bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial Experience with Oral Gold Salts in the Treatment of Rheumatoid Arthritis in Patients Followed up for One Year
Authors: Lignère G Chérié , Giavarini S , Longatti S 
Published: September 2014

Fifteen patients, eight males and seven females, suffering from classic or definite rheumatoid arthritis were treated for 1 year with Auranofin*, a new gold salt active by the oral route, different from parenteral gold as far as dosage, mechanism of action and toxicity are concerned. Patients received a dosage of 3 mg twice daily, equivalent to 0·85 mg of elemental gold, in order to evaluate the therapeutic efficacy and tolerability of this new compound. Subjective and objective parameters were monitored during the trial and serum gold levels were assayed every 2 months by atomic absorption spectrophotometry. Our study, which is on-going, shows the therapeutic efficacy of Auranofin which seems better tolerated than parenteral gold salts and will probably become a widely used drug in the long-term treatment of rheumatoid arthritis.
Effects of Buflomedil Hydrochloride in Occlusive Arterial Disease of the Lower Limbs Stage IV
Authors: Briguglio F , Briguglio E , Di Marco V , Swat M , Materia G , Intilisano A 
Published: September 2014

Ten patients affected by occlusive arterial disease and presenting with skin lesions of the limbs were treated with buflomedil first i.v. and then orally, at a dosage of 600 mg/day. After a treatment period of 30 to 60 days, eight patients showed lesion regression with complete recovery; the remaining two patients dropped out of the study. The mechanism of action of buflomedil in healing skin lesions is also discussed.
The Steady-State Pharmacokinetics of Tamoxifen and its Metabolites in Breast Cancer Patients
Authors: Soininen Kari , Kleimola Terttu , Elomaa Inkeri , Salmo Matti , Rissanen Pentti 
Published: September 2014

The steady-state pharmacokinetics of tamoxifen and its metabolites was studied in sixteen patients with advanced mammary cancer. Patients were randomized to receive tamoxifen given as Tamofen®, Leiras, or as Nolvadex®, ICI, 20 mg twice daily for 16 weeks in a cross-over study. Plasma and urine samples were analyzed during one dose interval (12 h) after treatment for 8 and 16 weeks. The concentrations of tamoxifen, N-desmethyltamoxifen, N,N-desdimethyltamoxifen, and metabolite Y were determined in plasma and the areas under the plasma level curves were calculated. 4-Hydroxytamoxifen was not found in plasma. In urine samples only tamoxifen and N-desmethyltamoxifen were above the detection limits even though metabolite Y was also analyzed after acid hydrolysis. There were no statistically significant differences in the concentrations of tamoxifen and its metabolites between the two preparations. The results of nonresponders did not differ from those of responders. Liver metastases had no effect on the metabolism of tamoxifen.
Breast cancer mortality trends in Italy by region and screening programme, 1980–2008
Authors: Gorini Giuseppe , Zappa Marco , Cortini Barbara , Martini Andrea , Mantellini Paola , Ventura Leonardo , Carreras Giulia 
Published: September 2014

Objectives To describe trends in breast cancer mortality in 14 Italian regions representing 90% of the Italian population, and in the country overall, in relation to the diffusion of organized or opportunistic breast cancer screening programmes. Settings: Breast cancer mortality figures from 1980–2008 in Italy and 14 Italian regions were retrieved from the National Statistics Institute. Methods Estimated annual percent change (EAPC) was calculated for three time-periods (1980–1989, 1990–1999, 2000–2008). To estimate the age-adjusted and age-specific EAPC, trends in mortality based on annual data were examined using a log-linear regression model, and the year of death as a regressor variable. Results In the period 1980–1989 an increasing trend was observed in Italy overall (EAPC = +1.1%; 95% confidence interval [95%CI]: + 0.9%; + 1.3%) and in the 14 regions. In the second decade a decreasing trend was recorded both overall in Italy (EAPC = −1.6%; 95CI:−1.8%;−1.4%) and in all the regions. Between 2000–2008 a slightly decreasing trend was observed in Italy overall (EAPC = −0.8%; 95%CI:−1.0%;−0.5%). A steeper and earlier decrease compared with the rest of Italy was observed in 1990–1999 in Liguria (EAPC = −3.1%; 95%CI:−4.0%,−2.1%), Lombardy (EAPC = −2.3%; 95%CI:−2.8%;−1.9%), and Tuscany (EAPC = −3.0%; 95%CI:−3.7%;−2.2%), mainly due to the 55–64 age−group. There were significant EAPCs between −4.1% and −3.7% in these three regions, 2.5–3.0 times greater than in the rest of Italy (EAPC = −1.4%). Conclusions This earlier decline in three Italian regions could be partially attributable to local organized screening programmes implemented earlier than in the rest of Italy, and to opportunistic screening that became more common in 1990s.
End of life care: The experiences of advance care planning amongst family caregivers of people with advanced dementia – A qualitative study
Authors: Ashton Susan Elizabeth , Roe Brenda , Jack Barbara , McClelland Bob 
Published: September 2014

Background End of life decisions for people with advanced dementia are reported as often being difficult for families as they attempt to make appropriate and justified decisions. Aim To explore the experiences of advance care planning amongst family caregivers of people with advanced dementia. Design Qualitative research including a series of single cases (close family relatives). Methods A purposive sample of 12 family caregivers within a specialist dementia unit was interviewed about their experiences of advance care planning between August 2009 and February 2010. Results/Findings Family caregivers need encouragement to ask the right questions during advance care planning to discuss the appropriateness of nursing and medical interventions at the end of life. Conclusions Advance care planning can be facilitated with the family caregiver in the context of everyday practice within the nursing home environment for older people with dementia.
The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells
Authors: Staber Philipp B. , Zhang Pu , Ye Min , Welner Robert S. , Levantini Elena , Di Ruscio Annalisa , Ebralidze Alexander K. , Bach Christian , Zhang Hong , Zhang Junyan , Vanura Katrina , Delwel Ruud , Yang Henry , Huang Gang , Tenen Daniel G. 
Published: September 2014

Key Points
Runx factors are critical for HSC function, preventing HSC exhaustion by maintaining levels of PU.1. Runx factors are required for leukemia survival by maintaining the stemness of leukemic cells through their downstream target PU.1.
Impact of interferon-γ on hematopoiesis
Authors: de Bruin Alexander M. , Voermans Carlijn , Nolte Martijn A. 
Published: September 2014

AbstractThe proinflammatory cytokine interferon-γ (IFN-γ) is well known for its important role in innate and adaptive immunity against intracellular infections and for tumor control. Yet, it has become clear that IFN-γ also has a strong impact on bone marrow (BM) output during inflammation, as it affects the differentiation of most hematopoietic progenitor cells. Here, we review the impact of IFN-γ on hematopoiesis, including the function of hematopoietic stem cells (HSCs) and more downstream progenitors. We discuss which hematopoietic lineages are functionally modulated by IFN-γ and through which underlying molecular mechanism(s). We propose the novel concept that IFN-γ acts through upregulation of suppressor of cytokine signaling molecules, which impairs signaling of several cytokine receptors. IFN-γ has also gained clinical interest from different angles, and we discuss how chronic IFN-γ production can lead to the development of anemia and BM failure and how it is involved in malignant hematopoiesis. Overall, this review illustrates the wide-ranging effect of IFN-γ on the (patho-)physiological processes in the BM.
Early exposure to bio-contaminants and asthma up to 10 years of age: results of the HITEA study
Authors: Tischer Christina , Casas Lidia , Wouters Inge M. , Doekes Gert , Garcia-Esteban Raquel , Gehring Ulrike , Hyvärinen Anne , Oldenwening Marieke , Kerkhof Marjan , Sunyer Jordi , Standl Marie , Thiering Elisabeth , Torrent Maties , Heinrich Joachim 
Published: September 2014

Inverse associations have been found between exposure to bio-contaminants and asthma and allergies. The aim of this study was to prospectively assess whether early exposure to bio-contaminants in dust is associated with asthma and allergy later in childhood among children from (sub)-urban areas.In subsets of three European birth cohorts (PIAMA: n=553; INMA: n=481; and LISAplus: n=395), endotoxin, (1,3,)-β-d-glucan and extracellular polysaccharide were measured in dust from living rooms shortly after birth. Current asthma at 6 years and 10 years of age and ever asthma up to 10 years of age were assessed by parental questionnaires. Specific IgE levels at 8 years (PIAMA) and 10 years (LISAplus) were available. Adjusted, cohort-specific logistic regression analyses were performed.Higher endotoxin concentrations were positively associated with current asthma at 6 years of age in PIAMA (adjusted OR 1.96, 95% CI 1.07–3.58), but were inversely related with ever asthma up to 10 years of age in INMA (adjusted OR 0.39, 95% CI 0.16–0.94). No associations with asthma were found for LISAplus. No associations were observed with atopic sensitisation in all cohorts. All associations with (1,3)-β-d-glucan and extracellular polysaccharide were statistically nonsignificant.The suggested immunological mechanisms of early exposure to bio-contaminants with regards to asthma and allergy might be different for children growing up in (sub)-urban environments.
Microscopic observation drug susceptibility assay for the diagnosis of TB and MDR-TB in HIV-infected patients: a systematic review and meta-analysis
Authors: Wikman-Jorgensen Philip , Llenas-García Jara , Hobbins Michael , Ehmer Jochen , Abellana Rosa , Gonçalves Alessandra Queiroga , Pérez-Porcuna Tomàs Maria , Ascaso Carlos 
Published: September 2014

The objective of the present study was to assess the diagnostic accuracy of the microscopic observation drug susceptibility (MODS) assay for tuberculosis (TB) diagnosis in HIV-infected patients.MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, African Index Medicus, ResearchGate, SciELO, and the abstracts of the main conferences on infectious diseases and tropical medicine were searched, and other sources investigated. Only studies including HIV-infected patients evaluating MODS for the diagnosis of TB and using culture-based diagnostic tests as a gold standard were analysed. Summary sensitivity and specificity were calculated with a bivariate model.3259 citations were found, 29 were selected for full-text review and 10 studies including 3075 samples were finally analysed. Overall diagnostic accuracy of MODS for the diagnosis of TB was a sensitivity of 88.3% (95% CI 86.18–90.2%) and specificity 98.2% (95% CI 97.75–98.55%). For multidrug-resistant (MDR)-TB, sensitivity was 89% (95% CI 66.07–97%) and specificity was 100% (95 CI 94.81–100%). For smear-negative pulmonary TB, a sensitivity of 88.2% (95% CI 86.1–89.9%) and specificity of 98.2% (95% CI 96.8–98.9%) were found. Costs varied between USD 0.72 and 7.31 per sample. Mean time to positivity was 8.24 days.MODS was found to have a good accuracy for the diagnosis of TB and MDR-TB in HIV-infected patients with low cost and fast results.
Macrophage activation, age and sex effects of immunometabolism in obese asthma
Authors: Periyalil Hashim A. , Wood Lisa G. , Scott Hayley A. , Jensen Megan E. , Gibson Peter G. 
Published: September 2014

Obese asthma is characterised by infiltration of adipose tissue by activated macrophages and mast cells. The aim of this study was to examine the age and sex effects of immunometabolism in obese asthma.Obese and non-obese asthmatic children and adults underwent spirometry, body composition assessment by dual energy X-ray absorptiometry and measurement of serum soluble CD163 (sCD163), tryptase, C-reactive protein (CRP) and other adipocytokines.Plasma CRP (p<0.01) and leptin (p<0.01) were elevated in obese asthmatic adults, and sCD163 (p=0.003) was elevated in obese asthmatic children. We observed significantly higher sCD163 in obese female children compared to obese female adults and male children, and higher CRP in obese female adults compared to obese male children and adults. Serum tryptase concentrations were not significantly different across age groups. sCD163 positively correlated with the proportion of android fat in obese female children (r=0.70, p=0.003) and obese female adults (r=0.65, p=0.003). In obese female children, sCD163 was inversely associated with forced expiratory volume in 1 s % predicted (r=−0.55, p=0.02) and was positively associated with the Asthma Control Questionnaire (r=0.57, p=0.02).Obese children with asthma have sex-specific macrophage activation, which may contribute to worse asthma control and lung function. The heterogeneous systemic inflammatory profile across age and sex suggests the existence of sub-phenotypes in obese asthma at the molecular level.
Generalized inequalities on warped product submanifolds in nearly trans-Sasakian manifolds
Authors: Mustafa Abdulqader , Uddin Siraj , Wong Bernardine Renaldo 
Published: September 2014

AbstractIn this paper, we study warped product submanifolds of nearly trans-Sasakian manifolds. The non-existence of warped product semi-slant submanifolds of typeNθ×fNTis shown, whereas some characterization and new geometric obstructions are obtained for the warped products of typeNT×fNθ. We establish two general inequalities for the squared norm of the second fundamental form. The first inequality generalizes derived inequalities for some contact metric manifolds (Kadriet al.in J. Korean Math. Soc. 42:1101-1110, 2005; Munteanu in Publ. Math. (Debr.) 66:75-120, 2005; Mustafaet al.in Taiwan. J. Math. 17:1473-1486, 2013; Uddin and Khan in J. Inequal. Appl. 2012:304, 2012), while by a new technique, the second inequality is constructed to express the relation between extrinsic invariant (second fundamental form) and intrinsic invariant (scalar curvatures). The equality cases are also discussed.MSC:53C40, 53C42, 53C15.
Do federal and state audits increase compliance with a grant program to improve municipal infrastructure (AUDIT study): study protocol for a randomized controlled trial
Authors: De La O Ana L , Martel García Fernando 
Published: September 2014

Abstract
Background
Poor governance and accountability compromise young democracies’ efforts to provide public services critical for human development, including water, sanitation, health, and education. Evidence shows that accountability agencies like superior audit institutions can reduce corruption and waste in federal grant programs financing service infrastructure. However, little is know about their effect on compliance with grant reporting and resource allocation requirements, or about the causal mechanisms. This study protocol for an exploratory randomized controlled trial tests the hypothesis that federal and state audits increase compliance with a federal grant program to improve municipal service infrastructure serving marginalized households.

Methods/Design
The AUDIT study is a block randomized, controlled, three-arm parallel group exploratory trial. A convenience sample of 5 municipalities in each of 17 states in Mexico (n=85) were block randomized to be audited by federal auditors (n=17), by state auditors (n=17), and a control condition outside the annual program of audits (n=51) in a 1:1:3 ratio. Replicable and verifiable randomization was performed using publicly available lottery numbers. Audited municipalities were included in the national program of audits and received standard audits on their use of federal public service infrastructure grants. Municipalities receiving moderate levels of grant transfers were recruited, as these were outside the auditing sampling frame – and hence audit program – or had negligible probabilities of ever being audited. The primary outcome measures capture compliance with the grant program and markers for the causal mechanisms, including deterrence and information effects. Secondary outcome measure include differences in audit reports across federal and state auditors, and measures like career concerns, political promotions, and political clientelism capturing synergistic effects with municipal accountability systems. The survey firm and research assistants assessing outcomes were blind to treatment status.

Discussion
This study will improve our understanding of local accountability systems for public service delivery in the 17 states under study, and may have downstream policy implications. The study design also demonstrates the use of verifiable and replicable randomization, and of sequentially partitioned hypotheses to reduce the Type I error rate in multiple hypothesis tests.

Trial registration
Controlled-trials.com Identifier ISRCTN22381841: Date registered 02/11/2012
Optimization of a Cisplatin Model of Chemotherapy-Induced Peripheral Neuropathy in Mice: Use of Vitamin C and Sodium Bicarbonate Pretreatments to Reduce Nephrotoxicity and Improve Animal Health Status
Authors: Guindon Josée , Deng Liting , Fan Baochang , Wager-Miller Jim , Hohmann Andrea G 
Published: September 2014

Background: Cisplatin, a platinum-derived chemotherapeutic agent, produces antineoplastic effects coupled with toxic neuropathic pain and impaired general health status. These side-effects complicate long term studies of neuropathy or analgesic interventions in animals. We recently demonstrated that pretreatment with sodium bicarbonate (4% NaHCO3) prior to cisplatin (3 mg/kg i.p. weekly up to 5 weeks) was associated with improved health status (i.e. normal weight gain, body temperature, creatinine and ketone levels, and kidney weight ratio) in rats (Neurosci Lett 544:41–46, 2013). To reduce the nephrotoxic effects of cisplatin treatment in mice, we compared effects of sodium bicarbonate (4% NaHCO3 s.c.), vitamin C (25 mg/kg s.c.), resveratrol (25 mg/kg s.c)*** and saline (0.9% NaCl) pretreatment on cisplatin-induced changes in animal health status, neuropathic pain and proinflammatory cytokine levels in spinal cord and kidney. Results: Cisplatin-treated mice receiving saline pretreatment exhibited elevated ketone, creatinine and kidney weight ratios, representative of nephrotoxicity. Vitamin C and sodium bicarbonate lowered creatinine/ketone levels and kidney weight ratio whereas resveratrol normalized creatinine levels and kidney weight ratios similar to saline pretreatment. All pretreatments were associated with decreased ketone levels compared to saline pretreatment. Cisplatin-induced neuropathy (i.e. mechanical and cold allodynia) developed equivalently in all pretreatment groups and was similarly reversed by either morphine (6 mg/kg i.p.) or ibuprofen (6 mg/kg i.p.) treatment. RT-PCR showed that mRNA levels for IL-1β were increased in lumbar spinal cord of cisplatin-treated groups pretreated with either saline, NaHCO3 or resveratrol/cisplatin-treated groups. However, IL-6 and TNF-alpha were elevated in the kidneys in all cisplatin-treated groups. Our studies also demonstrate that 60 days after the last cisplatin treatment, body weight, body temperature, kidney functions and mRNA levels have returned to baseline although the neuropathic pain (mechanical and cold) is maintained. Conclusions: Studies employing cisplatin should include NaHCO3 or vitamin C pretreatment to improve animal health status and reduce nephrotoxicity (lower creatinine and kidney weight ratio) without affecting the development of chemotherapy-induced neuropathy or analgesic efficacy.
Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ
Authors: Estévez Laura G , Suarez-Gauthier Ana , García Elena , Miró Cristina , Calvo Isabel , Fernández-Abad María , Herrero Mercedes , Marcos Manuel , Márquez Cristina , Lopez Ríos Fernando , Perea Sofía , Hidalgo Manuel 
Published: September 2014

Abstract
Introduction
Human epidermal growth factor receptor 2 (HER2) amplification is frequent in ductal carcinoma in situ (DCIS) of the breast and is associated with poorly differentiated tumors and adverse prognosis features. This study aimed to determine the molecular effects of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS.

Methods
Patients with HER2 positive DCIS received 1,500 mg daily of lapatinib for four consecutive weeks prior to surgical resection. Magnetic resonance imaging (MRI) was used to determine changes in tumor volume. The molecular effects of lapatinib on HER2 signaling (PI3K/AKT and RAS/MAPK pathways), cell proliferation (Ki67 and p27) and apoptosis (TUNEL) were determined in pre and post-lapatinib treatment samples.

Results
A total of 20 patients were included. Lapatinib was well tolerated with only minor and transient side effects. The agent effectively modulated HER2 signaling decreasing significantly pHER2 and pERK1 expression, together with a decrease in tumor size evaluated by MRI. There was no evidence of changes in Ki67.

Conclusions
Four weeks of neoadjuvant lapatinib in patients with HER2-positive DCIS resulted in inhibition of HER2 and RAS/MAPK signaling pathway.

Trial registration
2008-004492-21 (Registered June 25th 2008).
Coordinative interaction of microcrystalline chitosan with oxovanadium (IV) ions in aqueous solution
Authors: Lichawska Marta E , Bodek Kazimiera H , Jezierska Julia , Kufelnicki Aleksander 
Published: September 2014

Abstract

Background
Chitosan, a non-toxic, biodegradable and biocompatible polysaccharide has attained great interest in pharmaceutical applications, as versatile drug delivery agent. Chitosan has been already shown to serve as vehicle for sustained drug release by chitosan-vanadium(IV) complex from a chitosan gel matrix. Therefore, chitosan gel proved to retain vanadium and preserve its insulin-mimetic efficacy. Nevertheless, there is a lack of reports concerning complexing equilibria in aqueous solution, in particular when using the more advantageous microcrystalline form of chitosan (MCCh). Microcrystalline chitosan shows a number of valuable features as compared with unmodified chitosan.

Results
Experimental studies on complexing interaction between a special form of biomaterial - microcrystalline chitosan as ligand, L = MCCh, of two exemplary degrees of deacetylation DD (lower 79.8%; higher 97.7%) with M = oxovanadium (IV) ions have been carried out potentiometrically at four ligand-to-metal concentration ratios (2:1, 5:1, 8:1, 10:1). Among the five hydrolysis equilibria of VO2+ reported up to now in the literature, under the conditions of the present work i.e. aqueous solutions of ionic strength I = 0.1 (KNO3) and temperature 25.0 ± 0.1°C, the predominating one was (VO)2(OH)2
2+ formation: log β
20-2 = -7.01(2). Analysis of potentiometric results permitted to note that degree of deacetylation does not essentially influence the coordination mode of the complexes formed. In the case of both the two DD values, as well as for all the ligand-to-metal ratios, formation of hydroxyl deprotonated MLH-1 and ML2H-2 moieties has been confirmed potentiometrically (log β
11-1 = -0.68(2) for DD = 79.8% and -0.68(2) for DD = 97.7%, log β
12-2 = -7.64(6) for DD = 79.8% and -5.38(7) for DD = 97.7%).

Conclusion
Microcrystalline chitosan coordinates the vanadyl ions by the hydroxyl groups. Interaction of MCCh with VO2+ ions in aqueous solution occurs within pH 5-7. Amounts of alkali excessive towards -NH2 are needed to deprotonate the OH groups. Deprotonation occurring at the chitosan hydroxyl groups permits a “pendant” or “bridge” model of coordination with VO(IV). Lack of complexation via deprotonation of amine groups, typical for simple cations and the molybdenum anion, has been indicated also by FTIR spectroscopy and EPR.