Age dependent mechanical properties of the infant porcine parietal bone and a correlation to the human.

An infant less than 18 months of age with a skull fracture has a one in three chance of abuse. Injury biomechanics are often used in the investigation of these cases. In addition to case-based investigations, computer modeling, and test dummies, animal model studies can aid in these investigations.

Dynamic calibration of pharmacokinetic parameters in dose-finding studies.

We introduce a dose-finding algorithm to be used to identify a level of dose that corresponds to some given targeted response. Our motivation arises from problems where the response is a continuously measured quantity, typically some pharmacokinetic parameter. We consider the case where an agreed level of response has been determined from earlier studies on some population and the purpose of the current trial is to obtain the same, or a comparable, level of response in a new population.

T cell responses of HIV-infected children after administration of inactivated or live attenuated influenza vaccines.

Live-attenuated influenza vaccine (LAIV) prevents significantly more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the T cell responses to LAIV or TIV in HIV-infected children. IFN-gamma-ELISPOT for the three vaccine-contained influenza strains, two mismatched strains, and phytohemagglutinin (PHA), was performed at 0, 4, and 24 weeks postimmunization in 175 HIV-infected children randomly assigned to LAIV or TIV.

Histone acetyltransferases interact with and acetylate p70 ribosomal S6 kinases in vitro and in vivo.

The 70kDa ribosomal protein S6 kinases (S6K1 and S6K2) play important roles in the regulation of protein synthesis, cell growth and survival. S6Ks are activated in response to mitogen stimulation and nutrient sufficiency by the phosphorylation of conserved serine and threonine residues. Here we show for the first time, that in addition to phosphorylation, S6Ks are also targeted by lysine acetylation.

CYP2C19 genetic variants affect nelfinavir pharmacokinetics and virologic response in HIV-1-infected children receiving highly active antiretroviral therapy.

Background: The objective of this research was to identify the impact of genetic variants of P-glycoprotein (ABCB1) and cytochrome P450 (CYP) on nelfinavir pharmacokinetics and response to highly active antiretroviral therapy (HAART) in HIV-1-infected children.

Methods: HIV-1-infected children (n = 152) from Pediatric AIDS Clinical Trial Group 366 or 377 receiving nelfinavir as a component of HAART were evaluated. Genomic DNA was assayed for ABCB1 and CYP genetic variants using real-time polymerase chain reaction Nelfinavir oral clearance (CL/F), M8 to nelfinavir ratios, CD4 T cells, and HIV-1-RNA were measured during HAART.

Phosphate decreases urine calcium and increases calcium balance: a meta-analysis of the osteoporosis acid-ash diet hypothesis.

Background: The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate.

Colorectal surgery patients prefer simple solid foods to clear fluids as the first postoperative meal.

Purpose: Randomized controlled trials have established that there is no benefit to withholding oral food and fluids from colorectal surgery patients postoperatively. The aim of this survey was to determine food preferences for the first postoperative meal and compare these with a traditional clear-fluid diet.

Methods: One hundred forty-five elective colorectal surgery patients were surveyed about their preferences for 35 common foods within 72 hours of surgery and their levels of nausea, hunger, and pain.

Immunogenicity and immunologic memory after hepatitis B virus booster vaccination in HIV-infected children receiving highly active antiretroviral therapy.

Background: Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)-infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated.

Methods: HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received 3 doses of HBV vaccine were given an HBV vaccine booster.

Virologic and immunologic correlates with the magnitude of antibody responses to the hepatitis A vaccine in HIV-infected children on highly active antiretroviral treatment.

Background: HIV-infected individuals mount poor antibody responses to vaccines. We sought to identify the immunologic and virologic factors associated with a robust response to hepatitis A virus (HAV) vaccine in children on highly active antiretroviral treatment.

Methods: One hundred fifty-two pediatric highly active antiretroviral treatment recipients immunized against HAV at weeks 0 and 24 had anti-HAV antibodies, CD4+, CD8+, and CD19+ cell percent assessed at weeks 0 and 32.

Low 5-year stability of within-patient ion excretion and urine pH in fasting-morning-urine specimens.

Most analyses of urine ion excretion and pH are based on 24-hour urine collections. However, fasting morning urine, collected in the morning after an initial void and a short fast, is easier to collect and may be sensitive to dietary intake. The objective of this study was to determine whether the within-subject dietary acid load is stable by testing the levels of urine pH and ion excretion (ie, calcium, chloride, magnesium, phosphate, potassium, sodium, sulfate) in fasting morning urine specimens collected at a 5-year interval.

Optimization and limitations of use of cryopreserved peripheral blood mononuclear cells for functional and phenotypic T-cell characterization.

The goals of this study were to optimize processing methods of cryopreserved peripheral blood mononuclear cells (PBMC) for immunological assays, identify acceptance parameters for the use of cryopreserved PBMC for functional and phenotypic assays, and to define limitations of the information obtainable with cryopreserved PBMC. Blood samples from 104 volunteers (49 human immunodeficiency virus-infected and 55 uninfected) were used to assess lymphocyte proliferation in response to tetanus, candida, and pokeweed-mitogen stimulation and to enumerate CD4(+) and CD8(+) T cells and T-cell subpopulations by flow cytometry. We determined that slowly diluting the thawed PBMC significantly improved viable cell recovery, whereas the use of benzonase improved cell recovery only sometimes.

Meta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balance.

The acid-ash hypothesis posits that protein and grain foods, with a low potassium intake, produce a diet acid load, net acid excretion (NAE), increased urine calcium, and release of calcium from the skeleton, leading to osteoporosis. The objectives of this meta-analysis were to assess the effect of changes in NAE, by manipulation of healthy adult subjects' acid-base intakes, on urine calcium, calcium balance, and a marker of bone metabolism, N-telopeptides. This meta-analysis was limited to studies that used superior methodological quality for the study of calcium metabolism.

Safety and immunogenicity of recombinant poxvirus HIV-1 vaccines in young adults on highly active antiretroviral therapy.

A trial to evaluate the safety and immunogenicity of recombinant modified vaccinia Ankara (MVA) and fowlpox (FP) vectors expressing multiple HIV-1 proteins was conducted in twenty HIV-1 infected youth with suppressed viral replication on HAART. The MVA and FP-based multigene HIV-1 vaccines were safe and well tolerated. Increased frequencies of HIV-1 specific CD4+ proliferative responses and cytokine secreting cells were detected following immunization.

Meta-analysis of the quantity of calcium excretion associated with the net acid excretion of the modern diet under the acid-ash diet hypothesis.

Background: The acid-ash diet hypothesis of osteoporosis suggests that acid from the modern diet causes a demineralization of the skeleton, and mobilized bone calcium is excreted. A systematic approach has not been used to summarize the findings of the numerous studies about the hypothesis.

Objectives: The purpose of this meta-analysis was to estimate the quantity of net acid excretion and calciuria associated with the modern diet, to assess the association between acid excretion and calcium excretion, and to assess the influence of urine preservatives on calcium measurement.

Impaired immunity to recall antigens and neoantigens in severely immunocompromised children and adolescents during the first year of effective highly active antiretroviral therapy.

Background: We studied whether severely immunocompromised, human immunodeficiency virus (HIV)-infected children who were beginning highly active antiretroviral therapy (HAART) or changing HAART regimens could spontaneously respond to a recall antigen (tetanus toxoid [TT] vaccine) or respond to a recall antigen and neoantigen (hepatitis A virus [HAV] vaccine) after 3 vaccinations.

Methods: A total of 46 children who had CD4 cell percentages <15% and who demonstrated a >0.75-log reduction in plasma HIV RNA levels within 4 weeks of starting HAART were randomized to receive vaccinations with either TT or HAV vaccines during the first 6 months of HAART.

Pharmacokinetics of high-dose lopinavir-ritonavir with and without saquinavir or nonnucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected pediatric and adolescent patients previously treated with protease inhibitors.

Human immunodeficiency virus (HIV)-infected children and adolescents who are failing antiretrovirals may have a better virologic response when drug exposures are increased, using higher protease inhibitor doses or ritonavir boosting. We studied the pharmacokinetics and safety of high-dose lopinavir-ritonavir (LPV/r) in treatment-experienced patients, using an LPV/r dose of 400/100 mg/m(2) orally every 12 h (p.o.

An age-dependent association of mannose-binding lectin-2 genetic variants on HIV-1-related disease in children.

Background: Mannose-binding lectin (MBL) is part of the lectin pathway of complement activation against various pathogens; however, its role in innate immune responses against HIV-1 infection in children is unknown.

Objective: This study evaluated the effects of mannose-binding lectin-2 (MBL2) alleles on HIV-1 disease progression and central nervous system (CNS) impairment in children.

Methods: A cohort of 1037 HIV-1-infected children enrolled in Pediatrics AIDS Clinical Trial Group protocols P152 and P300 before the availability of effective antiretroviral therapy was genotyped for MBL2 and evaluated for disease progression.

Shedding of live vaccine virus, comparative safety, and influenza-specific antibody responses after administration of live attenuated and inactivated trivalent influenza vaccines to HIV-infected children.

HIV-infected children (N=243), >or=5 to <18 years old, receiving stable antiretroviral therapy, were stratified by immunologic status and randomly assigned to receive intranasal live attenuated influenza vaccine (LAIV) or intramuscular trivalent inactivated influenza vaccine (TIV). The safety profile after LAIV or TIV closely resembled the previously reported tolerability to these vaccines in children without HIV infection. Post-vaccination hemagglutination inhibition (HAI) antibody responses and shedding of LAIV virus were also similar, regardless of immunological stratum, to antibody responses and shedding previously reported for children without HIV infection.

Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia.

We assessed the effect of progressively longer antiretroviral structured treatment interruptions (STIs) starting with 3 days, increasing by 2 days in length each cycle on HIV-specific immune responses. As well, we correlated these responses with control of HIV viremia. Eight individuals became viremic and reached cycle 13 with an STI of > or =27 days.

Planned multiple exposures to autologous virus in HIV type 1-infected pediatric populations increases HIV-specific immunity and reduces HIV viremia.

We tested to determine if planned multiple exposures to autologous HIV in pediatric patients with HIV-1 infection will induce cellular immunity that controls viremia. A prospective multicenter study of aviremic pediatric patients on highly active antiretroviral therapy who underwent progressively longer antiretroviral treatment interruptions in cycles starting with 3 days, increasing by 2 days in length each consecutive cycle, was conducted. Eight individuals became viremic and reached Cycle 13 or greater with an "off-therapy" interval of >or=27 days.

Regulation of ribosomal protein S6 kinases by ubiquitination.

Ribosomal protein S6 kinase (S6K) is a key player in the regulation of cell growth and energy metabolism via the mTOR and PI3K signalling pathways. The activity and subcellular localization of S6K are regulated by multiple S/T phosphorylations in response to diverse extracellular stimuli. Downregulation of S6K signalling occurs through the action of S/T phosphatases (PP2A and PP1) and tumor suppressors (TSC1/2 and PTEN).

Skull-photo superimposition and border deaths: identification through exclusion and the failure to exclude.

We report on the application of video skull-photo superimposition as an identification method in a case from Ajo, Arizona in which five individuals died after crossing into southern Arizona from Mexico. Initial analyses at the Pima County Forensic Science Center in Tucson, Arizona determined that the disarticulated skeletal remains represented two adult Hispanic males and three adult Hispanic females. Based on biological profiles, both the males and one of the females were tentatively identified and assigned names.

Identifying Southwest Hispanics using nonmetric traits and the cultural profile.

Due to the increasing number of Southwest Hispanics in the United States, as well as the overwhelming number of foreign nationals that die every year trying to enter the United States along the southern United States border with Mexico, new methods for classifying individuals have been established at the Pima County Office of the Medical Examiner in Tucson, Arizona (PCOME). For each of the past 5 years, the PCOME has investigated a record number of deaths associated with these border crossings. The overwhelming majority of the identified decedents are Mexican Nationals.

CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children.

Background: Cytochrome P450 2B6 (CYP2B6)-G516T genotype is associated with altered activity of hepatic CYP2B6 and efavirenz pharmacokinetics, but the relationship between the CYP2B6-G516T genotype and nevirapine (NVP) pharmacokinetics in plasma and cerebrospinal fluid (CSF) is limited.

Methods: In 126 children who received NVP and protease inhibitors from PACTG 366 and 377 cohorts, CYP2B6 and ATP-binding cassette, sub-family B, member 1 (ABCB1) gene polymorphisms were analyzed using real-time PCR. Plasma NVP pharmacokinetics and clinical data were collected and levels of NVP in CSF were evaluated in children with HIV-related neurologic diseases.

Malignant astrocytic glioma: genetics, biology, and paths to treatment.

Malignant astrocytic gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, resistance to traditional and newer targeted therapeutic approaches, destruction of normal brain tissue, and certain death. The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized our understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma.