PsAID12 Provisionally Endorsed at OMERACT 2018 as Core Outcome Measure to Assess Psoriatic Arthritis-specific Health-related Quality of Life in Clinical Trials

OBJECTIVE: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group is developing a Core Outcome Measurement Set for PsA clinical trials [randomized controlled trials (RCT) and longitudinal observational studies (LOS)] using the OMERACT Filter 2.1 instrument selection algorithm. Our objective was to assess the Psoriatic Arthritis Impact of Disease questionnaire (PsAID12) for the measurement of the core domain PsA-specific health-related quality of life (HRQOL).METHODS: PsAID12 measurement property evidence gathered in a systematic literature review, and additional analyses conducted in LOS, were used to inform a consensus process. Analyses that had not been published were independently reviewed by the OMERACT technical advisory group. Data and process were presented, discussed in breakout groups, and voted on at the OMERACT conference (Terrigal, Australia, May 2018).RESULTS: PsAID12 fulfilled the green (good to go) OMERACT standards for domain match, feasibility, reliability, and construct/longitudinal construct validity. Discrimination and thresholds of meaning were amber (caution but good enough to go forward). The overall working group recommendation was amber/provisional endorsement of PsAID12 for measuring PsA-specific HRQOL in RCT and LOS. Of 96 participants who voted at the PsA OMERACT workshop, 87.5% (84) voted "yes" to endorse this recommendation; 14 of the 96 were patient research partners (PRP) and 93% of them (13) voted "yes"; 82 participants were not PRP and 87% of them (71) voted "yes."CONCLUSION: At OMERACT 2018, PsAID12 was the first patient-reported outcome measure provisionally endorsed as a core outcome measure for disease-specific HRQOL in PsA clinical trials. PsAID12 discrimination and improvement thresholds will be studied in future RCT.</p

Loss of Prolyl Hydroxylase-1 Protects Against Colitis Through Reduced Epithelial Cell Apoptosis and Increased Barrier Function

Background &amp; Aims Hypoxia inducible factor (HIF) prolyl hydroxylase inhibitors are protective in mouse models of inflammatory bowel disease (IBD). Here, we investigated the therapeutic target(s) and mechanism(s) involved. Methods The effect of genetic deletion of individual HIF-prolyl hydroxylase (PHD) enzymes on the development of dextran sulphate sodium (DSS)induced colitis was examined in mice. Results PHD1-/-, but not PHD2+/- or PHD3-/-, mice were less susceptible to the development of colitis than wild-type controls as determined by weight loss, disease activity, colon histology, neutrophil infiltration, and cytokine expression. Reduced susceptibility of PHD1-/- mice to colitis was associated with increased density of colonic epithelial cells relative to wild-type controls, which was because of decreased levels of apoptosis that resulted in enhanced epithelial barrier function. Furthermore, with the use of cultured epithelial cells it was confirmed that hydroxylase inhibition reversed DSS-induced apoptosis and barrier dysfunction. Finally, PHD1 levels were increased with disease severity in intestinal tissue from patients with IBD and in colonic tissues from DSS-treated mice. Conclusions These results imply a role for PHD1 as a positive regulator of intestinal epithelial cell apoptosis in the inflamed colon. Genetic loss of PHD1 is protective against colitis through decreased epithelial cell apoptosis and consequent enhancement of intestinal epithelial barrier function. Thus, targeted PHD1 inhibition may represent a new therapeutic approach in IBD. © 2010 AGA Institute

Web-based telemonitoring of visual function and self-reported postoperative outcomes in cataract care: international multicenter randomized controlled trial

Purpose: To compare web-based, self-administered follow-up after cataract surgery to conventional face-to-face follow-up. Setting: Eye clinics in the Netherlands, Austria, and Germany. Design: Randomized controlled trial with an embedded method comparison study (ClinicalTrials. gov: NCT04809402). Methods: Routine patients with cataract were randomized into 2 groups: The telemonitoring group undertook web-based vision self-assessments and questionnaires from home, while the usual care group received conventional care. All participants had a 4- to 6-week postoperative clinic visit for safety and validation purposes. Outcomes included, the web test's accuracy for assessing postoperative visual acuity (VA) and refractive error, adverse event rates, and patient-reported outcome measurements (PROMs). Results: 94 participants (188 eyes) were enrolled. Web-based uncorrected distance VA testing demonstrated a negligible mean difference (-0.03 ± 0.14 logMAR) when compared with conventional Early Treatment Diabetic Retinopathy Study chart testing, with 95% limits of agreement ranging from -0.30 to 0.24 logMAR. The web-based refraction assessment overestimated the postoperative refractive error (mean difference in spherical equivalent 0.15 ± 0.67 diopters), resulting in a poorer corrected distance VA compared with subjective refraction (mean 0.1 vs -0.1 logMAR). Rates of adverse events and unscheduled consultations were minimal across both groups. Preoperative and postoperative PROM questionnaires had a 100% response rate. Visual functioning (Catquest-9SF and National Eye Institute Visual Function Questionnaire-25) improved postoperatively (mean improvement -0.80 and 16.70, respectively) and did not significantly differ between the 2 groups. Conclusions: The patients with cataract in this study effectively provided postoperative outcome data using a web interface. Both conventional and web-based follow-ups yielded similar PROMs and adverse event rates. Future developments should reduce the variability in the web-based VA test and yield representative refraction outcomes

Oct4-Induced Reprogramming Is Required for Adult Brain Neural Stem Cell Differentiation into Midbrain Dopaminergic Neurons

Neural stem cells (NSCs) lose their competency to generate region-specific neuronal populations at an early stage during embryonic brain development. Here we investigated whether epigenetic modifications can reverse the regional restriction of mouse adult brain subventricular zone (SVZ) NSCs. Using a variety of chemicals that interfere with DNA methylation and histone acetylation, we showed that such epigenetic modifications increased neuronal differentiation but did not enable specific regional patterning, such as midbrain dopaminergic (DA) neuron generation. Only after Oct-4 overexpression did adult NSCs acquire a pluripotent state that allowed differentiation into midbrain DA neurons. DA neurons derived from Oct4-reprogrammed NSCs improved behavioural motor deficits in a rat model of Parkinson's disease (PD) upon intrastriatal transplantation. Here we report for the first time the successful differentiation of SVZ adult NSCs into functional region-specific midbrain DA neurons, by means of Oct-4 induced pluripotency

Decay and Fission Hindrance of Two- and Four-Quasiparticle K Isomers in (254)Rf

Two isomers decaying by electromagnetic transitions with half-lives of 4.7(1.1) and 247(73)μs have been discovered in the heavy Rf254 nucleus. The observation of the shorter-lived isomer was made possible by a novel application of a digital data acquisition system. The isomers were interpreted as the Kπ=8-, ν2(7/2+[624],9/2-[734]) two-quasineutron and the Kπ=16+, 8-ν2(7/2+[624],9/2-[734])⊗ - 8-π2(7/2-[514],9/2+[624]) four-quasiparticle configurations, respectively. Surprisingly, the lifetime of the two-quasiparticle isomer is more than 4 orders of magnitude shorter than what has been observed for analogous isomers in the lighter N=150 isotones. The four-quasiparticle isomer is longer lived than the Rf254 ground state that decays exclusively by spontaneous fission with a half-life of 23.2(1.1)μs. The absence of sizable fission branches from either of the isomers implies unprecedented fission hindrance relative to the ground state

Periodontal diseases in the child and adolescent

Background: Periodontal diseases are among the most frequent diseases affecting children and adolescents. These include gingivitis, localized or generalized aggressive periodontitis (a.k.a., early onset periodontitis which includes generalized or localized prepubertal periodontitis and juvenile periodontitis) and periodontal diseases associated with systemic disorders. The best approach to managing periodontal diseases is prevention, followed by early detection and treatment. Methods: This paper reviews the current literature concerning the most common periodontal diseases affecting children: chronic gingivitis (or dental plaque-induced gingival diseases) and early onset periodontitis (or aggressive periodontitis), including prepubertal and juvenile periodontitis. In addition, systemic diseases that affect the periodontium and oral lesions commonly found in young children are addressed. The prevalence, diagnostic characteristics, microbiology, host-related factors, and therapeutic management of each of these disease entities are thoroughly discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73561/1/j.1600-051X.2002.290504.x.pd