Effect of calibration and environmental condition on the performance of direct-reading organic vapor monitors.
The performance of three MIRAN SapphIRe Portable Infrared Ambient Air Analyzers and three Century Portable Toxic Vapor Analyzers equipped with photoionization (PID) and flame ionization (FID) detectors was compared with charcoal tube sampling. Relationships were investigated using two different calibration methods at four cyclohexane concentrations, three temperatures, and four relative humidities. For the first method, the TVA monitors were calibrated with a single concentration of methane for the FID, and isobutylene for the PID. The SapphIRe monitors were zeroed and the monitor's manufacturer-supplied library was used. For the second method, a five-point cyclohexane calibration curve was created for each monitor. Comparison of the monitor results of each calibration method (pooled data) indicated a significant difference between methods (t-test, p < 0.001), The SapphIRe group had results closer to the charcoal tubes with the second calibration method, while the PID and FID monitor groups performed better using the first calibration method. The PID monitor group's performance was affected only at the 90% relative humidity (RH) condition. Using the first method, the monitor readings were compared with the charcoal tube average using mixed linear model analyses of variance (ANOVAs) and regression. The ANOVA results showed there was a statistically significant difference among readings from all monitor types (p <0.0001). The regression results demonstrated that the SapphIRe (r² = 0.97) and FID (r² = 0.92) monitor groups correlated well with the charcoal tubes. The PID monitor group had a similar correlation when 90% RH was excluded (r² = 0.94) but had a weaker correlation when it was included (r² = 0.58). The operator should take care when using these monitors at high concentrations and the PID monitors at high humidities, consider the variability between units of the same monitor, and conduct performance verification of the monitor being used.


Resection of hepatocellular carcinoma without cirrhosis.
The aim of this study was to examine the features and outcomes of noncirrhotic patients undergoing resection for hepatocellular carcinoma. Ten percent to 40% of hepatocellular carcinoma cases arise within a noncirrhotic liver parenchyma. Resection is the standard therapy, yet the published resection series from the West are small. From January 1987 to December 2009, our center performed 206 partial liver resections for nonfibrotic or minimally fibrotic (Scheuer stage 0-2) hepatocellular carcinoma. We retrospectively reviewed these cases and performed univariate and multivariate analyses for predictors of long-term outcomes. Eighty-one patients (39.3%) had chronic hepatitis B infection and 23 patients (11.2%) had chronic hepatitis C. The remaining 83 (39.8%) had no underlying liver disease. Average age was 60.2 years, and 68.4% of the patients were male. Average tumor size was 8.2 cm. Overall survival at 5 years was 46.3%. Recurrence at 5 years was 50.0%. Independent predictors for decreased survival were tumor size larger than 7.0 cm, creatinine more than 1.0 mg/dL, satellite nodules, albumin less than 3.5 gm/dL, alpha-fetoprotein more than 100 ng/mL, and any vascular invasion. Chronic hepatitis B virus infection predicted longer survival. Independent predictors for decreased time to recurrence were albumin less than 3.5 gm/dL, any vascular invasion, age more than 60 years, tumor size larger than 7.0 cm, and alpha-fetoprotein more than 100 ng/mL. Treatment of recurrence with either repeat resection or ablation was associated with a median survival of 50.4 months from time of recurrence. Hepatocellular carcinoma can develop in a minimally fibrotic hepatitis C patient. Tumor-related factors such as vascular invasion primarily determine long-term outcomes. Hepatitis B virus-associated tumors seem to have a better prognosis in the nonfibrotic or minimally fibrotic population. Aggressive treatment of recurrence is warranted.


Sentinel lymph node as a target of molecular diagnosis of lymphatic micrometastasis and local immunoresponse to malignant cells.
The sentinel lymph node (SLN) is defined as the lymph node(s) first receiving lymphatic drainage from the site of the primary tumor. The histopathological status of SLN is one of the most significant predictors of recurrence and overall survival for most clinical stage I/II solid tumors. Recent progress in molecular techniques has demonstrated the presence of micrometastatic tumor cells in SLN. There is now a growing body of data to support the clinical relevance of SLN micrometastasis in a variety of solid tumors. Increasing the sensitivity of occult tumor cell detection in the SLN, using molecular-based analysis, should enable a more accurate understanding of the clinical significance of various patterns of micrometastatic nodal disease. The establishment of metastasis to SLN might not be simply reflected by the flow dynamics of lymphatic fluid that drains from the primary site to the SLN, and the transportation of viable cancer cells. Recent studies have demonstrated that primary tumors can actively induce lymphangiogenesis and promote SLN metastasis. Moreover chemokine receptors in tumor cells may facilitate organ-specific tumor metastasis in many human cancers and some experimental models. In contrast, recent clinical and preclinical studies regard SLN as the first lymphoid organ to respond to tumor antigenic stimulation. SLN dramatically show morphological, phenotypical and functional changes that indicate immune suppression by tumor cells. The immune suppression in SLN results in failure of prevention or eradication of tumor metastasis. The mechanism of immunomodulation remains unclear; however, several regulatory molecules produced by tumor cells and tumor-associated macrophages or lymphocytes are likely to be responsible for inducing the immune suppression in SLN. Further studies may develop a novel immunotherapy that overcomes tumor-induced immune suppression and can prevent or eradicate SLN metastasis.


Psychosocial factors affecting a child's capacity to cope with surgery and recovery.
Medical stressors associated with illness and surgery make extraordinary psychological demands on children. A child's coping abilities, both emotional and cognitive, are at the heart of adjustment to these demands. Social support is also an important element in the child's ability to recover psychologically. Finally, a child's previous medical experiences, psychiatric problems, and learning disabilities may affect the child's behavior.


Clinical and the prognostic characteristics of lung adenocarcinoma patients with ROS1 fusion in comparison with other driver mutations in East Asian populations.
The prevalence, demographic features, and clinical outcomes of lung adenocarcinoma patients with novel ROS1 oncogenic rearrangement in East Asian populations are not clear. This study aimed to investigate the clinical and prognostic characteristics of lung adenocarcinoma in patients with ROS1 fusion compared with other driver mutations. Multiplex reverse transcription-polymerase chain reaction was used to detect the ROS1 fusion gene in lung adenocarcinoma cases. Immunohistochemistry was used to confirm the expression of ROS1. The demographic data and clinical outcomes of patients with the ROS1 fusion gene were compared with those of patients without the ROS1 fusion gene, including those with the EGFR mutation, EML4-ALK fusion, KRAS mutation, and quadruple-negative patients. Of 492 patients with lung adenocarcinoma, 12 (2.4%) had the ROS1 fusion gene. Their median age was 45.0 years, significantly younger than that of the ROS1 fusion-negative cohorts (p < 0.001). Acinar (including cribriform) and solid patterns were the two most common histologic subtypes in the ROS1 fusion tumors (7 of 12, 58.3%) and were predominantly seen in CD74-ROS1 fusion tumors (66.7%). There was no significant survival difference between the ROS1 fusion-positive and ROS1 fusion-negative cohorts in surgical group, but ROS1 fusion-positive patients might have worse outcomes than EGFR-mutant patients in the stage IV group. The ROS1 fusion gene can be successfully detected in East Asian patients with lung adenocarcinoma using multiplex reverse transcription-polymerase chain reaction. These patients tend to be younger and have characteristic histologic subtypes. Due to the small number of ROS1 fusion patients, the prognostic value of ROS1 fusion need further studies to confirm.


Learning to perceive the world as articulated: an approach for hierarchical learning in sensory-motor systems.
This paper describes how agents can learn an internal model of the world structurally by focusing on the problem of behavior-based articulation. We develop an on-line learning scheme-the so-called mixture of recurrent neural net (RNN) experts-in which a set of RNN modules become self-organized as experts on multiple levels, in order to account for the different categories of sensory-motor flow which the robot experiences. Autonomous switching of activated modules in the lower level actually represents the articulation of the sensory-motor flow. In the meantime, a set of RNNs in the higher level competes to learn the sequences of module switching in the lower level, by which articulation at a further, more abstract level can be achieved. The proposed scheme was examined through simulation experiments involving the navigation learning problem. Our dynamical system analysis clarified the mechanism of the articulation. The possible correspondence between the articulation mechanism and the attention switching mechanism in thalamo-cortical loops is also discussed.


Changes in T-cell receptor subsets after cardiac surgery in children.
T cells are divided into two subsets, alphabeta and gammadelta, according to the T-cell receptor (TCR) expressed. Recent findings indicate that gammadelta T cells serve as the first defense against microbial pathogens, and represent a link between innate and acquired immunity. We conducted a study to investigate the changes in circulating TCR subsets after cardiac surgery in children. Blood samples from 24 children who underwent cardiac surgery with cardiopulmonary bypass (CPB) were collected serially to analyze TCR subsets by flow cytometry. The alphabeta T cells reached a nadir on postoperative day (POD) 1, but recovered to pre-CPB levels on POD 3. On the other hand, the gammadelta T cells decreased after CPB and did not recover to pre-CPB levels even after POD 7. The alphabeta/gammadelta T-cell ratio was increased after POD 3. In children, gammadelta T cells recover more slowly than alphabeta T cells after cardiac surgery. These changes in TCR subsets may contribute to postoperative immunosuppression.


Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats.
Non-contingent chronic nicotine exposure procedures have evolved rapidly in recent years, culminating in electronic nicotine delivery systems (ENDS or e-cigarettes) to deliver vaporized drugs to rodents in standard housing chambers. The aim of the current work was to use ENDS to test concentration-dependent effects of nicotine e-cigarette vapor inhalation on blood-nicotine concentrations, blood-cotinine concentrations, and somatic withdrawal signs over time in rats. Male Wistar rats were exposed to vapor containing various concentrations of nicotine (20, 40, 80 mg/mL) for 11 days through ENDS, and blood concentrations of nicotine and cotinine, the major proximate metabolite of nicotine, as well as spontaneous and precipitated somatic withdrawal signs, were measured over time (across days of exposure and over hours after termination of vapor exposure). Exposing male Wistar rats to non-contingent nicotine vapor inhalation through ENDS produces somatic withdrawal symptoms and measurable blood-nicotine and blood-cotinine levels that change according to (1) concentration of nicotine in vape solution, (2) number of days of nicotine vapor exposure, (3) time since termination of nicotine vapor exposure, and (4) relative to the withdrawal signs, whether withdrawal was spontaneous or precipitated (by mecamylamine). The data presented here provide parameters that can be used as a reasonable starting point for future work that employs ENDS to deliver non-contingent nicotine vapor in rats, although many parameters can and should be altered to match the specific goals of future work.


The Significance of Screening for HLA Antibodies in the Long-Term Follow-up of Pediatric Liver Transplant Recipients.
Post-transplant donor-specific anti-HLA antibodies (DSA) reportedly have detrimental effects on the outcomes of organ transplantation. However, the prevalence of post-transplant DSA in the long term after pediatric liver transplantation remains unclear, and the significance of post-transplant DSA is unknown. The aim of this cross-sectional study was to determine the prevalence of and characteristics of patients with post-transplant DSA. Of the 84 pediatric liver transplant recipients who were followed up in the outpatient department of our institution, 34 patients with available HLA typing data were included after they or their parent(s) provided informed consent for DSA evaluations. Luminex single-antigen bead assays were performed, and a mean fluorescence intensity of ≥1000 was used as the cut-off for a positive reaction. No class I DSA were detected, whereas class II DSA were detected in 11 patients (32%). There were no differences in age at transplantation, immunosuppressive drugs, or follow-up period between the DSA-positive and DSA-negative patients. The rate of positive pre-transplant complement-dependent cytotoxicity crossmatch was higher with class II DSA than without, although the difference was not statistically significant. The utility of screening for class I DSA was insignificant in the long-term follow-up of pediatric liver transplant recipients. The prevalence of class II DSA was relatively high; therefore, screening for class II DSA might be justified, although a follow-up survey of the association between post-transplant class II DSA and the long-term clinical course needs to be conducted.


[Ca2+ exit from intracellular stores of growing and fully grown native and devitrified porcine oocytes].
The exit of Ca2+ from intracellular stores in growing and fully grown native and devitrified porcine oocytes stimulated by somatotropin and GTP was investigated using fluorescent dye chlortetracycline. In native as well as in the devitrified porcines oocytes, in their fully grown phase, joint action of somatotropin and GTP stimulated additional freeing of Ca2+ from intracellular stores, but during subsequent processing of the cell with nocodazole (a polymerization inhibitor of microtubules), additional exit of calcium did not occur. In the growing phase of native oocytes during the joint acting of somatotropin and GTP additional exit for Ca2+ from the intracellular stores did not occur. Join action of somatotropin and GTP on growing devitrified oocytes lead to the additional freeing of Ca2+ from intracellular stores. Injection of nocodazole inhibited the exit for calcium in growing devitrified oocytes treated with somatotropin and GTP. The data obtained points to the absence of difference of signal transduction mechanisms in growing and fully grown oocytes after devitrification.


[Homogeneous phase fluorescence assay based on NaYF4 : Er3+, Yb3+ UCNPs as donors].
Upconversion nanoparticles (UCNPs) of small size have great potential in homogeneous assay based on fluorescence resonance energy transfer (FRET). A novel approach of surface ligand-exchange for preparing water-soluble and amido-functionalized NaYF4 : Er3+, Yb3+ UCNPs with 12 nm was developed. The ligand exchange process was confirmed by Fourier transform infrared spectra. Investigations by scan electron microscopy showed no obvious variations in the size and shape of the UCNPs. The circular dichroism characterization demonstrates that the secondary structure of the avidin remains largely intact after the conjugation. Avidin-biotin served as a bridge to make the short enough distance for FRET between the acceptor biotinylated R-phycoerythrin and the donors avidin-conjugated UCNPs. When the free biotins were added into this system, they competitively combined with avidin on the UCNPs surface and impede the FRET to triggered fluorescence changes. According to the relationship between this change and the addition of the amount of biotin, such FRET-based approach can reach a limit of detection in the nanomolar concentration range.


Rapid detection of dihydropteroate polymorphism in AIDS-related Pneumocystis carinii pneumonia by restriction fragment length polymorphism.
Sulpha agents, which act by inhibiting the enzyme dihydropteroate synthase (DHPS), are used widely for the treatment and prophylaxis of Pneumocystis carinii pneumonia (PCP). Recently, we have shown that mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis carinii f.sp hominis are associated with failure of sulpha prophylaxis and increased mortality in HIV-1 positive patients with PCP, suggesting that DHPS mutations may cause sulpha resistance. To facilitate detection of DHPS mutations we developed a restriction fragment length polymorphism (RFLP) assay, detecting mutations at codon 55 and 57 of the P. carinii DHPS gene. The RFLP-assay was compared with direct DNA sequencing on 27 PCP isolates from HIV-1 positive patients with a mixture of wildtype and mutant DHPS types. In all samples the RFLP-assay correctly identified wildtype or DHPS mutation at codon 55 or 57. Combined with DNA extraction by a Chelex-based method, this method can be performed within 1 d and allows a fast, cost-efficient and reliable method of detection of DHPS mutations in P. carinii.


Recent methodological advances in MALDI mass spectrometry.
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is widely used for characterization of large, thermally labile biomolecules. Advantages of this analytical technique are high sensitivity, robustness, high-throughput capacity, and applicability to a wide range of compound classes. For some years, MALDI-MS has also been increasingly used for mass spectrometric imaging as well as in other areas of clinical research. Recently, several new concepts have been presented that have the potential to further advance the performance characteristics of MALDI. Among these innovations are novel matrices with low proton affinities for particularly efficient protonation of analyte molecules, use of wavelength-tunable lasers to achieve optimum excitation conditions, and use of liquid matrices for improved quantification. Instrumental modifications have also made possible MALDI-MS imaging with cellular resolution as well as an efficient generation of multiply charged MALDI ions by use of heated vacuum interfaces. This article reviews these recent innovations and gives the author's personal outlook of possible future developments.


Platelet aggregation in young men with contrasting predisposition to high blood pressure.
In essential hypertension, abnormal platelet function may induce vasospasm and predispose to thrombotic vascular occlusion. We studied in vitro aggregability in platelets from young men with contrasting predisposition to hypertension, defined by their own blood pressure and blood pressures of their parents. Among offspring of parents with low blood pressure, higher blood pressure was associated with impaired aggregation in response to epinephrine (2 x 10(-8) to 5 x 10(-6) mol/L), which was unaffected by endothelin-1 (10(-9) mol/L). By contrast, among offspring of parents with high blood pressure, higher blood pressure was associated with normal aggregation to epinephrine and potentiation of the primary phase of aggregation by endothelin-1. We conclude that enhanced platelet sensitivity to endothelin-1 appears to be a feature of the familial predisposition to hypertension, rather than a nonspecific consequence of high blood pressure.


Validation and inter-laboratory study of selective hydride generation for fast screening of inorganic arsenic in seafood.
It is advisable to monitor and regulate inorganic arsenic (iAs) in food and feedstuff. This work describes an update and validation of a method of selective hydride generation (HG) with inductively coupled plasma mass spectrometry (ICP-MS) for high-throughput screening of iAs content in seafood samples after microwave-assisted extraction with diluted nitric acid and hydrogen peroxide. High concentration of HCl (8 M) for HG along with hydrogen peroxide in samples of a same concentration as used for extraction leads to a selective conversion of iAs to volatile arsine that is released and transported to the detector. A minor contribution from methylarsonate (≈20% to iAs) was found, while HG from dimethylarsinate, trimethylarsine oxide is substantially suppressed (less than 1% to iAs). Methodology was applied to Certified Reference Materials (CRMs) TORT-3, DORM-3, DORM-4, DOLT-4, DOLT-5, PRON-1, SQID-1 and ERM-CE278k, in some of them iAs has been determined for the first time, and to various seaweed samples from a local store. The results were always compared with a reference method and selectivity of iAs determination was evaluated. An inter-laboratory reproducibility was tested by comparative analyses of six fish and four seaweed samples in three European laboratories, with good agreement of the results. The method of HG-ICP-MS is sensitive (limit of detection 2 μg kg-1 iAs), well suited for screening of large number of samples and selective at iAs concentration levels at which maximum limits are expected to be set into EU legislation for marine samples.


Comparison of saccade-associated neuronal activity in the primate central mesencephalic and paramedian pontine reticular formations.
The oculomotor system must convert signals representing the target of an intended eye movement into appropriate input to drive the individual extraocular muscles. Neural models propose that this transformation may involve either a decomposition of the intended eye displacement signal into horizontal and vertical components or an implicit process whereby component signals do not predominate until the level of the motor neurons. Thus decomposition models predict that premotor neurons should primarily encode component signals while implicit models predict encoding of off-cardinal optimal directions by premotor neurons. The central mesencephalic reticular formation (cMRF) and paramedian pontine reticular formation (PPRF) are two brain stem regions that likely participate in the development of motor activity since both structures are anatomically connected to nuclei that encode movement goal (superior colliculus) and generate horizontal eye movements (abducens nucleus). We compared cMRF and PPRF neurons and found they had similar relationships to saccade dynamics, latencies, and movement fields. Typically, the direction preference of these premotor neurons was horizontal, suggesting they were related to saccade components. To confirm this supposition, we studied the neurons during a series of oblique saccades that caused "component stretching" and thus allowed the vectorial (overall) saccade velocity to be dissociated from horizontal component velocity. The majority of cMRF and PPRF neurons encoded component velocity across all saccades, supporting decomposition models that suggest horizontal and vertical signals are generated before the level of the motoneurons. However, we also found novel vectorial eye velocity encoding neurons that may have important implications for saccade control.


Transplantation of the second toe to the hand. A preliminary report of sixteen cases.
Nine patients had replacement of the thumb and seven, reconstruction of a finger in a mutilated hand in which the thumb or all fingers had been amputated. There were twelve successes, three partial successes, and one failure. A clear knowledge of the anatomy of the dorsalis pedis artery, avoidance of kinking of the vessels, and adequate precautions against postoperative edema and venous congestion were essential for success. The donor foot did not suffer functionally despite the absent second toe.


Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia.
To study the neurobehavioral, biochemical and histopathological consequences of permanent focal brain ischemia, and the putative neuroprotective action of ketoprofen. One-hundred-and-three Wistar rats divided into groups A and B were respectively submitted to 48 hours and 15 days of ischemia. Each group was divided into 4 subgroups: ischemic not treated, ischemic treated, sham not treated, and sham treated. Ischemic animals had the left middle cerebral artery coagulated. Ketoprofen was administered to treated subgroups 15 minutes before arterial coagulation (manipulation in the sham group). Exploratory activity and defecation were reduced in all ischemic animals in the first postoperative days and constant histopathological changes were observed in each group. The total brain glutamate levels were higher in treated animals 48 hours after surgery. No clear parallelism among behavioral, biochemical and histopathological findings was observed. Ketoprofen demonstrated no neuroprotective effect on the behavioral or histopathological aspects of focal permanent brain ischemia.


Opposing effects of androgen and estrogen on pituitary-adrenal function in nonpregnant primates.
Maternal administration of androstenedione produces a sustained fall in maternal plasma adrenocorticotropic hormone (ACTH) concentrations in the pregnant nonhuman primate. We hypothesize a negative feedback influence on the maternal hypothalamo-pituitary-adrenal (HPA) axis by androgens in primates. This may reflect an important maternal adaptation during pregnancy in primates preventing premature induction of labor by maternal stress. However, androstenedione is precursor for placental estradiol-17beta synthesis, and infusion of androstenedione into pregnant primates elevates maternal plasma estradiol-17beta to term concentrations. Thus, it could be argued that 1) the effects attributed to androstenedione on the maternal HPA axis are mediated by estrogen rather than by androgen and 2) the negative influence of androgens may be on placental ACTH rather than, or in addition to, pituitary ACTH. To discriminate between androgenic and estrogenic effects of androstenedione on pituitary and/or placental ACTH function in primates we measured plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations in nonpregnant baboons after treatment with either androstenedione or estradiol-17beta. Nine female baboons were studied between 14 and 22 days postpartum prior to estrous cycling. After 2 days of baseline, a continuous i.v. infusion of androstenedione (1.5 mg/kg per h in 10% intralipid, IL) was started at 0900 h and maintained for 9 days in 3 baboons. A similar protocol was carried out in another 3 baboons that received a continuous i.v. infusion of estradiol-17beta (10 microg/kg per h in 10% IL) instead of androstenedione. Three additional baboons received continuous i.v. IL vehicle alone and served as controls. Arterial blood samples (0.5 ml) for measurement of plasma hormones were taken during baseline and after 1, 3, 5, 7, and 9 days of infusion. Baseline plasma ACTH, DHEAS, and cortisol concentrations were similar among all groups. Plasma ACTH did not change during IL, increased following estradiol-17beta, and fell during androstenedione treatment. Accordingly, plasma cortisol and DHEAS concentrations were also unaltered by IL, and both steroids increased during estradiol-17beta treatment. In contrast, plasma cortisol and DHEAS remained unaltered from baseline during androstenedione treatment, despite the fall in plasma ACTH measured at this time. These data in the nonpregnant baboon 1) are consistent with negative feedback on pituitary ACTH by androgens and 2) demonstrate a positive influence on pituitary-adrenal function by estrogen in primates.


The effect of low vitamin D status on sexual functioning and depressive symptoms in apparently healthy men: a pilot study.
Hypovitaminosis D is associated with sexual dysfunction in apparently healthy women and with erectile dysfunction in men with the presence of concomitant disorders. This study was aimed at investigating sexual functioning and depressive symptoms in young men with low vitamin D status. The study included 15 apparently healthy men (18-40 years old) with vitamin D deficiency (group A), 16 subjects with vitamin D insufficiency (group B), and 16 men with normal vitamin D status (group C). All participants of the study completed questionnaires investigating their sexual function (the International Index of Sexual Function-15-IIEF-15 for heterosexual men), as well as the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition-BDI-II). Compared with healthy men, subjects with vitamin D deficiency obtained lower scores for erectile function, orgasmic function, and sexual desire, while individuals with vitamin D insufficiency lower scores only for erectile function. Erectile dysfunction was more prominent in group A than group B. The total BDI-II score was higher in group A than in the other study groups. The results of the study suggest that low vitamin D status impairs male sexual functioning and severity of sexual dysfunction correlates with the degree of hypovitaminosis D.


Metabolic disposition of the non-steroidal anti-inflammatory agent isoxicam in man.
The metabolic fate of isoxicam, a long half-life non-steroidal anti-inflammatory agent, in human subjects was investigated using isoxicam labelled with 14C in the N-methyl position. Three healthy male subjects were each administered a single oral 200 mg dose (90.7 microCi) with plasma and urine collected. Total plasma radioactivity peaked between 8 and 24 h postdose with mean 14C plasma radioactivity half-life of 36.1 h. Low levels of plasma radioactivity precluded plasma metabolic profiling. In urine, 37% of the administered radioactivity was recovered through 168 h. Metabolic profiling of urine confirmed the major oxidative excretion product as the hydroxymethylisoxazole metabolite. Identified and confirmed as minor urinary metabolites were radiolabelled open-ring sulfonamide and N-methylsaccharin. Non-labelled saccharin formed by oxidative loss of the 14C N-methyl group from N-methylsaccharin, was also observed. The role of this 'saccharin pathway' in the overall human disposition of isoxicam remains to be elucidated.


Effects of feeding dairy cows protein supplements of varying ruminal degradability.
Twenty-five (10 ruminally cannulated) Holstein cows averaging 82 +/- 34 d in milk were assigned to 5 x 5 Latin squares (21-d periods) and fed diets supplemented with one of four different proteins to assess effects on production, ruminal metabolism, omasal flow of N fractions, and degradation rates of protein supplements. Total mixed diets contained (dry matter basis) 44% corn silage, 22% alfalfa silage, 2% urea, and 31% concentrate. Five concentrate mixes were fed: 31% high-moisture shelled corn (HMSC; basal); 9% solvent soybean meal (SSBM), 22% HMSC; 10% expeller soybean meal (ESBM), 21% HMSC; 5.5% blood meal (BM), 25.5% HMSC; and 7% corn gluten meal (CGM), 24% HMSC. Diets averaged, respectively, 15.8, 19.1, 19.7, 20.3, and 19.3% crude protein. Feeding the basal diet reduced intake and yield of milk, fat-corrected milk (FCM), and all milk components compared to the protein-supplemented diets. Milk yield was higher for cows fed ESBM and CGM, fat yield was higher for cows fed SSBM and CGM, but FCM and protein yields were not different among cows fed supplemental protein. Based on omasal sampling, mean in vivo estimates of ruminal degradation rate for the crude protein in SSBM, ESBM, BM, and CGM was, respectively, 0.417, 0.179, 0.098, and 0.051/h (computed using passage rates observed for the small particle phase; mean = 0.14/h), and 0.179, 0.077, 0.042, and 0.026/h (computed using a passage rate of 0.06/h). The in vivo degradation rate computed for SSBM at a passage rate = 0.06/h was similar to that estimated using the inhibitor in vitro method. However, in vivo degradation rates computed at passage rate = 0.06/h for ESBM, BM, and CGM were about two, four, and three times more rapid than those estimated by inhibitor in vitro. Experimental proteins fed in this trial will be used as standards for developing in vitro methods for predicting rates of ruminal protein degradation.


Clonal anergy blocks the response to IL-4, as well as the production of IL-2, in dual-producing T helper cell clones.
In this report we extend the in vitro clonal anergy model to examine the regulation of proliferation in T cells that secrete both IL-2 and IL-4. Newly cloned Ag-specific murine T cells are shown to depend on both IL-2 and IL-4 synthesis for maximal proliferation. Whereas IL-2 responsiveness is constitutive in these cells, IL-4 responsiveness develops only after Ag and APC stimulation. Remarkably, proliferation of these cells to Ag is sensitive to inhibition by clonal anergy, even though IL-4 synthesis remains inducible. Anergy in these cells is associated with an inability to respond to IL-4, in addition to the development of an IL-2 production defect. The results suggest that anergy induction may be capable of preventing the clonal expansion of autoreactive T cells producing both IL-2 and IL-4 in vivo.


Iron supports myogenic cell differentiation to the same degree as does iron-bound transferrin.
T. Hasegawa, K. Saito, I. Kimura, and E. Ozawa (1981, Proc. Jopan Acad. B 57, 206-210) have shown that Fe ion can promote myogenic cell growth as Fe-bound transferrin. In the present work, the effects of these substances in supporting myogenic cell differentiation were examined. The hallmarks of differentiation adopted were appearance of structural and regulatory proteins, myofibrils, sarcoplasmic reticulum, and Ca-activated activities of myosin B and phosphorylase kinase; isoform transition of creatine kinase; and acquisition of cell membrane excitability and contractility following electrical stimulation of myotubes. The degree of differentiation of myotubes cultured in the presence of Fe ion was almost the same as that of myotubes cultured in the presence of Fe-bound transferrin. These facts suggest that transferrin protein molecules do not play a primary role in differentiation. Further, it has also been shown that myotubes acquire excitation-contraction and metabolism coupling qualitatively similar to that of adult muscle fiber.


Troponin T switching in the developing rat heart.
A monoclonal antibody specific for cardiac troponin T has been used to investigate troponin changes during development in the rat heart. Specificity of the antibody was determined by immunoblot analysis with purified bovine cardiac troponin. In the rat heart, immunoblot analysis shows that anticardiac troponin T reacts with a 42.5-kDa band in fetal ventricles and with a 41-kDa band in adult ventricles. The faster migrating troponin T is present in traces in the fetal heart and increases markedly during the first 2 weeks after birth, concomitantly with the progressive decrease of the slower migrating form that is no longer detectable in the adult. The pattern of reactivity of the monoclonal antibody is not modified by alkaline phosphatase pretreatment, suggesting that the antibody is not specific for a phosphorylated epitope. Conditions known to affect cardiac myosin composition, such as hypothyroidism and hypertrophy secondary to systemic hypertension, do not change the troponin T isoform profile of adult rat ventricles. The expression and accumulation of the adult isoforms of troponin T are not suppressed by propylthiouracil treatment of pregnant and nursing rats.


Mapping caries prevalence and water distribution in Wales-- Iechyd Morgannwg Health Authority as a case study.
To investigate the use of mapping in targeting water fluoridation to areas of high need in lechyd Morgannwg Health Authority, as defined by the upper quintile of the distribution of the percentage with dmft > 0 in dental planning areas. Data from the 1997/98 childhood dental epidemiological survey and the Welsh Water Company water supply zones (as at 1997) were plotted. Maps were generated to identify the relationship between water supply areas, water supply sources and areas of high caries prevalence. Maps focussed upon one Welsh health authority, Iechyd Morgannwg Health Authority. Examinations for the childhood epidemiology programme took place in schools. 5-year-old children examined in the 1997/98 survey. Data presented by very different geographical boundaries were compared without having to carry out complex mathematical transformations. It was possible to quickly identify areas of Iechyd Morgannwg Health Authority with high levels of oral disease, the associated water supply zones and their water treatment centres with a view to possible future targeting of fluoridation. The maps identify the possibility of dilution, when a particular water supply zone was served by more than one treatment works. This technique enables disparate and complex data bases to be combined enabling visual analysis of the results. The maps facilitate decision making as to the most beneficial areas to fluoridate. The results will be of value in determining the feasibility and targeting of water fluoridation in Wales.


Mathematical analysis of isovolemic hemodilution indicates that it can decrease the need for allogeneic blood transfusion.
The implementation of acute isovolemic hemodilution prior to surgical blood loss is a strategy used in an attempt to diminish the need for or obviate allogeneic transfusion and to avert the potential, attendant complications. Studies examining the efficacy of this technique have produced conflicting results. The present mathematical analysis was undertaken to resolve these conflicts by determining the efficacy of hemodilution and examining the influence of the variables affecting the outcome. Efficacy was defined as the volume of additional blood loss permitted and the volume and number of units of allogeneic blood saved from transfusion. A mathematical analysis evaluated the impact of circulating blood volume and initial and target hematocrits on the efficacy of isovolemic hemodilution. It was assumed that 1) hemodilution was completed before surgical blood loss; 2) transfusion of removed blood was begun when the target hematocrit was reached and lost surgical blood was replaced at a rate that maintained the target hematocrit; 3) allogeneic transfusion was begun after all autologous blood drawn was transfused; 4) normovolemia was maintained; and 5) a unit of allogeneic blood contains 175 mL of red cells. The analysis showed that isovolemic hemodilution can result in substantial additional allowable surgical blood loss that can diminish the need for or obviate allogeneic transfusion of red cells. Larger circulating blood volume, higher initial hematocrits, and lower target hematocrits increase the efficacy of hemodilution. Removal and isovolemic replacement of 1 to 2 units of blood provide minimal potential savings, as does hemodilution to a circulating (target) hematocrit of 30 percent. The extension of hemodilution to a hematocrit of (or below) 20 percent allows a disproportionately greater surgical blood loss and diminishes the need for allogeneic transfusion. It allows, for example, an additional 4.5 L of surgical blood loss, which represents a savings of 4 units of allogeneic blood when a patient with an initial blood volume of 5.0 L and a hematocrit of 45 percent undergoes isovolemic hemodilution to a hematocrit of 15 percent. Isovolemic hemodilution can diminish or in some circumstances eliminate the need for allogeneic transfusion.


Mode crystallography of distorted structures.
The description of displacive distorted structures in terms of symmetry-adapted modes is reviewed. A specific parameterization of the symmetry-mode decomposition of these pseudosymmetric structures defined on the setting of the experimental space group is proposed. This approach closely follows crystallographic conventions and permits a straightforward transformation between symmetry-mode and conventional descriptions of the structures. Multiple examples are presented showing the insight provided by the symmetry-mode approach. The methodology is shown at work, illustrating its various possibilities for improving the characterization of distorted structures, for example: detection of hidden structural correlations, identification of fundamental and marginal degrees of freedom, reduction of the effective number of atomic positional parameters, quantitative comparison of structures with the same or different space group, detection of false refinement minima, systematic characterization of thermal behavior, rationalization of phase diagrams and various symmetries in families of compounds etc. The close relation of the symmetry-mode description with the superspace formalism applied to commensurate superstructures is also discussed. Finally, the application of this methodology in the field of ab initio or first-principles calculations is outlined. At present, there are several freely available user-friendly computer tools for performing automatic symmetry-mode analyses. The use of these programs does not require a deep knowledge of group theory and can be applied either a posteriori to analyze a given distorted structure or a priori to parameterize the structure to be determined. It is hoped that this article will encourage the use of these tools. All the examples presented here have been worked out using the program AMPLIMODES [Orobengoa et al. (2009). J. Appl. Cryst. 42, 820-833].


Epidemiology, therapeutic agents and cost of management of paediatric malaria in a Nigerian tertiary hospital.
Malaria is the most widespread parasitic disease in sub-Saharan Africa with associated high morbidity and mortality especially among the highly predisposed population of pregnant women and children of age five years and below. Living in malaria endemic regions of the world has become associated with health and economic hazards placing financial and productive burden on affected households. A prospective study of children treated for malaria and other associated illnesses at a Nigeria tertiary health institution between May and October 2003 was undertaken. The various malaria-associated diseases treated were determined from their provisional diagnosis, hospital records and causative agents confirmed from their diagnostic laboratory results. Cost of treatment was determined from the patients' guardian and confirmed from relevant hospital departments. Common drugs for malaria treatment, their costs, relative effectiveness and frequency of use were determined through a completed questionnaire by health officers and patients' guidance. Of 5356 paediatric patients suspected of having malaria, 5100 (95.2%) were confirmed positive for malaria parasites microscopically. Of these, 4119 (80.8%) were aged 0 - 6 years, with children aged 1 to 3 years being mostly affected. Eight hundred and twenty (16.1%) of them were in-patients spending an average of six days on hospital bed. Over 22 million naira (dollar 0.22 m) was spent on the treatment of malaria with drugs accounting for the major cost (66.81%). About 33.7% of the patients had malaria complicated with other diseases. The effectiveness of common therapeutic agents used for malaria treatment, their costs and associated side effects is discussed. Recommendations are made for appropriate care and government subsidy for paediatric malaria management in sub-Saharan Africa.


Genetic patterns in thalassemia intermedia (constitutional microcytic anemia). Familial, hematologic and biosynthetic studies.
Globin chain synthesis has been studied in 17 patients with thalassemia intermedia, and their relatives, also investigated by routine hematologic and hemoglobinic tests. The mean a/non a ratio was always around 2.20-2.30. In patients with severe thalassemia major, used as a control, the mean a/non a ratio was significantly higher, that is 3.11-3.07. Therefore, the hypothesis that the cause of the lesser severity of the thalassemia intermedia is a lesser imbalance of globin chain synthesis, is suggested. One or both the parents of patients with thalassemia intermedia have mild beta-thalassemia and normal alpha/beta ratio, whereas the parents of patients with severe thalassemia major show a marked beta-thalassemia and a mean alpha/beta ration of 1.76. These data suggest that genes for beta +-thalassemia are responsible for thalassemia intermedia, and genes for beta o-thalassemia are responsible for thalassemia major. In two patients with thalassemia intermedia, the association of an alpha-thalassemia gene with homozygous beta-thalassemia that it is well known to reduce the globin chain imbalance typical of the beta-thalassemia, has also been observed.


Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages.
The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5-10 mM). Low doses of metformin (1-3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5'-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis.


The Response regulator HrpY of Dickeya dadantii 3937 regulates virulence genes not linked to the hrp cluster.
HrpX/Y is a putative two-component system (TCS) encoded within the type III secretion system (T3SS) gene cluster of Dickeya dadantii. A linear regulatory cascade initiated by HrpX/Y that leads to activation of the downstream T3SS genes via HrpS and HrpL was described previously. Therefore, in D. dadantii, HrpX/Y plays an important role in regulation of genes involved in bacteria-plant interactions and bacterial aggregation via the T3SS. HrpX/Y is the only TCS shared among the plant-pathogenic enterobacteria that is not also present in animal-associated enterobacteria. To date, the genes known to be regulated by HrpY are restricted to the hrp and hrc genes and no signal has been identified that triggers HrpY-dependent gene expression. We demonstrated that HrpY interacts with the hrpS promoter in vitro. We then used a transposon-based system to isolate previously unidentified HrpY-dependent genes, including genes previously shown to affect virulence, including kdgM and acsC. HrpY is a dual regulator, positively regulating at least 10 genes in addition to those in the hrp gene cluster and negatively regulating at least 5 genes. The regulatory effect on one gene depended on the culture medium used. Of the 16 HrpY-regulated genes identified in this screen, 14 are not present in Pectobacterium atrosepticum, the nearest relative of D. dadantii with a sequenced genome. None of the newly identified HrpY-regulated genes were required for bacterial aggregation; thus, neither acyl-homoserine lactone-mediated quorum sensing nor the Rcs signal transduction system which regulates colanic acid, a molecule that plays an important role in biofilm formation in other enterobacteria, are required for D. dadantii aggregation.


Separation and determination of tetrandrine and fangchinoline in herbal medicines by flow injection-micellar electrokinetic capillary chromatography with internal standard method.
A simple, rapid and precision flow injection-micellar electrokinetic capillary chromatography (FI-MEKC) system with trimethoprim as internal standard (IS) for automated quantitative analysis of tetrandrine (TET) and fangchinoline (FAN) in various herbal medicines was demonstrated. The real sample throughput was 19-40 samples per hour using the background electrolyte (BGE) containing 15mM acetic acid-15mM sodium acetate-3% (v/v) polyoxyethylene sorbitan monolaurate (Tween 20)-5% (v/v) methanol at pH 5.5. The method resulted in excellent linearity, with correlation coefficient of regression equation of 0.9996 and 0.9991 for TET and FAN, respectively. Recoveries were in the range 95-109% and 92-106% for TET and FAN, respectively.


Preventive dentistry: what do Australian patients endorse and recall of smoking cessation advice by their dentists?
To investigate patients' views regarding dentists' smoking cessation advice. Survey questionnaire. One hundred and thirty five dental practices in Sydney Australia. Subjects Two thousand, four hundred and fifty one dental patients. One thousand, one hundred and sixty pre-consultation questionnaires were obtained (RR=80%), 302 (26%) were self-reported smokers. From these, 623 post-consultation questionnaires were returned (RR = 54%). Most patients expected dentists to be interested in their smoking status (n = 847/1160, 73%, 95% CI: 70% to 76%) and to discuss smoking with them (n = 713/1160, 61%, 95% CI: 59% to 64%), however, smokers were significantly less likely to respond as such compared with non-smokers (P < 0.001). Smokers and non-smokers equally would not change dentist even if asked about their smoking status opportunistically (59% versus 62%) (OR = 0.91, 95% CI: 0.67 to 1.22). Less than one third of all smokers would try to quit if their dentist suggested they do so (n = 90/302, 30%, 95% CI: 25% to 35%). Smokers' recall of quit advice from their recent consultation was low (n = 22/124, 18%). Smoking cessation advice by dentists is not self-evidently effective. These findings behove interventional research to ascertain efficacy of smoking cessation advice delivered by dentists before admonishing changes in routine clinical practice.


The birth of American neurology and highlights from the first 100 years of the Philadelphia Neurological Society, 1884-1984.
The Philadelphia Neurological Society was founded 100 years ago by Charles K. Mills, together with Wharton Sinkler, J.T. Eskridge, and Francis X. Dercum. S. Weir Mitchell was the first president and served for 5 additional years. American neurology was born in Philadelphia at the Orthopedic Hospital and the Infirmary for Nervous Diseases. The growth in neurology in this country is reflected in the activities of the Philadelphia Neurological Society.


Analysis by gas chromatography-mass spectrometry of the essential oils from the aerial parts of Pimpinella anagodendron Bolle and Pimpinella rupicola Svent., two endemic species to the Canary Islands, Spain.
The essential oils from the aerial parts of Pimpinella anagodendron Bolle and Pimpinella rupicola Svent., two endemic species growing in Tenerife, Canary Islands, Spain, were studied by gas chromatography and gas chromatography-mass spectrometry. The major components of the flowering tops (flowers+unripe fruits) of P. rupicola (PRFT) were found to be beta-bisabolene (34.8%), limonene (10.9%) and alpha-zingiberene (10.5%), whereas in the flowering tops of P. anagodendron (PAFT), the main constituents were alpha-zingiberene (32.9%), beta-bisabolene (17.9%), beta-pinene (15.8%) and ar-curcumene (11.5%). The major compounds found in the stems+leaves of P. rupicola (PRSL) were beta-bisabolene (31.6%), alpha-zingiberene (11.4%) and limonene (10.8%), whereas those of P. anagodendron (PASL) were alpha-zingiberene (32.3%), beta-bisabolene (14.0%) and ar-curcumene (12.6%). In all the oils were found the characteristic constituents of genus Pimpinella, the pseudoisoeugenol esters. In accordance with the morphological, chorological and chemical differences between both species, we suggest that P. rupicola Svent. is a good taxon and not a synonym of P. anagodendron.


Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.
Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in Chronic Fatigue Syndrome (CFS) patients. Previous investigations have reported decreased carnitine levels in CFS. Orally administered L-carnitine is an effective medicine in treating the fatigue seen in a number of chronic neurologic diseases. Amantadine is one of the most effective medicines for treating the fatigue seen in multiple sclerosis patients. Isolated reports suggest that it may also be effective in treating CFS patients. Formal investigations of the use of L-carnitine and amantadine for treating CFS have not been previously reported. We treated 30 CFS patients in a crossover design comparing L-carnitine and amantadine. Each medicine was given for 2 months, with a 2-week washout period between medicines. L-Carnitine or amantadine was alternately assigned as fist medicine. Amantadine was poorly tolerated by the CFS patients. Only 15 were able to complete 8 weeks of treatment, the others had to stop taking the medicine due to side effects. In those individuals who completed 8 weeks of treatment, there was no statistically significant difference in any of the clinical parameters that were followed. However, with L-carnitine we found statistically significant clinical improvement in 12 of the 18 studied parameters after 8 weeks of treatment. None of the clinical parameters showed any deterioration. The greatest improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1 patient was unable to complete 8 weeks of treatment due to diarrhea. L-Carnitine is a safe and very well tolerated medicine which improves the clinical status of CFS patients. In this study we also analyzed clinical and laboratory correlates of CFS symptomatology and improvement parameters.


Mammalian ferrochelatase. Overexpression in Escherichia coli as a soluble protein, purification and characterization.
Ferrochelatase (protoheme ferrolyase, EC 4.99.1.1), a membrane-bound protein, catalyzes the terminal step of the heme biosynthesis in all living systems. A cDNA encoding the murine ferrochelatase (Taketani, S., Nakahashi, Y., Osumi, T., and Tokunaga, R. (1990) J. Biol. Chem. 265, 19377-19380) has been expressed in Escherichia coli, using the alkaline phosphatase promoter. Ferrochelatase was not only overexpressed in an active form, but more importantly, was produced as a "soluble protein" (i.e. associated with the soluble bacterial protein fraction). A simple purification from the ferrochelatase overproducing bacterial strain yielded approximately 50 mg of protein/2-3 liters of bacterial culture. Recombinant ferrochelatase exhibited identical physical and catalytic properties to those of mammalian ferrochelatases. Specifically, the recombinant ferrochelatase has iron and porphyrin as substrates, and N-methylprotoporphyrin and metal ions (e.g. Hg2+ and Mn2+), as strong inhibitors of its enzyme activity. The Km values are 112.5 microM for iron and 95 microM for deuteroporphyrin IX, which are in the same range of the Km values determined for the ferrochelatases isolated from natural sources. This report describes the overexpression of a mammalian ferrochelatase in E. coli, as a soluble protein, and its purification from an overproducing strain. The production of a functional and "soluble" ferrochelatase has significance for the pursuit of structural and functional studies of this enzyme.


Dicyclohexylcarbodiimide interaction with the voltage-dependent anion channel from sarcoplasmic reticulum.
In a recent study [Shoshan-Barmatz, V., Orr, I., Weil, S., Meyer, H., Varsanyi, M. & Heilmeyer, L. M. G. (1996) FEBS Lett. 386, 205-210] we have demonstrated the presence of the voltage-dependent anion channel (VDAC) in skeletal muscle sarcoplasmic reticulum (SR) as supported here by co-localization of VDAC and (Ca2+ + Mg2+)ATPase in the SR using double-immunogold labeling. The interaction of the carboxyl-modifying reagent dicyclohexylcarbodiimide with the SR-VDAC is characterized by labeling with [14C]dicyclohexylcarbodiimide and by dicyclohexylcarbodiimide modification of the reconstituted-purified VDAC channel activity. In both SR and mitochondrial membranes, [14C]dicyclohexylcarbodiimide most specifically labeled a 35-kDa protein, identified as VDAC by specific anti-VDAC Ig. Labeling of the SR-VDAC was about twofold higher than that of the mitochondrial VDAC, which could result either form higher labeling of the SR protein or from relatively higher amounts of VDAC/mg total protein in the SR membranes. [14C]Dicyclohexylcarbodiimide labeling of the SR, but not the mitochondrial VDAC, was biphasic with respect to time and concentration of [14C]dicyclohexylcarbodiimide. Partial digestion of [14C]dicyclohexylcarbodiimide-labeled SR-VDAC with chymotrypsin yielded five proteolytic fragments which were recognized by the anti-VDAC Ig, and the dicyclohexylcarbodiimide-binding site was localized in the 19-kDa fragment. VDAC was purified from SR and mitochondrial membranes by spermine-agarose column. The interaction of dicyclohexylcarbodiimide with functional carboxyl residue(s) in the purified VDAC is demonstrated by recording its channel activity, following its reconstitution into planar lipid bilayer (PLB). Dicyclohexylcarbodiimide inhibited the channel activity in a voltage-dependent manner, requiring incubation with dicyclohexylcarbodiimide at high (negative or positive) potentials. Dicyclohexylcarbodiimide slowed down the transition from the high-conducting to a long-lived low-conducting states of the channel (approximately 20% of its maximal conductance), by stabilizing the intermediate states. Similar results were also obtained with purified-reconstituted mitochondrial VDAC. Hydrophilic carboxyl reagents [[1-ethyl-3-(3-dimethylamino)propyl] carbodiimide, N-ethyl-phenylisoxazolium-3'-sulfonate] neither modified the channel activity nor prevented [14C]dicyclohexylcarbodiimide labeling. These results indicate that dicyclohexylcarbodiimide interacts with a carboxyl group located in a hydrophobic region of the protein which is involved in the channel gating.


Allergic disease as an association of steroid sulphatase deficiency.
Ten of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease.


A Uranium Tri-Rhenium Triple Inverse Sandwich Compound.
Salt metathesis between the anionic rhenium(I) compound, Na[Re(η5-Cp)(BDI)] (BDI = N, N'-bis(2,6-diisopropylphenyl)-3,5-dimethyl-β-diketiminate), and the uranium(III) salt, UI3(1,4-dioxane)1.5, generated the triple inverse sandwich complex, U[(μ-η5:η5-Cp)Re(BDI)]3, which was isolated and structurally characterized as the Lewis base adducts, (L)U[(μ-η5:η5-Cp)Re(BDI)]3 (1·L, L = THF, 1,4-dioxane, DMAP). The assignment as one uranium(III) and three rhenium(I) centers was supported by X-ray crystallography, NMR and EPR spectroscopies, and computational studies. An unusual shortening of the rhenium-Cp bond distances in 1·L relative to Na[Re(η5-Cp)(BDI)] was observed in the solid-state and reproduced in calculated structures of 1·THF and the anionic fragment, [Re(η5-Cp)(BDI)]-. Calculations suggest that the electropositive uranium center pulls electron density away from the electron-rich rhenium centers, reducing electron-electron repulsions in the rhenium-Cp moieties and thereby strengthening those interactions, while also making uranium-Cp bonding more favorable.


The pollen metamorphosis phenomenon in Panax ginseng, Aralia elata and Oplopanax elatus; an addition to discussion concerning the Panax affinity in Araliaceae.
To find more morphological characteristics useful for discussion on aralian or non-aralian Panax affinity, pollen morphological diversity was comparatively analysed in P. ginseng, Aralia elata and Oplopanax elatus collected during their pollination periods. In the anthers of both the buds and open flowers, the pollen average diameter varied between some species-specific maximum and minimal measurement. However, the larger pollen grains were typically found in the buds whereas the smaller pollen prevailed in the open flowers, testifying to the pollen size diminution during anther maturation. Based on this finding, the subsequent examination of pollen according to size decrease was put into operation as a method of pollen modification for the study. The structural mechanisms of pollen metamorphosis were identified as not being species specific but rather universal. These mechanisms are suggested to be the shrinkage of the pollen vegetative cytoplasm, the intine enlargement, the deepening of three colporate apertures provided by exine sunken into enlarged intine areas, the aperture accretion as well as the transformation of the exine from thick/sculptured into thin/less sculptured. During 'size-reducing metamorphosis', the pollen grains changed dramatically, going through a species-specific set of intermediate morphs to the final species-specific morphotype. In P. ginseng this morphotype is round (diameter is about 16 microm), in A. elata it is round with a single projection (diameter is about 15 microm) and in O. elatus it is ovoid with a single projection (average diameter is about 18 microm). In addition, every species is peculiar in having the unique vegetative cytoplasm inclusions and individual construction of the largest pollen exine. From a phylogenetic perspective, these findings presumably add support to the option of equal remoteness of P. ginseng from A. elata and O. elatus. The characteristics found seem to be suitable for examination of Panax affinity, by the subsequent study of more Araliaceae representatives.


Real-time physical random bit generation at Gbps based on random fiber lasers.
We demonstrate for the first time, to the best of our knowledge, a high-speed physical random bit generator at gigabits/second without the time-delay signature based on chaotic power fluctuations of a random fiber laser. The random fiber laser is configured using a ring structure with semiconductor optical amplifiers as the optical gain and a fiber random grating as the random feedback medium. The long-length ring cavity provides a large number of densely spaced cavity modes that co-exist within the gain bandwidth tailored by the optical filter. Unlike fixed cavity modes in conventional fiber ring lasers, these modes are less phase-correlated due to the random distributed feedback from the fiber random grating fabricated by a plane-by-plane inscription technique without phase control, leading to intensified lasing output fluctuations with high-dimensional chaotic dynamic natures without specific cavity features, when the random fiber laser is operated slightly above the lasing threshold. Random bit generation at a bit rate up to ∼1.6 Gbps is achieved with verified randomness through standard tests. Different from the previously reported schemes requiring offline post-processing procedures, this physical random number generator can function in real time, offering high-quality randomness and security assurance for pertinent applications.


Mutual respect in healthcare: assessing cultural competence for the University of Utah Interdisciplinary Health Sciences.
The University initiated an Interdisciplinary Health Sciences Students (IHSS) education program, Cultural Competency & Mutual Respect (CCMR), for medicine (MED), pharmacy (PHARM), nursing (NSG), physical (PT) and occupational therapy (OT). This study assessed CCMR pre/post learning outcomes through the Inventory for Assessing the Process of Cultural Competence-Revised((c)) (IAPCC-R). Subjects included: 100 MED, 140 NSG, 36 PT, 11 OT and 53 PHARM IHSS. IAPCC-R(c) completed by IHSS: 263 Fall, 2003; 48 Spring, 2004. Controls included 100 MED and 36 PT. Pre/post test scores were calculated. Paired analyses performed, comparing overall CC scores and constructs, p < 0.05. Overall pre versus post mean scores: 2003: 69.75 and 71.62; 2004: 66.77 and 71.85. Paired t-test 2003: MED t = -3.1976 P > t = 0.0020; NSG t = 0.5196 P > t = 0.6064; PT t = 4.7181 P > t=0.0000; 2004: PHARM t =-3.7861 P > t=0.0006; All other t = -1.7392 P > t = 0.1425. Two sample t-test, significant only for post-module for Hispanic/Asian/other, 77.50, White, Non-Hispanic 70.37. Results indicate PT, MED, PHARM attained significant scores for constructs: Attitudes, Knowledge, and Skills; but not Encounters and Desires. Post-test scores indicated progressions approaching CC, however not yet Culturally Proficient. Results indicate IHSS are becoming more Culturally Aware as a result of CCMR participation; however, they have not achieved Cultural Proficiency. The constructs of Cultural Desire and Encounters warrant curricular enhancement for progression towards Cultural Proficiency.


Effects of bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor antagonist, on the rat isolated left atria and portal vein.
1. The effects of treatment with bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor antagonist, for 30 min on the contractile responses of the rat left atria and portal vein have been determined. 2. On the electrically driven rat left atria, BAAM at 10(-5) M followed by a 60-min wash-out caused parallel rightward shifts of the isoprenaline response curves with no reduction in the maximal response to isoprenaline. 3. Treatment of the atria with BAAM at 3 x 10(-5) M caused non-parallel rightward shifts of isoprenaline response curves with a reduction in the maximum response to isoprenaline. The KA (dissociation constant) for isoprenaline at beta 1-adrenoceptors was 7.3 x 10(-7) M. Calculation of receptor occupancy demonstrated that in order to produce a maximal response of the rat left atria, isoprenaline had to occupy 12% of the beta 1-adrenoceptors. 4. Treatment of the atria with higher concentrations of BAAM (greater than or equal to 6 x 10(-5) M) caused a non-specific action, the reduction of the response to electrical stimulation. 5. On the rat portal vein, BAAM at 3 x 10(-7)-3 x 10(-6) M followed by a 45-min wash-out had no effect on the spontaneous contractile activity, caused non-parallel rightward shifts of isoprenaline response curves with a depression of the isoprenaline maximum responses. Using data derived from experiments with 3 x 10(-7), 10(-6) and 3 x 10(-6) M BAAM, the KA for isoprenaline at beta 2-adrenoceptor was 6.4, 3.7 and 7.7 x 10(-7) M and the calculated receptor occupancy was that in order to produce a maximal response of the rat portal vein, isoprenaline had to occupy 14, 21 and 12%, respectively of the beta 2-adrenoceptors. 6. The present study with the rat left atria and portal vein has shown that it is possible to determine treatments with BAAM that produce no non-specific actions and consequently BAAM may be used as an experimental tool in KA and receptor occupancy determinations in these tissues.


Characterization of two molluscan crystal-modulating biomineralization proteins and identification of putative mineral binding domains.
Ethylenediamine-tetraacetic acid extracted water-soluble matrix proteins in molluscan shells secreted from the mantle epithelia are believed to control crystal nucleation, morphology, orientation, and phase of the deposited mineral. Previously, atomic force microscopy demonstrated that abalone nacre proteins bind to growing step edges and to specific crystallographic faces of calcite, suggesting that inhibition of calcite growth may be one of the molecular processes required for growth of the less thermodynamically stable aragonite phase. Previous experiments were done with protein mixtures. To elucidate the role of single proteins, we have characterized two proteins isolated from the aragonitic component of nacre of the red abalone, Haliotis rufescens. These proteins, purified by hydrophobic interaction chromatography, are designated AP7 and AP24 (aragonitic protein of molecular weight 7 kDa and 24 kDa, respectively). Degenerate oligonucleotide primers corresponding to N-terminal and internal peptide sequences were used to amplify cDNA clones by a polymerase chain reaction from a mantle cDNA library; the deduced primary amino acid sequences are presented. Preliminary crystal growth experiments demonstrate that protein fractions enriched in AP7 and AP24 produced CaCO(3) crystals with morphology distinct from crystals grown in the presence of the total mixture of soluble aragonite-specific proteins. Peptides corresponding to the first 30 residues of the N-terminal sequences of both AP7 and AP24 were generated. The synthetic peptides frustrate the progression of step edges of a growing calcite surface, indicating that sequence features within the N-termini of AP7 and AP24 include domains that interact with CaCO(3). CD analyses demonstrate that the N-terminal peptide sequences do not possess significant percentages of alpha-helix or beta-strand secondary structure in solution. Instead, in both the presence and absence of Ca(II), the peptides retain unfolded conformations that may facilitate protein-mineral interaction.


Quantification of the visceral and subcutaneous fat by computed tomography: interobserver correlation of a single slice technique.
To assess the interobserver reproducibility of the quantification of the visceral and subcutaneous fat by computed tomography from an umbilical slice and study the effect of the level of the slice (slice going through the navel versus a slice going through disc L3-L4). Forty-four breast cancer patients who had a CT-scan were included in this study. This is a double blind (junior versus senior) retrospective study to determine the interobserver reproducibility. A junior observer studied the variation between two levels of slice by selecting an image going through L3-L4 and the navel. The measurement of the fat obtained from an umbilical slice seemed to be well correlated and consistent with that obtained from a slice with a disc reference (L3-L4). The interobserver reproducibility is good for the quantification of the umbilical fat (Spearman and Lin at 0.9921 and 0.985 [P<0.001] for the visceral fat). The interobserver reproducibility of the single slice CT-scan measurement going through the navel (easily detected) is excellent and may therefore be used in oncology as a predictive tool to measure a characteristic of the host and not the tumor.


The extracellular matrix components, tenascin and fibronectin, in Hirschsprung's disease: an immunohistochemical study.
Previous in vitro studies have suggested that successful neural crest cell migration in the developing gut could be influenced by the composition of the extracellular matrix components, tenascin and fibronectin. The authors aimed to gain insight into the pathogenesis of Hirschsprung's disease (HD) by studying the distribution of tenascin and fibronectin in bowel specimens of patients with HD. Immunohistochemical examination was performed in specimens from 10 HD patients (8 aganglionic, 5 transitional, and 10 normoganglionic zones) and 18 age- and site-matched controls undergoing other types of gastrointestinal surgery. The distribution of tenascin was restricted to the basement membranes of the smooth muscle and vasculature, and in the basement membranes surrounding neuronal ganglia in all the controls and in 10 proximal normoganglionic HD specimens. More intense tenascin immunofluorescence was observed in the smooth muscle basement membranes of the muscularis externa of eight aganglionic and five transitional zones of HD. Wide-spread distribution of fibronectin was found in all the basement membranes as well as in the lamina propria and submucosa of all control and 10 normoganglionic HD sections. However, more intense immunofluorescence with fibronectin was observed in all the layers of eight aganglionic and five transitional zones of HD specimens. The present findings show that the mesenchymal and basement membrane extracellular matrix constitution is abnormal in the affected bowel of HD. Although a causal relationship has not been demonstrated, corroborative evidence from earlier animal experiments in other studies suggests that the extracellular matrix abnormalities may contribute to the pathogenesis of HD.


Effect of gold salts on adherent mononuclear cells in tissue culture.
Adherent mononuclear cells from normals and patients with rheumatoid arthritis (RA) were isolated and effects of gold salts on cell cultures assessed in vitro. Phagocytic function of adherent mononuclear cells was assessed by the injestion of opsonized chicken red blood cells. Absolute numbers of phagocytic cells were higher in the RA patients than normals. Gold salts in concentrations 0.5-5.0 microgram/ml significantly reduced the numbers of both adherent and phagocytic cells when compared to control cultures. This suppression was particularily marked in the RA patients and was dose and time dependent. However, mononuclear cells surviving incubation with gold salts appeared to maintain phagocytic function in similar proportions to control cultures.


An evaluation of a measure of the proportion of the treatment effect explained by a surrogate marker.
Time-dependent markers, such as CD4 and viral load, are potential surrogate markers in AIDS clinical trials. A critical issue with surrogate markers is whether changes in these markers explain the beneficial effect of treatment on the real end point of the clinical trial. A statistic to measure the proportion of the treatment effect explained by the surrogate is p(FGS) = 1 - gamma/alpha, where alpha is the treatment effect coefficient in a Cox model and gamma is the treatment effect coefficient from a time-dependent Cox model adjusted for the marker. In this article we evaluate the statistical properties of p(FGS). Using a Monte Carlo study we show that the statistic is not well calibrated, because it can fall outside the range zero to one, even in very large samples. In the simulation study we consider situations where the time-dependent marker is measured with error at a fixed number of times. We show that a method of fitting a time-dependent Cox model involving smoothing the marker reduces the bias in the estimate of p(FGS) compared with the standard method of using the current or last observed marker value. We also show that the estimate of p(FGS) has considerable variability and can have wide confidence intervals. We conclude that p(FGS) is only likely to be useful in large trials with a strong treatment effect. The methods are illustrated using CD4 counts from an AIDS clinical trial of zidovidine versus placebo.


[Treatment of hypospadias].
Treatment of all forms of hypospadias is difficult. Several abnormal components have to be differentiated and corrected in a very tight space, in addition to which the blood supply must be preserved and infection prevented. Technical progress now allows early correction (around the age of 12 months) in a single procedure, using methods that date back to the last century. Cosmetic results are as important as functional ones. The glans should be reconstructed around the neomeatus, and the penile shaft should be straight. Microsurgical techniques, short transurethral urinary diversion and reliable dressings are important. Strategies, the sequences of surgical procedures and a selection of practical methods are presented and discussed.


Production and characterization of pyrolytic oils by pyrolysis of waste machinery oil.
The main objective of this work is to propose an alternative method for evaluation of the waste machinery oil which is an environmental problem in Turkey. For this purpose, pyrolysis of waste machinery oil was conducted in a tubular reactor. Effect of the experimental conditions (various temperatures, catalyst type) on the formation of pyrolytic oil, gas, and char was investigated. Nickel supported on silica and zeolite (HZSM-5) were used as catalysts. Properties of the pyrolytic oils were characterized by gas chromatograph equipped with a mass selective detector (GC-MS), gas chromatography with flame ionization detector (GC-FID for boiling point range distribution), nuclear magnetic resonance ((1)H NMR) spectroscopy, higher heating value measurement, and elemental analysis. The behavior of the metals in the waste machinery oil and the pyrolytic oil samples was also quantitatively detected by inductively coupled plasma (ICP) analysis. As, Cd and Cr contents of the all pyrolytic oils were found as <0.05 ppm, while Cu content of the pyrolytic oils varied between 0.3 ppm and 0.61 ppm. Only Vanadium contents of the pyrolytic oils obtained at 800 degrees C (0.342 ppm) and in the presence of HZSM5 (0.57 ppm) increased compared to that obtained by waste machinery oil (0.1 ppm). Lower metal contents of the pyrolytic oils reveal that pyrolysis of the waste machinery oils leads to the formation of environmental friendly pyrolytic oils with higher heating values.


On the nature of nonverbal working memory fractionation: a case of selective spatial short-term memory deficit in a child.
Several lines of research on adult subjects demonstrate a visual/spatial fractionation of nonverbal working memory (WM), while behavioral studies on normal children support the idea of a static/dynamic distinction. In the present paper, we report a child (Z.M.) who failed on nonverbal WM tasks. To verify the nature of his defect, we carried out two experiments: in Experiment 1, Z.M. failed on spatial WM tasks but not on visual WM tasks and was not affected by the static/dynamic format of stimulus presentation; in Experiment 2, this visual/spatial dissociation was extended to the imagery domain. These results are best accounted for within the visual/spatial fractionation of WM and confirmed the role of WM in mental imagery. Clinical and rehabilitative implications of the present findings are also discussed.


Formulation optimization of etoposide loaded PLGA nanoparticles by double factorial design and their evaluation.
Etoposide is one of the most commonly used drugs in chemotherapy of acute lymphocytic leukemia and acute myelogenous leukaemia. Etoposide has variable oral bioavailability ranging from 24-74% and has terminal half life of 1.5 hours by intravenous route. The conventional parenteral therapy causes inconvenience and pain to the patients as it has to be given through a continuous IV infusion over 24-34 h. The present investigation was aimed at developing etoposide loaded biodegradable nanoparticles which would be a sustained release formulation and replace the conventional therapy of continuous intravenous administration. Nanoparticles were prepared by emulsion solvent evaporation method using high pressure homogenization. The process parameters like homogenization cycles (four) and homogenization pressure (10000 psi) were first optimized using a 3(2) factorial design based on response Y1(mean particle size of 98+/-1nm). Then a 32 factorial design was carried out to study the effect of two independent variables, ratio of drug and polymer (X1) and surfactant concentration (X2) on the two responses to obtain their optimized values, percentage entrapment efficiency (Y2, 83.12+/-8.3%) and mean particle size (Y3, 105+/-5.4 nm) for Etoposide loaded PLGA Nanoparticles. Contour plots and response surface plots showed visual representation of relationship between the experimental responses and the set of input variables. The adequacy of the regression model was verified by a check point analysis. The zeta potential values ranged between -23.0 to -34.2 mV, indicating stability. Sucrose was used as cryoprotectant during lyophilization. DSC and XRD studies indicated that etoposide was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. The electron micrographs showed spherical, discrete and homogenous particles. Drug release study showed that etoposide loaded PLGA nanoparticles sustained release up to 72h. The release from the nanoparticles followed first order kinetics and mechanism of drug release was Fickian. Stability studies indicated that it was best to store nanoparticle formulations in the freeze dried state at 2-8 degrees C where they remained stable in terms of both size and drug content upto three months.


The natural course of hemodynamically stable pulmonary embolism: Clinical outcome and risk factors in a large prospective cohort study.
Pulmonary embolism (PE) is a potentially fatal disease with risks of recurrent venous thrombotic events (venous thromboembolism [VTE]) and major bleeding from anticoagulant therapy. Identifying risk factors for recurrent VTE, bleeding, and mortality may guide clinical decision making. To evaluate the incidence of recurrent VTE, hemorrhagic complications, and mortality in patients with PE, and to identify risk factors and the time course of these events. We evaluated consecutive patients with PE derived from a prospective management study, who were followed for 3 months, treated with anticoagulants, and underwent objective diagnostic testing for suspected recurrent VTE or bleeding. Of 673 patients with complete follow-up, 20 patients (3.0%; 95% confidence interval [CI], 1.8 to 4.6%) had recurrent VTE. Eleven of 14 patients with recurrent PE had a fatal PE (79%; 95% CI, 49 to 95%), occurring mostly in the first week after diagnosis of initial PE. In 23 patients (3.4%; 95% CI, 2.2 to 5.1%), a hemorrhagic complication occurred, 10 of which were major bleeds (1.5%; 95% CI, 0.7 to 2.7%), and 2 were fatal (0.3%; 95% CI, 0.04 to 1.1%). During the 3-month follow-up, 55 patients died (8.2%; 95% CI, 6.2 to 10.5%). Risk factors for recurrent VTE were immobilization for > 3 days and being an inpatient; having COPD or malignancies were risk factors for bleeding. Higher age, immobilization, malignancy, and being an inpatient were risk factors for mortality. Recurrent VTE occurred in a small percentage of patients treated for an acute PE, and the majority of recurrent PEs were fatal. Immobilization, hospitalization, age, COPD, and malignancies were risk factors for recurrent VTE, bleeding, and mortality. Close monitoring may be indicated in these patients, precluding them from out-of-hospital start of treatment.


Staging and prognosis of melanoma.
Prognosis and survival for patients diagnosed with melanoma depends on a number of interrelated factors, including histological, clinical, immunologic, and surgical parameters. Tumor thickness and depth of invasion is the most important prognostic factor, and helps to guide treatment and management plans. Besides tumor thickness, other histological criteria include melanoma growth phase (nodal v. vertical), host response, angiolymphatic invasion, mitotic rate, regression, satellitosis, and neurotropism. Important clinical prognostic factors include anatomic location of the melanoma and the patient's age and sex. Surgical factors to be examined involve excisional margin size, and elective lymph node dissection. Finally, the staging of patients with melanomas (nodal or visceral metastases) helps to define survival.


[Examination of relation among the generation effect, the level-of-processing effect, and the modality effect in explicit memory tasks].
The main purpose of the present study was to examine the relationship among generation effect, level-of-processing effect, and modality effect in explicit memory. In Experiment 1, the results in the category-name cued recall task showed generation effect. The results in the word-fragment cued recall task showed equal performance level in both read condition and generate condition. In Experiment 2, level-of-processing effect and modality effect were investigated in the word-fragment cued recall task. The results showed the level-of-processing effect, but did not show the modality effect. In Experiment 3, construction of materials and the way of presentation of study list were manipulated in the word-fragment cued recall task. The results showed generation effect, and suggested that the blocked presentation of a study list enhanced conceptually-driven processing. The results of these three experiments were discussed from the following four points: relationship among generation effect, level-of-processing effect, and modality effect in explicit memory tasks; classification of memory task; comparison between word-fragment cued recall task and category-name cued recall task; and conceptually driven processing in explicit memory tasks.


3D Printing: 3D Printing of Conductive Complex Structures with In Situ Generation of Silver Nanoparticles (Adv. Mater. 19/2016).
On page 3712, E. Fantino, A. Chiappone, and co-workers fabricate conductive 3D hybrid structures by coupling the photo-reduction of metal precursors with 3D printing technology. The generated structures consist of metal nanoparticles embedded in a polymer matrix shaped into complex multilayered architectures. 3D conductive structures are fabricated with a digital light-processing printer incorporating silver salt into photocurable formulations.


Effective stochastic resonance under noise of heterogeneous amplitude.
Stochastic resonance is numerically and analytically studied using a model wherein two coupled particles are exposed to noise of heterogeneous (i.e., particle-dependent) amplitude. In a certain range of coupling constant and under noise of heterogeneous amplitude, a particle is observed to resonate intensively to the external field. In other words, one particle under noise of very small or zero amplitude exhibits intensive resonance with the assistance of a highly fluctuating second particle under noise of large amplitude. This intensive resonance is interpreted as a product of the unique combinatory dynamics between one particle that stochastically fluctuates and another particle that classically resonates to the external field.


Prognostic factors for the surgical management of peripheral nerve lesions.
Although the evaluation and treatment of patients with peripheral nerve injuries has evolved and improved over the years, there are still some arguments on the methods and results of surgery. We reviewed retrospectively the clinical, electrophysiological and surgical characteristics of peripheral nerve lesions for 1,636 nerves in 1,565 patients who had been managed in our department in a 10-year period. The most common cause of injuries was gunshot wound in 56.3% of all patients, followed by sharp lacerations (20.6%), fractures (10.6%) and tractions (5.1%). Among 1,636 cases of nerve injuries, the most frequently wounded nerve was median nerve (32.3%), followed by ulnar (24.1%), radial (12.1%), sciatic (10.7%) and peroneal nerves (7.7%), and brachial plexus (7.7%). Simple decompression was the most preferred technique for nerve repair in 27.8%. The electrophysiological improvement was observed in 66.8%, as assessed by electromyography. Clinical improvement was found in 58.4%, as judged by muscle strength grading. If the nerve is compressed or contused, but remains intact, the improvement is satisfactory after surgery. The type of injury, its time of occurrence, initial deficit, and degree of recovery expected are important issues in establishing the treatment plan, which may range from skilled observation to extensive surgical intervention.


Predicting prostate carcinoma volume and stage at radical prostatectomy by assessing needle biopsy specimens for percent surface area and cores positive for carcinoma, perineural invasion, Gleason score, DNA ploidy and proliferation, and preoperative serum prostate specific antigen: a report of 454 cases.
DNA ploidy analysis of prostate carcinoma is a generally accepted prognostic marker, particularly when tumors are extraprostatic at the time of surgery. In the past decade, the DNA content of prostate carcinoma frequently has been assessed in needle biopsy specimens based on the assumption that ploidy, in conjunction with serum prostate specific antigen (PSA) and Gleason score, provides valuable pretreatment information. Between 1995 and 1998, the authors identified a consecutive series of 454 prostate carcinomas, verified by needle biopsies and followed by radical retropubic prostatectomies (RRP). Based on the needle biopsies, DNA ploidy and MIB-I immunostaining were measured by digital image analysis (DIA). The authors also quantified the percent of nuclei in four categories from the DNA histograms. The DIA data were combined with the age of the patient at diagnosis, the serum PSA, Gleason score, percent cores and percent surface area positive for carcinoma, and status of perineural invasion in multivariate models using tumor volume and risk of extraprostatic extension (EPE) at RRP as the outcome variables. Joint predictors of tumor volume at RRP were the percent cores positive for carcinoma (P < 0.0001), serum PSA (P < 0.0001), the percent surface area positive for carcinoma (P < 0.0001), and the percent nuclei classified by DNA quantification to be in the "S-phase" category (P = 0.03). Joint predictors of risk of EPE were the percent cores positive for carcinoma (P = 0.0004), a Gleason score of 7 (P < 0.0001), a Gleason score of 8 or 9 (P < 0.0001), serum PSA (P = 0.006) and perineural invasion (P = 0.02). After adjusting for traditional prognostic markers, DNA ploidy interpretation and MIB-I quantitation of prostate carcinoma did not appear to jointly predict either outcome variable in the multivariate models. However, a quantitative measure related to both ploidy and proliferation, the percent of nuclei in the putative "S-phase" category from the DIA histograms, was found to jointly predict for tumor volume.


A computational study of the protonation of simple amines in water clusters.
The microsolvation study of a group of amines with a variable number of water molecules was performed by conducting a theoretical analysis of the properties of the clusters formed by the amines with up to seven molecules of water. We describe the microsolvation of several amines focusing on the dissociation of a water molecule that transfers a proton to the amine and forms a hydroxide ion. Ab initio calculations were performed on these clusters employing the DFT/B3LYP and MP2 methods with the 6-311++G(2d,p) basis set. Several stationary points for each cluster were thus located and characterized as minima from frequency calculations. Intermolecular BSSE corrected interaction energies were obtained. The protonation mechanism of the amines was examined in terms of some parameters that include the lengths of the bonds involved in the process of proton transfer and the frequencies associated with certain O-H and N-H stretching modes. On the basis of the calculations, all studied amines present similar behavior but trimethylamine, whose limitations to be integrated in the water hydrogen bond network cause the instability of some of their complexes. The cyclic configurations are the most stable structures up to five water molecules due to the presence of cooperative effects associated with the hydrogen bonds of water molecules. However, when the number of water molecules increases the spatial forms become the most stable configurations. The dissociated forms were not found to have the most stable configuration in any of the studied systems but energetic differences between the dissociated and non-dissociated forms decrease with the number of water molecules.


Trends in hip fracture incidence and mortality in Chinese population from Hong Kong 2001-09.
there is a suggestion that while the age-adjusted incidence of hip fracture in the West may be declining, the incidence may be rising in Asia. this study examines the incidence and post-fracture mortality from 2001 to 2009 among the population aged 65 years and over. hip fracture incidence rates and case-fatality rates among Hong Kong population aged 65 and over for the period 2001-09 were obtained from the Hong Kong Hospital Authority (HA) database. Rates were adjusted for age. Poisson and logistic regressions were used to examine trends in incidence and post-fracture mortality, respectively. the age-adjusted incidence rate of hip fracture among the population aged 65 and over in Hong Kong (per 100,000 population) decreased from 381.6 for men and 853.3 for women in 2001 to 341.7 and 703.1, respectively, in 2009. There were no significant changes in post-fracture mortality trends. there is a downward trend in age-specific hip fracture incidence rates since 2001 among Hong Kong Chinese, but no change in post-fracture mortality trends.


Impact of ventilator-associated pneumonia on resource utilization and patient outcome.
To assess the effect of ventilator-associated pneumonia on resource utilization, morbidity, and mortality. Retrospective matched cohort study based on prospectively collected data. Medical intensive care unit of a university teaching hospital. Case-patients were all patients receiving mechanical ventilation for 48 hours or more who experienced an episode of ventilator-associated pneumonia. Control-patients were matched for number of discharge diagnoses, duration of mechanical support before the onset of pneumonia among case-patients, age, admission diagnosis, gender, and study period. One hundred six cases of ventilator-associated pneumonia were identified in 452 patients receiving mechanical ventilation. The matching procedure selected 97 pairs. Length of stay in the intensive care unit and duration of mechanical ventilation were greater among case-patients by a mean of 7.2 days (P< .001) and 5.1 days (P< .001), respectively. Median costs were $24,727 (interquartile range, $18,348 to $39,703) among case-patients and $17,438 (interquartile range, $12,261 to $24,226) among control-patients (P < .001). The attributable mortality rate was 7.3% (P = .26). The attributable extra hospital stay was 10 days with an extra cost of $15,986 per episode of pneumonia. Ventilator-associated pneumonia negatively affects patient outcome and represents a significant burden on intensive care unit and hospital resources.


Netropsin . dG-dG-dA-dA-dT-dT-dC-dC complex. Antibiotic binding at adenine . thymine base pairs in the minor groove of the self-complementary octanucleotide duplex.
The structure of the netropsin . dG-dG-dA-dA-dT-dT-dC-dC complex (one antibiotic molecule/self-complementary octanucleodide duplex) and its dynamics as a function of temperature have been monitored by the nuclear magnetic resonances of the Watson-Crick protons, the nonexchangeable base and sugar protons and the backbone phosphates. The antibiotic forms a complex with the nucleic acid duplex at the dA . dT-containing tetranucleotide segment dA-dA-dT-dT, with slow migration amongst potential binding sites at low temperature. The downfield shifts in the exchangeable protons of netropsin on complex formation demonstrate the contributions of hydrogen-bonding interactions between the antibiotic and the nucleic acid to the stability of the complex. Complex formation results in changes in the glycosidic torsion angles of both thymidine residues and one deoxyadenosine residue as monitored by chemical shift changes in the thymine C-6 and adenine C-8 protons. The close proximity of the pyrrole rings of the antibiotic and the base-pair edges in the minor groove is manifested in the downfield shifts (0.3--0.5 ppm) of the pyrrole C-3 protons of netropsin and one adenine C-2 proton and one thymine N-3 base-pair proton on complex formation. The internucleotide phosphates of the octanucleotide undergo 31P chemical shift changes on addition of netropsin and these may reflect, in part, contributions from electrostatic interactions between the charged ends of the antibiotic and the backbone phosphates of the nucleic acid.


Adrenal insufficiency in the surgical intensive care unit patient.
Adrenocortical dysfunction is unusual in the unselected critically ill patient. Case reports document a state of corticosteroid responsive vasopressor dependence, resembling the systemic inflammatory response syndrome. The exact incidence of this disorder is unknown. We prospectively studied the incidence of adrenal insufficiency during a 9-month period in a surgical intensive care unit (ICU) population. Trauma, general surgery, urology, and gynecologic-oncology patients were included. Patients who met criteria were given a cosyntropin stimulation test. Overall, the incidence of adrenal insufficiency was 0.66%. In the subgroup of patients with greater than 14 days stay in the ICU, 6% were found to have adrenal insufficiency. In patients aged more than 55 years and with ICU stays of 14 days or greater, 11% were adrenally insufficient. Screening of critically ill patients for adrenal insufficiency, particularly those with prolonged ICU stay and age greater than 55 years, is warranted.


The impact of gestational age on dysmaturity/postmaturity.
The medical records of 403 infants admitted to the neonatal intensive care unit were reviewed. All were postterm (greater than or equal to 42 weeks' gestation) infants or infants who were full term (greater than or equal to 38 weeks' gestation) and had clinical diagnoses associated with the neonatal postmaturity/dysmaturity syndrome. Data collected from these 403 records were used to generate frequency distribution tables for a variety of obstetric and neonatal outcome variables. Regression analyses were used to assess associations among these variables and the presence or absence of fetal malnutrition (dysmaturity) or postdatism. Fetal distress and neonatal acidosis were associated with both dysmaturity and postdatism. Primigravidas, meconium-stained amniotic fluid, cesarean section, birth trauma, and neonatal death were associated with postdatism but not with dysmaturity. Preeclampsia, maternal smoking, oligohydramnios, low Apgar score, neonatal pulmonary hypertension, neurologic abnormalities, and a need for extracorporeal membrane oxygenation were associated with dysmaturity. No interaction between postdatism and dysmaturity was seen for any outcome variable. Postdatism and dysmaturity appear to contribute risk factors independently to infants admitted to the intensive care unit.