bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management
Authors: Bacigaluppi S , Retta SF , Pileggi S , Fontanella M , Goitre L , Tassi L , La Camera A , Citterio A , Patrosso MC , Tredici G , Penco S
Published: April 2012

Bacigaluppi S, Retta SF, Pileggi S, Fontanella M, Goitre L, Tassi L, La Camera A, Citterio A, Patrosso MC, Tredici G, Penco S. Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management.

Cerebral cavernous malformations (CCMs) are a diffuse cerebrovascular disease affecting approximately 0.5% of the population. A CCM is characterized by abnormally enlarged and leaky capillaries arranged in mulberry‐like structures with no clear flow pattern. The lesion might predispose to seizures, focal neurological deficits or fatal intracerebral hemorrhage. However, a CCM can also remain neurologically silent. It might either occur sporadically or as an inherited disorder with incomplete penetrance and variable expressivity. Due to advances in imaging techniques, the incidence of CCM diagnoses are increasing, and the patient must be managed on a multidisciplinary basis: genetic counselling, treatment if needed, and follow‐up. Advances have been made using radiological and pathological correlates of CCM lesions adding to the accumulated knowledge of this disease, although management of these patients is very variable among centers. This review is aimed at providing an update in genetic and molecular insights of this condition. Included are implications for genetic counselling, and possible approaches to prevention and treatment that derive from the understanding of pathogenetic mechanisms.
Hyperlipidemia after allogeneic stem cell transplantation: prevalence, risk factors, and impact on prognosis
Authors: Kagoya Yuki , Seo Sachiko , Nannya Yasuhito , Kurokawa Mineo
Published: April 2012

Hyperlipidemia is one of the late complications after allogeneic stem cell transplantation (SCT). Although intrahepatic cholestasis caused by chronic graft‐versus‐host disease (GVHD) or calcineurin inhibitors has been considered as possible etiologies, its prevalence, risk factors, and impact on prognosis have not been investigated well. We performed a retrospective analysis of 194 patients who underwent allogeneic SCT between 1995 and 2008 in our institute and survived more than 100 d after SCT. Overall, 83 (42.8%) and 99 (50.8%) patients developed hypercholesterolemia (≥240 mg/dL) and hypertriglyceridemia (≥200 mg/dL), respectively. In multivariate analysis, the development of chronic GVHD (hazard ratio [HR] 2.04, p < 0.05) and steroid use (HR 2.24, p < 0.01) were independently associated with hypercholesterolemia, while administration of calcineurin inhibitors was not. As for the prognostic impact, multivariate analysis showed that the patients with hypercholesterolemia had a tendency of lower rate of relapse (HR: 0.44, p = 0.07). There was no difference in non‐relapse mortality or overall survival between the groups. In conclusion, the development of hypercholesterolemia is regarded as one of the symptoms accompanied with chronic GVHD and might indicate a better control of the primary disease.
High frequency of CD4+CD25−CD69+T cells is correlated with a low risk of acute graft‐versus‐host disease in allotransplants
Authors: Lu Sheng‐Ye , Huang Xiao‐Jun , Liu Kai‐Yan , Liu Dai‐Hong , Xu Lan‐Ping
Published: April 2012

Regulatory T cells (Tregs) maintain transplantation tolerance and suppress graft‐versus‐host disease (GvHD) in humans. We monitored 17 subjects with acute GvHD to determine whether Treg frequency correlates with acute GvHD. We found the percent of CD4+CD25−CD69+ Tregs decreases when acute GvHD develops and increases after acute GvHD is controlled. We next sequentially studied 50 subjects receiving conventional allotransplants. We show a high frequency and increased numbers of CD4+CD25−CD69+ Tregs are associated with a reduced risk of acute GvHD. We also show that CD4+CD25−CD69+ Treg numbers increase substantially early after allografts and that a low percent of CD4+CD25−CD69+ Tregs is associated with an increased risk of acute GvHD. Reconstitution of Tregs early post‐transplant is associated with less acute GvHD. These data imply that CD4+CD25−CD69+ Tregs are a novel subset of regulatory T cells that may protect against acute GvHD after allotransplants.
Balanced efficacy, safety, and tolerability recommendations for the clinical management of bipolar disorder
Authors: Malhi Gin S , Bargh Danielle M , McIntyre Roger , Gitlin Michael , Frye Mark A , Bauer Michael , Berk Michael
Published: April 2012

Malhi GS, Bargh DM, McIntyre R, Gitlin M, Frye MA, Bauer M, Berk M. Balanced efficacy, safety, and tolerability recommendations for the clinical management of bipolar disorder. Bipolar Disord 2012: 14 (Suppl. 2): 1–21. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objective:  To provide practical and clinically meaningful treatment recommendations that amalgamate clinical experience and research findings for each phase of bipolar disorder.

Methods:  A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Cochrane reviews) using key words (e.g., bipolar depression, mania, treatment). All relevant randomised controlled trials were examined, along with review papers, meta‐analyses, and book chapters known to the authors. In addition, the recommendations from accompanying papers in this supplement have been distilled and captured in the form of summary boxes. The findings, in conjunction with the clinical experience of international researchers and clinicians who are practiced in treating mood disorders, formed the basis of the treatment recommendations within this paper.

Results:  Balancing clinical experience with evidence informed and lead to the development of practical clinical recommendations that emphasise the importance of safety and tolerability alongside efficacy in the clinical management of bipolar disorder.

Conclusions:  The current paper summarises the treatment recommendations relating to each phase of bipolar disorder while providing additional, evidence‐based, practical insights. Medication‐related side effects and monitoring strategies highlight the importance of safety and tolerability considerations, which, along with efficacy information, should be given equal merit.
Efficacy of antimanic treatments in mixed states
Authors: McIntyre Roger S , Yoon Jinju
Published: April 2012

McIntyre RS, Yoon J. Efficacy of antimanic treatments in mixed states. Bipolar Disord 2012: 14 (Suppl. 2): 22–36. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objective:  To review the efficacy of pharmacological agents in bipolar mixed states.

Methods:  We conducted a PubMed search of all English‐language articles involving Food and Drug Administration (FDA)‐approved agents for manic/mixed states in adults with bipolar I disorder. We also included names of agents established as efficacious in acute mania/mixed states that have not received FDA approval for bipolar disorder. Bibliographies from relevant articles were also searched. The efficacy of each agent in the mixed state subpopulation was reviewed, as evidenced by change from baseline on total scores of mania [e.g., Young Mania Rating Scale (YMRS)] and depression [e.g., Montgomery–Åsberg Depression Rating Scale (MADRS)] measures.

Results:  No available study is dedicated exclusively to the evaluation of mixed state populations. Although key inclusion and exclusion criteria are similar across treatment studies, mixed states have been variably defined and measured. The use of conventional manic and depressive metrics in bipolar mixed states perpetuates the unproven notion that mixed states are the consequence of coexisting depression and mania. Notwithstanding the methodological limitations, there are numerically more studies that exist for atypical antipsychotic agents than for any other class. On the basis of symptomatic improvement, recommendations for and/or strong admonishments against any established antimanic agents (e.g., lithium) cannot be made. An emergent signal supports combination treatment strategies (e.g., atypical antipsychotic plus divalproex) over mood stabilizer monotherapy (e.g., divalproex). Available evidence does not empirically support the hypothesis that conventional antipsychotics engender and/or amplify depressive symptoms in bipolar mixed states.

Conclusions:  All proven antimanic agents (including lithium), can be recommended in the treatment of mixed/dysphoric states. The totality of evidence with attention paid to the therapeutic index of each agent would suggest that atypical antipsychotics and divalproex be considered as first‐line treatment, with lithium and carbamazepine as second‐line. Most individuals will require combination therapy for the treatment of mixed states; variable combinations of atypical antipsychotics and conventional mood stabilizers have the most replicated evidence.
The clinical management of bipolar disorder complexity using a stratified model
Authors: Malhi Gin S , Bargh Danielle M , Cashman Emma , Frye Mark A , Gitlin Michael
Published: April 2012

Malhi GS, Bargh DM, Cashman E, Frye MA, Gitlin M. The clinical management of bipolar disorder complexity using a stratified model. Bipolar Disord 2012: 14 (Suppl. 2): 66–89. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objective:  To provide practical and clinically meaningful treatment recommendations that amalgamate clinical and research considerations for several common, and as yet understudied, bipolar disorder complex presentations, within the framework of a proposed stratified model.

Methods:  A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Web of Science) using key words (e.g., bipolar disorder, anxiety, rapid cycling, and subsyndromal). All relevant randomised controlled trials were examined, in addition to review papers, meta‐analyses, and book chapters known to the authors. The findings formed the basis of the treatment recommendations within this paper.

Results:  In light of the many broad presentations of bipolar disorder, a stratified model of bipolar disorder complexity was developed to facilitate consideration of the myriad of complexities that can occur during the longitudinal course of illness and the appropriate selection of treatment. Evidence‐based treatment recommendations are provided for the following bipolar disorder presentations: bipolar II disorder, subsyndromal symptoms, mixed states, rapid cycling, comorbid anxiety, comorbid substance abuse, and for the following special populations: young, elderly, and bipolar disorder around the time of pregnancy and birth. In addition, some key strategies for countering treatment non‐response and alternative medication recommendations are provided.

Conclusions:  Treatment recommendations for the more challenging presentations of bipolar disorder have historically received less attention, despite their prevalence. This review acknowledges the weaknesses in the current evidence base on which treatment recommendations are generally formulated, and additionally emphasises the need for high‐quality research in this area. The stratified model provides a means for conceptualizing the complexity of many bipolar disorder presentations and considering their management.
Anatomicohistological Characteristics of the Tubular Genital Organs of the Female Red Brocket Deer (Mazama americana) in the Peruvian Amazon
Authors: Mayor P. , López‐Plana C. , López‐Béjar M.
Published: April 2012

This study examined the anatomical and histological characteristics of tubular genital organs of 51 adult female red brocket deer in the wild in different reproductive stages, collected by rural hunters in the north‐eastern Peruvian Amazon. The infundibulum was characterized by a large diameter and the presence of a highly folded and ciliated epithelium, and the isthmus has a growing secretor epithelium and a thicker muscular layer. Whereas ciliated cells are more frequent in the infundibulum, epithelial secretory cells showing abundant apical secretory blebs are more frequent in the isthmus. In non‐pregnant females in luteal phase, the endometrium transforms from a proliferative to a secretory type, showing a significant proliferation of endometrial uterine glands. The red brocket deer has four large circular folds in the cervix. The epithelium of the cervix is composed primarily of secretory cells. In pregnant females, the lumen of the endocervical canal is occupied by abundant mucous secretion. All pregnant females had one embryo or fetus, with a fetal sex ratio of 54.0% females to 46.0% males. This species has a cotyledonary, syndesmochorial and partially deciduate placenta, with 6–7 dome‐shaped caruncles per female. The red brocket deer does not present a true cornification of the vaginal epithelial cells, and no vaginal epithelial pattern was determined according the reproductive state of the female.
NAT2 and CYP2E1 polymorphisms associated with antituberculosis drug‐induced hepatotoxicity in Chinese patients
Authors: An Hui‐Ru , Wu Xue‐Qiong , Wang Zhong‐Yuan , Zhang Jun‐Xian , Liang Yan
Published: April 2012

The present study investigated the relationship between antituberculosis (anti‐TB) drug‐induced hepatotoxicity and genetic polymorphisms of two important drug‐metabolizing enzymes involved in the metabolism of isoniazid, namely
N
‐acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1).

A polymerase chain reaction direct sequencing approach was used to detect genetic polymorphisms of the
NAT2
and
CYP2E1
genes in tuberculosis (TB) patients with (n = 101) or without (n = 107) anti‐TB drug‐induced hepatotoxicity. Associations between various genetic polymorphisms and anti‐TB drug‐induced hepatotoxicity were then determined.

Patients with
NAT2
(282TT
, 590AA
and 857GA
) alleles had an increased susceptibility to anti‐TB drug‐induced hepatotoxicity. The slow acetylator
NAT2
genotypes (especially
NAT2*6A/7B and NAT2*6A/6A
) were risk factors for hepatotoxicity (odds ratio (OR) 9.57 (P < 0.001) for
NAT2*6A/7B
; OR 5.24 (P = 0.02) for
NAT2*6A/6A
).

The
CYP2E1
genotype per se was not significantly associated with the development of anti‐TB drug‐induced hepatotoxicity. However, the combination of the
CYP2E1

C1/
C1 genotype with a slow acetylator
NAT2
genotype increased the risk of anti‐TB drug‐induced hepatotoxicity (OR 5.33; P = 0.003) compared with the combination of a rapid acetylator
NAT2
genotype with either a
C1/
C2 or
C2/
C2 genotype.

Thus, slow acetylators with the
NAT2*6A/7B
and
NAT2*6A/6A
genotypes combined with the
C1/
C1

CYP2E1
genotype may be involved in the pathogenesis of anti‐TB drug‐induced hepatotoxicity.

The present findings may be explained, in part, by changes in the metabolism of the anti‐TB drug isoniazid induced via NAT2 and CYP2E1, a metabolic process known to produce hepatotoxic intermediates.
Feasibility study of secure closure of gastric fundus perforation using over‐the‐scope clips in a dog model
Authors: Zhang Xiu‐Li , Qu Jian‐Hui , Sun Gang , Tang Ping , Yang Yun‐Sheng
Published: April 2012

Background and Aim:  Gastric fundus perforation is a serious complication of endoscopic mucosal resection and endoscopic submucosal dissection performed for the removal of early gastric cancers or subepithelial tumors. The novel over‐the‐scope clip (OTSC) has recently been found to be effective for closing gastrointestinal‐tract perforations and accesses for natural orifice transluminal endoscopic surgery. However, feasibility studies of OTSCs in gastric fundus perforation are still lacking. The aim of this study was therefore to demonstrate the feasibility of endoscopic closure of gastric fundus perforation using the OTSC system in a dog model.

Methods:  Gastric fundus perforations were created by needle‐knife electrocautery in seven dogs. The perforations were then closed using the OTSC clipping system. Stomach distension was maintained by maximum insufflation with air and methylene blue solution (500 mL) was instilled to submerge the closed perforation. Leaks were detected laparoscopically.

Results:  Perforations were closed in all seven cases with a mean time of 18.5 ± 6.4 min (11–28 min). Twin Grasper assistance failed to release the OTSCs in two of the seven cases (2/7, 28.6%) because of difficulties associated with the J‐maneuver (retroflexion of endoscope) required for the gastric fundus procedure, and OTCS were forced into place by suction. Minor leakage was observed in one case (1/7, 14.3%). No damages related to the clip system were found during postmortem examinations.

Conclusions:  Despite difficulties associated with the J‐maneuver of the endoscope, this small series demonstrated that sufficient closure of gastric fundus perforation could be achieved using the OTSC system.
ENDOSCOPIC REMOVAL OF A SPONTANEOUSLY FRACTURED BILIARY UNCOVERED SELF‐EXPANDABLE METAL STENT
Authors: KAWAKUBO KAZUMICHI , ISAYAMA HIROYUKI , TSUJINO TAKESHI , NAKAI YOUSUKE , SASAHIRA NAOKI , KOGURE HIROFUMI , HAMADA TSUYOSHI , NAGANO RIE , MIYABAYASHI KOUJI , YAMAMOTO KEISUKE , MOHRI DAI , SASAKI TAKASHI , ITO YUKIKO , YAMAMOTO NATSUYO , HIRANO KENJI , TADA MINORU , KOIKE KAZUHIKO
Published: April 2012

Self‐expandable metal stents (SEMS) are widely used for the palliative treatment of unresectable malignant biliary obstruction. However, the long‐term durability of SEMSs in biliary strictures is not clear. We describe a case of endoscopic removal of spontaneously fractured uncovered biliary SEMS. A 59‐year‐old woman presented to our institution with a 1‐year history of recurrent cholangitis. Her medical history included a proctectomy for rectal cancer and right hemihepatectomy for liver metastasis 10 years earlier. Five years after these operations, she developed a benign hilar stricture and had an uncovered SEMS placed in another hospital. Endoscopic retrograde cholangiopancreatography demonstrated that the SEMS was torn in half and the distal part of the stent was floating in the dilated common bile duct. The papillary orifice was dilated by endoscopic papillary large balloon dilation (EPLBD) using a 15‐mm wire‐guided balloon catheter. Subsequently, we inserted biopsy forceps into the bile duct and grasped the distal end of the broken SEMS under fluoroscopy. We successfully removed the fragment of the SEMS from the bile duct, along with the endoscope. The patient was discharged without complications. Placement of an uncovered biliary SEMS is not the preferred treatment for benign biliary strictures. Spontaneous fracture of an uncovered biliary SEMS is an extremely rare complication. We should be aware that stent fracture can occur when placing uncovered biliary SEMSs in patients with a long life expectancy. EPLBD is very useful for retrieving the fractured fragment of SEMS.
Categorical representation of objects in the central nucleus of the monkey amygdala
Authors: Kuraoka Koji , Nakamura Katsuki
Published: April 2012

The primate amygdala consists of several subnuclei. Neurons in this brain area have been known to respond to stimuli belonging to specific categories of objects, such as faces, animals, and artifacts. However, little is known about the functional differences among the nuclei of the primate amygdala. To clarify functional differences among these subnuclei in object categorization, we compared the responsiveness of neuronal populations among the lateral, basal and central nuclei of the monkey amygdala. The activity of 203 neurons was recorded while video clips of 13 stimuli belonging to three categories (monkey, human, and artifact) were presented. Of these neurons, 37, 39 and 37 neurons in the lateral, basal and central nuclei, respectively, responded to at least one of the stimuli. We applied a cluster analysis to the neuronal population responses from these nuclei, and also calculated information about the three categories and monkey identity from each neuronal population. We found that the three categories and monkey identity could be more properly classified by neuronal responsiveness in the central nucleus, which is an output gate of the amygdala, than by that in the lateral and basal nuclei. These results suggest that the information about objects suitable for the generation of appropriate emotional response is built up within the primate amygdala via an intra‐amygdala network from the lateral nucleus to the central nucleus.
Imbalanced suppression of excitatory and inhibitory synaptic transmission onto mouse striatal projection neurons during induction of anesthesia with sevoflurane in vitro
Authors: Oose Yoshiyuki , Miura Masami , Inoue Ritsuko , Andou Nozomi , Aosaki Toshihiko , Nishimura Kinya
Published: April 2012

Suppression of movement during induction of anesthesia is mediated through subcortical structures. We studied the effects of a brief, 5‐min application of a clinically relevant concentration of sevoflurane (two minimum alveolar concentration) on the electrophysiological activities of the medium spiny neurons (MSNs) of the striatum in brain slice preparations, using a whole‐cell patch‐clamp technique. We found that sevoflurane slightly depolarized principal neurons in the cortex and the striatum without a significant alteration in spike threshold. Furthermore, it depressed the peak, as well as the net, charge transfer of intrastriatally evoked inhibitory postsynaptic currents (eIPSCs) much more strongly than those of excitatory postsynaptic currents (EPSCs), and this inhibition was accompanied by an elevated paired‐pulse ratio. The strong suppression of eIPSCs paralleled a significant suppression of the frequency, but not the amplitude, of miniature IPSCs (mIPSCs), and was associated with a transient increase in the frequency of spontaneous EPSCs. Treatment with the Ca2+ channel blocker Cd2+ restored the frequency of mIPSCs to the control level, indicating sevoflurane’s strong presynaptic suppression of γ‐aminobutyric acid release in the striatum. In contrast, in hippocampal CA1 pyramidal neurons sevoflurane produced an enhancement of the net charge transfer of IPSCs, while it suppressed EPSCs to an equivalent degree to that in striatal MSNs. These results suggest that, in contrast to its effects on other brain structures, sevoflurane shifts the balance between synaptic excitation and inhibition in the direction of excitation in the striatum, thereby causing involuntary movements during induction of anesthesia by sevoflurane.
Obstacle avoidance locomotor tasks: adaptation, memory and skill transfer
Authors: Kloter Evelyne , Dietz Volker
Published: April 2012

The aim of this study was to explore the neural basis of adaptation, memory and skill transfer during human stepping over obstacles. Whilst walking on a treadmill, subjects had to perform uni‐ and bilateral obstacle steps. Acoustic feedback information about foot clearance was provided. Non‐noxious electrical stimuli were applied to the right tibial nerve during the mid‐stance phase of the right leg, i.e. ‘prior’ to the right or ‘during’ the left leg swing over the obstacle. The electromyogram (EMG) responses evoked by these stimuli in arm and leg muscles are known to reflect the neural coordination during normal and obstacle steps. The leading and trailing legs rapidly adapted foot clearance during obstacle steps with small further changes when the same obstacle condition was repeated. This adaptation was associated with a corresponding decrease in arm and leg muscle reflex EMG responses. Arm (but not leg) muscle EMG responses were greater when the stimulus was applied ‘during’ obstacle crossing by the left leg leading compared with stimulation ‘prior’ to right leg swing over the obstacle. A corresponding difference existed in arm muscle background EMG. The results indicate that, firstly, the somatosensory information gained by the performance and adaptation of uni‐ and bilateral obstacle stepping becomes transferred to the trailing leg in a context‐specific manner. Secondly, EMG activity in arm and leg muscles parallels biomechanical adaptation of foot clearance. Thirdly, a consistently high EMG activity in the arm muscles during swing over the obstacle is required for equilibrium control. Thus, such a precision locomotor task is achieved by a context‐specific, coordinated activation of arm and leg muscles for performance and equilibrium control that includes adaptation, memory and skill transfer.
Top‐down determinants of niche structure and adaptation among African Acacias
Authors: Staver A. Carla , Bond William J. , Cramer Michael D. , Wakeling Julia L.
Published: April 2012

Ecology Letters (2012) 15: 673–679

The role of top‐down factors like herbivory and fire in structuring species’ niches, even in disturbance‐dependent biomes like savanna, remains poorly understood. Interactions between herbivory and fire may set up a potential tradeoff axis, along which unique adaptations contribute to structuring communities and determining species distributions. We examine the role of herbivory and fire in structuring distributions of Acacia saplings in Hluhluwe iMfolozi Park in South Africa, and the relationship of species’ niche structure to traits that help them survive herbivory or fire. Results suggest that (1) fire and herbivory form a single trade‐off axis, (2) Acacia sapling distributions are constrained by fire and herbivory, and (3) Acacia saplings have adaptations that are structured by the tradeoff axis. Herbivory‐adapted species tend to have ‘cage’‐like architecture, thicker bark, and less starch storage, while fire‐adapted species tend to have ‘pole’‐like architecture, relatively thinner bark, and more starch storage.
Tracking differential incorporation of dissolved organic carbon types among diverse lineages of Sargasso Sea bacterioplankton
Authors: Nelson Craig E. , Carlson Craig A.
Published: April 2012

Bacterioplankton are the primary trophic conduit for dissolved organic carbon (DOC) and linking community structure with DOC utilization is central to understanding global carbon cycling. We coupled stable isotope probing (SIP) with 16S rRNA pyrosequencing in dark seawater culture experiments on euphotic and mesopelagic communities from the Sargasso Sea. Parallel cultures were amended with equimolar quantities of four DO13C substrates to simultaneously evaluate community utilization and population‐specific incorporation. Of the substrates tested – two cyanobacterial products (exudates or lysates from a culture of Synechococcus) and two defined monosaccharides (glucose or gluconic acid) – the cyanobacterial exudates were incorporated by the greatest diversity of oligotrophic bacterioplankton populations in surface waters, including taxa from > 10 major subclades within the Flavobacteria, Actinobacteria, Verrucomicrobia and Proteobacteria (including SAR11). In contrast, the monosaccharide glucose was not incorporated by any taxa belonging to extant oligotrophic oceanic clades. Conversely, proteobacterial copiotrophs, which were rare in the ambient water (< 0.1% of sequences), grew rapidly on all DOC amendments at both depths, but with different substrate preferences among lineages. We present a new analytical framework for using SIP to detect DOC incorporation across diverse oligotrophic bacterioplankton and discuss implications for the ecology of bacterial–DOC interactions among populations of diverging trophic strategies.
In situsurvey of life cycle phases of the coccolithophoreEmiliania huxleyi(Haptophyta)
Authors: Frada Miguel J. , Bidle Kay D. , Probert Ian , de Vargas Colomban
Published: April 2012

The cosmopolitan coccolithophoreEmiliania huxleyiis characterized by a strongly differentiated haplodiplontic life cycle consisting of a diploid phase, generally bearing coccoliths (calcified) but that can be also non‐calcified, and a non‐calcified biflagellated haploid phase. Given most studies have focused on the bloom‐producing calcified phase, there is little‐to‐no information about non‐calcified cells in nature. Using field mesocoms as experimental platforms, we quantitatively surveyed calcified and non‐calcified cells using the combined calcareous detection fluorescentin situhybridization (COD‐FISH) method and qualitatively screened for haploid specific transcripts using reverse transcription‐PCR duringE. huxleyibloom successions. Diploid, calcified cells formed dense blooms that were followed by the massive proliferation ofE. huxleyiviruses (EhVs), which caused bloom demise. Non‐calcified cells were also detected throughout the experiment, accounting for a minor fraction of the population but becoming progressively more abundant during mid‐late bloom periods concomitant withEhV burst. Non‐calcified cell growth also paralleled a distinct window of haploid‐specific transcripts and the appearance of autotrophic flagellates morphologically similar to haploid cells, both of which are suggestive of meiosis and sexual life cycling during natural blooms of this prominent marine phytoplankton species.
Ciliate and bacterial communities associated with White Syndrome and Brown Band Disease in reef‐building corals
Authors: Sweet Michael , Bythell John
Published: April 2012

White Syndrome (WS) and Brown Band Disease (BrB) are important causes of reef coral mortality for which causal agents have not been definitively identified. Here we use culture‐independent molecular techniques (DGGE and clone libraries) to characterize ciliate and bacterial communities in these diseases. Bacterial (16S rRNA gene) and ciliate (18S rRNA gene) communities were highly similar between the two diseases. Four bacterial and nine ciliate ribotypes were observed in both diseases, but absent in non‐diseased specimens. Only one of the bacteria, Arcobacter sp. (JF831360) increased substantially in relative 16S rRNA gene abundance and was consistently represented in all diseased samples. Four of the eleven ciliate morphotypes detected contained coral algal symbionts, indicative of the ingestion of coral tissues. In both WS and BrB, there were two ciliate morphotypes consistently represented in all disease lesion samples. Morph1 (JN626268) was observed to burrow into and underneath the coral tissues at the lesion boundary. Morph2 (JN626269), previously identified in BrB, appears to play a secondary, less invasive role in pathogenesis, but has a higher population density in BrB, giving rise to the visible brown band. The strong similarity in bacterial and ciliate community composition of these diseases suggests that they are actually the same syndrome.
Resistant ticks inhibit Metarhizium infection prior to haemocoel invasion by reducing fungal viability on the cuticle surface
Authors: Ment Dana , Churchill Alice C. L. , Gindin Galina , Belausov Eduard , Glazer Itamar , Rehner Stephen A. , Rot Asael , Donzelli Bruno G. G. , Samish Michael
Published: April 2012

We studied disease progression of, and host responses to, four species in the Metarhizium anisopliae complex expressing green fluorescent protein (GFP). We compared development and determined their relative levels of virulence against two susceptible arthropods, the cattle tick Rhipicephalus annulatus and the lepidopteran Galleria mellonella, and two resistant ticks, Hyalomma excavatum and Rhipicephalus sanguineus. Metarhizium brunneum Ma7 caused the greatest mortality of R. annulatus, Metarhizium robertsii ARSEF 2575 and Metarhizium pingshaense PPRC51 exhibited intermediate levels of virulence, and Metarhizium majus PPRC27 caused low mortality of cattle ticks. Conidia of all four species germinated on all hosts examined, but on resistant hosts, sustained hyphal growth was inhibited and GFP emission steadily and significantly decreased over time, suggesting a loss of fungal viability. Cuticle penetration was observed only for the three most virulent species infecting susceptible hosts. Cuticles of resistant and susceptible engorged female ticks showed significant increases in red autofluorescence at sites immediately under fungal hyphae. This is the first report (i) of tick mortality occurring after cuticle penetration but prior to haemocoel colonization and (ii) that resistant ticks do not support development of Metarhizium germlings on the outer surface of the cuticle. Whether reduced Metarhizium viability on resistant tick cuticles is due to antibiosis or limited nutrient availability is unknown.
Utility of non‐high‐density lipoprotein cholesterol in assessing incident type 2 diabetes risk
Authors: Ley S. H. , Harris S. B. , Connelly P. W. , Mamakeesick M. , Gittelsohn J. , Wolever T. M. , Hegele R. A. , Zinman B. , Hanley A. J.
Published: April 2012

Aims: Traditional lipid indices have been associated with type 2 diabetes, but limited data are available regarding non‐high‐density lipoprotein (non‐HDL) cholesterol. In view of recent guidelines for the clinical management of dyslipidemia recommending the monitoring of non‐HDL cholesterol as a secondary target after achieving the low‐density lipoprotein (LDL) cholesterol goal, we aimed to assess the association of non‐HDL cholesterol with incident type 2 diabetes and compare its utility as a risk predictor with traditional lipid variables in Aboriginal Canadians.

Methods: Of 606 diabetes‐free participants at baseline, 540 (89.1%) returned for 10‐year follow‐up assessments. Baseline anthropometry, blood pressure, fasting insulin and serum lipids were measured. Fasting and 2‐h postload glucose were obtained at baseline and follow‐up to determine the incidence of type 2 diabetes.

Results: The cumulative incidence of type 2 diabetes was 17.5%. Higher non‐HDL cholesterol, total‐to‐HDL cholesterol ratio, apolipoprotein B, triglyceride and LDL cholesterol and lower HDL cholesterol concentrations were individually associated with incident type 2 diabetes in univariate analyses (all p < 0.05). Non‐HDL cholesterol was a superior determinant of incident diabetes compared with LDL cholesterol (comparing C‐statistics of univariate models p = 0.01) or HDL cholesterol (p = 0.004). With multivariate adjustment including waist circumference, non‐HDL cholesterol remained associated with incident diabetes [odds ratio (OR) 1.42 (95% confidence interval, CI 1.07–1.88)], while LDL cholesterol and HDL cholesterol became non‐significant.

Conclusions: Non‐HDL cholesterol was associated with incident type 2 diabetes and was superior to LDL cholesterol as a risk predictor in this population. Further studies are required to establish the utility of non‐HDL cholesterol in non‐Aboriginal populations.
Fasting hyperglycaemia blunts the reversal of impaired glucose tolerance after exercise training in obese older adults
Authors: Malin S. K. , Kirwan J. P.
Published: April 2012

Aim: Lifestyle modification, consisting of exercise and weight loss, delays the progression from prediabetes to type 2 diabetes (T2D). However, no study has determined the efficacy of exercise training on glucose metabolism in the different prediabetes subtypes.

Methods: Seventy‐six older (65.1 ± 0.6 years) obese adults with impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 9) and combined glucose intolerance (IFG + IGT = CGI; n = 22) were compared with normal glucose tolerant (NGT; n = 15) and T2D (n = 18) groups after 12 weeks of exercise training (60 min/day for 5 days/week at ∼85% HRmax). An oral glucose tolerance test was used to assess glucose levels. Insulin sensitivity (IS; euglycaemic hyperinsulinaemic clamp at 40 mU/m2/min), β‐cell function (glucose‐stimulated insulin secretion corrected for IS), body composition (hydrostatic weighing/computed tomography scan) and cardiovascular fitness (treadmill VO2max) were also assessed.

Results: Exercise training reduced weight and increased cardiovascular fitness (p < 0.05). Exercise training lowered fasting glucose levels in IFG, CGI and T2D (p < 0.05) and 2‐h glucose levels in IGT, CGI and T2D (p < 0.05). However, 2‐h glucose levels were not normalized in adults with CGI compared with IGT (p < 0.05). β‐Cell function improved similarly across groups (p < 0.05). Although not statistically significant, IS increased approximately 40% in IFG and IGT, but only 17% in CGI.

Conclusion: The magnitude of improvement in glucose metabolism after 12 weeks of exercise training is not uniform across the prediabetes subtypes. Given the high risk of progressing to T2D, adults with CGI may require more aggressive therapies to prevent diabetes.
Screening for pre‐diabetes to predict future diabetes using various cut‐off points for HbA1c and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4)
Authors: Heianza Y. , Arase Y. , Fujihara K. , Tsuji H. , Saito K. , Hsieh S. D. , Kodama S. , Shimano H. , Yamada N. , Hara S. , Sone H.
Published: April 2012

Diabet. Med. 29, e279‐e285 (2012)

Aim  To evaluate various screening criteria for pre‐diabetes to identify which combination of impaired fasting glucose and elevated HbA1c values performs most effectively in predicting future diabetes in a large cohort of Japanese individuals.

Methods  The study included 4670 men and 1571 women without diabetes (diabetes: fasting plasma glucose ≥ 7.0 mmol/l, HbA1c≥ 48 mmol/mol (≥ 6.5%), or self‐reported clinician‐diagnosed diabetes). Pre‐diabetes was diagnosed by a combination of impaired fasting glucose (fasting plasma glucose 5.6–6.9 mmol/l or 6.1–6.9 mmol/l) and elevated HbA1c [39–46 mmol/mol (5.7–6.4%) or 42–46 mmol/mol (6.0–6.4%)].

Results  During a 5‐year follow‐up, 338 incident cases of diabetes occurred. The combination of HbA1c 39–46 mmol/mol (5.7–6.4%) and fasting plasma glucose 5.6–6.9 mmol/l yielded the highest sensitivity (86%) and generated a large population‐attributable per cent risk (78%) for predicting development of diabetes. Among individuals classified as having pre‐diabetes by any of the four combined criteria, 20.5–32.0% reverted to the normoglycaemic state as having neither elevated HbA1c nor impaired fasting glucose at the last follow‐up examination. At 5.6 years after the baseline examination, however, pre‐diabetic individuals who fulfilled both HbA1c 42–46 mmol/mol (6.0–6.4%) and fasting plasma glucose 6.1–6.9 mmol/l had a 100% cumulative risk of developing diabetes.

Conclusions  The combination of HbA1c 39–46 mmol/mol (5.7–6.4%) and fasting plasma glucose 5.6–6.9 mmol/l would have the best performance in reducing the likelihood of missing future cases of diabetes. Identifying pre‐diabetic individuals who strictly fulfil HbA1c 42–46 mmol/mol (6.0–6.4%) and fasting plasma glucose 6.1–6.9 mmol/l would predict definite progression to diabetes.
Peer supporters for cardiac patients with diabetes: a randomized controlled trial
Authors: Wu C.‐J. (Jo) , Chang A.M. , Courtney M. , Kostner K.
Published: April 2012

WU C.‐J., CHANG A.M., COURTNEY M. & KOSTNER K. (2012) Peer supporters for cardiac patients with diabetes: a randomized controlled trial. International Nursing Review59, 345–352

Aims:  To determine whether incorporation of patient peer supporters in a Cardiac‐Diabetes Self‐Management Program (Peer‐CDSMP) led to greater improvement in self‐efficacy, knowledge and self‐management behaviour in the intervention group compared to a control group.

Background:  Promoting improved self‐management for those with diabetes and a cardiac condition is enhanced by raising motivation and providing a model. Peer support from former patients who are able to successfully manage similar conditions could enhance patient motivation to achieve better health outcomes and provide a model of how such management can be achieved. While studies on peer support have demonstrated the potential of peers in promoting self‐management, none have examined the impact on patients with two co‐morbidities.

Methods:  A randomized controlled trial was used to develop and evaluate the effectiveness of the Peer‐CDSMP from August 2009 to December 2010. Thirty cardiac patients with type 2 diabetes were recruited. The study commenced in an acute hospital, follow‐up at participants' homes in Brisbane, Australia.

Results:  While both the control and intervention groups had improved self‐care behaviour, self‐efficacy and knowledge, the improvement in knowledge was significantly greater for the intervention group.

Conclusions:  Significant improvement in knowledge was achieved for the intervention group. Absence of significant improvements in self‐efficacy and self‐care behaviour represents an inconclusive effect; further studies with larger sample sizes are recommended.
HOMEOPATHY IS UNSCIENTIFIC AND UNETHICAL
Authors: SMITH KEVIN
Published: April 2012

In opposition to the premises of Against Homeopathy – a Utilitarian Perspective, all four respondents base their objections on the central claims that homeopathy is in fact scientifically plausible and is supported by empirical evidence. Despite ethical aspects forming the main thrust of Against Homeopathy, the respondents’ focus on scientific aspects represents sound strategy, since the ethical case against homeopathy would be weakened concomitant with the extent to which any plausibility for homeopathy could be demonstrated. The trouble here is that the respondents are attempting to perpetuate a sterile debate. The notion that homeopathic preparations could have any biological effects represents a fringe viewpoint, one not entertained by serious scientists nor supported by reason and evidence.

In the present article, I shall endeavour to explain why the respondents do not have a valid case. I will deal firstly with their general approach to scientific plausibility and evidence, and then consider some of the specific claims they have made. Finally, I will answer the philosophical arguments some of the respondents have raised.
FOR HOMEOPATHY: A PRACTISING PHYSICIAN'S PERSPECTIVE
Authors: MOSKOWITZ RICHARD
Published: April 2012

This article is a rebuttal to Kevin Smith's ‘Against Homeopathy,’ which was posted on 14 February 2011.1 It contends that his argument rests entirely on the assumption that homeopathic remedies are nothing but placebos. His argumentation is good, but his assumption is false. Evidence is presented to show that the Law of Similars is plausible and that ultradilute remedies do indeed have biological activity.
ETHICOVIGILANCE IN CLINICAL TRIALS
Authors: SHAW DAVID , MCMAHON ALEX
Published: April 2012

This article provides an ethical critique of the Good Clinical Practice (GCP) and Declaration of Helsinki (DoH) documents. While the previous criticisms of GCP are entirely correct, there is much more wrong with the document than has previously been acknowledged, including a circular definition and an astonishing vagueness about ethical principles. In addition to its failure to provide adequate ethical protection of participants, the procedurally dense nature of GCP lends itself to a box‐ticking culture where important ethical issues are overlooked because they are not ‘mentioned on the form’. In contrast, the DoH is a much more effective ethical document, but actually goes too far in one respect. It transpires that the best ethical guidelines for clinical research would be neither over‐prescriptive in regard to particular ethical issues (as the DoH is) nor neglectful of them (as GCP is); correctly framed ethical principles will provide sufficient protection to participants while also ensuring a culture of ethicovigilance in clinical trials.
Social Support Matters: Longitudinal Effects of Social Support on Three Dimensions of School Engagement From Middle to High School
Authors: Wang Ming‐Te , Eccles Jacquelynne S.
Published: April 2012

This study examined the relative influence of adolescents’ supportive relationships with teachers, peers, and parents on trajectories of different dimensions of school engagement from middle to high school and how these associations differed by gender and race or ethnicity. The sample consisted of 1,479 students (52% females, 56% African American). The average growth trajectories of school compliance, participation in extracurricular activities, school identification, and subjective valuing of learning decreased from 7th to 11th grades (mean ages = 12.9 years to 17.2 years). Different sources of social support were not equally important in their impact on school engagement, and the effect of these sources differed by the aspect of engagement studied. For instance, peer social support predicted adolescents’ school compliance more strongly and school identification less strongly than teacher social support.
Increasing Young Children’s Contact With Print During Shared Reading: Longitudinal Effects on Literacy Achievement
Authors: Piasta Shayne B. , Justice Laura M. , McGinty Anita S. , Kaderavek Joan N.
Published: April 2012

Longitudinal results for a randomized‐controlled trial (RCT) assessing the impact of increasing preschoolers’ attention to print during reading are reported. Four‐year‐old children (N = 550) in 85 classrooms experienced a 30‐week shared reading program implemented by their teachers. Children in experimental classrooms experienced shared‐book readings 2 or 4 times per week during which their teachers verbally and nonverbally referenced print. Children in comparison classrooms experienced their teachers’ typical book reading style. Longitudinal results (n = 356, 366) showed that use of print references had significant impacts on children’s early literacy skills (reading, spelling, comprehension) for 2 years following the RCT’s conclusion. Results indicate a causal relation between early print knowledge and later literacy skills and have important implications concerning the primary prevention of reading difficulties.
Migration, Foreign Aid and the Welfare State
Authors: Hatzipanayotou Panos , Michael Michael S.
Published: April 2012

Aspects related to the links between international migration, foreign aid and the welfare state are highlighted in this paper. Migration is modeled as a costly movement from an aid‐recipient developing country with low income and no welfare state, towards a rich donor, developed country with a well‐developed welfare state. Within this model, it is found, among other things, that the best response of the developed donor country is to increase aid as the co‐financing rate by the recipient country increases. When the immigration cost decreases, e.g. as a result of greater economic integration between the two countries, it is beneficial for the donor country to increase aid and the recipient country to increase the co‐financing rate.
Aid and Income Stabilization
Authors: Jeanneney S. Guillaumont , Tapsoba S. J‐A.
Published: April 2012

The potential stabilization of output shocks through official assistance flows is investigated is this paper. It contributes to the current debate on aid instability and argues that official assistance might cope with exogenous output shocks in recipient countries and stabilize resources available for national expenditure, including consumption and investment. High aid dependency and vulnerability to output shocks positively affect the stabilization property of aid. Contrasting with the current literature, the paper documents that aid volatility is not a significant determinant of the stabilizing or destabilizing impact of aid.
Intersectoral Spillovers, Relative Prices and Development Traps
Authors: Chen Been‐Lon , Lee Shun‐Fa
Published: April 2012

Why is the economic growth rate so low in poor countries? This paper offers an explanation by using a simple two‐sector AK growth model with intersectoral linkages and high relative prices of intermediate goods. Intersectoral linkages lead to two balanced growth paths (BGPs). The high‐growth BGP is a source. The low‐growth BGP is a sink because it has a small final goods sector, small intersectoral spillovers from the final goods sector to the intermediate goods sector, and small marginal products in the intermediate goods sector, yielding high relative prices of intermediate goods. The low‐growth BGP is an attractor and thus development trap. To produce a big push effect, this paper analyzes the first‐best policy and finds that a subsidy to own consumption and a provision of public goods to the final goods sector can internalize the external effect and render the low‐growth BGP infeasible. As a result, there is only the high‐growth BGP.