Showing papers by "Temple University published in 2008"

A High Phase-Space-Density Gas of Polar Molecules

Abstract: A quantum gas of ultracold polar molecules, with long-range and anisotropic interactions, not only would enable explorations of a large class of many-body physics phenomena but also could be used for quantum information processing We report on the creation of an ultracold dense gas of potassium-rubidium (40K87Rb) polar molecules Using a single step of STIRAP (stimulated Raman adiabatic passage) with two-frequency laser irradiation, we coherently transfer extremely weakly bound KRb molecules to the rovibrational ground state of either the triplet or the singlet electronic ground molecular potential The polar molecular gas has a peak density of 1012 per cubic centimeter and an expansion-determined translational temperature of 350 nanokelvin The polar molecules have a permanent electric dipole moment, which we measure with Stark spectroscopy to be 0052(2) Debye (1 Debye = 3336 × 10–30 coulomb-meters) for the triplet rovibrational ground state and 0566(17) Debye for the singlet rovibrational ground state

JNK signaling in apoptosis.

Abstract: Jun N-terminal kinases or JNKs play a critical role in death receptor-initiated extrinsic as well as mitochondrial intrinsic apoptotic pathways. JNKs activate apoptotic signaling by the upregulation of pro-apoptotic genes through the transactivation of specific transcription factors or by directly modulating the activities of mitochondrial pro- and antiapoptotic proteins through distinct phosphorylation events. This review analyses our present understanding of the role of JNK in apoptotic signaling and the various mechanisms by which JNK promotes apoptosis.

Age differences in sensation seeking and impulsivity as indexed by behavior and self-report: evidence for a dual systems model.

Abstract: It has been hypothesized that sensation seeking and impulsivity, which are often conflated, in fact develop along different timetables and have different neural underpinnings, and that the difference in their timetables helps account for heightened risk taking during adolescence. In order to test these propositions, the authors examined age differences in sensation seeking and impulsivity in a socioeconomically and ethnically diverse sample of 935 individuals between the ages of 10 and 30, using self-report and behavioral measures of each construct. Consistent with the authors' predictions, age differences in sensation seeking, which are linked to pubertal maturation, follow a curvilinear pattern, with sensation seeking increasing between 10 and 15 and declining or remaining stable thereafter. In contrast, age differences in impulsivity, which are unrelated to puberty, follow a linear pattern, with impulsivity declining steadily from age 10 on. Heightened vulnerability to risk taking in middle adolescence may be due to the combination of relatively higher inclinations to seek excitement and relatively immature capacities for self-control that are typical of this period of development.

Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety

Abstract: Background Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. Methods In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. Results The percentages of children who were rated as very much or much improved on the Clinician Global Impression–Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Conclusions Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.)

The parietal cortex and episodic memory: an attentional account

Abstract: The contribution of the parietal cortex to episodic memory is a fascinating scientific puzzle. On the one hand, parietal lesions do not normally yield severe episodic-memory deficits; on the other hand, parietal activations are seen frequently in functional-neuroimaging studies of episodic memory. A review of these two categories of evidence suggests that the answer to the puzzle requires us to distinguish between the contributions of dorsal and ventral parietal regions and between the influence of top-down and bottom-up attention on memory.

Location, control and innovation in knowledge-intensive industries

Abstract: The rising share of intangibles in economies worldwide highlights the crucial role of knowledge-intensive and creative industries in current and future wealth generation. The recognition of this trend has led to intense competition in these industries. At the micro-level, firms from both advanced and emerging economies are globally dispersing their value chains to control costs and leverage capabilities. The geography of innovation is the outcome of a dynamic process whereby firms from emerging economies strive to catch-up with advanced economy competitors, creating strong pressures for continued innovation. However, two distinct strategies can be discerned with regard to the control of the value chain. A vertical integration strategy emphasizes taking advantage of ‘linkage economies’ whereby controlling multiple value chain activities enhances the efficiency and effectiveness of each one of them. In contrast, a specialization strategy focuses on identifying and controlling the creative heart of the value chain, while outsourcing all other activities. The global mobile handset industry is used as the template to illustrate the theory.

Opioids and the management of chronic severe pain in the elderly: Consensus statement of an international expert panel with focus on the six clinically most often used world health organization step III opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)

Abstract: SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation--fentanyl and buprenorphine--fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2. The use of opioids in noncancer-related pain: Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3. The use of opioids in neuropathic pain: The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4. The use of opioids in elderly patients with impaired hepatic and renal function: Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that--except for buprenorphine--doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5. Opioids and respiratory depression: Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6. Opioids and immunosuppression: Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7. Safety and tolerability profile of opioids: The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.

Implant success, survival, and failure: the International Congress of Oral Implantologists (ICOI) Pisa Consensus Conference.

Abstract: The primary function of a dental implant is to act as an abutment for a prosthetic device, similar to a natural tooth root and crown. Any success criteria, therefore, must include first and foremost support of a functional prosthesis. In addition, although clinical criteria for prosthetic success are beyond the scope of this article, patient satisfaction with the esthetic appearance of the implant restoration is necessary in clinical practice. The restoring dentist designs and fabricates a prosthesis similar to one supported by a tooth, and as such often evaluates and treats the dental implant similarly to a natural tooth. Yet, fundamental differences in the support system between these entities should be recognized. The purpose of this article is to use a few indices developed for natural teeth as an index that is specific for endosteal root-form implants. This article is also intended to update and upgrade what is purported to be implant success, implant survival, and implant failure. The Health Scale presented in this article was developed and accepted by the International Congress of Oral Implantologists Consensus Conference for Implant Success in Pisa, Italy, October 2007.

Comparing capitalisms: understanding institutional diversity and its implications for international business

Abstract: This paper examines the role of institutional analysis within the field of international business (IB) studies. Within IB, institutions matter, but the view of institutions tends to be “thin”, utilizing summary indicators rather than detailed description, and thus approaches institutions as unidimensional “variables” that impact on particular facets of business activity. This paper argues that IB research would be usefully advanced by greater attention to comparing the topography of institutional landscapes and understanding their diversity. A number of alternative case-based approaches are outlined that draw on a growing “comparative capitalisms” literature in sociology and political science. The paper develops a number of empirical examples to show the utility and limits of these approaches for IB scholars.

Evaluating Contextual Variables Affecting Productivity Using Data Envelopment Analysis

Abstract: A DEA-based stochastic frontier estimation framework is presented to evaluate contextual variables affecting productivity that allows for both one-sided inefficiency deviations as well as two-sided random noise. Conditions are identified under which a two-stage procedure consisting of DEA followed by ordinary least squares (OLS) regression analysis yields consistent estimators of the impact of contextual variables. Conditions are also identified under which DEA in the first stage followed by maximum likelihood estimation (MLE) in the second stage yields consistent estimators of the impact of contextual variables. This requires the contextual variables to be independent of the input variables, but the contextual variables may be correlated with each other. Monte Carlo simulations are carried out to compare the performance of our two-stage approach with one-stage and two-stage parametric approaches. Simulation results indicate that DEA-based procedures with OLS, maximum likelihood, or even Tobit estimation in the second stage perform as well as the best of the parametric methods in the estimation of the impact of contextual variables on productivity. Simulation results also indicate that DEA-based procedures perform better than parametric methods in the estimation of individual decision-making unit (DMU) productivity. Overall, the results establish DEA as a nonparametric stochastic frontier estimation (SFE) methodology.

Intra-individual change over time in DNA methylation with familial clustering.

Abstract: Context Changes over time in epigenetic marks, which are modifications of DNA such as by DNA methylation, may help explain the late onset of common human diseases. However, changes in methylation or other epigenetic marks over time in a given individual have not yet been investigated. Objectives To determine whether there are longitudinal changes in global DNA methylation in individuals and to evaluate whether methylation maintenance demonstrates familial clustering. Design, Setting, and Participants We measured global DNA methylation by luminometric methylation assay, a quantitative measurement of genome-wide DNA methylation, on DNA sampled at 2 visits on average 11 years apart in 111 individuals from an Icelandic cohort (1991 and 2002-2005) and on average 16 years apart in 126 individuals from a Utah sample (1982-1985 and 1997-2005). Main Outcome Measure Global methylation changes over time. Results Twenty-nine percent of Icelandic individuals showed greater than 10% methylation change over time (P Conclusion These data indicate that methylation changes over time and suggest that methylation maintenance may be under genetic control.

The unfoldomics decade: an update on intrinsically disordered proteins

Abstract: Our first predictor of protein disorder was published just over a decade ago in the Proceedings of the IEEE International Conference on Neural Networks (Romero P, Obradovic Z, Kissinger C, Villafranca JE, Dunker AK (1997) Identifying disordered regions in proteins from amino acid sequence. Proceedings of the IEEE International Conference on Neural Networks, 1: 90–95). By now more than twenty other laboratory groups have joined the efforts to improve the prediction of protein disorder. While the various prediction methodologies used for protein intrinsic disorder resemble those methodologies used for secondary structure prediction, the two types of structures are entirely different. For example, the two structural classes have very different dynamic properties, with the irregular secondary structure class being much less mobile than the disorder class. The prediction of secondary structure has been useful. On the other hand, the prediction of intrinsic disorder has been revolutionary, leading to major modifications of the more than 100 year-old views relating protein structure and function. Experimentalists have been providing evidence over many decades that some proteins lack fixed structure or are disordered (or unfolded) under physiological conditions. In addition, experimentalists are also showing that, for many proteins, their functions depend on the unstructured rather than structured state; such results are in marked contrast to the greater than hundred year old views such as the lock and key hypothesis. Despite extensive data on many important examples, including disease-associated proteins, the importance of disorder for protein function has been largely ignored. Indeed, to our knowledge, current biochemistry books don't present even one acknowledged example of a disorder-dependent function, even though some reports of disorder-dependent functions are more than 50 years old. The results from genome-wide predictions of intrinsic disorder and the results from other bioinformatics studies of intrinsic disorder are demanding attention for these proteins. Disorder prediction has been important for showing that the relatively few experimentally characterized examples are members of a very large collection of related disordered proteins that are wide-spread over all three domains of life. Many significant biological functions are now known to depend directly on, or are importantly associated with, the unfolded or partially folded state. Here our goal is to review the key discoveries and to weave these discoveries together to support novel approaches for understanding sequence-function relationships. Intrinsically disordered protein is common across the three domains of life, but especially common among the eukaryotic proteomes. Signaling sequences and sites of posttranslational modifications are frequently, or very likely most often, located within regions of intrinsic disorder. Disorder-to-order transitions are coupled with the adoption of different structures with different partners. Also, the flexibility of intrinsic disorder helps different disordered regions to bind to a common binding site on a common partner. Such capacity for binding diversity plays important roles in both protein-protein interaction networks and likely also in gene regulation networks. Such disorder-based signaling is further modulated in multicellular eukaryotes by alternative splicing, for which such splicing events map to regions of disorder much more often than to regions of structure. Associating alternative splicing with disorder rather than structure alleviates theoretical and experimentally observed problems associated with the folding of different length, isomeric amino acid sequences. The combination of disorder and alternative splicing is proposed to provide a mechanism for easily "trying out" different signaling pathways, thereby providing the mechanism for generating signaling diversity and enabling the evolution of cell differentiation and multicellularity. Finally, several recent small molecules of interest as potential drugs have been shown to act by blocking protein-protein interactions based on intrinsic disorder of one of the partners. Study of these examples has led to a new approach for drug discovery, and bioinformatics analysis of the human proteome suggests that various disease-associated proteins are very rich in such disorder-based drug discovery targets.

Cognitive-behavioral therapy for anxiety disordered youth: a randomized clinical trial evaluating child and family modalities

Abstract: This randomized clinical trial compared the relative efficacy of individual (child) cognitive-behavioral therapy (ICBT), family cognitive-behavioral therapy (FCBT), and a family-based education/support/ attention (FESA) active control for treating anxiety disordered youth ages 7-14 years (M = 10.27). Youth (N = 161; 44% female; 85% Caucasian, 9% African American, 3% Hispanic, 3% other/mixed) with a principal diagnosis of separation anxiety disorder, social phobia, or generalized anxiety disorder and their parents participated. Outcome analyses were conducted using hierarchical linear models on the intent-to-treat sample at posttreatment and 1-year follow-up using diagnostic severity, child self-reports, parent reports, and teacher reports. Chi-square analyses were also conducted on diagnostic status at post and 1-year follow-up. Children evidenced treatment gains in all conditions, although FCBT and ICBT were superior to FESA in reducing the presence and principality of the principal anxiety disorder, and ICBT outperformed FCBT and FESA on teacher reports of child anxiety. Treatment gains, when found, were maintained at 1-year follow-up. FCBT outperformed ICBT when both parents had an anxiety disorder. Implications for treatment and suggestions for research are discussed.

A Policy-Based School Intervention to Prevent Overweight and Obesity

Abstract: BACKGROUND. The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic settings. Schools are ideal settings for population-based interventions to address obesity. OBJECTIVE. The purpose of this work was to examine the effects of a multicomponent, School Nutrition Policy Initiative on the prevention of overweight (85.0th to 94.9th percentile) and obesity (>95.0th percentile) among children in grades 4 through 6 over a 2-year period. METHODS. Participants were 1349 students in grades 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50% of students eligible for free or reduced-price meals. Schools were matched on school size and type of food service and randomly assigned to intervention or control. Students were assessed at baseline and again after 2 years. The School Nutrition Policy Initiative included the following components: school self-assessment, nutrition education, nutrition policy, social marketing, and parent outreach. RESULTS. The incidences of overweight and obesity after 2 years were primary outcomes. The prevalence and remission of overweight and obesity, BMI z score, total energy and fat intake, fruit and vegetable consumption, body dissatisfaction, and hours of activity and inactivity were secondary outcomes. The intervention resulted in a 50% reduction in the incidence of overweight. Significantly fewer children in the intervention schools (7.5%) than in the control schools (14.9%) became overweight after 2 years. The prevalence of overweight was lower in the intervention schools. No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years. CONCLUSION. A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grades 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals.

Earnings Forecasting Research: Its Implications for Capital Markets Research

Abstract: Since the early 198Os, earnings forecasting research has become much more closely aligned with capital markets research. Capital markets research requires a proxy for the (unobservable) market earnings expectation and earnings forecasting research has provided such proxy measures. Questions considered in this paper include: (1) if annual earnings follow a random walk or an IMA (1, 1) model, does this mean that earnings changes cannot be predicted? (2) Do stock prices act as if quarterly earnings follow a seasonal random walk with drift process? (3) Is the predictive mode1 which is best on the forecast accuracy dimension also best on the market association dimension? (4) How do analysts formulate their earnings expectations? (5) What is the role of earnings forecasting in `earnings response coefficient' and `post-earnings announcement drift' studies? (6) What is the likely role of earnings forecasting research in future capital market studies?

Security Analyst Superiority Relative to Univariate Time-Series Models in Forecasting Quarterly Earnings

Abstract: Evidence is provided of security analyst (SA) superiority relative to univariate time-series (TS) models in predicting firms' quarterly earnings numbers. It is demonstrated that SA forecast superiority in the sample is attributable to: 1. better use of information that exists on the date that TS model forecasts can be initiated, a contemporaneous advantage, and 2. use of information acquired between the date of initiation of TS model forecasts and the date when SA forecasts are published, a timing advantage.

Workplace Values and Outcomes: Exploring Personal, Organizational, and Interactive Workplace Spirituality

Abstract: Spiritual values in the workplace, increasingly discussed and applied in the business ethics literature, can be viewed from an individual, organizational, or interactive perspective. The following study examined previously unexplored workplace spirituality outcomes. Using data collected from five samples consisting of full-time workers taking graduate coursework, results indicated that perceptions of organizational-level spirituality (“organizational spirituality”) appear to matter most to attitudinal and attachment-related outcomes. Specifically, organizational spirituality was found to be positively related to job involvement, organizational identification, and work rewards satisfaction, and negatively related to organizational frustration. Personal spirituality was positively related to intrinsic, extrinsic, and total work rewards satisfaction. The interaction of personal spirituality and organizational spirituality was found related to total work rewards satisfaction. Future workplace spirituality research directions are discussed.

Apoptotic signaling by c-MYC

Abstract: c-MYC has a pivotal function in growth control, differentiation and apoptosis, and its abnormal expression is associated with many tumors. Overexpression of c-MYC sensitizes cells to apoptosis by a variety of stimuli. The decision of a cell to undergo apoptosis and how this apoptotic response is regulated by c-MYC depends on the specific cell type and the physiological status of the cell. Multiple cooperating molecular pathways of cell survival and apoptosis determine whether a cell lives or dies, and understanding how c-MYC interfaces with these pathways to influence the survival of cells is important to understand normal and abnormal development, tumor initiation and progression, and response of tumors to different treatment regimens. This article will provide an overview of the function of the tumor suppressor gene product p53 in the c-MYC-mediated apoptotic response and how c-MYC amplifies the intrinsic mitochondrial pathway and triggers and/or amplifies the death receptor pathways. Finally, a model for how deregulated c-MYC prematurely triggers the normal apoptotic response associated with terminal myeloid differentiation while also blocking the differentiation program is presented.

Abusive supervision and subordinates' organization deviance.

Abstract: The authors developed an integrated model of the relationships among abusive supervision, affective organizational commitment, norms toward organization deviance, and organization deviance and tested the framework in 2 studies: a 2-wave investigation of 243 supervised employees and a cross-sectional study of 247 employees organized into 68 work groups. Path analytic tests of mediated moderation provide support for the prediction that the mediated effect of abusive supervision on organization deviance (through affective commitment) is stronger when employees perceive that their coworkers are more approving of organization deviance (Study 1) and when coworkers perform more acts of organization deviance (Study 2).

Increase in Endoplasmic Reticulum Stress–Related Proteins and Genes in Adipose Tissue of Obese, Insulin-Resistant Individuals

Abstract: OBJECTIVE—To examine fat biopsy samples from lean insulin-sensitive and obese insulin-resistant nondiabetic individuals for evidence of endoplasmic reticulum (ER) stress. RESEARCH DESIGN AND METHODS—Subcutaneous fat biopsies were obtained from the upper thighs of six lean and six obese nondiabetic subjects. Fat homogenates were used for proteomic (two-dimensional gel and MALDI-TOF/TOF), Western blot, and RT-PCR analysis. RESULTS—Proteomic analysis revealed 19 differentially upregulated proteins in fat of obese subjects. Three of these proteins were the ER stress–related unfolded protein response (UPR) proteins calreticulin, protein disulfide-isomerase A3, and glutathione-S-transferase P. Western blotting revealed upregulation of several other UPR stress–related proteins, including calnexin, a membrane-bound chaperone, and phospho c-jun NH2-terminal kinase (JNK)-1, a downstream effector protein of ER stress. RT-PCR analysis revealed upregulation of the spliced form of X-box binding protein-1s, a potent transcription factor and part of the proximal ER stress sensor inositol-requiring enzyme-1 pathway. CONCLUSIONS—These findings represent the first demonstration of UPR activation in subcutaneous adipose tissue of obese human subjects. As JNK can inhibit insulin action and activate proinflammatory pathways, ER stress activation of JNK may be a link between obesity, insulin resistance, and inflammation.

Cryoablation or Radiofrequency Ablation of the Small Renal Mass: A Meta-analysis

Abstract: Background: The incidence of renal cell carcinoma(RCC) is rising due to incidental detection of small renal masses(SRMs). While surgical resection remains the standard of care, cryoablation and radiofrequency ablation(RFA) have emerged as minimally-invasive treatment alternatives. We performed a comparative meta-analysis evaluating cryoablation and RFA as primary treatment for SRMs.