Alternative Birth Plans and Unintended Maternal and Neonatal Consequences: A Review of the Literature.

IMPORTANCE: Birth plans are an important part of childbirth preparation for many women. OBJECTIVE: The aim of this review was to discuss some common requests, specifically home birth, water birth, placentophagy, lotus birth, vaccination refusal, and vaginal seeding, including evidence-based recommendations, perceived benefits, and potential maternal and neonatal consequences. EVIDENCE ACQUISITION: A literature search for each topic was undertaken using PubMed and Web of Science. For the home birth section, the MeSH terms home AND birth OR childbirth AND outcomes OR complications OR recommendations OR guidelines were used. For the vaccination section, birth OR childbirth OR maternal AND vaccination refusal were searched. For the remainder of the sections, umbilical cord AND nonseverance OR placentophagy OR vaginal seeding OR lotus birth were searched. A total of 523 articles were identified. The abstracts were reviewed by 2 authors (J.R.W. and J.A.R.); 60 of these articles were selected and used for this review. RESULTS: Home birth is currently not recommended in the United States. Immersion in water for labor is acceptable, but delivery should not occur in water. Placentophagy and lotus birth should be discouraged because of risk of neonatal infection. Vaccines should be administered in accordance with national guidelines. Vaginal seeding should be discouraged until more is known about the practice. CONCLUSIONS AND RELEVANCE: These evidence-based recommendations provide clear guidance for physicians so that the birthing experience can be enhanced for both mother and neonate without compromising safety. RELEVANCE STATEMENT: This is an evidence-based literature review of alternative birth plans and recommendations for directive counseling.

Peds PLACE: quality continuing medical education in Arkansas.

The University of Arkansas for Medical Sciences (UAMS) and Arkansas Children's Hospital (ACH) sponsor Peds PLACE (Pediatric Physician Learning and Collaborative Education), a telemedicine continuing education program. This study assessed to what extent participants were satisfied with Peds PLACE and how to improve it. It was found that 95% of the participants agreed that the presentations related to their professional needs and 98% that it increased their knowledge. In addition, 81% evaluated the presentations as some of the best they have attended and 93% agreed that the information would translate into professional practice and enhance patient care. Comments were positive and correlated with the survey data. Participants recommended several ways to improve Peds PLACE.

Rural school-based telehealth: how to make it happen.

When organizing new health care interventions among a rural population, a careful planning process respecting community-specific considerations should be used. The project objective centered on the successful implementation of a school-based telehealth clinic serving a rural, health-disparate population. Using an American Academy of Pediatrics Community Access to Child Health planning grant, a needs assessment of the Delta community was conducted. In synthesizing the results of this planning project, consensually addressed issues led to establishing a pilot school-based telehealth clinic within the rural county schools. Seven essential steps emerged as a set of guidelines that entities might consider in introducing a telemedicine school-based service in a rural community. The steps included assessing local and regional needs, securing community support and establishing goals, evaluating resources, configuring logistics, training staff, informing parents, and launching the clinic. Proper planning is crucial to the establishment of a rural school-based telehealth clinic.

Newborn hyperbilirubinemia: an update.

Newborn hyperbilirubinemia can lead to kernicterus, which is increasing in America. An overview of the newest American Academy of Pediatric Guideline on Hyperbilirubinemia is presented in order to assist Arkansas physicians in dealing with newborn hyperbilirubinemia.

Multilineage polyclonal engraftment of Cal-1 gene-modified cells and in vivo selection after SHIV infection in a nonhuman primate model of AIDS.

We have focused on gene therapy approaches to induce functional cure/remission of HIV-1 infection. Here, we evaluated the safety and efficacy of the clinical grade anti-HIV lentiviral vector, Cal-1, in pigtailed macaques (Macaca nemestrina). Cal-1 animals exhibit robust levels of gene marking in myeloid and lymphoid lineages without measurable adverse events, suggesting that Cal-1 transduction and autologous transplantation of hematopoietic stem cells are safe, and lead to long-term, multilineage engraftment following myeloablative conditioning. Ex vivo, CD4+ cells from transplanted animals undergo positive selection in the presence of simian/human immunodeficiency virus (SHIV). In vivo, Cal-1 gene-marked cells are evident in the peripheral blood and in HIV-relevant tissue sites such as the gastrointestinal tract. Positive selection for gene-marked cells is observed in blood and tissues following SHIV challenge, leading to maintenance of peripheral blood CD4+ T-cell counts in a normal range. Analysis of Cal-1 lentivirus integration sites confirms polyclonal engraftment of gene-marked cells. Following infection, a polyclonal, SHIV-resistant clonal repertoire is established. These findings offer strong preclinical evidence for safety and efficacy of Cal-1, present a new method for tracking protected cells over the course of virus-mediated selective pressure in vivo, and reveal previously unobserved dynamics of virus-dependent T-cell selection.

Telemedicine: Pediatric Applications.

Telemedicine is a technological tool that is improving the health of children around the world. This report chronicles the use of telemedicine by pediatricians and pediatric medical and surgical specialists to deliver inpatient and outpatient care, educate physicians and patients, and conduct medical research. It also describes the importance of telemedicine in responding to emergencies and disasters and providing access to pediatric care to remote and underserved populations. Barriers to telemedicine expansion are explained, such as legal issues, inadequate payment for services, technology costs and sustainability, and the lack of technology infrastructure on a national scale. Although certain challenges have constrained more widespread implementation, telemedicine's current use bears testimony to its effectiveness and potential. Telemedicine's widespread adoption will be influenced by the implementation of key provisions of the Patient Protection and Affordable Care Act, technological advances, and growing patient demand for virtual visits.

Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector.

We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT) mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC) either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection.

Smooth implementation of critical congenital heart defect screening in a newborn nursery.

In January of 2012, University of Arkansas for Medical Sciences began implementation of a critical congenital heart disease screening program to identify newborns with structural heart defects. The screening used motion tolerant pulse oximeters in direct sequence to measure the oxygen levels in the right hand and either foot of eligible newborns. Exclusion criteria included echocardiogram prior to discharge, age greater than 7 days with continuous neonatal intensive care unit monitoring, or death or transfer prior to discharge. Of the 1905 infants screened, 3 infants failed screening. Two of the infants had atrial septal defects, and 1 had a patent foramen ovale, which was considered a false positive. After planning and education, the implementation of critical congenital heart disease pulse oximetry screening was successful. With only 1 false positive in our high-risk population, this should encourage other institutions to begin screening eligible infants.

Preclinical safety and efficacy of an anti-HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor.

Gene transfer has therapeutic potential for treating HIV-1 infection by generating cells that are resistant to the virus. We have engineered a novel self-inactivating lentiviral vector, LVsh5/C46, using two viral-entry inhibitors to block early steps of HIV-1 cycle. The LVsh5/C46 vector encodes a short hairpin RNA (shRNA) for downregulation of CCR5, in combination with the HIV-1 fusion inhibitor, C46. We demonstrate here the effective delivery of LVsh5/C46 to human T cell lines, peripheral blood mononuclear cells, primary CD4(+) T lymphocytes, and CD34(+) hematopoietic stem/progenitor cells (HSPC). CCR5-targeted shRNA (sh5) and C46 peptide were stably expressed in the target cells and were able to effectively protect gene-modified cells against infection with CCR5- and CXCR4-tropic strains of HIV-1. LVsh5/C46 treatment was nontoxic as assessed by cell growth and viability, was noninflammatory, and had no adverse effect on HSPC differentiation. LVsh5/C46 could be produced at a scale sufficient for clinical development and resulted in active viral particles with very low mutagenic potential and the absence of replication-competent lentivirus. Based on these in vitro results, plus additional in vivo safety and efficacy data, LVsh5/C46 is now being tested in a phase 1/2 clinical trial for the treatment of HIV-1 disease.

CCR5 as a natural and modulated target for inhibition of HIV.

Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection-this without detrimental effects to the host-and transplantation of CCR5-delta32 stem cells in a patient with HIV ("Berlin patient") achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells.

Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.

Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against HIV-1 in patients. Using the humanized bone marrow/liver/thymus (hu-BLT) mouse model which allows investigation of human hematopoietic stem/progenitor cell (HSPC) transplant and immune system reconstitution as well as HIV-1 infection, we previously demonstrated stable inhibition of CCR5 expression in systemic lymphoid tissues via transplantation of HSPCs genetically modified by lentiviral vector transduction to express short hairpin RNA (shRNA). However, CCR5 down-regulation will not be effective against existing CXCR4-tropic HIV-1 and emergence of resistant viral strains. As such, combination approaches targeting additional steps in the virus lifecycle are required. We screened a panel of previously published shRNAs targeting highly conserved regions and identified a potent shRNA targeting the R-region of the HIV-1 long terminal repeat (LTR). Here, we report that human CD4(+) T-cells derived from transplanted HSPC engineered to co-express shRNAs targeting CCR5 and HIV-1 LTR are resistant to CCR5- and CXCR4- tropic HIV-1-mediated depletion in vivo. Transduction with the combination vector suppressed CXCR4- and CCR5- tropic viral replication in cell lines and peripheral blood mononuclear cells in vitro. No obvious cytotoxicity or interferon response was observed. Transplantation of combination vector-transduced HSPC into hu-BLT mice resulted in efficient engraftment and subsequent stable gene marking and CCR5 down-regulation in human CD4(+) T-cells within peripheral blood and systemic lymphoid tissues, including gut-associated lymphoid tissue, a major site of robust viral replication, for over twelve weeks. CXCR4- and CCR5- tropic HIV-1 infection was effectively inhibited in hu-BLT mouse spleen-derived human CD4(+) T-cells ex vivo. Furthermore, levels of gene-marked CD4(+) T-cells in peripheral blood increased despite systemic infection with either CXCR4- or CCR5- tropic HIV-1 in vivo. These results demonstrate that transplantation of HSPCs engineered with our combination shRNA vector may be a potential therapy against HIV disease.

HIV latency is influenced by regions of the viral genome outside of the long terminal repeats and regulatory genes.

We have previously described an in vitro primary thymocyte model for HIV latency that recapitulates several important aspects of latently infected cells obtained from patients. Our original model included a truncated HIV genome expressing only Tat, Rev, and Vpu along with a reporter gene. We have now expanded these studies to include reporter viruses encoding more complete viral genomes. We show here that regions of the viral genome outside of the long terminal repeat promoter and Tat/Rev regulatory genes can substantially affect both the basal level of HIV transcription prior to stimulation, and also the level of viral expression following costimulation via CD3 and CD28 ligation. These differences in latency phenotype between truncated and more complete HIV genomes demonstrate the importance of accessory genes in the context of HIV latency and indicate that care should be taken when interpreting data derived from heavily modified HIV genomes in latency models.

Through with the flu: how free family and caregiver immunization protects sick neonates.

Newborns represent the pediatric population most at risk for influenza-related morbidity and mortality, especially premature newborns and those with chronic disease. Compounding this problem is the fact that influenza immunizations are ineffective until 6 months of age. This article describes a successful program that follows the "cocoon" theory of immunization. Free influenza vaccines were given in the nursery to all family members, caregivers, and others living in the homes of discharged infants. Planning and implementation steps are described, along with lessons learned during implementation. The response to the program exceeded expectations, with 185 contacts immunized. Future plans include the expansion of the current program to include the H1N1 influenza vaccine and the Tdap vaccine. The described vaccination effort encourages and substantiates the benefits of cocoon immunization in other nurseries across the nation.

The use of cell-delivered gene therapy for the treatment of HIV/AIDS.

HIV/AIDS is a disease that impairs immune function, primarily by decreasing T-lymphocyte count. Its progression can be contained by highly active antiretroviral therapy (HAART), but there are side effects that can be severe, and the development of resistance often forces the physician to modify the HAART regimen. There are no vaccines available for HIV. An alternative approach that could provide a path to a curative therapy is the use of cell-delivered gene therapy in which an anti-HIV gene(s) is introduced into hematopoietic cells to produce a population that is protected from the effects of HIV. In this paper, we review the field and discuss an approach using a short hairpin RNA to CCR5, an important co-receptor for HIV.