A Randomized,Controlled Trial to Investigate the Effect of Ciclesonide and Beclomethasone Dipropionate on Eye Lens Opacity

Background. Inhaled corticosteroids (ICS) are recommended first-line therapy for the treatment of persistent asthma. However, reports from observational studies have suggested that the use of ICS may be associated with systemic adverse events, such as glaucoma and cataract (opacity of the lens) formation. Objective. To compare two ICS over 1 year regarding the formation/progression of lenticular opacities in patients with asthma. Methods. Adults (≥ 18 years of age) with moderate-to-severe asthma were randomized to ciclesonide 640 μ g/day (n = 785) or beclomethasone dipropionate 640 μ g/day (n = 783) in a multinational, double-blind, active-controlled, parallel-group study. The primary endpoint was the occurrence of a positive Class I grading shift (increase [worsening] in Lens Opacities Classification System [LOCS] III score of ≥ 0.5 for nuclear opalescence, ≥ 0.8 for cortical opacification, or ≥ 0.5 for posterior subcapsular opacification, or cataract surgery) in either eye at any visit over the 12-month, double-blind treatment period. Results. Mean changes (± standard error) in nuclear opalescence and cortical and posterior subcapsular opacification were small and similar between groups (ciclesonide 640 μ g/day: 0.10 ± 0.02, 0.07 ± 0.02 and 0.04 ± 0.01, respectively; beclomethasone dipropionate 640 μ g/day: 0.11 ± 0.02, 0.09 ± 0.02 and 0.03 ± 0.01, respectively). Class I shifts were observed in 34.3% versus 36.8% of ciclesonide-treated and beclomethasone dipropionate-treated patients, respectively. Ciclesonide 640 μ g/day was non-inferior to beclomethasone dipropionate 640 μ g/day regarding Class I shifts (risk ratio of ciclesonide to beclomethasone dipropionate, 0.940 [95% confidence interval, 0.820–1.077]); the 95% confidence interval upper bound was lower than the pre-specified non-inferiority bound of 1.333 (p < 0.0001), thereby excluding the possibility of higher risk ratio values. Conclusions. Mean changes in LOCS III scores were very small in both groups. Treatment with ciclesonide 640 μ g/day or beclomethasone dipropionate 640 μ g/day for 1 year has a minimal impact on lenticular opacities development and/or progression.     

Generational sex work and HIV risk among Indigenous women in a street-based urban Canadian setting

In Canada, Indigenous women are over-represented among new HIV infections and street-based sex workers. Scholars suggest that Aboriginal women's HIV risk stems from intergenerational effects of colonisation and racial policies. This research examined generational sex work involvement among Aboriginal and non-Aboriginal women and the effect on risk for HIV acquisition. The sample included 225 women in street-based sex work and enrolled in a community-based prospective cohort, in partnership with local sex work and Aboriginal community partners. Bivariate and multivariate logistic regression modeled an independent relationship between Aboriginal ancestry and generational sex work and the impact of generational sex work on HIV infection among Aboriginal sex workers. Aboriginal women (48%) were more likely to be HIV-positive, with 34% living with HIV compared to 24% non-Aboriginal women. In multivariate logistic regression model, Aboriginal women remained three times more likely to experience generational sex work (AOR:2.97; 95%CI:1.5,5.8). Generational sex work was significantly associated with HIV (AOR = 3.01, 95%CI: 1.67–4.58) in a confounder model restricted to Aboriginal women. High prevalence of generational sex work among Aboriginal women and three-fold increased risk for HIV infection are concerning. Policy reforms and community-based, culturally safe and trauma informed HIV-prevention initiatives are required for Indigenous sex workers.     

Declining blood lead and zinc protoporphyrin levels in Ecuadorian Andean children

ObjectivesTo investigate current lead (Pb) exposure in children living in Andean Ecuadorian communities. Blood Pb (PbB) and zinc protoporphyrin (ZPP) levels were used respectively as biomarkers of acute and chronic Pb poisoning. The current PbB–ZPP levels were compared with previous pediatric PbB–ZPP levels recorded over years in the study area.Design and methodsSamples of whole blood were collected from 22 Andean children of Quechua and Mestizo backgrounds and measured for PbB concentrations by graphite furnace atomic absorption spectroscopy. ZPP/heme ratio and ZPP whole blood (ZPP WB) levels were measured with a hematofluorometer.ResultsThe mean PbB level for children in the current study group was 14.5 μg/dL, which was significantly lower than the mean PbB level of 41.1 μg/dL found in the same study area in the 1996–2000 test period, and lower than the 22.2 μg/dL mean level found in the 2003–2007 period. The current mean ZPP/heme ratio was 102.1 μmol/mol, and the mean ZPP WB level was 46.3 μg/dL, both lower than values previously found in children in the study area.ConclusionWhile the current pediatric PbB–ZPP levels in the study area remain elevated in some children, the overall levels indicate a decline relative to levels observed in the same Pb-contaminated area in the period between 1996 and 2007. The elevated ZPP levels suggest a history of chronic Pb exposure, and potential iron deficiency in some children. The overall reduction in PbB–ZPP levels suggests a positive outcome of a Pb-exposure education and prevention program, and the therapeutic intervention of succimer chelation therapy.     

Clinical and Local Effects of Antacids and Physical Therapy as Shown Gastroscopically

All physicians should be alert to indications of suicidal intent on the part of depressed or mentally ill patients. Hospital personnel generally should also know the importance of immediately reporting unusual behavior on the part of patients. Patients who seem likely to attempt suicide should be hospitalized and carefully supervised. Treatment should not be undertaken at home. Some of the newer antidepressant drugs are effective in treating potentially suicidal patients.     

TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved

The newly identified tripartite motif (TRIM) family of proteins mediate innate immunity and other critical cellular functions. Here we show that TRIM21, which mediates the autoimmune diseases rheumatoid arthritis, systemic lupus erythematosus, and Sjögren''s syndrome, is a previously undescribed IgG receptor with a binding mechanism unlike known mammalian Fcγ receptors. TRIM21 simultaneously targets conserved hot-spot residues on both Ig domains of the Fc fragment using a PRYSPRY domain with a preformed multisite interface. The binding sites on both TRIM21 and Fc are highly conserved to the extent that the proteins are functionally interchangeable through murine, canine, primate, and human species. Pre-steady-state analysis exposes mechanistic conservation at the level of individual residues, which make the same energetic and kinetic contributions to binding despite varying in sequence. Together, our results reveal that TRIM21 is a previously undescribed type of IgG receptor based on a non-Ig scaffold whose interaction at the fundamental level—structural, thermodynamic, and kinetic—is evolutionarily conserved.