bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine
Authors: O’Connor Erin K , Ivey Jan R , Bowles Douglas K
Published: June 2012

Background

Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine.

Methods

Pigs received intracoronary infusions of physiologic levels (1–100 nM) of testosterone, the metabolite 5α-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1–100 nM) of testosterone, 5α-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels.

Results

In vivo, testosterone and 5α-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5α-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males.

Conclusions

Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.
Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo
Authors: Holen Ingunn , Whitworth Jacob , Nutter Faith , Evans Alyson , Brown Hannah K , Lefley Diane V , Barbaric Ivana , Jones Mark , Ottewell Penelope D
Published: June 2012

Introduction

The majority of deaths from breast cancer are a result of metastases; however, little is understood about the genetic alterations underlying their onset. Genetic profiling has identified the adhesion molecule plakoglobin as being three-fold reduced in expression in primary breast tumors that have metastasized compared with nonmetastatic tumors. In this study, we demonstrate a functional role for plakoglobin in the shedding of tumor cells from the primary site into the circulation.

Methods

We investigated the effects of plakoglobin knockdown on breast cancer cell proliferation, migration, adhesion, and invasion in vitro and on tumor growth and intravasation in vivo. MCF7 and T47D cells were stably transfected with miRNA sequences targeting the plakoglobin gene, or scramble vector. Gene and protein expression was monitored by quantitative polymerase chain reaction (qPCR) and Western blot. Cell proliferation, adhesion, migration, and invasion were measured by cell counting, flow cytometry, and scratch and Boyden Chamber assays. For in vivo experiments, plakoglobin knockdown and control cells were inoculated into mammary fat pads of mice, and tumor growth, shedding of tumor cells into the bloodstream, and evidence of metastatic bone lesions were monitored with caliper measurement, flow cytometry, and microcomputed tomography (μCT), respectively.

Results

Plakoglobin and γ-catenin expression were reduced by more than 80% in all knockdown cell lines used but were unaltered after transfection with the scrambled sequence. Reduced plakoglobin resulted in significantly increased in MCF7 and T47D cell proliferation in vitro and in vivo, compared with control, with significantly more tumor cells being shed into the bloodstream of mice bearing plakoglobin knockdown tumors. In addition, plakoglobin knockdown cells showed a >250% increase in invasion through basement membrane and exhibited reduced cell-to-cell adhesion compared with control cells.

Conclusion

Decreased plakoglobin expression increases the invasive behavior of breast cancer cells. This is the first demonstration of a functional role for plakoglobin/γ-catenin in the metastatic process, indicating that this molecule may represent a target for antimetastatic therapies.
Association of gender with outcomes in critically ill patients
Authors: Mahmood Kamran , Eldeirawi Kamal , Wahidi Momen M
Published: June 2012

Introduction

The influence of gender on mortality and other outcomes of critically ill patients is not clear. Different studies have been performed in various settings and patient populations often yielding conflicting results. We wanted to assess the relationship of gender and intensive care unit (ICU) outcomes in the patients included in the Acute Physiology and Chronic Health Evaluation (APACHE) IV database (Cerner Corporation, USA).

Methods

We performed a retrospective review of the data available in the APACHE IV database. A total of 261,255 consecutive patients admitted to adult ICUs in United States from 1 January 2004 to 31 December 2008 were included. Readmissions were excluded from the analysis. The primary objective of the study was to assess the relationship of gender with ICU mortality. The secondary objective was to evaluate the association of gender with active therapy, mechanical ventilation, length of stay in the ICU, readmission rate and hospital mortality. The gender-related outcomes for disease subgroups including acute coronary syndrome, coronary artery bypass graft (CABG) surgery, sepsis, trauma and chronic obstructive pulmonary disease (COPD) exacerbation were assessed as well.

Results

ICU mortality was 7.2% for men and 7.9% for women, odds ratio (OR) for death for women was 1.07 (95% confidence interval (CI): 1.04 to 1.1). There was a statistically significant interaction between gender and age. In patients <50 years of age, women had a reduced ICU mortality compared with men, after adjustment for acute physiology score, ethnicity, co-morbid conditions, pre-ICU length of stay, pre-ICU location and hospital teaching status (adjusted OR 0.83, 95% CI: 0.76 to 0.91). But among patients ≥50 years of age, there was no significant difference in ICU mortality between men and women (adjusted OR 1.02, 95% CI: 0.98 to 1.06).

A higher proportion of men received mechanical ventilation, emergent surgery, thrombolytic therapy and CABG surgery. Men had a higher readmission rate and longer length of ICU stay. The adjusted mortality of women compared to men was higher with CABG, while it was lower with COPD exacerbation. There was no significant difference in mortality in acute coronary syndrome, sepsis and trauma.

Conclusions

Among the critically ill patients, women less than 50 years of age had a lower ICU mortality compared to men, while 50 years of age or older women did not have a significant difference compared to men. Women had a higher mortality compared to men after CABG surgery and lower mortality with COPD exacerbation. There was no difference in mortality in acute coronary syndrome, sepsis or trauma.
Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study
Authors: Vermeulen Windsant Iris C , de Wit Norbert CJ , Sertorio Jonas TC , Beckers Erik AM , Tanus-Santos Jose E , Jacobs Michael J , Buurman Wim A
Published: June 2012

Introduction

The increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied.

Methods

Thirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearson's chi-square test or Fisher's exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation.

Results

Storage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P < 0.001 and P < 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations.

Conclusion

These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.
Comparative multi-omics systems analysis of Escherichia coli strains B and K-12
Authors: Yoon Sung Ho , Han Mee-Jung , Jeong Haeyoung , Lee Choong Hoon , Xia Xiao-Xia , Lee Dae-Hee , Shim Ji Hoon , Lee Sang Yup , Oh Tae Kwang , Kim Jihyun F
Published: June 2012

Background

Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced.

Results

We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation testing. This systems analysis revealed that E. coli B is well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B has an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions.

Conclusions

This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture conditions but also to design recombinant hosts.
Trauma equals danger—damage control by the immune system
Authors: Stoecklein Veit M , Osuka Akinori , Lederer James A
Published: June 2012

Review on how traumatic injuries influence immune system phenotypes and functions.

Traumatic injuries induce a complex host response that disrupts immune system homeostasis and predisposes patients to opportunistic infections and inflammatory complications. The response to injuries varies considerably by type and severity, as well as by individual variables, such as age, sex, and genetics. These variables make studying the impact of trauma on the immune system challenging. Nevertheless, advances have been made in understanding how injuries influence immune system function as well as the immune cells and pathways involved in regulating the response to injuries. This review provides an overview of current knowledge about how traumatic injuries affect immune system phenotype and function. We discuss the current ideas that traumatic injuries induce a unique type of a response that may be triggered by a combination of endogenous danger signals, including alarmins, DAMPs, self-antigens, and cytokines. Additionally, we review and propose strategies for redirecting injury responses to help restore immune system homeostasis.
Cognitive development in children with 22q11.2 deletion
syndrome
Authors: Duijff Sasja N. , Klaassen Petra W. J. , de Veye Henriette F. N. Swanenburg , Beemer Frits A. , Sinnema Gerben , Vorstman Jacob A. S.
Published: June 2012

Background

People with 22q11.2 deletion syndrome (velo-cardio-facial syndrome) have
a 30-fold risk of developing schizophrenia. In the general population the
schizophrenia phenotype includes a cognitive deficit and a decline in
academic performance preceding the first episode of psychosis in a
subgroup of patients. Findings of cross-sectional studies suggest that
cognitive abilities may decline over time in some children with 22q11.2
deletion syndrome. If confirmed longitudinally, this could indicate that
one or more genes within 22q11.2 are involved in cognitive decline.

Aims

To assess longitudinally the change in IQ scores in children with 22q11.2
deletion syndrome.

Method

Sixty-nine children with the syndrome were cognitively assessed two or
three times at set ages 5.5 years, 7.5 years and 9.5 years.

Results

A mean significant decline of 9.7 Full Scale IQ points was found between
ages 5.5 years and 9.5 years. In addition to the overall relative decline
that occurred when results were scored according to age-specific IQ
norms, in 10 out of a group of 29 children an absolute decrease in
cognitive raw scores was found between ages 7.5 years and 9.5 years. The
decline was not associated with a change in behavioural measures.

Conclusions

The finding of cognitive decline can be only partly explained as the
result of ‘growing into deficit’; about a third of 29 children showed an
absolute loss of cognitive faculties. The results underline the
importance of early psychiatric screening in this population and indicate
that further study of the genes at the 22q11.2 locus may be relevant to
understanding the genetic basis of early cognitive deterioration.
Methodology and reporting of systematic reviews and meta-analyses of observational studies in psychiatric epidemiology: Systematic review
Authors: Brugha Traolach S. , Matthews Ruth , Morgan Zoe , Hill Trevor , Alonso Jordi , Jones David R.
Published: June 2012

Background

Relatively little is known of the use of systematic review and synthesis methods of non-randomised psychiatric epidemiological studies, which play a vital role in aetiological research, planning and policy-making.

Aims

To evaluate reviews of psychiatric epidemiological studies of functional mental disorders that employed synthesis methods such as systematic review or meta-analysis, or other forms of quantitative review.

Method

We searched the literature to identify appropriate reviews published during the period 1996 to April 2009. Selected reviews were evaluated using published review guidelines.

Results

We found 106 reviews in total, of which 38 (36%) did not mention method of data abstraction from primary studies at all. Many failed to mention study quality, publication bias, bias and confounding. In 73 studies that performed a meta-analysis, 58 (79%) tested for heterogeneity and of these, 47 found significant heterogeneity. Studies that detected heterogeneity made some allowance for this. A major obstacle facing reviewers is the wide variation between primary studies in the use of instruments to measure outcomes and in sampling methods used.

Conclusions

Many deficiencies found in systematic reviews are potentially remediable, although synthesis of primary study findings in a field characterised by so many sources of heterogeneity will remain challenging.
Childhood maltreatment and DSM-IV adult mental disorders: Comparison of prospective and retrospective findings
Authors: Scott Kate M. , McLaughlin Katie A. , Smith Don A. R. , Ellis Pete M.
Published: June 2012

Background

Prior research reports stronger associations between childhood maltreatment and adult psychopathology when maltreatment is assessed retrospectively compared with prospectively, casting doubt on the mental health risk conferred by maltreatment and on the validity of retrospective reports.

Aims

To investigate associations of psychopathology with prospectivev.retrospective maltreatment ascertainment.

Method

A nationally representative sample of respondents aged 16–27 years (n= 1413) in New Zealand completed a retrospective assessment of maltreatment and DSM-IV mental disorders. Survey data were linked with a national child protection database to identify respondents with maltreatment records (prospective ascertainment).

Results

Childhood maltreatment was associated with elevated odds of mood, anxiety and drug disorders (odds ratios = 2.1–4.1), with no difference in association strength between prospective and retrospective groups. Prospectively ascertained maltreatment predicted unfavourable depression course involving early onset, chronicity and impairment.

Conclusions

Prospectively and retrospectively assessed maltreatment elevated the risk of psychopathology to a similar degree. Prospectively ascertained maltreatment predicted a more unfavourable depression course.
Better care for depression in the workplace: Integrating
occupational and mental health services
Authors: Gilbody Simon , Bower Peter , Rick Jo
Published: June 2012

People with depression in the workplace are less productive and at risk of
losing their job. Many never work again. Intervention should ideally begin
before sickness absence occurs and early return to work should be the focus
of care. This will require closer integration of primary care, mental health
and occupational health services.
Role of mental health professionals in the management of
functional somatic symptoms in primary care
Authors: Morriss Richard
Published: June 2012

Functional somatic symptoms associated with persistent frequent attendance
is emotionally demanding, costly and intractable to treat. Such patients are
hard to engage in practice and research by mental health professionals,
whose main role may be indirect training, supporting and advising primary
care professionals rather than direct patient care.
Psychodynamic psychiatry's green shoots
Authors: Holmes Jeremy
Published: June 2012

Psychodynamic psychiatry makes a significant educational, scientific and therapeutic contribution to contemporary psychiatry. Recent developments in gene–environment interaction, neuropsychoanalysis and the accumulating evidence base for psychoanalytic therapies and their implications for practice are reviewed.
Preventing chronic disease in people with mental health problems: the HEALTH Passport approach
Authors: Anderson Naomi , Sridharan Sanjana , Megson Matthew , Evans Amy , Vallance James , Singh Swaran , Shukla Rashmi , Patel Vinod
Published: June 2012

Aims and method

The HEALTH Passport is a tool to help patients make lifestyle changes to reduce the future burden of chronic disease. This study assesses the potential of this behaviour change strategy in psychiatric patients. We introduced 50 psychiatric in-patients to the HEALTH Passport and asked them to complete a semi-qualitative questionnaire. Results were compared with those of 100 controls.

Results

Psychiatric in-patients are exposed to almost twice as many modifiable risk factors of chronic disease compared with controls. Although psychiatric in-patients are less motivated to address their risk factors, the HEALTH Passport could almost halve the proportion of psychiatric patients at high risk of chronic disease.

Clinical implications

The low level of health literacy among psychiatric patients must be addressed to reduce their risk exposure. Potentially, the HEALTH Passport provides a cost-effective tool for this purpose.
MAPPA and mental health — 10 years of controversy
Authors: Yakeley Jessica , Taylor Richard , Cameron Angus
Published: June 2012

Multiagency public protection arrangements (MAPPAs) were established in England and Wales 10 years ago to oversee statutory arrangements for public protection by the identification, assessment and management of high-risk offenders. This article reviews MAPPAs' relationship with mental health services over the past decade. Despite areas of progress in the management of mentally ill offenders, inconsistent practice persists regarding issues of confidentiality and information-sharing between agencies, which calls for clearer and more consistent guidance from the Royal College of Psychiatrists, the Ministry of Justice and the Department of Health.
Macrophage Mineralocorticoid Receptor Signaling Plays a Key Role in Aldosterone-Independent Cardiac Fibrosis
Authors: Bienvenu Laura A. , Morgan James , Rickard Amanda J. , Tesch Greg H. , Cranston Greg A. , Fletcher Elizabeth K. , Delbridge Lea M. D , Young Morag J.
Published: June 2012

Mineralocorticoid receptor (MR) activation promotes the development of cardiac fibrosis and heart failure. Clinical evidence demonstrates that MR antagonism is protective even when plasma aldosterone levels are not increased. We hypothesize that MR activation in macrophages drives the profibrotic phenotype in the heart even when aldosterone levels are not elevated. The aim of the present study was to establish the role of macrophage MR signaling in mediating cardiac tissue remodeling caused by nitric oxide (NO) deficiency, a mineralocorticoid-independent insult. Male wild-type (MRflox/flox) and macrophage MR-knockout (MRflox/flox/LysMCre/+; mac-MRKO) mice were uninephrectomized, maintained on 0.9% NaCl drinking solution, with either vehicle (control) or the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 150 mg/kg/d) for 8 wk. NO deficiency increased systolic blood pressure at 4 wk in wild-type l-NAME/salt-treated mice compared with all other groups. At 8 wk, systolic blood pressure was increased above control in both l-NAME/salt treated wild-type and mac-MRKO mice by approximately 28 mm Hg by l-NAME/salt. Recruitment of macrophages was increased 2- to 3-fold in both l-NAME/salt treated wild-type and mac-MRKO. Inducible NOS positive macrophage infiltration and TNFα mRNA expression was greater in wild-type l-NAME/salt-treated mice compared with mac-MRKO, demonstrating that loss of MR reduces M1 phenotype. mRNA levels for markers of vascular inflammation and oxidative stress (NADPH oxidase 2, p22phox, intercellular adhesion molecule-1, G protein-coupled chemokine receptor 5) were similar in treated wild-type and mac-MRKO mice compared with control groups. In contrast, l-NAME/salt treatment increased interstitial collagen deposition in wild-type by about 33% but not in mac-MRKO mice. mRNA levels for connective tissue growth factor and collagen III were also increased above control treatment in wild-type (1.931 ± 0.215 vs. 1 ± 0.073) but not mac-MRKO mice (1.403 ± 0.150 vs. 1.286 ± 0.255). These data demonstrate that macrophage MR are necessary for the translation of inflammation and oxidative stress into interstitial and perivascular fibrosis after NO deficiency, even when plasma aldosterone is not elevated.
IGF-I Regulates Pheochromocytoma Cell Proliferation and Survival In Vitro and In Vivo
Authors: Fernández María Celia , Venara Marcela , Nowicki Susana , Chemes Héctor E. , Barontini Marta , Pennisi Patricia A.
Published: June 2012

IGFs are involved in malignant transformation and growth of several tissues, including the adrenal medulla. The present study was designed to evaluate the impact of IGF-I on pheochromocytoma development. We used a murine pheochromocytoma (MPC) cell line (MPC4/30) and an animal model with a reduction of 75% in circulating IGF-I levels [liver-IGF-I-deficient (LID) mice] to perform studies in vitro and in vivo. We found that, in culture, IGF-I stimulation increases proliferation, migration, and anchorage-independent growth, whereas it inhibits apoptosis of MPC cells. When injected to control and to LID mice, MPC cells grow and form tumors with features of pheochromocytoma. Six weeks after cell inoculation, all control mice developed sc tumors. In contrast, in 73% of LID mice, tumor development was delayed to 7–12 wk, and the remaining 27% did not develop tumors up to 12 wk after inoculation. LID mice harboring MPC cells and treated with recombinant human IGF-I (LID+) developed tumors as controls. Tumors developed in control, LID, and LID+ mice had similar histology and were similarly positive for IGF-I receptor expression. The apoptotic index was higher in tumors from LID mice compared with those from control mice, whereas vascular density was decreased. In summary, our work demonstrates that IGF-I has a critical role in maintaining tumor phenotype and survival of already transformed pheochromocytoma cells and is required for the initial establishment of these tumors, providing encouragement to carry on research studies to address the IGF-I/IGF-I receptor system as a target of therapeutic strategies for pheochromocytoma treatment in the future.
Effects of β4 integrin expression on microRNA patterns in breast cancer
Authors: Gerson Kristin D. , Maddula V. S. R. Krishna , Seligmann Bruce E. , Shearstone Jeffrey R. , Khan Ashraf , Mercurio Arthur M.
Published: June 2012

The integrin α6β4 is defined as an adhesion receptor for laminins. Referred to as ‘β4’, this integrin plays a key role in the progression of various carcinomas through its ability to orchestrate key signal transduction events and promote cell motility. To identify novel downstream effectors of β4 function in breast cancer, microRNAs (miRNAs) were examined because of their extensive links to tumorigenesis and their ability to regulate gene expression globally. Two breast carcinoma cell lines and a collection of invasive breast carcinomas with varying β4 expression were used to assess the effect of this integrin on miRNA expression. A novel miRNA microarray analysis termed quantitative Nuclease Protection Assay (qNPA) revealed that β4 expression can significantly alter miRNA expression and identified two miRNA families, miR-25/32/92abc/363/363-3p/367 and miR-99ab/100, that are consistently downregulated by expression of this integrin. Analysis of published Affymetrix GeneChip data identified 54 common targets of miR-92ab and miR-99ab/100 within the subset of β4-regulated mRNAs, revealing several genes known to be key components of β4-regulated signaling cascades and effectors of cell motility. Gene ontology classification identified an enrichment in genes associated with cell migration within this population. Finally, gene set enrichment analysis of all β4-regulated mRNAs revealed an enrichment in targets belonging to distinct miRNA families, including miR-92ab and others identified by our initial array analyses. The results obtained in this study provide the first example of an integrin globally impacting miRNA expression and provide evidence that select miRNA families collectively target genes important in executing β4-mediated cell motility.
Interleukin-1 receptor antagonist is beneficial after subarachnoid haemorrhage in rat by blocking haem-driven inflammatory pathology
Authors: Greenhalgh Andrew D. , Brough David , Robinson Emily M. , Girard Sylvie , Rothwell Nancy J. , Allan Stuart M.
Published: June 2012

Subarachnoid haemorrhage (SAH) is a major contributor to the burden of stroke on society. Treatment options are limited and animal models of SAH do not always mimic key pathophysiological hallmarks of the disease, thus hindering development of new therapeutics. Inflammation is strongly associated with brain injury after SAH in animals and patients, and inhibition of the pro-inflammatory cytokine interleukin-1 (IL-1) represents a possible therapeutic target. Here we report that a rupture of the middle cerebral artery in the rat produces heterogeneous infarct patterns similar to those observed in human SAH. Administration of the IL-1 receptor antagonist (IL-1Ra) reduced blood-brain barrier breakdown, and the extent of breakdown correlated with brain injury. After SAH, haem oxygenase-1 (HO-1) was strongly expressed around the bleed site and in the cortex and striatum, indicating the presence of free haem, a breakdown product of haemoglobin. HO-1 expression was also found in the same regions as microglial/macrophage expression of IL-1α. The direct effect of haem on IL-1α expression was confirmed in vitro using organotypic slice culture (OSC). Haem-induced cell death was dependent on IL-1 signalling, with IL-1Ra completely blocking cellular injury. Furthermore, stimulation of mouse primary mixed glial cells with haem induced the release of IL-1α, but not IL-1β. Thus, we suggest that haem, released from lysed red blood cells (RBCs) in the subarachnoid space, acts as a danger-associated molecular pattern (DAMP) driving IL-1-dependent inflammation. These data provide new insights into inflammation after SAH-induced brain injury and suggest IL-1Ra as a candidate therapeutic for the disease.
Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells
Authors: Yin Yan , Lin Congxing , Veith G. Michael , Chen Hong , Dhandha Maulik , Ma Liang
Published: June 2012

Developmental exposure to diethylstilbestrol (DES) causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of the Peroxisome Proliferator-Activated Receptor gamma (PPARγ)-mediated adipogenic/lipid metabolic pathway, including PPARγ itself, are targets of DES in the neonatal uterus. TEM and Oil Red O staining further demonstrate a dramatic increase in lipid deposition in the uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor induced reproductive abnormalities.
Rapid Preparation of Cycloheptane Ring from 1,2-Diketone and Bis(iodozincio)methane via Oxy-Cope Rearrangement Using Microflow System
Authors: Haraguchi Ryosuke , Takada Yoshiaki , Matsubara Seijiro
Published: June 2012

Treatment of 1,6-dialkylhexa-1,5-diene-3,4-diones with bis(iodozincio)methane at −78 °C for several hours gave cis-dialkenylcyclopropane-1,2-diols which rearranged into the zinc alkoxides of cis-5,6-dialkylcyclohepta-3,7-diene-1,3-diol in good yields at room temperature as a one-pot reaction. The reaction should be performed under the careful temperature control. When the reaction was performed using a microflow system, these two-step reactions were able to be performed in a few seconds at room temperature.
Manganese Oxide-catalyzed Additive- and Solvent-free Aerobic Oxidative Synthesis of Primary Amides from Primary Amines
Authors: Yamaguchi Kazuya , Wang Ye , Mizuno Noritaka
Published: June 2012

Various kinds of primary amides could be synthesized through indirect aerobic oxygenation of primary amines using simple amorphous MnO2 under additive- and solvent-free conditions. The catalyst/product separation was very easy, and the retrieved MnO2 catalyst could be reused without an appreciable loss of its high catalytic performance.
A Facile Access to 3,5-Disubstituted Oxazolones Featuring a Cu-catalyzed Cyclization of N-Alkynyl tert-Butyl Carbamates
Authors: Lu Zenghui , Yang Zhaozhen , Cui Weijian , Zhu Gangguo
Published: June 2012

Using cheap and readily accessible CuCl as the catalyst, an operationally simple and efficient method for the synthesis of 3,5-disubstituted oxazolones has been realized by the cyclization of N-alkynyl tert-butyl carbamates. The reaction proceeds under mild reaction conditions and shows good functional group compatibility.
Porous ZnFe2O4 Nanospheres Grown on Graphene Nanosheets as a Superior Anode Material for Lithium Ion Batteries
Authors: Chen Xianglan , Cheng Bin , Xu Huayun , Yang Jian , Qian Yitai
Published: June 2012

A facile solvothermal approach has been developed to grow porous ZnFe2O4 nanospheres on the surface of graphene nanosheets. The porous structure of ZnFe2O4 and the presence of graphene could significantly improve the electrochemical performance of the composite. The composite exhibits the reversible capacities of 970 mA h g−1 at 50 mA g−1 and 700 mA h g−1 at 600 mA g−1, suggesting its promising potential as a superior anode material for lithium ion batteries.
New Class of Thiocyanate-free Ruthenium(II) Complex as a Near-IR Sensitizer for Dye-sensitized Solar Cells
Authors: Funaki Takashi , Funakoshi Hiromi , Onozawa-Komatsuzaki Nobuko , Kasuga Kazuyuki , Sayama Kazuhiro , Sugihara Hideki
Published: June 2012

A new class of thiocyanate-free ruthenium(II) complex containing a 2,6-pyridinedicarboxylate ligand was designed and synthesized as a near-IR sensitizer for dye-sensitized solar cells, and its photophysical and photochemical properties were characterized. The solar cell sensitized with this complex exhibited efficient panchromatic sensitization over the entire visible wavelength region extending into the near-IR region. An overall conversion efficiency of 6.5% was attained under standard AM 1.5 irradiation (100 mW cm−2).
A Neutral Five-coordinated Organoruthenium(0) Complex: X-ray Structure and Unique Solvatochromism
Authors: Jeong Kihun , Nakamori Harutaka , Imai Shunsuke , Matsumoto Takahiro , Ogo Seiji , Nakai Hidetaka
Published: June 2012

The structure of a neutral five-coordinated organoruthenium(0) complex [(η6-C6Me6)Ru0(bpy)] (1, bpy: 2,2′-bipyridine) was determined by X-ray diffraction analysis. The solvent-induced reversible color change based on the interconversion between the purple Ru0 complex 1 and a yellow RuII–hydride complex [(η6-C6Me6)RuII(bpy)H]+ is presented.
Nanosecond Time-resolved Infrared Spectra and Structure of the Charge-transfer State of 9,9′-Bianthryl in Acetonitrile
Authors: Asami Nobuyuki , Yabumoto Sohshi , Shigeto Shinsuke , Takaya Tomohisa , Hamaguchi Hiro-o , Iwata Koichi
Published: June 2012

Nanosecond time-resolved infrared spectra of photoexcited 9,9′-bianthryl (BA) and its deuterated derivative (BA-d18) were recorded in acetonitrile-d3 and cyclohexane-d12. The charge-transfer (CT) bands observed at the 1200–1400 cm−1 region are contributed mostly by the intra- and inter-ring CC stretch vibrations. The intrinsic frequency of the inter-ring CC stretch falls within the 1200–1400 cm−1 region, which is consistent more with a twisted structure than with a fully conjugated planar structure of the CT state.
Characteristic MR and CT imaging findings of hepatobiliary paragonimiasis and their pathologic correlations
Authors: Lu Chun-yan , Hu Ya-jun , Chen Wei-xia
Published: June 2012

Background

Hepatobiliary paragonimiasis (HP) is not commonly encountered and may be confused with hepatobiliary tumors; however, computed tomography (CT) and magnetic resonance imaging (MRI) features of HP allow this entity to be distinguished from other diseases.

Purpose

To present the CT and MRI findings in patients with HP and to describe some specific imaging findings along with their pathological correlations.

Material and Methods

Imaging and clinical findings of 21 patients (9 boys/men and 12 girls/women; age range 3–67 years; mean age 40 years) who were diagnosed with HP were retrospectively evaluated. Among these patients, 16 underwent CT examination only, two had MR examination only, and three underwent both CT and MR. All patients underwent surgery, and the HP diagnosis was confirmed by the surgical and histopathologic results.

Results

Chronic abdominal pain or back pain was reported by 14 patients, severe abdominal pain with acute onset was reported by one patient, and six patients were asymptomatic and were discovered incidentally. Peripheral eosinophilia was present in 14 patients (14/21, 66.7%), and abnormal liver function tests were found in 16 patients (16/21, 76.2%). Of the 19 patients who underwent CT imaging, 17 patients showed multiple mixed hypodense lesions or multiple cysts with inlaying septation with separate irregular rims or circular enhancement on post-contrast CT images. Tunnel-shaped microabscesses and necrotic cavities were found in the lesions of 12 of those 17 patients. The other two patients showed smaller cystic masses. MRI showed faveolate T1 hypointense and T2 hyperintense areas in the liver parenchyma with rim or peripheral enhancement. Nodular or circular hyperintense materials were found scattered in the lesions on T1-weighted imaging.

Conclusion

CT and MRI can reveal the radiological-pathological features of HP. Together with laboratory findings, MRI and CT findings may provide diagnostic clues, especially in endemic areas, that are very important for the selection of treatment methods.
Bedside diagnosis of pleural effusion with a latest generation hand-carried ultrasound device in intensive care patients
Authors: Schleder Stephan , Dornia C , Poschenrieder F , Dendl L , Cojocaru L , Bein T , Schmid C , Stroszczynski C , Jung EM , Heiss P
Published: June 2012

Background

Further development established hand-carried ultrasound (HCU) imagers in daily clinical workflow providing several advantages such as fast bedside availability and prompt diagnosis.

Purpose

To evaluate the diagnostic yield of a latest generation HCU imager compared to chest radiography (CR) for the detection of pleural effusion (PE) in intensive care patients.

Material and Methods

Forty-eight hemithoraces of 24 patients on surgical intensive care units were enrolled in this study. All hemithoraces were evaluated using both HCU and CR. Definite diagnosis of PE was achieved using a high-end ultrasound system as standard of reference. Statistical analysis was performed using 2 × 2 tables and a McNemar test. A P value of <0.05 was considered statistically significant.

Results

PE was present in 35 of 48 hemithoraces (73%). The HCU examination was carried out technically successfully in all hemithoraces. Sensitivity and specificity of HCU for the diagnosis of PE was 91% and 100%, respectively, whereas sensitivity and specificity of CR was 74% and 31%, respectively. The difference between HCU and CR was statistically significant with respect to specificity but not sensitivity ( P = 0.008 and P = 0.11, respectively).

Conclusion

Due to its ease of use and its high diagnostic yield HCU systems of the latest generation constitute a helpful technique for the primary assessment of PE.
Embedding online patient record access in UK primary care: a survey of stakeholder experiences
Authors: Pagliari Claudia , Shand Tim , Fisher Brian
Published: June 2012

Summary

Objectives

To explore the integration of online patient Record Access within UK Primary Care, its perceived impacts on workload and service quality, and barriers to implementation.

Design

Mixed format survey of clinicians, administrators and patients. Telephone interviews with non-users.

Setting

Primary care centres within NHS England that had offered online record access for the preceding year.

Participants

Of the 57 practices initially agreeing to pilot the system, 32 had adopted it and 16 of these returned questionnaires. The 42 individual respondents included 14 practice managers, 15 clinicians and 13 patients. Follow-up interviews were conducted with one participant from 15 of the 25 non-adopter practices.

Results

Most professionals believed that the system is easy to integrate within primary care; while most patients found it easy to integrate within their daily lives. Professionals perceived no increase in the volume of patient queries or clinical consultations as a result of Record Access; indeed some believed that these had decreased. Most clinicians and patients believed that the service had improved mutual trust, communication, patients’ health knowledge and health behaviour. Inhibiting factors included concerns about security, liability and resource requirements. Non-adoption was most frequently attributed to competing priorities, rather than negative beliefs about the service.

Conclusions

Record access has an important role to play in supporting patient-focused healthcare policies in the UK and may be easily accommodated within existing services. Additional materials to facilitate patient recruitment, inform system set-up processes, and assure clinicians of their legal position are likely to encourage more widespread adoption.
What It Takes to Win on the PGA TOUR (If Your Name Is “Tiger” or If It Isn't)
Authors: Connolly Robert A. , Rendleman Richard J.
Published: June 2012

In this study, we show what it takes to win on the PGA TOUR for Tiger Woods and other professional golfers as a function of individual player skill, random variation in scoring, strength of field, and depth of field. When Woods wins, he wins by scoring an average of 0.71 strokes per round less than other winning players. This difference reflects (1) that Woods may play better than other winning players when he wins and (2) that Woods tends to play in tournaments with the strongest fields, which require lower scores to win. To make this assessment, we develop a novel simulation-based estimate of relative tournament difficulty—the mean score per round that it takes to win a PGA TOUR event. We also explore the extent to which players could have won tournaments on the PGA TOUR by playing their normal game, with no favorable random variation in scoring. We estimate that Woods is the only player who could have won events on the PGA TOUR over the 2003–2009 seasons by simply playing his normal game.
Cysteine cathepsin S processes leptin, inactivating its biological activity
Authors: Oliveira Marcela , Assis Diego M , Paschoalin Thaysa , Miranda Antonio , Ribeiro Eliane B , Juliano Maria A , Brömme Dieter , Christoffolete Marcelo Augusto , Barros Nilana M T , Carmona Adriana K
Published: June 2012

Leptin is a 16 kDa hormone mainly produced by adipocytes that plays an important role in many biological events including the regulation of appetite and energy balance, atherosclerosis, osteogenesis, angiogenesis, the immune response, and inflammation. The search for proteolytic enzymes capable of processing leptin prompted us to investigate the action of cysteine cathepsins on human leptin degradation. In this study, we observed high cysteine peptidase expression and hydrolytic activity in white adipose tissue (WAT), which was capable of degrading leptin. Considering these results, we investigated whether recombinant human cysteine cathepsins B, K, L, and S were able to degrade human leptin. Mass spectrometry analysis revealed that among the tested enzymes, cathepsin S exhibited the highest catalytic activity on leptin. Furthermore, using a Matrigel assay, we observed that the leptin fragments generated by cathepsin S digestion did not exhibit angiogenic action on endothelial cells and were unable to inhibit food intake in Wistar rats after intracerebroventricular administration. Taken together, these results suggest that cysteine cathepsins may be putative leptin activity regulators in WAT.
What lies behind chemotherapy-induced ovarian toxicity?
Authors: Ben-Aharon Irit , Shalgi Ruth
Published: June 2012

Seminal advances in anticancer therapy as well as supportive care strategies have led to improved survival rates, posing an emphasis on preserving an optimum quality of life after cancer treatment. This recognition has paved the way to an increasing research of long-term side effects, both clinical and preclinical and to an ongoing design of a supportive care system to evaluate and treat long-term adverse effects of anticancer treatments, including the impact on fertility. As with many adverse effects induced by anticancer treatments, the literature comprised mostly clinical data with regard to chemotherapy-induced gonadotoxicity, while understanding of the biological mechanism is lagging. The impact of anticancer treatments on female fertility depends on the women's age at the time of treatment, the chemotherapy protocol, the duration, and total cumulative dose administered. Several suggested mechanisms that underlie chemotherapy-induced gonadotoxicity have been described. This review illustrates the clinical evidence, as well as its supportive preclinical studies, while proceeding from the ‘bedside to the bench work’ and provides an insight to what lies behind chemotherapy-induced gonadotoxicity.
Genetic Interactions Between Drosophila sialyltransferase and β1,4-N-acetylgalactosaminyltransferase-A Genes Indicate Their Involvement in the Same Pathway
Authors: Nakamura Michiko , Pandey Dheeraj , Panin Vladislav M
Published: June 2012

Sialylated glycans play a prominent role in the Drosophila nervous system where they are involved in the regulation of neural transmission. However, the functional pathway of sialylation in invertebrates, including Drosophila, remains largely unknown. Here we used a combination of genetic and behavioral approaches to shed light on the Drosophila sialylation pathway. We examined genetic interactions between Drosophila sialyltransferase (DSiaT) and β1,4-N-acetylgalactosaminyltransferase (β4GalNAcT) genes. Our results indicated that β4GalNAcTA and DSiaT cooperate within the same functional pathway that regulates neural transmission. We found that β4GalNAcTA is epistatic to DSiaT. Our data suggest an intriguing possibility that β4GalNAcTA may participate in the biosynthesis of sialylated glycans.