bluuebunny/crossref_metadata_2025 huggingface dataset:
Concentration of osmoregulated periplasmic glucans (OPGs) modulates the activation level of the RcsCD RcsB phosphorelay in the phytopathogen bacteria Dickeya dadantii
Authors: Bontemps‐Gallo Sébastien , Madec Edwige , Dondeyne Jacqueline , Delrue Brigitte , Robbe‐Masselot Catherine , Vidal Olivier , Prouvost Anne‐France , Boussemart Gilles , Bohin Jean‐Pierre , Lacroix Jean‐Marie
Published: November 2012

Osmoregulated periplasmic glucans (OPGs) are general constituents of many Proteobacteria. Synthesis of these oligosaccharides is repressed by increased osmolarity of the medium. OPGs are important factors required for full virulence in many zoo‐ or phytopathogens including Dickeya dadantii. The phytopathogen enterobacterium D. dadantii causes soft‐rot disease on a wide range of plant species. The total loss of virulence of opg‐negative strains of D. dadantii is linked to the constitutive activation of the RcsCD RcsB phosphorelay highlighting relationship between this phosphorelay and OPGs. Here we show that OPGs control the RcsCD RcsB activation in a concentration‐dependent manner, are required for proper activation of this phosphorelay by medium osmolarity, and a high concentration of OPGs in planta is maintained to achieve the low level of activation of the RcsCD RcsB phosphorelay required for full virulence in D. dadantii.
Tooth Cementum Annulation for Estimation of Age‐at‐Death in Thermally Altered Remains
Authors: Gocha Timothy P. , Schutkowski Holger
Published: November 2012

Assessment of tooth cementum annulations (TCA) is acknowledged for its potential as a more accurate method for estimating age‐at‐death than conventional macroscopic methods typically employed. Thermal alteration of remains in a forensic context is not uncommon; however, the use ofTCAin heat‐treated remains has hitherto received no quantitative assessment of accuracy. This study appliesTCAto a sample of modern teeth of known demographics after experimental heat treatment at 600, 800 and 1000°C. Cementum annulations do survive thermal alteration; however, their visibility is dependent on exposure temperature. Physical and chemical changes resulted inTCAbeing applicable to only 63.3% of samples. An overall correlation to known age ofr = 0.522 (p < 0.05) was found, while correlations ofr = 0.868 (p < 0.01),r = 0.249, andr = −0.185, were found for 600, 800, and 1000°C subsets, respectively. These results indicate that in teeth exposed to temperatures >600°C,TCAno longer yields accurate enough results to be of use in forensic investigations.
The Use of Leptodyctium riparium (Hedw.)Warnst in the Estimation of Minimum Postmortem Interval
Authors: Lancia Massimo , Conforti Federica , Aleffi Michele , Caccianiga Marco , Bacci Mauro , Rossi Riccardo
Published: November 2012

The estimation of the postmortem interval (PMI) is still one of the most challenging issues in forensic investigations, especially in cases in which advanced transformative phenomena have taken place. The dating of skeletal remains is even more difficult and sometimes only a rough determination of the PMI is possible. Recent studies suggest that plant analysis can provide a reliable estimation for skeletal remains dating, when traditional techniques are not applicable. Forensic Botany is a relatively recent discipline that includes many subdisciplines such as Palynology, Anatomy, Dendrochronology, Limnology, Systematic, Ecology, and Molecular Biology. In a recent study, Cardoso et al. (Int J Legal Med 2010;124:451) used botanical evidence for the first time to establish the PMI of human skeletal remains found in a forested area of northern Portugal from the growth rate of mosses and shrub roots. The present paper deals with a case in which the study of the growth rate of the bryophyte Leptodyctium riparium (Hedw.) Warnst, was used in estimating the PMI of some human skeletal remains that were found in a wooded area near Perugia, in Central Italy.
The Effect of Environmental Conditions on the Persistence of Common Lubricants on Skin for Cases of Sexual Assault Investigation
Authors: Tonkin Megan , Yeap Li Foong , Bartle Emma K. , Reeder Anthony
Published: November 2012

The potential for lubricant trace evidence to be used as associative evidence is often overlooked in forensic investigations. Published studies in this area have focused on the identification of analytical techniques suitable for the detection of this evidence type. However, detection of trace lubricant is also dependent on the length of time it persists on skin and mucosal surfaces. The objective of this study was to investigate the effect of environmental conditions on the persistence of oil‐ and glycerol‐based lubricants on skin surfaces. Lubricated skin samples exposed to three different test environments were swabbed at regular intervals over a 24‐h period. Compounds of interest were extracted from the swabs and analyzed using gas chromatography–mass spectrometry (GC‐MS). The effect of glycerol derivatization prior to GC‐MS analysis was also investigated. In general, oil‐based lubricants persisted longer than glycerol‐based. Persistence on skin was greatest in lower temperature conditions away from direct sunlight exposure. The results of this investigation are relevant in the context of sexual assault investigations given the possible detection of lubricant on the skin of the external genitalia.
Sudden Death Due to Undiagnosed Primary Amyloidosis
Authors: Morin Jason , Schreiber William E. , Lee Carol
Published: November 2012

Amyloidosis is a disease characterized by abnormal deposition of amyloid protein within tissues throughout the body. The site of deposition can differ between patients, and therefore, clinical presentation can vary. Here, we present a case of previously undiagnosed amyloidosis presenting with sudden death. Autopsy demonstrated amyloid infiltration of intramural myocardial vessels, in the absence of myocardial involvement, leading to acute myocardial infarction and death. Postmortem analysis on femoral blood demonstrated an increase in the concentration of free lambda light chains with a significantly decreased kappa‐to‐lambda ratio, confirming the amyloidosis to be of AL type. While cardiac involvement in AL amyloidosis is not uncommon, isolated intramural vessel involvement is rarely seen, and to our knowledge, no reported cases have resulted in sudden death. This case highlights the importance of investigating angina‐like symptoms in patients with amyloidosis. It also demonstrates that free light chain analysis can be a useful tool for diagnosing and classifying amyloidosis in postmortem investigations.
Economic impact of antidepressant treatment duration in naturalistic conditions
Authors: Tournier M. , Crott R. , Gaudron Y. , Verdoux H.
Published: November 2012

Objective

To assess the economic impact of the duration of antidepressant drug treatment in a real‐life setting.

Method

A historical fixed cohort study included 27 917 patients aged 18 and over with a new antidepressant treatment registered in the national insurance database. The economic impact concerned healthcare expenditure in the first 3 months after treatment discontinuation. Generalized linear models were used to compare two groups of treatment duration: <6 months and 6 months and over.

Results

After adjustment for care costs before and during treatment episode, gender, age, chronic diseases, welfare and prescriber specialty, total healthcare costs (in log) [−0.06 (−0.14;0.01) P = 0.11] and psychiatric care costs (in square root) [−0.08 (−0.41;0.25) P = 0.6] were similar in both groups. Non‐psychiatric care costs were significantly lower in the ‘long treatment duration’ group compared with the ‘short treatment duration’ group [−11.4 (−15.8; −7.0) P < 0.0001]. The decreases in total and non‐psychiatric care costs over the antidepressant treatment episode were larger in the ‘long treatment duration’ group compared with the ‘short treatment duration’ group.

Conclusion

With regard to healthcare costs and global health, antidepressant drug treatments of short duration appear less effective than treatment of recommended duration.
Validation of a proxy for estrogen receptor status in breast cancer patients using dispensing data
Authors: Srasuebkul Preeyaporn , Dobbins Timothy A ,   Elements of Cancer Care (EoCC) Investigators, Pearson Sallie‐Anne
Published: November 2012

Aim

To assess the performance of a proxy for estrogen receptor (ER) status in breast cancer patients using dispensing data.

Methods

We derived our proxy using 167 patients. ER+ patients had evidence of at least one dispensing record for hormone therapy during the lookback period, irrespective of diagnosis date and ER‐ had no dispensing records for hormone therapy during the period. We validated the proxy against our gold standard, ER status from pathology reports or medical records. We assessed the proxy's performance using three lookback periods: 4.5 years, 2 years, 1 year.

Results

More than half of our cohort (62%) were >50 years, 54% had stage III/IV breast cancer at recruitment, (46%) were diagnosed with breast cancer in 2009 and 23% were diagnosed before 2006. Sensitivity and specificity were high for the 4.5 year lookback period (93%, 95% CI: 86–96%; and 95%: 83–99%), respectively) and remained high for the 2‐year lookback period (91%: 84–95%; and 95%: 83–99%). Sensitivity decreased (83%: 75.2–89%) but specificity remained high (95%: 83–99%) using the 1‐year lookback period and the period is long enough to allow sufficient time for hormone therapy to be dispensed.

Conclusion

Our proxy accurately infers ER status in studies of breast cancer treatment based on secondary health data. The proxy is most robust with a minimum lookback period of 2 years.
Anthracycline‐based chemotherapy in metastatic endometrial carcinoma: An update
Authors: Colloca Giuseppe , Venturino Antonella
Published: November 2012

The purpose of this review is to analyze clinical evidence about the activity and efficacy of anthracycline‐based chemotherapy in metastatic endometrial cancer and to identify the most important preclinical findings that would address future clinical trials. A literature search of published studies was undertaken. Studies were selected by predefined criteria. Clinical trials and preclinical studies were analyzed. The search identified eight phase 3 and 13 phase 2 clinical trials of patients with metastatic endometrial carcinoma treated with an anthracycline‐based regimen. The planned dose intensity of the anthracycline had no effect on response rates and survival. Survival increased for patients with a good performance status, and sometimes the duration of responses to anthracycline monotherapy can be very long‐lasting. The major findings of anthracycline resistance in preclinical models are reported. Possible future biomarkers targeting mechanisms of anthracycline resistance are suggested, and efforts to define a molecular classification of endometrial cancer are desirable.
Descriptive analysis of molecular subtypes in Tunisian breast cancer
Authors: Fourati Asma , Boussen Hamouda , El May Michéle V , Goucha Aida , Dabbabi Bouthaina , Gamoudi Amor , Sfar Rachida , Rahal Khaled , El May Ahmed , Ben Abdallah Mansour
Published: November 2012

Aim

The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women.

Methods

This retrospective study concerned data of 966 breast cancer cases collected from 2007 to 2009 at Salah Azaiz Institute of Tunis. These cases were classified by an immunohistochemistry test for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2) status in the four molecular subtypes, namely luminal A, luminal B, HER2+ and triple negative. The molecular classifications were correlated with the clinicopathological characteristics of the tumors.

Results

Luminal A (50.7% of cases) was the most common subtype, with triple negative subtype 22.5%, luminal B 13.4% and HER2+ 13.4%. Triple negative and HER2+ subtypes were significantly associated with large tumor size (>5 cm, P < 0.001), younger age (<40 years, P < 0.03) and high grade (P < 0.001). Conversely, there was no correlation with the lymph node status.

Conclusion

Our data demonstrated that the luminal A subtype, associated with a favorable prognosis, was the most frequent subtype in the Tunisian population; however the triple negative subtype occurred at a high incidence in Tunisia compared to Western countries. The molecular subtypes are correlated to the tumor size, histological grade and patient's age.
Preimplantation Human Blastocyst‐Endometrial Interactions: The Role of Inflammatory Mediators
Authors: Van Sinderen Michelle , Menkhorst Ellen , Winship Amy , Cuman Carly , Dimitriadis Evdokia
Published: November 2012

Immune factors such as cytokines, chemokines, and growth factors are known to play important roles in the preimplantation interactions and communication between the blastocyst and receptive endometrium. This crucial dialog occurs during the stages when the blastocyst is in the uterine cavity immediately preceding implantation and the establishment of pregnancy. Human preimplantation processes are difficult to study due to restrictions on tissue availability. This review focuses on the expression and role of immune factors in human blastocyst‐endometrial dialog during the very early stages of implantation. It highlights the importance of immune regulators and the need to develop new models to study human implantation.
Is Early Sexual Debut a Risk Factor for HIV Infection Among Women in Sub‐Saharan Africa? A Systematic Review
Authors: Stöckl Heidi , Kalra Naira , Jacobi Jantine , Watts Charlotte
Published: November 2012

Problem

In Africa, adolescent girls have high HIV risk. Early sexual debut may be a risk factor, although evidence has not been systematically compiled.

Methods

A systematic review was conducted. Quantitative studies from sub‐Saharan Africa with biologically confirmed HIV infection measures were included.

Results

A total of 128 full texts were screened. Twenty‐five met the inclusion criteria, most cross‐sectional. Half of studies, and all with large sample sizes, reported significant bivariate associations. These remained significant in all three studies controlling for socio‐demographic factors; both studies controlling for sexual activity duration and four of eight studies controlling for subsequent risk behaviour.

Conclusions

Higher‐quality studies consistently find significant bivariate associations between early sexual debut and HIV. In some studies, the increase in women's HIV infection risk seems to result from women's later engagement in risky sexual behaviours, rather than being directly related to early onset of sexual debut. In other studies, the increase in risk did not seem to be due to specific behavioural risk characteristics of the respondents or their sexual partners, suggesting that the risk may relate more to the potential for biological factors, for example, genital trauma, or other factors that have not been captured by the studies in this review.
Asthma symptoms and nasal congestion as independent risk factors for insomnia in a general population: results from the GA2LEN survey
Authors: Sundbom F. , Lindberg E. , Bjerg A. , Forsberg B. , Franklin K. , Gunnbjörnsdottir M. , Middelveld R. , Torén K. , Janson C.
Published: November 2012

Background

Asthma and rhinitis have been related to insomnia. The aim of this study was to further analyse the association between asthma, nasal symptoms and insomnia and to identify risk factors for sleep disturbance among patients with asthma, in a large population‐based set of material.

Method

In 2008, a postal questionnaire was sent to a random sample of 45 000 adults in four Swedish cities. The questionnaire included questions on insomnia, asthma, rhinitis, weight, height, tobacco use and physical activity.

Results

Twenty‐five thousand six hundred and ten subjects participated. Asthma was defined as either current medication for asthma or at least one attack of asthma during the last 12 months, and 1830 subjects (7.15%) were defined as asthmatics. The prevalence of insomnia symptoms was significantly higher among asthmatics than non‐asthmatics (47.3% vs 37.2%, <0.0001). In the subgroup reporting both asthma and nasal congestion, 55.8% had insomnia symptoms compared with 35.3% in subjects without both asthma and nasal congestion. The risk of insomnia increased with the severity of asthma, and the adjusted OR for insomnia was 2.65 in asthmatics with three symptoms compared with asthmatics without symptoms. Nasal congestion (OR 1.50), obesity (OR 1.54) and smoking (OR 1.71) also increased the risk of insomnia.

Conclusion

Insomnia remains a common problem among asthmatics. Uncontrolled asthma and nasal congestion are important, treatable risk factors for insomnia. Lifestyle factors, such as smoking and obesity, are also risk factors for insomnia among asthmatics.
Purinergic signalling in the lower urinary tract
Authors: Burnstock G.
Published: November 2012

The aim of this review is to describe the conceptual steps contributing to our current knowledge of purinergic signalling and to consider its involvement in the physiology and pathophysiology of the lower urinary tract. The voiding reflex involves ATP released as a cotransmitter with acetylcholine from parasympathetic nerves supplying the bladder and ATP released from urothelial cells during bladder distension to initiate the voiding reflex via P2X3 receptors on suburothelial low threshold sensory nerve fibres. This mechanosensory transduction pathway also participates, via high threshold sensory nerve fibres, in the initiation of pain in bladder and ureter. Treatment of prostate and bladder cancer with ATP is effective against the primary tumours in animal models and human cell lines, via P2X5 and P2X7 receptors, and also improves the systemic symptoms associated with advanced malignancy. Acupuncture is widely used for the treatment of urinary disorders, and a purinergic hypothesis is discussed for the underlying mechanism.
Short‐term hypercaloric diet induces blunted aortic vasoconstriction and enhanced vasorelaxation via increased nitric oxide synthase 3 activity and expression in Dahl salt‐sensitive rats
Authors: Spradley F. T. , Kang K.‐T. , Pollock J. S.
Published: November 2012

Aim

To elucidate the role of the O2‐, H2O2 or NO pathways in aortic angiotensin (Ang)II‐induced vasoconstriction in Dahl salt‐sensitive (SS) rats compared with control SS‐13BN rats on a normal or hypercaloric diet.

Methods

Aortic function was assessed using wire myography in 16‐week‐old rats maintained on a normal diet or a 4‐week hypercaloric diet. Nitric oxide synthase (NOS) activity and expression was determined by the conversion of radio‐labelled arginine to citrulline and Western blot analysis respectively.

Results

On normal diet, AngII‐induced vasoconstriction was greater in SS than SS‐13BN rats. Polyethylene glycol superoxide dismutase (PEG‐SOD) reduced the aortic AngII response similarly in both strains on normal diet. Catalase blunted, whereas Nω‐Nitro‐L‐arginine methyl ester (L‐NAME) did not affect the AngII response in SS rats. In SS‐13BN rats, catalase had no effect and L‐NAME enhanced AngII response. On hypercaloric diet, aortic AngII responsiveness was reduced in SS but unaltered in SS‐13BN rats compared with their normal diet counterparts. PEG‐SOD reduced the AngII response in both rats on hypercaloric diet. Catalase treatment did not alter aortic AngII response, while L‐NAME increased the response in SS rats on hypercaloric diet. In SS‐13BN rats on hypercaloric diet, catalase reduced and L‐NAME did not alter the AngII response. Furthermore, aortic endothelial‐dependent vasorelaxation was increased in SS rats on hypercaloric diet compared with normal diet and aortic NOS3 activity and expression was increased.

Conclusion

A short‐term hypercaloric diet induces a blunted vasoconstrictive and enhanced vasodilatory phenotype in SS rats, but not in SS‐13BN rats, via reduced H2O2 and increased NOS3 function.
Improvement of the metabolic status recovers cardiac potassium channel synthesis in experimental diabetes
Authors: Torres‐Jacome J. , Gallego M. , Rodríguez‐Robledo J. M. , Sanchez‐Chapula J. A. , Casis O.
Published: November 2012

Aims

The fast transient outward current, Ito,fast, is the most extensively studied cardiac K+ current in diabetic animals. Two hypotheses have been proposed to explain how type‐1 diabetes reduces this current in cardiac muscle. The first one is a deficiency in channel expression due to a defect in the trophic effect of insulin. The second one proposes flawed glucose metabolism as the cause of the reduced Ito,fast. Moreover, little information exists about the effects and possible mechanisms of diabetes on the other repolarizing currents of the human heart: Ito,slow, IKr, IKs, IKur, IKslow and IK1.

Methods

We recorded cardiac action potentials and K+ currents in ventricular cells isolated from control and streptozotocin‐ or alloxan‐induced diabetic mice and rabbits. Channel protein expression was determined by immunofluorescence.

Results

Diabetes reduces the amplitude of Ito,fast, Ito,slow and IKslow, in ventricular myocytes from mouse and rabbit, with no effect on Iss, IKr or IK1. The absence of changes in the biophysical properties of the currents and the immunofluorescence experiments confirmed the reduction in channel protein synthesis. Six‐hour incubation of myocytes with insulin or pyruvate recovered current amplitudes and fluorescent staining. The activation of AMP‐K reduced the same K+ currents in healthy myocytes and prevented the pyruvate‐induced current recovery.

Conclusion

Diabetes reduces K+ current densities in ventricular myocytes due to a defect in channel protein synthesis. Activation of AMP‐K secondary to deterioration in the metabolic status of the cells is responsible for K+ channel reductions.
Structural organization of the toe pads in the amphibian Philautus annandalii (Boulenger, 1906)
Authors: Chakraborti Saurabh , Das Debasish , De Subrata K. , Nag Tapas C.
Published: November 2012

We describe the morphology of toe pads in the Himalayan tree frog Philautus annandalii. These are expanded tips of digits and show modifications of their ventral epidermis for adhesion. The outer cells of toe pad epidermis (TPE) bear surface microstructures (0.7 × 0.2 μm), which are keratinized. Their cytoplasm contains no organelles, but pleomorphic nuclei and mucous granules (0.4–0.5 μm) that glue the keratin filaments. In the intermediate cell layer of TPE, similar keratinized microstructures as in the outer cells are present, so that when the outer layer is shed, it is ready with features for adhesion. These cells contain more keratin than the outer cells. The basal cell layer contains thin keratin bundles and usual cell organelles. The dermis contains mucous‐secreting glands, whose ducts open in the outer epidermal cell layer in channels. The dorsal epidermal cells lack surface microstructures and keratin bundles. Ultrastructural features suggest that toe pads utilize the surface microstructures for adhesion aided by mucus, in which the intermediate cell layer seems to bear the shear stress generated during locomotion. Further, TPE can expand and fit into an increased contact area of the substrate. The long, surface microstructures may also help in mechanical interlocking with rough surfaces on plants.
Presentation design for “conceptual model” learning objects
Authors: Churchill Daniel
Published: November 2012

This paper discusses a set of recommendations for the presentation design of “conceptual model” learning objects. A conceptual model is a learning object designed to support conceptual learning. Often, it is interactive and multimodal and allows a learner to examine and interrogate displayed content. Presentation design is concerned primarily with the arrangement of content and screen design features that are optimized for educational purpose. The paper presents the following set of recommendations for presentation design: present information visually, design for interaction, design a holistic scenario, design for a single screen, design for small space, use audio and video only if they are the only option, use color in moderation, avoid unnecessary decorative elements, design with a single font, and use frames to logically divide the screen area. The recommendations were explicated from a study that involved a review of a collection of conceptual models by a team of five independent reviewers. These recommendations should prove useful to designers of educational multimedia resources.
The new KCNQ2 activator 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid displays anticonvulsant potential
Authors: Boehlen A , Schwake M , Dost R , Kunert A , Fidzinski P , Heinemann U , Gebhardt C
Published: November 2012

Background and Purpose

KCNQ2‐5 channels are voltage‐gated potassium channels that regulate neuronal excitability and represent suitable targets for the treatment of hyperexcitability disorders. The effect of Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid was tested on KCNQ subtypes for its ability to alter neuronal excitability and for its anticonvulsant potential.

Experimental Approach

The effect of 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid was evaluated using whole‐cell voltage‐clamp recordings from CHO cells and Xenopus laevis oocytes expressing different types of KCNQ channels. Epileptiform afterdischarges were recorded in fully amygdala‐kindled rats in vivo. Neuronal excitability was assessed using field potential and whole cell recording in rat hippocampus in vitro.

Key Results

4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid caused a hyperpolarizing shift of the activation curve and a pronounced slowing of deactivation in KCNQ2‐mediated currents, whereas KCNQ3/5 heteromers remained unaffected. The effect was also apparent in the Retigabine‐insensitive mutant KCNQ2‐W236L. In fully amygdala‐kindled rats, it elevated the threshold for induction of afterdischarges and reduced seizure severity and duration. In hippocampal CA1 cells, 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid strongly damped neuronal excitability caused by a membrane hyperpolarization and a decrease in membrane resistance and induced an increase of the somatic resonance frequency on the single cell level, whereas synaptic transmission was unaffected. On the network level, 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid caused a significant reduction of γ and θ oscillation peak power, with no significant change in oscillation frequency.

Conclusion and Implications

Our data indicate that 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid is a potent KCNQ activator with a selectivity for KCNQ2 containing channels. It strongly reduces neuronal excitability and displays anticonvulsant activity in vivo.
Engaging in cyberspace: seeking help for sexual assault
Authors: Webber Ruth , Moors Rosetta
Published: November 2012

Many young people who have been sexually assaulted are accessing the Internet through question and answer (Q&A) social networking sites in order to obtain information, advice and counselling on sexual assault. This paper reports on a study that was conducted on the Q&As on sexual assault that were posted on Yahoo! Answers. It focuses on comparing answers supplied by counsellors who work at a sexual assault centre with those posted by other Yahoo members. It reports on an analysis of content, tone and ‘best’ answer. Sixty‐five questions and 392 answers were analysed using interpretive description which is an inductive analytic approach. The responses by counsellors were voted ‘best’ by posters of questions (Askers) in the majority of cases. Their responses were dispassionate, accurate and systematic and contained information about how and where Askers could access help. In contrast, the answers by general Yahoo members were inconsistent and lacked specificity. While most of their responses contained supportive comments, many contained condemnatory remarks about perpetrators and Askers, which were potentially damaging to both Askers and other Yahoo members who were accessing the site.
Determination of lingual vascular canals in the interforaminal region before implant surgery to prevent life‐threatening bleeding complications
Authors: Kilic Erdem , Doganay Selim , Ulu Murat , Çelebi Nükhet , Yikilmaz Ali , Alkan Alper
Published: November 2012

Objectives

Profuse hemorrhage and airway obstruction may occur during or after the implant surgery in the interforaminal region. The prevention from this complication requires identifying the location of the mandibular lingual vascular canals (MLVCs). The purpose of this study was to evaluate the anatomical variations of MLVCs and to determine the safety margins for implant placement in interforaminal region.

Materials and methods

Computer tomography (CT) images of 200 consecutive patients were reexamined retrospectively by a radiologist and a maxillofacial surgeon to evaluate the presence of the MLVCs entering the mandible. The diameter and the number of the canals, the distance between the entrance of the canal and mandibular midline, and the height of the entrances of the canals from the inferior mandibular margin were measured.

Results

Two hundred and thirty‐six median lingual canals (MLCs) and 159 lateral lingual canals (LLCs) were found in 200 patients. Significant differences were found between the number of lingual canals in the midline and canine regions (P < 0.001).

Conclusion

There is a potential risk of complications due to the injuries of the vessels entering the lingual cortical bone through a number of bone canals during implant placement in the interforaminal region.
Human cadaveric histomorphological and metallurgical analysis of dental implants following 12.5 years of service
Authors: Abbott John R. , Marino Victor , Bartold P. Mark
Published: November 2012

Objectives

To provide a metallurgical and histomorphological analysis of hybrid bridgework and associated dental implants which have been in a clinical load bearing situation for a period of 12.5 years.

Material and methods

The physical integrity of the hybrid framework was examined with stereoimaging microscopy and scanning electron microscopy for signs of wear, fatigue cracks, corrosion. Elemental spectra and maps of the surface were analysed with anEDAX®DetectingUnit (AMETEK,Inc,Mahwah,NJ,USA). Similarly, the supporting titanium abutments screwed into the implants were examined for fatigue and corrosion. Bone density scans and bone trabecular patterns were obtained from radiographs. Microcomputer tomography was used to assess the bone–implant interface and bone architecture around the implants. Histological sections were stained with 1% basic fuchsin to assess osseous microdamage.

Results

The study demonstrated that the gold alloy framework to be in satisfactory condition with little indication of corrosion or cracking. The interface between the gold alloy and the titanium abutments likewise demonstrated no obvious corrosion cells. No radiographic evidence of any adverse loss of bone around the implants was noted. Bone mineral density was related to implant position, being higher between the implants. Scanning electron micrograph images confirmed the good bone integration with the implant threads with a high level of organisation, maturation and adaptation for the entire length of the implant. There was no evidence of any microdamage.

Conclusions

The implants, abutments and hybrid framework were in remarkably good condition considering their length of service.
The multiple origins of Type 1 diabetes
Authors: Pugliese A.
Published: November 2012

It is widely accepted that Type 1 diabetes is a complex disease. Genetic predisposition and environmental factors favour the triggering of autoimmune responses against pancreatic β‐cells, eventually leading to β‐cell destruction. Over 40 susceptibility loci have been identified, many now mapped to known genes, largely supporting a dominant role for an immune‐mediated pathogenesis. This role is also supported by the identification of several islet autoantigens and antigen‐specific responses in patients with recent onset diabetes and subjects with pre‐diabetes. Increasing evidence suggests certain viruses as a common environmental factor, together with diet and the gut microbiome. Inflammation and insulin resistance are emerging as additional cofactors, which might be interrelated with environmental factors. The heterogeneity of disease progression and clinical manifestations is likely a reflection of this multifactorial pathogenesis. So far, clinical trials have been mostly ineffective in delaying progression to overt diabetes in relatives at increased risk, or in reducing further loss of insulin secretion in patients with new‐onset diabetes. This limited success may reflect, in part, our incomplete understanding of key pathogenic mechanisms, the lack of truly robust biomarkers of both disease activity and β‐cell destruction, and the inability to assess the relative contributions of various pathogenic mechanisms at various time points during the course of the natural history of Type 1 diabetes. Emerging data and a re‐evaluation of histopathological, immunological and metabolic findings suggest the hypothesis that unknown mechanisms of β‐cell dysfunction may be present at diagnosis, and may contribute to the development of hyperglycaemia and clinical symptoms.
Differential associations between depressive symptoms and glycaemic control in outpatients with diabetes
Authors: Bot M. , Pouwer F. , de Jonge P. , Tack C. J. , Geelhoed‐Duijvestijn P. H. L. M. , Snoek F. J.
Published: November 2012

Aims

Depression is common in people with diabetes, and related to higher HbA1c levels. Depression, however, is a heterogeneous construct that involves a variety of symptoms. As little is known about the associations of individual depressive symptoms with HbA1c, we explored these associations in outpatients with diabetes.

Methods

The study was conducted in three tertiary diabetes clinics in the Netherlands. At baseline, the presence of the nine depressive symptoms that are listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was assessed with the nine‐item Patient Health Questionnaire (PHQ‐9). At baseline and after a 1‐year follow‐up, HbA1c was derived from the medical charts.

Results

A total of 288 out of 646 subjects with diabetes (45%) reported one or more depressive symptom(s). Depressed mood (β = 0.11, P = 0.005), sleeping difficulties (β = 0.16, P < 0.001), appetite problems (β = 0.15, P < 0.001) and suicidal ideation (β = 0.14, P = 0.001) were significantly related to higher baseline HbA1c values. Furthermore, depressed mood (β = 0.09, P = 0.03) sleeping difficulties (β = 0.12, P = 0.004), appetite problems (β = 0.11, P = 0.01) and psychomotor agitation/retardation (β = 0.09, P = 0.04) were significantly related to higher HbA1c values at 1‐year follow‐up. Associations were more pronounced in Type 1 diabetes than in Type 2 diabetes. None of the depressive symptoms were related to change in HbA1c over time, except suicidal ideation.

Conclusion

In people with diabetes, several individual depressive symptoms were related to higher HbA1c levels. These associations persisted over time. More research is needed to investigate potential mechanistic pathways.
Small platelet microparticle levels are increased in pulmonary arterial hypertension
Authors: Nadaud Sophie , Poirier Odette , Girerd Barbara , Blanc Catherine , Montani David , Eyries Mélanie , Imbert‐Bismut Françoise , Pacheco Antoine , Vigne Jacques , Tregouet David‐Alexandre , Humbert Marc , Soubrier Florent
Published: November 2012

Eur J Clin Invest 2012

Background  The various aetiologies and risk factors for pulmonary arterial hypertension (PAH) lead to close phenotypes with small differences. Plasma microparticles have been shown to be increased in vascular pathologies including PAH. The aim of this study was to determine whether the levels of endothelial and platelet‐derived microparticles could vary between different forms of PAH: idiopathic PAH (iPAH), heritable PAH associated with BMPR2 (Bone morphogenetic protein receptor, type II) mutation (hPAH) and PAH associated with connective tissue diseases (aPAH).

Materials and methods  Microparticles were analysed using flow cytometry in plasma from controls and iPAH, hPAH and aPAH patients. Platelet‐derived MP (PMP) were defined as CD31+/CD41+ and endothelial‐derived MP (EMP) as CD31+/CD41−. Two populations of PMP were isolated according to their size, defining small PMP (0·3–0·5 μm) and large PMP (0·5–0·9 μm). BMPR2 genotype, clinical and biologic parameters were recorded.

Results  EMP and small PMP levels in iPAH, hPAH and aPAH were similar and were significantly increased as compared with controls. No differences in large PMP levels were observed. After adjusting for age, sex, proBNP and CRP, EMP and small PMP levels did not correlate with clinical parameters.

Conclusions  iPAH, hPAH and aPAH were characterized by increased levels of EMP and of small PMP, a new class of PMP which seems to be differentially produced than large PMP.
Endothelial function does not relate to haemoglobin or serum erythropoietin concentrations and these do not explain the gender difference in endothelial function in healthy middle‐aged men and women
Authors: Tilling Lindsey , Hunt Joanne , Jiang Benyu , Sanders Thomas A. B. , Clapp Brian , Chowienczyk Philip
Published: November 2012

Background

Haemoglobin scavenges nitric oxide, and a previous study has shown a negative association between flow‐mediated vasodilation (FMD), a measure of nitric oxide (NO)‐dependent vasomotor function and haemoglobin concentrations [Hb]. Circulating erythropoietin (EPO) is also negatively associated with [Hb] and could influence availability of NO. The purpose of this study was to examine the association of FMD with [Hb] and EPO concentrations and to determine whether these contribute to the sex difference in FMD. FMD (by high‐resolution ultrasound), [Hb], circulating immunoreactive EPO and cardiovascular risk factors were measured in 317 healthy middle‐aged men and women (183 women, 33 premenopausal, mean age ± SD, 55 ± 6·8 years) participating in a dietary study.

Results

In the whole mixed‐sex group, FMD was negatively correlated with [Hb] (R = −0·23, P < 0·001). However, in a multivariable model, incorporating sex and other confounding factors, FMD was independently negatively correlated only with age, male sex and systolic blood pressure: standardized regression coefficients −0·21 (P < 0·01), −0·17 (P < 0·05) and −0·20 (P < 0·05) respectively and not with [Hb]. Similarly, when the analysis was restricted to men or to postmenopausal women, there was no significant relationship between FMD and Hb. There was no significant correlation between FMD and EPO on either univariate analysis in the whole group, in each sex, or in multivariate analysis.

Conclusion

These results suggest that in healthy middle‐aged subjects, FMD is not influenced by [Hb] or EPO and these do not contribute to the gender difference in FMD.
The changing role of education in the distribution of earnings and household income
Authors: Večerník Jiří
Published: November 2012

This article draws on income surveys from the last two decades to report on trends in earnings disparities and household income inequality in the Czech Republic. Education has been the main axis of change in this area, having acquired a much greater role in the entire process of collecting and distributing income. First, an increasing influence of education is evident in the personal earnings of employees, returns to education having doubled. Second, in couples, education has an important impact on both women’s employment and their earnings. Third, the importance of marital partners’ education levels on household income grew even more than its effect on earnings.
Offspring investment in wild Atlantic salmon (Salmo salar): relationships with smolt age and spawning condition
Authors: Burton Tim , McKelvey Simon , Stewart Dave C. , Armstrong John D. , Metcalfe Neil B.
Published: November 2012

We investigated the independent effects of age at smolting and body condition at the time of spawning on egg production by female Atlantic salmon (Salmo salar). For a given body size, female salmon that had smolted as juveniles after 2 years in fresh water produced smaller, more numerous eggs than females that smolted 1 year later. Furthermore, fecundity (but not egg size) was related positively to maternal body condition at spawning. Given that age at smolting is closely related to juvenile growth rate; results from this study suggest that conditions experienced by female Atlantic salmon during both early life and adulthood have implications for the size and number of eggs that they produce.
Infection patterns and hosts ofArceuthobium oxycedri(DC.)M.Bieb. inSlovenia
Authors: Gajšek D. , Jarni K. , Brus R.
Published: November 2012

Eleven mixed populations ofJuniperus oxycedrusL. andJuniperus communisL. were inventoried for the presence of parasitic woody speciesArceuthobium oxycedri(DC.)M. Bieb. infections. BothJ. oxycedrusandA. oxycedriare rare and distributed in marginal populations inSlovenia. To our knowledge, this is the first detailed research on the host species as well as on the infection and spreading patterns ofA. oxycedriinEurope. Assessment of the infection rate was based on theHawksworth six‐class dwarf mistletoe rating system (DMR). The dimensions ofA. oxycedrispecimens were surprisingly large and often exceeded 25 cm in diameter, the largest even measuring up to 40 cm. Six juniper populations of 11 were infected, and the proportion of infected host individuals in these ranged between 29.17 and 82.93%. The proportion of infectedJ. oxycedrusspecimens in infected populations was 76.56%, while this percentage forJ. communiswas 54.90%, which is surprisingly high for this species. A different pattern of infection was observed for the two hosts. A typical infection onJ. communiswas more localized. Usually, only a single infection was present and was most common on the trunk in the middle third of the crown and much less common on the branches. InJ. oxycedrus, infections were also most common in the middle third, but also frequent in other areas of the trunk as well as on the branches. Mostly, we observed a dotted pattern of infection with uninfected areas in between. We assume thatA. oxycedriwill continue to slowly spread in Slovenia, primarily in areas where it is already present. However, its control is probably not yet necessary.
Modelling the evolution of genetic instability during tumour progression
Authors: S. Datta Ruchira , Gutteridge Alice , Swanton Charles , Maley Carlo C. , Graham Trevor A.
Published: November 2012

The role of genetic instability in driving carcinogenesis remains controversial. Genetic instability should accelerate carcinogenesis by increasing the rate of advantageous driver mutations; however, genetic instability can also potentially retard tumour growth by increasing the rate of deleterious mutation. As such, it is unclear whether genetically unstable clones would tend to be more selectively advantageous than their genetically stable counterparts within a growing tumour. Here, we show the circumstances where genetic instability evolves during tumour progression towards cancer. We employ a Wright–Fisher type model that describes the evolution of tumour subclones. Clones can acquire both advantageous and deleterious mutations, and mutator mutations that increase a cell's intrinsic mutation rate. Within the model, cancers evolve with a mutator phenotype when driver mutations bestow only moderate increases in fitness: very strong or weak selection for driver mutations suppresses the evolution of a mutator phenotype. Genetic instability occurs secondarily to selectively advantageous driver mutations. Deleterious mutations have relatively little effect on the evolution of genetic instability unless selection for additional driver mutations is very weak or if deleterious mutations are very common. Our model provides a framework for studying the evolution of genetic instability in tumour progression. Our analysis highlights the central role of selection in shaping patterns of mutation in carcinogenesis.
The Myth of Closure
Authors: Boss Pauline , Carnes Donna
Published: November 2012

Therapies for grief and loss have traditionally focused on the work of grieving. The goal was to reach an endpoint, now popularly called closure. There are, however, many people who, through no fault of their own, find a loss so unclear that there can be no end to grief. They have not failed in the work of grieving, but rather have suffered ambiguous loss, a type of loss that is inherently open ended. Instead of closure, the therapeutic goal is to help people find meaning despite the lack of definitive information and finality. Hope lies in increasing a family's tolerance for ambiguity, but first, professionals must increase their own comfort with unanswered questions. In this article, the authors, one a poet, the other a family therapist and theorist, offer a unique blending of theory, reflection, and poetry to experientially deepen the process of self‐reflection about a kind of loss that defies closure.
Exogenous NAD+ supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1‐p53 pathway
Authors: Liu Ling , Wang Ping , Liu Xinwei , He Dongwei , Liang Canxin , Yu Ying
Published: November 2012

Nicotinamide adenine dinucleotide (NAD+) not only transfers electrons in mitochondrial respiration, but also acts as an indispensable cosubstrate for Sirt1, the class III histone/nonhistone deacetylase. However, NAD+ is depleted in myocardial ischemia/reperfusion (IR) injury. The objective of this study was to investigate the role of exogenous NAD+ supplementation in hypoxia/reoxygenation (HR)‐stressed H9c2 cardiac myoblasts. Firstly, the effects of distinct treating time points and doses of NAD+ supplementation on the viability of HR‐stressed H9c2 cells were detected. Secondly, intracellular NAD+ levels in HR‐stressed H9c2 cells at various extracellular NAD+ concentrations were determined. Thirdly, the role of NAD+ supplementation in HR‐induced cell apoptosis and its relevance to Sirtuin 1‐p53 pathway were investigated. Exogenous NAD+ supplementation elevated intracellular NAD+ level and reduced HR‐induced cell death in both time‐ and concentration‐dependent manners. It appeared that NAD+ supplementation exerted the greatest protection when extracellular concentration ranged from 500 to 1000 μm and when NAD+ was added immediately after reoxygenation began. NAD+ replenishment restored Sirt1 activity, reduced the acetylation level of p53 (Lys373 & 382), and attenuated cell apoptosis in HR‐stressed H9c2 cells, whereas inhibition of Sirt1 activity alleviated the effects of NAD+ replenishment. These results indicated that exogenous NAD+ supplementation attenuated HR‐induced cell apoptosis, which was at least partly mediated by restoring Sirt1 activity and subsequently inhibiting p53 activity via deacetylating p53 at lysine 373 and 382.
Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes
Authors: Li Yingxiu , Shin Donghee , Kwon So Hee
Published: November 2012

Histone deacetylase (HDAC) 6 is the best‐characterized class IIb deacetylase that regulates many important biological processes via the formation of complexes with its partner proteins. HDAC6 is important both for cytoplasmic and nuclear functions. Unlike other deacetylases, HDAC6 has unique substrate specificity for nonhistone proteins. Such diverse functions of HDAC6 suggest that it serves a potential therapeutic target for the treatment of a wide range of diseases. This therapeutic interest in HDAC6 stems from the observation that HDAC6 may be overexpressed or deregulated in various cancers, neurodegenerative diseases and inflammatory disorders. Despite extensive efforts, however, very few HDAC6‐selective inhibitors have been identified and the precise structural determinants remain undefined. Future efforts aiming to better define the structure and function of HDAC6 should provide the basis for the discovery of novel effective inhibitors. In this review, we focus on recent studies that highlight the importance of HDAC6‐mediated biological processes, disease mechanisms and HDAC6‐selective inhibitors.