Posterior reversible encephalopathy syndrome in a adult female.
Posterior reversible encephalopathy syndrome is a clinico-neuroradiologic diagnosis, with rapidly evolving neurologic condition, characterized by headache, confusion, altered mental status, seizures, cortical blindness, lethargy, stupor, and occasionally, focal neurological signs accompanied by a typical computed tomography or magnetic resonance imaging pattern. With early recognition and treatment, complete resolution of symptoms occurs. Typical imaging findings characteristically involve the white matter bilaterally in the parieto-occipital regions. Atypical imaging finding of contrast enhancement of lesion can occur, but is less common. A 20-year-old primiparous lady presented with posterior reversible encephalopathy syndrome. To the best of our knowledge, this is the first documented case in Nigeria. This case-report highlights the importance of recognizing the salient imaging features in this lethal but reversible entity with prompt management.


The role of interleukin-17 in intrahepatic cholestasis of pregnancy.
Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease, is characterized by pruritus, abnormal liver function and elevated serum bile acid levels. The main cause of ICP has not yet been identified. We aimed to provide a new perspective to the pathogenesis of by investigating the possible association of circulating interleukin-17 (IL-17) that is a recently discovered proinflammatory cytokine levels with ICP. In this controlled cross-sectional study, maternal venous blood samples were obtained from 33 consecutive pregnant women with ICP (15 with mild and 18 with severe forms of the disease) and 25 healthy women with uncomplicated pregnancies (as the control group) and IL-17 levels were compared among the groups. Although serum IL-17 levels were significantly higher in the severe ICP group than in the control group (p = 0.022), there were no significant differences between the mild and severe ICP groups or between the control and mild ICP groups. Explaining the mechanisms of hepatocyte injury might contribute to the existing therapeutic strategies for treating cholestatic diseases. Changes in IL-17 levels may shed light on the pathogenesis of ICP.


The vimentin intermediate filament network restrains regulatory T cell suppression of graft-versus-host disease.
Regulatory T cells (Tregs) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control Treg function may allow for the augmentation of therapeutic efficacy. In contrast to activated conventional T cells, in which protein kinase C-θ (PKC-θ) localizes to the contact point between T cells and antigen-presenting cells, in human and mouse Tregs, PKC-θ localizes to the opposite end of the cell in the distal pole complex (DPC). Here, using a phosphoproteomic screen, we identified the intermediate filament vimentin as a PKC-θ phospho target and show that vimentin forms a DPC superstructure on which PKC-θ accumulates. Treatment of mouse Tregs with either a clinically relevant PKC-θ inhibitor or vimentin siRNA disrupted vimentin and enhanced Treg metabolic and suppressive activity. Moreover, vimentin-disrupted mouse Tregs were significantly better than controls at suppressing alloreactive T cell priming in graft-versus-host disease (GVHD) and GVHD lethality, using a complete MHC-mismatch mouse model of acute GVHD (C57BL/6 donor into BALB/c host). Interestingly, vimentin disruption augmented the suppressor function of PKC-θ-deficient mouse Tregs. This suggests that enhanced Treg activity after PKC-θ inhibition is secondary to effects on vimentin, not just PKC-θ kinase activity inhibition. Our data demonstrate that vimentin is a key metabolic and functional controller of Treg activity and provide proof of principle that disruption of vimentin is a feasible, translationally relevant method to enhance Treg potency.


Genomic variation in C. albicans.
Candida albicans displays many types of variation which affect a broad spectrum of phenotypes. Among them are antigenic, chromosomal, morphologic, and biochemical variation. The ability to modulate many phenotypes is clearly an important factor in the success of this fungus as a pathogen and variation at the genomic level may be the common denominator among the different systems. Genomic variation in C. albicans has been studied by many researchers and a number of different mechanisms have been identified. Among them are ploidy fluctuations, which allow the organism to cycle from 2n chromosome number to 4n or higher; translocation, which has been demonstrated to involve many different chromosomes and affects many phenotypes including virulence; mitotic recombination, which has been demonstrated to increase resistance to certain drugs; and nondisjunction, which has been shown to have morphological consequences. The number and diversity of these mechanisms combine to make C. albicans a highly successful organism. Although normally a commensal of humans, when invasive, C. albicans can inhabit almost any site in the body. It is not known what governs the transition of C. albicans from a commensal to pathogenic invader, however, variation at the genomic level likely plays a role. One possible consequence of variation is the generation of atypical strains, further expanding the documented phenotypic plasticity of this organism. The exposure of patients to cytotoxic drugs during treatment of such diseases as AIDS or cancer increases the selective pressure and has exacerbated both the frequency and degree of variability observed in C. albicans. The molecular analysis of genomic variation in C. albicans is proving to be a fertile area of research and future investigations can only be expected to add to the mechanisms documented in this review.


[Cardiorespiratory response during exercise in heart transplant recipients. Comparative ergoespirometric analysis with normal health subjects].
To evaluate the cardiorespiratory response of heart transplant (HT) recipients. Nine HT recipients (GI) underwent ergospirometric tests and were compared to 9 apparently healthy, sedentary subjects with similar sex, age, weight and height (GII). All were male patients aging 48 +/- 12 years, in functional class I (NYHA) an average of 23 +/- 21 months after HT. They were receiving cyclosporin, azathioprine, prednisone, dipyridamole and antihypertensive drugs. The tests were symptom-limited and they were interrupted due to exhaustion. During peak exercise, GI had a significantly lower physical performance related to lower VO2, VE, VEO2, HR, endurance time and work load. At the anaerobic threshold, VO2, endurance time and work load levels were also significantly lower in GI. The physical performance was similar between the groups in the 40W load. The cardiorespiratory performance in GI was significantly lower at peak exercise and similar to GII in the 40W load, showing the HT benefits cardiac patients during usual activities.


[Unilateral exophthalmos caused by a prolactin producing ectopic pituitary adenoma: case report].
We report a case of a patient with a prolactin (PRL) producing ectopic pituitary adenoma presenting a unilateral exophthalmos. This 70-year-old woman presented an ophthalmologist with progressive left-sided exophthalmos over the previous 2 months. Bone window CT scan revealed extensive bony destructions of the skull base including the clivus, sphenoid sinus and medial aspect of the middle cranial fossa. Gd-DTPA MRI revealed an abnormal enhancement lesion in the sphenoid sinus, but no abnormal enhancement was seen in the sella turcica. Since these findings suggested malignant tumors of the cranial base, several biopsies through the transnasal route were carried out to confirm the diagnosis. This procedure caused the complication of cerebrospinal fluid (CSF) leakage. Because the biopsy specimen revealed a PRL producing adenoma (serum PRL-level 645.7 ng/ml), the patient was admitted to our department. On admission neurological examination showed an exophthalmos with external ocular movement disorders and disturbance of visual acuity on the left side. She underwent transsphenoidal surgery to remove the tumor and to reconstruct the sphenoid sinus and the sellar floor. Surgical exploration revealed a yellowish and soft tumor underneath the normal mucous membrane in the sphenoid sinus. The sellar floor was destructed extensively, but the dura mater of the pituitary fossa was intact except for a small pin-hole which was thought to be produced during the several biopsy procedures. No surgical procedure was applied to the intrasellar region. The sphenoid sinus was packed with a piece of fascia and fat applied with the aid of fibrin glue to prevent CSF leakage. The patient followed a satisfactory postoperative course. Her visual acuity disturbance and exophthalmos disappeared one year after surgery. Postoperative serum PRL level remained high (66.9 ng/ml), but, subsequently, was normalized (9.5 ng/ml) with a bromocriptine therapy (15 mg daily). As far as we are aware, this is the first case report of an ectopic pituitary adenoma causing unilateral exophthalmos. Although it is extremely rare, pituitary adenomas should be kept in mind in a differential diagnosis of exophthalmos.


Three immunoidentical cytochromes P-450 from liver microsomes of phenobarbital-treated rats.
Three forms of cytochrome P-450 were purified to homogeneity from liver microsomes of Wistar-strain rats treated with phenobarbital. They had minimum mol.wts. of 52 000, 53 000 and 54 000 as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and are designated as P-450(L), P-450(M) and P-450(H) respectively. They were shown to be immunoidentical by Ouchterlony double-diffusion analysis. Several criteria, such as isoelectric points, substrate specificities and sensitivities to tryptic digestion, however, indicated that these cytochromes are distinct isoenzymes of cytochrome P-450. Whereas P-450(L) was highly active on various substrates, P-450(H) had generally low catalytic activities, except on aminopyrine. The cytochromes purified by immunoaffinity chromatography using anti-P-450(L) showed a marked variation in their distribution depending on the strain and colony of rat. Limited tryptic digestion of P-450(H) gave one tryptic peptide showing the same mobility as P-450(L) by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and their primary structures were very similar. The result suggests a possibility that such limited proteolysis is involved in the post-translational modification of the cytochrome or its destruction.


Celiac disease and irritable bowel-type symptoms.
Previous reports have linked irritable bowel syndrome (IBS) etiologically with various forms of mucosal inflammation, including infectious enterocolitides and inflammatory bowel disease. The mechanism is uncertain but may involve sensitization by inflammatory mediators. The enteropathy of celiac disease has theoretical advantages as a study model because it can be controlled with dietary gluten exclusion; however, whether it also predisposes to functional bowel disorders is unclear. Therefore, we assessed the prevalence of IBS-type symptoms in adult celiac patients and correlated this with dietary compliance with gluten exclusion. Adult patients (n = 150; 106 women and 44 men) with confirmed celiac disease were randomly selected from a computerized database of >350 patients, and were asked to complete a bowel questionnaire and the Short Form 36 Health Survey (SF-36). The control group (n = 162; 133 women and 29 men) had no history of celiac disease and had similar mean age and sex profile. Of 150 celiac patients reviewed, 30 of 150 (20%) fulfilled the Rome criteria compared with eight of 162 (5%) ontrols. Of the celiac patients 10 of 46 (22%) had partial or no compliance with a gluten-free diet, whereas 20 of 104 patients (19%) adhered to the diet; this difference did not achieve statistical significance. Celiac patients with IBS-type symptoms had a markedly lower quality of life than those without, all eight domains being impaired to a clinically significant extent. Dietary gluten exclusion improved QOL in four of eight scales measured. The hypothesis that mucosal inflammation in celiac disease may have a sensitizing effect or may predispose to IBS-type symptoms is supported by these results. Failure to attain optimal subjective well-being is common in celiac patients, particularly in those with coexisting IBS. Compliance with a gluten-free diet confers some benefit.


Microscopic features of enamel and dentinal caries under confocal laser scanning microscopy (CLSM) and image analyzer: preliminary experimental study.
This study was designed to identify surface and subsurface microscopic changes in different carious lesions by using Confocal Laser Scanning Microscope (CLSM) and Image analyzer (light microscopy). Thirty extracted carious posterior teeth were fixed, embedded and polymerized in plastic fixation medium. The final thin sections (80mm) were stained with H&E and Masson Goldner's Tricome while others were left unstained. Under Confocal, marked differences between control sound enamel and dentin, and carious area of the samples were observed which illustrated that a correlation existed between the zone of autofluoresence, demineralization and carious enamel and dentin. Compared to CLSM, Image Analyzer only produce two-dimensional images but the histopathological changes were better appreciated by using various staining methods.


Upper bounds on noise and model misspecification for robust estimation of real-time brain activity from functional near infrared spectroscopy.
The robust characterization of real-time brain activity carries potential for many applications. However, the contamination of measured signals by various instrumental, environmental, and physiological sources of noise introduces a substantial amount of signal variance and, consequently, challenges real-time estimation of contributions from underlying neuronal sources. Functional near infrared spectroscopy (fNIRS) is an emerging imaging modality whose real-time potential is yet to be fully explored. The objectives of the current study are to (i) validate a time-dependent linear model of hemodynamic responses in fNIRS, and (ii) test the robustness of this approach against measurement noise (instrumental and physiological) and mis-specification of the hemodynamic response basis functions (amplitude, latency, and duration). We propose a linear hemodynamic model with time-varying parameters, which are estimated (adapted and tracked) using a dynamic recursive least square algorithm. Owing to the linear nature of the activation model, the problem of achieving robust convergence to an accurate estimation of the model parameters is recast as a problem of parameter error stability around the origin. We show that robust convergence of the proposed method is guaranteed in the presence of an acceptable degree of model misspecification and we derive an upper bound on noise under which reliable parameters can still be inferred. While here applied to fNIRS, the proposed methodology is applicable to other hemodynamic-based imaging technologies such as functional magnetic resonance imaging.


Psoriasis and Psoriatic Arthritis Video Project 2010: a report from the GRAPPA annual meeting.
Investigators use several physical examination measures to assess clinical features and severity of psoriasis and psoriatic arthritis (PsA) in clinical trials, clinical registries, and clinical practice; however, no relevant training modules are widely available to teach and standardize the performance of these measures. At a GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) meeting adjacent to the 2009 International Federation of Psoriasis Associations in Stockholm, members were updated on the development status of online training videos of psoriasis and PsA examination measures. Dermatology assessment modules include the Psoriasis Area and Severity Index, the Static Physician Global Assessment, body surface area, the original and modified Nail Psoriasis Severity Index, the Palmar-Plantar Pustular Psoriasis Area and Severity Index, and the Psoriasis Scalp Severity Index. Rheumatology modules include assessment of tender and swollen joint counts used in the American College of Rheumatology criteria, Disease Activity Score, and other composite arthritis scores; enthesitis assessment used in various enthesitis scoring systems; dactylitis; and spine disease. Each module will include background information for each measure, diagrams and photographs to emphasize teaching points, demonstration video of examination where applicable, and an optional examination at the end. Future plans include evaluating the modules for their influence on interrater and intrarater reliability and development of additional modules.


Technology-aided verbal instructions to help persons with mild or moderate Alzheimer's disease perform daily activities.
These two studies extended previous research on the use of verbal instructions and support technology for helping persons with mild or moderate Alzheimer's disease perform daily activities. Study I included seven participants who were to carry out one of two previously targeted activities (i.e., either coffee preparation or table setting). Study II included four participants who were to carry out two new activities (i.e., preparation of a fruit salad and of a vegetable salad). The effects of activity engagement on mood (i.e., indices of happiness) were assessed by recording the participants' behavior during the activity trials and parallel non-activity periods. The participants of Study I reached percentages of correct activity performance, which normally exceeded 85. Five of them also showed higher indices of happiness during the activity trials as opposed to the non-activity periods. Three of the participants of Study II reached high percentages of correct performance on both activities available. One of these participants also showed higher indices of happiness during the activity trials. The findings were discussed in relation to previous research outcomes and in terms of their practical implications for intervention programs.


Functional Outcomes After Surgery for Total Colonic, Long-Segment, Versus Rectosigmoid Segment Hirschsprung Disease.
Knowledge on long-term outcomes in patients with Hirschsprung disease is progressing. Nevertheless, differences in outcomes according to aganglionic lengths are unclear. We compared long-term bowel function and generic quality of life in Hirschsprung patients with total colonic or long-segment versus rectosigmoid aganglionosis. In this nationwide, cross-sectional study participants with proven Hirschsprung disease received the Defecation and Fecal Continence questionnaire, and the Child Health Questionnaire Child Form-87, or the WHO Quality of Life-100. We excluded deceased patients, patients who were younger than 8 years, lived abroad, had a permanent enterostomy, or were intellectually impaired. The study population (n = 334) was operated for rectosigmoid (83.9%), long-segment (8.7%), or total colonic aganglionosis (7.5%). Fecal incontinence in general was not significantly different between the three groups, but liquid fecal incontinence was significantly associated with total colonic aganglionosis (odds ratio [OR] = 6.00, 95% confidence interval [CI] 2.07-17.38, P = 0.001). Regarding constipation, patients with total colonic or long-segment aganglionosis were less likely to suffer from constipation than the rectosigmoid group (OR = 0.21, 95% CI, 0.05-0.91, P = 0.038 and OR = 0.11, 95% CI, 0.01-0.83, P = 0.032). Quality of life was comparable between the three groups, except for a lower physical score in children with total colonic aganglionosis (P = 0.016). Over time Hirschsprung patients with total colonic or long-segment aganglionosis do not suffer from worse fecal incontinence in general. A difference in stool consistency may underlie the association between liquid fecal incontinence and total colonic aganglionosis and constipation in patients with rectosigmoid aganglionosis. Despite these differences, generic quality of life is comparable on reaching adulthood.


The Impact of a Digital Intervention (Happify) on Loneliness During COVID-19: Qualitative Focus Group.
Loneliness is a growing area of concern, attracting attention as a public health concern due to its association with a variety of psychological and physical health problems. However, interventions targeting loneliness are less common than interventions for other mental health problems, such as depression and anxiety, and existing interventions focus primarily on building social skills and increasing opportunities for social interaction despite research suggesting these techniques are not the most effective. Furthermore, although there is an increasing need for scalable and convenient interventions, digital interventions for loneliness are even less common. Using a qualitative approach, we explore how adults (18-64 years of age) who express wanting to be more connected to others experience loneliness and react to a digital mental health intervention targeting loneliness. A total of 11 participants were recruited from a pilot randomized controlled trial exploring the impact of a digital mental health intervention, Happify Health, on loneliness among adults aged 18-64 years who indicated wanting to feel more connected to others when signing up for the platform. Participants were invited to participate in a 3-day asynchronous focus group about their experiences with loneliness, with Happify Health, and with social distancing during the COVID-19 pandemic. All 11 participants completed the focus group in May 2020. Participants' responses were coded using thematic analysis, which led to identifying five themes, each with separate subthemes, that could be applied across the 3-day focus group: loneliness, relationships, social distancing, skill acquisition, and coping. Overall, we observed variability across participants in terms of the source of their loneliness, their perceptions of their social connections, and their motivation to reduce feelings of loneliness; however, participants commonly referred to negative self-perceptions as a cause or consequence of loneliness. Participants also varied in the extent to which they felt social distancing increased or decreased feelings of loneliness. In regard to the intervention, participants showed evidence of adopting skills they used to address their loneliness, particularly mindfulness and gratitude, and then using these skills to shift toward more active coping strategies following the intervention, including during the COVID-19 pandemic. The heterogeneity in participants' experiences with loneliness described during this focus group emphasizes the subjective and complex nature of loneliness. This highlights the importance of developing loneliness interventions that use a variety of strategies, including both direct and indirect strategies for reducing loneliness. However, based on our data, a key component to loneliness interventions is incorporating strategies for addressing underlying negative self-perceptions that stem from, but also contribute to, loneliness. This data also provides preliminary evidence that digital platforms may be an effective tool for disseminating loneliness interventions while providing the added benefit of offering a productive distraction when feeling lonely.


Targeted reconstruction of T cell receptor sequence from single cell RNA-seq links CDR3 length to T cell differentiation state.
The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed. Here we present TRAPeS, a publicly available tool that can efficiently extract TCR sequence information from short-read scRNA-seq libraries. We apply it to investigate heterogeneity in the CD8+ T cell response in humans and mice, and show that it is accurate and more sensitive than existing approaches. Coupling TRAPeS with transcriptome analysis of CD8+ T cells specific for a single epitope from Yellow Fever Virus (YFV), we show that the recently described 'naive-like' memory population have significantly longer CDR3 regions and greater divergence from germline sequence than do effector-memory phenotype cells. This suggests that TCR usage is associated with the differentiation state of the CD8+ T cell response to YFV.


Clinical and in vitro evaluation of cefazolin, a new cephalosporin antibiotic.
Cefazolin sodium, a cephalosporin for parenteral use, was evaluated in vitro and in 26 patients. Cefazolin had activity equivalent to cephalothin against Streptococcus pneumoniae, Staphylococcus aureus, group A streptococci, and Proteus mirabilis. Cefazolin was four- to eightfold more active against Escherichia coli and slightly more active against Klebsiella pneumoniae, whereas cephalothin was slightly more active against indole-positive Proteus species. After a 500-mg dose of cefazolin intramuscularly, peak concentrations in the serum were high enough to inhibit all strains of S. pneumoniae, S. aureus, group A streptococci, E. coli, K. pneumoniae, and P. mirabilis, as well as 60% of strains of Proteus species other than P. mirabilis. All of 26 patients (18 with pneumonia, 6 with urinary tract infection, and 2 with skin infections) responded clinically and bacteriologically to cefazolin therapy. There were no major side effects of therapy, and no patient complained of pain at the site of intramuscular injection. Cefazolin is an effective cephalosporin which can be used intramuscularly for therapy of serious bacterial infections. Its major advantages over other cephalosporins are higher, more sustained concentrations in the blood and apparent lack of pain on intramuscular injection.


Predicting and preventing acute drug-induced liver injury: what's new in 2010?
The field of drug-induced liver injury (DILI) continues to expand in terms of global registries and with new agents added every year. Given the need to improve on our current methods of preclinical testing and monitoring for DILI during both clinical trials and in the post-approval setting, there is increasing research aimed at better understanding why injury occurs and who is most susceptible. To this end, the active pursuit of biomarkers that will predict injury prior to its occurrence and genetic testing that can identify individuals at risk of DILI continue to be at the forefront. While alanine aminotransferase (ALT) testing remains the workhorse of biochemical monitoring, it only detects hepatic injury after it has occurred and, therefore, is not a true predictor. The utility and shortcomings of ALT and other liver tests are reviewed along with a synopsis of several other candidate biomarkers that are being studied. In addition, we review the recent data supporting testing for genetic predisposition to DILI and how identifying clinical risk factors may translate into better means for preventing DILI. We update the basis on which age and gender are considered risk factors for DILI, and review the latest reports detailing the association of several candidate genes and the development of DILI in a susceptible patient. Human leukocyte antigen-B*5701 is closely linked to the hypersensitivity reaction seen with abacavir, and such screening has been successfully incorporated into HIV treatment around the globe and offers the promise that testing for other genetic markers will soon become a routine part of clinical practice. At present, candidate genes conferring specific susceptibility to DILI have been identified for a relatively few agents (e.g., flucloxacillin, amoxicillin-clavulanate, ximelagatran and isoniazid), but many more are under study. Preventing DILI often comes down to avoiding the use of potentially hepatotoxic drugs in certain situations, and we review the clinical scenarios in which this is most relevant. Given the number and range of studies aimed at identifying predictors of DILI, the focus of this review is to summarize what we consider to be the most relevant new information published on the topics of clinical and genetic factors that predispose to DILI, the use of biomarkers as predictors of acute DILI, along with advances in prevention strategies.


Molecular epidemiology and antimicrobial susceptibility of Clostridium difficile isolates from two Korean hospitals.
Clostridium difficile is one of the main etiological agents causing antibiotic-associated diarrhea. This study investigated the genetic diversity of 70 toxigenic C. difficile isolates from two Korean hospitals by employing toxinotyping, ribotyping, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Toxin gene amplification resulted in 68 A⁺B⁺ and two A-B+ isolates. Most isolates (95.7-100%) were susceptible to daptomycin, metronidazole, and vancomycin. Seventy C. difficile isolates were classified into five toxinotypes, 19 ribotypes, 16 sequence types (STs), and 33 arbitrary pulsotypes. All C. difficile isolates of ribotype 018 (n = 38) were classified into ST17, which was the most prevalent ST in both hospitals. However, C. difficile isolates of ST17 (ribotype 018) exhibited pulsotypes that differed by hospital. ST2 (ribotype 014/020), 8 (ribotypes 002), 17 (ribotype 018), and 35 (ribotypes 015) were detected in both hospitals, whereas other STs were unique to each hospital. Statistical comparison of the different typing methods revealed that ribotyping and PFGE were highly predictive of STs. In conclusion, our epidemiological study indicates that C. difficile infections in both hospitals are associated with the persistence of endemic clones coupled with the emergence of many unique clones. A combination of MLST with PFGE or ribotyping could be useful for monitoring epidemic C. difficile strains and the emergence of new clones in hospitals.


The palmitoylethanolamide family: a new class of anti-inflammatory agents?
The discovery of anandamide as an endogenous ligand for the cannabinoid receptors has led to a resurgence of interest in the fatty acid amides. However, N-palmitoylethanolamine (PEA), a shorter and fully saturated analogue of anandamide, has been known since the fifties. This endogenous compound is a member of the N-acylethanolamines, found in most mammalian tissues. PEA is accumulated during inflammation and has been demonstrated to have a number of anti-inflammatory effects, including beneficial effects in clinically relevant animal models of inflammatory pain. It is now engaged in phase II clinical development, and two studies regarding the treatment of chronic lumbosciatalgia and multiple sclerosis are in progress. However, its precise mechanism of action remains debated. In the present review, the biochemical and pharmacological properties of PEA are discussed, in particular with respect to its analgesic and anti-inflammatory properties.


Enzymatic hydrolyzed feather peptide, a welcoming drug for multiple-antibiotic-resistant Staphylococcus aureus: structural analysis and characterization.
This study aimed to explore the bactericidal activity of a feather-degraded active peptide against multiple-antibiotic-resistant (MAR) Staphylococcus aureus. An antibacterial peptide (ABP) was isolated from the chicken feathers containing fermented media of Paenibacillus woosongensis TKB2, a keratinolytic soil isolate. It was purified by HPLC, and its mass was found to be 4666.87 Da using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) spectroscopy. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of this peptide were 22.5 and 90 μg/ml, respectively. SEM study revealed the distorted cell wall of the test strain along with pore formation. The possible reason for bactericidal activity of the peptide is due to generation of reactive oxygen species (ROS), resulting in membrane damage and leakage of intracellular protein. Complete sequence of the peptide was predicted and retrieved from the sequence database of chicken feather keratin after in silico trypsin digestion using ExPASy tools. Further, net charge, hydrophobicity (77.7 %) and molecular modelling of the peptide were evaluated for better understanding of its mode of action. The hydrophobic region (17 to 27) of the peptide may facilitate for initial attachment on the bacterial membrane. The ABP exhibited no adverse effects on RBC membrane and HT-29 human cell line. This cytosafe peptide can be exploited as an effective therapeutic agent to combat Staphylococcal infections.


Glutamic acid inducing kidney stone biomimicry by a brushite/gelatin composite.
Brushite is a well known precursor of calcium oxalate monohydrate, the main mineral found in kidney stones having a monoclinic crystal structure. Here, we present a new method for biomimicking brushite using a single tube diffusion technique for gel growth. Brushite crystals were grown by precipitation of calcium hydrogen phosphate hydrate in a gelatin/glutamic acid network. They are compared with those produced in gel in the presence of urea. The aggregates were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), infrared spectroscopy (IR) and thermal gravimetric analysis (TGA). SEM revealed a change of morphology by glutamic acid from spherulitic growth to plate-shaped and mushroom-like forms consisting of crystal plates and highly ordered prismatic needles, respectively. Furthermore, brushite crystals grown in a gelatin/glutamic acid/urea network showed needle-shaped morphology being different from other brushite growth forms. The XRD method showed that cell parameters for brushite specimens were slightly larger than those of the American Mineral Society reference structure. The mushroom-like biomimetic composite bears a strong resemblance to the brushite kidney stones which may open up new future treatment options for crystal deposition diseases. Hence, suitable diets from glutamic acid rich foods could be recommended to inhibit and control brushite kidney stones.


Herbivory and competition slow down invasion of a tall grass along a productivity gradient.
Competition models including competition for light predict that small plant species preferred by herbivores will be outshaded by taller unpreferred plant species with increasing productivity. When the tall plant species is little grazed by the herbivores, it can easily invade and dominate short vegetation. The tall-growing grass Elymus athericus dominates the highly productive stages of a salt-marsh succession in Schiermonnikoog and is not preferred by the herbivores which occur there, hares and geese. We studied how interspecific competition and herbivory affected performance during early establishment of this species with increasing productivity. Seedlings were planted in the field in a full factorial design, manipulating both interspecific competition and herbivory. The experiment was replicated along a natural productivity gradient. Competition reduced above-ground biomass production and decreased the number of ramets that were produced but did not affect survival of seedlings. The negative effects of competition on seedling performance increased with increasing productivity. In contrast to our expectations, herbivory strongly reduced seedling survival, especially at the unproductive sites and had only small effects on seedling growth. The present study shows that unpreferred tall-growing species cannot easily invade vegetation composed of short preferred species. Grazing by (intermediate-sized) herbivores can prevent establishment at unproductive sites, and increased competition can prevent a rapid invasion of highly productive sites. Herbivores can have a long-lasting impact on vegetation succession by preventing the establishment of tall-growing species, such as E. athericus, in a window of opportunity at young unproductive successional stages.


[The benefit of external version in full-term breech presentation].
We report a randomised controlled trial of external version in 52 women with breech presentation after 36 weeks' gestation; 83% gave informed consent to undergo the management to which they had been randomized. Only 5% of initial attempts without tocolysis succeeded, but 31% of the failures subsequently had a successful version under tocolysis. External version resulted in a small decrease in the frequency of breech presentation at birth (64% vs. 74%), and in an unexpected increase in the caesarean section rate (28% vs. 11%). The increase in caesarean section rate could be attributed to failed versions, which apparently greatly influenced the choice between abdominal and vaginal delivery. Our findings and data from similar research suggest that benefits of external version at term may not apply to populations with a low caesarean rate, unless versions are carried out with maximal efficiency (which, on the basis of available data, would imply tocolysis) or so indifferently that failed attempts do not influence the choice between abdominal and vaginal delivery.


Humor and laughter may influence health. I. History and background.
Articles in both the lay and professional literature have extolled the virtues of humor, many giving the impression that the health benefits of humor are well documented by the scientific and medical community. The concept that humor or laughter can be therapeutic goes back to biblical times and this belief has received varying levels of support from the scientific community at different points in its history. Current research indicates that using humor is well accepted by the public and is frequently used as a coping mechanism. However, the scientific evidence of the benefits of using humor on various health related outcomes still leaves many questions unanswered.


Neural control of gastrointestinal motility: evidence for noncholinergic regulatory influences.
Although it is well known that neural control of gastric motility occurs via sympathetic, parasympathetic, noncholinergic, and nonadrenergic fibers contained in the vagus nerve, the central sites of origin of these influences are largely unknown. Recent experiments in our laboratory indicate that noncholinergic neural pathways originating in the posterior hypothalamus can markedly influence gastric motility. At least 2 weeks prior to the experiment, mongrel dogs were surgically prepared with bipolar recording electrodes fixed to the serosal surface of the stomach. This prevented violation of the abdominal cavity on the day of testing. Experiments were performed with the animals under alpha-chloralose anesthesia (100 mg kg-1) in temperature-controlled settings. Under stereotactic guidance, bipolar stimulation of the posterior periventricular hypothalamus produced profound reproducible excitatory or inhibitory effects on gastric myoelectric and motor activity. Changes in the frequency and amplitude of pacesetter potentials (PPs) and in the incidence of action potentials associated with them were observed. Stimulation of various loci in 14 dogs resulted in a 71 +/- 7.5% increase in the incidence of action potentials associated with gastric PPs in "excitatory" areas (n = 7) and a 69.1 +/- 4% decrease in this ratio in "inhibitory" areas (n = 19). In general, more lateral stimulation produced greater inhibitory effects. Responses were frequency dependent, with a threshold greater than 25 Hz in most cases. Excitatory gastric responses to hypothalamic stimulation occurred despite full systemic atropinization (0.1 mg kg-1). The physiologic significance of these noncholinergic excitatory pathways influencing distal gastric motility and the neurotransmitters they employ are as yet unknown.


Recurrent bacterial vaginosis--an old approach to a new problem.
Bacterial vaginosis (BV) is a common cause of abnormal malodorous vaginal discharge and can be frustrating to manage in its recurrent form. Metronidazole is the standard treatment, but is unacceptable to many women when given repeatedly. Results of treating recurrent BV using a single vaginal washout with 3% hydrogen peroxide are analysed. A total of 30 symptomatic women with clinically confirmed recurrent BV in the absence of other genital infections were recruited after informed consent. Hydrogen peroxide (3%) was instilled into the vagina, left for 3 minutes and drained. Reassessment was at 3 weeks after treatment. A total of 23 women completed the study. Symptoms cleared completely in 78% (18/23), improved in 13% (3/23) and remained unchanged in 9% (2/23). All the 3 women with improved symptoms had a mild vaginal discharge, but only one of them was still able to perceive the malodour. The amine test was negative in all 23 women including the 2 (9%) who felt no change in their symptoms following treatment. Mixed anaerobes isolated in all women before treatment were not re-isolated, and microscopy did not show 'clue cells' in the vaginal discharge following treatment. Vaginal acidity was restored to normal in all but one (96%). No side-effects were observed in the treated women. Hydrogen peroxide (3%) used as a single vaginal wash was as effective as any other agent in current use in clearing the vaginal malodour of bacterial vaginosis at 3 weeks after treatment.


Routine repeat head CT may not be indicated in patients on anticoagulant/antiplatelet therapy following mild traumatic brain injury.
Evaluation recommendations for patients on anticoagulant and antiplatelet (ACAP) therapy that present after mild traumatic brain injury (TBI) are controversial. At our institution, an initial noncontrast head computed tomography (HCT) is performed, with a subsequent HCT performed six hours later to exclude delayed intracranial hemorrhage (ICH). This study was performed to evaluate the yield and advisability of this approach. We performed a retrospective review of subjects undergoing evaluation for ICH after mild TBI in patients on ACAP therapy between January of 2012 and April of 2013. We assessed for the frequency of ICH on both the initial noncontrast HCT and on the routine six-hour follow-up HCT. Additionally, chart review was performed to evaluate the clinical implications of ICH, when present, and to interrogate whether pertinent clinical and laboratory data may predict the presence of ICH prior to imaging. We used multivariate generalized linear models to assess whether presenting Glasgow Coma Score (GCS), loss of consciousness (LOC), neurological or physical examination findings, international normalized ratio, prothrombin time, partial thromboplastin time, platelet count, or specific ACAP regimen predicted ICH. 144 patients satisfied inclusion criteria. Ten patients demonstrated initial HCT positive for ICH, with only one demonstrating delayed ICH on the six-hour follow-up HCT. This patient was discharged without any intervention required or functional impairment. Presenting GCS deviation (p<0.001), LOC (p=0.04), neurological examination findings (p<0.001), clopidogrel (p=0.003), aspirin (p=0.03) or combination regimen (p=0.004) use were more commonly seen in patients with ICH. Routine six-hour follow-up HCT is likely not indicated in patients on ACAP therapy, as our study suggests clinically significant delayed ICH does not occur. Additionally, presenting GCS deviation, LOC, neurological examination findings, clopidogrel, aspirin or combination regimen use may predict ICH, and, in the absence of these findings, HCT may potentially be forgone altogether.


Short-Term Effects of Kinesio Taping in Women with Pregnancy-Related Low Back Pain: A Randomized Controlled Clinical Trial.
BACKGROUND Pregnancy-related low back pain is a common condition during pregnancy. Kinesio tape is a drug-free elastic therapeutic tape used for treating various musculoskeletal problems. The aim of this study was to investigate the short-term effects of lumbar Kinesio taping on pain intensity and disability in women with pregnancy-related low back pain. MATERIAL AND METHODS A total of 65 patients with pregnancy-related low back pain were randomly allocated into either Kinesio taping (n=33) or control (n=32) groups. The intervention group was treated with paracetamol plus Kinesio taping, while the control group received only paracetamol. Kinesio taping was applied in the lumbar flexion position, and four I-shaped bands were used. Two bands were attached horizontally, with space correction technique. The remaining 2 bands, 1 on each side of the lumbar spine, were placed vertically, with inhibition technique. Low back pain intensity was measured on a 10-cm visual analogue scale (VAS), and the Roland-Morris Disability Questionnaire (RMDQ) was used for evaluation of disability. RESULTS Pain intensity and RMDQ scores improved significantly in both groups at 5 days compared with baseline. Considering the degree of treatment effect (the change from baseline to day 5), the Kinesio taping group was significantly superior than the control group in all outcome measures (for all, P<0.001). CONCLUSIONS The results of this study indicate that Kinesio taping can be used as a complementary treatment method to achieve effective control of pregnancy-related low back pain.


Energy- and temperature-dependent in vitro export of RNA from synthetic nuclei.
We describe a novel assay for the study of RNA export from the nucleus in vitro. Nuclei are assembled in Xenopus egg extract on paramagnetic beads coated with DNA containing a specific template for transcription. T7 RNA polymerase, to which a nuclear localisation signal is attached, is added to the nuclei, and after its import into the assembled nuclei, transcription is allowed to proceed. The use of radioactive NTPs coupled with the possibility to purify the nuclei on a magnet and thus rapidly change the extract in which the nuclei are incubated allows pulse-chase labelling experiments. Using these protocols we show that U1 snRNA-derived templates are transcribed inside the synthetic nuclei, and that the transcripts leave the intact nuclei in a time-, temperature- and energy-dependent way. This offers the possibility of a biochemical approach to the dissection of RNA export.


The enigmatic drug binding site for sodium channel inhibitors.
Local anesthetics have been in clinical use since 1884, and different aspects of the local anesthetic binding site have been studied in enormous detail. In spite of all these efforts, some of the most fundamental questions--such as which exact residues constitute the binding site, how many binding sites exist, do local anesthetics share their binding site(s) with other sodium channel inhibitors, and what are the mechanisms of inhibition--are still largely unanswered. We review accumulated data on the "local anesthetic receptor"and discuss controversial points, such as possible mechanisms of inhibition, the possibility of additional binding sites, the orientation of S6 helices, and the internal vs. external position of the anticonvulsant binding site. We describe the four following specific groups of functionally important residues: i) conserved asparagines six residues below the hinge residues; we propose that they are oriented toward the external surface of S6 helices, and have a critical role in the coupling of voltage sensors to gating, ii) residues lining the inner vestibule and constructing the "orthodox" binding site, iii) residues around the outer vestibule, which have been proposed to constitute an alternative external binding site, and iv) residues determining external access for quaternary amine inhibitors, such as QX314. We conclude that sodium channel inhibitors must be heterogenous in terms of binding sites and inhibition mechanisms, and propose that this heterogeneity should be taken into consideration during drug development.


Time-response evaluation by transcriptomics of methylmercury effects on neural differentiation of murine embryonic stem cells.
Current globally harmonized Organisation for Economic Co-operation and Development (OECD) animal test guidelines for developmental toxicity require high numbers of experimental animals. To reduce animal use in this field, alternative developmental toxicity assays are highly desirable. We previously developed a dynamic in vitro model for screening effects of possible neurodevelopmental toxicants, using neural cell differentiation of pluripotent murine embryonic stem cells. To further mechanistically characterize the mouse neural embryonic stem cell test (ESTn) and to improve detection of possible neurodevelopmental toxicants, gene expression patterns were studied describing neural cell differentiation over time, as well as the impact on gene expression of exposure to the well-known neurotoxicant methylmercury (MeHg). A transcriptomics study was performed to examine whole-genome expression changes during the first 7 days of the cell differentiation protocol. Specific gene clusters were identified and enrichment analysis of Gene Ontology (GO) terms and gene sets derived from literature was performed using DAVID and T-profiler. Over time, a decrease of blastocyst and trophectoderm GO terms was observed, which included well-characterized pluripotency genes. Furthermore, an increase in the range of neural development-related GO terms, such as neuron differentiation and the wnt pathway, was observed. Analysis of gene expression using principle component analysis showed a time-dependent track in untreated cells, describing the process of neural differentiation. Furthermore, MeHg was shown to induce deviation from the predefined differentiation track. The compound inhibited general development GO terms and induced neural GO terms over time. This system appears promising for studying compound effects on neural differentiation in a mechanistic approach.


Hand preference in gestures and signs in the deaf and hearing: some notes on early evidence and theory.
Research has shown that when persons with normal hearing accompany their speech with gestures, right-handers use more right-hand gestures, and left-handers use more left-hand gestures, although to a lesser extent (D. Kimura, 1973a, 1973b, Neuropsychologia, 11, 45-50, 51-55.). Comparable differences have been found in deaf persons when signing, with the direction of hand dominance for signing in both right- and left-handers corresponding to that for nonlinguistic actions (J. Vaid, D. Schemenauer, U. Bellugi, & H. Poizner, 1984, Hand dominance in a visual-gesture language. Paper presented at BABBLE, March, Niagara Falls, Ontario, Canada). In this paper, I recount early theories and observational data about hand dominance for gesture and signing, both in the hearing and the deaf. Several of these early theories and observations anticipate current work and also suggest new avenues for investigation.


[Genetic factors in familial combined hyperlipidemia and insulin resistance syndrome associated with dyslipidemia].
Familial combined hyperlipidemia, (FCHL) and dyslipidemia occurring in insulin resistant syndrome (IRS) share similar lipid abnormalities. Additionally insulin resistance is frequent in families affected by FCHL. The genetics of FCHL, an oligogenic disorder influenced by environmental factors is not established. Many genes that modulate dyslipidemia such as, LPL, apo E, the cluster A I-C III-A IV, have been identified. However the major gene which determines hypertriglyceridemia remains unknown. The community between HCF and insulin resistance syndrome might have:--either a metabolic origin: the increase in FFA which is a characteristic of IRS, capable to stimulate the hepatic production of triglycerides;--and/or a common genetic mechanism involving the alteration of many genes implied in the control of lipoprotein metabolism and insulin sensitivity.


Reduced levels of GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy.
We tested the hypothesis that reduced levels of the GABA-benzodiazepine receptor occur in alcohol dependency using single photon emission tomography (SPET) and the specific GABA-benzodiazepine ligand, 123I-iomazenil. Neurologically and cognitively unimpaired abstinent alcohol-dependent (n = 12) and non-alcohol-dependent male subject (n = 14) underwent a 123I-iomazenil SPET scan. SPET and magnetic resonance images were co-registered and voxel-based statistical tests performed. Subjects' clinical and alcohol history were obtained with standard questionnaires. The relationships between clinical and alcohol variables and the regional level of GABA-benzodiazepine receptors were investigated using multiple regression analysis. Abstinent alcohol-dependent subjects had decreased levels of GABA-benzodiazepine receptor compared with non-alcohol-dependent subjects within the frontal, parietal and temporal cortices, including regions in which grey matter atrophy was absent. Alcohol dependency is associated with reduced GABA-benzodiazepine receptor levels in the absence of grey matter atrophy in some cortical regions, such as within the parietal lobe. Regional variability of reduction in GABA-benzodiazepine receptors demonstrates that alcohol does not have a global, toxic effect on the brain.


Human and murine cytotoxic T cells specific to respiratory syncytial virus recognize the viral nucleoprotein (N), but not the major glycoprotein (G), expressed by vaccinia virus recombinants.
The viral antigens recognized by cytotoxic T cells (CTL) have not been defined in most viruses infecting mouse or man. Natural or artificial virus recombinants can be used to determine the antigen specificity of CTL directed against viruses with segmented genomes, such as influenza, but this technique is more difficult to apply to the study of unsegmented viruses. We describe here the use of recombinant vaccinia viruses, containing cDNA corresponding to either the nucleoprotein (N) gene or the major surface glycoprotein (G) gene of human respiratory syncytial virus (RSV), to examine the antigen specificity of anti-RSV cytotoxic T cells from humans and mice. The results demonstrate that the RSV N protein is one of the target antigens for CTL in man and mouse, whereas the G protein was not recognized and can at best represent a minor target antigen for CTL.


Mechanisms establishing TLR4-responsive activation states of inflammatory response genes.
Precise control of the innate immune response is required for resistance to microbial infections and maintenance of normal tissue homeostasis. Because this response involves coordinate regulation of hundreds of genes, it provides a powerful biological system to elucidate the molecular strategies that underlie signal- and time-dependent transitions of gene expression. Comprehensive genome-wide analysis of the epigenetic and transcription status of the TLR4-induced transcriptional program in macrophages suggests that Toll-like receptor 4 (TLR4)-dependent activation of nearly all immediate/early- (I/E) and late-response genes results from a sequential process in which signal-independent factors initially establish basal levels of gene expression that are then amplified by signal-dependent transcription factors. Promoters of I/E genes are distinguished from those of late genes by encoding a distinct set of signal-dependent transcription factor elements, including TATA boxes, which lead to preferential binding of TBP and basal enrichment for RNA polymerase II immediately downstream of transcriptional start sites. Global nuclear run-on (GRO) sequencing and total RNA sequencing further indicates that TLR4 signaling markedly increases the overall rates of both transcriptional initiation and the efficiency of transcriptional elongation of nearly all I/E genes, while RNA splicing is largely unaffected. Collectively, these findings reveal broadly utilized mechanisms underlying temporally distinct patterns of TLR4-dependent gene activation required for homeostasis and effective immune responses.


The control of fracture healing and its therapeutic targeting: improving upon nature.
Fracture repair is a complex process involving timed cellular recruitment, gene expression, and synthesis of compounds that regenerate native tissue to restore the mechanical integrity, and thus function of injured bone. While the majority of fractures heal without complication, this takes time and a subset of patients ( approximately 10%) experience healing delays, extending their morbidity and treatment costs. Consequently, there is a need for efficacious therapeutics for the intervention of fracture healing. Recent studies into the molecular control of fracture repair and advances in the understanding of the skeleton as a whole have resulted in the identification of numerous novel targets and compounds for such intervention. These include traditional agents such bone morphogenetic proteins and other growth factors, but also relatively newer compounds such as parathyroid hormone and modulators of the Wnt signaling pathway. These agents, along with others, are discussed in the current article in terms of their investigative status and potential for clinical implementation. Hopefully, these agents, as well as others yet to be discovered, will demonstrate sufficient clinical utility for successful intervention of fracture healing. This may have significant implications for the duration of morbidity and costs associated with traumatic bone fractures.


Anthropogenic Sulfur Perturbations on Biogenic Oxidation: SO2 Additions Impact Gas-Phase OH Oxidation Products of α- and β-Pinene.
In order to probe how anthropogenic pollutants can impact the atmospheric oxidation of biogenic emissions, we investigated how sulfur dioxide (SO2) perturbations impact the oxidation of two monoterpenes, α-and β-pinene. We used chemical ionization mass spectrometry to examine changes in both individual molecules and gas-phase bulk properties of oxidation products as a function of SO2 addition. SO2 perturbations impacted the oxidation systems of α-and β-pinene, leading to an ensemble of products with a lesser degree of oxygenation than unperturbed systems. These changes may be due to shifts in the OH:HO2 ratio from SO2 oxidation and/or to SO3 reacting directly with organic molecules. Van Krevelen diagrams suggest a shift from gas-phase functionalization by alcohol/peroxide groups to functionalization by carboxylic acid or carbonyl groups, consistent with a decreased OH:HO2 ratio. Increasing relative humidity dampens the impact of the perturbation. This decrease in oxygenation may impact secondary organic aerosol formation in regions dominated by biogenic emissions with nearby SO2 sources. We observed sulfur-containing organic compounds following SO2 perturbations of monoterpene oxidation; whether these are the result of photochemistry or an instrumental artifact from ion-molecule clustering remains uncertain. However, our results demonstrate that the two monoterpene isomers produce unique suites of oxidation products.


Assessment of intraspinal and intracranial conduction by P30 and P39 tibial nerve somatosensory evoked potentials in cervical cord, brainstem, and hemispheric lesions.
In routine recordings of tibial nerve somatosensory evoked potentials (SEPs), a global central conduction time is evaluated by measuring the interval between the segmental spinal N22 potential, recorded in the lumbar region, and the cortical P39 potential. In this study, we tested the reliability of the scalp far-field P30 potential, which originates in the vicinity of the cervico-medullary junction, in order to evaluate separately intraspinal and intracranial conduction in normal subjects and patients with cervical cord and intracranial lesions. P30 and cortical P39 potentials were studied in 23 healthy subjects and in 70 patients with cervical cord (n = 47), brainstem (n = 11) or hemispheric lesions (n = 12) selected on the basis of neuroimaging--computed tomography (CT) or magnetic resonance (MR)--findings. Median nerve SEPs were also recorded in all patients. Of the several montages tested to obtain the P30 potential, the Fpz-Cv6 derivation gave the highest signal-to-noise ratio; it permitted to obtain a P30 potential that peaked at 29.2 +/- 1.6 ms in all normal subjects. P30 abnormalities were observed only in patients with cervical or cervico-medullary lesions; these were associated with a normal P39 in only two of 33 abnormal recordings. Conversely, P30 was consistently normal in lesions situated above the cervico-medullary junction whether associated with normal, delayed, or reduced P39. P30 abnormalities were subclinical in 42% of abnormal recordings. All patients with normal tibial and median nerve SEPs on both sides had normal touch, joint, and vibration sensation in the four limbs. There was a strong correlation between tibial nerve P30 and median nerve P14 data in the whole series of patients; both potentials behaved similarly in all cases of intracranial supramedullary lesions. Combined abnormalities of P30 and P39 potentials thus indicate that conduction is impaired at the spinal level and proved to be particularly informative for detecting spinal cord dysfunction in patients with neuroimaging evidence of a narrowed cervical canal. Recording of abnormal N13, P14, or P30 potentials provided evidence of a cervical cord dysfunction in 66% of patients who had a suspected spondylotic myelopathy. Recording of tibial nerve P30 potential has proven to give reliable and useful information when a separate assessment of intraspinal and intracranial somatosensory conduction is needed; it merits inclusion, as does the upper limb N13 potential, in the evaluation of patients whose MR image indicates cervical canal narrowing.


The reliability and distinguishability of ultrasound diagnosis of ovarian masses.
For any radiologist, intra-observer agreement in observing and decision making in diagnosis of any disease is of great importance, and so is observing and reading ultrasound pictures of ovarian masses and distinguishing amongst their categories. In this study, the reliability and consistency of ultrasound diagnosis of ovarian tumors have been evaluated. Two experienced and three less experienced radiologists assessed ultrasounds of 40 patients of Mirza Koochak Khan Hospital in Tehran, Iran, in 2005. In this prospective observational study, the ultrasounds were performed by an expert radiologist, with a single apparatus. These ultrasounds have been evaluated separately and independently in two periods (with a 1-week interval). Weighted kappa was used to calculate intra-observer agreement (reliability), and two statistical models were applied to assess category distinguishability (consistency). SPSS version 10, SAS version 8, and EXCEL 2003 have been used to do an appropriate statistical analysis. Mean of weighted kappa was 0.81, and mean of distinguishability was 0.995 for our experienced radiologists, due to their superior results. Because of weaker results obtained by the less experienced radiologists, mean of weighted kappa and mean of distinguishability were 0.65 and 0.967 respectively. Overall mean of distinguishability for benign and borderline categories was 0.969; and for malignant and borderline categories, it was 0.987. Although experienced radiologists functioned better than the less experienced radiologists, all of them showed appropriate distinguishability and intra-observer agreement in diagnosis and categorization of the ovarian masses. Distinguishing benign category from borderline was more difficult than distinguishing malignant category from borderline. In general, experienced radiologists showed better results compared to less experienced radiologists.


Influences of sex and activity level on physiological changes in individual adult sockeye salmon during rapid senescence.
A noninvasive biopsy protocol was used to sample plasma and gill tissue in individual sockeye salmon (Oncorhynchus nerka) during the critical life stage associated with spawning-arrival at a spawning channel through senescence to death several days later. Our main objective was to characterize the physiological changes associated with rapid senescence in terms of the physiological stress/cortisol hypersecretion model and the energy exhaustion model. Salmon lived an average of 5 d in the spawning channel, during which time there were three major physiological trends that were independent of sexual status: a large increase in plasma indicators of stress and exercise (i.e., lactate and cortisol), a decrease in the major plasma ions (i.e., Cl(-) and Na(+)) and osmolality, and a decrease in gross somatic energy reserves. Contrary to a generalized stress response, plasma glucose decreased in approximately 2/3 of the fish after arrival, as opposed to increasing. Furthermore, plasma cortisol levels at spawning-ground arrival were not correlated with the degree of ionoregulatory changes during rapid senescence. One mechanism of mortality in some fish may involve the exhaustion of energy reserves, resulting in the inability to mobilize plasma glucose. Sex had a significant modulating effect on the degree of physiological change. Females exhibited a greater magnitude of change for gross somatic energy, osmolality, and plasma concentrations of Cl(-), Na(+), cortisol, testosterone, 11-ketotestosterone, 17,20beta-progesterone, and estradiol. The activity level of an individual on the spawning grounds appeared to influence the degree of some physiological changes during senescence. For example, males that received a greater frequency of attacks exhibited larger net decreases in plasma 11-ketotestosterone while on the spawning grounds. These results suggest that rapid senescence on spawning grounds is influenced by multiple physiological processes and perhaps behavior. This study provides some of the first data to look at sex differences in senescence in Pacific salmon.


Recent Advances in Oncological Submissions of Dendrimer.
Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients. Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body. Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation. Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.


Forgoing life-sustaining treatments: comparison of attitudes between Israeli and North American intensive care healthcare professionals.
Physicians' decisions regarding provision of life-sustaining treatment may be influenced considerably by non-medical variables. To examine physicians' attitudes towards end-of-life decisions in Israel, comparing them to those found in the United States. A survey was conducted among members of the Israel Society of Critical Care Medicine using a questionnaire analogous to that used in a similar study in the USA. Forty-three physicians (45%) responded, the majority of whom hold responsibility for withholding or withdrawing life-sustaining treatments. Preservation of life was considered the most important factor by 31 responders (72%). The quality of life as viewed by the patient was generally considered less important than the quality of life as viewed by the physician. Twenty-one responders (49%) considered withholding treatment more acceptable than withdrawing it. The main factors for decisions to withhold or withdraw therapy were a very low probability of survival of hospitalization, an irreversible acute disorder, and prior existence of chronic disorders. An almost similar percent of physicians (93% for Israel and 94% for the U.S.) apply Do Not Resuscitate orders in their intensive care units, but much less (28% vs. 95%) actually discuss these orders with the families of their patients. Critical care physicians in Israel place similar emphasis on the value of life as their U.S. counterparts and assign DNR orders with an incidence equaling that of the U.S. They differ from their U.S. counterparts in that they confer less significance to the will of the patient, and do not consult as much with families of patients regarding DNR orders.


Reproductive challenges facing the cattle industry at the beginning of the 21st century.
The aim of this review is to pinpoint the areas that require further research for greatest impact to improve the efficiency of dairy and beef production. Increased knowledge about the principal causes of reduced fertility is essential. Increases in milk yield have been at the expense of reduced fertility in dairy cows and although diet has a major impact, the precise interaction between nutrition and reproduction still needs to be characterized in both beef and dairy cows. Furthermore, during periods of inadequate nutrition or stress, the intensity of oestrus is reduced by inadequate exposure to oestradiol. However, it is still unclear which pheromones are involved at oestrus, how synthesis is controlled and how pheromones are detected in herd-mates. GnRH may be involved in behaviour but the brain centres that translate hormonal messages are unknown. Attempts to overcome poor oestrous detection include measurements of milk progesterone, telemetric pressure detectors and devices that record the extra activity at oestrus. Substitution of heat detection by 'hormone treatment remedies' has met strong consumer resistance in Europe. The creation of larger cattle units and increased movements world-wide render herds more susceptible to infectious agents, such as Neospora, Leptospira, Trypanosoma and Bovine Viral Diarrhoea virus (BVDv), but it is unclear how other clinical conditions, such as lameness or endometritis, also interfere with ovarian function. The future of dominant follicles selected within 14 days after parturition is crucial--normal ovulation, prolonged persistence or atresia. Calving carries the greatest risk in the reproductive life of a cow and yet little work has focused on reducing the frequency of this event. For dairy cows, a greater understanding about induced or extended lactation is required. For beef animals, precise induction of twinning and nutritional adjustments could produce two offspring per pregnancy. At the start of pregnancy, the trophoblast produces interferon to prevent luteolysis, but the immunological implications are unknown and it is not clear how the rest of pregnancy is maintained. Profiles of pregnancy specific protein B (PSPB) have increased understanding of embryonic death. However, 25% of cows in abattoirs are pregnant, even though 30% of involuntary cullings are 'for failing to conceive'. Clearly, this is an area of wastage that requires urgent resolution. It is unknown why undernutrition at the time of insemination or in early pregnancy leads to delayed births, low fetal weights and later adverse health. At the end of pregnancy, the fetus controls the onset of parturition, but very little is known about the biochemical control of cervical dilation and placental separation. On the male side, bulls are selected for optimal freezability of semen; however, there is as yet no reliable predictor for semen fertility. Methods for accurately pre-determining the sex of both semen and embryos will revolutionize the dairy and beef industries.


Donor characteristics can influence overall transplant activities: the Italian experience.
The notable increase in organ donations and transplants in Italy in recent years has lead to the development of an atypical approach to kidney transplantation. All propitious considerations left aside regarding the organ donation rate which has placed Italy among the European leaders, a careful comparative evaluation of the data taken from Italian and international registries demonstrates that renal transplantations in Italy have not shared the same significant growth. The typology of the donors has influenced in a decisive way not only the number of renal transplantations, but also the access to transplant for some age groups and probably even the quality and cost. The overall view which emerges is complex and somewhat contradictory, but we believe that this perspective can furnish solid arguments for choices that need not to be delayed for the living donor transplant, the divulgence of a donation culture in the population, and the criteria for the allocation of the organs.


TIQ (Technical IQ)--a survival skill for the new millennium.
Managing in the new technocracy of the new millennium will be challenging but also much more exciting than the work we do now. Twenty years ago, nurse managers weren't held accountable for the level of knowledge about financial outcomes that is expected now. The same will be true for technology. With electronic medical records, innovations in medical treatments, and the impact of the information and technologic revolution on the entire world, the interface between technology assessment, operationalizing technology, and continually upgrading staff to know what the implications of the technology revolution are will be imperative for success. That means that we must influence schools of nursing to include technology in their content now, and to help us prepare this generation of health care leaders to take a full seat at the leadership table to manage these complexities in the future. The success of the leader of the future will be measured by that person's ability to integrate the very complex issues of patient care and technology in a way that makes sense for patients, the organization, and the staff who will be working in a very complex environment. The leader's TIQ will be as important as other intelligences in the next 20 years.


Neuroprotective effect of neurotropin on chronic oxaliplatin-induced neurotoxicity in stage II and stage III colorectal cancer patients: results from a prospective, randomised, single-centre, pilot clinical trial.
Oxaliplatin is effective in adjuvant and first-line colorectal cancer chemotherapy. Oxaliplatin-induced severe chronic neurotoxicity is the main dose-limiting adverse event. No standard treatment for oxaliplatin-induced chronic neurotoxicity has been identified. We conducted a prospective pilot clinical trial to explore whether neurotropin has neuroprotective effects on chronic neurotoxicity. From May 1, 2010 to May 1, 2011, 80 stage II and III colorectal cancer patients who were eligible to receive oxaliplatin-based chemotherapy voluntarily enrolled in the trial. The patients were randomly divided into two groups, one of which received neurotropin treatment. The patients in the control group experienced significantly ≥ grade 2 and ≥ grade 3 neurotoxicity (by NCI CTCAE grading) than those in the neurotropin group (60.9 vs. 21.1 %, for at least grade 2 neurotoxicity, P = 0.001; 39 vs. 2.7 %, for at least grade 3 neurotoxicity, P < 0.001). If neurotoxicity was assessed by oxaliplatin-specific neurotoxicity grading, the patients in the control group also experienced significantly more ≥ grade 2 neurotoxicity (51.2 vs. 12.5 %, P = 0.001). Neurotropin was the only factor that affected the incidence of ≥ grade 2 neurotoxicity in the multivariate Cox proportional hazards regression analysis. Neurotropin combined with oxaliplatin decreases chronic neurotoxicity effectively and safely.


Histological, chemical, and crystallographic analysis of four calcium phosphate cements in different rabbit osseous sites.
Four calcium phosphate cement formulations were implanted in the rabbit distal femoral metaphysis and middiaphysis. Chemical, crystallographic, and histological analyses were made at 2, 4, and 8 weeks after implantation. When implanted into the metaphysis, part of the brushite cement was converted into carbonated apatite by 2 weeks. Some of the brushite cement was removed by mononuclear macrophages prior to its conversion into apatite. Osteoclastlike cell mediated remodeling was predominant at 8 weeks after brushite had converted to apatite. The same histological results were seen for brushite plus calcite aggregate cement, except with calcite aggregates still present at 8 weeks. However, when implanted in the diaphysis, brushite and brushite plus calcite aggregate did not convert to another calcium phosphate phase by 4 weeks. Carbonated apatite cement implanted in the metaphysis did not transform to another calcium phosphate phase. There was no evidence of adverse foreign body reaction. Osteoclastlike cell mediated remodeling was predominant at 8 weeks. The apatite plus calcite aggregate cement implanted in the metaphysis that was not remodeled remained as poorly crystalline apatite. Calcite aggregates were still present at 8 weeks. There was no evidence of foreign body reaction. Osteoclastlike cell remodeling was predominant at 8 weeks. Response to brushite cements prior to conversion to apatite was macrophage dominated, and response to apatite cements was osteoclast dominated. Mineralogy, chemical composition, and osseous implantation site of these calcium phosphates significantly affected their in vivo host response.


Getting to grips with wildlife research by citizen scientists: What role for regulation?
Wildlife research by citizen scientists, involving the capture and handling of animals, provides clear scientific benefits, but also potential risks to animal welfare. We explore debates about how best to regulate such work to ensure that it is undertaken in an ethical manner.We focus on the UK as a case study, drawing on qualitative research and stakeholder engagement events. We show that because trapping and marking of certain species requires minimal licensing, training and justification, some argue for increased formal regulation to minimise risks to animal welfare. However, others have reflected on the already complex regulatory landscape affecting wildlife research, and have expressed concern that introducing additional formal regulations could potentially make citizen science working with wildlife more difficult. Informal regulation could therefore offer a preferable alternative.We set out three steps that could be taken to open up conversations about ethics and regulation of wildlife-focussed citizen science, in the UK and elsewhere: (a) take stock of wildlife-focussed citizen science in terms of numbers and harms to animal welfare; (b) assess the state of formal regulations and consider reforms; and (c) consider informal regulations as alternatives or additions to formal regulations.


The Leukotriene B4 and its Receptor BLT1 Act as Critical Drivers of Neutrophil Recruitment in Murine Bullous Pemphigoid-Like Epidermolysis Bullosa Acquisita.
Recruitment of neutrophils and eosinophils into the skin is a hallmark of pemphigoid diseases. The molecular cues regulating granulocyte recruitment into the skin and the individual contributions of neutrophils and eosinophils to pemphigoid diseases are, however, poorly understood. The lipid mediator leukotriene B4 (LTB4) is a potent granulocyte chemoattractant and is abundant in the skin blister fluid of bullous pemphigoid (BP) patients, but its pathogenic significance is unknown. Using mouse models of BP-like epidermolysis bullosa acquisita and of BP, we show that LTB4 and its receptor BLT1 act as critical drivers of neutrophil entry into the skin upon antibody deposition at the dermal-epidermal junction. Mice deficient in 5-lipoxygenase, a key enzyme in LTB4 biosynthesis, or in BLT1 exhibited dramatic resistance to neutrophil recruitment and, consequently, skin inflammation. Accordingly, liquid chromatography-mass spectrometry, used to comprehensively profile lipid mediator generation in the first 48 hours after antibody deposition, showed a pronounced parallel increase in LTB4 and in neutrophils in the skin. Subsequent mechanistic studies in BP-like epidermolysis bullosa acquisita uncovered that neutrophils are necessary for skin inflammation, whereas eosinophils are dispensable, thus identifying neutrophils as major culprits of blister formation. Our results highlight LTB4/BLT1 as absolutely critical drivers of murine pemphigoid disease-like skin inflammation.


[The Pvu II and Xba I polymorphisms in the estrogen receptor alpha gene in Chinese patients with severe preeclampsia].
To assess the allele and genotype frequencies of the estrogen receptor alpha ( ESR alpha) Pvu II and Xba I polymorphisms in patients with severe preeclampsia and compare them with those of normal pregnant women. Blood samples from 131 patients with severe preeclampsia and 223 normal pregnant women from Chinese Han in Chengdu area were analyzed, using PCR-RFLP method. Pregnant patients with blood pressure exceeding 140/90 mmHg (or 18.7/12 kPa) were recruited with a strict definition of preeclampsia. Genotyping was performed using PCR-RFLP for Pvu II and Xba I polymorphisms in the ESR alpha gene. The T and C allele frequencies for Pvu II site were 0.580 and 0.420 in the patient group, and 0.576 and 0.424 in the controls, respectively. The A and G allele frequencies for Xba I site were 0.763 and 0.237 in the patient group, and 0.807 and 0.193 in control group, respectively. No significant difference in the allele frequencies of either site was observed between the two groups. However, the CC homozygotes or CT heterozygotes in the control pregnant women had higher systolic blood pressure levels than TT homozygotes for Pvu II site after the data was adjusted for age and BMI (114.00+/-21.44 mmHg or 114.33+/-1.21 mmHg vs. 108.62+/-1.91 mmHg, P<0.05). No genotype effect on the blood pressures was found for Pvu II site in the case group, nor for Xba I site in either group. Our work has excluded the association of the ESRalpha Pvu II and Xb I polymorphism with severe preeclampsia in a Southwest Chinese population, although this polymorphism may be associated with the systolic blood pressure level in the normal pregnant women.


Malleal processus brevis is dispensable for normal hearing in mice.
The mammalian middle ear cavity contains a chain of three ossicles (the malleus, incus, and stapes), which develop from the mesenchyme of the first two branchial arches. Mice deficient in the Msx1 homeobox gene exhibit craniofacial abnormalities, including the absence of the malleal processus brevis that is normally attached to the upper part of the tympanic membrane. Here, we show that the expression of Msx1 and Msx2 overlaps in the malleal primordium during early embryonic development. A functional redundancy of Msx1 and Msx2 in the development of the middle ear is suggested by the stronger hypomorphism in the malleus of Msx1(-/-)/Msx2(-/-) embryos, including the absence of the malleal manubrium and the malleal processus brevis. The expression of Bmp4, a known downstream target of Msx1 in several developing craniofacial organs, was down-regulated in the malleal primordium, particularly in the region of the developing malleal manubrium, of Msx1 and Msx1(-/-)/Msx2(-/-) embryos. Msx genes, thus, appear to act in a cell autonomous manner, possibly by regulating Bmp4 expression, in the formation of the malleus. Transgenic rescue of the cleft palate of Msx1(-/-) mice overcame the neonatal lethality and allowed Msx1(-/-) mice to grow into adulthood but retain the phenotype of the absence of the malleal processus brevis. The availability of this animal model for the first time allowed us to measure auditory evoked potentials to assess the functional significance of the malleal processus brevis. The results demonstrated unimpaired auditory function in Msx1(-/-) mice. In addition, mutant mice appeared normal in balance behavior and in the vestibular evoked potential screening test. These results indicate that the malleal processus brevis is not necessary for sound transmission and seems dispensable for normal hearing and balance in mammals.


Exendin-4 Treatment Improves LPS-Induced Depressive-Like Behavior Without Affecting Pro-Inflammatory Cytokines.
Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration. To investigate whether exendin-4 directly reduces inflammation in the brain following an insult that involves neuroinflammation but not neurodegeneration, namely systemic administration of lipopolysaccharide (LPS). Rats were administered LPS systemically and were treated with either 0.5 μg/kg exendin-4 or saline vehicle injections over 5 days. Behavior was evaluated with forced swim test. We assayed TNF-α and IL-1β levels in cerebrospinal fluid and cytokine mRNA expression in striatal, hippocampal and cortical tissues using qPCR. We determined brain monoamines using high-performance liquid chromatography. Finally, we isolated primary brain microglia from rats and measured cytokine production after exendin-4 treatment and LPS stimulation. Exendin-4 treatment did not affect cytokine mRNA expression in brain, cytokine levels in cerebrospinal fluid or cytokine production from cultured microglia, although there was a trend towards increased striatal dopamine. Importantly, exendin-4 significantly prevented depressive-like behavior at 24 hours after LPS injection, indicating that the drug engaged a target in the brain. Depressive-like behavior was associated with altered dopamine turnover in the striatum. We did not detect any anti-inflammatory effects of exendin-4. In previous studies exploring the effects of exendin-4 on brain insults involving neurodegeneration, observations of reduced inflammation might have been secondary to mitigation of neuronal death. Our results indicate that the effects of exendin-4 on behavior may be due to effects on dopamine synthesis or metabolism.


[Diagnosis and therapy of acute bacterial infections of the eye].
New knowledge in the understanding of infection immunology and the development of more effective antibiotics will influence the therapeutic options for extra- and intraocular bacterial diseases. The role of mucin with its high sIgA content, the glycoconjugate-mediated bacterial adherence phenomena of the cornea and conjunctiva, and the exact biomicroscopic classification can be constrated with the highly effective topically and systemically applicable antibiotics (e.g., Cephalosporins, Aminoglycosides, New Quinolones and Carbapenems). Recognition of the fact that the amplification mechanisms of the immune system are already fully activated when the clinical features of a serpent ulcer appear and that the destructive phase only represents an unwanted side-effect of the host defense mechanisms towards its own structures has resulted in the application of corticosteroids with simultaneous antibiotic medication and early tectonic perforating keratoplasty. Many intraocular inflammations of heretofore unknown etiology may be detected by modern diagnostic approaches as being localized manifestations of a systemic disease that can be properly treated (e.g., borreliosis, atypical syphilis). The incidence of "metastatic" endophthalmitis could be diminished in high-risk inpatients by preventive measures, including the elimination of potentially pathogenic agents with antibiotics (and antifungal drugs). Infection-associated intraocular inflammations ("Reiter's syndrome") have been linked to persisting pathogenic organisms at distant sites, thereby rendering themselves etiologically treatable (e.g., infections from Yersinia, Campylobaster, Urea-plasma, and Chlamydia). Except for a very few cases (use of monoclonal antibodies, serological methods and immunoblots), the diagnosis of bacterial infections is based on isolation of the organism concerned, which also represents a requirement for antibiotic susceptibility testing and, consequently a specific medication. Close cooperation with microbiologists and the direct culturing of isolates within ophthalmology clinics have seen a revival since the days of Theodor Axenfeld.


A report of an adult case of tubulointerstitial nephritis and uveitis (TINU) syndrome, with a review of 102 Japanese cases.
Although TINU syndrome is characterized by idiopathic TIN with bilateral anterior uveitis, few reports have provided a comprehensive summary of the features of this disorder. Previous reports have suggested that many Japanese patients had HLA-A2 and -A24 (7), but there is no evidence. A 44-year-old female was referred to our hospital due to renal dysfunction in March 2012. After admission, her symptoms improved spontaneously without medication within 2 weeks. In the outpatient clinic, she was diagnosed with idiopathic bilateral anterior uveitis in May, and her renal dysfunction relapsed in November. A renal biopsy showed diffuse TIN. We made a diagnosis of TINU syndrome because we could not explain the origin, and treated her with a systemic corticosteroid. Her renal function and ocular symptoms have been improving. The patient had HLA-A24, -B7, -DR1, -C*07: 02 and -DQB1*05: 01: 01. We collected 102 Japanese cases in PubMed, Ovid MEDLINE, and the Japanese Medical Abstracts Society and compared our case with the previous cases. This disorder affects primarily young females (median age, 14 years), and the most common symptom is fever (44/102 cases). We conducted a statistical analysis using contingency table and Pearson's chi-square test, for HLA-A2 and A24, and calculated the odds ratio (OR). There are no significant differences (A2 was present in 7/22 cases and in 19/50 controls, p value (P) 0.61, OR 0.76 (95% confidence interval (CI)) 0.27-2.2; A24 was present in 10/22 cases and in 33/50 controls, P 0.10, OR 0.43, CI 0.16-1.2).


Nonhepatic hyperammonemic encephalopathy following bariatric surgery: A systematic review.
Nonhepatic Hyperammonemic encephalopathy (NHAE) following Bariatric Surgery (BS), mainly Roux-en-Y Gastric Bypass (RYGB) and Biliopancreatic Diversion (BPD) is a potentially devastating condition if not diagnosed and managed promptly. A literature review was performed using PRISMA guidelines. Eighteen studies and 3 conference abstracts with a total of 33 patients were included in this review. Majority (28 patients, 84.8 %) had RYGB. Seven patients (21.2 %) had associated metabolic disorders. 60 % of patients presented with neurological symptoms or signs such as confusion, cognitive and/or psychomotor changes, and decreased reflexes. Two patients presented with status epilepticus. In 30 of the 33 patients an elevated serum ammonia levels was reported (90.9 %). The overall mortality was 39.3 %. NHAE is a rare condition following bariatric surgery (in particular bypass procedures), carrying a high mortality rate. The signs and symptoms are predominantly neurological and may be mistaken for Wernicke's encephalopathy or other more common neurological conditions. Serum ammonia levels should be checked in those who present with these symptoms and signs. Prompt treatment might be life saving in patients with NHAE.


Chinese parents' perception of support received and recommendations regarding children's postoperative pain management.
The aims of this study are to describe Chinese parents' perceptions of informational and emotional support received from nurses and their recommendations for improvement in the management of their child's postoperative pain. Data were collected using a questionnaire survey completed by 206 parents of 6- to 12-year-old child hospitalized in 12 wards in five provincial hospitals in Fujian Province, China, in 2004. Findings indicated that parents experienced negative feelings such as worry (91%) and anxiety (59%). Most of them reported they had received sufficient information on outcomes of surgical procedure (85%) and postoperative recovery process (84%), but fewer reported they had received sufficient information on pain medication (51%) and non-pharmacological pain-relieving methods (59%). Parents made some recommendations, which centred mainly on nurses' use of non-pharmacological methods. Findings suggest that parents need more information related to pain management and their understanding of the information should be ensured.


Asparagine Deprivation Causes a Reversible Inhibition of Human Cytomegalovirus Acute Virus Replication.
As obligate intracellular pathogens, viruses rely on the host cell machinery to replicate efficiently, with the host metabolism extensively manipulated for this purpose. High-throughput small interfering RNA (siRNA) screens provide a systematic approach for the identification of novel host-virus interactions. Here, we report a large-scale screen for host factors important for human cytomegalovirus (HCMV), consisting of 6,881 siRNAs. We identified 47 proviral factors and 68 antiviral factors involved in a wide range of cellular processes, including the mediator complex, proteasome function, and mRNA splicing. Focused characterization of one of the hits, asparagine synthetase (ASNS), demonstrated a strict requirement for asparagine for HCMV replication which leads to an early block in virus replication before the onset of DNA amplification. This effect is specific to HCMV, as knockdown of ASNS had little effect on herpes simplex virus 1 or influenza A virus replication, suggesting that the restriction is not simply due to a failure in protein production. Remarkably, virus replication could be completely rescued 7 days postinfection with the addition of exogenous asparagine, indicating that while virus replication is restricted at an early stage, it maintains the capacity for full replication days after initial infection. This study represents the most comprehensive siRNA screen for the identification of host factors involved in HCMV replication and identifies the nonessential amino acid asparagine as a critical factor in regulating HCMV virus replication. These results have implications for control of viral latency and the clinical treatment of HCMV in patients.IMPORTANCE HCMV accounts for more than 60% of complications associated with solid organ transplant patients. Prophylactic or preventative treatment with antivirals, such as ganciclovir, reduces the occurrence of early onset HCMV disease. However, late onset disease remains a significant problem, and prolonged treatment, especially in patients with suppressed immune systems, greatly increases the risk of antiviral resistance. Very few antivirals have been developed for use against HCMV since the licensing of ganciclovir, and of these, the same viral genes are often targeted, reducing the usefulness of these drugs against resistant strains. An alternative approach is to target host genes essential for virus replication. Here we demonstrate that HCMV replication is highly dependent on levels of the amino acid asparagine and that knockdown of a critical enzyme involved in asparagine synthesis results in severe attenuation of virus replication. These results suggest that reducing asparagine levels through dietary restriction or chemotherapeutic treatment could limit HCMV replication in patients.


Bovine neutrophils ingest but do not kill Haemophilus somnus in vitro.
Phagocytosis of Haemophilus somnus by bovine blood neutrophils required opsonization of the bacteria with antibodies against H. somnus. Few bacteria were phagocytosed in the absence of serum; in addition, absorption of immune serum with Formalin-killed H. somnus significantly reduced ingestion of H. somnus. Heat inactivation of antiserum (56 degrees C for 30 min) to eliminate complement activity had little effect on its ability to opsonize H. somnus for uptake by bovine neutrophils. Antiserum from an H. somnus-immunized calf and autologous sera from adult cattle supported equivalent phagocytosis of H. somnus by bovine neutrophils, suggesting that normal, healthy cattle may contain sufficient antibodies in their sera to facilitate phagocytosis of H. somnus. Although bovine neutrophils readily ingested H. somnus, they were unable to kill the bacterium in vitro. These same neutrophils readily killed opsonized Escherichia coli and Staphylococcus epidermidis, suggesting that H. somnus is able to survive and perhaps multiply within bovine neutrophils. Because bovine neutrophils stimulated with opsonized H. somnus demonstrated a reduced oxidative burst (as measured by chemiluminescence) compared with neutrophils stimulated by opsonized E. coli, we suggest that reduced production of reactive oxygen intermediates during the phagocytosis of H. somnus may account, in part, for the enhanced survival of H. somnus in bovine neutrophils.