bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct functional roles of homologous Cu+ efflux ATPases in Pseudomonas aeruginosa
Authors: González‐Guerrero Manuel , Raimunda Daniel , Cheng Xin , Argüello José M.
Published: September 2010

In bacteria, most Cu+‐ATPases confer tolerance to Cu by driving cytoplasmic metal efflux. However, many bacterial genomes contain several genes coding for these enzymes suggesting alternative roles. Pseudomonas aeruginosa has two structurally similar Cu+‐ATPases, CopA1 and CopA2. Both proteins are essential for virulence. Expressed in response to high Cu, CopA1 maintains the cellular Cu quota and provides tolerance to this metal. CopA2 belongs to a subgroup of ATPases that are expressed in association with cytochrome oxidase subunits. Mutation of copA2 has no effect on Cu toxicity nor intracellular Cu levels; but it leads to higher H2O2 sensitivity and reduced cytochrome oxidase activity. Mutation of both genes does not exacerbate the phenotypes produced by single‐gene mutations. CopA1 does not complement the copA2 mutant strain and vice versa, even when promoter regions are exchanged. CopA1 but not CopA2 complements an Escherichia coli strain lacking the endogenous CopA. Nevertheless, transport assays show that both enzymes catalyse cytoplasmic Cu+ efflux into the periplasm, albeit CopA2 at a significantly lower rate. We hypothesize that their distinct cellular functions could be based on the intrinsic differences in transport kinetic or the likely requirement of periplasmic partner Cu‐chaperone proteins specific for each Cu+‐ATPase.
Double‐blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder
Authors: Pavuluri Mani N , Henry David B , Findling Robert L , Parnes Stephanie , Carbray Julie A , Mohammed Tahseen , Janicak Philip G , Sweeney John A
Published: September 2010

Pavuluri MN, Henry DB, Findling RL, Parnes S, Carbray JA, Mohammed T, Janicak PG, Sweeney JA. Double‐blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder. Bipolar Disord 2010: 12: 593–605. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  To determine the relative effects of risperidone and divalproex in pediatric mania.

Methods:  This is a double‐blind, randomized, outpatient clinical trial with 66 children and adolescents (mean age = 10.9 ± 3.3 years; age range = 8–18 years) with mania who were randomly assigned to either risperidone (0.5–2 mg/day, n = 33) or divalproex (60–120 μg/mL, n = 33) for a six‐week period. Measures included the Young Mania Rating Scale (YMRS) and Child Depression Rating Scale‐Revised (CDRS‐R).

Results:  Mixed‐effects regression models, with interaction between time and the active drug as predictors, found that the risperidone group had more rapid improvement than the divalproex group (p < 0.05), although final scores did not differ significantly between groups. Mixed models using only those subjects who completed the six‐week study found similar results. The response rate on YMRS was 78.1% for risperidone and 45.5% for divalproex (p < 0.01). The remission rate for risperidone was 62.5%, compared with 33.3% for divalproex (p < 0.05). Improvement on the CDRS‐R was significantly higher for the risperidone group relative to the divalproex group (p < 0.05). There were no significant differences between groups in safety, but subject retention was significantly higher at study endpoint in the risperidone group (p < 0.01). Dropout rate was 24% in the risperidone group and 48% in the divalproex group, with increased irritability being the most common reason for dropout in the latter. There was no significant weight gain in either group.

Conclusion:  Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex. Although the results suggest that both drugs are safe, risperidone’s lower attrition rate and lower rate of adverse events may suggest better toleration. Clinical trials with larger samples are required to confirm these preliminary findings.
Family‐focused treatment for caregivers of patients with bipolar disorder
Authors: Perlick Deborah A , Miklowitz David J , Lopez Norma , Chou James , Kalvin Carla , Adzhiashvili Victoria , Aronson Andrew
Published: September 2010

Perlick DA, Miklowitz DJ, Lopez N, Chou J, Kalvin C, Adzhiashvili V, Aronson A. Family‐focused treatment for caregivers of patients with bipolar disorder. Bipolar Disord 2010: 12: 627–637. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Family members of patients with bipolar disorder experience high rates of subjective and objective burden which place them at risk for adverse physical health and mental health outcomes. We present preliminary efficacy data from a novel variation of Family Focused Treatment [Miklowitz DJ. Bipolar Disorder: A Family‐Focused Treatment Approach (2nd ed.). New York: The Guilford Press, 2008] that aimed to reduce symptoms of bipolar disorder by working with caregivers to enhance illness management skills and self‐care.

Methods:  The primary family caregivers of 46 patients with bipolar I (n = 40) or II (n = 6) disorder, diagnosed by the Structured Clinical Interview for DSM‐IV Axis I Disorders, were assigned randomly to receive either: (i) a 12–15‐session family‐focused, cognitive‐behavioral intervention designed to provide the caregiver with skills for managing the relative’s illness, attaining self‐care goals, and reducing strain, depression, and health risk behavior [Family‐Focused Treatment‐Health Promoting Intervention (FFT‐HPI)]; or (ii) an 8‐ to 12‐session health education (HE) intervention delivered via videotapes. We assessed patients pre‐ and post‐treatment on levels of depression and mania and caregivers on levels of burden, health behavior, and coping.

Results:  Randomization to FFT‐HPI was associated with significant decreases in caregiver depressive symptoms and health risk behavior. Greater reductions in depressive symptoms among patients were also observed in the FFT‐HPI group. Reduction in patients’ depression was partially mediated by reductions in caregivers’ depression levels. Decreases in caregivers’ depression were partially mediated by reductions in caregivers’ levels of avoidance coping.

Conclusions:  Families coping with bipolar disorder may benefit from family interventions as a result of changes in the caregivers’ ability to manage stress and regulate their moods, even when the patient is not available for treatment.
Autoimmune diseases, bipolar disorder, and non‐affective psychosis
Authors: Eaton William W , Pedersen Marianne G , Nielsen Philip R , Mortensen Preben Bo
Published: September 2010

Eaton WW, Pedersen MG, Nielsen PR, Mortensen PB. Autoimmune diseases, bipolar disorder, and non‐affective psychosis. Bipolar Disord 2010: 12: 638–646. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  Clinic‐based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non‐affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non‐affective psychosis.

Methods:  A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non‐affective psychosis, and 9,920 cases of bipolar disorder.

Results:  As in prior studies, there was a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first‐degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non‐affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain‐Barré syndrome, Crohn’s disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder.

Conclusions:  The familial relationship of schizophrenia to a range of autoimmune diseases extends to non‐affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non‐affective psychosis and bipolar disorder.
Theory of mind and neurocognitive functioning in patients with bipolar disorder
Authors: Wolf Frederike , Brüne Martin , Assion Hans‐Jörg
Published: September 2010

Wolf F, Brüne M, Assion H‐J. Theory of mind and neurocognitive functioning in patients with bipolar disorder. Bipolar Disord 2010: 12: 657–666. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Studies into social cognition in psychiatric disorders have recently been expanded to address the question of whether or not theory of mind (ToM), i.e., the ability to represent one’s own and others’ mental states, is impaired in bipolar affective disorder (BPD). Results have been mixed so far, mainly due to possible confounding effects of neurocognition, as well as clinical factors such as acuity and current mood. Here, we explored ToM and its associations with neurocognitive functioning in BPD.

Methods:  A total of 33 patients with bipolar I disorder (of whom 12 were currently depressed, 10 manic, and 11 remitted) and 29 healthy controls were assessed using a test battery that was identical to the one that was used in previous studies in schizophrenia, comprising diverse neurocognitive tasks, including measures of intelligence, executive functioning, and ToM tasks.

Results:  The bipolar disorder patient group as a whole and all three clinical subgroups were impaired on all measures of ToM relative to controls, but did not differ from each other in most ToM scores. Patients’ poorer performance on executive tasks did not fully explain ToM differences between patients and controls, suggesting a partially selective ToM deficit in BPD.

Conclusions:  Patients with BPD are impaired in ToM, partially independent of other cognitive dysfunctions and current mood.
The association of weight gain with mood symptoms and functional outcomes following a first manic episode: prospective 12‐month data from the Systematic Treatment Optimization Program for Early Mania (STOP‐EM)
Authors: Bond David J , Kunz Mauricio , Torres Ivan J , Lam Raymond W , Yatham Lakshmi N
Published: September 2010

Bond DJ, Kunz M, Torres IJ, Lam RW, Yatham LN. The association of weight gain with mood symptoms and functional outcomes following a first manic episode: prospective 12‐month data from the Systematic Treatment Optimization Program for Early Mania (STOP‐EM). Bipolar Disord 2010: 12: 616–626. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Up to 75% of patients with bipolar I disorder (BD‐I) are overweight or obese. Obesity is associated with an increased liability for mood episodes in patients with established BD‐I, but data from early in the illness are lacking. Obesity in the general population is also consistently associated with functional impairment, but the relationship between weight gain and functional outcomes in BD‐I has received little attention.

Methods:  We measured rates of clinically significant weight gain (CSWG), defined as gaining ≥ 7% of baseline weight, over 12 months in 46 patients with BD‐I who recently recovered from their first manic episode. We compared patients with and without CSWG for (i) the amount of time spent with mood symptoms, assessed using standard clinical rating scales and National Institute of Mental Health Life Charts, and (ii) functioning at 12 months, measured using the Multidimensional Scale of Independent Functioning (MSIF).

Results:  A total of 41% of patients (n = 19) experienced CSWG by 12 months. We did not detect an association between CSWG and the number of days with mood symptoms. Patients with CSWG had significantly poorer 12‐month global functioning than those without CSWG [MSIF score = 2.26 (SD = 1.24) versus 1.74 (0.98); p = 0.011]. Functional impairment was independent of recent or current mood symptoms, which were entered as covariates in our analyses.

Conclusions:  Weight gain may be an overlooked, but potentially modifiable, cause of functional impairment in BD‐I. Clinicians should consider the possibility of weight gain when making the earliest treatment decisions in BD‐I.
Self‐esteem in remitted bipolar disorder patients: a meta‐analysis
Authors: Nilsson Kristine Kahr , Jørgensen Carsten René , Craig Tom K J , Straarup Krista Nielsen , Licht Rasmus W
Published: September 2010

Nilsson KK, Jørgensen CR, Craig TKJ, Straarup KN, Licht RW. Self‐esteem in remitted bipolar disorder patients: a meta‐analysis.  Bipolar Disord 2010: 12: 585–592. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Low self‐esteem has been found to be a risk factor for depression in major depressive disorder (MDD). In contrast, the role of self‐esteem in bipolar disorder (BD) is still uncertain. In order to examine the characteristics of self‐esteem in BD, we synthesized studies comparing self‐esteem in BD patients with self‐esteem in MDD patients and in normal controls.

Methods:  Database searches and identification of studies were conducted by two of the authors independently. Remission of BD and MDD was a major selection criterion. The results were generated through meta‐analyses.

Results:  Random‐effects models of 19 between‐group comparisons (N = 1,838) suggested that the self‐esteem of remitted BD patients was significantly lower than that of normal controls (Cohen’s d = −0.83), while significantly higher than that of remitted MDD patients (Cohen’s d = 0.54). Fail‐safe numbers and tests for funnel plot asymmetry indicated that the results were robust and unlikely to reflect publication biases. Additional studies indicated that self‐esteem may take a fluctuating course during remission of BD.

Conclusions:  By revealing that BD patients do experience low self‐esteem, the findings implicate a need for further understanding the causes and therapeutic impact of such abnormality in BD.
Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder
Authors: Kulkarni Sandip , Jain Sanjeev , Janardhan Reddy YC , Kumar Keshav J , Kandavel Thennarasu
Published: September 2010

Kulkarni S, Jain S, Janardhan Reddy YC, Kumar KJ, Kandavel T. Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder. Bipolar Disord 2010: 12: 647–656. © 2010 The Authors.  Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls.

Methods:  We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education.

Results:  Unaffected siblings performed poorly on the Tower of London test (TOL), the Rey’s auditory verbal learning test (RAVLT), and the Rey’s complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001).

Conclusions:  Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.
The common adolescent bipolar phenotype shows positive biases in emotional processing
Authors: Rock Philippa L , Goodwin Guy M , Harmer Catherine J
Published: September 2010

Rock PL, Goodwin GM, Harmer CJ. The common adolescent bipolar phenotype shows positive biases in emotional processing. Bipolar Disord 2010: 12: 606–615. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Bipolar disorder is associated with abnormalities in emotional processing that persist into periods of remission. However, studies of euthymic bipolar disorder patients may be confounded by the experience of mood episodes and medication. We therefore assessed an adolescent group for vulnerability markers associated with the bipolar phenotype.

Methods:  The Mood Disorder Questionnaire (MDQ) is a screening tool for bipolar disorder that targets mood‐elevation symptoms. We selected 32 high‐scoring students (≥ 7 symptoms) with the adolescent bipolar phenotype and 30 low‐scoring controls (≤ 3 symptoms) and screened them with the Mini International Neuropsychiatric Interview–Plus for bipolar disorder and other psychiatric disorders. We investigated emotional processing by assessing facial expression recognition, emotional memory, emotion‐potentiated startle, and a dot‐probe task.

Results:  Of the high‐MDQ participants, 12 were in remission from bipolar disorder defined by DSM‐IV‐TR and interview (bipolar II disorder/bipolar disorder not otherwise specified) and 3 from major depressive disorder. High‐MDQ participants had higher levels of neuroticism, low mood, and lifetime anxiety comorbidity and alcohol dependence compared with low‐MDQ participants. The high‐MDQ group showed facilitated recognition of surprised and neutral facial expressions and enhanced processing of positive versus negative information in emotional recognition memory and emotion‐potentiated startle. There were no effects on emotional categorisation/recall memory or attentional bias in the dot‐probe task.

Conclusions:  These results suggest that students with the common adolescent bipolar phenotype show positive emotional processing biases despite increased levels of neuroticism, low mood, and anxiety. Such effects may represent a psychological vulnerability marker associated with the bipolar phenotype.
Cleavage and gastrulation in the Kuruma shrimp Penaeus (Marsupenaeus) japonicus (Bate): A revised cell lineage and identification of a presumptive germ cell marker
Authors: Pawlak John B. , Sellars Melony J. , Wood Andrew , Hertzler Philip L.
Published: September 2010

A previous study suggested that mesendoderm (ME) cell arrest occurred at the 64‐cell stage and a ring of eight presumptive naupliar mesoderm cells or crown cells surrounded the blastopore in the Kuruma shrimp Penaeus (Marsupenaeus) japonicus. Since this varied from the pattern observed in other penaeoidean shrimp, cleavage and gastrulation was re‐examined in P. japonicus using the nucleic acid stain Sytox Green and confocal microscopy. In contrast to the earlier study, cleavage and gastrulation followed the pattern observed in other penaeoidean shrimp. The ME cells arrested at the 32‐cell stage, ingressed into the blastocoel, and resumed division after a three cell cycle delay. Nine naupliar mesoderm or crown cells surrounded the blastopore and their descendants invaginated during gastrulation. An intracellular body (ICB) was detected by Sytox Green and SYTO RNASelect staining to be segregated to one ME cell in P. japonicus, as described previously in Penaeus monodon. Staining of the ICB was eliminated by pre‐treatment with RNase but not DNase. The ICB was also found in two other penaeoidean shrimp, Penaeus vannamei (Family Penaeidae) and Sicyonia ingentis (Family Sicyoniidae). The results support the hypothesis that the ICB is a germ granule found in the Dendrobranchiata.
Delivery of small interfering RNA with a synthetic collagen poly(Pro‐Hyp‐Gly) for gene silencing in vitro and in vivo
Authors: Adachi Taro , Kawakami Emi , Ishimaru Naozumi , Ochiya Takahiro , Hayashi Yoshio , Ohuchi Hideyo , Tanihara Masao , Tanaka Eiji , Noji Sumihare
Published: September 2010

Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro‐Hyp‐Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long‐term gene silencing in vivo. We found that the SYCOL‐mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti‐luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL‐based non‐viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro.
Steps towards a centralized nervous system in basal bilaterians: Insights from neurogenesis of the acoelSymsagittifera roscoffensis
Authors: Semmler Henrike , Chiodin Marta , Bailly Xavier , Martinez Pedro , Wanninger Andreas
Published: September 2010

Due to its proposed basal position in the bilaterian Tree of Life, Acoela may hold the key to our understanding of the evolution of a number of bodyplan features including the central nervous system. In order to contribute novel data to this discussion we investigated the distribution of α‐tubulin and the neurotransmitters serotonin and RFamide in juveniles and adults of the sagittiferidSymsagittifera roscoffensis. In addition, we present the expression pattern of the neuropatterning geneSoxB1. Adults and juveniles exhibit six serotonergic longitudinal neurite bundles and an anterior concentration of serotonergic sensory cells. While juveniles show an “orthogon‐like” arrangement of longitudinal neurite bundles along the anterior‐posterior axis, it appears more diffuse in the posterior region of adults. Commissures between the six neurite bundles are present only in the anterior body region of adults, while irregularly distributed individual neurites, often interconnected by serotonergic nerve cells, are found in the posterior region. Anti‐RFamide staining shows numerous individual neurites around the statocyst. The orthogon‐like nervous system ofS. roscoffensisis confirmed by α‐tubulin immunoreactivity. In the region of highest neurotransmitter density (i.e., anterior), the HMG‐box geneSrSoxB1, a transcription factor known to be involved in neurogenesis in other bilaterians, is expressed in juvenile specimens. Accordingly,SoxB1expression inS. roscoffensisfollows the typical pattern of higher bilaterians that have a brain. Thus, our data support the notion that Urbilateria already had the genetic toolkit required to form brain‐like neural structures, but that its morphological degree of neural concentration was still low.
Myofibroblasts protect myoblasts from intrinsic apoptosis associated with differentiation via β1 integrin‐PI3K/Akt pathway
Authors: Zhang Yu , Li Hai , Lian Zhengxing , Li Ning
Published: September 2010

Skeletal myoblasts withdrawing from cell cycle is a prerequisite for myodifferentiation, while upon proliferation/differentiation transformation, a large portion of myoblasts will undergo apoptosis. Skeletal fibroblasts, residing in muscle tissue both during and post myogenesis, have been proofed to play pivotal roles in muscle development, while their effect on myoblast apoptosis being coincident with differentiation has not been reported. Using a membrane insert co‐culture system, we studied it and found that the mitochondrial pathway played a crucial role in myoblast apoptosis during differentiation, and fibroblasts promoted not only cell cycle withdrawal but also myoblast survival in a paracrine fashion, which was coupled with upregulations of β1 integrin, phosphorylated Akt and anti‐apoptotic protein Bcl2. To determine the effect of β1 integrin in the process, we transfected myoblasts with siRNA specific for β1 integrin before co‐culture and found that β1 integrin knockdown abolished anti‐apoptotic ability of myoblasts and inhibited Akt activation and Bcl2 expression. Blockage of PI3K/Akt pathway with wortmannin also seriously impaired the protective effect of fibroblasts on myoblasts and fibroblast‐induced Bcl2 expression. The data demonstrated that fibroblasts protected myoblasts from intrinsic apoptosis associated with differentiation, and β1 integrin‐PI3K/Akt pathway activation was required for the process.
An alternative 1‐day smear microscopy protocol for the diagnosis of pulmonary tuberculosis
Authors: RAWAT Jagdish , BISWAS Debasis , SINDHWANI Girish , MASIH Victor
Published: September 2010

Background and objective:  This study was undertaken to assess the feasibility of diagnosing pulmonary tuberculosis (PTB) by collecting two sputum samples on a single day (1‐day protocol), and to compare this protocol with the national policy of collecting two samples on consecutive days (2‐day protocol).

Methods:  A total of 513 individuals with cough that had persisted for more than 2 weeks were screened for PTB by collection of three sputum samples: a spot sample on the first day, a sample collected 1 h after the first sample and a sample collected the following morning. For the 2‐day protocol, the diagnostic performance of the first and third samples was considered, while the 1‐day protocol was evaluated using the two samples collected on the first day. Staining and microscopy were performed in a blinded manner by two different technicians.

Results:  Of the 513 patients, 40 defaulted on the second day. Of the total number of patients recruited, 124 (24.2%) were smear‐positive. Using the 2‐day protocol, 121 patients (97.6%) were identified as smear‐positive, whereas with the 1‐day protocol 118 patients (95.2%) were identified as smear‐positive (P = 0.3). Of the patients who defaulted, seven (17.5%) were smear‐positive. Comparison of the variation in results indicated that collection of a morning sample on the second day provided no significant benefit over collection of a second spot sample on the first day.

Conclusions:  As the 2‐day protocol did not show a statistically significant difference in diagnostic performance compared with the 1‐day protocol, the latter may be adopted as an alternative protocol, particularly for patients who are more likely to default.
High MW hyaluronan inhibits smoke inhalation‐induced lung injury and improves survival
Authors: HUANG Pei‐ming , SYRKINA Olga , YU Lunyin , DEDAJ Rejmon , ZHAO Hang , SHIEDLIN Aviva , LIU Yung‐yang , GARG Hari , QUINN Deborah A. , HALES Charles A.
Published: September 2010

Background and objective:  High MW hyaluronan (HMW HA) as opposed to low MW hyaluronan (LMW HA) has been shown to have anti‐inflammatory and anti‐apoptotic effects. We hypothesized that treatment with HMW HA would block smoke inhalation lung injury by inhibiting smoke‐induced lung inflammation and airway epithelial cell apoptosis.

Methods:  Anesthetized, intubated male rats were randomly allocated to either control or smoke inhalation injury groups. Rats were treated with 3‐mL subcutaneous normal saline solution (sham) or LMW HA (35 kDa) or HMW HA (1600 kDa) 18 h before exposure to 15 min of cotton smoke (n = 5 each). Rats were also treated post smoke inhalation with 1600 kDa HA by intra‐peritoneal injection (3 mL) or intra‐tracheal nebulization (200 µL). Lung neutrophil infiltration, airway apoptosis, airway mucous plugging and lung injury were assessed 4 h after smoke inhalation injury.

Results:  Rats pretreated with 1600 kDa HA had significantly less smoke‐induced neutrophil infiltration, lung oedema, airway apoptosis and mucous plugging. Pretreatment with 35 kDa HA, in contrast, increased smoke‐induced neutrophil infiltration and lung injury score. Intra‐tracheal administration of a single dose 1600 kDa HA, but not intra‐peritoneal injection, significantly improved survival post smoke inhalation.

Conclusions:  High MW hyaluronan (1600 kDa) may prove to be a beneficial therapy for smoke inhalation through inhibition of smoke‐induced inflammation, lung oedema, airway epithelial cell apoptosis and airway mucous plugging.
Setting up a specialist pleural disease service
Authors: HOOPER Clare E. , LEE Y.C. Gary , MASKELL Nick A.
Published: September 2010

The past decade has seen a dramatic rise in clinical and research interests in pleural disease in parallel with rising incidences of pleural cancers and infection worldwide. Development of specialist pleural services can streamline patient diagnosis and therapy, reduce health‐care resource consumption, improve procedural training and safety and facilitate clinical research. Pleural ultrasound, pleuroscopy, indwelling pleural catheter services and pleural procedural education programmes for junior staff are important elements of most specialist pleural units. An integrated service including radiology, pathology, oncology and thoracic surgery input is pivotal to success. Establishing funding support and referral sources are the common initial hurdles. This article provides an overview of the need for specialist pleural disease units, the essential elements required and the likely challenges encountered in setting a service up.
Upfront transection and subsequent ligation of the dorsal vein complex during laparoscopic radical prostatectomy
Authors: Sasaki Hiroshi , Miki Jun , Kimura Takahiro , Yamamoto Yoshinori , Koike Yusuke , Miki Kenta , Egawa Shin
Published: September 2010

Laparoscopic radical prostatectomy for localized prostate cancer offers several advantages, including creation of a pneumoperitoneum that results in less blood loss than is seen with the corresponding open procedure. Transection of the deep dorsal vein complex remains among the most challenging aspects, however. Safe and secure completion of this procedure is important to minimize blood loss and maximize the chance of cure. Liberal use of coagulation for hemostasis at the dorsal vein complex (DVC) risks thermal damage to the sphincteric muscle. DVC ligation before transection, though commonly performed, can cause loss of some sphincteric fibers and potentially result in delayed recovery of urinary continence. Furthermore, ligation may at times prove difficult, especially in obese patients with a short and broad DVC, a large prostate gland, and a narrow pelvis. The presence of prominent pubic tubercles may further increase the difficulty. We have found that bleeding from the DVC is easily controlled without suture ligation through a combination of a modest pneumoperitoneum with pinpoint coagulation of one or two small arteries that are consistently found in the superficial layer of the complex. Precise, even‐level transection is possible under direct vision with no more than modest blood loss. A stitch in a Z‐shaped fashion is then applied to the entire transected stump of the DVC. This procedure is simple and easily performed, even by those with limited experience. Here we provide an overview of our current technique.
Cervical cancer screening in north east Thailand using the visual inspection with acetic acid (VIA) test and its relationship to high‐risk human papillomavirus (HR‐HPV) status
Authors: Ekalaksananan Tipaya , Pientong Chamsai , Thinkhamrop Jedsada , Kongyingyoes Bunkerd , Evans Mark F. , Chaiwongkot Arkom
Published: September 2010

Aim:  This study investigated the utility of visual inspection with acetic acid (VIA) as a method for cervical cancer screening in Thailand and examined the relationship of VIA to high‐risk human papillomavirus (HR‐HPV) status.

Methods:  Cervical cells were collected from 160 patients receiving a Pap smear. VIA was performed on the cervix of the patients by application of 5% acetic acid. HPV screening of DNA extracted from cytology samples was performed by PCR using the GP5+/6+ primer system followed by reverse line blot hybridization genotyping.

Results:  The majority (96.9%) of the patients were diagnosed with normal or inflammatory cytologic changes. 32.8% of normal cytology and 42.0% of inflammation cases showed positive acetowhite staining. 3.1%, 38.1% and 42.5% of subjects were positive for an abnormal Pap test, VIA test, and HPV DNA, respectively. VIA demonstrated 50% sensitivity and 66.7% specificity for abnormal histology with PPV and NPV values of 50% and 66.7%, respectively, whereas HPV DNA test showed 100% sensitivity. HPV16 was the most common (54.4%) and HR‐HPV was detected in 36.3% of all cases. 48.5% of HR‐HPV positive and 36.8% of HR‐HPV negative cervices stained with acetowhite following the VIA test.

Conclusion:  The VIA test is a simple method for cervical cancer screening; however, a significant proportion of patients with normal or inflammatory cytology were positive by this test. Further, HR‐HPV in women without acetowhite staining was demonstrated. Therefore, some form of HR‐HPV detection test may be required for combination with cervical cell screening even in low‐resource nations.
The systematics of Zoochlorella revisited employing an integrative approach
Authors: Pröschold Thomas , Darienko Tatyana , Silva Paul C. , Reisser Werner , Krienitz Lothar
Published: September 2010

Symbiosis of green algae with protozoa and invertebrates has been studied for more than 100 years. Endosymbiotic green algae are widely distributed in ciliates (e.g. Paramecium, Stentor, Climacostomum, Coleps, Euplotes), heliozoa (e.g. Acanthocystis) and invertebrates (e.g. Hydra, Spongilla), and have traditionally been identified as named or unnamed species of Chlorella Beij. or Zoochlorella K. Brandt or referred to as Chlorella‐like algae or zoochlorellae. We studied 17 strains of endosymbionts isolated from various hosts and geographical localities using an integrative approach (nuclear encoded small subunit and internal transcribed spacer regions of rRNA gene sequences including their secondary structures, morphology, physiology and virus sensitivity). Phylogenetic analyses have revealed them to be polyphyletic. The strains examined belong to five independent clades within the Trebouxiophyceae (Choricystis‐, Elliptochloris‐, Auxenochlorella‐ and Chlorella‐clades) and Chlorophyceae (Scenedesmus‐clade). The most studied host organism, Paramecium bursaria, harbours endosymbionts representing at least five different species. On the basis of our results, we propose a taxonomic revision of endosymbiotic ‘Chlorella’‐like green algae. Zoochlorella conductrix K. Brandt is transferred to Micractinium Fresen. and Zoochlorella parasitica K. Brandt to Choricystis (Skuja) Fott. It was shown that Choricystis minor (Skuja) Fott, the generitype, is a later heterotypic synonym of Choricystis parasitica (K. Brandt) comb. nov. A new species, Chlorella heliozoae, is proposed to accommodate the endosymbiont of Acanthocystis turfacea.
Optimizing the offloading properties of the total contact cast for plantar foot ulceration
Authors: Burns J. , Begg L.
Published: September 2010

Diabet. Med. 28, 179–185 (2011)

Aims  Total contact casting is the gold standard offloading treatment for plantar foot ulceration, but the optimal technique and preferred materials are poorly defined and not readily prescribed in daily practice. We investigated in‐cast pressure offloading in two types of total contact casts vs. a control condition, in patients with plantar foot ulceration.

Methods  In‐cast walking pressures were collected using the Novel Pedar‐X system in 20 participants with a plantar foot ulcer in two types of total contact casts: a conventional total contact cast and a cushion‐modified total contact cast incorporating an inlay of 6 mm slow‐rebound cellular urethane and 6 mm soft cellular urethane. Casts were compared with a canvas cast shoe to establish baseline pressure values.

Results  Compared with the cast shoe, the conventional total contact cast significantly reduced peak pressure at the ulcer site by 44%, mean pressure by 47% and pressure–time integral by 37% (P < 0.001), while the cushion‐modified total contact cast significantly reduced peak pressure at the ulcer site by 70%, mean pressure by 60% and pressure–time integral by 69% (P < 0.001). Plantar pressure across the entire foot and each region of the foot was also reduced with the conventional total contact cast compared with the cast shoe, and further reduced by the cushion‐modified total contact cast (P < 0.05).

Conclusions  The offloading properties of the total contact cast can be enhanced with a 12 mm cellular urethane cushion modification. Further well‐designed trials are required to understand and validate this cast technique and to demonstrate healing rates and safety in different patient populations.
Increased risk of cardiovascular disease in Type 1 diabetes: arterial exposure to remnant lipoproteins leads to enhanced deposition of cholesterol and binding to glycated extracellular matrix proteoglycans
Authors: Mangat R. , Su J. W. , Lambert J. E. , Clandinin M. T. , Wang Y. , Uwiera R. R. , Forbes J. M. , Vine D. F. , Cooper M. E. , Mamo J. C. , Proctor S. D.
Published: September 2010

Diabet. Med. 28, 61–72 (2011)

Aims  To determine fasting and postprandial metabolism of apolipoprotein B48 (apoB48) remnant lipoproteins in subjects with Type 1 diabetes and the relationship to progressive cardiovascular disease, and to investigate the impact of remnant lipoprotein cholesterol accumulation associated with arterial wall biglycan using a rodent model of Type 1 diabetes.

Methods  Normolipidaemic subjects (n = 9) with long‐standing Type 1 diabetes (and advanced cardiovascular disease) and seven healthy control subjects were studied. Fasting and postprandial apoB48 concentration was determined following a sequential meal challenge. A rodent model of streptozotocin‐induced diabetes was used to investigate the ex vivo retention of fluorescent‐conjugated remnants. Binding of remnant lipoproteins to human recombinant biglycan was assessed in vitro.

Results  A significantly higher concentration of fasting plasma apoB48 remnants was observed in patients with Type 1 diabetes compared with control subjects. Patients with Type 1 diabetes exhibited a greater total plasma apoB48 area under the curve (AUC) and an increased incremental AUC following a second sequential meal compared with control subjects. The arterial retention of remnants ex vivo and associated cholesterol was increased sevenfold in Type 1 diabetes rats relative to controls. Remnants were shown to bind with significant affinity to human biglycan in vitro and a further 2.3‐fold increased binding capacity was observed with glycated biglycan. Remnants were shown to colocalize with both arterial biglycan and glycated matrix proteins in the Type 1 diabetes rodent model.

Conclusion  Impaired metabolism of remnant lipoproteins associated with enhanced binding to proteoglycans appears to contribute to the arterial cholesterol deposition in Type 1 diabetes. Our findings support the hypothesis that impaired remnant metabolism may contribute to accelerated progression of atherosclerosis in the hyperglycaemic and insulin‐deficient state.
Genomic expression profiles of blood and placenta reveal significant immune‐related pathways and categories in Chinese women with gestational diabetes mellitus
Authors: Zhao Y.‐H. , Wang D.‐P. , Zhang L.‐L. , Zhang F. , Wang D.‐M. , Zhang W.‐Y.
Published: September 2010

Diabet. Med. 28, 237–246 (2011)

Aims  We used microarray as well as quantitative real‐time PCR (Q‐RT‐PCR) validation to define the genes and/or pathways that are involved in gestational diabetes mellitus (GDM) in patients of Chinese ethnicity.

Methods  We used the Illumina microarray platform to obtain comprehensive gene expression profiles of blood and placenta taken from GDM‐positive and GDM‐negative women.

Results  We found 5197 genes in blood and 243 genes in placenta, which had significantly altered expression profiles attributable to GDM. Genes previously known to have altered expressions as a result of GDM (such as TNF, IL1B, LEP, IFNG and HLA‐G) were also validated. In addition, we identified a number of previously unreported genes: VAV3, PTPN6, CD48 and IL15, which had expression patterns that were significantly different from our GDM and control samples, as determined by both microarray and Q‐RT‐PCR assays. Two significant pathways were identified as GDM‐associated pathways through integrated functional annotation. These pathways were: ‘Natural killer cell mediated cytotoxicity’ in blood and ‘Cytokine–cytokine receptor interaction’ in placenta. Furthermore, despite differences between blood and placenta in terms of the quantity of gene expression, we nonetheless observed similar functional distributions in both tissues in terms of immune‐related genes.

Conclusions  These newly identified key genes and pathways may provide valuable information about the pathogenesis of GDM and can be used to improve early diagnosis, prevention, medication design and clinical treatment.
Association of insulin sensitivity to lipids across the lifespan in people with Type 1 diabetes
Authors: Maahs D. M. , Nadeau K. , Snell‐Bergeon J. K. , Schauer I. , Bergman B. , West N. A. , Rewers M. , Daniels S. R. , Ogden L. G. , Hamman R. F. , Dabelea D.
Published: September 2010

Diabet. Med. 28, 148–155 (2011)

Aims  Insulin resistance and dyslipidaemia both increase cardiovascular risk in Type 1 diabetes. However, little data exist on the associations of insulin resistance to lipids in Type 1 diabetes. Our objective was to explore the associations between insulin resistance (assessed by glucose infusion rate) and lipids in people with Type 1 diabetes and determine whether adiposity and/or average glycaemia influence these associations.

Methods  Hyperinsulinaemic–euglycaemic clamp studies were performed in 60 subjects with Type 1 diabetes aged 12–19 years (age 15 ± 2 years, 57% female, duration of diabetes 6.3 ± 3.8 years, HbA1c 8.6 ± 1.5%, IFCC = 70 mmol/mol) and 40 subjects with Type 1 diabetes aged 27–61 years (age 45 ± 9 years, 53% female, duration of diabetes 23 ± 8 years, HbA1c 7.5 ± 0.9%, IFCC = 58 mmol/mol). Multiple linear regression models were fit to examine the association between glucose infusion rate and fasting lipid levels with adjustment for possible confounders.

Results  Lower glucose infusion rate was significantly associated with lower levels of HDL cholesterol in youths with Type 1 diabetes and with higher levels of triglycerides and higher triglyceride/HDL ratio in both youths and adults. The magnitude of the associations between glucose infusion rate and lipid levels translate into interquartile differences of 0.098 mmol/l for HDL cholesterol, 0.17 mmol/l for triglycerides and 1.06 for triglycerides/HDL in the adolescents and 0.20 mmol/l for triglycerides and 1.01 for triglycerides/HDL in the adults. The associations were attenuated and no longer statistically significant by adjustment for adiposity among adults, while adjustment for HbA1c had a small effect in youths and adults.

Conclusions  Lower insulin sensitivity is associated with a more atherogenic lipid profile in both youths and adults with Type 1 diabetes.
Impaired glucose tolerance, but not impaired fasting glucose, is a risk factor for early‐stage atherosclerosis
Authors: Ando T. , Okada S. , Niijima Y. , Hashimoto K. , Shimizu H. , Tsuchiya T. , Yamada M. , Ohshima K. , Mori M. , Ono K.
Published: September 2010

Diabet. Med. 27, 1430–1435 (2010)

Aims  The study aimed to investigate early‐stage atherosclerosis in patients with impaired fasting glucose compared with patients with impaired glucose tolerance.

Methods  Body mass index, systolic blood pressure, fasting plasma glucose, lipid variables, ankle–brachial pressure index and brachial–ankle pulse wave velocity were measured in 2842 subjects from Takasaki city located approximately 100 km north of Tokyo in Japan. The subjects were divided into the following five groups based on a 75‐g oral glucose tolerance test: (i) normal fasting plasma glucose/normal glucose tolerance group, (ii) impaired fasting glucose group, (iii) impaired glucose tolerance group, (iv) combined glucose intolerance group and (v) diabetic glucose intolerance group.

Results  In comparison with fasting plasma glucose levels (r = 0.269, P < 0.0001), 2‐h post‐challenge glucose levels were more closely correlated with pulse wave velocity values (r = 0.300, P < 0.0001). The groups with impaired glucose tolerance, combined glucose intolerance and diabetic glucose intolerance had significantly higher pulse wave velocity values compared with the groups with normal glucose tolerance and impaired fasting glucose. Multiple regression analyses showed an independent association of age, systolic blood pressures, total cholesterol, fasting and 2h plasma glucose with pulsewave velocityvalues. Furthermore, pulse wave velocity was not significantly correlated with fasting plasma glucose, but was correlated with increased 2h plasma glucose.

Conclusions  Groups with impaired glucose tolerance and combined glucose intolerance had significantly higher brachio‐ankle pulse wave velocity values compared with the group with normal glucose tolerance. Although the group with impaired fasting glucose showed a marginal increase in pulse wave velocity values compared with the group with normal glucose tolerance, the difference was not significant. Thus impaired glucose tolerance, but not impaired fasting glucose, is a risk factor for early‐stage atherosclerosis.
Large artery biomechanics and diastolic dysfunctionin patients with Type 2 diabetes
Authors: Soldatos G. , Jandeleit‐Dahm K. , Thomson H. , Formosa M. , D’orsa K. , Calkin A. C. , Cooper M. E. , Ahimastos A. A. , Kingwell B. A.
Published: September 2010

Diabet. Med. 28, 54–60 (2011)

Aims  To comprehensively characterize large artery biomechanical properties and examine their relationship to cardiac function in patients with Type 2 diabetes mellitus (DM).

Methods  Fifty‐five individuals with Type 2 DM were compared with 66 age‐ and sex‐matched healthy control subjects. Arterial biomechanical properties were assessed by systemic arterial compliance (SAC; two‐element Windkessel model), carotid–femoral pulse wave velocity (PWVc‐f), femoral–dorsalis pedis pulse wave velocity (PWVf‐d) and carotid augmentation index. Cardiac structure and function were assessed by echocardiography.

Results  Individuals with Type 2 DM had lower SAC and higher PWVc‐f when compared with the healthy population. The PWVc‐f was significantly lower than the PWVf‐d in control individuals, but this difference was not evident in individuals with Type 2 DM due to higher PWVc‐f. Augmentation index was similar in both groups, but the time to the first systolic inflection (time to reflection) was shorter in the individuals with Type 2 DM. The individuals with Type 2 DM had a greater prevalence of diastolic abnormalities when compared with the control group. Arterial stiffness indices, including SAC and pulse pressure, correlated with left ventricular filling pressure (defined as peak velocity during early diastolic filling divided by the velocity of movement of the mitral valve annulus in early diastole; r= −0.33 and 0.36 respectively.

Conclusions  Patients with Type 2 DM on standard medication showed preferential stiffening of the large central arteries. However, carotid augmentation index was not different between the two groups and is therefore not a reliable indicator of large artery stiffening in this patient group. Diastolic dysfunction, present in a significant proportion of this population with Type 2 DM, was closely associated with arterial stiffening, suggesting a common aetiology.