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A comparison of computational models for the extracellular potential of neurons. The extracellular space has an ambiguous role in neuroscience. It is present in every physiologically relevant system and often used as a measurement site in experimental recordings, but it has received subordinate attention compared to the intracellular domain. In computational modeling, it is often regarded as a passive, homogeneous resistive medium with a constant conductivity, which greatly simplifies the computation of extracellular potentials. However, novel studies have shown that local ionic diffusion and capacitive effects of electrically active membranes can have a substantial impact on the extracellular potential. These effects can not be described by traditional models, and they have been subject to recent theoretical and experimental analyses. We strive to give an overview over current progress in modeling the extracellular space with special regard towards the concentration and potential dynamics on different temporal and spatial scales. Three models with distinct assumptions and levels of detail are compared both theoretically and by means of numerical simulations: the classical volume conductor (VC) model, which is most frequently used in form of the line source approximation (LSA); the biophysically detailed, but computationally intensive Poisson-Nernst-Planck model of electrodiffusion (PNP); and an intermediate model called the electroneutral model (EN). The results clearly show that there is no one model for all applications, as they show significantly different responses - especially close to neuronal membranes. Finally, we list some common use cases for model simulations and give recommendations on which model to use in each situation.

The relevant anatomy of the approach for axial lumbar interbody fusion. Prospective trial. To perform a precise anatomical study of the presacral space and to examine the approach safety of AxiaLIF (axial lumbar interbody fusion) in an anatomical aspect. AxiaLIF is a novel, minimally invasive surgery. Though there were a few clinical reports on its safety, AxiaLIF is less used in current practice because of the unfamiliarity of surgeons with the regional anatomy of presacral space. METHODS.: Sixteen adult cadaveric pelvic specimens were divided along the median sagittal plane. The presacral fascial structures, the rectosacral fascia, and the pelvic splanchnic nerves were dissected and measured. In the simulated operation, a blunt guide pin was inserted bilaterally to determine the relation of the guide pin's path with important anatomic structures. Mean distances with 95% confidence intervals (CIs) were calculated. The results showed that the fascial structures of the presacral space were divided into 5 layers, and the pelvic splanchnic nerves limited the dissection of the lower rectum, the mean length of which was 2.2 cm (1.9-2.5 cm). In the simulated operation, the mean minimum distance from the guide pin to the pelvic splanchnic nerves was 0.8 cm (0.4-1.2 cm), and the mean vertical distance to the S3-S4 junction was 1.5 cm (1.2-1.7 cm). Our study suggests that the approach for AxiaLIF is risky and requires further modification. We should choose the accurate surgical plane when performing the presacral approach.

Comparative performance of bread wheat and hexaploid triticale cytoplasms. Thirteen wheat-like advanced-generation triticale x wheat derivatives, having tetraploid wheat cytoplasm from triticale, were reciprocally crossed with three improved bread wheats, and the resulting F1s were evaluated for determining the comparative performance of the bread wheat and triticale cytoplasms for different traits. Significant reciprocal differences in the mean performance were observed for days to heading, days to maturity, spikes/plant, flag-leaf area, peduncle length, plant height, spike length, grains/spike, 1,000-grain weight, grain yield and grain protein content, and most of them were in favour of hexaploid wheat cytoplasm. However, this superiority of the hexaploid cytoplasm was not universal for a particular trait, implying that the differences in the performance of the evaluated reciprocal crosses depended not solely on the cytoplasmic background, but also on the interplay of the specific genotype with the cytoplasm.

Deletion of nonconserved helices near the 3' end of the rRNA intron of Tetrahymena thermophila alters self-splicing but not core catalytic activity. The self-splicing rRNA intron of Tetrahymena thermophila contains two stem-loop structures (P9.1 and P9.2) near its 3' end that are not conserved among group I introns. As a step toward deriving the smallest active self-splicing RNA, 78 nucleotides encompassing P9.1 and P9.2 have been deleted. This deletion has no effect on the core catalytic activity of the intron, as judged by its ability to catalyze poly(C) polymerization and other related reactions. In contrast, reactions at the 3' splice site of the rRNA precursor--exon ligation and intermolecular exon ligation--take place with reduced efficiency, and exon ligation becomes rate-limiting for self-splicing. Moreover, intermolecular exon ligation with pentaribocytidylic acid is inaccurate, occurring primarily at a cryptic site in the 3' exon. A deletion of 79 nucleotides that disrupts P9, as well as removing P9.1 and P9.2, has more severe effects on both the first and second steps of splicing. P9, a conserved helix at the 5' edge of the deletion point, can form stable alternative structures in the deletion mutants. This aberrant folding may be responsible for the reduced activity and accuracy of reactions with mutant precursors. Analysis of the cryptic site suggests that choice of the 3' splice site may not only depend on sequence but also on proximity to P9. In the course of these studies, evidence has been obtained for an alternative 5' exon-binding site distinct from the normal site in the internal guide sequence.

Antioxidants and reactive oxygen species in human fertility. The cellular components of the human reproductive system are as vulnerable as other cells to the potential detrimental effects of reactive oxygen species (ROS). Antioxidant protection is thus required, though not yet fully characterized, at sites of gametogenesis, fertilization and implantation. Spermatozoa are highly susceptible to oxidative damage due to the high content of polyunsaturated fatty acids within their plasma membrane and such damage may underlie certain aspects of male infertility. However, oral antioxidant therapy with, for example, Vitamin E or glutathione has to date only achieved limited success in treatment programmes. Infertility treatments involve in vitro manipulation of gametes and embryos, ranging from simple spermatozoa preparation techniques to several days culture, exposing cells to increased oxygen levels and potential oxidative stress compared with in vivo. A considerable body of data has demonstrated the benefits for animal embryo culture and human sperm preparation of antioxidant supplementation as well as the removal of sources of ROS such as leucocytes, although data supporting supplementation for human embryo culture are limited. However, the use of exogenous superoxide dismutase may improve embryo development to the blastocyst stage. Evidence is accumulating for a role for ROS in signalling events mediating both sperm capacitation and luteal function. Potential also exists for ROS (including nitric oxide) to fulfill as yet unidentified roles in modulation signalling, gene expression and/or apoptotic events during fertilization, embryo development and implantation. Increasing knowledge of the mechanisms whereby ROS and endogenous antioxidant systems influence reproductive processes can assist to optimise the application of exogenous antioxidants to fertility treatment.

Rembrandt's late self-portraits: psychological and medical aspects. The Dutch painter Rembrandt (1606-1669) left behind the largest series of self-portraits in the history of art. These paintings were produced over a period of time from age 22 years until just a few months before Rembrandt's death at age 63. This series gives us a unique opportunity to explore the development, maturity, and aging of the artist. The changes in Rembrandt's face and expression from one self-portrait to the next may be attributable to any combination of the following factors: normal aging changes, modifications and developments of his artistic style, alterations in the way he viewed himself, and changes in the way Rembrandt wanted us to see him. In addition, the modifications may be attributed in part to some illnesses from which the artist may have suffered and/or to a decline in his eyesight that may have influenced both his ability to detect details and his ability to paint.

Oral toxicity of Kintoki bean (Phaseolus vulgaris) lectin. There are several antinutritive factors in the Kintoki bean such as lectin, trypsin inhibitor, lack of methionine etc. The present experiment has revealed that lectin is mainly responsible for the growth impairment of experimental animals orally fed raw Kintoki bean. Mice fed raw Kintoki bean as the only protein source lost their body weight and died in 8 days, while mice fed the heated bean grew normally. When mice on a 10% albumin diet ingested 20 mg or 40 mg or 60 mg Kintoki bean lectin by daily stomach-feeding, their body weights were reduced to 84%, 74%, 71% of the control group after 5 days respectively and some of them could not live to complete the experiment. The apparent rates of the intestinal absorption of carbohydrate, lipid, and protein were considerably reduced, when rats were fed a diet containing 0.4% lectin. Especially, the rate of protein absorption was decreased to 26.3% from 55.5% of the control rate. The main tissues of mice that had ingested Kintoki bean lectin by stomach-feeding were subjected to microscopic observation. No changes were observed in the liver, kidney, spleen and pancreas. But in the small intestine, the epithelial cells lining the villi were considerably disordered and conspicuously disrupted. These results indicate that the Kintoki bean lectin is one of the most promoting factors for growth impairment in experimental animals and that the first target organ in the case of oral feeding is the small intestine.

Ten-year follow-up of hepatitis B relapse after cessation of lamivudine or telbivudine treatment in chronic hepatitis B patients. The high rate of relapse after cessation of nucleos(t)ide analogues (NUCs) treatment in chronic hepatitis B (CHB) patients leads us to reassess the feasibility for off-therapy, but long-term follow-up data are scarce. We assessed the feasibility for off-therapy by a long-term observation of relapse in response to lamivudine (LAM) and telbivudine (LdT). Eighty-six NUC-naive CHB patients, treated with LAM (n = 46) or LdT (n = 40) who reached the guidelines recommended for off-therapy, were followed for up to 10 years. Hepatitis B virus (HBV), viral serology and biochemistries were periodically determined. COX model was used to predict the risk of relapse. A total of 52.3% of patients experienced relapse within a median of 115 months (range, 61-122 months). A total of 93.3% of relapses occurred within 48 months. Relapse rates in hepatitis B e antigen (HBeAg)-positive (n = 56) and HBeAg-negative (n = 30) patients were 39.3% and 76.7%, respectively (p < 0.01). HBeAg-positive patients who achieved an early viral response (EVR), defined as undetectable HBV DNA within 6 months, had a lower relapse rate compared to non-EVR patients (21.4% vs. 59.2%, p < 0.01). EVR patients who had both lower HBV DNA (<10(6) copies/mL) at baseline and lower hepatitis B surface antigen (HBsAg) at end of treatment had a relapse rate of 10.7%. The high relapse rates in CHB patients over this 10-year follow-up make LAM or LdT off therapy infeasible in most of the cases, except in the case of HBsAg loss and/or seroconversion. HBeAg-positive patients with EVR, lower HBV DNA and HBsAg had lower relapse rates and could be good candidates for off-therapy. Long-term monitoring, especially during the first 4 years, is critical for patients off-therapy.

SICONA: the development of signal conditioning communication aids for the severely hearing impaired. Project SICONA endeavours to satisfy the specific needs of the severely hearing impaired. A complex system is introduced, consisting of several speech processing modules to achieve an improvement of the communication ability within the target group. The basic methods are improving the S/N-ratio by multichannel wireless FM transmission, enhancing weak consonants and second formant information and transposing the unvoiced fricative /s/ into the residual hearing area. Single case studies indicate the effectiveness of the proposed methods; improved reception of speech features within the F2 range and successful integration of the replacement /s/ could be shown. Practical useability is achieved by introducing wireless coupling between the miniaturized (SMD technology, ASIC) system components.

Formation of osteoblast-like cells from human mononuclear bone marrow cultures. Osteoblast-like cells are commonly found in the vicinity of osteoclasts formed in long-term human bone marrow cultures, and they are believed to be derived from osteogenic cell precursors belonging to the stromal cell system. This paper describes a new culture method for human osteoblasts from the adherent cell population of long-term human mononuclear bone marrow cultures. The cells obtained exhibited all the classic characteristics of osteoblasts. They contained high intracellular concentrations of alkaline phosphatase and they secreted the osteoblast-specific marker bone Gla protein. Collagen production was mainly (95-98%) procollagen type I propeptide and only minute quantities of procollagen type III propeptide were detectable by radioimmunoassay in the conditioned medium. After eight weeks the cells formed a mineralized matrix on exposure to beta-glycerophosphate and ascorbic acid. This system provides a model for the study of osteoblast differentiation in vitro and may form the basis for the use of defined media in bone cell cultures due to the presence of high concentrations of osteoblast precursors.

Localization and regulation of the renal kallikrein kinin system: possible relations to renal transport functions. The complete renal kallikrein kinin system has recently been localized in defined nephron segments. Kallikrein was found to be formed and secreted by connecting tubule cells in the late distal convoluted tubule, whereas kininogen and a novel kininase were located in collecting tubules. Kinins were shown to act on collecting tubule as well as medullary interstitial cells and the renal vasculature. The literature on interactions of this system with renal sodium transport is conflicting. Renal and urinary kallikrein was found to be increased under sodium restricted conditions, whereas kinin has a diuretic and natriuretic effect in the collecting tubule, when added from the basolateral surface. On the other hand renal kallikrein activity and connecting tubule cell morphology change in parallel with dietary potassium load indicating a coupling to potassium secretion. The possible role of the renal kallikrein kinin system in regulating collecting tubule function by tubular and vascular effects is outlined in spite of many open questions which remain to be answered.

Microarterial anastomosis using a noncontact diode laser versus a control study. A series of direct carotid end-to-end laser anastomosis vs. direct manual suture was carried out on a series of 70 Wistar rats (mean weight 260 g). Both common carotids (0.8-1.2 mm) were sectioned and repaired. The left side (n = 70) was submitted to laser-assisted microvascular anastomosis (LAMA) performed by means of a diode laser device (wavelength 830 nm and power output 3 W in continuous wave) without chromophore. The right side (n = 70) underwent a control manual suture (CMA). The diode laser energy was delivered into a micromanipulator coupled to a Zeiss operating microscope with a focused spot of 300 microns in diameter. After placement of three 10.0 stitches for edge coaptation, the LAMA was achieved using laser shots (average 3) of 500 mW power, 4.5 s duration, and 700 W/cm2 irradiance each. The CMA was performed by means of six 10.0 stitches. The good vascular flow was confirmed by Doppler spectral analysis (n = 466) carried out from day 0 to day 90. Light and scanning electron microscopy (n = 82) showed that re-endothelialization after LAMA was gaining ground on day 3, whereas collagenous network developed in the media scar by day 10. In contrast, after CMA the arterial repair was delayed on day 20, inducing a media fibrotic scar. The patency rate was 93% in both anastomoses. The shorter operating time (13 min for LAMA vs. 22 min for CMA) and the noncontact laser technique are the main intraoperative advantages. The technical benefits of the diode laser are pointed out.

An optimized compression algorithm for real-time ECG data transmission in wireless network of medical information systems. Recent medical information systems are striving towards real-time monitoring models to care patients anytime and anywhere through ECG signals. However, there are several limitations such as data distortion and limited bandwidth in wireless communications. In order to overcome such limitations, this research focuses on compression. Few researches have been made to develop a specialized compression algorithm for ECG data transmission in real-time monitoring wireless network. Not only that, recent researches' algorithm is not appropriate for ECG signals. Therefore this paper presents a more developed algorithm EDLZW for efficient ECG data transmission. Results actually showed that the EDLZW compression ratio was 8.66, which was a performance that was 4 times better than any other recent compression method widely used today.

Inhibition of hamster adrenal 11 beta/19-hydroxylase activity. Increased mineralocorticoid activity has been associated with elevated urinary levels of 19-nordeoxycorticosterone in several forms of experimental and human hypertension. Biosynthesis of 19-norsteroids involves hydroxylation of the C-19 methyl group. We synthesized the 4-hydroxy analogs of deoxycorticosterone, deoxycorticosterone acetate, progesterone, and androstenedione and evaluated them as inhibitors of deoxycorticosterone 11 beta/19-hydroxylase using hamster adrenal mitochondrial preparations. These 4-hydroxy analogs were inhibitors of this P 450 hydroxylase, with approximately 10 times weaker affinity than their respective natural substrates. 4-Hydroxydeoxycorticosterone was the most potent inhibitor evaluated in this study. The half-maximal inhibitory concentration of deoxycorticosterone hydroxylation was 5 microM, 15 microM, more than 50 microM, and 14 microM, respectively, for the above compounds.

Estrogen receptor-1 genotype is related to coronary intima thickness in young to middle-aged women. The incidence of coronary disease in premenopausal women is about one-half that in men of similar age. The estrogen receptor-1 (ESR1, c.454-397T>C) CC variant genotype is associated with the severity of coronary artery disease (CAD) and an increased risk of myocardial infarction in men. The purpose of the present study was to investigate whether this ESR1 CC variant also disposes to atherosclerosis in women in terms of increased total coronary artery intima thickness. A total of 125 forensic autopsy cases of women aged 15 to 49 years were investigated. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The ESR1 c.454-397T>C genotype was determined by polymerase chain reaction (PCR). The mean intima thicknesses in the three genotype groups were 428+/-298 microm (TT), 494+/-371 microm (CT) and 636+/-436 microm (CC). We found that, on average, women with the CC genotype had a thicker coronary intima compared with that of women with the TT genotype, even after adjusting for age and body mass index (BMI) (p = 0.030). The intermediate group (TC) did not significantly differ from either the CC or the TT genotype group in this respect. Our results point to the importance of ESR1 genotype in relation to cardiovascular disease susceptibility.

Effect of fibrostatin C, an inhibitor of prolyl 4-hydroxylase, on collagen secretion by human Tenon's capsule fibroblasts in vitro. To investigate the effect of fibrostatin C, a prolyl 4-hydroxylase (PH) inhibitor produced by Streptomyces catenulae subsp. griseospora, on type I collagen secretion by human Tenon's capsule fibroblasts (TCFs) in vitro, as an indication of the potential therapeutic efficacy of this compound in antifibrotic therapy after glaucoma filtering surgery. The concentrations of type II procollagen COOH-terminal peptide (PIP) in culture medium or cell lysate were determined by immunoassays. For comparison with its effect on PIP secretion, we determined the effects of the agent on the secretion of other peptides, including laminin, vitronectin receptor, and a metalloproteinase inhibitor. The expression of collagens I and III, fibronectin, and PH by TCFs was examined by immunohistochemistry, and cellular ultrastructure was evaluated by transmission electron microscopy. Fibrostatin C (50 microM) significantly reduced the concentration of PIP in culture medium and increased its concentration in the cell lysate in a dose-dependent manner, but it had no effect on the secretion of other peptides. Cell viability and proliferation were not affected by fibrostatin C. Fibrostatin C also increased the number of cytoplasmic granules immunoreactive with antibodies to collagen I or III, but had no effect on fibronectin or PH immunoreactivity. Ultrastructurally, cisternae of the endoplasmic reticulum were dilated in fibrostatin C-treated TCFs, consistent with the retention of underhydroxylated collagen precursors in this organelle. Fibrostatin C inhibits the secretion of type I collagen by cultured TCFs. This agent may thus prove therapeutically beneficial for inhibiting the excess fibrosis in the wound of filtering surgery.

The Impact of the National HPV Vaccination Program in England Using the Bivalent HPV Vaccine: Surveillance of Type-Specific HPV in Young Females, 2010-2016. The national human papillomavirus (HPV) immunization program was introduced in England in September 2008 using the bivalent vaccine. We collected residual vulva-vaginal swab specimens from 16 to 24-year-old women attending for chlamydia screening between 2010 and 2016 and tested for HPV DNA. We compared changes in type-specific (vaccine and nonvaccine) HPV prevalence over time and association with vaccination coverage. For women with known vaccination status, vaccine effectiveness was estimated. HPV DNA testing was completed for 15459 specimens. Prevalence of HPV16/18 decreased between 2010/2011 and 2016 from 8.2% to 1.6% in 16-18 year olds and from 14.0% to 1.6% in 19-21 year olds. Declines were also seen for HPV31/33/45 (6.5% to 0.6% for 16-18 year olds and 8.6% to 2.6% for 19-21 year olds). Vaccine effectiveness for HPV16/18 was 82.0% (95% confidence interval [CI], 60.6%-91.8%) and for HPV31/33/45 was 48.7% (95% CI, 20.8%-66.8%). Prevalence of HPV16/18 was compared to findings in 2007-2008 (prevaccination) and to predictions from Public Health England's mathematical model. Eight years after the introduction of a national HPV vaccination program, substantial declines have occurred in HPV16/18 and HPV31/33/45. The prevalence of other high-risk HPV types has not changed.

One face or two? Contrasting different versions of the chimeric faces test. The chimeric faces test is a frequently used behavioural test of lateralisation; however the methodologies used vary considerably. In this experiment the one- and two-face versions of the test, using neutral/happy chimeras, were compared to see whether the laterality biases found are correlated. Both versions showed a significant left visual field (or half face) bias, indicating that both reflect the underlying right hemisphere superiority for processing positive facial emotion. Furthermore, the laterality bias was significantly correlated in both versions although reliability was higher for the two-face version.

Neuropharmacology. With virologically suppressive antiretroviral therapy, immune system recovery is now achievable for persons living with HIV (PLWH). This immune recovery is associated with dramatic reductions in acquired immune deficiency syndrome (AIDS) defining illnesses including HIV dementia. However, milder form of cognitive disturbances are widely reported in PLWH despite effective antiretroviral therapy. The underlying pathogenic mechanisms of these cognitive disturbances remain elusive, with many potential pathogenic mechanisms including residual brain damage prior to the initiation of antiretroviral therapy and neuroinflammation and ongoing immune system disturbances despite antiretroviral therapy. Lifestyle factors and concomitant infections and medical problems are also likely to be major contributing factors. The penetration of antiretroviral agents into the central nervous system compartment resulting in a lack of suppression of HIV viremia in the brain has generated much interest as well as potential neuro-toxicities from antiretroviral agents themselves. This chapter reviews the clinical pharmacology, both the pharmacokinetic and pharmacodynamic effects, of antiretroviral therapy in the central nervous system compartment.

Social anxiety and narrowed attentional breadth toward faces. The amount of information that can be perceived and processed will be partly determined by attentional breadth (i.e., the scope of attention), which might be narrowed in social anxiety due to a negative attentional bias. The current study examined the effects of stimulus valence on socially anxious individuals' attentional breadth. Seventy-three undergraduate students completed a computerized dual-task experiment during which they were simultaneously presented with a facial picture at the center of the screen and a black circle (i.e., a target) at the periphery. Participants' task was to indicate the gender of the model in the picture and the location of the peripheral target. The peripheral target was presented either close to or far from the central picture. Higher levels of social anxiety were significantly associated with greater difficulties detecting the target presented far from the central facial pictures, suggesting that social anxiety is associated with narrowed attentional breadth around social cues. Narrowing of attentional breadth among socially anxious individuals might hamper their ability to process all available social cues, thereby perpetuating social anxiety.

MicroRNA-488 inhibits progression of colorectal cancer via inhibition of the mitogen-activated protein kinase pathway by targeting claudin-2. Colorectal cancer (CRC) affects people globally, and lymph node metastasis (LNM) is an important indicator of poor clinical outcome in CRC. The current study aims to evaluate the role of microRNA-448 (miR-488) and claudin-2 (CLDN2) in epithelial-mesenchymal transition (EMT) and LNM of CRC through the MAPK signaling pathway. First, microarray analysis indicated that miR-488 was poorly expressed in CRC, whereas CLDN2 was highly expressed. Additionally, the bioinformatics website MicroRNA.org and the dual luciferase reporter gene assay found that CLDN2 was a target gene of miR-488. Next, the results for the correlations between expression of miR-488 and clinicopathological characteristics of CRC indicated that the expression of miR-488 was closely associated with differentiation degree, LNM, and Dukes stages in CRC patients. Moreover, overexpression of miR-488 inhibited the activation of the MAPK signal transduction pathway. Notably, loss- and gain-of-function experiments demonstrated that upregulation of miR-488 suppressed SW480 cell viability, invasion, and migration and promoted apoptosis in SW480 cells. Finally, overexpression of miR-488 inhibited LNM, microlymphatic vessel density, and tumor growth in nude mice. We conclude that overexpression of miR-488 could suppress the cell proliferation, EMT, and LNM of CRC cells via inhibition of the CLDN2-mediated MAPK signaling pathway, which could be a new molecular therapy target for CRC.

Ophthalmic cyclosporine in equine keratitis and keratouveitis: 11 cases. Topical cyclosporine A was safely used in a series of 11 cases of equine keratitis and keratouveitis and appeared to be an effective anti-inflammatory agent in 9 cases. The clinical diagnoses included interstitial keratouveitis, endotheliitis, multifocal punctate keratopathy and a melting stromal ulcer. In most cases, the presence or absence of insidious bacterial infection was not conclusively determined. Topical cyclosporine A had no deleterious effects in this series of cases. The authors suggest that topical cyclosporine in both aqueous and lipid base vehicles should be investigated and evaluated as an alternative mode of achieving ocular immunosuppression.

Adverse Outcomes Associated with Prescription Opioids for Acute Low Back Pain: A Systematic Review and Meta-Analysis. Acute low back pain (ALBP) is a common clinical complaint that can last anywhere from 24 hours to 12 weeks. In recent years, there has been an opioid epidemic which is linked to the increased availability of prescription opioids. Though guidelines recommend that in the treatment of ALBP, opioids should be used when other treatments fail, we have seen an increase in opioid prescriptions for ALBP. With this crisis, it is important to examine if there are any adverse outcomes associated with prescribing opioids for ALBP. We aim to review the published literature to examine the adverse outcomes associated with opioid use for ALBP. We performed a systematic review with meta-analysis in accordance with our published protocol and PRISMA guidelines. The review was conducted at McMaster University. Various electronic databases for articles published from inception to September 30, 2017, inclusive. Both randomized clinical trials and observational studies on the impact of opioid use in ALBP in the adult population were included. Eight pairs of independent reviewers performed screening, data extraction, and assessment of methodological quality. The identified articles were assessed for risk of bias using sensitivity analysis. Trials with comparative outcomes were reported in a meta-analysis using a fixed effects model. A total of 13,889 studies were initially screened for the review and a total of 4 studies were included in the full review, of which 2 studies were meta-analyzed. Our results showed that prescribing opioids for ALBP was significantly associated with long-term continued opioid use (1.57, 95% CI, 1.06-2.33). There was no significant association found between unemployment duration and prescribing opioids for ALBP (3.54, 95% CI, -7.57 to 14.66). Due to the limited number of studies that considered unemployment, only an unpooled analysis was conducted. Among the included studies there was both statistical and clinical heterogeneity due to differences in methodology, study design, risk of selection or performance bias. Most of the studies had an unclear or high risk of bias and poorly defined side effects. Due to the lack of literature examining long-term adverse outcomes associated with prescribing opioids for ALBP, no definitive conclusions can be made. However, with the literature available, there does seem to be risk associated with prescribing opioids for ALBP so there is a great need to conduct further investigations examining these adverse outcomes for ALBP patients. Acute low back pain, opioids, prescriptions, low back pain, long-term use, opioid use disorder.

6-Methoxyflavanone attenuates mechanical allodynia and vulvodynia in the streptozotocin-induced diabetic neuropathic pain. Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain. 6-MeOF was evaluated for analgesic effect in the hot plate test and streptozotocin-induced diabetic neuropathic pain in female rats using von Frey hairs. The possible involvement of opioidergic and GABAergic mechanisms was investigated using naloxone and pentylenetetrazole (PTZ) antagonists, respectively. The biodistribution of 6-MeOF in plasma and CNS was examined using a validated HPLC/UV analytical method. The binding affinity of 6-MeOF with opioid and GABA receptors was studied using molecular docking simulation approach. 6-MeOF (10 and 30mg/kg) attenuated the acute phasic thermal nociception in the hot plate test while in the case of streptozotocin-induced diabetic neuropathy model, 6-MeOF (10 and 30mg/kg) produced static/dynamic anti-allodynic (increased paw withdrawal threshold and latency) as well as static/dynamic anti-vulvodynic effects (increased flinching response threshold and latency), when compared to the vehicle and standard gabapentin (75mg/kg). In silico studies depicted the preference of 6-MeOF for the delta- and kappa-opioid and GABAA receptors. Moreover, the pharmacokinetic profile revealed a quick appearance of 6-MeOF in the systemic circulation and brain areas with maximum concentration observed after 30min in the amygdala, brain stem and cerebral cortex. 6-MeOF readily crosses the blood brain barrier and may be effective in attenuating the diabetes-induced allodynia as well as vulvodynia, probably through interactions with the GABAergic and opioidergic systems.

Malignancy of congenital cystic adenomatoid malformation of lung in aged. Congenital cystic adenomatoid malformation is rare in adults, and often asymptomatic. We describe a case of malignant degeneration of a congenital cystic adenomatoid malformation in a 77-year-old man. Congenital cystic adenomatoid malformation must be considered a premalignant lesion, even in older patients. Rigorous preoperative staging must be undertaken. Anatomic resection with extensive lymphadenectomy remains the treatment of choice.

Potential misinterpretation of the nutritional value of dietary fiber: correcting fiber digestibility values for nondietary gut-interfering material. The aim of this review is to identify the origin and implications of a nondietary material present in digesta and feces that interferes with the determination of dietary fiber in gastrointestinal contents. Negative values for ileal and fecal digestibility of dietary fiber are commonly reported in the literature for monogastric animal species, including humans. As negative values are not possible physiologically, this suggests the existence of a nondietary material in the gastrointestinal contents and feces that interferes with the accurate determination of dietary fiber digestibility when conventional methods of fiber determination are applied. To date, little attention has been given to this nondietary interfering material, which appears to be influenced by the type and concentration of fiber in the diet. Interestingly, estimates of dietary fiber digestibility increase substantially when corrected for the nondietary interfering material, which suggests that currently reported values underestimate the digestibility of dietary fiber and may misrepresent where, in the digestive tract, fermentation of fiber occurs. A new perspective of dietary fiber digestion in the gastrointestinal tract is developing, leading to a better understanding of the contribution of dietary fiber to health.

Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Allogeneic stem cell transplantation is curative for certain cancers, but the high doses of chemotherapy/radiotherapy lead to toxicity. Here, we treat patients with refractory cancer with 100 cGy total body irradiation (TBI) followed by infusion of nonmobilized pheresed allogeneic peripheral blood cells. Twenty-five patients, with a median age of 47 years, with refractory cancers were enrolled. Eighteen patients received sibling and 7 received unrelated cord blood cells. Donor chimerism was assessed at weeks 1, 2, 3, 4, and 8 after transplantation. Seven patients with solid tumors received a sibling transplant and 6 received a cord blood transplant; none achieved donor chimerism, but 1 treated at the higher dose level of 1 x 10(8) CD3+ cells/kg had a transient nodal response. Twelve patients with hematologic malignancies were treated; 1 received a cord blood transplant and 11 received sibling donor cells. Nine of these 11 patients achieved donor chimerism, ranging from 5% to 100%. Four patients had sustained complete remission of their cancers, including one patient with transient 5% donor chimerism. The development of chimerism correlated with hematologic malignancy (P <.001), total previous myelotoxic chemotherapy (P <.001), T-cell dose (P =.03), and graft-versus-host disease (P =.01). Tumor response correlated with donor chimerism (P =.01). Engraftment was achieved in patients with hematologic malignancies who had been heavily pretreated, suggesting the degree of immunosuppression may be a determinant of engraftment. Low-dose TBI and allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy.

An industrial perspective on bioreactor scale-down: what we can learn from combined large-scale bioprocess and model fluid studies. For industrial bioreactor design, operation, control and optimization, the scale-down approach is often advocated to efficiently generate data on a small scale, and effectively apply suggested improvements to the industrial scale. In all cases it is important to ensure that the scale-down conditions are representative of the real large-scale bioprocess. Progress is hampered by limited detailed and local information from large-scale bioprocesses. Complementary to real fermentation studies, physical aspects of model fluids such as air-water in large bioreactors provide useful information with limited effort and cost. Still, in industrial practice, investments of time, capital and resources often prohibit systematic work, although, in the end, savings obtained in this way are trivial compared to the expenses that result from real process disturbances, batch failures, and non-flyers with loss of business opportunity. Here we try to highlight what can be learned from real large-scale bioprocess in combination with model fluid studies, and to provide suitable computation tools to overcome data restrictions. Focus is on a specific well-documented case for a 30-m(3) bioreactor. Areas for further research from an industrial perspective are also indicated.

[Clinical observation on ziyin tongbi decoction in treating benign prostatic hyperplasia]. To evaluate the efficacy and safety of Ziyin Tongbi Decoction (ZTD) in treating benign prostatic hyperplasia (BPH). Adopting randomized positive controlled clinical trial method, the 100 BPH patients were assigned to two groups equally. The treatment group was medicated with ZTD, one dose per day, consisting of wild weed 12 g, yellow cocktree bark 12 g, rehmannia root 10 g, Chinese yam 15 g, bitter cardamon 10 g, red sage root 10 g, burreed tuber 8 g, tumeric rhizome 8 g, mantis egg-case 8 g, ground beetle 8 g, Zhejiang fritillary bulb 10 g, and prunella spike 15 g, etc., by decocting with water, taking twice daily and 150 mL each time. The control group was treated by Longbishu Capsule, a product of Kedi Pharmaceutical Co., Ltd., consisting of psoralea fruit, motherwort, and lysimachia, etc., twice a day, 0.9 g each time. A course of 4 weeks was given to both groups. The therapeutic efficacy was evaluated by changes in TCM symptoms after treatment (including frequency of night urination, degree of dysuria, condition of urinary thread, soreness and weakness in loin and knees, lower abdominal distention, spiritless and general weakness), the International Prostate Syndrome Score (I-PSS), maximum flow rate (Qmax), residual urine volume and prostate volume. The TCM symptoms were improved in the treatment group after treatment, showing significant as compared with those before treatment (P < 0.05); as compared with the control group, the difference in urinary thread and lower abdominal distention in treatment group was significant improved (P < 0.05). The total effective rate in the treatment group was 89.00% (43/48), while that in the control group was 73.46% (36/49), showing statistically significant difference between them (P < 0.01). The efficacy in the treatment group in aspect of improving I-PSS and Qmax was better than that in the control group (P < 0.05, P < 0.01). The residual urine volume was reduced in both group, as compared with that before treatment (P < 0.05), but showed no significant difference between the two groups (P > 0.05). No obvious change of the prostate volume was found in both two groups after treatment (P > 0.05). There are 4 patients in the treatment group and 5 in the control group complained of slight adverse reactions as gastric discomfort and dry mouth, but these were not attended and showed no affection on the treatment. ZTD is effective and safe for the treatment of benign prostatic hyperplasia.

Futility without a dichotomy: towards an ideal physician-patient relationship. The futility debate may be considered as an effort to provide a clear and justified borderline between physician and patient decision-making authority. In this paper we argue that the search for a definition of futility that provides physicians with a final argument in discussions about life-prolonging treatment, is misplaced. An acceptable and meaningful criterion of futility that satisfies this effort seems impossible. As a consequence, we reject a dichotomous domain of decision-making power as the starting point for definitions of futility. A good decision about withholding life-sustaining treatment should be justified from the perspectives of both physician and patient. In this light, a range of definitions of futility is still useful as it can clarify intuitions that a treatment is inappropriate.

Comparative trial on the therapeutic effectiveness of the new anthelmintic drug: ciclobendazole. In a double-blind study in Cameroon the vermicidal effect of Ciclobendazole, a new Benzimidazole derivative, was evaluated and compared to Mebendazole. Ciclobendazole and Mebendazole were equally effective in the treatment of Ascaris and Hookworm infestations. An increase in the dosis of Ciclobendazole from 600 mg to 1200 mg did not lead to an improvement in the effectiveness. When treating trichuriasis significantly better results were achieved with Mebendazole (p = 0.01). Both drugs were tolerated equally well. Side effects, such as vomiting and diarrhoea, only occurred in a small percentage of cases.

Are routine peritoneal fluid cultures during appendicectomy justified? To determine the impact of obtaining routine peritoneal fluid cultures during appendicectomy, on the treatment and the clinical outcomes. The case notes of 137 consecutive patients having appendicectomy, selected from the microbiology database over a period of 1 year were reviewed. The microorganisms in peritoneal cultures, selection of antibiotics and clinical outcomes were recorded. Patients were subdivided into two groups; group I: uncomplicated appendicitis and group II: complicated appendicitis. The study included 137 patients with a median age of 19 years. Cultures were obtained from 79.5% of patients (group I: 67/84, group II: 42/53). Cultures were positive in 28.3% (19/67) patients in group I and 69% (29/ 42) in group II. Wound infection (5.6%), prolonged ileus (7.5%) and intra-abdominal abscess (3.7%) were the recorded complications in group II. Antibiotics were modified in 3 out of 109 patients. Intra-operative peritoneal cultures during appendicectomy do not significantly contribute towards patient management.

Coronary heart disease in residents of Rochester, Minnesota. IV. Prognostic value of the resting electrocardiogram at the time of initial diagnosis of angina pectoris. The data in this study were based on the 1,154 Rochester residents in whom a resting electrocardiogram had been obtained at the time of diagnosis of angina pectoris as the initial manifestation of coronary heart disease during the 26-year period 1950 through 1975. The finding of a normal electrocardiogram at the time of the initial diagnosis of angina pectoris was associated with a good prognosis. Survival at 5 years was equal to that expected, for the given age and sex distribution, under a cohort life table for the Minnesota white population. In contrast, in those patients who had an abnormal electrocardiogram at the time of diagnosis, the observed survival rate was 86% of that expected at 5 years.

Catheter valves: a welcome alternative to leg bags. Catheterisation is commonly used to manage long-term bladder drainage. If intermittent catheterisation is not possible an indwelling urethral or suprapubic catheter will be used. There are a choice of drainage systems for use with indwelling urinary catheters including bed bags, link systems and catheter valves. Catheter valves are not suitable for everybody and patient assessment is vital: only patients with the cognitive ability and manual dexterity to operate a valve should be offered this option for bladder drainage. Catheter valves offer a number of advantages over drainage bags including improved privacy and dignity, prevention of bladder-neck trauma, reduced catheter encrustation and maintenance of normal detrusor muscle function. A number of catheter valves are available, including the EZ-Flow valve, and patient choice is important when selecting an appropriate product.

Effects of novel retinoid X receptor-selective ligands on myeloid leukemia differentiation and proliferation in vitro. The biologic effects of retinoids such as all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid on proliferation and differentiation of hematopoietic cells are mediated by binding and activating two distinct families of transcription factors: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). The RARs require heterodimerization with RXRs; in addition, RXRs can form homodimers, which can bind to DNA response elements that are either distinct or the same as those bound by the RAR/RXR heterodimers. Therefore, the two retinoid pathways provide sequences that are specific for effective DNA binding and activation of target genes. We have developed several series of novel synthetic retinoids that selectively interact with RXR/RXR homodimers and RAR/RXR heterodimers. We show here that SR11236 and SR11246, which are RXR-selective analogs, had little ability to inhibit clonal growth and induce differentiation of leukemic cells (HL-60 cells and fresh acute myeloid leukemia cells). However, SR11249, SR11256, and LGD1069, which activated both RXR/RXR homodimers and RAR/RXR heterodimers, could inhibit clonal growth and induce differentiation of HL-60 cells as well as leukemic cells from patients, including those with acute promyelocytic leukemia (APL). This is similar to results observed with RAR/RXR-specific ligands. Interestingly, the combination of ATRA and either SR11249, SR11256, or LGD1069 showed synergistic effects in inducing differentiation of HL-60 cells. A retinoid (SR11238) with strong anti-AP-1 activity that did not activate the RARs and RXRs for gene transcription from the response element TREpal was inactive in our assay systems, suggesting that the antiproliferative effects of retinoids on leukemic cells is not mediated by inhibiting the AP-1 pathway. We conclude that the RAR/RXR pathway is more important than RXR/RXR pathway for differentiation and proliferation of acute myeloid leukemic cells, and certain retinoids or combination of retinoids with both RAR and RXR specificities may synergistically enhance the differentiation activity of ATRA, which may be relevant in several clinical situations.

Placental thromboxane and prostacyclin production in an ovine diabetic model. We hypothesized that streptozocin-induced ovine diabetes would cause alterations in the placental production of thromboxane and prostacyclin. With a tissue incubation technique, we examined the placental production of thromboxane and prostacyclin in cotyledons from seven normal near-term ewes (127 +/- 3 days' gestation) and six streptozocin-induced diabetic ewes (125 +/- 3 days' gestation). Diabetic status was verified with serial fasting blood glucose assessments. Placental tissue was incubated in Dulbecco's modified Eagle's medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide. Samples were collected at 0, 1, 2, 4, 8, 20, 32, and 48 hours. Radioimmunoassay of the stable metabolites thromboxane B2 and 6-keto-prostaglandin F1 alpha were used to determine thromboxane and prostacyclin production, respectively. Placental thromboxane production was reduced in diabetic animals when compared with control animals (5.63 +/- 2.81 vs 7.32 +/- 1.37 pg/mg per hour, respectively; p less than 0.05). Prostacyclin production was also significantly reduced in the diabetic placentas compared with control placentas (11.44 +/- 4.06 vs 16.29 +/- 4.59 pg/mg per hour, respectively; p less than 0.05). We conclude that the ovine placenta produces thromboxane and prostacyclin. The ovine thromboxane production rate is comparable to that of the human placenta but the prostacyclin production rate is approximately two to three times higher. The observed decrease in the placental production of thromboxane and prostacyclin may reflect an adverse effect of hyperglycemia directly on eicosanoid production or indirectly through decreased placental cellular proliferation.

Soft-tissue accumulation of lead in the blue tilapia, Oreochromis aureus (Steindachner), and the modifying effects of cadmium and mercury. The interaction of mercury and cadmium with lead was investigated by exposing Oreochromis aureus to two heavy metals simultaneously. The chronic accumulation profile of lead was determined by analyzing the liver, brain, gill filaments, intestine, caudal muscle, spleen, trunk kidney, and gonads following exposure to lead alone and in mixtures with mercury and cadmium. Nominal exposure concentrations of lead were 0.05, 0.10, 0.50, and 1.00 mg/L. Mixtures of lead (0.50 or 0.05 mg/L) with cadmium (0.05 mg/L) and lead (0.50 or 0.05 mg/L) with mercury (0.05 mg/L) were also used. Following 140 d of exposure to lead, the highest concentrations of lead consistently accumulated in the trunk kidney. The concentration of lead in the kidney was decreased by coexposure to mercury or cadmium, but increased in the muscle and liver. Under all exposure regimes, the median concentration of lead in the muscle exceeded safety levels recommended for human consumption. In a food fish, such as O. aureus, a knowledge of toxic metal accumulation patterns is of great importance.

Autoantibodies in Autoimmune Liver Diseases-Methods of Detection and Interpretation: An Update for the Reporting Pathologist. Autoimmune liver disease (AILD) is a type of chronic liver disease with autoimmune etiology. The diagnosis of the disease is multipronged and detection of autoantibodies in AILDs is an important diagnostic tool and it also helps in the classification of the disease. There are multiple autoantibodies that are detected in AILDs but none is diagnostic. Moreover, these autoantibodies are detected in many other pathological and nonpathological conditions. So the significance of seropositivity for these autoantibodies should be known by both the pathologists as well as the clinicians. In addition, there is prognostic significance associated with some of the antibodies and they also sometimes help in the disease monitoring. The whole array of antibodies detected in AILDs is discussed in detail in this review along with their clinical significance and interpretation.

The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients. We sought to investigate whether two polymorphisms located in the promoter (T(-786)C) and exon 7 (Glu298Asp) of the endothelial nitric oxide (NO) synthase (eNOS) gene affected agonists-mediated NO release. Endothelial dysfunction can be genetically determined. Therefore, we investigated whether two polymorphisms located in the eNOS gene affected agonists-mediated NO release. We compared endothelial-dependent and -independent vasodilation of the different eNOS genotypes in a cross-sectional study on 187 subjects, of whom 137 were uncomplicated essential hypertensive patients (PH) (49 +/- 9 years, 151 +/- 11/99 +/- 5 mm Hg) and 50 healthy normotensive subjects (NT) (43 +/- 16 years, 123 +/- 10/78 +/- 7 mm Hg). Endothelial-dependent and -independent vasodilation was assessed as the forearm blood flow response to incrementally increasing doses of acetylcholine (0.15, 0.45, 1.5, 4.5, 15 microg/100 ml/min) and sodium nitroprusside (1, 2, 4 microg/100 ml/min), respectively. Genotyping was performed with melting curve analysis (Lightcycler) of polymerase chain reaction products from acceptor (5' end-labeled with LCRed 640) and donor probes (3' end-labeled with fluorescein) specific for each polymorphism. The genotype distribution of T(-786)C (CC = 21.9%, CT = 48.7%, TT = 29.4%) and Glu298Asp (GG = 39.0%, GT =51.9%, TT = 9.1%) was similar in PH and NT. A repeated measure analysis of variance showed a blunting of endothelium-dependent vasodilation in PH compared with NT (p < 0.001). A significant effect of the T(-786)C (p = 0.002) but not of the Glu298Asp (p = NS) eNOS polymorphism on endothelial-dependent vasodilation was found. However, we also detected a significant interaction between the T(-786)C and Glu298Asp polymorphism (p < 0.001). No effect on either polymorphism on endothelial-independent vasodilation was seen. The T(-786)C promoter polymorphism and its interaction with exon 7 Glu298Asp affect endothelium-dependent vasodilation in mild-to-moderate PH patients and NT Caucasian subjects.

Reproductive biology of Astyanax janeiroensis (Osteichthyes, Characidae) from the Ubatiba river, Maricá, RJ, Brazil. Aspects of the reproductive biology of Astyanax janeiroensis in the Ubatiba river in Maricá, RJ, Brazil were evaluated in order to ascertain whether the strategy adopted by the species is causally related to environmental variables. Specimens were collected on a monthly basis from October 1994 to September 1995, through electrofishing. The Sex ratio was not significantly different from the expected frequency of 1:1 (G = 1.29; p > 0.50); nonetheless, considering three standard length classes, significantly larger numbers of females were recorded for the higher SL class (G = 11.07; p < 0.01). Size at first maturation showed no significant differences between sexes. Length-weight ratio analyses showed negative allometry for males and isometry, for females. Length structure was significantly different between sexes, suggesting that females are larger than males (D = 0.027, p < 0.01). Reproductive specimens were recorded during nine months of the annual cycle. Seasonal variations of reproductive specimens belonging to two different standard length classes displayed an asynchronous behavior, with larger specimens having a longer reproductive period and smaller ones reproducing for fewer months during the annual cycle. High values of fecundity (F), varying from 3169 to 18714 oocytes, were recorded for fish of 9.1 and 10.2 cm lengths, respectively. The correlation between weight and number of oocytes/unit of weight was positive, indicating that larger specimens produced more eggs.

Induction of thrombospondin expression in vascular smooth muscle cells by angiotensin II. Vascular smooth muscle cells (VSMCs), unlike cardiac or skeletal myocytes, are capable of undergoing reversible phenotypic modulation from "contractile" to "proliferative/synthetic" cells in vivo. We have investigated the ability of angiotensin II (Ang II) to influence this process via modulation of extracellular matrix synthesis. Ang II induced a rapid (within 2 h), dose (10(-6)-10(-9) M)-dependent stimulation (14-fold) of thrombospondin (TSP) gene expression in rat VSMCs in the absence of additional factors. This was followed by an enhanced platelet-derived growth factor (PDGF) A chain and transforming growth factor-beta (TGF beta) gene expression. These effects of Ang II could be negated by the simultaneous addition of saralasin (IC50 approximately 10(-9) M for Ang II at 10(-7) M) to cells. Transcription levels for TSP were further enhanced (to 28 X control values) by 6 h, at which time the synthesis of PDGF A chain mRNA was maximal. Although exposure of cells to TSP (5 X 10(-8) M) stimulated signal transduction pathways, it did not enhance levels of either PDGFA or TGF beta transcripts. The glycoconjugate content of extracellular matrices elaborated by cells chronically exposed to Ang II was elevated compared to control cultures and there was a small increase in cell number.

Familial Leydig cell hypoplasia as a cause of male pseudohermaphroditism. A case of familial Leydig cell hypoplasia as a cause of male pseudohermaphroditism is described in two 46,XY female sibs. Biochemical and histologic evidence for such diagnosis is presented.

High Coulombic Efficiency Na-O2 Batteries Enabled by a Bilayer Ionogel/Ionic Liquid. Sodium-oxygen (Na-O2) cells are a promising high energy density storage technology with a theoretical specific energy of 1605 Wh kg-1. However, this technology faces certain challenges in order to achieve both a high practical energy density as well as long-term cycling capability. In this Letter, a superior Coulombic cyclic efficiency, close to 100%, has been demonstrated by the use of a bilayer electrolyte composed of an ionogel and an ionic liquid electrolyte, reported herein for the first time. The presence of the ionogel plays a major role in the prevention of side reactions originating at the anode, providing a promising route to extend cell cycling, whereas the ionic liquid is essential to support high reaction rates at the cathode.

Effects of etamsylate on equine platelets: in vitro and in vivo studies. The aim of this study was to investigate whether etamsylate produces equine platelet activation. In vitro and in vivo studies were designed in which seven and eight adult healthy horses were included, respectively. In the in vitro study, citrated blood was incubated with different concentrations of etamsylate, and P-selectin expression and annexin V binding were determined by flow cytometry. In the in vivo study, blood was collected before and 1 and 2h after IV administration of etamsylate, and P-selectin expression was evaluated. In the in vitro study, a significant increase in P-selectin expression, leukocyte-platelet aggregate formation and annexin V binding were observed. In the in vivo study, a marked increase in P-selectin expression and heterotypic aggregate formation was seen in two and five horses, respectively, although no significant differences were detected when analyzing results from all the animals together. The results of the in vitro study indicate that etamsylate produces a pre-activation state in equine platelets, but this fact could be confirmed by the in vivo study.

Sex ratio in the offspring of parents with chronic radiation exposure from nuclear testing in Kazakhstan. The former Soviet Union conducted a nuclear test program in the Semipalatinsk region of northeastern Kazakhstan in 1949-1989. The population in the vicinity of the test site was chronically exposed to radiation fallout, especially from above-ground tests during 1949-1956. Male:female sex ratio has been proposed as a measure of reproductive health, with some reports suggesting an alteration in the sex ratio of offspring of parents exposed to radiation. We investigated the impact of radiation exposure and other factors on the sex ratio in the population inhabiting the exposed region. A total of 11,464 singleton births of 3,992 mothers exposed to radiation during 1949-1956 were analyzed. The overall sex ratio was 1.07, similar to the current sex ratio in Kazakhstan (1.06). The sex ratio increased from 1.04 where mothers received <20.0 cSv to 1.12 where mothers received > or =60.0 cSv. However, the linear trend across exposures was not significant (P = 0.42). No consistent association was found between the sex ratio and the time since parental radiation exposure, parental age at exposure, or year of birth. Sex ratio was significantly associated with maternal age, birth order and possibly ethnicity but not with paternal age, parental educational level or season. In conclusion, no significant association was found between radiation exposure level and sex ratio, but some previously suggested demographic factors were positively associated with sex ratio.

Effects of gliadin stimulation on bone marrow-derived dendritic cells from HLA-DQ8 transgenic MICE. Gliadin presentation by HLA-DQ2/8 molecules to T cells plays a crucial role in triggering the inflammatory cascade in coeliac disease. We aimed to study the immunological effects of gliadin stimulation on dendritic cells (DCs) from HLA-DQ8 transgenic and BALB/c mice. Bone marrow-derived DCs were stimulated with alpha-chymotrypsin-digested gliadin or ovoalbumin (100 microg/ml). Modification of DC maturation, through HLA-DQ8 and MHC class II expression, and activation, by CD80 and CD86, was assessed by flow cytometry. The ability of pulsed and unpulsed DCs to prime T cells was evaluated by mixed leucocyte reaction. The expression of interleukin-4, -10, -12p70 and interferon-alpha, as well as of Toll-like receptor-4, -7, -8, -9 was determined by ELISA and real-time RT-PCR, respectively. Gliadin stimulation induced DC maturation (p<0.001 in BALB/c, p<0.01 in DQ8) but not activation, whereas ovoalbumin upregulated all markers (p<0.01 for maturation and p<0.001 for activation in both DC populations). No increase of T proliferation was elicited by pulsed DCs with respect to unpulsed DCs. Only in DQ8 DCs, gliadin induced Toll-like receptor-4 (p<0.001), -7 (p<0.001), -8 (p<0.005) expression and interferon-alpha (p<0.001) secretion. Gliadin resulted unable to activate DC, but stimulated Toll-like receptor expression and interferon-alpha secretion.

Guidelines for the diagnosis and management of hereditary spherocytosis--2011 update. Guidelines on hereditary spherocytosis (HS) published in 2004 (Bolton-Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical management, (particularly the indications for concomitant splenectomy with cholecystectomy in children with mild HS, and concomitant cholecystectomy with splenectomy in those with asymptomatic gallstones). Further potential long term hazards of splenectomy are now recognised. Advances have been made in our understanding of the biochemistry of the red cell membrane which underpins the choice of tests. Biochemical assays of membranes proteins and genetic analysis may be indicated (rarely) to diagnose atypical cases. The diagnostic value of the eosin-5-maleimide (EMA) binding test has been validated in a number of studies with understanding of its limitations.

Interaction among alliance, psychodynamic-interpersonal and cognitive-behavioural techniques in the prediction of post-session change. The current study examined the interaction of clients' perceptions of the psychodynamic-interpersonal (PI) and cognitive-behavioural (CB) techniques that their therapist utilized in their most recent therapy session and working alliance in the prediction of post-session changes. Seventy-five clients were treated by 25 therapists at a counselling centre in the USA. We posited that alliance would interact with clients' perceptions of their therapists' use of PI and CB techniques in the prediction of post-session changes. The results revealed a three-way interaction between clients' perceptions of the alliance, PI techniques and CB techniques in the prediction of post-session changes. More PI and more CB techniques and more PI but fewer CB techniques were associated with better post-sessions changes in the context of higher alliances. More CB techniques but fewer PI techniques and fewer PI and fewer CB techniques were not significantly associated with post-session changes in the context of higher (or lower) alliances. Clients' perceptions of PI techniques in the context of stronger alliances were most beneficial for post-session outcomes. Thus, a high alliance will likely maximize the impact of PI techniques. Clients who rated their therapist as being relatively inactive reported fewer positive post-session outcomes, suggesting that an idle therapeutic approach is not advantageous. Therapist differences explained two to three times more variation in session outcomes than client ratings of alliance or techniques. Some therapists are better at facilitating positive session outcomes as compared with others, suggesting that a potential key barometer of therapists' effectiveness may be captured by session outcomes.

Lymph node metastasis of presacral ependymoblastoma in a young child. Ependymoblastoma presenting outside the brain is rare in children. The overwhelming majority of presacral ependymal tumors are of the benign myxpapillary type. We present a case of ependymoblastoma in the presacral region of a four-year old child. The patient presented with a presacral mass and ipsilateral inguinal lymph node metastasis. Both masses revealed histologic and immunophenotypic features of ependymoblastoma associated with myxoid areas and high Ki-67 proliferation index. The masses were excised and the patient remained well for a year after diagnosis with no other therapy. This report emphasizes ependymoblastoma as rare entity in the differential diagnosis of presacral tumors in children and, up to our knowledge, the first report of inguinal lymph node metastasis of ependymoblastoma.

Changes in plasma amino acid patterns in chronic alcoholic patients during ethanol withdrawal syndrome: their clinical implications. Changes or imbalances in plasma amino acid patterns during withdrawal from ethanol were recorded in six randomly selected male chronic alcoholic patients (age range 23-47 years). Duration of drinking ranged from 4-15 years and their average daily amount of ethanol intake was more than 100G. Plasma amino acids (taurine, threonine, serine, glutamate, glutamine, proline, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, tryptophan, ornithine, lysine and arginine) were estimated by autoanalyzer in all patients on admission before starting conventional detoxification therapy for ethanol withdrawal syndrome, and during therapy on day 3 and day 6. On admission, there was a statistically significant rise in the plasma levels of almost all aminoacids, particularly glutamate, glutamine, phenylalanine, proline, glycine, methionine, cysteine, lysine, tyrosine, valine, isoleucine, leucine, serine, threonine, alanine and arginine (in comparison to those of normal controls) in five out of six patients. During the following six days of treatment and total abstinence, the pattern of plasma aminoacid levels did not change significantly despite considerable clinical improvement. Plasma tryptophan levels were undetectable in all patients on admission, day 3 and also on day 6 except in one patient with lesser amount and shorter duration of drinking, the levels just returned to within normal range only on day 6. Plasma levels of histidine and taurine were found to be slightly lower than normal.

[Chronic hepatitis C and risk for hepatitis A infection]. The aim of this study was to determine the prevalence of anti-HAV antibodies and factors associated with HAV infection amongst patients with chronic hepatitis C. The prevalence of anti-HAV antibodies in hepatitis C patients was 69.2% and did not differ significantly from 63.3% observed in the group of healthy controls. In patients with chronic hepatitis C the occurrence of HAV antibodies was not associated with the duration of HCV infection, history of transfusions and surgeries. There was a tendency towards higher prevalence of anti-HAV in persons with history of numerous hospitalizations (60.8% of persons with the history of up to 5 hospitalizations were positive for anti-HAV and more than 84.6% of those with more than 5 hospitalizations). Only 38.5% of patients under 35 years had anti-HAV antibodies. In conclusion immunization against hepatitis A should be recommended for hepatitis C patients under 35 years of age, most of whom are not immune to HAV. Testing for anti-HAV prior to vaccination should be performed in individuals older than 35 because natural immunity is common.

Nephrogenic systemic fibrosis. A debilitating disease causing fibrosis of the skin and inner organs in patients with kidney failure. Nephrogenic systemic fibrosis (NSF) is a rare and debilitating disease which affects patients with kidney failure. The most obvious manifestation is fibrosis of the skin, but it also frequently involves the locomotor system and the inner organs. An association has been found with the administration of gadolinium-containing contrast agents, which are given to provide enhanced contrast during magnetic resonance imaging. It is thought that unstable chelate complexes release toxic gadolinium. Other triggers or co-triggers may also be relevant. No effective treatment currently exists for NSF, so prevention of the disease is of the utmost importance. If gadolinium-containing contrast agents need to be administered to patients who have kidney failure, a cyclic agent should be used, and the dosage should be as low as possible. Although no proof is yet available that hemodialysis prevents NSF, it is effective in the clearance of gadolinium and should therefore be considered as a treatment immediately after the imaging.

[Principles of self-adjusting staining of sections of cerebral cortex for automatic structural analysis]. The development of methods of an automatic structural analysis which uses modern methods of image processing has put forward requirements to standardize the staining of the preparations studied. However, the examination of autopsy material of the human brain shows that the standard procedure of staining does not always lead to standard results. The author presents a formalized description of changes in the quality of preparation staining at different stages, which is based on the measurement of distributions of the mean gradients of the section image obtained with the help of the textural analysis system TAS produced by Leitz. The procedure of adaptive staining based on this description is proposed, which will help to compensate for differences in tinctural properties of different samples of autopsy material.

Multiple loss-of-function 5-O-glucosyltransferase alleles revealed in Vitis vinifera, but not in other Vitis species. Wild and loss-of-function alleles of the 5 - O - glucosyltransferase gene responsible for synthesis of diglucoside anthocyanins in Vitis were characterized. The information aids marker development for tracking this gene in grape breeding. Anthocyanins in red grapes are present in two glycosylation states: monoglucoside (3-O-glucoside) and diglucoside (3, 5-di-O-glucoside). While monoglucoside anthocyanins are present in all pigmented grapes, diglucoside anthocyanins are rarely found in the cultivated grape species Vitis vinifera. Biochemically 3-O-glucoside anthocyanins can be converted into 3,5-di-O-glucoside anthocyanins by a 5-O-glucosyltransferase. In this study, we surveyed allelic variation of the 5-O-glucosyltransferase gene (5GT) in 70 V. vinifera ssp. vinifera cultivars, 52 V. vinifera ssp. sylvestris accessions, 23 Vitis hybrid grapes, and 22 accessions of seven other Vitis species. Eighteen 5GT alleles with apparent loss-of-function mutations, including seven premature stop codon mutations and six frameshift indel mutations, were discovered in V. vinifera, but not in the other Vitis species. A total of 36 5GT alleles without apparent loss-of-function mutations (W-type) were identified. These W-type alleles were predominantly present in wild Vitis species, although a few of them were also found in some V. vinifera accessions. We further evaluated some of these 5GT alleles in producing diglucoside anthocyanins by analyzing the content of diglucoside anthocyanins in a set of representative V. vinifera cultivars. Through haplotype network analysis we revealed that V. vinifera ssp. vinifera and its wild progenitor V. vinifera ssp. sylvestris shared many loss-of-function 5GT alleles and extensive divergence of the 5GT alleles was evident within V. vinifera. This work advances our understanding of the genetic diversity of 5GT and provides a molecular basis for future marker-assisted selection for improving this important wine quality trait.

Kinetics of benzene metabolism in rats in inhalation exposure. Rats inhaling benzene concentrations 400, 800, 2,000, or 4,000 mg m-3 for 6 h excreted similar amounts of phenol in urine; hence benzene metabolism was already capacity-limited at 400 mg m-3. The rate of phenol elimination in the course of 12 h inhalation of benzene, 2,000 mg m-3, was increasing; the in vitro rate of hepatic microsomal benzene metabolism was increasing accordingly. Phenobarbital (PB) pretreatment significantly increased phenol excretion in rats exposed to benzene at 800 mg m-3 and higher concentrations. This effect disappeared during 12 h benzene inhalation, although the in vitro hepatic microsomal benzene metabolism in PB rats was significantly higher than in the controls.

Development of neural systems for reading in the monolingual and bilingual brain: new insights from functional near infrared spectroscopy neuroimaging. What neural changes underlie reading development in monolingual and bilingual children? We examined neural activation patterns of younger (ages 6-8) and older (ages 8-10) children and adults to see whether early-life language experience influences the development of neural systems for reading. Using functional Near Infrared Spectroscopy, we observed an age-related shift in neural recruitment of language areas (left inferior frontal gyrus [LIFG], superior temporal gyrus [STG]). Bilinguals showed a greater extent and variability of neural activation in bilateral IFG and STG, and higher cognitive areas (dorsolateral prefrontal cortex, rostrolateral prefrontal cortex). This bilingual "neural signature" reveals the extent that neural systems underlying reading development can be modified through differences in early-life language experience.

Safety of endoscopic sphincterotomy in patients under dual antiplatelet therapy. Dual antiplatelet therapy has to be used for at least one month after placement of bare metal coronary stents and for a minimum of one year after placement of drug eluting stents. Because of the higher risk of bleeding, guidelines strongly recommend to delay elective surgery until dual antiplatelet therapy is terminated. However, no data are available regarding the bleeding risk in patients on combined aspirin/clopidogrel therapy undergoing high-risk endoscopic procedures, such as emergency endoscopic biliary sphincterotomy. We retrospectively analyzed the medical reports of patients who had to undergo endoscopic retrograde cholangiography with endoscopic sphincterotomy (ES) while on dual antiplatelet therapy in our unit between January 2009 and December 2011. In our series, ES was safely performed in eight consecutive patients on dual antiplatelet therapy with no evidence of bleeding. ES may be safely performed in patients on dual antiplatelet therapy.

On the nature of the oxygen uptake in the light by Chondrus crispus. Effects of inhibitors, temperature and light intensity. The nature of the different processes of O2 uptake involved in the light in the red macroalga Chondrus crispus Stackhouse (Rhodophyta, Gigartinales) was investigated. At limiting CO2, INH (2.5 mM) did not alter the O2 uptake rate. Glycolate was not excreted and did not accumulate within the cells. KCN reduced the rate of O2 uptake in the light by 76% at limiting CO2 and by 43% at saturating CO2, but caused > 95% inhibition of O2 evolution. DCMU (5 μM) totally blocked the photosynthetic electron transport chain, but allowed a residual O2 uptake of 3.0±0.6 μmol O2 .h(-1).g(-1) FW, irrespective of the CO2 concentration. In saturating CO2, a high light intensity pretreatment significantly stimulated the rate of O2 uptake compared to net O2 evolution, suggesting the persistence, in the light, of mitochondrial respiration. Irrespective of the CO2 concentration, the optimum temperature for O2 evolution was 17°C whereas dark O2 uptake increased linearly with temperature. In contrast, O2 uptake in the light showed an optimum at 17°C in limiting CO2, and 21-25° C in saturating CO2; its Q10 was 2.4 at limiting CO2, a value close to that of RuBP oxygenase, and 3.1 at saturating CO2, a value close to that of dark respiration. It is concluded that: 1) mitochondrial respiration and Mehler reaction are both involved at all CO2 concentrations, 2) RuBP oxygenase activity cannot account for more than 45%, and Mehler reaction for less than 20%, of the total O2 uptake observed in the light at limiting CO2.

Initiation and duration of laryngeal closure during the pharyngeal swallow in post-stroke patients. As a bolus enters the pharynx during the swallow, the airway is protected by laryngeal closure, a process characterized by approximation of the vocal folds plus approximation of the arytenoid cartilages to the base of the epiglottis. The purpose of this study was to measure initiation of laryngeal closure (ILC) and laryngeal closure duration (LCD) in three groups of subjects: (1) ten stroke patients who aspirated before and during the swallow (aspirators), (2) ten stroke patients who did not aspirate (nonaspirators), and (3) ten normal control subjects. Means and standard deviations of ILC and LCD were analyzed for both 5-ml and 10-ml thin-liquid boluses using a 100-ms timer during subsequent analysis of videofluoroscopic swallowing examinations. There were significant differences between aspirators and control subjects for both ILC and LCD, and significant differences between aspirators and nonaspirators for ILC. There were no significant differences between aspirators and nonaspirators for LCD. Both delayed ILC and reduced LCD were associated with post-stroke aspiration. Delayed ILC is a significant indicator of overall risk of aspiration. Clinical implications for these findings are discussed.

Immunotherapy of B-cell non-Hodgkin lymphoma by targeting the chemokine receptor CXCR5 in a preclinical mouse model. Bispecific antibodies are promising agents for immunotherapy. Here, we describe a quadroma-based trifunctional bispecific antibody binding the chemokine receptor CXCR5 and the T-cell antigen CD3 that efficiently prevents tumor growth in a mouse B-cell lymphoma model. CXCR5 regulates the tissue homeostasis of mature B cells and is highly expressed on B-cell non-Hodgkin and lymphocyte-predominant Hodgkin lymphoma, as well as on a subset of CD4(+) T cells known as follicular T-helper cells. In vitro, the bispecific CXCR5::CD3 antibody efficiently recruited effector T cells to CXCR5 expressing B cells and induced a co-stimulation-independent activation of CD8(+) and CD4(+) T cells as demonstrated by the de novo expression of CD25 and CD69, and secretion of the cytokines IFN-γ, TNF-α, IL-6 and IL-10 by peripheral blood mononuclear cells. Notably, at low antibody concentrations, CXCR5::CD3 displayed a significantly higher cytotoxic activity against autologous B cells than its parental antibodies or rituximab. In vivo imaging revealed that CXCR5::CD3 and its parental CXCR5 antibody efficiently prevent tumor growth in a xenograft model of B-cell lymphoma in mice and prolong their survival. Taken together, our results identify CXCR5 as a promising target for antibody-based therapies in the treatment of B-cell malignancies.

Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes. 1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood. 2. Using g.c.-m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01-11.90) versus 18.60 (3.20-32.60) micrograms/100 micrograms of protein, P less than 0.02]. 3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity (LS/S) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean +/- SEM, 37.6 +/- 1.3 versus 33.8 +/- 0.6, P less than 0.02). 4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically (LS/S correlated negatively with glycophorin sialic acid content, r = 0.73, P less than 0.05). 5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes.

Optimal timing of surgical intervention following adult laryngeal trauma. Laryngeal trauma is an infrequent diagnosis with a scarcity of published data. We aim to further define the factors associated with positive surgical outcomes of adult laryngeal trauma. Multi-institution database analysis. Of the 1.9 million trauma cases from the National Trauma Database (NTDB), 564 adult trauma events were selected with ICD-9 codes specific to laryngeal trauma. Laryngeal trauma was seen predominately in white (61.5%), middle-aged (40.6 years), male (83.7%) patients experiencing blunt (70.7%) laryngeal injury with multiorgan system (92.2%) trauma. There was an overall 17.9% mortality rate. Within the 564 cases, 133 direct laryngoscopies, 185 tracheostomies, 53 laryngeal suturing, and 60 laryngeal fracture repairs were performed. In univariate negative binomial regression models, trauma severity (P ≤ .01), placement of tracheostomy (P lt; .01), and delayed tracheostomy placement (P = .04, .03, .048) were associated with increased ventilator dependence, intensive care unit (ICU) stay, and overall hospital admission duration. Multivariate regression models demonstrated significant associations between tracheostomy performed within 24 hours and shortened ICU stay (P = .03, β = -.28, SE = 1.7) and overall hospital stay (P = .009, β = -.23, SE = 3.1). The NTDB allows study of the largest laryngeal trauma cohort in modern literature. Although complexities arise in the treatment of laryngeal traumas, when indicated, surgical airway should be placed within 24 hours of presentation to improve the overall hospital course.

Information processing in post-traumatic stress disorder. Previous research has established that patients suffering from anxiety disorders, including post-traumatic stress disorder (PTSD), exhibit a cognitive bias that selectively favours the processing of threat material. This information processing bias has frequently been demonstrated by subjects' performance on the Stroop colour-naming task. The current experiment investigated the selective processing of threat information in people with PTSD using a modified Stroop procedure. Subjects were 13 ferry disaster survivors with high PTSD symptomatology, 20 survivors of the same disaster with low PTSD symptomatology, and 12 non-traumatized control subjects. All were asked to colour-name five types of words: ferry disaster words, general threat words, neutral semantically-unrelated words, neutral semantically-related words, and positive words. The disaster survivors with high levels of PTSD symptomatology evidenced a significantly longer response latency for colour-naming disaster-related words than for other word types. The results of the low-PTSD survivors and non-traumatized controls showed no significant difference between response latencies for general threat words and disaster word, although all 3 groups showed increased latencies for threat words compared with neutral words. The mechanisms proposed to underlie this response pattern are discussed, and clinical implications are considered.

Evidence for bradykinin mediation of carrageenin-induced inflammatory pain: a study using kininogen-deficient Brown Norway Katholiek rats. Inflammatory pain was induced following an intradermal injection of carrageenin into rat paws, and the hyperalgesia was measured in terms of withdrawal time following thermal pain stimulation of the inflamed paw. This hyperalgesia was significantly less in kininogen-deficient Brown Norway (B/N)-Katholiek rats, which also showed less swelling in carrageenin-induced paw edema, than in normal B/N-Kitasato rats at 1 approximately 4 hr after the carrageenin injection (at the early phase). However, 24 hr after the injection, hyperalgesia and the swelling volume of the kininogen-deficient rats were almost the same as those in normal rats. The bradykinin B2 receptor antagonist FR173657, (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinolinyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide, attenuated the carrageenin-induced swelling and hyperalgesia of the normal rats at the early phase to almost the levels of the B/N-Katholiek rats. Pretreatment with indomethacin, a cyclooxygenase inhibitor, also inhibited the carrageenin-induced responses significantly in normal rats. These results indicate that bradykinin, acting on the B2 receptor, is the main mediator at the early phase of inflammatory pain of carrageenin edema and that prostaglandins, produced by cyclooxygenase, potentiate the effects of bradykinin.

A Note on the "One Case per Stagger Position" Character of Common Multiple-Baseline Intervention Designs. To overcome the constraint of common multiple-baseline designs that only one case per stagger position is permitted. Three alternative strategies for assigning more than one case to each stagger position are examined. The three recommended strategies achieve the objective while maintaining the study's internal and statistical-conclusion validities. ExPRT, a freely available Excel-based randomization-test package, can be used to assist in both the design and statistical analysis associated with each of the strategies.

An alternative approach to debonding lingual brackets. This clinical pearl describes a technique of debonding the lingual brackets with minimum discomfort to the patient. It also reduces the risk of swallowing or aspirating the brackets and decreases the risk of enamel damage.

The Effects of AS160 Modulation on Fatty Acid Transporters Expression and Lipid Profile in L6 Myotubes. AS160 is a key intracellular regulator of energy utilization in cells. It was shown to regulate GLUT4 translocation from intracellular depots to the plasma membrane, with subsequent changes in facilitated glucose uptake into the skeletal muscles. Similarly, also free fatty acids (FFAs) transmembrane transport seems to be largely protein-mediated. Therefore, the objective of this study was to examine the effects of moderate AS160 depletion (-82% mRNA, -25% of protein content) on the expression of fatty acid transporters and subsequent changes in lipid profile in L6 myotubes. Surprisingly, moderate down regulation of AS160 expression was followed by increased AS160 phosphorylation (∼40%). These resulted in a greater expression of fatty acid transporters, namely FABPpm and FAT/CD36, with subsequently increased FAs cellular influx. No changes in the expression of FATP1 and 4 were noticed. Accordingly, we have observed a reduction in total TAG content. This was mainly caused by a significant changes in TAG fatty acids composition favouring a decrease in the amount of palmitic and stearic fatty acid moieties. In contrast, our experimental intervention led to distinctively increased total content of DAG and PL, but concomitantly decreased the content of all measured sphingolipids, e.g. SFA, SA1P, CER, SFO and S1P, in the AS160 knockdown group. Modulation of AS160 level and activity led to significant increase in the concentration of DAG and PL, which was associated with changes in FAs composition and expression of fatty acid transporters. Interestingly, the intervention also simultaneously decreased the content of sphingolipids.

[Treatment possibility of a horizontal tibial fracture in performance athletes]. Short oblique and horizontal fractures of the tibia, which frequently occur during sports activities tend to result in delayed unions. We describe two cases where the incidence of delayed fracture healing and duration of treatment were reduced by internal fixation and secondary decortication.

Self-help groups for families of schizophrenic patients: formation, development and therapeutic impact. In recent years, self-help groups for relatives of schizophrenic patients have become a vital organization in Germany. The commitment of group members is often impressive, but an empirical study investigating the impact of the activity in such groups has yet to be published. An initial approach was made possible by the Münster Families Study, a prospective evaluation study designed to register the impact of relatives' self-help schizophrenic patients. Following a 1-year therapeutic phase, two relatives' self-help groups were formed; these were followed for 2 years. The study showed that relatives of severely mentally ill male patients with high levels of expressed emotion (EE) were most likely to join self-help groups. In the 2-year follow-up period, there was a tendency towards a more favourable development among these patients than among the comparably ill patients forming a control group, whose relatives were not involved in self-help. What was more marked, however, was the positive development among involved relatives, whose EE levels remained unchanged but who displayed higher levels of social contacts and fewer physical complaints. When encouraging the formation of such self-help groups, however, it has to be borne in mind that only a small proportion of relatives can be motivated to, or are capable of, active long-term involvement.

Reliability of the long case. The use of long cases for summative assessment of clinical competence is limited by concerns about unreliability. This study aims to explore the reliability of long cases and how reliability is affected by supplementation with short cases. We performed a statistical analysis of examinations held by the Royal Australasian College of Physicians in 2005 and 2006 to determine overall reliability and sources of variance in reliability according to candidate ability, case difficulty and inter-examiner differences. Scores for 546 long cases in 2005 and 773 long cases in 2006 were analysed. In 2006, 38% of the total variation in long case data was explained by variation in candidate ability, with other significant contributors to variance being candidate x case and candidate x examiner interactions. Similar figures were found for the 2005 examinations. A short case is less reliable than a long case, but when examiner time is taken into account, three short cases are as reliable as one long case. Any combination of short and long cases would require 4-5 hours of testing time in order to achieve dependability > 0.7. Long cases can be optimised for reliability but time limits their use as the sole tool in a high-stakes examination. Further examiner training, better case selection, or greater use of short cases would have minimal impact on reliability. Reliability can be improved by either increasing examination time or including additional methods of summative assessment, such as might be provided by workplace assessment.

Saphenous vein graft aneurysm and fistula with compression mimicking mitral stenosis. We present the case of a patient who presented with acute coronary syndrome and was found to have a mass compressing the left atrium. An angiogram revealed a large saphenous vein graft aneurysm with a fistula into a cardiac chamber, presumed to be the left ventricle. The patient also developed a functional mitral stenosis secondary to this mass causing left atrial compression. The patient passed away prior to receiving surgery. We describe a rare case of venous graft aneurysm with compression and fistula to a chamber other than the right atrium, that to our knowledge has yet to be reported.

Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients. Probiotics (PRO) modulate immunity in humans, while the effect of prebiotics (PRE) and synbiotics (SYN) on the human immune system are not well studied yet. The objective of this study was to investigate whether daily intake of a SYN modulates immune functions. In a randomised double-blind, placebo-controlled trial, thirty-four colon cancer patients who had undergone 'curative resection' and forty polypectomised patients participated. Subjects of the SYN group daily received encapsulated bacteria (1 x 10(10) colony-forming units of Lactobacillus rhamnosus GG (LGG) and 1 x 10(10) colony-forming units of Bifidobacterium lactis Bb12 (Bb12)) and 10 g of inulin enriched with oligofructose. Controls received encapsulated maltodextrin and 10 g of maltodextrin. Prior to intervention (T1), and 6 (T2) and 12 weeks after the start of the intervention (T3), phagocytic and respiratory burst activity of neutrophils and monocytes, lytic activity of natural killer cells and production of interleukin (IL)-2, IL-10 and IL-12, as well as tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) by activated peripheral blood mononuclear cells (PBMC) were measured. In faeces, the concentrations of transforming growth factor-beta1 and prostaglandin E2 were measured. IL-2 secretion by activated PBMC from the polyp group increased significantly between T1 or T2 and T3 (P < 0.05). In the cancer group, SYN treatment resulted in an increased capacity of PBMC to produce IFN-gamma at T3 (P < 0.05). Other immunity-related parameters were not affected by SYN treatment, neither in the cancer nor in the polyp group. In conclusion, supplementation with this SYN has minor stimulatory effects on the systemic immune system of the two study groups. Further studies in humans should aim to focus on the gut-associated immune system.

Got mold? Hospitals make progress in the fight against fungus. Mold is everywhere and there is no such thing as a mold-free facility. The author reports on how hospitals (some spurred by mold-related lawsuits) are becoming more adept at responding to water damage and finding, removing and preventing mold.

Beyond a sense of safety: a psychologist's tale of serious chronic illness. Based on a narrative account, this paper highlights and reviews the experiences of the author, a psychologist, experiencing a chronic illness. Areas covered include coping with doctors and medical personnel, adjusting to illness, complying, actively coping, and even, at times, resisting unwarranted medical procedures. Experiences such as loss of trust, a sense of isolation, re-working relationships, and generative reaching-out are also covered. Some positive consequences of chronic illness for personal growth are suggested. Suggestions for conducting psychotherapy with clients who are dealing with serious chronic illness are made.

Responses of parasitoids to saproxylic hosts and habitat: a multi-scale study using experimental logs. Species belonging to higher trophic levels are particularly vulnerable to habitat loss and consequential host population declines, but detection of effects depends on observation scale. We investigated the effects of habitat and host availability at multiple scales on parasitoids of early successional saproxylic beetles in middle boreal Sweden, where forestry has led to habitat fragmentation and coarse woody debris (CWD) loss. Parasitoid wasps and beetle hosts were collected from nine locations, each containing three spruce-dominated stand types (clear-cut, mature managed and unmanaged stands), using emergence traps on experimental CWD. We measured local CWD volumes and determined the availability of forests of a suitable age within the landscape. We tested parasitoid responses to stand type, CWD volume, abundance of known and probable hosts and longitude. Additionally, we tested whether parasitoids responded to the area of habitat of a suitable age within radii from 0.2 to 10 km. Stand type appeared in best-fit models for all common species, suggesting that wasps respond strongly to habitat at local scales. Longitude (largely climate) featured commonly, but CWD volume was never significant. Host abundance appeared in best-fit models for three of five common species, proving significant only for Bracon obscurator, the abundance of which correlated with that of Orthotomicus laricis at both trap and site levels. Rhimphoctona spp. also correlated significantly with its known host Tetropium castaneum at the trap level. B. obscurator responded to habitat area at scales of 0.6-1 km and Cosmophorus regius responded at radii greater than 7 km, while the larger species did not respond strongly to habitat area. The role of habitat area at greater scales thus varied greatly amongst species, but our data suggest that dispersal of these common early successional species may not be strongly restricted at the current scale of fragmentation of their boreal habitats.

High-dose cytosine arabinoside-induced cutaneous reactions. High-dose cytosine arabinoside (HDAC) is being used increasingly to treat haematological malignancies. The therapy is associated with various non-haematological negative side-effects, frequently involving the skin. Our aim was to evaluate the actual occurrence of adverse skin reactions to HDAC over the 10-year period from 1989 to 1999. One hundred and seventy-two subjects, 118 with acute myelogenous leukaemia and 54 with acute lymphoblastic leukaemia, between 16 and 71 years of age were treated with 226 post-remission consolidation regimens with HDAC (54 subjects underwent two cycles of treatment). Treatment was combined with standard doses of other cytotoxic drugs. A prospective study of the skin changes was then performed. The overall incidence of cutaneous reactions was almost 53%, with rashes occurring in 72.7% and 40.6% of subjects who received total doses of 30 and 24 g/m2, respectively. In the group of subjects who received a second cycle of treatment not all of those who experienced exanthema after the first cycle (44.4%) experienced this reaction after the second cycle (only 33.3%). The most commonly observed reactions were morbilliform eruptions on the trunk and extremities and acral erythema, although severe reactions with swelling and generalized urticaria developed in some cases. HDAC-induced cutaneous reactions in 53% of subjects. The skin changes were found to be dose related and most cleared spontaneously without requiring treatment. A clinical grading of cutaneous toxicity has been proposed to allow better comparison of cutaneous adverse effects in different reports.

Differential cardiovascular regulatory activities of the alpha 1B- and alpha 1D-adrenoceptor subtypes. The regulation of cardiac and vascular function by the alpha 1B- and alpha 1D-adrenoceptors (ARs) has been assessed in two lines of transgenic mice, one over-expressing a constitutively active alpha 1B-AR mutation (alpha 1B-ARC128F) and the other an alpha 1D-AR knockout line. The advantage of using mice expressing a constitutively active alpha 1B-AR is that the receptor is tonically active, thus avoiding the use of nonselective agonists that can activate all subtypes. In hearts from animals expressing alpha 1B-ARC128F, the activities of the mitogen-activated protein kinases, extracellular signal-regulated kinase, and c-Jun N-terminal kinase were significantly elevated compared with nontransgenic control animals. Mice over-expressing the alpha 1B-ARC128F had echocardiographic evidence of contractile dysfunction and increases in chamber dimensions. In isolated-perfused hearts or left ventricular slices from alpha 1B-ARC128F-expressing animals, the ability of isoproterenol to increase contractile force or increase cAMP levels was significantly decreased. In contrast to the prominent effects on the heart, constitutive activation of the alpha 1B-AR had little effect on the ability of phenylephrine to induce vascular smooth muscle contraction in the isolated aorta. The ability of phenylephrine to stimulate coronary vasoconstriction was diminished in alpha 1D-AR knockout mice. In alpha 1D-AR knockout animals, no negative effects on cardiac contractile function were noted. These results show that the alpha1-ARs regulate distinctly different physiologic processes. The alpha 1B-AR appears to be involved in the regulation of cardiac growth and contractile function, whereas the alpha 1D-AR is coupled to smooth muscle contraction and the regulation of systemic arterial blood pressure.

Clinicoepidemiologic study of posttransplant diabetes after living-donor renal transplant. We sought to evaluate posttransplant diabetes mellitus with regard to its incidence, risk factors for occurrence, complications, impact on graft function, and impact on patient and graft survival rates. A total of 1,580 patients received living-donor renal allografts at Mansoura University, Egypt, between March 1976 and November 2004. Of these, 286 recipients developed diabetes after transplant (diabetic group). These patients were matched with 316 kidney transplant recipients who did not develop diabetes after transplant (control group). A complete clinical history was obtained and a clinical examination was done. Laboratory analyses including urine analysis, complete blood count, total serum cholesterol, fasting and 2-hour postprandial plasma glucose, Hb A1c, serum creatinine, and creatinine clearance were obtained in all patients. In each patient, presence of hepatitis B and C was determined with polymerase chain reaction, and a graft biopsy was obtained to diagnose renal allograft rejection. The onset of diabetes mellitus among our recipients occurred primarily during the first 6 months after transplant (in 52.4% of the patients). Significant correlations were found between posttransplant diabetes mellitus and the recipients' age (P = .0001), obesity (P = .001), positive family history of diabetes mellitus (P = .001), hepatitis C virus infection (P = .039), cumulative dose of steroids in the first 3 months (P = .047), and calcineurin inhibitor-based immunosuppressive therapy (P = .001). Moreover, posttransplant diabetes mellitus significantly affected rates of coronary heart disease (P = .001), hypertension (P = .02), and hypercholesterolemia (P = .001). Graft survival was similar in both groups until 15-year follow-up, at which time graft survival began to decrease in patients with diabetes mellitus compared with those without diabetes mellitus (43.5% vs 53.6%, P = .013). Similarly, patient survival was similar until 8-year follow-up, at which time survival rates began to decline in patients with diabetes as compared with patients without diabetes (79.9% vs 86.1%, P = .001); this trend continued to the 15-year follow-up (60.6% vs 77.8%, P = .001). Posttransplant diabetes mellitus is a major problem that endangers patient and graft survival. In our population, the incidence of posttransplant diabetes mellitus was 18.2%. Further studies are recommended to screen for patients with impaired fasting glucose and impaired glucose tolerance for prediction, early detection, and better management of posttransplant diabetes mellitus.

Sense receptors with electron-dense supporting structures, and centrioles in the nerve fibres of Gieysztoria and Rhinolasius (Platyhelminthes, Rhabdocoela). The ultrastructure of two types of sense receptors each is described for Gieysztoria and Rhinolasius. In Gieysztoria, one receptor possesses a number of long microvilli, a cilium with a cross-striated rootlet, a septate desmosome, and an electron-dense band apical to the desmosome. The band forms a complex reticulate extension into the base of the receptor. The second receptor is without microvilli, has a cilium with a long cross-striated rootlet, and a septate desmosome with a short basal electron-dense extension or extensions which do not form a complete ring. In Rhinolasius, one receptor possesses a short bulbous cilium without a rootlet, with a septate desmosome of the pleated sheet (comb) type and a weakly developed electron-dense band beneath it. The second receptor has a long cilium with cross-striated rootlet, and a septate desmosome with a weakly developed electron-dense band apical to it. Centrioles were found in nerve fibres of both species.

Ultrastructural studies of alterations induced by microwaves in Toxocara canis eggs: prophylactic interest. The ultrastructure of Toxocara canis eggs is described before and after exposure to microwaves. The morphology of normal eggs is compared to that of eggs from other helminths. Following treatment, the complete disorganization of the surface structure of the shell and the loss of much turgidity of the egg are observed. The destruction of the internal structure is most marked in the center of the egg and is associated with the disappearance of some layers of the shell. In addition, there is substantial damage to the synthesis apparatus (ribosomes, endoplasmic reticulum, lipid cisternae). An explanation based on the specific action of microwaves and micro-overheating is proposed, and the prophylactic use of this technique is considered.

[How to analyze periodontal morphotypes in order to reduce the risk of periodontal recession]. The periodontal morphotype is a leading feature to be born in mind during surgical, implant, prosthetic, restorative as well as orthodontic treatment. A fragile morphotype will rapidly trigger severe and worrying clinical repercussions for the patient. In order to minimize the risks involved, sound knowledge of the different morphotypes and of the techniques for clinically evaluating them is a major requirement. These factors need to be regularly reassessed since morphotypes can vary throughout the course of treatment. Detecting and controlling mucogingival risk factors will enable an appropriate clinical approach designed to avoid the onset of secondary recessions or other gingival pathologies.

[Sacral nerve root cysts. Discussion on the mechanism of nerve root suffering. Apropos of 4 cases]. Low back pain, sciatia or perineal chronic pain are sometimes related to perineural sacral cysts. Surgical treatment is difficult and may lead to pain or neurological worsening. We report four cases of symptomatic perineural cysts; three of them where operated on with two good results and one increasing perineal pain. Anatomical and radiological description are reviewed. From a therapeutical point of view, we can distinguish two clinical types of radicular suffering. Perineural cyst can cause a commun radicular extrinsic compression; in such a case surgical operation will improve radicular pain. The cystic nerve root can present an intrinsic suffering because of on intradural dilaceration. Then surgery must be avoided specially when many roots are involved because it may worsen the pluriradicular suffering.

Mechanisms of antimicrobial resistance in bacteria. The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.

Growth and menarche during remission in children with juvenile idiopathic arthritis. Growth retardation is a common complication of juvenile chronic arthritis. The aim of this study was to determine how physical development in children with juvenile chronic arthritis is affected by the subtype and duration of the disease, and by the type of therapy used. The study group included 71 children, 24 boys and 47 girls, ranging in age from five to eighteen years diagnosed and treated with juvenile chronic arthritis in Wrocław. At the time the subjects were examined, the disease was in remission. Anthropometric parameters were expressed in terms of standard deviations score using age and sex-specific reference values for Warsaw children. Anthropometric parameters measured included body height, body weight and BMI. 4.3% of the children were short in stature. Growth was inhibited only in those subjects that had been receiving glycocorticosteroids for more than one year. This can probably be attributed both to the effects of glycocorticosteroid treatment, and to the fact that the course of the disease in these children was severe enough to warrant the use of glycocorticosteroids, in the first place. The mean age of menarche for the girls in the study group was 12.8 years. This was not statistically different from the mean for the reference group. Regular evaluation of physical development is an essential component of the protocol for monitoring the progress of the disease and the effect of the therapeutic strategy used, in children suffering from juvenile chronic arthritis.

Interaction of diazoxide, tolbutamide and ATP4- on nucleotide-dependent K+ channels in an insulin-secreting cell line. The single-channel current recording technique has been used to study the effects of diazoxide, tolbutamide and ATP, separately and combined, on the gating of nucleotide-regulated K+ channels in the insulin-secreting cell line RINm5F. The effects of diazoxide, tolbutamide and ATP4- were studied at the intracellular membrane surface, using the open-cell membrane patch configuration. Alone diazoxide was found only inconsistently to evoke channel stimulation, 57% of all applications of the drug (72 times in 48 separate patches) having no effect at concentrations between 0.02 and 0.4 mM. In the presence of ATP, however, diazoxide consistently evoked channel activation (seen 87 times in 49 patches, 95% of all applications). The interactions of diazoxide and ATP seemed competitive. Stimulation of channels by diazoxide in the presence of 1 mM ATP was suppressed if the concentration of ATP was elevated to 2 or 5 mM. In solutions in which Mg2+ had been chelated with EDTA, diazoxide failed to activate channels closed by 1 mM ATP; however, this was not due to a direct effect on the channels caused by the absence of Mg2+, but could be explained by the enhanced ATP4- concentration after Mg2+ removal. When the total ATP concentration was lowered to give the same [ATP4-] in the absence of Mg2+ to that present in the control experiments, diazoxide was able to evoke full activation. Channel inhibition evoked by tolbutamide, 0.01 to 1.0 mM, did not require the presence of either ATP or Mg2+. In the presence of ATP tolbutamide further reduced the number of channel openings. Diazoxide was able to compete with tolbutamide for control of channel activity, an effect that was augmented by the presence of ATP. In the presence of 0.1 mM tolbutamide, diazoxide was unable to stimulate channel openings; however, if the dose of tolbutamide was lowered or ATP made available to the inside of the membrane, channel stimulation occurred.

Coping with cancer: creative teaching strategies in an elective for nursing students. Many people find it difficult to imagine that working with cancer patients can be a positive and rewarding experience. A variety of creative teaching strategies was used in teaching an elective, "Coping with Cancer," to nursing students in a baccalaureate program. The use of these teaching strategies was expected to foster an interest in oncology nursing. This article describes the journey in the teaching-learning process that allowed students to experience the adventure of cancer nursing. Drawing exercises, communication dyads, gaming strategies, and case study analysis are among the teaching strategies described in this article.

[The role of the serotoninergic system of the brain in cimetidine-stimulated prolactin secretion]. Pharmacological studied were made on serotoninergic drugs (5-hydroxytryptophane, metisergid and p-chlorphenylalanin) to clarify mechanisms of cymetidine-stimulating secretion of prolactin. The experiments were carried out on white male rats at two stages: the first stage, in which dose-dependent influence of cymetidine on the release of prolactin was determined; and second stage, in which studies with indicated serotoninergic drugs after their 5-day administration were made on prolactin content after treatment with cymetidine in two doses of 20 mg/kg and 80 mg/kg of body mass. Prolactin content was determined in sera of male rats by a radioimmunological method. The results showed the influence of drugs--agonists and antagonists of serotonine on the release of prolactin after cymetid action and gave foundation to discuss them as a possible serotoninergic mechanism after cymetidine-stimulating secretion of prolactin. The results indicate the possibilities for clinical trial of serotoninergic drugs as correction of the side effect of cymetidine on prolactin secretion.

In-vitro cytotoxicity and combination effects of the docetaxel-conjugated and doxorubicin-conjugated poly(lactic acid)-poly(ethylene glycol)-folate-based polymeric micelles in human ovarian cancer cells. The pH-sensitive doxorubicin (DOX)-conjugated and docetaxel (DTX)-conjugated poly(lactic acid)-poly(ethylene glycol)-folate (PLA-PEG-FOL)-based polymeric micelles were developed and characterized in this study. The drugs were released from the micelles (particle size, ~185 nm) in a pH-dependent manner. The drug-conjugated PLA-PEG-FOL micelles showed higher cellular uptake than nontargeting ones. Single agent and combination in-vitro cytotoxicity studies were also performed using the two drugs in both free and their micellar forms in SKOV3 human ovarian cancer cells using three different cytotoxicity assays. Like the free drugs, DOX-conjugated and DTX-conjugated targeting micelles showed significant cytotoxic effects in SKOV3 cell line. Moreover, the drug-conjugated targeting micelles improved cytotoxicity compared to the FOL-free ones. Different ratios of IC50 of free drugs were used for combination therapy, and synergistic, additive or antagonistic effects were evaluated. The synergistic effect was observed in specific DOX : DTX mixing ratios, which result in the increase in therapeutic efficacy using low doses of each test compound without formulation related side effects. The prepared micelles may provide appropriate delivery systems for doxorubicin and docetaxel in both single and combination therapies.

Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy. High resolution PCR-SSOP typing methods for HLA-B identification have been established and applied to a Northern Ireland population, using large enough numbers to give dependable allele frequencies. The six systems, which operate independently of each other, are intended for use as secondary typing systems following HLA-B identification with a medium resolution PCR-SSOP technique.

Effects of thalamic stroke on energy metabolism of the cerebral cortex. A positron tomography study in man. Positron emission tomography was used to study the effects of unilateral vascular thalamic lesions on cortical oxygen and glucose utilization in 10 patients. There was significant ipsilateral cortex hypometabolism in 9 of the 10 patients, affecting the whole cortical mantle diffusely. The only patient spared was free of neuropsychological deficit at the time of positron emission tomography. In 4 patients, the magnitude of ipsilateral cortical hypometabolism was significantly less at a follow-up PET study, when neuropsychological function had improved. When taken together, the 14 studies showed a significant tendency for the hypometabolism to improve with time after clinical onset. These data suggest that the ipsilateral cortical hypometabolism results from damage to the thalamocortical connections and reflect either loss of nonspecific activating afferences or a degenerative deafferentation-deafferentation process, or both. Its links with the concept of diaschisis are suggested by its tendency to recover. A causal relationship between cortical hypometabolism and neuropsychological deficit, however, although strongly suggested, cannot be firmly established from the present data.

Diagnosis and treatment of obsessive compulsive disorder. Obsessive compulsive disorder (OCD) is a common anxiety disorder that appears to be due to a disturbance in central serotonergic functioning. Drugs, such as clomipramine, that inhibit neuronal reuptake of serotonin are effective in treating OCD. Behavioral therapy techniques are also effective.

Development of a web-based SEM specifically for K-12 education. The scanning electron microscope (SEM) is uniquely suited for use in education due to its ability to produce clear three-dimensional-looking images of virtually any sample. Elementary and secondary science textbooks regularly contain SEM images of bugs, plants, human tissue, rocks, etc. as a means of illustrating the microscopic world to students. However, despite the widespread use of SEM images for educational purposes microscope companies have virtually ignored the area of education in their development and design of SEMs, due presumably to a perceived lack of marketing potential in this area. This article presents the results of a program aimed at developing a Web-based SEM that is specifically designed for educational use by students and teachers in pre-college classrooms. While virtually all companies tout some form of remote control, no concerted effort has been made to fully develop these capabilities for use by the education sector. The microscope under development, termed the WebSEM, seeks to remedy this situation and address this neglected market. Remote control of the WebSEM is possible by means of a simple web interface that allows the users a wide range of controls, depending on the skill of the operator at the remote site. The web interface is specifically designed to be simple and reliable such that little or no training is required for use. This joint effort between educators and a microscope manufacturer is the first attempt at the development of a truly education-oriented SEM suitable for use in the classroom.

Reassessment of electrovectorcardiographic signs of left atrial enlargement. Echocardiographic left atrial size was correlated with 27 electrovectorcardiographic parameters in 93 subjects. In 20 of them hemodynamic studies, including calculation of the left atrial volume, were performed. Subjects were divided into four groups as follows: Group I, 21 healthy subjects; group II, 45 patients with heart disease but no left atrial enlargement; group III, 15 patients with heart disease and left atrial size from 4.1 to 5 cm; and group IV, 12 patients with heart disease and a left atrial size exceeding 5 cm. A good correlation was found between left atrial size and the following parameters: Duration of P wave in standard lead II, voltage of both terminal forces of P wave in lead V1 and its maximal vector in the frontal and sagittal planes. A new index (duration/voltage of P wave in lead II) was postulated, which showed an excellent correlation with left atrial size (p less than 0.001). In all cases the superposition between groups was excessive. These findings indicate the limitations of the classical patterns and raise interest in new parameters concerning the electrocardiographic diagnosis of left atrial enlargement.

Sepsis associated with hematological malignancies: prophylaxis of Pseudomonas aeruginosa sepsis. Underlying diseases, pathogenic bacteria, clinical background and outcome were studied during 91 febrile episodes complicated by sepsis in 55 patients with hematological malignancies, who had been admitted to our hospital (Jikei University Kashiwa Hospital) between January 1990 and December 1994. Particularly in patients with P. aeruginosa sepsis, we compared the prophylactic effect of ciprofloxacin (CPFX) alone with that of the combination of polymyxin B (PL-B) plus kanamycin (KM). The major underlying diseases were acute myelocytic leukemia and malignant lymphoma, followed by myelodysplastic syndrome, acute lymphocytic leukemia and chronic myelocytic leukemia. Nearly two-thirds of the pathogenic microorganisms isolated were gram-positive bacteria (including coagulase-negative staphylococci and Staphylococcus aureus); approximately one-quarter were gram-negative bacteria (such as Pseudomonas aeruginosa), and the remainder were fungi. These microorganisms usually induced sepsis when granulocyte counts were decreased. Sepsis was a direct cause of death in about 60% of the patients and P. aeruginosa sepsis had the worst outcome. Oral administration of CPFX was more effective than PL-B plus KM in preventing P. aeruginosa sepsis. The difference in effectiveness might depend on the absorption profile of the drugs.

Early clinical trials of chemopreventive and biologic agents: Designs, populations, and endpoints. The optimal design for initial clinical trials of chemopreventive agents for cancer has not been determined. A single design is unlikely to be the model for chemoprevention of cancer, even for prevention of a single subtype of cancer, because of the heterogeneity of drugs under investigation and the variety of biologic effects being targeted. Factors that are important in designing initial clinical trials include the proposed mechanisms of drug action, the ability and types of assays available to detect that activity or pharmacodynamic effect, and the extent of prior clinical experience. In this article, we present a discussion of the factors to be considered in initial activity studies, followed by a specific example of early clinical assessment of a noncytotoxic agent (R-flurbiprofen, E-7869) as a potential chemopreventive agent for prostate cancer.

MRI of facial skeleton and parapharyngeal space. The diagnostic value of magnetic resonance imaging is examined in relation to computed tomography on the basis of 66 patients, who had pathological processes in the midfacial and nasopharyngeal space. The high power of contrast resolution in imaging soft tissue masses and the direct multiplanar capability of magnetic resonance offer advantages over computed tomography in respect of space occupying lesions in the median and lower parts of the craniofacial skull. Lymph nodes of more than 1 cm. in diameter were detected by both modalities. A disadvantage is the poorer detectability of tumour conditioned bone destruction at the base of the skull. In such cases, computed tomography remains the method of choice.

Comparative analysis of new innovative vaccine formulations based on the use of procaryotic display systems. A T helper epitope was expressed in three innovative delivery vehicles recently developed in our laboratories and based respectively, on the filamentous bacteriophage fd, the E2 protein from the PDH complex of Bacillus stearothermophilus and the protein CotC of Bacillus subtilis spores. Studies of antigenicity and immunogenicity were performed by using a specific T cell hybridoma and by priming mononuclear cells isolated from the venous blood of human donors. The results indicate that the E2 system is the best suited for inducing a specific immune response towards a CD4 T cell epitope. Importantly, TCR clonal analysis demonstrated the persistence over years of a previously described antigen specific clonotype and its presence correlates with the immunogenic strength of the antigen delivery system.

Coping behaviors of young children during a chest tube procedure in the pediatric intensive care unit. This descriptive correlational study examined the coping behaviors of young children experiencing a chest tube procedure in the pediatric intensive care unit (PICU) and explored specific variables that may affect coping. A developmental model of stress and coping among children provided the theoretical framework for the study. A sample of 24 children, age 2.9 to 6.8 years old, participated. Mothers completed the Dimensions of Temperament Scale-Revised and a demographic information form. In the PICU, children's coping behaviors during chest tube removal were observed and recorded on the Children's Coping Strategies Checklist-Intrusive Procedures. Analysis used descriptive statistics, correlations, chi-squares, t-tests, and repeated-measures analysis of variance. Findings indicate that the predominant coping behaviors represented a self-protective approach to the procedure, followed by reaching out and controlling behaviors, and information-seeking behaviors. Correlations between coping and nine temperament dimensions revealed significant results between coping and Activity-General, Activity-Sleep, and Flexibility.

Aspirin "resistance". Recent clinical studies have shown that the expected antiplatelet effect of aspirin is not always achieved. From the laboratory point of view, resistance to aspirin is the inability to achieve the expected inhibition of platelet cyclooxygenase-(COX-)1 with prevention of platelet thromboxane (TX) A2 formation. The failure to prevent atherothrombotic events (treatment failure) must be distinguished from aspirin resistance. Nevertheless, different definitions of aspirin resistance complicate the assessment of published data, a problem aggravated by discordant results of the available diagnostic laboratory techniques.The pharmacological mechanisms of aspirin resistance are not completely understood. Potential causes include pharmacokinetic and pharmacodynamic issues, such as reduced bioavailability, increased platelet turnover, interactions with nonsteroidal anti-inflammatory drugs, comorbidities (hypercholesterolemia or diabetes mellitus), alternative pathways of platelet activation, and genetic polymorphisms. Clinical trials demonstrated a negative impact of aspirin resistance on the clinical outcome: an about fourfold increased risk of major atherothrombotic events has been found in aspirin nonresponders suffering from vascular disease.An individualized antiplatelet therapy with aspirin will have to consider the possibility of aspirin resistance. Thus, standardized and inexpensive diagnostic assays are needed. The identification of aspirin-resistant patients is essential to individually tailor antiplatelet treatment. For example, increasing the dosage of aspirin or alternative antiplatelet drugs are potential therapeutic concepts, but these require careful future investigation.

Toxicity of algicidal extracts from Mangrovimonas yunxiaonensis strain LY01 on a HAB causing Alexandrium tamarense. Toxicity of algicidal extracts from Mangrovimonas yunxiaonensis strain LY01 on Alexandrium tamarense were measured through studying the algicidal procedure, nuclear damage and transcription of related genes. Medium components were optimized to improve algicidal activity, and characteristics of algicidal extracts were determined. Transmission electron microscope analysis revealed that the cell structure was broken. Cell membrane integrity destruction and nuclear structure degradation were monitored using confocal laser scanning microscope, and the rbcS, hsp and proliferating cell nuclear antigen (PCNA) gene expressions were studied. Results showed that 1.0% tryptone, 0.4% glucose and 0.8% MgCl2 were the optimal nutrient sources. The algicidal extracts were heat and pH stable, non-protein and less than 1kD. Cell membrane and nuclear structure integrity were lost, and the transcription of the rbcS and PCNA genes were significantly inhibited and there was up-regulation of hsp gene expression during the exposure procedure. The algicidal extracts destroyed the cell membrane and nuclear structure integrity, inhibited related gene expression and, eventually, lead to the inhibition of algal growth. All the results may elaborate firstly the cell death process and nuclear damage in A. tamarense which was induced by algicidal extracts, and the algicidal extracts could be potentially used as bacterial control of HABs in future.