Effect of frequency and rhythmicity on flicker light-induced hallucinatory phenomena

Flicker light stimulation (FLS) uses stroboscopic light on closed eyes to induce transient visual hallucinatory phenomena, such as the perception of geometric patterns, motion, and colours. It remains an open question where the neural correlates of these hallucinatory experiences emerge along the visual pathway. To allow future testing of suggested underlying mechanisms (e.g., changes in functional connectivity, neural entrainment), we sought to systematically characterise the effects of frequency (3 Hz, 8 Hz, 10 Hz and 18 Hz) and rhythmicity (rhythmic and arrhythmic conditions) on flicker-induced subjective experiences. Using a novel questionnaire, we found that flicker frequency and rhythmicity significantly influenced the degree to which participants experienced simple visual hallucinations, particularly the perception of Klüver forms and dynamics (e.g., motion). Participants reported their experience of geometric patterns and dynamics was at highest intensity during 10 Hz rhythmic stimulation. Further, we found that frequency-matched arrhythmic FLS strongly reduced these subjective effects compared to equivalent rhythmic stimulation. Together, these results provide evidence that flicker rhythmicity critically contributes to the effects of FLS beyond the effects of frequency alone, indicating that neural entrainment may drive the induced phenomenal experience

Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

Abstract 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed [1] -hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20- HETE on mesenchymal stem cell (MSC)-derived adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1–1 M) increased adipogenesis in a dose dependent manner in these cells ( P \u3c 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE 2 , enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE 2 resulted in the increased expression of the adipogenic regulators PPAR and -catenin in MSC-derived adipocytes. Taken together we show for the fi rst time that 20-HETE-derived COX-2-dependent 20-OH-PGE 2 enhances mature infl amed adipocyte hypertrophy in MSC undergoing adipogenic differentiation. — Kim, D. H., N. Puri, K. Sodhi, J. R. Falck, N. G. Abraham, J. Shapiro, and M. L. Schwartzman. Cyclooxygenase-2 dependent metabolism of 20-HETE increasesadiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes

CCR5 Is Essential for NK Cell Trafficking and Host Survival following Toxoplasma gondii Infection

The host response to intracellular pathogens requires the coordinated action of both the innate and acquired immune systems. Chemokines play a critical role in the trafficking of immune cells and transitioning an innate immune response into an acquired response. We analyzed the host response of mice deficient in the chemokine receptor CCR5 following infection with the intracellular protozoan parasite Toxoplasma gondii. We found that CCR5 controls recruitment of natural killer (NK) cells into infected tissues. Without this influx of NK cells, tissues from CCR5-deficient (CCR5(−/−)) mice were less able to generate an inflammatory response, had decreased chemokine and interferon γ production, and had higher parasite burden. As a result, CCR5(−/−) mice were more susceptible to infection with T. gondii but were less susceptible to the immune-mediated tissue injury seen in certain inbred strains. Adoptive transfer of CCR5(+/+) NK cells into CCR5(−/−) mice restored their ability to survive lethal T. gondii infection and demonstrated that CCR5 is required for NK cell homing into infected liver and spleen. This study establishes CCR5 as a critical receptor guiding NK cell trafficking in host defense

Patch Materials for Pulmonary Artery Arterioplasty and Right Ventricular Outflow Tract Augmentation: A Review

Patch augmentation of the right ventricular outflow tract (RVOT) and pulmonary artery (PA) arterioplasty are relatively common procedures in the surgical treatment of patients with congenital heart disease. To date, several patch materials have been applied with no agreed upon clinical standard. Each patch type has unique performance characteristics, cost, and availability. There are limited data describing the various advantages and disadvantages of different patch materials. We performed a review of studies describing the clinical performance of various RVOT and PA patch materials and found a limited but growing body of literature. Short-term clinical performance has been reported for a multitude of patch types, but comparisons are limited by inconsistent study design and scarce histologic data. Standard clinical criteria for assessment of patch efficacy and criteria for intervention need to be applied across patch types. The field is progressing with improvements in outcomes due to newer patch technologies focused on reducing antigenicity and promoting neotissue formation which may have the ability to grow, remodel, and repair

Does changing examiner stations during UK postgraduate surgery objective structured clinical examinations influence examination reliability and candidates' scores?

Objective Objective structured clinical examinations (OSCE) are widely used for summative assessment in surgery. Despite standardizing these as much as possible, variation, including examiner scoring, can occur which may affect reliability. In study of a high-stakes UK postgraduate surgical OSCE, we investigated whether examiners changing stations once during a long examining day affected marking, reliability, and overall candidates’ scores compared with examiners who examined the same scenario all day. Design, Setting, and Participants An observational study of 18,262 examiner-candidate interactions from the UK Membership of the Royal College of Surgeons examination was carried at 3 Surgical Colleges across the United Kingdom. Scores between examiners were compared using analysis of variance. Examination reliability was assessed with Cronbach’s alpha, and the comparative distribution of total candidates’ scores for each day was evaluated using t-tests of unit-weighted z scores. Results A significant difference was found in absolute scores differences awarded in the morning and afternoon sessions between examiners who changed stations at lunchtime and those who did not (p < 0.001). No significant differences were found for the main effects of either broad content area (p = 0.290) or station content area (p = 0.450). The reliability of each day was not affected by examiner switching (p = 0.280). Overall, no difference was found in z-score distribution of total candidate scores and categories of examiner switching. Conclusions This large study has found that although the range of marks awarded varied when examiners change OSCE stations, examination reliability and the likely candidate outcome were not affected. These results may have implications for examination design and examiner experience in surgical OSCEs and beyond

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Determinants of Multidrug-Resistant Tuberculosis Clusters, California, USA, 2004–2007

TOC summary: Type of isoniazid resistance–conferring mutation may be a determinant of genotypic clustering