Ocular and orbital manifestations of granulomatosis with polyangiitis: a systematic review of published cases.

Objective: Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by necrotizing granulomatous inflammation of small and medium-sized vessels. This systematic review aimed to highlight the most common ophthalmic manifestations and to uncover their associations with antineutrophil cytoplasmic antibody (ANCA) positivity and the presence of granulomas. Methods: A literature search of PubMed, Web of Science, and Scopus electronic databases was performed from journal inception to March 21, 2021, for case reports and a series of ophthalmic GPAs. Cytoplasmic-ANCA (c-ANCA), perinuclear-ANCA (p-ANCA), and granulomas were analyzed against many ophthalmic signs and symptoms. 306 patients with GPA were retrospectively studied. Results: Granulomas were present in 47.7% of our sample, c-ANCA in 59.2%, and p-ANCA in 10.8%. Scleritis was significantly associated with higher odds for c-ANCA positivity. Eye discharge, episcleritis, proptosis, and central nervous system (CNS) involvement were each significantly associated with lower odds for c-ANCA positivity. Orbital mass was significantly associated with lower odds for p-ANCA positivity. CNS involvement was significantly associated with higher odds for p-ANCA positivity (OR:3.08, 95% CI:1.02, 9.36, p=0.047) and orbital mass was significantly associated with lower odds for p-ANCA positivity. Conclusions: We recommend that clinicians should consider ocular or orbital GPA in patients presenting with non-specific eye complaints, such as vision impairment, orbital mass, or proptosis, and obtain further assessments to determine the possible presence of granuloma, c-ANCA, or p-ANCA. Abbreviations: GPA = Granulomatosis with Polyangiitis, ANCA = antineutrophil cytoplasmic antibody, c-ANCA = cytoplasmic-ANCA, p-ANCA = perinuclear-ANCA, CNS = central nervous system, AAVs = ANCA-associated vasculitides, SD = standard deviation, GU = genitourinary, ENT = ear nose and throat, OR = odds ratio, CI = confidence interval.

Effectiveness of Waterpik® for oral hygiene maintenance in orthodontic fixed appliance patients: A randomised controlled trial.

OBJECTIVE: To establish whether the use of a WaterPik® alongside a manual toothbrush (WaterPik® + MTB) is more effective for maintaining oral hygiene compared to the use of a manual toothbrush alone (MTB) in patients wearing fixed orthodontic appliances. DESIGN: A single-centre, two-arm, parallel-group, single-blind, randomised controlled clinical trial with a 1:1 allocation ratio. SETTING: Orthodontic department at York Hospital, York Teaching Hospitals NHS Foundation Trust, UK. PARTICIPANTS: A total of 40 fit and well participants, aged 10-20 years, being treated with upper and lower fixed orthodontic appliances. METHODS: Participants were randomly allocated, using stratified block randomisation, to the control group (MTB) or intervention group '(Waterpik® + MTB)'. Plaque, gingival and interdental bleeding indices were recorded at baseline, 8 weeks, 32 weeks and 56 weeks. A generalised linear mixed model was used to assess differences between groups. RESULTS: An interim analysis of results was performed with 40 patients recruited and 85% of data collected. The overall mean differences between the groups were as follows: plaque index = 0.199 (P = 0.88, 95% confidence interval [CI] -0.24 to 0.27); gingival index = -0.008 (P = 0.94, 95% CI -0.22 to 0.20); and interdental bleeding index = 5.60 (P = 0.563, 95% CI -13.22 to 24.42). No statistical difference between the two groups was found for any variable. The trial was stopped at this point. CONCLUSIONS: In terms of oral hygiene, our study did not find evidence to support the claim of benefit of using a Waterpik® in addition to a manual toothbrush for patients wearing fixed orthodontic appliances.

Discovery and Characterization of the Phospholemman/SIMP/Viroporin Superfamily.

Using bioinformatic approaches, we present evidence of distant relatedness among the Ephemerovirus Viroporin family, the Rhabdoviridae Putative Viroporin U5 family, the Phospholemman family, and the Small Integral Membrane Protein family. Our approach is based on the transitivity property of homology complemented with five validation criteria: (1) significant sequence similarity and alignment coverage, (2) compatibility of topology of transmembrane segments, (3) overlap of hydropathy profiles, (4) conservation of protein domains, and (5) conservation of sequence motifs. Our results indicate that Pfam protein domains PF02038 and PF15831 can be found in or projected onto members of all four families. In addition, we identified a 26-residue motif conserved across the superfamily. This motif is characterized by hydrophobic residues that help anchor the protein to the membrane and charged residues that constitute phosphorylation sites. In addition, all members of the four families with annotated function are either responsible for or affect the transport of ions into and/or out of the cell. Taken together, these results justify the creation of the novel Phospholemman/SIMP/Viroporin superfamily. Given that transport proteins can be found not just in cells, but also in viruses, the ability to relate viroporin protein families with their eukaryotic and bacterial counterparts is an important development in this superfamily.

Mars Perihelion Cloud Trails as revealed by MARCI: Mesoscale Topographically Focussed Updrafts and Gravity Wave Forcing of High Altitude Clouds.

Daily, global wide angle imaging of Mars clouds in MARCI (MARs Color Imager, (Malin et al., 2008)) ultraviolet and visible bands reveals the spatial/seasonal distributions and physical characteristics of perihelion cloud trails (PCT); a class of high altitude (40-50 km), horizontally extended (200-1000 km, trending W to WSW) water ice clouds formed over specific southern low-to-mid latitude (5S-40S), mesoscale (~50 km) locations during the Mars perihelion, southern summer season. PCT were first reported in association with rim regions of Valles Marineris (Clancy et al., 2009). The current study employs MARCI 2007-2011 imaging to sample the broader distributions and properties of PCT; and indicates several distinct locations of peak occurrences, including SW Arsia Mons, elevated regions of Syria, Solis, and Thaumasia Planitia, along Valles Marineris margins, and the NE rim of Hellas Basin. PCT are present over Mars solar longitudes (L S ) of 210-310°, in late morning to mid afternoon hours (10am-3pm), and are among the brightest and most distinctive clouds exhibited during the perihelion portion of the Mars orbit. Their locations (i.e., eastern margin origins) correspond to strong local elevation gradients, and their timing to peak solar heating conditions (perihelion, subsolar latitudes and midday local times). They occur approximately on a daily basis among all locations identified (i.e., not daily at a single location). Based on cloud surface shadow analyses, PCT form at 40-50 km aeroid altitudes, where water vapor is generally at near-saturation conditions in this perihelion period (e.g. Millour et al., 2014). They exhibited notable absences during periods of planet encircling and regional dust storm activity in 2007 and 2009, respectively, presumably due to reduced water saturation conditions above 35-40 km altitudes associated with increased dust heating over the vertically extended atmosphere (e.g., Neary et al., 2019). PCT exhibit smaller particle sizes (R eff =0.2-0.5µm) than typically exhibited in the lower atmosphere, and incorporate significant fractions of available water vapor at these altitudes. PCT ice particles are inferred to form continuously (over ~4 hours) at their PCT eastern origins, associated with localized updrafts, and are entrained in upper level zonal/meridional winds (towards W or WSW with ~50 m/sec speeds at 40-50 km altitudes) to create long, linear cloud trails. PCT cloud formation is apparently forced in the lower atmosphere (≤10-15 km) by strong updrafts associated with distinctive topographic gradients, such as simulated in mesoscale studies (e.g., Tyler and Barnes, 2015) and indicated by the surface-specific PCT locations. These lower scale height updrafts are proposed to generate vertically propagating gravity waves (GW), leading to PCT formation above ~40 km altitudes where water vapor saturation conditions promote vigorous cloud ice formation. Recent mapping of GW amplitudes at ~25 km altitudes, from Mars Climate Sounder 15 µm radiance variations (Heavens et al., 2020), in fact demonstrates close correspondences to the detailed spatial distributions of observed PCT, relative to other potential factors such as surface albedo and surface elevation (or related boundary layer depths).

Meta-analysis comparing efficacy of antibiotics versus oral contraceptives in acne vulgaris.

BACKGROUND: Both antibiotics and oral contraceptive pills (OCPs) have been found to be effective in managing acne vulgaris. Despite widespread use, few direct comparisons of efficacy between the 2 modalities have been published. OBJECTIVE: We compared the efficacy of antibiotics and OCPs in managing acne. METHODS: A meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane collaboration guidelines. RESULTS: A review of 226 publications yielded 32 randomized controlled trials that met our inclusion criteria. At 3 and 6 months, compared with placebo, both antibiotics and OCPs effected greater percent reduction in inflammatory, noninflammatory, and total lesions; the 2 modalities at each time point demonstrated statistical parity, except that antibiotics were superior to OCPs in percent reduction of total lesions at 3 months (weighted mean inflammatory lesion reduction: 3-month course of oral antibiotic treatment = 53.2%, 3-month course of OCPs = 35.6%, 3-month course of placebo treatment = 26.4%, 6-month course of oral antibiotic treatment = 57.9%, 6-month course of OCPs = 61.9%, 6-month course of placebo treatment = 34.2%; weighted mean noninflammatory lesion reduction: 3-month course of oral antibiotic treatment = 41.9%, 3-month course of OCPs = 32.6%, 3-month course of placebo treatment = 17.1%, 6-month course of oral antibiotic treatment = 56.4%, 6-month course of OCPs = 49.1%, 6-month course of placebo treatment = 23.4%; weighted mean total lesion reduction: 3-month course of oral antibiotic treatment = 48.0%, 3-month course of OCPs = 37.3%, 3-month course of placebo treatment = 24.5%, 6-month course of oral antibiotic treatment = 52.8%, 6-month course of OCPs = 55.0%, 6-month course of placebo treatment = 28.6%). LIMITATIONS: Investigative treatment heterogeneity and publication bias are limitations. CONCLUSIONS: Although antibiotics may be superior at 3 months, OCPs are equivalent to antibiotics at 6 months in reducing acne lesions and, thus, may be a better first-line alternative to systemic antibiotics for long-term acne management in women.

Effects of 17alpha-ethinylestradiol on immune parameters in the lizard Sceloporus occidentalis.

We examined the effect of 17alpha-ethinylestradiol on immunity of the Western fence lizard, Sceloporus occidentalis. Injection of 17alpha-ethinylestradiol resulted in dose-dependent suppression of peripheral blood leukocyte levels as determined by cell counts, whereas total spleen cell levels were decreased only at higher doses of 17alpha-ethinylestradiol. In contrast, spleen cell proliferation was enhanced by 17alpha-ethinylestradiol as measured by reduction of MTT to formazan following a two-way mixed lymphocyte reaction. Antibody responses were unaffected. Effects on peripheral blood leukocyte levels and spleen cell proliferation similar to those observed in response to injection of 17alpha-ethinylestradiol were observed following injection of a single dose of hydrocortisone. However, injection of lizards with 17alpha-ethinylestradiol did not result in a significant increase in serum cortisol. Results of this study suggest that exposure of Western fence lizards to 17alpha-ethinylestradiol leads to decreased numbers of circulating leukocytes and total spleen cell numbers and the enhancement of spleen cell proliferation in a two-way mixed lymphocyte reaction. These effects probably involve mechanisms other than or in addition to the induction of cortisol release.