bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersal limitation and spatial scale affect model based projections of Pinus uncinata response to climate change in the Pyrenees
Authors: Martínez Isabel , González‐Taboada Fernando , Wiegand Thorsten , Camarero Jesus Julio , Gutiérrez Emilia
Published: February 2012

Species Distribution Models (SDMs) were employed to assess the potential impact of climate change on the distribution of Pinus uncinata in the Pyrenees, where it is the dominant tree species in subalpine forest and alpine tree lines. Predicting forest response to climate change is a challenging task in mountain regions but also a conservation priority. We examined the potential impact of spatial scale on SDM projections by conducting all analyses at four spatial resolutions. We further examined the potential effect of dispersal constraints by applying a threshold distance of maximal advancement derived from a spatially explicit, individual‐based simulation model of tree line dynamics. Under current conditions, SDMs including climatic factors related to stress or growth limitation performed best. These models were then employed to project P. uncinata distribution under two emission scenarios, using data generated from several regional climate models. At the end of this century, P. uncinata is expected to migrate northward and upward, occupying habitat currently inhabited by alpine plant species. However, consideration of dispersal limitation and/or changing the spatial resolution of the analysis modified the assessment of climate change impact on mountain ecosystems, especially in the case of estimates of colonization and extinction at the regional scale. Our study highlights the need to improve the characterization of biological processes within SDMs, as well as to consider simultaneously different scales when assessing potential habitat loss under future climate conditions.
Phylogeography of a species complex of lowland Neotropical rain forest trees (Carapa, Meliaceae)
Authors: Scotti‐Saintagne Caroline , Dick Christopher W. , Caron Henri , Vendramin Giovanni G. , Guichoux Erwan , Buonamici Anna , Duret Caroline , Sire Pierre , Valencia Renato , Lemes Maristerra R. , Gribel Rogério , Scotti Ivan
Published: February 2012

Aim  Many tropical tree species have poorly delimited taxonomic boundaries and contain undescribed or cryptic species. We examined the genetic structure of a species complex in the tree genus Carapa in the Neotropics in order to evaluate age, geographic patterns of diversity and evolutionary relationships, and to quantify levels of introgression among currently recognized species.

Location  Lowland moist forests in the Guiana Shield, the Central and Western Amazon Basin, Chocó and Central America.

Methods  Genetic structure was analysed using seven nuclear simple sequence repeats (nuSSR), five chloroplast SSRs (cpSSR), and two chloroplast DNA (cpDNA) intergenic sequences (trnH–psbA and trnC–ycf6). Bayesian clustering analysis of the SSR data was used to infer population genetic structure and to assign 324 samples to their most likely genetic cluster. Bayesian coalescence analyses were performed on the two cpDNA markers to estimate evolutionary relationships and divergence times.

Results  Two genetic clusters (nu_guianensis and nu_surinamensis) were detected, which correspond to the Neotropical species C. guianensis (sensu latu) and C. surinamensis. Fourteen cpDNA haplotypes clustered into six haplogroups distributed between the two nuclear genetic clusters. Divergence between the haplogroups was initiated in the Miocene, with some haplotype structure evolving as recently as the Pleistocene. The absence of complete lineage sorting between the nuclear and chloroplast genomes and the presence of hybrid individuals suggest that interspecific reproductive barriers are incomplete. NuSSR diversity was highest in C. guianensis and, within C. guianensis, cpDNA diversity was highest in the Central and Western Amazon Basin. Regional genetic differentiation was strong but did not conform to an isolation‐by‐distance process or exhibit a phylogeographical signal.

Main conclusions  The biogeographical history of Neotropical Carapa appears to have been influenced by events that took place during the Neogene. Our results point to an Amazonian centre of origin and diversification of Neotropical Carapa, with subsequent migration to the Pacific coast of South America and Central America. Gene flow apparently occurs among species, and introgression events are supported by inconsistencies between chloroplast and nuclear lineage sorting. The absence of phylogeographical structure may be a result of the ineffectiveness of geographical barriers among populations and of reproductive isolation mechanisms among incipient and cryptic species in this species complex.
Hsp33 confers bleach resistance by protecting elongation factor Tu against oxidative degradation in Vibrio cholerae
Authors: Wholey Wei‐Yun , Jakob Ursula
Published: February 2012

The redox‐regulated chaperone Hsp33 protects bacteria specifically against stress conditions that cause oxidative protein unfolding, such as treatment with bleach or exposure to peroxide at elevated temperatures. To gain insight into the mechanism by which expression of Hsp33 confers resistance to oxidative protein unfolding conditions, we made use of Vibrio cholerae strain O395 lacking the Hsp33 gene hslO. We found that this strain, which is exquisitely bleach‐sensitive, displays a temperature‐sensitive (ts) phenotype during aerobic growth, implying that V. cholerae suffers from oxidative heat stress when cultivated at 43°C. We utilized this phenotype to select for Escherichia coli genes that rescue the ts phenotype of V. cholerae ΔhslO when overexpressed. We discovered that expression of a single protein, the elongation factor EF‐Tu, was sufficient to rescue both the ts and bleach‐sensitive phenotypes of V. cholerae ΔhslO. In vivo studies revealed that V. cholerae EF‐Tu is highly sensitive to oxidative protein degradation in the absence of Hsp33, indicating that EF‐Tu is a vital chaperone substrate of Hsp33 in V. cholerae. These results suggest an ‘essential client protein’ model for Hsp33's chaperone action in Vibrio in which stabilization of a single oxidative stress‐sensitive protein is sufficient to enhance the oxidative stress resistance of the whole organism.
Aerial development in Streptomyces coelicolor requires sortase activity
Authors: Duong Andrew , Capstick David S. , Di Berardo Christina , Findlay Kim C. , Hesketh Andrew , Hong Hee‐Jeon , Elliot Marie A.
Published: February 2012

Streptomyces coelicolor is a multicellular bacterium whose life cycle encompasses three differentiated states: vegetative hyphae, aerial hyphae and spores. Among the factors required for aerial development are the ‘chaplins’, a family of eight secreted proteins that coat the surface of aerial hyphae. Three chaplins (the ‘long’ chaplins, ChpA, B and C) possess an LAXTG‐containing C‐terminal sorting signal and are predicted sortase substrates. The five remaining ‘short’ chaplins are presumed to be associated with the cell surface through interactions with the long chaplins. We show here that two sortase enzymes, SrtE1 and SrtE2, cleave LAXTG‐containing peptides at two distinct positions in vitro, and are required for cell wall anchoring of ChpC in vivo. srtE1/E2 double mutants are delayed in aerial hyphae formation, do not sporulate and fail to display all short chaplins on their aerial surfaces. Surprisingly, these mutant characteristics were not shared by a long chaplin mutant, which exhibited only modest delays in aerial development, leading us to revise the current model of chaplin‐mediated aerial development. The sortase mutant phenotype, instead, appears to stem from an inability to transcribe aerial hyphae‐specific genes, whose products have diverse functions. This suggests that sortase activity triggers an important, and previously unknown, developmental checkpoint.
Expression of the RNA recognition motif protein RBP10 promotes a bloodstream‐form transcript pattern in Trypanosoma brucei
Authors: Wurst Martin , Seliger Beate , Jha Bhaskar Anand , Klein Cornelia , Queiroz Rafael , Clayton Christine
Published: February 2012

When Trypanosoma brucei differentiates from the bloodstream form to the procyclic form, there are decreases in the levels of many mRNAs encoding proteins required for the glycolytic pathway, and the mRNA encoding the RNA recognition motif protein RBP10 decreases in parallel. We show that RBP10 is a cytoplasmic protein that is specific to bloodstream‐form trypanosomes, where it is essential. Depletion of RBP10 caused decreases in many bloodstream‐form‐specific mRNAs, with increases in mRNAs associated with the early stages of differentiation. The changes were similar to, but more extensive than, those caused by glucose deprivation. Conversely, forced RBP10 expression in procyclics induced a switch towards bloodstream‐form mRNA expression patterns, with concomitant growth inhibition. Forced expression of RBP10 prevented differentiation of bloodstream forms in response to cis‐aconitate, but did not prevent expression of key differentiation markers in response to glucose deprivation. RBP10 was not associated with heavy polysomes, showed no detectable in vivo binding to RNA, and was not stably associated with other proteins. Tethering of RBP10 to a reporter mRNA inhibited translation, and halved the abundance of the bound mRNA. We suggest that RBP10 may prevent the expression of regulatory proteins that are specific to the procyclic form.
Ligand and antagonist driven regulation of the Vibrio cholerae quorum‐sensing receptor CqsS
Authors: Wei Yunzhou , Ng Wai‐Leung , Cong Jianping , Bassler Bonnie L.
Published: February 2012

Quorum sensing, a bacterial cell–cell communication process, controls biofilm formation and virulence factor production in Vibrio cholerae, a human pathogen that causes the disease cholera. The major V. cholerae autoinducer is (S)‐3‐hydroxytridecan‐4‐one (CAI‐1). A membrane bound two‐component sensor histidine kinase called CqsS detects CAI‐1, and the CqsS → LuxU → LuxO phosphorelay cascade transduces the information encoded in CAI‐1 into the cell. Because the CAI‐1 ligand is known and because the signalling circuit is simple, consisting of only three proteins, this system is ideal for analysing ligand regulation of a sensor histidine kinase. Here we reconstitute the CqsS → LuxU → LuxO phosphorylation cascade in vitro. We find that CAI‐1 inhibits the initial auto‐phosphorylation of CqsS whereas subsequent phosphotransfer steps and CqsS phosphatase activity are not CAI‐1‐controlled. CAI‐1 binding to CqsS causes a conformational change that renders His194 in CqsS inaccessible to the CqsS catalytic domain. CqsS mutants with altered ligand detection specificities are faithfully controlled by their corresponding modified ligands in vitro. Likewise, pairing of agonists and antagonists allows in vitro assessment of their opposing activities. Our data are consistent with a two‐state model for ligand control of histidine kinases.
Role of Lactobacillus acidophilus loaded floating beads in chronic fatigue syndrome: behavioral and biochemical evidences
Authors: Singh P. K. , Chopra K. , Kuhad A. , Kaur I. P.
Published: February 2012

Background  In recent years the interface between neuropsychiatry and gastroenterology has converged in to a new discipline referred to as enteric neuroscience. Implications of brain–gut communication in the pathogenesis of psychiatric disorders indicate a possible role of suitably packaged/delivered probiotics as newer therapeutic options. In the present study probable role of per‐oral administration of free Lactobacillus acidophilus (LAB) and LAB loaded alginate beads in attenuation of the symptoms associated with chronic fatigue syndrome (CFS) were evaluated.

Methods  Chronic fatigue syndrome following physical fatigue was induced in rats by forcing them to swim (forced swim test; FST) in water till exhaustion, after weighing them down with 10% their body weight, daily for 28 days. Immobility (I) and postswim fatigue time (PSF) were taken as suitable markers. Free LAB and LAB loaded floating beads (FBs) were administered, from 21 to 28 days.

Key Results  Immobility and PSF were found to increase considerably in FST rats (665 ± 22 s and 196 ± 6 s) as compared with the naïve (32 ± 7 s and 22 ± 2 s) at 20 days, establishing severe fatigue like behavior. FST control group exhibited significant (P < 0.05) hypertrophy of spleen, hypotrophy of thymus, and increased oxido‐nitrosative stress in brain and tumor necrosis factor‐α (TNF‐α) levels in serum. Treatment with LAB and LAB FBs significantly decreased I and PSF and attenuated (P < 0.05) oxido‐nitrosative stress and TNF‐α levels. Spleen and thymus were also restored to their original size in this group.

Conclusions & Inferences  The findings suggest a valuable therapeutic role of LAB especially when incorporated into alginate beads for the treatment of CFS.
Assessing the impact of deliberative processes on the views of participants: is it ‘in one ear and out the other’?
Authors: Stafinski Tania , Menon Devidas , Yasui Yutaka
Published: February 2012

Background  Interest in citizens’ juries for eliciting the views of the public to inform coverage decisions on new health technologies has grown. However, evaluative information, particularly regarding their short‐ and/or longer‐term impact on participants’ views is limited. As citizens’ juries can be resource intensive, such information is required to make ‘evidence‐based’ decisions about their use.

Objectives  To assess the impact of citizens’ juries on participants’ preferences for the distribution of health care across populations over time.

Setting and participants  Two citizens’ juries, involving a different representative sample of the public, were held. Participants completed identical questionnaires before (T1), directly after (T2) and 6 weeks following the jury (T3). Questionnaires comprised rating, ranking and choice‐based questions related to four characteristics of competing patient populations (age, current health, life expectancy without treatment and health gain resulting from an intervention). Semi‐structured telephone interviews were also conducted to explore the impact of the jury on participants’ distributive preferences. Changes in responses to the self‐administered survey over the three time points were assessed quantitatively, while interview questions were analysed using qualitative techniques.

Results  No significant differences in responses to rating questions were observed. Pre/post‐jury changes in the rankings of two factors were statistically significant in one of the juries. However, in both juries, T1–T2 changes in responses to several of the choice‐based questions reached statistical significance. The number was lower between T2 and T3, suggesting that jurors retained their views. According to findings from the interviews, jurors’ views changed or were clarified through participation in the jury.

Conclusions  There appears to be evidence suggesting that the views of individuals who participate in citizens’ juries change as a result of the experience, and those ‘informed’ views are sustained.
Genetic variations in loci relevant to natural killer cell function are affected by ethnicity but are generally not correlated with susceptibility to HIV‐1
Authors: Aghafar M. Z. K. A. , Witt C. , Kamarulzaman A. , Ismail R. , Lederman M. M. , Rodriguez B. , Senitzer D. , Lee S. , Price P.
Published: February 2012

Polymorphisms in cell surface receptors of natural killer cells and their ligands on target cells can affect susceptibility to viral infections including human immunodeficiency virus (HIV)‐1. We found that the carriage of the human leukocyte antigen (HLA)‐G minus 14‐bp polymorphism, LILRB1 single nucleotide polymorphism rs1061680, and activating and inhibitory killer immunoglobulin‐like receptors (KIRs) were different when data were compared between Caucasian, African Americans and Asian populations. However, carriage was similar when HIV‐1 patients were compared with control donors, with the exception of the African American cohort.
Phenotypic and genetic divergence among harbour porpoise populations associated with habitat regions in the North Sea and adjacent seas
Authors: DE LUNA C. J. , GOODMAN S. J. , THATCHER O. , JEPSON P. D. , ANDERSEN L. , TOLLEY K. , HOELZEL A. R.
Published: February 2012

Abstract Determining the mechanisms that generate population structure is essential to the understanding of speciation and the evolution of biodiversity. Here, we investigate a geographical range that transects two habitat gradients, the North Sea to North Atlantic transition, and the temperate to subpolar regions. We studied the harbour porpoise (Phocoena phocoena), a small odontocete inhabiting both subpolar and temperate waters. To assess differentiation among putative populations, we measured morphological variation at cranial traits (N = 462 individuals) and variation at eight microsatellite loci for 338 of the same individuals from Norwegian, British and Danish waters. Significant morphological differentiation reflected the size of the buccal cavity. Porpoises forage in relatively shallow waters preying mainly on benthic species in British and Danish waters, and on mesopelagic and pelagic fish off the coast of Norway. We suggest that the observed differentiation may be explained by resource specialization and either adaptation or developmental responses to different local habitats.
Hsp70 protein levels and thermotolerance in Drosophila subobscura: a reassessment of the thermal co‐adaptation hypothesis
Authors: CALABRIA G. , DOLGOVA O. , REGO C. , CASTAÑEDA L. E. , REZENDE E. L. , BALANYÀ J. , PASCUAL M. , SØRENSEN J. G. , LOESCHCKE V. , SANTOS M.
Published: February 2012

Theory predicts that geographic variation in traits and genes associated with climatic adaptation may be initially driven by the correlated evolution of thermal preference and thermal sensitivity. This assumes that an organism’s preferred body temperature corresponds with the thermal optimum in which performance is maximized; hence, shifts in thermal preferences affect the subsequent evolution of thermal‐related traits. Drosophila subobscura evolved worldwide latitudinal clines in several traits including chromosome inversion frequencies, with some polymorphic inversions being apparently associated with thermal preference and thermal tolerance. Here we show that flies carrying the warm‐climate chromosome arrangement O3+4 have higher basal protein levels of Hsp70 than their cold‐climate Ost counterparts, but this difference disappears after heat hardening. O3+4 carriers are also more heat tolerant, although it is difficult to conclude from our results that this is causally linked to their higher basal levels of Hsp70. The observed patterns are consistent with the thermal co‐adaptation hypothesis and suggest that the interplay between behaviour and physiology underlies latitudinal and seasonal shifts in inversion frequencies.
Embryonic and Fetal Development in – Pigmy Rice Rat – Oligoryzomys sp. (Rodentia, Sigmodontinae) and its Significance for Being a new Experimental Model
Authors: Favaron P. O. , Rodrigues M. N. , Oliveira M. F. , Biasi C. M. , Miglino M. A.
Published: February 2012

Oligoryzomys (Cricetidae, Sigmodontinae) is a common rodent genus from South America that includes a couple of very similar species. Related species have been used as experimental model for understanding several diseases for which these species are reservoirs. In order to provide a better understanding of the embryological aspects of this group, herein we showed data on the embryonic and fetal development in Oligoryzomys sp. Eight specimens of different stages of gestation were obtained from the Collection of the Zoology Museum of University of Sao Paulo, Brazil. Gestational ages were estimated by crown‐rump‐length according to Evans and Sack (1973). To address our analysis after examining the gross morphology, tissues from several organs were processed for light and scanning electron microscopy. Morphological data on the systems (nervous system, cardiorespiratory system, intestinal tract and urogenital system) were described in detail. Finally, the findings were compared with what is known about embryological aspects in other rodent species in order to establish similarities and differences during the organogenesis in different species.
Aripiprazole may be free from tachyphylaxis: Preliminary findings
Authors: Goto Shinjiro , Terao Takeshi , Tomita Masaru , Uchimura Naohisa
Published: February 2012

Loss of antipsychotic efficacy (tachyphylaxis), possibly linked to an increase in D2 receptor number and sensitivity, is a significant impediment to treatment in chronic schizophrenia patients. Animal studies, however, suggest that aripiprazole may be free from tachyphylaxis. The aim of the present study was to investigate this hypothesis. In this preliminary study, aripiprazole‐treated patients were retrospectively investigated for the presence or absence of tachyphylaxis. Clinical Global Impression‐Improvement (CGI‐I) scores did not significantly change and there was no significant association of CGI scores with fixed dose duration. This suggests that aripiprazole may be free from tachyphylaxis.
Right hemispheric dominance and interhemispheric cooperation in gaze‐triggered reflexive shift of attention
Authors: Okada Takashi , Sato Wataru , Kubota Yasutaka , Toichi Motomi , Murai Toshiya
Published: February 2012

Aims:  The neural substrate for the processing of gaze remains unknown. The aim of the present study was to clarify which hemisphere dominantly processes and whether bilateral hemispheres cooperate with each other in gaze‐triggered reflexive shift of attention.

Methods:  Twenty‐eight normal subjects were tested. The non‐predictive gaze cues were presented either in unilateral or bilateral visual fields. The subjects localized the target as soon as possible.

Results:  Reaction times (RT) were shorter when gaze‐cues were congruent toward than away from targets, whichever visual field they were presented in. RT were shorter in left than right visual field presentations. RT in mono‐directional bilateral presentations were shorter than both of those in left and right presentations. When bi‐directional bilateral cues were presented, RT were faster when valid cues were presented in the left than right visual fields.

Conclusion:  The right hemisphere appears to be dominant, and there is interhemispheric cooperation in gaze‐triggered reflexive shift of attention.
Identification and molecular phylogenetics of the cryptic species of the Gonipterus scutellatus complex (Coleoptera: Curculionidae: Gonipterini)
Authors: Mapondera Tendai S , Burgess Treena , Matsuki Mamoru , Oberprieler Rolf G
Published: February 2012

The Eucalyptus Weevil, generally referred to as Gonipterus scutellatus Gyllenhal, 1833 is a significant pest of Eucalyptus species in Africa, America, Europe and New Zealand. It has recently become a pest of Eucalyptus globulus plantations in Western Australia, despite the presence there of the mymarid egg‐parasitoid Anaphes nitens (Girault). Recent taxonomic study has indicated G. scutellatus to comprise a complex of cryptic species, obscuring the identity of the various pest populations of the weevil in the world. We examined (1) whether the apparent cryptic species identifiable on genital differences have a genetic basis; (2) the distribution of these species; and (3) the origin of the population in Western Australia. We studied specimens from across the distribution range of Eucalyptus Weevil in Australia and obtained sequences of three genes from them: cytochrome oxidase I mtDNA, elongation‐factor 1‐α nuclear DNA and 18s rDNA. The cladogram of COI haplotypes resolved 10 well supported clades fully corresponding with genital‐morphologically distinct species, eight of them constituting a monophyletic G. scutellatus complex. Only four of these species proved to be described, as G. balteatusLea, 1897G. platensis (Marelli, 1926), G. pulverulentusLea, 1897 and G. scutellatus Gyllenhal, 1833. The pest species in the world were found to be G. platensis (New Zealand, America, western Europe), G. pulverulentus (eastern South America) and an undescribed species (Africa, France, Italy). The population of G. platensis in Western Australia showed little genetic variation and is indicated to be a recent introduction from Tasmania. The discrimination of the cryptic species of the G. scutellatus complex enables improvements in the management of the pest species in terms of biological control and plantation practices. Our study highlights the critical importance of proper taxonomic studies underpinning biocontrol programs.
Neonates presenting with temperature symptoms: Role in the diagnosis of early onset sepsis
Authors: Hofer Nora , Müller Wilhelm , Resch Bernhard
Published: February 2012

Background:  In this study, we aimed to evaluate the role of fever, hypothermia, and temperature instability in term and preterm newborns during the first 3 days of life and to identify risk factors for early onset sepsis (EOS) among newborns presenting with these temperature symptoms.

Methods:  In this retrospective cohort study set in our level III neonatal intensive care unit, we included all newborns hospitalized within the first 24 h of life from 2004 to 2007.

Results:  Of 851 newborns, 127 presented with temperature symptoms during the first 3 days of life (15%): 69 had fever, 69 had hypothermia, and 55 had temperature instability (8%, 8%, and 6%, respectively). Of 127 newborns presenting with temperature symptoms, 14 had culture‐proven EOS/pneumonia (33% of all 42 newborns with culture‐proven EOS/pneumonia), 67 had clinical EOS (30% of all 209 newborns with clinical EOS) and 46 were EOS‐negative (8% of all 600 EOS‐negatives). Factors associated with culture‐proven EOS/pneumonia in newborns presenting with temperature symptoms were maternal fever (P= 0.009), chorioamnionitis (P < 0.001), antibiotic therapy of the mother (P= 0.04), poor skin color (P= 0.001) and syndrome of persistent fetal circulation (P= 0.01).

Conclusions:  Every seventh newborn hospitalized at our neonatal intensive care unit developed fever, hypothermia and/or temperature instability during the first 3 days of life. Two‐thirds of them had culture‐proven or clinical sepsis. Temperature symptoms were rarely observed in EOS‐negative newborns (8%) but despite low sensitivity, were highly specific for bacterial infection in preterm and term newborns.
Pilot randomized trial of a nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular oedema
Authors: Casson Robert J , Raymond Grant , Newland Henry S , Gilhotra Jagjit S , Gray Tim L
Published: February 2012

Abstract

Background:  To assess the efficacy of a new nanopulse laser, retinal regeneration therapy for the treatment of diabetic macular oedema.

Design:  Randomized, non‐inferiority, trial.

Participants:  20 eyes of 17 subjects in the retinal regeneration therapy group and 18 eyes of 14 subjects in the conventional group were analysed.

Methods:  The treatment group received retinal regeneration therapy laser, and the control group received photocoagulation.

Main Outcome Measures:  The primary outcome was the optical coherence tomography‐measured change in central retinal thickness at 6 months. A secondary outcome was the change in logarithm of minimum angle of resolution visual acuity at 6 months. Non‐inferiority required the one‐sided 95% confidence interval of the mean retinal thickness reduction after retinal regeneration therapy to be within 35 µm of the reduction after control laser.

Results:  When outliers were included in the dataset, the difference in retinal thickness reduction by analysis of covariance was 10.9 (standard deviation 17.6) mm in favour of the control laser. The difference between groups in retinal thickness reduction was 40.8 mm. If two extreme outliers were excluded, the difference was 5.6 (standard deviation 14.2) mm in favour of the retinal regeneration therapy laser, and the D optical coherence tomography was 18.5 mm. The visual acuity difference between groups was 0.059, meeting non‐inferiority requirements.

Conclusions:  Although retinal thickness reduction was not unambiguously non‐inferior, in the short‐term, retinal regeneration therapy approximates the clinical efficacy of conventional photocoagulation, stabilizing visual acuity and providing motivation for larger trials assessing retinal regeneration therapy.
Predictors of long‐term visual outcome after chemoreduction for management of intraocular retinoblastoma
Authors: Narang Subina , Mashayekhi Arman , Rudich Danielle , Shields Carol L
Published: February 2012

Abstract

Background:  To determine the predictors of long‐term visual outcome after chemoreduction for management of intraocular retinoblastoma.

Design:  Retrospective case series.

Participants:  One hundred and forty eyes of 96 new retinoblastoma patients.

Methods:  The clinical records were reviewed for demographical profile, tumour characteristics, treatment methods, treatment side effects and final visual outcome. Multivariate analysis was used to evaluate factors predictive of final visual acuity.

Main Outcome Measure:  The clinical data were analysed for main outcome measures of good vision (visual acuity ≥6/12) or ambulatory vision (visual acuity ≥6/60). The correlation among predictor variables was determined using Pearson's product moment correlation for continuous variables, and t‐test and analysis of variance test for categorical baseline variables.

Results:  Follow‐up ranged from 2 years to 14 years (median 75 months). The final mean logarithm of minimum angle of resolution visual acuity was 0.79. Ambulatory vision (≥6/60) was achieved in 100 of 140 (71%) eyes, and vision of ≥6/12 was seen in 52 eyes (37%). Extrafoveolar tumour and greater number of tumours in the eye were the only predictors of visual acuity ≥20/40. Greater number of tumours correlated with smaller mean basal tumour diameter. The mean basal tumour diameter was 9.8 mm in eyes with multiple tumours and 12.2 mm in eyes with single tumours (P = 0.03).

Conclusion:  Long‐term ambulatory vision (≥6/60) was achieved in the majority (71%) of retinoblastoma containing eyes not requiring enucleation after treatment with chemoreduction and adjunctive therapy. Absence of foveolar involvement and greater number of tumours were the predictor of long‐ term visual outcome of 6/12 or better.
Fluids of the ocular surface: concepts, functions and physics
Authors: Cher Ivan
Published: February 2012

Abstract

General adoption of the ocular surface (OS) concept has advanced the therapy of the external eye. Fresh physical findings have prompted new concepts; examples taken from each section of the text are: (i) ever‐present lipid sealant bridges the palpebral fissure capping the three‐dimensional ‘OS’ sac. The muco‐aqueous pool (MAP) is thus enclosed, secluded from atmosphere, evaporation mitigated. Hence, the OS is conceptually, a compartment. The term ‘dacruon’ (otherwise ‘tear film’) has been coined for the combined fluids of the OS, viz. lipid film and MAP. (ii) Investigative techniques of physics yield data on (say) surface tension and viscosity, and on functions such as anchorage of dacruon base to the varied mucosae of the OS, lubrication, renovation of intermarginal fluid layers as the eye opens after each blink, and refinement of optics and vision by the fluids attached to the cornea. (iii) Physical events in the opening eye produce the unique ‘black line’ phenomenon in which capillary force induces subsurface flows into thirsty menisci, bringing about parameniscal dark grooves, pupil‐ward of each meniscus. Attenuation of fluorescein in the shallowed fluid gaps behind each groove makes the dye appear unilluminated (‘black lines’) relative to adjacent full‐thickness MAP fluid glowing under cobalt‐blue illumination. Isolated from cornea by grooves and gaps, the meniscal fluid cannot pass freely over the cornea. It therefore streams through the menisci to nasolacrimal outflow.
Relationship between progression of visual field damage and choroidal thickness in eyes with normal‐tension glaucoma
Authors: Hirooka Kazuyuki , Fujiwara Atsushi , Shiragami Chieko , Baba Tetsuya , Shiraga Fumio
Published: February 2012

Abstract

Background:  To measure choroidal thickness in normal eyes and in patients with normal‐tension glaucoma using enhanced depth imaging optical coherence tomography and evaluate the association between choroidal thickness and progression of visual field damage.

Design:  Cross‐sectional comparative study.

Participants:  A total of 62 eyes of 62 normal subjects and 45 eyes of 45 normal‐tension glaucoma patients were examined.

Methods:  The choroid was measured at the fovea and 3 mm nasal and temporal from the fovea. In the separate study, both eyes of the patients with normal‐tension glaucoma were included in the analyses. Visual fields were measured with automated perimetry. Changes in mean deviation per year (dB/year), that is, mean deviation slope, were calculated.

Main Outcome Measures:  Difference in the choroidal thickness between the normal subjects and the patients with normal‐tension glaucoma. The relationship between mean deviation slope and the choroidal thickness in eyes with normal‐tension glaucoma was analysed.

Results:  Compared with normal subjects, the choroidal thickness was significantly thinner in eyes with normal‐tension glaucoma at 3 mm nasal from the fovea (P = 0.02). There was a significant correlation between the choroidal thickness at 3 mm nasal from the fovea and the mean deviation slope (Pearson's r = 0.413; P < 0.001).

Conclusion:  The decrease in the thickness of the choroid at 3 mm nasal from the fovea in eyes with normal‐tension glaucoma may be associated with progressive visual field loss. Thus, choroidal abnormalities may play a role in the pathogenesis of normal‐tension glaucoma.
Singapore Malay Eye Study: rationale and methodology of 6‐year follow‐up study (SiMES‐2)
Authors: Rosman Mohamad , Zheng Yingfeng , Wong Wanling , Lamoureux Ecosse , Saw Seang‐Mei , Tay Wan‐Ting , Wang Jie Jin , Mitchell Paul , Tai E‐Shyong , Wong Tien Y
Published: February 2012

Abstract

Background:  To describe the rationale and study design of a follow‐up epidemiological eye study among Singaporean Malay adults.

Design:  Follow‐up prospective population‐based study.

Participants:  Participants of the Singapore Malay Eye Study (SiMES‐1), which was conducted from August 2004 to June 2006.

Methods:  This is a follow‐up study of the 3280 participants who participated in the SiMES‐1 and are residing in Singapore. All participants of this follow‐up study will undergo various standardized validated questionnaires on socio‐demographics, quality of life and impact of visual impairment. Participants will undergo assessment of blood pressure, anthropometry, presenting and best corrected visual acuity, subjective refraction, ocular biometry, slit lamp and dilated eye examination, Goldmann tonometry, optic disc imaging, digital lens and retinal photography. Retinal tomography, retinal optical coherence topography and fundus autofluorescence will also be performed. Gonioscopy and visual fields examination will be performed on selected individuals.

Main Outcome Measures:  Incidence, risk factors and impact of visual impairment and major eye diseases.

Results:  A total of 3280 people who participated in the SiMES‐1 will be contacted and invited to participate in this follow‐up study. It is estimated that 12.8% of the participants will be deceased and there will be an 80% participation rate for the survivors of SiMES‐1 (approximately 2288 participants).

Conclusion:  SiMES‐2 will be one of the few follow‐up epidemiological eye studies among Asians and will determine the cumulative 6‐year incidence, progression, risk factors and impact of major eye diseases in Singaporean Malay adults.
Clinical signs of uveitis associated with latent tuberculosis
Authors: Ang Marcus , Hedayatfar Alireza , Zhang Rongli , Chee Soon‐Phaik
Published: February 2012

Abstract

Background:  To identify the clinical ocular signs of uveitis associated with latent tuberculosis.

Design:  Retrospective case‐control study.

Participants:  Consecutive patients from Singapore National Eye Centre Uveitis over 9 years. Sixty‐two patients with uveitis associated with latent tuberculosis were compared with 72 matched controls diagnosed with other known uveitides.

Methods:  Patients were categorized as: (A) predominantly anterior segment inflammation (anterior uveitides) and (B) predominantly posterior segment inflammation (intermediate, posterior or pan‐uveitides). The diagnostic performance of combining these clinical signs with investigations such as interferon‐gamma release assay positivity and chest X‐ray results suggestive of pulmonary tuberculosis was done using area under the receiver operator characteristic curve.

Main Outcome Measures:  Sensitivity, specificity and likelihood of association with tuberculosis of various clinical signs.

Results:  Extensive posterior synechiae and concomitant anterior scleritis in Group A; low‐grade anterior chamber activity, retinal phlebitis and severe vitritis in Group B were significantly associated with latent tuberculosis. Combining these clinical signs with a positive interferon‐gamma release assay and tuberculin skin test improved the diagnostic performance in both groups (area under the receiver operator characteristic curve for Group A = 0.779; Group B = 0.789).

Conclusion:  Patients with a combination of suggestive clinical signs with positive interferon‐gamma release assay and tuberculin skin test are more likely to be accurately diagnosed with uveitis associated with latent tuberculosis, which responds to anti‐tuberculosis therapy.
Perceived age of facial features is a significant diagnosis criterion for age‐related carotid atherosclerosis in Japanese subjects: J‐SHIPP study
Authors: Kido Miwako , Kohara Katsuhiko , Miyawaki Saori , Tabara Yasuharu , Igase Michiya , Miki Tetsuro
Published: February 2012

Aim:  Vascular aging is known to be a major determinant of life expectancy. Recently, perceived age was reported to be a better predictor for mortality than chronological age. Based on these findings, we investigated whether or not perceived age was related to atherosclerosis in a general population.

Methods:  The participants were 273 individuals aged ≥50 years who participated in the Skin‐doc in Anti‐Aging Doc program. Facial photos were taken under a shadowless lamp from three directions (antero‐posterior, and 60° right and left oblique projection) using a high‐resolution digital camera. Perceived age was assessed either by 19 professional nurses in the geriatric ward or using facial identification program software. Carotid intima‐media thickness (IMT), radial augmentation index (AI) and brachial‐ankle pulse wave velocity (baPWV) were measured as indices for atherosclerosis.

Results:  The perceived age difference (expressed as the difference between perceived age and chronological age), when estimated either by nurses or software, was significantly and negatively associated with chronological age. Subjects who were evaluated by nurses to be younger than their chronological age had significantly lower carotid IMT after adjustment for chronological age. Conversely, carotid IMT was an independent and negative determinant of looking young, as perceived by nurses. Similar observations were also made between perceived age using facial identification software and carotid IMT. Radial AI and baPWV were not associated with perceived age.

Conclusion:  These findings show that carotid atherosclerosis is related to perceived age. This association might underlie previous findings showing that perceived age predicts life expectancy. Geriatr Gerontol Int 2012; ••: ••–••.
3‐(2,4‐Dimethoxybenzylidene)‐anabaseine: A promising candidate drug for Alzheimer's disease?
Authors: Zawieja Philippe , Kornprobst Jean‐Michel , Métais Patrick
Published: February 2012

3‐(2,4‐Dimethoxybenzylidene)‐anabaseine is an analog of the paralytic alkaloid, anabaseine, from the ribbon worms Amphiporus sp., that shows numerous properties, in particular an agonist activity on alpha7 nicotinic acetylcholine receptors. This article reviews these properties and explains to what extent they could be valuable to control symptomatology and/or neurodegeneration in Alzheimer's disease. Geriatr Gerontol Int 2012; 12: 365–371.
Insulin use is not significantly predictive for prostate cancer mortality in diabetic patients: a 12‐year follow‐up study
Authors: Tseng Chin‐Hsiao
Published: February 2012

Study Type – Prognosis (inception cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

Even though a lower risk of prostate cancer has been reported in patients with diabetes, they may have a higher risk of cancer development involving the liver, pancreas, endometrium, colorectum, breast and bladder. Insulin may have mitogenic properties besides its metabolic function. However, whether exogenous insulin use for glycaemic control in diabetic patients could increase the risk of prostate cancer has rarely been studied.

This is the first prospective follow‐up study for up to 12 years to show that exogenous insulin use for glycaemic control in the diabetic patients is not significantly predictive for prostate cancer mortality.

OBJECTIVE

To evaluate whether insulin use in diabetic patients could be predictive for prostate cancer mortality.

PATIENTS AND METHODS

A total of 39 135 diabetic men aged ≥40 years from a nationally representative cohort were followed prospectively from 1995 to 2006 for prostate cancer mortality.

Cox proportional hazards models were used to estimate the hazard ratios for the following independent variables: age, diabetes type, diabetes duration, body mass index, smoking, insulin use and area of residence.

The models were created for patients aged ≥40 years and ≥65 years, separately; and before and after excluding patients with a duration between onset of diabetes and prostate cancer mortality <5 years.

RESULTS

A total of 105 diabetic men died of prostate cancer during follow‐up.

Age was the only significant risk factor.

Insulin use was associated with an insignificantly higher risk of prostate cancer mortality ranging from 24% to 49%.

When stratified by the duration of insulin use <5 and ≥5 years, a lack of significant association was also observed.

CONCLUSIONS

Insulin use in diabetic patients does not significantly predict the mortality from prostate cancer.

Further confirmation in other ethnicities is needed.
REEXAMINATION OF THE ETHICS OF PLACEBO USE IN CLINICAL PRACTICE
Authors: ASAI ATSUSHI , KADOOKA YASUHIRO
Published: February 2012

A placebo is a substance or intervention believed to be inactive, but is administered by the healthcare professional as if it was an active medication. Unlike standard treatments, clinical use of placebo usually involves deception and is therefore ethically problematic. Our attitudes toward the clinical use of placebo, which inevitably includes deception or withholding information, have a tremendous effect on our practice regarding truth‐telling and informed consent. A casual attitude towards it weakens the current practice based on shared decision‐making and mutual trust between patients and healthcare professionals. Issues concerning the clinical use of placebo are thus intimately related to patient‐provider relationships, the public's trust in medicine, and medical education. A review of recent survey studies suggests that the clinical use of placebo appears to be fairly well accepted among healthcare professionals and is common in clinical settings in various countries. However, we think that an ethical discussion is urgently needed because of its controversial nature. If judged to be ethically wrong, the practice should end. In the present paper, we discuss the ethicality of the clinical use of placebo with deception and argue against it, concluding that it is unethical and should be banned. We will show that most arguments in favor of the clinical use of placebo can be refuted and are therefore incorrect or weak. These arguments will be presented and examined individually. Finally, we will briefly consider issues relevant to the clinical use of placebo without deception.
MORAL FICTION OR MORAL FACT? THE DISTINCTION BETWEEN DOING AND ALLOWING IN MEDICAL ETHICS
Authors: HUDDLE THOMAS S.
Published: February 2012

Opponents of physician‐assisted suicide (PAS) maintain that physician withdrawal‐of‐life‐sustaining‐treatment cannot be morally equated to voluntary active euthanasia. PAS opponents generally distinguish these two kinds of act by positing a possible moral distinction between killing and allowing‐to‐die, ceteris paribus. While that distinction continues to be widely accepted in the public discourse, it has been more controversial among philosophers. Some ethicist PAS advocates are so certain that the distinction is invalid that they describe PAS opponents who hold to the distinction as in the grip of ‘moral fictions’. The author contends that such a diagnosis is too hasty. The possibility of a moral distinction between active euthanasia and allowing‐to‐die has not been closed off by the argumentative strategies employed by these PAS advocates, including the contrasting cases strategy and the assimilation of doing and allowing to a common sense notion of causation. The philosophical debate over the doing/allowing distinction remains inconclusive, but physicians and others who rely upon that distinction in thinking about the ethics of end‐of‐life care need not give up on it in response to these arguments.
DISPUTING THE ETHICS OF RESEARCH: THE CHALLENGE FROM BIOETHICS AND PATIENT ACTIVISM TO THE INTERPRETATION OF THE DECLARATION OF HELSINKI IN CLINICAL TRIALS
Authors: WOODS SIMON , MCCORMACK PAULINE
Published: February 2012

In this paper we argue that the consensus around normative standards for the ethics of research in clinical trials, strongly influenced by the Declaration of Helsinki, is perceived from various quarters as too conservative and potentially restrictive of research that is seen as urgent and necessary. We examine this problem from the perspective of various challengers who argue for alternative approaches to what ought or ought not to be permitted. Key themes within this analysis will examine these claims and argue they have implications for the interests of the research subject, research governance and regulation. Using our work with TREAT‐NMD, the neuromuscular clinical trials network, we posit that there is a place for advancing the discourse of moral rights and moral duties in the context of research, especially from the perspective of patients and their families, and for including the politics of patient activism and empowerment. At the same time we remain vigilant to the danger that the therapeutic misconception and other serious vulnerabilities for the patient population in clinical trials, are at risk of being overlooked.