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Background We asked whether, after excluding familial hypercholesterolemia, individuals with high low‐density lipoprotein cholesterol (LDL‐C) or triacylglyceride levels and a family history of the same hyperlipidemia have greater coronary artery disease risk or different lipidomic profiles compared with population‐based hyperlipidemias. Methods and Results We determined incident coronary artery disease risk for 755 members of 66 hyperlipidemic families (≥2 first‐degree relatives with similar hyperlipidemia) and 19 644 Finnish FINRISK population study participants. We quantified 151 circulating lipid species from 550 members of 73 hyperlipidemic families and 897 FINRISK participants using mass spectrometric shotgun lipidomics. Familial hypercholesterolemia was excluded using functional LDL receptor testing and genotyping. Hyperlipidemias (LDL‐C or triacylglycerides >90th population percentile) associated with increased coronary artery disease risk in meta‐analysis of the hyperlipidemic families and the population cohort (high LDL‐C: hazard ratio, 1.74 [95% CI, 1.48–2.04]; high triacylglycerides: hazard ratio, 1.38 [95% CI, 1.09–1.74]). Risk estimates were similar in the family and population cohorts also after adjusting for lipid‐lowering medication. In lipidomic profiling, high LDL‐C associated with 108 lipid species, and high triacylglycerides associated with 131 lipid species in either cohort (at 5% false discovery rate; P‐value range 0.038–2.3×10−56). Lipidomic profiles were highly similar for hyperlipidemic individuals in the families and the population (LDL‐C: r=0.80; triacylglycerides: r=0.96; no lipid species deviated between the cohorts). Conclusions Hyperlipidemias with family history conferred similar coronary artery disease risk as population‐based hyperlipidemias. We identified distinct lipidomic profiles associated with high LDL‐C and triacylglycerides. Lipidomic profiles were similar between hyperlipidemias with family history and population‐ascertained hyperlipidemias, providing evidence of similar and overlapping underlying mechanisms.

Background: Atrial fibrillation (AF) has been proposed as a risk factor for exercise-induced pulmonary haemorrhage (EIPH) due to increased pressure in the left atrium., Objective: To evaluate if AF was associated with EIPH following a standardised exercise test (SET) to fatigue., Study Design: Two-arm controlled experiment., Methods: Ten untrained Standardbred mares mean (standard deviation [SD]) age 6 (2) years performed a SET on the treadmill in sinus rhythm (SR) (SET1) and 25-44 days after induction of self-sustained AF (SET2). AF was induced by tachypacing using a pacing device. Endoscopy, including tracheal wash and bronchoalveolar lavage (BAL), was performed 48-72 h before and 24 h after the two SETs. In addition, endoscopic grading of tracheal blood was performed 2 h after each SET., Results: After SET1, none of the horses showed blood in the trachea, and two horses showed erythrophagocytosis. Following SET2, two horses had grade 1 blood in the trachea and free erythrocytes and erythrophagocytosis in the BAL, while another two horses had erythrophagocytosis in the BAL. In SET2, the overall performance on the treadmill was decreased with a lower maximum velocity (SET1 10.3 ± 0.8 m/s vs. SET2 8.9 ± 0.9 m/s, p = 0.004), a higher heart rate (284 ± 21 vs. 221 ± 18 bpm, p = 0.003) and more abnormal QRS complexes (p < 0.001) compared with SET1., Conclusions: Two horses showed signs of EIPH, resulting in visible blood in the trachea, when exercising in AF compared with SR. However, a possible link between EIPH, pulmonary pressure and AF needs to be further elucidated., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Studies in people have found neutrophil gelatinase-associated lipocalin (NGAL) concentrations are increased in asthma and can be used to distinguish between asthma subtypes. NGAL has not yet been investigated in equine asthma (EA)., Objectives: To investigate the ability of NGAL concentrations in bronchoalveolar lavage (BAL) fluid and serum to distinguish between control horses, horses with mild-moderate EA (MEA) and horses with severe EA (SEA)., Study Design: Retrospective cross-sectional study., Methods: Details of endoscopic examination including tracheal mucus score (TMS, scale 0-5) and BAL cytology performed on 227 horses were extracted from records and NGAL concentrations were measured on stored serum and BAL fluid samples. The horses were divided into groups (control group n = 73, MEA n = 98, SEA n = 56) based on clinical signs and BAL cytology results. Differences between groups were evaluated with the Mann-Whitney test and correlation between BAL NGAL, serum NGAL, and BAL cytology were evaluated using Spearman's correlation., Results: BAL NGAL concentrations were higher in EA than in control horses (median: 25.6 and 13.3 μg/L, respectively, p < 0.001). Concentrations of NGAL in BAL differed between groups, with higher concentrations in MEA than in control horses (median: 18.5 and 13.3 μg/L, respectively, p < 0.001), and higher concentrations in SEA than in MEA horses (median: 54.1 and 18.5 μg/L, respectively, p < 0.001). BAL NGAL concentration differed between horses with TMS ≤2 an >2 (median 15.6 and 21.1 μg/L, respectively, p = 0.004). No differences were found in serum NGAL concentration between any of the groups., Main Limitation: Only 66 of the 227 (29%) horses had haematology and serum NGAL measured., Conclusion: BAL NGAL concentration differed between control and EA and reflected severity of disease. These results justify further research into the potential of NGAL as a biomarker of EA., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Posttraumatic stress disorder (PTSD) brings with it diagnostic symptoms that can be debilitating and persist for years. Left untreated, PTSD can have far-reaching and damaging consequences for the individual, families, communities, and society at large. Although early detection and intervention are recognized as key to the effective treatment of PTSD, many individuals who suffer from PTSD do not seek essential health services. The aim of the present study was to identify the barriers and facilitators to help-seeking for individuals with PTSD, based on existing literature. A systematic review, modeled on the Joanna Briggs Institute methodology for systematic reviews, examined studies cited in PsycINFO, Medline, Embase, CINAHL, and PILOTS published from January 1980 to January 2019. Eligible studies measured barriers and facilitators to help-seeking for adults with PTSD. Two reviewers independently screened citations, and double data extraction was exercised. Of 2,391 potentially relevant citations, 21 studies, published between 1989 and 2018 and based in six countries, were included. Seventeen studies focused on military as a target population. We identified 10 principal barrier and facilitator themes: trauma-related; treatment; therapist or provider; knowledge; access; health care system; sociocultural environment; values, beliefs, and priorities; past experiences; and medical care needs and illness burden. In identifying prominent barriers and facilitators to help-seeking for individuals with PTSD, this review highlights opportunities to inform policies and programs that promote PTSD knowledge and recognition, reduce public and personal stigma, improve access and quality of care, and encourage support for patients and families living with PTSD., (© 2019 International Society for Traumatic Stress Studies.)

Icelandic horses are often stabled in loose-housing systems, and to date this type of stabling has not been evaluated with regard to its potential impact on respiratory health. The objective was to assess if differences in management systems (eg, conventional stable, loose housing and pasture only) affect the degree of airway inflammation, evaluated by cytology of tracheal aspirate (TA) and bronchoalveolar lavage (BAL) fluid. In total, 84 Icelandic horses (aged 8.1±4.6 years) housed under three different management systems (conventional stables [n=29], loose-house systems [n=29] and pasture [n=26]) were included. Endoscopy including mucus scoring, TA and BAL was performed. TA and BAL cytologies were evaluated by performing both the total cell count (TCC) and the differential cell count (DCC). Significantly higher BAL neutrophil DCC (P=0.032, P=0.040) and TA TCC (P=0.007, P=0.028) were found for each of the two groups of horses with indoor access (conventional stable and loose housing) compared with the pasture group. Regardless of stabling environment, weak positive correlations were found between TA and BAL TCC (r=0.37, P<0.001), between TA TCC and TA neutrophil ratio (r=0.33, P=0.002), as well as between TA and BAL neutrophil ratio (r=0.39, P=<0.001). A larger proportion of horses with indoor access showed evidence of subclinical airway inflammation characterised by an increase in TA and BAL neutrophil ratios., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: "Negotiated standards" describe a level of quality of care that is acceptable and achievable within a specific health system, based on consensus between key stakeholders. This paper presents the development of negotiated standards for effective labor and childbirth care in selected hospitals and communities in Nigeria and Uganda., Methods: A four-step development process involving different methodologies. The process included: (1) review and synthesis of internationally recognized intrapartum clinical principles and practices; (2) primary qualitative research to assess values and preferences of women and healthcare providers, and practices that align with these preferences; (3) draft contextualization of effective and ineffective behaviors to reflect values and preferences; and (4) WHO-mediated negotiations between relevant stakeholders, including community members, providers, and administrators., Results: The primary outcomes of this process were a comprehensive set of effective behaviors and clinical practices covering the main domains of quality of care, which are practical and easy to communicate, implement, and audit across all levels of healthcare delivery., Conclusion: The process demonstrates that health facilities and providers can be motivated to adopt standards of care that uphold the values and preferences of both service users and providers, while adhering to international best practices., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

The World Health Organization's (WHO) Strategic Framework for the Elimination of New HIV Infections among Children in Africa by 2015 identifies important synergies for the elimination of mother-to-child transmission of HIV and syphilis in terms of prevention interventions, implementation logistics and service delivery, monitoring and evaluation systems, and need for sustained political commitment. The WHO advocates the use of an integrated, rights-based dual approach with partnerships and collaboration to make the best use of available resources. Through a consultative approach, six countries in the African Region committed to dual elimination and developed and implemented action plans for this purpose. Where interest and commitment are high, this may also be possible and effective in other African countries., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Cross-talk between adipose tissue and liver is disturbed in the metabolic syndrome. Moreover, the relative fatty acid composition of adipose and liver fat is poorly characterized. Long-TE (1)H MRS can determine the unsaturation and polyunsaturation of adipose tissue. The aim of this study was to use long-TE (1)H MRS to determine the composition of liver fat and its relation to adipose tissue composition. Sixteen subjects with increased liver fat (>5%) were recruited for the study. Using TE = 200  ms, we were able to resolve the olefinic (=CH, 5.3  ppm) and water (H(2)O, 4.7  ppm) resonances in liver spectra and to obtain a repeatable estimate of liver fat unsaturation (coefficient of variation, 2.3%). With TE = 135  ms, the diallylic (=C-CH(2)-C=, 2.8  ppm) resonance was detectable in subjects with a liver fat content above 15%. Long-TE (1)H MRS was also used to determine the unsaturation in subcutaneous (n = 16) and visceral (n = 11) adipose tissue in the same subjects. Liver fat was more saturated (double bonds per fatty acid chain, 0.812 ± 0.022) than subcutaneous (double bonds per fatty acid chain, 0.862 ± 0.022, p < 0.0004) or visceral (double bonds per fatty acid chain, 0.865 ± 0.033, p < 0.0004) fat. Liver fat unsaturation correlated with subcutaneous unsaturation (R = 0.837, p < 0.0001) and visceral unsaturation (R = 0.879, p < 0.0004). The present study introduces a new noninvasive method for the assessment of the composition of liver fat. The results suggest that liver fat is more saturated than subcutaneous or visceral adipose tissue, which may be attributed to differences in de novo lipogenesis., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background and Purpose: The angiotensin II type 1 (AT(1)) receptor belongs to family A of 7 transmembrane (7TM) receptors. The receptor has important roles in the cardiovascular system and is commonly used as a drug target in cardiovascular diseases. Interaction of 7TM receptors with G proteins or beta-arrestins often induces higher binding affinity for agonists. Here, we examined interactions between AT(1A) receptors and beta-arrestins to look for differences between the AT(1A) receptor interaction with beta-arrestin1 and beta-arrestin2., Experimental Approach: Ligand-induced interaction between AT(1A) receptors and beta-arrestins was measured by Bioluminescence Resonance Energy Transfer 2. AT(1A)-beta-arrestin1 and AT(1A)-beta-arrestin2 fusion proteins were cloned and tested for differences using immunocytochemistry, inositol phosphate hydrolysis and competition radioligand binding., Key Results: Bioluminescence Resonance Energy Transfer 2 analysis showed that beta-arrestin1 and 2 were recruited to AT(1A) receptors with similar ligand potencies and efficacies. The AT(1A)-beta-arrestin fusion proteins showed attenuated G protein signalling and increased agonist binding affinity, while antagonist affinity was unchanged. Importantly, larger agonist affinity shifts were observed for AT(1A)-beta-arrestin2 than for AT(1A)-beta-arrestin1., Conclusion and Implications: beta-Arrestin1 and 2 are recruited to AT(1A) receptors with similar ligand pharmacology and stabilize AT(1A) receptors in distinct high-affinity conformations. However, beta-arrestin2 induces a receptor conformation with a higher agonist-binding affinity than beta-arrestin1. Thus, this study demonstrates that beta-arrestins interact with AT(1A) receptors in different ways and suggest that AT(1) receptor biased agonists with the ability to recruit either of the beta-arrestins selectively, would be possible to design.

The aim of this study was to investigate the use of (1)H-MRS with various echo times to characterize subcutaneous human adipose tissue (SAT) triglyceride composition and to validate the findings with fatty acid (FA) analysis of SAT biopsies by gas chromatography (GC). (1)H-MRS spectra were acquired with a 1.5 Tesla clinical imager from the SAT of 17 healthy volunteers, with 10 undergoing SAT biopsy. Spectra were localized with PRESS and a series of echo times; 30, 50, 80, 135, 200, 300 and 540 ms were acquired with TR = 3000 ms. Prior knowledge from phantom measurements was used to construct AMARES fitting models for the lipid spectra. SAT FA composition were compared with serum lipid levels and subject characteristics in 17 subjects.Long TE (135, 200 ms) spectra corresponded better with the GC data than short TE (30, 50 ms) spectra. TE = 135 ms was found optimal for determining diallylic content (R = 0.952, p < 0.001) and TE = 200 ms was optimal for determining olefinic content (R = 0.800, p < 0.01). The improved performance of long TE spectra is a result of an improved baseline and better peak separation, due to J-modulation and suppression of water. The peak position of the diallylic resonance correlated with the average double bond content of polyunsatured fatty acids with R = 0.899 (p < 0.005). The apparent T(2) of the methylene resonance displayed relatively small inter-individual variation, 88.1 +/- 1.1 ms (mean +/- SD). The outer methyl triplet line of omega-3 PUFA at 1.08 ppm could be readily detected and quantitated from spectra obtained at TE = 540. The omega-3 resonance correlated with the omega-3 content determined by GC with R = 0.737 (p < 0.05, n = 8). Age correlated significantly with SAT diallylic content (R = 0.569, p = 0.017, n = 17), but serum lipid levels showed no apparent relation to SAT FA composition. We conclude that long TE (1)H-MRS provides a robust non-invasive method for characterizing adipose tissue triglycerides in vivo.