bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Proximal Tibial Slope on Dynamic Stability Testing of the Posterior Cruciate Ligament– and Posterolateral Corner–Deficient Knee
Authors: Petrigliano Frank A. , Suero Eduardo M. , Voos James E. , Pearle Andrew D. , Allen Answorth A. 
Published: March 2012

Background: Proximal tibial slope has been shown to influence anteroposterior translation and tibial resting point in the posterior cruciate ligament (PCL)–deficient knee. The effect of proximal tibial slope on rotational stability of the knee is unknown. Hypothesis: Change in proximal tibial slope produced via osteotomy can influence both static translation and dynamic rotational kinematics in the PCL/posterolateral corner (PLC)–deficient knee. Study Design: Controlled laboratory study. Methods: Posterior drawer, dial, and mechanized reverse pivot-shift (RPS) tests were performed on hip-to-toe specimens and translation of the lateral and medial compartments measured utilizing navigation (n = 10). The PCL and structures of the PLC were then sectioned. Stability testing was repeated, and compartmental translation was recorded. A proximal tibial osteotomy in the sagittal plane was then performed achieving either +5° or −5° of tibial slope variation, after which stability testing was repeated (n = 10). Analysis was performed using 1-way analysis of variance (ANOVA; α = .05). Results: Combined sectioning of the PCL and PLC structures resulted in a 10.5-mm increase in the posterior drawer, 15.5-mm increase in the dial test at 30°, 14.5-mm increase in the dial test at 90°, and 17.9-mm increase in the RPS (vs intact; P < .05). Increasing the posterior slope (high tibial osteotomy [HTO] +5°) in the PCL/PLC-deficient knee reduced medial compartment translation by 3.3 mm during posterior drawer (vs deficient; P < .05) but had no significant effect on the dial test at 30°, dial test at 90°, or RPS. Conversely, reversing the slope (HTO −5°) caused a 4.8-mm increase in medial compartment translation (vs deficient state; P < .05) during posterior drawer and an 8.6-mm increase in lateral compartment translation and 9.0-mm increase in medial compartment translation during RPS (vs deficient state; P < .05). Conclusion: Increasing posterior tibial slope diminished static posterior instability of the PCL/PLC-deficient knee as measured by the posterior drawer test but had little effect on rotational or dynamic multiplanar stability as assessed by the dial and RPS tests, respectively. Conversely, decreasing posterior slope resulted in increased posterior instability and a significant increase in the magnitude of the RPS. Clinical Relevance: These results suggest that increasing posterior tibial slope may improve sagittal stability in the PCL/PLC-deficient knee. Moreover, a knee with diminished posterior tibial slope may demonstrate greater multiplanar instability in this setting. Consequently, proximal tibial slope should be considered when treating combined PCL/PLC injuries of the knee.
Efficacy and safety of a single-pill fixed-dose combination of high-dose telmisartan/hydrochlorothiazide in patients with uncontrolled hypertension
Authors: Shiga Yuhei , Miura Shin-ichiro , Mitsutake Ryoko , Norimatsu Kenji , Nagata Itsuki , Arimura Tadaaki , Shimizu Tomohiko , Morii Joji , Kuwano Takashi , Uehara Yoshinari , Inoue Asao , Shirotani Tetsuro , Fujisawa Kazuaki , Matsunaga Eiyu , Saku Keijiro 
Published: March 2012

Objective: Many patients still have high blood pressure (BP) after treatment with high-dose angiotensin II type 1 receptor blockers (ARBs) or Preminent® (medium-dose of losartan (50 mg/day)/hydrochlorothiazide (HCTZ) (12.5 mg/day)). Therefore, we analyzed whether Micombi®BP (high-dose telmisartan (80 mg/day)/HCTZ (12.5 mg/day)) could provide better results with regard to efficacy and safety for patients with uncontrolled hypertension. Methods: In total, 44 hypertensive patients (22 males, age 71±14 years) who showed uncontrolled BP despite the use of high-dose ARBs or Preminent® were enrolled in this study. We used a changeover design in which the patients were switched from high-dose ARBs or Preminent® to Micombi®BP. We analyzed BP, heart rate (HR), and biochemical parameters before and after treatment for 3 months. Results: Systolic BP and diastolic BP significantly decreased (125±15/69±11 mmHg) and 85% of the patients achieved their target BP at 3 months after changeover. Patients who switched from ARBs and those who switched from Preminent® showed similar BP-lowering effects. In addition, the reductions in BP after 3 months in patients with or without chronic kidney disease and in those with or without metabolic syndrome (MetS) were also similar. There were no significant changes in HR during the study period. Although blood levels of potassium, hemoglobin A1c and uric acid (UA) significantly increased after 3 months for all of the patients, none of the patients showed serious adverse effects. Conclusion: High-dose telmisartan/HCTZ therapy was associated with a significant reduction in BP and helped patients achieve their target BP.
Attitudes to shared care for patients with dementia: A survey of general practitioners
Authors: Russ Tom C , Calvert Lucy , Morling Joanne R 
Published: March 2012

Early diagnosis of dementia is important, but implications for care shared between primary and secondary care remain uncertain. We explored attitudes and expectations of Edinburgh’s general practitioners (GPs) regarding current sharing of care for dementia. Surveys were distributed to all 335 Edinburgh GPs; 79.7% were returned. Attitudes and expectations were examined, specifically whether dementia care was currently appropriately shared. Two-thirds of GPs were sure of their role and a similar number felt that care was appropriately shared. The latter opinion was not associated with individual GP factors, such as gender or length of time since qualification, or local levels of deprivation. However, there was a significant association with sector consultant psychiatrist (F = 2.79, df = 6, p = 0.012) and with the proportion of the practice list diagnosed with dementia (ρ = −0.13, p = 0.038). The endangered relationship between GP and specialist could be a key target to improve shared care and early diagnosis of dementia.
An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model
Authors: Bergerson Rachel J. , Collier Lara S. , Sarver Aaron L. , Been Raha A. , Lugthart Sanne , Diers Miechaleen D. , Zuber Johannes , Rappaport Amy R. , Nixon Molly J. , Silverstein Kevin A. T. , Fan Danhua , Lamblin Anne-Francoise J. , Wolff Linda , Kersey John H. , Delwel Ruud , Lowe Scott W. , O'Sullivan M. Gerard , Kogan Scott C. , Adams David J. , Largaespada David A. 
Published: March 2012

Abstract
Patients with a t(9;11) translocation (MLL-AF9) develop acute myeloid leukemia (AML), and while in mice the expression of this fusion oncogene also results in the development of myeloid leukemia, it is with long latency. To identify mutations that cooperate with Mll-AF9, we infected neonatal wild-type (WT) or Mll-AF9 mice with a murine leukemia virus (MuLV). MuLV-infected Mll-AF9 mice succumbed to disease significantly faster than controls presenting predominantly with myeloid leukemia while infected WT animals developed predominantly lymphoid leukemia. We identified 88 candidate cancer genes near common sites of proviral insertion. Analysis of transcript levels revealed significantly elevated expression of Mn1, and a trend toward increased expression of Bcl11a and Fosb in Mll-AF9 murine leukemia samples with proviral insertions proximal to these genes. Accordingly, FOSB and BCL11A were also overexpressed in human AML harboring MLL gene translocations. FOSB was revealed to be essential for growth in mouse and human myeloid leukemia cells using shRNA lentiviral vectors in vitro. Importantly, MN1 cooperated with Mll-AF9 in leukemogenesis in an in vivo BM viral transduction and transplantation assay. Together, our data identified genes that define transcription factor networks and important genetic pathways acting during progression of leukemia induced by MLL fusion oncogenes.
Expression of XBP1s in bone marrow stromal cells is critical for myeloma cell growth and osteoclast formation
Authors: Xu Guoshuang , Liu Kai , Anderson Judy , Patrene Kenneth , Lentzsch Suzanne , Roodman G. David , Ouyang Hongjiao 
Published: March 2012

Abstract
BM stromal cells (BMSCs) are key players in the microenvironmental support of multiple myeloma (MM) cell growth and bone destruction. A spliced form of the X-box–binding protein-1 (XBP1s), a major proximal effector of unfolded protein response signaling, is highly expressed in MM cells and plays an indispensable role in MM pathogenesis. In the present study, we found that XBP1s is induced in the BMSCs of the MM microenvironment. XBP1s overexpression in healthy human BMSCs enhanced gene and/or protein expression of VCAM-1, IL-6, and receptor activator of NF-κB ligand (RANKL), enhancing BMSC support of MM cell growth and osteoclast formation in vitro and in vivo. Conversely, deficiency of XBP1 in healthy donor BMSCs displayed a range of effects on BMSCs that were opposite to those cells with overexpression of XBP1s. Knock-down of XBP1 in MM patient BMSCs greatly compromised their increased VCAM-1 protein expression and IL-6 and RANKL secretion in response to TNFα and reversed their enhanced support of MM-cell growth and osteoclast formation. Our results demonstrate that XBP1s is a pathogenic factor underlying BMSC support of MM cell growth and osteoclast formation and therefore represents a therapeutic target for MM bone disease.
Mitochondrial myopathy caused by arsenic trioxide therapy
Authors: Echaniz-Laguna Andoni , Benoilid Aurélien , Vinzio Stéphane , Fornecker Luc-Matthieu , Lannes Béatrice , Goullé Jean-Pierre , Broly Frank , Mousson de Camaret Bénédicte 
Published: March 2012

Abstract
Arsenic trioxide (ATO) has been successfully used as a treatment for acute promyelocytic leukemia (APL) for more than a decade. Here we report a patient with APL who developed a mitochondrial myopathy after treatment with ATO. Three months after ATO therapy withdrawal, the patient was unable to walk without assistance and skeletal muscle studies showed a myopathy with abundant cytoplasmic lipid droplets, decreased activities of the mitochondrial respiratory chain complexes, multiple mitochondrial DNA (mtDNA) deletions, and increased muscle arsenic content. Six months after ATO treatment was interrupted, the patient recovered normal strength, lipid droplets had decreased in size and number, respiratory chain complex activities were partially restored, but multiple mtDNA deletions and increased muscle arsenic content persisted. ATO therapy may provoke a delayed, severe, and partially reversible mitochondrial myopathy, and a long-term careful surveillance for muscle disease should be instituted when ATO is used in patients with APL.
CD47 functions as a molecular switch for erythrocyte phagocytosis
Authors: Burger Patrick , Hilarius-Stokman Petra , de Korte Dirk , van den Berg Timo K. , van Bruggen Robin 
Published: March 2012

AbstractCD47 on erythrocytes inhibits phagocytosis through interaction with the inhibitory immunoreceptor SIRPα expressed by macrophages. Thus, the CD47-SIRPα interaction constitutes a negative signal for erythrocyte phagocytosis. However, we report here that CD47 does not only function as a “do not eat me” signal for uptake but can also act as an “eat me” signal. In particular, a subset of old erythrocytes present in whole blood was shown to bind and to be phagocytosed via CD47-SIRPα interactions. Furthermore, we provide evidence that experimental aging of erythrocytes induces a conformational change in CD47 that switches the molecule from an inhibitory signal into an activating one. Preincubation of experimentally aged erythrocytes with human serum before the binding assay was required for this activation. We also demonstrate that aged erythrocytes have the capacity to bind the CD47-binding partner thrombospondin-1 (TSP-1) and that treatment of aged erythrocytes with a TSP-1–derived peptide enabled their phagocytosis by human red pulp macrophages. Finally, CD47 on erythrocytes that had been stored for prolonged time was shown to undergo a conformational change and bind TSP-1. These findings reveal a more complex role for CD47-SIRPα interactions in erythrocyte phagocytosis, with CD47 acting as a molecular switch for controlling erythrocyte phagocytosis.
Necrotizing fasciitis involving the chest and abdominal wall caused by Raoultella planticola
Authors: Kim Si-Hyun , Roh Kyoung Ho , Yoon Young Kyung , Kang Dong Oh , Lee Dong Woo , Kim Min Ja , Sohn Jang Wook 
Published: March 2012

Abstract

Background

Raoultella planticola was originally considered to be a member of environmental Klebsiella. The clinical significance of R. planticola is still not well known.

Case presentation
We describe the first case of necrotizing fasciitis involving the chest and abdominal wall caused by R. planticola. The identity of the organism was confirmed using 16S rRNA sequencing. The patient was successfully treated with the appropriate antibiotics combined with operative drainage and debridement.

Conclusions

R. planticola had been described as environmental species, but should be suspected in extensive necrotizing fasciitis after minor trauma in mild to moderate immunocompromised patients.
Single channel speech separation in modulation frequency domain based on a novel pitch range estimation method
Authors: Mahmoodzadeh Azar , Abutalebi Hamid Reza , Soltanian-Zadeh Hamid , Sheikhzadeh Hamid 
Published: March 2012

Abstract
Computational Auditory Scene Analysis (CASA) has been the focus in recent literature for speech separation from monaural mixtures. The performance of current CASA systems on voiced speech separation strictly depends on the robustness of the algorithm used for pitch frequency estimation. We propose a new system that estimates pitch (frequency) range of a target utterance and separates voiced portions of target speech. The algorithm, first, estimates the pitch range of target speech in each frame of data in the modulation frequency domain, and then, uses the estimated pitch range for segregating the target speech. The method of pitch range estimation is based on an onset and offset algorithm. Speech separation is performed by filtering the mixture signal with a mask extracted from the modulation spectrogram. A systematic evaluation shows that the proposed system extracts the majority of target speech signal with minimal interference and outperforms previous systems in both pitch extraction and voiced speech separation.
Intraneuronal Aβ detection in 5xFAD mice by a new Aβ-specific antibody
Authors: Youmans Katherine L , Tai Leon M , Kanekiyo Takahisa , Stine Jr W Blaine , Michon Sara-Claude , Nwabuisi-Heath Evelyn , Manelli Arlene M , Fu Yifan , Riordan Sean , Eimer William A , Binder Lester , Bu Guojun , Yu Chunjiang , Hartley Dean M , LaDu Mary Jo 
Published: March 2012

Abstract

Background
The form(s) of amyloid-β peptide (Aβ) associated with the pathology characteristic of Alzheimer's disease (AD) remains unclear. In particular, the neurotoxicity of intraneuronal Aβ accumulation is an issue of considerable controversy; even the existence of Aβ deposits within neurons has recently been challenged by Winton and co-workers. These authors purport that it is actually intraneuronal APP that is being detected by antibodies thought to be specific for Aβ. To further address this issue, an anti-Aβ antibody was developed (MOAB-2) that specifically detects Aβ, but not APP. This antibody allows for the further evaluation of the early accumulation of intraneuronal Aβ in transgenic mice with increased levels of human Aβ in 5xFAD and 3xTg mice.

Results
MOAB-2 (mouse IgG2b) is a pan-specific, high-titer antibody to Aβ residues 1-4 as demonstrated by biochemical and immunohistochemical analyses (IHC), particularly compared to 6E10 (a commonly used commercial antibody to Aβ residues 3-8). MOAB-2 did not detect APP or APP-CTFs in cell culture media/lysates (HEK-APPSwe or HEK-APPSwe/BACE1) or in brain homogenates from transgenic mice expressing 5 familial AD (FAD) mutation (5xFAD mice). Using IHC on 5xFAD brain tissue, MOAB-2 immunoreactivity co-localized with C-terminal antibodies specific for Aβ40 and Aβ42. MOAB-2 did not co-localize with either N- or C-terminal antibodies to APP. In addition, no MOAB-2-immunreactivity was observed in the brains of 5xFAD/BACE-/- mice, although significant amounts of APP were detected by N- and C-terminal antibodies to APP, as well as by 6E10. In both 5xFAD and 3xTg mouse brain tissue, MOAB-2 co-localized with cathepsin-D, a marker for acidic organelles, further evidence for intraneuronal Aβ, distinct from Aβ associated with the cell membrane. MOAB-2 demonstrated strong intraneuronal and extra-cellular immunoreactivity in 5xFAD and 3xTg mouse brain tissues.

Conclusions
Both intraneuronal Aβ accumulation and extracellular Aβ deposition was demonstrated in 5xFAD mice and 3xTg mice with MOAB-2, an antibody that will help differentiate intracellular Aβ from APP. However, further investigation is required to determine whether a molecular mechanism links the presence of intraneuronal Aβ with neurotoxicity. As well, understanding the relevance of these observations to human AD patients is critical.
Bacterial reprogramming of PBMCs impairs monocyte phagocytosis and modulates adaptive T cell responses
Authors: André Maya C , Gille Christian , Glemser Philip , Woiterski Jeanette , Hsu Hsin-Yun , Spring Baerbel , Keppeler Hildegard , Kramer Boris W , Handgretinger Rupert , Poets Christian F , Lauber Kirsten , Orlikowsky Thorsten W 
Published: March 2012

ABSTRACTSeptic diseases are characterized by an initial systemic, proinflammatory phase, followed by a period of anti-inflammation. In the context of the latter, monocytes have been described to display altered functions, including reduced TNF secretion and T cell-stimulating capacities in response to recall antigens. This hyporesponsiveness is supposed to be detrimental for coping with secondary infections. We here characterize bacterially reprogrammed PBMC-derived monocytes with special focus on their phagocytic activity. Hence, we have implemented a surrogate model of the early, postinflammatory period by exposing PBMCs to Escherichia coli on d0 and rechallenging them with bacteria on d2. This induced the emergence of a distinct monocytic phenotype with profound phagocytic impairments but a preserved ability for naïve T cell stimulation. The compromising effects on phagocytosis required the presence of bacteria and were not mimicked by TLR4 ligation or exposure to isolated cytokines alone. Moreover, the impairments were specific for the engulfment of bacteria and were coupled to a selective down-regulation of FcγR and SR expression. Intriguingly, this monocytic phenotype contributed to the stimulation of a TH17-polarized adaptive immune response in the context of secondary infection. Our findings extend the current knowledge of monocytic reprogramming and identify the phagocytic capacity of monocytes as a putative sepsis biomarker.
Role of IL-6 in the resolution of pancreatitis in obese mice
Authors: Pini Maria , Rhodes Davina H , Castellanos Karla J , Hall Andrew R , Cabay Robert J , Chennuri Rohini , Grady Eileen F , Fantuzzi Giamila 
Published: March 2012

ABSTRACTObesity increases severity of acute pancreatitis and risk of pancreatic cancer. Pancreatitis and obesity are associated with elevated IL-6, a cytokine involved in inflammation and tumorigenesis. We studied the role of IL-6 in the response of lean and obese mice to pancreatitis induced by IL-12 + IL-18. Lean and diet-induced obese (DIO) WT and IL-6 KO mice and ob/ob mice pretreated with anti-IL-6 antibodies were evaluated at Days 1, 7, and 15 after induction of pancreatitis. Prolonged elevation of IL-6 in serum and visceral adipose tissue was observed in DIO versus lean WT mice, whereas circulating sIL-6R declined in DIO but not lean mice with pancreatitis. The severe inflammation and lethality of DIO mice were also observed in IL-6 KO mice. However, the delayed resolution of neutrophil infiltration; sustained production of CXCL1, CXCL2, and CCL2; prolonged activation of STAT-3; and induction of MMP-7 in the pancreas, as well as heightened induction of serum amylase A of DIO mice, were blunted significantly in DIO IL-6 KO mice. In DIO mice, production of OPN and TIMP-1 was increased for a prolonged period, and this was mediated by IL-6 in the liver but not the pancreas. Results obtained in IL-6 KO mice were confirmed in ob/ob mice pretreated with anti-IL-6 antibodies. In conclusion, IL-6 does not contribute to the increased severity of pancreatitis of obese mice but participates in delayed recovery from acute inflammation and may favor development of a protumorigenic environment through prolonged activation of STAT-3, induction of MMP-7, and sustained production of chemokines.
Metabolic Heterogeneity in Polycystic Ovary Syndrome Is Determined by Obesity: Plasma Metabolomic Approach Using GC-MS
Authors: Escobar-Morreale Héctor F , Samino Sara , Insenser María , Vinaixa María , Luque-Ramírez Manuel , Lasunción Miguel A , Correig Xavier 
Published: March 2012

Abstract

BACKGROUND
Abdominal adiposity and obesity influence the association of polycystic ovary syndrome (PCOS) with insulin resistance and diabetes. We aimed to characterize the intermediate metabolism phenotypes associated with PCOS and obesity.

METHODS
We applied a nontargeted GC-MS metabolomic approach to plasma samples from 36 patients with PCOS and 39 control women without androgen excess, matched for age, body mass index, and frequency of obesity.

RESULTS
Patients with PCOS were hyperinsulinemic and insulin resistant compared with the controls. The increase in plasma long-chain fatty acids, such as linoleic and oleic acid, and glycerol in the obese patients with PCOS suggests increased lipolysis, possibly secondary to impaired insulin action at adipose tissue. Conversely, nonobese patients with PCOS showed a metabolic profile consisting of suppression of lipolysis and increased glucose utilization (increased lactic acid concentrations) in peripheral tissues, and PCOS patients as a whole showed decreased 2-ketoisocaproic and alanine concentrations, suggesting utilization of branched-chain amino acids for protein synthesis and not for gluconeogenesis. These metabolic processes required effective insulin signaling; therefore, insulin resistance was not universal in all tissues of these women, and different mechanisms possibly contributed to their hyperinsulinemia. PCOS was also associated with decreased α-tocopherol and cholesterol concentrations irrespective of obesity.

CONCLUSIONS
Substantial metabolic heterogeneity, strongly influenced by obesity, underlies PCOS. The possibility that hyperinsulinemia may occur in the absence of universal insulin resistance in nonobese women with PCOS should be considered when designing diagnostic and therapeutic strategies for the management of this prevalent disorder.