bluuebunny/crossref_metadata_2025 huggingface dataset:
Fighting parasites and predators: How to deal with multiple threats?
Authors: Hesse Olivia , Engelbrecht Wolfgang , Laforsch Christian , Wolinska Justyna
Published: July 2012

Background

Although inducible defences have been studied extensively, only little is known about how the presence of parasites might interfere with these anti-predator adaptations. Both parasites and predators are important factors shaping community structure and species composition of ecosystems. Here, we simultaneously exposedDaphnia magnato predator cues (released by the tadpole shrimp,Triops, or by a fish) and spores of the yeast parasiteMetschnikowiasp. to determine how life history and morphological inducible defences against these two contrasting types of predators are affected by infection.

Results

The parasite suppressed someTriops-induced defences:Daphnialost the ability to produce a greater number of larger offspring, a life-history adaptation toTriopspredation. In contrast, the parasite did not suppress inducible defences against fish: induction (resulting in smaller body length of the mothers as well as of their offspring) and infection acted additively on the measured traits. Thus, fish-induced defences may be less costly than inducible defences against small invertebrate predators likeTriops; the latter defences could no longer be expressed when the host had already invested in fighting off the parasite.

Conclusions

In summary, our study suggests that as specific inducible defences differ in their costs, some might be suppressed if a target prey is additionally infected. Therefore, adding parasite pressure to predator–prey systems can help to elucidate the costs of inducible defences.
Effect of Alpinia zerumbet components on antioxidant and skin diseases-related enzymes
Authors: Chompoo Jamnian , Upadhyay Atul , Fukuta Masakazu , Tawata Shinkichi
Published: July 2012

Background

The skin is chronically exposed to endogenous and environmental pro-oxidant agents, leading to the harmful generation of reactive oxygen species. Antioxidant is vital substances which possess the ability to protect the body from damage cause by free radicals induce oxidative stress. Alpinia zerumbet, a traditionally important economic plant in Okinawa, contains several interesting bioactive constituents and possesses health promoting properties. In this regard, we carried out to test the inhibitory effect of crude extracts and isolated compounds from A. zerumbet on antioxidant and skin diseases-related enzymes.

Methods

The antioxidant activities were examined by DPPH, ABTS and PMS-NADH radical scavenging. Collagenase, elastase, hyaluronidase and tyrosinase were designed for enzymatic activities to investigate the inhibitory properties of test samples using a continuous spectrophotometric assay. The inhibitory capacity of test samples was presented at half maximal inhibitory concentration (IC50).

Results

The results showed that aqueous extract of the rhizome was found to have greater inhibitory effects than the others on both of antioxidant and skin diseases-related enzymes. Furthermore, 5,6-dehydrokawain (DK), dihydro-5,6-dehydrokawain (DDK) and 8(17),12-labdadiene-15,16-dial (labdadiene), isolated from rhizome, were tested for antioxidant and enzyme inhibitions. We found that DK showed higher inhibitory activities on DPPH, ABTS and PMS-NADH scavenging (IC50 = 122.14 ± 1.40, 110.08 ± 3.34 and 127.78 ± 4.75 μg/ml, respectively). It also had stronger inhibitory activities against collagenase, elastase, hyaluronidase and tyrosinase (IC50 = 24.93 ± 0.97, 19.41 ± 0.61, 19.48 ± 0.24 and 76.67 ± 0.50 μg/ml, respectively) than DDK and labdadiene.

Conclusion

Our results indicate that the rhizome aqueous extract proved to be the source of bioactive compounds against enzymes responsible for causing skin diseases. Moreover, DK could be used as a potent inhibitor and be further exploited to be used in anti-skin disease formulations.
Impact of alternative reimbursement strategies in the new cooperative medical scheme on caesarean delivery rates: a mixed-method study in rural China
Authors: Huang Kun , Tao Fangbiao , Bogg Lennart , Tang Shenglan
Published: July 2012

Background

The rate of caesarean delivery (CD) in rural China has been rapidly increasing in recent decades. Due to the exorbitant costs associated with CD, paying for this expensive procedure is often a great challenge for the majority of rural families. Since 2003, the Chinese government has re-established the New Cooperative Medical Scheme (NCMS), aimed to improve the access of essential healthcare to rural residents and reduce financial burden owing to high out of pocket payments. This paper seeks to test the hypothesis that NCMS may provide service users and providers with financial incentives to select CD. It also assesses the effect of different health insurance reimbursement strategies of NCMS on CD rates in rural China.

Methods

Mixed quantitative and qualitative methods were adopted for data collection. Two cross-sectional household surveys were conducted with women having babies delivered in 2006 and 2009; 2326 and 1515 women, respectively, from the study sites were interviewed using structured questionnaires, to collect demographic and socio-economic data, maternal and child care characteristics and health-related expenditures. Focus group discussions (FGDs) and in-depth key informant interviews (KIIs) were undertaken with policy makers, health managers, providers and mothers to understand their perceptions of the influence of NCMS on the choices of delivery mode.

Results

The CD rates in the two study counties were 46.0 percent and 64.7 percent in 2006, increasing to 63.6 percent and 82.1 percent, respectively, in 2009. The study found that decisions on the selection of CD largely came from the pregnant women. Logistic regression analysis, after adjusting for socio-economic, maternal and fetal characteristics, did not indicate a significant effect of either proportional reimbursement or fixed amount reimbursement on the choice of CD for both study years. Interviews with stakeholders reflected that different reimbursable rates for CD and vaginal deliveries did not have a significant effect on controlling the rising CD rate in the study countries.

Conclusion

NCMS reimbursement strategies adopted in the study counties of China did not have a significant effect on the selection of CD for baby deliveries. The rapid rise of the CD rates of rural China has remained a serious issue. Other effective measures, such as health education to increase awareness of mothers' knowledge, and improving training of health staff in evidence-based delivery care, maybe could do more to promote rational baby delivery in rural China.
Moloney murine leukemia virus glyco-gag facilitates xenotropic murine leukemia virus-related virus replication through human APOBEC3-independent mechanisms
Authors: Nitta Takayuki , Lee Sangouk , Ha Dat , Arias Maribel , Kozak Christine A , Fan Hung
Published: July 2012

Background

One of the unique features of gammaretroviruses is that they contain an additional extended form of Gag, glyco-gag, which initiates in the leader sequence. MuLV glyco-gag, gPr80Gag, promotes retrovirus replication and disease progression. Although virtually all infectious MuLVs encode glyco-gag, XMRV (xenotropic murine leukemia virus-related virus) lacks the classical gPr80Gag sequence. We examined XMRV to determine if its leader sequence contains glyco-gag activity, whether the presence of conventional gPr80Gag affects replication of XMRV, and we describe the evolution of glyco-gag-deficient MuLVs in Mus.

Results

We introduced several mutations disrupting two putative but noncanonical glyco-gag proteins in the leader sequence region in XMRV and found that those mutations did not affect virus release nor susceptibility to the antiviral activity of hA3G (human APOBEC3G). A chimeric XMRV encoding the Moloney MuLV (M-MuLV) leader sequence (MXMRV) demonstrated that M-MuLV glyco-gag facilitated MXMRV release and increased infectivity. Infectivity assays with several cell lines showed that glyco-gag increases XMRV infectivity in all cell lines tested, but the level of this increase varies in different cell lines. Because MuLV glyco-gag counteracts mouse APOBEC3, we investigated whether M-MuLV glyco-gag enhances XMRV infection by counteracting human APOBEC3. Comparison of hAPOBEC3 isoforms expressed in different cell lines indicated that hA3B was the most likely candidate for a restrictive hA3. However over-expression of hA3B showed no enhanced restriction of infection by XMRV compared to MXMRV. Endogenous MuLVs in the sequenced mouse genome were screened for canonical glyco-gag, which was identified in two clades of xenotropic MuLVs (X-MuLVs) and ecotropic MuLVs, but not in other X-MuLVs or in any polytropic MuLVs.

Conclusions

M-MuLV glyco-gag facilitates XMRV replication, and the leader sequence region in XMRV does not encode proteins equivalent to M-MuLV glyco-gag. The fact that the ability of glyco-gag to enhance XMRV infection varies in different cell lines suggests a glyco-gag sensitive restrictive factor that further reduces XMRV infectivity. The M-MuLV glyco-gag enhancement for XMRV replication is through a hAPOBEC3 independent mechanism. The absence of glyco-gag in MuLVs carried by western European mice suggests that loss of this sequence is a relatively recent event with limited subspecies distribution.
Evaluation of the brain activation induced by functional electrical stimulation and voluntary contraction using functional magnetic resonance imaging
Authors: Joa Kyung-Lim , Han Yong-Hee , Mun Chi-Woong , Son Bong-Kyung , Lee Chang-Hyung , Shin Yong-Beom , Ko Hyun-Yoon , Shin Yong-Il
Published: July 2012

Background

To observe brain activation induced by functional electrical stimulation, voluntary contraction, and the combination of both using functional magnetic resonance imaging (fMRI).

Methods

Nineteen healthy young men were enrolled in the study. We employed a typical block design that consisted of three sessions: voluntary contraction only, functional electrical stimulation (FES)-induced wrist extension, and finally simultaneous voluntary and FES-induced movement. MRI acquisition was performed on a 3.0 T MR system. To investigate activation in each session, one-sample t-tests were performed after correcting for false discovery rate (FDR; p < 0.05). To compare FES-induced movement and combined contraction, a two-sample t-test was performed using a contrast map (p < 0.01).

Results

In the voluntary contraction alone condition, brain activation was observed in the contralateral primary motor cortex (MI), thalamus, bilateral supplementary motor area (SMA), primary sensory cortex (SI), secondary somatosensory motor cortex (SII), caudate, and cerebellum (mainly ipsilateral). During FES-induced wrist movement, brain activation was observed in the contralateral MI, SI, SMA, thalamus, ipsilateral SII, and cerebellum. During FES-induced movement combined with voluntary contraction, brain activation was found in the contralateral MI, anterior cingulate cortex (ACC), SMA, ipsilateral cerebellum, bilateral SII, and SI.

The activated brain regions (number of voxels) of the MI, SI, cerebellum, and SMA were largest during voluntary contraction alone and smallest during FES alone. SII-activated brain regions were largest during voluntary contraction combined with FES and smallest during FES contraction alone. The brain activation extent (maximum t score) of the MI, SI, and SII was largest during voluntary contraction alone and smallest during FES alone. The brain activation extent of the cerebellum and SMA during voluntary contraction alone was similar during FES combined with voluntary contraction; however, cerebellum and SMA activation during FES movement alone was smaller than that of voluntary contraction alone or voluntary contraction combined with FES. Between FES movement alone and combined contraction, activated regions and extent due to combined contraction was significantly higher than that of FES movement alone in the ipsilateral cerebellum and the contralateral MI and SI.

Conclusions

Voluntary contraction combined with FES may be more effective for brain activation than FES-only movements for rehabilitation therapy. In addition, voluntary effort is the most important factor in the therapeutic process.
Protective immunity to Japanese encephalitis virus associated with anti-NS1 antibodies in a mouse model
Authors: Li Yize , Counor Dorian , Lu Peng , Duong Veasna , Yu Yongxin , Deubel Vincent
Published: July 2012

Background

Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described.

Results

JEV NS1 was expressed in and purified from Drosophila S2 cells in a native glycosylated multimeric form, which induced T-cell and antibody responses in immunized C3H/HeN mice. Mice vaccinated with 1 μg NS1 with or without water-in-oil adjuvant were partially protected against viral challenge and higher protection was observed in mice with higher antibody titers. IgG1 was preferentially elicited by an adjuvanted NS1 protein, whereas a larger load of IFN-γ was produced in splenocytes from mice immunized with aqueous NS1. Mice that passively received anti-NS1 mouse polyclonal immune sera were protected, and this phenomenon was dose-dependent, whereas protection was low or delayed after the passive transfer of anti-NS1 MAbs.

Conclusion

The purified NS1 subunit induced protective immunity in relation with anti-NS1 IgG1 antibodies. NS1 protein efficiently stimulated Th1-cell proliferation and IFN-γ production. Protection against lethal challenge was elicited by passive transfer of anti-NS1 antisera, suggesting that anti-NS1 antibodies play a substantial role in anti-viral immunity
Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans
Authors: Cox Chad L , Stanhope Kimber L , Schwarz Jean Marc , Graham James L , Hatcher Bonnie , Griffen Steven C , Bremer Andrew A , Berglund Lars , McGahan John P , Keim Nancy L , Havel Peter J
Published: July 2012

Background

Prospective studies in humans examining the effects of fructose consumption on biological markers associated with the development of metabolic syndrome are lacking. Therefore we investigated the relative effects of 10 wks of fructose or glucose consumption on plasma uric acid and RBP-4 concentrations, as well as liver enzyme (AST, ALT, and GGT) activities in men and women.

Methods

As part of a parallel arm study, older (age 40–72), overweight and obese male and female subjects (BMI 25–35 kg/m2) consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 wks. Fasting and 24-h blood collections were performed at baseline and following 10 wks of intervention and plasma concentrations of uric acid, RBP-4 and liver enzyme activities were measured.

Results

Consumption of fructose, but not glucose, led to significant increases of 24-h uric acid profiles (P < 0.0001) and RBP-4 concentrations (P = 0.012), as well as plasma GGT activity (P = 0.04). Fasting plasma uric acid concentrations increased in both groups; however, the response was significantly greater in subjects consuming fructose (P = 0.002 for effect of sugar). Within the fructose group male subjects exhibited larger increases of RBP-4 levels than women (P = 0.024).

Conclusions

These findings suggest that consumption of fructose at 25% of energy requirements for 10 wks, compared with isocaloric consumption of glucose, may contribute to the development of components of the metabolic syndrome by increasing circulating uric acid, GGT activity, suggesting alteration of hepatic function, and the production of RBP-4.
Upper limb amputation due to a brachial arterial embolism associated with a superior mesenteric arterial embolism: a case report
Authors: Yamada Tsuyoshi , Yoshii Toshitaka , Yoshimura Hideya , Suzuki Koji , Okawa Atsushi
Published: July 2012

Background

Acute mesenteric ischemia due to an embolism of the superior mesenteric artery is associated with a high mortality rate. Over 20 percent of acute mesenteric embolism cases consist of multiple emboli, and the long-term prognosis depends on the incidence of subsequent embolic events at other sites. The incidence of emboli in the upper extremity associated with a superior mesenteric arterial embolism has rarely been described. The signs and symptoms of ischemic change in the upper limb can be masked by other circumstances, such as postoperative conditions or complications. In these cases, a late presentation or delayed diagnosis and treatment can result in limb loss.

Case presentation

We present a rare case of a 67-year-old Japanese woman with atrial fibrillation who developed an embolic occlusion of the brachial artery associated with a superior mesenteric arterial embolism. She developed gangrene in her right hand, which had progressed to the point that amputation was necessary by the time the gastrointestinal surgeon had consulted the Department of Orthopedic Surgery. The brachial arterial embolism diagnosis was delayed by the severe abdominal symptoms and shock conditions that followed the emergency enterectomy, resulting in amputation of the upper limb despite anticoagulation therapy. In this case, multiple infarctions of the spleen were also observed, indicating a shower embolism.

Conclusions

When treating a superior mesenteric arterial embolism in a patient with atrial fibrillation, the possibility of recurrent or multiple arterial thromboembolic events should be considered, even after the procedure is completed.
Application of the antibiotic batumin for accurate and rapid identification of staphylococcal small colony variants
Authors: Churkina Larisa N , Bidnenko Svetlana I , Lopes dos Santos Santiago Guido , Vaneechoutte Mario , Avdeeva Lilja V , Lutko Olga B , Oserjanskaja Nadya M
Published: July 2012

Background

Staphylococcus aureus is a major human pathogen causing significant morbidity and mortality. The S. aureus colonies in osteomyelitis, in patients with cystic fibrosis and patients with endoprosthesis rejection frequently have an atypical morphology, i.e. staphylococcal small-colony variants, which form a naturally occurring subpopulation of clinically important staphylococci. Identification of these small colony variants is difficult, because of the loss of typical phenotypic characteristics of these variants.

We wanted to improve and simplify the diagnosis of staphylococcal infection using a diagnostic preparation, consisting of 5 μg batumin paper disks. Batumin possesses a unique selective activity against all studied Staphylococcus spp., whereas all other species tested thus far are batumin resistant. We assessed the efficacy of the batumin diagnostic preparation to identify staphylococcal small colony variants, isolated from osteomyelitis patients.

Findings

With the batumin diagnostic preparation, all 30 tested staphylococcal small-colony variants had a growth inhibition zone around the disk of minimum 25 mm, accordant with the inhibition zones of the parent strains, isolated from the same patients.

Conclusions

The batumin diagnostic preparation correctly identified the small-colony variants of S. aureus, S. haemolyticus and S. epidermidis as belonging to the genus Staphylococcus, which differ profoundly from parental strains and are difficult to identify with standard methods. Identification of staphylococcal small-colony variants with the batumin diagnostic preparation is technically simple and can facilitate practical laboratory work.
Validation of Aedes aegypti Aag-2 cells as a model for insect immune studies
Authors: Barletta Ana Beatriz Ferreira , Silva Maria Clara L Nascimento , Sorgine Marcos H Ferreira
Published: July 2012

Background

The understanding of mosquito immune responses can provide valuable tools for development of novel mosquito control strategies. Aiming the study at insect innate immunity, continuous insect cell lines have been established and used as research tools due to the fact that they constitute more homogeneous, sensitive, and reproducible systems than the insects from which they originated. More recently, Aag-2, an Aedes aegypti cell lineage, began to be frequently used as a model for studies of mosquito immunity. Nevertheless, to our knowledge, no study has systematically characterized the responses of Aag-2 cell line against different kinds of pathogens and compared its response to those exhibited by whole mosquitoes. For this reason, in this study we characterized gene expression profiles of the Aag-2 cell line in response to different kinds of immune challenges, such as Gram negative and positive bacteria, fungi and viruses, comparing the obtained results with the ones already described in the literature for whole mosquitoes.

Methods

Aedes aegypti Aag-2 cells were exposed to different immune stimuli (gram-positive and gram negative heat inactivated bacteria, zymosan or Sindbis virus) for 24 hours and the expression of selected marker genes from toll, IMD and Jak/STAT pathways was analyzed by qPCR. Also, cells were incubated with fluorescent latex beads for evaluation of its phagocytosis capacity.

Results

Aag-2 cells were stimulated with two concentrations of heat-killed Gram negative (Enterobacter cloacae) or Gram positive (Micrococcus luteus) bacteria, Zymosan or infected with Sindbis virus and the expression of key genes from the main immune related pathways, Toll, IMD and Jak/STAT, were investigated. Our results suggest that Toll and IMD pathways are activated in response to both Gram positive and negative bacteria and Zymosan in Aag-2 cells, displaying an immune profile similar to those described in the literature for whole mosquitoes. The same stimuli were also capable of activating Jak/STAT pathway in Aag-2 cells. Infection with Sindbis virus led to an up-regulation of the transcription factor STAT but was not able to induce the expression of any other gene from any of the pathways assayed. We also showed that this cell line is able to phagocytose latex beads in culture.

Conclusions

Our results characterize the expression profile of Aag-2 cells in response to different immune stimuli and demonstrate that this cell lineage is immune-competent and closely resembles the response described for whole Ae. aegypti mosquitoes. Hence, our findings support the use of Aag-2 as a tool to comprehend Ae. aegypti immune response both at cellular and humoral levels.
A one-year observational study of all hospitalized acute poisonings in Oslo: complications, treatment and sequelae
Authors: Lund Cathrine , Drottning Per , Stiksrud Birgitte , Vahabi Javad , Lyngra Marianne , Ekeberg Ivind , Jacobsen Dag , Hovda Knut Erik
Published: July 2012

Objectives

Changes in poisoning trends may affect both complications and outcomes in patients with acute poisoning. This study reports the treatments given and the frequency of complications, also related to treatment, mortality and sequelae related to various toxic agents.

Methods

All acute poisonings in adults (≥16 years) admitted to the five hospitals in Oslo were included consecutively during one year (2008 to 2009) in an observational cross-sectional multicenter study. A standardized form was completed by the treating physician, which covered the study aims.

Results

There were 1065 admissions in 912 patients. The median length of hospital stay was one day, and 49% were observed in an intensive care unit (ICU). Active treatment was given to 83%, and consisted of supportive therapy (70%), antidote(s) (38%), activated charcoal (16%) and gastric lavage (9%). The most commonly used antidotes were flumazenil (19%), naloxone (17%) and N-acetylcysteine (11%). The rate of treatment-related complications was 2.4% (21/884). Neither flumazenil, naloxone, nor the combination, was associated with convulsions or other complications. Among those receiving N-acetylcysteine, 5% (6/120) developed allergic reactions, one of which mandated discontinuation of treatment. Nineteen percent presented in a coma. Complications developed in 30%, compared with 18% in a 2003 study, mainly respiratory depression (12%), prolonged QTc interval (6%) and hypotension (5%). Eight patients died (0.8%) and five (0.5%) survived with permanent sequelae, mainly anoxic brain damage.

Discussion

Few patients stayed more than two days. The use of the ICU was liberal, considering that only one out of five presented in a coma. Antidotes were frequently given diagnostically. Although N-acetylcysteine induced allergic reactions, most were mild and treatment discontinuation was only necessary once. The frequency of complications had almost doubled in five years, although the poisoning pattern was largely unchanged. However, few patients developed permanent sequelae.
Genetic structure of Thai rice and rice accessions obtained from the International Rice Research Institute
Authors: Chakhonkaen Sriprapai , Pitnjam Keasinee , Saisuk Wachira , Ukoskit Kittipat , Muangprom Amorntip
Published: July 2012

Background

Although the genetic structure of rice germplasm has been characterized worldwide, few studies investigated germplasm from Thailand, the world’s largest exporter of rice. Thailand and the International Rice Research Institute (IRRI) have diverse collections of rice germplasm, which could be used to develop breeding lines with desirable traits. This study aimed to investigate the level of genetic diversity and structures of Thai and selected IRRI germplasm. Understanding the genetic structure and relationships among these germplasm will be useful for parent selection used in rice breeding programs.

Results

From the 98 InDel markers tested for single copy and polymorphism, 19 markers were used to evaluate 43 Thai and 57 IRRI germplasm, including improved cultivars, breeding lines, landraces, and 5 other Oryza species. The Thai accessions were selected from all rice ecologies such as irrigated, deep water, upland, and rainfed lowland ecosystems. The IRRI accessions were groups of germplasm having agronomic desirable traits, including temperature-sensitive genetic male sterility (TGMS), new plant type, early flowering, and biotic and abiotic stress resistances. Most of the InDel markers were genes with diverse functions. These markers produced the total of 127 alleles for all loci, with a mean of 6.68 alleles per locus, and a mean Polymorphic Information Content (PIC) of 0.440. Genetic diversity of Thai rice were 0.3665, 0.4479 and 0.3972 for improved cultivars, breeding lines, and landraces, respectively, while genetic diversity of IRRI improved and breeding lines were 0.3272 and 0.2970, respectively. Cluster, structure, and differentiation analyses showed six distinct groups: japonica, TGMS, deep-water, IRRI germplasm, Thai landraces and breeding lines, and other Oryza species.

Conclusions

Thai and IRRI germplasm were significantly different. Thus, they can be used to broaden the genetic base and trait improvements. Cluster, structure, and differentiation analyses showed concordant results having six distinct groups, in agreement with their development, and ecologies.
Ventilatory support in critically ill hematology patients with respiratory failure
Authors: Molina Rosario , Bernal Teresa , Borges Marcio , Zaragoza Rafael , Bonastre Juan , Granada Rosa María , Rodriguez-Borregán Juan Carlos , Núñez Karla , Seijas Iratxe , Ayestaran Ignacio , Albaiceta Guillermo M ,   the EMEHU study investigators
Published: July 2012

Introduction

Hematology patients admitted to the ICU frequently experience respiratory failure and require mechanical ventilation. Noninvasive mechanical ventilation (NIMV) may decrease the risk of intubation, but NIMV failure poses its own risks.

Methods

To establish the impact of ventilatory management and NIMV failure on outcome, data from a prospective, multicenter, observational study were analyzed. All hematology patients admitted to one of the 34 participating ICUs in a 17-month period were followed up. Data on demographics, diagnosis, severity, organ failure, and supportive therapies were recorded. A logistic regression analysis was done to evaluate the risk factors associated with death and NIVM failure.

Results

Of 450 patients, 300 required ventilatory support. A diagnosis of congestive heart failure and the initial use of NIMV significantly improved survival, whereas APACHE II score, allogeneic transplantation, and NIMV failure increased the risk of death. The risk factors associated with NIMV success were age, congestive heart failure, and bacteremia. Patients with NIMV failure experienced a more severe respiratory impairment than did those electively intubated.

Conclusions

NIMV improves the outcome of hematology patients with respiratory insufficiency, but NIMV failure may have the opposite effect. A careful selection of patients with rapidly reversible causes of respiratory failure may increase NIMV success.
Metformin attenuates ventilator-induced lung injury
Authors: Tsaknis George , Siempos Ilias I , Kopterides Petros , Maniatis Nikolaos A , Magkou Christina , Kardara Matina , Panoutsou Stefania , Kotanidou Anastasia , Roussos Charis , Armaganidis Apostolos
Published: July 2012

Introduction

Diabetic patients may develop acute lung injury less often than non-diabetics; a fact that could be partially ascribed to the usage of antidiabetic drugs, including metformin. Metformin exhibits pleiotropic properties which make it potentially beneficial against lung injury. We hypothesized that pretreatment with metformin preserves alveolar capillary permeability and, thus, prevents ventilator-induced lung injury.

Methods

Twenty-four rabbits were randomly assigned to pretreatment with metformin (250 mg/Kg body weight/day per os) or no medication for two days. Explanted lungs were perfused at constant flow rate (300 mL/min) and ventilated with injurious (peak airway pressure 23 cmH2O, tidal volume ≈17 mL/Kg) or protective (peak airway pressure 11 cmH2O, tidal volume ≈7 mL/Kg) settings for 1 hour. Alveolar capillary permeability was assessed by ultrafiltration coefficient, total protein concentration in bronchoalveolar lavage fluid (BALF) and angiotensin-converting enzyme (ACE) activity in BALF.

Results

High-pressure ventilation of the ex-vivo lung preparation resulted in increased microvascular permeability, edema formation and microhemorrhage compared to protective ventilation. Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation. In contrast, no differences regarding pulmonary artery pressure and BALF total cell number were noted. Administration of metformin did not impact on outcomes of lungs subjected to protective ventilation.

Conclusions

Pretreatment with metformin preserves alveolar capillary permeability and, thus, decreases the severity of ventilator-induced lung injury in this model.
Toward almost closed genomes with GapFiller
Authors: Boetzer Marten , Pirovano Walter
Published: July 2012

De novo assembly is a commonly used application of next-generation sequencing experiments. The ultimate goal is to puzzle millions of reads into one complete genome, although draft assemblies usually result in a number of gapped scaffold sequences. In this paper we propose an automated strategy, called GapFiller, to reliably close gaps within scaffolds using paired reads. The method shows good results on both bacterial and eukaryotic datasets, allowing only few errors. As a consequence, the amount of additional wetlab work needed to close a genome is drastically reduced. The software is available at http://www.baseclear.com/bioinformatics-tools/.
Risk of Colorectal Cancer After Detection and Removal of Adenomas at Colonoscopy: Population-Based Case-Control Study
Authors: Brenner Hermann , Chang-Claude Jenny , Rickert Alexander , Seiler Christoph M. , Hoffmeister Michael
Published: July 2012

Purpose

Empirical evidence for recommendations of surveillance intervals after detection and removal of adenomas at colonoscopy is still sparse and mostly based on observations of adenoma recurrence. We aimed to assess risk of colorectal cancer (CRC) according to time since polypectomy and factors that might be relevant for risk stratification.

Methods

In a population-based case-control study conducted in Germany, detailed history and results of previous large-bowel endoscopies were obtained by interview and from medical records. Risk of CRC among participants with detection of at least one adenoma at a preceding colonoscopy compared with participants without previous large-bowel endoscopy was assessed according to time since polypectomy among 2,582 cases with CRC and 1,798 matched controls.

Results

Adjusted odds ratios (95% CIs) of CRC for participants with polypectomy less than 3, 3 to 5, and 6 to 10 years ago (using participants without previous endoscopy as reference group) were 0.2 (0.2 to 0.3), 0.4 (0.3 to 0.6), and 0.9 (0.5 to 1.5), respectively. Strong, significant risk reduction within 5 years was consistently seen for women and men, younger and older participants, patients with and without high-risk polyps (three or more polyps, at least one polyp ≥ 1 cm, at least one polyp with villous components), and those with and without polypectomy in the right colon. With adjusted odds ratios of 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.5) and 0.4 (0.2 to 0.8) for patients with polypectomy less than 3, 3 to 5, and 6 to 10 years ago, risk reduction was particularly strong for left-sided CRC.

Conclusion

Extension of surveillance intervals to 5 years should be considered, even after detection and removal of high-risk polyps.
Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage
Authors: Relaix Frederic , Zammit Peter S.
Published: July 2012

Following their discovery in 1961, it was speculated that satellite cells were dormant myoblasts, held in reserve until required for skeletal muscle repair. Evidence for this accumulated over the years, until the link between satellite cells and the myoblasts that appear during muscle regeneration was finally established. Subsequently, it was demonstrated that, when grafted, satellite cells could also self-renew, conferring on them the coveted status of ‘stem cell’. The emergence of other cell types with myogenic potential, however, questioned the precise role of satellite cells. Here, we review recent recombination-based studies that have furthered our understanding of satellite cell biology. The clear consensus is that skeletal muscle does not regenerate without satellite cells, confirming their pivotal and non-redundant role.
Negative regulators of integrin activity
Authors: Pouwels Jeroen , Nevo Jonna , Pellinen Teijo , Ylänne Jari , Ivaska Johanna
Published: July 2012

Integrins are heterodimeric transmembrane adhesion receptors composed of α- and β-subunits. They are ubiquitously expressed and have key roles in a number of important biological processes, such as development, maintenance of tissue homeostasis and immunological responses. The activity of integrins, which indicates their affinity towards their ligands, is tightly regulated such that signals inside the cell cruicially regulate the switching between active and inactive states. An impaired ability to activate integrins is associated with many human diseases, including bleeding disorders and immune deficiencies, whereas inappropriate integrin activation has been linked to inflammatory disorders and cancer. In recent years, the molecular details of integrin ‘inside-out’ activation have been actively investigated. Binding of cytoplasmic proteins, such as talins and kindlins, to the cytoplasmic tail of β-integrins is widely accepted as being the crucial step in integrin activation. By contrast, much less is known with regard to the counteracting mechanism involved in switching integrins into an inactive conformation. In this Commentary, we aim to discuss the known mechanisms of integrin inactivation and the molecules involved.
The Bro1 domain-containing Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration
Authors: Chen Dong-Yuan , Li Meng-Yen , Wu Shih-Yun , Lin Yu-Ling , Tsai Sung-Po , Lai Pei-Lun , Lin Yu-Tsen , Kuo Jean-Cheng , Meng Tzu-Ching , Chen Guang-Chao
Published: July 2012

Protein tyrosine phosphatases (PTPs) are a group of tightly regulated enzymes that coordinate with protein tyrosine kinases to control protein phosphorylation during various cellular processes. Using genetic analysis in Drosophila non-transmembrane PTPs, we identified one role that Myopic (Mop), the Drosophila homolog of the human His domain phosphotyrosine phosphatase (HDPTP), plays in cell adhesion. Depletion of Mop results in aberrant integrin distribution and border cell dissociation during Drosophila oogenesis. Interestingly, Mop phosphatase activity is not required for its role in maintaining border cell cluster integrity. We further identified Rab4 GTPase as a Mop interactor in a yeast two-hybrid screen. Expression of the Rab4 dominant negative mutant leads to border cell dissociation and suppresses Mop-induced wing-blade adhesion defects, suggesting a critical role of Rab4 in Mop-mediated signaling. In mammals, it has been shown that Rab4-dependent recycling of integrins is necessary for cell adhesion and migration. We found that human HDPTP regulates the spatial distribution of Rab4 and integrin trafficking. Depletion of HDPTP resulted in actin reorganization and increased cell motility. Together, our findings suggest an evolutionarily conserved function of HDPTP-Rab4 in the regulation of endocytic trafficking, cell adhesion and migration.
Mph1 kinetochore localization is crucial and upstream in the hierarchy of spindle assembly checkpoint protein recruitment to kinetochores
Authors: Heinrich Stephanie , Windecker Hanna , Hustedt Nicole , Hauf Silke
Published: July 2012

The spindle assembly checkpoint (SAC) blocks entry into anaphase until all chromosomes have stably attached to the mitotic spindle through their kinetochores. The checkpoint signal originates from unattached kinetochores, where SAC proteins enrich. Whether the enrichment of all SAC proteins is crucial for SAC signalling is unclear. Here we provide evidence that in fission yeast, recruitment of the kinase Mph1 is of vital importance for a stable SAC arrest. An Mph1 mutant that eliminates kinetochore enrichment abolishes SAC signalling, whereas forced recruitment of this mutant to kinetochores restores SAC signalling. In bub3Δ cells, the SAC is functional with only Mph1 and the Aurora kinase Ark1, but no other SAC proteins, enriched at kinetochores. We analysed the network of dependencies for SAC protein localization to kinetochores and identify a three-layered hierarchy with Ark1 and Mph1 on top, Bub1 and Bub3 in the middle, and Mad3 as well as the Mad1-Mad2 complex at the lower end of the hierarchy. If Mph1 is artificially recruited to kinetochores, Ark1 becomes dispensable for SAC activity. Our results highlight the critical role of Mph1 at kinetochores and suggest that the Mad1-Mad2 complex does not necessarily need to enrich at kinetochores for functional SAC signalling.
The fallacy of ratio correction to address confounding factors
Authors: Karp Natasha A , Segonds-Pichon Anne , Gerdin Anna-Karin B , Ramírez-Solis Ramiro , White Jacqueline K
Published: July 2012

Scientists aspire to measure cause and effect. Unfortunately confounding variables, ones that are associated with both the probable cause and the outcome, can lead to an association that is true but potentially misleading. For example, altered body weight is often observed in a gene knockout; however, many other variables, such as lean mass, will also change as the body weight changes. This leaves the researcher asking whether the change in that variable is expected for that change in weight. Ratio correction, which is often referred to as normalization, is a method used commonly to remove the effect of a confounding variable. Although ratio correction is used widely in biological research, it is not the method recommended in the statistical literature to address confounding factors; instead regression methods such as the analysis of covariance (ANCOVA) are proposed. This method examines the difference in means after adjusting for the confounding relationship. Using real data, this manuscript demonstrates how the ratio correction approach is flawed and can result in erroneous calls of significance leading to inappropriate biological conclusions. This arises as some of the underlying assumptions are not met. The manuscript goes on to demonstrate that researchers should use ANCOVA, and discusses how graphical tools can be used readily to judge the robustness of this method. This study is therefore a clear example of why assumption testing is an important component of a study and thus why it is included in the Animal Research: Reporting of In Vivo Experiment (ARRIVE) guidelines.
Combining general practice with international work: online survey of experiences of UK GPs
Authors: Smith Chris , Pettigrew Luisa M , Seo Ha-Neul , Dorward Jienchi
Published: July 2012

Objectives

To conduct an exploratory study to learn about the experiences of GPs who have undertaken international work.

Design

Cross-sectional survey

Setting

Online survey of UK-based GPs. Members of all UK RCGP faculties were invited to participate by email and the survey was publicised on the RCGP website

Participants

All UK-based GPs

Main outcome measures

Types of UK and international work undertaken, barriers, competencies gained, influence on career and future plans.

Results

The study identified 439 respondents, in a variety of GP roles at all career stages, who had undertaken international work in their role as a doctor. GPs are undertaking international work in both high and low/middle-income countries, engaging in a wide range of clinical and non-clinical activities. Respondents reported gaining a range of competencies from international work, which could be transferred back to the UK setting to a variable degree. Commonly cited barriers to international work were having to leave friends and family, and concerns regarding future employment and pension. Most reported that engaging in international work had influenced the direction of their career, with the largest proportion stating that they wish to work predominantly in the UK, with some international work in the future.

Conclusion

The study highlights the variety of ways in which UK GPs are combining UK general practice and international work, competencies gained with such work, and ability to transfer these back to the UK setting. Historical barriers to international work still exist and future research could further examine the value of such work.
Dimensions of Community and Organizational Readiness for Change
Authors: Castañeda Sheila F. , Holscher Jessica , Mumman Manpreet K. , Salgado Hugo , Keir Katherine B. , Foster-Fishman Pennie G. , Talavera Gregory A.
Published: July 2012

Background: Readiness can influence whether health interventions are implemented in, and ultimately integrated into, communities. Although there is significant research interest in readiness and capacity for change, the measurement of these constructs is still in its infancy. Objective: The purpose of this review was to integrate existing assessment models of community and organizational readiness. Data Sources: The database PubMed was searched for articles; articles, book chapters, and practitioner guides identified as references cited in the list of core articles. Review Methods: Studies were included if they met the following criteria: (1) Empirical research, (2) identified community or organizational readiness for innovative health programming in the study's title, purpose, research questions, or hypotheses, and (3) identified methods to measure these constructs. Duplicate articles were deleted and measures published before 1995 were excluded. The search yielded 150 studies; 13 met all criteria. Results: This article presents the results of a critical review of 13 community and organizational readiness assessment models, stemming from articles, chapters, and practitioner's guides focusing on assessing, developing, and sustaining community and organizational readiness for innovative public health programs. Conclusions: Readiness is multidimensional and different models place emphasis on different components of readiness, such as (1) community and organizational climate that facilitates change, (2) attitudes and current efforts toward prevention, (3) commitment to change, and (4) capacity to implement change. When initiating the program planning process, it is essential to assess these four domains of readiness to determine how they apply to the nuances across different communities. Thus, community-based participatory research (CBPR) partnerships, in efforts to focus on public health problems, may consider using readiness assessments as a tool for tailoring intervention efforts to the needs of the community.
Development of the Live Well Curriculum for Recent Immigrants: A Community-Based Participatory Approach
Authors: Tovar Alison , Vikre Emily Kuross , Gute David M. , Kamins Christina Luongo , Pirie Alex , Boulos Rebecca , Metayer Nesly , Economos Christina D.
Published: July 2012

Background: There are few weight gain prevention interventions aimed at new immigrants. Live Well, a community-based participatory research (CBPR) study, was designed to address this gap. Objective: The goal of this paper is to describe the development of the Live Well nutrition and physical activity curriculum. Methods: The curriculum draws on behavioral theory and popular education and was co-created, implemented, and will be evaluated by community partners and academic researchers. Results: The time it took to develop the curriculum exceeded initial estimates. However, the extra time taken was spent engaging in needed dialogue to create a better product, fully co-created by academic and community partners. Additionally, working with an outside expert created the opportunity for all partners to train together, build capacity, and increase cohesion. Our approach developed relationships and trust, and resulted in a unique curriculum. Conclusions: The commitment to partnership resulted in a curriculum to empower immigrant women to improve health decisions and behaviors. This will inform future research and programming targeting other at-risk and new immigrant communities.