Strategic memory in adults with anorexia nervosa: Are there similarities to obsessive compulsive spectrum disorders?

OBJECTIVE: There is growing interest in the relationship between anorexia nervosa (AN) and obsessive-compulsive (OC) spectrum disorders (e.g., OCD, body dysmorphic disorder [BDD]). Previous neuropsychological investigations of OC spectrum disorders have identified problems with the efficient use of strategy on complex measures of learning and memory. This study evaluated nonverbal strategic memory in AN outpatients using an approach previously applied to OC spectrum disorders. METHOD: Eighteen patients with AN and 19 healthy control participants completed the Rey-Osterrieth Complex Figure Test (RCFT), a widely used measure of nonverbal strategic planning, learning, and memory. RESULTS: Individuals with AN differed significantly from healthy controls in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in learning were mediated by copy organizational strategies. CONCLUSION: These results are identical to study findings in OCD and BDD, indicating important shared neuropsychological features among AN and these OC spectrum disorders. As in OCD and BDD, the essential cognitive deficit in AN was impaired use of organizational strategies, which may inform our understanding of the pathophysiology of AN and potentially offer treatment implications.     

Identification of novel ErbB3-interacting factors using the split-ubiquitin membrane yeast two-hybrid system

Analysis of membrane protein interactions is difficult because of the hydrophobic nature of these proteins, which often renders conventional biochemical and genetic assays fruitless. This is a substantial problem because proteins that are integral or associated with membranes represent approximately one-third of all proteins in a typical eukaryotic cell. We have shown previously that the modified split-ubiquitin system can be used as a genetic assay for the in vivo detection of interactions between the two characterized yeast transmembrane proteins, Ost1p and Wbp1p. This so-called split-ubiquitin membrane yeast two-hybrid (YTH) system uses the split-ubiquitin approach in which reconstitution of two ubiquitin halves is mediated by a protein-protein interaction. Here we converted the split-ubiquitin membrane YTH system into a generally applicable in vivo screening approach to identify interacting partners of a particular mammalian transmembrane protein. We have demonstrated the effectiveness of this approach by using the mammalian ErbB3 receptor as bait and have identified three previously unknown ErbB3-interacting proteins. In addition, we have confirmed one of the newly found interactions between ErbB3 and the membrane-associated RGS4 protein by coimmunoprecipitating the two proteins from human cells. We expect the split-ubiquitin membrane YTH technology to be valuable for the identification of potential interacting partners of integral membrane proteins from many model organisms.     

Characteristics, epidemiology and clinical importance of emerging strains of Gram-negative bacilli producing extended-spectrum beta-lactamases

Beta-lactam antimicrobial agents represent the most common treatment for bacterial infections and continue to be the leading cause of resistance to beta-lactam antibiotics among Gram-negative bacteria worldwide. The persistent exposure of bacterial strains to a multitude of beta-lactams has induced dynamic and continuous production and mutation of beta-lactamases in these bacteria, expanding their activity even against the newly developed beta-lactam antibiotics. These enzymes are known as extended-spectrum beta-lactamases (ESBLs). The majority of ESBLs are derived from the widespread broad-spectrum beta-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including the CTX-M and OXA-type enzymes as well as novel unrelated beta-lactamases. In recent years, there has been an increased incidence and prevalence of ESBLs. ESBLs are mainly found in strains of Escherichia coli and Klebsiella pneumoniae but have also been reported in other Enterobacteriaceae strains and Pseudomonas aeruginosa. Infections with ESBL-producing bacterial strains are encountered singly or in outbreaks, especially in critical care units in hospitals, resulting in increasing cost of treatment and prolonged hospital stays. Not only may nursing home patients be an important reservoir of ESBL-containing multiple antibiotic-resistant organisms, but ambulatory patients with chronic conditions may also harbor ESBL-producing organisms.     

Preferential recognition of epitopes on AGE–IgG by the autoantibodies in rheumatoid arthritis patients

Incubation of proteins with glucose lead to their non-enzymatic glycation ultimately resulting in the formation of advanced glycation end products (AGEs) in vivo. AGEs alter unique three dimensional structures of various plasma proteins such as IgG. The role of oxidative stress in the pathogenesis of rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease, is well established. In view of this, commercially available human IgG was glycated in vitro with physiological concentration of glucose (5 mM) and the possible involvement of glycated IgG (AGE–IgG) in RA was evaluated. The RA patients were divided into two groups on the basis of disease onset with respect to age: group I (early onset: 20–32 years) and group II (late onset: 36–54 years). AGE–IgG and oxidative stress levels were detected in RA patients and normal healthy individuals by nitroblue tetrazolium (NBT) assay and carbonyl content estimation respectively. Binding characteristics and specificity of RA antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA). We observed preferential binding of RA antibodies to AGE–IgG in comparison to native IgG. Band shift assay further substantiated the enhanced recognition of AGE–IgG by RA antibodies. The results suggest that glycation of IgG results in the generation of neo-epitopes, making it a potential immunogen. Our findings project AGE–IgG as one of the factors for induction of circulating RA autoantibodies.     

Intravenous ketamine attenuates injection pain and arterial pressure changes during the induction of anesthesia with propofol: a comparison with lidocaine

Objective: To compare the effects of lidocaine and ketamine pretreatment on injection pain and hypotension due to propofol induction. Design: Double blinded randomized controlled clinical trial. Place and Duration of the Study: Department of Anesthesiology, Surgical Intensive Care Unit and Pain Management, Dow University of Health Sciences and Civil Hospital, Karachi from February 2005 to December 2005. Patients and Methods: One hundred patients, age 20-60 years, of either gender, ASA I and II scheduled for elective gynaecological, urological, orthopedic or general surgical procedures under general anesthesia were randomly allocated into two groups i.e. group A to receive ketamine 0.5 mg/kg in volume of 2 ml with venous occlusion and group B to receive 2 ml of 1% lidocaine with venous occlusion as pretreatment before propofol induction. Venous occlusion was performed using rubber tourniquet after elevating the arm for 30 seconds, which was released 60 seconds after giving the pretreatment bolus and anesthesia was induced with propofol (2 mg/ml). Fifteen seconds after injection of 25%, the calculated dose of propofol and severity of injection pain was evaluated. Heart rate (HR) and noninvasive blood pressure were recorded pre-operatively, just before propofol induction, after propofol induction, immediately after intubation and 3 minutes after intubation. Results: Comparing the lidocaine group, the intensity and incidence of pain after propofol injection was lower in ketamine group but remained statistically insignificant. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in ketamine group after induction with propofol. The maximum fall in SBP from baseline in ketamine group was 16% and 29.1% in lidocaine group, while maximum decrease in DBP in ketamine group was found to be12.66% vs. 26.47% in lidocaine group. There was no significant change in heart rate from baseline in either group. Conclusion: Ketamine pre-treatment with venous occlusion is an effective method in reducing pain and providing hemodynamic stability after propofol induction.     

The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

DNGR-1 (CLEC9A) is a receptor for necrotic cells required by DCs to cross-prime CTLs against dead cell antigens in mice. It is currently unknown how DNGR-1 couples dead cell recognition to cross-priming. Here we found that DNGR-1 did not mediate DC activation by dead cells but rather diverted necrotic cell cargo into a recycling endosomal compartment, favoring cross-presentation to CD8(+) T cells. DNGR-1 regulated cross-priming in non-infectious settings such as immunization with antigen-bearing dead cells, as well as in highly immunogenic situations such as infection with herpes simplex virus type 1. Together, these results suggest that DNGR-1 is a dedicated receptor for cross-presentation of cell-associated antigens. Our work thus underscores the importance of cross-priming in immunity and indicates that antigenicity and adjuvanticity can be decoded by distinct innate immune receptors. The identification of specialized receptors that regulate antigenicity of virus-infected cells reveals determinants of antiviral immunity that might underlie the human response to infection and vaccination.     

Crowdsourcing for research data collection in rosacea

Several medical crowdsourcing sites are available to patients online, but few studies in the literature have compared crowdsourced data to clinical trials. Herein, we compare data from rosacea patients from a major medical crowdsourcing site with those from randomized controlled trials.