[Lipopolysaccharide stimulates macrophages to secrete exosomes containing miR-155-5p to promote activation and migration of hepatic stellate cells].

OBJECTIVE: To observe the effect of exosomes secreted by lipopolysaccharides (LPS)-stimulated macrophages on hepatic stellate cell activation and migration and explore the underlying molecular mechanism. METHODS: Human monocyte THP-1 cells were induced to differentiate into macrophages using propylene glycol methyl ether acetic acid (PMA, 100 ng/mL, 24 h) followed by stimulation with LPS, and the culture supernatant of macrophages was collected for extraction of the exosomes by ultracentrifugation. The expression of miR-155-5p in the exosomes was detected using qRT-PCR. A Transwell co-culture system was used to observe the effects of the macrophage-derived exosomes on LX2 cell (a hepatic stellate cell line) proliferation, migration, oxidative stress and the expression of fibrosis biomarkers, which were also observed in LX2 cells transfected with miR-155-5p-mimics or miR-155-5p-inhibitors. Western blotting was used to detect the expressions of SOCS1 and its downstream signal pathway proteins. RESULTS: Treatment with the exosomes from LPS-stimulated macrophages significantly enhanced the proliferation and migration ability of LX2 cells and increased the levels of oxidative stress and expressions of the fibrosis markers such as type Ⅰ collagen (P < 0.05). The expression of miR-155-5p in the exosomes secreted by macrophages was significantly increased after LPS treatment (P < 0.01). LX2 cells overexpressing miR-155-5p also exhibited significantly enhanced proliferation and migration with increased oxidative stress levels and expression of type Ⅰ collagen (P < 0.05), and interference of miR-155-5p expression produced the opposite effects. Western blotting showed that miR-155-5p overexpression obviously inhibited SOCS1 expression and promoted p-Smad2/3, Smad2/3 and RhoA protein expressions in LX2 cells (P < 0.05). CONCLUSION: LPS stimulation of the macrophages increases miR-155-5p expression in the exosomes to promote activation and migration and increase oxidative stress and collagen production in hepatic stellate cells.

Analyzing implementation of public health interventions: A need for rigor, and the challenges of stakeholder involvement.

OBJECTIVES: This article shows how conceptual models can help to develop and evaluate public health interventions. It also reports on the challenges of getting stakeholders involved. METHOD: The analysis is based on the reflexive approach applied by the authors during their participation in two public health intervention research (PHIR) projects, in France and in Burkina Faso. RESULTS: In Paris, PHIR aimed to enable sub-Saharan immigrants to appropriate the existing means of prevention and sexual health care and to strengthen their empowerment in view of preserving their health. Evaluation was carried out using mixed methods. The intervention process theory is based on Ninacs' conceptual model of individual empowerment. The Consolidated Framework For Implementation Research (CFIR) was mobilized a posteriori to analyze the process. PHIR stemmed from collaboration between a research team and two associations. The different stakeholders were involved in the evaluation process, as were, at certain times, persons in highly precarious situations. In Ouagadougou, a community-based dengue vector control intervention was deployed to address an essential but neglected need. As regards evaluation, we opted for a holistic, mixed method approach (effectiveness and process). The contents of the intervention were determined based on tacit knowledge, a community preference survey and solid evidence. The theoretical framework of the intervention consisted in an eco-biological model of vector control. The implementation analysis combined an internal assessment of implementation fidelity with an external CFIR process analysis. All stakeholders were involved in the evaluation process. DISCUSSION: Analysis confirmed not only the value of process evaluations in PHIR, but also the primordial importance of a rigorous approach. Stakeholder involvement is a major challenge to be addressed early in the planning of RISPs; with this in mind, effective and ethically sound assessment mechanisms need to be drawn up. Interdisciplinary evaluative approaches should be preferred, and the use of justified, relevant, and flexible frameworks is highly recommended. CONCLUSION: Lessons learned for those wishing to engage in the process evaluation of a public health intervention are hereby presented.

Hyperspectral microscopy of subcutaneously released silver nanoparticles reveals sex differences in drug distribution.

Biomaterials have a great potential to improve human health, however in vitro and in vivo studies are necessary to provide information on their efficacy and safety. This study reports on a comprehensive evaluation of core-shell electrospun fibers loaded with silver nanoparticles (Ag NP) where the delivery rate was controlled by different sizes of Ag NP and thermoresponsive poly(n-isopropylacrylamide) (PNIPAM) hydrogel particles. Fiber meshes also contain zinc oxide nanoparticles (ZnO NP), to improve pore structure for controlled release of Ag NP. In vitro cytotoxicity studies using cultured human A549 epithelial cells demonstrated that the ZnO NP component, which is known to cause cytotoxicity, of the fiber meshes did cause measurable cell death. In vitro antibacterial efficacy of the fiber meshes was shown with rapid and efficient growth inhibition in E. coli bacterial culture. Fiber meshes were implanted subcutaneously for up to 27 days in male and female C57BL/6 mice to evaluate the in vivo drug release and biocompatibility. Hyperspectral microscopy was used as an advanced tool to determine precise location of released Ag NP into the skin compared to the conventional tissue staining methods. Results suggested that Ag NP were continuously released over 27 days of implantation in mice. Hyperspectral imaging revealed that released Ag NP dispersed in the dermis of male mice, however, Ag NP accumulated in the hair follicles of female mice (Figure). Mice implanted with fiber meshes containing ZnO NP had better hair regrowth and wound healing, which was in contrast to in vitro cytotoxicity results. These findings suggest that these newly developed fiber meshes can have unique long-term release of drugs loaded in the fiber core and appear to be biocompatible. The differences in the sex-bias outcome suggest the opportunity for development of sex-specific drug delivery systems.

Missplicing due to a synonymous, T96= exonic substitution in the T-box transcription factor TBX19 resulting in isolated ACTH deficiency.

SUMMARY: Congenital isolated ACTH deficiency (IAD) is a rare condition characterised by low plasma ACTH and serum cortisol with normal production of other pituitary hormones. TBX19 (also known as TPIT) is a T-box pituitary restricted transcription factor important for POMC gene transcription and terminal differentiation of POMC-expressing cells. TBX19 gene mutations have been shown to cause neonatal-onset congenital IAD. We report a neonate of Romanian origin, who presented at 15 h of life with respiratory arrest and hypoglycaemia which recurred over the following 2 weeks. Biochemical investigations revealed IAD, with undetectable serum cortisol (cortisol < 1 µg/dL; normal range (NR): 7.8-26.2) and plasma ACTH levels within the normal range (22.1 pg/mL; NR: 4.7-48.8). He responded to hydrocortisone treatment. Patient DNA was analysed by a HaloPlex next-generation sequencing array targeting genes for adrenal insufficiency. A novel homozygous synonymous mutation p.Thr96= (Chr1:168260482; c.288G>A; rs376493164; allele frequency 1 × 10-5, no homozygous) was found in exon 2 of the TBX19 gene. The effect of this was assessed by an in vitro splicing assay, which revealed aberrant splicing of exon 2 giving rise to a mutant mRNA transcript whereas the WT vector spliced exon 2 normally. This was identified as the likely cause of IAD in the patient. The predicted protein product would be non-functional in keeping with the complete loss of cortisol production and early presentation in the patient. LEARNING POINTS: Synonymous variants (a nucleotide change that does not alter protein sequence) usually thought to be benign may still have detrimental effects on RNA and protein function causing disease. Hence, they should not be ignored, especially if very rare in public databases. In vitro splicing assays can be employed to characterise the consequence of intronic and exonic nucleotide gene changes that may alter splicing. Establishing a diagnosis due to a TBX19 mutation is important as it defines a condition of isolated ACTH deficiency not associated with additional pituitary deficiencies.

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.

Loss of Nnt Increases Expression of Oxidative Phosphorylation Complexes in C57BL/6J Hearts.

Nicotinamide nucleotide transhydrogenase (NNT) is a proton pump in the inner mitochondrial membrane that generates reducing equivalents in the form of NAPDH, which can be used for anabolic pathways or to remove reactive oxygen species (ROS). A number of studies have linked NNT dysfunction to cardiomyopathies and increased risk of atherosclerosis; however, biallelic mutations in humans commonly cause a phenotype of adrenal insufficiency, with rare occurrences of cardiac dysfunction and testicular tumours. Here, we compare the transcriptomes of the hearts, adrenals and testes from three mouse models: the C57BL/6N, which expresses NNT; the C57BL/6J, which lacks NNT; and a third mouse, expressing the wild-type NNT sequence on the C57BL/6J background. We saw enrichment of oxidative phosphorylation genes in the C57BL/B6J in the heart and adrenal, possibly indicative of an evolved response in this substrain to loss of Nnt. However, differential gene expression was mainly driven by mouse background with some changes seen in all three tissues, perhaps reflecting underlying genetic differences between the C57BL/B6J and -6N substrains.

Senna (Cassia) alata (Linn.) Roxb. leaf decoction as a treatment for tinea imbricata in an indigenous tribe in Southern Philippines.

BACKGROUND: Tinea imbricata, a rare form of tinea corporis caused by Trichophyton concentricum, is endemic to the T'boli tribe in the Southern Philippines. Temporary remissions and limited access to antifungal medications make its treatment a pressing public health concern. Anecdotal reports about the use of Senna alata leaf decoction as treatment exist. OBJECTIVE: To determine the efficacy of community-prepared S alata leaf decoction in the treatment of tinea imbricata. METHODS: Tinea imbricata patients were instructed to apply S alata leaf decoction for 4 weeks (28 ± 3 days). Disease severity, pruritus visual analogue scale scores (VAS) and potassium hydroxide (KOH) mounts of skin scrapings were evaluated before and after treatment. Two assessors evaluated disease severity based on photographs. Cohen's kappa statistics were used to assess diagnostic concordance. Adverse drug events were recorded. RESULTS: Twenty patients were enrolled. After 4 weeks, 95% had decreased pruritus VAS scores, with a mean decreased of 4.05 after treatment (P < .0001). There was a significant difference in disease severity scores before and after treatment (P ≤ .05) with an overall agreement of 'moderate' for both assessors (κ = 0.6, 95% CI [0.33, 0.87]). Forty per cent had negative KOH tests after treatment. None had adverse drug events. CONCLUSION: This is the first study that showed the potential of a community-prepared leaf decoction as a treatment option for tinea imbricata. Larger clinical trials establishing its efficacy, effectiveness and safety profile are recommended to enable its promotion among the indigenous people and health authorities as an accessible and affordable treatment for tinea imbricata.

Mylk3 null C57BL/6N mice develop cardiomyopathy, whereas Nnt null C57BL/6J mice do not.

The C57BL/6J and C57BL/6N mice have well-documented phenotypic and genotypic differences, including the infamous nicotinamide nucleotide transhydrogenase (Nnt) null mutation in the C57BL/6J substrain, which has been linked to cardiovascular traits in mice and cardiomyopathy in humans. To assess whether Nnt loss alone causes a cardiovascular phenotype, we investigated the C57BL/6N, C57BL/6J mice and a C57BL/6J-BAC transgenic rescuing NNT expression, at 3, 12, and 18 mo. We identified a modest dilated cardiomyopathy in the C57BL/6N mice, absent in the two B6J substrains. Immunofluorescent staining of cardiomyocytes revealed eccentric hypertrophy in these mice, with defects in sarcomere organisation. RNAseq analysis identified differential expression of a number of cardiac remodelling genes commonly associated with cardiac disease segregating with the phenotype. Variant calling from RNAseq data identified a myosin light chain kinase 3 (Mylk3) mutation in C57BL/6N mice, which abolishes MYLK3 protein expression. These results indicate the C57BL/6J Nnt-null mice do not develop cardiomyopathy; however, we identified a null mutation in Mylk3 as a credible cause of the cardiomyopathy phenotype in the C57BL/6N.

[Practices and Factors Associated with Recent HIV Testing in the General Population, Côte d'Ivoire: Results of the ANRS Study 12323 DOD-CI]. / Pratiques et facteurs associés au dépistage récent du VIH en population générale, Côte d'Ivoire. Résultats de l'étude ANRS 12323 DOD-CI.

With 2.9% of HIV prevalence in the general population, Côte d'Ivoire is one of the countries most affected by the HIV epidemic in West Africa. In this country, only 63% of people infected with HIV are aware of their status. A cross-sectional phone survey was conducted with a representative sample of 3,867 individuals to describe the practices and factors associated with a recent HIV testing (≤ 1 year) in Côte d'Ivoire. Data relative to the last done HIV test as well as the socio-demographic characteristics, sexual behavior, access to information, perceptions, capacities and autonomy as well as social and geographical environment of the participants were collected. Logistical regression models were used to identify the associated factors with a recent HIV test (≤ 1 year). Lack of information is one of the main barriers to HIV testing (only 60% of individuals know a place to get tested). For men, despite the fact that HIV testing is free of charge, poor economic conditions seem to be a barrier to testing. The social environment, including peer influence, also appears to have an effect on testing among men. For women, testing is associated with their perceptions of HIV exposure. There is a need to rethink the current HIV testing communication in Côte d'Ivoire and to identify economic or social incentives to remove access barriers to HIV testing.

Avec 2,9 % de sa population infectée par le VIH, la Côte d'Ivoire fait partie des pays d'Afrique de l'Ouest les plus touchés par l'épidémie à VIH. On estime que seules 63 % des personnes infectées par le VIH connaissent leur statut. Une enquête transversale, par téléphone, a été réalisée auprès d'un échantillon représentatif de 3 867 personnes afin de décrire les pratiques et les facteurs associés à la réalisation récente (≤ 1 an) d'un dépistage du VIH en Côte d'Ivoire. Les données collectées concernaient le dernier test réalisé ainsi que les caractéristiques sociodémographiques, comportements sexuels, accès à l'information, perceptions, capacités, autonomies ainsi que l'environnement social et géographique des participants. Des modèles de régression logistique ont été réalisés afin d'identifier les facteurs associés à la réalisation récente d'un test du VIH (≤ 1 an). Le manque d'information est l'un des principaux freins au dépistage (seuls 60 % des individus connaissent un lieu où réaliser un test). Chez les hommes, malgré la gratuité du dépistage, une faible condition économique semble être un frein à la réalisation d'un test. L'environnement social, notamment l'influence des pairs, semble aussi avoir un effet sur le recours au dépistage chez les hommes. Chez les femmes, le dépistage est associé à leurs perceptions d'exposition au VIH. L'offre de dépistage actuelle en Côte d'Ivoire nécessite de repenser la communication autour du test ainsi que d'identifier des incitatifs économiques ou sociaux permettant de lever les freins au dépistage.

Effect of organizational models of provider-initiated testing and counseling (PITC) in health facilities on adult HIV testing coverage in sub-Saharan Africa.

The purpose of this paper is to identify which Provider-Initiated HIV Testing and Counseling (PITC) organizational models are the most efficient to maximize testing coverage. We conducted a systematic literature review to identify published articles that evaluated routine PITC programs implemented in adult health facilities in Sub-Saharan Africa. We considered only articles measuring PITC offer, PITC acceptability and PITC coverage. Adjusted meta-regression models were performed to measure the association between PITC offer, acceptability and coverage with PITC organizational model. A total of 30 articles were included in the meta-analysis. Overall, 85.4% [95%CI: 77.2-93.5] of patients were offered a test, and 87.1% [82.4-91.7] accepted the test resulting in a PITC coverage of 74.3% [66-82.6]. Four types of PITC organizational models were identified: PITC initiated and performed during the consultation (model A), PITC initiated before consultation (model B), PITC referred on-site (model C) and PITC referred off-site (model D). Compared to model A, model B had a similar coverage (aOR: 1.02 [0.82-1.26]). However, coverage was lower for model C (aOR: 0.81 [0.68-0.97]) and model D (aOR: 0.58 [0.44-0.77]). Initiating the testing process before or during medical consultation is recommended for maximizing testing coverage among patients.

Gender differences among surgical fellowship program directors.

BACKGROUND: Although women are increasingly represented in American surgery, data regarding sex and academic rank of the leadership of fellowship programs are lacking. METHODS: Demographics and academic ranks for fellowship program directors were analyzed for 811 surgery fellowship programs across 14 specialties. Associations between academic rank and sex were assessed using a χ2 independence test. Correlation between subspecialty compensation and percentage of female fellowship program directors was assessed using Pearson r. RESULTS: Women represented 18% of all fellowship program directors. Eighteen percent of fellowship program directors were assistant professors (25% women vs 17% men, P = .049), 36% were associate professors (39% women vs 35% men, P = .379), and 46% were full professors (36% women vs 48% men, P = .018). The percentage of women program directors was greatest in breast surgery (65%) and least in minimally invasive surgery (6%). There was a negative correlation between subspecialty compensation and percentage of female fellowship program directors (r = -0.62, P = .04). CONCLUSION: Women are underrepresented among surgery fellowship program directors. Female fellowship program directors had lesser academic ranks compared with males. It remains unclear whether women surgeons achieve program director appointments at lesser academic ranks or if promotion among fellowship program directors is influenced by sex.

Dispersal and genetic differentiation of Syntrichia caninervis populations across different desert regions in China.

The moss Syntrichia caninervis is widely distributed in cool temperate and cold deserts where environmental pressures create a dependence on asexual reproduction (fragment reproduction). However, when compared to sporophyte-producing mosses, there is a lack of evidence to support the capacity of drought-tolerant mosses that predominantly fragment and produce protonema to disperse over long distances. We used 20 microsatellite loci to study genetic variation and structure in six populations (five natural populations and one population from a regeneration site) in three contrasting and widely separated regions of China. The genetic diversity and expected heterozygosity were lower in populations from the Tengger Desert than in populations from the other regions. Using PCoA, UPGMA and Structure analysis, the genetic grouping divided the three regions into three distinct groups. This may indicate that in regions where S. caninervis reproduces predominantly asexually, propagules are spread mainly by short-distance dispersal. The genetic diversity of the population from the regeneration site in the Tengger Desert was slightly higher than that of the nearby, naturally occurring population, and included some input from the Pamir Plateau almost 2,300 km to the west, suggesting long-distance dispersal of S. caninervis propagules across the region. Predominantly asexually reproducing populations of S. caninervis are mainly dependent on short-distance dispersal. Long-distance dispersal of S. caninervis propagules across the region is difficult. Establishment of populations with dominant asexual reproduction will eventually result in genetic differentiation.

Renal protection by atorvastatin in a murine model of sickle cell nephropathy.

Recent studies have demonstrated pleiotropic effects of statins in various mouse models of kidney disease. In this study, Townes humanized sickle cell mice were treated for 8 weeks with atorvastatin at a dose of 10 mg/kg/day starting at 10 weeks of age. Treatment with atorvastatin significantly reduced albuminuria, and improved both urine concentrating ability and glomerular filtration rate. Atorvastatin also decreased markers of kidney injury and endothelial activation, and ameliorated oxidant stress in renal tissues and peripheral macrophages. Atorvastatin downregulated the expression of mRNA levels of the NADPH oxidases, Cybb (also termed Nox2) and Nox4, which are major sources of oxidant stress in the kidney. These findings highlight the pleiotropic effects of atorvastatin and suggest that it may provide beneficial effects in sickle cell nephropathy.

Exercise Perception and Behaviors in Individuals Living with Primary Immunodeficiency Disease.

BACKGROUND: Routine exercise has been established as an effective way to improve overall health. The value of exercise has been established in many diseases, however, there are no studies investigating the impact of exercise for individuals with primary immunodeficiency disease (PID). The purpose of this study was to investigate exercise perceptions and behaviors in individuals diagnosed with PID. METHODS: An online survey was distributed over a four-week period. RESULTS: Of the 264 responses collected, most were females, 45-54 years old. Respondents reported a measurable loss of function impairing their daily activities due to loss of mobility/physical activity (41.32%), or loss of lung/pulmonary function (40.08%,). They felt exercise decreased stress level and improved their mental well-being (46.25%). Some indicated they participate in exercise (33.20%), while 36.84% had not participated in exercise for at least 1 year. Exercise was limited primarily due to fatigue (86.97%). CONCLUSION: Exercise is important for those with chronic medical conditions. Most individuals living with PID can participate in low/moderate physical activity, but struggle with vigorous physical activity, since fatigue is the greatest barrier. Respondents view exercise as beneficial, and would like to increase participation in an exercise program.

Feasibility of transthoracic echocardiographic imaging in non-sedated ovine subjects using a commercial restraint device.

Transthoracic echocardiography (TTE) is a valuable non-invasive imaging research technique. In ovine models of cardiac disease, restraint for TTE often involves sedation even with currently available restraint equipment; our goal was to determine the feasibility of using a commercial restraint device, commonly known as the sheep chair, in minimizing animal stress and the need for sedation while achieving a complete TTE examination. A total of 10 healthy adult Dorset sheep were restrained in a sheep chair for TTE and observed for signs of stress. No animals displayed overt evidence of stress and none required sedation. While individual anatomic variation existed, image quality was sufficient to determine cardiac function. These observations suggest that a sheep chair is a useful aid in minimizing the need for sedation to acquire a full TTE study in ovine subjects.

Lower Extremity Revascularization Using Optical Coherence Tomography-Guided Directional Atherectomy: Final Results of the EValuatIon of the PantheriS OptIcal COherence Tomography ImagiNg Atherectomy System for Use in the Peripheral Vasculature (VISION) Study.

PURPOSE: To evaluate the safety and efficacy of a novel optical coherence tomography (OCT)-guided atherectomy catheter in treating patients with symptomatic femoropopliteal disease. METHODS: The VISION trial ( ClinicalTrials.gov identifier NCT01937351) was a single-arm, multicenter, global investigational device exemption study enrolling 158 subjects (mean age 67.2±10.5 years; 87 men) across 20 participating sites. In this cohort, 198 lesions were treated with an average length of 53±40 mm using the Pantheris catheter alone or Pantheris + adjunctive therapy. The primary safety endpoint was the composite of major adverse events (MAEs) through 6 months (objective performance goal 43.2%). Technical success (primary efficacy outcome) was defined as the percent of target lesions with a residual diameter stenosis ≤50% after treatment with the Pantheris device alone (objective performance goal 87.0%). Procedural success was defined as reduction in stenosis to ≤30% after Pantheris ± adjunctive therapy. Tissue specimens retrieved from each treated lesion were histologically analyzed to evaluate the accuracy and precision of OCT image guidance. RESULTS: The primary efficacy outcome was achieved in 192 (97.0%) of the 198 lesions treated with the Pantheris catheter. Across all lesions, mean diameter stenosis was reduced from 78.7%±15.1% at baseline to 30.3%±11.8% after Pantheris alone (p<0.001) and to 22.4%±9.9% after Pantheris ± adjunctive therapy (p<0.001). Of the 198 target lesions, 104 (52.5%) were treated with the Pantheris alone, 84 (42.4%) were treated with Pantheris + adjunctive angioplasty, and 10 (5.1%) with Pantheris + angioplasty + stenting. The composite MAE outcome through 6 months occurred in 25 (16.6%) of 151 subjects. There were no clinically significant perforations, 1 (0.5%) catheter-related dissection, 4 (2%) embolic events, and a 6.4% clinically driven target lesion revascularization rate at 6 months. The 40-lesion chronic total occlusion (CTO) subset (mean lesion length 82±38 mm) achieved a similar significant reduction in stenosis to 35.5%±13.6% after Pantheris alone (p<0.001). Histological analysis of atherectomy specimens confirmed <1% adventitia in 82.1% of the samples, highlighting the precision of OCT guidance. Characterization of the OCT-guided lesions revealed evidence of an underestimation of disease burden when using fluoroscopy. CONCLUSION: OCT-guided atherectomy for femoropopliteal disease is safe and effective. Additionally, the precision afforded by OCT guidance leads to greater removal of plaque during atherectomy while sparing the adventitia.

Primary Adrenocortical Insufficiency Case Series: Genetic Etiologies More Common than Expected.

BACKGROUND/AIMS: Primary adrenal insufficiency (AI) is an important cause of morbidity in children. Our objectives were: (1) to describe the clinical presentation of children with new-onset primary AI, and (2) to identify monogenic causes of primary AI in children. METHODS: Chart review and mutation detection in candidate genes were conducted for 11 patients with primary AI. RESULTS: The likely cause of AI was determined in 9 patients. One had a homozygous MC2R mutation associated with familial glucocorticoid deficiency. Two had the same homozygous mutation in the AIRE gene which is associated with type 1 autoimmune polyglandular syndrome. One patient had a heterozygous change in this gene of undetermined significance. Five were homozygous for the previously reported p.R188C STAR mutation causing nonclassic lipoid congenital adrenal hyperplasia, representing the largest cohort of such patients from a single geographic area. In the remaining 2 patients, no clear etiology was identified. CONCLUSIONS: We recommend genetic testing for patients who have negative anti-adrenal antibodies or suggestive family history. Diagnosing a genetic etiology can provide information about prognosis and treatment, and is therefore beneficial for patients. Our high proportion of patients with nonclassic lipoid congenital adrenal hyperplasia likely represents a founder effect.

Additive solution-7 reduces the red blood cell cold storage lesion.

BACKGROUND: Transfusion of long-stored red blood cells (RBCs) is associated with decreased in vivo RBC recovery, delivery of RBC breakdown products, and increased morbidity and mortality. Reducing the burden of this RBC "storage lesion" is a major challenge in transfusion medicine. Additive solution-7 (AS-7) is a new RBC storage solution designed to improve RBC metabolism by providing phosphate and increasing buffering capacity. STUDY DESIGN AND METHODS: Storage quality in AS-7 was measured in a prospective, randomized, three-center trial using units of whole blood from healthy human subjects whose RBCs were stored for up to 56 days in AS-7 (n = 120) or for 42 days in the control solution AS-1 (n = 60). RESULTS: Hemolysis and shedding of protein-containing microvesicles were significantly reduced in RBCs stored in AS-7 for 42 and 56 days compared with RBCs stored in AS-1. Autologous in vivo recoveries of RBCs stored in AS-7 was 88 ± 5% at 42 days (n = 27) and 82 ± 3% at 56 days (n = 27), exceeding recoveries of RBCs stored in currently used solutions. CONCLUSION: Increasing the phosphate, pH range, and buffer capacity of a RBC storage system allowed RBCs to be stored better and longer than currently approved storage systems. AS-7 ameliorates the long-term storage lesion resulting in significantly increased viability in vitro and in vivo.