bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Transition from Inhaled Iloprost to Inhaled Treprostinil in Patients with Pulmonary Arterial Hypertension
Authors: Bourge Robert C. , Tapson Victor F. , Safdar Zeenat , Benza Raymond L. , Channick Richard N. , Rosenzweig Erika B. , Shapiro Shelley , White R. James , McSwain Christopher Shane , Gotzkowsky Stephen Karl , Nelsen Andrew C. , Rubin Lewis J.
Published: September 2012

Background

Inhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy.

Aims

In this open‐label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6–9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed.

Results

Most patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6‐min walk distance (+16.0; P < 0.001), N‐terminal pro‐B‐type natriuretic peptide (−74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001).

Conclusions

Pulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status.
Prolonging the female reproductive lifespan and improving egg quality with dietary omega‐3 fatty acids
Authors: Nehra Deepika , Le Hau D. , Fallon Erica M. , Carlson Sarah J. , Woods Dori , White Yvonne A. , Pan Amy H. , Guo Lankai , Rodig Scott J. , Tilly Jonathan L. , Rueda Bo R. , Puder Mark
Published: September 2012

Women approaching advanced maternal age have extremely poor outcomes with both natural and assisted fertility. Moreover, the incidence of chromosomal abnormalities and birth defects increases with age. As of yet, there is no effective and practical strategy for delaying ovarian aging or improving oocyte quality. We demonstrate that the lifelong consumption of a diet rich in omega‐3 fatty acids prolongs murine reproductive function into advanced maternal age, while a diet rich in omega‐6 fatty acids is associated with very poor reproductive success at advanced maternal age. Furthermore, even short‐term dietary treatment with a diet rich in omega‐3 fatty acids initiated at the time of the normal age‐related rapid decline in murine reproductive function is associated with improved oocyte quality, while short‐term dietary treatment with omega‐6 fatty acids results in very poor oocyte quality. Thus, omega‐3 fatty acids may provide an effective and practical avenue for delaying ovarian aging and improving oocyte quality at advanced maternal age.
Stress‐associated H3K4 methylation accumulates during postnatal development and aging of rhesus macaque brain
Authors: Han Yixing , Han Dali , Yan Zheng , Boyd‐Kirkup Jerome D. , Green Christopher D. , Khaitovich Philipp , Han Jing‐Dong J.
Published: September 2012

Epigenetic modifications are critical determinants of cellular and developmental states. Epigenetic changes, such as decreased H3K27me3 histone methylation on insulin/IGF1 genes, have been previously shown to modulate lifespan through gene expression regulation. However, global epigenetic changes during aging and their biological functions, if any, remain elusive. Here, we examined the histone modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual rhesus macaques at different ages by chromatin immunoprecipitation, followed by deep sequencing (ChIP‐seq) at the whole genome level. Through integrative analysis of the ChIP‐seq profiles with gene expression data, we found that H3K4me2 increased at promoters and enhancers globally during postnatal development and aging, and those that correspond to gene expression changes in cis are enriched for stress responses, such as the DNA damage response. This suggests that metabolic and environmental stresses experienced by an organism are associated with the progressive opening of chromatin. In support of this, we also observed increased expression of two H3K4 methyltransferases, SETD7 and DPY30, in aged macaque brain.
Morphometric Changes in the Dog Trochlear Nerve with Growth
Authors: Vivo J. , Galisteo A. M. , Miró F. , Agüera E. , Plaza C. , Díz A.
Published: September 2012

The objective of this work was to analyse changes in morphometric characteristics related to growth in the trochlear nerve in dogs. Twenty beagles, split into four dog age groups (A, 7 days; B, 21 days; C, 35 days; D, 49 days and E, 4 years), were used. The right intracranial portion of the nerve was analysed by light and electron microscopy. The nerve cross‐sectional area was calculated. Number, diameter and cross‐sectional area of unmyelinated and myelinated fibres were also calculated. In myelinated fibres, the corresponding axon area and diameter and myelin sheath thickness were also calculated. The number of myelinated and unmyelinated fibres was 1070.25 ± 112.07 and 592.25 ± 467.53 in group A, 1367 ± 57.98 and 143.67 ± 54.37 in group B, 1574.20 ± 299.50 and 151.67 ± 51.73 in group C, 1340.33 ± 151 and 127 ± 48.75 in group D and 1476 ± 260.71 and 284 ± 101.82 in group E. The mean diameter for myelinated and unmyelinated fibres was 4.37 ± 0.17 μm and 0.41 ± 0.08 μm for group A; 6.21 ± 0.12 μm and 0.30 ± 0.03 μm for B; 6.90 ± 0.91 μm and 0.32 ± 0.03 μm for C; 7.86 ± 1.19 μm and 0.32 ± 0.02 μm for D; 10.63 ± 0.50 μm and 0.30 ± 0.01 μm for E, respectively. This nerve possesses similar structural and ultrastructural features to the same nerve in other species and modifies its morphometry with growth. Results could enhance the understanding of pathological disorders.
Ovarian Structure and Oogenesis of Catfish Pimelodella vittata (Lütken, 1874) (Siluriformes, Heptapteridae)
Authors: Sales N. G. , dos Santos S. A. , Arantes F. P. , Hojo R. E. S. , dos Santos J. E.
Published: September 2012

The morphology of the ovaries and oogenesis of Pimelodella vittata were studied using anatomical and histological techniques to provide information of its reproductive biology. Eighty adult females were captured trimonthly during the period November 2005 to October 2006. The ovaries are paired, saculiform organs, which are coated with tunica albuginea and contain ovigerous lamellae, where the oocytes develop before being released into the ovarian lumen and following the ovarian duct until reaching the genital papilla. Oogenesis was divided into stages based on the alterations to the nucleus, ooplasm and surrounding follicular layers. Oogonia form groups from the germinal epithelium have asynchronous development and differentiate into initial perinucleolar oocytes. The formation of the zona pellucida is initiated in the advanced perinucleolar oocytes reaching a thickness of 1.46 ± 0.58 μm in the vitellogenic oocytes. The follicular cells are squamous in perinucleolar oocytes, become cubical in the pre‐vitellogenic oocytes and prismatic in the vitellogenic oocytes with a height of 11.20 ± 4.74 μm. The histochemical reactions indicate that zona pellucida, cortical alveoli and yolk globules contain neutral glycoproteins and the follicular cells contain neutral glycoproteins in association with carboxylated and sulphated glycoconjugates. Statistical analyses showed significant differences in the diameter of the oocytes and follicular cells height as oocytes matured. This study represents the first data about the ovarian structure and oogenesis of this species.
How not to miss autoinflammatory diseases masquerading as urticaria
Authors: Krause K. , Grattan C. E. , Bindslev‐Jensen C. , Gattorno M. , Kallinich T. , de Koning H. D. , Lachmann H. J. , Lipsker D. , Navarini A. A. , Simon A. , Traidl‐Hoffmann C. , Maurer M.
Published: September 2012

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash, such as urticarial vasculitis and autoinflammatory disorders. The latter include cryopyrin‐associated periodic syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated by increased interleukin‐1 secretion. Apart from the urticarial rash, patients are suffering from a variety of systemic symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long‐term complications such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss their clinical picture and management.
The experience of mothers caring for a child with a brain tumour
Authors: Shortman R. I. , Beringer A. , Penn A. , Malson H. , Lowis S. P. , Sharples P. M.
Published: September 2012

Background

Brain tumours are the second most common form of childhood cancer, accounting for over 20% of all cases in European children. Understanding the impact of diagnosis and treatment of a brain tumour on the family is an essential pre‐requisite to identifying ways to provide effective support.

Aim

(1) To explore the impact of having a child with a brain tumour on the main caregiver in the family; (2) to describe mothers' experiences of coping with their child's illness, including personal barriers and strengths; and (3) to identify causes of stress and sources of support to inform improvements in care delivery.

Method

Participants were drawn from a group of caregivers enrolled in a longitudinal study of outcome following diagnosis of a childhood brain tumour. Six caregivers took part, two from each of the high‐, medium‐ and low‐impact groups based on their Impact on Families Scale scores. Semi‐structured interviews were used, with questions covering: (1) impact of the diagnosis on main caregiver and family; (2) personal barriers and strengths; and (3) causes of stress and sources of support. Interviews were transcribed verbatim and coded manually into five themes, which comprised 19 subthemes.

Findings

Coping methods and provision of help and support were major preoccupations for main caregivers from all impact groups. Caregivers in the high‐impact group reported less conflict. High‐ and medium‐impact group caregivers had experienced less ‘hindrance and heartache’, than those with low impact scores, suggesting that the stress associated with diagnosis and treatment of the tumour may have increased cohesion and acceptance within these families.

Conclusion

Families of children diagnosed with a brain tumour experience considerable negative impact and may perceive themselves as struggling to cope. Provision of help and support, within and outside the extended family, including from health, education and other services, is perceived as helpful.
Neuroprotective Effects of Flax Lignan Against NMDA‐Induced Neurotoxicity In Vitro
Authors: Li Xu‐Bo , Yang Zhao‐Xu , Yang Le , Chen Xiao‐Li , Zhang Kun , Yang Qi , Wu Yu‐Mei , Liu Shui‐Bing , Tao Kai‐Shan , Zhao Ming‐Gao
Published: September 2012

Aims

Flax Lignan (FLL), a chemical widespread within the plant and animal kingdoms, has antioxidant, antiinfectious, and antitumor activities. However, little is known about the effects of FLL on the central nervous system (CNS).

Methods

The neuroprotective actions of FLL against N‐methyl‐d‐aspartate (NMDA) are investigated in primary cultured cortical neurons by MTT assay. The expression levels of proteins related to apoptosis and GluN2‐containing receptor were detected by Western blot analysis. Intracellular Ca2+ was measured under a confocal laser scanning microscope.

Results

After challenged with 100 μM NMDA for 30 min, loss of cell viability and excessive apoptotic cell death were observed in cultured cortical neurons. FLL protected the neurons against the NMDA‐induced cell loss in a concentration‐dependent manner. FLL also significantly inhibited the neuronal apoptosis induced by NMDA exposure through reversing intracellular concentration of Ca2+ overload and balancing of Bcl‐2 and Bax expression. Furthermore, FLL significantly reversed the upregulation of GluN2B‐containing NMDA receptors by exposure to NMDA, but did not affect the expression of GluN2A‐containing NMDA receptor.

Conclusions

These findings suggest that FLL protects cortical neurons by inhibiting the expression of GluN2B‐containing NMDA receptor and regulating the Bcl‐2 family.
Closure of defunctioning loop ileostomy is associated with considerable morbidity
Authors: Sharma A. , Deeb A.‐P. , Rickles A. S. , Iannuzzi J. C. , Monson J. R. T. , Fleming F. J.
Published: September 2012

Aim  An elective defunctioning ileostomy is commonly employed to attenuate the morbidity that may arise from distal anastomotic leakage. The magnitude of risk associated with subsequent ileostomy closure is difficult to estimate as many of the data arise from small series. This study looked at the rate of complications and predictive factors in a large series of patients.

Methods  The National Surgical Quality Improvement Program database was queried for patients who had an elective closure of ileostomy between 2005 and 2010. Patient demographics, preoperative risk factors and operative variables were recorded. The primary outcome was occurrence of major (mortality, sepsis, return to the operating room, renal failure, major cardiac, neurological or respiratory episode) or minor (wound infection, urinary tract infection) complications within 30 days. Univariate and multivariate regression was used to evaluate the effect of these clinical factors on the complication rate.

Results  In total, 5401 patients underwent closure of ileostomy, of whom 502 (9.3%) patients had major complications. The incidence of minor complications was 8.4% (452 patients). There were 32 (0.6%) deaths. American Society of Anesthesiologists grade, functional status, prolonged operative time, history of chronic obstructive pulmonary disease, dialysis and disseminated cancer were independent predictors of major complications. There was no significant increase in complication rates in patients over the age of 80. Major complications were associated with a significant increase in postoperative stay (13.9 vs 4.7 days, P < 0.0001).

Conclusion  Closure of ileostomy is associated with a significant complication rate. It may use as many resources as the primary surgery and is not a minor follow‐up operation.
The source of autumn and spring downstream migrating juvenile Atlantic salmon in a small lowland river
Authors: Ibbotson Anton T. , Riley William D. , Beaumont William R.C. , Cook Alastair C. , Ives Mark J. , Pinder Adrian C. , Scott Luke J.
Published: September 2012

Over 3 years, 32,444 age‐0 group Atlantic salmon (Salmo salar) parr tagged with passive integrated transponder tags throughout the River Frome catchment were assigned to one of three groups, nonmigrants, autumn migrants and spring smolts, depending on the detection and the timing of detection at downstream tag readers (situated 8.6 km above the tidal limit). We examined the effect of density at the time of tagging (n·m−2), distance upstream from the tidal limit (km), fish length (mm), Fulton condition index, habitat type (divided into two types, main river and carrier), days after 1 September that each fish was tagged and year (replication) on the proportions of fish in each of the migration groups. Distance upstream from tidal limit was strongly negatively related to the proportion of autumn migrants and positively related to the proportion of spring smolts. Nonmigrants had a lower average body size than migrants, although there were no differences in the sizes of autumn migrants and spring smolts in September prior to migration. Fish density had no effect on migration strategy. A lower proportion of fish migrated as autumn migrants from the smaller carrier habitats than the main river channel. There is some evidence that those parr destined to become autumn migrants underwent a lower mortality rate during September before tagging than those destined to become spring migrants indicating possible physiological or behavioural differences between these two groups of fish at that time. More research into the factors responsible for initiating the autumn migration is required.
Does the use of a visualised decision board by undergraduate students during shared decision‐making enhance patients' knowledge and satisfaction? – A randomised controlled trial
Authors: Kupke J. , Wicht M. J. , Stützer H. , Derman S. H. M. , Lichtenstein N. V. , Noack M. J.
Published: September 2012

Objectives

Aim of this RCT was to evaluate whether the added use of a decision board (DB) during shared decision‐making improves patients' knowledge as for different treatment options and overall satisfaction with the consultation.

Methods

Forty‐nine undergraduate students were trained in shared decision‐making (SDM) and evaluated by an Objective Structured Clinical Examination (OSCE). According to their test results, all participants were randomly allocated to either the test‐ (DB) or the control‐group (Non‐DB). Both groups performed SDM with patients showing a defect in a posterior tooth (Class‐II defect). Prior to the interview, patients of the DB group were given the decision aid for review. In the Non‐DB group, patients were consulted without additional aids. After treatment decision, a questionnaire was completed by all patients to measure knowledge (costs, survival rate, characteristics and treatment time) and overall satisfaction with the consultation. Fifty DB patients and 31 Non‐DB patients completed the questionnaire.

Results

DB patients (n = 50) demonstrated a statistically significant increase in knowledge compared to the Non‐DB group (n = 31) (Mann–Whitney U‐test; DB group = 10.04; Non‐DB group = 4.16; P = 0.004). There was no significant difference between groups regarding satisfaction with the consultation (t‐test; P > 0.05).

Conclusions

During the shared decision‐making process, the use of a decision board yielding information about Class‐II treatment options leads to a significantly higher patient knowledge compared to knowledge gained through consultation alone. It is therefore desirable to provide DBs for dental diagnoses with several treatment options to increase transparency for the patient.
Differentiated hamster sebocytes exhibit apoptosis‐resistant phenotype by the augmentation of intracellular calcium level in vitro
Authors: Kurihara Hirokazu , Sato Takashi , Akimoto Noriko , Ito Akira
Published: September 2012

Sebaceous glands play important roles in the maintenance of the skin barrier function by secreting sebum onto the skin surface. In our study, we demonstrated that differentiated hamster sebocytes (DHS) exhibited apoptosis resistance and the loss of Ca2+ influx against a calcium ionophore, A23187 treatment, which induced both apoptosis and Ca2+ influx in undifferentiated hamster sebocytes (unDHS). The Fluo‐3‐related signal of intracellular Ca2+ in the DHS was higher than that in unDHS and was sustained even though there was a depletion of Ca2+ from the culture medium. Furthermore, the intracellular Ca2+ chelator, BAPTA‐AM, was found to decrease the Ca2+ signal in the DHS, which induced apoptosis. Thus, these results provide novel evidence that the cell differentiation‐dependent increase in store‐operated Ca2+ release is associated with apoptosis resistance in the DHS. Moreover, these findings should accelerate the understanding of the mechanisms of sebogenesis and/or sebum production and secretion under physiological conditions.
Orthopaedic co‐morbidities in the elderly haemophilia population: a review
Authors: Stephensen D. , Rodriguez‐Merchan E. C.
Published: September 2012

Due to improvements in the treatment and medical care of haemophilia, the life expectancy of individuals with haemophilia has approached that of the general population. To review the main co‐morbidities of the musculoskeletal system in elderly persons with haemophilia, we have performed a review of the literature on the musculoskeletal problems of elderly haemophiliacs. Chronic arthropathy is the main co‐morbidity in the ageing person with haemophilia. Age‐related orthopaedic co‐morbidities include degenerative joint changes, osteoporosis, muscle atrophy or sarcopenia, muscle weakness and disturbance of gait and balance. Increased pain, muscle weakness and atrophy along with an increased risk of falling are key features of advanced haemophilic arthropathy and ageing. An ageing haemophilia population in which arthropathy continues to be the primary co‐morbidity is a current challenge for those responsible for their care. Exercise programmes undertaken two to three times per week for at least 12 weeks seem most effective in reducing the impact of age‐related changes on the musculoskeletal system. Establishing effective exercise programmes and strategies to identify individuals who would benefit from early surgical intervention together with presurgical physiotherapy prehabilitation is a priority for future research.
Physical and mechanical properties of twisted or ground nickel–titanium instruments
Authors: Braga L. C. , Magalhães R. R. S. , Nakagawa R. K. L. , Puente C. G. , Buono V. T. L. , Bahia M. G. A.
Published: September 2012

Aim

To compare the flexibility, torsional resistance and structural and dimensional characteristics of instruments produced by twisting with those of a geometrically similar nickel–titanium (NiTi) system produced by a grinding process.

Methodology

The mean diameters along the flute and the pitch length of size 25, .04 taper, size 25, .06 taper, and size 25, .08 taper Twisted File (TF) (SybronEndo, Orange, CA, USA), and size 25, .04 taper, and size 25, .06 taper RaCe instruments (FKG, La Chaux‐de‐Fonds, Switzerland) (n = 10 each) were measured according to ANSI/ADA specification No. 101. Two pairs of instruments were found to have similar diameters at 3 mm from the tip: TF size 25, .06 taper and RaCe size 25, .04 taper, and TF size 25, .08 taper and RaCe size 25, .06 taper. The cross‐sectional areas at 3 mm from the tip were determined. These instruments were then submitted to energy‐dispersive X‐ray spectroscopy, X‐ray diffraction, differential scanning calorimetry (DSC), and Vickers microhardness measurements. Bending moment at 45° and maximum torque at fracture were measured (n = 10) according to specification ISO 3630‐1. Data were analysed using analysis of variance (α = 0.05).

Results

The two types of instruments had approximately the same chemical composition, phase constitution, and austenite finishing temperatures. TF instruments had significantly (P ≤ 0.001) lower Vickers microhardness values and were more flexible than RaCe instruments (P = 0.016), but had similar (TF size 25, .08 taper and RaCe size 25, .06 taper, P = 0.916) or significantly higher (TF size 25, .06 taper and RaCe size 25, .04 taper, P ≤ 0.001) torsional resistance.

Conclusions

Comparison of TF and RaCe instruments of similar measured dimensions revealed that the different manufacturing methods employed for producing these instruments gave rise to different mechanical behaviours.
Development and characterization of 11 novel microsatellite loci for the roundscale spearfish Tetrapturus georgii and their cross‐species amplification among other istiophorid species
Authors: Bernard A. M. , Feldheim K. A. , Shivji M. S.
Published: September 2012

Eleven novel polymorphic microsatellite loci were developed and characterized for the recently validated roundscale spearfish Tetrapturus georgii. Characterization of these markers, based on 35 roundscale spearfish from the western North Atlantic, revealed two to 21 alleles per locus with an average expected heterozygosity (HE) of 0·09–0·94, and all loci conformed to Hardy–Weinberg expectations. Cross‐amplification of these 11 loci against all other eight known istiophorid species indicates promising prospects for the utility of these markers for istiophorids in general.
South African Auditors Blowing the Whistle without Protection: A Challenge for Trust and Legitimacy
Authors: Maroun Warren , Gowar Christin
Published: September 2012

South Africa is one of the few countries in the world where auditors of financial statements are required to whistle‐blow on transgressions of a client. This statutory duty places the auditor in a dilemma. On the one hand, a failure to blow the whistle is a criminal offence. On the other hand, compliance with the legislation, in good faith, does not automatically afford the auditor protection against civil claims. Under the lens of legitimacy theory, external regulation has an important role to play in legitimising accounting and auditing systems but, in order for legislation to effect meaningful change, it is paramount that it be accepted as legitimate and worthy of trust in its own right. In this context, the need for improved levels of protection against civil liability for auditors has received increased attention in the United Kingdom and the United States. Here, auditors are already afforded some protection against civil claims in connection with more limited duties to whistle‐blow. Despite the increasing acceptance of the idea that such protection is instrumental in improving the effectiveness of the audit industry, this study shows that South Africa lags behind its international counterparts in this regard. As a result, the essence of the South African auditor's whistle‐blowing duties as an instrument of legitimisation is questionable.
Racial differences in the relationship between tobacco dependence and nicotine and carcinogen exposure
Authors: St.Helen Gideon , Dempsey Delia , Wilson Margaret , Jacob Peyton , Benowitz Neal L.
Published: September 2012

Aims

To investigate the relationships between tobacco dependence, biomarkers of nicotine and carcinogen exposure and biomarkers of nicotine and carcinogen exposure per cigarette in back and white smokers.

Design, setting and participants

A total of 204 healthy black (n = 69) and white (n = 135) smokers were enrolled into two clinical studies.

Measurement

Nicotine equivalents (nicotine and its metabolites), 4‐(methylnitrosamino)‐1‐(3)pyridyl‐1‐butanol (NNAL) and polycyclic aromatic hydrocarbon (PAH) metabolites were measured in urine. The Fagerström Test for Nicotine Dependence (FTND) and time to first cigarette (TFC) measured tobacco dependence.

Findings

Average TFC and FTND for blacks and whites were not significantly different. Urine NNAL and nicotine equivalents increased with increasing FTND in whites but did not increase in blacks (race × FTND interaction, both P < 0.031). The interaction term was not significant for PAHs. An inverse relationship was seen between FTND and nicotine equivalents, NNAL and PAH metabolites per cigarette in blacks but remained flat in whites (race × FTND interaction, all P ≤ 0.039). Regardless of dependence (low dependence, TFC >15 minutes; high dependence, TFC ≤15 minutes), FTND and TFC were not correlated significantly with urine nicotine equivalents and carcinogen exposure in blacks. We found moderate correlations between FTND and TFC and nicotine equivalents and carcinogen exposure among whites of low dependence and non‐significant correlations among whites of high dependence.

Conclusion

In the United States, tobacco dependence measures were related linearly to nicotine intake and carcinogen exposure in white but not in black smokers. The relationship between dependence measures and tobacco biomarkers in black smokers regardless of level of dependence resembled highly dependent white smokers.
Half‐life prolongation of therapeutic proteins by conjugation to ATIII‐binding pentasaccharides: a first‐in‐human study of CarboCarrier® insulin
Authors: Miltenburg André M. M. , Prohn Marita , van Kuijk Jacqueline H. M. , Tiessen Renger G. , de Kort Martin , Berg Rob J. W.
Published: September 2012

Aim

Conjugation to antithrombin III ATIII‐binding pentasaccharides has been proposed as a novel method to extend the half‐life of therapeutic proteins. We aim to validate this technological concept in man by performing a first‐in‐human study using CarboCarrier® insulin (SCH 900948) as an example. A rising single dose phase 1 study was performed assessing safety, tolerability, pharmacokinetics and relative bioactivity of CarboCarrier® insulin. Safety, tolerability and pharmacokinetics (PK) of single doses of CarboCarrier® insulin in healthy volunteers were explored, and the dose–response relationship and relative bioactivity of CarboCarrier® insulin in subjects with type 2 diabetes were investigated.

Methods

After an overnight fast, subjects were randomized to a treatment sequence. PK and pharmacodynamic (glucose, insulin and C‐peptide) samples were obtained for up to 72 h post‐dose. Effects of CarboCarrier® insulin were compared with those of NPH‐insulin.

Results

CarboCarrier® insulin was safe and well‐tolerated and no consistent pattern of adverse events occurred. CarboCarrier® insulin exposure (Cmax and AUC) increased proportionally with dose. The mean terminal elimination half‐life ranged between 3.11 and 5.28 h. All CarboCarrier® insulin dose groups showed decreases in the mean change from baseline of plasma glucose concentrations compared with the placebo group.

Conclusions

CarboCarrier® insulin is pharmacologically active showing features of insulin action in man. The elimination half‐life of the molecule was clearly extended compared with endogenous insulin, indicating that conjugation to ATIII‐binding pentasaccharides is a viable approach to extend the half‐life of therapeutic proteins in humans. This is an important step towards validation of the CarboCarrier® technology by making use of CarboCarrier® insulin as an example.
A methodology for characterization and analysis of plant functional composition in grassland‐based farms
Authors: Duru M. , Hossard L. , Martin G. , Theau J. P.
Published: September 2012

Understanding the relationships between farmers' land‐use and management decisions, and plant diversity is a challenge. It requires characterization of plant diversity within and between fields and investigation of land‐use allocation to fields. To analyse how grassland functional composition [mean plant trait and functional diversity index (FD)] varies according to scale (field, land‐use type: cutting, grazing, farm), grasslands were characterized according to leaf dry‐matter content (leaf DM) and FD computed from leaf DM values. A leaf DM‐αFD framework was used to analyse how leaf DM‐based plant strategies were distributed at land‐use type and farm scales (βFD). The study was conducted on eight dairy and beef farms (169 grasslands) differing in their stocking rate. At field and land‐use type scales, leaf DM was significantly decreased and increased with N fertilizer rate and field elevation respectively. It was significantly higher for grazing than for cutting. At the farm scale, the main differences between farms resulted from differences in plant strategy distribution between land‐use types within a farm and among farms for a given land‐use type in relation to management intensity. Farms that contributed the most to αFD had the highest stocking rate, and those which had the most contrasting grasslands for management intensity had the highest βFD. Management practices need to be examined at a land‐use type scale for evaluating the within‐ and between‐field plant functional compositions. By contrast, the value of the analysis was reduced if data were collected and averaged at the farm scale.
Hepatoprotective effect of Bathysa cuspidata in a murine model of severe toxic liver injury
Authors: Gonçalves Reggiani V. , Novaes Rômulo D. , Leite João P. V. , Vilela Emerson F. , Cupertino Marli C. , Nunes Líria G. , Matta Sérgio L. P.
Published: September 2012

The objective of this study was to investigate the hepatoprotective effect of a bark extract of Bathysa cuspidata extract (BCE) in a murine model of severe liver injury induced by carbon tetrachloride (CCl4). Forty‐two Wistar rats were randomized into six groups of seven animals each: Group 1(G1): CCl4; Group 2 (G2): dimethyl sulfoxide (DMSO) + CCl4; Group 3 (G3): BCE 400 mg/kg alone; Group 4 (G4): BCE 200 mg/kg + CCl4; Group 5 (G5): BCE 400 mg/kg + CCl4; Group 6 (G6): DMSO alone. The extract was administered by gavage for 18 days beginning 6 days prior to the first application of CCl4. After completing CCl4 administration, the animals were euthanized. The animals in G1, G2, G4 and G5 experienced significant body weight loss and had an increased liver somatic index compared with G3 and G6 (P < 0.05). A significant reduction in serum aspartate and alanine transaminase and gamma‐glutamyl transferase (P < 0.05) and a significant increase in the activity of the anti‐oxidant enzyme superoxide dismutase were found in G5 (P < 0.05). Lower proportions of cellular necrosis and lipid droplets were found in the livers of animals in G4 and G5 compared with G1 and G2 (P < 0.05). These results confirm the marked hepatoprotective activity of the bark extract of Bathysa cuspidata in severe injuries induced by CCl4 in rats and suggest that this effect may be associated with the inhibition of oxidative damage.
Spatial analysis of ectomycorrhizal fungi reveals that root tip communities are structured by competitive interactions
Authors: Pickles Brian J. , Genney David R. , Anderson Ian C. , Alexander Ian J.
Published: September 2012

Microbial ecology has made large advances over the last decade, mostly because of improvements in molecular analysis techniques that have enabled the detection and identification of progressively larger numbers of microbial species. However, determining the ecological patterns and processes taking place in communities of microbes remains a significant challenge. Are communities randomly assembled through dispersal and priority effects, or do species interact with each other leading to positive and negative associations? For mycorrhizal fungi, evidence is accumulating that stochastic and competitive interactions between species may both have a role in shaping community structure. Could the methodological approach, which is often incidence based, impact the outcomes detected? Here, we applied an incidence‐basedTerminalRestrictionFragmentLengthPolymorphism (T‐RFLP) database approach to examine species diversity and ecological interactions within a community of ectomycorrhizal (ECM) fungi. Co‐occurrence analysis revealed that theECMcommunity colonizing root tips was strongly structured by competitive interactions, or ecological processes generating a similar spatial pattern, rather than neutral processes. Analysis of β‐diversity indicated that community structure was significantly more similar (spatially autocorrelated) at distances equal to or <3.41 m. The eight most frequently encountered species in the root tip community ofECMfungi displayed significant competitive interactions with at least one other species, showing that the incidence‐based approach was capable of detecting this sort of ecological information.
Prevalence of childhood and adolescent overweight and obesity in Benue State, Nigeria
Authors: Musa Danladi I. , Toriola Abel L. , Monyeki Makama A. , Lawal Badamasi
Published: September 2012

Objective  To evaluate demographic variation in the prevalence of overweight (OW) and obesity (OB) among 3240 children and adolescents (girls: n = 1714; boys: n = 1526) aged 9–16 years attending primary and secondary schools in Benue State of Nigeria.

Methods  Participants’ anthropometric characteristics (body weight, stature, body mass index: BMI and lean body mass: LBM) were determined using standard protocols. OW and OB were estimated using International Obesity task Force diagnostic criteria. Data were analysed with one‐way anova and binary logistic regression method.

Results  Overall, 88.5%, 9.7% and 1.8% of the adolescents had normal BMI and were OW and obese, respectively. Prevalence of OW was higher among girls (20.3%) than boys (16.2%), whereas a relatively higher incidence of OB was noted among the boys (3.5%). Girls in urban areas had a significantly higher BMI (t524 = 3.61, P = 0.002) than their rural peers, but the rural girls were more significantly OW than their urban counterparts (BMI: t1186 = 2.506). Logistic regression models assessing the influence of age, gender and location on OW/OB in children (α2(3, N = 1014) = 6.185, P = 0.103) and adolescents (α2(3, N = 2226) = 1.435, P = 0.697) did not turn up significant results. In the gender‐specific analysis, the younger boys’ model was also not significant (α2(2, N = 488) = 1.295, P = 0.523) in contrast to the girls’ (α2(2, N = 526) = 15.637, P = 0.0005), thus discriminating between OW and healthy weight among the children. Overall, the model explained 2.9–4.4% of the variance in weight status and correctly classified 76.8% of the cases. Age wise, the model yielded a significant odds ratio of 1.49, suggesting that the likelihood of being OW increases by a factor of 1.5 with a unit increase in age. Also, the likelihood of an urban girl becoming OW or obese was 0.57 times that of a rural girl.

Conclusions  In general, girls in urban areas had higher prevalence of OW and OB than girls in rural settings. Among the boys, similar but less marked trends were found, except that the rural boys tended to be more OW on average than their peers in urban areas. In view of its public health significance, it is important to periodically evaluate the prevalence of weight disorders in children and adolescents so that appropriate preventative strategies can be instituted.
Reduced expression of α‐synuclein in alcoholic brain: influence of SNCA‐Rep1 genotype
Authors: Janeczek Paulina , MacKay Rachel K. , Lea Rodney A. , Dodd Peter R. , Lewohl Joanne M.
Published: September 2012

α‐Synuclein has recently been implicated in the pathophysiology of alcohol abuse due to its role in dopaminergic neurotransmission. In these studies, genetic variability in the α‐synuclein gene influences its expression which may contribute to susceptibility to chronic alcohol abuse. Real‐time PCR was used to quantify α‐synuclein mRNA expression in autopsy samples of human dorsolateral prefrontal cortex. Because of the association between length of the α‐synuclein‐repeat 1 microsatellite marker and expression levels of the gene, this marker was genotyped in a Caucasian sample of 126 controls and 117 alcoholics using capillary gel electrophoresis. The allele and genotype frequencies of α‐synuclein‐repeat 1 marker differed significantly between alcoholics and controls. Alcoholics had greater frequencies of the shortest allele found (267 bp). The shortest allele of the α‐synuclein‐repeat 1 marker was associated with decreased expression of α‐synuclein in prefrontal cortex. Individuals with at least one copy of the 267 bp allele were more likely to exhibit an alcohol abuse phenotype. These results suggest that individuals with the 267 bp allele may be at increased risk of developing alcoholism and that genetic variation at the α‐synuclein‐repeat 1 locus may influence α‐synuclein expression in the prefrontal cortex.
Renal grafts from anti‐hepatitis B core‐positive donors: a quantitative review of the literature
Authors: Mahboobi N. , Tabatabaei S.V. , Blum H.E. , Alavian S.M.
Published: September 2012

Backgrounds and aims

Organ shortage is a major problem in transplantation. The use of organs from hepatitis B surface antigen (HBsAg)‐negative and hepatitis B core antibody (HBcAb)‐positive donors could significantly increase the donor pool. However, little information is available about the impact of HBcAb status of renal donors on viral transmission to recipients. To address this issue, the present quantitative review of relevant studies has been performed.

Materials and methods

Electronic databases including Medline, EMBASE, ISI, and Scopus were systematically searched for studies that evaluated risk of hepatitis B virus (HBV) transmission through renal transplantation from HBsAg‐/HBcAb+ donors. Eligible studies were identified according to predefined criteria. The final outcome was one of HBV markers seroconversion defined as HBsAg, hepatitis B surface antibody (HBsAb), or HBcAb detection in previously seronegative end‐stage renal disease (ESRD) patients after transplantation, and without other identified major sources of infection.

Results

Nine studies with 1385 eligible kidney recipients were included. In total, 45 subjects showed seroconversion of HBV markers as follows: HBsAg (n = 4) (0.28%; 95% confidence interval [CI] 0.006; 0.57), HBcAb (n = 32), HBsAb (n = 5), and either HBcAb or HBsAb (n = 4). The total rate of seroconversion after renal transplantation was calculated to be 3.24% (95% CI: 2.31–4.18).

Conclusion

Our review indicates that the risk of HBV transmission from HBcAb‐positive kidney donors is extremely low. Therefore, kidneys from these donors can be transplanted safely into ESRD patients.
Anti‐gal antibodies in α1,3‐galactosyltransferase gene‐knockout pigs
Authors: Fang Jason , Walters Anneke , Hara Hidetaka , Long Cassandra , Yeh Peter , Ayares David , Cooper David K. C. , Bianchi John
Published: September 2012

Fang J, Walters A, Hara H, Long C, Yeh P, Ayares D, Cooper DKC, Bianchi J. Anti‐gal antibodies in α1,3‐galactosyltransferase gene‐knockout pigs. Xenotransplantation 2012; 19: 305–310. © 2012 John Wiley & Sons A/S.

Abstract  Serum anti‐galactose‐α1,3‐galactose (Gal) IgM and IgG antibody levels were measured by ELISA in α1,3‐galactosyltransferase gene‐knockout (GTKO) pigs (78 estimations in 47 pigs). A low level of anti‐Gal IgM was present soon after birth, and rose to a peak at 4–6 m, which was maintained thereafter even in the oldest pigs tested (at >2 yr). Anti‐Gal IgG was also present at birth, peaked at 3 m, and after 6 m steadily decreased until almost undetectable at 20 m. No differences in this pattern were seen between pigs of different gender. Total IgM followed a similar pattern as anti‐Gal IgM, but total IgG did not decrease after 6m. The data provide useful baseline data for future experimental studies in GTKO pigs, e.g., relating to the antibody response to WT pig allografts.
Postoperative phosphodiesterase type 5 inhibitor administration increases the rate of urinary continence recovery after bilateral nerve‐sparing radical prostatectomy
Authors: Gandaglia Giorgio , Albersen Maarten , Suardi Nazareno , Gallina Andrea , Abdollah Firas , Castiglione Fabio , Capitanio Umberto , Salonia Andrea , Rigatti Patrizio , Hedlund Petter , Montorsi Francesco , Briganti Alberto
Published: September 2012

Objectives

To investigate the effect of phosphodiesterase type 5 inhibitor on urinary continence recovery after bilateral nerve‐sparing radical prostatectomy.

Methods

We analyzed data of 393 open bilateral nerve‐sparing radical prostatectomies carried out between 2005 and 2010. Patients who recovered urinary continence within the first month after catheter removal (n = 52) were excluded. This resulted in 341 evaluable patients. Urinary continence recovery was defined as being completely pad free over a period of 24 h. Patients were stratified according to postoperative daily (n = 58; 17%), on‐demand (n = 112; 32.8%) and no (n = 171; 50.1%) phosphodiesterase type 5 inhibitor use. The effect of phosphodiesterase type 5 inhibitor use on urinary continence was assessed using the Kaplan–Meier method. Uni‐ and multivariable Cox regression analyses were used to test the association between phosphodiesterase type 5 inhibitor and urinary continence recovery after adjusting for cofounders.

Results

At a mean follow up of 36.4 months after surgery (median: 33), 288 patients (84.5%) recovered urinary continence after bilateral nerve‐sparing radical prostatectomy. Patients who did not use phosphodiesterase type 5 inhibitor after surgery had lower rates of urinary continence recovery at 1‐ and 2‐year follow up as compared with patients taking phosphodiesterase type 5 inhibitor (67.1 vs 86.7% and 76 vs 94.4%, respectively; P < 0.001). After adjusting for all confounders, multivariable analysis showed that phosphodiesterase type 5 inhibitor use, either on demand or daily, had a positive impact on urinary continence recovery (P = 0.03).

Conclusions

Patients taking phosphodiesterase type 5 inhibitor have higher urinary continence recovery rates as compared with patients left untreated after bilateral nerve‐sparing radical prostatectomy. An improvement in sphincteric and pelvic floor blood supply might be responsible for this beneficial effect associated with the use of phosphodiesterase type 5 inhibitor.
The genome of the ammonia‐oxidizing CandidatusNitrososphaera gargensis: insights into metabolic versatility and environmental adaptations
Authors: Spang Anja , Poehlein Anja , Offre Pierre , Zumbrägel Sabine , Haider Susanne , Rychlik Nicolas , Nowka Boris , Schmeisser Christel , Lebedeva Elena V. , Rattei Thomas , Böhm Christoph , Schmid Markus , Galushko Alexander , Hatzenpichler Roland , Weinmaier Thomas , Daniel Rolf , Schleper Christa , Spieck Eva , Streit Wolfgang , Wagner Michael
Published: September 2012

The cohort of the ammonia‐oxidizing archaea (AOA) of the phylum Thaumarchaeota is a diverse, widespread and functionally important group of microorganisms in many ecosystems. However, our understanding of their biology is still very rudimentary in part because all available genome sequences of this phylum are from members of the Nitrosopumilus cluster. Here we report on the complete genome sequence of Candidatus Nitrososphaera gargensis obtained from an enrichment culture, representing a different evolutionary lineage of AOA frequently found in high numbers in many terrestrial environments. With its 2.83 Mb the genome is much larger than that of other AOA. The presence of a high number of (active) IS elements/transposases, genomic islands, gene duplications and a complete CRISPR/Cas defence system testifies to its dynamic evolution consistent with low degree of synteny with other thaumarchaeal genomes. As expected, the repertoire of conserved enzymes proposed to be required for archaeal ammonia oxidation is encoded by N. gargensis, but it can also use urea and possibly cyanate as alternative ammonia sources. Furthermore, its carbon metabolism is more flexible at the central pyruvate switch point, encompasses the ability to take up small organic compounds and might even include an oxidative pentose phosphate pathway. Furthermore, we show that thaumarchaeota produce cofactor F420 as well as polyhydroxyalkanoates. Lateral gene transfer from bacteria and euryarchaeota has contributed to the metabolic versatility of N. gargensis. This organisms is well adapted to its niche in a heavy metal‐containing thermal spring by encoding a multitude of heavy metal resistance genes, chaperones and mannosylglycerate as compatible solute and has the genetic ability to respond to environmental changes by signal transduction via a large number of two‐component systems, by chemotaxis and flagella‐mediated motility and possibly even by gas vacuole formation. These findings extend our understanding of thaumarchaeal evolution and physiology and offer many testable hypotheses for future experimental research on these nitrifiers.