprises highly pathogenic as well as opportunistic or apathogenic species exhibiting a great variability with respect to their ability to persist or multiply within monocytic host cells. The impact of the permeability of the mycobacterial outer membrane on intracellular persistence was studied. For this purpose, a Mycobacterium smegmatis mutant with a deletion of the major porin gene mspA and a second mutant lacking mspA and the homologous porin gene mspC were used. Deletion of mspA together with mspC significantly enhanced intracellular persistence in murine bone marrow macrophages, the mouse macrophage cell line J774A.1 and Acanthamoeba castellanii. Complementation of mspA in the porin mutant strains resulted in restoration of the wild-type phenotype with respect to intracellular persistence. This is the first report to show that the deletion of porins of mycobacteria results in improved persistence in eukaryotic cells, demonstrating that the intracellular persistence of M. smegmatis depends upon the permeability of the outer membrane.


An alternate road home to electronic media claims.
All agencies are not large enough to make going electronic cost effective--yet automation is inevitable for health care. The Missouri Alliance for Home Care found a way to bring electronic claims to these smaller agencies.


Cooperative bending of the 21-base-pair repeats of the SV40 viral early promoter by human Sp1.
The overall structural features of the multimeric complex between Sp1 and the 21-base-pair repeat of the early promoter region of SV40 DNA have been determined using hydroxyl-radical footprinting; (+)-CC-1065, a sequence-specific minor groove bending probe; and circularization experiments. The results show that the 21-base-pair repeat region has an intrinsically in-phase bent structure that is stabilized upon saturation Sp1 binding by protein-DNA and protein-protein interactions to produce a looping structure. The direction of the Sp1-stabilized bending of DNA occurs into the minor groove and is localized between each of the Sp1 binding sites. These results are used as the basis to propose a looping structure for the multimeric Sp1 21-base-pair repeat region of SV40 DNA. Last, these results provide a rationale for the recently observed inhibition of basal transcriptional levels by site-specific triple-helical DNA complexes.


Pathophysiological and morphological aspects of cellular lesions.
Cell injury can result in cell death with sufficient intensity and prolongation of various noxae. Cell death exhibits specific local characteristics but is generally monomorphic. Since a cell cannot be considered as an individual unit, knowledge of the interactions among various cells and their systems provides the basis for effective cell and organ protection. In the case of cell or organ injury which threatens to generalize, with far-reaching consequences for the entire organism, the following therapeutic measures should be considered: timely intervention in the disturbed prostaglandin metabolism; activation of the RES; for example, substitution of opsonins; minimizing of the secondary invasion of enterogenic toxins.


Sleep electroencephalography in depressive illness. A collaborative study by the World Health Organization.
Eight WHO research centres from Europe, North America and Asia took part in a WHO study aimed at assessing the reliability and consistency of sleep-EEG abnormalities in major depression. Each centre was asked to include in the study ten depressed patients aged 20-65 years meeting the Research Diagnostic Criteria for a major depressive disorder, and to match them by age and gender with ten controls. There were 67 patients and 66 controls included in the study. Compared with controls, depressed patients showed sleep-continuity disturbances such as increase in sleep-onset latency, and decrease in total sleep time and in sleep efficiency. Stages 2 and 3, as percentages of total sleep time, were reduced in depressed patients, REM latency was shortened and REM density increased. These findings confirm the presence of specific sleep-EEG abnormalities in major depression.


Estimating the age of mutant disease alleles based on linkage disequilibrium.
With more and more disease genes being mapped and/or cloned, there is a growing interest in dating the age of underlying mutations. The knowledge of the age of mutation is important to finely map disease genes by linkage disequilibrium mapping. It would also help us understand the origin, evolution, and dispersion of the mutant disease genes. Despite increasing interests in dating disease mutations, the development of appropriate statistical methods is largely fragmentary, and there is a lack of systematic treatment of the topic. We propose two classes of methods for estimating the age of mutant allele at the disease locus based on linked marker data. Our methods can not handle only single-locus marker data, but also multi-locus marker data as well. Moreover, our methods can be used even when the location of the disease locus is unknown, and/or when there are mutations at the marker or disease locus. We show that some previous results are special cases of our methods. We also derive a recursive equation previously obtained by Serre et al. [Hum Genet 1990;84:449-454] and provide an explicit solution to the equation. To illustrate our methods, we applied them to two groups of data sets, one is cystic fibrosis data collected from several European populations, and the other is data on several genetic diseases (diastrophic dysplasia, progressive myoclonus epilepsy, congenital chloride diarrhea, and Batten disease) all collected from the Finnish population. The former data set allows us to trace the origin and dispersion of the most common mutation for cystic fibrosis. The latter provides an opportunity to examine whether all mutations for these diseases have the same age.


Autobiographical memory specificity in dissociative identity disorder.
A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a specific event from memory located in time and place. Previous studies of overgeneral memory have not included patients with dissociative disorders. These patients are interesting to consider, as they are hypothesized to have the ability to selectively compartmentalize information linked to negative emotions. This study examined avoidance and overgeneral memory in patients with dissociative identity disorder (DID; n = 12). The patients completed the autobiographical memory test (AMT). Their performance was compared with control groups of posttraumatic stress disorder (PTSD) patients (n = 26), healthy controls (n = 29), and DID simulators (n = 26). Specifically, we compared the performance of separate identity states in DID hypothesized to diverge in the use of avoidance as a coping strategy to deal with negative affect. No significant differences in memory specificity were found between the separate identities in DID. Irrespective of identity state, DID patients were characterized by a lack of memory specificity, which was similar to the lack of memory specificity found in PTSD patients. The converging results for DID and PTSD patients add empirical evidence for the role of overgeneral memory involved in the maintenance of posttraumatic psychopathology.


Dynamics of Cl (2Pj) atom formation in the photodissociation of fumaryl chloride (ClCO - CH = CH - COCl) at 235 nm: a resonance enhanced multiphoton ionization (REMPI) time-of-flight (TOF) study.
The photodissociation dynamics of fumaryl chloride (ClCO-CH═CH-COCl) has been studied in a supersonic molecular beam around 235 nm using resonance enhanced multiphoton ionization (REMPI) time-of-flight (TOF) technique by detecting the nascent state of the primary chlorine atom. A single laser has been used for excitation of fumaryl chloride and the REMPI detection of chlorine atoms in their spin-orbit states, Cl ((2)P(3/2)) and Cl* ((2)P(1/2)). We have determined the translational energy distribution, the recoil anisotropy parameter, β, and the spin-orbit branching ratio for chlorine atom elimination channels. To obtain these, measured polarization-dependent and state-specific TOF profiles are converted into kinetic energy distributions, using a least-squares fitting method, taking into account the fragment recoil anisotropies, β(i). The TOF profiles for both Cl and Cl* are found to be independent of laser polarization; i.e., β is well characterized by a value of 0.0, within the experimental uncertainties. Two components, namely, the fast and the slow, are observed in the translational energy distribution, P(E(T)), of Cl and Cl* atoms, and assigned to be formed from different potential energy surfaces. The average translational energies for the fast components of the Cl and Cl* channels are 14.9 ± 1.6 and 16.8 ± 1.6 kcal/mol, respectively. Similarly, for the slow components, the average translational energies of the Cl and Cl* channels are 3.4 ± 0.8 and 3.1 ± 0.8 kcal/mol, respectively. The energy partitioning into the translational modes is interpreted with the help of various models, such as impulsive and statistical models. Apart from the chlorine atom elimination channel, molecular hydrogen chloride (HCl) elimination is also observed in the photodissociation process. The HCl product has been detected, using a REMPI scheme in the region of 236-237 nm. The observation of the molecular HCl in the dissociation process highlights the importance of the relaxation process, in which the initially excited parent molecule relaxes to the ground state from where the molecular (HCl) elimination takes place.


Frequent false-positive results of lupus anticoagulant tests in plasmas of patients receiving the new oral anticoagulants and enoxaparin.
Oral direct thrombin and Xa inhibitors are worldwide distributed for prevention and treatment of thrombosis. It is important to recognize their effects on lupus anticoagulant (LA) testing. The aim of the study is to describe the rate of false-positive results of LA tests on plasmas of patients with previous negative LA tests results that receive dabigatran etexilate (DAB) 110 mg/twice a day, rivaroxaban (RIV) 10 mg/day or 15 mg/twice a day, or enoxaparin 40 mg/day. Blood was taken between 1.5 and 4 h post administration. Tests evaluated are as follows: prothrombin time, APTT, dilute Russell viper venom time (DRVVT) screen, APTT, and DRVVT mixing studies, index of circulating anticoagulant (ICA) with normal plasma, screen/confirm normalized ratio (NR) for DRVVT and silica clotting time (SCT). Plasmas from patients taking DAB (n = 22) presented 100% prolonged APTT and DRVVT with ICA above the cutoff point and 81.8% positive screen/confirm NR, 100% prolonged SCT screen, but 4.5% positive confirmatory NR. All patients receiving RIV at 15 mg/twice a day (n = 4) presented positive DRVVT screen, mixing, and confirmatory tests, 75% and 100% prolonged APTT and SCT screen, with negative screen/confirm NR. Those taking RIV 10 mg/day (n = 22) showed 81.8% prolonged DRVVT screen, 82.3% and 76.5% of them with positive mixing and confirmatory studies. Patients receiving enoxaparin also presented high prevalence of APTT and DRVVT false-positive results. Dabigatran etexilate, RIV, and enoxaparin affect tests for LA not only in screening and mixing, but also in confirmatory studies. We considered that LA testing should not to be performed when patients are taken these drugs, particularly if blood is collected at peak, in order to avoid false-positive results.


Ameliorative effect of vanadyl(IV)-ascorbate complex on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, and oxidative stress in mice.
There is mounting evidence demonstrating causative links between hyperglycemia, oxidative stress, and insulin resistance, the core pathophysiological features of type 2 diabetes mellitus. Using a combinational approach, we synthesized a vanadium-antioxidant (i.e., l-ascorbic acid) complex and examined its effect on insulin resistance and oxidative stress. This study was designed to examine whether vanadyl(IV)-ascorbate complex (VOAsc) would reduce oxidative stress, hyperglycemia, and insulin resistance in high-fat high-sucrose diet (HFSD)-induced type 2 diabetes in mice. Male C57BL/6J mice were fed a HFSD for 12 weeks to induce insulin resistance, rendering them diabetic. Diabetic mice were treated with rosiglitazone, sodium l-ascorbate, or VOAsc. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index, and serum adipocytokine levels were measured. Serum levels of nitric oxide (NO) parameters were also determined. The liver was isolated and used for determination of malondialdehyde, reduced glutathione, and catalase levels, and superoxide dismutase and glutathione peroxidase activities. VOAsc groups exhibited significant reductions in serum adipocytokine and NO levels, and oxidative stress parameters compared to the corresponding values in the untreated diabetic mice. The results indicated that VOAsc is non-toxic. In conclusion, we identified VOAsc as a potentially effective adjunct therapy for the management of type 2 diabetes.


Activation patterns in the left atrium during counterclockwise and clockwise atrial flutter.
Activation of the left atrium (LA) in patients with isthmus-dependent right atrial flutter (AFL) has not yet been studied. The aim of this study was to analyze the activation patterns in the LA in patients with counterclockwise and clockwise AFL. The study population consisted of 12 patients (10 men and 2 women; mean age 61+/-13 years) with documented AFL and atrial fibrillation referred for ablation. The LA was mapped with a 64-electrode basket catheter inserted through a transseptal approach (10 patients) or an open foramen ovale (2 patients). In patients with counterclockwise AFL (10 episodes), the LA was activated for a mean of 133+/-28 msec. Two endocardial breakthroughs of earliest activity on the left side of the interatrial septum, separated in time by an interval of 38+/-15 msec, were observed in 9 episodes (90%). Two wavefronts originated from these breakthroughs, which activated the posterior and the anterior LA walls, respectively. In one patient, the entire LA was activated from the inferior breakthrough. In patients with clockwise AFL (five episodes), the LA activation time was 130+/-13 msec. During ongoing episodes, two early electrical breakthroughs, separated in time by an interval of 41+/-15 msec, appeared in the high anteroseptal and low posteroseptal LA regions. The superior wavefront that emerged from the high anterolateral LA region was the dominant activation pathway in 4 (80%) of 5 episodes. In patients with AFL, the LA is activated by two wavefronts originating from the high anterior and the low posterior regions of the interatrial septum. The sequence of activation of these interatrial connections in counterclockwise or clockwise AFL and the conductive properties of the LA conduction pathways determine the activation patterns in the LA.


Haplotype associations of 90 rare alleles from the National Marrow Donor Program.
The National Marrow Donor Program maintains an HLA database of over 4.1 million US adult volunteers, 43,000 cord blood units, and 111,000 patients from which we identified 1,999,424 samples having allele-level HLA-A, HLA-B, or HLA-DRB1 results. We analyzed 811 rare alleles reported at a frequency of less than 1 in 50,000 in this study pool and found strong predicted haplotype associations for 90 of them. The data set includes the number of times the allele was seen, the predicted haplotypes, and the racial or ethnic groups in which it was identified. This information can be helpful in designing search strategies for patients with rare alleles requiring hematopoietic stem cell therapy.


Adrenergic and non-adrenergic control of active skeletal muscle blood flow: implications for blood pressure regulation during exercise.
Blood flow to active skeletal muscle increases markedly during dynamic exercise. However, despite the massive capacity of skeletal muscle vasculature to dilate, arterial blood pressure is well maintained. Sympathetic nerve activity is elevated with increased intensity of dynamic exercise, and is essential for redistribution of cardiac output to active skeletal muscle and maintenance of arterial blood pressure. In addition, aside from the sympathetic nervous system, evidence from human studies is now emerging that supports roles for non-adrenergic vasoconstrictor pathways that become active during exercise and contribute to vasoconstriction in active skeletal muscle. Neuropeptide Y and adenosine triphosphate are neurotransmitters that are co-released with norepinephrine from sympathetic nerve terminals capable of producing vasoconstriction. Likewise, plasma concentrations of arginine vasopressin, angiotensin II (Ang II) and endothelin-1 (ET-1) increase during dynamic exercise, particularly at higher intensities. Ang II and ET-1 have both been shown to be important vasoconstrictor pathways for restraint of blood flow in active skeletal muscle and the maintenance of arterial blood pressure during exercise. Indeed, although both adrenergic and non-adrenergic vasoconstriction can be attenuated in exercising muscle with greater intensity of exercise, with the higher volume of blood flow, the active skeletal muscle vasculature remains capable of contributing importantly to the maintenance of blood pressure. In this brief review we provide an update on skeletal muscle blood flow regulation during exercise with an emphasis on adrenergic and non-adrenergic vasoconstrictor pathways and their potential capacity to offset vasodilation and aid in the regulation of blood pressure.


Generating doughnut-shaped beams with large charge numbers by use of liquid-crystal spiral phase plates.
Liquid-crystal spiral phase plates with cell gaps of 7 and 20 microm have been used to generate doughnut-shaped beams (doughnut beams) with charges of 1 and 4, respectively. Stacking these liquid-crystal spiral phase plates yielded doughnut beams with charge numbers up to 8. High efficiency and flexibility are the advantages of generating doughnut beams by stacking liquid-crystal spiral phase plates. Interference of doughnut beams generated by liquid-crystal spiral phase plates and plane waves has been studied. Fingerlike interference patterns were obtained with a doughnut beam tilted from a Gaussian beam; spiral fanlike patterns were obtained with a doughnut beam and a Gaussian beam collimated coaxially. The experimental results are supported qualitatively by simulation. By rotating a glass slide in the path of the Gaussian beam, one can rotate the fanlike interference pattern in a controlled fashion. With the liquid-crystal display technology that we have developed and report here, these liquid-crystal spiral phase plates should find applications in optical tweezers.


On the mechanism of the ascorbic acid-induced release of nitric oxide from N-nitrosated tryptophan derivatives: scavenging of NO by ascorbyl radicals.
During the past years, there has been increasing interest in endogenous nitric oxide storage compounds. Recently, we briefly reported on the ascorbate-dependent release of nitric oxide ((.)NO) from N-nitrosotryptophan derivatives. In the present study, the underlying mechanism of (.)NO release is studied in more detail, primarily utilizing N-acetyl-N-nitrosotryptophan (NANT) as a model compound. The initial rate of the ascorbate-induced release of nitric oxide has been found to correspond to the rate of NANT decay. In this process, N-acetyltryptophan (NAT) is produced almost quantitatively. The final yield of nitrite amounted to around 90 % with respect to the applied amount of NANT. However, the total release of nitric oxide was only 60 %, as determined by using an FNOCT-4(fluorescent nitric oxide cheletropic trap number 4) assay. Besides nitric oxide, a second volatile product, dinitrogen oxide (N(2)O), has been identified by using (15)N NMR spectrometry, strongly indicating the intermediacy of nitroxyl (HNO). The formation of intermediate ascorbyl radical anions during the NANT-ascorbate reaction has been monitored by using ESR spectrometry. Unexpectedly, it was found that the primary oxidized product of vitamin C, dehydroascorbic acid (DHA), efficiently consumes nitric oxide. Since ESR spectrometry further revealed that ascorbyl radical anions are also generated during the spontaneous decay of DHA, the DHA-nitric oxide reaction is related to recombination of (.)NO with the thus formed ascorbyl radical anions. A conclusively established mechanism of the NANT-ascorbate reaction is presented, with O-nitrosoascorbate as a key intermediate, as additionally supported by CBS-QB3 calculations. The present study suggests that vitamin C and its oxidation products can chemically counterbalance endogenous nitric oxide levels.


Diet and vitamin D status among pregnant Pakistani women in Oslo.
In the present study the diet and the nutritional status of pregnant Pakistani immigrant women have been compared with a group of Norwegian women. A cross-sectional survey of women in the 18th week of pregnancy. Women referred to routine ultrasound examination at Aker and Ullevål Hospitals in Norway. All (58) healthy women of Pakistani origin referred from October of 1991 to January of 1992 were included, of whom 38 (66%) participated. Forty-five Norwegian women were randomly included in the same period and 38 (84%) of these women participated. The serum levels of 25-hydroxyvitamin D3 were significantly lower in the Pakistanis compared with the Norwegians (median 19 nmol/l vs 55 nmol/l, P < 0.001) and 83% of the Pakistani women had 25-hydroxyvitamin D3 levels below the reference value (< 30 nmol/l). The Pakistanis had higher levels of serum parathyroid hormone (median 2.6 vs 1.6 pmol/l, P < 0.001). The Pakistanis also had a lower dietary intake of vitamin D than that of the Norwegians (median 2.2 vs 3.3 micrograms/day, P < 0.05), and a lower total intake, including supplements (median 2.9 vs 7.0 micrograms/day, P < 0.001). Among the Pakistanis a correlation was found between the dietary intake of margarine, the main source of vitamin D in the diet, and the concentration of 25-hydroxyvitamin D3 in serum, r = 0.48 (P = 0.01). In general, the Pakistanis avoided any direct sunshine exposure, and no relation between outdoor activity and serum level of 25-hydroxyvitamin D3 was found. The Pakistani women had a lower intake of calcium than the Norwegians (median 793 vs 1134 mg/day, P < 0.001). This study has shown that Pakistani women living in Oslo are at great risk of developing vitamin D deficiency during pregnancy. The main reasons for this are avoidance of sun exposure, a low dietary intake of vitamin D, and no or little use of supplementation.


Ambulatory blood pressure profiles in familial dysautonomia.
Familial dysautonomia (FD) is a rare genetic disease that involves extreme blood pressure fluctuations secondary to afferent baroreflex failure. The diurnal blood pressure profile, including the average, variability, and day-night difference, may have implications for long-term end organ damage. The purpose of this study was to describe the circadian pattern of blood pressure in the FD population and relationships with renal and pulmonary function, use of medications, and overall disability. We analyzed 24-h ambulatory blood pressure monitoring recordings in 22 patients with FD. Information about medications, disease severity, renal function (estimated glomerular filtration, eGFR), pulmonary function (forced expiratory volume in 1 s, FEV1) and an index of blood pressure variability (standard deviation of systolic pressure) were analyzed. The mean (± SEM) 24-h blood pressure was 115 ± 5.6/72 ± 2.0 mmHg. The diurnal blood pressure variability was high (daytime systolic pressure standard deviation 22.4 ± 1.5 mmHg, nighttime 17.2 ± 1.6), with a high frequency of a non-dipping pattern (16 patients, 73%). eGFR, use of medications, FEV1, and disability scores were unrelated to the degree of blood pressure variability or to dipping status. This FD cohort had normal average 24-h blood pressure, fluctuating blood pressure, and a high frequency of non-dippers. Although there was evidence of renal dysfunction based on eGFR and proteinuria, the ABPM profile was unrelated to the measures of end organ dysfunction or to reported disability.


Rayleigh-Brillouin spectrum in special relativistic hydrodynamics.
In this paper we calculate the Rayleigh-Brillouin spectrum for a relativistic simple fluid according to three different versions available for a relativistic approach to nonequilibrium thermodynamics. An outcome of these calculations is that Eckart's version predicts that such spectrum does not exist. This provides an argument to question its validity. The remaining two results, which differ one from another, do provide a finite form for such spectrum. This raises the rather intriguing question as to which of the two theories is a better candidate to be taken as a possible version of relativistic nonequilibrium thermodynamics. The answer will clearly require deeper examination of this problem.


Identification and characterization of the low-affinity receptor for immunoglobulin E (FcepsilonRII/CD23) on murine Langerhans cells.
CD23 is a low-affinity receptor for immunoglobulin E and expressed on various hemopoietic cells. Although human epidermal cultured Langerhans cells express CD23, the study to identify CD23 on murine Langerhans cells has so far failed. In this study, using highly enriched (> 95%) Langerhans cells from murine epidermis obtained by the panning method, we investigated whether murine Langerhans cells express CD23. As the result of a series of experiments using fluorescence activated cell sorter analysis and the polymerase chain reaction method, it was revealed that CD23 is expressed on cultured Langerhans cells, but not on freshly isolated Langerhans cells. Comparison of the DNA sequence of polymerase chain reaction products of CD23 from cultured Langerhans cells with that from spleen leukocytes demonstrated that there were the same sequences between the two polymerase chain reaction products. The expression of CD23 on cultured Langerhans cells was downregulated when Langerhans cells were cultured with keratinocyte-derived cytokines: interleukin-1alpha, interleukin-18, macrophage colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Moreover, it was shown that murine IgE bound to cultured Langerhans cells and this binding was partially inhibited when Langerhans cells were cultured with monoclonal antibody against CD23 (B3B4). Thus this study revealed murine cultured Langerhans cells do express CD23 and the discrepancy from previous reports may be due to the influence of cytokines derived from keratinocytes. Furthermore, the finding that murine cultured Langerhans cells bind IgE through CD23 suggests that CD23 on murine Langerhans cells may be involved in IgE-mediated immune responses.


Histopathology of inner ear malformations: Do we have enough evidence to explain pathophysiology?
To investigate the histopathology of inner ear malformations (IEMs) in order to explain their pathophysiology. Light microscopy was used to study 33 specimens exhibiting various IEMs in the collection of the Otopathology Laboratory at Harvard University's Massachusetts Eye and Ear Infirmary. The investigation found 18 incidences of cochlear hypoplasia (CH) (3 CH-I, 10 CH-II, 5 CH-III), 11 incomplete partitions (IPs) (5 IP-I, 6 IP-II), 2 vestibular dilatations, and 2 cases of cochlear nerve aplasia. The IP-I cases had characteristic defective endosteums, while the IP-II cases showed hydropic changes in the scala vestibuli. The CH cases were small in size externally, with normal or defective internal architecture. In combination with embryological data, these findings suggest that cases of CH-III and CH-IV are most probably genetically predetermined to be small in size, and that development of the membranous labyrinth stops at a point earlier than normal, so that it is shorter. At the time of complete ossification, this results in a cochlea with small external dimensions and normal internal architecture. In CH-I and CH-II cases, there is arrested development of the internal architecture, in addition to a small cochlea; it is most likely that in these cases, there is a severely defective vascular supply from the internal auditory canal (IAC). IP-I may be the result of a defective vascular supply from the blood vessels of the IAC. In IP-II, an enlarged endolymphatic sac (EES) appears to be the genetic abnormality that causes the other abnormalities, as it allows high pressure to be transmitted into the cochlea and vestibule. In IP-III, the pathophysiology appears to be an abnormal vascular supply from the middle ear mucosa, caused by a genetic abnormality and resulting in a thinner otic capsule and the absence of the modiolus.


Ethics -- perceived or reasoned from principles?: a rejoinder to Korn, Huelsman, and Reed.
In response to Korn, Huelsman, and Reed's (1992) question, "Who defines those interests, and how serious must the setback be?" (p. 126), we argue that a wrongful (unjust) harm (a setback of interest) is not equivalent to a hurt (a temporary distressing mental state) and that the interests of importance are welfare interests (general means to our ulterior aims), not just a desire to avoid unpleasant mental states (hurts). To set back a welfare interest is to reverse its course or to impede, thwart, defeat, or doom it. It is the primary responsibility of the investigator to define both welfare interests and the risk of harm. An informed consent -- one with substantial understanding, in substantial absence of control by others, and given intentionally -- allows participants to autonomously authorize participation in research, including their toleration of acts of mental discomfort or distress during an experiment. Not only were our participants not wrongfully harmed, they benefited and were willing to volunteer for future research. No strong evidence has been advanced or linked to guided imagery in a way that would justify its restraint; to so claim evokes a standard of legal paternalism that fails to respect participants' competence and autonomy to choose to participate in research on rape using guided imagery.


Effects of somatostatin and oral potassium administration on terbutaline-induced hypokalemia.
Terbutaline, a beta 2-adrenergic agonist, has been shown to cause hypokalemia and an increase of plasma glucose and serum insulin concentrations. We considered that terbutaline-induced hypokalemia may be due to the insulin-induced shift of potassium (K+) from the extracellular to the intracellular space. If so, then inhibition of insulin secretion by somatostatin would prevent terbutaline-induced hypokalemia. Further, we wondered whether oral potassium pretreatment could prevent terbutaline-induced hypokalemia. Therefore, 10 healthy volunteers (5 men, 5 women; mean age, 23 yr +/- 3 SD) received either sodium chloride (NaCl) or somatostatin intravenously together with 0.25 mg terbutaline subcutaneously in a double-blind crossover design. On a third test day, they received 39 mval of K+ powder orally before terbutaline injection in an open trial. Terbutaline caused a significant decrease of K+ (from 3.96 +/- 0.08 to 3.3 +/- 0.13 mmol/L +/- SEM; p less than 0.0005), accompanied by a significant increase in plasma glucose (from 83 +/- 3.6 to 101 +/- 4.4 mg/dl +/- SEM; p less than 0.01) and serum insulin concentrations (from 11.7 +/- 0.9 to 19.9 +/- 1.1 microU/ml +/- SEM; p less than 0.001), confirming earlier data. Somatostatin pretreatment inhibited the terbutaline-induced hypokalemia; the small fall of K+ (from 3.7 +/- 0.08 to 3.5 +/- 0.2 mmol/L) was no longer significant. Insulin secretion was completely blocked by somatostatin, leading to an even more pronounced increase of blood glucose. Hypokalemia after terbutaline injection was not prevented by oral potassium pretreatment. In summary, the present findings confirm that terbutaline-induced hypokalemia is associated with increased plasma glucose and insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunologic quantitation of the carcinoma specific human carcinoma antigen in clinical samples.
Based on the cross-reactivity of the human carcinoma antigen, HCA, with epiglycanin, a mouse mammary carcinoma cell surface glycoprotein, HCA has been detected in the tissue and blood of patients with every type of epithelium-derived cancer tested. Competitive binding assays utilized the following antiepiglycanin antibodies: a polyclonal rabbit antiserum (immunoglobulin [Ig] G and IgM) in a radioimmunoassay; mouse monoclonal antibodies (Ab-1, IgM) on immunoplates; anti-idiotypic (Ab-2) and anti-anti-idiotypic (Ab-3) monoclonal antibodies (both IgG) from spleen cells of C57BL mice immunized, respectively, with Ab-1 and Ab-2, and utilized on immunoplates. IgG and IgM antibodies were evaluated for their ability to detect HCA and to distinguish between the blood of patients with, or without, carcinomas. Assays with the rabbit antiserum distinguished plasmas of metastatic breast carcinoma patients from those of patients with benign breast disease with a sensitivity of approximately 93% (specificity 90%). Antiepiglycanin IgM monoclonal antibodies (i.e., AE3) showed high specificity and sensitivity (> 90%) with sera from advanced carcinoma patients when compared with normal sera. The IgG anti-anti-idiotypic (Ab-3) monoclonal antibodies (i.e., AF2), which bind the same epitope as Ab-1, appear to possess less nonspecific binding capacity, however, than the Ab-1 (IgM) antibodies. Anti-Ab-1 (i.e., C8F2) anti-idiotypic monoclonal antibodies, which bear an idiotope equivalent to the epitope present in epiglycanin and the HCA, demonstrated greater consistency as a standard calibrator and for coating wells than epiglycanin. The concentration of the HCA in the body fluids of patients with carcinomas may be accurately determined by competitive binding assays. It is suggested that the use of anti-idiotypic antibodies (IgG), rather than epiglycanin/HCA, and Ab-3 anti-anti-idiotypic antibodies (IgG), rather than Ab-1 (IgM), will improve the consistency, as well as the sensitivity and specificity, of the assay.


Individual differences, exercise and leisure activity in predicting affective well-being in young adults.
This study focuses on the prevalence of exercise and health-related leisure activities (smoking, drinking), across groups of subjects, defined by personality and gender, in relation to subjective well-being. Results from a cross-sectional survey of 187 participants are reported. Males (n = 80) reported more drinking (p < 0.001) and smoking (p < 0.001) than females, though they also reported higher habitual physical activity levels (p < 0.001). Females (n = 107) reported more frequent use of social support coping (p < 0.01). There was a positive association between extraversion and self-reported habitual physical activity as well as alcohol consumption (even when controlling for gender). Neuroticism was not related to any of the exercise and leisure activity variables. Multiple regression analyses predicted 34% of variance for the depression-enthusiasm and 39% of the variance for the anxiety-contentment measures of affective well-being. Neuroticism (p < 0.001) and avoidance coping (p < 0.05) were the only significant predictors of both anxiety-contentment and depression-enthusiasm. It is concluded that the influence of individual differences such as personality and gender on coping behaviour and well-being is consistent with social learning theory research. Limitations of cross-sectional research designs necessitate caution with inferring causal paths. Recommendations for future research are presented concerning the use and value of repeated measures designs within research into exercise and well-being.


Effect of intravenous administration of sodium-lactate on retinal blood flow in healthy subjects.
The present study was designed to investigate the effect of intravenously administered sodium lactate on ocular blood flow. Twelve healthy male volunteers received either sodium lactate (0.6 mol/L) or physiologic saline solution in a randomized, double-masked, two-way crossover study. Sodium lactate or placebo were administered at an infusion speed of 500 and 1000 mL/h for 30 minutes each. Blood flow measurements were performed in the last 10 minutes of the infusion periods. Retinal blood flow was calculated based on the measurement of maximum erythrocyte velocity, assessed with bidirectional laser Doppler velocimetry, and retinal vessel diameter obtained with a retinal vessel analyzer. Choroidal blood flow was assessed with laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude. Administration of lactate increased blood lactate concentration from 1.3 +/- 0.4 to 3.9 +/- 0.7 mmol/L (P < 0.001) and to 7.1 +/- 1.4 mmol/L (P < 0.001) at infusion speeds of 500 and 1000 mL/h, respectively. At these blood lactate concentrations, retinal blood flow increased by 15% +/- 20% and by 24% +/- 37% (ANOVA, P = 0.01). Fundus pulsation amplitude increased by 3% +/- 6% and 10% +/- 5% (ANOVA, P = 0.04) at the two plasma lactate concentrations. Subfoveal choroidal blood flow measured with laser Doppler flowmetry tended to increase by 10% +/- 15% and 13% +/- 20% (ANOVA, P = 0.19), but this effect was not significant. Infusion of sodium lactate induced alkalosis in arterial blood taken from the earlobe (7.41 +/- 0.03 at baseline; 7.50 +/- 0.03 during lactate infusion; P = 0.001). The data indicate that intravenously administered sodium lactate increases retinal blood flow. Whether this is related to a cytosolic redox impairment or to other hitherto unidentified mechanism remains to be clarified. Further studies are needed to determine whether lactate plays a role in regulation of choroidal blood flow.


Kaposi' s sarcoma in HIV-positive patients: the state of art in the HAART-era.
Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunodeficiency, i.e. coinfection with Human Immonodeficiency Virus (HIV) or transplantation. The incidence of KS has dramatically decreased in both US and Europe in the Highly Active Antiretroviral Therapy (HAART) era. However, KS remains the second most frequent tumor in HIV-infected patients worldwide and it has become the most common cancer in Sub-Saharan Africa. In 1994, Yuan Chang et al discovered a novel γ-herpesvirus in biopsy specimens of human KS. Epidemiologic studies showed that KS-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was the etiological agent associated with all subtypes of KS. KS has a variable clinical course ranging from very indolent forms to a rapidly progressive disease. HAART represents the first treatment step for slowly progressive disease. Chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease. The current understanding of KS as a convergence of immune evasion, oncogenesis, inflammation and angiogenesis has prompted investigators to develop target therapy, based on anti-angiogenic agents as well as metalloproteinase and cytokine signaling pathway inhibitors. These drugs may represent effective strategies for patients with AIDS-associated KS, which progress despite chemotherapy and/or HAART. In this review, we focus on the current state of knowledge on KSHV epidemiology, pathogenesis and therapeutic options.


Statistical models suggest presence of two distinct subpopulations of miniature EPSCs in fast-spiking interneurons of rat prefrontal cortex.
Properties of excitatory synaptic responses in fast-spiking interneurons (FSIs) and pyramidal neurons (PNs) are different; however, the mechanisms and determinants of this diversity have not been fully investigated. In the present study, voltage-clamp recording of miniature excitatory post-synaptic currents (mEPSCs) was performed of layer 2-3 FSIs and PNs in the medial prefrontal cortex of rats aged 19-22days. The average mEPSCs in the FSIs exhibited amplitudes that were two times larger than those of the PNs and with much faster rise and decay. The mEPSC amplitude distributions in both cell types were asymmetric and in FSIs, the distributions were more skewed and had two-times larger coefficients of variation than in the PNs. In PNs but not in FSIs, the amplitude distributions were fitted well by different skewed unimodal functions that have been used previously for this purpose. In the FSIs, the distributions were well approximated only by a sum of two such functions, suggesting the presence of at least two subpopulations of events with different modal amplitudes. According to our estimates, two-thirds of the mEPSCs in FSIs belong to the high-amplitude subpopulation, and the modal amplitude in this subpopulation is approximately two times larger than that in the low-amplitude subpopulation. Using different statistical models, varying binning size, and data subsets, we confirmed the robustness and consistency of these findings.


[Endoscopic ultrasonography--indications and results in diseases of the esophagus and stomach].
Based on own experience and on published data we report about indications and efficacy of endoscopic ultrasonography (EUS) in esophageal and gastric diseases. At the present time the following conclusions can be drawn: Submucous tumors can be clearly demonstrated and unequivocally distinguished from extramural compressions. Although the EUS aspect does not allow to differentiate benign from malignant lesions, EUS findings can give hints as to the nature of a submucous tumor (leiomyoma, lipoma, cyst). The main indication for EUS ist local tumor staging. The pT stage of esophageal carcinoma can be assessed correctly in 84% (73 to 92%) and that of gastric carcinoma in 80% (69 to 92%) of the cases by EUS. Especially in early tumor stages, EUS is superior to computed tomography. Regional lymph node metastases can be visualized in 70 to 90% of the cases. EUS is also helpful in the follow-up of patients with operative resection of esophageal cancer and in patients with gastric non-Hodgkin lymphoma during radio-/chemotherapy.


BRAF-mutated clear cell sarcoma is sensitive to vemurafenib treatment.
We report a patient with a metastatic relapse of clear cell sarcoma, whose tumor harbored BRAF V600E mutation. Standard chemotherapy with doxorubicin and ifosfamide failed to slow the disease progression. Subsequent administration of vemurafenib (960 mg twice a day) resulted in complete tumor response after 8 weeks of treatment. Literature data on the use of vemurafenib and dabrafenib in non-melanoma BRAF-mutated tumors are reviewed.


Progressive supranuclear palsy: neuropathologic and clinical heterogeneity.
To investigate potential heterogeneity in progressive supranuclear palsy (PSP), we examined 13 patients with neuropathologically diagnosed PSP. The clinical diagnosis of PSP was made in eight of these individuals, whereas probable AD was the primary diagnosis in the remaining five. In addition to PSP neuropathology, seven of the 13 patients (54%) showed concomitant pathologic changes of Alzheimer's disease (AD), Parkinson's disease (PD), or both disorders. These observations indicate that AD and PD changes coexist with PSP neuropathology in a substantive proportion of patients and provide further evidence of clinical and neuropathologic heterogeneity in neurodegenerative disorders. Moreover, our results suggest that PSP may be underdiagnosed and deserves more prominence in the differential diagnosis of dementing illness.


Leisure time physical activities and dietary quality of the general and indigenous Taiwanese populations are associated with fat distribution and sarcopenia.
Indigenous peoples are at greater risk of obesity-related health problems for various reasons. These have been explored in the adulthood (>=19 yrs) section of the nationally-representative Nutrition and Health Survey in Taiwan (NAHSIT) for 2005-2008 in Indigenous mountain-dwelling (IndT) (n=226) and general (mainly Han Chinese) (GenT) (n=1486) Taiwanese. Physical activity, BMI, fat distribution (waist circum-ference (WC) and triceps skinfold (TSF)) and mid arm muscle circumference (MAMC) have been com-pared. Leisure-time physical activities (LTPA) were assigned metabolic equivalents (METs). Comparisons were made by ethnicity-locality. Indigenous men and women were 3.81 and 5.47 times more obese (WHO criteria BMI>=30 kg/m2) than the GenT, respectively. Some 55% of the IndT and 34% of the GenT reported no LTPA. All LTPA types were less evident in the IndT. Multivaiable adjusted ORs (95% CIs) against inactivity as referent were, for sarcopenic MAMC, in Indigenes with MVI-LTPA 0.13 (0.03-0.67) and in the GenT 0.61 (0.37-1.01); in the GenT with LTPA for BMI >=30 kg/m2 and obese TSF, they were 0.53 (0.31-0.91) and 0.77 (0.60-0.98), respectively. Without dietary quality adjustment, the sarcopenia risk in GenT with LTPA was significant (OR=0.60, 95% CI: 0.37-0.97). Having adjusted for dietary quality, the significance disappeared. Less sarcopenia was found with ambulation in the GenT (OR=2.07, 95% CI: 1.26-3.43). More over-fatness in an IndT than GenT is associated with less LTPA. LTPA reduces sarcope-nic risk irrespective of ethnicity, is partly dependent on diet, and reduces obesity indices in the GenT.


Long-term results of chemoradiotherapy for locally advanced esophageal cancer, using daily low-dose 5-fluorouracil and cis-diammine-dichloro-platinum (CDDP).
We evaluated the efficacy and toxicity of radiation combined with daily, low-dose protracted chemotherapy for locally advanced esophageal cancer. We analyzed data for 68 patients with locally advanced esophageal cancer, including 18 surgical candidates. Standard fractionation (total dose range, 60 to 70 Gy) was used for radiotherapy. The chemotherapy consisted of a daily 5-fluorouracil dose of 250 mg/m2, with a cis-diammine-dichloro-platinum dose of 3 mg/m2 administered on radiotherapy days. Sixty-four patients (94%) received at least 60 Gy. Grade 3 acute hematological toxicity was observed in 13 (19%) patients; there was no grade 4 hematological toxicity. Complete response, partial response, no change, and progressive disease were obtained in 22, 35, 7, and 4 patients, respectively. Minimum follow-up for surviving patients was 45 months. Locoregional progression-free rates at 3 and 5 years were 47% and 47%. Four patients died of late cardiac toxicity; the primary site for all 4 patients was the middle thoracic esophagus. Overall survival rates at 2, 3, and 5 years were 40%, 32%, and 20%. The 3- and 5-year survival rates in patients with T2-3M0 disease were 43% and 27%, and the rates were 24% and 15% in patients with T4/M1. Given the large proportion of patients in this study with inoperable disease (roughly three quarters), our treatment seemed to provide equivalent efficacy and less hematological toxicity than standard-dose chemoradiotherapy.


Cellular repopulation and recovery of the phytogemagglutinine (PHA) responding cell pool in the thymus of sublethally irradiated mice.
Cellular repopulation and recovery of PHA reactivity was investigated in the thymus of mice exposed to 400 R either on the whole body or with one leg protected. In the whole body irradiated cases both the cellular repopulation and the restoration of PHA reactivity in the thymus showed a cyclic pattern: an initial depression and a subsequent first recovery being followed by a secondary cellular depletion and decrease of reactivity before another recovery phase started. The phase of the secondary decrease lasted fo a similar period for both the cell number and reactivity, but was shifted in time and the reduction in reactivity began some 12 days later than that in the cell number. In the leg-shielded animals, the cellular repopulation progressed without cyclic changes, but the recovery of PHA reactivity maintained a cyclic pattern. However, due to a smaller secondary decrease, it was less pronounced than in the whole body irradiated cases. During the aging of mice from 50 to 90 day old, the cell number in the involuting thymus decreased to half of the original. The decrease in the cell population was associated with an about four-fold increase of PHA reactivity. The results were discussed in regard to the origin of the immunoreactive thymic cells. Arguments were presented in favour of the hypothesis that both the reactive and nonreactive cells originate from precursors in common, but require different lengths of time for maturation.


Results of a prospective, 18-month clinical evaluation of culture, cytotoxin testing, and culturette brand (CDT) latex testing in the diagnosis of Clostridium difficile-associated diarrhea.
An 18-mo evaluation of culture, cytotoxin, and latex testing for Clostridium difficile was performed between July 1, 1985, and December 31, 1986, on 1,536 specimens from 1,406 patients during evaluation of diarrhea. All cases with at least one test positive were investigated for clinical status. There were 144 Clostridium difficile-associated diarrhea (CAD) patients; 139 (97%) were positive by culture, 96 (67%) by cytotoxin, and 98 (68%) by latex testing. In the 1,262 non-CAD patients with diarrheal stool, 89 (7.1%) were positive by culture, 18 (1.4%) by cytotoxin, and 68 (5.4%) by the latex test. No CAD patient was positive by cytotoxin testing only, and two were positive by latex testing only. The culture and cytotoxin positivity were similar to our previous reports of 90-97% and 70-73%, respectively. Latex sensitivity (68%) was comparable to that of cytotoxin testing in this large group of patients (p greater than 0.5). Overall, in the 1,262 patients without clinical evidence of Clostridium difficile disease, positive tests by latex testing (5.4%) were intermediate between those of culture (7.1%, p less than 0.1) and cytotoxin (1.4%, p less than 0.001).


An analysis of infant feeding content found within the Hong Kong print media.
Worldwide public media greatly affect women's decisions about infant feeding and may not reflect evidence-based practices. The aims of this research were to (1) describe the characteristics of printed articles having infant-feeding content, (2) describe this thematic content, and (3) compare the thematic content found in groupings based on media type and language (English and Chinese). Four Chinese-language newspapers, the English-language newspaper, and 3 bilingual parenting magazines were analyzed. A multiphase qualitative and quantitative content analysis found 5 themes (social context, mothers' information, effects on baby, the value of breast milk, and the utility of formula). Significant differences were found based on media type and language. Although breastfeeding was usually positively framed in all the media, Chinese media had more inaccurate information. Through this analysis, areas where actions could be taken to improve the quality of information about infant feeding received by the public have been identified.


A generalized many-body expansion and a unified view of fragment-based methods in electronic structure theory.
Fragment-based quantum chemistry methods are a promising route towards massively parallel electronic structure calculations in large systems. Unfortunately, the literature on this topic consists of a bewildering array of different methods, with no clear guiding principles to choose amongst them. Here, we introduce a conceptual framework that unifies many of these ostensibly disparate approaches. The common framework is based upon an approximate supersystem energy formula for a collection of intersecting (i.e., overlapping) fragments. This formula generalizes the traditional many-body expansion to cases where the "bodies" (fragments) share some nuclei in common, and reduces to the traditional many-body expansion for non-overlapping fragments. We illustrate how numerous fragment-based methods fit within this framework. Preliminary applications to molecular and ionic clusters suggest that two-body methods in which dimers are constructed from intersecting fragments may be a route to achieve very high accuracy in fragment-based calculations.


What is the relative impact of primary health care quality and conditional cash transfer program in child mortality?
Evaluate how coverage and quality of primary health care (PHC) and a conditional cash transfer (CCT) program associate with child mortality in Brazil. Multivariate linear regression models and least absolute shrinkage and selection estimator (LASSO) were utilized with the municipal level child mortality rate as the key dependent variable. PHC quality with PHC and CCT coverage were the independent variables. The quality of the Brazilian PHC was assessed using the Brazilian National Program for Access and Quality Improvement in PHC data. PHC and CCT coverage were calculated based on Brazilian official databases. Human developmental index (HDI), municipality size, and country region were used as control variables. A total of 3441 municipalities were evaluated. We found that ESF (Estratégia Saúde da Família) quality variables PLANNING [Family Health Team Planning activities], CITYSUPPORT [municipality support for Family Health Strategy activities], EXAMS [exams offered and priority groups seen by the family health team], and PRENATAL [prenatal care and exams provided by the family health team], as well as HDI, percentage of PHC coverage, percentage of CCT coverage, and population size have significant and negative relationships with 1-year-old child mortality. LASSO regression results confirmed these associations. Quality is an important element of effective social service provision. This exploration represents one of the first investigations into the role of PHC system quality, and how it is related to health outcomes, while also considering PHC and conditional cash transfer program coverage. Quality of PHC, measured by work process variables, plays an important role in child mortality. Efforts on PHC quality and coverage, as well as on CCT program coverage, are important to child mortality reduction. Therefore, this is an important finding to other PHC public health services.


Responses of rabbit aorta to tyramine in relation to the surface of drug entry.
The contraction elicited by submaximally effective concentrations of tyramine in the rabbit aortic strip occurs after a shorter latency and increases at a higher initial velocity to a greater steady-state level when drug entry is limited to the adventitial than when it is limited to the intimal surface. The reverse was true for noradrenaline. Both amines elicited equal maximum responses with independence of the surface of entry into the vascular wall. Differences between steady-state contractions disappear when the intramural disposition pathways of tyramine are blocked pharmacologically by a combination of pargyline and semicarbazide. Incubation with cocaine and pretreatment with reserpine resulted in a reversal of the surface of entry related differences between steady-state contractions to tyramine related to differences of the surface of entry. This reflected the unmasking of the direct component of the action of tyramine. Thus, the technique of limited drug entry into the vascular wall together with blockade of disposition pathways allows us to characterize the pre- and postsynaptic components of the action of tyramine.


[Interleukins as highly informative markers of the activity of the inflammatory process of the adnexa uteri].
Interleukins are highly informatively markers of the activity of the inflammatory process in the uterine appendages. Interleukin-6 and tumornecrotic factor allow to diagnose chronic inflammation in uterine appendages without clinical manifestation.


Clinical and prognostic significance of coagulation assays in gastric cancer.
Activation of coagulation and fibrinolysis is frequently found among cancer patients. Such tumors are considered to be associated with a higher risk of invasion, metastases, and eventually, worse outcome. The aim of this study is to explore the clinical and prognostic value of blood coagulation tests in gastric cancer (GC) patients. A total of 44 consecutive patients with a pathologically confirmed diagnosis of GC were enrolled into the study. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were evaluated. Control group comprised 50 age- and sex-matched individuals without history of malignancy and coagulation disorder. Median age at diagnosis was 55 years, range 19-80 years; most had men (n = 32, 73 %) and metastatic disease (n = 31, 70 %). The level of blood coagulation tests showed a statistically significant difference between the patient and the control groups (P < 0.001 for all, but p = 0.07 for PT). DD levels were significantly associated with elevated PLT and LDH levels (p = 0.009 and p = 0.01, respectively). Patients with metastatic disease had higher levels of F (p = 0.001) and INR (p = 0.027) levels. Elevated DD levels tended to be a poor prognostic factor on outcome (p = 0.06). Change in almost all coagulation tests are found in GC patients and only DD level seems to be of prognostic value.


Subshell fitting of relativistic atomic core electron densities for use in QTAIM analyses of ECP-based wave functions.
Scalar-relativistic, all-electron density functional theory (DFT) calculations were done for free, neutral atoms of all elements of the periodic table using the universal Gaussian basis set. Each core, closed-subshell contribution to a total atomic electron density distribution was separately fitted to a spherical electron density function: a linear combination of s-type Gaussian functions. The resulting core subshell electron densities are useful for systematically and compactly approximating total core electron densities of atoms in molecules, for any atomic core defined in terms of closed subshells. When used to augment the electron density from a wave function based on a calculation using effective core potentials (ECPs) in the Hamiltonian, the atomic core electron densities are sufficient to restore the otherwise-absent electron density maxima at the nuclear positions and eliminate spurious critical points in the neighborhood of the atom, thus enabling quantum theory of atoms in molecules (QTAIM) analyses to be done in the neighborhoods of atoms for which ECPs were used. Comparison of results from QTAIM analyses with all-electron, relativistic and nonrelativistic molecular wave functions validates the use of the atomic core electron densities for augmenting electron densities from ECP-based wave functions. For an atom in a molecule for which a small-core or medium-core ECPs is used, simply representing the core using a simplistic, tightly localized electron density function is actually sufficient to obtain a correct electron density topology and perform QTAIM analyses to obtain at least semiquantitatively meaningful results, but this is often not true when a large-core ECP is used. Comparison of QTAIM results from augmenting ECP-based molecular wave functions with the realistic atomic core electron densities presented here versus augmenting with the limiting case of tight core densities may be useful for diagnosing the reliability of large-core ECP models in particular cases. For molecules containing atoms of any elements of the periodic table, the production of extended wave function files that include the appropriate atomic core densities for ECP-based calculations, and the use of these wave functions for QTAIM analyses, has been automated.


[Radiosensitivity and postradiation kinetics of megakaryocyte release of the bone marrow (analysis based on data of the Chernobyl AES accident sequelae)].
The radiosensitivity of cellular elements of megakaryocytic spring in accordance of their maturity has been evaluated on the basis of analysis of changes in thrombocyte level in peripheral blood of the Chernobyl disaster victims. The radiosensitivity of committed cellular elements of megakaryocytic spring by the criterion D0 is presumably 1.6-1.7 Gy(n = 1). More mature polyploid cells (megakaryoblasts, megakaryocytes) apparently are "absolutely" radioresistant and within the analysed range of doses (0.1-13.7 Gy) their function of thrombocyte producing remains intact. It has been proved that the rate of thrombocyte escape from peripheral blood rises with the acute radiation disease under going in the comparison with the norm that seriously affects the lifetime of thrombocytes. The transit time of megakaryocyte starting from primarily committed cell and ending with a cellular element, producing thrombocytes, is not a constant value. The normal transit time is approximately 28 days.


The effect of recombinant activated factor VII on mortality in combat-related casualties with severe trauma and massive transfusion.
The majority of patients with potentially survivable combat-related injuries die from hemorrhage. Our objective was to determine whether the use of recombinant activated factor VII (rFVIIa) decreased mortality in combat casualties with severe trauma who received massive transfusions and if its use was associated with increased severe thrombotic events. We retrospectively reviewed a database of combat casualty patients with severe trauma (Injury Severity Score [ISS] >15) and massive transfusion (red blood cell [RBCs] >/=10 units/24 hours) admitted to one combat support hospital in Baghdad, Iraq, between December 2003 and October 2005. Admission vital signs and laboratory data, blood products, ISS, 24-hour and 30-day mortality, and severe thrombotic events were compared between patients who received rFVIIa (rFVIIa) and did not receive rFVIIa (rFVIIa). Of 124 patients in this study, 49 patients received rFVIIa and 75 did not. ISS, laboratory values, and admission vitals did not differ between rFVIIa and rFVIIa groups, except for systolic blood pressure (mm Hg) 105 +/- 33 and 92 +/- 28, p = 0.02 and temperature ( degrees F) 96.3 +/- 2.1 and 95.2 +/- 2.4, p = 0.03, respectively. Interactions between all vital signs and laboratory values measured upon admission, to include systolic blood pressure and temperature, were not significant when measured between rFVIIa use and 30-day mortality. Twenty-four-hour mortality was 7 of 49 (14%) in rFVIIa and 26 of 75 (35%) in rFVIIa, (p = 0.01); 30-day mortality was 15 of 49 (31%) and 38 of 75 (51%), (p = 0.03). Death from hemorrhage was 8 of 14 (57%) for rFVIIa patients compared with 29 of 37 (78%) for rFVIIa patients, (p = 0.12). The incidence of severe thrombotic events was similar in both groups. The early use of rFVIIa was associated with decreased 30-day mortality in severely injured combat casualties requiring massive transfusion, but was not associated with increased risk of severe thrombotic events.


Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: selective inhibitors of dopamine D₁ receptor.
A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D(1) and D(2)) and serotonin (5-HT(1A) and 5-HT(2A)) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D(1) receptor, as well as high selectivity for the D(1) receptor over the D(2), 5-HT(1A), and 5-HT(2A) receptors. Among these, compound 19c exhibited a promising D(1) receptor binding affinity (K(i)=2.53nM) and remarkable selectivity versus D(2)R (inhibition=81.87%), 5-HT(1A)R (inhibition=61.70%), and 5-HT(2A)R (inhibition=24.96%). Compared with l-(S)-stepholidine (l-SPD) (D(1)K(i)=6.23nM, D(2)K(i)=56.17nM), compound 19c showed better binding affinity for the D(1) receptor (2.5-fold higher) and excellent D(2)/D(1) selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D(1) receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D(1) receptor. These results are in accord with molecular docking studies.


[Postoperative sequential testing of cytotoxic activity against the autologous and allogeneic tumor cells in patients with primary lung resected cancer].
The objective of this study of 27 primary lung resected cancer patients was to evaluate sequentially the cytotoxic activity against autologous and allogeneic tumor cells during the postoperative period. In patients given a complete resection, the cytotoxic activity against the autologous tumor cells during the postoperative 1-2 weeks was significantly higher than during the postoperative 4-5 weeks (P less than 0.05, Student t test). In patients given an incomplete resection, however, no significant difference was demonstrated between the postoperative 1-2 weeks and during the postoperative 4-5 weeks. In contrast, the cytotoxic activity against the PC-3 cells or K562 cells during the postoperative 4-5 weeks tended to rise in comparison to those at the postoperative 1-2 weeks all patients in any cancer stage and whatever the amount of their lung resection. The phenotype of the effector cells which mediated the cytotoxic activity to the autologous tumor cells was the monoclonal antibody OKT 3(+), 8(+), 4(-) OKM 1(-) and the cells which were cytotoxic to the K562 cells had an OKT 3(-), 4(-), 8(-), OKM 1(+) phenotype. These results suggest that the effectors which mediate cytotoxic activity to the autologous tumor cells and to the K562 cells seems to be different and a concomitant immunity may exist in primary lung resected cancer patients.