bluuebunny/crossref_metadata_2025 huggingface dataset:
BLM–DNA2–RPA–MRN and EXO1–BLM–RPA–MRN constitute two DNA end resection machineries for human DNA break repair
Authors: Nimonkar Amitabh V. , Genschel Jochen , Kinoshita Eri , Polaczek Piotr , Campbell Judith L. , Wyman Claire , Modrich Paul , Kowalczykowski Stephen C.
Published: February 2011

Repair of dsDNA breaks requires processing to produce 3′-terminated ssDNA. We biochemically reconstituted DNA end resection using purified human proteins: Bloom helicase (BLM); DNA2 helicase/nuclease; Exonuclease 1 (EXO1); the complex comprising MRE11, RAD50, and NBS1 (MRN); and Replication protein A (RPA). Resection occurs via two routes. In one, BLM and DNA2 physically and specifically interact to resect DNA in a process that is ATP-dependent and requires BLM helicase and DNA2 nuclease functions. RPA is essential for both DNA unwinding by BLM and enforcing 5′ → 3′ resection polarity by DNA2. MRN accelerates processing by recruiting BLM to the end. In the other, EXO1 resects the DNA and is stimulated by BLM, MRN, and RPA. BLM increases the affinity of EXO1 for ends, and MRN recruits and enhances the processivity of EXO1. Our results establish two of the core machineries that initiate recombinational DNA repair in human cells.
The ERGonomics of hematopoietic stem cell self-renewal: Figure 1.
Authors: Lacadie Scott A. , Zon Leonard I.
Published: February 2011

Stem cells make more of themselves by self-renewing cell divisions. In the February 1, 2011, issue of Genes & Development, Taoudi and colleagues (pp. 251–262) show an essential role for the ETS transcription factor ERG in the self-renewal of embryonic hematopoietic stem cells. A model is presented in which the redundant functions of GATA2 and RUNX1 in self-renewal are under direct control of ERG.
Environmental factors in drinking venues and alcohol‐related harm: the evidence base for European intervention
Authors: Hughes Karen , Quigg Zara , Eckley Lindsay , Bellis Mark , Jones Lisa , Calafat Amador , Kosir Matej , van Hasselt Ninette
Published: February 2011

Aims  Reducing alcohol‐related harm in young people is a major priority across Europe. Much alcohol use and associated harm in young people occurs in public drinking environments. This review aims to identity environmental factors in drinking establishements that are associated with increased alcohol consumption and associated harm and to understand the extent of study in this area across Europe.

Methods  A systematic literature search identified studies that had explored associations between physical, staffing and social factors in drinking environments and increased alcohol use or alcohol‐related harm.

Results  Fifty‐three papers were identified, covering 34 studies implemented in nine countries. Most studies had been implemented in non‐European countries and many had collected data more than a decade prior to the review. The majority had used observational research techniques. Throughout the studies, a wide range of physical, staffing and social factors had been associated with higher levels of alcohol use and related harm in drinking environments. Factors that appeared particularly important in contributing to alcohol‐related problems included a permissive environment, cheap alcohol availability, poor cleanliness, crowding, loud music, a focus on dancing and poor staff practice. However, findings were not always consistent across studies.

Conclusions  Drinking establishments, their management and the behaviours of the young people who use them vary widely across Europe. While international research shows that environmental factors in drinking settings can have an important influence on alcohol‐related harm, there is currently a scarcity of knowledge on the relevance and impacts of such factors in modern European settings. Developing this knowledge will support the implementation of strategies to create drinking environments in Europe that are less conducive to risky drinking and alcohol‐related harm.
Indicators of alcohol consumption and attributable harm for monitoring and surveillance in European Union countries
Authors: Rehm Jürgen , Scafato Emanuele
Published: February 2011

Aims  Alcohol is a major risk factor for burden of disease and injury in Europe, and contributes markedly to between region differences in life expectancy. Monitoring and surveillance systems have shown to be a key factor in implementing effective policies. The aim of this paper is to propose a system of indicators for alcohol consumption and attributable harm which can be used as an over‐time monitoring tool at the country level as well as for comparisons between countries.

Design  A systematic research in electronic data bases was conducted but most of the information was derived from ongoing international efforts to establish alcohol monitoring and surveillance systems.

Setting  European Union.

Participants  Countries.

Measurements  Exposure to alcohol, mortality, burden of disease.

Findings  Adult per capita alcohol consumption, prevalence of abstention, and frequency of drinking more than 60g pure alcohol in one occasion are proposed as a minimal set of alcohol exposure indicators, which can quickly be implemented in all EU countries. With respect to health harm indicators, the best minimal choice which can be implemented quickly in all countries of the EU would be alcohol‐attributable years of life lost due to premature death. In addition, country specific indicators could be added, when alcohol places specific burden on specific diseases.

Conclusions  National and European Union‐wide monitoring systems for alcohol exposure and attributable harm to inform public health‐related policy decisions could be implemented easily. The establishement of such monitoring systems would follow the recent World Assembly resolution for a global strategy to reduce alcohol‐related harm.
Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals
Authors: Khoo A-L , Chai L Y A , Koenen H J P M , Sweep F C G J , Joosten I , Netea M G , van der Ven A J A M
Published: February 2011

The immune modulating capacity of vitamin D3 is well-recognized. Ultra-violet (UV) exposure determines production of vitamin D3in vivo and varies through the course of the year, especially in temperate regions. However, it is not known whether the human innate immune response differs due to seasonality. To validate the seasonal effects of vitamin D3, the effect of 1,25(OH)2D3 on peripheral blood mononuclear cells (PBMC) cytokine response was first determined in vitro. 1,25(OH)2D3 decreased interleukin (IL)-6 and tumour necrosis factor (TNF)-α release by PBMC stimulated with tripalmitoyl-S-glycerylcysteine (Pam3Cys) or lipopolysaccharide (LPS). Subsequently, ex-vivo stimulation studies were performed in 15 healthy volunteers through the course of the four seasons of the year. PBMC were isolated and stimulated with Toll-like receptor (TLR)-2 and TLR-4 ligands Pam3Cys and LPS, respectively. Circulating concentrations of 25(OH)D3 and 1,25(OH)2D3 were higher during summer (P < 0·05) and a down-regulation of TLR-4-mediated IL-1β, IL-6, TNF-α, interferon (IFN)-γ and IL-10 production in summer was observed compared to winter (P < 0·05). The variation in cytokine response upon TLR-2 (Pam3Cys) stimulation was moderate throughout the four seasons. The repressed cytokine production during the summer months could be explained partly by the reduced cell-membrane expression of TLRs. Physiological variation in vitamin D3 status through the four seasons of the year can lead to alteration in the innate immune responses. Elevated vitamin D3 level in vivo is associated with down-regulation of cytokine response through diminished surface expression of pattern recognition receptors.
Changes in the expression of oestrogen receptors and E‐cadherin as molecular markers of progression from normal epithelium to invasive cancer in elderly patients with vulvar squamous cell carcinoma
Authors: Zannoni Gian F. , Prisco Maria G. , Vellone Valerio G. , De Stefano Ilaria , Scambia Giovanni , Gallo Daniela
Published: February 2011

Zannoni G F, Prisco M G, Vellone V G, De Stefano I, Scambia G & Gallo D (2011) Histopathology58, 265–275 Changes in the expression of oestrogen receptors and E‐cadherin as molecular markers of progression from normal epithelium to invasive cancer in elderly patients with vulvar squamous cell carcinoma

Aims:  The most common vulvar squamous cell carcinoma (conventional SCC) occurs in elderly women and develops following a human papillomavirus (HPV)‐negative pathway. Because the highest incidence of conventional SCC is observed in patients with low oestrogen levels (postmenopausal women), the aim was to investigate whether hormonal factors could play a role in the development of cancer.

Methods and results:  The expression profile of oestrogen receptor α (ERα), ERβ and progesterone receptor (PR) in a section containing both normal and tumour tissue, as well as the SCC‐associated vulvar lesion, was evaluated in 34 elderly patients. Also, as recent studies have identified E‐cadherin as a novel transcriptional target of oestrogen signalling, the modulation of this epithelial–mesenchymal transition (EMT) marker was studied. Finally, the expression of the proliferation marker Ki67 and of the apoptotic marker p53 was assessed. Results showed that changes in both ERα and ERβ expression characterize the transition from normal epithelium to cancer in patients with vulvar SCC: ERα was lost in cancer while ERβ decreased, mainly showing cytoplasmic localization. A reduction in the expression of E‐cadherin was also observed in tumours, compared to normal epithelium.

Conclusions:  The data put the ER signalling pathway into the spotlight as a potentially important factor in vulvar carcinogenesis.
Sox10‐positive sustentacular cells in neuroendocrine carcinoma of the lung
Authors: Tsuta Koji , Raso Maria G , Kalhor Neda , Liu Diane C , Wistuba Ignacio I , Moran Cesar A
Published: February 2011

Tsuta K, Raso M G, Kalhor N, Liu D C, Wistuba I I & Moran C A (2011) Histopathology 58, 276–285 Sox10‐positive sustentacular cells in neuroendocrine carcinoma of the lung

Aims:  Sustentacular cells are found in approximately half of pulmonary carcinoid tumours. However, most studies of sustentacular cells have used the less‐specific antibody to the S100 protein, and any correlation between the presence of sustentacular cells and other clinicopathological factors is unclear. The aim of this study was to analyse the significance of sustentacular cells in pulmonary neuroendocrine carcinomas (NECs).

Methods and results:  A Sox10 antibody was used to investigate 113 pulmonary NECs. Sustentacular cells were observed in 66.7% of typical carcinoid (TC) and 58.3% of atypical carcinoid (AC) cases, but not in high‐grade NECs. Sustentacular‐rich tumours had a statistically significant correlation with peripheral locations. We found no statistical differences in age, gender, smoking history, overall survival, or the occurrence of lymph node metastasis. In all but one case, when sustentacular cells were present in the primary site, they were also present in the metastatic lymph nodes. The presence of sustentacular cells differed in morphological subtypes, with the spindle pattern being the most common subtype.

Conclusions:  Sox10‐positive sustentacular cells were observed in carcinoid tumours but not in high‐grade NECs. Sustentacular‐rich carcinoid tumours did not show a correlation with the occurrence of lymph node metastasis or survival. The sustentacular cells found differed in morphological subtypes.
Distinct histological features characterize primary angiosarcoma of bone
Authors: Verbeke Sofie L J , Bertoni Franco , Bacchini Patrizia , Sciot Raf , Fletcher Christopher D M , Kroon Herman M , Hogendoorn Pancras C W , Bovée Judith V M G
Published: February 2011

Verbeke S L J, Bertoni F, Bacchini P, Sciot R, Fletcher C D M, Kroon H M, Hogendoorn P C W & Bovée J V M G (2011) Histopathology 58, 254–264 Distinct histological features characterize primary angiosarcoma of bone

Aims:  To define the histological criteria of primary angiosarcoma of bone.

Methods and results:  Forty‐two angiosarcomas of bone in 23 males and 15 females were studied. Histological criteria were related to patients’ outcome. Eleven patients had multifocal lesions. Lesions were located in the long and short tubular bones followed by the pelvis, spine and trunk. Tumour cells were positive for CD31 in 38 of 40, von Willebrand Factor in 21 of 35, CD34 in 15 of 38, smooth muscle actin in 22 of 36, D2–40 in 11 of 35 and keratinAE1AE3 in 27 of 39. Thirty‐nine tumours showed an epithelioid phenotype. One‐ and 5‐year survival rates were 55% and 33%, respectively. Survival analysis showed that a macronucleolus, three or more mitoses per 10 high‐power field (HPF) and fewer than five eosinophilic granulocytes per 10 HPF within a tumour was associated with an even worse survival compared to the overall group.

Conclusions:  Because keratin positivity is seen in the majority of cases, pathologists should avoid misinterpretation as metastatic carcinoma. A macronucleolus, three or more mitoses per 10 HPF and fewer than five eosinophilic granulocytes per 10 HPF can be used to further define angiosarcoma of bone.
Increased mucin 1 expression in recurrence and malignant transformation of salivary gland pleomorphic adenoma
Authors: Soares Andresa Borges , Demasi Ana Paula Dias , Altemani Albina , de Araújo Vera Cavalcanti
Published: February 2011

Soares A B, Demasi A P D, Altemani A & de Araújo V C (2011) Histopathology58, 377–382 Increased mucin 1 expression in recurrence and malignant transformation of salivary gland pleomorphic adenoma

Aims:  Pleomorphic adenoma (PA) is the most common salivary gland tumour with a tendency to recur (RPA) and a risk of malignant transformation. Mucin 1 (MUC‐1) plays a role in the progression of many tumours and may be a marker to predict RPA. The aim of this study was to evaluate MUC‐1 expression in different phases of the adenoma to carcinoma sequence.

Methods and results:  Twenty‐one cases of PA, 18 cases of RPA, three cases of RPA with focal transformation (TRPA) and 11 cases of carcinoma ex‐pleomorphic adenoma (CXPA) were analysed immunohistochemically for MUC1 expression using an antibody to MUC1/DF3. MUC1 reactivity in RPA was stronger than that observed in PA and, in all the different carcinoma groups, MUC‐1 expression was significantly higher in carcinoma than in RPA and PA.

Conclusion:  This study has confirmed that MUC‐1 is related to the recurrence of PA and that this molecule is associated with malignant transformation of PA with carcinoma cells overexpressing MUC‐1.
The retinoblastoma protein/p16INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma
Authors: Stankiewicz Elzbieta , Prowse David M , Ktori Elena , Cuzick Jack , Ambroisine Laurence , Zhang Xiaoxi , Kudahetti Sakunthala , Watkin Nicholas , Corbishley Catherine , Berney Daniel M
Published: February 2011

Stankiewicz E, Prowse D M, Ktori E, Cuzick J, Ambroisine L, Zhang X, Kudahetti S, Watkin N, Corbishley C & Berney D M (2011) Histopathology58, 433–439 The retinoblastoma protein/p16INK4Apathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma

Aims:  The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell‐cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell‐cycle proteins: p53, p21, p16INK4A and retinoblastoma (RB) protein.

Methods and results:  One hundred and forty‐eight PSCC samples were examined immunohistochemically for RB, p16INK4A, p53 and p21 protein expression. One hundred and two cases were typed for HPV by PCR. HPV DNA was detected in 56% of tumours, with HPV16 present in 81%. Basaloid tumours were related strongly to HPV infection (10 of 13), while verrucous were not (three of 13). Fifty‐nine per cent (38 of 64) of usual type SCCs had HPV infection. RB protein correlated negatively (P < 0.0001) and p16INK4A (P < 0.0001) and p21 (P = 0.0002) correlated positively with HPV infection. p53 did not correlate with HPV infection.

Conclusions:  HPV infection is present in more than half of penile cancers and it is responsible for RB pathway disruption. However, no link between HPV and p53 immunodetection was found. Only basaloid and half of usual‐type PSSCs correlate with HPV infection, confirming possible separate aetiologies for those tumours.
Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy‐associated T cell lymphoma in Japan
Authors: Takeshita Morishige , Nakamura Shotaro , Kikuma Kanta , Nakayama Yoshifuku , Nimura Satoshi , Yao Takashi , Urabe Shogo , Ogawara Satoshi , Yonemasu Hirotoshi , Matsushita Yoshifumi , Karube Kennosuke , Iwashita Akinori
Published: February 2011

Takeshita M, Nakamura S, Kikuma K, Nakayama Y, Nimura S, Yao T, Urabe S, Ogawara S, Yonemasu H, Matsushita Y, Karube K & Iwashita A (2011) Histopathology58, 395–407 Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy‐associated T cell lymphoma in Japan

Aims:  To elucidate the clinicopathological findings of primary intestinal enteropathy‐associated T cell lymphoma (EATL) in Japan, a non‐endemic area for coeliac disease.

Methods and results:  Of the 24 cases, four (17%) had large‐cell lymphoma (type I), and the remaining 20 (83%) had medium‐sized lymphoma (type II). Lymphoma cells of the three type I cases were CD56‐positive. Only one (4%) case showed typical CD56‐ and CD8‐negative and CD30‐positive type I EATL. In type II EATL, lymphoma cells of the 16 (80%) and 11 (55%) cases were positive for CD56 and CD8, respectively. Intramucosal tumour spreading and adjacent enteropathy‐like lesions were detected in 15 (71%) and 16 (76%) of 21 cases, with a severe increase of intraepithelial lymphocytes (IELs) in 12 (57%). IELs of enteropathy‐like lesions in five (24%) cases expressed T‐bet, with no cases of CD30‐positive IELs. Characteristic findings from comparative genomic hybridization of 15 cases indicated gains of 8q2 (47%), Xp (53%) and Xq (73%), but no gain of 9q3. Regarding, human leucocyte antigen (HLA) status, six cases examined did not express the DQB1*02 allele.

Conclusions:  Japanese EATL exhibited different histology, cytogenetic findings and HLA status from those of typical type I EATL. The rare incidence of coeliac disease may influence the tumour cell characteristics of EATL and IELs.
Extensive retraction artefact predicts biochemical recurrence‐free survival in prostatic carcinoma
Authors: Tomas Davor , Spajić Borislav , Milošević Milan , Demirović Alma , Marušić Zlatko , Krušlin Božo
Published: February 2011

Tomas D, Spajić B, Milošević M, Demirović A, Marušić Z & Krušlin B (2011) Histopathology58, 447–454 Extensive retraction artefact predicts biochemical recurrence‐free survival in prostatic carcinoma

Aims:  To determine whether the presence and extent of peritumoral retraction artefact could be used to predict biochemical recurrence‐free survival in prostatic carcinoma.

Methods and results:  The study included 162 consecutive patients treated by radical retropubic prostatectomy and bilateral lymphadenectomy for clinically localized prostatic carcinoma. A variable degree of retraction artefact was present in all 162 analysed tumours. The extent of retraction artefact in prostatic carcinomas ranged from 5% to 55% with a median value of 15% (interquartile range 10–25%). We found no correlation between the extent of retraction artefact in the tumours and patient’s age (P = 0.608), preoperative (P = 0.362) and postoperative (P = 0.279) Gleason score or lymph node metastases (P = 0.084). In contrast, the extent of retraction artefact correlated with high preoperative prostate‐specific antigen (P  < 0.001), short follow‐up time (P  < 0.001), seminal vesicle invasion and/or extracapsular extension of the tumour (T3 stage tumours) (P  < 0.001) and positive surgical margins (P  < 0.001). Furthermore, extensive retraction artefact was associated with poor biochemical recurrence‐free survival in both univariate (P  < 0.001) and multivariate analyses (P = 0.013).

Conclusion:  The presence of extensive retraction artefact in prostatic carcinoma correlates with tumour characteristics signifying aggressive behaviour and indicates poor biochemical recurrence‐free survival.
Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy
Authors: Santi Raffaella , Cetica Valentina , Franchi Alessandro , Pepi Monica , Cesinaro Anna M , Miracco Clelia , Paglierani Milena , De Giorgi Vincenzo , Delfino Chiara , Difonzo Elisa M , Pimpinelli Nicola , Bianchi Simonetta , Sardi Iacopo , Santucci Marco , Massi Daniela
Published: February 2011

Santi R, Cetica V, Franchi A, Pepi M, Cesinaro A M, Miracco C, Paglierani M, De Giorgi V, Delfino C, Difonzo E M, Pimpinelli N, Bianchi S, Sardi I, Santucci M & Massi D (2011) Histopathology58, 455–466 Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy

Aims:  Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well‐documented complication in the setting of breast‐conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation‐induced AVL and angiosarcomas (AS).

Methods and results:  Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon.

Conclusions:  The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation‐associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.
Cord blood monocyte subsets are similar to adult and show potent peptidoglycan‐stimulated cytokine responses
Authors: Sohlberg Ebba , Saghafian‐Hedengren Shanie , Bremme Katarina , Sverremark‐Ekström Eva
Published: February 2011

Human monocytes can be divided into two major subpopulations, CD14++ CD16− and CD14+ CD16+ cells, which are suggested to play different roles in antimicrobial responses. In neonates, characteristics and functional responses of monocyte subsets have not previously been explored, and might contribute to the qualitative difference between neonatal and adult cytokine profiles. We report that at baseline, monocyte subsets in cord blood and adult peripheral blood are present in similar frequencies, and show similar expression of CD11c, CD80/CD86, CD163 and HLA‐DR. In response to the bacterial ligand peptidoglycan, cord blood monocytes had high inherent capacity for production of the early‐response cytokines with levels of tumour necrosis factor and interleukin‐12p70 exceeding adult levels, and also a higher phosphorylation of p38‐mitogen‐activated protein kinase. The CD14+ CD16+ cells expressed more interleukin‐12p70 than CD14++ CD16− cells and were present in a higher frequency in peptidoglycan‐stimulated cord blood mononuclear cell cultures. Together, the behaviour of cord blood CD14+ CD16+ cells following peptidoglycan stimulation might indicate a qualitative difference between the neonatal antimicrobial response and that of the adult. In addition we found that serum factors in cord blood and adult sera affected cytokine production similarly, with the exception of tumour necrosis factor, regardless of the source of serum or cells. Overall, our data provide new insights into monocyte heterogeneity in cord blood and monocyte subset responses to a bacterial ligand at birth.
Care recipients’ and family members’ perceptions of quality of older people care: a comparison of home‐based care and nursing homes
Authors: Hasson Henna , Arnetz Judith E
Published: February 2011

Aims.  To compare care recipients’ and their relatives’ perceptions of quality of care in nursing homes and home‐based care.

Background.  Older people care is increasingly being provided in community care facilities and private homes instead of hospitals. A few studies have compared care recipients’ and relatives’ perceptions of care quality in nursing homes as opposed to home‐based care.

Design.  Cross‐sectional surveys.

Methods.  Care recipients’ and relatives’ perceptions of quality of care were measured by questionnaire in 2003 in two older people care organisations. Quality measures were compared between care settings. Multiple regression was used to determine the predictors of overall quality ratings for each group, and possible interactions between quality measures and care settings were tested.

Results.  Care recipients rated their opportunities for activities significantly lower in home care than in nursing homes. Relatives of care recipients in home‐based care rated several aspects of care quality significantly lower than relatives of nursing home residents. No significant interaction effects regarding predictors of overall quality ratings between the care settings were found. Staff behaviour was the strongest predictor of care recipients’ overall quality rating, and staff professional skills were the strongest predictor of relatives’ overall quality rating.

Conclusions.  Compared with nursing homes, home‐based older people care seems to be in greater need of development regarding staff competence, staff interaction with relatives and activities offered to older people. In both settings, nursing staff behaviour influences these stakeholders’ satisfaction with care.

Relevance to clinical practice.  These results point to a need to improve services in both care settings, but especially in home‐based care. It is suggested that care recipients’ preferences for social and physical activities be investigated on a regular basis in both care settings. Efforts should also be made to improve communication and interaction between family members and older people care staff, especially in home‐based care.
Pharmacokinetics of ceftiofur crystalline‐free acid sterile suspension in the equine
Authors: COLLARD W. T. , COX S. R. , LESMAN S. P. , GROVER G. S. , BOUCHER J. F. , HALLBERG J. W. , ROBINSON J. A. , BROWN S. A.
Published: February 2011

Collard, W. T., Cox, S. R., Lesman, S. P., Grover, G. S., Boucher, J. F., Hallberg, J. W., Robinson, J. A., Brown, S. A. Pharmacokinetics of ceftiofur crystalline‐free acid sterile suspension in the equine. J. vet. Pharmacol. Therap.34, 476–481.

Absolute bioavailability and dose proportionality studies were performed with ceftiofur in horses. In the absolute bioavailability study, thirty animals received either an intravenous dose of ceftiofur sodium at 1.0 mg/kg or an intramuscular (i.m.) dose of ceftiofur crystalline‐free acid (CCFA) at 6.6 mg/kg. In the dose proportionality study, 48 animals received daily i.m. ceftiofur sodium injections at 1.0 mg/kg for ten doses or two doses of CCFA separated by 96 h, with CCFA doses of 3.3, 6.6, or 13.2 mg/kg. Noncompartmental and mixed‐effect modeling procedures were used to assess pharmacokinetics (PK). CCFA was well absorbed with a bioavailability of 100%. AUC0–∞ and Cmax increased in a dose‐related manner following administration of the two doses of CCFA at 3.3, 6.6, and 13.2 mg/kg. The least‐squares mean terminal half‐life (t½) following the tenth daily i.m. injection of ceftiofur sodium at 2.2 mg/kg was 40.8 h, but the least‐squares mean t½ following the second i.m. injection of CCFA at 6.6 mg/kg was 100 h. The time that plasma ceftiofur equivalent concentrations remain above a threshold concentration of 0.2 μg/mL has been associated with efficacy, and following administration of two 6.6 mg/kg doses of CCFA, the mean time above 0.2 μg/mL was 262 h. Simulations with the nonlinear mixed‐effect PK model predicted that more than 97.5% of horses will have plasma ceftiofur equivalent concentrations >0.2 μg/mL for 96 h after the second 6.6 mg/kg dose of CCFA.
EFFICIENT GRID SCHEDULING THROUGH THE INCREMENTAL SCHEDULE‐BASED APPROACH
Authors: Klusáček Dalibor , Rudová Hana
Published: February 2011

Although Grid users demand good performance for their jobs, this requirement is often not satisfied by the widely used queue‐based scheduling approaches. This article concentrates on the application of schedule‐based methods that improve on both the service delivered to the user and the traditional objective of machine usage. Importantly, the interaction between the incremental application of these methods and the dynamic character of the problem allows reasonable runtimes to be achieved. Two new schedule‐based methods that are designed to schedule dynamically arriving jobs on machines in a computational Grid are formally described in the article. The Earliest Gap — Earlier Deadline First (EG‐EDF) policy fills the earliest gap in the known schedule with newly arriving jobs, incrementally building a new schedule. If the gap is not suitable for an incoming job, the EDF policy is used to modify the existing schedule. A Tabu search algorithm is used to further optimize the schedule by moving selected jobs into the earliest suitable gaps. The proposed incremental schedule‐based methods are compared with some of the most common queue‐based scheduling algorithms such as FCFS (First Come First Served), EASY backfilling (Extensible Argonne Scheduler sYstem), Flexible backfilling as well as with the nonincremental version of the EG‐EDF schedule‐based policy.
Subsistence and Sustainability in Post‐industrial Europe: The Politics of Small‐scale Farming in Europeanising Lithuania
Authors: Mincyte Diana
Published: February 2011

This article examines the marginalisation of small‐scale semi‐subsistence farming in the context of the European Union's sustainable development reforms as implemented in the new member countries. In documenting how small‐scale farming in post‐socialist Lithuania has been redefined from being a solution to the environmental and social degradation of industrialised agriculture under socialism to becoming a major obstacle in building sustainable agriculture, this case study offers a critique of sustainability as a developmental project and the asymmetrical relationships implicit in the rural development politics in Europe. Taking a historical‐comparative approach, this study demonstrates that the notion of sustainability has been built on assumptions about the industrialisation and globalisation of agri‐food systems that exclude alternative local forms of production, consumption and distribution. As a result, the implementation of such sustainable development policies leads to the reproduction of the industrialised agriculture and the exclusion of small‐scale farmers from the vision of sustainable rural societies.
The Influence of Urban Street Characteristics on Pedestrian Heat Comfort Levels in Philadelphia
Authors: Oka Masayoshi
Published: February 2011

This article demonstrates a way to model the urban microclimate using a combination of statistical analysis and a geographic information system (GIS). Field measurements of ambient temperature and relative humidity were collected in various urban settings at ground level over two surface materials and at two different times of the day. A panel autoregressive (PAR) model was created to conduct a regression analysis capable of accounting for the spatial autocorrelation. With the PAR analyses, selected urban street characteristics showed varying effects over the different surface materials and at different times of the day. The overall influences were consistent with previous findings. PAR models were then applied in GIS to create thermal prediction maps for the study area to determine the hot and cool spots. Since GIS is the most commonly used technology among a wide range of researchers and professionals, this article provides a means to improve the synthesis, integration, and sharing of information to understand the relationship between the heat‐vulnerable population and heat stress within the urban environment. This methodology will be useful in the effort to reduce the heat‐related morbidity and mortality, which are expected to increase with projected global warming.
Evidence‐Based Guidelines for the Care and Maintenance of Complete Dentures: A Publication of the American College of Prosthodontists
Authors: Felton David , Cooper Lyndon , Duqum Ibrahim , Minsley Glenn , Guckes Albert , Haug Steven , Meredith Patricia , Solie Caryn , Avery David , Deal Chandler Nancy
Published: February 2011

The current rates of edentulism have been estimated to be between 7% and 69% of the adult population internationally. In the United States, while the incidence of edentulism continues to decline, rapid population growth coupled with current economic conditions suggest that edentulism and conventional denture use will continue at current or higher numbers. Unfortunately, evidence‐based guidelines for the care and maintenance of removable complete denture prostheses do not exist. In 2009, the American College of Prosthodontists (ACP) formed a task force to establish evidence‐based guidelines for the care and maintenance of complete dentures. The task force comprised members of the ACP, the Academy of General Dentistry, American Dental Association (ADA) Council on Scientific Affairs, the American Dental Hygienists' Association, the National Association of Dental Laboratories, and representatives from GlaxoSmithKline Consumer Healthcare. The review process included the assessment of over 300 abstracts and selection of over 100 articles meeting inclusion criteria of this review. The task force reviewed synopses of the literature and formulated 15 evidence‐based guidelines for denture care and maintenance. These guidelines were reviewed by clinical experts from the participating organizations and were published in February 2011 issue of The Journal of the American Dental Association for widespread distribution to the dental community. These guidelines reflect the views of the task force.
Proresolving lipid mediators: potential for prevention and treatment of periodontitis
Authors: Van Dyke Thomas E.
Published: February 2011

Van Dyke TE. Proresolving lipid mediators: potential for prevention and treatment of periodontitis. J Clin Periodontol 2011; 38 (Suppl. 11): 119–125. doi: 10.1111/j.1600‐051X.2010.01662.x.

Aim: Periodontitis is an inflammatory disease initiated by microbial biofilm. The host response to the biofilm destroys the periodontium mediated by an overly robust inflammatory response in susceptible individuals. Whether the excessive host response is genetic, epigenetic or mediated by environment is unknown. New pathways of resolution of inflammation have been discovered. Resolution of inflammation is an active, agonist‐mediated, programmed return to tissue homeostasis.

Materials and Methods: Various computer‐based search engines were employed to identify papers relevant to resolution of inflammation.

Results: Recent data suggest that chronic inflammatory periodontal disease may be a failure of resolution pathways as well as overexpression of proinflammatory pathways. In this review, the biology of resolution of inflammation will be examined in normal tissues and periodontal disease. Anti‐inflammatory pharmacologic agents [non‐steroidal anti‐inflammatory drugs (NSAIDs)] have been shown to prevent and slow the progression of periodontitis in animals and humans. However, the side effect profile of NSAIDS or other inhibitors or receptor antagonists preclude their use in periodontal therapy.

Conclusion: The isolation and characterization of proresolving lipid mediators that are receptor agonists has opened a new area of research for potential therapeutic agents for the management of inflammatory periodontitis.
Micronutritional approaches to periodontal therapy
Authors: Van der Velden U. , Kuzmanova D. , Chapple I. L. C.
Published: February 2011

Van der Velden U, Kuzmanova D, Chapple ILC. Micronutritional approaches to periodontal therapy. J Clin Periodontol 2011; 38 (Suppl. 11): 142–158. doi: 10.1111/j.1600‐051X.2010.01663.x.

Aim: Periodontitis results from the loss of a delicate balance between microbial virulence factors and a proportionate host response. Nutritional factors have been implicated in several chronic inflammatory diseases that are associated with periodontitis. This manuscript reviews the evidence for nutritional exposures in the etiology and therapeutic management of periodontitis, and makes recommendations for daily nutritional intake for vitamin C (ascorbic acid), vitamin D, calcium, and antioxidants.

Results and conclusion: Periodontitis is associated with low serum/plasma micronutrient levels, which may result from dietary and/or life‐style factors as well as nutrigenetic characteristics. Early evidence suggests beneficial outcomes from nutritional interventions; supporting the contention that daily intake of certain nutrients should be at the higher end of recommended daily allowances. For prevention and treatment of periodontitis daily nutrition should include sufficient antioxidants, vitamin D, and calcium. Inadequate antioxidant levels may be managed by higher intake of vegetables, berries, and fruits (e.g. kiwi fruit), or by phytonutrient supplementation. Current evidence is insufficient to support recommendations of mono‐antioxidant vitamin supplements and randomised controlled double‐blind intervention studies are needed to provide evidence to underpin future recommendations. Inadequate supply of vitamin D and calcium may be addressed by implementing changes in diet/life style or by supplements.
Do probiotics offer opportunities to manipulate the periodontal oral microbiota?
Authors: Teughels Wim , Loozen Gitte , Quirynen Marc
Published: February 2011

Teughels W, Loozen G, Quirynen M: Do probiotics offer opportunities to manipulate the periodontal oral microbiota? J Clin Periodontol 2011; 38 (Suppl. 11): 159–177. doi: 10.1111/j.1600‐051X.2010.01665.x.

Background: As in other fields of healthcare, probiotics have been introduced for prevention and treatment of periodontal diseases.

Objective: This review was initiated to explore whether the use of probiotics can influence the periodontal microbiota and periodontal health.

Materials and Methods: Literature on the mode of action of oral probiotics was reviewed and a systematic review was performed on the microbiological and clinical effects of oral probiotics on periodontal health.

Results: Three animal and 11 in vivo human studies were retrieved. Six studies reported on microbiological effects whereas eight studies report on clinical effects. Seven studies were performed on healthy or gingivitis patients and four studies on periodontitis patients. Many of the retrieved studies are pilot in nature and with low quality. The high degree of heterogeneity between studies hampered analysis.

Conclusion: Taking into consideration all limitations, the currently available data indicate an effect of probiotics on the oral microbiota and a more limited effect on clinical periodontal outcome measures. However, there is an urgent need for properly conducted clinical trials where probiotics are used as adjuncts to standard periodontal care, similar to antibiotics, using probiotic strains with, at least at an in vitro level, proven periodontal probiotic effects.
Periodontal microbial complexes associated with specific cell and tissue responses
Authors: Kebschull Moritz , Papapanou Panos N.
Published: February 2011

Kebschull M, Papapanou PN. Periodontal microbial complexes associated with specific cell and tissue responses. J Clin Periodontol 2011; 38 (Suppl. 11): 17–27. doi: 10.1111/j.1600‐051X.2010.01668.x.

Aims: In this review, we summarize data on the association between specific periodontal bacterial profiles and tissue gene/protein expression, generated from cell culture models and in vivo studies.

Material and Methods: A PubMed search was conducted to identify publications related to the effects of periodontal microbiota on host cells/tissues.

Results and Conclusions: The data indicate the presence of specific host tissue responses to particular microbial complexes, evident by differential regulation of gene or protein expression, ultimately resulting in distinct clinical phenotypes. Transcriptomic analyses showed that periodontal pathogens induce a small, “common core” of differentially regulated genes encoding for an inflammatory response, and a larger variable set of genes that may reflect pathogen‐specific cellular responses. Limitations of available studies include (i) the unclear role of hundreds of subgingival species not yet investigated, (ii) the fact that in vitro studies utilizing single populations of oral cells challenged with mono‐infections of planktonic bacteria may not adequately portray human periodontal diseases and (iii) the cross‐sectional nature of most human studies that makes them inherently incapable of allowing temporal or causal inferences. Longitudinal studies in humans hold the potential to be superior to any model, but need to be adequately powered and controlled.
How is the development of dental biofilms influenced by the host?
Authors: Marsh Philip D. , Devine Deirdre A.
Published: February 2011

Marsh PD, Devine DA. How is the development of dental biofilms influenced by the host? J Clin Periodontol 2011; 38 (Suppl. 11): 28–35. doi: 10.1111/j.1600‐051X.2010.01673.x.

Background: The host provides environmental conditions that support diverse communities of microorganisms on all environmentally‐exposed surfaces of the body.

Materials and Methods: To review the literature to determine which properties of the host substantially influence the development of dental biofilms.

Results: The mouth facilitates the growth of a characteristic resident microbiota. The composition of the oral microbiota is influenced by temperature, pH, and atmosphere, as well as by the host defences and host genetics. In addition, the host supplies endogenous nutrients and a variety of surfaces for biofilm formation. In health, the resident oral microbiota forms a symbiotic relationship with the host, regulated by active host–microbe cross talk. This resident microbiota is sensitive to perturbations in the host environment, especially to changes in nutrient supply and pH, so that previously minor components of the microbiota can become more competitive (and vice versa), resulting in reorganization of biofilm community structure.

Conclusion: The host environment dictates the composition and gene expression of the resident microbiota. Changes in oral environmental conditions can disrupt the normal symbiotic relationship between the host and its resident microbes, and increase the risk of disease.
Periodontal infections: understanding the complexity – Consensus of the Seventh European Workshop on Periodontology
Authors: Sanz Mariano , van Winkelhoff Arie Jan ,   on Behalf of Working Group 1 of the Seventh European Workshop on Periodontology
Published: February 2011

Introduction: Periodontal diseases are the pathological manifestation of the host response against the bacterial challenge from the dental biofilm at the tooth/gingival interface. The remit of this working group was to update the existing knowledge on the infectious nature of periodontal diseases.

Material and Methods: The literature was systematically searched and critically reviewed. Four manuscripts were produced in specific topics identified as key areas to understand the importance of the microorganisms in the etio‐pathogenesis of periodontal diseases.

Results/Conclusions: The results and conclusions of the review process are presented in the following papers, together with the group consensus statements aiming to answer the following questions: (1) Has the use of molecular methods for the characterization of the human oral microbiome changed our understanding of the role of bacteria in the pathogenesis of periodontal disease process? (2) Are the periodontal microbial complexes associated with specific cell and tissue responses? (3) How is the development of dental biofilms influenced by the host? (4) What can we learn about biofilm/host interactions from the study of inflammatory bowel disease? This consensus report provides answers to these questions with the most updated information on periodontal microbiology
The Role of Genital Nerve Afferents in the Physiology of the Sexual Response and Pelvic Floor Function
Authors: Tajkarimi Kambiz , Burnett Arthur L.
Published: February 2011

Introduction

Our understanding of genital and pelvic floor physiology is rapidly expanding. Penile erection is a neurovascular event controlled by spinal autonomic centers, the activity of which is dependent on input from supraspinal centers and the genitalia. Genital afferent stimulation excites spinal autonomic nuclei and supraspinal sexual centers of both genders.

Aim

To present a detailed understanding of the functional importance of genital afferent neuroanatomy and neurophysiology.

Methods

English-written articles of diverse disciplines from 1980 to 2010 that contained information on genital anatomy, pudendal/dorsal/perineal/cavernous nerves, vibratory stimulation, reflexogenic erection, peripheral/central nervous system-mediated erectile and micturition pathways, and sexual arousal in animals and humans were reviewed.

Main Outcome Measures

Analysis of supporting evidence for the role of genital afferents in the physiology of erectile response and pelvic floor function.

Results

Basic science and clinical studies support the concept that pudendal nerve circuitry serves an essential purpose for sexual behavior, erectile function, penile rigidity, ejaculation, and micturition. Males and females share a comparable pattern of genital afferent neuroanatomy and neurophysiology, and sexual and micturition reflexes are similar in both genders. Pudendal nerve branches communicate with the cavernous nerves and are nitric oxide synthase positive. Genital afferents activate multiple spinal reflexes that modulate erection and micturition. Genital sensory information is transmitted to supraspinal centers important for sexual function.

Conclusions

There is expanding support for the critical role of genital afferent neurophysiology in the mechanisms of erectile function and micturition. Genital afferent stimulation is a safe and natural modality that can be harnessed to amplify autonomic and somatic activity within the penis, female genitalia, spinal cord, and higher centers via established neurological principles. Such physiological adaptive processes may be beneficial in improving sexual response, erectile function, and micturition in many disease states, including in men after radical pelvic surgery. Well-designed and -executed studies in each specific population are needed to authenticate such prospects.