bluuebunny/crossref_metadata_2025 huggingface dataset:
Access to safe abortion: building choices for women living with HIV and AIDS
Authors: Orner Phyllis J , de Bruyn Maria , Barbosa Regina Maria , Boonstra Heather , Gatsi‐Mallet Jennifer , Cooper Diane D
Published: November 2011

In many areas of the world where HIV prevalence is high, rates of unintended pregnancy and unsafe abortion have also been shown to be high. Of all pregnancies worldwide in 2008, 41% were reported as unintended or unplanned, and approximately 50% of these ended in abortion. Of the estimated 21.6 million unsafe abortions occurring worldwide in 2008 (around one in 10 pregnancies), approximately 21.2 million occurred in developing countries, often due to restrictive abortion laws and leading to an estimated 47,000 maternal deaths and untold numbers of women who will suffer long‐term health consequences. Despite this context, little research has focused on decisions about and experiences of women living with HIV with regard to terminating a pregnancy, although this should form part of comprehensive promotion of sexual and reproductive health rights.

In this paper, we explore the existing evidence related to global and country‐specific barriers to safe abortion for all women, with an emphasis on research gaps around the right of women living with HIV to choose safe abortion services as an option for dealing with unwanted pregnancies. The main focus is on the situation for women living with HIV in Brazil, Namibia and South Africa as examples of three countries with different conditions regarding women's access to safe legal abortions: a very restrictive setting, a setting with several indications for legal abortion but non‐implementation of the law, and a rather liberal setting.

Similarities and differences are discussed, and we further outline global and country‐specific barriers to safe abortion for all women, ending with recommendations for policy makers and researchers.
Transgenic overexpression of γ-cytoplasmic actin protects against eccentric contraction-induced force loss in mdx mice
Authors: Baltgalvis Kristen A , Jaeger Michele A , Fitzsimons Daniel P , Thayer Stanley A , Lowe Dawn A , Ervasti James M
Published: November 2011

Background

γ-cytoplasmic (γ-cyto) actin levels are elevated in dystrophin-deficient mdx mouse skeletal muscle. The purpose of this study was to determine whether further elevation of γ-cyto actin levels improve or exacerbate the dystrophic phenotype of mdx mice.

Methods

We transgenically overexpressed γ-cyto actin, specifically in skeletal muscle of mdx mice (mdx-TG), and compared skeletal muscle pathology and force-generating capacity between mdx and mdx-TG mice at different ages. We investigated the mechanism by which γ-cyto actin provides protection from force loss by studying the role of calcium channels and stretch-activated channels in isolated skeletal muscles and muscle fibers. Analysis of variance or independent t-tests were used to detect statistical differences between groups.

Results

Levels of γ-cyto actin in mdx-TG skeletal muscle were elevated 200-fold compared to mdx skeletal muscle and incorporated into thin filaments. Overexpression of γ-cyto actin had little effect on most parameters of mdx muscle pathology. However, γ-cyto actin provided statistically significant protection against force loss during eccentric contractions. Store-operated calcium entry across the sarcolemma did not differ between mdx fibers compared to wild-type fibers. Additionally, the omission of extracellular calcium or the addition of streptomycin to block stretch-activated channels did not improve the force-generating capacity of isolated extensor digitorum longus muscles from mdx mice during eccentric contractions.

Conclusions

The data presented in this study indicate that upregulation of γ-cyto actin in dystrophic skeletal muscle can attenuate force loss during eccentric contractions and that the mechanism is independent of activation of stretch-activated channels and the accumulation of extracellular calcium.
Gemcitabine Plus Docetaxel Versus Docetaxel in Patients With Predominantly Human Epidermal Growth Factor Receptor 2–Negative Locally Advanced or Metastatic Breast Cancer: A Randomized, Phase III Study by the Danish Breast Cancer Cooperative Group
Authors: Nielsen Dorte L. , Bjerre Karsten D. , Jakobsen Erik H. , Cold Søren , Stenbygaard Lars , Sørensen Peter G. , Kamby Claus , Møller Susanne , Jørgensen Charlotte L.T. , Andersson Michael
Published: November 2011

Purpose

The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer.

Patients and Methods

Predominantly human epidermal growth factor receptor 2 (HER2) –negative patients were randomly assigned to gemcitabine (1,000 mg/m2) on days 1 and 8 plus docetaxel (75 mg/m2) on day 8 or to docetaxel (100 mg/m2) on day 1, every 21 days. Patients were untreated or had prior (neo)adjuvant chemotherapy or a single anthracycline-based chemotherapy regimen for metastatic breast cancer. The primary end point was time to progression (TTP), and secondary end points were overall survival (OS), response rate (RR), and toxicity.

Results

A total of 170 patients were allocated to GD, and 167 were allocated to docetaxel. Median TTP on GD was 10.3 months versus 8.3 months on docetaxel (hazard ratio [HR], 0.77; 95% CI, 0.59 to 1.01; log-rank P = .06). The adjusted Cox proportional model for TTP showed a significant difference favoring the combination (HR, 0.68; 95% CI, 0.51 to 0.90; P = .007). However, RR was similar (GD, 36%; docetaxel, 34%), and OS was not different (P = .57). Grades 3 to 4 neutropenia was common (GD, 75%; docetaxel, 69%); infection was reported in 26% and 21% of patients in the GD and docetaxel groups, respectively. Grades 3 to 4 thrombocytopenia was more frequent with GD (GD, 16%; docetaxel, 0.6%), and peripheral neuropathy was higher with docetaxel (GD, 5%; docetaxel, 16%).

Conclusion

GD compared with docetaxel demonstrated increased TTP in metastatic breast cancer. However, RR and OS were similar. Thus, the addition of gemcitabine failed to demonstrate any clinically meaningful benefit when combined with docetaxel.
Medical Oncologists' Attitudes and Practice in Cancer Pain Management: A National Survey
Authors: Breuer Brenda , Fleishman Stewart B. , Cruciani Ricardo A. , Portenoy Russell K.
Published: November 2011

Purpose

To evaluate the attitudes, knowledge, and practices of US medical oncologists that are related to management of cancer pain.

Methods

An anonymous survey was mailed to a geographically representative sample of medical oncologists randomly selected from the American Medical Association's Physician Master File.

Results

From a total of 2,000 oncologists, 354 responded to the original questionnaire and 256 responded to one of two subsequent shortened versions (overall response rate, 32%). Responders were demographically similar to all US medical oncologists. Using numeric rating scales of 0 to 10, oncologists rated their specialty highly for the ability to manage cancer pain (median, 7; interquartile range [IQR], 6 to 8) but rated their peers as more conservative prescribers than themselves (median, 3; IQR, 2 to 5). The quality of pain management training during medical school and residency was rated as 3 (IQR, 1 to 5) and 5 (IQR, 3 to 7), respectively. The most important barriers to pain management were poor assessment (median, 6; IQR, 4 to 7) and patient reluctance to take opioids (median, 6; IQR, 5 to 7) or report pain (median, 6; IQR, 4 to 7). Other barriers included physician reluctance to prescribe opioids (median, 5; IQR, 3 to 7) and perceived excessive regulation (median, 4; IQR, 2 to 7). In response to two vignettes describing challenging clinical scenarios, 60% and 87%, respectively, endorsed treatment decisions that would be considered unacceptable by pain specialists. Frequent referrals to pain or palliative care specialists were reported by only 14% and 16%, respectively.

Conclusion

These data suggest that, for more than 20 years, a focus on cancer pain has not adequately addressed the perception of treatment barriers or limitations in pain-related knowledge and practice within the oncology community. Additional efforts are needed to achieve meaningful progress.
Adverse Prognostic Impact of Abnormal Lesions Detected by Genome-Wide Single Nucleotide Polymorphism Array–Based Karyotyping Analysis in Acute Myeloid Leukemia With Normal Karyotype
Authors: Yi Jun Ho , Huh Jungwon , Kim Hee-Jin , Kim Sun-Hee , Kim Hyeoung-Joon , Kim Yeo-Kyeoung , Sohn Sang Kyun , Moon Joon Ho , Kim Sung Hyun , Kim Kyoung Ha , Won Jong Ho , Mun Yeung Chul , Kim Hawk , Park Jinny , Jung Chul Won , Kim Dong Hwan
Published: November 2011

Purpose

This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) –based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses.

Patients and Methods

A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis.

Results

Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020).

Conclusion

Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes.
Predicting Survival After Curative Colectomy for Cancer: Individualizing Colon Cancer Staging
Authors: Weiser Martin R. , Gönen Mithat , Chou Joanne F. , Kattan Michael W. , Schrag Deborah
Published: November 2011

Purpose

Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy.

Methods

Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves.

Results

Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line.

Conclusion

Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer.
Prognostic Impact of Morphologic and Phenotypic Features of Childhood ALK-Positive Anaplastic Large-Cell Lymphoma: Results of the ALCL99 Study
Authors: Lamant Laurence , McCarthy Keith , d'Amore Emanuele , Klapper Wolfram , Nakagawa Atsuko , Fraga Maximo , Maldyk Jadwiga , Simonitsch-Klupp Ingrid , Oschlies Ilske , Delsol Georges , Mauguen Audrey , Brugières Laurence , Le Deley Marie-Cécile
Published: November 2011

Purpose

The prognostic value of pathologic characteristics of childhood ALK-positive anaplastic large-cell lymphomas (ALCL), such as histologic subtypes, immunophenotype, and presence of the t(2;5) translocation or its variants, was assessed.

Patients and Methods

All 375 patients with systemic ALK-positive ALCL included in an international trial launched by the European Intergroup for Childhood Non-Hodgkin's Lymphoma were reviewed by an international panel of pathologists based on conventional hematoxylin and eosin–stained and immunostained sections and classified according to the 2001 WHO classification.

Results

A small-cell (SC) or lymphohistiocytic (LH) component was observed in 114 (32%) of 361 patients, whereas ALCL of common type was diagnosed in 235 (65%) of 361 patients. Regarding the histologic subtyping of patients within the two categories of ALCL (with v without SC/LH component), the concordance between the national and international reviews was quite good, with a κ index equal to 0.67 (95% CI, 0.57 to 0.75). The presence of an SC/LH component was significantly associated with a high risk of failure (hazard ratio [HR], 2.0; 95% CI, 1.3 to 3.0; P = .002) in the multivariate analysis controlling for clinical characteristics, as well as the perivascular pattern (HR, 1.7; 95% CI, 1.1 to 2.7; P = .01), whereas CD3 positivity was significantly associated with a high risk of failure only in univariate analysis.

Conclusion

Our study, which to our knowledge includes the largest series of childhood systemic ALK-positive ALCL so far, demonstrates the adverse prognostic value of SC and/or LH morphologic features. Combining these histologic characteristics with other biologic or clinical factors might have a high potential for future risk stratification and treatment.
Novel Staging System for Predicting Disease-Specific Survival in Patients With Breast Cancer Treated With Surgery As the First Intervention: Time to Modify the Current American Joint Committee on Cancer Staging System
Authors: Yi Min , Mittendorf Elizabeth A. , Cormier Janice N. , Buchholz Thomas A. , Bilimoria Karl , Sahin Aysegul A. , Hortobagyi Gabriel N. , Gonzalez-Angulo Ana Maria , Luo Sheng , Buzdar Aman U. , Crow Jaime R. , Kuerer Henry M. , Hunt Kelly K.
Published: November 2011

Purpose

American Joint Committee on Cancer (AJCC) staging is used to determine breast cancer prognosis, yet patient survival within each stage shows wide variation. We hypothesized that differences in biology influence this variation and that addition of biologic markers to AJCC staging improves determination of prognosis.

Patients and Methods

We identified a cohort of 3,728 patients who underwent surgery as the first intervention between 1997 and 2006. A Cox proportional hazards model, with backward stepwise exclusion of factors and stratification on pathologic stage (PS), was used to test the significance of adding grade (G), lymphovascular invasion (L), estrogen receptor (ER) status (E), progesterone receptor (PR) status, combined ER and PR status (EP), or combined ER, PR, and human epidermal growth factor receptor 2 status (M). We assigned values of 0 to 2 to these disease-specific survival (DSS) –associated factors and assessed six different staging systems: PS, PS + G, PS + G L, PS + G E, PS + G EP, and PS + G M. We compared 5-year DSS rates, Akaike's information criterion (AIC), and Harrell's concordance index (C-index) between systems. Surveillance, Epidemiology, and End Results data were used as the external validation cohort (n = 26,711).

Results

Median follow-up was 6.5 years, and 5-year DSS rate was 97.4%. The PS + G E status staging system was most precise, with a low AIC (1,931.9) and the highest C-index (0.80). PS + G E status was confirmed to stratify outcomes in internal bootstrapping samples and the external validation cohort.

Conclusion

Our results validate an improved breast cancer staging system that incorporates grade and ER status. We recommend that biologic markers be incorporated into revised versions of the AJCC staging system.
Certification of Sustainable Bio Fuels
Authors: Walther-Thoß Jenny
Published: November 2011

If two people meet each other and discuss the matter of certification in the field of sustainable biomass they can use the same words and mean different things. A better understanding what in Europe with the term sustainable biomass is defined, is the aim of this article.
Fusion Energy Research for ITER and Beyond
Authors: Romanelli Francesco , Laxåback Martin
Published: November 2011

The achievement in the last two decades of controlled fusion in the laboratory environment is opening the way to the realization of fusion as a source of sustainable, safe and environmentally responsible energy. The next step towards this goal is the construction of the International Thermonuclear Experimental Reactor (ITER), which aims to demonstrate net fusion energy production on the reactor scale. This paper reviews the current status of magnetic confinement fusion research in view of the ITER project and provides an overview of the main remaining challenges on the way towards the realization of commercial fusion energy production in the second half of this century.
Formation and Characterisation of Solution Processed “Pseudo-Bilayer” Organic Solar Cells
Authors: Heinemann Marc Daniel , Ananthanarayanan Krishnamoorthy , Thummalakunta L. N. S. A. , Yong Chian Haw , Luther Joachim
Published: November 2011

The current state of the art solution processed organic photovoltaic (OPV) cells are based on the bulk heterojunction (BHJ) architecture, consisting of an active layer, in which the donor and the acceptor material are dissolved in a common solvent. In this report, we show that by sequential processing of the active components and by subsequent annealing a “pseudo-bilayer” can be formed which results in an enhanced nanomorphology for efficient charge generation and extraction. The enhanced nanomorphology arises from the inter-diffusion of the PCBM nanoparticles into a layer of pre-organised polymer P3HT instead of a phase separation that happens at the time of spin-coating and annealing in the case of conventional BHJ devices. To get a further insight into the inter-diffusion process, TOF-SIMS depth profiling and XPS measurements were carried out for different thermal annealing treatments of these pseudo-bilayer devices, which show full inter-diffusion after only seconds of annealing at 140°C. The optimised photovoltaic devices that were fabricated showed an efficiency of 4.1%.
Orthostatic hypotension in the anesthetized rabbit in the sitting position exceeds cerebral autoregulation
Authors: Willeford Breanna
Published: November 2011

Background: Orthostatic hypotension and cerebral autoregulation have been extensively studied in the rabbit. However, these physiologic responses have not been previously studied utilizing a rabbit in the sitting position under anesthesia.

Methods: This unusual position was obtained as the preferred orientation based on geometry requirements of associated equipment for a study of osteoarthritis of the knee. Rabbits for this experiment did not survive and an additional experimental condition was developed to elucidate the mechanism and cause of death. The carotid artery pressure was measured under general anesthesia with incremental tilt testing to achieve the sitting position.

Results: Under this condition, rabbits developed orthostatic hypotension and did not survive.

Conclusions: According to previous studies of orthostatic hypotension and limits of cerebral autoregulation, it is concluded that orthostatic hypotension in the anesthetized rabbit in the sitting position exceeds cerebral autoregulation.
MECHANISMS IN ENDOCRINOLOGY: Micro-RNAs: targets for enhancing osteoblast differentiation and bone formation
Authors: Taipaleenmäki Hanna , Bjerre Hokland Lea , Chen Li , Kauppinen Sakari , Kassem Moustapha
Published: November 2011

Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.
Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'étude des Tumeurs Endocrines database
Authors: Gatta-Cherifi B , Chabre O , Murat A , Niccoli P , Cardot-Bauters C , Rohmer V , Young J , Delemer B , Du Boullay H , Verger M F , Kuhn J M , Sadoul J L , Ruszniewski Ph , Beckers A , Monsaingeon M , Baudin E , Goudet P , Tabarin A
Published: November 2011

Objective

Limited data regarding adrenal involvement in multiple endocrine neoplasia type 1 (MEN1) is available. We describe the characteristics of MEN1-associated adrenal lesions in a large cohort to provide a rationale for their management.

Methods

Analysis of records from 715 MEN1 patients from a multicentre database between 1956 and 2008. Adrenal lesions were compared with those from a multicentre cohort of 144 patients with adrenal sporadic incidentalomas.

Results

Adrenal enlargement was reported in 20.4% (146/715) of patients. Adrenal tumours (>10 mm in size) accounted for 58.1% of these cases (10.1% of the whole patient cohort). Tumours were bilateral and >40 mm in size in 12.5 and 19.4% of cases respectively. Hormonal hypersecretion was restricted to patients with tumours and occurred in 15.3% of them. Compared with incidentalomas, MEN1-related tumours exhibited more cases of primary hyperaldosteronism, fewer pheochromocytomas and more adrenocortical carcinomas (ACCs; 13.8 vs 1.3%). Ten ACCs occurred in eight patients. Interestingly, ACCs occurred after several years of follow-up of small adrenal tumours in two of the eight affected patients. Nine of the ten ACCs were classified as stage I or II according to the European Network for the Study of Adrenal Tumors. No evident genotype/phenotype correlation was found for the occurrence of adrenal lesions, endocrine hypersecretion or ACC.

Conclusions

Adrenal pathology in MEN1 differs from that observed in sporadic incidentalomas. In the absence of relevant symptoms, endocrine biology can be restricted to patients with adrenal tumours and should focus on steroid secretion including the aldosterone–renin system. MEN1 is a high-risk condition for the occurrence of ACCs. It should be considered regardless of the size of the tumour.
Inhibin removes the inhibitory effects of activin on steroid enzyme expression and androgen production by normal ovarian thecal cells
Authors: Young J M , McNeilly A S
Published: November 2011

Activin and inhibin are important local modulators of theca cell steroidogenesis in the ovary. Using a serum-free primary theca cell culture system, this study investigated the effects of inhibin on theca cell androgen production and expression of steroidogenic enzymes. Androstenedione secretion from theca cells cultured in media containing activin, inhibin and follistatin was assessed by RIA over 144 h. Activin (1–100 ng/ml) suppressed androstenedione production. Inhibin (1–100 ng/ml) blocked the suppressive effects of added activin, but increased androstenedione production when added alone, suggesting it was blocking endogenous activin produced by theca cells. Addition of SB-431542 (activin receptor inhibitor) and follistatin (500 ng/ml) increased androstenedione production, supporting this concept. Infection of theca cells with adenoviruses expressing inhibitory Smad6 or 7 increased androstenedione secretion, confirming that the suppressive effects of activin required activation of the Smad2/3 pathway. Activin decreased the expression levels of steroidogenic acute regulatory protein (STAR), whereas STAR expression was increased by inhibin and SB-431542, alone and in combination. CYP11A was unaffected. The expression of CYP17 encoding 17α-hydroxylase was unaffected by activin but increased by inhibin and SB-431542, and when added in combination the effect was further enhanced. The expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) was significantly decreased by activin, while inhibin alone and in combination with SB-431542 both potently increased the expression of 3β-HSD. In conclusion, activin suppressed theca cell androstenedione production by decreasing the expression of STAR and 3β-HSD. Inhibin and other blockers of activin action reversed this effect, supporting the concept that endogenous thecal activin modulates androgen production in theca cells.
Urocortin is a novel regulator of osteoclast differentiation and function through inhibition of a canonical transient receptor potential 1-like cation channel
Authors: Combs Charlotte E , Fuller Karen , Kumar Hashethra , Albert Anthony P , Pirianov Grisha , McCormick James , Locke Ian C , Chambers Timothy J , Lawrence Kevin M
Published: November 2011

This study investigated the role of urocortin (UCN), a member of the corticotrophin-releasing factor (CRF) family of peptides, in osteoclast maturation and function. We found that 10−7 M UCN significantly (P<0.05) suppressed osteoclast differentiation from bone marrow precursor cells in culture and reduced the expression of several osteoclastic markers. Furthermore, UCN potently suppressed osteoclast bone resorption, by significantly inhibiting both the plan area of bone resorbed by osteoclasts and actin ring formation within osteoclasts at 10−9 M (P<0.05), with complete inhibition at 10−7 M (P<0.001). UCN also inhibited osteoclast motility (10−7 M) but had no effect on osteoclast survival. Osteoclasts expressed mRNA encoding both UCN and the CRF receptor 2β subtype. Pre-osteoclasts however, expressed CRF receptor 2β alone. Unstimulated osteoclasts contained constitutively active cation channel currents with a unitary conductance of 3–4 pS, which were inhibited by over 70% with UCN (10−7 M). Compounds that regulate calcium signalling and energy status of the cell, both crucial for osteoclast activity were investigated. The non-selective cation channel blockers, lanthanum (La3+) and gadolinium (Gd3+), inhibited actin ring formation in osteoclasts, whereas modulators of voltage-dependent Ca2+channels and KATPchannels had no effect. These findings show for the first time that UCN is a novel anti-resorptive molecule that acts through a direct effect on osteoclasts and their precursor cells.
Yeast: An Experimental Organism for 21st Century Biology
Authors: Botstein David , Fink Gerald R
Published: November 2011

In this essay, we revisit the status of yeast as a model system for biology. We first summarize important contributions of yeast to eukaryotic biology that we anticipated in 1988 in our first article on the subject. We then describe transformative developments that we did not anticipate, most of which followed the publication of the complete genomic sequence of Saccharomyces cerevisiae in 1996. In the intervening 23 years it appears to us that yeast has graduated from a position as the premier model for eukaryotic cell biology to become the pioneer organism that has facilitated the establishment of the entirely new fields of study called “functional genomics” and “systems biology.” These new fields look beyond the functions of individual genes and proteins, focusing on how these interact and work together to determine the properties of living cells and organisms.
DNA Sequence-Mediated, Evolutionarily Rapid Redistribution of Meiotic Recombination Hotspots
Authors: Wahls Wayne P , Davidson Mari K
Published: November 2011

Hotspots regulate the position and frequency of Spo11 (Rec12)-initiated meiotic recombination, but paradoxically they are suicidal and are somehow resurrected elsewhere in the genome. After the DNA sequence-dependent activation of hotspots was discovered in fission yeast, nearly two decades elapsed before the key realizations that (A) DNA site-dependent regulation is broadly conserved and (B) individual eukaryotes have multiple different DNA sequence motifs that activate hotspots. From our perspective, such findings provide a conceptually straightforward solution to the hotspot paradox and can explain other, seemingly complex features of meiotic recombination. We describe how a small number of single-base-pair substitutions can generate hotspots de novo and dramatically alter their distribution in the genome. This model also shows how equilibrium rate kinetics could maintain the presence of hotspots over evolutionary timescales, without strong selective pressures invoked previously, and explains why hotspots localize preferentially to intergenic regions and introns. The model is robust enough to account for all hotspots of humans and chimpanzees repositioned since their divergence from the latest common ancestor.
Medical-Legal Partnership: Impact on Patients With Sickle Cell Disease
Authors: Pettignano Robert , Caley Sylvia B. , Bliss Lisa R.
Published: November 2011

OBJECTIVE:

To determine the types of legal problems addressed by the Health Law Partnership (HeLP) and the impact of the legal interventions in pediatric patients with sickle cell disease (SCD) or its variants. We hypothesized that an interdisciplinary team that includes lawyers would positively affect the social determinants of health that affect patients with SCD.

METHODS:

The HeLP database was retrospectively queried for all patients with the diagnosis of SCD or 1 of its variants who had been seen by the lawyers of HeLP between April 2004 and September 2010. Data collected in this cohort of patients included income level of the patient/client, the initial presenting problems, any patient/parent/guardian problems identified during the legal checkup, and the type of legal assistance provided. Estimated annualized financial outcomes were calculated.

RESULTS:

From April 2004 through September 2010, 71 parents/guardians with 76 children with SCD were referred to the HeLP for legal intervention. Of the 71 parents/guardians, 33 were at <100% of the federal poverty level. There were 106 initial case problems identified in the 71 parents/guardians; 51 of 106 problems were directly related to the child. An additional 93 issues were identified during the legal checkup. Of 106 cases, 99 were closed with 21 resulting in a measurable gain of benefits.

CONCLUSIONS:

In a cohort of families of children with SCD, incorporating access to legal services as part of the care plan resulted in a positive impact on these patients/parents/guardians. The impact was directly attributable to the intervention of the HeLP.
Adolescent Vaccination-Coverage Levels in the United States: 2006–2009
Authors: Stokley Shannon , Cohn Amanda , Dorell Christina , Hariri Susan , Yankey David , Messonnier Nancy , Wortley Pascale M.
Published: November 2011

BACKGROUND:

From 2005 through 2007, 3 vaccines were added to the adolescent vaccination schedule: tetanus-diphtheria-acellular pertussis (TdaP); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) for girls.

OBJECTIVE:

To assess implementation of new adolescent vaccination recommendations.

METHODS:

Data from the 2006–2009 National Immunization Survey–Teen, an annual provider-verified random-digit-dial survey of vaccination coverage in US adolescents aged 13 to 17 years, were analyzed. Main outcome measures included percentage of adolescents who received each vaccine according to survey year; potential coverage if all vaccines were administered during the same vaccination visit; and, among unvaccinated adolescents, the reasons for not receiving vaccine.

RESULTS:

Between 2006 and 2009, ≥1 TdaP and ≥1 MenACWY coverage increased from 11% to 56% and 12% to 54%, respectively. Between 2007 and 2009, ≥1 HPV coverage among girls increased from 25% to 44%; between 2008 and 2009, ≥3 HPV coverage increased from 18% to 27%. In 2009, vaccination coverage could have been >80% for Td/TdaP and MenACWY and as high as 74% for the first HPV dose if providers had administered all recommended vaccines during the same vaccination visit. For all years, the top reported reasons for not vaccinating were no knowledge about the vaccine, provider did not recommend, and vaccine is not needed/necessary (for TdaP and MenACWY) and adolescent is not sexually active, no knowledge about the vaccine, and vaccine is not needed/necessary (for HPV).

CONCLUSIONS:

Adolescent vaccination coverage is increasing but could be improved. Strategies are needed to increase parental knowledge about adolescent vaccines and improve provider recommendation and administration of all vaccines during the same visit.
Attitudes Toward Newborn Screening for Cytomegalovirus Infection
Authors: Din Erica S. , Brown Cedric J. , Grosse Scott D. , Wang Chengbin , Bialek Stephanie R. , Ross Danielle S. , Cannon Michael J.
Published: November 2011

OBJECTIVE:

Newborns are not routinely screened for cytomegalovirus (CMV), the leading infectious cause of developmental disability. Congenital CMV satisfies a number of criteria for inclusion in newborn screening, and screening potentially offers benefits. Screening could also introduce harms such as anxiety and unnecessary costs for the families of the substantial proportion of CMV-infected children who never develop CMV-related disabilities. Our objective was to assess attitudes toward newborn screening for CMV.

METHODS:

We analyzed responses to 5 statements about CMV and newborn screening from 3922 participants in the 2009 HealthStyles survey, a national mail survey designed to include a group similar to the US population with respect to gender, age, race/ethnicity, income, and household size. Two-step cluster analysis was performed to identify clusters of parental attitudes.

RESULTS:

The majority of respondents strongly or somewhat agreed that they would want to have their newborn tested for CMV even if it was not performed routinely (84%), they had to pay $20 (87%), or CMV-related problems never developed (84%). Nearly half (47%) of them “would worry that the CMV test would lead to unneeded doctor visits and expenses,” and 32% “think CMV problems are too rare to worry about.” Three clusters of parent respondents were identified on the basis of their attitudes toward CMV screening: “strongly in favor” (31%), “moderately in favor” (49%), and “weakly opposed” (20%).

CONCLUSIONS:

Among most parents, costs, worry, and anxiety associated with newborn screening for CMV would be acceptable. Although attitudes were generally favorable, a minority of the parents were weakly opposed to newborn screening for CMV.
Postmortem small babesia-like morphology of Babesia canis — Short communication
Authors: Demeter Zoltán , Palade Elena , Balogh Éva , Jakab Csaba , Farkas Róbert , Tánczos Balázs , Hornok Sándor
Published: November 2011

Here we report a case of canine babesiosis with unusual morphology of the causative agent. A male, seven-week-old Labrador retriever puppy, exhibiting severe anaemia and haemoglobinuria, was presented at the Clinic of Internal Medicine in February 2011. The puppy was euthanised. The most relevant pathological changes were icterus, severe splenomegaly, generalised lymphadenopathy and haemoglobin nephrosis. Samples were collected from various organs for histology within one hour post mortem. Impression smears were also prepared from the spleen after overnight storage at 4 °C. Tissue sections and smears showed the presence of multiple, coccoid intraerythrocytic bodies that measured 1–2 μm and resembled small babesiae. No large piroplasms were seen. DNA was extracted from the spleen, and a conventional PCR was performed for the amplification of a 450-bp region of the 18S rRNA gene of piroplasms. The causative agent was identified as Babesia canis canis, with 99% sequence identity to other European isolates. Sequence identity to B. gibsoni was only 91%. This is the first account to verify that the morphology of the large canine piroplasm, B. canis, can be uniformly small babesia-like post mortem or following the storage of tissue samples.
Osteoblastic osteosarcoma in a Grey Mouse Lemur (Microcebus murinus) — Short communication
Authors: Liptovszky Mátyás , Perge Edina , Molnár Viktor , Sós Endre
Published: November 2011

The Grey Mouse Lemur (Microcebus murinus) is a nocturnal lemur species that lives only in Madagascar. It is one of the most abundant lemur species and its native populations are not endangered, but animals belonging to this species are rarely exhibited in zoos. While tumours are quite frequently described in other primates, there are very few publications about neoplasia in lemurs. In this case report we describe a mandibular osteoblastic osteosarcoma in a Grey Mouse Lemur (Microcebus murinus). To the best of the authors’ knowledge, this is the first scientific article describing osteosarcoma in a prosimian and also reporting a tumour in the mandible in this taxon.
Solitary adenoma in the proventriculus of a budgerigar (Melopsittacus undulatus) diagnosed by immunochemistry — Short communication
Authors: János Gál , Marosán Miklós , Kozma Attila , Mándoki Míra
Published: November 2011

The authors describe a solitary adenoma in a 5.5-year-old female Budgerigar (Melopsittacus undulatus). The tumour was partially blocking the lumen of the proventriculus and filled it almost completely. Decreased passage of food towards the gizzard and the intestines developed in the bird as result of the obstruction, which periodically hindered the passage, leading to slow emaciation. An epithelial tumour composed of irregular glandular acini was diagnosed by histological examination. Immunohistochemical reaction with pancytokeratin showed a positive cytoplasmic reaction both in the neoplastic and the normal glandular structures.
Effect of the periparturient period on serum lipid and cholesterol lipoprotein concentrations in goats (Capra hircus)
Authors: Skotnicka Ewa , Muszczyński Zbigniew , Suska Maria
Published: November 2011

Blood samples were taken from 12 goats during the periparturient period (4 and 1 weeks before and 2, 10 and 30 days after delivery), and from 10 nonpregnant goats. The following variables were determined: total lipids (TL), triacylglycerol (TG), total cholesterol (TCH) and high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol fractions. One week before delivery TL (2.32 ± 0.12 g/l, P ≤ 0.05), TG (0.32 ± 0.16 mmol/l, P ≤ 0.001) and TCH concentrations (1.65 ± 0.42 mmol/l, P ≤ 0.05) were significantly increased as compared to non-pregnant goats (2.08 ± 0.28 g/l, 0.15 ± 0.05 mmol/l, 1.38 ± 0.19 mmol/l, respectively). After delivery, the concentrations of TL, TG, TCH and HDL decreased significantly. The lowest TG concentration was observed 2 days after delivery (0.18 ± 0.02 mmol/l), while TL (1.73 ± 0.21 g/l), TCH (0.95 ± 0.21 mmol/l) and HDL (0.74 ± 0.16 mmol/l) reached the lowest level 10 days after delivery. Two days after delivery a significant increase of LDL concentration was observed (0.38 ± 0.04 mmol/l); however, ten days after delivery a threefold decrease was shown in the LDL concentration (0.12 ± 0.04 mmol/l). A month after delivery all the variables studied reached levels similar to those measured in non-pregnant goats.
Tetrodotoxin- and resiniferatoxin-induced changes in paracervical ganglion ChAT- and nNOS-IR neurons supplying the urinary bladder in female pigs
Authors: Burliński Piotr , Gonkowski Sławomir , Całka Jarosław
Published: November 2011

The aim of the present study was to establish the effect of intravesical administration of resiniferatoxin (RTX) and tetrodotoxin (TTX) on the chemical coding of paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. In order to identify the PCG neurons innervating the bladder, retrograde tracer Fast Blue was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in the control group 76.82% of Fast Blue positive PCG neurons contain nitric oxide synthetase (nNOS), and 66.92% contain acetylcholine transferase (ChAT). Intravesical infusion of RTX resulted in a reduction of the nNOS-IR neurons to 57.74% and ChAT-IR to 57.05%. Alternative administration of TTX induced an increase of nNOS-IR neurons up to 79.29% and a reduction of the ChAT-IR population down to 3.73% of the Fast Blue positive PCG cells. Our data show that both neurotoxins affect the chemical coding of PCG cells supplying the porcine urinary bladder, but the effects of their action are different. Moreover, these results shed light on the possible involvement of NO-ergic and cholinergic neurons in the mechanisms of therapeutic action exerted by RTX and TTX in curing the overactive bladder disorder.
Impact of oxidative stress on male fertility — A review
Authors: Tvrdá Eva , Kňažická Zuzana , Bárdos László , Massányi Péter , Lukáč Norbert
Published: November 2011

Oxidative stress is a state related to increased cellular damage caused by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). It is a serious condition, as ROS and their metabolites attack DNA, lipids and proteins, alter enzymatic systems and cell signalling pathways, producing irreparable alterations, cell death and necrosis. While small amounts of ROS have been shown to be required for several functions of spermatozoa, their excessive levels can negatively impact the quality of spermatozoa and impair their overall fertilising capacity. These questions have recently attracted the attention of the scientific community; however, research aimed at exploring the role of oxidative stress and antioxidants associated with male fertility is still at its initial stages. This review summarises the current facts available in this field and intends to stimulate interest in basic and clinical research, especially in the development of effective methods for the diagnosis and therapy of semen damage caused by oxidative stress.
Effect of season and photoperiod on the time of first postpartum ovulation in Awassi ewes
Authors: Faigl Vera , Keresztes Mónika , Márton Alíz , Fébel Hedvig , Kulcsár Margit , Nagy Sándor , Cseh Sándor , Solti László , Huszenicza Gyula
Published: November 2011

Seasonal differences in the resumption of postpartum ovarian activity, milk production and periparturient metabolic status were investigated in lactating non-suckling dairy Awassi sheep in two consecutive experiments. In Experiment 1, autumn-lambing (AL, n = 27) and spring-lambing (SL, n = 37) ewes were investigated. Ovarian activity was monitored by means of individual progesterone (P4) profiles from day 5 to day 100 post partum. Most of the AL dams (89%) ovulated till day 35 after parturition and became cyclic thereafter. Incidence of persistent corpus luteum (CLP) and short luteal phases (sCL) was frequent (18% and 29%, respectively) among non-conceiving dams. In contrast, only 24% of the SL ewes ovulated before day 35. P4 levels during the luteal phase were lower in cyclic animals, and the cycle was longer in SL than in AL animals. No CLP or sCL was detected in the spring-lambing group, and 61% of SL ewes remained acyclic till the end of the trial. Lactation length was significantly longer in SL dams than in AL ewes (P = 0.008). According to the plasma metabolites (BHB, NEFA) and metabolic hormones (insulin, IGF-I, thyroxine) examined, negative energy balance did not appear in any of the animals. However, seasonal differences were seen in IGF-I and thyroxine levels, which were higher in the SL dams. In Experiment 2, influence of additional lighting was studied in autumn-lambing ewes. The long-day photoperiod (LD, n = 23) group was exposed to artificial light from sunset till midnight (approx. 16 h light/8 h dark) from some weeks before the expected date of delivery in mid-September until the end of December. The control group (n = 25) experienced only natural daylength. The first postpartum ovulation tended to occur later in the LD animals than in the controls (P = 0.047). The lactation of the LD group tended to be longer (P = 0.061). NEFA, BHB, insulin, IGF-I and thyroxine levels did not differ between the groups. Conclusions: (i) The ovarian function of the Awassi population is seasonal under temperate continental climate conditions. (ii) The first postpartum ovulation of non-suckling, autumn-lambing dams may occur very early, even before the completion of uterine involution. (iii) Additional artificial lighting may delay the time of first postpartum ovulation in AL ewes. (iv) Postpartum negative energy balance is unlikely to occur in dairy Awassi ewes even in high-producing intensive systems.
The physiology of incretins
Authors: Winkler Gábor
Published: November 2011

The discovery of incretins − glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrop peptide (GIP) −, clarification of their physiological properties as well as therapeutic application of incretin-based blood glucose lowering drugs opened new perspectives in the medical management of type 2 diabetes. New results of basic research investigations led to revaluation of the role of GIP in metabolic processes and a more established use of GLP-1 action. The article overviews the most relevant data of production and effects of incretins, as well as future possibilities of their therapeutic use. Orv. Hetil., 2011, 152, 1922–1930.
Soil nutrient supply modulates temperature‐induction cues in mast‐seeding grasses
Authors: Tanentzap Andrew J. , Lee William G. , Coomes David A.
Published: November 2011

Synchronous and intermittent reproduction in long‐lived plants, known as mast seeding, is induced by climatic cues, but the mechanism explaining variation in masting among neighboring but edaphically segregated species is unknown. Soil nutrients can enhance flowering, and thus, populations on nutrient‐rich soils may require less‐favorable growing temperatures to flower. We tested this hypothesis by predicting the probability of flowering in response to air temperature for five species of alpine Chionochloa grasses in South Island, New Zealand, over 37 years and relating our predictions to soil N supply (NH4+ + NO3−). Summer air temperatures better predicted flowering than spring air temperatures, which were correlated with soil N mineralization. Species on N‐rich soils required lower mean temperatures to induce flowering and/or responded more consistently across a gradient of air temperatures, contributing to the higher probability of their tillers and tussocks flowering at low summer temperatures. Our results suggest that flowering primarily occurs in response to warm summer temperatures, but species on N‐rich soils require less favorable growing conditions because they invest relatively less N in seeds. Thus, predicting masting requires a consideration of the interactions among climate, the internal resources of plants, and mineral nutrient uptake.