Numerical Construction of the Aizenman-Wehr Metastate.
Chaotic size dependence makes it extremely difficult to take the thermodynamic limit in disordered systems. Instead, the metastate, which is a distribution over thermodynamic states, might have a smooth limit. So far, studies of the metastate have been mostly mathematical. We present a numerical construction of the metastate for the d=3 Ising spin glass. We work in equilibrium, below the critical temperature. Leveraging recent rigorous results, our numerical analysis gives evidence for a dispersed metastate, supported on many thermodynamic states.


Factors affecting the sorption of trivalent chromium by zeolite synthesized from coal fly ash.
This research was initiated to determine the effects of different constituents and properties of zeolite synthesized from fly ash (ZFA) on Cr(III) sorption. The uptake of Cr(III) by ZFA was influenced greatly by pH, increasing with the increase in pH. The pH was controlled mainly by calcium-related components (especially CaCO3 and free CaO) and zeolite components in ZFAs. Sorption maximum of Cr(III) (Qm), determined by a repeated batch equilibration method, ranged from 22.29 to 99.91 mg/g for the 14 ZFAs. The Q(m) value correlated significantly with Ca-related components. The correlation coefficients were 0.9467, 0.5469, 0.7521, and 0.9195 for total Ca, CaCO3, CaSO4, and f.CaO, respectively. The Qm value was also closely related to cation-exchange capacity (r=0.6872) and specific surface area (r=0.7249). Correlation coefficients of Qm with dissociated Fe2O3 and Al2O3 were much higher than those of total Fe and total Al contents, respectively. It was suggested that, in ZFAs, zeolite and iron oxide acted as ion exchanger and adsorbent for Cr(III), respectively, while Ca components elevated the pH of the reaction system and consequently promoted ion exchange and adsorption and caused the surface precipitation of chromium hydroxide.


The scaling of safety factor in spider draglines.
This study documents the effect of body mass on the size and strength of draglines produced by the orb-weaving spider Araneus diadematus and the jumping spider Salticus scenicus. Silk samples obtained from individuals spanning the range from first-instar juveniles to gravid adults were tested to determine both the properties of the silk material and the strength and static safety factor of the draglines produced by each individual spider. Analysis of material properties indicates that the tensile strength and extensibility of the silks employed by each species are identical over the entire size range of the species. Analysis of the breaking forces for individual draglines, however, indicates that the draglines scale allometrically with the spider's body mass. For Araneus, breaking force (N) scales with body mass (kg) as Fmax=11.2M0.786, and the static safety factor (S(BW)=Fmax/Mg) scales as S(BW)=1.14M(-0.214). For Salticus, Fmax=0.363M0.66 and S(BW)=0.037M(-0.34). Thus, static safety factors decrease as these spiders grow, with values falling to 4-6 for adult Araneus and to 1-2 for adult Salticus. Analysis of these results suggests that the safety lines produced by these two species are not able to absorb the impact energy of most falls with a fixed length of pre-existing silk, except in the smallest of the Araneus spiders. It is therefore likely that both spiders must draw new silk from their spinnerets during falls to keep the dynamic loads on their safety-lines below failure levels.


Phase I/II study of neoadjuvant intraarterial chemotherapy with mitomycin-C, vincristine, and cisplatin in patients with stage IIb bulky cervical carcinoma.
Stage IIb bulky cervical carcinomas have been considered difficult to treat successfully by radiation and/or surgery, compared with smaller lesions. This study was designed to evaluate the efficacy of neoadjuvant pelvic intraarterial chemotherapy (IAC) and to determine the optimal dosage of cisplatin for reducing tumor volume in these patients. Twenty-one previously untreated patients with primary cervical carcinoma of more than 4 cm in greatest dimension and parametrial invasion were included in this study. Pelvic IAC was administered using a combination of mitomycin-C, 10 mg/m2; vincristine, 1 mg/m2; and cisplatin, 50 mg/m2 (MVC; group 1, 8 patients) or 75 mg/m2 (group 2, 13 patients). Tumor volumes were measured three-dimensionally by magnetic resonance imaging (MRI) before and after three courses of IAC. Clinical responses were evaluated with gynecologic examination and MRI; pathologic responses were evaluated with histologic examinations of surgical specimens. The mean volume reduction rate (74.2% vs. 97.2% in groups 1 and 2, respectively, P = 0.0022), the clinical complete response rate (0% vs. 69.2%, P = 0.0033), and the pathologic complete response rate (0% vs. 46.2%, P = 0.0445) were significantly higher in group 2. Type III radical hysterectomy was possible in 19 patients (90.5%). Toxicities of grades 2-3 (World Health Organization criteria) were nausea and/or vomiting (38.1%), leukopenia (33.3%), and fever (14.2%). These preliminary results suggest that neoadjuvant pelvic IAC with MVC (especially with cisplatin at a dose of 75 mg/m2) is effective in reducing tumor volume, increasing the clinical and pathologic complete response rate, and improving the operability in most patients with Stage IIb bulky cervical carcinoma, generally considered inoperable.


Five-year multicenter study of magnetic attachments used for natural overdenture abutments.
The purpose of this study was to examine a longitudinal clinical performance of magnetic attachments used for natural overdenture abutments. The study included 131 patients who had used removable prostheses (complete overdentures 31%, partial dentures 69%) more than 5 years (40-90 years old) with 211 magnetic attachments on natural abutments (Magfit 400 or 600; Aichi Steel co., Aichi, Japan) treated in 15 clinics using a standardized protocol. Analyses were performed on the degree of patient satisfaction regarding retention, complications of magnets (corrosion, detachment from denture base), abutments (pain during mastication, periodontal pocket formation, inflammation, mobility), and dentures (fracture etc.). Ninety-seven percent of patients were satisfied with the retention and stability of their dentures. No corrosion of magnet was observed, and 19 magnets were detached. Most frequent complication of abutments was periodontal pocket formation (52%), followed by the inflammation (29%), increase in mobility (27%) and pain (4%). Magnetic attachment on natural tooth abutments provided a viable and long-term treatment option.


[Analyzing the posterior ethmoid sinus in Chinese-using multi planar reconstruction in spiral CT].
To study the anatomical character of the ethmoid sinus with spiral CT, and provide correlated data for diagnosis and surgery operation. One hundred patients whose vertebra artery was injected with Angiografin underwent axial consecutive computed tomography and these data were studied with multiplanar reformation. Based on the relation of posterior ethmoid sinus to sphenoid sinus, the posterior ethmoid sinus was divided into antero sphenoid types and super sphenoid types. According to the relation between the posterior ethmoid and the optic canal, the posterior ethmoid sinus was divided into antero canal, seminal abut types, canal abut types. According to the degree of the bulging of the optic canal, the posterior ethmoid sinus was divided into notch types, seminal cover types, canal cover types. Bulging of the optic canal formed on the lateral wall of the posterior ethmoid sinus was 40 sides (20%). MPR in spiral CT is powerful tool for the anatomical study of the ethmoid sinus, it could provide accuracy evaluation and analyzation, these results are helpful in directing the diagnose and therapy.


Statistical Models for the Analysis and Design of Digital Polymerase Chain Reaction (dPCR) Experiments.
Statistical methods for the analysis and design of experiments using digital PCR (dPCR) have received only limited attention and have been misused in many instances. To address this issue and to provide a more general approach to the analysis of dPCR data, we describe a class of statistical models for the analysis and design of experiments that require quantification of nucleic acids. These models are mathematically equivalent to generalized linear models of binomial responses that include a complementary, log-log link function and an offset that is dependent on the dPCR partition volume. These models are both versatile and easy to fit using conventional statistical software. Covariates can be used to specify different sources of variation in nucleic acid concentration, and a model's parameters can be used to quantify the effects of these covariates. For purposes of illustration, we analyzed dPCR data from different types of experiments, including serial dilution, evaluation of copy number variation, and quantification of gene expression. We also showed how these models can be used to help design dPCR experiments, as in selection of sample sizes needed to achieve desired levels of precision in estimates of nucleic acid concentration or to detect differences in concentration among treatments with prescribed levels of statistical power.


ALK rearrangements-associated renal cell carcinoma (RCC) with unique pathological features in an adult.
We report an exceptional case of renal cell carcinoma (RCC) associated with ALK translocation in an adult. The tumor was located in the left kidney and measured 4cm. The tumor was composed of sheets of large eosinophilic cells with frequently intracytoplasmic vacuoles. The nuclei were large with a nucleolar grade 3. At immunohistochemistry, tumor cells were diffusely positive for PAX8 and vimentin and focally stained with CK7. ALK immunostaining was diffuse and fluorescent in situ hybridization showed a rearrangement of ALK in numerous tumor cells. To date, less than 17 cases of RCCs with ALK rearrangements are reported in children and adults. The prognosis remains uncertain but ALK rearrangement may be of potential value for target therapy with crizotinib.


Benzene homologues in environmental matrixes from a pesticide chemical region in China: Occurrence, health risk and management.
The contamination status and health risks of benzene, toluene, ethylbenzene and xylene (BTEX) in air, soil, dust and groundwater were evaluated in a pesticide chemical region located in Hebei province, China. The concentrations of BTEX in air ranged from 7.80 to 238ug/m(3) and those in soil and dust ranged from lower than limit of detection (LOD) to 32,360ng/g dw, and those in groundwater varied from 2.68 to 98.6ug/L. Generally, the levels of BTEX in multimedia matrixes were all below the standards established in China. Health risk assessment was performed based on the monitoring data via inhalation, dermal contact and ingestion pathways and hazard quotient (HQ) was calculated to be on the order of 10(-7), below 10(-6), and Hazard index (HI) levels of BTEX were lower than 1.0. However, both HQ and HI ascended with an increase in work experience/exposure. Integrated risk management was proposed to eliminate BTEX pollution and to protect occupational health of workers in those industries.


A simplified polyacrylamide gel electrophoresis apparatus for simultaneous application of multiple buffer systems or detergent combinations.
A previous design of an apparatus for the simultaneous fractionation by polyacrylamide gel electrophoresis in 10 different buffer systems (1) was replaced by a greatly simplified new design, employing small, cylindrical buffer partitions within the lower buffer reservoir and/or upper buffer reservoir of a conventional, temperature-regulated polyacrylamide gel electrophoresis apparatus for cylindrical gels. The apparatus was tested in application to the problem of simultaneous polyacrylamide gel electrophoresis in different buffer systems with the purpose of optimizing the operative pH for a particular fractionation problem. It was also applied to fractionations in a single buffer system to which various combinations of ionic and nonionic detergents were admixed.


[Immunological and morphological comparisons in toxic goiter].
Histostructural peculiarities of the toxic goiter tissue were compared with humoral parameters of the autoimmune aggression and with the lymphoblasttransformation intensity in 29 patients operated on for thyrotoxicosis. The intensity of intradermal hypersensitivity reaction of delayed type in response to homologous and autologous tissue of the toxic goiter was also investigated. The majority of the patients displayed marked signs of autoimmune aggression, regardless of the structure of the goiter parenchyma and the intensity of ilt lymphoid infiltration. Immunological disturbances increase with the rise in the clinical severity of thyrotoxicosis. It is suggested that immunological changes of toxic goiter have phasic development. Humoral manifestation of autoimmune aggression were marked and stable, whereas changes of cellular immunity were less significant and specific; they were apparently due to a secondary increase in the lymphocytic immunological activity.


Economic impact of syndesmosis hardware removal.
Ankle syndesmosis injuries are commonly seen with 5-10% of sprains and 10% of ankle fractures involving injury to the ankle syndesmosis. Anatomic reduction has been shown to be the most important predictor of clinical outcomes. Optimal surgical management has been a subject of debate in the literature. The method of fixation, number of screws, screw size, and number of cortices are all controversial. Postoperative hardware removal has also been widely debated in the literature. Some surgeons advocate for elective hardware removal prior to resuming full weightbearing. Returning to the operating room for elective hardware removal results in increased cost to the patient, potential for infection or complication(s), and missed work days for the patient. Suture button devices and bioabsorbable screw fixation present other options, but cortical screw fixation remains the gold standard. This retrospective review was designed to evaluate the economic impact of a second operative procedure for elective removal of 3.5mm cortical syndesmosis screws. Two hundred and two patients with ICD-9 code for "open treatment of distal tibiofibular joint (syndesmosis) disruption" were identified. The medical records were reviewed for those who underwent elective syndesmosis hardware removal. The primary outcome measurements included total hospital billing charges and total hospital billing collection. Secondary outcome measurements included average individual patient operative costs and average operating room time. Fifty-six patients were included in the study. Our institution billed a total of $188,271 (USD) and collected $106,284 (55%). The average individual patient operating room cost was $3579. The average operating room time was 67.9 min. To the best of our knowledge, no study has previously provided cost associated with syndesmosis hardware removal. Our study shows elective syndesmosis hardware removal places substantial economic burden on both the patient and the healthcare system.


Perturbation of polyamine metabolism and its relation to cell death in human colon cancer cells treated by 7beta-hydroxycholesterol and 7beta-hydroxysitosterol.
7beta-OHsitosterol and 7beta-OHcholesterol are natural compounds of plant and animal cells with high structural similarity. Recently it was reported that both compounds induced apoptosis on human colon cancer cells by targeting different signalling pathways. Our study aimed at comparing their effects on polyamine metabolism and its relation to apoptosis. When human colon cancer cells were exposed to 7beta-OHsitosterol and to 7beta-OHcholesterol at concentrations inhibiting growth by the same degree, both compounds caused a reduction of polyamine biosynthetic enzyme activity, of the polyamine pools, and an increase of N1-acetylspermidine concentration indicating the enhancement of polyamine catabolism. Exogenous putrescine did not prevent cell death caused by 7beta-OHsitosterol, whereas 7beta-OHcholesterol-induced apoptosis was inhibited. MDL 72527, an inhibitor of polyamine oxidase, an enzyme of the polyamine catabolic pathway, potentiated the antiproliferative effects of 7beta-OHcholesterol by increasing the N1-acetylspermidine pool and enhanced the accumulation of apoptotic cells. In contrast, MDL 72527 did not change the apoptosis rate and the N1-acetylspermidine content in cells treated with 7beta-OHsitosterol. These data indicate that polyamine metabolic perturbations triggered by 7beta-OHcholesterol but not by 7beta-OHsitosterol are related to cell death.


[Determination of the dispersity of suspensions using photoelectric colorimeters of different makes].
Different conditions of measuring the suspension dispersity of photoelectric colorimeters of two brands,KFK-2 and FEK-56, result in distorted data: the dispersity index (DI) measured by KFK according to the method developed for FEK is inaccurate. The presence of 2 photoreceptors in the KFK apparatus, in contrast to the FEK one, results in elevated values of optic density (D) when the apparatus sensitivity is changed, starting from 590 nm wavelength (this fact is mentioned in the operation instructions) and eventually breaks the inversely proportional relationships between the D value and wavelength. DI estimation is based on the proportional relationships between wavelengths and D values obtained with a selected light filter pair. The wavelength selection mode had to be changed in the procedure of DI measurement by KFK-2 (or by KFK-MP) so that the light filter pair was placed in the same sensitivity zone; the distance between the cuvette and photo element was also changed (the cuvette with the sample was placed not in the cuvette holder but at a maximum distance from the photo element, closer to the source of light). Such modifications helped obtain compatible results of optic density measurements and DI values with photoelectric colorimeters of various brands. This is true only for suspensions rather than for transparent solutions, which fact is explained by the theory of light dispersion by suspension particles.


Oxidative stress and cognition amongst adults without dementia or stroke: Implications for mechanistic and therapeutic research in psychiatric disorders.
Oxidative stress has been implicated in cognitive deficits in disease states such as dementia and stroke. However, growing evidence shows similar associations in individuals without these conditions. We therefore set out to systematically review the literature on this topic. MEDLINE searches were conducted of medical subject-headings neuropsychology, cognition, cognition disorders, or neuropsychological tests, cross-referenced with oxidative stress, or superoxide. Exclusion criteria were dementia and stroke studies, absence of human subjects, and absence of quantifiable oxidative stress/cognition measures. The search yielded 883 results, of which 19 studies (consisting of 3662 total subjects) were included in this review. The majority of studies indicated that frontal cognitive functions were most often impaired, and lipid peroxidation was most commonly associated with impairments. Literature on learning, memory, and general cognitive function was less robust. A substantial proportion of the literature on this topic is based on psychiatric populations. Frontal-executive dysfunction implicates frontal brain regions, which are known to be susceptible to oxidative damage. Further studies are needed, and those examining psychiatric populations may be especially fruitful. Focusing on youth may yield enhanced signal detection. Further study is needed to identify which antioxidant interventions work best for which cognitive functions and for which patients.


Designing evidence-based medicine training to optimize the transfer of skills from the classroom to clinical practice: applying the four component instructional design model.
Evidence-based medicine (EBM) skills, although taught in medical schools around the world, are not optimally practiced in clinical environments because of multiple barriers, including learners' difficulty transferring EBM skills learned in the classroom to clinical practice. This lack of skill transfer may be partially due to the design of EBM training. To facilitate the transfer of EBM skills from the classroom to clinical practice, the authors explore one instructional approach, called the Four Component Instructional Design (4C/ID) model, to guide the design of EBM training. On the basis of current cognitive psychology, including cognitive load theory, the premise of the 4C/ID model is that complex skills training, such as EBM training, should include four components: learning tasks, supportive information, procedural information, and part-task practice. The combination of these four components can inform the creation of complex skills training that is designed to avoid overloading learners' cognitive abilities; to facilitate the integration of the knowledge, skills, and attitudes needed to execute a complex task; and to increase the transfer of knowledge to new situations. The authors begin by introducing the 4C/ID model and describing the benefits of its four components to guide the design of EBM training. They include illustrative examples of educational practices that are consistent with each component and that can be applied to teaching EBM. They conclude by suggesting that medical educators consider adopting the 4C/ID model to design, modify, and/or implement EBM training in classroom and clinical settings.


Angioimmunoblastic T-Cell Lymphoma.
Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common types of T-cell lymphoma, representing about 15-20% of cases of peripheral T-cell lymphoma (PTCL). It is characterized by a unique clinical presentation and distinct pathologic and molecular features. Classes of drugs particularly active in AITL are emerging; however, treatment of relapsed and refractory disease remains a challenge. This chapter reviews the epidemiology, clinical presentation, pathogenesis, diagnosis, and treatment of AITL.


pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.
Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in L-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity.


Interleukin 2 production in lymphocyte cultures: a rapid test for cancer-associated immunodeficiency in malignant cervical neoplasia.
Peripheral blood lymphocytes of patients with malignant cervical neoplasia were studied for their capacity to produce interleukin-2 (IL-2) upon in vitro mitogen stimulation. Patients with early disease (Stage I/IIA) showed levels comparable to normal controls but those with advanced disease showed reduced levels, the reduction increasing with tumour load. These findings excellently correlated with our previous observations on a depressed cellular immunity in these patients. On follow up of the patients it was noticed that those who developed recurrent disease showed sustained lower levels of IL-2 production compared to those who remained disease free. These results stress the importance of a deranged immune system in these patients and also shows the clinical and prognostic value of such an assay.


Quantitative aspects of IgD and secretory immunoglobulins in middle ear effusions.
Levels of the true secretory immunoglobulins, secretory IgA (SIgA) and secretory IgM (SIgM) were determined in middle ear effusions (MEEs) from children with secretory otitis media (SOM) and correlated to the MEE levels of IgD. Double sandwich enzyme-linked immunosorbent assays (ELISA) were used for the quantitative determinations. The levels of SIgM were expressed arbitrarily in units using a nasopharyngeal secretion pool as a standard. The quantitative data substantiated a local synthesis of IgD to the middle ear cavity. In 8/45 MEEs more than 600 mg/l of IgD could be calculated and between 70% and 98% could be considered to be locally produced. A statistically significant correlation was observed between SIgA and SIgM. The results are discussed in the context of the possibility that IgD plasma cells located in the middle ear cavity may primarily originate from the nasopharyngeal tonsils.


Early Screening for Posttraumatic Stress Disorder in Inpatient Detoxification and Motivation Treatment: Results and Consequences.
Posttraumatic stress disorder (PTSD) is a significant comorbidity in substance use disorders (SUDs). While most studies have addressed trauma/PTSD in abstinent patients, little is known about trauma/PTSD in early detoxification treatment. The current study therefore addresses the systematic evaluation of trauma/PTSD in early inpatient detoxification. A cross-sectional survey was accomplished in three German-speaking clinics (n = 134) specialized in inpatient detoxification and motivation treatment. All measures are based on self-report using trauma-specific questionnaires and measures for general psychopathological burden. Participation rate was 60.1% and patients did not show clinically obvious psychological distress during or after assessment. DSM-IV traumatic events were reported by 66.4%. Of the total sample, 38.1% screened positive for PTSD, and 14.9% screened positive for subsyndromal PTSD. PTSD patients reported significantly more childhood adversities and significantly higher scores in depression and -general psychopathology compared to subsyndromal PTSD and SUD-only patients. Early and systematic evaluation of PTSD in SUD inpatient detoxification treatment is largely safe and yields important information for individual treatment. The high PTSD-rate and the high symptom load in SUD patients during inpatient detoxification treatment highlight the need for a more stringent address of trauma/PTSD in early SUD treatment.


[Documentation of haemophilia treatment supported by the German Hemophilia Registry].
The DHR (Deutsches Hämophilieregister, German Haemophilia Register) records patient data on haemophilia A, haemophilia B, von Willebrand disease, and other coagulation factor deficiency disorders. The DHR has been online since 2009. The participation in the DHR leads to additional administrative workload for the hospitals and physicians, but provides many advantages as well: A standard of documentation will be developed to give evidence for the hospitals. They may use their own data as well as with new possibilities for data processing at any time. Reports in accordance with Section21 TFG (Transfusionsgesetz, German Transfusion Act) are compiled automatically and transmitted to the Paul-Ehrlich-Institut. The DHR may support the searching for patients fulfilling the requirements for participation in a study.


Vandetanib inhibits cisplatin‑resistant neuroblastoma tumor growth and invasion.
Resistance is the major cause of cisplatin treatment failure in neuroblastoma (NB). Vandetanib is widely used in the treatment of several cancers. In the present study, we aimed to determine the potential of vandetanib in cisplatin‑resistant NB therapy. Immunohistochemistry (IHC) staining was employed to detect p‑RET and CXCR4 expression in cisplatin‑resistant or ‑sensitive NB tissues from patients. Vandetanib was added to treat selected cisplatin‑resistant SH‑SY5Y cells (SH‑SY5Y‑R); this was followed by CCK8 assay, colony formation assay, and invasion assay. Furthermore, the effect of vandetanib on subcutaneous tumor growth was investigated in mice. Our results demonstrated greater expression of p‑RET and CXCR4 in cisplatin‑resistant neuroblastomas (NBs). Vandetanib significantly inhibited SH‑SY5Y‑R cell proliferation, colony formation, and invasion, while downregulating p‑RET and CXCR4 expression. Furthermore, vandetanib was as effective as high‑dose cisplatin in impairing cisplatin‑resistant NB subcutaneous tumor growth. Notably, vandetanib caused less severe liver toxicity in mice compared with high‑dose cisplatin. In summary, this study identified Vandetanib as a potential drug for cisplatin‑resistant NB treatment.


Phytase activity in rabbit cecal bacteria.
The presence of phytase activity was demonstrated in 26 strains of rabbit cecal bacteria. In 25 strains a low phytase activity, 0.10-0.62 micromol phosphate released per min per mg protein, was found. High activity (2.61 micromol/min per mg protein) was found in the strain PP2 identified as Enterococcus hirae. Phytase activity was cell-associated, being higher in the cell extract than in the cell walls. Extracellular phytase activity and cell-associated phosphatase activity were not detected. Phytase activity was optimal around pH 5.0, which is below the physiological cecal pH range. The K (m) determined using the Lineweaver-Burk plot was 0.19 micromol/mL. Cations Fe(3+), Cu(2+) and Zn(2+) at 0.5 mmol/L decreased phytase activity in sonicated cells of E. hirae by 99.4, 90.7 and 96.5 %, respectively. In contrast, Mg(2+) increased activity by 11.0 %. Characteristics of E. hirae phytase (pH optimum, K (m), cation sensitivity) were similar to those of other bacterial phytases reported in the literature. Other bacteria with a high phytase activity may be present in the rabbit cecum but remain to be identified.


[Basic studies of ultrasound surgery. VIII. Experimental animal studies of power ultrasound surgery of the swine pancreas].
The technique of the power ultrasound was tested in vitro and in vivo in 20 porcine pancreas. Simultaneous temperature measurements and laboratory tests do not produce any restriction. Enzymatic disorders were provable adequate to the clinical course. The ultrasonic effect guarantees a nearly riskless dissection in the layer. Joining processes, by adding Ligament-FIMOMED, produced a waterproof occlusion of parenchymal wounds. The cross-section of the pancreas with the pancreatic duct was sealed sufficiently. Also the jointed pancreato-jejunostomy remained sufficient. The reaction of the pancreatic parenchyma to the power ultrasound was small. A scarred metaplasia evolved immediately at the adhesive as a chronic atrophic interstitial pancreatitis. Only in case of occlusion of the pancreatic duct this alteration comprehended the whole pancreas.


Anti-tumorigenic chalcones.
On the basis of our recent findings that licochalcone A isolated from Xin-jiang licorice showed anti-inflammatory and anti-tumorigenic activities, we synthesized more than 40 chalcone derivatives to examine their anti-tumorigenic activities. In vitro inhibitory activity against phosphorylation of phospholipids promoted by tetradecanoylphorbol-13-acetate (TPA) in HeLa cells was adopted as a screening test for anti-tumor-promoting effect. In vivo experimental mouse skin tumors initiated by dimethylbenz[a]-anthracene (DMBA) and promoted by TPA were used to test the anti-tumor-promoting effect of chalcones. In the results, 3'- and 4'-methyl-3-hydroxychalcone showed the highest potency in inhibiting tumorigenesis. They also showed a remarkable inhibitory effect on the proliferation of HGC-27 cells derived from human gastric cancer. We discuss the structure-activity relationship, including stereo-chemical phototransformation, of some chalcone derivatives with reference to their ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopic data.


Simulation of the performance of aerobic granular sludge SBR using modified ASM3 model.
The activated sludge model No. 3 (ASM3) was modified to describe the biological reactions in aerobic granular sludge SBR. The simultaneous storage and growth, nitrification and denitrification were all accounted for in modified model. The sensitivities of effluent COD, NH(4)(+) -N, and TN toward the stoichiometric and kinetic coefficients were analyzed. A standard set of parameters obtained from a combination of literature data was chosen for the model. The experimental results for the time profile of COD, NH(4)(+) -N, and TN in a typical cycle were used to verify the ASM3 model. The verification results show the model established is applicable for simulating the perfo rmance of an aerobic granule-based SBR. A comparison of the measured and predicted values of substrate removal for both the modified ASM3 and the original ASM3 was also performed. The verification and comparison results show the modified ASM3 model describes the aerobic granule-based SBR better and more mechanistically.


Novel flowering time variation in the resynthesized polyploid Brassica napus.
Recent molecular data using resynthesized polyploids of Brassica napus established that genome changes can occur rapidly after polyploid formation. In this study we present data that de novo phenotypic variation for flowering time also occurs rapidly after polyploidization. Two initial polyploid plants were developed by reciprocal crosses of B. rapa and B. oleracea followed by chromosome doubling to establish two lineages, each of which was expected to be homozygous and homogeneous. Several sublineages of each lineage were advanced by self-pollination. The range in days to flower of the sixth generation plants was 39-75 and 43-64 for the two lineages. Analysis of seventh generation progeny indicated that the variation was heritable. Lines were selected and self-pollinated to the eighth generation and also testcrossed to a natural B. napus cultivar; the testcross plants were then self-pollinated. Differences in flowering time were also inherited in these advanced generations. Days to flower was significantly correlated with leaf number in each generation. The rapid evolution of new phenotypic variation, like that observed in this model system, may have contributed to the success and diversification of natural polyploid organisms.


Genome-wide identification of flowering time genes in cucurbit plants and revealed a gene ClGA2/KS associate with adaption and flowering of watermelon.
Watermelon (Citrullus lanatus) is one of the major cucurbit crop that cultivated all over the world. Adaptability and flowering time are important agronomic characteristics that influence the quality and yield of watermelon, however, the molecular basis underlying these traits were still unclear. In this study, we identified 166, 182, 178, and 279 flowering genes in watermelon, melon, cucumber and pumpkin, respectively, and found that a lot of genes in the photoperiodic, autonomous, and vernalization pathways were absence in the four cucurbits. A higher ratio of flowering time genes was identified in the hormone pathway in cucurbits than in Arabidopsis, and a higher average ka/ks value of hormone pathway genes than the photoperiodic and vernalization pathway genes was identified in watermelon. Moreover, a gene ClGA2/KS (Cla005482) were found to associated with ecotype differentiation, flowering time, and whole growth period in watermelon. This study added knowledge to the molecular basis of flowering time regulation in cucurbits, and the molecule marker of ClGA2/KS gene may facilitate the breeding progress for selecting watermelon varieties with superior adaption and flowering time.


Mineral phases and some reexamined characteristics of the International Union Against Cancer standard asbestos samples.
Standard asbestos samples to be used for biomedical research were first prepared by the International Union Against Cancer (UICC) in 1966 in the United Kingdom and South Africa. Using modern techniques, X-ray diffractometry, analytical transmission electron microscopy, and thermal analysis, we have now analyzed these UICC samples to determine the mineral compositions (mineral phases) and their respective quantities. UICC chrysotile A (from Zimbabwe) contains 2% fibrous anthophyllite as impurity; chrysotile B (from Canada) does not contain any fibrous impurities, only non-fibrous minerals. UICC amosite and crocidolite are almost pure. UICC anthophyllite has 20-30% talc as impurity. The chemical compositions and fiber size distributions of the UICC asbestos samples have also been determined. The mean widths of the fibers of chrysotile A and B are smaller than those of the amphibole fibers. This agrees well with the earlier results which showed the two chrysotile samples to have a larger respirable fraction than the amphiboles.


Progressive declines in neurocognitive function among survivors of hematopoietic stem cell transplantation for pediatric hematologic malignancies.
Neurocognitive function of pediatric patients is of great concern after hematopoietic stem cell transplantation (HSCT). We evaluated the neurocognitive function of pediatric patients pre-HSCT, 1, 3, and 5 years post-HSCT. All patients had a hematologic malignancy and received therapy to their central nervous system. Healthy siblings were tested as a comparison group. Pediatric patients with a hematologic malignancy did not have a significant decrease in their cognitive function before HSCT compared with their siblings except in areas of academic achievement. Our study population had significant declines in visual motor skills and memory test scores within the first year post-HSCT. By 3 years post-HSCT, there was an improvement in the visual motor development scores and memory scores, but there were new deficits in verbal skills. By 5 years post-HSCT, there were progressive declines in verbal skills (P=0.005), performance skills (0.04), and new deficits seen in long-term verbal memory scores (0.04). On the basis of the raw scores, most of these tests showed that patients had an inability to acquire new skills at a rate comparable to their age-matched healthy peers. However, long-term memory scores showed definite declines. The greatest decline in neurocognitive function occurred in those patients who received cranial irradiation either as part of their initial therapy or as part of their HSCT conditioning. Pediatric patients who received HSCT for hematologic malignancies have neurocognitive deficiencies that are both acute and chronic. Although some patients have acute deficits that appear and improve over time, other patients have progressive declines in neurocognitive function that are chronic.


Effects of ammonium chloride on urinary pH and cigarette smoking behavior.
We determined the effects of acidification of urinary pH on cigarette smoking behavior to assess the postulated relationships between stress, urinary pH, and cigarette smoking. Urine was acidified by short-term administration of 12.5, 25, and 50 mg/kg ammonium chloride and long-term administration of 50 mg/kg ammonium chloride. Measurements of cigarette smoking behavior included the number of cigarettes smoked as well as automated measures of puff frequency and duration. Short- and long-term administration of ammonium chloride induced decreases in urinary pH but failed to induce any substantial changes in number of cigarettes smoked, puff frequency, or puff duration.


Simple and efficient in vitro fertilization with cryopreserved C57BL/6J mouse sperm.
Archiving of mouse stocks by cryopreservation of sperm has great potential, because it is simple, rapid, and cheap. However, for some of the most commonly used inbred strains, including C57BL/6J, the postthaw fertility of the sperm (0%-12%) is too low to be useful without recourse to zona nicking or intracytoplasmic sperm injection to aid penetration of the zona pellucida. In the present study, nonmotile sperm and cell debris were removed from thawed suspensions of C57BL/6J mouse sperm, and the remaining, largely progressively motile sperm were used for in vitro fertilization. These sperm fertilized 38%-88% of denuded, zona-intact eggs, and when 2-cell embryos were transferred to pseudopregnant recipient mice, 40%-63% produced live-born young. The production of 2-cell embryos and the birth of live pups at these rates indicate that cryopreservation of sperm is a practical way to archive the haploid genome of genetically altered C57BL/6J mice.


[Study of murine hematopoietic stem/progenitor cell mobilized by recombinant human interleukin 11 combination with granulocyte-colony stimulating factor].
To study the recombinant human interleukin 11 (rhIL-11) in combination with granulocyte-colony stimulating factor (rhG-CSF) for mobilizing peripheral blood stem/progenitor cells in C57BL/6 mice. rhIL-11,250 micro g x kg(-1) x d(-1) per mouse alone or in combination with rhG-CSF 250 micro g x kg(-1) x d(-1) per mouse was administered to C57BL/6 mice from day 1 to 7. The changes of peripheral white blood cell count (WBC), platelet counts (BPC) and hematopoietic stem/progenitor cells yields were observed. The results showed that rhIL-11 alone or in combination with rhG-CSF resulted in increase in absolute numbers of WBC, BPC, CD(34)(+) cells, and CFU-GM, CFU-E, CFU-MK yields in peripheral blood more than those of control (P < 0.001). The yields of CFU-MK was significantly more than that of rhG-CSF group (P < 0.001). rhIL-11 alone or in combination with G-CSF could significantly mobilize hematopoietic stem/progenitor cells from bone marrow into peripheral blood.


In vivo production of recombinant proteins using occluded recombinant AcMNPV-derived baculovirus vectors.
Trichoplusia ni insect larvae infected with vectors derived from the Autographa californica multiple nucleopolyhedrovirus (AcMNPV), are an excellent alternative to insect cells cultured in conventional bioreactors to produce recombinant proteins because productivity and cost-efficiency reasons. However, there is still a lot of work to do to reduce the manual procedures commonly required in this production platform that limit its scalability. To increase the scalability of this platform technology, a current bottleneck to be circumvented in the future is the need of injection for the inoculation of larvae with polyhedrin negative baculovirus vectors (Polh-) because of the lack of oral infectivity of these viruses, which are commonly used for production in insect cell cultures. In this work we have developed a straightforward alternative to obtain orally infective vectors derived from AcMNPV and expressing recombinant proteins that can be administered to the insect larvae (Trichoplusia ni) by feeding, formulated in the insect diet. The approach developed was based on the use of a recombinant polyhedrin protein expressed by a recombinant vector (Polh+), able to co-occlude any recombinant Polh- baculovirus vector expressing a recombinant protein. A second alternative was developed by the generation of a dual vector co-expressing the recombinant polyhedrin protein and the foreign gene of interest to obtain the occluded viruses. Additionally, by the incorporation of a reporter gene into the helper Polh+ vector, it was possible the follow-up visualization of the co-occluded viruses infection in insect larvae and will help to homogenize infection conditions. By using these methodologies, the production of recombinant proteins in per os infected larvae, without manual infection procedures, was very similar in yield to that obtained by manual injection of recombinant Polh- AcMNPV-based vectors expressing the same proteins. However, further analyses will be required for a detailed comparison of production yields reached by injection vs oral infections for different recombinant proteins. In conclusion, these results open the possibility of future industrial scaling-up production of recombinant proteins in insect larvae by reducing manual operations.


Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease.
Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease.


Exponential cluster synchronization of impulsive delayed genetic oscillators with external disturbances.
This paper investigates the problem of the exponential cluster synchronization of coupled impulsive genetic oscillators with external disturbances and communication delay. Based on the Kronecker product, some new cluster synchronization criteria for coupled impulsive genetic oscillators with attenuation level are derived. The derived results are related to the impulsive strength, and the derived results also indicate that the maximal allowable bound of time delay is inversely proportional to the decay rate, the decay rate is proportional to the couple strength, the maximal allowable bound of time delay is proportional to attenuation level, and the attenuation level is inversely proportional to the couple strength. Moreover, the case when the feedback have different self-delay is also investigated. Finally, numerical examples are given to illustrate the effectiveness of the derived results.


Control of autophagosome size and number by Atg7.
The induction of bulk autophagy by nitrogen starvation in baker's yeast (S. cerevisiae) involves the upregulation of many autophagy related proteins, including Atg7. One way to investigate the importance of this upregulation is to measure the size and number of autophagosomes formed when insufficient amounts of that protein are available. Atg8 is known to affect autophagosome size, consistent with its role in phagophore expansion. Atg7 is upstream of Atg8, and might therefore be expected to affect only autophagosome size. We used electron microscopy to measure the size and number of autophagosomes formed with limiting amounts of Atg7 and found them to be both smaller and fewer than normal. This suggests that Atg7 may have an Atg8-independent role in autophagosome initiation in addition to its Atg8-dependent role in autophagosome expansion. We also present an improved simulation for estimating original autophagic body number based on the number of cross-sections observed in ultrathin sections.


Female sex: a protective role in suspected myocardial ischemia.
Women are felt to have poor outcomes in coronary artery disease, largely on the basis of secondary observations in acute coronary syndrome trials. We sought to examine the neglected topic of sex differences in workup and outcomes in the general population presenting with chest pain. We examined 439 consecutive patients admitted via the emergency department with ongoing chest pain. Cardiac testing was defined as any cardiac catheterization or stress test. Positive testing was defined as a 70% or greater stenosis in an epicardial coronary artery on catheterization, or a positive stress test result. Follow-up was obtained via telephone contact at 4 months following discharge. Further cardiac testing was deemed necessary in 68% (164/241) of women and 77% (153/198) of men (P=0.038). Among women undergoing further testing, only 21% (35/164) had positive tests, whereas 41% (62/153) of men had positive tests (P=0.002). At 4 months, women were less likely to have suffered the combined endpoint of subsequent myocardial infarction, revascularization, or death, than men (15 vs. 23%, P=0.027). Events were more likely to occur in patients who had further testing, and especially in those who had positive testing. These data suggest that women admitted with chest pain are less likely to have active coronary artery disease, and much less likely to have poor outcomes at 4 months than men. This apparent 'gender protection' effect warrants further study.


Plasma concentrations of NT-pro-BNP and cardiac troponin-I in relation to doxorubicin-induced cardiomyopathy and cardiac function in childhood malignancy.
Anthracyclines are well established as highly efficacious antineoplastic agents for childhood malignancy, but they frequently cause dose-related cardiotoxicity. For this reason, children who have received anthracyclines need periodical cardiac evaluation. The plasma levels of B-type natriuretic peptide (BNP) have been shown to increase in proportion to severity of cardiac dysfunction. N-terminal BNP (NT-pro-BNP) is secreted from the cardiac ventricles in response to volume expansion and pressure overload. The aim of our study was to investigate whether plasma levels of NT-pro-BNP and cardiac troponin I (cTnI) can be used as specific markers for doxorubicin-induced cardiotoxicity in children with malignancy. We performed the study in Dicle University Hospital, Pediatric Hematology and Oncology clinic. Were measured plasma NT-pro-BNP and cTnI in 31 patients (14 boys and 17 girls) who received doxorubicin-containing chemotherapy for their malignancy at cumulative doses of 30-600 mg/m2, between October 2000 and December 2004. Cardiac evaluation of the patients included recording of electrocardiography and assessment of systolic and diastolic functions of the heart by echocardiography. Of the 31 patients, 4 (12.9%) had left ventricular dysfunction as assessed by echocardiography. Plasma NT-pro-BNP levels in these patients were significantly elevated in comparison with healthy controls (p<0.001). Plasma NT-pro-BNP levels were significantly elevated in patients with cardiac dysfunction when compared with normal cardiac function (p<0.008). The cTnI levels were found under normal value in all patients. Measurement of NT-pro-BNP level may be an easy and practical tool, and during treatment may allow earlier-identification of individuals at risk for monitoring cardiac damage. Plasma NT-pro-BNP concentration may be a useful and sensitive indicator of cardiac dysfunction in children receiving doxorubicin therapy.


Refolding and purification of histidine-tagged protein by artificial chaperone-assisted metal affinity chromatography.
This article has proposed an artificial chaperone-assisted immobilized metal affinity chromatography (AC-IMAC) for on-column refolding and purification of histidine-tagged proteins. Hexahistidine-tagged enhanced green fluorescent protein (EGFP) was overexpressed in Escherichia coli, and refolded and purified from urea-solubilized inclusion bodies by the strategy. The artificial chaperone system was composed of cetyltrimethylammonium bromide (CTAB) and beta-cyclodextrin (beta-CD). In the refolding process, denatured protein was mixed with CTAB to form a protein-CTAB complex. The mixture was then loaded to IMAC column and the complex was bound via metal chelating to the histidine tag. This was followed by washing with a refolding buffer containing beta-CD that removed CTAB from the bound protein and initiated on-column refolding. The effect of the washing time (i.e., on-column refolding time) on mass and fluorescence recoveries was examined. Extensive studies by comparison with other related refolding techniques have proved the advantages of AC-IMAC. In the on-column refolding, the artificial chaperone system suppressed protein interactions and facilitated protein folding to its native structure. So, the on-column refolding by AC-IMAC led to 99% pure EGFP with a fluorescence recovery of 80%. By comparison at a similar final EGFP concentration (0.6-0.8 mg/mL), this fluorescence recovery value was not only much higher than direct dilution (14%) and AC-assisted refolding (26%) in bulk solutions, but also superior to its partner, IMAC (60%). The operating conditions would be further optimized to improve the refolding efficiency.


Hypothermic cardiac arrest: an 11 year review of ED management and outcome.
The purpose of this study was to examine the emergency department (ED) management of hypothermic cardiac arrest and its outcome. The medical records of all patients with hypothermic cardiac arrest treated in the ED from January 1, 1988 to January 31, 1999 were retrospectively reviewed. Data collected included initial body temperature, serum potassium, methods of rewarming, return of perfusing rhythm, and morbidity and mortality. Data were analyzed by descriptive methods. Eleven patients were treated in the ED resuscitation room for hypothermic cardiac arrest. Six patients were found in cardiac arrest in the field, one patient arrested during transport, and four patients arrested after ED arrival. The average initial temperature was 79.1 degrees F (range 69.0 degrees F to 86.7 degrees F). Seven patients received an ED thoracotomy with internal cardiac massage and warm mediastinal irrigation. Four patients had airway management in the ED and then direct transport to the operating room for cardiac bypass rewarming. Three of the seven patients who received an ED thoracotomy subsequently went to intraoperative cardiac bypass rewarming. Five of the seven (71.4%) patients who received an ED thoracotomy survived, versus none of the four patients (0%) who went directly to intraoperative cardiac bypass. A direct comparison of immediate ED thoracotomy versus intraoperative cardiac bypass without ED thoracotomy is cautiously made as this was an unmatched and nonrandomized study. Three of the surviving patients underwent intraoperative cardiac bypass rewarming after receiving an ED thoracotomy. In two of these patients a perfusing rhythm had been established after thoracotomy in the ED and before transport to the operating room for cardiac bypass. Only one of seven (14.3%) patients who arrested prehospital survived versus four of four (100%) who arrested in the ED. ED thoracotomy with internal cardiac massage and mediastinal irrigation rewarming is effective in the management of hypothermic cardiac arrest.


Human neutrophil peptides sputum levels in symptomatic smokers and COPD patients.
Human Neutrophil Peptides (HNP) are major neutrophils' products which may contribute to the airway inflammation and lung remodelling during chronic obstructive pulmonary disease (COPD). We aimed to assess whether HNP sputum concentrations could be used as indicators of airway inflammation and progression towards pulmonary functional impairment, and correlate with the degree of airways obstruction. We measured, by ELISA tests, HNP concentrations from 37 symptomatic smokers and 34 COPD patients. All participants underwent pulmonary function tests. Sputum samples were collected at the enrolment, and 6 months after smoking cessation. Differences between groups and correlation coefficients between variables were determined using non parametric tests. Sputum HNP concentrations were higher in COPD patients as compared to symptomatic smokers (14 +/- 1.5 microg/ml vs 1.6 +/- 0.4 microg/ml; p < 0.0001). Among COPD patients HNP concentrations were higher in individuals with severe obstruction than in patients with mild to moderate COPD (19.9 +/- 2.3 microg/ml vs 10.3 +/- 0.8 microg/ml, p = 0.003). A negative correlation was observed between HNP levels and FEV1 (rho = -0.38, p = 0.02), and FEV1/FVC (rho = -0.42, p = 0.01). No differences were found in HNP levels before and after 6 months of smoking withdrawal (1.1 microg/ml +/- 0.3 vs 1.1 microg/ml +/- 0.3 for symptomatic smokers, p = 0.9, and 14.4 microg/ml +/- 1 vs 16 microg/ml +/- 1.1 for COPD, p = 0.6). Sputum levels of HNP may represent a marker of severity of functional impairment in COPD. Our data support the hypothesis that HNP may have a role in smoking- and COPD-related lung inflammation.


Hormonal regulators of food intake and weight gain in Parkinson's disease after subthalamic nucleus stimulation.
Weight gain has been reported in patients with Parkinson's disease (PD) treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). To evaluate the influence of STN-DBS on weight changes, we studied food-related hormones. Anthropometric parameters and food-related hormones (leptin, adiponectin, resistin, ghrelin, cortisol, insulin, and thyroid stimulating hormone) were measured in 27 patients with STN-DBS during a 12 month period following electrode implantation. Besides marked motor improvements on STN-DBS, PD patients significantly gained weight. The mean weight gain at 12 months was 5.2±(SD)5.8 kg. A significant decrease in cortisol levels compared to baseline appeared at month 2 and persisted at 12 months (p<0.01, corrected), with no significant changes in other hormones tested. Changes in peripheral food-related hormones do not appear to cause weight gain in PD patients. Direct effects of STN-DBS on hypothalamic catabolic/anabolic peptide balance remain hypothetical and necessitate further elucidation.


Is antibiotic prophylaxis to prevent infective endocarditis worthwhile?
Infective endocarditis (IE) is a rare condition which is associated with considerable morbidity and mortality. Almost 100 years ago, the links between endocarditis and procedures, particularly dental procedures, were postulated. Over 50 years ago the first guidelines recommending antibiotic prophylaxis (AP), with the aim of preventing IE developing after procedures, were proposed. However, there has only ever been circumstantial evidence in humans that AP prevents IE. The rarity of IE has made a randomised controlled clinical trial impractical to date. This article outlines the history of AP and reviews the evidence base for the use of AP to prevent IE.


Differential distribution of KChIPs mRNAs in adult mouse brain.
The K(+) channel interacting proteins (KChIPs1-4) interact with and modulate activity and trafficking of Kv4 potassium channels. We report here the distribution of KChIPs in adult mouse brain. KChIP1 was expressed in a subpopulation of neurons widely distributed in brain and enriched in Purkinje cells of the cerebellum and in the reticular thalamic and medial habenular nuclei. KChIP2 transcripts were highly expressed in layer IV of the cerebral cortex and in striatum and hippocampus, but expressed at low levels in cerebellum. KChIP3 transcripts were detected primarily in the layer V and deep layer VI of the cerebral cortex, the hippocampus, and the entire cerebellum. KChIP4 was highly expressed by neurons in layers II-IV of cortex and in hippocampus, thalamus and the Purkinje cell layer of the cerebellum. Collectively, different KChIPs appear to be expressed by selected neuronal populations in different brain regions where expression of Kv4.2 and Kv4.3 have been reported. These findings support the likelihood of functional interactions between KChIPs and Kv4 K(+) channels in brain.


Mechanisms of Notch signaling: a simple logic deployed in time and space.
Most cells in our body communicate during development and throughout life via Notch receptors and their ligands. Notch receptors relay information from the cell surface to the genome via a very simple mechanism, yet Notch plays multiple roles in development and disease. Recent studies suggest that this versatility in Notch function may not necessarily arise from complex and context-dependent integration of Notch signaling with other developmental signals, but instead arises, in part, from signaling dynamics. Here, we review recent findings on the core Notch signaling mechanism and discuss how spatial-temporal dynamics contribute to Notch signaling output.


Case report: Use of a remifentanil infusion with the tri-service anaesthetic apparatus.
During a recent deployment to Iraq, it was noticed that patients' recovery times from general anaesthesia were significantly prolonged. We postulated that this was because of a lack of nitrous oxide--thereby creating a requirement for greater concentrations of volatile agent to maintain adequate depth of anaesthesia. We chose to adopt the technique of running a remifentanil infusion with the Tri-Service apparatus in an attempt to reduce the administered volatile and thus shorten recovery times.


Spray-induced frostbite in a child: a new hazard with novel aerosol propellants.
A case of deep frostbite occurred in an 8.5-year-old child. The lesion was due to the improper use of a toilet air freshener and was severe enough to require a skin graft. The propellants contained in the spray were propane and butane. We measured the temperature of this aerosol during spraying (-40 degrees) in comparison with an ethyl chloride spray (-3 degrees) widely used for local skin anesthesia. This difference is mainly due to the much lower evaporation temperature of propane (-42.2 degrees) and butane (-0.6 degrees) compared with ethyl chloride (12.5 degrees). This child aimed the spray directly toward his skin, thus producing a deep frostbite. We wish to draw the attention of clinicians to this potential hazard with new propellants, since they should soon replace chlorohydrofluorocarbons throughout the world for ecologic reasons.


Alcohol esterification reactions and mechanisms of snake venom 5'-nucleotide phosphodiesterase.
In a previous study we have shown that snake venom 5'-nucleotide phosphodiesterase (SVP) catalyzes methanol-esterification reactions [García-Díaz, M., Avalos, M. & Cameselle, J. C. (1991) Eur. J. Biochem. 196, 451-457]. Now we have demonstrated that SVP catalyzes AMP transfer from ATP to propanol, ethanol, methanol, ethylene glycol, glycerol, 2-chloroethanol or 2,2-dichloroethanol. The AMP-O-alkyl ester products were identified by HPLC, enzyme analysis, ultraviolet and NMR spectroscopy. Those results show the potential of SVP as a tool to prepare 5'-nucleotide esters and agree with the formation of a covalent 5'-nucleotidyl-SVP intermediate susceptible to nucleophilic attack by short-chain (poly)alcohols as acceptors alternative to water. To test the kinetic influence of the solvent nucleophile in SVP mechanisms, initial rates of ATP solvolysis were assayed in different water/alcohol mixtures. Relatively high alcohol concentrations inactivated SVP but lower concentrations gave proportional rates of alcoholysis. An efficiency parameter (EA), defined as the ratio of the mole fraction of AMP-O-alkyl ester as a product to that of alcohol as an acceptor in water/alcohol mixtures, made possible the comparison of alcohols and water as AMP acceptors at low concentrations, as it could be reasoned that EA = 1 for water. Rates of hydrolysis (VH) of substrates yielding AMP and different leaving groups were also assayed. The higher EA and VH values corresponded, respectively, to those acceptors and leaving-group conjugate acids with lower pKa and higher polar-substituent constants (sigma*). The results support the occurrence of general acid-base catalysis in the active center of SVP and the identification of rate-limiting steps. A model is proposed for the mechanisms of SVP-catalyzed hydrolysis and alcoholysis which accounts for the influence of the acid-base properties of alcohols on the kinetic profile of SVP reaction sequences.


Treatment of an epithelioma cuniculatum plantare by local excision and a plantar skin flap.
Differentiation between benign and malignant lesions on the plantar surfaces is sometimes clinically impossible and requires biopsy. A case of epithelioma cuniculatum plantare is reported that was futilely treated for years as a plantar wart and then upon proper diagnosis was successfully treated by complete excision and rotation of a flap of plantar skin.


Phase-locked patterns and amplitude death in a ring of delay-coupled limit cycle oscillators.
We study the existence and stability of phase-locked patterns and amplitude death states in a closed chain of delay coupled identical limit cycle oscillators that are near a supercritical Hopf bifurcation. The coupling is limited to nearest neighbors and is linear. We analyze a model set of discrete dynamical equations using the method of plane waves. The resultant dispersion relation, which is valid for any arbitrary number of oscillators, displays important differences from similar relations obtained from continuum models. We discuss the general characteristics of the equilibrium states including their dependencies on various system parameters. We next carry out a detailed linear stability investigation of these states in order to delineate their actual existence regions and to determine their parametric dependence on time delay. Time delay is found to expand the range of possible phase-locked patterns and to contribute favorably toward their stability. The amplitude death state is studied in the parameter space of time delay and coupling strength. It is shown that death island regions can exist for any number of oscillators N in the presence of finite time delay. A particularly interesting result is that the size of an island is independent of N when N is even but is a decreasing function of N when N is odd.


The cryogenic storage ring CSR.
An electrostatic cryogenic storage ring, CSR, for beams of anions and cations with up to 300 keV kinetic energy per unit charge has been designed, constructed, and put into operation. With a circumference of 35 m, the ion-beam vacuum chambers and all beam optics are in a cryostat and cooled by a closed-cycle liquid helium system. At temperatures as low as (5.5 ± 1) K inside the ring, storage time constants of several minutes up to almost an hour were observed for atomic and molecular, anion and cation beams at an energy of 60 keV. The ion-beam intensity, energy-dependent closed-orbit shifts (dispersion), and the focusing properties of the machine were studied by a system of capacitive pickups. The Schottky-noise spectrum of the stored ions revealed a broadening of the momentum distribution on a time scale of 1000 s. Photodetachment of stored anions was used in the beam lifetime measurements. The detachment rate by anion collisions with residual-gas molecules was found to be extremely low. A residual-gas density below 140 cm(-3) is derived, equivalent to a room-temperature pressure below 10(-14) mbar. Fast atomic, molecular, and cluster ion beams stored for long periods of time in a cryogenic environment will allow experiments on collision- and radiation-induced fragmentation processes of ions in known internal quantum states with merged and crossed photon and particle beams.


[Paucisymptomatic pneumonia due to Rothia mucilaginosa: case report and literature review].
Rothia mucilaginosa is a Gram-positive, coagulase-negative, encapsulated, non-spore-forming coccus considered part of the commensal flora of the oral cavity and the upper respiratory tract in humans. Its involvement has been reported in an increasing spectrum of infections, above all among immunocompromised patients. To date, only 11 cases of pneumonia due to Rothia mucilaginosa have been described in the literature. The authors report a case of pneumonia due to Rothia mucilaginosa in a 72-year-old man with laryngeal cancer and review the published cases of pneumonia due to this pathogen.


Pravastatin up-regulates transforming growth factor-beta1 in THP-1 human macrophages: effect on scavenger receptor class A expression.
Statins have been shown to interact with several monocyte/macrophage functions. We tested the effect of pravastatin on transforming growth factor-beta1 (TGF-beta1) production and its possible involvement in scavenger receptors class A (SRA) expression in human THP-1 cells. TGF-beta1s biological activity in THP-1 cell conditioned medium, evaluated by luciferase activity of transfected cell with a TGF-beta responsive promoter, was increased in a dose-dependent manner after incubation with pravastatin (1-20 microM). Pravastatin (1-20 microM) induced a dose-dependent increase in TGF-beta1 mRNA expression and protein production in THP-1 cells. PMA-induced SRA gene and protein expression was suppressed by pravastatin with a mean 3-fold decrease at 10 microM. This last effect was reversed by a mouse monoclonal anti-TGF-beta1 neutralizing antibody. PD98059, a specific inhibitor of MAP kinase cascade, completely reversed pravastatin-induced SRA down-regulation. p44 and p42 isoforms showed a dose-dependent phosphorylation after treatment with pravastatin (1-20 microM) which was inhibited by a mouse monoclonal anti-TGF-beta1 antibody. Our results demonstrate that pravastatin significantly up-regulates TGF-beta1 expression which may be in involved in down-regulation of SRA expression in THP-1 cell cultures. A new pathway for pravastatin effects in atherogenesis can be suggested.


Soybean seeds expressing feedback-insensitive cystathionine γ-synthase exhibit a higher content of methionine.
Soybean seeds provide an excellent source of protein for human and livestock nutrition. However, their nutritional quality is hampered by a low concentration of the essential sulfur amino acid, methionine (Met). In order to study factors that regulate Met synthesis in soybean seeds, this study used the Met-insensitive form of Arabidopsis cystathionine γ-synthase (AtD-CGS), which is the first committed enzyme of Met biosynthesis. This gene was expressed under the control of a seed-specific promoter, legumin B4, and used to transform the soybean cultivar Zigongdongdou (ZD). In three transgenic lines that exhibited the highest expression level of AtD-CGS, the level of soluble Met increased significantly in developing green seeds (3.8-7-fold). These seeds also showed high levels of other amino acids. This phenomenon was more prominent in two transgenic lines, ZD24 and ZD91. The total Met content, which including Met incorporated into proteins, significantly increased in the mature dry seeds of these two transgenic lines by 1.8- and 2.3-fold, respectively. This elevation was accompanied by a higher content of other protein-incorporated amino acids, which led to significantly higher total protein content in the seeds of these two lines. However, in a third transgenic line, ZD01, the level of total Met and the level of other amino acids did not increase significantly in the mature dry seeds. This line also showed no significant change in protein levels. This suggests a positive connection between high Met content and the synthesis of other amino acids that enable the synthesis of more seed proteins.


Relation of chlorine, copper and sulphur to dioxin emission factors.
Dioxin emission factors for different combustion categories range over five orders of magnitude. Both chlorine (Cl(2)) and transition metals, including copper (Cu) have been suggested to promote the formation of dioxin in incinerators, and sulphur (S) has been suggested to inhibit dioxin formation. We show that dioxin (PCDD and PCDF) emission factors from 17 different combustion categories are approximately linearly correlated with the average copper or chlorine content of the combusted material, and inverse linearly correlated with the average sulphur content of the material. Copper and chlorine are correlated and, thus cannot be distinguished. The analysis suggests that the wide range of dioxin emission factors could be explained by the content of sulphur and transition metals or chlorine in combusted materials.


Groin hernia repair in Scotland.
The use of mesh for groin hernia repair has dramatically changed the way this common operation is performed. The aim of this study was to survey the methods of groin hernia repair in Scotland and to assess patient satisfaction with the operation. Between 1 April 1998 and 31 March 1999 all patients who underwent groin hernia repair in the National Health Service in Scotland were identified. As well as looking at the type of hernia repair performed and postoperative morbidity, patients were sent a Short Form-36 about 3 months after the operation to assess satisfaction and return to normal activity. Information was obtained on 5506 (97 per cent) of patients who underwent groin hernia repair during the study period. Eighty-five per cent of patients had an open mesh repair and 4 per cent had a laparoscopic repair. Most operations (85 per cent) were performed using general anaesthesia on an inpatient basis (78 per cent), and 8 per cent were for repair of a recurrent hernia. Potentially serious intraoperative complications were rare (seven patients), although they were significantly (P < 0. 001) more likely to be associated with a laparoscopic approach or repair of a femoral hernia: relative risk compared with open inguinal hernia repair 33 (95 per cent confidence interval (c.i.) 6-197) and 22 (95 per cent c.i. 3-152) respectively. Wound complications were common and 10 per cent of patients required a district nurse to attend the wound. Patients expressed a high degree of satisfaction; 94 per cent would recommend the same operation to someone else if required. An open mesh repair using general anaesthesia has become the repair of choice for a groin hernia in Scotland. Despite a high incidence of wound complications, patients are satisfied with this operation.


Assessment of the potential of plasma fractionation processes to remove causative agents of transmissible spongiform encephalopathy.
Although there is no evidence that classical CJD (cCJD) can be transmitted by human blood or blood products in clinical practice, uncertainties surrounding new variant CJD (nvCJD) have led to the safety of plasma products derived from UK donors being questioned. To better define whether or not there is a risk of nvCJD being transmitted it is necessary to determine how the causative agent would partition across the separations processes used in the preparation of plasma products. The abnormal prion protein which is associated with transmissible spongiform encephalopathies (TSEs), such as CJD, has a low solubility, a high tendency to form aggregates and adheres to surfaces readily. If the physicochemical properties of the agent of nvCJD are similar to those of abnormal prion protein then nvCJD may be removed by precipitation and adsorption technologies used in plasma fractionation. Available data on the removal of TSE agents by such bioprocess technologies have been used to estimate the potential degree of reduction expected from each step in the plasma fractionation processes used by the SNBTS. The overall process reduction factors estimated are: 10(13) (albumin). 10(9) (immunoglobulins), 10(7) (factor IX, thrombin), 10(5) (fibrinogen), 10(4) (factor VIII) and 10(3) (factor II, IX and X); however, it will be necessary to establish the accuracy of these estimates by practical validation studies.


Significance of hepatic preneoplasia for cancer chemoprevention.
Hepatic preneoplasia represents an early stage in neoplastic development, preceding both benign and malignant neoplasia. This applies particularly to foci of altered hepatocytes (FAH), that precede the manifestation of hepatocellular adenomas and carcinomas in all species investigated. Morphological, microbiochemical and molecular biological approaches in situ have provided evidence for striking similarities in specific changes of the cellular phenotype of preneoplastic FAH emerging in experimental and human hepatocarcinogenesis, irrespective of whether this was elicited by chemicals, hormones, radiation, viruses or, in animal models, by transgenic oncogenes or Helicobacter hepaticus. Different types of FAH have been distinguished and related to three main preneoplastic hepatocellular lineages: (1) the glycogenotic-basophilic cell lineage, (2) its xenomorphic-tigroid cell variant, and (3) the amphophilic-basophilic cell lineage. The predominant glycogenotic-basophilic and tigroid cell lineages develop especially after exposure to DNA-reactive chemicals, radiation, hepadnaviridae, transgenic oncogenes and local hyperinsulinism, their phenotype indicating initiation by insulin or insulinomimetic effects of the oncogenic agents. In contrast, the amphophilic cell lineage of hepatocarcinogenesis has been observed mainly after exposure of rodents to peroxisome proliferators that are not directly DNA-reactive or to hepadnaviridae, the biochemical pattern mimicking an effect of thyroid hormone, including mitochondrial proliferation and activation of mitochondrial enzymes. Hepatic preneoplastic lesions are increasingly used as end-points in carcinogenicity testing, particularly in medium-term carcinogenesis bioassays. This has been complemented more recently by the use of FAH as indicators of chemoprevention, although possible pitfalls of this approach have to be considered carefully. Our ever-increasing knowledge on the metabolic and molecular changes that characterize preneoplastic lesions and their progression to neoplasia provides a new basis for rational approaches to chemoprevention by drugs, hormones or components of the diet.


The orexin OX(1) receptor exists predominantly as a homodimer in the basal state: potential regulation of receptor organization by both agonist and antagonist ligands.
It is unclear what proportion of a G-protein-coupled receptor is present in cells as dimers or oligomers. Saturation bioluminescence resonance energy transfer studies demonstrated the orexin OX(1) receptor to be present in such complexes. Forms of this receptor containing a minimal epitope tag, with the C-terminus linked to yellow fluorescent protein or modified at the N-terminus to incorporate a SNAP tag, migrated in SDS/PAGE gels as monomers, indicating a lack of covalent interactions. Solubilization with dodecylmaltoside, followed by Blue native-PAGE, indicated that the receptor constructs migrated predominantly as anticipated for dimeric species with evidence for further, higher-order, complexes, and this was true over a wide range of expression levels. Addition of SDS prior to separation by Blue native-PAGE resulted in much of the previously dimeric, and all of the higher-order, complexes being dissociated and now migrating at the size predicted for monomeric species. Expression of forms of the OX(1) receptor capable of generating enzyme complementation confirmed that solubilization itself did not result in interaction artefacts. Addition of the endogenous agonist orexin A enhanced the proportion of higher-order OX(1) receptor complexes, whereas selective OX(1) antagonists increased the proportion the OX(1) receptor migrating in Blue native-PAGE as a monomer. The antagonist effects were produced in a concentration-dependent manner, consistent with the affinity of the ligands for the receptor. Homogeneous time-resolved fluorescence resonance energy transfer studies using Tag-Lite™ reagents on cells expressing the SNAP-tagged OX(1) receptor identified cell-surface OX(1) homomers. Predominantly at low receptor expression levels, orexin A increased such fluorescence resonance energy transfer signals, also consistent with ligand-induced reorganization of the homomeric complex.


Role of posterior capsulotomy for the treatment of extension deficits of the knee.
Chronic flexion contracture of the knee is difficult to treat, especially in cases with long-standing extension deficits and with generalised arthrofibrosis. We present a technique combining arthroscopic or open anterior debridement with a posterior capsulotomy. This capsulotomy is performed via a posteromedial incision and a posteromedial arthrotomy. All scar tissue is resected, and the entire posterior capsule is detached from its femoral attachment. Of 24 patients treated with arthroscopic arthrolysis and posterior capsulotomy from 1989 to 1993, 21 were reviewed with a mean follow-up of 18 months (range 6-38 months). The mean extension deficit preoperatively was 17 degrees (range 10-30 degrees), and symptoms and persisted from 6 months to 7 years. Extension improved to a mean value of 2 degrees; no patient had more than 5 degrees of extension deficit at follow-up. The knee function improved significantly (Lysholm Score preoperative 62, postoperative 88, Tegner Scale preoperative 2.2, postoperative 4.0). No neurovascular complications were observed, and we conclude that posterior capsulotomy is a safe and efficient adjunct procedure to anterior arthrolysis and is indicated in cases with chronic flexion contracture.


Identification of the 3-sulfate isomer as the major product of enzymatic sulfation of chenodeoxycholate conjugates.
Thin layer and high performance liquid chromatography identified the 3-monosulfate ester as the predominant product of in vitro enzymatic sulfation of glyco- and taurochenodeoxycholate by rat liver and kidney and hamster liver. The rate of synthesis of the 7-sulfate ester was less than 20% that of the 3-sulfate isomer; in vitro synthesis of the 3,7-disulfate was not definitely seen. Reaction of the enzymatic products with 7 alpha-hydroxysteroid dehydrogenase indicated a molar ratio of 7 alpha-hydroxyl function and SO4 which further supported the identification of the 3-sulfate isomer as the major product.


Integrating hierarchical bioavailability and population distribution into potential eco-risk assessment of heavy metals in road dust: A case study in Xiandao District, Changsha city, China.
Modified eco-risk assessment method (MEAM) integrated with the hierarchical bioavailability determined by the fraction detection of Cd, Pb, Zn, Cu, Cr in road dust samples and the local population distribution derived from the local land use map, was proposed to make the hierarchical eco-risk management strategy in Xiandao District (XDD), China. The geo-accumulation index (Igeo), the original potential eco-risk index (Er(i)) and the modified eco-risk assessment index (MEAI) were used to identify the priority pollutant. Compared with the Hunan soil background values, evaluated metal concentrations were found to different extent. The results of mean Igeo, Er(i) and bioavailability of studied metals revealed the following orders: Cd>Pb ≈ Zn>Cu ≈ Cr, Cd>Pb>Cu>Cr>Zn and Cd>Zn>Cu ≈ Pb>Cr, respectively. Therefore, Cd was regarded as the priority pollutant. To identify the priority areas taking into account cost consideration, the hierarchical risk map based on the results of the modified eco-risk assessment index with overlay of the population density map was needed and made. The west and partly south areas of XDD were under higher eco-risk generally. Moreover, the whole XDD area was divided into 4 area categories with different management priorities based on the possibility of occurrence of eco-risk, and the hierarchical risk management strategy associated with protecting local population was suggested to facilitate allocation of funds for risk management.


Comparative histochemical localization of some hydrolytic enzymes in mammalian epididymides.
The activity of enzymes hydrolyzing sodium-beta-glycerophosphate, adenosine triphosphate, adenosine monophosphate, and glucose-6-phosphate in the epididymides of adult ram, rabbit, rat and hamster has been investigated histochemically. The enzymes hydrolyzing sodium-beta-glycerophosphate, adenosine triphosphate and adenosine monophosphate were rather similar in their distribution in the intertubular connective tissue of the epididymides of the four species studied. However, the distribution and activity of these enzymes in the stereocilia varied. There was a high activity in the stereocilia of the middle segments of ram, rabbit and rat and in the proximal part of the terminal segment of hamster epididymides. Glucose-6-phosphatase was distributed homogeneously in the epithelial cells of the epididymides throughout the duct. The possible functions of these enzymes in the mammalian epididymis are briefly discussed.


Committee opinion no. 619: Gynecologic surgery in the obese woman.
Obesity is a serious problem worldwide and particularly in the United States, and in women is associated with an increased risk of death and morbid conditions (including hypertension, diabetes mellitus, obstructive sleep apnea, and hypercholesterolemia) as well as malignancies such as endometrial and postmenopausal breast cancer. Adverse effects after gynecologic surgery, such as surgical site infection, venous thromboembolism, and wound complications, are more prevalent in obese women than in normal-weight women. Preoperative consultation with an anesthesiologist should be considered for the obese patient in whom the possibility of obstructive sleep apnea is suspected on clinical grounds or who is at risk of coronary artery disease, has a difficult airway, or has poorly controlled hypertension. Gynecologic surgeons should have the knowledge to counsel obese women on the risks specific to this group. As with all patients, evidence demonstrates that, in general, vaginal hysterectomy is associated with better outcomes and fewer complications than laparoscopic or abdominal hysterectomy. Postoperative care of the obese patient is similar to postoperative care of the normalweight patient and comorbid conditions should be taken into consideration.


Comparison of renal function following anesthesia with low-flow sevoflurane and isoflurane.
To evaluate postoperative renal function after patients were administered sevoflurane under conditions designed to generate high concentrations of compound A. A multicenter (11 sites), multinational, open-label, randomized, comparative study of perioperative renal function in patients who have received low-flow (< or = 1 L/min) sevoflurane or isoflurane. 254 ASA physical status I, II and III patients requiring endotracheal intubation for elective surgery lasting more than 2 hours. After induction, low-flow anesthesia was initiated at a flow rate < or = 1 L/min. Blood and urine samples were studied to assess postoperative renal function. Measurements of serum BUN and creatinine, and urine glucose, protein, pH, and specific gravity were used to assess renal function preoperatively and up to 3 days postoperatively. Serum inorganic fluoride ion concentration was measured at preinduction, emergence, and 2, 24 and 72 hours postoperatively. Compound A concentrations were measured at two sites for those patients receiving sevoflurane. Adverse experience data were analyzed. One hundred eighty-eight patients were considered evaluable (98 sevoflurane and 90 isoflurane). Peak serum fluoride concentrations were significantly higher after sevoflurane (40 +/- 16 microM) than after isoflurane (3 +/- 2 microM). Serum creatinine and BUN decreased in both groups postoperatively; glucosuria and proteinuria occurred in 15% to 25% of patients. There were no clinically significant differences in BUN, creatinine, glucosuria, and proteinuria between the low-flow sevoflurane and low-flow isoflurane patients. There were no statistically significant differences in the renal effects of sevoflurane or isoflurane in surgical patients undergoing low-flow anesthesia for up to 8 hours. Low-flow sevoflurane anesthesia under clinical conditions expected to produce high levels of compound A appears as safe as low-flow isoflurane anesthesia.


JunB induced by constitutive CD30-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling activates the CD30 promoter in anaplastic large cell lymphoma and reed-sternberg cells of Hodgkin lymphoma.
High expression of CD30 and JunB is characteristic of tumor cells in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL). Possible interactions of CD30 and JunB were examined in this study. We found that the CD30 promoter in tumor cells of both nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)-positive and NPM-ALK-negative ALCL and HL is regulated by a constitutively active CD30-extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK). Phosphorylation of ERK1/2 MAPK was confirmed in nuclei of tumor cells in both ALCL and HL. CD30-ERK1/2 MAPK signals induce JunB expression, which maintains high activity of the CD30 promoter. JunB induction seems to be largely independent of nuclear factor kappaB in ALCL and HL. These results show a common mechanism of CD30 overexpression in ALCL and HL, although the outcome of CD30 signaling differs between NPM-ALK-positive ALCL and NPM-ALK-negative ALCL, cutaneous ALCL, and HL as we recently reported.


Cryptorchidism: incidence of chromosomal anomalies in 50 cases.
We studied testicular tissue and peripheral blood samples for chromosomal anomalies in 50 consecutive patients who underwent orchiopexy. Of the 50 subjects 48 demonstrated karyotypes of 46XY in blood and testicular tissue, 1 had Klinefelter's syndrome and 1 had mosaic trisomy 8 with a discrepancy between the blood and testicular chromosomal complement. Over-all, the study showed no significant discrepancy between the chromosomal complements of the testicular tissue and blood. The incidence of these anomalies is not statistically significant compared to the observed frequency of chromosomal anomalies in this age group.


Late results of surgical treatment of transposition of the great arteries.
In summary, many of these patients have achieved a normal working capacity, but as a group there is a statistically significant reduction when compared to healthy children (p < 0.01). There was no significant difference between the group of patients who had their Mustard operation in infancy and later. As yet, there is no suggestion that the older patients, or those with the longest time interval between the operation and the exercise test, have a progressive reduction in working capacity. The decreased working capacity and moderate increase in ventilation suggests restricted cardiac output on exercise. This could be related to the abnormal heart rate response rather than indicating poor ventricular function. Equally, a restricted cardiac output on exercise may be due to inefficiency of atrial transport, tricuspid regurgitation or unmasked pulmonary vascular obstructive disease. Further studies may clarify these points. This study demonstrated that the exercise performance of asymptomatic patients 6-13 years after Mustard's operation was somewhat diminished, compared with a group of normal children. Nevertheless, these patients did lead and enjoy a normal life. Only longitudinal studies may bring the final answer to the important question: How many patients will be alive with normal or near normal exercise tolerance 40-50 years after Mustard's operation? Until such an answer is available, we believe that the Mustard operation should be used in the treatment of TGA, while the alternative techniques are carefully explored.


Comparative day/night metatranscriptomic analysis of microbial communities in the North Pacific subtropical gyre.
Metatranscriptomic analyses of microbial assemblages (< 5 microm) from surface water at the Hawaiian Ocean Time-Series (HOT) revealed community-wide metabolic activities and day/night patterns of differential gene expression. Pyrosequencing produced 75 558 putative mRNA reads from a day transcriptome and 75 946 from a night transcriptome. Taxonomic binning of annotated mRNAs indicated that Cyanobacteria contributed a greater percentage of the transcripts (54% of annotated sequences) than expected based on abundance (35% of cell counts and 21% 16S rRNA of libraries), and may represent the most actively transcribing cells in this surface ocean community in both the day and night. Major heterotrophic taxa contributing to the community transcriptome included alpha-Proteobacteria (19% of annotated sequences, most of which were SAR11-related) and gamma-Proteobacteria (4%). The composition of transcript pools was consistent with models of prokaryotic gene expression, including operon-based transcription patterns and an abundance of genes predicted to be highly expressed. Metabolic activities that are shared by many microbial taxa (e.g. glycolysis, citric acid cycle, amino acid biosynthesis and transcription and translation machinery) were well represented among the community transcripts. There was an overabundance of transcripts for photosynthesis, C1 metabolism and oxidative phosphorylation in the day compared with night, and evidence that energy acquisition is coordinated with solar radiation levels for both autotrophic and heterotrophic microbes. In contrast, housekeeping activities such as amino acid biosynthesis, membrane synthesis and repair, and vitamin biosynthesis were overrepresented in the night transcriptome. Direct sequencing of these environmental transcripts has provided detailed information on metabolic and biogeochemical responses of a microbial community to solar forcing.


Pyrimethamine for primary prophylaxis of toxoplasmic encephalitis in patients with human immunodeficiency virus infection: a double-blind, randomized trial. ANRS 005-ACTG 154 Group Members. Agence Nationale de Recherche sur le SIDA. AIDS Clinical Trial Group.
Pyrimethamine (50 mg) with folinic acid (15 mg) given three times weekly was assessed as primary prophylaxis for toxoplasmic encephalitis (TE) in 554 human immunodeficiency virus-infected patients seropositive for Toxoplasma gondii and with < 200 CD4 cells/mm3. At 1 year, the incidence of TE was similar in pyrimethamine, 12%, and placebo, 13%, groups (relative risk [RR], 0.9; 95% confidence interval [CI], 0.6-1.4), and the survival rate was also similar, 85% and 80%, respectively (RR, 0.9; 95% CI, 0.7-1.2). Rash was the only adverse event that appeared significantly more frequently in the pyrimethamine arm (7% vs. 1%). In the on-treatment analysis, the incidence of TE was lower in the pyrimethamine arm, 4%, than in the placebo arm, 12% (P < .006). Thus, pyrimethamine cannot be recommended as a first-line regimen for primary prophylaxis of TE if the patient can take cotrimoxazole. However, it should be considered for patients who are intolerant to cotrimoxazole, especially in high-risk patients with < 100 CD4 cells/mm3.


Parenting begets parenting: A neurobiological perspective on early adversity and the transmission of parenting styles across generations.
The developing brains of young children are highly sensitive to input from their social environment. Nurturing social experience during this time promotes the acquisition of social and cognitive skills and emotional competencies. However, many young children are confronted with obstacles to healthy development, including poverty, inappropriate care, and violence, and their enhanced sensitivity to the social environment means that they are highly susceptible to these adverse childhood experiences. One source of social adversity in early life can stem from parenting that is harsh, inconsistent, non-sensitive or hostile. Parenting is considered to be the cornerstone of early socio-emotional development and an adverse parenting style is associated with adjustment problems and a higher risk of developing mood and behavioral disorders. Importantly, there is a growing literature showing that an important predictor of parenting behavior is how parents, especially mothers, were parented themselves. In this review, we examine how adversity in early-life affects mothering behavior in later-life and how these effects may be perpetuated inter-generationally. Relying on studies in humans and animal models, we consider evidence for the intergenerational transmission of mothering styles. We then describe the psychological underpinnings of mothering, including responsiveness to young, executive function and affect, as well as the physiological mediators of mothering behavior, including hormones, brain regions and neurotransmitters, and we consider how development in these relevant domains may be affected by adversity experienced in early life. Finally, we explore how genes and early experience interact to predict mothering behavior, including the involvement of epigenetic mechanisms. Understanding how adverse parenting begets adverse parenting in the next generation is critical for designing interventions aimed at preventing this intergenerational cycle of early adversity.


Regeneration of multiple adjacent bone dehiscences with guided tissue regeneration after orthodontic proclination: a corrective treatment approach.
Transverse expansion or proclination of the teeth are valid alternatives to extraction in cases of crowding, but lack of stability and development of bone dehiscences have been demonstrated as side effects subsequent to anterior displacement of the incisors. The aim of this study was to repair the osseous dehiscence associated with incisor proclination. The multiple adjacent bone dehiscences were treated with a titanium membrane and bone matrix. Exposed root surfaces were covered with newly formed tissues. The patients in this study are the first to demonstrate the treatment of bone dehiscences that may occur as a result of orthodontic proclination.


Evaluation of current clinical trial methodology in analgesimetry based on experts' opinions and analysis of several analgesic studies.
There is general agreement that the controlled clinical trial is the best method for analgesic evaluation. Current practice in clinical analgesimetry, however, varies considerably with regard to design, measurement of pain, and statistical analysis. We attempted to assess the degree of this diversity by a questionnaire survey of a sample of investigators who are currently conducting clinical pain studies. To examine how various statistical methods perform in practice, we reanalyzed data from four of our published analgesic studies using a number of standard methods.