Neurotización del nervio circunflejo por vía axilar, estudio cadavérico / Neurotization of the circumflex nerve through an axillary approach, cadaveric study

Objetivo Confirmar factibilidad técnica de la neurotización del nervio axilar por la rama motora de la porción larga del tríceps con el fin de definir la anatomía quirúrgica de los nervios radial y axilar. Materiales y métodos Veinte hombros de cadáver fueron intervenidos para transferencia de la rama del Nervio Radial para la porción larga del tríceps a la rama anterior del Nervio Axilar por abordaje axilar. Se confirmó la escogencia correcta del nervio receptor por abordaje posterior. Resultados Se logró una disección adecuada de la primera rama motora del nervio radial del nervio axilar y de la rama anterior del Nervio Axilar. El origen de la rama motora se encontró en promedio a 3,8mm (+/- 7,3mm) distal al borde superior del tendón del dorsal ancho. El nervio axilar se encontró cefálico al borde superior del dorsal ancho a una distancia promedio de 11,3mm (+/-2,13mm) y distal al redondo menor 3.05mm (+/- 1,3mm), sutura con la primera rama del radial en el 100% de los casos sin tensión y se confirmó la adecuada transferencia en todos los casos. Conclusión La neurotización del nervio axilar con la primera rama del nervio radial se logró con éxito en el 100% por vía axilar. Este abordaje es adecuado, evitando tener que realizar cambios de posición a prono y doble abordaje, y si se requiere procedimientos adicionales de reconstrucción en el mismo tiempo quirúrgico tipo Oberlin y exploraciones supraclaviculares del plexo braquial se pueden realizar sin cambio de posición.

Objective To confirm the technical feasibility of neurotization of the axillary nerve by the motor branch of the long head of the triceps in order to define the surgical anatomy of the radial and axillary nerves. Materials and method Twenty cadaver shoulders were operated on for transfer of the radial nerve branch for the long head of the triceps to the anterior branch of the axillary nerve by axillary approach. The correct choice of the receiving nerve was confirmed by posterior approach. Results An adequate dissection of the first motor branch of the radial nerve of the axillary nerve and of the anterior branch of the Axillary Nerve was achieved, The origin of the motor branch was found on average at 3.8mm (+/−7.3mm) distal to the superior border of the latissimus dorsi tendon. The axillary nerve was found 11.3mm (+/−2.13mm) cephalad to the upper border of the latissimus dorsi and 3.05mm (+/−1.3mm) distal to the teres minor. A tensionless coaptation was obtained in all cases. Conclusion Neurotization of the axillary nerve with the first branch of the radial nerve was successfully achieved through the axillary approach. This approach is adequate, avoiding position change to prone and double approach, and if additional reconstruction procedures are required at the same surgical time, Oberlin type and supraclavicular explorations of the brachial plexus can be performed without changing position.

Inestabilidad persistente de codo secundaria a luxación traumática con reconstrucción ligamentaria aguda. Caso clínico / Persistent elbow instability secondary to traumatic dislocation with acute ligamentous reconstruction. Clinical case

Introducción: La luxación de codo es un evento frecuente de consulta a urgencias. Su diagnóstico se basa en el examen clínico y radiológico, y su manejo con frecuencia consiste en una reducción cerrada. En algunas ocasiones, la persistencia de inestabilidad posterior a la reducción se convierte en un reto para el médico tratante. Caso clínico: Presentamos el caso de un paciente hombre de 58 años, quien requiere intervenciónaguda por persistencia de luxación simple posterior a tres intentos de reducción cerrada. Aunque se descartó compromiso óseo, la evidencia de inadecuada reducción articular fue la indicación para realizar reconstrucción ligamentaria emergente. Resultados: El paciente requirió manejo quirúrgico para reconstrucción ligamentaria. Después de 6 meses de seguimiento, el paciente presenta ligera rigidez del codo dado por un arco de movilidad de 50 grados. El paciente no presentó nuevos episodios de reluxación posterior a la reconstrucción ligamentaria. Discusión: La luxación simple es la forma de presentación más frecuente en las luxaciones de codo, sin embargo, la estabilidad articular después de realizar una reducción cerrada es muy importante. Una minoría de pacientes requieren ser llevados a procedimientos quirúrgicos para restaurar los estabilizadores ligamentarios y musculares del codo. Se realiza un análisis del caso y se resaltan algunos de los aspectos más importantes bajo la evidencia de la literatura.

Introduction: Elbow dislocation is a frequent emergency consultation event. Its diagnosis is based on clinical and radiological examination, and its management frequently consists of a closed reduction. On some occasions, the persistence of instability after reduction becomes a challenge for the treating physician. Clinical case: We present the case of a 58-year-old male patient, who requires acute intervention due to persistence of simple dislocation after three attempts at closed reduction. Although bone involvement was ruled out, evidence of inadequate joint reduction was the indication to perform emergent ligament reconstruction. Results: The patient required surgical management for ligament reconstruction. After 6 months of follow-up, the patient presents slight elbow stiffness due to a 50-degree arc of mobility. The patient did not present new episodes of redislocation after ligament reconstruction. Discussion: Simple dislocation is the most common presentation of elbow dislocations; however, joint stability after performing a closed reduction is very important. A minority of patients require surgical procedures to restore the ligamentous and muscular stabilizers of the elbow. An analysis of the case is carried out and some of the most important aspects are highlighted based on the evidence of the literature.

Prevalence and Correlates of Homelessness Among American Indian and Alaska Native Youth.

Youth homelessness is a serious national challenge affecting millions of young people every year. However, due to their relatively small population size, together with limitations related to data and research efforts on homelessness to date, prevalence estimates and evidence of homelessness experiences among American Indian and Alaska Native (AIAN) youth have been scarce. This is particularly the case at the national level. We report findings on the prevalence, characteristics, and correlates of AIAN youth experiencing homelessness that are based on a nationally representative survey on homelessness among adolescents and young adults, age 13 to 25. The overall national survey sample included 25,492 respondents. During a 12-month period, approximately 10.2% of AIAN households with 13-17 year olds reported youth homelessness or runaway experiences that lasted at least one night. For AIAN 18-25 year olds, the 12-month population prevalence of homelessness experiences was 12.2%. AIAN young adults had three times the prevalence rate of homelessness as their White non-Hispanic peers. Furthermore, most AIAN youth experiencing homelessness, like most AIAN people overall, reside in predominantly urban counties. Controlling for other variables, lower educational attainment, and parenting (especially if unmarried) were associated with higher likelihood of homelessness. There is a clear and urgent need for tailored, culturally-responsive homelessness prevention and intervention strategies, along with focused housing and support investments, for AIAN young people and the communities in which they live. The federal government and local jurisdictions need to take policy actions to address high rates of AIAN youth homelessness in urban and suburban communities, in addition to policies centered on AIAN reservations and rural communities.

Tuberculosis patients display a high proportion of CD8+ T cells with a high cytotoxic potential.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major cause of morbidity and mortality worldwide. In the host's immune response system, T cells play a critical role in mediating protection against Mtb infection, but the role of CD8+ T cells is still controversial. We evaluated the phenotypical characterization and cytotoxic ability of CD8+ T cells by flow cytometry-based assay. Cytokine levels in serum were measured by multiplex cytokine assay. Our data show that cells from TB patients have an increased percentage of peripheral blood CD8+ αß+ T (p = 0.02) and CD56+ CD8+ T (p = 0.02) and a decreased frequency of NKG2D+ CD8+ T (p = 0.02) compared with healthy donors. Unlike CD8+ T cells from healthy donors, CD8+ T cells from TB patients exhibit greater cytotoxicity, mediated by HLA class I molecules, on autologous monocytes in the presence of mycobacterial antigens (p = 0.005). Finally, TB patients have a proinflammatory profile characterized by serum high level of TNF-α (p = 0.02) and IL-8 (p = 0.0001), but, interestingly, IL-4 (p = 0.002) was also increased compared with healthy donors. Our data show evidence regarding the highly cytotoxic status of CD8+ T cells in Mtb infection. These cytotoxic cells restricted to HLA-A, B, and C could be used to optimize strategies for designing new TB vaccines or for identifying markers of disease progression.

Metabolic Syndrome Exacerbates the Recognition Memory Impairment and Oxidative-Inflammatory Response in Rats with an Intrahippocampal Injection of Amyloid Beta 1-42.

An important worldwide health problem as the result of current lifestyle is metabolic syndrome (MS). It has been shown that MS induced by a high-calorie diet (HCD) in rats produces cognitive deterioration in the novel object recognition test (NORt) and decreases synaptic connections and dendritic order in the hippocampus and temporal cortex. However, it is unknown whether MS induced by an HCD participates in the cognitive process observed with the injection of Aß1-42 into the hippocampus of rats as a model of Alzheimer disease (AD). The induction of MS in rats produces a deterioration in NORt; however, rats with MS injected with Aß1-42 show a major deterioration in the cognitive process. This event could be explained by the increment in the oxidative stress in both cases studied (MS and Aß1-42): together, the hippocampus and temporal cortex produce an enhancer effect. In the same way, we observed an increment in interleukin-1ß, TNF-α, and GFAP, indicative of exacerbated inflammatory processes by the combination of MS and Aß1-42. We can conclude that MS might play a key role in the apparition and development of cognitive disorders, including AD. We propose that metabolic theory is important to explain the apparition of cognitive diseases.

Prevalence and Correlates of Youth Homelessness in the United States.

PURPOSE: Unaccompanied youth homelessness is a serious concern. Response, however, has been constrained by the absence of credible data on the size and characteristics of the population and reliable means to track youth homelessness over time. We sought to address these gaps. METHODS: Using a nationally representative phone-based survey (N = 26,161), we solicited household and individual reports on different types of youth homelessness. We collected household reports on adolescents aged 13-17 and young adults aged 18-25, as well as self-reports from young adults aged 18-25. Follow-up interviews with a subsample (n = 150) provided additional information on youth experiences and enabled adjustment for inclusion errors. RESULTS: Over a 12-month period, approximately 3.0% of households with 13- to 17-year-olds reported explicit youth homelessness (including running away or being asked to leave) and 1.3% reported experiences that solely involved couch surfing, resulting in an overall 4.3% household prevalence of any homelessness, broadly defined. For 18- to 25-year-olds, household prevalence estimates were 5.9% for explicitly reported homelessness, 6.6% for couch surfing only, and 12.5% overall. The 12-month population prevalence estimates, available only for 18- to 25-year-olds, were 5.2%, 4.5%, and 9.7%, respectively. Incidence rates were about half as high as prevalence rates. Prevalence rates were similar across rural and nonrural counties. Higher risk of homelessness was observed among young parents; black, Hispanic, and lesbian, gay, bisexual, or transgender (LGBT) youth; and those who did not complete high school. CONCLUSIONS: The prevalence and incidence of youth homelessness reveal a significant need for prevention and youth-centric systems and services, as well as strategies to address disproportionate risks of certain subpopulations.

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration.

Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aß-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly.

The places parents go: understanding the breadth, scope, and experiences of activity spaces for parents.

Neighborhood environments are related to parenting behaviors, which in turn have a life-long effect on children's health and well-being. Activity spaces, which measure individual routine patterns of movement, may be helpful in assessing how physical and social environments shape parenting. In this study we use qualitative data and GIS mapping from 4 California cities to examine parental activity spaces. Parents described a number of factors that shape their activity spaces including caregiving status, the age of their children, and income. Parental activity spaces also varied between times (weekends vs. weekdays) and places (adult-only vs. child-specific places). Knowing how to best capture and study parental activity spaces could identify mechanisms by which environmental factors influence parenting behaviors and child health.

Tissue and cellular characterisation of nucleolin in a murine model of corneal angiogenesis.

PURPOSE: Corneal neovascularisation (CNV), with consequent loss of transparency, is due to an imbalance of proangiogenic factors. Cell-surface nucleolin (NCL) has been associated with neo-angiogenesis. There are studies identifying NCL translocation from nucleus to the cell surface, which is essential for endothelial cell proliferation. To find the possible role of NCL in the generation of corneal neovessels, the aim of this study is to characterise the NCL presence and cell-localisation in non-injured corneas, as well as to describe the changes in NCL cell and tissue localisation in CNV, and to analyse the effect of bevacizumab on NCL cellular and tissular distribution. METHODS: Suture-induced CNV was performed in mice. The corneal tissues were obtained and the histological and co-immunofluorescence assays were performed using different proteins, such as CD31, cadherin and isolectin B4. To determine the possible role of VEGF in NCL presence and localisation in our CNV model, bevacizumab was concomitantly used. RESULTS: Nucleolin was principally observed in the nucleus of the basal epithelial cells of normal corneas. Interestingly, angiogenesis-induced changes were observed in the localisation of NCL, not only in tissue but also at the cellular level where NCL was extranuclear in epithelial cells, stromal cells and neovessels. In contrast, these changes were reverted when bevacizumab was used. Besides, NCL was able to stain only aberrant corneal neovessels in comparison with retinal vessels. CONCLUSIONS: NCL mobilisation outside the nucleus during angiogenesis could have a possible role as a proangiogenic molecule in the corneal tissue.

"Just make sure you can get up and parent the next day": Understanding the contexts, risks, and rewards of alcohol consumption for parents.

Little is known about how parents make drinking decisions and weigh the risks and rewards of alcohol consumption in specific contexts. This qualitative study examined two questions: 1. What factors influence parental drinking decisions in different drinking contexts? 2. What do parents perceive as the risks and rewards of alcohol consumption in different drinking contexts? Purposive sampling was used to select sixty parents of children aged 10 or younger living in four mid-sized California cities. Data were collected via in-depth, semi-structured interviews. Many parents viewed drinking at family get-togethers or parties as protective of children, since the presence of multiple adults and children provide buffers when parents become intoxicated. In contrast, parents noted that drinking at home, and particularly drinking alone, transmitted potentially negative messages. Social pressures and contexts influence alcohol consumption among parents and could provide potential avenues for intervention against alcohol-related harms.

Amaranthus leucocarpus lectin recognizes a moesin-like O-glycoprotein and costimulates murine CD3-activated CD4(+) T cells.

The Galß1,3GalNAcα1,O-Ser/Thr specific lectin from Amaranthus leucocarpus (ALL) binds a ∼70 kDa glycoprotein on murine T cell surface. We show that in the absence of antigen presenting cells, murine CD4(+) T cells activated by an anti-CD3 antibody plus ALL enhanced cell proliferation similar to those cells activated via CD3/CD28 at 48 h of culture. Moreover, ALL induced the production of IL-4, IL-10, TNF-alpha, and TGF-beta in CD3-activated cells. Proteomic assay using two-dimensional electrophoresis and far-Western blotting, ALL recognized two prominent proteins associated to the lipid raft microdomains in CD3/CD28-activated CD4(+) T cells. By mass spectrometry, the peptide fragments from ALL-recognized proteins showed sequences with 33% homology to matricin (gi|347839 NCBInr) and 41% identity to an unnamed protein related to moesin (gi|74186081 NCBInr). Confocal microscopy analysis of CD3/CD28-activated CD4(+) T cells confirmed that staining by ALL colocalized with anti-moesin FERM domain antibody along the plasma membrane and in the intercellular contact sites. Our findings suggest that a moesin-like O-glycoprotein is the ALL-recognized molecule in lipid rats, which induces costimulatory signals on CD4(+) T cells.

DNA methylation at IL32 in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 (IL32) is reduced in JIA CD4+ T cells. To extend this finding, we measured IL32 methylation in CD4+ T-cells from an additional sample of JIA cases and age- and sex-matched controls, and found a reduction in methylation associated with JIA consistent with the prior data (combined case-control dataset: 25.0% vs 37.7%, p = 0.0045). Further, JIA was associated with reduced IL32 methylation in CD8+ T cells (15.2% vs 25.5%, p = 0.034), suggesting disease-associated changes to a T cell precursor. Additionally, we measured regional SNPs, along with CD4+ T cell expression of total IL32, and the γ and ß isoforms. Several SNPs were associated with methylation. Two SNPs were also associated with JIA, and we found evidence of interaction such that methylation was only associated with JIA in minor allele carriers (e.g. rs10431961 p(interaction) = 0.011). Methylation at one measured CpG was inversely correlated with total IL32 expression (Spearman r = -0.73, p = 0.0009), but this was not a JIA-associated CpG. Overall, our data further confirms that reduced IL32 methylation is associated with JIA, and that SNPs play an interactive role.

Intracellular IL-4, IL-5, and IFN-γ as the main characteristic of CD4+CD30+ T cells after allergen stimulation in patients with vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a severe form of allergic conjunctivitis, in which inflammatory infiltrates of the conjunctiva are characterized by CD3+ and CD30+ cells. Until today, the functional involvement of CD30+ T cells in VKC was unclear. Our aim was to evaluate the functional characteristics of CD30+ T cells after allergen stimulation in peripheral blood mononuclear cells obtained from patients with VKC. METHODS: Seventeen consecutive patients at the Institute of Ophthalmology with active forms of VKC were included. RESULTS: After allergen stimulation, we observed the frequency of CD30+ T cells increased compared with non-stimulated cells (p<0.0001). The CD30+ T cells responded to the specific allergen-inducing expression of intracellular interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-γ) compared with the CD30- T cells (p<0.0001). Increased early secretion of soluble CD30 was observed in the supernatant of the cultured cells from patients with keratoconjunctivitis, compared with healthy controls (p=0.03). Blockage with IL-4 significantly diminished CD30 frequency in the allergen-stimulated cells. CONCLUSIONS: Our results suggest that after allergenic stimulation, CD4+CD30+ cells are the most important source of IL-4, IL-5, and IFN-γ. IL-4 acts as an activation loop that increases CD30 expression on T cells after specific stimulation. These findings suggest that CD4+CD30+ T cells are effector cells and play a significant role in the immune pathogenic response in patients with vernal keratoconjunctivitis.

Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a leading cause of childhood-onset disability. Although epistasis (gene-gene interaction) is frequently cited as an important component of heritability in complex diseases such as JIA, there is little compelling evidence that demonstrates such interaction. PTPN2, a vitamin D responsive gene, is a confirmed susceptibility gene in JIA, and PTPN2 has been suggested to interact with vitamin D pathway genes in type 1 diabetes. We therefore, tested for evidence of epistasis amongst PTPN2 and the vitamin D pathway genes GC, VDR, CYP24A1, CYP2R1, and DHCR7 in two independent JIA case-control samples (discovery and replication). In the discovery sample (318 cases, 556 controls), we identified evidence in support of epistasis across six gene-gene combinations (e.g., GC rs1155563 and PTPN2 rs2542151, ORint=0.45, p=0.00085). Replication was obtained for three of these combinations. That is, for GC and PTPN2, CYP2R1 and VDR, and VDR and PTPN2, similar epistasis was observed using the same SNPs or correlated proxies in an independent JIA case-control sample (1008 cases, 9287 controls). Using SNP data imputed across a 4 MB region spanning each gene, we obtained highly significant evidence for epistasis amongst all 6 gene-gene combinations identified in the discovery sample (p-values ranging from 5.6×10(-9) to 7.5×10(-7)). This is the first report of epistasis in JIA risk. Epistasis amongst PTPN2 and vitamin D pathway genes was both demonstrated and replicated.

Independent confirmation of juvenile idiopathic arthritis genetic risk loci previously identified by immunochip array analysis.

BACKGROUND: Our understanding of the genetic factors underlying juvenile idiopathic arthritis (JIA) is growing, but remains incomplete. Recently, a number of novel genetic loci were reported to be associated with JIA at (or near) genome-wide significance in a large case-control discovery sample using the Immunochip genotyping array. However, independent replication of findings has yet to be performed. We therefore attempted to replicate these newly identified loci in the Australian CLARITY JIA case-control sample. FINDINGS: Genotyping was successfully performed on a total of 404 JIA cases (mean age 6.4 years, 68% female) and 676 healthy child controls (mean age 7.1 years, 42% female) across 19 SNPs previously associated with JIA. We replicated a significant association (p < 0.05, odds ratio (OR) in a direction consistent with the previous report) for seven loci, six replicated for the first time--C5orf56-IRF1 (rs4705862), ERAP2-LNPEP (rs27290), PRR5L (rs4755450), RUNX1 (rs9979383), RUNX3 (rs4648881), and UBE2L3 (rs2266959). CONCLUSIONS: We have carried out the first independent replication of association for six genes implicated in JIA susceptibility. Our data significantly strengthens the evidence that these loci harbor true disease associated variants. Thus, this study makes an important contribution to the growing body of international data that is revealing the genetic risk landscape of JIA.

Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets.

Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n=5), PP (n=4) and HP (n=5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n=5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in "pathways in cancer". Interactome networks revealed that >50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with "pathways in cancer" in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura.

Aminoguanidine treatment ameliorates inflammatory responses and memory impairment induced by amyloid-beta 25-35 injection in rats.

Alzheimer disease (AD) is a neurodegenerative disorder caused by accumulation of the amyloid-beta peptide (Aß) in neuritic plaques. Its neurotoxic mechanisms are associated with inflammatory responses and nitrosative stress generation that promote expression of inducible nitric oxide synthase (iNOS) and increased nitric oxide causing neuronal death and memory impairment. Studies suggest that treatment with anti-inflammatory and anti-oxidant agents decreases the risk of developing AD. Aminoguanidine (AG) is an iNOS inhibitor with anti-inflammatory and anti-oxidant effects. In this study, we evaluated the effects of systemic administration of AG (100 mg/kg/day for 4 days) on spatial memory and inflammatory responses induced by an injection of Aß(25-35) [100 µM] into the temporal cortex (TCx) of rats. A significant improvement of spatial memory was evident in the Aß(25-35)-treated group at day 30 post-injection subjected to AG treatment; this effect was correlated with decreases in reactive gliosis, IL-1ß, TNF-α, and nitrite levels, as well as a reduction in neurodegeneration in the TCx and hippocampus (Hp). These results suggest that AG treatment inhibited glia activation and cytokine release, which may help to counteract neurodegenerative events induced by the toxicity of Aß.

O-glycosylation of NnTreg lymphocytes recognized by the Amaranthus leucocarpus lectin.

O-glycosidically-linked glycans have been involved in development, maturation, homing, and immune regulation in T cells. Previous reports indicate that Amaranthus leucocarpus lectin (ALL), specific for glycans containing galactose-N-acetylgalactosamine and N-acetylgalactosamine, recognizes human naïve CD27(+)CD25(+)CD4(+) T cells. Our aim was to evaluate the phenotype of CD4(+) T cells recognized by ALL in peripheral blood mononuclear cells obtained from healthy volunteers. CD4(+) T cells were isolated by negative selection using magnetic beads-labeled monoclonal antibodies; the expression of T regulatory cell phenotypic markers was assessed on ALL-recognized cells. In addition, IL-4, IL-10, IFN-γ, and TGF-ß intracellular production in ALL (+) cells was also evaluated. The analyses of phenotypic markers and intracellular cytokines were performed through flow cytometry. ALL-recognized CD4(+) T cells were mainly CD45RA(+), CCR7(+) cells. Although 52 ± 10% CD25(+)Foxp3(+) cells were positive to ALL, only 34 ± 4% of ALL (+) cells corresponded to CD25(+)Foxp3(-) cells. Intracellular cytokines in freshly obtained ALL (+)CD4(+) T cells exhibited 8% of IL-4, 15% of IL-10, 2% of IFN-γ, and 15% of TGF-ß, whereas ALL (-)CD4(+) T cells depicted 1% of IL-4, 2% of IL-10, <1% of IFN-γ, and 6% of TGF-ß. Our results show that galactose-N-acetylgalactosamine and N-galactosamine-bearing CD4(+) T cells expressed phenotypic markers of NnTreg cells.

Independent replication analysis of genetic loci with previous evidence of association with juvenile idiopathic arthritis.

BACKGROUND: Over the last five years, there have been numerous reports of association of juvenile idiopathic arthritis with single nucleotide polymorphisms (SNPs) at various loci outside the major histocompatibility complex (MHC) region. However, the majority of these association findings have been generated using a limited number of international cohorts, and thus there is benefit in further independent replication. To address this, we examined a total of 56 SNPs in 42 non-MHC gene regions previously reported to be associated with JIA, in the ChiLdhood Arthritis Risk factor Identification sTudY (CLARITY), a new Australian collection of cases and healthy child controls. FINDINGS: Genotyping was performed on a total of 324 JIA cases (mean age 9.7 years, 67.3% female) and 568 controls (mean age 7.8 years, 40.7% female). We demonstrated clear evidence for replication of association of JIA with SNPs in or around c12orf30, c3orf1, PTPN22, STAT4, and TRAF1-C5, confirming the involvement of these loci in disease risk. Further, we generated evidence supportive of replication of association of JIA with loci containing AFF3, CD226, MBL2, PSTPIP1, and RANTES (CCL5). These results were robust to sensitivity analyses for ethnicity. CONCLUSION: We have provided valuable independent data as to the underlying genetic architecture of this understudied pediatric autoimmune disease, further confirming five loci outside the MHC, and supporting a role for a further five loci in determining disease risk.

CLARITY - ChiLdhood Arthritis Risk factor Identification sTudY.

BACKGROUND: The aetiology of juvenile idiopathic arthritis (JIA) is largely unknown. We have established a JIA biobank in Melbourne, Australia called CLARITY - ChiLdhood Arthritis Risk factor Identification sTudY, with the broad aim of identifying genomic and environmental disease risk factors. We present here study protocols, and a comparison of socio-demographic, pregnancy, birth and early life characteristics of cases and controls collected over the first 3 years of the study. METHODS: Cases are children aged ≤18 years with a diagnosis of JIA by 16 years. Controls are healthy children aged ≤18 years, born in the state of Victoria, undergoing a minor elective surgical procedure. Participant families provide clinical, epidemiological and environmental data via questionnaire, and a blood sample is collected. RESULTS: Clinical characteristics of cases (n = 262) are similar to those previously reported. Demographically, cases were from families of higher socio-economic status. After taking this into account, the residual pregnancy and perinatal profiles of cases were similar to control children. No case-control differences in breastfeeding commencement or duration were detected, nor was there evidence of increased case exposure to tobacco smoke in utero. At interview, cases were less likely to be exposed to active parental smoking, but disease-related changes to parent behaviour may partly underlie this. CONCLUSIONS: We show that, after taking into account socio-economic status, CLARITY cases and controls are well matched on basic epidemiological characteristics. CLARITY represents a new study platform with which to generate new knowledge as to the environmental and biological risk factors for JIA.