bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of microdissected neurons by 18O mass spectrometry reveals altered protein expression in Alzheimer's disease
Authors: Hashimoto Masakazu , Bogdanovic Nenad , Nakagawa Hiroyuki , Volkmann Inga , Aoki Mikio , Winblad Bengt , Sakai Jun , Tjernberg Lars O.
Published: September 2011

It is evident that the symptoms of Alzheimer's disease (AD) are derived from severe neuronal damage, and especially pyramidal neurons in the hippocampus are affected pathologically. Here, we analysed the proteome of hippocampal neurons, isolated from post‐mortem brains by laser capture microdissection. By using 18O labelling and mass spectrometry, the relative expression levels of 150 proteins in AD and controls were estimated. Many of the identified proteins are involved in transcription and nucleotide binding, glycolysis, heat‐shock response, microtubule stabilization, axonal transport or inflammation. The proteins showing the most altered expression in AD were selected for immunohistochemical analysis. These analyses confirmed the altered expression levels, and showed in many AD cases a pathological pattern. For comparison, we also analysed hippocampal sections by Western blot. The expression levels found by this method showed poor correlation with the neuron‐specific analysis. Hence, we conclude that cell‐specific proteome analysis reveals differences in the proteome that cannot be detected by bulk analysis.
Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis
Authors: Dragt S. , Nieman D. H. , Schultze‐Lutter F. , van der Meer F. , Becker H. , de Haan L. , Dingemans P. M. , Birchwood M. , Patterson P. , Salokangas R. K. R. , Heinimaa M. , Heinz A. , Juckel G. , Graf von Reventlow H. , French P. , Stevens H. , Ruhrmann S. , Klosterkötter J. , Linszen D. H. ,   on behalf of the EPOS group
Published: September 2011

Dragt S, Nieman DH, Schultze‐Lutter F, van der Meer F, Becker H, de Haan L, Dingemans PM, Birchwood M, Patterson P, Salokangas RKR, Heinimaa M, Heinz A, Juckel G, Graf von Reventlow H, French P, Stevens H, Ruhrmann S, Klosterkötter J, Linszen DH, on behalf of the EPOS group. Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis.

Objective:  Numerous studies have found a robust association between cannabis use and the onset of psychosis. Nevertheless, the relationship between cannabis use and the onset of early (or, in retrospect, prodromal) symptoms of psychosis remains unclear. The study focused on investigating the relationship between cannabis use and early and high‐risk symptoms in subjects at clinical high risk for psychosis.

Method:  Prospective multicenter, naturalistic field study with an 18‐month follow‐up period in 245 help‐seeking individuals clinically at high risk. The Composite International Diagnostic Interview was used to assess their cannabis use. Age at onset of high risk or certain early symptoms was assessed retrospectively with the Interview for the Retrospective Assessment of the Onset of Schizophrenia.

Results:  Younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of six symptoms (0.33 < rs < 0.83, 0.004 < P < 0.001). Onset of cannabis use preceded symptoms in most participants.

Conclusion:  Our results provide support that cannabis use plays an important role in the development of psychosis in vulnerable individuals. Cannabis use in early adolescence should be discouraged.
Nice weather for bettongs: using weather events, not climate means, in species distribution models
Authors: Bateman Brooke L. , VanDerWal Jeremy , Johnson Christopher N.
Published: September 2011

Current applications of species distribution models (SDM) are typically static, in that they are based on correlations between where a species has been observed (ignoring the date of the observation) and environmental features, such as long‐term climate means, that are assumed to be constant for each site. Because of this SDMs do not account for temporal variation in the distribution of suitable habitat across the range of a species. Here, we demonstrate the temporal variability in the potential geographic distributions of an endangered marsupial, the northern bettong Bettongia tropica as a case study. Models of the species distribution using temporally matched observations of the species with weather data (including extreme weather events) at the time of species observations, were better able to define habitat suitability, identify range edges and uncover competitive interactions than models based on static long‐term climate means. Droughts and variable temperature are implicated in low densities and local extinctions of northern bettong populations close to range edges. Further, we show how variable weather can influence the results of competition with the common rufous bettong Aepyprymnus rufescens. Because traditional SDMs do not account for temporal variability of suitable habitat, static SDMs may underestimate the impacts of climate change particularly as the incidence of extreme weather events is likely to rise.
Fine‐needle aspiration cytology: a reliable tool in the diagnosis of salivary gland lesions
Authors: Singh Nanda Kanwar Deep , Mehta Anurag , Nanda Jasmine
Published: September 2011

J Oral Pathol Med (2012) 41: 106–112

Background:  Fine‐needle aspiration cytology (FNAC) is used as the main initial diagnostic investigation for lumps in the head and neck region. Major salivary glands and some minor salivary glands are easily accessible; therefore, they are optimal targets for FNAC. The aim of this study was to discuss the advantages and pitfalls of FNAC as compared to histopathology in the salivary gland lesions.

Material and methods:  A total of 127 FNAC were carried out on salivary gland lesions from January 2006 to December 2010 – a 5‐year period. Histopathological follow‐up data were obtained in 56 cases. The study was conducted to examine the sensitivity, specificity, and accuracy of FNAC for salivary gland swellings in comparison with histopathology.

Results:  The male‐to‐female ratio was 2.4:1. Parotid gland was involved in 51.1%, submandibular gland in 37%, sublingual gland in 4.7%, and minor salivary glands in 7% of patients. There were 55.9% cases of non‐neoplastic lesions and 44.1% cases of neoplastic lesions on biopsy. Sensitivity, specificity, positive predictive value, and negative predictive value of FNAC for malignant neoplastic lesions were 84.61%, 86.48%, 68.75%, and 94.11%, respectively, whereas for benign neoplastic lesions, they were 84.61%, 91.66%, 91.6%, and 85%, respectively.

Conclusion:  Fine‐needle aspiration cytology is found to be a good sensitive and specific technique for the diagnosis of most of the salivary gland lesions. FNAC should be adopted as an initial investigation for all salivary gland swellings in conjunction with other investigations where appropriate.
The Effect of Major Depression on Sexual Function in Women
Authors: Fabre Louis F. , Smith Louis C.
Published: September 2011

Introduction

Eleven hundred eighty-four depressed women were entered into five short-term (8 weeks) studies of gepirone-extended release (ER) vs. placebo for treatment of major depressive disorder (MDD) (134001, 134002, and 134017), or atypical depressive disorder (ADD) (134004 and 134006). The effect of depression on sexual function was examined prior to treatment.

Aim

To determine the effect of depression on the prevalence of Diagnostic and Statistical Manual Fourth Edition (DSM-IV) sexual dysfunction diagnoses and the Derogatis Inventory of Sexual Function (DISF) total score and domain scores and to measure the effect of severity of depression.

Main Outcome Measures

Hamilton Depression Rating Scale (HAMD-17), DSM-IV diagnoses, and DISF total and domain scores.

Methods

DSM-IV diagnoses—hypoactive sexual desire disorder (HSDD), sexual aversion disorder (SAD), female arousal disorder (FAD), and female orgasmic disorder (FOD)—were made by a trained psychiatrist. The HAMD-17 measured antidepressant efficacy. The DISF or its self-report version measured sexual function. To access the effect of severity of depression, baseline HAMD-17 scores were stratified as mild (<18), moderate (19–22), severe (23–25), or extreme (26–33). All measures were taken at baseline.

Results

In this depressed female population, prevalence rates were HSDD 17.7%, SAD 3.4%, FAD 5.8%, and FOD 7.7%. These rates for females are within the reported normal (nondepressed) values. However, DISF scores are one or more standard deviations below population norms for total score. DISF domains are not equally affected: orgasm is most impaired, while sexual desire and sexual arousal are somewhat preserved. Higher HAMD scores result in lower DISF scores (greater sexual dysfunction).

Conclusions

In women, depression affects DISF scores more than DSM-IV diagnoses for sexual dysfunction. With increasing severity of depression (increased HAMD scores), sexual dysfunction becomes greater (lower DISF scores). For equal HAMD scores, DISF scores for MDD and ADD are the same.
Analytical Models of Steady‐State Plumes Undergoing Sequential First‐Order Degradation
Authors: Burnell Daniel K. , Mercer James W. , Sims Lawrence S.
Published: September 2011

An exact, closed‐form analytical solution is derived for one‐dimensional (1D), coupled, steady‐state advection‐dispersion equations with sequential first‐order degradation of three dissolved species in groundwater. Dimensionless and mathematical analyses are used to examine the sensitivity of longitudinal dispersivity in the parent and daughter analytical solutions. The results indicate that the relative error decreases to less than 15% for the 1D advection‐dominated and advection‐dispersion analytical solutions of the parent and daughter when the Damköhler number of the parent decreases to less than 1 (slow degradation rate) and the Peclet number increases to greater than 6 (advection‐dominated). To estimate first‐order daughter product rate constants in advection‐dominated zones, 1D, two‐dimensional (2D), and three‐dimensional (3D) steady‐state analytical solutions with zero longitudinal dispersivity are also derived for three first‐order sequentially degrading compounds. The closed form of these exact analytical solutions has the advantage of having (1) no numerical integration or evaluation of complex‐valued error function arguments, (2) computational efficiency compared to problems with long times to reach steady state, and (3) minimal effort for incorporation into spreadsheets. These multispecies analytical solutions indicate that BIOCHLOR produces accurate results for 1D steady‐state, applications with longitudinal dispersion. Although BIOCHLOR is inaccurate in multidimensional applications with longitudinal dispersion, these multidimensional multispecies analytical solutions indicate that BIOCHLOR produces accurate steady‐state results when the longitudinal dispersion is zero. As an application, the 1D advection‐dominated analytical solution is applied to estimate field‐scale rate constants of 0.81, 0.74, and 0.69/year for trichloroethene, cis‐1,2‐dichloroethene, and vinyl chloride, respectively, at the Harris Palm Bay, FL, CERCLA site.
The Outerbridge – Kashiwagi Technique for Fixation of a Transarticular Coronal Shear Fracture of the Distal Humerus
Authors: Modi Chetan S. , Saithna Adnan , Wainwright David T.
Published: September 2011

Transarticular coronal shear fractures of the distal humerus pose a significant challenge to the surgeon in obtaining an anatomical reduction and rigid fixation. A variety of approaches have been described, including extended lateral and anterolateral approaches and arthroscopically-assisted fixation for noncomminuted fractures. Fixation methods include open or percutaneous cannulated screws and headless compression screws directed either anterior to posterior or posterior to anterior. We describe a novel approach to this fracture utilizing a fenestration of the olecranon fossa with a 4-cm triceps split (i.e. similar to the Outerbridge – Kashiwagi procedure) to insert a bone lever and achieve an anatomical reduction. The fracture was then fixed with headless compression screws directed from posterior to anterior. Early mobilization and rehabilitation were commenced and follow-up clinical examination and radiographs demonstrated full restoration of function with anatomical bony union. We consider that this technique comprises a feasible approach for fixing mild to moderately displaced transarticular coronal shear fractures with medial extension, where the fracture fragment is one block and there is no associated posterior comminution.
Helping young weight controllers develop healthy obsessions: preliminary test of the Healthy Obsession Model
Authors: Byrne S. , Kirschenbaum D. S.
Published: September 2011

The Healthy Obsession Model posits that successful weight controllers must develop a preoccupation with the planning and execution of target behaviours, including eating on programme, consistent activity and self‐monitoring. When barriers emerge, committed weight controllers are expected to feel distressed (e.g. anxious or frustrated), which should motivate them to reinstate these behaviours. This study investigated the effects on moods of sudden withdrawal of self‐monitoring among obese adolescents within an immersion treatment programme. Fifty‐five (55% female) adolescents participated in a weight loss camp and received four weekly cognitive‐behaviour therapy sessions focused on maximizing commitment to programme behaviours. During the fourth week, campers and staff completed daily mood ratings using the Positive and Negative Affect Schedule. After 3 d of ratings, campers' self‐monitoring journals were removed without warning for 1 d. As expected, journal removal resulted in decreased positive affect for the campers, according to staff ratings. Also in accord with hypotheses, campers who demonstrated heightened commitment to the programme based on higher levels of activity and more writing in their journals reacted more negatively to the withdrawal of the opportunity to self‐monitor. Mood ratings by campers did not show the effects hypothesized by the Healthy Obsession Model. These results provide preliminary support for the Healthy Obsession Model by showing some of the anticipated negative reactions to the removal of access to self‐monitoring, especially among those who demonstrated strong commitments to the process.
Computed Tomographic Findings in the Pituitary Gland and Brain of Horses with Pituitary Pars Intermedia Dysfunction
Authors: Pease A.P. , Schott H.C. , Howey E.B. , Patterson J.S.
Published: September 2011

Background:

Pituitary pars intermedia dysfunction (PPID) is the most common endocrinologic disorder of aged horses.

Hypothesis/Objectives:

Pituitary glands of PPID‐affected horses are larger than those of aged horses without signs of PPID, and the size difference can be detected using computed tomography (CT) imaging.

Animals:

Eight horses with clinical signs of PPID and supportive endocrinologic test results and 3 aged control (PPID‐negative) horses.

Methods:

Computed tomography examination of the brain and pituitary gland was performed twice in 10 of the 11 horses, approximately 6 months apart. Six PPID‐affected horses were treated with pergolide for 6 months between CT scans. The second CT scan was followed by euthanasia and pathologic examination of 6 PPID‐affected horses (4 treated horses).

Results:

On initial examination, pituitary glands of PPID‐affected horses were larger in height (P < .01) and width (P < .01) than controls, but the difference in length was not significant (P = .06). After 6 months of pergolide treatment of PPID‐affected horses, pituitary gland length increased (P < .05), but height and width were not different from pretreatment values. There was no difference between pituitary gland measurements made at the terminal CT scans and necropsy. Furthermore, pituitary gland volume calculated from the measurements was highly correlated to pituitary gland weight. Additional CT findings were bilaterally symmetrical mineralization in the thalamus and cholesterol granulomas adjacent to the lateral and fourth ventricles.

Conclusions and Clinical Importance:

CT is a useful imaging modality to determine pituitary gland size of PPID‐affected horses,and CT measurements are similar to gross pathologic measurements.
Possible role of carpal hyperextension in superficial digital flexor tendinopathy
Authors: WHITLOCK D. , GARCIA T. C. , VALLANCE S. A. , STOVER S. M.
Published: September 2011

Reasons for performing study:The specific biomechanical circumstances that induce excessive superficial digital flexor tendon (SDFT) strain in horses are unknown.

Hypothesis:Carpal joint hyperextension during axial limb loading during the middle of stance disproportionately enhances SDFT strains compared to suspensory ligament (SL) strains.

Methods:Superficial digital flexor tendon and SL strains were measured in 7 cadaver limbs duringin vitroloading that maintained carpal extension or allowed carpal hyperextension by constraining, or allowing rotation of, the radius during loading conditions that simulated the middle of stance at the walk. The effect of carpal hyperextension on SDFT and SL strains and joint angles was assessed using repeated measures ANOVA.

Results:Limb loading generally resulted in higher SL strains than SDFT strains for both carpal extension and hyperextension loading conditions. Compared to carpal extension, carpal hyperextension resulted in increased strains in both the SDFT and the SL; however, a greater increase in strain was seen in the SDFT. On average, carpal hyperextension caused approximately 3° greater carpal extension, 1° greater metacarpophalangeal joint hyperextension, 1° greater proximal interphalangeal joint flexion and <1° greater distal interphalangeal joint flexion than did carpal extension.

Conclusions and clinical relevance:Carpal joint hyperextension is likely to induce disproportionately higher strain in the SDFT than in the SL. Factors that affect carpal stability are likely to affect the risk for superficial digital flexor tendinopathy.
Soot Modeling for Advanced Control of Diesel Engine Aftertreatment
Authors: Mulone V. , Cozzolini A. , Abeyratne P. , Littera D. , Thiagarajan M. , Besch M. C. , Gautam M.
Published: September 2011

Diesel particulate filters (DPFs) are well assessed aftertreatment devices, equipping almost every modern diesel engine on the market to comply with today’s stringent emission standards. However, an accurate estimation of soot loading, which is instrumental to ensuring optimal performance of the whole engine-after-treatment assembly, is still a major challenge. In fact, several highly coupled physical-chemical phenomena occur at the same time, and a vast number of engine and exhaust dependent parameters make this task even more daunting. This challenge may be solved with models characterized by different degrees of detail (0-D to 3-D) depending on the specific application. However, the use of real-time, but accurate enough models, may be the primary hurdle that has to be overcome when confronted with advanced exhaust emissions control challenges, such as the integration of the DPF with the engine or other critical aftertreatment components (selective catalytic reduction or other NOx control components), or to properly develop model-based OBD sensors. This paper aims at addressing real time DPF modeling issues with special regard to key parameter settings, by using the 1-D code called ExhAUST (exhaust aftertreatment unified simulation tool), which was jointly developed by the University of Rome Tor Vergata and West Virginia University. ExhAUST is characterized by a novel and unique full analytical treatment of the wall that allows a highly detailed representation of the soot loading evolution inside the DPF porous matrix. Numerical results are compared with experimental data gathered at West Virginia University engine laboratory using a MY2004 Mack®MP7-355E, an 11 liter, 6-cylinder, inline heavy-duty diesel engine coupled to a Johnson Matthey CCRT diesel oxidation catalyst + CDPF, catalyzed DPF exhaust aftertreatment system. To that aim, the engine test bench was equipped with a DPF weighing system to track soot loading over a specifically developed engine operating procedure. Results indicate that the model is accurate enough to capture soot loading and back pressure histories with regard to different steady state engine operating points, without a need for any tuning procedure of the key parameters. Thus, the use of ExhAUST for application to advanced after-treatment control appears to be a promising tool at this stage.
Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells
Authors: Xie Zhen , Wroblewska Liliana , Prochazka Laura , Weiss Ron , Benenson Yaakov
Published: September 2011

A synthetic biomolecular circuit identifies abnormal cell states by the integration of multiple endogenous microRNA inputs.
Biological Dark Matter Exerts Irresistible Pull in Yunnan
Authors: Stone Richard
Published: September 2011

Researchers hope a 5-year study launched this summer at the Rehai hot springs in Tengchong, a volcanic landscape in southwest China's Yunnan Province, will yield clues about the hundreds of unknown organisms they harbor.
The Life Hacker
Authors: Bohannon John
Published: September 2011

He is a pioneer of genome sequencing, but Harvard University's George Church wants to do more than read DNA. He is changing the genetic code itself
Human Cytomegalovirus Infection Causes Degradation of Sp100 Proteins That Suppress Viral Gene Expression
Authors: Kim Young-Eui , Lee Jin-Hyoung , Kim Eui Tae , Shin Hye Jin , Gu Su Yeon , Seol Hyang Sook , Ling Paul D. , Lee Chan Hee , Ahn Jin-Hyun
Published: September 2011

The interferon-inducible Sp100 proteins are thought to play roles in the chromatin pathway and in transcriptional regulation. Sp100A, the smallest isoform, is one of the major components of PML nuclear bodies (NBs) that exhibit intrinsic antiviral activity against several viruses. Since PML NBs are disrupted by the immediate-early 1 (IE1) protein during human cytomegalovirus (HCMV) infection, the modulation of Sp100 protein expression or activity during infection has been suggested. Here, we show that Sp100 proteins are lost largely in the late stages of HCMV infection. This event required viral gene expression and involved posttranscriptional control. The mutant virus with deletion of the sequence for IE1 (CR208) did not have Sp100 loss. In CR208 infection, PML depletion by RNA interference abrogated the accumulation of SUMO-modified Sp100A and of certain high-molecular-weight Sp100 isoforms but did not significantly affect unmodified Sp100A, suggesting that the IE1-induced disruption of PML NBs is not sufficient for the complete loss of Sp100 proteins. Sp100A loss was found to require proteasome activity. Depletion of all Sp100 proteins by RNA silencing enhanced HCMV replication and major IE (MIE) gene expression. Sp100 knockdown enhanced the acetylation level of histones associated with the MIE promoter, demonstrating that the repressive effect of Sp100 proteins may involve, at least in part, the epigenetic control of the MIE promoter. Sp100A was found to interact directly with IE1 through the N-terminal dimerization domain. These findings indicate that the IE1-dependent loss of Sp100 proteins during HCMV infection may represent an important requirement for efficient viral growth.
The Infectivity of prM-Containing Partially Mature West Nile Virus Does Not Require the Activity of Cellular Furin-Like Proteases
Authors: Mukherjee Swati , Lin Tsai-Yu , Dowd Kimberly A. , Manhart Carolyn J. , Pierson Theodore C.
Published: September 2011

Cleavage of the flavivirus prM protein by a cellular furin-like protease is a hallmark of virion maturation. While this cleavage is a required step in the viral life cycle, it can be inefficient. Virions that retain uncleaved prM may be infectious. We investigated whether cleavage by furin of prM on partially mature West Nile virus (WNV) during virus entry contributes to infectivity. Using quantitative assays of WNV infection, we found that virions incorporating considerable amounts of uncleaved prM protein were insensitive to treatment of cells with a potent inhibitor of furin activity. Thus, partially mature WNV does not require furin-like proteases for infectivity.
Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model
Authors: Gerlier Denis , Lyles Douglas S.
Published: September 2011

The discovery of a new class of cytosolic receptors recognizing viral RNA, called the RIG-like receptors (RLRs), has revolutionized our understanding of the interplay between viruses and host cells. A tremendous amount of work has been accumulating to decipher the RNA moieties required for an RLR agonist, the signal transduction pathway leading to activation of the innate immunity orchestrated by type I interferon (IFN), the cellular and viral regulators of this pathway, and the viral inhibitors of the innate immune response. Previous reviews have focused on the RLR signaling pathway and on the negative regulation of the interferon response by viral proteins. The focus of this review is to put this knowledge in the context of the virus replication cycle within a cell. Likewise, there has been an expansion of knowledge about the role of innate immunity in the pathophysiology of viral infection. As a consequence, some discrepancies have arisen between the current models of cell-intrinsic innate immunity and current knowledge of virus biology. This holds particularly true for the nonsegmented negative-strand viruses (Mononegavirales), which paradoxically have been largely used to build presently available models. The aim of this review is to bridge the gap between the virology and innate immunity to favor the rational building of a relevant model(s) describing the interplay betweenMononegaviralesand the innate immune system.
Hydraulic conductivity of zeolite–bentonite mixtures in comparison with sand–bentonite mixtures
Authors: Ören Ali Hakan , Kaya Abidin , Kayalar Arif Şengün
Published: September 2011

Hydraulic conductivity tests were conducted using tap water on zeolite–bentonite mixtures (ZBMs), sand–bentonite mixtures (SBMs), and a zeolite–sand–bentonite mixture (ZSBM) at various bentonite contents (BCs). The hydraulic conductivities of ZBMs were at least one order of magnitude higher than those of SBMs at the same BCs. It was also determined that the hydraulic conductivity of 30% ZBM (i.e., 30% bentonite and 70% zeolite) was still higher than that of 10% SBM (i.e., 10% bentonite and 90% sand). The higher hydraulic conductivity of ZBMs with respect to SBMs is attributed to the porous structure of zeolite. Zeolite grains form a network in ZBMs that helps transmit water throughout this network. Moreover, bentonite water contents were calculated using a model proposed previously. Through the modified model, it is shown that not only the zeolite network, but also larger pores between bentonite particles may cause higher hydraulic conductivities for ZBMs. Finally, the influence of zeolite particle size on the hydraulic conductivity was tested. It was observed that the hydraulic conductivities of ZBMs were more or less the same, indicating that the hydraulic conductivity of ZBM is independent of zeolite particle size within the considered BC range.
The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease
Authors: Odermatt Alex
Published: September 2011

The Western-style diet is characterized by its highly processed and refined foods and high contents of sugars, salt, and fat and protein from red meat. It has been recognized as the major contributor to metabolic disturbances and the development of obesity-related diseases including type 2 diabetes, hypertension, and cardiovascular disease. Also, the Western-style diet has been associated with an increased incidence of chronic kidney disease (CKD). A combination of dietary factors contributes to the impairment of renal vascularization, steatosis and inflammation, hypertension, and impaired renal hormonal regulation. This review addresses recent progress in the understanding of the association of the Western-style diet with the induction of dyslipidemia, oxidative stress, inflammation, and disturbances of corticosteroid regulation in the development of CKD. Future research needs to distinguish between acute and chronic effects of diets with high contents of sugars, salt, and fat and protein from red meat, and to uncover the contribution of each component. Improved therapeutic interventions should consider potentially altered drug metabolism and pharmacokinetics and be combined with lifestyle changes. A clinical assessment of the long-term risks of whole-body disturbances is strongly recommended to reduce metabolic complications and cardiovascular risk in kidney donors and patients with CKD.
Monocyte/macrophage chemokine receptor CCR2 mediates diabetic renal injury
Authors: Awad Alaa S. , Kinsey Gilbert R. , Khutsishvili Konstantine , Gao Ting , Bolton W. Kline , Okusa Mark D.
Published: September 2011

Monocyte/macrophage recruitment correlates strongly with the progression of renal impairment in diabetic nephropathy (DN). C-C chemokine receptor (CCR)2 regulates monocyte/macrophage migration into injured tissues. However, the direct role of CCR2-mediated monocyte/macrophage recruitment in diabetic kidney disease remains unclear. We report that pharmacological blockade or genetic deficiency of CCR2 confers kidney protection in Ins2Akita and streptozotocin (STZ)-induced diabetic kidney disease. Blocking CCR2 using the selective CCR2 antagonist RS504393 for 12 wk in Ins2Akita mice significantly attenuated albuminuria, the increase in blood urea nitrogen and plasma creatinine, histological changes, and glomerular macrophage recruitment compared with vehicle. Furthermore, mice lacking CCR2 (CCR2−/−) mimicked CCR2 blockade by reducing albuminuria and displaying less fibronectin mRNA expression and inflammatory cytokine production compared with CCR2+/+ mice, despite comparable blood glucose levels. Bone marrow-derived monocytes from CCR2+/+ or CCR2−/− mice adoptively transferred into CCR2−/− mice reversed the renal tissue-protective effect in diabetic CCR2−/− mice as evaluated by increased urinary albumin excretion and kidney macrophage recruitment, indicating that CCR2 is not required for monocyte migration from the circulation into diabetic kidneys. These findings provide evidence that CCR2 is necessary for monocyte/macrophage-induced diabetic renal injury and suggest that blocking CCR2 could be a novel therapeutic approach in the treatment of DN.
Perception of Recurrent Stroke Risk among Black, White and Hispanic Ischemic Stroke and Transient Ischemic Attack Survivors: The SWIFT Study
Authors: Boden-Albala Bernadette , Carman Heather , Moran Megan , Doyle Margaret , Paik Myunghee C.
Published: September 2011

Objectives: Risk modification through behavior change is critical for primary and secondary stroke prevention. Theories of health behavior identify perceived risk as an important component to facilitate behavior change; however, little is known about perceived risk of vascular events among stroke survivors. Methods: The SWIFT (Stroke Warning Information and Faster Treatment) study includes a prospective population-based ethnically diverse cohort of ischemic stroke and transient ischemic attack survivors. We investigate the baseline relationship between demographics, health beliefs, and knowledge on risk perception. Regression models examined predictors of inaccurate perception. Results: Only 20% accurately estimated risk, 10% of the participants underestimated risk, and 70% of the 817 study participants significantly overestimated their risk for a recurrent stroke. The mean perceived likelihood of recurrent ischemic stroke in the next 10 years was 51 ± 7%. We found no significant differences by race-ethnicity with regard to accurate estimation of risk. Inaccurate estimation of risk was associated with attitudes and beliefs [worry (p < 0.04), fatalism (p < 0.07)] and memory problems (p < 0.01), but not history or knowledge of vascular risk factors. Conclusion: This paper provides a unique perspective on how factors such as belief systems influence risk perception in a diverse population at high stroke risk. There is a need for future research on how risk perception can inform primary and secondary stroke prevention.
Celecoxib, a Selective Cyclooxygenase-2 Inhibitor, Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity
Authors: Suddek Ghada M. , El-kenawi Asmaa E. , Abdel-Aziz Azza , El-Kashef Hassan A.
Published: September 2011

Background: Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors. Nevertheless, nephrotoxicity has restricted its clinical use. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. Celecoxib, a selective cyclooxygenase-2 inhibitor used as anti-inflammatory, may therefore have a protective effect on cisplatin-induced renal injury. Methods: In the present study, rats were injected intraperitoneally with a single dose of cisplatin (7 mg/kg) and/or celecoxib (30 mg/kg) for 5 days. Results: Nephrotoxicity manifested biochemically by elevations in serum creatinine, blood urea nitrogen, and proteinuria, and an increase in kidney weight as a percentage of total body weight. In addition, a marked decrease in serum albumin was observed. Lipid peroxidation in the kidney was monitored by measuring the malondialdehyde level and glutathione content, which were increased and depleted, respectively. Administration of celecoxib with cisplatin attenuated cisplatin-induced changes in kidney function parameters and oxidative stress markers. Histopathological examination of the kidney confirmed these results. Conclusion: In conclusion, this study indicates that celecoxib may be a promising drug for clinical use as a nephroprotectant against cisplatin-induced nephrotoxicity.
Different Types of ENSO Influences on the Indian Summer Monsoon Variability
Authors: Wu Renguang , Chen Jilong , Chen Wen
Published: September 2011

Observational analysis reveals three types of El Niño–Southern Oscillation (ENSO) influences on the Indian summer monsoon (ISM): indirect influence of the preceding winter [December–February (DJF)] eastern equatorial Pacific (EEP) sea surface temperature (SST) anomalies (DJF-only cases), direct influence of the concurrent summer [June–September (JJAS)] EEP SST anomalies (JJAS-only cases), and coherent influence of both the preceding winter and concurrent summer EEP SST anomalies (DJF&JJAS cases). The present study distinguishes the three types of ENSO influences and investigates the processes connecting ENSO to the ISM separately.

In the DJF-only cases, the preceding winter EEP SST anomalies induce north Indian Ocean (NIO) SST anomalies through air–sea interaction processes in the tropical Indian Ocean. The SST anomalies over the western Indian Ocean alter the surface air humidity there. Both processes favor an anomalous ISM. In the JJAS-only cases, an anomalous ISM is directly induced by ENSO through large-scale circulation changes. The meridional thermal contrast may also contribute to an anomalous ISM. In the DJF&JJAS cases, the preceding winter EEP SST anomalies induce NIO SST anomalies and change the surface air humidity over the western Indian Ocean. Concurrent summer EEP SST anomalies induce large-scale vertical motion anomalies over South Asia. Together, they lead to an anomalous ISM. The anomalous meridional thermal contrast may contribute to an anomalous ISM in late summer.

Impacts of the preceding winter EEP SST anomalies in the DJF and JJAS cases may contribute to the contemporaneous correlation between ISM and EEP SST. There are more DJF&JJAS cases before than after the late 1970s. This provides an alternative interpretation for the observed weakening in the ISM–ENSO relationship around the late 1970s.
Identification and Climatology of Southern Hemisphere Mobile Fronts in a Modern Reanalysis
Authors: Simmonds Ian , Keay Kevin , Tristram Bye John Arthur
Published: September 2011

Presented here is an objective approach to identify, characterize, and track Southern Hemisphere mobile fronts in hemispheric analyses of relatively modest resolution, such as reanalyses. Among the principles in its design were that it should be based on broadscale synoptic considerations and be as simple and easily understood as possible. The resulting Eulerian scheme has been applied to the European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA)–Interim and a climatology of frontal characteristics, at both the 10-m and 850-hPa levels, derived for the period 1 January 1989–28 February 2009. The knowledge of the character of these features is central to understanding weather and climate over the hemisphere.

In both summer and winter the latitude belt 40°–60°S hosts the highest frequency of frontal points, but there are significant zonal asymmetries within this band. The climatology reveals that the longest fronts are in the Indian Ocean where mean lengths exceed 2000 km. The mean frontal intensity over the hemisphere tends to be greater at 850 hPa than at 10 m, and greater in winter than in summer. The frontal intensity also shows its maximum in the Indian Ocean. In the mean, the meridional tilt of these fronts is northwest–southeast over much of the midlatitudes and subtropics, and increases with latitude toward the equator. The tilts are of overwhelmingly opposite sign in the coastal Antarctic and subantarctic regions.

Broadly speaking, the number of fronts and their mean length and mean intensity exhibit maxima in winter in the midlatitudes (30°–50°S), but show a sizeable semiannual variation (maxima in fall and spring) during the year at higher latitudes.
Psychosocial Complaints Are Associated With Venous Access–Device Related Complications in Patients on Home Parenteral Nutrition
Authors: Huisman‐de Waal Getty , Versleijen Michelle , van Achterberg Theo , Jansen Jan B. , Sauerwein Hans , Schoonhoven Lisette , Wanten Geert
Published: September 2011

Background: Complications related to venous access devices (VADs) remain the major drawback of home parenteral nutrition (HPN) support. In addition to technical issues, patients also experience psychosocial problems. The aim of this study is to present an overview of VAD‐related complications in patients on long‐term HPN and to assess whether these adversities are related to experienced psychosocial problems and quality of life (QOL). Methods: Information on VAD‐related complications was collected from the medical charts of 110 adult HPN patients who were followed by the 2 major referral centers in the Netherlands. In addition, a survey was conducted in this group to characterize psychosocial problems and assess their association with technique‐related complications; 75 patients (68%) responded. Results: At the time of survey, the majority of patients (76%) had developed 1 or more episodes of catheter‐related sepsis at some point during their HPN treatment. The overall incidence of VAD‐related blood stream infections (BSIs) was 3 per 1,000 venous access days. The incidence of VAD occlusions was 0.8 per 1,000 venous access days. During the observation period, there was a highly significant association between the incidence of VAD‐related complications and the occurrence of psychosocial complaints (eg, depression, fatigue, social impairment, and decreased QOL). Conclusions: Psychosocial complaints are associated with previously experienced VAD‐related complications in patients on HPN therapy. Although only an association, and not a causal relationship is demonstrated by these findings, our results underscore the need for preventive and therapeutic measures regarding both types of problems in these patients.
Obesity Epidemic
Authors: Hurt Ryan T. , Frazier Thomas H. , McClave Stephen A. , Kaplan Lee M.
Published: September 2011

Obesity is one of the leading causes of preventable death in the United States, second only to smoking. The annual number of deaths attributed to obesity is estimated to be as high as 400,000. Nearly 70% of the adult U.S. population is overweight or obese. The historical viewpoint toward obesity has deemed it to be a lifestyle choice or characterological flaw. However, given the emerging research into the development of obesity and its related complications, our perspective is changing. It is now clear that obesity is a heterogeneous disease with many different subtypes, which involves an interplay between genetic and environmental factors. The current epidemic of obesity is the result of an obesogenic environment (which includes energy‐dense foods and a lack of physical activity) in individuals who have a genetic susceptibility for developing obesity. The pathophysiology associated with weight gain is much more complex than originally thought. The heterogeneous nature of the disease makes the development of treatment strategies for obesity difficult. Obesity in general is associated with increased all‐cause mortality and cause‐specific mortality (from cardiovascular, diabetic, hepatic, and neoplastic causes). Yet despite increased overall mortality rates, current evidence suggests that when these same patients are admitted to the intensive care unit (ICU), the obesity provides some protection against mortality. At present, there is no clear explanation for this obesity conundrum in critical illness.
Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH
Authors: Zhang Kejian , Jordan Michael B. , Marsh Rebecca A. , Johnson Judith A. , Kissell Diane , Meller Jarek , Villanueva Joyce , Risma Kimberly A. , Wei Qian , Klein Peter S. , Filipovich Alexandra H.
Published: September 2011

Familial hemophagocytic lymphohistiocytosis (HLH) is a rare primary immunodeficiency disorder characterized by defects in cell-mediated cytotoxicity that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well recognized in children but rarely diagnosed in adults. We conducted a retrospective review of genetic and immunologic test results in patients who developed HLH in adulthood. Included in our study were 1531 patients with a clinical diagnosis of HLH; 175 patients were 18 years or older. Missense and splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%). The preponderance of hypomorphic mutations in familial HLH–causing genes correlates with the later-onset clinical symptoms and the more indolent course in adult patients. We conclude that late-onset familial HLH occurs more commonly than was suspected previously.
Repression of GW/P body components and the RNAi microprocessor impacts primary ciliogenesis in human astrocytes
Authors: Moser Joanna J , Fritzler Marvin J , Rattner Jerome B
Published: September 2011

Background

In most cells, the centriolar component of the centrosome can function as a basal body supporting the formation of a primary cilium, a non-motile sensory organelle that monitors information from the extracellular matrix and relays stimuli into the cell via associated signaling pathways. Defects in the formation and function of primary cilia underlie multiple human diseases and are hallmarks of malignancy. The RNA silencing pathway is involved in the post-transcriptional silencing of > 50% of mRNA that occurs within GW/P bodies. GW/P bodies are found throughout the cytoplasm and previously published live cell imaging data suggested that in a malignant cell type (U2OS), two GW/P bodies reside at the centrosome during interphase. This led us to investigate if a similar relationship exists in primary cells and if the inhibition of the miRNA pathway impairs primary cilium formation.

Results

Two GW/P bodies as marked by GW182 and hAgo2 colocalized to the basal body of primary human astrocytes as well as human synoviocytes during interphase and specifically with the distal end of the basal body in the pericentriolar region. Since it is technically challenging to examine the two centrosomal GW/P bodies in isolation, we investigated the potential relationship between the global population of GW/P bodies and primary ciliogenesis. Astrocytes were transfected with siRNA directed to GW182 and hAgo2 and unlike control astrocytes, a primary cilium was no longer associated with the centrosome as detected in indirect immunofluorescence assays. Ultrastructural analysis of siRNA transfected astrocytes revealed that knock down of GW182, hAgo2, Drosha and DGCR8 mRNA did not affect the appearance of the earliest stage of ciliogenesis but did prevent the formation and elongation of the ciliary axoneme.

Conclusions

This study confirms and extends a previously published report that GW/P bodies reside at the centrosome in U2OS cells and documents that GW/P bodies are resident at the centrosome in diverse non-malignant cells. Further, our study demonstrates that repression of key effector proteins in the post-transcriptional miRNA pathway impairs primary cilium formation.
A review of mixed malaria species infections in anopheline mosquitoes
Authors: Imwong Mallika , Nakeesathit Supatchara , Day Nicholas PJ , White Nicholas J
Published: September 2011

Background

In patients with malaria mixed species infections are common and under reported. In PCR studies conducted in Asia mixed infection rates often exceed 20%. In South-East Asia, approximately one third of patients treated for falciparum malaria experience a subsequent Plasmodium vivax infection with a time interval suggesting relapse. It is uncertain whether the two infections are acquired simultaneously or separately. To determine whether mixed species infections in humans are derived from mainly from simultaneous or separate mosquito inoculations the literature on malaria species infection in wild captured anopheline mosquitoes was reviewed.

Methods

The biomedical literature was searched for studies of malaria infection and species identification in trapped wild mosquitoes and artificially infected mosquitoes. The study location and year, collection methods, mosquito species, number of specimens, parasite stage examined (oocysts or sporozoites), and the methods of parasite detection and speciation were tabulated. The entomological results in South East Asia were compared with mixed infection rates documented in patients in clinical studies.

Results

In total 63 studies were identified. Individual anopheline mosquitoes were examined for different malaria species in 28 of these. There were 14 studies from Africa; four with species evaluations in individual captured mosquitoes (SEICM). One study, from Ghana, identified a single mixed infection. No mixed infections were identified in Central and South America (seven studies, two SEICM). 42 studies were conducted in Asia and Oceania (11 from Thailand; 27 SEICM). The proportion of anophelines infected with Plasmodium falciparum parasites only was 0.51% (95% CI: 0.44 to 0.57%), for P. vivax only was 0.26% (95% CI: 0.21 to 0.30%), and for mixed P. falciparum and P. vivax infections was 0.036% (95% CI: 0.016 to 0.056%). The proportion of mixed infections in mosquitoes was significantly higher than expected by chance (P < 0.001), but was one fifth of that sufficient to explain the high rates of clinical mixed infections by simultaneous inoculation.

Conclusions

There are relatively few data on mixed infection rates in mosquitoes from Africa. Mixed species malaria infections may be acquired by simultaneous inoculation of sporozoites from multiply infected anopheline mosquitoes but this is relatively unusual. In South East Asia, where P. vivax infection follows P. falciparum malaria in one third of cases, the available entomological information suggests that the majority of these mixed species malaria infections are acquired from separate inoculations.