bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diminazene aceturate (Berenil) modulates LPS induced pro-inflammatory cytokine production by inhibiting phosphorylation of MAPKs and STAT proteins
Authors: Kuriakose Shiby , Muleme Helen , Onyilagha Chukwunonso , Okeke Emeka , Uzonna Jude E 
Published: November 2013

Although diminazene aceturate (Berenil) is widely used as a trypanolytic agent in livestock, its mechanisms of action remain poorly understood. We previously showed that Berenil treatment suppresses pro-inflammatory cytokine production by splenic and liver macrophages leading to a concomitant reduction in serum cytokine levels in mice infected with Trypanosoma congolense or challenged with LPS. Here, we investigated the molecular mechanisms through which Berenil alters pro-inflammatory cytokine production by macrophages. We show that pre-treatment of macrophages with Berenil dramatically suppressed IL-6, IL-12 and TNF-α production following LPS, CpG and Poly I:C stimulation without altering the expression of TLRs . Instead, it significantly down-regulated phosphorylation of mitogen-activated protein kinases (p38, extracellular signal-regulated kinase and c-Jun N-terminal kinases), signal transducer and activator of transcription (STAT) proteins (STAT1 and STAT3) and NF-кB p65 activity both in vitro and in vivo. Interestingly, Berenil treatment up-regulated the phosphorylation of STAT5 and the expression of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, which are negative regulators of innate immune responses, including MAPKs and STATs. Collectively, these results show that Berenil down-regulates macrophage pro-inflammatory cytokine production by inhibiting key signaling pathways associated with cytokine production and suggest that this drug may be used to treat conditions caused by excessive production of inflammatory cytokines.
Eradication of non-Hodgkin lymphoma through the induction of tumor-specific T-cell immunity by CD20-Flex BiFP
Authors: Zhao Lei , Tong Qin , Qian Weizhu , Li Bohua , Zhang Dapeng , Fu Tuo , Duan Shuyan , Zhang Xueguang , Zhao Jian , Dai Jianxin , Wang Hao , Hou Sheng , Guo Yajun 
Published: November 2013

Key Points
Targeting of both CD20 and Flt3 proteins by CrossMab technology can efficiently evoke tumor-specific T-cell immunity. Induction of tumor-specific T-cell response by CD20–Flt3 ligand extracellular domain BiFP provides a long-lasting protection from tumor recurrence.
Measuring central pulmonary pressures during exercise in COPD: how to cope with respiratory effects
Authors: Boerrigter Bart G. , Waxman Aaron B. , Westerhof Nico , Vonk-Noordegraaf Anton , Systrom David M. 
Published: November 2013

Respiratory influences are major confounders when evaluating central haemodynamics during exercise. We studied four different methods to assess mean pulmonary artery pressure (mPAP) and pulmonary capillary wedge pressure (PCWP) in cases of respiratory swings.Central haemodynamics were measured simultaneously with oesophageal pressure during exercise in 30 chronic obstructive pulmonary disease (COPD) patients. mPAP and PCWP were assessed at the end of expiration, averaged over the respiratory cycle and corrected for the right atrial pressure (RAP) waveform estimated intrathoracic pressure, and compared with the transmural pressures.Bland–Altman analyses showed the best agreement of mPAP averaged over the respiratory cycle (bias (limits of agreement) 2.5 (-6.0–11.8) mmHg) and when corrected with the nadir of RAP (-3.6 (-11.2–3.9) mmHg). Measuring mPAP at the end of expiration (10.3 (0.5–20.3) mmHg) and mPAP corrected for the RAP swing (-9.3 (-19.8–2.1) mmHg) resulted in lower levels of agreement. The respiratory swings in mPAP and PCWP were similar (r2=0.82, slope±se0.95±0.1).Central haemodynamics measured at the end of expiration leads to an overestimation of intravascular pressures in exercising COPD patients. Good measurement can be acquired even when oesopghageal pressure is omitted, by averaging pressures over the respiratory cycle or using the RAP waveform to correct for intrathoracic pressure. Assessment of the pulmonary gradient is unaffected by respiratory swings.
Longitudinal relationship between physical activity and lung health in patients with cystic fibrosis
Authors: Schneiderman Jane E. , Wilkes Donna L. , Atenafu Eshetu G. , Nguyen Thanh , Wells Greg D. , Alarie Nancy , Tullis Elizabeth , Lands Larry C. , Coates Allan L. , Corey Mary , Ratjen Felix 
Published: November 2013

Exercise is beneficial for patients with cystic fibrosis (CF) but long-term effects of physical activity on lung function evolution are unknown. We evaluated the longitudinal relationship between changes in habitual physical activity (HPA) and rate of decline in lung function in patients with CF.We tracked HPA using the Habitual Activity Estimation Scale, forced expiratory volume in 1 s (FEV1) and Stage I exercise tests in 212 patients with CF over a 9-year period.Adjusting for sex, baseline age and FEV1, mucoidPseudomonas aeruginosaand CF-related diabetes, mean±sdFEV1% predicted decreased by 1.63±0.08% per year (p<0.0001) while mean±sdHPA increased by 0.28±0.03 h·day−1per year (p<0.0001) over the study period. A greater increase in HPA was associated with a slower rate of decline in FEV1(r=0.19, p<0.0069). Dividing subjects into “high” and “low” activity (above or below the mean rate of change of activity, respectively), a steeper rate of FEV1decline was observed for low (-1.90% per year) compared to high (-1.39% per year) (p=0.002).Increases in HPA are feasible despite progression of lung disease and are associated with a slower rate of decline in FEV1, highlighting the benefit of regular physical activity, and its positive impact on lung function in patients with CF.
IDSA/ATS minor criteria aid pre-intensive care unit resuscitation in severe community-acquired pneumonia
Authors: Lim Hui Fang , Phua Jason , Mukhopadhyay Amartya , Ngerng Wang Jee , Chew Mei Ying , Sim Tiong Beng , Kuan Win Sen , Mahadevan Malcolm , Lim Tow Keang 
Published: November 2013

The effect of employing severity scores to identify severe community-acquired pneumonia (SCAP) cases for early aggressive resuscitation is unknown. Optimising pre-intensive care unit (ICU) care may improve outcomes in patients at risk of SCAP.We conducted a before-and-after study of patients classified into control and intervention groups (January 2004 to December 2007 and January 2008 to December 2010, respectively). Our intervention was two-pronged, using the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) minor criteria to identify SCAP for aggressive emergency department resuscitation. Patients with SCAP, defined as those with three or more IDSA/ATS minor criteria, were targeted. Differences in mortality, triage and compliance with emergency department resuscitation were compared between the groups.The hospital mortality rate was lower in the interventionversusthe control group (5.7%versus23.8%, p<0.001). On multivariate analysis, the intervention group was associated with lower mortality (OR 0.24, 95% CI 0.09–0.67). ICU admission rates decreased from 52.9% to 38.6% (p=0.008) and inappropriately delayed ICU admissions decreased from 32.0% to 14.8% (p<0.001). There was increased compliance with the aggressive resuscitation protocol after the intervention.A combined intervention, using a pneumonia score to identify those at risk of SCAP early and an aggressive pre-ICU resuscitation protocol may reduce mortality and ICU admissions.
Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study
Authors: Mahler Donald A. , Decramer Marc , D'Urzo Anthony , Worth Heinrich , White Tracy , Alagappan Vijay K.T. , Chen Hungta , Gallagher Nicola , Kulich Károly , Banerji Donald 
Published: November 2013

We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate-to-severe chronic obstructive pulmonary disease.In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once-daily QVA149 110/50 μg, placebo or tiotropium 18 μg. Superiority of QVA149versusplacebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoeaviathe self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety.After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149versusplacebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0–4 h post-doseversusplacebo and tiotropium at day 1 and week 6 (all p<0.001). Rescue medication use was significantly lower with QVA149versusplacebo (p<0.001) and tiotropium (p=0.002). All treatments were well tolerated.Once-daily QVA149 provided superior improvements in patient-reported dyspnoea and lung functionversusplacebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication.
A low-cost, multiplexable, automated flow cytometry procedure for the characterization of microbial stress dynamics in bioreactors
Authors: Brognaux Alison , Han Shanshan , Sørensen Søren J , Lebeau Frédéric , Thonart Philippe , Delvigne Frank 
Published: November 2013

AbstractBackgroundMicrobial cell population heterogeneity is now recognized as a major source of issues in the development and optimization of bioprocesses. Even if single cell technologies are available for the study of microbial population heterogeneity, only a few of these methods are available in order to study the dynamics of segregation directly in bioreactors. In this context, specific interfaces have been developed in order to connect a flow cytometer directly to a bioreactor for automated analyses. In this work, we propose a simplified version of such an interface and demonstrate its usefulness for multiplexed experiments.ResultsA low-cost automated flow cytometer has been used in order to monitor the synthesis of a destabilized Green Fluorescent Protein (GFP) under the regulation of thefispromoter and propidium iodide (PI) uptake. The results obtained showed that the dynamics of GFP synthesis are complex and can be attributed to a complex set of biological parameters, i.e. on the one hand the release of protein into the extracellular medium and its uptake modifying the activity of the fis promoter, and on the other hand the stability of the GFP molecule itself, which can be attributed to the protease content and energy status of the cells. In this respect, multiplexed experiments have shown a correlation between heat shock and ATP content and the stability of the reporter molecule.ConclusionThis work demonstrates that a simplified version of on-line FC can be used at the process level or in a multiplexed version to investigate the dynamics of complex physiological mechanisms. In this respect, the determination of new on-line parameters derived from automated FC is of primary importance in order to fully integrate the power of FC in dedicated feedback control loops.
NLRP3 promotes autophagy of urate crystals phagocytized by human osteoblasts
Authors: Allaeys Isabelle , Marceau François , Poubelle Patrice E 
Published: November 2013

Abstract
Introduction
Monosodium urate (MSU) microcrystals present in bone tissues of chronic gout can be ingested by nonprofessional phagocytes like osteoblasts (OBs) that express NLRP3 (nucleotide-binding domain and leucine-rich repeat region containing family of receptor protein 3). MSU is known to activate NLRP3 inflammasomes in professional phagocytes. We have identified a new role for NLRP3 coupled to autophagy in MSU-stimulated human OBs.

Methods
Normal human OBs cultured in vitro were investigated for their capacity for phagocytosis of MSU microcrystals by using confocal microscopy. Subsequent mineralization and matrix metalloproteinase activity were evaluated, whereas regulatory events of phagocytosis were deciphered by using signaling inhibitors, phosphokinase arrays, and small interfering RNAs. Statistics were carried out by using paired or unpaired t tests, and the one-way ANOVA, followed by multiple comparison test.

Results
Most of the OBs internalized MSU in vacuoles. This process depends on signaling via PI3K, protein kinase C (PKC), and spleen tyrosine kinase (Syk), but is independent of Src kinases. Simultaneously, MSU decreases phosphorylation of the protein kinases TOR (target of rapamycin) and p70S6K. MSU activates the cleavage of microtubule-associated protein light chain 3 (LC3)-I into LC3-II, and MSU microcrystals are coated with GFP-tagged LC3. However, MSU-stimulated autophagy in OBs absolutely requires the phagocytosis process. We find that MSU upregulates NLRP3, which positively controls the formation of MSU-autophagosomes in OBs. MSU does not increase death and late apoptosis of OBs, but reduces their proliferation in parallel to decreasing their competence for mineralization and to increasing their matrix metalloproteinase activity.

Conclusions
MSU microcrystals, found locally encrusted in the bone matrix of chronic gout, activate phagocytosis and NLRP3-dependent autophagy in OBs, but remain intact in permanent autophagosomes while deregulating OB functions.
Ixmyelocel-T, an expanded multicellular therapy, contains a unique population of M2-like macrophages
Authors: Ledford Kelly J , Zeigler Frank , Bartel Ronnda L 
Published: November 2013

Abstract
Introduction
M2 macrophages promote tissue repair and regeneration through various mechanisms including immunomodulation and scavenging of tissue debris. Delivering increased numbers of these cells to ischemic tissues may limit tissue injury and promote repair. Ixmyelocel-T is an expanded, autologous multicellular therapy cultured from bone-marrow mononuclear cells (BMMNCs). The purpose of this study was to characterize further a unique expanded population of M2-like macrophages, generated in ixmyelocel-T therapy.

Methods
Approximately 50 ml of whole bone marrow was obtained from healthy donors and shipped overnight. BMMNCs were produced by using density-gradient separation and cultured for approximately 12 days to generate ixmyelocel-T. CD14+ cells were isolated from ixmyelocel-T with positive selection for analysis. Cell-surface phenotype was examined with flow cytometry and immunofluorescence, and expression of cytokines and chemokines was analyzed with enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR was used to analyze expression of genes in BMMNCs, ixmyelocel-T, the CD14+ population from ixmyelocel-T, and M1 and M2 macrophages. Ixmyelocel-T was cultured with apoptotic BMMNCs, and then visualized under fluorescence microscopy to assess efferocytosis.

Results
Macrophages in ixmyelocel-T therapy expressed surface markers of M2 macrophages, CD206, and CD163. These cells were also found to express several M2 markers, and few to no M1 markers. After stimulation with lipopolysaccharide (LPS), they showed minimal secretion of the proinflammatory cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) compared with M1 and M2 macrophages. Ixmyelocel-T macrophages efficiently ingested apoptotic BMMNCs.

Conclusions
Ixmyelocel-T therapy contains a unique population of M2-like macrophages that are characterized by expression of M2 markers, decreased secretion of proinflammatory cytokines after inflammatory stimuli, and efficient removal of apoptotic cells. This subpopulation of cells may have a potential role in tissue repair and regeneration.
Potential beneficial effects of ixmyelocel-T in the treatment of atherosclerotic diseases
Authors: Ledford Kelly J , Murphy Nikki , Zeigler Frank , Bartel Ronnda L 
Published: November 2013

Abstract
Introduction
Advanced atherosclerotic lesions are characterized by lipid accumulation, inflammation, and defective efferocytosis. An ideal therapy should address all aspects of this multifactorial disease. Ixmyelocel-T therapy, an expanded autologous multicellular therapy showing clinical promise in the treatment of diseases associated with advanced atherosclerosis, includes a novel population of M2-like macrophages. Here, we examine the macrophages of ixmyelocel-T and determine their ability to influx modified cholesterol in an atheroprotective manner, maintaining cholesterol homeostasis and preventing cellular dysfunction and death, ultimately promoting reverse cholesterol efflux.

Methods
Approximately 50 ml of whole bone marrow was obtained from healthy donors and shipped overnight. Bone marrow mononuclear cells (BMMNCs) were produced by using density gradient separation and cultured for approximately 12 days to generate ixmyelocel-T. CD14+ cells were isolated from ixmyelocel-T via positive selection for analysis. Ixmyelocel-T and human leukemia monocyte (THP-1) cells were loaded with acetylated low-density lipoprotein (Ac-LDL) for analysis. Flow cytometry and immunofluorescence were used to examine Ac-LDL uptake, expression of cytokines was analyzed by enzyme-linked immunofluorescence assay (ELISA), and quantitative real-time PCR was used to analyze expression of cholesterol-transport genes. Both the in vitro cholesterol efflux assay and in vivo reverse cholesterol transport assay were used to examine cholesterol transport.

Results
Ixmyelocel-T macrophages take up acetylated low-density lipoprotein and express the scavenger receptors CD36 and scavenger receptor-B1 (SR-B1). Ixmyelocel-T did not become apoptotic or proinflammatory after lipid loading. The cholesterol transporter genes ABAC1 and ABCG1 were both statistically significantly upregulated when ixmyelocel-T macrophages were loaded with cholesterol. Ixmyelocel-T also exhibited enhanced apolipoprotein A-I (ApoAI)-mediated cholesterol efflux. In addition, in vivo reverse cholesterol-transport assay demonstrated that ixmyelocel-T was able to efflux cholesterol in this model.

Conclusions
Ixmyelocel-T macrophages influx modified cholesterol, remained anti-inflammatory in the face of lipid loading and inflammatory challenge, and displayed enhanced cholesterol efflux capabilities. These combined features suggest that this autologous multicellular therapy may exert beneficial effects in atherosclerotic diseases.
Use of seclusion for managing behavioural disturbance in
patients
Authors: Newton-Howes Giles 
Published: November 2013

SummarySeclusion is a tool used by psychiatrists primarily to manage aggressive and
disturbed behaviour that is presumed to be due to the patient's mental
disorder. In most parts of the world there are guidelines to using seclusion
that are designed to maximise a patient's freedoms and protect their liberty
while providing a safe environment. Arguments against the use of seclusion
revolve around the deprivation of liberty, the potential for misuse and the
concept of seclusion as a form of social control, and patients generally
report seclusion as a negative, coercive experience. There is little
evidence that seclusion provides long-term benefits in terms of treating
symptoms or reducing aggression, although the literature is mixed in this
regard. Expert opinion recommends a combination of national policy, ward
management and patient-centred interventions to reduce seclusion rates.
A guide to intellectual disability psychiatry assessments in the
community
Authors: Eng Bennett , Addison Paul , Ring Howard 
Published: November 2013

SummaryPsychiatric assessment in the community is an important part of both the
initial assessment process and delivery of follow-up care in adult
intellectual disability services in the UK. This article examines how such
assessments can be carried out safely and explores the clinical skills
required to perform them effectively. Use of the psychiatric interview and
mental state examination to elicit information is discussed. Communication
difficulties experienced by people with intellectual disabilities and
strategies that may be employed to address these in the assessment process
are also explored. The article is directed at psychiatrists, in particular
specialty trainees, and other healthcare professionals who work with
intellectually disabled people.
Addition of N-Acyliminium Ion Pools to Alkenes Having a Nucleophilic Moiety: Integration of Intermolecular and Intramolecular Reactions
Authors: Ashikari Yosuke , Kiuchi Yohei , Takeuchi Tomoya , Ueoka Koji , Suga Seiji , Yoshida Jun-ichi 
Published: November 2013

Abstract
The reaction of electrochemically generated N-acyliminium ion pools with alkenes bearing a heteroatom nucleophilic functionality such as a hydroxy group, a carboxy group, and an oxime moiety led to intermolecular carbon–carbon bond formation followed by intramolecular carbon–heteroatom bond formation to give the corresponding heterocyclic compounds such as cyclic ethers, lactones, and 2-isoxazolines, respectively.
Efficiency of use of increasing doses of mineral and organic fertilizers on potato in the middle Volga steppe
Authors: Владимиров  , Vladimirov Sergey 
Published: November 2013

The article titles the role of mineral nutrition in the formation of the potato crop of Aroza variety on gray forest soils. During the research years the highest tuber yield on average was obtained 22.56 tons per hectare while treatment by ZHUSS -1 for the treatment of tubers before planting and ZHUSS -2 for conjunction with foliar fertilizers at a dose N150, P150, K150. The yield increased in this variant to 12.89 tons per hectare.	The significant fluctuations in productivity of potato Aroza variety were revealed on gray forest soils due to climatic factors. In 2010 dry year the yield ranged from 7.10 tons per hectare up to 12.10 tons per hectare against 80 tons per hectare of organic fertilizers. In humid provided 2012 year, it amounted up 11.43 tons per hectare to 28.87 tons per hectare in the way of application of ZHUSS-1 for the treatment of tubers before planting and ZHUSS-2 in conjunction with foliar fertilizers at a dose N150, P150, K150.	16.90% of nitrogen, 8.27% of phosphorus and 20.03% of potassium were used from the potato plant soil. The fertilizer, depending on the dose were introduced at the following amount: 43,05-43,74% of nitrogen, 15,68-18,06 % of phosphorus, 70,05-75,26 % of potassium. As for the organic fertilizer, the plants have learned 17,34-20,28% of nitrogen, 15,19-17,38% of phosphorus and 25,68-31,31% of potassium.	Despite the increase in costs with increasing doses of fertilizers, the highest net income 73001 rubles per hectare and the level of profitability - 106.65% were obtained at the option of applying ZHUSS -1 for the treatment of tubers before planting and ZHUSS -2 in conjunction with foliar fertilizers in N150, P150, K150 dose . In this version there was the lowest cost - 3034 rubles per ton.
THE ROLE OF FAMILY IN ENCOURAGING CORRECTIONAL SCHOOL PUPILS TO ATTEND ADAPTIVE PHYSICAL TRAINING CLASSES
Authors: �������  , Kozlova Mariya 
Published: November 2013

The topical issue of interrelation between a child�s motivation to go in for
sports and exercises and the parents� attitude to the active and healthy lifestyle is
explored. It is pointed that correctional schools staff should closely cooperate with
the parents and families of their pupils. Such cooperation could encourage children
to attend sports classes and help them overcome many of their psychological and
dyskinesia problems.
The results of introducing the methodic of joint after-school activities of heterogenic
groups� children and their parents are given. The perspectives of developing adaptive
physical education at special correctional schools are forecasted. Such research, the
author confirms, is conducive to elaborating new approaches to adaptive physical
education and improving performance and methodological framework of correctional
schools. The results can be helpful for sports organizations, correctional schools,
educational and health and leisure institutions.