Assessing Front Office Staff Awareness on Mental Health Resources at Youth Friendly Clinics in Los Angeles County.

Introduction: Mental illness is a global health challenge and continues to rise among minors. Community clinics are well positioned to provide mental health services to young people.

Objective: To assess community clinic front staff awareness of recent legislation mandating access by minors to mental health services and the actual services delivered by these clinics.

The Value of a Patient-Level Modeling Approach and Need for Better Reporting in Economic Evaluations of Osteoporosis.

No funding was involved in the writing of this letter. Outside of the submitted work, Hiligsmann has received research grants through institution from Amgen, Radius Health, UCB, and Teva/Theramex. Reginster has received research grants and/or consulting fees from Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed-Takeda, NPS, IBSA Genevrier, Theramex, UCB, Asahi Kasei, Endocyte, Merck Sharp and Dohme, Rottapharm, Teijin, Teva, Analis, NovoNordisk, Ebewee Pharma, Zodiac, Danone, Will Pharma, Meda, Bristol Myers Squibb, Pfizer, Organon, Therabel, Boehringer, Chiltern, and Galapagos.

Commercial Laboratory Reproducibility of Serum CTX in Clinical Practice.

In 2011, the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine selected serum collagen type-I crosslinked C-peptide (s-CTX) as the reference standard for bone resorption. This study aimed to determine the within and between laboratory reproducibility for s-CTX assays. To create standardized pools, serum was collected from 10 premenopausal and 10 postmenopausal women.

Tocilizumab (Anti-IL-6R) Suppressed TNFα Production by Human Monocytes in an In Vitro Model of Anti-HLA Antibody-Induced Antibody-Dependent Cellular Cytotoxicity.

Background: We previously demonstrated that natural killer (NK) cells activated via FcγRIIIa (CD16) interactions with anti-HLA antibodies binding to peripheral blood mononuclear cells (PBMCs) in the in vitro antibody-dependent cellular cytotoxicity (ADCC) assay produced IFNγ. Here we investigate if other CD16 bearing cells are responsive to alloantigen via alloantibody in the in vitro ADCC and if the ADCC-induced cytokine reactions and cytotoxicity can be modified by the anti-interleukin 6 receptor (IL-6R) monoclonal antibody, Tocilizumab (TCZ).

Methods: Whole blood from a normal individual was incubated overnight with irradiated allo-PBMCs pretreated with anti-HLA antibody positive (in vitro ADCC) or negative sera (mixed lymphocyte reaction [MLR]), with or without TCZ or control IgG.

Foam soap is not as effective as liquid soap in eliminating hand microbial flora.

Foam soaps are aerosolized liquid soaps dispensed through a special pump mechanism. Currently there are no studies comparing liquid soap with foam soap in regard to efficacy of reducing hand microbial burden. In 3 separate experiments and with 2 different brands of foam soap, it was observed that nonantimicrobial foam soap was not as effective in reducing hand bacterial load as the liquid soap.

Cytomegalovirus Immunity After Alemtuzumab Induction in Desensitized Kidney Transplant Patients.

Background: Desensitization with IVIG + rituximab combined with alemtuzumab induction gives HLA-sensitized patients an opportunity for successful kidney transplantation. However, it may be associated with a high risk for viral infections due to combined T cell and B cell depletion.

Methods: Anti-cytomegalovirus (CMV) activity was assessed in 280 pretransplant and posttransplant blood samples from 33 desensitized patients who received alemtuzumab induction.

Genes associated with antibody-dependent cell activation are overexpressed in renal biopsies from patients with antibody-mediated rejection.

Introduction: Antibody-mediated rejection (ABMR) is dependent on complement activating donor-specific anti-HLA antibodies (DSA). This is commonly detected by C4d deposition in allografts. However, recent data define a C4d negative ABMR phenotype suggesting a role for complement-independent DSA injury, antibody-dependent cellular cytotoxicity (ADCC).

Regulation of anti-HLA antibody-dependent natural killer cell activation by immunosuppressive agents.

Background: It was demonstrated that human natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC)-like mechanism, increase IFNγ production after exposure to alloantigens. This finding was associated with an increased risk for antibody-mediated rejection (ABMR). Although the effects of various immunosuppressive drugs on T cells and B cells have been extensively studied, their effects on NK cells are less clear.

Significant reduction of ATP production in PHA-activated CD4+ cells in 1-day-old blood from transplant patients.

Background: Global immunosuppression can be measured by assessing adenosine triphospate (ATP) levels in mitogen-stimulated CD4+ T cells.

Methods: We investigated the effect of storage time on ATP levels in 234 blood samples from 18 healthy individuals and 152 transplant patients. The difference between day 0 (<13 hours post-blood draw) and day 1 (24-37 hours) measurements was analyzed and compared with various factors; a subset of samples was also analyzed in 6-hour intervals.

IFNγ production by NK cells from HLA-sensitized patients after in vitro exposure to allo-antigens.

Using a novel cytokine flow cytometry test (allo-CFC), we have previously shown that incubation of allogeneic cells with peripheral blood from highly-HLA sensitized (HS) patients results in reproducible gamma-interferon (IFNγ production in CD3(-) cells, and high (+) allo-CFC levels correlated with risk for antibody-mediated rejection (AMR). Here we report on identification of the cells and mechanisms responsible. The allo-CFC with/without modification was performed using blood from HS or normal individuals.

Calcium and vitamin D controversies.

Controversies regarding appropriate use of vitamin D and calcium are predominately related to the extraskeletal effects. Calcium and vitamin D are essential for bone health. The concerns regarding calcium and cardiovascular complications are inconclusive at best, and do not warrant a change in our approach to supplementation at this time.

Dominant-negative mechanism of leukemogenic PAX5 fusions.

PAX5 encodes a master regulator of B-cell development. It fuses to other genes associated with acute lymphoblastoid leukemia (ALL). These fusion products are potent dominant-negative (DN) inhibitors of wild-type PAX5, resulting in a blockade of B-cell differentiation.

Immunologic parameters and viral infections in patients desensitized with intravenous immunoglobulin and rituximab.

Desensitization with IVIG and rituximab followed by transplantation with alemtuzumab or daclizumab induction is an effective clinical protocol. Here, we examined the effects of this protocol on immune cell number, T cell function by Cylex ImmuKnow®, CMV-specific CD8+ T cell (CMV-Tc) activity, total and viral-specific immunoglobulin levels and viral infections. In 17 highly HLA-sensitized (HS) patients who received desensitization, CD19+ cells were undetectable immediately after desensitization, while other immune cells were unchanged.

In vitro effects of everolimus and intravenous immunoglobulin on cell proliferation and apoptosis induction in the mixed lymphocyte reaction.

Targeting multiple pathways in the activation of alloimmune responses by multi-drug immunosuppressive regimens with complementary mechanisms of action enhances allograft survival and improves quality of life, owing to the reduction of adverse drug effects. In this report we investigated the effect of the combination of everolimus and intraveneous immunoglobulin (IVIG) on cell proliferation and apoptosis induction in human two-way mixed lymphocyte reaction (MLR). Everolimus alone (0.

Cellular allo reactivity against paternal HLA antigens in normal multiparous females as detected by intracellular cytokine flow cytometry remains elevated over years despite diminution of anti-HLA antibody levels.

Background: Sensitization to allo-antigens (Ags) resulting from previous transplants, blood transfusion or pregnancy (PG), is a significant obstacle to kidney transplantation and risk factor for antibody-mediated rejection (AMR). We have previously shown that allo-Ag-specific CD3 negative (-) cells as analyzed by cytokine flow cytometry (CFC) are elevated in many highly HLA-sensitized (HS) patients, but not most normal individuals. HS patients with high(+) CFC, especially to donor Ags, may be at high risk for AMR and may need additional pre-transplant desensitization.

Mycophenolic acid and intravenous immunoglobulin exert an additive effect on cell proliferation and apoptosis in the mixed lymphocyte reaction.

Background: Intravenous immunoglobulin (IVIG) has known immunomodulatory effects in autoimmune diseases and transplantation and is commonly used in desensitization protocols and for treatment of antibody-mediated rejection (AMR). IVIG inhibits the MLR and induces apoptosis in immune cells. Mycophenolate mofetil inhibits immune cell proliferation and is an effective immunsuppressive agent.

Intracellular IFNgamma production in CD3 negative cells exposed to allo-antigens is an indicator of prior sensitization.

Background: Sensitization to HLA antigens (Ags) is a significant obstacle to kidney transplantation and risk factor for antibody-mediated rejection (AMR). Current screening methods to assess HLA Ag exposure include various antibody assays. However, tools to accurately measure cell-mediated immunity to allo-Ags in a clinical setting are lacking.

Identified hidden genomic changes in mantle cell lymphoma using high-resolution single nucleotide polymorphism genomic array.

Objective: Mantle cell lymphoma (MCL) is a lymphoma characterized by aberrant activation of CCND1/cyclin D1 followed by sequential genetic abnormalities. Genomic abnormalities in MCL have been extensively examined by classical cytogenetics and microarray-based comparative genomic hybridization techniques, pointing out a number of alterations in genomic regions that correlate with the neoplastic phenotype and survival. Recently, single nucleotide polymorphism genomic microarrays (SNP-chip) have been developed and used for analysis of cancer genomics.

Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) cells at relapse are frequently more resistant to treatment than primary clones and this may be caused by further genetic changes in the ALL cells at relapse. These acquired genomic abnormalities have not been fully characterized. To examine the additional genomic alterations of ALL at relapse, we performed single nucleotide polymorphism genomic microarry (SNP-chip) analysis on 14 ALL bone marrow samples at initial diagnosis, remission and relapse.

Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray.

Objective: Myeloproliferative disorders (MPD) are clonal hematopoietic diseases that include polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). Mutations in JAK2 are present in many MPD patients. Additional genomic abnormalities are not fully examined in MPD.

Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.

High-resolution single nucleotide polymorphism genomic microarray (SNP-chip) is a useful tool to define gene dosage levels over the whole genome, allowing precise detection of deletions and duplications/amplifications of chromosomes in cancer cells. We found that this new technology can also identify breakpoints of chromosomes involved in unbalanced translocations, leading to identification of fusion genes. Using this technique, we found that the PAX5 gene was rearranged to a variety of partner genes including ETV6, FOXP1, AUTS2, and C20orf112 in pediatric acute lymphoblastic leukemia (ALL).

Clinical significance of peripheral blood Epstein-Barr viral load monitoring using polymerase chain reaction in renal transplant recipients.

PTLD is a complication of EBV infection. We examined the efficacy of EBV-PCR monitoring to detect early replication in an attempt to prevent EBV-associated PTLD. Blood EBV levels in 156 renal transplant recipients (58 children) from three institutions over nine yr were retrospectively analyzed.

2C4, a monoclonal antibody against HER2, disrupts the HER kinase signaling pathway and inhibits ovarian carcinoma cell growth.

Background: Human epidermal growth factor receptor 2 (HER2) is overexpressed in 25-30% of ovarian carcinoma cases and a correlation between increased HER2 expression and decreased survival has been demonstrated. HER2 is a ligand-less member of the HER family that functions as the preferred coreceptor for epidermal growth factor receptor (EGFR), HER3, and HER4.

Methods: An approach was developed to target HER2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders HER2's recruitment into a functional HER complex.