bluuebunny/crossref_metadata_2025 huggingface dataset:
Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients
Authors: Sánchez Fructuoso A.I. , Calvo N. , Perez‐Flores I. , Valero R. , Rodríguez‐Sánchez B. , García de Viedma D. , Muñoz P. , Barrientos A.
Published: May 2011

A.I. Sánchez Fructuoso, N. Calvo, I. Perez‐Flores, R. Valero, B. Rodríguez‐Sánchez, D. García de Viedma, P. Muñoz, A. Barrientos. Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients. Transpl Infect Dis 2011: 13: 584–591. All rights reserved

Abstract: BK virus (BKV) nephropathy is a common viral infection in renal transplant patients, with a prevalence of 1–9% at approximately 12 months after surgery. While it is widely agreed that reduction of immunosuppression should be the first intervention after diagnosis of BKV infection, there is no consensus on whether calcineurin inhibitors or antiproliferative drugs should be reduced first. Furthermore, target levels of immunosuppressive drugs are poorly defined, as are criteria for replacing one immunosuppressive agent with another.

Results. We report our series of 15 renal transplant patients who underwent surgery between September 2004 and March 2010 and who developed BKV infection. The first 8 patients were treated with reduction of immunosuppression; 7 of these patients received cidofovir and 6 received intravenous immunoglobulin. The remaining 7 renal transplant recipients received mammalian target of rapamycin inhibitors (imTOR). In this group, we observed faster and more efficacious BKV clearance in plasma and urine and a steady improvement in allograft function, with no episodes of acute allograft rejection during follow‐up. The polymerase chain reaction assay for BKV in urine became positive in 2 patients in whom imTOR were stopped due to severe side effects.

Conclusions. The use of imTOR should be considered a first step in the treatment of renal transplant recipients with BKV infection. In our experience, this change in treatment was safe and resulted in viral clearance.
Spatio‐temporal heterogeneity in Arabidopsis thaliana leaves under drought stress
Authors: Sperdouli I. , Moustakas M.
Published: May 2011

Using chlorophyll (chl) fluorescence imaging, we studied the effect of mild (MiDS), moderate (MoDS) and severe (SDS) drought stress on photosystem II (PSII) photochemistry of 4‐week‐old Arabidopsis thaliana. Spatio‐temporal heterogeneity in all chl fluorescence parameters was maintained throughout water stress. After exposure to drought stress, maximum quantum yield of PSII photochemistry (Fv/Fm) and quantum efficiency of PSII photochemistry (ΦPSΙΙ) decreased less in the proximal (base) than in the distal (tip) leaf. The chl fluorescence parameter Fv/Fm decreased less after MoDS than MiDS. Under MoDS, the antioxidant mechanism of A. thaliana leaves seemed to be sufficient in scavenging reactive oxygen species, as evident by the decreased lipid peroxidation, the more excitation energy dissipated by non‐photochemical quenching (NPQ) and decreased excitation pressure (1−qp). Arabidopsis leaves appear to function normally under MoDS, but do not seem to have particular metabolic tolerance mechanisms under MiDS and SDS, as revealed by the level of lipid peroxidation and decreased quantum yield for dissipation after down‐regulation in PSII (ΦNPQ), indicating that energy dissipation by down‐regulation did not function and electron transport (ETR) was depressed. The simultaneous increased quantum yield of non‐regulated energy dissipation (ΦNO) indicated that both the photochemical energy conversion and protective regulatory mechanism were insufficient. The non‐uniform photosynthetic pattern under drought stress may reflect different zones of leaf anatomy and mesophyll development. The data demonstrate that the effect of different degrees of drought stress on A. thaliana leaves show spatio‐temporal heterogeneity, implying that common single time point or single point leaf analyses are inadequate.
Rapid and Precise Detection of Latent Infections of Wheat Stripe Rust in Wheat Leaves using Loop‐Mediated Isothermal Amplification
Authors: Huang Chong , Sun Zhenyu , Yan Jiahui , Luo Yong , Wang Haiguang , Ma Zhanhong
Published: May 2011

Wheat stripe rust caused by Puccinia striiformis f.sp. tritici (Pst) is one of the most important diseases of wheat worldwide. Detection of latent infection in leaves is critical for estimating the initial inoculum potential of epidemics. A loop‐mediated isothermal amplification (LAMP) assay was developed and evaluated for the detection of Pst DNA in spores and wheat seedlings with latent infections. LAMP assay could detect as low as 2 pg/μl template DNA and detect latent infections from leaves as early as 24 h after inoculation. This provides a rapid and accurate method of estimating latent infection levels.
Role of mineralocorticoid action in the brain in salt‐sensitive hypertension
Authors: Oki Kenji , Gomez‐Sanchez Elise P , Gomez‐Sanchez Celso E
Published: May 2011

1. The mechanisms by which excessive salt causes hypertension involve more than retention of sodium and water by the kidneys and are far from clear. Mineralocorticoids act centrally to increase salt appetite, sympathetic drive and vasopressin release, resulting in hypertension that is prevented by the central infusion of mineralocorticoid receptor (MR) antagonists. The MR has similar affinity for aldosterone and the glucocorticoids corticosterone or cortisol. Specificity is conferred in transport epithelia by the colocalization of the MR with 11β‐hydroxysteroid dehydrogenase Type 2. Coexpression also occurs in some neurons, notably those of the nucleus tractus solitarius that are activated by sodium depletion and aldosterone and mediate salt‐seeking behaviour.

2. The salt‐induced hypertension of the Dahl salt‐sensitive rat is mitigated by the central infusion of a mineralocorticoid antagonist even though circulating aldosterone is normal or reduced in salt‐sensitive (SS). Contrary to reports that salt appetite in the Dahl salt‐sensitive rat is depressed, we found that it is increased compared with that in Spraque‐Dawley rats.

3. Extra‐adrenal aldosterone synthesis in the brain occurs in minute amounts that could only be relevant locally. Expression of aldosterone synthase mRNA and aldosterone concentrations in the brain of Dahl salt‐sensitive rats are increased compared with Spraque‐Dawley rats. The central infusion of inhibitors of aldosterone synthesis lowers salt‐induced hypertension in the Dahl salt‐sensitive rat, suggesting a role for excessive Dahl salt‐sensitive synthesis in the brain. Brain MR, particularly those in the paraventricular nuclei, regulate inflammatory processes that are exacerbated by sodium and lead to cardiovascular dysfunction.
Evolution of developmental cyclic adenosine monophosphate signaling in the Dictyostelia from an amoebozoan stress response
Authors: Schaap Pauline
Published: May 2011

The Dictyostelid social amoebas represent one of nature’s several inventions of multicellularity. Though normally feeding as single cells, nutrient stress triggers the collection of amoebas into colonies that form delicately shaped fruiting structures in which the cells differentiate into spores and up to three cell types to support the spore mass. Cyclic adenosine monophosphate (cAMP) plays a very dominant role in controlling morphogenesis and cell differentiation in the model species Dictyostelium discoideum. As a secreted chemoattractant cAMP coordinates cell movement during aggregation and fruiting body morphogenesis. Secreted cAMP also controls gene expression at different developmental stages, while intracellular cAMP is extensively used to transduce the effect of other stimuli that control the developmental program. In this review, I present an overview of the different roles of cAMP in the model D. discoideum and I summarize studies aimed to resolve how these roles emerged during Dictyostelid evolution.
Signaling mechanisms for chemotaxis
Authors: Wang Yu , Chen Chun‐Lin , Iijima Miho
Published: May 2011

Cells recognize external chemical gradients and translate these environmental cues into amplified intracellular signaling that results in elongated cell shape, actin polymerization toward the leading edge, and movement along the gradient. Mechanisms underlying chemotaxis are conserved evolutionarily from Dictyostelium amoeba to mammalian neutrophils. Recent studies have uncovered several parallel intracellular signaling pathways that crosstalk in chemotaxing cells. Here, we review these signaling mechanisms in Dictyostelium discoideum.
Collective oscillations in developing cells: Insights from simple systems
Authors: Kamino Keita , Fujimoto Koichi , Sawai Satoshi
Published: May 2011

From hormonal secretion to gene expression, multicellular dynamics are rich in oscillatory regulation. When organized in space and time, periodic cell–cell signaling can give rise to long‐range coordination of gene expression and cell movement in tissues. Lack of synchrony of the oscillations on the other hand can serve as a source of initial divergence of cell fate in stem cells. How properties of individual cells can account for collective rhythmic behaviors at the tissue level remains elusive in most cases. Recently, studies in chemical reactions, synthetic gene circuits, yeast and social amoeba Dictyostelium have greatly enhanced our view of collective oscillations in cell populations. From these relatively simple systems, a unified view of how excitable and oscillatory regulations could be tuned and coupled to give rise to tissue‐level oscillations is emerging. The review focuses on recent progress in cyclic adenosine monophosphate oscillations in Dictyostelium and highlights similarities and differences with other systems. We will see that the autonomy of single‐cell level oscillations and different ways in which cells are coupled influence how group‐level information can be encoded in collective oscillations.
Regulation of spatiotemporal expression of cell–cell adhesion molecules during development of Dictyostelium discoideum
Authors: Siu Chi‐Hung , Sriskanthadevan Shrivani , Wang Jun , Hou Liansheng , Chen Gong , Xu Xiaoqun , Thomson Alexander , Yang Chunxia
Published: May 2011

The social amoeba Dictyostelium discoideum is a simple but powerful model organism for the study of cell–cell adhesion molecules and their role in morphogenesis during development. Three adhesive systems have been characterized and studied in detail. The spatiotemporal expression of these adhesion proteins is stringently regulated, often coinciding with major shifts in the morphological complexity of development. At the onset of development, amoeboid cells express the Ca2+‐dependent cell–cell adhesion molecule DdCAD‐1, which initiates weak homophilic interactions between cells and assists in the recruitment of individuals into cell streams. DdCAD‐1 is unique because it is synthesized as a soluble protein in the cytoplasm. It is targeted for presentation on the cell surface by an unconventional protein transport mechanism via the contractile vacuole. Concomitant with the aggregation stage is the expression of the contact sites A glycoprotein csA/gp80 and TgrC1, both of which mediate Ca2+/Mg2+‐independent cell–cell adhesion. Whereas csA/gp80 is a homophilic binding protein, TgrC1 binds to a heterophilic receptor on the cell. During cell aggregation, csA/gp80 associates preferentially with lipid rafts, which facilitate the rapid assembly of adhesion complexes. TgrC1 is synthesized at low levels during aggregation and rapid accumulation occurs initially in the peripheral cells of loose mounds. The extracellular portion of TgrC1 is shed and becomes part of the extracellular matrix. Additionally, analyses of knockout mutants have revealed important biological roles played by these adhesion proteins, including size regulation, cell sorting and cell‐type proportioning.
Nuclear organization and transcriptional dynamics in Dictyostelium
Authors: Stevense Michelle , Chubb Jonathan R. , Muramoto Tetsuya
Published: May 2011

The Dictyostelium model has a set of features uniquely well‐suited to developing our understanding of transcriptional control. The complete Dictyostelium discoideum genome sequence has revealed that many of the molecular components regulating transcription in larger eukaryotes are conserved in Dictyostelium, from transcription factors and chromatin components to the enzymes and signals that regulate them. In addition, the system permits visualization of single gene firing events in living cells, which provides a more detailed view of transcription and its relationships to cell and developmental processes. This review will bring together the available knowledge of the structure and dynamics of the Dictyostelium nucleus and discuss recent transcription imaging studies and their implications for stability and accuracy of cell decisions.
How social evolution theory impacts our understanding of development in the social amoebaDictyostelium
Authors: Strassmann Joan E. , Queller David C.
Published: May 2011

Dictyostelium discoideumhas been very useful for elucidating principles of development over the last 50 years, but a key attribute means there is a lot to be learned from a very different intellectual tradition: social evolution. BecauseDictyosteliumarrives at multicellularity by aggregation instead of through a single‐cell bottleneck, the multicellular body could be made up of genetically distinct cells. If they are genetically distinct, natural selection will result in conflict over which cells become fertile spores and which become dead stalk cells. Evidence for this conflict includes unequal representation of two genetically different clones in spores of a chimera, the poison‐like differentiation inducing factor (DIF) system that appears to involve some cells forcing others to become stalk, and reduced functionality in migrating chimeras. Understanding how selection operates on chimeras of genetically distinct clones is crucial for a comprehensive view ofDictyosteliummulticellularity. In nature,Dictyosteliumfruiting bodies are often clonal, or nearly so, meaning development will often be very cooperative. Relatedness levels tell us what benefits must be present for sociality to evolve. Therefore it is important to measure relatedness in nature, show that it has an impact on cooperation in the laboratory, and investigate genes thatDictyosteliumuses to discriminate between relatives and non‐relatives. Clearly, there is a promising future for research at the interface of development and social evolution in this fascinating group.
Ethylene as a potent inducer of sexual development
Authors: Amagai Aiko
Published: May 2011

A novel and critical function of ethylene, a potent plant hormone, has been well documented in Dictyostelium, because it leads cells to the sexual development (macrocyst formation) by inducing zygote formation. Zygote formation (sexual cell fusion) and the subsequent nuclear fusion are the characteristic events occurring during macrocyst formation. A novel gene, zyg1 was found to be predominantly expressed during the sexual development, and its enforced expression actually induces zygote formation. As expected, the zygote inducer, ethylene enhances the expression of zyg1. Thus the function of ethylene has been verified at all of individual (macrocyst formation), cellular (zygote formation), and molecular levels (zyg1 expression). Based on our recent studies concerning the behavior and function of the zyg1 product (ZYG1 protein), the signal transduction pathways involved in zygote formation are proposed in this review.
Hepatitis C recurrence after liver transplantation: Has the human leukocyte antigen mismatching at individual loci a role?
Authors: Audet Maxime , Piardi Tullio , Cag Murat , Navarro Francis , Ornis Sara , Cinqualbre Jacques , Wolf Philippe , Panaro Fabrizio
Published: May 2011

Background and Aim:  The objective of this 11‐year cohort retrospective study conducted in adult patients with chronic hepatitis C virus (HCV) who underwent liver transplantation (LT) was to identify whether human leukocyte antigen (HLA) mismatching is associated with the recurrence of HCV and with the time to recurrence of HCV.

Methods:  Among the 181 patients (74% men; mean age: 54 years, range 25–71) who underwent a LT between 1995 and 2006 in the study center, 163 had relevant data in their medical chart documenting HCV recurrence, and 107 (65.64%) reported a histological evidence of HCV recurrence.

Results:  Survival was 78% at 5 years. There was no significant relationship between the total score of HLA‐mismatches and the recurrence of HCV. Similarly, there was no significant relationship between the total score of HLA mismatches and the time to recurrence of HCV. For the analyses at each individual locus, a significant relationship between the individual scores of HLA‐mismatches and the recurrence of HCV were observed. Out of the 40 patients who experienced a rejection, the rate of recurrence was not different according to the severity of the rejection (75% mild, 64% moderate and 64% for severe rejection).

Conclusions:  In conclusion, this large study did not demonstrate any relationship between the total score of HLA mismatches and HCV‐recurrence. Contrarily a significant relationship between the individual scores of HLA mismatches (HLA‐A3, HLA‐B35, HLA‐DR3, HLA‐DR7, HLA‐DQ2, HLA‐DQ2‐0) and the recurrence of HCV were observed.
Role of hepatic stellate cells on graft injury after small‐for‐size liver transplantation
Authors: Chen Wei , Liang Liang , Ma Tao , Li Junjian , Xu Guodong , Zhang Yun , Bai Xueli , Liang Tingbo
Published: May 2011

Background and Aim: Small‐for‐size grafts are prone to mechanical injury and a series of chemical injuries that are related to hemodynamic force. Hepatic stellate cells activate andtrans‐differentiate into contractile myofibroblast‐like cells during liver injury. However, the role of hepatic stellate cells on sinusoidal microcirculation is unknown with small‐for‐size grafts.

Methods: Thirty‐five percent of small‐for‐size liver transplantation was performed with rats as donors and recipients. Endothelin‐1 levels as well as hepatic stellate cells activation‐related protein expression, endothelin‐1 receptors, and ultrastructural changes were examined. The cellular localizations of two types of endothelin‐1 receptors were detected. Furthermore, liver function and sinusoidal microcirculation were analyzed using two different selective antagonists of endothelin‐1 receptor.

Results: Intragraft expression of hepatic stellate cells activation‐related protein such as desmin, crystallin‐B and smooth muscle α‐actin was upregulated as well as serum endothelin‐1 levels and intragraft expression of the two endothelin receptors. The antagonist to endothelin‐1 A receptor not to the endothelin‐1 B receptor could attenuate microcirculatory disturbance and improve liver function.

Conclusions: Small‐for‐size liver transplantation displayed increased hepatic stellate cells activation and high level of endothelin‐1 binding to upregulation of endothelin‐1 A receptor on hepatic stellate cells, which contracted hepatic sinusoid inducing graft injury manifested as reduction of sinusoidal perfusion rate and elevation of sinusoidal blood flow.
Factors associated with a protracted hospital stay after hip fracture surgery in Japan
Authors: Takahashi Chihiro , Fushimi Kiyohide , Matsuda Shinya
Published: May 2011

Aim:  Hip fracture is a major injury in the elderly and has a high impact on quality of life and use of health‐care resources. In this study, we aimed to identify the factors related to prolonged hospital stay and poor outcome after hip fracture surgery.

Methods:  We evaluated data from 8920 cases at 398 acute‐care hospitals in Japan. Multivariate logistic regression analysis was used to determine the factors associated with the length of postoperative hospital stay.

Results:  A shorter postoperative hospital stay was associated with admission to a high surgical volume hospital (P < 0.001). On the other hand, a longer postoperative hospital stay was associated with infective complications, admission to a private hospital, an interval of more than 3 days between admission and surgery (P < 0.001 for all), and an interval of more than 1 day between surgery and start of rehabilitation (P = 0.01). Further analysis revealed that infective complications were more likely in older patients (P = 0.003) and patients with comorbidities (P = 0.03).

Conclusion:  The results imply that hospital stay, and, therefore, use of medical resources, can be decreased by performing surgeries shortly after patients are admitted, preventing postoperative infections, and starting rehabilitation on the next day of the surgery. One of the limitations of our study was that data of the length of hospital stay at transferred hospitals were not available. Therefore, further prospective studies will be needed to address significance of early surgery and rehabilitation. Geriatr Gerontol Int 2011; 11: 474–481.
Effects of insulin and amyloid β1–42 oligomers on glucose incorporation and mitochondrial function in cultured rat hippocampal neurons
Authors: Miichi Yoshiaki , Sakurai Takashi , Akisaki Taichi , Yokono Koichi
Published: May 2011

Aim:  The molecular basis for impaired glucose metabolism in patients with Alzheimer's disease (AD) has not been fully clarified. We tested whether insulin and amyloid (A)β1–42 oligomers would regulate glucose metabolism and energy homeostasis directly in cultured rat hippocampal neurons and evaluated possible interactions between insulin signaling and Aβ1–42 oligomers.

Methods:  Dissociated hippocampal neurons were prepared from Wistar rat embryos at day 21 of gestation and cultured for 14 days. Cultured neurons were exposed to insulin (1 µM) for 30 min, and Aβ1–42 oligomers (1 µM) were added to culture media for 10–30 min. The glucose uptake of cultured neurons was measured by enzymatic fluorescence assay using 2‐deoxy‐d‐glucose (2DG), and adenosine triphosphate (ATP) contents were quantified using a luciferin/luciferase luminescence assay.

Results:  Aβ1–42 oligomers did not suppress 2DG uptake, reflecting the activities of glucose transporters and/or hexokinase, but led to disrupted ATP contents in the presence and absence of monocarboxylates (lactate/pyruvate). Insulin and C‐peptide did not change glucose uptake or ATP concentrations.

Conclusion:  The primary target of Aβ1–42 oligomers might be mitochondria, which could explain the reduced cerebral glucose levels in patients with AD. Moreover, insulin signaling was not directly linked to glucose metabolism or energy homeostasis in cultured rat hippocampal neurons. Geriatr Gerontol Int 2011; 11: 517–524.
Postoperative hyponatremia following calvarial vault remodeling in craniosynostosis
Authors: Cladis Franklyn P. , Bykowski Michael , Schmitt Erica , Naran Sanjay , Moritz Michael L. , Cray James , Grunwaldt Lorelei , Losee Joseph
Published: May 2011

Background:  The incidence, severity, and risk factors for the development of hyponatremia in patients undergoing craniosynostosis surgery are not well known.

Objective:  To determine the incidence and severity of hyponatremia as a complication in surgical correction of craniosynostosis and to identify risk factors for postoperative hyponatremia.

Methods:  A retrospective medical record review for 2003–2008 of the Cleft and Craniofacial Database was made. Specific data collected included sodium values, age, weight, type of surgery, duration of surgery, administration of DDAVP, composition and volume of pre‐operative, intra‐operative, postoperative parenteral fluids, volume of blood, colloid, and crystalloid transfused, estimated blood loss (EBL), medications, comorbidities, pre‐operative signs of elevated intracranial pressure (ICP), syndromic vs nonsyndromic craniosynostosis, and the complications associated with hyponatremia.

Results:  A total of 72 records were reviewed. The incidence of postoperative hyponatremia was 30.6%. There was no intra‐operative hyponatremia. While hospital stay was not prolonged, ICU stay was significantly longer (1.9 vs 2.9 days, P = 0.001). Elevated ICP was significantly associated with hyponatremia (P < 0.002). A greater volume of blood loss (EBL) was associated with postoperative hyponatremia (P = 0.019). Patients with normal pre‐operative ICP were more likely to become hyponatremic if they were female (relative risk = 2.43; P < 0.05). The average decrease in sodium was greater in patients receiving hyponatremic (hypotonic) vs normonatremic (isotonic) postoperative IVF’s (5.5 vs 3.2 mEq·l−1, P = 0.039). There were no postoperative complications related to hyponatremia.

Conclusions:  The incidence of postoperative hyponatremia after calvarial vault remodeling was determined to be 30.6%. Hyponatremia was significantly associated with increased pre‐operative ICP, blood loss, and female gender (normal pre‐operative ICP). The average decrease in sodium was greater in patients receiving hyponatremic postoperative IVF’s.
Time‐dependent perioperative anesthetic management and outcomes of the first 100 consecutive cases of spring‐assisted surgery for sagittal craniosynostosis
Authors: Ririe Douglas G. , Smith Timothy E. , Wood Benjamin C. , Glazier Steven S. , Couture Daniel E. , Argenta Louis C. , David Lisa R.
Published: May 2011

Background:  The anesthetic risks and outcomes of the first 100 consecutive spring‐assisted surgeries (SAS) for cranial expansion from a single institution are reported. The effect of number of procedures was also tested on hematocrit postoperative day 1 (POD1), anesthesia time, and surgery time of the first procedure.

Methods:  The records of 100 consecutive patients undergoing SAS were reviewed. Anesthesia management and related complications are presented. Time series linear regression analysis was performed on hematocrit POD1, anesthesia time, and surgery time of the first procedure.

Results:  The average age of the first insertion procedure was 4.4 and 9.0 months for the second removal procedure. Two patients were inadvertently extubated during positioning. Thirty‐eight children had a decrease in blood pressure >20% from baseline. No child was admitted to the intensive care unit. No patient received any blood or blood product transfusion. Anesthesia time, surgery time, and hematocrit POD1 were correlated with procedure number or experience.

Conclusions:  Changes in anesthetic management resulted from changing the procedure. The reduction in volume resuscitation reduces the need for invasive monitoring. Facility and comfort with the surgical procedure increase with time and number of procedures performed. This experience further reduces blood loss and risk of transfusion.
Pediatric sedation – evolution and revolution
Authors: Cravero Joseph P. , Havidich Jeana E.
Published: May 2011

Pediatric sedation continues to change in terms of the professionals who provide this care, those who produce original research on this topic, guidelines and literature concerning risk, medications employed, and methods for training for new providers. Some of the changes could be categorized as ‘evolutionary’ or gradual in nature and predictable – such as the changing role of anesthesiologists in the field of pediatric sedation and the use of the well‐established dissociative sedative, ketamine. Other changes in pediatric sedation are more radical or ‘revolutionary’. They include reconsideration of what is defined as an ‘adverse event’ during sedation, the use of propofol or dexmedetomidine, and the application of human patient simulation for training. This review will highlight the ongoing changes in the dynamic field of pediatric sedation by focusing on some of the important progress (both evolutionary and revolutionary) that has occurred across the varied specialties that provide this care.
Role of combination of l‐arginine and α‐tocopherol in renal transplantation ischaemia/reperfusion injury: a randomized controlled experimental study in a rat model
Authors: Shokeir Ahmed A. , Barakat Nashwa , Hussein Abdel‐Aziz M. , Awadalla Amira , Abdel‐Aziz Azza , Abo‐Elenin Hassan
Published: May 2011

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

Renal ischaemia/reperfusion (I/R) injury is an inevitable consequence of kidney transplantation. It contributes to delayed graft function (DGF), acute renal failure and graft rejection.

The present study investigates for the first time the impact of a combination of l‐arginine and alpha tocopherol on the renal ischemia/reperfusion injury in a rodent model of kidney transplation. We found that concomitant administration of l‐arginine and α‐tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys.

OBJECTIVES

To investigate the role of l‐arginine and α‐tocopherol in ischaemia/reperfusion injury in a kidney transplanted rat model.

MATERIALS AND METHODS

In total, 40 male Sprague‐Dawley rats subjected to renal transplantation received FK506 (tacrolimus) to overcome early acute rejection episodes. Animals were divided randomly into four groups (ten rats each). Group I were treated with FK506 (2 mg/kg/bw/day) and served as the control group. Group II were treated with l‐arginine 300 mg/kg/bw. Group III were treated with α‐tocopherol 30 mg/kg/bw. Group IV were treated with l‐arginine and α‐tocopherol. Urine and blood samples were taken at 0 (before operation), 2, 7 and 14 days post‐transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium and blood urea nitrogen. Histological examination and measurement of malondialdehyde in kidney tissues were also performed.

RESULTS

Serum creatinine and blood urea nitrogen significantly decreased in l‐arginine and α‐tocopherol, as well as combination groups, compared to the control group. Malondialdehyde was significantly decreased in the combination group compared to l‐arginine and α‐tocopherol alone. Histological examination of the control group showed that acute tubular necrosis was markedly decreased in transplanted kidneys treated with a combination of both l‐arginine and α‐tocopherol.

CONCLUSIONS

Concomitant administration of l‐arginine and α‐tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys.
Peripheral neuropathy: an underdiagnosed cause of erectile dysfunction
Authors: Valles‐Antuña Consuelo , Fernandez‐Gomez Jesus , Fernandez‐Gonzalez Fernando
Published: May 2011

OBJECTIVES

• To assess the prevalence of peripheral neuropathy in patients with erectile dysfunction (ED).

• To evaluate the reliability of clinical tests such as the five‐item version of the International Index of Erectile Function (IIEF‐5) and the Neuropathy Symptom Score (NSS) classification system in predicting the concurrence of peripheral neuropathy.

PATIENTS AND METHODS

• We studied 90 patients who were consecutively recruited from the Department of Andrology of the Central Hospital of Asturias.

• Anamnesis included questions about risk factors related to ED.

• The severity of ED was classified according to IIEF‐5 scores and symptoms of peripheral neuropathy were assessed using the NSS.

• Neurophysiological tests included electromyography, nerve conduction studies, evoked potentials from pudendal and tibial nerves as well as bulbocavernosus reflex.

• Small fibre function was assessed using quantitative sensory tests and sympathetic skin response. Statistical analysis was performed using the SPSS‐11 program.

RESULTS

• Patients with more severe symptoms of peripheral neuropathy showed lower (worse) IIEF‐5 scores (P= 0.015) and required more aggressive therapies (P < 0.001).

• Neurophysiological exploration confirmed neurological pathology in 68.9% of patients, of whom 7.8% had myelopathy and 61.1% peripheral neuropathy.

• Polyneuropathy was found in 37.8% of the patients, of whom 8.9% had pure small fibre polyneuropathy, and pudendal neuropathy was diagnosed in 14.4%.

• No association between neurophysiological diagnosis and IIEF‐5 score was detected, but a statistical association was found between neuropathy and NSS scores.

CONCLUSIONS

• Up to now, the impact of peripheral neuropathy in the pathogenesis of ED has been underestimated. The combination of anamnesis and an ad hoc neurophysiological protocol showed its high prevalence and provided a more accurate prognosis.

• In future, clinical practice should optimize the assessment of pelvic small fibre function.
Second to fourth digit ratio, adult testosterone level and testosterone deficiency
Authors: García‐Cruz Eduardo , Huguet Jorge , Piqueras Marta , Ribal María J. , Alcaraz Antonio
Published: May 2011

Study Type – Diagnostic (exploratory cohort)

Level of Evidence 2b

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

2D/4D digit ratio is inversely related to intrauterus exposure to androgens. Our experience suggests that 2D/4D digit ratio inversely predicts adult testosterone levels and is directly related to hypogonadism.

OBJECTIVES

• The ratio of the second and fourth finger lengths (2D/4D) is related to intrauterine exposure to testosterone. The relationship between 2D/4D and adult hormonal pattern is controversial.

• The aim of our study was to determine if there was a relationship between adult serum testosterone levels and the 2D/4D ratio.

PATIENTS AND METHODS

• We prospectively recruited 204 consecutive patients referred for transrectal prostate biopsy between January 2008 and June 2009. The same physician performed clinical examinations, 2D/4D measurements and the transrectal biopsy in all cases.

• Cut‐off points of 231 and 346 ng/dL testosterone (8 and 12 nmol/L) were used. 2D/4D determination was done with a vernier calliper on the left hand.

• The hormonal profile (testosterone and sexual hormone binding globulin) of the patients was determined between 7.00 am and 11.00 am.

• Age, weight, height, body mass index, toxic habits, digital rectal examination, prostate‐specific antigen and 2D and 4D measurements were recorded prospectively.

RESULTS

• The mean age was 67 ± 7 years and the mean testosterone level was 413 ± 18 ng/dL (14.33 ± 0.62 nmol/L).

• The percentages of patients with testosterone <231 ng/dL (8 nmol/L) and testosterone <346 ng/dL (12 nmol/L) were 6.1 and 30.6 respectively.

• Univariate analysis showed that low 2D/4D ratios were related to higher levels of testosterone (B=−741.98; β=−0.165, P= 0.045) and also with low prevalence of biochemical hypogonadism (testosterone <346 ng/dL).

• Mean 2D/4D ratio in patients with testosterone >346 ng/dL was lower than in patients with testosterone <346 ng/dL (2D/4D 0.97 ± 0.037 vs 0.99 ± 0.043 depending on their hormonal status, P= 0.05). High 2D/4D ratio was associated with low testosterone serum levels (P= 0.046).

CONCLUSIONS

• The 2D/4D ratio is related to adult testosterone levels and the presence of testosterone deficiency syndrome.

• Patients with high 2D/4D ratios have lower testosterone levels and higher risk of testosterone deficiency syndrome.
Histopathological variables and biomarkers enhancer of zeste homologue 2, Ki‐67 and minichromosome maintenance protein 7 as prognosticators in primarily endocrine‐treated prostate cancer
Authors: Tolonen Teemu T. , Tammela Teuvo L.J. , Kujala Paula M. , Tuominen Vilppu J. , Isola Jorma J. , Visakorpi Tapio
Published: May 2011

Study Type – Prognosis (case series)

Level of Evidence 4

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

Gleason score is a strong prognostic factor, but its reproducibility is not optimal. Our data show that multipte perineural invasion and Ki‐67 index are signs of early biochemical progression in patients treated with hormonal therapy.

OBJECTIVE

• To evaluate the prognostic value of histopathological variables and immunostainings of biomarkers enhancer of zeste homologue 2 (EZH2), Ki‐67 and minichromosome maintenance protein 7 (MCM7) from core biopsies of hormonally treated patients with prostate cancer.

PATIENTS AND METHODS

• Biopsies of 247 primarily endocrine‐treated patients were analysed for histopathological characteristics and Gleason scores (GS) according to the revised guidelines of International Society of Urologic Pathology (ISUP) consensus conference 2005.

• Immunohistochemical stainings were analysed with the aid of digital image analysis.

• The prognostic value of the histopathological variables and the biomarkers was analysed with univariate and multivariate Cox regression analysis, with biochemical recurrence as an endpoint.

RESULTS

• Biomarkers EZH2 (relative risk [RR] 2.0, 95% confidence interval 1.2–3.3), Ki‐67 (3.4, 2.1–5.5) and MCM7 (2.4, 1.5–3.9) were significantly associated with progression‐free survival in a univariate analysis.

• Ki‐67 immunostaining index detected high‐risk patients with GS of 7 (9.1, 8.0–10.3).

• In a multivariate analysis with non‐conventional GS groups 5–7 (3 + 4), 7(4 + 3)–8, and 9–10, the independent prognostic markers were pretreatment GS (2.2, 1.5–3.2), prostate‐specific antigen (PSA) level (2.1, 1.1–4.2), perineural invasion (PNI) (1.6, 1.2–2.2), and clinical T‐stage (cT) (1.9, 1.0–3.7).

• Combination of the independent markers (PSA level >20 ng/mL or GS >3 + 4 or PNI >3 or cT >2) yielded best risk stratification (RR 11.6, 10.4–12.7).

CONCLUSIONs

• GS remains one of the most important prognostic factors in prostate cancer. However, the refined guidelines by ISUP 2005 might have shifted the threshold between low‐grade and high‐grade cancers from GS 6 vs 7 to GS 3 + 4 vs 4 + 3.

• PNI is an independent prognostic marker superior to cT.

• Ki‐67 is the most useful biomarker in detecting patients with GS = 7 at high risk for progression.
Changing patterns of bladder cancer in the USA: evidence of heterogeneous disease
Authors: Zhang Yawei , Zhu Cairong , Curado Maria Paula , Zheng Tongzhang , Boyle Peter
Published: May 2011

Study Type – Disease prevalence (retrospective cohort)

Level of Evidence 2b

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

The incidence of bladder cancer has shown a slightly decreasing trend during the past several decades. All published epidemiological studies have trended papillary transitional cell carcinoma (PTCC) and non‐papillary transitional cell carcinoma (NPTCC) as one single disease called transitional cell carcinoma (TCC).

This study for the first time examined the time trends by PTCC and NPTCC and found that these two histological subtypes presented different temporal trends. The study results support the hypothesis that bladder cancer is a heterogeneous disease and taking disease’s heterogeneity into consideration in future epidemiological studies is essential.

OBJECTIVE

• To test the hypothesis that bladder cancer is a heterogeneous disease.

PATIENTS AND METHODS

• We examined the temporal trends of bladder cancer by histological subtype and by disease stage and grade using the National Cancer Institute’s Surveillance, Epidemiology, and End Results data collected in 1973–2007.

RESULTS

• The age‐adjusted incidence rates of bladder cancer showed a slight decrease from 1973 to 2007 (annual percentage change [APC]=−0.4, P < 0.05).

• Although the age‐adjusted incidence rates of non‐papillary transitional cell carcinoma decreased by about 53% from 7.9 per 100 000 in 1973 to 3.7 per 100 000 in 2007 (APC =−2.2, P < 0.05), the age‐adjusted incidence rates of papillary transitional cell carcinoma increased by about 56% from 6.8 per 100 000 in 1973 to 10.6 per 100 000 in 2007 (APC = 0.5, P < 0.05).

• Among other rare histological subtypes, except for small cell carcinoma which showed a slightly rising trend, squamous cell carcinoma, adenocarcinoma and others all presented a decreasing trend.

• Similar patterns were found for different stages (localized, regional and distant), but a dramatic increasing trend of grade IV was found between 1998 and 2007 when a corresponding decreasing trend was shown for grades I, II and III.

CONCLUSION

• The results support the hypothesis that bladder cancer is a heterogeneous disease and taking disease heterogeneity into consideration in future epidemiological studies is essential.
The breast care nurse: the care specialist in breast centres
Authors: Voigt B. , Grimm A. , Loßack M. , Klose P. , Schneider A. , Richter‐Ehrenstein C.
Published: May 2011

VOIGT B., GRIMM A., LOßACK M., KLOSE P., SCHNEIDER A. & RICHTER‐EHRENSTEIN C. (2011) The breast care nurse: the care specialist in breast centres. International Nursing Review58, 450–453

Background:  In Europe, breast cancer is the most common form of cancer in women; 26.5 per cent of all new malignant diseases and 17.5 per cent of all cancer deaths are due to this type of cancer. In Germany, approximately every tenth woman is diagnosed with breast cancer during her lifetime.

Objective:  In order to increase the quality of life of breast cancer patients, the European Society of Mastology (EUSOMA) requires the availability of, and an integration of qualified and specialized care into the interdisciplinary team. Thus, in Germany, a new type of job profile for ‘breast nurse’ as a qualified care specialist has to be established and has to be oriented towards the international standards of a breast care nurse (BCN).

Methods:  The Charité's Academy of Health – in cooperation with the Interdisciplinary Breast Centre of the Charité– has offered a career advisory service curriculum for the BCN since 2006 in accordance with the EUSOMA guidelines.

Results:  In three courses, 45 BCNs have been trained. In the first refresher seminar in May 2009, the BCNs were given an opportunity to exchange with fellow BCNs their experiences.

Conclusion:  We were able to set up a new curriculum to train nurses as BCNs as to improve the quality of care for breast cancer patients and to orientate the training towards the international standards of a BCN qualification.
The psychological neuroscience of depression: Implications for understanding effects of deep brain stimulation
Authors: SJÖBERG RICKARD L. , BLOMSTEDT PATRIC
Published: May 2011

Sjöberg, R. L. & Blomstedt, P. (2011). The psychological neuroscience of depression: Implications for understanding effects of deep brain stimulation.Scandinavian Journal of Psychology 52, 411–419.

In this article it is suggested that current psychological theories of depression presuppose that this condition will develop as a result of a vicious circle involving negatively biased communication between systems of emotional stress‐/alarm‐signaling, executive functions and mood regulation. These systems may from a neuroanatomical point of view be located in the limbic system, the orbitofrontal and lateral prefrontal cortex and the hypothalamus‐pituitary‐adrenal (HPA‐) axis respectively. The theoretical and practical implications of this model for the understanding of pharmacological treatments of depression are briefly discussed and this theory is related to the catecholamine hypothesis of depression. The model is furthermore discussed in relation to deep brain stimulation (DBS) of treatment resistant major depression. Similarities and differences between this perspective and the one advocated by the “homeostatic theory” of depression are discussed. It is concluded that a topographical psychological theory may offer a useful heuristic in thinking about depression and that it offers several testable predictions about treatments of the disorder.
The rumouring of SARS during the 2003 epidemic in China
Authors: Tai Zixue , Sun Tao
Published: May 2011

By analysing rumour content as covered by major Chinese newspapers, this article explores the multiple dimensions of SARS‐related rumouring throughout China during the 2003 epidemic. Findings indicate a strong correlation between the scale of SARS infections and level of rumour activities across regions. As for channels of dissemination, the rumour process still found a natural habitat in word of mouth, while internet‐based platforms and cell phone text messaging emerged as viable grapevines. Our particular typology of SARS‐incurred rumours leads us to identify four distinct types of rumours: legendary rumours; aetiological narratives; proto‐memorates; and bogies. The four types of rumours are discussed against the background of superstitious beliefs, folklore practices, popular mentalities, and China’s particular socio‐political information environment.
Tissue donation to biobanks: a review of sociological studies
Authors: Lipworth Wendy , Forsyth Rowena , Kerridge Ian
Published: May 2011

Collections of human tissue (biobanks) are thought to be an essential resource for biomedical research. Biobanks have, however, been a source of debate in both bioethics and sociology. In recent years this theorising has been supplemented with empirical research, including a significant body of qualitative research, into donors’ experiences and attitudes. To date, this literature has not been synthesised. We report the findings of a review of qualitative literature regarding the ways in which lay people construct and experience the process of donation to biobanks. Our aim was to determine what the qualitative research literature tells us about the process of donating to biobanks, and how this can enrich existing insights from quantitative research and from theoretical sociology and bioethics. Qualitative research shows that donation to biobanks is a complex process shaped by donors’ embeddedness in a number of social contexts; by complex relations of trust in biomedicine; and by the ambiguous status of human tissue. While these findings are theoretically and practically useful, current sociological theorising is very general. A more detailed and nuanced ‘sociology of biobanking’ is needed, and this might be best achieved by exploring specific theoretical questions in a variety of biobanking settings.
Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China
Authors: Zhao L.P. , Di Z. , Zhang L. , Wang L. , Ma L. , Lv Y. , Hong Y. , Wei H. , Chen H.D. , Gao X.H.
Published: May 2011

Background  Defect in the SPINK5 gene is known to be implicated in Netherton syndrome (NS), and has been suggested to be a locus predisposing to atopy in general. Coding polymorphisms in SPINK5 exons 13, 14 and 26 have been reported to be associated with atopic dermatitis (AD), asthma and high level of IgE.

Objectives  To examine whether the SPINK5 gene polymorphisms are associated with AD in Northeast China, and to assess how variants influence selected phenotypic traits.

Methods  A case–control study was conducted on four non‐synonymous polymorphisms in the coding region of SPINK5 in AD and controls. The SPINK5 gene polymorphisms were analyzed using the PCR and RFLP methods.

Results  For the four non‐synonymous SNPs, A1103G(Asn368Ser), G1156A(Asp386Asn), G1258A(Glu420Lys), G2475T(Glu825Asp) in SPINK5, the allelic frequencies in the AD cohort were 0.55 for 1103G, 0.57 for 1156A, 0.54for 1258A, 0.62 for 2475T, consistent with those already published in the original British and Japanese cohorts. The T allele of SNP 2475G > T was found to be significantly associated with AD. There were significant differences in genotype frequencies for G1258A(Glu420Lys) and G2475T(Glu825Asp) but not for A1103G(Asn368Ser) and G1156A(Asp386Asn). Genotypes GA(420Glu/Lys), TT (2475Asp/Asp) and GT(2475Glu/Asp) were significantly more frequent in AD. However, the SPINK5 gene polymorphisms was found not to be associated with AD in regard to either serum IgE levels, concurrent allergic asthma or early onset of AD.

Conclusions  Our study confirms the association between SPINK5 and AD.