APAC treatment limits collar-induced carotid atherosclerotic plaque development in apoE-/- mice

Biopharmaceutic

Postprandial Energy Metabolism in the Regulation of Body Weight: Is there a Mechanistic Role for Dietary Calcium?

There has been much interest in the mechanisms by which calcium may attenuate weight gain or accelerate body fat loss. This review focuses on postprandial energy metabolism and indicates that dietary calcium increases whole body fat oxidation after single and multiple meals. There is, as yet, no conclusive evidence for a greater diet induced thermogenesis, an increased lipolysis or suppression of key lipogenic enzyme systems. There is however convincing evidence that higher calcium intakes promote a modest energy loss through increased fecal fat excretion. Overall, there is a role for dietary calcium in human energy metabolism. Future studies need to define threshold intakes for metabolic and gastrointestinal outcomes

Blockade of the BLT1-LTB4 axis does not affect mast cell migration towards advanced atherosclerotic lesions in LDLr-/- mice

Mast cells have been associated with the progression and destabilization of advanced atherosclerotic plaques. Reducing intraplaque mast cell accumulation upon atherosclerosis progression could be a potent therapeutic strategy to limit plaque destabilization. Leukotriene B4 (LTB4) has been reported to induce mast cell chemotaxis in vitro. Here, we examined whether antagonism of the LTB4-receptor BLT1 could inhibit mast cell accumulation in advanced atherosclerosis. Expression of genes involved in LTB4 biosynthesis was determined by single-cell RNA sequencing of human atherosclerotic plaques. Subsequently, Western-type diet fed LDLr-/- mice with pre-existing atherosclerosis were treated with the BLT1-antagonist CP105,696 or vehicle control three times per week by oral gavage. In the spleen, a significant reduction in CD11b+ myeloid cells was observed, including Ly6Clo and Ly6Chi monocytes as well as dendritic cells. However, atherosclerotic plaque size, collagen and macrophage content in the aortic root remained unaltered upon treatment. Finally, BLT1 antagonism did not affect mast cell numbers in the aortic root. Here, we show that human intraplaque leukocytes may be a source of locally produced LTB4. However, BLT1-antagonism during atherosclerosis progression does not affect either local mast cell accumulation or plaque size, suggesting that other mechanisms participate in mast cell accumulation during atherosclerosis progression.Biopharmaceutic

Quality of life in patients with CRB1-associated retinal dystrophies:A longitudinal study

Purpose: To assess the longitudinal vision-related quality of life among patients with CRB1-associated inherited retinal dystrophies. Methods: A longitudinal questionnaire study included 22 patients with pathogenic CRB1 variants. The National Eye Institute Visual Function Questionnaire (39 items, NEI VFQ-39) was applied at baseline, two-year follow-up, and 4-year follow-up. Classical test theory was performed to obtain subdomain scores and in particular ‘near activities’ and ‘total composite’ scores. The Rasch analysis based on previous calibrations of the NEI VFQ-25 was applied to create visual functioning and socio-emotional subscales. Results:In total, 22 patients with pathogenic CRB1 variants were included, with a median age of 25.0 years (IQR: 13–31 years) at baseline and mean follow-up of 4.0 ± 0.3 years. A significant decline at 4 years was observed for ‘near activities’ (51.0 ± 23.8 vs 35.4 ± 14.7, p = 0.004) and ‘total composite’ (63.0 ± 13.1 vs 52.0 ± 12.1, p = 0.001) subdomain scores. For the Rasch-scaled scores, the ‘visual functioning’ scale significantly decreased after 4 years (−0.89 logits; p = 0.012), but not at 4-year follow-up (+0.01 logits; p = 0.975). The ‘socio-emotional’ scale also showed a significant decline after 2 years (−0.78 logits, p = 0.033) and 4 years (−0.83 logits, p = 0.021). Conclusion: In the absence of an intervention, a decline in vision-related quality of life is present in patients with pathogenic CRB1 variants at 4-year follow-up. Patient-reported outcome measures should be included in future clinical trials, as they can be a potential indicator of disease progression and treatment efficacy.</p

Clinical characteristics and natural history of rho-associated retinitis pigmentosa : a long-term follow-up study

Purpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP. Results: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20 degrees) and blindness (central visual field <10 degrees), respectively. For the best-corrected visual acuity (BCVA), the median age to reach mild impairment (20/67 <= BCVA < 20/40) was 72 years, whereas this could not be computed for lower acuities. Disease progression was significantly faster in patients with a generalized RP phenotype (n = 75; 75%) than that in patients with a sector RP phenotype (n = 25; 25%), in terms of decline rates of the BCVA (P < 0.001) and V4e retinal seeing areas (P < 0.005). The foveal thickness of the photoreceptor-retinal pigment epithelium (PR + RPE) complex correlated significantly with BCVA (Spearman's rho = 0.733; P < 0.001). Conclusion: Based on central visual fields, the optimal window of intervention for RHO-associated RP is before the 5th decade of life. Significant differences in disease progression are present between generalized and sector RP phenotypes. Our findings suggest that the PR + RPE complex is a potential surrogate endpoint for the BCVA in future studies

Accessing parental perspectives to inform the development of parent training in autism in south-eastern Europe

Parent training has been shown to be an important means of supporting families living with autism – but such services are not universally accessible. A multinational project funded by the European Commission has been developed in order to establish such parent training in three south-eastern European countries. To ensure that the training was relevant and appropriate, a survey was carried out in autumn 2015 to ascertain the attitudes of parents of children with autism in Croatia, Cyprus and the Former Yugoslav Republic of Macedonia regarding this issue, and to identify the areas of training that they felt most important. Two hundred and fifty-three surveys were distributed, and 148 were returned, a response rate of 58%. Respondents in the three counties were overwhelmingly positive about parent training, with almost 90% stating that they would like to attend such training. Weekend training sessions were preferred by the majority of respondents. There was wide variation between the three countries with regard to what content was felt important to be included, with parents in the FYR of Macedonia seeking information in the greatest number of areas. Five topics were prioritised by parents across all three countries. These were: • Strategies for enhancing my child’s communication • Strategies on facilitating my child’s interaction with other children • Sensory integration and development • General information on behavioural management strategies • Identifying and/or developing socialisation opportunitie

Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa.

Immune reconstitution inflammatory syndrome (IRIS) is a widely recognised complication of antiretroviral therapy (ART), but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa

Leukemia inhibitory factor receptor inhibition in atherosclerosis

Biopharmaceutic

Long term follow up of premature infants: detection of strabismus, amblyopia, and refractive errors

AIM—To establish recommendations for long term ophthalmological follow up of prematurely born infants.
METHODS—130 infants with a gestational age (GA) <37 weeks and born between 1 November 1989 and 31 October 1990 were enrolled in a prospective study about the development of strabismus, amblyopia, and refractive errors. Infants were subdivided in three groups according to GA: A <28 weeks (n=32), B ⩾28-⩽32 weeks (n=64), C >32-<37 weeks (n=34). Ophthalmological assessment took place at the postconceptional age of 32 weeks, at term and at 3, 6, 12,( )and 30 months post term. At the age of 5 years parents received a questionnaire and a majority of the children was examined again (n=99).
RESULTS—At the age of 5 years 46 infants were known to have strabismus (n=29) and/or amblyopia (n=22) and/or refractive errors (n=22). Statistical analysis showed that gestational age, duration of supplementary oxygen, and duration of hospitalisation were important predictive variables for the development of strabismus, amblyopia, or refractive errors (SAR) at the age of 5 years (p<0.05). Infants with a GA ⩽32 weeks had a significantly higher risk of developing SAR than infants with a GA >32 weeks, who developed an incidence comparable with the normal population. Strabismus developed mainly in the first year of life and at the age of 5 years. Most infants with amblyopia were detected at the age of 2-3 years. Refractive errors were found in the first year of life and at the age of 2.5 and 5( )years.
CONCLUSION—Infants with a GA <32 weeks should be selected for long term ophthalmological follow up. These infants should be screened at the age of 1 year, in the third year of life (preferably at 30 months), and just before school age (including testing of visual acuity with optotypes).