Chemical Addressability of Ultraviolet-Inactivated Viral Nanoparticles (VNPs)

. Thus, inactivation of the virus RNA genome is important for biosafety considerations, however the surface characteristics and chemical reactivity of the particles must be maintained in order to preserve chemical and structural functionality. were shown to maintain particle structure and chemical reactivity, and cellular binding properties were similar to CPMV-WT. applications

Treatment Outcomes and Cost-Effectiveness of Shifting Management of Stable ART Patients to Nurses in South Africa: An Observational Cohort

Lawrence Long and colleagues report that “down-referring” stable HIV patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health facility provides good health outcomes and cost-effective treatment for patients

The effects of an enhanced simulation programme on medical students' confidence responding to clinical deterioration

BACKGROUND: Clinical deterioration in adult hospital patients is an identified issue in healthcare practice globally. Teaching medical students to recognise and respond to the deteriorating patient is crucial if we are to address the issue in an effective way. The aim of this study was to evaluate the effects of an enhanced simulation exercise known as RADAR (Recognising Acute Deterioration: Active Response), on medical students’ confidence. METHODS: A questionnaire survey was conducted; the instrument contained three sections. Section 1 focused on students’ perceptions of the learning experience; section 2 investigated confidence. Both sections employed Likert-type scales. A third section invited open responses. Questionnaires were distributed to a cohort of third-year medical students (n = 158) in the North East of Scotland 130 (82 %) were returned for analysis, employing IBM SPSS v18 and ANOVA techniques. RESULTS: Students’ responses pointed to many benefits of the sessions. In the first section, students responded positively to the educational underpinning of the sessions, with all scores above 4.00 on a 5-point scale. There were clear learning outcomes; the sessions were active and engaging for students with an appropriate level of challenge and stress; they helped to integrate theory and practice; and effective feedback on their performance allowed students to reflect and learn from the experience. In section 2, the key finding was that scores for students’ confidence to recognise deterioration increased significantly (p. < .001) as a result of the sessions. Effect sizes (Eta(2)) were high, (0.68–0.75). In the open-ended questions, students pointed to many benefits of the RADAR course, including the opportunity to employ learned procedures in realistic scenarios. CONCLUSIONS: The use of this enhanced form of simulation with simulated patients and the judicious use of moulage is an effective method of increasing realism for medical students. Importantly, it gives them greater confidence in recognising and responding to clinical deterioration in adult patients. We recommend the use of RADAR as a safe and cost-effective approach in the area of clinical deterioration and suggest that there is a need to investigate its use with different patient groups

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis