bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the mammalian middle ear and jaw: adaptations and novel structures
Authors: Anthwal Neal , Joshi Leena , Tucker Abigail S.
Published: June 2012

Having three ossicles in the middle ear is one of the defining features of mammals. All reptiles and birds have only one middle ear ossicle, the stapes or columella. How these two additional ossicles came to reside and function in the middle ear of mammals has been studied for the last 200 years and represents one of the classic example of how structures can change during evolution to function in new and novel ways. From fossil data, comparative anatomy and developmental biology it is now clear that the two new bones in the mammalian middle ear, the malleus and incus, are homologous to the quadrate and articular, which form the articulation for the upper and lower jaws in non‐mammalian jawed vertebrates. The incorporation of the primary jaw joint into the mammalian middle ear was only possible due to the evolution of a new way to articulate the upper and lower jaws, with the formation of the dentary‐squamosal joint, or TMJ in humans. The evolution of the three‐ossicle ear in mammals is thus intricately connected with the evolution of a novel jaw joint, the two structures evolving together to create the distinctive mammalian skull.
The impact of live trapping and trap model on the stress profiles of North American red squirrels
Authors: Bosson C.O. , Islam Z. , Boonstra R.
Published: June 2012

Live‐capture is a necessary component for the scientific study and management of most mammals, but it may negatively affect their health and physiology. We compared blood parameters related to the stress response (nominal base levels) from red squirrels Tamiasciurus hudsonicus after capture of up to 4.5 h in five different live trap models (Hava‐hart, Sherman, Tomahawk 102, Tomahawk 103 and ‘Special Squirrel’ trap) with true base levels (obtained in less than three minutes). In addition, we evaluated the capture rate in the five trap models. We found that (1) prolonged time in live traps altered stress hormone concentrations compared with true base levels, but maximum corticosteroid‐binding capacity was unaffected; (2) squirrels captured in a trap model with reduced visibility (a roof cover – Hava‐hart) had significantly lower (c. 50%) mean free cortisol levels compared with those captured in a trap model with full visibility (Tomahawk 102), but all other blood parameters were similar; (3) cortisol levels and white blood cell counts (mainly neutrophil counts) were positively related to duration of capture; (4) a non‐covered trap (Tomahawk 102) was most effective and fully covered trap (Sherman) was least effective at capturing squirrels. We discuss the use of effective, yet less stress‐inducing trap models to mitigate the stress caused by live‐capture on these animals. We conclude that covered traps such as the Hava‐hart may reduce trap‐induced stress in red squirrels, but at the same time also reduces their capture rates.
Opportunities for improving phosphorus‐use efficiency in crop plants
Authors: Veneklaas Erik J. , Lambers Hans , Bragg Jason , Finnegan Patrick M. , Lovelock Catherine E. , Plaxton William C. , Price Charles A. , Scheible Wolf‐Rüdiger , Shane Michael W. , White Philip J. , Raven John A.
Published: June 2012

Limitation of grain crop productivity by phosphorus (P) is widespread and will probably increase in the future. Enhanced P efficiency can be achieved by improved uptake of phosphate from soil (P‐acquisition efficiency) and by improved productivity per unit P taken up (P‐use efficiency). This review focuses on improved P‐use efficiency, which can be achieved by plants that have overall lower P concentrations, and by optimal distribution and redistribution of P in the plant allowing maximum growth and biomass allocation to harvestable plant parts. Significant decreases in plant P pools may be possible, for example, through reductions of superfluous ribosomal RNA and replacement of phospholipids by sulfolipids and galactolipids. Improvements in P distribution within the plant may be possible by increased remobilization from tissues that no longer need it (e.g. senescing leaves) and reduced partitioning of P to developing grains. Such changes would prolong and enhance the productive use of P in photosynthesis and have nutritional and environmental benefits. Research considering physiological, metabolic, molecular biological, genetic and phylogenetic aspects of P‐use efficiency is urgently needed to allow significant progress to be made in our understanding of this complex trait.

Contents

Summary
306

I.
The need to use phosphorus efficiently
307

II.
P‐use efficiency and P dynamics in a growing crop
307

III.
P pools in plants
307

IV.
Phosphorus pools and growth rates
310

V.
Are crops different from other plants in their P concentration?
310

VI.
Phosphorus use and photosynthesis
311

VII.
Crop development and canopy P distribution
312

VIII.
Internal redistribution of P in a growing vegetative plant
313

IX.
Allocation of P to reproductive structures
314

X.
Constraints to P remobilisation
315

XI.
Do physiological or phylogenetic trade‐offs constrain traits that could improve PUE?
316

XII.
Identifying genetic loci associated with PUE
316

XIII.
Conclusions
317

Acknowledgements
317

References
317
The evolution of land plant cilia
Authors: Hodges Matthew E. , Wickstead Bill , Gull Keith , Langdale Jane A.
Published: June 2012

Eukaryotic cilia/flagella are ancient organelles with motility and sensory functions. Cilia display significant ultrastructural conservation where present across the eukaryotic phylogeny; however, diversity in ciliary biology exists and the ability to produce cilia has been lost independently on a number of occasions. Land plants provide an excellent system for the investigation of cilia evolution and loss across a broad phylogeny, because early divergent land plant lineages produce cilia, whereas most seed plants do not. This review highlights the differences in cilia form and function across land plants and discusses how recent advances in genomics are providing novel insights into the evolutionary trajectory of ciliary proteins. We propose a renewed effort to adopt ciliated land plants as models to investigate the mechanisms underpinning complex ciliary processes, such as number control, the coordination of basal body placement and the regulation of beat patterns.

ContentsSummary526I.Introduction526II.Plant cilia: a model for evolution and development530III.Future perspectives:MarchantiaandCeratopterisas models for cilia research535Acknowledgements536References536
Hypometabolism precedes limbic atrophy and spontaneous recurrent seizures in a rat model of TLE
Authors: Jupp Bianca , Williams John , Binns David , Hicks Rodney J. , Cardamone Lisa , Jones Nigel , Rees Sandra , O’Brien Terence J.
Published: June 2012

Purpose:  Temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG‐PET) is a common finding in patients with drug‐resistant temporal lobe epilepsy (TLE). The pathophysiology underlying the hypometabolism, including whether it reflects a primary epileptogenic process, or whether it occurs later as result of limbic atrophy or as a result of chronic seizures, remains unknown. This study aimed to investigate the ontologic relationship among limbic atrophy, histological changes, and hypometabolism in rats.

Methods:  Serial in vivo imaging with FDG‐PET and volumetric magnetic resonance imaging (MRI) was acquired before and during the process of limbic epileptogenesis resulting from kainic acid–induced status epilepticus in the rat. The imaging data were correlated with histologic measures of cell loss, and markers of astrogliosis (glial fibrillary acid protein [GFAP]), synaptogenesis (synaptophysin), glucose transporter 1 (Glut1) and energy metabolism (cytochrome oxidase C), on brains of the animals following the final imaging point.

Key Findings:  Hippocampal hypometabolism on FDG‐PET was found to be present 24 h following status epilepticus, tending to lessen by 1 week and then become more marked again following the onset of spontaneous seizures. Atrophy of limbic structures was evident from 7 days post‐SE, becoming progressively more marked on serial MRI over subsequent weeks. No relationship was observed between the severity of MRI‐detected atrophy or CA1 pyramidal cell loss and the degree of the hypometabolism on FDG‐PET. However, an inverse relationship was observed between hypometabolism and increased expression of the Glut1 and synaptophysin in the hippocampus.

Significance:  These findings demonstrate that hypometabolism occurs early in the processes of limbic epileptogenesis and is not merely a consequence of pyramidal cell loss or the progressive atrophy of limbic brain structures that follow. The hypometabolism may reflect cellular mechanisms occurring early during epileptogenesis in addition to any effects of the subsequent recurrent spontaneous seizures.
Focal neocortical epilepsy affects hippocampal volume, shape, and structural integrity: A longitudinal MRI and immunohistochemistry study in a rat model
Authors: Otte Willem M. , Bielefeld Pascal , Dijkhuizen Rick M. , Braun Kees P.J.
Published: June 2012

Purpose: Extratemporal epilepsy often coincides with cognitive decline, which may be associated with hippocampal dysfunction. Severe hippocampal sclerosis can be detected with conventional neuroimaging in some patients with chronic extrahippocampal epilepsy (so‐called dual pathology). However, subtle structural hippocampal changes may already develop at a much earlier phase, and in a larger number of patients. Our goal was to longitudinally characterize the development of bilateral hippocampal pathology in an experimental neocortical focal epilepsy model.

Methods: Focal unilateral neocortical epilepsy was induced by microinjection of tetanus toxin in the primary motor cortex in adult male Sprague‐Dawley rats. Another group of age‐matched rats served as controls. In both groups, structural magnetic resonance imaging (MRI) was performed at 1, 3, 7, and 10 weeks of follow‐up. Bilateral hippocampi were outlined and macroscopically analyzed using a state‐of‐the‐art point‐based morphometry model. Hippocampal microstructural changes at the end of follow‐up, 10 weeks after epilepsy induction, were assessed with postmortem standard cresyl‐violet, Fluoro‐Jade, proteolipid protein 1, vimentin, glial fibrillary acidic protein, and ionized calcium binding adaptor molecule 1 stainings.

Key Findings: All rats in the injected group developed seizures. The ipsilateral hippocampal volume was on average 8.76 (mean) ± 3.32% (standard deviation) smaller in the epileptic animals as compared to controls (p = 0.01) during the 10 weeks of follow‐up. The contralateral hippocampus showed a similar reduction of 8.49 (mean) ± 3.27% (standard deviation) in total volume (p = 0.02). Clear hippocampal shape differences were found between the two groups. The most affected areas after epilepsy induction were the bilateral dorso‐mediorostral, dorsolateral, and ventrolateral areas of the hippocampi. Normal developmental shape changes of the hippocampus, as detected in control rats, were largely absent in the ipsilateral hippocampus of epileptic rats. Quantitative histologic analysis revealed significant neuronal loss in the hippocampus, most pronounced in the hilar subregion, globally impaired myelination, reactive astrocytosis, and activated microglia. We found a weak but significant correlation between the number of neurons and hippocampal volume (r = 0.25, p = 0.0025).

Significance: We found evidence of hippocampal pathology in both hemispheres following experimental focal neocortical epilepsy. The observed development of bilateral hippocampal pathology, with onset in the early stages of focal neocortical epilepsy, may be a significant factor in comorbidities, such as cognitive dysfunction, found in patients with extratemporal localization‐related epilepsy.
Topiramate increases the risk of valproic acid–induced encephalopathy
Authors: Noh Young , Kim Dong Wook , Chu Kon , Lee Soon‐Tae , Jung Keun‐Hwa , Moon Hye‐Jin , Lee Sang Kun
Published: June 2012

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA‐induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA‐induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA‐induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA‐induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA‐induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment.
Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy
Authors: Poduri Annapurna , Chopra Sameer S. , Neilan Edward G. , Christina Elhosary P. , Kurian Manju A. , Meyer Esther , Barry Brenda J. , Khwaja Omar S. , Salih Mustafa A. M. , Stödberg Tommy , Scheffer Ingrid E. , Maher Eamonn R. , Sahin Mustafa , Wu Bai‐Lin , Berry Gerard T. , Walsh Christopher A. , Picker Jonathan , Kothare Sanjeev V.
Published: June 2012

Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome‐wide and long‐range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCβ1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes.
Acute Alcohol Exposure Impairs Fracture Healing and Deregulates β‐Catenin Signaling in the Fracture Callus
Authors: Lauing Kristen L. , Roper Philip M. , Nauer Rachel K. , Callaci John J.
Published: June 2012

Background

Alcohol abuse is a risk factor for bone damage and fracture‐related complications. Through precise β‐catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol‐induced impaired fracture healing.

Methods

Male C57Bl/6 or T cell factor (TCF)‐transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid‐shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post‐fracture for the analysis of biomechanical strength, callus tissue composition, and Wnt/β‐catenin signaling.

Results

Acute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post‐fracture. Histology revealed an alcohol‐related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3‐fold increase in total β‐catenin protein at day 6 and a significant decrease of 53 and 56% at days 9 and 14, respectively.
lacZ
staining in β‐galactosidase‐expressing TCF‐transgenic mice revealed spatial and quantitative differences in Wnt‐specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post‐fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total β‐catenin protein levels observed at these time points.

Conclusions

Acute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein β‐catenin, and disruption of normal Wnt‐mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone and may partially explain why impaired fracture healing is observed in alcohol‐abusing individuals.
Comparing Growth Rates of Nickel and Stainless Steel Use in the Early 2000s
Authors: Reck Barbara K. , Rotter Vera Susanne
Published: June 2012

This study introduces the 2005 life cycle data for nickel in 50 countries and presents a comparative analysis of the 2000 and 2005 nickel and stainless steel cycles for these countries. The life cycles of the two metals are linked by nickel's role as a major alloying element in most stainless steels. Between 2000 and 2005, the global use of both metals grew, driven by China's extraordinary growth and despite the fact that many industrialized countries decreased their metal use during that time. China's and India's growth of stainless steel use was greater than that of nickel use, a result of price‐driven substitution away from nickel‐containing stainless steels. The intensity of use (IU) in industrialized countries is about 30 to 50 kilograms (kg) nickel/million U.S. dollars (USD), and 300 to 500 kg stainless steel/million USD. High‐income countries decreased their IU of both metals between 2000 and 2005, while low‐ and medium‐income countries increased their IU of stainless steel. At the per capita level, average industrialized countries use about 1 kg of nickel and 11 kg of stainless steel. Were China's and India's projected urban areas in 2025 to use similar amounts of the two metals, they alone would require the equivalent of global nickel production in 2000, and 200% of the world's stainless steel production in 2005. In China, substantial nickel and stainless steel end‐of‐life flows will arise between 2015 and 2020, and efficient collection and separation systems should be prepared now to maximize the potential environmental and resource benefits of recycling.
An Effectiveness and Cost‐Benefit Analysis of a Hospital‐Based Discharge Transition Program for Elderly Medicare Recipients
Authors: Saleh Shadi S. , Freire Chris , Morris‐Dickinson Gwendolyn , Shannon Trip
Published: June 2012

Objective

To investigate the business case of postdischarge care transition (PDCT) among Medicare beneficiaries by conducting a cost‐benefit analysis.

Design

Randomized controlled trial.

Setting

A general hospital in upstate New York State.

Participants

Elderly Medicare beneficiaries being treated from October 2008 through December 2009 were randomly selected to receive services as part of a comprehensive PDCT program (intervention—173 patients) or regular discharge process (control—160 patients) and followed for 12 months.

Intervention

The intervention comprised five activities: development of a patient‐centered health record, a structured discharge preparation checklist of critical activities, delivery of patient self‐activation and management sessions, follow‐up appointments, and coordination of data flow.

Measurements

Cost‐benefit ratio of the PDCT program; self‐management skills and abilities.

Results

The 1‐year readmission analysis revealed that control participants were more likely to be readmitted than intervention participants (58.2% vs 48.2%; P = .08); with most of that difference observed in the 91 to 365 days after discharge. Findings from the cost‐benefit analysis revealed a cost‐benefit ratio of 1.09, which indicates that, for every $1 spent on the program, a saving of $1.09 was realized. In addition, participating in a care transition program significantly enhanced self‐management skills and abilities.

Conclusion

Postdischarge care transition programs have a dual benefit of enhancing elderly adults' self‐management skills and abilities and producing cost savings. This study builds a case for the inclusion of PDCT programs as a reimbursable service in benefit packages.
The Family Empowerment Program: An Interdisciplinary Approach to Working with Multi‐Stressed Urban Families
Authors: Cleek Elizabeth N. , Wofsy Matt , Boyd‐Franklin Nancy , Mundy Brian , Howell Tamika J.
Published: June 2012

The family empowerment program (FEP) is a multi‐systemic family therapy program that partners multi‐stressed families with an interdisciplinary resource team while remaining attached to a “traditional” mental health clinic. The rationale for this model is that far too often, families presenting at community mental health centers struggle with multiple psychosocial forces, for example problems with housing, domestic violence, child care, entitlements, racism, substance abuse, and foster care, as well as chronic medical and psychiatric illnesses, that exacerbate symptoms and impact traditional service delivery and access to effective treatment. Thus, families often experience fragmented care and are involved with multiple systems with contradictory and competing agendas. As a result, services frequently fail to harness the family's inherent strengths. The FEP partners the family with a unified team that includes representatives from Entitlements Services, Family Support and Parent Advocacy, and Clinical Staff from the agency's Outpatient Mental Health Clinic practicing from a strength‐based family therapy perspective. The goal of the FEP is to support the family in achieving their goals. This is accomplished through co‐construction of a service plan that addresses the family's needs in an efficient and coherent manner—emphasizing family strengths and competencies and supporting family self‐sufficiency.
Couples' Cultural Values, Shared Parenting, and Family Emotional Climate Within Mexican American Families
Authors: Sotomayor‐Peterson Marcela , Figueredo Aurelio J. , Christensen Donna H. , Taylor Angela R.
Published: June 2012

This study tested a model of shared parenting as its centerpiece that incorporates cultural values as predictors and family emotional climate as the outcome variable of interest. We aimed to assess the predictive power of the Mexican cultural values of familismo and simpatia over couples' shared parenting practices. We anticipated that higher levels of shared parenting would predict family emotional climate. The participants were 61 Mexican American, low income couples, with at least one child between 3 and 4 years of age, recruited from a home‐based Head Start program. The predictive model demonstrated excellent goodness of fit, supporting the hypothesis that a positive emotional climate within the family is fostered when Mexican American couples practice a sufficient level of shared parenting. Empirical evidence was previously scarce on this proposition. The findings also provide evidence for the role of cultural values, highlighting the importance of family solidarity and avoidance of confrontation as a pathway to shared parenting within Mexican American couples.
A Narrative Evaluation of a Psychoeducation and a Therapeutic Alliance Intervention for Parents of Persons with a Severe Mental Illness
Authors: Levy‐Frank Itamar , Hasson‐Ohayon Ilanit , Kravetz Shlomo , Roe David
Published: June 2012

Most attempts to study the impact of psychosocial interventions on parents of persons with severe mental illness (SMI) are quantitative. The purpose of the present study was to investigate the subjective experience of parents of persons with SMI who participated in either a psychoeducational intervention which emphasized providing information on the illness and support, or a therapeutic alliance focused intervention (TAFI) which emphasized the alliance between the group members and group leaders. Ninety‐three parents, who participated in either one of these two interventions, were interviewed using the Narrative Evaluation of Intervention Interview.

Results show that participants found both interventions to be beneficial with no statistical differences in the level of perceived change. Themes describing change in relating to illness were significantly more frequently mentioned by participants in the TAFI group, whereas significantly more participants in the family psychoeducation interventions reported that implementation and information provided contributed to positive change. Also participants in the TAFI reported significantly more often that group regulation contributed to change. As both interventions were perceived as contributing, the findings support the relationship orientation to psychosocial interventions, which stresses the quality of the social support and interpersonal interaction as the source of positive outcomes of intervention.
Intraoperative injection of bupivacaine‐adrenaline close to the fascia reduces morphine requirements after cesarean section: a randomized controlled trial
Authors: NIKLASSON BOEL , BÖRJESSON ASTRID , CARMNES ULLA‐BRITT , SEGERDAHL MÄRTA , ÖHMAN SUSANNE GEORGSSON , BLANCK AGNETA
Published: June 2012

Objective. The purpose of this study was to investigate whether a single injection of bupivacaine with adrenaline close to the fascia could decrease opiate consumption and pain in patients undergoing cesarean section in spinal anesthesia. Design. Randomized double‐blind controlled study. Settings. Karolinska University Hospital, Huddinge, Sweden. Population. 260 women scheduled for elective cesarean section were enrolled in the study. Methods. The treatment group (n= 130) received 40 mL bupivacaine (2.5 mg/mL) with adrenaline (5 μg/mL) (Marcain® adrenalin) and the control group (n= 130) received 40 mL saline solution (0.9%), which was, in both groups, injected close to the fascia before closure of the wound. Main outcome measures. Morphine consumption and mean resting pain intensity numerical rating scale at 12 and 24 hours were the primary outcome variables. Other assessments for pain as well as mobilization parameters were considered secondary. Results. Morphine requirements were significantly less in the bupivacaine group, 19.0 mg/woman, compared with 24.0 mg/woman in the placebo group, during the first 12 postoperative hours. During this time period there was also a trend towards a difference between groups in mean pain intensity, but significant only during the first six hours. Over the whole first postoperative 24 hours, there were no differences in either morphine requirement or pain intensity between groups. Conclusions. A single injection of bupivacaine with adrenaline in the surgical wound decreases the need for morphine requirements for the first 12 postoperative hours and contributes to safe and effective pain management in women undergoing cesarean section.
An Increase of Treg Cells in the Peripheral Blood is Associated with a Better In Vitro Fertilization Treatment Outcome
Authors: Zhou Jianjun , Wang Zhiqun , Zhao Xia , Wang Junxia , Sun Haixiang , Hu Yali
Published: June 2012

Problem

The objective of this study was to determine whether there was any association between the peripheral blood CD4+
CD25+
Foxp3+ regulatory T cells (Treg cells) and implantation success in patients undergoing in vitro fertilization (IVF) treatment.

Method of study

Prospective observational study of 101 randomly selected women who underwent IVF treatment for tubal factor from May 2011 to June 2011. The percentage of peripheral blood Treg cells and the expression levels of Foxp3 and CTLA4 mRNA in peripheral blood mononuclear cells (PBMCs) were recorded and their relations to IVF treatment outcomes were analyzed.

Results

Treg cells were significantly elevated in the pregnant group (
P = 0.03). The expression level of Foxp3 mRNA in PBMCs from pregnant group also significantly increased (
P = 0.02). A receiver operating characteristic analysis (area under curve = 0.631) found that those women with Treg cells >0.6%, the pregnancy rate and live birth rate were much higher as compared to women with Treg cells below this level (
P < 0.05). An increase of Treg cells in the peripheral blood was associated with a better IVF treatment outcome (OR 4.3, 95% CI = 1.76–10.48), with a sensitivity of 64%, specificity of 71%.

Conclusion

An elevated level of circulating Treg cells was associated with increased rates of pregnancy and live birth in IVF treatment.
Leg swelling after inguinal sentinel lymph node biopsy and primary melanoma excision with a safety margin
Authors: Kretschmer Lutz , Pratsch Aila Luise
Published: June 2012

Background: Risk‐factors for leg swelling following primary melanoma excision and inguinal sentinel lymphadenectomy (SLNE) have not been sufficiently investigated.

Patients and Methods: We prospectively studied three parameters in 105 subjects: 1) subjectively perceived swelling, 2) clinically diagnosed swelling and 3) photo‐optical measurement of volume differences between both legs.

Results: Perceived swelling, clinically diagnosed swelling, and manifest edema occurred in 31%, 15%, and 7% of patients respectively. Following inguinal SLNE, there was a mean volume increase of 1.5% in the operated leg. Both the lower leg and the thigh increased in volume. Obesity, primary melanoma location on the lower leg, and inguinal seromas were identified as significant risk factors for postoperative swelling. Wider excision margins around a primary melanoma on the thigh were also associated with a significant increase in volume. Age, sex, the number of sentinel lymph nodes, the drainage fluid volume, and the time since SLNE were non‐significant.

Conclusions: Both inguinal SLNE and primary melanoma excision may contribute to minimal fluid accumulation in the leg. More than two‐thirds of patients did not have any swelling. Obesity, location of the primary melanoma at a distal site on the leg, a wide safety margin, and seromas are associated with postoperative leg swelling.
Healing of Fresh Extraction Sockets Filled with Bioactive Glass Particles: Histological Findings in Humans
Authors: Clozza Emanuele , Pea Maurizio , Cavalli Fabio , Moimas Loredana , Di Lenarda Roberto , Biasotto Matteo
Published: June 2012

Purpose: The aim of the present study was to histologically evaluate fresh human sockets filled with bioactive glass after 6 months of healing.

Materials and Methods: In 13 patients, 32 single extraction sites in the anterior area underwent socket ridge preservation procedure (RPP) with a bioactive glass (BioRestore™, Inion Oy, Tampere, Finland). At implant installation, 22 bone cores were trephined out and processed for histomorphometric and immunohistochemical analysis.

Results: Newly formed immature bone around residual particles of bioactive glass was found in all 22 biopsies. The histomorphometry of the amount of bone, provisional matrix, and residual graft returned a mean ± SD value of 54 ± 31%, 37.9 ± 25.6%, and 8.1 ± 7.8, respectively, 6 months after RPP.

Conclusion: The use of this grafting material in fresh extraction sockets appears to delay the healing processes of the alveolar bone; therefore, its indication as a material for RPP when implant placement is considered within 6 months after extraction should be revised.
Robbing Banks
Authors: Reilly Barry , Rickman Neil , Witt Robert
Published: June 2012

Robbing a bank is the staple crime of thrillers, movies and newspapers. But, say Barry Reilly, Neil Rickman and Robert Witt, bank robbery is not all it is cracked up to be. With access to a unique data set, they give us the low-down on the economics of the bank heist.
What Petri Dishes Have to do with Your Research
Authors: VanDerwerken Douglas
Published: June 2012

This article, by Douglas VanDerwerken, was a runner-up in the Young Statisticians Group/Significance Writing competition. It nicely explains why throwing away data is not a good idea.
In the name of charity: Institutional support for and resistance to redefining the meaning of charity in Canada
Authors: Levasseur Karine
Published: June 2012

This article examines how state institutions shape the meaning of charity in Canada. It concludes that the courts have made limited changes to the meaning of charity and that the Department of Finance has resisted redefining charity. In contrast, the Canada Revenue Agency's Charities Directorate has worked to update the meaning of charity, but it does not have the power to amend the tax laws so its changes have been primarily administrative. While these administrative changes may not overcome the central public policy issue related to a narrow interpretation of the meaning of charity, they could shape future definitions depending on the voluntary sector's ability to mobilize around this issue and the receptiveness of the federal government.
Lipid profiling of pre‐treatment liver biopsy tissue predicts sustained virological response in patients with chronic hepatitis C
Authors: Cobbold Jeremy F. L. , Cox I. Jane , Brown Ashley S. , Williams Horace R. T. , Goldin Robert D. , Thomas Howard C. , Thursz Mark R. , Taylor‐Robinson Simon D.
Published: June 2012

Aim:  Hepatic lipid is important in the pathogenesis and progression of hepatitis C‐related liver disease. Polyunsaturated fatty acids have been shown to reduce viral replication in cell culture. Proton magic angle spinning magnetic resonance spectroscopy (1H MAS MRS) enables metabolic analysis of intact tissue. The aim was to examine the relationship between hepatic lipid composition by metabolic profiling of liver tissue at baseline and treatment response to pegylated‐Interferon alfa2 and Ribavirin.

Methods:  Baseline liver biopsy samples from 31 patients with chronic hepatitis C were analyzed histologically and by 1H MAS MRS. Indices of lipid composition were derived and partial least squares discriminant analysis with cross‐validation was used to predict treatment outcome.

Results:  Of 31 patients, 14 achieved sustained virological response (SVR). Lipid polyunsaturation (median (IQR)) was higher in SVR (3.41% (2.31)) than in treatment failure (TF) (2.15% (1.51)), P = 0.02. Lipid saturation was lower in SVR (85.9% (3.39)) than TF (86.7% (2.17)), P = 0.04. The total lipid content was lower in SVR (1.54% (0.81)) than TF (2.72% (3.47)), P = 0.004. Total choline to lipid ratio was higher in SVR (11.51% (9.99)) than TF (7.5% (6.82)), P = 0.007. Cross‐validation correctly predicted the SVR group in 13 of 14 samples with 1 sample misclassified, and the TF group in all 17 samples.

Conclusions:  Lipid polyunsaturation was greater and total lipid lower in those with SVR, compared with TF. Metabolic profiling of intact liver biopsy samples predicted SVR with high accuracy. Hepatic lipid composition may impact on treatment success.
The effects of different learning environments on students’ motivation for learning and their achievement
Authors: Baeten Marlies , Dochy Filip , Struyven Katrien
Published: June 2012

Background. Research in higher education on the effects of student‐centred versus lecture‐based learning environments generally does not take into account the psychological need support provided in these learning environments. From a self‐determination theory perspective, need support is important to study because it has been associated with benefits such as autonomous motivation and achievement.

Aim. The purpose of the study is to investigate the effects of different learning environments on students’ motivation for learning and achievement, while taking into account the perceived need support.

Sample. First‐year student teachers (N= 1,098) studying a child development course completed questionnaires assessing motivation and perceived need support. In addition, a prior knowledge test and case‐based assessment were administered.

Method. A quasi‐experimental pre‐test/post‐test design was set up consisting of four learning environments: (1) lectures, (2) case‐based learning (CBL), (3) alternation of lectures and CBL, and (4) gradual implementation with lectures making way for CBL.

Results. Autonomous motivation and achievement were higher in the gradually implemented CBL environment, compared to the CBL environment. Concerning achievement, two additional effects were found; students in the lecture‐based learning environment scored higher than students in the CBL environment, and students in the gradually implemented CBL environment scored higher than students in the alternated learning environment. Additionally, perceived need support was positively related to autonomous motivation, and negatively to controlled motivation.

Conclusions. The study shows the importance of gradually introducing students to CBL, in terms of their autonomous motivation and achievement. Moreover, the study emphasizes the importance of perceived need support for students’ motivation.
Novel targets for sepsis‐induced kidney injury: the glomerular arterioles and the sympathetic nervous system
Authors: May Clive N. , Calzavacca Paolo , Ishikawa Ken , Langenberg Christoph , Wan Li , Ramchandra Rohit , Bellomo Rinaldo
Published: June 2012

Sepsis and septic shock are the most common causes of acute kidney injury (AKI) in the intensive care unit, and mortality remains high despite improvements in our ability to support vital organs. The lack of development of effective treatments is partly because there has been little advance in our understanding of the pathophysiology of septic AKI, owing to the difficulty in conducting experiments on critically ill patients and use of inappropriate experimental models. Recently, however, a number of new concepts have emerged that challenge existing dogma and give insights into the causes of AKI. Traditionally, renal ischaemia has been proposed as the main cause of AKI, but it is becoming apparent that in sepsis with a hyperdynamic circulation, the most common situation in septic patients, there is an increase or at least no decrease in renal blood flow. In this review, the possible role of changes in pre‐ and postglomerular resistance in setting the increased level of renal blood flow in the presence of a decreased glomerular filtration rate is discussed. New evidence also indicates that the increased sympathetic nerve activity that occurs in sepsis may contribute to the induction of organ failure. Experimental studies indicate that inhibition of central sympathetic outflow with α2‐adrenoceptor agonists or treatment with β1‐adrenoceptor antagonists might reduce mortality in experimental endotoxaemia and sepsis. The possibility that these beneficial actions are partly dependent on a reduction in the excessive cytokine release caused by marked and prolonged sympathetic activation is discussed.
Effects of chronic heart failure on neuronal nitric oxide synthase‐mediated control of microvascular O2 pressure in contracting rat skeletal muscle
Authors: Copp Steven W. , Hirai Daniel M. , Ferguson Scott K. , Holdsworth Clark T. , Musch Timothy I. , Poole David C.
Published: June 2012

Key points

Nitric oxide (NO) is an important vasodilatory signalling molecule that regulates O2 pressure within the skeletal muscle microvasculature (). In healthy subjects, NO is derived from two principal NO synthase (NOS) isoforms: neuronal NOS (nNOS) and endothelial NOS (eNOS).

Chronic heart failure (CHF) results in peripheral vascular dysfunction that is attributed, in part, to impaired NO function. This NO‐mediated impairment is attributed generally to eNOS dysfunction. It is unknown if nNOS‐mediated regulation of function is impaired in CHF.

Our present results demonstrate that skeletal muscle blood flow reductions and alterations during contractions observed following nNOS inhibition in healthy rats are markedly attenuated or absent in CHF rats, which is indicative of impaired nNOS function.

Identification of the mechanisms underlying impaired microvascular function in CHF is an important step in the development of treatments designed to improve CHF‐induced skeletal muscle microvascular pathology.

Abstract  Chronic heart failure (CHF) impairs nitric oxide (NO)‐mediated regulation of the skeletal muscle microvascular O2 delivery/ ratio (which sets the microvascular O2 pressure, ). Given the pervasiveness of endothelial dysfunction in CHF, this NO‐mediated dysregulation is attributed generally to eNOS. It is unknown whether nNOS‐mediated regulation is altered in CHF. We tested the hypothesis that CHF impairs nNOS‐mediated control. In healthy and CHF (left ventricular end diastolic pressure (LVEDP): 6 ± 1 versus 14 ± 1 mmHg, respectively, P < 0.05) rats spinotrapezius muscle blood flow (radiolabelled microspheres), (phosphorescence quenching), and (Fick calculation) were measured before and after 0.56 mg kg−1 i.a. of the selective nNOS inhibitor S‐methyl‐l‐thiocitrulline (SMTC). In healthy rats, SMTC increased baseline (Control: 29.7 ± 1.4, SMTC: 34.4 ± 1.9 mmHg, P < 0.05) by reducing (↓20%) without any effect on blood flow and speeded the mean response time (MRT, time to reach 63% of the overall kinetics response, Control: 24.2 ± 2.0, SMTC: 18.5 ± 1.3 s, P < 0.05). In CHF rats, SMTC did not alter baseline (Control: 25.7 ± 1.6, SMTC: 28.6 ± 2.1 mmHg, P > 0.05), at rest, or the MRT (Control: 22.8 ± 2.6, SMTC: 21.3 ± 3.0 s, P > 0.05). During the contracting steady‐state, SMTC reduced blood flow (↓15%) and (↓15%) in healthy rats such that was unaltered (Control: 19.8 ± 1.7, SMTC: 20.7 ± 1.8 mmHg, P > 0.05). In marked contrast, in CHF rats SMTC did not change contracting steady‐state blood flow, , or (Control: 17.0 ± 1.4, SMTC: 17.7 ± 1.8 mmHg, P > 0.05). nNOS‐mediated control of skeletal muscle microvascular function is compromised in CHF versus healthy rats. Treatments designed to ameliorate microvascular dysfunction in CHF may benefit by targeting improvements in nNOS function.
Interaction with Lipid II Induces Conformational Changes in Bovicin HC5 Structure
Authors: Paiva Aline Dias , Irving Nicole , Breukink Eefjan , Mantovani Hilário Cuquetto
Published: June 2012

Bovicin HC5 is a lantibiotic produced by
Streptococcus bovis
HC5 that targets the cell wall precursor lipid II. An understanding of the modes of action against target bacteria can help broadening the clinical applicability of lantibiotics in human and veterinary medicine. In this study, the interaction of bovicin HC5 with lipid II was examined using tryptophan fluorescence and circular dichroism spectroscopy with model membrane systems that do or do not allow pore formation by bovicin HC5. In the presence of lipid II, a blue-shift of 12 nm could be observed for the fluorescence emission maximum of the tryptophan residue for all of the membrane systems tested. This change in fluorescence emission was paralleled by a decrease in accessibility toward acrylamide and phospholipids carrying a spin-label at the acyl chain; the tryptophan residue of bovicin HC5 was located near the twelfth position of the membrane phospholipid acyl chains. Moreover, the binding of lipid II by bovicin HC5 induced remarkable conformational changes in the bovicin HC5 structure. The interaction of bovicin HC5 with lipid II was highly stable even at pH 2.0. These results indicate that bovicin HC5 interacts directly with lipid II and that the topology of this interaction changes under different conditions, which is relevant for the biological activity of the peptide. To our knowledge, bovicin HC5 is the only bacteriocin described thus far that is able to interact with its target in extreme pH values, and this fact might be related to its unique structure and stability.
In Vitro
Activity and Microbiological Efficacy of Tedizolid (TR-700) against Gram-Positive Clinical Isolates from a Phase 2 Study of Oral Tedizolid Phosphate (TR-701) in Patients with Complicated Skin and Skin Structure Infections
Authors: Prokocimer Philippe , Bien Paul , DeAnda Carisa , Pillar Chris M. , Bartizal Ken
Published: June 2012

Tedizolid (TR-700, formerly torezolid) is the active moiety of the prodrug tedizolid phosphate (TR-701), a next-generation oxazolidinone, with high potency against Gram-positive species, including methicillin-resistant
Staphylococcus aureus
(MRSA). A recently completed randomized, double-blind phase 2 trial evaluated 200, 300, or 400 mg of oral tedizolid phosphate once daily for 5 to 7 days in patients with complicated skin and skin structure infections. This report examines the
in vitro
activity of tedizolid and Zyvox (linezolid) against Gram-positive pathogens isolated at baseline and describes the microbiological and clinical efficacy of tedizolid. Of 196 isolates tested, 81.6% were
S. aureus
, and of these, 76% were MRSA. The MIC
50
and MIC
90
of tedizolid against both methicillin-susceptible
S. aureus
(MSSA) and MRSA were 0.25 μg/ml, compared with a MIC
50
of 1 μg/ml and MIC
90
of 2 μg/ml for linezolid. For coagulase-negative staphylococci (
n
= 7), viridans group streptococci (
n
= 15), and beta-hemolytic streptococci (
n
= 3), the MICs ranged from 0.03 to 0.25 μg/ml for tedizolid and from 0.12 to 1 μg/ml for linezolid. The microbiological eradication rates at the test-of-cure visit (7 to 14 days posttreatment) in the microbiologically evaluable population (
n
= 133) were similar in all treatment groups, with overall eradication rates of 97.7% for all pathogens, 97.9% for MRSA, and 95.7% for MSSA. The clinical cure rates for MRSA and MSSA infections were 96.9% and 95.7%, respectively, across all dose groups. This study confirms the potent
in vitro
activity of tedizolid against pathogenic Gram-positive cocci, including MRSA, and its 4-fold-greater potency in comparison with linezolid. All dosages of tedizolid phosphate showed excellent microbiological and clinical efficacy against MRSA and MSSA.