Deviant Strategy on the Modified Six Elements Test in Patients with Schizophrenia

Impaired executive functioning is found in a considerable proportion of schizophrenia patients. Neuropsychological tests are originally designed to measure the behavior of neurological patients and may therefore miss psychiatry-related cognitive deficits. Qualitative information on tests for executive functioning is important in psychiatric populations. The Modified Six Elements Test (MSET) is a planning test that consists of 6 tasks, for which subjects have limited time and have to obey to switching rules. This study concerns a qualitatively different approach schizophrenia patients use on the MSET, and its relationship with cognitive measures. MSET scores and strategies of schizophrenia patients were compared to those of healthy controls, closed-head-injury patients, and peripheral injury patients. Also, schizophrenia patients and healthy controls were compared on verbal memory and vigilance. Schizophrenia patients finish fewer assignments on the MSET, receive a lower profile score compared to healthy controls, and use a different strategy on the test compared to the other groups. They also perform below healthy controls on the tests for verbal memory and vigilance. Use of the different strategy in schizophrenia patients was related to impaired cognitive functioning. An interesting strategy used by schizophrenia patients on the MSET appears to be indicative of impaired cognitive functioning. This strategy may be a compensatory strategy to spare cognitive resources. It could also be the result of a concrete interpretation of the test instructions.     

Is it time for biosimilars in autoimmune diseases?

The last two decades have witnessed a revolution in the treatment of autoimmune diseases due to the introduction of biological agents which, although now included as standard treatment in patients with autoimmune rheumatological, dermatological and gastrointestinal diseases. The use of biological agents is associated with greater costs compared with the mainly anti-inflammatory and immunosuppressant drugs used in the pre-biological era. Biosimilars are highly similar copies of biological drugs, but not identical to approved ‘reference’ agents. Biological agents are complex proteins involved in the immune response and their exact replicas are extremely difficult, if not impossible, to obtain. Three scenarios have converged to provide a specific opportunity for biosimilars in autoimmune diseases: growing demand for biologics due to successful clinical use; the nearing of patent expiry for the four top-selling biological brands; and the search to reduce health costs due to the financial crisis. We aimed to review the crucial topics of efficacy, safety and regulatory approach of upcoming biosimilars.     

Implanted Microsensor Continuous IOP Telemetry Suggests Gaze and Eyelid Closure Effects on IOP—A Preliminary Study

PurposeTo explore the effect of gaze direction and eyelid closure on intraocular pressure (IOP).MethodsEleven patients with primary open-angle glaucoma previously implanted with a telemetric IOP sensor were instructed to view eight equally-spaced fixation targets each at three eccentricities (10°, 20°, and 25°). Nine patients also performed eyelid closure. IOP was recorded via an external antenna placed around the study eye. Differences of mean IOP between consecutive gaze positions were calculated. Furthermore, the effect of eyelid closure on gaze-dependent IOP was assessed.ResultsThe maximum IOP increase was observed at 25° superior gaze (mean ± SD: 4.4 ± 4.9 mm Hg) and maximum decrease at 25° inferonasal gaze (−1.6 ± 0.8 mm Hg). There was a significant interaction between gaze direction and eccentricity (P = 0.003). Post-hoc tests confirmed significant decreases inferonasally for all eccentricities (mean ± SEM: 10°: −0.7 ± 0.2, P = 0.007; 20°: −1.1 ± 0.2, P = 0.006; and 25°: −1.6 ± 0.2, P = 0.006). Eight of 11 eyes showed significant IOP differences between superior and inferonasal gaze at 25°. IOP decreased during eyelid closure, which was significantly lower than downgaze at 25° (mean ± SEM: −2.1 ± 0.3 mm Hg vs. −0.7 ± 0.2 mm Hg, P = 0.014).ConclusionsOur data suggest that IOP varies reproducibly with gaze direction, albeit with patient variability. IOP generally increased in upgaze but decreased in inferonasal gaze and on eyelid closure. Future studies should investigate the patient variability and IOP dynamics.     

The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins

OBJECTIVES: Many enveloped viruses carry carbohydrate-containing proteins on their surface. These glycoproteins are key to the infection process as they are mediators of the receptor binding and membrane fusion of the virion with the host cell. Therefore, they are attractive therapeutic targets for the development of novel antiviral therapies. Recently, carbohydrate-binding agents (CBA) were shown to possess antiviral activity towards coronaviruses. The current study further elucidates the inhibitory mode of action of CBA. METHODS: Different strains of two coronaviruses, mouse hepatitis virus and feline infectious peritonitis virus, were exposed to CBA: the plant lectins Galanthus nivalis agglutinin, Hippeastrum hybrid agglutinin and Urtica dioica agglutinin (UDA) and the non-peptidic mannose-binding antibiotic pradimicin A. RESULTS AND CONCLUSIONS: Our results indicate that CBA target the two glycosylated envelope glycoproteins, the spike (S) and membrane (M) protein, of mouse hepatitis virus and feline infectious peritonitis virus. Furthermore, CBA did not inhibit virus-cell attachment, but rather affected virus entry at a post-binding stage. The sensitivity of coronaviruses towards CBA was shown to be dependent on the processing of the N-linked carbohydrates. Inhibition of mannosidases in host cells rendered the progeny viruses more sensitive to the mannose-binding agents and even to the N-acetylglucosamine-binding UDA. In addition, inhibition of coronaviruses was shown to be dependent on the cell-type used to grow the virus stocks. All together, these results show that CBA exhibit promising capabilities to inhibit coronavirus infections.     

Plasma Apolipoprotein L1 Levels Do Not Correlate with CKD

Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m² (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.Nondiabetic CKD in individuals of African ancestry have been linked to polymorphisms in the gene for apolipoprotein L1 (APOL1),^1–5 a protein component of HDL particles with a known function in the immune clearance of Trypanosoma brucei infections.⁶ CKD is associated with two coding variants of the APOL1 gene known as G1 and G2, both of higher allele frequency in African and African descendent populations compared with white populations where they are almost absent. Evidence suggests that the prevalence of the G1 and G2 variants may have increased in African populations because of a selective advantage from their ability to kill a broader range of Trypanosoma species.^1,2,7 Individuals carrying at least one G1 or G2 allele have additional protection from trypanosomiasis; however, individuals with two G1 or G2 alleles are at increased risk for nondiabetic CKD.^2,4,5The pathogenic mechanisms responsible for CKD associated with APOL1 risk variants are unknown. We recently showed that, in addition to being secreted and circulated in the blood,⁸ APOL1 is localized in podocytes, proximal tubular epithelial cells, and small-artery endothelium in normal kidney.⁹ Thus, the contribution of circulating versus kidney-localized variant APOL1s to CKD pathogenesis is unknown. In kidney transplantation, two studies suggest that graft loss is associated with the APOL1 genotype of the allograft, not the recipient.^10,11 However, the association of APOL1 plasma levels with CKD phenotypes or APOL1 genotype has not been studied.To address these issues, we examined circulating APOL1 levels with APOL1 genotype and renal function in HIV-infected African Americans in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort because the occurrence of HIV-associated nephropathy (HIVAN) and renal outcomes in HIV-infected patients are strongly associated with APOL1 risk alleles.^12–14 In addition, we examined the relationship between circulating APOL1 levels and proinflammatory cytokines known to induce APOL1 expression and previously associated with CKD and HIV/AIDS progression.^15,16 Additional analyses examined associations of APOL1 levels with dyslipidemia and the role of APOL1 genotype on CKD progression using longitudinal data.     

The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

Heart Failure Reviews - The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important...