Interleukin-18 induces production of proinflammatory cytokines in mice: no intermediate role for the cytokines of the tumor necrosis factor family and interleukin-1beta.
Interleukin-18 (IL-18) is not only a co-stimulus for the induction of interferon-gamma but also has direct proinflammatory effects by inducing tumor necrosis factor-alpha (TNF-alpha), IL-1, IL-8 and IL-6. However, the cascade of events leading to induction of cytokines by IL-18 is unclear. The aim of the present study was to investigate whether murine IL-18 stimulates production of proinflammatory cytokines, and to assess whether induction of second-wave cytokines such as IL-6 by IL-18 is driven by intermediary induction of endogenous cytokines of the TNF family or IL-1beta. When mouse peritoneal macrophages were stimulated in vitro with recombinant murine IL-18, there was a dose-dependent induction of TNF, IL-1alpha, and IL-1beta. IL-6 synthesis was also strongly induced by IL-18 and, as revealed by studies in knockout mice, this production was not dependent on interactions between endogenous cytokines of the TNF/TNF receptor family: TNF-alpha, lymphotoxin-alpha, Fas/Fas ligand (L) or CD40/CD40L. Moreover, the induction of IL-6 was also independent of endogenous IL-1beta, as macrophages isolated from IL-1beta deficient mice produced normal amounts of IL-6 after stimulation with IL-18. In conclusion, murine IL-18 has pleiotropic proinflammatory activities by inducing production of TNF-alpha, IL-1alpha, IL-1beta and IL-6, which could have important consequences for the pathophysiology of infectious and autoimmune diseases.


A retrospective comparative study of in-hospital management of acute severe asthma: 1984 vs 1989.
Recent controversies examining the management of acute asthma prompted us to investigate whether there had been any significant changes in our management practices. We therefore audited the charts of all patients admitted to a large tertiary-care university-affiliated hospital with a primary diagnosis of acute asthma during the years of 1984 and 1989. A total of 67 patients' charts were reviewed (39 in 1984 and 28 in 1989). The mean age and initial flow rates (FEV1 or peak expiratory flow rate [PEFR]) were similar. In the emergency room, chest radiographs and arterial blood gas analyses were done more frequently than objective measures of flow. Fifty-one percent (20/39) of the patients had no measurement of flow in the emergency room in 1984 and 39 percent (11/28) in 1989 (p > 0.05). In both years, approximately 20 percent of the patients had no record of flow rates during their hospitalization (21 percent [8/39] in 1984 and 18 percent [5/28] in 1989). More studies of the blood were ordered in 1989, including hepatic enzyme and electrolyte measurements for no clear reasons. The clinical utility of chest radiographs was negligible. While the vast majority of patients received systemic corticosteroids in both years (85 percent [33/39] in 1984 and 96 percent [27/28] in 1989), 23 percent (9/39) and 18 percent (5/28) were discharged without oral steroid therapy in 1984 and 1989, respectively (p > 0.05). There was a significant decline in the use of aminophylline (95 percent [37/39] to 54 percent [15/28]; p < 0.05) and an increase in the use of ipratropium bromide (15 percent [6/39] to 75 percent [21/28]; p < 0.05) in 1989. Theophylline levels were less likely to be measured in 1989, and the majority of levels in both years were either subtherapeutic or toxic. No patients were discharged with peak flow meters or recorded action plans, although follow-up arrangements were recorded in 87 percent (34/39) and 96 percent (27/28) of the patients in 1984 and 1989. We conclude that while improvements in in-hospital management of asthma were noted in 1989, suboptimal management practices are still common.


A fatal cause of sexual inadequacy in men: adreno-leukodystrophy.
Diminished libido, impotence and infertility have been detected in 5 of 6 men with adreno-leukodystrophy, a universally fatal disease. The importance of the clinical recognition of these patients and their separation from others with relatively innocuous causes of testicular dysfunction are discussed.


Evaluation of a diphtheria and tetanus PLGA microencapsulated vaccine formulation without stabilizers.
Polymeric microspheres containing diphtheria and tetanus toxoids were prepared without protein stabilizers. A vaccine containing 2 Lf(tetanus) and 0.4 Lf(diphtheria) was injected either in BALB/c mice or in guinea-pigs. As control, a group received the alum-adsorbed unencapsulated toxoids. In mice, on day 44 one group and control received a booster and at day 111 the other group received the same booster dose. Before de booster, all groups had very low neutralizing antibodies, as determined by Toxin binding inhibition assay. One week after booster all groups had high antibody titers, especially those immunized with microencapsulated vaccine, which were at least 5 times higher than those immunized with alum vaccine for both antigens. Besides, guinea pigs receiving lower dose had antibodies titers as high as 60 UI/mL, and 30 times higher than those immunized with alum vaccine. Therefore by using an encapsulated vaccine without any kind of protein stabilizer we were able to induce in vivo protective responses irrespective of observed in vitro protein degradation by HPLC. Manipulating the vaccination schedule at the same time to the toxoids encapsulation does not only increase the antibody titers but also their specificity.


Total synthesis of dimeric pyrrole-imidazole alkaloids: sceptrin, ageliferin, nagelamide e, oxysceptrin, nakamuric acid, and the axinellamine carbon skeleton.
The dimeric pyrrole imidazole natural products are a growing class of alkaloids with exotic connectivity, unique topologies, high nitrogen content, and exciting bioactivities. This full account traces the evolution of a strategy that culminated in the first total syntheses of several members of this family, including sceptrin, ageliferin, nagelamide E, nakamuric acid (and its methyl ester), and oxysceptrin. Details on the fascinating conversion of sceptrin to ageliferin, which has been used to produce gram quantities of this sensitive natural product, are provided. In addition, the first enantioselective total synthesis of sceptrin and ageliferin are reported by programming the fragmentation of an oxaquadricyclane. A hallmark of our approach to this family of alkaloids is the minimal use of protecting groups despite the presence of 10 nitrogen atoms in the target compounds. Thus, the fundamental chemistry of the 2-aminoimidazole heterocycle was explored without masking its innate reactivity. Insights gained during these explorations led to total syntheses of oxysceptrin and nakamuric acid and a successful construction of the carbon skeleton of axinellamine.


Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET.
Chemotherapy is currently the treatment of choice for patients with high-risk metastatic breast cancer. Clinical response is determined after several cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures including CT, MRI, plain film radiography, or ultrasound. The aim of this study was to evaluate the use of sequential 18F-FDG PET to predict response after the first and second cycles of standardized chemotherapy for metastatic breast cancer. Eleven patients with 26 metastatic lesions underwent 31 (18)F-FDG PET examinations (240-400 MBq of 18F-FDG; 10-min 2-dimensional emission and transmission scans). Clinical response, as assessed by conventional imaging after completion of chemotherapy, served as the reference. 18F-FDG PET images after the first and second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients' blood glucose levels. In addition, whole-body 18F-FDG PET images were viewed for overall changes in the 18F-FDG uptake pattern of metastatic lesions within individual patients and compared with conventional imaging results after the third and sixth cycles of chemotherapy. After completion of chemotherapy, 17 metastatic lesions responded, as assessed by conventional imaging procedures. In those lesions, SUV decreased to 72% +/- 21% after the first cycle and 54% +/- 16% after the second cycle, when compared with the baseline PET scan. In contrast, 18F-FDG uptake in lesions not responding to chemotherapy (n = 9) declined only to 94% +/- 19% after the first cycle and 79% +/- 9% after the second cycle. The differences between responding and nonresponding lesions were statistically significant after the first (P = 0.02) and second (P = 0.003) cycles. Visual analysis of 18F-FDG PET images correctly predicted the response in all patients as early as after the first cycle of chemotherapy. As assessed by 18F-FDG PET, the overall survival in nonresponders (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). In patients with metastatic breast cancer, sequential 18F-FDG PET allowed prediction of response to treatment after the first cycle of chemotherapy. The use of 18F-FDG PET as a surrogate endpoint for monitoring therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.


[Genetic evidence for recombination and mutation in the emergence of human enterovirus 71].
We wished to understand the genetic recombination and phylogenetic characteristics of human en- terovirus A71 (EV-A71) and to explore its potential virulence-related sites. Full-length genomes of three EV-A71 strains isolated from patients in Chenzhou City (China) were sequenced and analyzed. Possible re- combination events and crossover sites were analyzed with Recombination Detection Program v4. 1. 6 by comparison with the complete genome sequences of 231 strains of EV-A71. Similarly, plot and bootscanning analyses were undertaken with SimPlot v3. 5. 1. Phylogenetic trees based on the sequences of VP1 regions were constructed with MEGA v5. 2 using the Kimura two-parameter model and neighbor-joining method. Results suggested that recombination events were detected among the three EV-A71 isolates from Chenzhou City. The common main parent sequence was from JF799986 isolated from samples in Guang- zhou City (China) in 2009, and the minor parent sequence was TW/70516/08. Intertypic recombination e- vents were found in the C4b strain (strain SHZH98 isolated in 1998) and C4a strain (Fuyang strain isola- ted in 2008) with the prototype strains of CVA4 and CVA14 in the 3D region. The chi-square test was used to screen-out potential virulence-related sites with nucleotide substitutions of different types of hand, foot, and mouth disease (HFMD) cases using SPSS v19.0. Results suggested that there were no significant nucleotide substitutions between death cases and severe-HFMD cases. Eighteen significant nucleotide substitutions were found between death/severe-HFMD cases and mild-HFMD cases, and all these 18 substitutions were distributed only in P2 and P3 regions. Intertypic recombination among the predominant circulating EV-A71 strains in the Chinese mainland and other EV-A strains probably dates before 1998, and intratypic recombination might have occurred frequently in the HFMD outbreak from 2008 to 2012. Substitutions in the non-capsid region may be correlated with the changes in virulence of EV-A71. These data suggest that researchers should pay more attention to the relationships between substitutions in the noncapsid region and the virulence of the virus.


Gas chromatographic determination of zopiclone in plasma after solid-phase extraction.
A gas chromatographic technique for determining zopiclone based on a solid-phase extraction procedure with C18 cartridge for sample clean-up is presented. Quantification can be achieved with 1 ml of plasma. The method uses prazepam as internal standard. Zopiclone is separated on a 5% phenyl methyl silicone analytical column and detected with an electron-capture detector, which consequently allows a limit of quantitation of 2 micrograms/l. It is thus simple, rapid, sensitive and linear over the range 5-2000 micrograms/l.


Agrobacterium rhizogenes-induced cotton hairy root culture as an alternative tool for cotton functional genomics.
Although well-accepted as the ultimate method for cotton functional genomics, Agrobacterium tumefaciens-mediated cotton transformation is not widely used for functional analyses of cotton genes and their promoters since regeneration of cotton in tissue culture is lengthy and labor intensive. In certain cases, A. rhizogenes-induced hairy root culture has been a suitable molecular tool for functional analyses of genes and promoters for plants that are difficult to regenerate by A. tumefaciens-mediated transformation. Similarly, A. rhizogenes-induced hairy root cultures are an alternative tool for cotton functional genomics. In this chapter, the advantages and disadvantages of using A. rhizogenes-induced cotton hairy root culture over A. tumefaciens-mediated cotton transformation are discussed. The procedures for transformation, generation, selection, and molecular analyses of transgenic cotton hairy roots are introduced by describing the functional analysis of a cotton promoter in cotton hairy roots generated by A. rhizogenes-mediated transformation.


Associations between viral infections and respiratory disease in artificially reared calves.
Market-purchased, week-old, dairy bred calves entering a commercial calf-rearing unit were blood sampled at six-week intervals until three months old. Viral infections were monitored by ELISA for antibodies to bovine herpesvirus 1, bovine respiratory syncytial virus, parainfluenzavirus-3, bovine adenovirus subgroup 1 and bovine viral diarrhoea virus (BVDV). The immunoperoxidase test was used to detect BVDV in serum. The total immunoglobulin concentration in the initial blood sample was measured by the zinc sulphate turbidity test. The relationship between clinical respiratory disease, viral seroconversion and the initial concentration of serum immunoglobulin was investigated by the use of the relative risk statistic, Fisher's exact test, chi 2 techniques and the correlation coefficient. Treatment rates for respiratory disease of 45 per cent were observed during the first period of the study and 19 per cent during the second period. During the first period there was a significant positive association between clinical respiratory disease and seroconversion for all the viruses except parainfluenzavirus-3 and BVDV but in the second period there was no such relationship. Similarly, in the first period, but not in the second, there was a significant negative association between clinical respiratory disease and both antiviral immunoglobulin as measured by ELISA and total immunoglobulin as measured by the zinc sulphate turbidity test. Two of the 536 calves that survived to three months of age were found to be persistently infected with BVDV.


Does growth hormone cause cancer?
The ability of GH, via its mediator peptide IGF-1, to influence regulation of cellular growth has been the focus of much interest in recent years. In this review, we will explore the association between GH and cancer. Available experimental data support the suggestion that GH/IGF-1 status may influence neoplastic tissue growth. Extensive epidemiological data exist that also support a link between GH/IGF-1 status and cancer risk. Epidemiological studies of patients with acromegaly indicate an increased risk of colorectal cancer, although risk of other cancers is unproven, and a long-term follow-up study of children deficient in GH treated with pituitary-derived GH has indicated an increased risk of colorectal cancer. Conversely, extensive studies of the outcome of GH replacement in childhood cancer survivors show no evidence of an excess of de novo cancers, and more recent surveillance of children and adults treated with GH has revealed no increase in observed cancer risk. However, given the experimental evidence that indicates GH/IGF-1 provides an anti-apoptotic environment that may favour survival of genetically damaged cells, longer-term surveillance is necessary; over many years, even a subtle alteration in the environmental milieu in this direction, although not inducing cancer, could result in acceleration of carcinogenesis. Finally, even if GH/IGF-1 therapy does result in a small increase in cancer risk compared to untreated patients with GH deficiency, it is likely that the eventual risk will be the same as the general population. Such a restoration to normality will need to be balanced against the known morbidity of untreated GH deficiency.


Alterations of the cell cycle regulators cyclin D1, cyclin A, p27, p21, p16, and pRb in apocrine metaplasia of the breast.
G1/S transition defects have been a proposed requirement for tumor development. Apocrine metaplasia (APM) in the breast has been held as a sign of benignity. Yet, a number of studies have reported the presence of molecular abnormalities in some forms of APM suggesting a possible oncogenic potential for some of these lesions. We currently investigate the role of some of the cell cycle proteins, previously reported to be de-regulated in breast cancer, in an attempt to assess their significance in APM. Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki-67 was examined in 93 cases of APM. The cases were divided into nonpapillary (NAPM) (30 cases) and papillary metaplasia (PAPM) (63 cases). PAPM was further subdivided into simple papillary (SPAPM) (29 cases), complex papillary (28 cases) and highly complex papillary (six cases). For statistical analysis, the last two groups were merged together (CPAPM). The results showed that increased histological complexity was associated with significant increase of proliferative capacity and alterations of the cell cycle control. The median Ki-67 index was 1.5% in SPAPM and 4.8% in the CPAPM. Also, alterations of the cell cycle regulators were significantly higher in the CPAPM than in the SPAPM. NAPM was generally similar to normal breast epithelium. Apocrine cells were negative for p16 while pRb was expressed in all cases. These findings suggest that in complex forms of APM, there is a considerable degree of cellular unrest. This may contribute to increased susceptibility to carcinogenesis.


Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology.
We performed a systematic immunohistochemical study on 378 brain tumors using 37 antibodies and tissue microarray (TMA) technology. The aim of this study was to find new diagnostic biomarkers using antibodies established in our laboratory. Our TMA consisted of a grid of 1.5-mm cores that were extracted from individual donor blocks. Staining for each antibody was scored using a three-point system. We used hierarchical clustering analysis to interpret these data, which resulted in separation of all the brain tumors into seven groups. Although there were some exceptions, cases with the same histological diagnosis were generally grouped together. We then carried out statistical analyses to find the most useful antibodies for grouping of brain tumors. Ten antibodies [glial fibrillary acidic protein (GFAP), Olig2, vimentin, epithelial membrane antigen (EMA), cytokeratin (AE1/AE3), alpha-internexin, nestin, pinealocytes PP5, aquaporin-4 (AQP4) M13d and AQP4M13e] discriminated between astrocytomas and oligodendroglial tumors. Six antibodies [EMA, AE1/AE3, TUJ1, nestin, neurofilament protein-MH (NF-MH) and perivascular cells GP-1] showed significant differences between high-grade and low-grade gliomas. Our data have revealed new antibodies with potential diagnostic utility (Olig2, PP5, GP-1) and demonstrate that TMA technology is highly useful for evaluating newly established antibodies in brain-tumor research.


Transport of messenger RNA into different classes of membrane-associated polyribosomes in Ehrlich-ascites-tumor cells.
The membrane-bound polyribosomes in Ehrlich ascites tumor cells can be separated into a loosely bound and a tightly bound fraction by means of a high salt treatment. Both membrane fractions as well as the free polyribosomes in the supernatant synthesize about the same set of proteins, suggesting a close relationship between these polyribosome fractions in the Ehrlich cell. Relatively high concentrations of cycloheximide do not prevent newly synthesized poly(A)-containing mRNA from entering the tightly bound polyribosome fraction. Nor had treatment of the cells with puromycin in the presence of cycloheximide, which released about 70% of the nascent chains, any significant effect on the entrance of newly synthesized mRNA into tightly bound polyribosomes. These results suggest that in ehrlich ascites tumor cells nascent polypeptide chains are not involved in the binding of polyribosomes to membranes.


Evaluation of the gut mucosal barrier: evidence for increased antigen transfer in children with atopic eczema.
Intestinal antigen handling determines subsequent immune response to the antigen. Antigens are absorbed across epithelium along two functional pathways. The main pathway is degradative, which reduces the immunogenicity of the antigen. A minor pathway allows the transport of intact proteins, which is crucial for antigen-specific immune responses. The Ussing chamber method allows the quantitative measurement of protein transfer across the intestinal mucosa. This study was designed to explore the theory that altered antigen transfer across the intestinal mucosa is a factor in the pathogenesis of atopic eczema, characterized by hyperactivity to environmental antigens. The absorption and degradation of horseradish peroxidase (molecular weight, 40,000 d) were studied in vitro in Ussing chambers. Eighteen biopsy specimens of upper small intestinal mucosa from 14 patients (aged 0.5 to 8 years) with atopic eczema and 18 specimens from 15 age-matched control subjects were examined. The mean (95% confidence interval) absorption of intact horseradish peroxidase was significantly higher in children with atopic eczema than in control subjects: 242 (81-404) pmol . hr(-1) . cm(-2) versus 23 (12-33) pmol . hr(-1) . cm(-2); t = 2.86, p = 0.007. The absorption of degraded horseradish peroxidase was 972 (732-1213) pmol . hr(-1) . cm(-2) in patients with atopic eczema and 672 (532-811) pmol . hr(-1) . cm(-2) in control subjects; t = 2.29, p = 0.03. Our results may reflect a primarily altered antigen transfer in patients who have atopic eczema, which may initiate and perpetuate prompt immune responses to common environmental antigens, including foods.


Encouraging Mindfulness in Medical House Staff via Smartphone App: A Pilot Study.
Stress and burnout are increasingly recognized as urgent issues among resident physicians, especially given the concerning implications of burnout on physician well-being and patient care outcomes. The authors assessed how a mindfulness and meditation practice among residents, supported via a self-guided, smartphone-based mindfulness app, affects wellness as measured by prevalidated surveys. Residents in the departments of general surgery, anesthesia, and obstetrics and gynecology were recruited for participation in this survey-based, four-week, single-arm study. All participants used the app (Headspace) on a self-guided basis, and took surveys at enrollment, at 2 weeks, and at 4 weeks. The Positive and Negative Affect Schedule (PANAS) assessed mood, and the Freiburg Mindfulness Inventory (FMI) measured mindfulness. Forty-three residents enrolled in this study from April 2015 to August 2016; 30 residents (90% female) completed two or more surveys, and so were included for further analysis. In a comparison of baseline scores to week four scores, there was a significant increase in FMI at week four (36.88 ± 7.00; Cohen's d = 0.77, p = 0.005), a trend toward increase in the positive affect score (PAS) (31.73 ± 6.07; Cohen's d = 0.38, p = 0.08), and no change in negative affect score (NAS) (21.62 ± 7.85; Cohen's d = -0.15, p = NS). In mixed-effect multivariate modeling, both the PAS and the FMI scores showed significant positive change with increasing use of the smartphone app (PAS, 0.31 (95% CI 0.03-0.57); FMI, 0.38 (95% CI 0.11-0.66)), while the NAS did not show significant change. Study limitations include self-guided app usage, a homogenous study subject population, insufficient study subjects to perform stratified analysis of the impact of specialty on the findings, lack of control group, and possible influence from the Hawthorne effect. This study suggests the feasibility and efficacy of a short mindfulness intervention delivered by a smartphone app to improve mindfulness and associated resident physician wellness parameters.


Analgesic ingestion and chronic peptic ulcer.
The patterns of analgesic ingestion in gastric and duodenal ulcer patients were compared with those of matched community controls in order to ascertain differences that may exist between ulcer and nonulcer subjects of comparable age and sex. The differences sought concerned amounts and types of analgesics ingested. The types of analgesics studied were aspirin and acetaminophen, ingested either alone or together. Analgesics such as dextropropoxyphene and codeine were disregarded. It was found that there was a strong positive association between heavy analgesic intake and chronic gastric ulcer with a relative risk of 29.5. The association was most marked in female patients (relative risk = 51.8). The involvement of aspirin-containing and acetaminophen-containing drugs was of similar significance with relative risk of 17.3 and 24.4, respectively. Aspirin alone was the least frequently ingested. The association was only partly related to painful nonulcer health problems and to ulcer pain. No association was found between chronic duodenal ulcer and analgesic intake. The strong association found between gastric ulcer and heavy analgesic intake does not, per se, necessarily indicate a causal relationship.


Hepatitis C virus: quantitation and distribution in liver.
The optimal method for viral quantitation and the most appropriate site for determining viral load in patients with chronic hepatitis C virus (HCV) infection are unknown. We developed a method for measuring HCV RNA in the liver with the following features: 1) efficient extraction of RNA from tissue (89% of RNA recovered); 2) accurate amplification using branched DNA with strong concordance between a single sample tested on multiple occasions either in the same or in different runs; 3) good sensitivity (95%) and specificity (100%). HCV RNA was detected in as little as 2 mg of tissue, and viral load determined in a needle biopsy was representative of viral load in other parts of the liver. Within individual livers, 68% of the samples quantitated were within 1.5-fold of the geometric mean, and 95% were within 2.2-fold of the geometric mean. The mean ratio of virus in the liver and serum was 103, range 17.4-286. A delay of 30 minutes before freezing the liver tissue resulted in a reduction in the measured viral load in some, but not all instances. A sensitive, specific and reproducible method for quantitating HCV RNA in the liver has been developed. Measurement of viral load at one site was representative of viral load at other sites. While hepatic HCV RNA levels are consistently greater than serum levels, the ratio of liver of serum viral load varies widely. The clinical use of measurement of viral load in the liver remains to be defined.


Effect of arousal on sympathetic overactivity in patients with obstructive sleep apnea.
Obstructive sleep apnea (OSA) is associated with sympathetic overactivity. Intermittent hypoxemia and repetitive arousals are the proposed mechanisms; however, the main contributing factor for sympathetic overactivity remains to be determined. We therefore investigated the independent effect of apnea or arousal on sympathetic activity in a large cohort of OSA patients using heart rate variability analysis. Frequency domain heart rate variability parameters were measured and compared between 782 patients with OSA (198 mild, 259 moderate, 325 severe) and 119 non-OSA controls. Univariate analysis was performed to identify associations between clinical and polysomnographic variables and heart rate variability measurements. Multivariate analysis was further performed to determine the potential contributing factors for sympathetic overactivity. Patients with OSA exhibited overall alterations in heart rate variability measures indicating sympathetic overactivity compared to controls, and this tendency was more pronounced in those with severe OSA. Univariate analysis showed that both apnea-hypopnea and arousal indices correlated with increased sympathetic activity and decreased parasympathetic activity. In multivariate analysis, arousal index was found to be more closely associated with sympathetic overactivity than apnea-hypopnea index. The present study showed that arousal may be a more potent contributing factor than apnea for sympathetic overactivity in OSA patients. Our results suggest that arousal index, rather than apnea-hypopnea index, could be considered as a surrogate marker for sympathetic overactivity in OSA. Further longitudinal studies should elucidate causal relationship between arousals and sympathetic overactivity in patients with OSA.


Committee opinion. Induction of labor for vaginal birth after cesarean delivery.
A recent population-based study of vaginal birth after cesarean delivery (VBAC) attempts observed uterine rupture rates of 24.5 per 1,000 with prostaglandin-induced labor, while the uterine rupture rates with spontaneous labor and labor induced without prostaglandins were lower (5.2/1,000 and 7.71/1,000 respectively). The authors did not confirm the diagnoses by examining individual medical records, so the actual incidence of uterine rupture may have been overstated. Despite this limitation, the Committee on Obstetric Practice concludes that the risk of uterine rupture during VBAC attempts is substantially increased with the use of various prostaglandin cervical ripening agents for the induction of labor, and their use for this purpose is discouraged.


[Annexins and recurrent pregnancy loss].
Recurrent Pregnancy Loss (RPL) affects public health and directly compromises the quality of life of hundreds of women, with a detrimental effect on their physical and mental health. Approximately 50% of RPL are not associated to any of the currently known etiology and will be considered idiopathic. Recently, it has been demonstrated that the expression of annexin 5 (ANXA5), a protein found on the trophoblastic surface, plays a fundamental role in the development of pregnancy due to its immunomodulator and anticoagulant function at the placentary level. Some genetic haplotypes of ANXA5 are associated to alterations in the expression of this gene, such as haplotype M2 which is associated to a decrease in the expression of ANXA5. The presence of this haplotype is related to the following conditions occurring during pregnancy: RPL, foetal intrauterine growth restriction, low child weight at birth, preeclampsia and maternal pulmonary thromboembolism. This review describes the structure, function and genetic expression of ANXA5, as well as its possible implication in RPL.


Antiplasmodial constituents from the fruit pericarp of Pentadesma butyracea.
Bioassay-guided fractionation of the fruit pericarp of Pentadesma butyracea, using the antiplasmodial test, led to the isolation of a new xanthone, named pentadexanthone (1), together with six known compounds: cratoxylone (2), α-mangostin (3), 1,3,5-trihydroxy-2-methoxyxanthone (4), garcinone E (5), (-)-epicathechin (6), and lupeol (7). The structure of 1 was elucidated by spectroscopic data analysis. An antiplasmodial assay was performed with the isolates, in which compounds 1- 3 and 5 exhibited potent activity in vitro against Plasmodium falciparum chloroquine-resistant strain W2, with IC₅₀ values below 3 µM.


Genetic analysis in Leber's hereditary optic neuropathy using the comparative genomic hybridization technique.
Nuclear genes are suggested to be involved in the pathogenesis of Leber's hereditary optic neuropathy (LHON) but it has not been confirmed. The aim of the present study was to investigate chromosomal abnormalities associated with LHON. In a prospective study, comparative genomic hybridization (CGH) was used to analyse genetic changes in five patients with LHON with an 11778 mitochondrial DNA mutation and three asymptomatic maternal relatives. There were no significant genetic copy number alterations detected in the five visually affected patients or in the three unaffected maternal relatives as compared to unrelated normal controls. The CGH technique did not detect any chromosomal abnormalities in LHON patients or in unaffected relatives. Nuclear gene involvement, however, cannot be ruled out.


Alpha-blocking treatment with alfuzosin in symptomatic benign prostatic hyperplasia: comparative study with prazosin. The PRAZALF Group.
Alfuzosin, a selective alpha 1-adrenoceptor antagonist which is effective in the symptomatic treatment of benign prostatic hyperplasia (BPH), was compared with prazosin, another drug commonly used for the same purpose. After a 1-week placebo run-in period, 103 patients with day-time frequency > or = 7 or nocturia > or = 2 and peak flow rate < 15 ml/s were randomised to receive either alfuzosin (2.5 mg tid) or prazosin (2 mg bid) for 3 weeks, with a gradual dose increase during the first week, in a double-blind, parallel group, multicentre study. Voiding symptoms, assessed on the basis of the Boyarsky scale and a micturition diary, were significantly improved in both groups, as were urinary flow rates. However, neither the clinical improvement nor the increase in flow rates differed significantly between the 2 groups. The peak flow rate increased similarly with alfuzosin (2.6 +/- 0.6 ml/s) and prazosin (2.9 +/- 0.7 ml/s); the mean flow rate and voided volume increase tended to be more marked with alfuzosin (30 and 22.2% respectively) than with prazosin (20.6 and 6.5%). Clinical safety was good in both groups. All 4 adverse events in the prazosin group but only 1 of the 4 adverse events in the alfuzosin group were related to a decrease in blood pressure. It was concluded that alfuzosin was at least as effective as prazosin in the treatment of symptomatic patients with BPH and the incidence of adverse events related to their vasodilatory properties was lower with alfuzosin.


Spectral analysis of structure functions and their scaling exponents in forced isotropic turbulence.
The pseudospectral method, in conjunction with a technique for obtaining scaling exponents ζ_{n} from the structure functions S_{n}(r), is presented as an alternative to the extended self-similarity (ESS) method and the use of generalized structure functions. We propose plotting the ratio |S_{n}(r)/S_{3}(r)| against the separation r in accordance with a standard technique for analyzing experimental data. This method differs from the ESS technique, which plots S_{n}(r) against S_{3}(r), with the assumption S_{3}(r)∼r. Using our method for the particular case of S_{2}(r) we obtain the result that the exponent ζ_{2} decreases as the Taylor-Reynolds number increases, with ζ_{2}→0.679±0.013 as R_{λ}→∞. This supports the idea of finite-viscosity corrections to the K41 prediction for S_{2}, and is the opposite of the result obtained by ESS. The pseudospectral method also permits the forcing to be taken into account exactly through the calculation of the energy input in real space from the work spectrum of the stirring forces.


Loss of FBXW7 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.
FBXW7 acts as a tumor suppressor gene by targeting several oncogenic regulators of proliferation, growth and apoptosis for proteasomal degradation. However, the significance of this protein is not yet well understood in intrahepatic cholangiocarcinoma (IHCC). In this study, we aimed to investigate the correlation between FBXW7 expression and clinicopathological variables in IHCC patients. Thirty-one patients with IHCC who underwent hepatic resection were enrolled. FBXW7 expression in tumor tissue was determined by immunohistochemistry and patients were divided into two groups, the FBXW7 high expression group (n = 11) and the FBXW7 low expression group (n = 20). We then compared clinicopathological variables including prognosis between the high and low expression groups in tumor tissue. FBXW7 expression was significantly correlated with staging (P = 0.006), and tended to correlate with lymph node metastasis. The FBXW7 low expression group had significantly poorer prognosis compared with the FBXW7 high expression group (P = 0.020); 3-year survival rates were 29.4% and 72.7%, respectively. Furthermore, the disease-free survival rate in the FBXW7 low expression group was significantly worse than in the FBXW7 high expression group (P = 0.022). On multivariate analysis, intrahepatic metastasis (P = 0.006) was a significant independent prognostic factor for disease-free survival, and FBXW7 low expression tended to be an independent prognostic factor for both overall (P = 0.067) and disease-free survival (P = 0.083). Our results confirmed that low expression of FBXW7 in IHCC correlates with tumor progression and poor prognosis in IHCC.


Effects of sex, gender role identification, and gender relevance of two types of stressors on cardiovascular and subjective responses: sex and gender match and mismatch effects.
The authors tested the hypothesis that a match between the gender relevance of a stressor and one's sex or gender role identification would elicit higher cardiovascular responses. Healthy female and male undergraduates (n = 108) were exposed to two stressors: the Cold Pressor Test (CPT) and the n-back task. Stressor relevance was manipulated to be masculine or feminine relevant or gender neutral. Data were analyzed using a Bayesian model selection procedure. The results showed stronger cardiovascular responses for the CPT in the case of a gender match effect. In contrast, results for the n-back task revealed stronger cardiovascular responses for sex and gender mismatch effects. These discrepant match and mismatch effects are discussed in terms of differential task appraisal (i.e., threat vs. challenge). Additional results (a) support the success of measuring gender role identification indirectly by means of the Gender Implicit Association Test, (b) do not show that the effect of stressor relevance is more pronounced on those hemodynamic parameters typically increased by the stressor, and (c) reveal differential effects of stressor relevance for subjective and cardiovascular stress responses. Taken together, it can be concluded that the process of the cognitive appraisal of stressor relevance outlines individual variability in cardiovascular responding to acute stress.


[New development in mammographic technique: Grid mammography (author's transl)].
Reduced scatter through antiscatter grids and improved filmscreen combinations produce definite improvement in image quality with large breasts, as well as a reduction in radiation dose. The problems of soft tissue grid technique are discussed and a new apparatus for this purpose is described. New and improved recording systems, which reduce radiation dose, are analysed and a comparison is made between the quality of grid mammograms and conventional techniques using industrial film.


Microsurgical treatment for hypothalamic hamartoma in children with precocious puberty.
We review the surgical treatment of hypothalamic hamartoma causing precocious puberty. Six children (three girls and three boys) with precocious puberty secondary to hypothalamic hamartoma were recruited for our study. The mean age of the patients was 30 months old (range 13 months to 5 years), and the mean age of the onset of puberty was 7.3 months. All patients were treated by microsurgery. All patients had higher then normal stature, body weight, bone growth, and serum levels of sexual hormones. The boys presented with mature external genitalia, pubic hair, frequent erection, and acne, while the girls presented with growth of breasts and menarche. Magnetic resonance image (MRI) revealed an isointense mass below the tuber cinereum extending into the supersellar and interpeduncular cistern, ranging from 4 to 12 mm in diameter, consistent with pedunculate hamartoma. The hamartoma was removed completely via a right pterional approach. The symptoms and signs of precocious puberty resolved completely, and sexual hormone levels decreased to the pre-pubertal range in all six patients without any postoperative complications. We report a series of six children with hypothalamic hamartoma-induced precocious puberty who underwent microsurgical treatment. All of them recovered completely to their age-appropriate state. Microsurgery is a good choice of treatment for pedunculate hypothalamic hamartoma.


Oral ulcers in patients with advanced breast cancer receiving everolimus: a case series report on clinical presentation and management.
We report the clinical features and management outcomes in 7 patients with everolimus-related stomatitis. Fifteen women with hormone-receptor-positive advanced breast cancer receiving everolimus combined with exemestane were prospectively evaluated to assess the development of stomatitis. Oral ulcers were diagnosed based on established criteria. Seven patients developed stomatitis (46.6%). All patients were treated with topical dexamethasone solution, while everolimus was temporarily discontinued in 4 patients. Stomatitis resolved within 1-2 weeks. Two of the 4 patients, who had interrupted everolimus, developed recurrent stomatitis following drug resume and everolimus was again discontinued and restarted after 2 weeks. To date, 5 patients receive everolimus in full dose. The 2 patients, who developed recurrent stomatitis, received a reduced dose. Everolimus-related oral ulcers were frequent and led to dose modifications. Controlled trials, endorsing a consensus in terminology, are needed to evaluate measures on prevention and management of this unique toxicity.


KTP laser-resistant properties of the reinforced laryngeal mask airway.
We have assessed, in vitro, the effect of KTP laser strike on the reinforced laryngeal mask airway (RLMA) under a variety of conditions. At power densities normally encountered in clinical practice, using a divergent KTP laser beam, the RLMA could not be penetrated and did not ignite with laser strike. The RLMA was penetrated at a high power density of 6.94 W mm-2 after 45-60 s. A flame appeared over the RLMA shaft at this power density after 12-35 s. The black marker line on the RLMA shaft was somewhat more vulnerable to the effects of laser strike. The flow of oxygen and nitrous oxide within the shaft did not appreciably alter the laser-resistant properties of the RLMA. The RLMA cuff was more vulnerable to laser strike than was the shaft and was penetrated at very low power densities. Filling the cuff with saline had a protective effect and penetration did not occur at power densities which caused penetration of air-filled cuffs (0.37 W mm-2).


Hepatic stellate cell line modulates lipogenic transcription factors.
Pre-adipocyte differentiation into adipocyte is a terminal differentiation process triggered by a cascade of transcription factors. Conversely, hepatic stellate cells (HSC) can switch between lipid storing and the myofibroblast phenotype in association with liver fibrotic processes. Here, adipogenic/lipogenic-related transcription factors and downstream-regulated genes were evaluated in a murine HSC cell line. GRX-HSC cells are transitional myofibroblasts that differentiate into lipocytes following retinol or indomethacin treatment. Specific mRNAs were quantified by a real-time polymerase chain reaction after 24 h or 7 days of cell culture with indomethacin or retinol. Proliferator-activated receptorgamma and Pex16 transcripts were increased either by retinol or indomethacin. Retinol induced a minor increase in C/enhancer binding proteinalpha transcripts, while only indomethacin increased adipsin transcripts. Our results showed that the myofibroblast to lipocyte phenotype switch follows partially different transcriptional pathways, according to the effector. Retinol induces lipid synthesis and storage without affecting characteristic adipocytic genes, while indomethacin treatment restores the lipocytic phenotype with increased adipisin expression.


Effects of two simplified methods of dialysate sampling on estimations of adequacy indices in automated peritoneal dialysis.
To assess the effects of two simplified methods of dialysate sampling on the estimation of adequacy markers in automated peritoneal dialysis (APD). Cross-sectional noninterventional study. Tertiary-care hospital. Forty-nine patients undergoing standard APD therapy (36 nontidal, 13 tidal with low reserve volume). We estimated creatinine clearance (CCr), Kt/V urea, sodium removal, and peritoneal protein loss using two simplified methods. We calculated separate diurnal and nocturnal adequacies. Nocturnal concentrations of urea, creatinine, sodium, and proteins were extrapolated from dialysate samples taken after the first (method A) or the last (method B) cycle of the night. For the reference method, we estimated adequacy from a complete 24-hour dialysate collection. Spearman correlations versus the reference method were, for CCr, 0.82 for method A and 0.87 for method B; and for Kt/V, 0.78 (A) and 0.72 (B). Method A overestimated CCr by 19.6% (4.5 L/week)(median values) and Kt/V by 8.8% (0.12). Method B overestimated CCr by 5.0% (1.7 L/week) and Kt/V by 4.4% (0.06). Both methods estimated sodium removal accurately, but estimated protein loss poorly. Tidal APD was associated with a clear overestimation of adequacy indices with both methods. In fact, when only nontidal patients were considered, method B slightly underestimated CCr and Kt/V. In APD, estimation of nocturnal adequacy from dialysate samples taken after the first cycle is inaccurate. Estimation from samples taken after the last cycle yields suboptimal but acceptable results; the deviation is small and the dose of dialysis delivered to the patients is not overestimated.


Prolonged fever and anemia as the sole manifestations of a false aneurysm in a transplant patient.
A patient with a false aneurysm of the iliac artery following removal of a right allograft developed a prolonged fever and anemia of unknown origin. The patient's condition was initially misinterpreted largely because these symptoms were attributed to dialysis treatment. This case emphasizes fever and anemia as the sole manifestations of a false aneurysm appearing as a late complication of kidney transplantation.


Relaxin inhibits central angiotensin II expression in killifish: a central osmoregulatory role for relaxin and angiotensin II in the killifish Fundulus heteroclitus.
We investigated whether relaxin and brain angiotensin II (AII) are osmoregulatory hormones in killifish. Four groups of killifish acclimatized to different saline environments (freshwater, 25% sea water, 50% sea water [brackish], and sea water) were euthanized and their brains were embedded in paraffin. A separate group of brackish water killifish were injected with relaxin 1 h before dissection and embedding. Serial sagittal sections were immunohistochemically stained for AII. Angiotensin II immunostaining did not differ between saline environments. Contrary to expectation, relaxin decreased the number of AII-immunoreactive cells in hypothalami of brackish water fish.


Towards a method for printing a network of chick forebrain neurons for biosensor applications.
The primary goal of this work is to establish a robust, repeatable method for printing arrays of neurons. This work has two endpoints. One is to use a neural array as an experimental testbed for investigating neuronal cell growth hypotheses. The other endpoint is to enable the next generation of cell-based sensors. Herein we compare microcontact printing results previously published by our group with a new method of dip-pen printing. We present preliminary results for neurons growing on these microprinted arrays, assessing contact frequencies and growth characteristics.


The Importance of the Anterior Septal Angle in the Open Dorsal Approach to Rhinoplasty.
Functional and aesthetic manipulation of the nose relies on a detailed understanding of nasal anatomy and a meticulous dissection. Maneuvers are performed in four regions of the nose: nasal tip, dorsum, posterior septum, and caudal septum. Positioned at the cornerstone of these regions, the anterior septal angle acts as a point of reference, especially in secondary rhinoplasty. Identification of the anterior septal angle early in the nasal dissection aids in reliable exposure, either wide or limited, and facilitates desired maneuvers. In addition, alteration of the position of the anterior septal angle can affect nasal tip projection, especially in cases such as the tension tip deformity. The authors emphasize the importance of the anterior septal angle in their simplified methodology for the open dorsal approach in rhinoplasty.


Bayesian inference for kappa from single and multiple studies.
Cohen's kappa coefficient is a widely popular measure for chance-corrected nominal scale agreement between two raters. This article describes Bayesian analysis for kappa that can be routinely implemented using Markov chain Monte Carlo (MCMC) methodology. We consider the case of m > or = 2 independent samples of measured agreement, where in each sample a given subject is rated by two rating protocols on a binary scale. A major focus here is on testing the homogeneity of the kappa coefficient across the different samples. The existing frequentist tests for this case assume exchangeability of rating protocols, whereas our proposed Bayesian test does not make any such assumption. Extensive simulation is carried out to compare the performances of the Bayesian and the frequentist tests. The developed methodology is illustrated using data from a clinical trial in ophthalmology.


Brief assessment of motor function: content validity and reliability of the fine motor scale.
The Brief Assessment of Motor Function Fine Motor Scale (FMS) allows rapid assessment, independent of age. This study was done to establish content validity of the FMS and to demonstrate FMS reliability. A standard questionnaire ("Disagree" to "Agree," 1-4) was emailed to 28 expert panel members. Ten children with diagnoses including Proteus, Sheldon-Freeman, Smith-Lemli-Opitz, and Smith-Magenis syndromes were videotaped for reliability trials. Expert panel members agreed that all 28 items should be included (means, 3.43-3.89); were functionally relevant (means, 2.93-3.82), were clearly worded (means, 2.71-3.61), and were easily discriminated (means, 3.32-4.0). Kappa values for interrater and intrarater reliability were 0.978 and 0.993, respectively. Feedback from an expert Panel supported content validity of the Brief Assessment of Motor Function FMS. Kappa values for interrater and intrarater reliability suggest this is a reliable instrument for rapid, objective fine motor assessment.


Aspects of the haemolytic reaction induced by Kanagawa haemolysin of Vibrio parahaemolyticus.
Vibrio parahaemolyticus, an important enteric pathogen, produces toxin (Kanagawa haemolysin, KH), the presence of which correlates well with pathogenicity. KH induced lysis of human red blood cells (HRBC); the kinetics were strongly dependent on KH concentration (0-1 HU/ml) and rather independent of target cell concentration [0.5 < or = haematocrit (%) < or = 6] and the ratio KH:HRBC. The suggestion that KH-induced haemolysis is due to colloid osmosis is supported by results indicating: (1) osmotic protection (by suspension in iso-osmotic choline chloride, D-sorbitol or L-valine, or MOPS-buffered saline with added sucrose), (2) a cell volume increase prior to lysis, and (3) an increase in HRBC cation (86Rb+) influx after KH addition, indicating raised passive cation permeation. The effect of temperature on KH-induced haemolysis indicates the importance of processes other than the action of a simple water-filled pore, because of the high activation energy [53.30 +/- 2.79 kJ (mol.)-1] involved. Although haemolytic rate was attenuated by washout after 5 min KH exposure, the KH-induced lesion itself was not susceptible to washout by either extracellular volume expansion (at constant osmolarity) or centrifugation/resuspension. This suggests that HRBC binding of KH from aqueous solution still continues after 5 min exposure at 37 degrees C. Pre-vortexing KH with dibutyl phthalate (DBP) dramatically reduced the haemolytic activity of the aqueous toxin preparation, suggesting a protein-lipid interaction, which may support the contention that KH can move from a hydrophilic to a hydrophobic environment. Two features were identified that are characteristic of highly purified TDH preparations: (1) thermostability of haemolysin, and (2) monovalent cation selectivity series of lesion: Cs+ > Li+ > K+ > Rb+ > Na+, confirming that TDH is the important leak-inducing agent of KH.


Assessing the evidence of a link between mental illness and violence.
The relationship of mental illness and violence is an issue of longstanding clinical and policy importance, and recent research on this association has sparked renewed debate. The author formulates six statements on the association that seem warranted by recent investigations and reviews the research evidence. In general, contrary to findings of earlier research, an association does appear to exist between mental illness and the likelihood of being involved in violent incidents. A dual diagnosis of mental illness and substance abuse probably significantly increases the risk for violence, and the association between mental illness and violence is probably significant even when demographic characteristics are taken into account. Given the considerable limitations of current research, priorities for future research include attention to the strength of the association for individual subjects, inclusion of adequate comparison groups of non-mentally-ill persons and a broad range of variables, and intensive studies of repetitively violent individuals over time.


Health promotion programs yield long-term savings.
Companies implement health promotion programs as an investment that they hope will result in decreased health care costs in the future. B&H reviews the health promotion programs of Coors, Waste Management, and Baker Hughes.


Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns.
Obesity has a heritable component; however, the heterogeneity of obesity complicates dissection of its genetic background. In this study, we therefore focused on eating patterns as specific traits within obesity. These traits have a heritable component; genes associated with a specific eating pattern have not yet been reported at the population level. In this study, we determined whether genetic variations in cholecystokinin (CCK) and leptin genes underlie specific eating patterns. We selected obese individuals showing extreme snacking behavior or use of excessive portion sizes from a large population-based sample (n = 17,357) from the Prospect-EPIC (European Prospective Study into Cancer and Nutrition) study. Using allele-specific PCRs, we tested several single nucleotide polymorphisms in the candidate genes and performed haplotype analysis. Obese carriers of common allelic variations in leptin or the leptin receptor gene had an increased risk to display extreme snacking behavior. In contrast, obese carriers of common allelic variations in CCK had an increased risk to eating increased meal sizes. In conclusion, we identified common allelic variants specifically associated with distinctly different eating patterns, namely extreme snacking behavior or excessive portion size.


A comparison of discectomy and chemonucleolysis.
When comparing two treatment modalities in the care of a herniated nucleus pulposus causing unremitting sciatica, it is difficult to be certain of complete accuracy, despite attentive evaluation. Eight series of patients are presented which compare the effectiveness of discectomy versus chemonucleolysis. Overall evaluation concludes that a similar success rate is obtained as an end result with proper patient selection, technically acceptable treatment, and intelligent follow-up study. Assured potency of the chymopapain is an added consideration in chemonucleolysis. There is evidence of significant decrease in hospitalization time and morbidity in the good result with chymopapain injection. The major advantage of a successful result in the use of chymopapain over discectomy is the absence of postoperative fibrosis, a compelling reason for the consideration of the enzyme in the treatment of a herniated nucleus pulposus where conservative measures have failed.


Comparison of direct fluorescent antibody, acridine orange, wet mount, and culture for detection of Trichomonas vaginalis in women attending a public sexually transmitted diseases clinic.
To define the performance characteristics of two newer tests for Trichomonas vaginalis (TV), the authors compared direct fluorescent antibody (DFA) (mixed monoclonal antibody, Integrated Diagnostics, Inc, Berkeley, CA) and acridine orange (AO) tests to standard wet mount (WM) preparations and culture (modified Diamond medium) of vaginal wash specimens in consecutively examined women presenting to a public sexually transmitted diseases (STD) clinic. Cultures for Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), and yeast were also performed on all patients. Of 104 women, 59 (57%) were infected with one or more pathogens. Trichomonas vaginalis was detected by WM and/or culture in 38 (37%) women and was the most prevalent infection. Of the 38 patients with TV, 95% were detected by culture, 83% by DFA, 66% by AO, and 66% by WM. An additional patient was DFA positive but negative for TV by all other methods. The sensitivity of DFA was superior to AO and WM in women with TV infection alone (96% compared to 67% and 53%, respectively). It was comparable to AO and WM in women with multiple infections (67% compared to 53% and 73%). Even in the presence of other pathogens, DFA appears to be a reasonable alternative to culture for detection of TV. In addition, DFA is rapid, easy to perform, and relatively inexpensive.


KIF20A silence inhibits the migration, invasion and proliferation of non-small cell lung cancer and regulates the JNK pathway.
An increasing number of studies have shown that kinesin family member 20A (KIF20A) was overexpressed in several types of cancer, and its overexpression correlated with the oncogenesis and prognosis of cancers. However, little is known about the roles of KIF20A in human non-small cell lung cancer (NSCLC). Thus, the aim of the present study was to demonstrate the expression of KIF20A in human NSCLC and reveal its biological functions and the underlying mechanisms. qRT-PCR, western blot and immunohistochemistry were used to assess the expression of NSCLC patient specimens and NSCLC cell lines. The functions of KIF20A in migration and invasion were determined using Transwell assay. Cell proliferation capacity was performed by CKK-8 assay. We demonstrated that KIF20A was overexpressed in NSCLC specimens compared with the adjacent non-tumorous specimens, and high expression of KIF20A was associated with clinical stage and metastasis in NSCLC. Decreased expression of KIF20A inhibited NSCLC cells migration, invasion and proliferation. Most importantly, further experiments demonstrated that decreased the expression of KLF20A significantly downregulated expression of p-JNK and MMP7, which indicated that knockdown of KIF20A alters lung cancer cell phenotype and regulates JNK pathways. These results suggest that KIF20A may act as a putative oncogene and a potential therapeutic target in NSCLC.


Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits.
Heterotrimeric G-proteins bind to cell-surface receptors and are integral in transmission of signals from outside the cell. Upon activation of the Galpha subunit by binding of GTP, the Galpha and Gbetagamma subunits dissociate and interact with effector proteins for signal transduction. Regulatory proteins with the 19-amino-acid GoLoco motif can bind to Galpha subunits and maintain G-protein subunit dissociation in the absence of Galpha activation. Here we describe the structural determinants of GoLoco activity as revealed by the crystal structure of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein signalling' protein RGS14. Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu-Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact with the GDP alpha- and beta-phosphates. The structural organization of the GoLoco Galpha(i1) complex, when combined with supporting data from domain-swapping experiments, suggests that the Galpha all-helical domain and GoLoco-region carboxy-terminal residues control the specificity of GoLoco Galpha interactions.


PARTICLE PHYSICS: CERN Collider Glimpses Supersymmetry--Maybe.
Last week, particle physicists at the CERN laboratory in Switzerland announced that by smashing together matter and antimatter in four experiments, they detected an unexpected effect in the sprays of particles that ensued. The anomaly is subtle, and physicists caution that it might still be a statistical fluke. If confirmed, however, it could mark the long-sought discovery of a whole zoo of new particles--and the end of a long-standing model of particle physics.


The quantitative analysis of neurodegenerative disease: classification, noda, constellations, and multivariate geometry.
A variety of methods are available for the quantitative description and analysis of neurodegenerative disease. If neurodegenerative disease exists as a series of distinct disorders, then classificatory methods such as hierarchical cluster analysis (HCA) and decision tree analysis (DTA) can be used to classify cases into groups more objectively. If neurodegenerative disease consists of overlapping phenotypes, then the Braun-Blanquet 'nodal' system and 'constellation diagrams' implicitly recognise intermediate cases and reveal their relationships to the main groupings. By contrast, if cases are more continuously distributed without easily distinguishable disease entities, then methods based on spatial geometry, such as a triangular system or principal components analysis (PCA), may be more appropriate as they display cases spatially according to their similarities and differences. This review compares the different methods and concludes that as a result of the heterogeneity and overlap commonly present plus the multiplicity of possible descriptive variables, methods such as PCA are likely to be particularly useful in the quantitative analysis of neurodegenerative disease. A more general application of such methods, however, has implications for studies of disease risk factors and pathogenesis and in clinical trials.


Lasertherapy efficacy in temporomandibular disorders: control study.
Temporomandibular dysfunction is characterized by the presence of painful joint/muscular symptoms muscle in the face. The main justification for the use of lasers in laser therapy dysfunction is its analgesic effect, which was observed in most studies in the literature. We evaluated the effectiveness of laser therapy in the treatment of temporomandibular disorders. 50 volunteers with temporomandibular disorders were divided into two groups (control and experimental) had amplitudes of movements of mouth opening, right and left laterality recorded before and after laser application. Was also recorded, the score the individual gave to pain by visual analog scale and, through physical examination, the pain points. We used the AsGaAl laser with a 40mW power, with 80J/cm(2) for 16 seconds at four selected points for just one session with reassessment after a week. Clinical. It was noted that laser therapy increased the mean amplitude of mandibular movements (p = 0.0317) and decreased significantly (43.6%) the pain intensity measured by the visual analog scale. The laser decreases the painful symptoms of the patient after application through its analgesic and/or a placebo effect.


Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy: effect of clinical node status at presentation.
Both neoadjuvant chemotherapy and selective sentinel lymphadenectomy (SSL) are increasingly being used in treating primary breast cancer. It is important to determine whether SSL can be used after neoadjuvant chemotherapy and whether clinical node status at presentation affects accuracy of SSL. Between 1995 and 2003, 53 evaluable cases of invasive breast cancer were treated with neoadjuvant chemotherapy followed by SSL and completion axillary node dissection. The accuracy of SSL and the number of failed SSLs were assessed in the entire group and in the subset that were clinically node positive at presentation. The sensitivity of SSL was 96%, the negative predictive value was 96%, and the sentinel node identification rate was 94%. Of the 53 evaluable patients, 23 had clinically node-positive disease at presentation (43%) and the remainder were clinically node negative (57%). Of the successfully completed SSL, the status of the sentinel lymph node corresponded to that of overall axillary status in 49 of 50 patients (accuracy rate 98%). Two of the 23 patients with clinically node-positive disease at presentation had unsuccessful SSL. Of the remaining 21 patients with a clinically positive axilla before systemic therapy, a false-negative SSL result occurred in 1 patient (accuracy 95%, sensitivity 91%). Selective sentinel lymphadenectomy after neoadjuvant chemotherapy is both feasible and accurate. Although early reports found a lower performance of SSL after neoadjuvant chemotherapy, this study suggests reevaluation of the current practice of full axillary lymph node dissection in this setting, particularly in those patients who are clinically node negative at presentation.


Patient expectations of treatment for back pain: a systematic review of qualitative and quantitative studies.
A systematic review of qualitative and quantitative studies. To summarize evidence from studies among patients with low back pain on their expectations and satisfaction with treatment as part of practice guideline development. Patients are often dissatisfied with treatment for acute or chronic back pain. We searched the literature for studies on patient expectations and satisfaction with treatment for low back pain. Treatment aspects related to expectations or satisfaction were identified in qualitative studies. Percentages of dissatisfied patients were calculated from quantitative studies. Twelve qualitative and eight quantitative studies were found. Qualitative studies revealed the following aspects that patient expectation from treatment for back pain or with which they are dissatisfied. Patients want a clear diagnosis of the cause of their pain, information and instructions, pain relief, and a physical examination. Next, expectations are that there are more diagnostic tests, other therapy or referrals to specialists, and sickness certification. They expect confirmation from the healthcare provider that their pain is real. Like other patients, they want a confidence-based association that includes understanding, listening, respect, and being included in decision-making. The results from qualitative studies are confirmed by quantitative studies. Patients have explicit expectations on diagnosis, instructions, and interpersonal management. New strategies need to be developed in order to meet patients' expectations better. Practice guidelines should pay more attention to the best way of discussing the causes and diagnosis with the patient and should involve them in the decision-making process.


Serum lipid profile in highly active antiretroviral therapy-naïve HIV-infected patients in Cameroon: a case-control study.
HIV status has commonly been found to affect the serum lipid profile. The aim of this study was to determine the effect of HIV infection on lipid metabolism; such information may be used to improve the management of HIV-infected patients. Samples were collected from December 2005 to May 2006 at Yaounde University Teaching Hospital, Yaounde, Cameroon. Lipid parameters were obtained using colorimetric enzyme assays, while low-density lipoprotein cholesterol (LDLC) values were calculated using the formula of Friedewald et al. (1972) and atherogenicity index by total cholesterol (TC)/high-density lipoprotein cholesterol (HDLC) and LDLC/HDLC ratios. HIV infection was most prevalent in subjects aged 31 to 49 years. Most of the HIV-positive patients belonged to Centers for Disease Control and Prevention categories B (43.0%) and C (30.23%). Compared with control subjects, patients with CD4 counts<50 cells/microL had significantly lower TC (P<0.0001) and LDLC (P<0.0001) but significantly higher triglyceride (TG) values (P<0.001) and a higher atherogenicity index for TC/HDLC (P<0.01) and HDLC/LDLC (P=0.02); patients with CD4 counts of 50-199 cells/microL had significantly lower TC (P<0.001) and significantly higher TG values (P<0.001); patients with CD4 counts of 200-350 cells/microL had significantly higher TG (P=0.003) and a higher atherogenicity index for TC/HDLC (P<0.0002) and HDLC/LDLC (P=0.04); and those with CD4 counts >350 cells/microL had a higher atherogenicity index for TC/HDLC (P<0.0001) and HDLC/LDLC (P<0.001). HDLC was significantly lower in HIV-positive patients irrespective of the CD4 cell count. Lipid parameters were also influenced by the presence of opportunistic infections (OIs). HIV infection is associated with dyslipidaemia, and becomes increasingly debilitating as immunodeficiency progresses. HDLC was found to be lower than in controls in the early stages of HIV infection, while TG and the atherogenicity index increased and TC and LDLC decreased in the advanced stages of immunodeficiency.


Quitline Tobacco Interventions in Hospitalized Patients: A Randomized Trial.
Hospitalization provides an opportunity for smokers to quit, but tobacco interventions can require specialized services that are not available to many hospitals. This study tests the hypothesis that a brief intervention to facilitate the use of telephone quitline services for both initial and follow-up counseling is effective in helping patients achieve sustained abstinence. This was a population-based RCT. Participants were Olmsted County, MN residents who reported current smoking and were admitted to Mayo Clinic hospitals in Rochester, MN between May 2012 and August 2014. A control group received brief (~5-minute) cessation advice; an intervention group received a brief (~5-minute) quitline facilitation intervention, with either warm handoff or faxed referral to a national quitline provider. All were offered a 2-week supply of nicotine patches at discharge. Outcomes included self-reported 7-day point prevalence abstinence at 6 months after hospitalization and quitline utilization. Data analysis was performed from September 2014 to March 2015. Of the 1,409 eligible patients who were approached, 600 (47%) were randomized. The quitline intake call was completed by 195 subjects (65% of the intervention group). Of these, 128 (66%) completed the first coaching call. Self-reported abstinence rates at 6 months after discharge were identical in both groups (24%). The quitline facilitation intervention did not improve self-reported abstinence rates compared with a standard brief stop-smoking intervention. These results do not support the effectiveness of quitlines in providing tobacco use interventions to a general population of hospitalized smokers.


Antitumor activity of 2-amino-4,4 alpha-dihydro-4 alpha, 7-dimethyl-3H-phenoxazine-3-one, a novel phenoxazine derivative produced by the reaction of 2-amino-5-methylphenol with bovine hemolysate.
2-Amino-4,4 alpha-dihydro-4 alpha,7-dimethyl-3H-phenoxazine-3-one (Phx) was synthesized by the reaction of 2-amino-5-methyl-phenol with bovine hemolysates. Since Phx is a phenoxazine derivative like actinomycin D, which exerts a strong anti-tumor effect by intercalating DNA, we examined the effects of Phx on cell proliferation and cell cycle progression in human epidermoid carcinoma cells (KB cells). Phx inhibited the proliferation of Kb cells in a dose-dependent manner. When KB cells were incubated for 9 h with medium containing 50 microM Phx, a transient accumulation of cells in S and G2/M phase was observed and at 24 h many of cells had lower DNA content. Although Phx had antitumor activity, the drug did not intercalate DNA, showing a different mode of action from actinomycin D.


Complete selection of a self-assembling homo- or hetero-cavitand cage via metal coordination based on ligand tuning.
Selective formation of a homo- or hetero-cavitand cage via metal-coordination, by using tetra(4-pyridyl)-cavitand (1), tetrakis(4-pyridylethynyl)-cavitand (2), or tetrakis(4-cyanophenyl)-cavitand (3) as deep cavitand ligands and Pd(dppp)(OTf)2 (4) as a connector, has been investigated by 1H NMR and CSI-MS. When the cavitand and 4 were mixed in CDCl3 in a 2:4 molar ratio, 1 gave a complicated mixture, whereas 2 or 3 formed a homo-cavitand cage {2(2).4[Pd(dppp)]}8+.8(TfO-) (5) or {2(3).4[Pd(dppp)]}8+.8(TfO-) (6), respectively, as a single species. In a 1:1:4 mixture of 2, 3, and 4, homo-cavitand cages 5 and 6 were observed in a 1:1 ratio. In marked contrast, a mixture of 1, 3, and 4 in a 1:1:4 ratio was exclusively self-assembled into a hetero-cavitand cage {1.3.4[Pd(dppp)]}8+.8(TfO-) (7). The selectivity for the self-assembly of the homo- or hetero-cavitand cage via metal coordination would arise from a combination of factors such as coordination ability and steric demand of cavitand ligands.


Parametric study of the forces on microspheres held by optical tweezers.
Optical-trapping forces exerted on polystyrene microspheres are predicted and measured as a function of sphere size, laser spot size, and laser beam polarization. Axial and transverse forces are in good and excellent agreement, respectively, with a ray-optics model when the sphere diameter is ≥ 10 µm. Results are compared with results from an electromagnetic model when the sphere size is ≤ 1 µm. Axial trapping performance is found to be optimum when the numerical aperture of the objective lens is as large as possible, and when the trapped sphere is located just below the chamber cover slip. Forces in the transverse direction are not as sensitive to parametric variations as are the axial forces. These results are important as a first-order approximation to the forces that can be applied either directly to biological objects or by means of microsphere handles attached to the biological specimen.


Pisotriquetral joint ganglion.
Physical examination of a woman with painful swelling about the ulnar side of her dominant right wrist but no history of trauma revealed a freely mobile soft-tissue mass on the ulnar aspect of the wrist. Radiographs of the wrist were normal. At surgery, a 1 cm x 1 cm ganglion immediately adjacent to the hypothenar muscles was dissected circumferentially and found to have a stalk originating from the ulnar aspect of the pisotriquetral joint. This report suggests that ganglions arising from the medial side of the pisotriquetral joint should be included in the differential diagnosis of ulnar wrist pain.


Strain tuned InSe/MoS2 bilayer van der Waals heterostructures for photovoltaics or photocatalysis.
The isolation of different two-dimensional materials and the possibility to combine them in vertical stacks have led to new material systems, namely heterostructures based on two-dimensional crystals. By using density functional theory, we found that the InSe/MoS2 bilayer shows an indirect band gap of 0.65 eV with optical absorption over a wide range (300-800 nm) and a preferable separation of photogenerated electron-hole pairs. Moreover, the band gap can be readily tuned by external strain engineering, leading to a transition from the indirect band gap to a direct band gap of 1.55 eV under 7% compressive strain, where there is an enhanced and continuous spectrum. In addition, under a tensile strain of 9%, the bilayer is metallic. All of these properties enable the development of excellent photoelectric devices from the heterostructures with strain engineering.


Pharmacological study of direction selectivity in the archer fish retina.
Direction selective cells have been found in the retina, the first level of the visual system, in mammals and recently also in the archer fish. These cells are involved in a variety of fast neural computation processes, from the control of eye movements to the detection of prey by the archer fish. The standard model for this mechanism in mammalian retina is well understood and is based on the asymmetry of inhibitory and excitatory inputs to the retinal ganglion cells. However, it remains unclear whether the mechanism that underlies direction selectivity is similar across animal classes. This study reports a pharmacological investigation designed to elucidate the mechanism that underlies motion detection in the archer fish retina. Direction selectivity in the retina was characterized under the influence of specific channel blockers that are known to be present in the different types of neurons of the retina. The results show that the direction-selective mechanism in the archer fish retina is modified only when the inhibitory channels of GABA and Glycine are manipulated. This suggests that the mechanism of direction selectivity in the archer fish retina is fundamentally different from the mechanism of direction selectivity in the mammalian retina.


A neurodynamic model of the attentional blink.
A brain-based neural model of attention is used to simulate results for the 'attentional blink', observed when a subject is exposed to a rapid stream of stimuli and required to monitor for two successive targets in the stream. The 'blink' occurs when the time between the first and second targets is 200-500 ms, when there is reduced accuracy for report of the second target. The model gives a qualitative explanation of the phenomenon, especially of how attention is bolstered, during the processing to report of a given stimulus, in order to defend reportable information from attack by distracters.


Heterotopic ossification following musculoskeletal trauma: modeling stem and progenitor cells in their microenvironment.
Heterotopic ossification (HO), characterized by the formation of mature bone in the soft tissues, is a complication that can accompany musculoskeletal injury, and it is a frequent occurrence within the military population that has experienced orthopaedic combat trauma. The etiology of this disease is largely unknown. Our laboratory has developed strategies to investigate the cellular and molecular events leading to HO using clinical specimens that were obtained during irrigation and debridement of musculoskeletal injuries. Our approach enables to study (1) the cell types that are responsible for pathological transformation and ossification, (2) the cell- and tissue-level signaling that induces the pathologic transformation, and (3) the effect of extracellular matrix topography and force transduction on HO progression. In this review, we will report on our findings in each of these aspects of HO etiology and describe our efforts to recapitulate our findings in an animal model for traumatic HO.


Surfactant systems: microemulsions and vesicles as vehicles for drug delivery.
Although surfactants have been widely used as pharmaceutical adjuvants for many years, it is only relatively recently that their phase structures have been seriously considered as drug delivery vehicles per se. This review highlights the work to date investigating the potential of microemulsions as drug carriers and also reports on preliminary studies performed on the use of vesicles formed from nonionic surfactants.


[Functional polymorphism of p53 and CCR5 genes in the long-lived of the Siberian region].
The P53 protein is a key regulator of modified-cell apoptosis. The functional oligonucleotide polymorphism of the p53 gene causes the substitution of arginine (Arg) for praline (Pro) in the codon 72. A reduced apoptotic activity of p53 and, as a consequence, development of oncology pathology is associated with the above polymorphism. CCR5 is a compound transmembrane receptor-protein, which apart from chemokines, binds with some molecules and is a coreceptor for HIV-1. 32 bp deletion within the CCR5 encoding region results in the loss of the protein's receptor function. It has been demonstrated that the transmission of the "external" (in respect to cell) stimulus, via the CCR5 system, induces expression of the p53 gene and initiates apoptosis. Allele variants and p53 and CCR5 genotypes (separately and in combinations) were investigated, within the present case study, for 131 long-livers from Novosibirsk and Tyumen Regions. A trend was detected towards accumulation of the p53 Pro alleles in association with the CCR5del32 allele in the study group, which, as the authors believe, can enhance the genome resistance to variable factors that cut the life span.


Avian dyschondroplasia: local deficiencies in growth factors are integral to the aetiopathogenesis.
Rabbit polyclonal antibodies to chicken transforming growth factor-beta 3 (TGF-/J3) and to insulin-like growth factor-I (IGF-I) were used to detect the two growth factors in normal and dyschondroplastic broiler growth plates (physes). Histo-morphometry was used to estimate the percentage of chondrocytes containing IGF-I and TGF-beta3 in the lower proliferative, transitional and hypertrophic zones of the growth plate. In the normal chick growth plates IGF-I was present in 63% of transitional chondrocytes and in 67% of hypertrophic chondrocytes and TGF-beta3 was present in 81% of transitional chondrocytes and in 93% of hypertrophic chondrocytes. Both growth factors were found to be deficient within transitional chondrocytes at sites of dyschondroplasia, a condition in which there is a local defect in chondrocyte differentiation and the subsequent replacement of the cartilage by bone. In addition, both growth factors were identified in chondrocytes within areas of repair, where chondrocyte differentiation and endochondral ossification have resumed. This supports the hypothesis that the reduction in TGF-beta3 and IGF-I in dyschondroplasia is integral to the aetiopathogenesis and indicative that both these growth factors are part of the cascade of events associated with chondrocyte differentiation during endochondral ossification.


Stress reduction and analgesia in patients exposed to calming music postoperatively: a randomized controlled trial.
This randomized controlled trial was designed to evaluate, first, whether intra- or postoperative music therapy could influence stress and immune response during and after general anaesthesia and second, if there was a different response between patients exposed to music intra- or postoperatively. Seventy-five patients undergoing open hernia repair as day care surgery were randomly allocated to three groups: intraoperative music, postoperative music and silence (control group). Anaesthesia and postoperative analgesia were standardized and the same surgeon performed all the operations. Stress response was assessed during and after surgery by determining the plasma cortisol and blood glucose levels. Immune function was evaluated by studying immunoglobulin A (IgA) levels. Patients' postoperative pain, anxiety, blood pressure (BP), heart rate (HR) and oxygen saturation were also studied as stress markers. There was a significantly greater decrease in the level of cortisol in the postoperative music group vs. the control group (206 and 72 mmol L(-1) decreases, respectively) after 2 h in the post anaesthesia care unit. The postoperative music group had less anxiety and pain and required less morphine after 1 h compared with the control group. In the postoperative music group the total requirement of morphine was significantly lower than in the control group. The intraoperative music group reported less pain after 1 h in the post anaesthesia care unit. There was no difference in IgA, blood glucose, BP, HR and oxygen saturation between the groups. This study suggests that intraoperative music may decrease postoperative pain, and that postoperative music therapy may reduce anxiety, pain and morphine consumption.


The Tower of Babel of CD8+ T-cell memory: known facts, deserted roads, muddy waters, and possible dead ends.
Adequate antigen stimulation can lead to permanent modifications of primed cells and to the generation of memory T cells that have astonishingly improved capacities to deal with antigen. The overall properties of memory T cells (increased survival, precocious and increased division capacities, and improved effector functions) can be used to identify this unique cell type. However, each immune response may lead to the generation of multiple primed types that do not necessarily possess all these characteristics. It is not known whether these different cell types are just side products of the immune reaction or whether they are involved in disease control. Control of different infections may involve different challenges and lead to the generation of different types of immune reactions. Our major challenge is to unravel this complexity, but we must overcome our handicapped experimental tests and our imperfect a priori definitions.


Controlled Construction of Supported Cu+ Sites and Their Stabilization in MIL-100(Fe): Efficient Adsorbents for Benzothiophene Capture.
Cu+-containing materials have drawn much attention in various applications because they are versatile, nontoxic, and low-cost. However, the difficulty of selective reduction and the poor stability of Cu+ species are now pretty much the agendas. Here, controlled construction of supported Cu+ sites in MIL-100(Fe) was realized under mild conditions (200 °C, 5 h) via a vapor-reduction strategy (VRS). Remarkably, the yield of Cu+ reaches 100%, which is quite higher than the traditional high-temperature autoreduction method with a yield less than 50% even at 700 °C for 12 h. More importantly, during the treatment via VRS some Fe3+ in MIL-100(Fe) are reduced to Fe2+, which prevent the frequently happened oxidation of Cu+ due to the higher oxidation potential of Fe2+. These properties make Cu+/MIL-100(Fe) efficient in the capture of typical aromatic sulfur, benzothiophene, with regard to both adsorption capacity and stability. To our knowledge, the stabilization of Cu+ using the oxidation tendency of supports is achieved for the first time, which may offer a new idea to utilize active sites with weak stability.


Translation and cultural adaptation of the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0).
To translate and culturally adapt the Pediatric Eosinophilic Esophagitis Symptom Score (version 2.0), a tool used to assess pediatric eosinophilic esophagitis symptoms reported by patients and/or their parents/caregivers. The Pediatric Eosinophilic Esophagitis Symptom Score was translated through the following stages: initial translation, back-translation, and consensus of independent reviewers through the Delphi technique. The pre-final version of the Pediatric Eosinophilic Esophagitis Symptom Score was applied to five 8-to-18-year-old patients and to ten parents of two-to-18-year-old patients from an outpatient pediatric gastroenterology service (pre-test). During the translation process, no translations presenting with difficult consensus in the review process or grammar inconsistencies were observed. During the pre-test, difficulties in comprehension of some unconventional terms, e.g., "náusea", were observed. Adverbs of frequency, such as "quase nunca" were also identified as being of difficult understanding by patients and parents, and the substitution by the term "raramente" was suggested. Such difficulties may be inherent to the pediatric age group. Age 8 years or above should be considered adequate for the self-reporting of symptoms. The study presents the Brazilian version of the Pediatric Eosinophilic Esophagitis Symptom Score, which is adapted to the Brazilian culture. This version may be introduced as a clinical and research tool for the assessment of patients with esophagic disease symptoms. The Pediatric Eosinophilic Esophagitis Symptom Score is a breakthrough in the evaluation of symptoms of pediatric eosinophilic esophagitis, since it reinforces the importance of self-reporting by patients who experience this disease.


Continuous in vivo monitoring of amino acid neurotransmitters by microdialysis sampling with on-line derivatization and capillary electrophoresis separation.
A separation-based biosensor has been developed that is capable of near-real-time analysis of aspartate and glutamate with a temporal resolution of less than 2 min in anesthetized or awake, freely moving animals. The instrument consists of a microdialysis sampling system, an on-line reactor, an injection interface, and a CE-LIF system. Primary amine analytes are derivatized with NDA/CN following microdialysis sampling using an on-line reactor to produce fluorescent CBI derivatives. The reaction takes approximately 1 min. The derivatized sample then travels to a microinjection valve which alternately sends CE running buffer and reacted microdialysis sample to the CE column via an injection interface. The interface allows a controllable volume of 10-20 nL to be injected onto the CE separation capillary. Separation of aspartate and glutamate from the other amino acids present in the microdialysis sample was achieved within 70 s. Detection limits for glutamate and aspartate using laser-induced fluorescence detection were 0.1 microM. The linear dynamic range was acceptable for the determination of aspartate and glutamate in dialysate samples where the levels are between 1 and 10 microM. Full automation of the system was achieved by computer control of the valve, the interface, and the data collection system. The performance of this system was demonstrated in an anesthetized rat by monitoring ECF levels of aspartate and glutamate released in brain after stimulation with high concentrations of K+.


Nickel-catalyzed efficient and practical Suzuki-Miyaura coupling of alkenyl and aryl carbamates with aryl boroxines.
Suzuki-Miyaura coupling of unactivated alkenyl carbamates is described to construct polysubstituted olefins. The developed process is also suitable for heteroaromatic and even electron-rich aromatic carbamates.


Disrespectful conduct seen in TV documentary makes me cringe.
I cringed when I watched the first two episodes of Confessions of a Nurse. Where has respect for patients gone?


Distal radioulnar joint dysfunction.
Dislocations of the DRUJ, when diagnosed promptly, may be successfully treated by closed reduction and immobilization. Symptomatic tears of the TFCC may be decompressed by ulnar shortening with or without debridement of the tear. Several operations are available for the treatment of derangements of the DRUJ. The Lauenstein procedure maintains TFCC function and restores stable painful forearm rotation.


Complex community and evolutionary responses to habitat fragmentation and habitat edges: what can we learn from insect science?
Habitat fragmentation is the primary factor leading to species extinction worldwide and understanding how species respond to habitat edges is critical for understanding the effects of fragmentation on insect diversity in both natural and managed landscapes. Most studies on insect responses to the habitat edge focus on bottom-up changes in resources. Only a few recent studies have examined multi-trophic responses to habitat edges; the results of these studies highlight the problem that we lack a conceptual framework to understand the complex results observed when a single species' response to an edge 'cascades' throughout the food web in ways that are currently not predictable. Recent research from insect systems suggests that habitat edge responses cascade both up and down multi-trophic foodwebs and these altered species interactions may affect evolutionary processes. Future studies that investigate the effects of habitat edges on both ecological and evolutionary dynamics can help to fill these knowledge gaps and we suggest that insects, with short generation times, present an ideal opportunity to do so.


Nuclear transport of trimeric assembly intermediates exerts a morphogenetic control on the icosahedral parvovirus capsid.
The connection between nuclear transport and morphogenesis of a large macromolecular entity has been investigated using the karyophylic capsid of the parvovirus minute virus of mice (MVM) as a model. The VP1 (82 kDa) and VP2 (63 kDa) proteins forming the T = 1 icosahedral MVM capsid at the respective 1:5 molar ratio of synthesis, could be covalently cross-linked with dimethyl suberimidate into two types of oligomeric assemblies, which were present at stoichiometric amounts in infected cell extracts and purified viral particles. The larger species contained VP1 and corresponded in size (200 kDa) to a heterotrimer of one VP1 and two VP2 subunits. The smaller species contained VP2 only and corresponded in size (180 kDa) to a homotrimer. The introduction of bulky residues or the truncation of side-chains involved in multiple interactions at the interfaces between trimers of VPs in the MVM capsid, produced the accumulation of trimeric intermediates that were competent in nuclear translocation but not in capsid assembly. These results indicate that MVM maturation proceeds by cytoplasmic oligomerization of the capsid subunits into two types of trimers, which are the assembly intermediates competent to translocate across the nuclear membrane. Consistent with this conclusion, mutations at basic residues that inactivate a previously identified beta-stranded nuclear localization motif, which notably are not involved in inter or intra-subunit contacts, led to cytoplasmic retention of the two types of trimers, with no evidence for other assembly intermediates. Although a fraction of the VP1-containing trimers were translocated into the nucleus driven by the conventional nuclear transport signal of VP1 N terminus, their further assembly in the absence of the VP2-only trimers yielded large molecular mass amorphous aggregates. Therefore, the nuclear transport stoichiometry of assembly intermediates may exert a morphogenetic quality control on macromolecular complexes like the MVM capsid.


Evolution of community mental health case management: considerations for clinical practice.
Case management has been the preferred method of helping persons with mental illness live in the community. This report examines the historical development of case management practice over the past 30 years. The analysis revealed that evolutionary growth in case management developed in response to expansion of community mental health services rather than consumer interests to improve their quality of life. Consequently, this reveals itself in the lack of outcome criteria needed to measure case management effectiveness. Currently, the concept of case management is undergoing a revolutionary paradigm shift that is "consumer-driven" and responds to consumer concerns. However, as mental health care costs rise within a rapidly growing community mental health care system, managed care is being implemented as a method to contain these rising costs. Because of major differences in philosophical underpinnings, developments in support of public mental health managed care may jeopardize the genesis of consumer-driven case management by supporting case management models that reflect managed care ideology.


[The expression of tumor related macrophages and matrix solution element in laryngeal squamous carcinoma tissue and the relationship with tumor microvascular density].
To study the expression of CD68 antibody marked tumor associated macrophage TAMs and matrix solution element MMP-7 in laryngeal squamous carcinoma tissue and the relationship with clinicopathological parameters, so that to explore the relationship between the expression of the two molecular markers and laryngeal cancer tissue microvascular density (MVD). Immunohistochemical method was employed to detect the expression of CD68 and MMP-7 in 65 cases (laryngeal squamous carcinoma tissue in 45 cases; peritumoral nontumor tissue in 20 cases) and CD 34 antibody marked MVD expression. CD68 positive rate in squamous carcinoma tissue (82.2%, 37/45) is obviously higher than that in the peritumoral tissue (15%, 3/20) (P < 0.05), and MMP-7 positive rate in squamous carcinoma tissue is significantly different from that in peritumoral tissue (71.1%; 25%) (P < 0.05). The expression rate of CD34-MVD in laryngeal squamous carcinoma tissue( 26.52 +/- 6.36 )is higher than that in peritumoral tissue (12.23 +/- 4.01) (P < 0.05). In lymph node metastasis group, the positive expression rates of CD68 and MMP-7 are higher than those in the group without lymph node metastasis. MMP-7 showed no correlation with cancer stage, and CD68 was related with cancer stage; CD68, MMP-7 and CD34- MVD have positive correlation. The high level of expression of TAMs and MMP-7 in laryngeal cancer tissue and the positive correlation with MVD illustrate that both of the markers play important roles in promoting laryngeal squamous carcinoma tissue metastasis and angiogenesis, which can be used as important markers to evaluate the invasion and metastasis of laryngeal cancer.