bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymph Nodes, Tumor Deposits, and TNM: Are We Getting Better?
Authors: Nagtegaal Iris D. , Tot Tibor , Jayne David G. , McShane Phil , Nihlberg Anders , Marshall Helen C. , Påhlman Lars , Brown Julia M. , Guillou Pierre J. , Quirke Philip
Published: May 2011

Purpose

New editions of the TNM staging system for colorectal cancer have been subject to extensive criticism. In the current study, we evaluate each edition of TNM and analyze stage migration caused by the different versions.

Patients and Methods

Two independent test populations were used: participants derived from a randomized surgical trial from the United Kingdom (n = 455) and patients from a population-based series from Sweden (n = 505). All slides from these patient cases were reviewed with special attention for the presence of tumor deposits. Tumor deposits were classified according to the fifth, sixth, and seventh editions of TNM and correlated with prognosis.

Results

Every change in edition of TNM led to a stage migration of between 33% and 64% in patients with tumor deposits. Reproducibility was best in the fifth edition of TNM. The prognostic value of the seventh edition was best only when all tumor deposits irrespective of size or contour were included as lymph nodes. The prognostic value of the fifth edition was better than that of the sixth.

Conclusion

We demonstrate there is a place for tumor deposits in the staging of patients with colorectal cancer. However, many questions remain about their definition and the reproducibility and use of this category in special situations, such as after neoadjuvant treatment. These should be the subject of additional research before use as a factor in TNM staging. This work demonstrates the necessity of testing modifications before their introduction.
Treatment of Patients With Metastatic Urothelial Cancer “Unfit” for Cisplatin-Based Chemotherapy
Authors: Galsky Matthew D. , Hahn Noah M. , Rosenberg Jonathan , Sonpavde Guru , Hutson Thomas , Oh William K. , Dreicer Robert , Vogelzang Nicholas , Sternberg Cora N. , Bajorin Dean F. , Bellmunt Joaquim
Published: May 2011

Purpose

Cisplatin-based combination chemotherapy is considered standard first-line treatment for patients with metastatic urothelial carcinoma. However, a large proportion of patients with metastatic urothelial carcinoma are considered “unfit” for cisplatin. The purpose of this review is to define unfit patients and to identify treatment options for this subgroup of patients.

Patients and Methods

In this review, the criteria used to define unfit patients are explored and the results of prospective clinical trials evaluating chemotherapeutic regimens in unfit patients are summarized.

Results

Several phase II trials and a single, large phase III trial have explored chemotherapeutic regimens for the treatment of unfit patients with metastatic urothelial carcinoma. Heterogeneous eligibility criteria have been used to define unfit patients in these studies. A uniform definition of unfit is proposed on the basis of the results of a survey of genitourinary medical oncologists. According to this definition, unfit patients would meet at least one of the following criteria: Eastern Cooperative Oncology Group performance status of 2, creatinine clearance less than 60 mL/min, grade ≥ 2 hearing loss, grade ≥ 2 neuropathy, and/or New York Heart Association Class III heart failure.

Conclusion

Additional studies to optimize treatment for this important subset of patients are needed. A uniform definition of unfit patients will lead to more uniform clinical trials, enhanced ability to interpret the results of these trials, and a greater likelihood of developing a viable strategy for regulatory approval.
The actin nucleator WASp is required for myoblast fusion during adultDrosophilamyogenesis
Authors: Mukherjee Priyankana , Gildor Boaz , Shilo Ben-Zion , VijayRaghavan K. , Schejter Eyal D.
Published: May 2011

Myoblast fusion provides a fundamental, conserved mechanism for muscle fiber growth. We demonstrate here that the functional contribution of Wsp, the Drosophila homolog of the conserved actin nucleation-promoting factor (NPF) WASp, is essential for myoblast fusion during the formation of muscles of the adult fly. Disruption of Wsp function results in complete arrest of myoblast fusion in all muscles examined. Wsp activity during adult Drosophila myogenesis is specifically required for muscle cell fusion and is crucial both for the formation of new muscle fibers and for the growth of muscles derived from persistent larval templates. Although Wsp is expressed both in fibers and individual myoblasts, its activity in either one of these cell types is sufficient. SCAR, a second major Arp2/3 NPF, is also required during adult myoblast fusion. Formation of fusion-associated actin ‘foci’ is dependent on Arp2/3 complex function, but appears to rely on a distinct, unknown nucleator. The comprehensive nature of these requirements identifies Arp2/3-based branched actin polymerization as a universal mechanism underlying myoblast fusion.
Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis
Authors: Barron Francie , Woods Crystal , Kuhn Katherine , Bishop Jonathan , Howard Marthe J. , Clouthier David E.
Published: May 2011

Lower jaw development is a complex process in which multiple signaling cascades establish a proximal-distal organization. These cascades are regulated both spatially and temporally and are constantly refined through both induction of normal signals and inhibition of inappropriate signals. The connective tissue of the tongue arises from cranial neural crest cell-derived ectomesenchyme within the mandibular portion of the first pharyngeal arch and is likely to be impacted by this signaling. Although the developmental mechanisms behind later aspects of tongue development, including innervation and taste acquisition, have been elucidated, the early patterning signals driving ectomesenchyme into a tongue lineage are largely unknown. We show here that the basic helix-loop-helix transcription factor Hand2 plays key roles in establishing the proximal-distal patterning of the mouse lower jaw, in part through establishing a negative-feedback loop in which Hand2 represses Dlx5 and Dlx6 expression in the distal arch ectomesenchyme following Dlx5- and Dlx6-mediated induction of Hand2 expression in the same region. Failure to repress distal Dlx5 and Dlx6 expression results in upregulation of Runx2 expression in the mandibular arch and the subsequent formation of aberrant bone in the lower jaw along with proximal-distal duplications. In addition, there is an absence of lateral lingual swelling expansion, from which the tongue arises, resulting in aglossia. Hand2 thus appears to establish a distal mandibular arch domain that is conducive for lower jaw development, including the initiation of tongue mesenchyme morphogenesis.
DPP-mediated TGFβ signaling regulates juvenile hormone biosynthesis by activating the expression of juvenile hormone acid methyltransferase
Authors: Huang Jianhua , Tian Ling , Peng Cheng , Abdou Mohamed , Wen Di , Wang Ying , Li Sheng , Wang Jian
Published: May 2011

Juvenile hormone (JH) biosynthesis in the corpus allatum (CA) is regulated by neuropeptides and neurotransmitters produced in the brain. However, little is known about how these neural signals induce changes in JH biosynthesis. Here, we report a novel function of TGFβ signaling in transferring brain signals into transcriptional changes of JH acid methyltransferase (jhamt), a key regulatory enzyme of JH biosynthesis. A Drosophila genetic screen identified that Tkv and Mad are required for JH-mediated suppression of broad (br) expression in young larvae. Further investigation demonstrated that TGFβ signaling stimulates JH biosynthesis by upregulating jhamt expression. Moreover, dpp hypomorphic mutants also induced precocious br expression. The pupal lethality of these dpp mutants was partially rescued by an exogenous JH agonist. Finally, dpp was specifically expressed in the CA cells of ring glands, and its expression profile in the CA correlated with that of jhamt and matched JH levels in the hemolymph. Reduced dpp expression was detected in larvae mutant for Nmdar1, a CA-expressed glutamate receptor. Taken together, we conclude that the neurotransmitter glutamate promotes dpp expression in the CA, which stimulates JH biosynthesis through Tkv and Mad by upregulating jhamt transcription at the early larval stages to prevent premature metamorphosis.
Coordinated expression of cell death genes regulates neuroblast apoptosis
Authors: Tan Ying , Yamada-Mabuchi Megumu , Arya Richa , St Pierre Susan , Tang Wei , Tosa Marie , Brachmann Carrie , White Kristin
Published: May 2011

Properly regulated apoptosis in the developing central nervous system is crucial for normal morphogenesis and homeostasis. In Drosophila, a subset of neural stem cells, or neuroblasts, undergo apoptosis during embryogenesis. Of the 30 neuroblasts initially present in each abdominal hemisegment of the embryonic ventral nerve cord, only three survive into larval life, and these undergo apoptosis in the larvae. Here, we use loss-of-function analysis to demonstrate that neuroblast apoptosis during embryogenesis requires the coordinated expression of the cell death genes grim and reaper, and possibly sickle. These genes are clustered in a 140 kb region of the third chromosome and show overlapping patterns of expression. We show that expression of grim, reaper and sickle in embryonic neuroblasts is controlled by a common regulatory region located between reaper and grim. In the absence of grim and reaper, many neuroblasts survive the embryonic period of cell death and the ventral nerve cord becomes massively hypertrophic. Deletion of grim alone blocks the death of neuroblasts in the larvae. The overlapping activity of these multiple cell death genes suggests that the coordinated regulation of their expression provides flexibility in this crucial developmental process.
p45NF-E2 represses Gcm1 in trophoblast cells to regulate syncytium formation, placental vascularization and embryonic growth
Authors: Kashif Muhammed , Hellwig Andrea , Kolleker Alexandre , Shahzad Khurrum , Wang Hongjie , Lang Siegfried , Wolter Juliane , Thati Madhusudhan , Vinnikov Ilya , Bierhaus Angelika , Nawroth Peter P. , Isermann Berend
Published: May 2011

Absence of the leucine zipper transcription factor p45NF-E2 results in thrombocytopenia, impaired placental vascularization and intrauterine growth restriction (IUGR) in mice. The mechanism underlying the p45NF-E2-dependent placental defect and IUGR remains unknown. Here, we show that the placental defect and IUGR of p45NF-E2 (Nfe2) null mouse embryos is unrelated to thrombocytopenia, establishing that embryonic platelets and platelet-released mediators are dispensable for placentation. Rather, p45NF-E2, which was hitherto thought to be specific to hematopoietic cells, is expressed in trophoblast cells, where it is required for normal syncytiotrophoblast formation, placental vascularization and embryonic growth. Expression of p45NF-E2 in labyrinthine trophoblast cells colocalizes with that of Gcm1, a transcription factor crucial for syncytiotrophoblast formation. In the absence of p45NF-E2, the width of syncytiotrophoblast layer 2 and the expression of Gcm1 and Gcm1-dependent genes (Synb and Cebpa) are increased. In vitro, p45NF-E2 deficiency results in spontaneous syncytiotrophoblast formation, which can be reversed by Gcm1 knockdown. Increased Gcm1 expression in the absence of p45NF-E2 is dependent on enhanced protein acetylation, including post-translational modification of Gcm1. Increasing and inhibiting acetylation in the placenta of wild-type control embryos phenocopies and corrects, respectively, the changes observed in p45NF-E2-deficient embryos. These studies identify a novel function of p45NF-E2 during placental development: in trophoblast cells, p45NF-E2 represses Gcm1 and syncytiotrophoblast formation via acetylation.
Non-cell-autonomous microRNA165 acts in a dose-dependent manner to regulate multiple differentiation status in the Arabidopsis root
Authors: Miyashima Shunsuke , Koi Satoshi , Hashimoto Takashi , Nakajima Keiji
Published: May 2011

In the development of multicellular organisms, cell fate is usually determined by exchanging positional information. Animals employ a class of intercellular signaling molecules that specify different cell fates by their dosage, but the existence of an equivalent system has not been demonstrated in plants, except that the growth regulator auxin has been proposed to act in a similar manner in certain developmental contexts. Recently, it has been reported that, in the Arabidopsis root meristem, endodermis-derived microRNA (miR) 165/166 non-cell-autonomously suppress the expression of the Class III HD-ZIP transcription factor PHABULOSA (PHB) in the peripheral stele, thereby specifying xylem differentiation. Here, we show that the miR165/166-dependent suppression of PHB is required not only for xylem specification, but also for differentiation of the pericycle, as well as for ground tissue patterning. Furthermore, using a plant system that allows quantitative control of miR165 production in the ground tissue, we show that endodermis-derived miR165 acts in a dose-dependent manner to form a graded distribution of PHB transcripts across the stele. These results reveal a previously unidentified role of miR165 in the differentiation of a broad range of root cell types and suggest that endodermis-derived miR165 acts in a dose-dependent manner to control multiple differentiation status in the Arabidopsis root.
A perfusion-independent role of blood vessels in determining branching stereotypy of lung airways
Authors: Lazarus Alon , Del-Moral Pierre Marie , Ilovich Ohad , Mishani Eyal , Warburton David , Keshet Eli
Published: May 2011

Blood vessels have been shown to play perfusion-independent roles in organogenesis. Here, we examined whether blood vessels determine branching stereotypy of the mouse lung airways in which coordinated branching of epithelial and vascular tubes culminates in their co-alignment. Using different ablative strategies to eliminate the lung vasculature, both in vivo and in lung explants, we show that proximity to the vasculature is indeed essential for patterning airway branching. Remarkably, although epithelial branching per se proceeded at a nearly normal rate, branching stereotypy was dramatically perturbed following vascular ablation. Specifically, branching events requiring a rotation to change the branching plane were selectively affected. This was evidenced by either the complete absence or the shallow angle of their projections, with both events contributing to an overall flat lung morphology. Vascular ablation also led to a high frequency of ectopic branching. Regain of vascularization fully rescued arrested airway branching and restored normal lung size and its three-dimensional architecture. This role of the vasculature is independent of perfusion, flow or blood-borne substances. Inhibition of normal branching resulting from vascular loss could be explained in part by perturbing the unique spatial expression pattern of the key branching mediator FGF10 and by misregulated expression of the branching regulators Shh and sprouty2. Together, these findings uncovered a novel role of the vasculature in organogenesis, namely, determining stereotypy of epithelial branching morphogenesis.
Mps1 at kinetochores is essential for female mouse meiosis I
Authors: Hached Khaled , Xie Stephanie Z. , Buffin Eulalie , Cladière Damien , Rachez Christophe , Sacras Marina , Sorger Peter K. , Wassmann Katja
Published: May 2011

In female meiosis, chromosome missegregations lead to the generation of aneuploid oocytes and can cause the development of trisomies or infertility. Because mammalian female meiosis I is error prone, the full functionality of control mechanisms, such as the spindle assembly checkpoint (SAC), has been put into question. The SAC monitors the correct orientation, microtubule occupancy and tension on proteinaceous structures named kinetochores. Although it has been shown previously that the SAC exists in meiosis I, where attachments are monopolar, the role of microtubule occupancy for silencing the SAC and the importance of certain essential SAC components, such as the kinase Mps1, are unknown in mammalian oocytes. Using a conditional loss-of-function approach, we address the role of Mps1 in meiotic progression and checkpoint control in meiosis I. Our data demonstrate that kinetochore localization of Mps1 is required for the proper timing of prometaphase and is essential for SAC control, chromosome alignment and aurora C localization in meiosis I. The absence of Mps1 from kinetochores severely impairs chromosome segregation in oocyte meiosis I and, therefore, fertility in mice. In addition, we settle a long-standing question in showing that kinetochore-microtubule attachments are present in prometaphase I at a time when most of the SAC protein Mad2 disappears from kinetochores.
Zebrafish cardiac development requires a conserved secondary heart field
Authors: Hami Danyal , Grimes Adrian C. , Tsai Huai-Jen , Kirby Margaret L.
Published: May 2011

The secondary heart field is a conserved developmental domain in avian and mammalian embryos that contributes myocardium and smooth muscle to the definitive cardiac arterial pole. This field is part of the overall heart field and its myocardial component has been fate mapped from the epiblast to the heart in both mammals and birds. In this study we show that the population that gives rise to the arterial pole of the zebrafish can be traced from the epiblast, is a discrete part of the mesodermal heart field, and contributes myocardium after initial heart tube formation, giving rise to both smooth muscle and myocardium. We also show that Isl1, a transcription factor associated with undifferentiated cells in the secondary heart field in other species, is active in this field. Furthermore, Bmp signaling promotes myocardial differentiation from the arterial pole progenitor population, whereas inhibiting Smad1/5/8 phosphorylation leads to reduced myocardial differentiation with subsequent increased smooth muscle differentiation. Molecular pathways required for secondary heart field development are conserved in teleosts, as we demonstrate that the transcription factor Tbx1 and the Sonic hedgehog pathway are necessary for normal development of the zebrafish arterial pole.
The Spalt family transcription factor Sall3 regulates the development of cone photoreceptors and retinal horizontal interneurons
Authors: de Melo Jimmy , Peng Guang-Hua , Chen Shiming , Blackshaw Seth
Published: May 2011

The mammalian retina is a tractable model system for analyzing transcriptional networks that guide neural development. Spalt family zinc-finger transcription factors play a crucial role in photoreceptor specification in Drosophila, but their role in mammalian retinal development has not been investigated. In this study, we show that that the spalt homolog Sall3 is prominently expressed in developing cone photoreceptors and horizontal interneurons of the mouse retina and in a subset of cone bipolar cells. We find that Sall3 is both necessary and sufficient to activate the expression of multiple cone-specific genes, and that Sall3 protein is selectively bound to the promoter regions of these genes. Notably, Sall3 shows more prominent expression in short wavelength-sensitive cones than in medium wavelength-sensitive cones, and that Sall3 selectively activates expression of the short but not the medium wavelength-sensitive cone opsin gene. We further observe that Sall3 regulates the differentiation of horizontal interneurons, which form direct synaptic contacts with cone photoreceptors. Loss of function of Sall3 eliminates expression of the horizontal cell-specific transcription factor Lhx1, resulting in a radial displacement of horizontal cells that partially phenocopies the loss of function of Lhx1. These findings not only demonstrate that Spalt family transcription factors play a conserved role in regulating photoreceptor development in insects and mammals, but also identify Sall3 as a factor that regulates terminal differentiation of both cone photoreceptors and their postsynaptic partners.
Long-term live imaging provides new insight into stem cell regulation and germline-soma coordination in the Drosophila ovary
Authors: Morris Lucy X. , Spradling Allan C.
Published: May 2011

The Drosophila ovariole tip produces new ovarian follicles on a 12-hour cycle by controlling niche-based germline and follicle stem cell divisions and nurturing their developing daughters. Static images provide a thumbnail view of folliculogenesis but imperfectly capture the dynamic cellular interactions that underlie follicle production. We describe a live-imaging culture system that supports normal ovarian stem cell activity, cyst movement and intercellular interaction over 14 hours, which is long enough to visualize all the steps of follicle generation. Our results show that live imaging has unique potential to address diverse aspects of stem cell biology and gametogenesis. Stem cells in cultured tissue respond to insulin and orient their mitotic spindles. Somatic escort cells, the glial-like partners of early germ cells, do not adhere to and migrate along with germline stem cell daughters as previously proposed. Instead, dynamic, microtubule-rich cell membranes pass cysts from one escort cell to the next. Additionally, escort cells are not replenished by the regular division of escort stem cells as previously suggested. Rather, escort cells remain quiescent and divide only to maintain a constant germ cell:escort cell ratio.
Primary breast sarcoma: prevalence, clinical signs, and radiological features
Authors: Surov Alexey , Holzhausen Hans-Jürgen , Ruschke Kathrin , Spielmann Rolf Peter
Published: May 2011

Background

Primary breast sarcoma is very rare. Most reports regarding sarcoma of the breast are clinical observations or pathological series and provide either no or inconstant radiological information. Radiological publications consist predominantly of isolated case reports or small series.

Purpose

To determine the prevalence, clinical signs, and radiological features of primary breast sarcoma.

Material and Methods

This is a retrospective review of 21 patients with breast sarcoma. All patients were female and their median age was 66 years (range 27–86). In all patients the diagnosis was confirmed histopathologically.

Results

The prevalence of breast sarcoma was 0.1% of all identified cases with breast malignancies. Clinically, all patients presented with solitary painless breast lumps. There was no uni- or bilateral axillary lymphadenopathy. On mammography ( n = 19), two mammographic patterns could be identified: breast masses (68%), and architectural distortion (32%). On ultrasound ( n = 8), most lesions were homogeneously hypoechoic, lobular or oval in shape with microlobulated or indistinct margins. On magnetic resonance imaging ( n = 3), marked inhomogeneous contrast enhancement was seen in all investigated cases.

Conclusion

The imaging findings of primary breast sarcoma are not pathognomonic. However, they should be taken into consideration in the differential diagnosis of breast lesions.
Dietary quercetin supplementation increases serum antioxidant capacity and alters hepatic gene expression profile in rats
Authors: Zhao Liting , Wu Jianquan , Yang Jijun , Wei Jingyu , Gao Weina , Guo Changjiang
Published: May 2011

The aim of this study was to determine the effect of quercetin on hepatic gene expression profile in rats. Twenty male Wistar rats were divided into the control group and the quercetin-treated group, in which a diet containing 0.5% quercetin was provided. After two weeks of feeding, serum and liver samples were collected. Biomarkers of oxidative stress, including serum ferric reducing antioxidant power (FRAP) values and levels of ascorbic acid, vitamin E (VE), glutathione (GSH) and malondialdehyde (MDA) were measured. The hepatic gene expression profile was examined using a microarray technique. The results showed that serum FRAP value, levels of ascorbic acid and VE were increased significantly, whereas serum levels of GSH and MDA were not changed significantly after quercetin supplementation. The microarray analysis revealed that some hepatic genes involved in phase 2 reaction, metabolism of cholesterol and homocysteine, and energy production were expressed differentially in response to quercetin administration. These findings provide a molecular basis for the elucidation of the actions played by quercetin in vivo.
Glutathione S-transferase M1 polymorphism and bladder cancer risk: a meta-analysis involving 33 studies
Authors: Jiang Zheng , Li Chunxiang , Wang Xishan
Published: May 2011

Glutathione S-transferase M1 ( GSTM1) might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. GSTM1 null status has been extensively studied as a risk factor in bladder cancer susceptibility. The aim of this study is to evaluate the role of GSTM1 null genotype in bladder cancer risk. All available studies were considered in this meta-analysis, including 7301 cases and 9405 controls from 33 studies. Significantly increased risk was detected between GSTM1 deletion and bladder cancer susceptibility in all subjects (odds ratio [OR] = 1.409 [1.267–1.568], P < 0.001). The same patterns were observed in Caucasians (OR = 1.434 [1.212–1.697], P < 0.001) and Asians (OR = 1.485 [1.295–1.704], P < 0.001). When stratified with study design, a positive association was also found in hospital-based studies (OR = 1.552 [1.382–1.744], P < 0.001), but no association in population-based ones (OR = 1.088 [0.970–1.221], P = 0.151). In summary, our meta-analysis suggested that GSTM1 null status is associated with a high increase in the risk of bladder cancer, and further studies based on population design are necessary to confirm our conclusion.
Atorvastatin improving renal ischemia reperfusion injury via direct inhibition of active caspase-3 in rats
Authors: Haylor John L , Harris Kevin P G , Nicholson Michael L , Waller Helen L , Huang Qiang , Yang Bin
Published: May 2011

Caspase-3 is a key molecule involved in the inflammation and apoptosis of ischemia reperfusion (IR) injury. Statins are known to inhibit IR injury, but the mechanism of action remains uncertain. In the present study, the effect and underlying mechanism of ischemia alone, and reperfusion with or without atorvastatin (AT) as a timed intervention were examined, since clinically the kidney is only exposed to drug delivery during reperfusion. Male Sprague‐Dawley rats were subjected to 45‐min clamping of the left renal hilus followed by four hours reperfusion with a right nephrectomy. AT 10 mg/kg was intravenously administered after clamping the renal hilus, but prior to kidney reperfusion. Ischemia alone did cause tubulointerstitial damage (TID), protein carbonylation and caspase-3 activation with an increase in 12 kDa subunit, while reperfusion further enhanced TID, monocyte (ED-1+ cell) infiltration, apoptosis and necrosis together with caspase-3 activity and 17 kDa subunit, but reversed protein carbonylation. AT significantly reduced TID (26%), ED-1+ cell infiltration (74%), tubular apoptosis (47%) and necrosis (73%), and interstitial apoptosis (64%), as well as caspase-3 activity (26%), but did not change serum creatinine and cholesterol. Importantly, without affecting either caspase-3 active protein cleavage or S-nitrosylation, AT directly inhibited caspase-3 active enzyme in a dose-dependent manner in vitro. In conclusions, IR and AT exerted opposing effects on caspase-3 activity by differing mechanisms, with IR stimulating caspase-3 proteolytic cleavage and AT inhibiting active caspase-3 enzyme. This new inhibitory mechanism of AT may improve reperfusion tolerance in ischemic kidneys and benefit transplant recipients.
Cefixime-resistant Neisseria gonorrhoeae in the UK: a time to reflect on practice and recommendations
Authors: Forsyth S , Penney P , Rooney G
Published: May 2011

A 40-year-old man who has sex with men (MSM) with urethral gonorrhoea failed to respond to treatment with 400 mg cefixime orally. Laboratory isolation of the post-treatment strain showed a minimum inhibitory concentration of ≥0.25 mg/L, which is a level of tolerance to cefixime that has not been previously documented in the UK. This case illustrates the importance of assessing all patients after treatment for gonorrhoea so that treatment failure and antibiotic resistance can be identified. It is vital that gonorrhoea culture continues to be attempted from all infected individuals to enable accurate diagnosis and antibiotic sensitivities. We also recommend that laboratories test for cefixime sensitivity routinely, given that it is one of the most commonly prescribed treatments for gonorrhoea.
Management of patients seen post-sexual assault at a north London inner city genitourinary medicine clinic 2005–2008
Authors: Adlington R , Browne R
Published: May 2011

An audit of all patients presenting to an inner city sexual health clinic post-sexual assault over a four-year period was undertaken to evaluate the overall management of these patients. Sixty-five cases were identified; 22.6% had a pre-existing vulnerability factor and 21.0% a sexually transmitted infection (STI). Recommendations from the audit included: to offer non-invasive methods of testing for STIs to patients presenting at less than one week, improve documentation by completing the specific clinic template and ensure all patients are offered emotional support when they first attend.
Co-factors of high-risk human papillomavirus infections display unique profiles in incident CIN1, CIN2 and CIN3
Authors: Syrjänen K , Shabalova I , Naud P , Derchain S , Sarian L , Kozachenko V , Zakharchenko S , Roteli-Martins C , Nerovjna R , Longatto-Filho A , Kljukina L , Tatti S , Branovskaja M , Branca M , Grunjberga V , Eržen M , Juschenko A , Hammes L Serpa , Costa S , Podistov J , Syrjänen S ,   NIS Cohort Study Group, Shabalova I , Petrovichev N , Kozachenko V , Zakharova T , Pajanidi J , Podistov J , Chemeris G , Sozaeva L , Lipova E , Tsidaeva I , Ivanchenko O , Pshepurko A , Zakharenko S , Nerovjna R , Kljukina L , Erokhina O , Branovskaja M , Nikitina M , Grunjberga V , Grunjberg A , Juschenko A , Santopietro R , Cintorino M , Tosi P
Published: May 2011

In addition to oncogenic ‘high-risk’ human papillomaviruses (HR-HPV), several co-factors are needed in cervical carcinogenesis, but it is poorly understood whether these HPV co-factors associated with incident cervical intraepithelial neoplasia (CIN) grade 1 are different from those required for progression to CIN2 and CIN3. To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV co-factors increasing the risk of incident CIN1, CIN2 and CIN3. Data from the New Independent States of the Former Soviet Union (NIS) Cohort ( n = 3187) and the Latin American Screening (LAMS) Study ( n = 12,114) were combined, and co-factors associated with progression to CIN1, CIN2 and CIN3 were analysed using multinomial logistic regression models with all covariates recorded at baseline. HR-HPV-positive women ( n = 1105) represented a subcohort of all 1865 women prospectively followed up in both studies. Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2 and CIN3, respectively. Baseline HR-HPV was the single most powerful predictor of incident CIN1, CIN2 and CIN3. When controlled for residual HPV confounding by analysing HR-HPV-positive women only, the risk profiles of incident CIN1, CIN2 and CIN3 were unique. Completely different HPV co-factors were associated with progression to CIN1, CIN2 and CIN3 in univariate and multivariate analyses, irrespective of whether non-progression, CIN1 or CIN2 was used as the reference outcome. HPV co-factors associated with progression to CIN1, CIN2 and CIN3 display unique profiles, implicating genuine biological differences between the three CIN grades, which prompts us to re-visit the concept of combining CIN2 with CIN3 or CIN1.
An audit of the contraception service offered to teenagers attending Scottish genitourinary medicine clinics in 2007
Authors: Nair V Ramachandran , Rafters S , Oroz C , Baguley S
Published: May 2011

An audit of contraception service offered to teenagers attending Scottish genitourinary (GU) medicine clinics in 2007 was carried out by collecting data from each main clinic of 11 Scottish health boards. The case notes of 579 women aged under 18 years were reviewed. In 553 (95.5%) cases, sufficient data were available to make an assessment regarding whether the women needed any advice on having a reliable method of contraception. Of these 553 women, 280 (50.6%) were assessed as requiring contraceptive advice. Of the 280 women who needed advice, 156 (56%) received it. Currently, there are some gaps in the provision of contraception services offered to teenagers attending GU medicine clinics, which could be improved by increasing awareness among staff and providing adequate resources.
Malignant syphilis with ocular involvement in an HIV–infected patient
Authors: De Socio G V L , Simonetti S , Tomasini C , Ansidei V , Pasticci M B , Baldelli F
Published: May 2011

Malignant syphilis is now considered a rare disease, more commonly affecting individuals with poor health, malnutrition or HIV infection. We present a 34-year-old man with HIV infection who developed multiple atypical cutaneous ulcerations, leonine facies, a scleral nodule and keratitis with visual loss. The diagnosis of malignant syphilis was delayed due to the insidious presentation, but was confirmed via immunohistochemical (IHC) staining with anti-Treponema antibodies of a skin biopsy. Significant clinical improvement was observed following a 15-day course of penicillin and tigecycline therapy. In advanced HIV disease, cutaneous manifestations are often difficult to identify and present a challenge for the clinician. Clinical manifestations of secondary syphilis vary greatly, earning the epigram of ‘the great imitator’. It is important to recognize atypical presentations of syphilis, especially among HIV-infected individuals. Unlike historical cases of malignant syphilis, Treponema pallidum was found in the tissue section using IHC staining methods. We emphasize the importance of lues maligna in the differential diagnosis of HIV-infected patients with diffuse ulceronodular lesions as well as the usefulness of histological investigations and IHC studies.
Giulio Cesare Aranzio (Arantius) (1530–89) in the pageant of anatomy and surgery
Authors: Gurunluoglu Raffi , Shafighi Maziar , Gurunluoglu Aslin , Cavdar Safiye
Published: May 2011

Giulio Cesare Aranzio in Italian (Julius Caesar Arantius in Latin) has not received full acclaim for his achievements in the field of anatomy and surgery that remain unknown to most physicians. His anatomical books Observationes Anatomicas, and De Humano Foetu Opusculum and surgical books De Tumoribus Secundum Locos Affectos and Hippocratis librum de vulneribus capitis commentarius brevis printed in Latin and additional existing literature on Aranzio from medical history books and journals were analysed extensively. Aranzio became Professor of Anatomy and Surgery at the University of Bologna in 1556. He established anatomy as a distinguished branch of medicine for the first time in medical history. Aranzio combined anatomy with a description of pathological processes. He discovered the ‘Nodules of Aranzio’ in the semilunar valves of the heart. He gave the first description of the superior levator palpebral and the coracobrachialis muscles. Aranzio wrote on surgical techniques for a wide spectrum of conditions that range from hydrocephalus, nasal polyp, goitre and tumours to phimosis, ascites, haemorrhoids, anal abscess and fistulae, and much more. Aranzio had an extensive knowledge in surgery and anatomy based in part on the ancient Greek and his contemporaries in the 16th century but essentially on his personal experience and practice.
The incidence of peripheral arterial embolism in association with a patent foramen ovale (right-to-left shunt)
Authors: Rushdi Yusuf Ali Kausar , Hina Hina , Patel Bijendra , Cross Frank W
Published: May 2011

Summary

Objectives

The aim of this study was to examine a cohort of patients who had suffered an arterial embolism to see whether a patent foramen ovale (PFO) was an identifiable cause.

Design

This study was conducted in two parts; a retrospective limb involving an audit of patient records over a period of 10 years, and a prospective limb including selected patients from that audit to search for a PFO using an agitated saline test with transcranial Doppler ultrasound monitoring of the anterior cerebral artery. Data on patients with peripheral vascular disease were collected using a structured questionnaire.

Setting

A clinical vascular department. All patients were seen in the vascular outpatients clinic.

Participants

Patients who had been identified from a retrospective search based on the headline diagnosis of arterial embolus. Collected data on the 71 patients revealed that 75% had predisposing factors for DVT, 70% were male smokers, and 84.4% had a significant past history of vascular symptoms.

Main outcome measures

Whether or not patients identified as having a possible PFO actually had one on objective testing with transcranial Doppler assessment of the cerebral circulation with an agitated saline solution.

Results

Fifteen patients who were suspected of having a PFO were selected from these 71 patients; 12 of these were found to have no PFO on testing, and three had already undergone a percutaneous PFO closure.

Conclusion

The incidence of a PFO in this small study group is no higher than that found in the general population (3/15, 20%). There was high prevalence of male smokers with associated predisposing factors leading to a DVT.
Behaviour of Recycled Aggregate Concrete-Filled Steel Tubular Columns under Long-Term Sustained Loads
Authors: Yang You-Fu
Published: May 2011

Recycled aggregate concrete-filled steel tube (RACFST) causes the recycled aggregate concrete (RAC) to be in a state of protection with the outer steel tube and thus the RAC is hardly affected by harmful environmental factors (e.g. wind, rain, moist). However, shrinkage and creep are the phenomena commonly associated with concrete-related structures, so studies on the behaviour of RACFST columns under long-term sustained loads are essential for the design of structures which include RACFST members. This study is an attempt to predict the time-dependent behaviour of RACFST columns by using the age-adjusted effective modulus method. The concrete shrinkage and creep in RACFST columns were studied experimentally, and the static bearing capacity of the tested specimens was also investigated. A theoretical model to account for the effects of concrete shrinkage and creep on RACFST columns under long-term sustained loading is developed, and comparisons of the results predicted using this model show good agreement with the test results. Formulae for the calculation of the bearing capacity of RACFST columns under long-term sustained loads are suggested.
Behaviour of Filled Rectangular Steel HSS Composite Columns under Bi-Axial Bending
Authors: Guo Lanhui , Zhang Sumei , Xu Zheng
Published: May 2011

The purpose of this study was to investigate the behaviour of concrete-filled rectangular steel hollow structural section (HSS) columns formed by slender plates with large depth-to-width ratio subjected to bi-axial bending. As part of this study, four large concrete-filled thin-walled rib-stiffened rectangular HSS columns have been tested. Their steel tubes possess a depth-to-width ratio of 2.38 and a depth-to-thickness ratio of 175. Rib stiffeners were welded to the plate walls such that the stiffened plate width-to-thickness ratio (= 45) was less than that specified (= 60) in the Chinese design code. The results showed that local buckling of steel plate appeared after the specimen reached the ultimate capacity. Also, the fiber element analysis method is adapted to analyze the behaviour of specimen, in which the change of neutral axis position is considered. At last, the experimental results are compared with the values calculated from design codes, namely EC4, LRFD, CECS and DBJ. The results show that all codes provide safe ultimate capacities. Among them, the capacities calculated from DBJ yield results closest to the experimental ones and the other three design codes produce safety over 20%.
Music links A music ensemble outreach programme for schools
Authors: Chong Sylvia
Published: May 2011

Professional music communities have realized that if they do not promote their art forms among the youth of today, the future of their music may be in question. Many local ethnic music groups have recognized the need to make the first move and go out to the audiences of the future and
bring their brand of music to these audiences. Their task is to somehow teach potential audiences that their music, culture and the arts are an important form of enjoyment and worthy of their attention. This article presents a Malay music ensemble outreach programme for schools, which is supported
by the National Arts Council (NAC) (Singapore) Arts Education Programme initiative.
Connections in China: Harmonizing stories of community music from around the world
Authors: Bartleet Brydie-Leigh
Published: May 2011

In this article the author offers a personal reflection on the 12th seminar of the ISME Commission for Community Music Activity in Hangzhou, China, 2010. She gives summaries of all the presentation topics, as well as personal narrative accounts of her experiences at the seminar. These
reflective descriptions bring the seminar to life for the reader and also tease out some of the cultural dimensions to the Commission's time in China. As such the article offers both macro and micro glimpses of the key themes covered at the seminar, as well as reflections on community music
making in the context of the seminar's hosting country, China.
Übungsklausur Schwerpunktbereich Informations- und Medienrecht, Recht des geistigen Eigentums Der besondere Katalog
Authors: Czychowski Christian
Published: May 2011

Der nachfolgend wiedergegebene Fall stellt eine einfache Urheberrechtsklausur dar, die einem neben der Struktur einer typischen urheberrechtlichen Verletzungsprüfung, insbesondere die Schrankenregelungen näher bringt.
Predation on Cacajao ouakary and Cebus albifrons (Primates: Platyrrhini) by harpy eagles
Authors: Barnett Adrian A. , Schiel Verena , Deveny Adrian , Valsko Jefferson , Spironello Wilson R. , Ross Caroline
Published: May 2011

Predation of tropical arboreal mammals is rarely observed. Here, we report the first observation of predation of a member of the genus Cacajao, and add to the knowledge of eagle predation in the genus Cebus. We compare responses to predation by Cacajao ouakary and Cebus albifrons with previous studies of congenerics and with other close relatives, and compare the alarm vocalizations of C. ouakary with those of other pitheciines. Reactions to non-predating raptors are reported. Constraints on primate anti-predator responses in flooded and non-flooded habitats are considered.
Diet of the Eurasian otter Lutra lutra on small watercourses in Western Poland
Authors: Krawczyk Agata J. , Skierczyński Michał , Tryjanowski Piotr
Published: May 2011

No abstract available
Privacy in Communications on the Internet
Authors: Panchenko Andriy
Published: May 2011

Privacy on the Internet is becoming a concern as an already significant and ever growing part of our daily activities is carried out online. While cryptography can be used to protect the integrity and confidentiality of contents of communication, everyone along the route on which a packet is traveling can still observe the addresses of the respective communication parties. This often is enough to uniquely identify persons participating in a communication. Anonymous communication is used to hide relationships between the communicating parties. These relationships as well as patterns of communication can often be as revealing as their content. Hence, anonymity is a key technology needed to retain privacy in communications.

This article gives a brief overview of my doctoral dissertation “Anonymous Communication in the Age of the Internet” [Panchenko, RWTH Aachen University, 2010] and then concisely focuses on one randomly selected aspect, namely, on secure node lookup in untrustworthy environments.
Impoverished environment, cognition, aging and dementia
Authors: Volkers Karin M. , Scherder Erik J.A.
Published: May 2011

Animals living in an impoverished environment, i.e., without the possibility of physical and social activity, perform worse on cognitive tests compared to animals in an enriched environment. The same cognitive difference is also observed in humans. However, it is not clear whether this difference is caused by a decrease in cognition due to an impoverished environment or an increase due to an enriched environment. This review discusses the impact of an impoverished environment on cognition in animal experimental studies and human experimental studies with community-dwelling and institutionalized older people. Results show that the cognitive functioning of old rats is more affected by an impoverished environment than young rats. Similarly, sedentary and lonely people (impoverished environment) have worse cognitive functioning and show a faster cognitive decline than physically and socially active people. Institutionalization further aggravates cognitive decline, probably due to the impoverished environment of nursing homes. In institutions, residents spend an unnecessary and excessive amount of time in bed; out of bed they show mainly sedentary or completely passive behavior. In conclusion, older people, especially those that have been institutionalized, have poor levels of physical and social activity, which in turn has a negative impact on cognitive functioning.
Development of a Substructure Instrumentation System at the New I-10 Twin Span Bridge and Its Use to Investigate the Lateral Behavior of Batter Piles
Authors: Abu-Farsakh Murad , Yoon Sungmin , Ha Da , Marr W. Allen , Zhang Zhongjie , Yu Xinbau
Published: May 2011

This paper presents the development of the substructure instrumentation system that was installed at a selected pier (M19 Eastbound) of the new I-10 Twin Span Bridge for short-term and long-term health monitoring of the bridge, and its use to monitor the behavior of the pier during a lateral load test. The selected pier is supported by 24–36 in. diameter batter pile foundation. The substructure instrumentation for the M19 Eastbound pier includes sister bar strain gauges and MEMS In-Place Inclinometers (IPI) installed inside the foundation piles, triaxial accelerometers to measure lateral movements pile cap, water pressure cells to measure wave forces, tiltmeters, and corrosion meters on the pile cap rebar. A unique lateral load test was designed and conducted to investigate the lateral behavior of the pier and to assess the validity of the analysis method used to design the batter pile foundations using the FB-MultiPier software. Two high strength steel strand tendons were used to impose about 1900 kips of lateral load. The horizontal movements of the pier caps and bents were monitored using an automated survey station with prisms. The strains and deformations within the foundation piles were measured using the strain gauges and IPI inclinometers. This paper will discuss the substructure instrumentation plan and the novel approaches to preparation and design of lateral load testing of batter pile group foundation. The results of lateral load tests will be presented, discussed and compared with the predicted values using FB-MultiPier software. The soils’ p-y curves were also back-calculated and presented.