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Presents a study which reported investigations aimed at learning the molecular basis for the polyadenylation of certain RNA species by Escherichia coli poly(A) polymerase I. Materials and methods; Results; Discussion.

A Continuing Medical Education Unit (CEU) is presented related to diagnosis and management of idiosyncratic drug-induced liver injury.

Compares the safety and efficacy of leflunomide with placebo and methotrexate treatment in patients with active rheumatoid arthritis (RA). Study conducted on rheumatology practices in the United States and Canada; Improved signs and symptoms of active RA; Delayed disease progression; Improved function and health-related quality of life.

Assesses the relative contribution of lateral inhibition to the Delboeuf and Wundt-Hering illusions. Increased lateral inhibition with the Delboeuf illusion; Increased magnitude of the Wundt-Hering illusion; Contribution of neural interactions in visual illusions.

Part III. Investigates the effects of teacher attire on student perceptions of instructors and instruction in contemporary college classrooms. Factors influencing students' judgment of teachers' approachability and credibility; Association of teachers' attire with the teachers' attributes; Ways to enhance the credibility, approachability and teacher evaluations.

Investigates separate roles of Escherichia coli replication proteins synthesis and partitioning of pSC101 plasmid DNA. Domain specificity of host proteins in the stabilization of pSC101; Cessation of pSC101 DNA replication consequent to temperature-sensitive mutation; Stabilization of pSC101 replicons by overproducing DnaB.

The article presents the experience of the author in a psychiatric hospital. There were two beginnings, the author supposes. The one when the students started moving in and the other when the author started noticing them. The author is not sure what the gap between these two moments was, probably not very long. Perhaps they started moving in right from the beginning of the year, the academic year the author means, in the first week of October. That would have been the obvious time if they had all planned it together. Though even at this stage, even after all that has happened, the author has no real evidence of any collaboration, any collusion between them. At the end they certainly saw each other, but that was all. Anyway, it was towards the end of January, a few weeks after the start of the second term, when he first noticed anything. Students often walked in and out of lecture courses. It was also not unusual to find those who claimed that it had taken them a whole term to get it together to find the right times and rooms.

Abstract. Chronic nonspecific diarrhea (CNSD) is the most common cause of prolonged diarrhea without failure to thrive. Although it is most commonly seen from ages 6 to 36 months, CNSD may persist until 54 months of age. Forty-four patients with this syndrome had complete dietary histories, and were divided into four groups on the basis of theft intakes and responses to its modification. Each of the four groups had significantly less fat in their diet at the time of presentation than did ten non-CNSD patients (P < .005) presenting similarly. In three of the groups, daily fat consumption was increased, irrespective of the adequacy of theft initial intakes. In all 38 patients in these groups, this dietary modification was associated with the resolution of symptoms. The fourth group, with initially normal dietary fat ingestion, did not respond to dietary therapy. The overall success rate of the regimen in this patient population was 82%. Carbohydrate, fiber, and caloric contents of the diets did not appear to play as significant a role as fat intake. Pediatrics 64:402-407, 1979; diarrhea, chronic nonspecific diarrhea, irritable colon, diet, dietary fat. [ABSTRACT FROM AUTHOR]

Studies the degradation of RNA in Escherichia coli regulated by 3' adenylation and 5' phosphorylation. Presence of poly A tails on bacterial RNA; Effect of adenylation and phosphorylation on the rate of digestion of RNA I by the 3' exonuclease.

This article attempts to identify some features of conference life that merit further study. The data derive mainly from conferences in the social sciences--sociology, criminology, anthropology, psychology--as well as social work and law. Criminology conferences supply the main data-set. As long as governments, foundations and research councils retain their touching faith that the crime problem can be solved by getting people together in hotels to talk about it, these will be rich sources for replication research. The findings are presented in the form of a guide--using guide both in the analytical and normative sense. No one believes anymore that observations are uncontaminated by the interests of the observer. So, this is like a tourist guide: what is there to be seen and how to extract the maximum benefits from the experience. Following the standard sociological distinction, we might divide benefit into its expressive and instrumental dimensions. The conference has two main expressive functions. First, there is the social need for regular gatherings to meet old friends, colleagues, students, research assistants, teachers and lovers--as well as find new ones. Second, there is the purely individual pleasures of travel, good hotels, gourmet food, exotic tourist sights and being away from family and work commitments.

The article examines how governments respond to human rights information. Though there are different types of human rights reports, they failed to provide complete and evenly distributed reports on human rights. There are clear reasons for this--both rational and contingent. The author made a rigorous study on human rights violations. He focuses on international organizations and targeted three different audiences: the official circuit of perpetrator and observer governments; the mass media; direct appeals to the general public. The article deals only with the first audience--reactions by perpetrator governments. These reactions arise in three settings: within their own country in response to criticism from domestic organizations; within their country in response to international organizations; and in the international arena in response to international organizations. This article concentrates on this third arena. Perpetrator governments, when framing their replies to allegation by human rights organizations have to address other audiences as--domestic public opinion and media, international public opinion and media, and international bodies. Despite the increasing influence of the human rights discourse in the international arena, no human rights organization has the power to undermine the standard lines of defense mounted by sovereign states and their patrons. The weapons, human rights activists advocate--accountability, shame, isolation, economic sanctions, arms, and cultural boycotts-might indeed are effective in bringing about desired improvement in the target country.

Most expectancy theory research has focused on work effort defined in general terms to cover the total job. The objective of this study is to narrow the focus to deal with content-specific work activities. Activity categories are differentiated in terms of (1) productive and supportive activities and (2) high and low situational structure. Extrinsic and intrinsic motivators and specific effort criteria are delineated. Differences in the configuration and strength of motivator -effort relationships as a function of the activity category classifications are demonstrated using two separate administration sessions in an Army work setting. The extrinsic motivator predicts better for the productive activities while the intrinsic motivator does better for the supportive activities. Motivator-effort relationships are stronger for low-structured than high-structured activities. Curvilinear as well as linear relationships exist for certain activities where structure may restrict maximum effort. Implications of the results for applied organizational development programs are discussed. [ABSTRACT FROM AUTHOR]

Identifies a gene (tsg101) where its homozygous functional disruption produces cell transformation. Experimental approaches and construction of gene search vectors; Experiments showing the isolation of clones; Sequence analysis and DNA cloning; Discussion and conclusion.

Discusses various biological functions of the multiple adenosine residues at the 3' terminal of prokaryotic transcripts. Effects of adenylation on transcript stability; Role of adenylation in the generation of functional messenger RNA and its decay; Isolation of polynucleotide phosphorylase (PNPase) responsible for adding and removing nucleotides at the 3' end.

Examines the replication at the telomeres of the Streptomyces linear plasmid SLA2. Filling of the recessed ends of lagging strands; Non-displacing DNA synthesis; Mechanism proposed for telomere replication in autonomous parvoviruses.

The article is about the relationships between crime and politics. It would be banal to say that the boundaries between crime and politics are now more complex than criminologists imagined thirty years ago. The question is what do people make of this complexity? The deconstructionist suggests one answer and post-modernist theories that have so seduced the intellectual avant-garde over this period. For them, crime and politics are always to be placed in inverted commas, to be seen not as terms depicting any identifiable object but as free-floating signifiers, capable of an infinite transferability from one realm to the other. All one can study is the construction of discourses about crime and politics. This solution is aesthetically appealing and can be carried quite far, far enough perhaps to make the author's two lists redundant or interchangeable. It leaves little room, though, to understand the substance of those shifts that the author has listed, such as the politicization of street crime and criminalization of certain forms of political action. And it leaves any normative, value, questions even further from reach in analytical terms, the original enterprise of looking for the links between crime and politics was justified. But do people really want a social order where there is no distinction between the two? The atrocities that have become daily life in so many parts of the world are an appalling expression of precisely the obliteration of any distinction between political dispute and criminal violence.

Reports on the isolation and characterization of the plasmid mutations that allow stable partitioning of pSC101 plasmids lacking the partition (par) locus. Absence of correlation between copy number increase and plasmid stability; Induction of pSC101 replication in the absence of integration host factor; Role of the RepA-DNA-DnA complex in partitioning.

During the course of the studies on the nerve growth factor of the submaxillary gland of the male mouse (1), it was observed that extracts of these glands, when injected into new-born mice, caused precocious opening of the eyelid and eruption of the incisors. A polypeptide responsible for this effect has been isolated (2). The biological activity was subsequently found to he due to a direct stimulation of the proliferation and keratinization of epidermal tissue. The following summary of the chemical and biological properties of the epidermal growth factor (EGF) is a condensation of a review (3). [ABSTRACT FROM AUTHOR]

The article presents a presidential address by Stanley B. Cohen, president of American College of Rheumatology, delivered at the 74th Annual Scientific Meeting of the American College of Rheumatology, held in November 7, 2010, in which he shared his experience with the American College of Rheumatology and the steps taken by ACR in coping up with the changing technology in medicine.

The author discusses the classification criteria for rheumatoid arthritis (RA) which was developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) in 1987. The two groups think that the criteria were useful in discriminating patients with RA from those with other inflammatory arthritides. They also believe that these criteria will be rapidly adopted in daily practice and will accelerate the use of more aggressive treatment for patients.

The article reflects on the recommendations of the American College of Rheumatology (ACR) on the use of nonbiologic and biologic disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis (RA). It discusses a study conducted by K. G. Saag and colleagues which focused on the indications for use of these drugs, its side effects, and the role of cost and patient preferences in decision making.

Abstract: The etiology and mechanisms of stroke could differ in cancer compared to non-cancer patients due to altered blood coagulability and/or non-bacterial thrombotic endocarditis (NBTE). These conditions could be either missed by using inappropriate diagnostic methods or misinterpreted. For instance, certain techniques (transthoracic echocardiography, TTE) may provide false-negative results and delay appropriate therapy. On the other hand, these patients, by having atypical findings, may challenge the differential between bacterial and sterile valvular heart disease. Cerebrovascular disease in cancer patients is often aggressive with tendency to recurrent events and rapid neurological devastation. Timely diagnosis is crucial. Current treatment approach to NBTE includes anticoagulation. We report a case of multiple embolic strokes in a patient diagnosed with lung cancer. Primary and secondary stroke prevention is discussed with relevant review of the literature. [Copyright &y& Elsevier]

Background: Recent studies suggest that dietary therapy may be effective for patients with inflammatory bowel disease (IBD), but limited published data exist on the usage and efficacy of dietary therapy.Aim: To evaluate the perspective of IBD patients using the specific carbohydrate diet (SCD).Methods: An anonymous online survey was conducted using REDCap, a Web-based survey tool. Survey links were sent to known Web sites as well as support groups in an attempt to characterize patient utilization of the SCD and perception of efficacy of the SCD.Results: There were 417 respondents of the online survey on the SCD with IBD. Mean age for individuals on the SCD was 34.9 ± 16.4 years. Seventy percent were female. Forty-seven percent had Crohn's disease, 43 % had ulcerative colitis, and 10 % had indeterminate colitis. Individuals perceived clinical improvement on the SCD. Four percent reported clinical remission prior to the SCD, while 33 % reported remission at 2 months after initiation of the SCD, and 42 % at both 6 and 12 months. For those reporting clinical remission, 13 % reported time to achieve remission of less than 2 weeks, 17 % reported 2 weeks to a month, 36 % reported 1-3 months, and 34 % reported greater than 3 months. For individuals who reported reaching remission, 47 % of individuals reported associated improvement in abnormal laboratory values.Conclusions: The SCD is utilized by many patients as a primary and adjunct therapy for IBD. Most patients perceive clinical benefit to use of the SCD. [ABSTRACT FROM AUTHOR]

Describes the synthesis of DNA in pSLA2 linear plasmids of Streptomyces rochei. Recession of linear duplex molecules acting as replication intermediaries; Overhanging 3' ends as templates for non-displacing synthesis of the lagging strand terminus.

The poem "Abandon All" by Stanley Cohen is presented. First Line: ER wastebaskets are full; Last Line: to the same magazines.

Determining the potential success of investigational therapies for rheumatoid arthritis early in the development process would enable better allocation of increasingly limited resources. Such ‘go or no-go’ decision-making could be improved by a method of analysing longitudinal clinical trial data to establish a threshold for success of a new drug. [ABSTRACT FROM AUTHOR]

A response by JM Kremer and colleagues to a letter to the editor about their article "A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib [CP-690,550] versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone," in the April 2012 issue is presented.

Introduction: This post hoc analysis evaluated influenza adverse events (AEs) across rheumatoid arthritis (RA), ulcerative colitis (UC), and psoriatic arthritis (PsA) tofacitinib clinical programs. Methods: Available data from phase 1, randomized phase 2/3/3b/4 clinical trials (completed by 2018), and long-term extension (LTE) studies (up to May 2019) in patients with RA, UC, and PsA were included [randomized or Overall (phase 1–3b/4 and LTE studies) tofacitinib cohorts]. Incidence rates (IRs; events per 100 patient-years) of combined influenza AEs (seasons 2004/2005 to 2018/2019) were analyzed, including by tofacitinib dose [5 or 10 mg twice daily (BID)] and age (< 65 versus ≥ 65 years). Logistic regression models evaluated risk factors for influenza AEs in the RA Overall tofacitinib cohort. Results: In randomized cohorts, combined influenza AE IRs were generally similar across tofacitinib, adalimumab, methotrexate, and placebo groups, across indications. Among Overall tofacitinib cohorts, combined influenza AE IRs with tofacitinib 5/10 mg BID, respectively, were higher in the UC (3.66/5.09) versus RA (2.38/2.19) and PsA (1.74/1.29) cohorts. IRs were generally similar across tofacitinib dose and age groups. Most influenza AEs were nonserious and did not require changes to tofacitinib treatment. Significant risk factors for influenza AEs in patients with RA were geographic region, baseline oral corticosteroid and methotrexate use, and tofacitinib dose. Conclusions: In the RA, UC, and PsA clinical programs, combined influenza AE IRs were highest in UC, while in each indication they were generally similar across tofacitinib, placebo, and comparator groups. Influenza AEs were predominantly nonserious and not associated with changes to tofacitinib treatment. Trial Registration Numbers: NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612, NCT01877668, NCT01882439, NCT01976364. [ABSTRACT FROM AUTHOR]

A preface to the journal "Analytical Cellular Pathology" is presented.

The article discusses a study by J. M. Grossman et al in a 2010 issue of "Arthritis Care & Research" on the impact of American College of Rheumatology (ACR) recommendations in 2010 for the prevention and treatment of glucocorticoid-induced osteoporosis. The researchers conducted a systematic literature review of randomised controlled trials in patients receiving glucocorticoids as part of the study. The team incorporated the FRAX tool to stratify patients' risk of fracture. They also determined the appropriateness of various possible recommendations.

Purpose SBI-087 is a Small Modular Immunopharmaceutical Protein™(SMIP™) drug that binds to CD20 and has been reported to deplete B cells in murine/primate studies. The safety, tolerability and pharmacokinetic/pharmacodynamic properties of SBI-087 were evaluated in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Methods Single-dose SBI-087 was evaluated in 2 Phase I, open-label, escalating-dose studies in patients with RA or SLE. The studies included 6 IV/4 SC escalating doses (RA) and 1 IV/4 SC escalating doses (SLE). Escalation was determined by tolerability/rate of B-cell depletion. Serum was collected for analyses of pharmacokinetic and pharmacodynamic (CD19 + B cells) properties and immunogenicity. Patients were followed until B-cell counts were normalized or stabilized. Safety, tolerability was evaluated from adverse events, physical examinations, vital sign measurements, ECG, and clinical laboratory results. Findings Sixty patients with RA (IV, 28; SC, 32) and 30 patients with SLE (6 per cohort) were enrolled. Mild to moderate infusion reactions occurred in several patients at the top doses in the RA study despite a pretreatment regimen of IV doses. Unanticipated reactions after SC administration of SBI-087 included fever, chills, and malaise, seen on the day of dosing in the lowest-dose cohorts in both studies. These events were abrogated in subsequent cohorts by a pre/postdose treatment regimen consisting of oral corticosteroids, acetaminophen, and an antihistamine. SBI-087 clearance (IV) ranged from 22 to 229 mL/h; volume of distribution at steady state ranged from 5 to 12 L. Apparent clearance (SC) ranged from 44.7 to 105 mL/h; volume of distribution ranged from 14.3 to 32.1 L. Overall, PK properties were similar at equivalent doses between IV/SC administrations in patients with RA/SLE. Mean t ½ (IV) ranged from 2.1 to 10.7 days (less at lower doses). SBI-087 concentration and B-cell depletion were generally dose proportional across IV and SC cohorts. However, the extent of B-cell depletion was less, and rate of repletion was faster, in patients with SLE versus RA. In both studies, B-cell repletion to baseline did not occur in the majority of patients by the end of the observation period. Overall, the prevalence and type of adverse events were similar to those seen with other anti-CD20–depleting agents. Implications In patients with mild RA/SLE, SBI-087 was well tolerated when administered intravenously or subcutaneously with pre- and posttreatment regimens. B-cell depletion is long lasting, and the duration and extent of depletion may be greater in RA compared with SLE. SBI-087 exhibited slow elimination and low distribution in both populations. Clinicaltrials.gov identifiers: NCT00641225 (RA) and NCT00714116 (SLE). [ABSTRACT FROM AUTHOR]

The poem "Scanned," by Stanley Cohen is presented. First Line: You see, I wear readers now, Last Line: Atlanta traffic worthwhile.

The poem "Child of Mine," by Stanley Cohen is presented. First Line: My sure hand stutters; Last Line: conceived at your birth.

The poem "'Far Too Often" by Stanley Cohen is presented. First Line: Too often purple saturates your skin Last Line: blushes and lipstick that cover it all.

The poem "Album" by Stanley Cohen is presented. First Line: Do I see my children; Last Line: for its replacement.

The poem "Deescalation" by Stanley Cohen is presented. First Line: What do you do when you come from the hospital; Last Line: Yet is all there is and isn't.

The poem "Awaited" by Stanley Cohen is presented. First Line: The fragile left hand waved; Last Line: the right number of toes.

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy.Methods: Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC.Results: By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation.Conclusions: Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX.Funding: Pfizer Inc.Trial registration: Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661]. [ABSTRACT FROM AUTHOR]

Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs.Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit.Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: -3.12 versus -2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments.Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point).Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background & aims: Both non-alcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection commonly result in hepatic fibrosis and may lead to cirrhosis. This study aims to determine the incidence of HCC in patients with HCV or NAFLD complicated by advanced fibrosis, inferred from measurements of liver stiffness. Methods: Using Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), we identified a nationwide cohort of patients with an existing diagnosis of HCV or NAFLD with liver transient elastography (TE) testing from 2015 to 2019. HCC cases, along with a random sample of non-HCC patients, were identified and validated, leading to calculation of incidence rates for HCC after adjustment for confounders. Results: 26,161 patients carried a diagnosis of HCV and 13,629 were diagnosed with NAFLD at the time of testing. In those with HCV, rates of HCC increased with liver stiffness with incidences of 0.28 (95% CI 0.24, 0.34), 0.93 (95% CI 0.72, 1.17), 1.28 (95% CI 0.89, 1.79), and 2.79 (95% CI 2.47, 3.14)/100,000 person years for TE score ranges <9.5 kPa, 9.5–12.5 kPa, 12.5–14.5 kPa and >14.5 kPa, respectively, after a median follow-up of 2.3 years. HCC incidence also increased with higher TE liver stiffness measures in NAFLD after a median follow-up of 1.1 years. Conclusion: In this retrospective cohort, the incidence of HCC in HCV and NAFLD increases with higher TE liver stiffness measures, confirming that advanced fibrosis portends risk in viral and non-viral fibrotic liver diseases. Additional comparative studies are needed to determine the optimal cut point of TE liver stiffness to inform HCC screening guidelines and approaches. [ABSTRACT FROM AUTHOR]

An introduction is presented which discusses various reports within the issue on topics including rheumatoid arthritis classification criteria, the definition of rheumatoid arthritis in different populations, and currently available treatment options for rheumatoid arthritis.

The article profiles Joan M. Bathon who has accepted the editorship of the periodical on July 1, 2010. Bathon earned her bachelor of science degree at Marquette University in Milwaukee, Wisconsin with magna cum Laude. She is a professor of Medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland. She founded the John Hopkins Arthritis WebSite in 1998. She is also a recipient of various awards including the Mary Betty Stevens Award. Her plans for the periodical are noted.

Proteins encoded by the mdm2 gene, which has a pivotal role in the regulation of growth and differentiation, exist principally in human and murine cells as two isoforms that migrate in gels as 75-kDa and 90-kDa proteins. There is limited understanding of the respective biological roles of these isoforms, their molecular nature, and their mechanism of formation. We report here that human p75MDM2 is an N-terminally truncated mixture of protein isoforms produced by the initiation of translation at two distinct internal AUG codons. The p75MDM2 doublets and p90MDM2, which is the full-length MDM2 protein, are expressed in approximately equal amounts from transcripts initiated at the constitutive P1 promoter of mdm2. Unlike murine transcripts initiated at the p53-activated P2 promoter, human cell transcripts initiated at the P2 promoter preferentially produce p90MDM2. The ubiquitin enzyme variant protein TSG101, which interacts functionally with MDM2 in an autoregulatory loop that parallels the p53/MDM2 feedback control loop, interferes with degradation of both isoforms; however, only p90MDM2 promotes proteolysis of TSG101 and p53. Our results reveal the mechanism of formation of the principal MDM2 isoforms, the differential effects of p53 on the production of these isoforms, and the differential abilities of human MDM2 isoforms as regulators of the MDM2/TSG101 and p53/MDM2 feedback control loops. [ABSTRACT FROM AUTHOR]