bluuebunny/crossref_metadata_2025 huggingface dataset:
KLF4 gene expression is inhibited by the notch signaling pathway that controls goblet cell differentiation in mouse gastrointestinal tract
Authors: Zheng Hai , Pritchard D. Mark , Yang Xiangdong , Bennett Elaine , Liu Gang , Liu Chunming , Ai Walden
Published: December 2008

In Kruppel-like factor (KLF)-4-deficient mice, colonic goblet cell numbers are significantly reduced. Goblet cell development is regulated by the Notch signaling pathway. The aim of this study was to examine whether Notch represses KLF4 expression to regulate goblet cell differentiation. We first detected that KLF4 gene expression was upregulated in a human progastrin-overexpressing mouse model where goblet cell hyperplasia has been observed. We then found that mice treated with a γ-secretase inhibitor (compound E, 10 μmol/kg) for 24 h, which inhibits the Notch signaling pathway, had significantly increased KLF4 mRNA levels in small intestine and colon, accompanied by an increased number of KLF4-expressing cells at the bottom of crypts in small intestine and colon. In a colon cancer cell line (HCT116 cells), KLF4 promoter activity was inhibited by a constitutively active form of Notch1 (ICN1) by transient cotransfection assays. This inhibition was significantly compromised by a dominant-negative RBPjk, a repressive mediator of the Notch signaling pathway. An ICN1-responsive element was then mapped in the human KLF4 promoter between −151 and −122 nucleotides upstream of the transcriptional start site. It was also found that an intact ICN1-responsive element is required for ICN1 to inhibit KLF4 promoter activity by transient cotransfection assays. Our findings thus reveal a possible mechanism by which KLF4 is inhibited by Notch, which controls goblet cell differentiation in mouse gastrointestinal tract.
Beneficial effects of rutin andl-arginine coadministration in a rat model of liver ischemia-reperfusion injury
Authors: Acquaviva Rosaria , Lanteri Raffaele , Li Destri Giovanni , Caltabiano Rosario , Vanella Luca , Lanzafame Salvatore , Di Cataldo Antonio , Li Volti Giovanni , Di Giacomo Claudia
Published: December 2008

Reperfusion following liver ischemia results in oxidative stress leading to liver injury. The aim of this study was to investigate the combined effects of two antioxidant agents, rutin and l-arginine, in rat liver ischemia-reperfusion (I/R). Male Wistar rats were divided into five groups: 1) sham operated, 2) I/R, 3) I/R + rutin, 4) I/R + l-arginine, and 5) I/R + rutin + l-arginine. Plasmatic and hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA fragmentation and liver histopathology. Furthermore, to elucidate the pathophysiological processes involved in the antioxidant mechanism(s) of rutin and l-arginine, we assessed the expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing key roles in the biochemical cascade of liver injury. Significant increase in plasmatic ALT and AST activities were observed in untreated I/R rats compared with sham-operated animals, whereas treatment with rutin or l-arginine in I/R rats reduced hepatic damage. Interestingly, combined therapy with rutin and l-arginine resulted in a further reduction of plasmatic ALT and AST activities compared with rutin or l-arginine alone. These results were further confirmed by the analysis of DNA fragmentation, LOOH, RSH groups, and liver histopathology, which showed the highest protective effects following the coadministration of rutin and l-arginine. Finally, the combined therapy protocol resulted in a significant induction of liver HO-1 and a concomitant reduction of iNOS expression that may both be responsible for the beneficial effects of the proposed pharmacological protocol.
CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation
Authors: Stokes Karen Y. , Calahan LeShanna , Hamric Candiss M. , Russell Janice M. , Granger D. Neil
Published: December 2008

Hypercholesterolemia is associated with phenotypic changes in endothelial cell function that lead to a proinflammatory and prothrombogenic state in different segments of the microvasculature. CD40 ligand (CD40L) and its receptor CD40 are ubiquitously expressed and mediate inflammatory responses and platelet activation. The objective of this study was to determine whether CD40/CD40L, in particular T-cell CD40L, contributes to microvascular dysfunction induced by hypercholesterolemia. Intravital microscopy was used to quantify blood cell adhesion in cremasteric postcapillary venules, endothelium-dependent vasodilation responses in arterioles, and microvascular oxidative stress in wild-type (WT) C57BL/6, CD40-deficient (−/−), CD40L−/−, or severe combined immune deficient (SCID) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2 wk. WT-HC mice exhibited an exaggerated leukocyte and platelet recruitment in venules and impaired vasodilation responses in arterioles compared with ND counterparts. A deficiency of CD40, CD40L, or lymphocytes attenuated these responses to HC. The HC phenotype was rescued in CD40L−/− and SCID mice by a transfer of WT T cells. Bone marrow chimeras revealed roles for both vascular- and blood cell-derived CD40 and CD40L in the HC-induced vascular responses. Hypercholesterolemia induced an oxidative stress in both arterioles and venules of WT mice, which was abrogated by either CD40 or CD40L deficiency. The transfer of WT T cells into CD40L−/− mice restored the oxidative stress. These results implicate CD40/CD40L interactions between circulating cells and the vascular wall in both the arteriolar and venular dysfunction elicited by hypercholesterolemia and identify T-cell-associated CD40L as a key mediator of these responses.
Mass loading of the upper airway extraluminal tissue space in rabbits: effects on tissue pressure and pharyngeal airway lumen geometry
Authors: Kairaitis Kristina , Howitt Lauren , Wheatley John R. , Amis Terence C.
Published: December 2008

Lateral pharyngeal fat pad compression of the upper airway (UA) wall is thought to influence UA size in patients with obstructive sleep apnea. We examined interactions between acute mass/volume loading of the UA extra-luminal tissue space and UA patency. We studied 12 supine, anesthetized, spontaneously breathing, head position-controlled (50°), New Zealand White rabbits. Submucosal extraluminal tissue pressures (ETP) in the anterolateral (ETPlat) and anterior (ETPant) pharyngeal wall were monitored with surgically inserted pressure transducer-tipped catheters (Millar). Tracheal pressure (Ptr) and airflow (V̇) were measured via a pneumotachograph and pressure transducer inserted in series into the intact trachea, with hypopharyngeal cross-sectional area (CSA) measured via computed tomography, while graded saline inflation (0–1.5ml) of a compliant tissue expander balloon in the anterolateral subcutaneous tissue was performed. Inspiratory UA resistance (Rua) at 20 ml/s was calculated from a power function fitted to Ptr vs. V̇ data. Graded expansion of the anterolateral balloon increased ETPlat from 2.3 ± 0.5 cmH2O ( n = 11, mean ± SEM) to 5.0 ± 1.1 cmH2O at 1.5-ml inflation ( P < 0.05; ANOVA). However, ETPant was unchanged from 0.5 ± 0.5 cmH2O ( n = 9; P = 0.17). Concurrently, Rua increased to 119 ± 4.2% of baseline value ( n = 12; P < 0.001) associated with a significant reduction in CSA between 10 and 70% of airway length to a minimum of 82.2 ± 4.4% of baseline CSA at 40% of airway length ( P < 0.05). We conclude that anterolateral loading of the upper airway extraluminal tissue space decreases upper airway patency via an increase in ETPlat, but not ETPant. Lateral pharyngeal fat pad size may influence UA patency via increased tissue volume and pressure causing UA wall compression.
Discrete Parieto-Frontal Functional Connectivity Related to Grasping
Authors: Hattori Noriaki , Shibasaki Hiroshi , Wheaton Lewis , Wu Tao , Matsuhashi Masao , Hallett Mark
Published: December 2008

The human inferior parietal lobule (IPL) is known to have neuronal connections with the frontal lobe, and these connections have been shown to be associated with sensorimotor integration to perform various types of movement such as grasping. The function of these anatomical connections has not been fully investigated. We studied the judgment of graspability of objects in an event-related functional MRI study in healthy subjects, and found activation in two different regions within IPL: one in the left dorsal IPL extending to the intraparietal sulcus and the other in the left ventral IPL. The former region was activated only in the judgment of graspable objects, whereas the latter was activated in the judgment of both graspable and nongraspable objects although the activation was greater for the graspable objects. Psychophysiological interaction analysis showed that these regions had similar but discrete functional connectivity to the lateral and medial frontal cortices. In relation to this particular task, the left dorsal IPL had functional connectivity to the left ventral premotor cortex, supplementary motor area (SMA) and right cerebellar cortex, whereas the left ventral IPL had functional connectivity to the left dorsolateral prefrontal cortex and pre-SMA. These findings suggest that the connection from the left dorsal IPL is associated specifically with automatic flow of information about grasping behavior. By contrast, the connection from the left ventral IPL might be related to motor imagination or enhanced external attention to the presented stimuli.
Modelling of the Production of Source Neutrons from Low-Voltage Accelerated Deuterons on Titanium-Tritium Targets
Authors: Milocco A. , Trkov A.
Published: December 2008

Fast quasi-monoenergetic neutrons can be produced by accelerating charged deuterons on tritium solid targets. Benchmark experiments were performed in many laboratories with intense D-T neutron sources. The aim is to validate the computational models and nuclear data for fusion applications. The detailed information on the neutron source term is highly important for the benchmark analyses. At present, the MCNP family of codes cannot explicitly model the D-T reaction for Deuterons in the KeV energy range. The physics for the D-T neutron production was modelled at ENEA (Italy) in the SOURCE and SRCDX subroutines to compile with the MCNP source code. Some improvements to the original subroutines were introduced. The differential cross-sections for the D-T reaction from the ENDF/B-VII library were built into the code. The relativistic approach was implemented for neutron kinematics. The new D-T neutron source model was applied to the MCNP5 simulation of the tungsten integral experiment performed at the OKTAVIAN facility. The uncertainty associated with the realistic D-T reactions was separated from the total uncertainty of the source term. The outcome of the benchmark analysis was an improvement in the quality of the computational model of the experiment.
Cavitation in Single‐Vane Sewage Pumps
Authors: Thamsen P. U. , Bubelach T. , Pensler T. , Springer P.
Published: December 2008

Chair fluidsystemdynamics at TU Berlin investigated the cavitation
behavior of a full‐size single‐vane sewage pump. Single‐vane pumps
are used for raw sewage with high content of dirt and sediments in
larger sewage pumping stations. Cavitation measurement was done by
using standard NPSH3% and the more sensitive
incipient cavitation NPSHIC. Also, vibration
and noise where observed. Contrary to very low
NPSH3% values, very high
NPSHIC values were measured. In a second
step, the impeller was modified with special cavitation bores to
reduce the cavitation effects. The NPSH3% values
increased with cavitation bores, which underlines that this value
is not a sufficient criteria describing cavitation. Using the much
more sensitive NPSHIC, a significant
reduction was obtained. Moreover, the cavitation formation was
changed from a relative concentrated cloud to a distributed bubble
form, which is much less aggressive in view of noise and erosion.
Operational behavior improved with cavitation bores,
noise and vibration levels especially came down to acceptable level. Practical
experience demonstrates also avoidance of cavitation erosion.
On the Flow Behavior in Rotor‐Stator System with Superposed Flow
Authors: Debuchy Roger , Abdel Nour Fadi , Bois Gérard
Published: December 2008

The flow between a rotor and a stator at high Reynolds number and small Ekman number is divided into three domains, two boundary layers adjacent to the discs separated by a central core. In the present work, a simple theoretical approach provides analytical solutions for the radial distribution of the core swirl ratio valid for a rotor‐stator system with a superposed radial inflow rate. At first, the flow in the rotor boundary layer is assumed to behave as expressed by Owen and Rogers (1989) in the case of a turbulent flow on a rotating single disc. On the stator side, a necessary compensation flow rate must take place according to the conservation of mass. It is found that this compensation flow rate cannot be estimated with a good accuracy using the hypotheses of a stationary disc in a rotating fluid by Owen and Rogers (1989). Thus, two innovative weighting functions are tested, leading to new analytical laws relating the core swirl ratio K to the coefficient of flow rate Cqr introduced by Poncet et al. (2005). The adequacy between the theoretical solutions and numerous results of the literature is clearly improved and the discussion allows a better understanding of the flow behavior.
A Novel Intraurethral Device Diagnostic Index to Classify Bladder Outlet Obstruction in Men with Lower Urinary Tract Symptoms
Authors: Reis Leonardo O. , Barreiro Guilherme C. , Prudente Alessandro , Silva Cleide M. , Bassani José W. M. , D'Ancona Carlos A. L.
Published: December 2008

Objectives. Using a urethral device at the fossa navicularis, bladder pressure during voiding can be estimated by a minimal invasive technique. This study purposes a new diagnostic index for patients with lower urinary tract symptoms (LUTSs).Methods. Fifty one patients presenting with LUTSs were submitted to a conventional urodynamic and a minimal invasive study. The results obtained through the urethral device and invasive classic urodynamics were compared. The existing bladder outlet obstruction index (BOOI) equation that classifies men with LUTSs was modified to allow minimal invasive measurement of isovolumetric bladder pressure in place of detrusor pressure at maximum urine flow. Accuracy of the new equation for classifying obstruction was then tested in this group of men.Results. The modified equation identified men with obstruction with a positive predictive value of 68% and a negative predictive value of 70%, with an overall accuracy of 70%.Conclusions. The proposed equation can accurately classify over 70% of men without resorting to invasive pressure flow studies. We must now evaluate the usefulness of this classification for the surgical treatment of men with LUTSs.
Comparison of Definitions of Metabolic Syndrome in Relation to the Risk of Developing Stroke and Coronary Heart Disease in Finnish and Swedish Cohorts
Authors: Qiao Qing , Laatikainen Tiina , Zethelius Björn , Stegmayr Birgitta , Eliasson Mats , Jousilahti Pekka , Tuomilehto Jaakko
Published: December 2008

Background and Purpose—

The purpose of this study was to compare definitions of metabolic syndrome with regard to their prediction of stroke and coronary heart disease incidence.

Methods—

The study comprises 4041 men and 3812 women of 6 Finnish and Swedish cohorts aged 25 to 74 years at baseline. Hazard ratio was estimated applying Cox regression analyses adjusting for cohort, cholesterol, and smoking and using age as a time scale. A paired homogeneity test was performed to compare the differences.

Results—

A total of 113 (47) ischemic and 43 (15) hemorrhagic stroke and 235 (50) coronary heart disease events were accumulated in men (women). Hazard ratios (95% CIs) for ischemic stroke in men were 1.59 (1.09 to 2.32), 1.52 (1.01 to 2.28), 1.16 (0.77 to 1.74), and 1.27 (0.87 to 1.86), respectively, for the World Health Organization, National Cholesterol Education Program, National Cholesterol Education Program revised, and the International Diabetes Federation definitions of metabolic syndrome, and in women 2.20 (1.15 to 4.19), 2.68 (1.47 to 4.87), 2.31 (1.27 to 4.20), and 1.91 (1.05 to 3.49), respectively. The corresponding hazard ratios (95% CIs) for coronary heart disease were 1.57 (1.21 to 2.04), 1.51 (1.15 to 1.99), 1.63 (1.25 to 2.13), and 1.46 (1.12 to 1.89) in men and 1.32 (0.69 to 2.51), 1.54 (0.85 to 2.79), 1.81 (1.02 to 3.21), and 2.47 (1.37 to 4.45) in women. None of the definitions of metabolic syndrome predicted hemorrhagic stroke. There was no difference between definitions of metabolic syndrome and between a full definition and its individual components.

Conclusions—

Metabolic syndrome as well as its individual components predicted the incidence of the ischemic stroke and the coronary heart disease equally well and should be treated equally as well.
Isolated Nodular Infarction
Authors: Moon In Soo , Kim Ji Soo , Choi Kwang Dong , Kim Min-Jeong , Oh Sun-Young , Lee Hyung , Lee Hak-Seung , Park Seong-Ho
Published: December 2008

Background and Purpose—

Isolated nodular infarction has rarely been described in human. The purpose of this study is to report clinical and laboratory findings of isolated nodular infarction.

Methods—

Eight patients with isolated nodular infarction were recruited from 6 hospitals in Korea. All patients underwent a complete and standardized neurotological evaluation including ocular torsion, bithermal caloric tests, and rotatory chair test in addition to MRI and MR angiography.

Results—

All patients presented with isolated vertigo and moderate to severe imbalance. The most common manifestation was unilateral nystagmus and falling in the opposite direction, which mimicked peripheral vestibulopathy. Six patients had unilateral lesion, and 2 showed bilateral lesions. The direction of the spontaneous nystagmus was all ipsilesional in the unilateral lesion. However, head impulse and bithermal caloric tests were normal. Other findings include periodic alternating nystagmus, perverted head shaking nystagmus, paroxysmal positional nystagmus, and impaired tilt suppression of the postrotatory nystagmus. Hypoplasia of the ipsilesional vertebral artery was the only abnormal finding on MR angiography in 3 patients. The prognosis was excellent.

Conclusions—

Isolated nodular infarction mostly presents with isolated vertigo mimicking acute peripheral vestibulopathy. However, severe imbalance and a negative head impulse test are important clinical discriminants between nodular infarcts and peripheral vestibular dysfunction. The findings of isolated nodular infarctions are consistent with impaired gravito-inertial processing of the vestibular signals and disrupted nodular inhibition on the vestibular secondary neurons and the velocity storage mechanism.
Costs of Stroke Using Patient-Level Data
Authors: Luengo-Fernandez Ramon , Gray Alastair M. , Rothwell Peter M.
Published: December 2008

Background and Purpose—With decision-analytic models becoming more popular to assess the cost-effectiveness of health care interventions, the need for robust estimates on the costs of cerebrovascular disease is paramount. This study reports the results from a literature review of the costs of cerebrovascular diseases, and assesses the quality of the published evidence against a set of defined criteria.

Methods—A broad literature search was conducted. Those studies reporting mean/median costs of cerebrovascular diseases derived from patient-level data in a developed country setting were included. Data were abstracted using standardized reporting forms and assessed against 4 predefined criteria: use of adequate methodologies, use of a population-based study, inclusion of premorbid resource use, and reporting of costs by different patient subgroups.

Results—A total of 120 cost studies were identified. The cost estimates of stroke were compared by taking into account the effects of inflation and price differentials between countries. Average costs of stroke ranged from $468 to $146 149. Differences in costs were also found within country, with estimates in the USA varying 20-fold. Although the costing methodologies used were generally appropriate, only 5 studies were based on population-based studies, which are the gold standard study design when comparing incidence, outcome, and costs.

Conclusions—This review showed large variations in the costs of stroke, mainly attributable to differences in the populations studied, methods, and cost categories included. The wide range of cost estimates could lead to selection bias in secondary health economic analyses, with authors including those costs that are more likely to produce the desired results.
An Elusive “We”
Authors: Leach Darcy K.
Published: December 2008

Recent research suggests that ideology and collective identity are important factors shaping the behavior of movements committed to radically democratic self-governance and that a coherent ideology and clearly defined identity are necessary for movement success. Examining this hypothesis in the context of the Germany “autonomous” movement, this study finds that a contradiction in the movement's ideology around the meaning of autonomy has generated a deeply ambivalent identity and a resistance to ideological dogmatism, both of which have functioned to help sustain the movement. This suggests that sustaining collectivist democracy may require that a movement resist both ideological coherence and a clearly defined identity. Because ideologies often contain deep contradictions, action in countercultural movements is more than a simple reflection of the activists' ideals, mediated by situational constraints. Rather, such value-rational action is better understood as an iterative process by which ideological contradictions and ideologically-driven practices are repeatedly renegotiated and reproduced.
A Paradigm Shift in Third Sector Theory and Practice
Authors: Van Til Jon
Published: December 2008

For the past quarter-century, the field of voluntary action/nonprofit organization/third sector research has been dominated by a paradigm that focuses on organizations certified as tax exempt by the IRS and subject to an inability to distribute economic assets. This definition has facilitated large-scale empirical research but has dropped from visibility a wide range of important community-based voluntary and nonprofit organizations, including in the United States some 9 million grassroots organizations and a wide range of cooperative and mutual benefit organizations. In recent years, a critical literature has developed that challenges this dominant conception. This perspective has taken form under the leadership of the EMES European Research Network and employs a more expansive conception of the third sector than does the conventional American view. That conception is explored and refined in this article, the argument being that the value of the third sector far exceeds the contributions of tax-certified nonprofit organizations.
The Existentialism of Rollo May
Authors: Pitchford Daniel B.
Published: December 2008

This article reviews the life and work of Rollo May and his influence on the author’s development of applying existential therapy to treating traumatic stress. An examination of May’s worldview, theory, and therapeutic philosophy is presented. Considerable importance is placed on May’s theoretical foundations as they apply to treating combat veterans diagnosed with posttraumatic stress disorder (PTSD). The data presented in this article reveal the significance of utilizing existential therapeutic principles within a group format to help facilitate combat veterans’ recovery from the internal damage inflicted by PTSD.
Balancing Uncertain Risks and Benefits in Human Subjects Research
Authors: Barke Richard
Published: December 2008

Composed of scientific and technical experts and lay members, thousands of research ethics committees—Institutional Review Boards (IRBs) in the United States—must identify and assess the potential risks to human research subjects, and balance those risks against the potential benefits of the research. IRBs handle risk and its uncertainty by adopting a version of the precautionary principle. To assess scientific merit, IRBs use a tacit ``sanguinity principle,'' which treats uncertainty as inevitable, even desirable, in scientific progress. In balancing human subjects risks and scientific benefits, IRBs use uncertainty as a boundary-ordering device that allows the mediation of the science and ethics aspects of their decisions. One effect is the entangling of methodological and ethical review. Some have suggested these should be more clearly separated, but decisions by research ethics committees depend in part on the negotiating space created by incommensurable approaches to uncertainty.
Children's Birthday Celebrations From the Lived Experiences of Low-Income Rural Mothers
Authors: Lee Jaerim , Katras Mary Jo , Bauer Jean W.
Published: December 2008

This exploratory study investigates how low-income rural families celebrate children's birthdays, using interview data from 128 mothers residing in five states. Findings from a qualitative content analysis show that the mothers make special efforts to have birthday celebrations as other families do despite their financial constraints. Making the birthday child feel happy and “normal” is the central goal of the birthday celebrations. Many of the mothers desire big parties and expensive gifts, which are socially expected characteristics of birthday celebrations. These mothers adopt various strategies to acquire, create, and allocate resources they need, including reducing expenditures, planning, changing priorities, pooling resources, and receiving assistance from their social networks. However, some mothers cannot celebrate birthdays the way they want because of financial constraints and may feel unsatisfied with their celebrations.
Early Environmental Predictors of the Affective and Interpersonal Constructs of Psychopathy
Authors: Daversa Maria T.
Published: December 2008

Early childhood maltreatment (i.e., physical, sexual, emotional abuse) and caregiver disruptions are hypothesized to be instrumental in altering the neurobiology of the brain, particularly the amygdala, and contributing to the development of the affective deficits examined in individuals with psychopathy. Exposure to early untoward life events in models of rodent and nonhuman primates changes the neurobiology of the stress response. It is hypothesized that these changes may permanently shape brain regions that mediate stress and emotion and therefore play a role in the etiology of affective disorders in humans. The significance of experience (e.g., the intensity/severity, chronicity/duration, and developmental timing of experiences) and how the accompanying changes in the activity of the hypothalamic—pituitary—adrenocortical system affect alterations in the amygdala are discussed as critical contributors to the etiology of psychopathy. A model is proposed in which early maltreatment experiences contribute to alterations to the amygdala and produce a blunted or dissociative response to stress, a key factor in the affective deficits observed in psychopaths.
Incidence of Subsequent Injury to Either Knee within 5 Years after Anterior Cruciate Ligament Reconstruction with Patellar Tendon Autograft
Authors: Shelbourne K. Donald , Gray Tinker , Haro Marc
Published: December 2008

Background

The risk of subsequent anterior cruciate ligament injury to either knee after surgery based on sex, age, and activity has not been extensively studied.

Hypotheses

Women have a higher incidence of anterior cruciate ligament injury to the contralateral knee after surgery than men but do not have a difference in injuries to the reconstructed knee. Young, competitive athletes have a higher incidence of injury than older patients. The time to return to full activities does not affect injury rate.

Study Design

Cohort study (prognosis); Level of evidence, 2.

Methods

The authors prospectively followed 1820 patients after primary anterior cruciate ligament reconstruction to determine if patients suffered an injury to either knee within 5 years after surgery. Subsequent injury was evaluated based on sex, age, and activity level.

Results

Minimum 5-year follow-up was obtained on 1415 patients (78%). Seventy-five patients (5.3%) had an injury to the contralateral knee, and 61 patients (4.3%) suffered an injury to the reconstructed knee (P =. 2185). Women suffered more injuries (7.8%) to the contralateral normal knee than men (3.7%; P <. 001) but not more injuries to the reconstructed knee (4.3% vs 4.1%; P =. 5543). The risk of subsequent injury to either knee was 17% for patients <18 years old, 7% for patients aged 18 to 25 years, and 4% for patients older than 25 years. There was no difference in injury rate between patients who returned before and after 6 months postoperatively.

Conclusion

Women have a higher incidence of anterior cruciate ligament injury to the contralateral knee than men after reconstruction. The incidence of injury to either knee after reconstruction is associated with younger age and higher activity level, but returning to full activities before 6 months postoperatively does not increase the risk of subsequent injury.
Mutual Partner Violence
Authors: Próspero Moisés , Kim Miseong
Published: December 2008

This study examines racial/ethnic and sex differences in the prevalence of mutual intimate partner violence (IPV) and mental health symptoms. The authors asked 676 university students in heterosexual relationships if they had experienced IPV, coercive victimization, and/or perpetration as well as symptoms of depression, anxiety, hostility, and somatization. Analyses were conducted separately for female and male respondents in four racial/ethnic groups, totaling eight groups (female and male groups each for African Americans, Asian Americans, Latinos, and European Americans). Men, as compared to women, reported stronger correlations between IPV perpetration and IPV victimization, with Asian American men reporting the highest associations of any group. Additionally, experiencing higher partner and coercive violence was significantly related to increased mental health symptoms for all groups except Asian American men. Taken together, these findings suggest that the majority of couples experience mutual violence that elicits mental health problems for both members of the couple.
Computerized History Games: Narrative Options
Authors: Kee Kevin
Published: December 2008

How may historians best express history through computer games? This article suggests that the answer lies in correctly correlating historians’ goals for teaching with the capabilities of different kinds of computer games. During the development of a game prototype for high school students, the author followed best practices as expressed in the literature on games for learning. The analysis that followed led the author to question the applicability of these best practices, and this literature, to history games for learning. He began the second iteration by asking, “What is it that we as historians want to teach?” After deciding on goals for history education, the author asked a second question, “How can these goals be best expressed in a game environment?” Different game genres afford different possibilities, and the author connects three epistemologies for history to three computer game genres, resulting in three options for history games for learning.
Terminological Ambiguity
Authors: Klabbers Jan H. G.
Published: December 2008

Since its introduction in academia and professional practice during the 1950s, gaming has been linked to simulation. Although both fields have a few important characteristics in common, they are distinct in their form and underlying theories of knowledge and methodology. Nevertheless, in the literature, hybrid terms such as gaming/simulation and simulation gaming are used for practical or pragmatic reasons, causing confusion and ambiguity about the marking out of gaming versus simulation. Generally it is not clear whether authors are talking about games and simulations as artifacts of certain forms or whether they are referring to their functionality. The author elaborates on the confusion about these terms and offers a frame of reference to bring more terminological coherence and reduce methodological ambiguity.
Serious Video Games for Health: How Behavioral Science Guided the Development of a Serious Video Game
Authors: Thompson Debbe , Baranowski Tom , Buday Richard , Baranowski Janice , Thompson Victoria , Jago Russell , Griffith Melissa Juliano
Published: December 2008

Serious video games for health are designed to entertain players while attempting to modify some aspect of their health behavior. Behavior is a complex process influenced by multiple factors, often making it difficult to change. Behavioral science provides insight into factors that influence specific actions that can be used to guide key game design decisions. This article reports how behavioral science guided the design of a serious video game to prevent Type 2 diabetes and obesity among youth, two health problems increasing in prevalence. It demonstrates how video game designers and behavioral scientists can combine their unique talents to create a highly focused serious video game that entertains while promoting behavior change.
In-Home Chronic Disease Management in Diabetes
Authors: Hartman Amy , Litchman Michelle L. , Reed Pat , Burr Robert E.
Published: December 2008

With the rate of diabetes increasing in the elderly, home health care agencies must creatively approach disease management in this high-risk population. Specialized training programs, standardized policies and procedures, and strategic staffing patterns support agencies to systematically and effectively manage diabetes in the home. Collaboration with endocrinology providers assists agencies to incorporate and appropriately use national standards in diabetes care. Additionally, home health partnership with endocrinology providers will enhance a disease management program with increased provider participation and oversight, improving patient clinical outcomes and serving as a resource for home health agencies managing patients with diabetes.
The Legal, Regulatory, and Policy Challenges of Infection Control in Home Health Care, 2008
Authors: Kenneley Irena , Madigan Elizabeth A.
Published: December 2008

The practice implications of the Centers for Medicare & Medicaid Services hospital payment policy change are likely to influence the relationships between home health care agencies and their referring/receiving hospitals. Maintaining infection control measures can be difficult in the home environment, which was not designed for health care provision and where family members, friends, and pets are present. In addition to the hospital payment changes, there have been epidemiologic changes, with increasing recognition of multidrug resistant organisms and increasing virulence. The purpose of this article is to identify the scope of the practice changes that might be expected in response to epidemiologic and policy changes and activities that home health care agencies can undertake in response. Increased calls for transparency, accountability, and high-quality care, along with threats of denied reimbursement, will force changes across the entire continuum of care.
Effects of Conventional Physical Therapy and Functional Strength Training on Upper Limb Motor Recovery After Stroke: A Randomized Phase II Study
Authors: Donaldson Catherine , Tallis Raymond , Miller Simon , Sunderland Alan , Lemon Roger , Pomeroy Valerie
Published: December 2008

Background. Functional training and muscle strength training may improve upper limb motor recovery after stroke. Combining these as functional strength training (FST) might enhance the benefit, but it is unclear whether this is better than conventional physical therapy (CPT). Comparing FST with CPT is not straightforward. Objective. This study aimed at assessing the feasibility of conducting a phase III trial comparing CPT with FST for upper limb recovery. Methods. Randomized, observer-blind, phase II trial. Subjects had upper limb weakness within 3 months of anterior circulation infarction. Subjects were randomized to CPT (no extra therapy), CPT + CPT, and CPT + FST. Intervention lasted 6 weeks. Primary outcome measure was the Action Research Arm Test (ARAT). Measurements were taken before treatment began, after 6 weeks of intervention, and 12 weeks thereafter. Attrition rate was calculated and differences between groups were interpreted using descriptive statistics. ARAT data were used to inform a power calculation. Results. Thirty subjects were recruited (8% of people screened). Attrition rate was 6.7% at outcome and 40% at follow-up. At outcome the CPT + FST group showed the largest increase in ARAT score and this was above the clinically important level of 5.7 points. Median (interquartile range) increases were 11.5 (21.0) for CPT; 8.0 (13.3) for CPT + CPT; and 19.5 (22.0) for CPT + FST. The estimated sample size for an adequately powered subsequent phase III trial was 279 subjects at outcome. Conclusion. Further work toward a phase III clinical trial appears justifiable.
Transcutaneously Coupled, High-Frequency Electrical Stimulation of the Pudendal Nerve Blocks External Urethral Sphincter Contractions
Authors: Gaunt Robert A. , Prochazka Arthur
Published: December 2008

Background. Detrusor-sphincter dyssynergia is a condition in which reflexive contractions of the external urethral sphincter occur during bladder contractions, preventing the expulsion of urine. High-frequency stimulation (kHz range) has been shown to elicit a fast-acting and reversible block of action potential propagation in peripheral nerves, which may be a useful technique in the management of this condition. Objective. The aim of these experiments was to see if a newly developed stimulus delivery system, capable of transmitting current transcutaneously to remote peripheral nerves using a passive implanted conductor, was an effective way to transmit high-frequency waveforms to the pudendal nerve to block ongoing sphincter contractions. Methods. High-frequency waveforms were delivered through the skin to the pudendal nerve using a passive implanted conductor in 6 adult cats anesthetized with isoflurane. Five of the experiments were acute, terminal procedures, and the remaining cat was implanted with a permanent electrode system allowing evaluation for 6 months. Typical stimulation parameters were in the range of 1 to 10 kHz and 1 to 10 mA. Results. Complete blocking of external urethral sphincter contractions was achieved in 5 of the 6 animals. High-frequency stimulation was also tested in the chronically implanted animal without anesthesia, and the stimulation was tolerated with minimal aversive reactions. Conclusions. The transcutaneous passive implanted conductor stimulus delivery system is an effective way to stimulate the pudendal nerve at high frequency, leading to sphincter relaxation. This system may provide a simple means to implement this stimulation paradigm in people with detrusor-sphincter dyssynergia.
Total Ankle Arthroplasty With Bone Defects
Authors: Reiley Mark A.
Published: December 2008

An alternative total ankle arthroplasty procedure has been developed that capitalizes on the strength of local bone when posterior bone stock of the talus is insufficient. This case report describes the 2-year postoperative results of a modular total ankle arthroplasty on a patient with significant bone loss of the posterior talus.
A role for MEIS1 in MLL-fusion gene leukemia
Authors: Kumar Ashish R. , Li Quanzhi , Hudson Wendy A. , Chen Weili , Sam Thien , Yao Qing , Lund Erik A. , Wu Baolin , Kowal Branden J. , Kersey John H.
Published: December 2008

Leukemias with MLL rearrangements are characterized by high expression of the homeobox gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplantation recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA-mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell-cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor.
Sphingosine kinase regulates the rate of endothelial progenitor cell differentiation
Authors: Bonder Claudine S. , Sun Wai Y. , Matthews Tyson , Cassano Carlos , Li Xiaochun , Ramshaw Hayley S. , Pitson Stuart M. , Lopez Angel F. , Coates P. Toby , Proia Richard L. , Vadas Mathew A. , Gamble Jennifer R.
Published: December 2008

Circulating endothelial progenitor cells (EPCs) are incorporated into foci of neovascularization where they undergo differentiation to mature endothelial cells (ECs). We show here that the enzyme sphingosine kinase-1 (SK-1) regulates the rate and direction of EPC differentiation without effect on the hematopoietic compartment. EPCs have high levels of SK-1 activity, which diminishes with differentiation and is, at least partially, responsible for maintaining their EPC phenotype. EPCs from SK-1 knockout mice form more adherent EC units and acquire a mature EC phenotype more rapidly. Conversely, EPCs from mice overexpressing SK-1 in the EC compartment are retarded in their differentiation. Exogenous regulation of SK-1 levels in normal EPCs, by genetic and pharmacologic means, including the immunomodulating drug FTY720, recapitulates these effects on EC differentiation. SK-1 knockout mice have higher levels of circulating EPCs, an exaggerated response to erythropoietin-induced EPC mobilization, and, in a mouse model of kidney ischemia reperfusion injury, exhibit a recovery similar to that of ischemic mice administered exogenous EPCs. Thus, SK-1 is a critical player in EPC differentiation into EC pointing to the potential utility of SK-1 modifying agents in the specific manipulation of endothelial development and repair.
The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation
Authors: Banno Fumiaki , Chauhan Anil K. , Kokame Koichi , Yang Jin , Miyata Shigeki , Wagner Denisa D. , Miyata Toshiyuki
Published: December 2008

ADAMTS13 is a multidomain protease that limits platelet thrombogenesis through the cleavage of von Willebrand factor (VWF). We previously identified 2 types of mouse Adamts13 gene: the 129/Sv-strain Adamts13 gene encodes the long-form ADAMTS13 having the same domains as human ADAMTS13, whereas the C57BL/6-strain Adamts13 gene encodes the short-form ADAMTS13 lacking the distal C-terminal domains. To assess the physiologic significance of the distal C-terminal domains of ADAMTS13, we generated and analyzed 129/Sv-genetic background congenic mice (Adamts13S/S) that carry the short-form ADAMTS13. Similar to wild-type 129/Sv mice (Adamts13L/L), Adamts13S/S did not have ultralarge VWF multimers in plasma, in contrast to 129/Sv-genetic background ADAMTS13-deficient mice (Adamts13−/−). However, in vitro thrombogenesis under flow at a shear rate of 5000 s−1 was accelerated in Adamts13S/S compared with Adamts13L/L. Both in vivo thrombus formation in ferric chloride–injured arterioles and thrombocytopenia induced by collagen plus epinephrine challenge were more dramatic in Adamts13S/S than in Adamts13L/L but less than in Adamts13−/−. These results suggested that the C-terminally truncated ADAMTS13 exhibited decreased activity in the cleavage of VWF under high shear rate. Role of the C-terminal domains may become increasingly important under prothrombotic conditions.
Chaperoning erythropoiesis
Authors: Weiss Mitchell J. , dos Santos Camila O.
Published: December 2008

Multisubunit complexes containing molecular chaperones regulate protein production, stability, and degradation in virtually every cell type. We are beginning to recognize how generalized and tissue-specific chaperones regulate specialized aspects of erythropoiesis. For example, chaperones intersect with erythropoietin signaling pathways to protect erythroid precursors against apoptosis. Molecular chaperones also participate in hemoglobin synthesis, both directly and indirectly. Current knowledge in these areas only scratches the surface of what is to be learned. Improved understanding of how molecular chaperones regulate erythropoietic development and hemoglobin homeostasis should identify biochemical pathways amenable to pharmacologic manipulation in a variety of red blood cell disorders including thalassemia and other anemias associated with hemoglobin instability.
Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families
Authors: Thangudu Ratna R , Manoharan Malini , Srinivasan N , Cadet Frédéric , Sowdhamini R , Offmann Bernard
Published: December 2008

Background

Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue.

Results

Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues.

Conclusion

We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function.