bluuebunny/crossref_metadata_2025 huggingface dataset:
Procalcitonin and C-reactive protein levels at admission as predictors of duration of acute brain dysfunction in critically ill patients
Authors: McGrane Stuart , Girard Timothy D , Thompson Jennifer L , Shintani Ayumi K , Woodworth Alison , Ely E Wesley , Pandharipande Pratik P
Published: March 2011

Introduction

Non-intensive care unit (ICU) cohorts have shown an association between inflammatory disturbances and delirium, though these relationships have not been studied in critically ill patients. This study sought to investigate the relationship between two inflammatory biomarkers, procalcitonin and C-reactive protein (CRP), and duration of acute brain dysfunction in ventilated patients.

Methods

Patients enrolled in the Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial were assessed daily for delirium using the Confusion Assessment Method-ICU. Plasma levels of procalcitonin and CRP were obtained within 24 hours of enrollment. Proportional odds logistic regression was used to examine the association between procalcitonin and CRP separately with delirium/coma-free days, adjusting for age, acute physiology score (APS) of the Acute Physiology And Chronic Health Evaluation (APACHE) II, sedation group (dexmedetomidine vs. lorazepam), and sepsis. Secondary analyses examined the association of these markers with other organ dysfunctions and 28-day survival.

Results

Eighty-seven patients were included in this analysis. The median age of the patients was 60 years with APACHE II scores of 28; 68% had sepsis within 48 hours of admission. Higher levels of procalcitonin were associated with fewer delirium/coma-free days [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3 to 1.0; P = 0.04], whereas higher CRP levels showed trends towards fewer delirium/coma-free days (OR, 0.6; 95% CI, 0.3 to 1.1; P = 0.08). Similar relationships were found regardless of the presence of sepsis. No associations were found between procalcitonin or CRP with 28-day survival (P = 0.40 and 0.16, respectively).

Conclusions

In our pilot study, high baseline inflammatory biomarkers predicted prolonged periods of acute brain dysfunction, implicating inflammation as an important mechanism in the pathophysiology of delirium and coma during critical illness, irrespective of whether patients had sepsis or not.
Comparative genomics of the social amoebae Dictyostelium discoideum and Dictyostelium purpureum
Authors: Sucgang Richard , Kuo Alan , Tian Xiangjun , Salerno William , Parikh Anup , Feasley Christa L , Dalin Eileen , Tu Hank , Huang Eryong , Barry Kerrie , Lindquist Erika , Shapiro Harris , Bruce David , Schmutz Jeremy , Salamov Asaf , Fey Petra , Gaudet Pascale , Anjard Christophe , Babu M Madan , Basu Siddhartha , Bushmanova Yulia , van der Wel Hanke , Katoh-Kurasawa Mariko , Dinh Christopher , Coutinho Pedro M , Saito Tamao , Elias Marek , Schaap Pauline , Kay Robert R , Henrissat Bernard , Eichinger Ludwig , Rivero Francisco , Putnam Nicholas H , West Christopher M , Loomis William F , Chisholm Rex L , Shaulsky Gad , Strassmann Joan E , Queller David C , Kuspa Adam , Grigoriev Igor V
Published: March 2011

Background

The social amoebae (Dictyostelia) are a diverse group of Amoebozoa that achieve multicellularity by aggregation and undergo morphogenesis into fruiting bodies with terminally differentiated spores and stalk cells. There are four groups of dictyostelids, with the most derived being a group that contains the model species Dictyostelium discoideum.

Results

We have produced a draft genome sequence of another group dictyostelid, Dictyosteliumpurpureum, and compare it to the D. discoideum genome. The assembly (8.41 × coverage) comprises 799 scaffolds totaling 33.0 Mb, comparable to the D. discoideum genome size. Sequence comparisons suggest that these two dictyostelids shared a common ancestor approximately 400 million years ago. In spite of this divergence, most orthologs reside in small clusters of conserved synteny. Comparative analyses revealed a core set of orthologous genes that illuminate dictyostelid physiology, as well as differences in gene family content. Interesting patterns of gene conservation and divergence are also evident, suggesting function differences; some protein families, such as the histidine kinases, have undergone little functional change, whereas others, such as the polyketide synthases, have undergone extensive diversification. The abundant amino acid homopolymers encoded in both genomes are generally not found in homologous positions within proteins, so they are unlikely to derive from ancestral DNA triplet repeats. Genes involved in the social stage evolved more rapidly than others, consistent with either relaxed selection or accelerated evolution due to social conflict.

Conclusions

The findings from this new genome sequence and comparative analysis shed light on the biology and evolution of the Dictyostelia.
Implementation of a Project-Based Molecular Biology Laboratory Emphasizing Protein Structure–Function Relationships in a Large Introductory Biology Laboratory Course
Authors: Treacy Daniel J. , Sankaran Saumya M. , Gordon-Messer Susannah , Saly Danielle , Miller Rebecca , Isaac Stefan R. , Kosinski-Collins Melissa S.
Published: March 2011

In introductory laboratory courses, many universities are turning from traditional laboratories with predictable outcomes to inquiry-inspired, project-based laboratory curricula. In these labs, students are allowed to design at least some portion of their own experiment and interpret new, undiscovered data. We have redesigned the introductory biology laboratory course at Brandeis University into a semester-long project-based laboratory that emphasizes concepts and contains an element of scientific inquiry. In this laboratory, students perform a site-directed mutagenesis experiment on the gene encoding human γD crystallin, a human eye lens protein implicated in cataracts, and assess the stability of their newly created protein with respect to wild-type crystallin. This laboratory utilizes basic techniques in molecular biology to emphasize the importance of connections between DNA and protein. This project lab has helped engage students in their own learning, has improved students’ skills in critical thinking and analysis, and has promoted interest in basic research in biology.
A Semester-Long Project for Teaching Basic Techniques in Molecular Biology Such as Restriction Fragment Length Polymorphism Analysis to Undergraduate and Graduate Students
Authors: DiBartolomeis Susan M.
Published: March 2011

Several reports on science education suggest that students at all levels learn better if they are immersed in a project that is long term, yielding results that require analysis and interpretation. I describe a 12-wk laboratory project suitable for upper-level undergraduates and first-year graduate students, in which the students molecularly locate and map a gene from Drosophila melanogaster called dusky and one of dusky's mutant alleles. The mapping strategy uses restriction fragment length polymorphism analysis; hence, students perform most of the basic techniques of molecular biology (DNA isolation, restriction enzyme digestion and mapping, plasmid vector subcloning, agarose and polyacrylamide gel electrophoresis, DNA labeling, and Southern hybridization) toward the single goal of characterizing dusky and the mutant allele dusky73. Students work as individuals, pairs, or in groups of up to four students. Some exercises require multitasking and collaboration between groups. Finally, results from everyone in the class are required for the final analysis. Results of pre- and postquizzes and surveys indicate that student knowledge of appropriate topics and skills increased significantly, students felt more confident in the laboratory, and students found the laboratory project interesting and challenging. Former students report that the lab was useful in their careers.
An Undergraduate Course to Bridge the Gap between Textbooks and Scientific Research
Authors: Wiegant Fred , Scager Karin , Boonstra Johannes
Published: March 2011

This article reports on a one-semester Advanced Cell Biology course that endeavors to bridge the gap between gaining basic textbook knowledge about cell biology and learning to think and work as a researcher. The key elements of this course are 1) learning to work with primary articles in order to get acquainted with the field of choice, to learn scientific reasoning, and to identify gaps in our current knowledge that represent opportunities for further research; 2) formulating a research project with fellow students; 3) gaining thorough knowledge of relevant methodology and technologies used within the field of cell biology; 4) developing cooperation and leadership skills; and 5) presenting and defending research projects before a jury of experts. The course activities were student centered and focused on designing a genuine research program. Our 5-yr experience with this course demonstrates that 1) undergraduate students are capable of delivering high-quality research designs that meet professional standards, and 2) the authenticity of the learning environment in this course strongly engages students to become self-directed and critical thinkers. We hope to provide colleagues with an example of a course that encourages and stimulates students to develop essential research thinking skills.
A Study Assessing the Potential of Negative Effects in Interdisciplinary Math–Biology Instruction
Authors: Madlung Andreas , Bremer Martina , Himelblau Edward , Tullis Alexa
Published: March 2011

There is increasing enthusiasm for teaching approaches that combine mathematics and biology. The call for integrating more quantitative work in biology education has led to new teaching tools that improve quantitative skills. Little is known, however, about whether increasing interdisciplinary work can lead to adverse effects, such as the development of broader but shallower skills or the possibility that math anxiety causes some students to disengage in the classroom, or, paradoxically, to focus so much on the mathematics that they lose sight of its application for the biological concepts in the center of the unit at hand. We have developed and assessed an integrative learning module and found disciplinary learning gains to be equally strong in first-year students who actively engaged in embedded quantitative calculations as in those students who were merely presented with quantitative data in the context of interpreting biological and biostatistical results. When presented to advanced biology students, our quantitative learning tool increased test performance significantly. We conclude from our study that the addition of mathematical calculations to the first year and advanced biology curricula did not hinder overall student learning, and may increase disciplinary learning and data interpretation skills in advanced students.
Neural activation and radial diffusivity in schizophrenia:
combined fMRI and diffusion tensor imaging study
Authors: Koch Kathrin , Wagner Gerd , Schachtzabel Claudia , Schultz C. Christoph , Güllmar Daniel , Reichenbach Jürgen R. , Sauer Heinrich , Schlösser Ralf G. M.
Published: March 2011

Background

Schizophrenia is associated with often widespread changes in white matter
structure. Most studies have investigated changes in fractional
anisotropy, whereas alterations in radial or axial diffusivity have
barely been investigated until now.

Aims

To investigate radial diffusivity as a potential marker of dysmyelination
in direct relation to abnormalities in neural activation.

Method

Neural activation in association with decision-making under uncertainty
was investigated in 19 people with schizophrenia and 20 healthy controls
and linked to radial diffusivity as measured by diffusion tensor
imaging.

Results

Decision-making under uncertainty was associated with a significantly
decreased activation in a frontostriatocingulate network in the
schizophrenia group. Structurally, they exhibited increased radial
diffusivity in temporal white matter that was negatively correlated with
activation in parts of the frontostriatocingulate network.

Conclusions

Present data indicate that altered diffusivity within relevant white
matter networks may be closely linked to abnormal neural activation in
schizophrenia.
Will current socioeconomic trends produce a depressing future
for men?
Authors: Dunlop Boadie W. , Mletzko Tanja
Published: March 2011

The changing economic and social environment of Western nations is having a
profound impact on men's lives. Men who assume a greater share of roles
traditionally filled by women will experience challenges to traditional
sources of male self-esteem, potentially heightening the risk for depressive
disorders among men.
Neurodevelopmental hypothesis of schizophrenia
Authors: Owen Michael J. , O'Donovan Michael C. , Thapar Anita , Craddock Nicholas
Published: March 2011

The neurodevelopmental hypothesis of schizophrenia provided a valuable framework that allowed a condition that usually presents with frank disorder in adolescence or early adulthood to be understood at least in part as a consequence of events occurring early in development. However, the implications of the neurodevelopmental hypothesis for nosological conceptions of the disorder can only now be fully appreciated. Recent research indicates genetic overlap between schizophrenia and syndromes in which psychopathology is manifest in childhood and that are often grouped together as ‘neurodevelopmental disorders' such as autism-spectrum disorders, intellectual disability and attention-deficit hyperactivity disorder. These findings challenge the aetiological basis of current diagnostic categories and, together with evidence for frequent comorbidity, suggest that we should view the functional psychoses as members of a group of related and overlapping syndromes that result in part from a combination of genetic and environmental effects on brain development and that are associated with specific and general impairments of cognitive function. This has important implications for future research and for the configuration of psychiatric services.
Off-label prescribing in people with recurrent depressive disorder attending a community mental health service
Authors: Uzoechina Chinedu E. , Hilvering Pieter , Rogers Cathryn , O'Brien Sinead , Pullela Ananth , Yousafzai Mushtaq , Meagher David J.
Published: March 2011

Aims and method

We investigated deliberate and inadvertent off-label prescribing in individuals with recurrent depressive disorder attending a community mental health service.

Results

Off-label prescribing occurred in 87 of 226 people with recurrent depressive disorder (38%) and involved antipsychotic agents (41), maintenance benzodiazepine use (33), antidepressant polypharmacy (28), high-dose antidepressants (19) and use of antidepressants outside of the recommended age range (16). Off-label prescribing was part of a deliberate and documented treatment plan for a half (n= 43) of individuals. Participants receiving off-label prescribing had higher total Health of the Nation Outcome Scale (HoNOS) scores, were attending more frequently and were older and had more chronic illness duration. Inadvertent off-label prescribing was related to higher scores on the behavioural disturbance subscale of the HoNOS.

Clinical implications

Off-label prescribing is a common phenomenon in people with recurrent depressive disorder and relates to greater illness severity and chronicity. Although off-label prescribing is frequently deliberate, in many cases it is undesirable and unplanned.
Impact of crisis resolution and home treatment services on user experience and admission to psychiatric hospital
Authors: Barker Victoria , Taylor Mark , Kader Ihsan , Stewart Kathleen , Le Fevre Pete
Published: March 2011

Aims and method

Crisis resolution and home treatment (CRHT) teams began operating in Edinburgh in late 2008. We ascertained service users' and carers' experiences of CRHT using a standardised questionnaire. We also assessed the impact of CRHT on psychiatric admissions and readmissions by analysing routinely collected data from November 2003 to November 2009.

Results

There was a 24% decrease in acute psychiatric admissions in the year after CRHT began operating, whereas the previous 5 years saw an 8% reduction in the admission rate. The mean duration of in-patient stay fell by 6.5 days (22% decrease) in the 12 months following CRHT introduction, alongside a 4% decrease in readmissions and a 17% reduction in Mental Health Act 1983 admissions. Although the mean response rate was low (29%), 93% of patients reported clinical improvement during CRHT care, 27% of patients felt totally recovered at discharge from CRHT, 90% of patients felt safe during CRHT treatment, and 94% of carers said their friend or relative got better with CRHT input.

Clinical implications

Crisis resolution and home treatment service in Edinburgh had a positive impact during the first 12 months in terms of reduced admissions, reduced duration of in-patient stay and reduced use of the Mental Health Act. The service can catalyse a more efficient use of in-patient care. Service users and carers report high rates of improvement and satisfaction with CRHT.
A Circadian Clock Entrained by Melatonin Is Ticking in the Rat Fetal Adrenal
Authors: Torres-Farfan C. , Mendez N. , Abarzua-Catalan L. , Vilches N. , Valenzuela G. J. , Seron-Ferre M.
Published: March 2011

The adrenal gland in the adult is a peripheral circadian clock involved in the coordination of energy intake and expenditure, required for adaptation to the external environment. During fetal life, a peripheral circadian clock is present in the nonhuman primate adrenal gland. Whether this extends to the fetal adrenal gland like the rat is unknown. Here we explored in vivo and in vitro whether the rat fetal adrenal is a peripheral circadian clock entrained by melatonin. We measured the 24-h changes in adrenal content of corticosterone and in the expression of clock genes Per-2 and Bmal-1 and of steroidogenic acute regulatory protein (StAR), Mt1 melatonin receptor, and early growth response protein 1 (Egr-1) expression. In culture, we explored whether oscillatory expression of these genes persisted during 48 h and the effect of a 4-h melatonin pulse on their expression. In vivo, the rat fetal adrenal gland showed circadian expression of Bmal-1 and Per-2 in antiphase (acrophases at 2200 and 1300 h, respectively) as well as of Mt1 and Egr-1. This was accompanied by circadian rhythms of corticosterone content and of StAR expression both peaking at 0600 h. The 24-h oscillatory expression of Bmal-1, Per-2, StAR, Mt1, and Egr-1 persisted during 48 h in culture; however, the antiphase between Per-2 and Bmal-1 was lost. The pulse of melatonin shifted the acrophases of all the genes studied and restored the antiphase between Per-2 and Bmal-1. Thus, in the rat, the fetal adrenal is a strong peripheral clock potentially amenable to regulation by maternal melatonin.
Androgens Modulate Structure and Function of the Suprachiasmatic Nucleus Brain Clock
Authors: Karatsoreos Ilia N. , Butler Matthew P. , LeSauter Joseph , Silver Rae
Published: March 2011

Gonadal hormones can modulate circadian rhythms in rodents and humans, and androgen receptors are highly localized within the core region of the mouse suprachiasmatic nucleus (SCN) brain clock. Although androgens are known to modulate neural plasticity in other CNS compartments, the role of androgens and their receptors on plasticity in the SCN is unexplored. In the present study, we ask whether androgens influence the structure and function of the mouse SCN by examining the effects of gonadectomy (GDX) on the structure of the SCN circuit and its responses to light, including induction of clock genes and behavioral phase shifting. We found that after GDX, glial fibrillary acidic protein increased with concomitant decreases in the expression of the synaptic proteins synaptophysin and postsynaptic density 95. We also found that GDX exerts effects on the molecular and behavioral responses to light that are phase dependent. In late night [circadian time (CT)21], GDX increased light-induced mPer1 but not mPer2 expression compared with intact (INT) controls. In contrast, in early night (CT13.5), GDX decreased light induced mPer2 but had no effect on mPer1. At CT13.5, GDX animals also showed larger phase delays than did INT. Treatment of GDX animals with the nonaromatizable androgen dihydrotestosterone restored glial fibrillary acidic protein, postsynaptic density 95, and synaptophysin in the SCN and reinstated the INT pattern of molecular and behavioral responses to light. Together, the results reveal a role for androgens in regulating circuitry in the mouse SCN, with functional consequences for clock gene expression and behavioral responses to photic phase resetting stimuli.
Loss of Agouti-Related Peptide Does Not Significantly Impact the Phenotype of Murine POMC Deficiency
Authors: Corander Marcus P. , Rimmington Debra , Challis Benjamin G. , O'Rahilly Stephen , Coll Anthony P.
Published: March 2011

The hypothalamic melanocortin system is unique among neuropeptide systems controlling energy homeostasis, in that both anorexigenic proopiomelanocortin (POMC)-derived and orexigenic Agouti related-peptide (AgRP)-derived ligands act at the same receptors, namely melanocortin 3 and 4 receptors (MC3/4R). AgRP clearly acts as a competitive antagonist at MC3R and MC4R but may also have an inverse agonist action at these receptors. The physiological relevance of this remains uncertain. We generated a mouse lacking both POMC and AgRP [double knockout (DKO) mouse]. Phenotyping was performed in the absence and presence of glucocorticoids, and the response to central peptide administration was studied. The phenotype of DKO mice is indistinguishable from that of mice lacking Pomc alone, with both exhibiting highly similar degrees of hyperphagia and increased body length, fat, and lean mass compared with wild-type controls. After a 24-h fast, there was no difference in the refeeding response between Pomc−/− and DKO mice. Similarly, corticosterone supplementation caused an equivalent increase in food intake and body weight in both genotypes. Although the central administration of [Nle4, d-Phe7]-α-MSH to DKO mice caused a decrease in food intake and an increase in brown adipose tissue Ucp1 expression, both of which could be antagonized with the coadministration of AgRP, there was no effect of AgRP alone. These data suggest AgRP acts predominantly as a melanocortin antagonist. If AgRP has significant melanocortin-independent actions, these are of insufficient magnitude in vivo to impact any of the detailed phenotypes we have measured under a wide variety of conditions.
The PPARβ/δ Activator GW501516 Prevents the Down-Regulation of AMPK Caused by a High-Fat Diet in Liver and Amplifies the PGC-1α-Lipin 1-PPARα Pathway Leading to Increased Fatty Acid Oxidation
Authors: Barroso Emma , Rodríguez-Calvo Ricardo , Serrano-Marco Lucía , Astudillo Alma M. , Balsinde Jesús , Palomer Xavier , Vázquez-Carrera Manuel
Published: March 2011

Metabolic syndrome-associated dyslipidemia is mainly initiated by hepatic overproduction of the plasma lipoproteins carrying triglycerides. Here we examined the effects of the peroxisome proliferator-activated receptors (PPAR)-β/δ activator GW501516 on high-fat diet (HFD)-induced hypertriglyceridemia and hepatic fatty acid oxidation. Exposure to the HFD caused hypertriglyceridemia that was accompanied by reduced hepatic mRNA levels of PPAR-γ coactivator 1 (PGC-1)-α and lipin 1, and these effects were prevented by GW501516 treatment. GW501516 treatment also increased nuclear lipin 1 protein levels, leading to amplification in the PGC-1α-PPARα signaling system, as demonstrated by the increase in PPARα levels and PPARα-DNA binding activity and the increased expression of PPARα-target genes involved in fatty acid oxidation. These effects of GW501516 were accompanied by an increase in plasma β-hydroxybutyrate levels, demonstrating enhanced hepatic fatty acid oxidation. Moreover, GW501516 increased the levels of the hepatic endogenous ligand for PPARα, 16:0/18:1-phosphatidilcholine and markedly enhanced the expression of the hepatic Vldl receptor. Interestingly, GW501516 prevented the reduction in AMP-activated protein kinase (AMPK) phosphorylation and the increase in phosphorylated levels of ERK1/2 caused by HFD. In addition, our data indicate that the activation of AMPK after GW501516 treatment in mice fed HFD might be the result of an increase in the AMP to ATP ratio in hepatocytes. These findings indicate that the hypotriglyceridemic effect of GW501516 in HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-lipin 1-PPARα pathway.
Nitric oxide is the primary mediator of cytotoxicity induced by GSH depletion in neuronal cells
Authors: Aquilano Katia , Baldelli Sara , Cardaci Simone , Rotilio Giuseppe , Ciriolo Maria Rosa
Published: March 2011

Glutathione (GSH) levels progressively decline during aging and in neurodegenerative disorders. However, the contribution of such event in mediating neuronal cell death is still uncertain. In this report, we show that, in neuroblastoma cells as well as in primary mouse cortical neurons, GSH decrease, induced by buthionine sulfoximine (BSO), causes protein nitration, S-nitrosylation and DNA strand breaks. Such alterations are also associated with inhibition of cytochrome c oxidase activity and microtubule network disassembly, which are considered hallmarks of nitric oxide (NO) toxicity. In neuroblastoma cells, BSO treatment also induces cell proliferation arrest through the ERK1/2-p53 pathway that finally results in caspase-independent apoptosis, as evident from the translocation of apoptosis-inducing factor from mitochondria towards nuclei. A deeper analysis of the signaling processes indicates that the NO-cGMP pathway is involved in cell proliferation arrest and death. In fact, these events are completely reversed by L-NAME, a specific NO synthase inhibitor, indicating that NO, rather than the depletion of GSH per se, is the primary mediator of cell damage. In addition, the guanylate cyclase (GC) inhibitor LY83583 is able to completely block activation of ERK1/2 and counteract BSO toxicity. In cortical neurons, NMDA (N-methyl-D-aspartic acid) treatment results in GSH decrease and BSO-mediated NO cytotoxicity is enhanced by either epidermal growth factor (EGF) or NMDA. These findings support the idea that GSH might represent the most important buffer of NO toxicity in neuronal cells, and indicate that the disruption of cellular redox buffering controlled by GSH makes neuronal cells susceptible to endogenous physiological flux of NO.
Microtubules and CESA tracks at the inner epidermal wall align independently of those on the outer wall of light-grownArabidopsishypocotyls
Authors: Chan Jordi , Eder Magdalena , Crowell Elizabeth Faris , Hampson Janet , Calder Grant , Lloyd Clive
Published: March 2011

Microtubules are classically described as being transverse, which is perpendicular to the direction of cell elongation. However, fixation studies have indicated that microtubules can be variably aligned across the epidermis of elongating shoots. In addition, microtubules are reported to have different orientations on inner and outer epidermal surfaces, undermining the idea of hoop-reinforcement. Here, long-term movies of Arabidopsis seedlings expressing GFP–TUA6 allowed microtubule alignment to be directly correlated with the rate of elongation within individual growing cells. We also investigated whether microtubule alignment at the inner or the outer epidermal wall better reflected the growth rate. Movies confirmed that transverse microtubules form on the inner wall throughout elongation, but orientation of microtubules is variable at the outer wall, where they tend to become transverse only during episodes of accelerated growth. Because this appears to contradict the concept that circumferential arrays of transverse microtubules or microfibrils are essential for cell elongation, we checked the organisation of cellulose synthase tracks using GFP–CESA3 and found a similar mismatch between trajectories on inner and outer epidermal surfaces. We conclude that microtubule alignment on the inner wall appears to be a more stable predictor of growth anisotropy, whereas outer-wall alignment is more sensitive to the elongation rate.
Mechanism of Heme Uptake by Heme Acquisition System A
Authors: Ozaki Shin-ichi , Nakahara Akira , Sato Takehiro
Published: March 2011

Heme acquisition system A (HasA), secreted by various gram-negative pathogens, uses a unique histidine–iron–tyrosine (His–Fe–Tyr) coordination to scavenge heme (i.e., protoporphyrin IX–Fe complex) as an iron source. In order to study heme uptake by HasA, we utilized axial ligand mutants and protoporphyrin IX. Our results suggest that the binding of heme in apoprotein is initiated by interactions between heme and hydrophobic residues in the heme pocket. Subsequently, the sequential coordination of Tyr-75 and His-32 with the iron appears to complete holoprotein formation.
Wittig Like Methylenation of Aldehydes in a Microflow System: Selective Methylenation by Differential of Plural Reactions
Authors: Takada Yoshiaki , Matsubara Seijiro
Published: March 2011

Methylenation of aldehydes with bis(iodozincio)methane was performed using a microflow system. Treatment of a dialdehyde with bis(iodozincio)methane in the system can divide two methylenation reactions and realize selective transformation.
Candida pelliculosa meningitis as an opportunistic infection in HIV: the first reported case
Authors: Ratcliffe L , Davies J , Anson J , Hales S , Beeching N J , Beadsworth M B J
Published: March 2011

We describe the first reported case of Candida pelliculosa meningitis in HIV infection. This case highlights the risk of uncommon opportunistic infections in association with the immunocompromised and the importance of autopsy as a diagnostic tool in HIV infection. We discuss the epidemiology, diagnosis and management of C. pelliculosa, a non-albicans species which is rarely associated with disease, and review current literature.
Men who have sex with men: estimating the size of at-risk populations in London primary care trusts
Authors: Ruf M , Delpech V , Osuagwu U , Brown A E , Robinson E , Chadborn T
Published: March 2011

The objective of this study was to estimate local at-risk populations of men who have sex with men (MSM) in London primary care trusts (PCTs) to inform the commissioning of targeted health interventions. Estimated population size and prevalence of diagnosed HIV in MSM in all of London were calculated using data from the British National Survey of Sexual Attitudes and Lifestyles (NATSAL), Greater London Authority population estimates and the annual survey of diagnosed MSM (Survey of Prevalent HIV Infections Diagnosed [SOPHID]). Estimated MSM population sizes at the PCT level were calculated using un-weighted and SOPHID-weighted methods and methods discussed. Four-fifths of MSM with diagnosed HIV infection in Greater London lived in inner London. Estimated population size of MSM 16–44 years in inner London was 66,000; estimated overall prevalence of diagnosed HIV infection among MSM was 9.5%. Our models show substantial variation at the PCT level between the two methods. Using the SOPHID-weighted method MSM account for up to 16% of the male population in some London PCTs, compared with as low as 3% in others. We provide a novel method of estimating at-risk MSM populations living in inner London PCTs indicating that proportions of MSM vary widely between PCTs. Significant proportions of MSM among the resident populations in several PCTs warrant inclusion of MSM health needs in core PCT prevention and service programming. In light of data source limitations further validation studies are needed.
Efavirenz-based combination antiretroviral therapy after peripartum single-dose nevirapine
Authors: Bolhaar M G , Karstaedt A S
Published: March 2011

Single-dose nevirapine (sdNVP) reduces mother-to-child HIV transmission, but induces NVP resistance and subsequent NVP-based combination antiretroviral therapy (cART) may fail. Some resistance mutations affect NVP more than efavirenz (EFV). We evaluated virological suppression of EFV-based cART in women after sdNVP. A retrospective analysis matched 107 women who had received sdNVP within the 24 months before cART (cases) with women who had never received sdNVP (controls). By total cohort (intention-to-continue treatment) at week 96, 65% of cases and 73% of controls had a viral load (VL) <400 copies/mL and 63% of cases and 64% of controls had VL <25 copies/mL. At weeks 48 and 96, women starting cART less than six months after sdNVP ( n = 20) had VL <400 copies/mL of 90% and 75%, respectively compared with 90% and 70%, respectively, for controls. Overall 172 (80%) women reached week 96. EFV-based cART, in field conditions, was effective for women after sdNVP, even within six months of sdNVP.
Prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection
Authors: Calza L , Masetti G , Piergentili B , Trapani F , Cascavilla A , Manfredi R , Colangeli V , Viale P
Published: March 2011

Metabolic complications of antiretroviral therapy in HIV-infected patients include insulin resistance, diabetes mellitus, dyslipidaemia and lipodystrophy syndrome. Metabolic syndrome is an aggregation of central obesity with glucose and lipid metabolism alterations that confers an increased risk of cardiovascular disease, which reproduces the antiretroviral-associated metabolic and morphological abnormalities. In this study, we report the prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection referred to our outpatients unit. The prevalence of diabetes mellitus and metabolic syndrome was 4.5% and 9.1%, respectively. A longer exposure to antiretroviral therapy and a diagnosis of lipodystrophy syndrome were significantly associated with both metabolic disturbances.
Completing the circle: follow-up screening of STD patients in three clinics of the United States Indian Health Service
Authors: Reilley B , Redd J T , Giberson S , Sunde S , Cullen T
Published: March 2011

We reviewed charts of newly diagnosed STD patients in three health facilities to determine the proportion who received follow-up STD screening. In a 12-month period, the three facilities had 140 STD cases. STD screening was not indicated for 50 (36%) patients. Among the 90 remaining STD patients, 29 (32%) were screened and 61 (68%) not screened. Among non-screened patients, 36% (22/61) were tested, but outside the time parameters allowed by the audit. The remaining 64% (39/61) received no screening at all, and represented clinical missed opportunities; in this group, nearly all (95%) had chlamydia but were not screened for HIV or syphilis. Linking chlamydia patients with a screen for HIV and syphilis using a clinical reminder in the facilities' electronic health record (EHR) or other tool, would eliminate 95% of the missed opportunities in this sample.
Leiomyosarcoma in an HIV-infected adult with renal and central nervous system involvement
Authors: Dhairyawan R , Aboud M
Published: March 2011

We describe a case of leiomyosarcoma in an HIV-infected adult with renal and central nervous system involvement and possibly the lungs.
European guideline for the management of genital herpes, 2010
Authors: Patel R , Alderson S , Geretti A , Nilsen A , Foley E , Lautenschlager S , Green J , van der Meijden W , Gomberg M , Moi H
Published: March 2011

This is the guideline for genital herpes simplex virus (HSV) management for the IUSTI/WHO Europe, 2010. They describe the epidemiology, diagnosis, clinical features, treatment and prevention of genital HSV infection. They include details on the management of HSV in pregnancy, those who are immunocompromised and the clinical investigation and management of suspected HSV-resistant disease.
Nuclear and cytoplasmic localization of neural stem cell microRNAs
Authors: Jeffries Clark D. , Fried Howard M. , Perkins Diana O.
Published: March 2011

Although generally regarded as functional in the cytoplasm, a number of microRNAs (miRNAs) have been found in the nucleus, possibly with a role in gene regulation. Here we report that, in fact, a substantial fraction of all human miRNAs are present in the nucleus of neural stem cells. Further, subsets of these miRNAs display consistently higher standardized rank in the nucleus than in the cytoplasm of these cells, as identified with an RT-qPCR technology and confirmed by microarray analysis. Likewise, other miRNAs display higher cytoplasmic standardized ranks. Three samples were partitioned into nuclear and cytoplasmic fractions in six assays for 373 miRNAs. From the 100 most highly expressed miRNAs, standard scores of nuclear and cytoplasmic concentrations were determined. Among those, 21 miRNAs had all three nuclear standard scores higher than all three cytoplasmic scores; likewise, 31 miRNAs had consistently higher cytoplasmic scores. Random concentrations would result in only five in each set. Remarkably, if one miRNA has a high standard score in a compartment, then other miRNAs having the same 5′ seeds and certain similar 3′ end patterns are also highly scored in the same way. That is, in addition to the seed sequence, 3′ sequence similarity criteria identify families of mature miRNAs with consistently high nuclear or cytoplasmic expression.
Squamous cell carcinoma of the vagina and cervix in sheep — Case report
Authors: Ferrer Luis , Lacasta Delia , Ramos Juan , Jalón Jose , Ruiz De Arcaute Marta , Conde Tomás
Published: March 2011

This report describes the clinical and histopathological characteristics of a squamous cell carcinoma infiltrating the cervix and the vaginal wall, producing reproductive symptoms and subnormal fertility in an adult ewe. Necropsy showed a large (15-cm-long) neoplastic mass infiltrating the vaginal wall and the cervix. Histopathological examination revealed atypical squamous epithelial cords invading the basal membrane and dermis, round anaplastic cells, focal areas of necrosis, keratinisation of isolated cells, and pronounced infiltration by mononuclear cells around the cords. No squamous cell carcinoma of such localisation has been reported from sheep before. In humans, this tumour is the most common gynaecological malignancy in the world.
Presence of antibodies against rabies in wild boars
Authors: Vengušt Gorazd , Hostnik Peter , Cerovšek Mojca , Cilenšek Polona , Malovrh Tadej
Published: March 2011

Serum samples of 746 shot wild boars collected throughout Slovenia during the hunting season of 2005/2006 were examined for the presence of antibodies against rabies virus: 541 samples were collected in areas subjected to yearly antirabies vaccination, and 205 samples were collected in areas where preventive antirabies vaccination was not practised. Using a modified enzyme-linked immunosorbent assay (ELISA), in 209 out of 746 sera (28%) the levels of antibodies against rabies virus were higher than 0.5 IU/ml and deemed positive. A total of 173/541 (32%) and 36/205 (18%) samples were positive in the vaccinated and nonvaccinated areas, respectively. Further analysis of 191 out of the 746 samples using the fluorescent antibody virus neutralisation (FAVN) test revealed the presence of antibodies against rabies virus in 122/191 (64%) samples. This is the first extended research reporting that antibodies against rabies virus that originate from preventive oral vaccination targeting the fox population are present in wild boar.
Sound recording and digital phonocardiography of cardiac murmurs in dogs by using a sensor-based electronic stethoscope
Authors: Vörös Károly , Nolte Ingo , Hungerbühler Stephan , Reiczigel Jenő , Ehlers Jan , Tater Guy , Mischke Reinhard , Zimmering Tanja , Schneider Matthias
Published: March 2011

The goals of this study were to present a technique of digitalised sound recordings and phonocardiograms (dPCGs), and to analyse its diagnostic capabilities. Heart sounds of 20 dogs were auscultated in vivo (on-line) and recorded with dPCGs by two authors using a Welch Allyn Meditron Stethoscope System. Sound recordings were auscultated off-line and blindly by four different observers having various auscultatory experiences, then listened to while viewing dPCGs. The results were compared to echocardiographic diagnoses. There was a significant agreement (p < 0.001) between on-line and off-line auscultatory findings regarding the four observers, ranging from 45% to 75% (weighted kappa values: 0.72 to 0.87). The best agreement was achieved by Observer 1 having the highest experience. Significant differences (p < 0.05) were found between Observer 1 and Observer 4 (with the lowest experience) in judging the quality of the murmurs during the off-line and blind auscultation. However, there were only minimal differences (95% to 100% agreements) in dPCG analyses among the four observers regarding intensity and quality of the murmurs while simultaneously listening to and viewing the dPCGs. Significant correlations were found between the traditional ‘0 to 6 scale’ and a new ‘0 to 3 scale’ murmur intensity gradings by all observers (correlation coefficients 0.640 to 0.908; p < 0.01 to p < 0.001). Analysis of dPCGs might be a valuable, additional tool helping with the diagnosis of canine cardiac murmurs, especially for those with less cardiological experience.
Optimising magnetic resonance image quality of the ear in healthy dogs
Authors: Wolf Davina , Lüpke Matthias , Wefstaedt Patrick , Klopmann Thilo , Nolte Ingo , Seifert Hermann
Published: March 2011

The aim of this study was to develop an examination protocol for magnetic resonance imaging, in order to display diagnostically important information of the canine middle and inner ear. To ensure that this protocol could also be used as a basis for determining pathological changes, the anatomical structures of the ear were presented in detail. To minimise stress through anaesthesia in live animals, preliminary examinations were carried out on four dog cadavers. During these initial examinations, three-dimensional (3D) sequences proved to be superior to two-dimensional ones. Therefore, only 3D sequences were applied for the main examinations performed on six clinically healthy Beagles. The anonymised MR images were rated by three experienced reviewers using a five-point scale. The most valuable sequence was a T2-weighted CISS sequence (TR = 16.7 ms, TE = 8.08 ms). This sequence proved to be most suitable for illustrating the inner ear structures and enabled good tissue contrasts. The sequence ranked second best was also a T2-weighted DESS sequence (TR = 19 ms, TE = 6 ms), allowing the imaging of the tympanic cavity and enabling 3D reconstruction due to its isotropic voxels. Due to low contrast and strong noise, the other sequences (TSE, FISP, MP RAGE) were not suitable for anatomical illustration of the middle and inner ear.
Effect of atorvastatin in a case of feline multicentric lymphoma — Case report
Authors: Hermo Guillermo , Farina Hernán , Alonso Daniel , Gomez Daniel
Published: March 2011

A case of feline multicentric lymphoma is reported in an 8-year-old male cat weighing 4.7 kg. At the time of the clinical consultation the animal presented weight loss, anorexia and generalised lymphadenomegaly. After careful clinical observation and a detailed laboratory workup, the diagnosis of small cleaved cell lymphoma was established. It was classified as a stage III b multicentric lymphoma. Chemotherapy was initiated according to a classical COP protocol to which atorvastatin was added. After 34 months, the cat continues to enjoy an excellent quality of life with no clinical or haematological signs of lymphoma. This is the first report in clinical veterinary medicine about a new effective adjuvant therapy in feline multicentric lymphoma. Further studies are needed to confirm that the addition of atorvastatin can provide a regular, safe and improved treatment in feline lymphoma cases.
Claudin-7-positive synchronous spontaneous intrahepatic cholangiocarcinoma, adenocarcinoma and adenomas of the gallbladder in a Bearded dragon (Pogona vitticeps)
Authors: Jakab Csaba , Rusvai Miklós , Szabó Zoltán , Gálfi Péter , Marosán Miklós , Kulka Janina , Gál János
Published: March 2011

In this study, synchronous spontaneous, independent liver and gallbladder tumours were detected in a Bearded dragon (Pogona vitticeps). The multiple tumours consisted of intrahepatic cholangiocarcinoma as well as in situ adenocarcinoma and two adenomas of the gallbladder. The biliary epithelial cells and the cholangiocarcinoma showed membranous cross-immunoreactivity for claudin-7. The gallbladder epithelial cells, its adenoma and adenocarcinoma showed basolateral cross-reactivity for claudin-7. We think that the humanised anti-claudin-7 antibody is a good marker for the detection of different primary cholangiocellular and gallbladder tumours in Bearded dragons. The cholangiocytes, the cholangiocarcinoma, the endothelial cells of the liver and the epithelial cells and gallbladder tumours all showed claudin-5 cross-reactivity. The humanised anti-cytokeratin AE1–AE3 antibody showed cross-reactivity in the biliary epithelial cells, cholangiocarcinoma cells, epithelial cells and tumour cells of the gallbladder. It seems that this humanised antibody is a useful epithelial marker for the different neoplastic lesions of epithelial cells in reptiles. The humanised anti-α-smooth muscle actin (α-SMA) antibody showed intense cross-reactivity in the smooth muscle cells of the hepatic vessels and in the muscle layer of the gallbladder. The portal myofibroblasts, the endothelial cells of the sinusoids and the stromal cells of the cholangiocarcinoma and gallbladder tumours were positive for α-SMA. The antibovine anti-vimentin and humanised anti-Ki-67 antibodies did not show crossreactivity in the different samples from the Bearded dragon.
Malignant insulinoma
Authors: Tóth Miklós , Szücs Nikolette , Jakab Zsuzsa , Doros Attila , Nemes Zoltán , Rácz Károly
Published: March 2011

Authors present the history of a 56-year-old man who was evaluated for recurrent epigastrial pain. Clinical investigation revealed a 4-cm tumor in the head of the pancreas and a solitary liver metastasis. Pathological examination of the surgically excised pancreatic tumor indicated a moderately differentiated neuroendocrine carcinoma and Ki-67 labeling index revealed moderate proliferative activity. Despite short-term chemotherapy combined with interferon and somatostatin analogue administration, the metastatic disease rapidly progressed. Octreotide scintigraphy disclosed abundant expression of somatostatin receptors both on primary tumor and hepatic metastases. 90Yttrium-DOTATOC treatment was performed in three sessions within 9 months (3×200 mCi) with a mixed therapeutic response. Endocrine symptoms were not observed during the first 33 months of the disease. 34 months after the initial diagnosis of the neoplastic disease, imaging studies and chromogranin A measurement revealed rapidly progressing disease and the patient developed frequent episodes of hypoglycemic attacks. Serum insulin and C-peptide measurements confirmed insulin oversecretion. Continuous administration of somatostatin analogue was supplemented with diazoxide, but the latter therapy was not tolerated because of severe water retention. The high dose oral carbohydrate intake was supplemented with continuous glucose infusion. As a rescue procedure, repeated liver chemoembolisation was performed, which resulted only in a short-term effect. The autopsy and the immunohistochemical investigations confirmed the diagnosis of insulin-producing, metastatic neuroendocrine carcinoma. Orv. Hetil., 2011, 152, 398–402.