bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular sampling of prostate cancer: a dilemma for predicting disease progression
Authors: Sboner Andrea , Demichelis Francesca , Calza Stefano , Pawitan Yudi , Setlur Sunita R , Hoshida Yujin , Perner Sven , Adami Hans-Olov , Fall Katja , Mucci Lorelei A , Kantoff Philip W , Stampfer Meir , Andersson Swen-Olof , Varenhorst Eberhard , Johansson Jan-Erik , Gerstein Mark B , Golub Todd R , Rubin Mark A , Andrén Ove
Published: March 2010

Background

Current prostate cancer prognostic models are based on pre-treatment prostate specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models.

Methods

We analyzed a Swedish Watchful Waiting cohort with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several statistical and machine learning models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases.

Results

Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors.

Conclusions

The determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses making the development of molecular biomarkers for prostate cancer progression challenging.
RRM1 single nucleotide polymorphism -37C→A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy
Authors: Dong Song , Guo Ai-Lin , Chen Zhi-Hong , Wang Zhen , Zhang Xu-Chao , Huang Ying , Xie Zhi , Yan Hong-Hong , Cheng Hua , Wu Yi-Long
Published: March 2010

Background

The ribonucleotide reductase M1 (RRM1) gene encodes the regulatory subunit of ribonucleotide reductase, the molecular target of gemcitabine. The overexpression of RRM1 mRNA in tumor tissues is reported to be associated with gemcitabine resistance. Thus, single nucleotide polymorphisms (SNPs) of the RRM1 gene are potential biomarkers of the response to gemcitabine chemotherapy. We investigated whether RRM1 expression in peripheral blood mononuclear cells (PBMCs) or SNPs were associated with clinical outcome after gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients.

Methods

PBMC samples were obtained from 62 stage IIIB and IV patients treated with gemcitabine-based chemotherapy. RRM1 mRNA expression levels were assessed by real-time PCR. Three RRM1 SNPs, -37C→A, 2455A→G and 2464G→A, were assessed by direct sequencing.

Results

RRM1 expression was detectable in 57 PBMC samples, and SNPs were sequenced in 56 samples. The overall response rate to gemcitabine was 18%; there was no significant association between RRM1 mRNA expression and response rate (P = 0.560). The median progression-free survival (PFS) was 23.3 weeks in the lower expression group and 26.9 weeks in the higher expression group (P = 0.659). For the -37C→A polymorphism, the median PFS was 30.7 weeks in the C(-)37A group, 24.7 weeks in the A(-)37A group, and 23.3 weeks in the C(-)37C group (P = 0.043). No significant difference in PFS was observed for the SNP 2455A→G or 2464G→A.

Conclusions

The RRM1 polymorphism -37C→A correlated with PFS in NSCLC patients treated with gemcitabine-based chemotherapy. No significant correlation was found between PBMC RRM1 mRNA expression and the efficacy of gemcitabine.
Ischemia as a possible effect of increased intra-abdominal pressure on central nervous system cytokines, lactate and perfusion pressures
Authors: Marinis Athanasios , Argyra Eriphili , Lykoudis Pavlos , Brestas Paraskevas , Theodoraki Kassiani , Polymeneas Georgios , Boviatsis Efstathios , Voros Dionysios
Published: March 2010

Introduction

The aims of our study were to evaluate the impact of increased intra-abdominal pressure (IAP) on central nervous system (CNS) cytokines (Interleukin 6 and tumor necrosis factor), lactate and perfusion pressures, testing the hypothesis that intra-abdominal hypertension (IAH) may possibly lead to CNS ischemia.

Methods

Fifteen pigs were studied. Helium pneumoperitoneum was established and IAP was increased initially at 20 mmHg and subsequently at 45 mmHg, which was finally followed by abdominal desufflation. Interleukin 6 (IL-6), tumor necrosis factor alpha (TNFa) and lactate were measured in the cerebrospinal fluid (CSF) and intracranial (ICP), intraspinal (ISP), cerebral perfusion (CPP) and spinal perfusion (SPP) pressures recorded.

Results

Increased IAP (20 mmHg) was followed by a statistically significant increase in IL-6 (p = 0.028), lactate (p = 0.017), ICP (p < 0.001) and ISP (p = 0.001) and a significant decrease in CPP (p = 0.013) and SPP (p = 0.002). However, further increase of IAP (45 mmHg) was accompanied by an increase in mean arterial pressure due to compensatory tachycardia, followed by an increase in CPP and SPP and a decrease of cytokines and lactate.

Conclusions

IAH resulted in a decrease of CPP and SPP lower than 60 mmHg and an increase of all ischemic mediators, indicating CNS ischemia; on the other hand, restoration of perfusion pressures above this threshold decreased all ischemic indicators, irrespective of the level of IAH.
Infections of respiratory or abdominal origin in ICU patients: what are the differences?
Authors: Volakli Elena , Spies Claudia , Michalopoulos Argyris , Groeneveld AB Johan , Sakr Yasser , Vincent Jean-Louis
Published: March 2010

Introduction

There are few data related to the effects of different sources of infection on outcome. We used the Sepsis Occurrence in Acutely ill Patients (SOAP) database to investigate differences in the impact of respiratory tract and abdominal sites of infection on organ failure and survival.

Methods

The SOAP study was a cohort, multicenter, observational study which included data from all adult patients admitted to one of 198 participating intensive care units (ICUs) from 24 European countries during the study period. In this substudy, patients were divided into two groups depending on whether, on admission, they had abdominal infection but no respiratory infection or respiratory infection but no abdominal infection. The two groups were compared with respect to patient and infection-related characteristics, organ failure patterns, and outcomes.

Results

Of the 3,147 patients in the SOAP database, 777 (25%) patients had sepsis on ICU admission; 162 (21%) had abdominal infection without concurrent respiratory infection and 380 (49%) had respiratory infection without concurrent abdominal infection. Age, sex, and severity scores were similar in the two groups. On admission, septic shock was more common in patients with abdominal infection (40.1% vs. 29.5%, P = 0.016) who were also more likely to have early coagulation failure (17.3% vs. 9.5%, P = 0.01) and acute renal failure (38.3% vs. 29.5%, P = 0.045). In contrast, patients with respiratory infection were more likely to have early neurological failure (30.5% vs. 9.9%, P < 0.001). The median length of ICU stay was the same in the two groups, but the median length of hospital stay was longer in patients with abdominal than in those with respiratory infection (27 vs. 20 days, P = 0.02). ICU (29%) and hospital (38%) mortality rates were identical in the two groups.

Conclusions

There are important differences in patient profiles related to the site of infection; however, mortality rates in these two groups of patients are identical.
Regional lung aeration and ventilation during pressure support and biphasic positive airway pressure ventilation in experimental lung injury
Authors: Gama de Abreu Marcelo , Cuevas Maximiliano , Spieth Peter M , Carvalho Alysson R , Hietschold Volker , Stroszczynski Christian , Wiedemann Bärbel , Koch Thea , Pelosi Paolo , Koch Edmund
Published: March 2010

Introduction

There is an increasing interest in biphasic positive airway pressure with spontaneous breathing (BIPAP+SBmean), which is a combination of time-cycled controlled breaths at two levels of continuous positive airway pressure (BIPAP+SBcontrolled) and non-assisted spontaneous breathing (BIPAP+SBspont), in the early phase of acute lung injury (ALI). However, pressure support ventilation (PSV) remains the most commonly used mode of assisted ventilation. To date, the effects of BIPAP+SBmean and PSV on regional lung aeration and ventilation during ALI are only poorly defined.

Methods

In 10 anesthetized juvenile pigs, ALI was induced by surfactant depletion. BIPAP+SBmean and PSV were performed in a random sequence (1 h each) at comparable mean airway pressures and minute volumes. Gas exchange, hemodynamics, and inspiratory effort were determined and dynamic computed tomography scans obtained. Aeration and ventilation were calculated in four zones along the ventral-dorsal axis at lung apex, hilum and base.

Results

Compared to PSV, BIPAP+SBmean resulted in: 1) lower mean tidal volume, comparable oxygenation and hemodynamics, and increased PaCO2 and inspiratory effort; 2) less nonaerated areas at end-expiration; 3) decreased tidal hyperaeration and re-aeration; 4) similar distributions of ventilation. During BIPAP+SBmean: i) BIPAP+SBspont had lower tidal volumes and higher rates than BIPAP+SBcontrolled; ii) BIPAP+SBspont and BIPAP+SBcontrolled had similar distributions of ventilation and aeration; iii) BIPAP+SBcontrolled resulted in increased tidal re-aeration and hyperareation, compared to PSV. BIPAP+SBspont showed an opposite pattern.

Conclusions

In this model of ALI, the reduction of tidal re-aeration and hyperaeration during BIPAP+SBmean compared to PSV is not due to decreased nonaerated areas at end-expiration or different distribution of ventilation, but to lower tidal volumes during BIPAP+SBspont. The ratio between spontaneous to controlled breaths seems to play a pivotal role in reducing tidal re-aeration and hyperaeration during BIPAP+SBmean.
Bedside adherence to clinical practice guidelines for enteral nutrition in critically ill patients receiving mechanical ventilation: a prospective, multi-centre, observational study
Authors: Quenot Jean-Pierre , Plantefeve Gaetan , Baudel Jean-Luc , Camilatto Isabelle , Bertholet Emmanuelle , Cailliod Romain , Reignier Jean , Rigaud Jean-Philippe
Published: March 2010

Introduction

The primary aim was to measure the amount of nutrients required, prescribed and actually administered in critically ill patients. Secondary aims were to assess adherence to clinical practice guidelines, and investigate factors leading to non-adherence.

Methods

Observational, multicenter, prospective study, including 203 patients in a total of 19 intensive care units in France. The prescribed calorie supply was compared with the theoretical minimal required calorie intake (25 Kcal/Kg/day) and with the supply actually delivered to the patient to calculate the ratio of calories prescribed/required and the ratio of calories delivered/prescribed. Clinical factors suspected to influence enteral nutrition were analyzed by univariate and multivariate analysis.

Results

The median ratio of prescribed/required calories per day was 43 [37-54] at day 1 and increased until day 7. From day 4 until the end of the study, the median ratio was > 80%. The median ratio of delivered/prescribed per day was > 80% for all 7 days from the start of enteral nutrition. Among the variables tested (hospital type, use of a local nutrition protocol, sedation, vasoactive drugs, number of interruptions of enteral nutrition and measurement of gastric residual volume), only measurement of residual volume was significant by univariate analysis. This was confirmed by multivariate analysis, where gastric residual volume measurement was the only variable independently associated with the ratio of delivered/prescribed calories (OR = 1.38; 95%CI, 1.12-2.10, p = .024).

Conclusions

The translation of clinical research and recommendations for enteral nutrition into routine bedside practice in critically ill patients receiving mechanical ventilation was satisfactory, but could probably be improved with a multidisciplinary approach.
Immunomodulatory properties of stem cells from human exfoliated deciduous teeth
Authors: Yamaza Takayoshi , Kentaro Akiyama , Chen Chider , Liu Yi , Shi Yufang , Gronthos Stan , Wang Songlin , Shi Songtao
Published: March 2010

Introduction

Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a population of postnatal stem cells capable of differentiating into osteogenic and odontogenic cells, adipogenic cells, and neural cells. Herein we have characterized mesenchymal stem cell properties of SHED in comparison to human bone marrow mesenchymal stem cells (BMMSCs).

Methods

We used in vitro stem cell analysis approaches, including flow cytometry, inductive differentiation, telomerase activity, and Western blot analysis to assess multipotent differentiation of SHED and in vivo implantation to assess tissue regeneration of SHED. In addition, we utilized systemic SHED transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice.

Results

We found that SHED are capable of differentiating into osteogenic and adipogenic cells, expressing mesenchymal surface molecules (STRO-1, CD146, SSEA4, CD73, CD105, and CD166), and activating multiple signaling pathways, including TGFβ, ERK, Akt, Wnt, and PDGF. Recently, BMMSCs were shown to possess an immunomodulatory function that leads to successful therapies for immune diseases. We examined the immunomodulatory properties of SHED in comparison to BMMSCs and found that SHED had significant effects on inhibiting T helper 17 (Th17) cells in vitro. Moreover, we found that SHED transplantation is capable of effectively reversing SLE-associated disorders in MRL/lpr mice. At the cellular level, SHED transplantation elevated the ratio of regulatory T cells (Tregs) via Th17 cells.

Conclusions

These data suggest that SHED are an accessible and feasible mesenchymal stem cell source for treating immune disorders like SLE.
Identification of Subtypes in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer Reveals a Gene Signature Prognostic of Outcome
Authors: Staaf Johan , Ringnér Markus , Vallon-Christersson Johan , Jönsson Göran , Bendahl Pär-Ola , Holm Karolina , Arason Adalgeir , Gunnarsson Haukur , Hegardt Cecilia , Agnarsson Bjarni A. , Luts Lena , Grabau Dorthe , Fernö Mårten , Malmström Per-Olof , Johannsson Oskar Th. , Loman Niklas , Barkardottir Rosa B. , Borg Åke
Published: March 2010

Purpose

Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) with variable prognosis and response to therapy. We aimed to investigate the heterogeneous biologic appearance and clinical behavior of HER2-positive tumors using molecular profiling.

Patients and Methods

Hierarchical clustering of gene expression data from 58 HER2-amplified tumors of various stage, histologic grade, and estrogen receptor (ER) status was used to construct a HER2-derived prognostic predictor that was further evaluated in several large independent BC data sets.

Results

Unsupervised analysis identified three subtypes of HER2-positive tumors with mixed stage, histologic grade, and ER status. One subtype had a significantly worse clinical outcome. A prognostic predictor was created based on differentially expressed genes between the subtype with worse outcome and the other subtypes. The predictor was able to define patient groups with better and worse outcome in HER2-positive BC across multiple independent BC data sets and identify a sizable HER2-positive group with long disease-free survival and low mortality. Significant correlation to prognosis was also observed in basal-like, ER-negative, lymph node–positive, and high-grade tumors, irrespective of HER2 status. The predictor included genes associated with immune response, tumor invasion, and metastasis.

Conclusion

The HER2-derived prognostic predictor provides further insight into the heterogeneous biology of HER2-positive tumors and may become useful for improved selection of patients who need additional treatment with new drugs targeting the HER2 pathway.
Psychological Outcomes and Health Beliefs in Adolescent and Young Adult Survivors of Childhood Cancer and Controls
Authors: Kazak Anne E. , DeRosa Branlyn Werba , Schwartz Lisa A. , Hobbie Wendy , Carlson Claire , Ittenbach Richard F. , Mao Jun J. , Ginsberg Jill P.
Published: March 2010

Purpose

The purpose of this study was to compare adolescent and young adult (AYA) pediatric cancer survivors and peers without a history of serious illness on psychological distress, health-related quality of life (HRQOL), health beliefs; examine age at diagnosis and cancer treatment intensity on these outcomes; and examine relationships between number of health problems and the outcomes.

Patients and Methods

AYA cancer survivors (n = 167) and controls (n = 170), recruited during visits to a cancer survivorship clinic and primary care, completed self-report questionnaires of distress, health problems, and health beliefs. For survivors, providers rated treatment intensity and health problems.

Results

There were no statistically significant differences between survivors and controls in psychological distress or HRQOL. Cancer survivors had less positive health beliefs. Survivors diagnosed as adolescents had significantly greater psychological distress and fewer positive health beliefs than those diagnosed earlier. Survivors with the highest level of treatment intensity had greater anxiety and fewer positive health beliefs than those with less intense treatments. Provider report of current health problems related to survivors' beliefs and mental HRQOL only, whereas patient report of health problems correlated significantly with most psychosocial outcomes and beliefs.

Conclusion

AYA cancer survivors did not differ from peers in psychological adjustment but did endorse less adaptive health beliefs. Survivors diagnosed during adolescence and who had more intensive cancer treatments evidenced poorer psychosocial outcomes. Beliefs about health may be identified and targeted for intervention to improve quality of life, particularly when patient perceptions of current health problems are considered.
Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group
Authors: Wen Patrick Y. , Macdonald David R. , Reardon David A. , Cloughesy Timothy F. , Sorensen A. Gregory , Galanis Evanthia , DeGroot John , Wick Wolfgang , Gilbert Mark R. , Lassman Andrew B. , Tsien Christina , Mikkelsen Tom , Wong Eric T. , Chamberlain Marc C. , Stupp Roger , Lamborn Kathleen R. , Vogelbaum Michael A. , van den Bent Martin J. , Chang Susan M.
Published: March 2010

Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.
Chemerin Exacerbates Glucose Intolerance in Mouse Models of Obesity and Diabetes
Authors: Ernst Matthew C. , Issa Mark , Goralski Kerry B. , Sinal Christopher J.
Published: March 2010

Obesity, characterized by an excess of adipose tissue, is an established risk factor for cardiovascular disease and type 2 diabetes. Different mechanisms linking obesity with these comorbidities have been postulated but remain poorly understood. Adipose tissue secretes a number of hormone-like compounds, termed adipokines, that are important for the maintenance of normal glucose metabolism. Alterations in the secretion of adipokines with obesity are believed to contribute to the undesirable changes in glucose metabolism that ultimately result in the development of type 2 diabetes. In the present study, we have shown that serum levels of the novel adipokine chemerin are significantly elevated in mouse models of obesity/diabetes. The expression of chemerin and its receptors, chemokine-like receptor 1, chemokine (C-C motif) receptor-like 2, and G protein-coupled receptor 1 are altered in white adipose, skeletal muscle, and liver tissue of obese/diabetic mice. Administration of exogenous chemerin exacerbates glucose intolerance, lowers serum insulin levels, and decreases tissue glucose uptake in obese/diabetic but not normoglycemic mice. Collectively, these data indicate that chemerin influences glucose homeostasis and may contribute to the metabolic derangements characteristic of obesity and type 2 diabetes.
Direct Action through the Sertoli Cells Is Essential for Androgen Stimulation of Spermatogenesis
Authors: O'Shaughnessy P. J. , Verhoeven G. , De Gendt K. , Monteiro A. , Abel M. H.
Published: March 2010

Androgens act to stimulate spermatogenesis through androgen receptors (ARs) on the Sertoli cells and peritubular myoid cells. Specific ablation of the AR in either cell type will cause a severe disruption of spermatogenesis. To determine whether androgens can stimulate spermatogenesis through direct action on the peritubular myoid cells alone or whether action on the Sertoli cells is essential, we crossed hypogonadal (hpg) mice that lack gonadotrophins and intratesticular androgen with mice lacking ARs either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO and hpg.SCARKO mice were treated with testosterone (T) or dihydrotestosterone (DHT) for 7 d and testicular morphology and cell numbers assessed. Androgen treatment did not affect Sertoli cell numbers in any animal group. Both T and DHT increased numbers of spermatogonia and spermatocytes in hpg mice, but DHT has no effect on germ cell numbers in hpg.SCARKO and hpg.ARKO mice. T increased germ cell numbers in hpg.SCARKO and hpg.ARKO mice, but this was associated with stimulation of FSH release. Results show that androgen stimulation of spermatogenesis requires direct androgen action on the Sertoli cells.
Long-Term Ritonavir Exposure Increases Fatty Acid and Glycerol Recycling in 3T3-L1 Adipocytes as Compensatory Mechanisms for Increased Triacylglycerol Hydrolysis
Authors: Adler-Wailes Diane C. , Guiney Evan L. , Wolins Nathan E. , Yanovski Jack A.
Published: March 2010

Lipodystrophy with high nonesterified fatty acid (FA) efflux is reported in humans receiving highly active antiretroviral therapy (HAART) to treat HIV infection. Ritonavir, a common component of HAART, alters adipocyte FA efflux, but the mechanism for this effect is not established. To investigate ritonavir-induced changes in FA flux and recycling through acylglycerols, we exposed differentiated murine 3T3-L1 adipocytes to ritonavir for 14 d. FA efflux, uptake, and incorporation into acylglycerols were measured. To identify a mediator of FA efflux, we measured adipocyte triacylglycerol lipase (ATGL) transcript and protein. To determine whether ritonavir-treated adipocytes increased glycerol backbone synthesis for FA reesterification, we measured labeled glycerol and pyruvate incorporation into triacylglycerol (TAG). Ritonavir-treated cells had increased FA efflux, uptake, and incorporation into TAG (all P < 0.01). Ritonavir increased FA efflux without consistently increasing glycerol release or changing TAG mass, suggesting increased partial TAG hydrolysis. Ritonavir-treated adipocytes expressed significantly more ATGL mRNA (P < 0.05) and protein (P < 0.05). Ritonavir increased glycerol (P < 0.01) but not pyruvate (P = 0.41), utilization for TAG backbone synthesis. Consistent with this substrate utilization, glycerol kinase transcript (required for glycerol incorporation into TAG backbone) was up-regulated (P < 0.01), whereas phosphoenolpyruvate carboxykinase transcript (required for pyruvate utilization) was down-regulated (P < 0.001). In 3T3-L1 adipocytes, long-term ritonavir exposure perturbs FA metabolism by increasing ATGL-mediated partial TAG hydrolysis, thus increasing FA efflux, and leads to compensatory increases in FA reesterification with glycerol and acylglycerols. These changes in FA metabolism may, in part, explain the increased FA efflux observed in ritonavir-associated lipodystrophy.
Mapping of the Fibroblast Growth Factors in Human White Adipose Tissue
Authors: Mejhert Niklas , Galitzky Jean , Pettersson Amanda T. , Bambace Clara , Blomqvist Lennart , Bouloumié Anne , Frayn Keith N. , Dahlman Ingrid , Arner Peter , Rydén Mikael
Published: March 2010

Context: Fibroblast growth factors (FGFs) regulate the development of white adipose tissue (WAT). However, the secretion and cellular origin of individual FGFs in WAT as well as the influence of obesity are unknown.

Objective: Our objective was to map FGFs in human sc WAT, the cellular source, and association with obesity.

Design: Secretion, mRNA, and circulatory levels of FGFs in human abdominal sc WAT from nonobese and obese donors were examined by microarray, real-time quantitative PCR, and ELISA. The activity of FGFs in cultured human adipocytes was determined by phosphorylation assays.

Results: Expression of five FGFs (FGF1, FGF2, FGF7, FGF9, and FGF18) and FGF homologous factor (FHF2) was identified in WAT. Only FGF1 was released in a time-dependent manner from sc WAT, and fat cells were the major source of FGF1 secretion. FGF1 expression increased and FGF2 decreased during adipocyte differentiation. Furthermore, FGF1 was not secreted into the circulation. Although FGF1 levels were 2-fold increased in obesity, they were unaltered by weight reduction. Only FGF1 and FGF2 induced a marked concentration-dependent phosphorylation of p44/42 in cultured human adipocytes.

Conclusions: Of the investigated FGFs, only FGF1 is secreted from sc WAT and predominantly so from the adipocyte fraction. The activity in adipocyte cultures and lack of secretion into the circulation suggest that FGF1 acts as an auto- or paracrine factor. FGF1 levels are increased in obesity but unaffected by weight reduction, suggesting a primary defect in obese individuals. In conclusion, FGF1 may play a superior role among the FGFs in sc WAT and obesity development.
Infants of Women with Polycystic Ovary Syndrome Have Lower Cord Blood Androstenedione and Estradiol Levels
Authors: Anderson Helen , Fogel Naomi , Grebe Stefan K. , Singh Ravinder J. , Taylor Robert L. , Dunaif Andrea
Published: March 2010

Context: Prenatal androgen excess can cause a phenocopy of polycystic ovary syndrome (PCOS) in mammals. Retrospective studies have suggested that girls at risk for PCOS have low birth weight, and prospective studies have suggested an increased prevalence of small-for-gestational-age offspring in women with PCOS.

Objective: The objective of the study was to determine whether infants of women with PCOS have reduced birth weight or increased intrauterine androgen levels.

Design: This was a prospective case-control study.

Participants: Thirty-nine PCOS and 31 control women and their infants participated in the study.

Main Outcome Measures: Birth weight and mixed cord blood testosterone, androstenedione (A), dehydroepiandrosterone, 17-hydroxyprogesterone, estradiol (E2), and dihydrotestosterone levels were measured.

Results: Mean birth weight did not differ, but there was a significant increase in the prevalence of large-for-gestational-age infants in the PCOS group. Cord blood E2 and A levels were lower (P < 0.05), but testosterone to E2 ratios did not differ in female PCOS compared with control offspring. There was no difference in E2 and A levels in the male PCOS and control offspring. There was no difference in 17-hydroxyprogesterone or other androgen levels in either male or female PCOS offspring compared with their respective control group.

Conclusion: Infants of women with PCOS were more likely to be large for gestational age. Female offspring of affected women have lower cord blood A levels; other cord blood androgen levels do not differ compared with female control offspring. Cord blood E2 levels are also significantly decreased in PCOS, without any difference in the testosterone to E2 ratio, suggesting decreased fetal or placental production of steroids.
Acid Violence against Women in Bangladesh
Authors: Govindnathan Pallavi
Published: March 2010

This essay defines the spread of acid attacks in South Asia and other regions, where disputes over land, inheritances, dowries, and declined marriage proposals often arouse greed and jealousy and lead to violence. Acid attacks are profoundly vicious crimes, the more so because the perpetrators intend to deface the victims rather than kill them. Easily obtained and cheap, acid is thrown at women, who are disfigured, often blinded, and severely traumatized. The lives of many Bangladeshi women, deprived of free choice and independence in this way, have been destroyed. Govindnathan's paintings attempt to find beauty in the hideous, to look beyond judgment without undermining the victims' struggle for freedom and dignity.
War, Poetry, Mourning: Darwish, Adonis, Iraq
Authors: Gana Nouri
Published: March 2010

Theodor W. Adorno's by now infamous dictum that “to write lyric poetry after Auschwitz is barbaric” still weighs heavily on various modern and contemporary representations of war and violence, especially in the Arab world, where the legacy of the Holocaust, entangled with differing or dueling national claims to Israel/Palestine, exerts enormous existential pressure. This essay draws on an eclectic but substantial number of poems composed by canonical contemporary figures such as Nizār Qabbānī, Adonis, and Mahmoud Darwish to demonstrate how Arab poets strategically (even routinely) conjure up the muse of impossibility of poetry, in the wake of every act of violence committed against Arab nations since 1948, to produce poetry. Because its veritable possibility has been stymied by historical violence, Arabic poetry today is largely postelegiac and intensely metapoetic in a very specific way: it is an accentuated yet attenuated form of poetry that simultaneously bears the burden of representation but never ceases to undermine any form of consolation; it is a poetry that emerges from the full consciousness of its impossibility or, worse still, its futility, if not its ineluctable complicity in Arab suffering.
Country First? Vinayak Damodar Savarkar (1883–1966) and the Writing of Essentials of Hindutva
Authors: Bakhle Janaki
Published: March 2010

This essay analyzes and historically contextualizes the timing and the rhetorical style of V. D. Savarkar's infamous extended essay Essentials of Hindutva, originally written in English. The author argues that the text was written as a response to both the Khilafat movement (1920–24) and Mohandas Karamchand Gandhi's support of it. She shows how Savarkar addressed this text, written behind prison walls, to a Hindu community to claim that Savarkar's territorial nationalism was more authentically Hindu than Gandhi's.
The UGC Hardness Threshold of the Lp Grothendieck Problem
Authors: Kindler Guy , Naor Assaf , Schechtman Gideon
Published: March 2010

For p ≥ 2 we consider the problem of, given an n × n matrix A = (aij) whose diagonal entries vanish, approximating in polynomial time the number [Formula: see text]

When p = 2 this is simply the problem of computing the maximum eigenvalue of A, whereas for p = ∞ (actually it suffices to take p ≈ log n) it is the Grothendieck problem on the complete graph, which was shown to have a O(log n) approximation algorithm in Nemirovski et al. [Nemirovski, A., C. Roos, T. Terlaky. 1999. On maximization of quadratic form over intersection of ellipsoids with common center. Math. Program. Ser. A 86(3) 463–473], Megretski [Megretski, A. 2001. Relaxations of quadratic programs in operator theory and system analysis. Systems, Approximation, Singular Integral Operators, and Related Topics (Bordeaux, 2000), Vol. 129. Operator Theory Advances and Applications. Birkhäuser, Basel, 365–392], Charikar and Wirth [Charikar, M., A. Wirth. 2004. Maximizing quadratic programs: Extending Grothendieck's inequality. Proc. 45th Annual Sympos. Foundations Comput. Sci., IEEE Computer Society, 54–60] and was used in the work of Charikar and Wirth noted above, to design the best known algorithm for the problem of computing the maximum correlation in correlation clustering. Thus the problem of approximating Optp(A) interpolates between the spectral (p = 2) case and the correlation clustering (p = ∞) case. From a physics point of view this problem corresponds to computing the ground states of spin glasses in a hard-wall potential well.

We design a polynomial time algorithm which, given p ≥ 2 and an n × n matrix A = (aij) with zeros on the diagonal, computes Optp(A) up to a factor p/e + 30 log p. On the other hand, assuming the unique games conjecture (UGC) we show that it is NP-hard to approximate Optp(A) up to a factor smaller than p/e + ¼. Hence as p → ∞ the UGC-hardness threshold for computing Optp(A) is exactly (p/e)(1 + o(1)).
On the Power of Robust Solutions in Two-Stage Stochastic and Adaptive Optimization Problems
Authors: Bertsimas Dimitris , Goyal Vineet
Published: March 2010

We consider a two-stage mixed integer stochastic optimization problem and show that a static robust solution is a good approximation to the fully adaptable two-stage solution for the stochastic problem under fairly general assumptions on the uncertainty set and the probability distribution. In particular, we show that if the right-hand side of the constraints is uncertain and belongs to a symmetric uncertainty set (such as hypercube, ellipsoid or norm ball) and the probability measure is also symmetric, then the cost of the optimal fixed solution to the corresponding robust problem is at most twice the optimal expected cost of the two-stage stochastic problem. Furthermore, we show that the bound is tight for symmetric uncertainty sets and can be arbitrarily large if the uncertainty set is not symmetric. We refer to the ratio of the optimal cost of the robust problem and the optimal cost of the two-stage stochastic problem as the stochasticity gap. We also extend the bound on the stochasticity gap for another class of uncertainty sets referred to as positive.

If both the objective coefficients and right-hand side are uncertain, we show that the stochasticity gap can be arbitrarily large even if the uncertainty set and the probability measure are both symmetric. However, we prove that the adaptability gap (ratio of optimal cost of the robust problem and the optimal cost of a two-stage fully adaptable problem) is at most four even if both the objective coefficients and the right-hand side of the constraints are uncertain and belong to a symmetric uncertainty set. The bound holds for the class of positive uncertainty sets as well. Moreover, if the uncertainty set is a hypercube (special case of a symmetric set), the adaptability gap is one under an even more general model of uncertainty where the constraint coefficients are also uncertain.
Toward carbyne: Synthesis and stability of really long polyynes
Authors: Tykwinski Rik R. , Chalifoux Wesley , Eisler Sara , Lucotti Andrea , Tommasini Matteo , Fazzi Daniele , Del Zoppo Mirella , Zerbi Giuseppe
Published: March 2010

Molecules composed of sp-hybridized carbon chains (polyynes) are the simplest of the known conjugated organic oligomers. In comparison to their counterparts such as polyacetylene and polydiacetylene, however, the formation of polyynes has traditionally posed a difficult synthetic challenge. In particular, there is no reliable method to form end-capped polyethynylene, and monodisperse polyynes have therefore been assembled. As a result, structure–property relationships for shorter polyynes have been relatively well established in recent years, while extension of these trends toward longer polyynes has remained a difficult task. Using the Fritsch–Buttenberg–Wiechell (FBW) rearrangement, the formation of diynes through decaynes has become possible and has provided a unique chance to explore the physical characteristics of conjugated polyyne chains. This paper highlights recent advances in the synthesis of extended polyynes, as well as interesting aspects of their NMR, Raman, and UV/vis spectroscopic analyses. These synthetic achievements offer the opportunity to predict some of the properties of the carbon allotrope carbyne. In particular, a set of X-ray crystallographic analyses of t-Bu end-capped polyynes (tBu[n]) shows a definitive experimental trend in reduced bond-length alternation (BLA).
Click synthesis of donor–acceptor-type aromatic polymers
Authors: Michinobu Tsuyoshi
Published: March 2010

A high-yielding addition reaction between electron-rich alkynes and a small acceptor molecule, tetracyanoethylene (TCNE), was employed as a new click reaction to construct donor–acceptor chromophores in the polymer main chains and side chains. The donor–acceptor alternating conjugated polymers were prepared from the ferrocene-containing poly(aryleneethynylene)s in one step and atom-economic fashion. The energy levels and thermal properties of the aromatic polyamines substituted by electron-rich alkynes as a side chain can be tunable by the amount of the added TCNE. The resulting donor–acceptor-type polymers feature broad charge-transfer (CT) bands in the visible region, potent redox activities, and improved thermal properties.
Fully conjugated macrocycles composed of thiophenes, acetylenes, and ethylenes
Authors: Iyoda Masahiko
Published: March 2010

Fully conjugated π-expanded macrocyclic oligothiophenes with 24π to 180π electron systems have been synthesized using a modified McMurry coupling reaction as the key step. For the synthesis of cyclo[n](2,5-thienylene-ethynylene)s composed of thiophenes and acetylenes, bromination-dehydrobromination and double elimination procedure were employed. X-ray analyses of macrocyclic oligothiophenes with 24π, 60π, and 72π systems revealed unique molecular and packing structures, reflecting planar cyclic frameworks with medium to large inner cavities. All the giant macrocycles exhibit multistep reversible redox behavior with a fairly low first-oxidation potentials, reflecting their cyclic conjugation. The doping of macrocycles with iodine forms semiconductors owing to their π-donor properties and π–π stacking ability. Interestingly, 90π, 108π, and 120π systems self-aggregate in the solid state to form red nanofibers or petal structure, whereas 150π to 180π systems form red nanoparticles. The structures of fibrous aggregates and particles have been established by scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses. Furthermore, two-photon properties of 72π, 108π, 144π, and 180π systems show that the increasing π-conjugation leads to an increase in the two-photon absorption cross-section with magnitudes as high as 100 000 GM in the visible spectral region.
Localization of Type-2 Angiotensin II Receptor in Adrenal Gland
Authors: Harada Keita , Matsuoka Hidetada , Fujimoto Naohiro , Endo Yutaka , Hasegawa Yoshitaka , Matsuo Akira , Kikuchi Yuta , Matsumoto Tetsuro , Inoue Masumi
Published: March 2010

The localization of the type-2 angiotensin II receptor (AT2) in the adrenal glands of rats, guinea pigs, bovines, and humans was examined at the mRNA and protein levels. PCR products for AT2 were detected in the adrenal cortices and adrenal medullae of all the mammals examined with an RT-PCR technique. Three different anti-AT2 antibodies (Abs), whose specificity was confirmed in our hands, recognized a 50-kDa protein in the adrenal glands of the four mammals, and this recognition was abolished by the preabsorption of an Ab with an antigen. Immunoblotting and immunohistochemistry revealed that the 50-kDa protein was expressed consistently and variably in the adrenal cortices and medullae of various mammals, respectively. We conclude that the 50-kDa AT2 is consistently expressed in the adrenal cortex in a wide variety of mammals.
Pediatric Lead Exposure From Imported Indian Spices and Cultural Powders
Authors: Lin Cristiane Gurgel , Schaider Laurel Anne , Brabander Daniel Joseph , Woolf Alan David
Published: March 2010

BACKGROUND:

Significant lead poisoning has been associated with imported nonpaint products.

OBJECTIVES:

To describe cases of pediatric lead intoxication from imported Indian spices and cultural powders, determine lead concentrations in these products, and predict effects of ingestion on pediatric blood lead levels (BLLs).

PATIENTS AND METHODS:

Cases and case-study information were obtained from patients followed by the Pediatric Environmental Health Center (Children's Hospital Boston). Imported spices (n = 86) and cultural powders (n = 71) were analyzed for lead by using x-ray fluorescence spectroscopy. The simple bioaccessibility extraction test was used to estimate oral bioavailability. The integrated exposure uptake biokinetic model for lead in children was used to predict population-wide geometric mean BLLs and the probability of elevated BLLs (>10 μg/dL).

RESULTS:

Four cases of pediatric lead poisoning from Indian spices or cultural powders are described. Twenty-two of 86 spices and foodstuff products contained >1 μg/g lead (for these 22 samples, mean: 2.6 μg/g [95% confidence interval: 1.9–3.3]; maximum: 7.6 μg/g). Forty-six of 71 cultural products contained >1 μg/g lead (for 43 of these samples, mean: 8.0 μg/g [95% confidence interval: 5.2–10.8]; maximum: 41.4 μg/g). Three sindoor products contained >47% lead. With a fixed ingestion of 5 μg/day and 50% bioavailability, predicted geometric mean BLLs for children aged 0 to 4 years increased from 3.2 to 4.1 μg/dL, and predicted prevalence of children with a BLL of >10 μg/dL increased more than threefold (0.8%–2.8%).

CONCLUSIONS:

Chronic exposure to spices and cultural powders may cause elevated BLLs. A majority of cultural products contained >1 μg/g lead, and some sindoor contained extremely high bioaccessible lead levels. Clinicians should routinely screen for exposure to these products.
Clinical Genetic Testing for Patients With Autism Spectrum Disorders
Authors: Shen Yiping , Dies Kira A. , Holm Ingrid A. , Bridgemohan Carolyn , Sobeih Magdi M. , Caronna Elizabeth B. , Miller Karen J. , Frazier Jean A. , Silverstein Iris , Picker Jonathan , Weissman Laura , Raffalli Peter , Jeste Shafali , Demmer Laurie A. , Peters Heather K. , Brewster Stephanie J. , Kowalczyk Sara J. , Rosen-Sheidley Beth , McGowan Caroline , Duda Andrew W. , Lincoln Sharyn A. , Lowe Kathryn R. , Schonwald Alison , Robbins Michael , Hisama Fuki , Wolff Robert , Becker Ronald , Nasir Ramzi , Urion David K. , Milunsky Jeff M. , Rappaport Leonard , Gusella James F. , Walsh Christopher A. , Wu Bai-Lin , Miller David T. ,   on behalf of the Autism Consortium Clinical Genetics/DNA Diagnostics Collaboration
Published: March 2010

BACKGROUND:

Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established.

PATIENTS AND METHODS:

A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared.

RESULTS:

Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%–2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%–0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%–21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%–8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changes in 7.3% (51 of 697) and 5.3% (8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients.

CONCLUSIONS:

CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance. Despite these limitations, CMA should be considered as part of the initial diagnostic evaluation of patients with ASD.
Fresh Goat's Milk for Infants: Myths and Realities—A Review
Authors: Basnet Sangita , Schneider Michael , Gazit Avihu , Mander Gurpreet , Doctor Allan
Published: March 2010

Many infants are exclusively fed unmodified goat's milk as a result of cultural beliefs as well as exposure to false online information. Anecdotal reports have described a host of morbidities associated with that practice, including severe electrolyte abnormalities, metabolic acidosis, megaloblastic anemia, allergic reactions including life-threatening anaphylactic shock, hemolytic uremic syndrome, and infections. We describe here an infant who was fed raw goat's milk and sustained intracranial infarctions in the setting of severe azotemia and hypernatremia, and we provide a comprehensive review of the consequences associated with this dangerous practice.