bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Complications in Elderly Adults with Chronic Kidney Disease
Authors: Drawz Paul E. , Babineau Denise C. , Rahman Mahboob
Published: January 2012

Objectives

To determine whether elderly adults with a low glomerular filtration rate (GFR) are at risk for anemia, hyperkalemia, acidosis, and hyperphosphatemia.

Design

Retrospective study.

Setting

Veterans Affairs Medical Center.

Participants

Thirteen thousand eight hundred seventy‐four veterans aged 65 and older with chronic kidney disease (CKD) and a GFR between 15 and 60 mL/min per 1.73 m2. Their average age was 79.

Measurements

Anemia was defined as a hemoglobin level of less than 10 g/dL, hyperkalemia as a potassium level greater than 5.5 mEq/L, acidosis as a bicarbonate level of less than 21 mEq/L, and hyperphosphatemia as a phosphorus level greater than 4.6 mg/dL. Multivariable logistic regression was used to evaluate whether age modifies the effect of low GFR on metabolic complications by including an interaction term between age and GFR in each model.

Results

The average GFR of participants was 46.5 mL/min per 1.73m2, 3.1% had anemia, 2.5% hyperkalemia, 2.3% acidosis, and 4.4% had hyperphosphatemia. Lower GFR was associated with higher rates of metabolic complications across all age groups (odds ratio per 5‐mL/min per 1.73 m2 decrease in GFR in multivariable models was 1.21 for anemia, 1.26 for hyperkalemia, 1.45 for acidosis, and 1.72 for hyperphosphatemia). There was no significant interaction between age and GFR in models including only age and GFR or in multivariable models (P‐values for age by GFR interaction term: 0.66 for anemia, 0.19 for hyperkalemia, 0.54 for acidosis, and 0.22 for hyperphosphatemia).

Conclusion

Elderly adults with CKD are at risk for anemia, hyperkalemia, acidosis, and hyperphosphatemia; age does not modify the relationship between GFR and development of metabolic complications. Elderly adults with low GFR should be monitored for metabolic complications, regardless of age.
Elder Self‐Neglect and Hospitalization: Findings from the Chicago Health and Aging Project
Authors: Dong XinQi , Simon Melissa A. , Evans Denis
Published: January 2012

Objectives

To quantify the relation between reported elder self‐neglect and rate of hospitalization in a community population of older adults.

Design

Prospective population‐based study.

Setting

Geographically defined community in Chicago.

Participants

Community dwelling older adults who participated in the Chicago Health and Aging Project. One thousand one hundred sixty‐five of the 6,864 participants in the Chicago Health and Aging Project was reported to social services agency for suspected elder self‐neglect.

Measurements

The primary predictor was elder self‐neglect reported to social services agency. The outcome of interest was the annual rate of hospitalization, obtained from the Centers for Medicare and Medicaid Services. Poisson regression models were used to assess these longitudinal relationships.

Results

The average annual rate of hospitalization was 0.6 ± 1.3 for participants without elder self‐neglect and 1.8 ± 3.2 for those with reported elder self‐neglect. After adjusting for sociodemographic and socioeconomic characteristics, medical commorbidities, and cognitive and physical function, older adults who neglected themselves had significantly higher rate of hospitalization (rate ratio = 1.47, 95% confidence interval = 1.39–1.55). Greater severity of self‐neglect (mild: standardized parameter estimate (PE) = 0.24, standard error (0.05); moderate: PE = 0.45 (0.03); severe: PE = 0.54, (0.11), all P < .001) was associated with higher annual rates of hospitalization after adjusting for the same confounders. Interaction term analyses suggest that medical conditions, cognitive impairment, and physical disability did not mediate the significant relationship between self‐neglect and hospitalization.

Conclusion

Reported elder self‐neglect was associated with higher rates of hospitalization in this community population. Greater severity of self‐neglect was associated with a greater rate of hospitalization.
Efficacy of Cognitive Behavioral Therapy for Anxiety Disorders in Older People: A Meta‐Analysis and Meta‐Regression of Randomized Controlled Trials
Authors: Gould Rebecca L. , Coulson Mark C. , Howard Robert J.
Published: January 2012

Objectives

To review the magnitude and duration of and factors associated with effects of cognitive behavioral therapy (CBT) for anxiety disorders in older people.

Design

Electronic literature databases and the Cochrane Trials Registry were searched for articles. A systematic critical review, random‐effects meta‐analysis, and meta‐regression of randomized controlled trials were conducted.

Setting

Community outpatient clinics.

Participants

People with diagnoses of anxiety disorders.

Measurements

Outcome measures of anxiety and depression.

Results

Twelve studies were included. CBT was significantly more effective than treatment as usual or being on a waiting list at reducing anxiety symptoms at 0‐month follow‐up, with the effect size being moderate, but when CBT was compared with an active control condition, the between‐group difference in favor of CBT was not statistically significant, and the effect size was small. At 6‐ but not 3‐ or 12‐month follow‐up, CBT was significantly more effective at reducing anxiety symptoms than an active control condition, although the effect size was again small. Meta‐regression analyses revealed only one factor (type of control group) to be significantly associated with the magnitude of effect sizes.

Conclusion

The review confirms the effectiveness of CBT for anxiety disorders in older people but is suggestive of lower efficacy in older than working‐age people. The small effect sizes in favor of CBT over an active control condition illustrate the need to investigate other treatment approaches that may be used to substitute or augment CBT to increase the effectiveness of treatment of anxiety disorders in older people.
Vitamin D Deficiency in Elderly Women in Nursing Homes: Investigation with Consideration of Decreased Activation Function from the Kidneys
Authors: Terabe Yasuhito , Harada Atsushi , Tokuda Haruhiko , Okuizumi Hiroyasu , Nagaya Masahiro , Shimokata Hiroshi
Published: January 2012

Objectives

To determine the approximate percentage of women in nursing homes who have vitamin D deficiency and to investigate whether, in assessing vitamin D status in elderly women, there are problems with measuring only 25 hydroxy‐vitamin D3 (25(OH)D3) and whether decreased vitamin D activation as a result of poor renal function needs to be considered.

Design

Cross‐sectional study.

Setting

Forty‐eight nursing homes in Japan.

Participants

Four hundred three women with a mean age of 86.5 living in nursing homes who had participated in a clinical trial for hip protectors and were not bedridden.

Measurements

At the start of the trial, in addition to general biochemical data, 25(OH)D3, 1,25‐dihydroxy‐vitamin D3 (1,25(OH)2D3), intact parathyroid hormone (intact PTH), calcium (Ca), phosphorus (P), bone alkaline phosphate (BAP), cross‐linked N‐telopeptide of type I collagen (NTx), and osteocalcin were measured in participants’ blood, and statistical analysis was performed.

Results

25(OH)D3, which is thought to reflect vitamin D status in the body, was surveyed and found to have a mean value of 16.7 ng/mL. 25(OH)D3 was less than 16 ng/mL in 49.1% of all participants. Creatinine clearance (CCr) was less than 30 mL/min in 20.1% of participants. Participants with serum 25(OH)D3 less than 16 ng/mL and CCr less than 30 mL/min had significantly higher levels of intact PTH and serum NTx. Participants with a CCr less than 30 mL/min had significantly lower levels of 1,25(OH)2D3.

Conclusion

Frail elderly adults living in nursing homes with poor renal function had lower 1,25(OH)2D3 and higher intact PTH levels and were thus thought to have poorer vitamin D activating capacity. Supplementation with cholecalciferol may be insufficient in people who have poor renal function.
Do Centenarians Have Higher Levels of Depression? Findings from the Georgia Centenarian Study
Authors: Scheetz Laura T. , Martin Peter , Poon Leonard W.
Published: January 2012

Objectives

To examine age differences on specific items and subscales of the Geriatric Depression Scale (GDS).

Design

Specific items, subscales, and total score on the GDS of three age groups were compared.

Setting

Community‐dwelling older adults.

Participants

One hundred thirty‐nine centenarians were compared with 93 octogenarians and 91 sexagenarians.

Measurements

GDS scores.

Results

Results indicated age group differences in overall depression score and in withdrawal‐apathy‐vigor (WAV), cognitive impairment, and hopelessness subscale scores. Significant age group differences were also obtained for 12 of the 30 items. Centenarians rated higher on all subscales, but there was no difference in dysphoric mood and worry.

Conclusion

It is important to distinguish different dimensions of depression when assessing very old populations because some of the questions on the GDS are associated with fatigue, mild cognitive decline, and decline in physical functioning, which increase with aging. Future research should revisit the concept of depression in very late life.
Depressive Symptoms, Chronic Pain, and Falls in Older Community‐Dwelling Adults: The MOBILIZE Boston Study
Authors: Eggermont Laura H.P. , Penninx Brenda W.J.H. , Jones Rich N. , Leveille Suzanne G.
Published: January 2012

Objectives

To examine whether overall depressive symptoms and symptom clusters are associated with fall risk and to determine whether chronic pain mediates the relationship between depression and fall risk in aging.

Design

Prospective cohort study.

Setting

Boston, Massachusetts, and surrounding communities.

Participants

Older community‐dwelling adults (N = 722, mean age 78.3).

Measurements

Depressive symptomatology was assessed at baseline using the 20‐item Hopkins Revision of the Center for Epidemiologic Studies Depression Scale (CESDR) as overall depression and two separate domains: cognitive and somatic symptoms. Chronic pain was examined at baseline as number of pain sites (none, single site, or multisite), pain severity, and pain interference with activities of daily living. Participants recorded falls on monthly postcards during a subsequent 18‐month period.

Results

According to negative binomial regression, the rate of incident falls was highest in those with the highest burden of depressive symptoms (according to total CESDR and the cognitive and somatic CESDR domains). After adjustment for multiple confounders and fall risk factors, fall rate ratios comparing the highest three CESDR quartiles with the lowest quartile were 1.91, 1.26, and 1.11, respectively. Similarly graded associations were observed according to the CESDR domains. Although pain location and interference were mediators of the relationship between depression and falls, adjustment for pain reduced fall risk estimates only modestly. There was no interaction between depression and pain in relation to fall risk.

Conclusion

Depressive symptoms are associated with fall risk in older adults and are mediated in part by chronic pain. Research is needed to determine effective strategies for reducing fall risk and related injuries in older people with pain and depressive symptoms.
Diabetes Mellitus in Centenarians
Authors: Davey Adam , Lele Uday , Elias Merrill F. , Dore Gregory A. , Siegler Ilene C. , Johnson Mary A. , Hausman Dorothy B. , Tenover J. Lisa , Poon Leonard W. ,   for the Georgia Centenarian Study
Published: January 2012

Objectives

To describe the prevalence of diabetes mellitus (DM) in centenarians.

Design

Cross‐sectional, population‐based.

Setting

Forty‐four counties in northern Georgia.

Participants

Two hundred forty‐four centenarians (aged 98–108, 15.8% male, 20.5% African American, 38.0% community dwelling) from the Georgia Centenarian Study (2001–2009).

Measurements

Nonfasting blood samples assessed glycosylated hemoglobin (HbA1c) and relevant clinical parameters. Demographic, diagnosis, and DM complication covariates were assessed.

Results

12.5% of centenarians were known to have DM. DM was more prevalent in African Americans (27.7%) than whites (8.6%, P < .001). There were no differences between men (16.7%) and women (11.7%, P = .41) or between centenarians living in the community (10.2%) and in facilities (13.9%, P = .54). DM was more prevalent in overweight and obese (23.1%) than nonoverweight (7.1%, P = .002) centenarians. Anemia (78.6% vs 48.3%, P = .004) and hypertension (79.3% vs 58.6%, P = .04) were more prevalent in centenarians with DM than in those without, and centenarians with DM took more nonhypoglycemic medications (8.6 vs 7.0, P = .02). No centenarians with HbA1c of less than 6.5% had random serum glucose levels greater than 200 mg/dL. DM was not associated with 12‐month all‐cause mortality, visual impairment, amputations, cardiovascular disease, or neuropathy. Thirty‐seven percent of centenarians reported onset before age 80 (survivors), 47% between age 80 and 97 (delayers), and 15% aged 98 and older (escapers).

Conclusion

Diabetes mellitus is a risk factor for cardiovascular disease and mortality but is seen in persons who live into very old age. Aside from higher rates of anemia and use of more medications, few clinical correlates of DM were observed in centenarians.
Coronary Artery Disease Is Associated with Cognitive Decline Independent of Changes on Magnetic Resonance Imaging in Cognitively Normal Elderly Adults
Authors: Zheng Ling , Mack Wendy J. , Chui Helena C. , Heflin Lara , Mungas Dan , Reed Bruce , DeCarli Charles , Weiner Michael W. , Kramer Joel H.
Published: January 2012

Objectives

To examine in cognitively normal elderly adults whether vascular factors predict cognitive decline and whether these associations are mediated by magnetic resonance imaging (MRI) measures of subclinical vascular brain injury.

Design

Prospective multisite longitudinal study of subcortical ischemic vascular diseases.

Setting

Memory and aging centers in California.

Participants

Seventy‐four participants who were cognitively normal at entry and underwent at least two neuropsychological evaluations and two MRI examinations over an average follow‐up of 6.9 years.

Measurements

Item response theory was used to create composite scores of global, verbal memory, and executive functioning. Volumetric MRI measures included white matter hyperintensities (WMHs), silent brain infarcts (SBIs), hippocampus, and cortical gray matter (CGM). Linear mixed‐effects models were used to examine the associations between vascular factors, MRI measures, and cognitive scores.

Results

History of coronary artery disease (CAD) was associated with greater declines in global cognition, verbal memory, and executive function. The CAD associations remained after controlling for changes in WMHs, SBIs, and hippocampal and CGM volumes.

Conclusion

History of CAD may be a surrogate marker for clinically significant atherosclerosis, which also affects the brain. Structural MRI measures of WMHs and SBIs do not fully capture the potential adverse effects of atherosclerosis on the brain. Future longitudinal studies of cognition should incorporate direct measures of atherosclerosis in cerebral arteries, as well as more sensitive neuroimaging measures.
Estimating the Evolution of Money’s Role in the U.S. Monetary Business Cycle
Authors: CASTELNUOVO EFREM
Published: January 2012

We assess money’s role in the post‐WWII U.S. business cycle by employing both fixed‐coefficient and rolling‐window Bayesian estimations of a structural model of the business cycle with money. Our empirical evidence favors a specification with drifting parameters for money‐consumption nonseparability and the Federal Reserve’s reaction to nominal money growth. The role of money is estimated to have been important during the 1970s and declined afterward. The omission of money produces severely distorted impulse response functions (relative to the model with money). Money is found to be important in replicating the U.S. output volatility during the Great Inflation.
Monetary Policy Response to Oil Price Shocks
Authors: NATAL JEAN‐MARC
Published: January 2012

How should monetary authorities react to an oil price shock? This paper shows that in a noncompetitive economy, policies that perfectly stabilize prices entail large welfare costs, hence explaining the reluctance of policymakers to enforce them. The policy trade‐off is nontrivial because oil (energy) is an input to both production and consumption. As welfare‐maximizing policies are hard to implement and communicate, I derive a simple interest rate rule that depends only on observables but mimics the optimal plan in all dimensions. The optimal rule is hard on core inflation but accommodates oil price changes.
The Taylor Rule and Forecast Intervals for Exchange Rates
Authors: WANG JIAN , WU JASON J.
Published: January 2012

In this paper, we examine the Meese–Rogoff puzzle from a different perspective: out‐of‐sample interval forecasting. While most studies in the literature focus on point forecasts, we apply semiparametric interval forecasting to a group of exchange rate models. Forecast intervals for 10 OECD exchange rates are generated and the performance of the empirical exchange rate models are compared with the random walk. Our contribution is twofold. First, we find that in general, exchange rate models generate tighter forecast intervals than the random walk, given that their intervals cover out‐of‐sample exchange rate realizations equally well. Our results suggest a connection between exchange rates and economic fundamentals: economic variables contain information useful in forecasting distributions of exchange rates. We also find that the benchmark Taylor rule model performs better than the monetary, PPP and forward premium models, and its advantages are more pronounced at longer horizons. Second, the bootstrap inference framework proposed in this paper for forecast interval evaluation can be applied in a broader context, such as inflation forecasting.
Real Time Three‐Dimensional Echocardiography for Evaluation of Congenital Heart Defects: State of the Art
Authors: Zhang Li , Xie Mingxing , Balluz Rula , Ge Shuping
Published: January 2012

Real time three‐dimensional echocardiography (RT3DE) has been increasingly used in the diagnosis and assessment of congenital heart disease. A growing body of literature suggests that this new technology can be used as an integrated approach to assess the morphology of simple and complex congenital heart defects, flow abnormality, and left, right, and single ventricular function both qualitatively and quantitatively. This review summarizes the available evidence for the use of RT3DE in each of these areas. Future technology refinement in RT3DE and development of practice guidelines will increase the utilization of this new technology as a valuable tool to compliment 2D echocardiography/Doppler in clinical care and research to improve the care and outcome of congenital heart disease. (Echocardiography 2012;29:232‐241)
Real Time Three‐Dimensional Stress Echocardiography Advantages and Limitations
Authors: Abusaid Ghassan H. , Ahmad Masood
Published: January 2012

The role of two‐dimensional stress echocardiography (2D‐SE) is well established for diagnosis and prognosis of patients with known or suspected coronary artery disease. 2D‐SE has its limitations as multiple views of the left ventricle (LV) must be obtained within 90 seconds of peak stress from more than window to completely visualize all LV segments. 2D‐SE is operator‐dependent and requires advanced skills to match the same myocardial segments during stress. LV foreshortening is a frequently encountered problem in 2D‐SE that may result in false negative studies. Real time three‐dimensional SE (RT‐3D‐SE) can overcome many limitations of 2D‐SE. In 3D‐SE, overall wall motion of the entire LV is assessed simultaneously in different planes. 3D images can be displayed in multiplane or multislice views for ease of comparison with greater accuracy and interobserver agreement when compared to 2D. 3D‐SE is quantitative, provides rapid image acquisition, requires lower level of operator skills, and avoids LV foreshortening by correct alignment of imaging planes. 3D‐SE is easily applied during pharmacologic stress and is feasible during exercise‐induced stress. Despite these advantages, 3D has lower temporal and spatial resolution than 2D and requires longer analysis time. With advances in transducer technology, smaller matrix footprints, and automated softwares, 3D full LV volume image acquisition can be obtained with a single beat that is less prone to artifacts. We will discuss the current application of RT‐3D‐SE, highlight the pros and cons of 3D‐SE over conventional 2D‐SE, and review major studies on 3D‐SE and future implications. (Echocardiography 2012;29:200‐206)
Continuing Medical Education Activity in Echocardiography
Authors: Fan Pohoey , Charles Luenda E. , Burchfiel Cecil M. , Andrew Michael E. , Gu Ja K. , Petrini Marcy F. , Butler, Jr. Kenneth R.
Published: January 2012

Article Title: Pulmonary Function and Left Ventricular Mass in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study (Echocardiography 2012;29:130)
Hull Structures as a System: Supporting Lifecycle Analysis
Authors: COLLETTE MATTHEW
Published: January 2012

As modular weapon systems allow cost‐effective upgrades of a vessel's war‐fighting capability, the degradation of the difficult‐to‐upgrade structure of the vessel may soon become one of the key drivers of vessel retirement and lifecycle maintenance costing. Existing structural design approaches are reviewed, along with recent developments in this field. It is argued that recent research has produced a number of ad hoc metrics for structural design, such as producability; however, to truly address the needs of future ship design teams it is necessary to integrate several such metrics in a systems‐engineering view to evaluate how the structural system contributes to the overall capabilities and costs of a proposed vessel. Potential architectures for this approach are discussed, along with key shortcomings. A comparative example is given for structural fatigue of a strength deck under global bending loading, comparing the traditional design approach with a systems‐oriented view.
Using Agents to Model the Kill Chain of the Ballistic Missile Defense System
Authors: HOLLAND O. THOMAS , WALLACE SARA E.
Published: January 2012

Deterministic models have long been used to model the individual effectiveness of elements of the Ballistic Missile Defense System (BMDS). Agent‐based models (ABMs) emphasize the specification of the individual components comprising a system and demonstrate higher order system properties through the interactions of those components. ABMs are particularly suited to (1) complex systems where it is easier to understand or observe the individual components rather than the dynamics that govern their interactions and (2) systems where empirical data is insufficient to provide statistical representations. New missions and capabilities desired by national leadership call for increased interaction between the BMDS elements and their subsystems. New capabilities and mission threads include launch on remote and engage on remote capabilities as well as a robust missile defense system capable of defending against threat raids, debris, and decoys. These new capabilities and mission threads may require modifications to kill chains and command and control constructs as well as improved coordination and performance. These capabilities must be realized through modifications to programs of record and integration across elements of the system that have their own independent programmatic momentum. A robust missile defense system must be achieved through a construct of layered defenses. Change in capabilities requires analysis of the complex interdependencies between Standard Missile (SM‐3), SPY, and BMDS elements such as PATRIOT, Terminal High‐Altitude Area Defense, Aegis Ashore Missile Defense System, etc. Synergy among the systems (termed “elements”) is required to meet the new challenges, which can be accomplished through systems of systems engineering. Definition and testing of the interactions between the systems are crucial to provide situational awareness via analysis of data transfer between the elements. ABMs are a tool that allows qualitative evaluation of these interactions of the complex BMDS. This paper presents an investigation of agent‐based modeling as a method to explore the system interrelationships and evaluate the indeterminacy of the BMDS kill chain.
Cathelicidin LL‐37: a defense molecule with a potential role in psoriasis pathogenesis
Authors: Dombrowski Yvonne , Schauber Jürgen
Published: January 2012

Abstract:  Epidermal keratinocytes produce and secrete antimicrobial peptides (AMPs) that subsequently form a chemical shield on the skin surface. Cathelicidins are one family of AMPs in skin with various further immune functions. Consequently, dysfunction of these peptides has been implicated in the pathogenesis of inflammatory skin disease. In particular, the cathelicidin LL‐37 is overexpressed in inflamed skin in psoriasis, binds to extracellular self‐DNA released from dying cells and converts self‐DNA in a potent stimulus for plasmacytoid dendritic cells (pDCs). Subsequently, pDCs secrete type I interferons and trigger an auto‐inflammatory cascade. Paradoxically, therapies targeting the vitamin D pathway such as vitamin D analogues or UVB phototherapy ameliorate cutaneous inflammation in psoriasis but strongly induce cathelicidin expression in skin at the same time. Current evidence now suggests that self‐DNA present in the cytosol of keratinocytes is also pro‐inflammatory active and triggers IL‐1β secretion in psoriatic lesions through the AIM2 inflammasome. This time, however, binding of LL‐37 to self‐DNA neutralizes DNA‐mediated inflammation. Hence, cathelicidin LL‐37 shows contrasting roles in skin inflammation in psoriasis and might serve as a target for novel therapies for this chronic skin disease.
MiR‐21 is up‐regulated in psoriasis and suppresses T cell apoptosis
Authors: Meisgen Florian , Xu Ning , Wei Tianling , Janson Peter C. , Obad Susanna , Broom Oliver , Nagy Nikoletta , Kauppinen Sakari , Kemény Lajos , Ståhle Mona , Pivarcsi Andor , Sonkoly Enikö
Published: January 2012

Abstract:  MicroRNAs are short non‐coding RNAs that regulate gene expression. Previously, in a genome‐wide screen, we found deregulation of microRNA expression in psoriasis skin. MicroRNA‐21 (miR‐21) is one of the microRNAs significantly up‐regulated in psoriasis skin lesions. To identify the cell type responsible for the increased miR‐21 level, we compared expression of miR‐21 in epidermal cells and dermal T cells between psoriasis and healthy skin and found elevated levels of miR‐21 in psoriasis in both cell types. In cultured T cells, expression of miR‐21 increased markedly upon activation. To explore the function of miR‐21 in primary human T helper cells, we inhibited miR‐21 using a tiny seed‐targeting LNA‐anti‐miR. Specific inhibition of miR‐21 increased the apoptosis rate of activated T cells. Our results suggest that miR‐21 suppresses apoptosis in activated T cells, and thus, overexpression of miR‐21 may contribute to T cell–derived psoriatic skin inflammation.
Evaluation of mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors
Authors: de Noronha Santos Netto Juliana , Pires Fábio Ramôa , da Fonseca Eliene Carvalho , Silva Licínio Esmeraldo , de Queiroz Chaves Lourenço Simone
Published: January 2012

J Oral Pathol Med (2012) 41: 630–636

Background:  Several cell types are associated with the development of cystic and tumoral odontogenic lesions. Among inflammatory cells, mast cells can be associated with their pathogenesis. The aim of this study was to analyze mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors.

Methods:  Tissue sections were submitted to toluidine blue staining and immunohistochemistry with antibody anti‐tryptase (clone G3). Mast cells were quantitated using Image‐Pro Plus software to obtain the mean number of mast cells in three regions: epithelial, superficial portion of the fibrous wall and deep portion of the fibrous wall from 20 periapical cysts, 20 dentigerous cysts (six non‐inflamed and 14 inflamed) and 20 keratocystic odontogenic tumors (four non‐inflamed and 16 inflamed).

Results:  The mean number of mast cells detected per lesion by immunohistochemistry (4.1) was higher than by histochemistry (1.5) (P < 0.0001). Inflamed dentigerous cysts and keratocystic odontogenic tumors showed a higher mean number of mast cells than non‐inflamed lesions in all regions. The deep region from all cysts showed the highest mean number of degranulated mast cells, except for non‐inflamed keratocystic odontogenic tumors analyzed by immunohistochemistry.

Conclusions:  Immunohistochemical staining detected higher number of mast cells than histochemistry. The higher number of mast cells observed in inflamed lesions could indicate the participation of these cells in the inflammatory response in odontogenic lesions. The prevalence of degranulated mast cells in the deep region suggests intense activity of these cells, possibly related to growth of cystic lesions.
Quality Control Compartments Coming of Age
Authors: Ben‐Gedalya Tziona , Cohen Ehud
Published: January 2012

Maintenance of proteome integrity (proteostasis) is essential for cellular and organismal survival. Various cellular mechanisms work to preserve proteostasis by ensuring correct protein maturation and efficient degradation of misfolded and damaged proteins. Despite this cellular effort, under certain circumstances subsets of aggregation‐prone proteins escape the quality control surveillance, accumulate within the cell and form insoluble aggregates that can lead to the development of disorders including late‐onset neurodegenerative diseases. Cells respond to the appearance of insoluble aggregates by actively transporting them to designated deposition sites where they often undergo degradation. Although several protein aggregate deposition sites have been described and extensively studied, key questions regarding their biological roles and how they are affected by aging remained unanswered. Here we review the recent advances in the field, describe the different subtypes of these cellular compartments and outline the evidence that these structures change their properties over time. Finally, we propose models to explain the possible mechanistic links between aggregate deposition sites, neurodegenerative disorders and the aging process.
Contribution of active site glutamine to rate enhancement in ubiquitin C‐terminal hydrolases
Authors: Boudreaux David A. , Chaney Joseph , Maiti Tushar K. , Das Chittaranjan
Published: January 2012

Ubiquitin C‐terminal hydrolases (UCHs) are cysteine proteases featuring a classical Cys–His–Asp catalytic triad, and also a highly conserved Gln that is thought to be a part of the oxyanion hole. However, the contribution of this side chain to catalysis by UCHs is not known. Herein, we demonstrate that the Gln side chain contributes to rate enhancement in UCHL1, UCHL3, and UCHL5. Mutation of the Gln to Ala in these enzymes impairs the catalytic efficiency, mainly because of a 16‐fold to 30‐fold reduction in kcat, which is consistent with a loss of approximately 2 kcal·mol−1 in transition state stabilization. However, the contribution to transition state stabilization observed here is rather modest for the side chain’s role in oxyanion stabilization. Interestingly, we discovered that the carbonyl oxygen of this side chain is engaged in a C–H···O hydrogen‐bonding contact with the CεH group of the catalytic His. Upon further analysis, we found that this interaction is a common active site structural feature in most cysteine proteases, including papain, belonging to families with the QCH(N/D) type of active site configuration. It is possible that removal of the Gln side chain might have abolished the C–H···O interaction, which typically accounts for 2 kcal·mol−1 of stabilization, leading to the effect on catalysis observed here. Additional studies performed on UCHL3 by mutating the Gln to Glu (strong C–H···O acceptor but oxyanion destabilizer) and to Lys (strong oxyanion stabilizer but lacking C–H···O hydrogen‐bonding capability) suggest that the C–H···O hydrogen bond could contribute to catalysis.
Structural basis for protein phosphatase 1 regulation and specificity
Authors: Peti Wolfgang , Nairn Angus C. , Page Rebecca
Published: January 2012

The ubiquitous serine/threonine protein phosphatase 1 (PP1) regulates diverse, essential cellular processes such as cell cycle progression, protein synthesis, muscle contraction, carbohydrate metabolism, transcription and neuronal signaling. However, the free catalytic subunit of PP1, while an effective enzyme, lacks substrate specificity. Instead, it depends on a diverse set of regulatory proteins (≥ 200) to confer specificity towards distinct substrates. Here, we discuss recent advances in structural studies of PP1 holoenzyme complexes and summarize the new insights these studies have provided into the molecular basis of PP1 regulation and specificity.
Synthesis and Preliminary Biologic Evaluation of 5‐Substituted‐2‐(4‐substituted phenyl)‐1,3‐Benzoxazoles as A Novel Class of Influenza Virus A Inhibitors
Authors: Li Zhenyu , Zhan Peng , Naesens Lieve , Vanderlinden Evelien , Liu Ailin , Du Guanhua , De Clercq Erik , Liu Xinyong
Published: January 2012

The diversity‐oriented chemistry synthesis together with the random screening approach has permitted the discovery and optimization of novel antiviral lead compounds. In this paper, a series of novel 5‐substituted‐2‐(4‐substituted phenyl)‐1,3‐benzoxazoles was synthesized and evaluated for their in vitro anti‐influenza A virus and anti‐influenza B virus activity. The activity was monitored by the MTS assay in the Madin–Darby canine kidney cells. Compound 7h showed excellent inhibitory activity and selective index against A/H3N2 (EC50 = 37.03 μm, SI > 5), which were all higher than that of the reference drug oseltamivir (EC50 > 59.00 μm, SI > 1). However, no compound displays inhibitory activity against influenza B virus.
Synthesis and Antimalarial Activity of Dihydroperoxides and Tetraoxanes Conjugated with Bis(benzyl)acetone Derivatives
Authors: Franco Lucas Lopardi , de Almeida Mauro Vieira , e Silva Luiz Francisco Rocha , Vieira Pedro Paulo Ribeiro , Pohlit Adrian Martin , Valle Marcelo Siqueira
Published: January 2012

Dihydroperoxides and tetraoxanes derived from symmetrically substituted bis(arylmethyl)acetones were synthesized in modest to good yields using several methods. Three of these compounds exhibit an important in vitro antimalarial activity (1.0 μm ≤ IC50 ≤ 5.0 μm) against blood forms of the human malaria parasite Plasmodium falciparum.
Cooling in Intracerebral Hemorrhage (CINCH) Trial: Protocol of a Randomized German–Austrian Clinical Trial
Authors: Kollmar Rainer , Juettler Eric , Huttner Hagen B. , Dörfler Arnd , Staykov Dimitre , Kallmuenzer Bernd , Schmutzhard Erich , Schwab Stefan , Broessner Gregor ,   for the CINCH investigators
Published: January 2012

Background

Intracerebral hemorrhage accounts for up to 15% of all strokes and is frequently associated with poor functional outcome and high mortality. So far, there is no clear evidence for a specific therapy, apart from general stroke unit or neurointensive care and management of secondary complications. Promising experimental and pilot clinical data support the use of therapeutic hypothermia after intracerebral hemorrhage.

Aims

The study aims to determine if therapeutic hypothermia improves survival rates and reduces cerebral lesion volume after large intracerebral hemorrhage compared with conventional treatment.

Material and methods

The Cooling in IntraCerebral Hemorrhage trial is a prospective, multicenter, interventional, randomized, parallel, two-arm (1 : 1) phase II trial with blinded end-point adjudication. Enrolment: 50 patients (age: 18 to 65 years) with large (25 to 64 ml on cranial computertomography), primary intracerebral hemorrhage of the basal ganglia or thalamus within 6 to 18 h after symptom onset are randomly allocated to therapeutic hypothermia for eight-days or conventional temperature management. In the therapeutic hypothermia group, a target temperature of 35·0°C is achieved by endovascular catheters and followed by slow controlled rewarming. Data analysis is based on the intent-to-treat population. The primary outcome measure of the study is the development in total lesion volume on cranial computertomography (intracerebral hemorrhage plus perihemorrhagic edema on day 8 ± 0·5 and day 11 ± 0·5 after intracerebral hemorrhage) and the mortality after 30 days. Secondary end-points are the in-hospital mortality, mortality, and functional outcome (modified Rankin Scale and Barthel-Index) after 90 and 180 days. Safety measures include any adverse events associated with therapeutic hypothermia.

Discussion

In the face of a lack of evidence-based therapies for patients with large intracerebral hemorrhage, new promising approaches are desperately needed, but need evaluation in randomized controlled trials.

Conclusion

The results of Cooling in IntraCerebral Hemorrhage trial are believed to directly influence future therapy of large intracerebral hemorrhage.
Fatigue after Stroke: A Systematic Review of Associations with Impaired Physical Fitness
Authors: Duncan Fiona , Kutlubaev Mansur A. , Dennis Martin S. , Greig Carolyn , Mead Gillian E.
Published: January 2012

Background

Fatigue is a common and distressing post stroke symptom. One important hypothesis is that fatigue after stroke may be triggered by physical deconditioning, which sets up a vicious, self-perpetuating cycle of fatigue, avoidance of physical activity, further deconditioning, and more fatigue. If an association between physical activity and fatigue after stroke could be established, this would provide a rationale for developing a physical activity-based treatment.

Aims

Systematically review all observational studies, which have measured both fatigue poststroke and one or more measures of physical fitness and/or physical activity at the same time-point and reported the association between fatigue and fitness variables.

Method

Publications were identified by systematically searching databases MEDLINE, EMBASE, CINAHL, PsychInfo, and Sportdiscus using keywords ‘fatigue’, ‘stroke’, ‘fitness’, or ‘activity’ and their associated terms or synonyms. Publications that provided data on associations between fatigue in stroke patients and levels of physical activity, cardiorespiratory fitness and/or muscle strength and mass were included.

Results

Twenty-nine potential studies were retrieved after scrutinizing the titles and abstracts, of which only three fulfilled our inclusion criteria. No association between fatigue and any measures of physical activity or fitness were found. One study did find, through structural equation modeling techniques that fatigue indirectly influences exercise through self-efficacy expectations.

Conclusions

There is very limited evidence regarding associations between exercise, fitness, and fatigue after stroke. It still remains highly plausible that exercise can have a positive influence on fatigue. Future research should be longitudinal in design.
Risks and Benefits of Thrombolysis in the Elderly
Authors: Asdaghi Negar , Butcher Kenneth S. , Hill Michael D.
Published: January 2012

Background and purpose

Stroke incidence continues to rise exponentially with age even as temporal trends in some population risk factors increase and others decline. In general, older patients with stroke have worse outcomes compared to their younger counterparts. Stroke severity, concurrent medical problems, prestroke disability, and less-aggressive acute and chronic management are a few contributing factors to account for this poor prognosis. Acute thrombolysis therapy is the only proven treatment in acute ischemic stroke. However, elderly patients have mostly been excluded from acute revascularization studies, due predominantly to their overall poor prognosis and the fear of hemorrhagic complications from these treatments. Despite this, there is no evidence to suggest that the risk benefit ratio of thrombolysis treatment is substantially different in the elderly than in younger ischemic stroke patients.

Summary of review

In this review, we briefly examine the stroke risk factor profile and outcome in the elderly and review the current evidence regarding intravenous and intra-arterial revascularization treatments.

Conclusion

We feel that carefully selected patients who meet eligibility criteria for thrombolysis should not be denied this therapy on the basis of age alone.
Urine specific gravity values in clinically healthy young pet ferrets (Mustela furo)
Authors: Eshar D. , Wyre N. R. , Brown D. C.
Published: January 2012

Objectives: To determine urine specific gravity values in clinically healthy pet ferrets and explore possible associations with sex, sampling techniques, hydration status and urine analytes.

Methods: Sixty‐nine entire ferrets of both sexes, under one year of age, were included in this study. Physical examination, complete blood count, blood biochemistry, urine microscopy, urine dipstick and urine specific gravity were performed on all ferrets. Urine specific gravity was determined using a handheld urine refractometer. Statistical analysis was performed to determine urine specific gravity value intervals and to test for associations with sex, sample collection method, packed cell volume, plasma total protein concentrations and urine analytes.

Results: Urine specific gravity differed by sex in ferrets as females exhibited a lower urine specific gravity (P<0·001). There was no significant correlation between urine specific gravity, sampling method, packed cell volume/total protein and urine dipstick analytes. Mean urine specific gravity reported in this study was 1·051 for entire males (sd ±9; range 1·034 to 1·070) and 1·042 for entire females (sd ±8; range 1·026 to 1·060).

Clinical Significance: Results of this study may allow clinicians to have a more accurate evaluation of the ability of those animals to concentrate urine by comparing their urine specific gravity results to those obtained from this cohort of clinically healthy animals.
A fresh look at the predictors of naming accuracy and errors in Alzheimer's disease
Authors: Cuetos Fernando , Rodríguez‐Ferreiro Javier , Sage Karen , Ellis Andrew W.
Published: January 2012

In recent years, a considerable number of studies have tried to establish which characteristics of objects and their names predict the responses of patients with Alzheimer's disease (AD) in the picture‐naming task. The frequency of use of words and their age of acquisition (AoA) have been implicated as two of the most influential variables, with naming being best preserved for objects with high‐frequency, early‐acquired names. The present study takes a fresh look at the predictors of naming success in Spanish and English AD patients using a range of measures of word frequency and AoA along with visual complexity, imageability, and word length as predictors. Analyses using generalized linear mixed modelling found that naming accuracy was better predicted by AoA ratings taken from older adults than conventional ratings from young adults. Older frequency measures based on written language samples predicted accuracy better than more modern measures based on the frequencies of words in film subtitles. Replacing adult frequency with an estimate of cumulative (lifespan) frequency did not reduce the impact of AoA. Semantic error rates were predicted by both written word frequency and senior AoA while null response errors were only predicted by frequency. Visual complexity, imageability, and word length did not predict naming accuracy or errors.
Relationship Education Research: Current Status and Future Directions
Authors: Markman Howard J. , Rhoades Galena K.
Published: January 2012

The overarching aim of this article is to review the research on relationship education programs and approaches that has been published or accepted for publication since the last review article in 2003. This article provides a critical overview of the relationship education field and sets an agenda for research and practice for the next decade. A theme weaved throughout the article is the ways in which relationship education is similar and different from couples therapy, and we conclude that there can be a synergistic, healthy marriage between the two. We then provide recommendations for future directions for research in the relationship education field. Finally, the coauthors comment on our experiences in both the relationship education field and the couples therapy field as both researchers and interventionists.
Intervention Research in Couple and Family Therapy: A Methodological and Substantive Review and an Introduction to the Special Issue
Authors: Sprenkle Douglas H.
Published: January 2012

This article serves as an introduction to this third version of research reviews of couple and family therapy (CFT) that have appeared in this journal beginning in 1995. It also presents a methodological and substantive overview of research in couple and family therapy from about 2001/2002 to 2010/2011 (the period covered in this issue), while also making connections with previous research. The article introduces quantitative research reviews of family‐based intervention research that appear in this issue on 10 substantive areas including conduct disorder/delinquency, drug abuse, childhood and adolescent disorders (not including the aforementioned), family psycho‐education for major mental illness, alcoholism, couple distress, relationship education, affective disorders, interpersonal violence, and chronic illness. The paper also introduces the first qualitative research paper in this series, as well as a paper that highlights current methodologies in meta‐analysis. The first part of this article rates the 10 content areas on 12 dimensions of methodological strength for quantitative research and makes generalizations about the state of quantitative methodology in CFT. The latter part of the papers summarizes and makes comments on the substantive findings in the 12 papers in this issue, as well as on the field as a whole.
Family Therapy for Drug Abuse: Review and Updates 2003–2010
Authors: Rowe Cynthia L.
Published: January 2012

Just 15 years ago, Liddle and Dakof (Journal of Marital and Family Therapy, 1995; 21, 511) concluded, based on the available evidence, that family therapy represented a “promising, but not definitive” approach for the treatment of drug problems among adolescents and adults. Seven years later, Rowe and Liddle (2003) review described considerable progress in this specialty with encouraging findings on adolescent‐focused models based on rigorous methodology, as well as advances with adult‐focused family‐based treatments. The current review brings the field up to date with highlights from research conducted in the intervening 7 years, cross‐cutting issues, recommendations for new research, and practice implications of these findings. Adolescent‐focused family‐based models that attend to the ecology of the teen and family show the most consistent and strongest findings in recent studies. Adult‐focused models based on behavioral and systems theories of change also show strong effects with drug abusers and their families. The overarching conclusion is that family‐based models are not only a viable treatment alternative for the treatment of drug abuse, but are now consistently recognized among the most effective approaches for treating both adults and adolescents with drug problems.