Global Delivery of Human Papillomavirus Vaccines

Worldwide, cervical cancer is the fourth most common cancer among women, with over half a million women diagnosed with cervical cancer in 2012. Human papillomavirus (HPV) vaccination, if broadly implemented, has the potential to significantly reduce global rates of morbidity and mortality associated with cervical and other HPV-related cancers. Over 100 countries around the world have licensed HPV vaccines. As of February, 2015, there were an estimated 80 national HPV immunization programs and 37 pilot programs, including many implemented in low- and middle-income countries. In this article, global implementation of HPV vaccination programs is discussed, including successes and ongoing challenges. Issues such as vaccine financing and different approaches to HPV vaccine delivery are presented

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

The Stereochemistry of Pyrrolidine Ring Biosynthesis in Tobacco

In four separate experiments, DL-[5-3H]/DL-[5-14C]ornithine, L-[5-3H]/DL- [5- 14C]ornithine, D-[5-3H]/DL- [5- 14C]ornithine and L-[2-3H]/L-[5- 14c]ornithine were administered to intact tobacco plants (Nicotiana tabacum). Nicotine, ornithine and proline were isolated in each of these experiments. In another experiment, R-[1-2H][l ,4-14C] putrescine was administered to intact tobacco plants and nicotine was isolated. The results of these experiments are consistent with the accepted mode of biosynthesis of nicotine from ornithine via putrescine (1,4-diaminobutane), N-methylputrescine, N-methyl-4-aminobutanal and N- methyl-1-pyrrolinium ion. The 3H:14c ratios of nicotine, the distribution of tritium within nicotine as established by chemical degradation and the distribution of deuterium within nicotine as established by 2H NMR are interpreted as showing that L-ornithine is the preferred enantiomer for nicotine biosynthesis, that the decarboxylation of L-ornithine to yield putrescine proceeds with retention of configuration at the reaction site, and that the oxidation of N-methylputrescine to N-methyl-4-aminobutanal proceeds with loss of the 4(S)hydrogen. Contrary to earlier reports, ornithine isolated in the 3H, 14C experiments had a changed 3:14c ratio from the ornithine which was fed. These results are interpreted as showing that L-ornithine is metabolised more rapidly than is D-ornithine in the tobacco plant. In all 3H, 14c experiments, proline was found to contain at least a small amount of tritium. In particular, when L-[2- 3H]/L-[5-14C] ornithine served as substrate, proline was found to contain 40 + 1% of the tritium, relative to 14C, that had been present in the feeding material. This result is interpreted as showing that, contrary to earlier reports, L-ornithine can be converted into proline via either a-keto-s-aminovaleric acid or glutamic semialdehyde. Together with the 3H: 14C ratios of proline in the other experiments, the results of this work are interpreted as showing that, when DL-ornithine serves as the substrate for proline biosynthesis in tobacco, 88 + 1% of the proline arises from D-ornithine via a-oxidation, 7 + 1% of the proline comes from L-ornithine via a-oxidation and 5 + 1% of the proline is produced from L-ornithine via s-oxidation. ThesisMaster of Science (MS

Left and right ventricular longitudinal strain-volume/area relationships in elite athletes.

We propose a novel ultrasound approach with the primary aim of establishing the temporal relationship of structure and function in athletes of varying sporting demographics. 92 male athletes were studied [Group IA, (low static-low dynamic) (n = 20); Group IC, (low static-high dynamic) (n = 25); Group IIIA, (high static-low dynamic) (n = 21); Group IIIC, (high static-high dynamic) (n = 26)]. Conventional echocardiography of both the left ventricles (LV) and right ventricles (RV) was undertaken. An assessment of simultaneous longitudinal strain and LV volume/RV area was provided. Data was presented as derived strain for % end diastolic volume/area. Athletes in group IC and IIIC had larger LV end diastolic volumes compared to athletes in groups IA and IIIA (50 ± 6 and 54 ± 8 ml/(m(2))(1.5) versus 42 ± 7 and 43 ± 2 ml/(m(2))(1.5) respectively). Group IIIC also had significantly larger mean wall thickness (MWT) compared to all groups. Athletes from group IIIC required greater longitudinal strain for any given % volume which correlated to MWT (r = 0.4, p < 0.0001). Findings were similar in the RV with the exception that group IIIC athletes required lower strain for any given % area. There are physiological differences between athletes with the largest LV and RV in athletes from group IIIC. These athletes also have greater resting longitudinal contribution to volume change in the LV which, in part, is related to an increased wall thickness. A lower longitudinal contribution to area change in the RV is also apparent in these athletes

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Hypertrophic cardiomyopathy with midventricular obstruction and apical aneurysm formation in a single family: case report

<p>Abstract</p> <p>Background</p> <p>Hypertrophic cardiomyopathy (HCM) is an extremely heterogeneous disease. An under recognized and very often missed subgroup within this broad spectrum concerns patients with left ventricular (LV) apical aneurysms in the absence of coronary artery disease.</p> <p>Case presentation</p> <p>We describe a case of HCM with midventricular obstruction and apical aneurysm formation in 3 patients coming from a single family. This HCM pattern was detected by 2D-echocardiography and confirmed by cardiac magnetic resonance imaging. A cardioverter defibrillator was implanted in one of the patients because of non-sustained ventricular tachycardia detected in 24-h Holter monitoring and an abrupt drop in systolic blood pressure during maximal exercise test. The defibrillator activated 8 months after implantation by suppression of a ventricular tachycardia providing anti-tachycardia pacing. The patient died due to refractory heart failure 2 years after initial evaluation. The rest of the patients are stable after a 2.5-y follow-up period.</p> <p>Conclusion</p> <p>The detection of apical aneurysm by echocardiography in HCM patients may be complicated. Ventricular tachycardia arising from the scarred aneurysm wall may often occur predisposing to sudden death.</p

First-in-Human Segmental Esophageal Reconstruction Using a Bioengineered Mesenchymal Stromal Cell-Seeded Implant

INTRODUCTION: Resection and reconstruction of the esophagus remains fraught with morbidity and mortality. Recently, data from a porcine reconstruction model revealed that segmental esophageal reconstruction using an autologous mesenchymal stromal cell-seeded polyurethane graft (Cellspan esophageal implant [CEI]) can facilitate esophageal regrowth and regeneration. To this end, a patient requiring a full circumferential esophageal segmental reconstruction after a complex multiorgan tumor resection was approved for an investigational treatment under the Food and Drug Administration Expanded Access Use (Investigational New Drug 17402). METHODS: Autologous adipose-derived mesenchymal stromal cells (Ad-MSCs) were isolated from the Emergency Investigational New Drug patient approximately 4 weeks before surgery from an adipose tissue biopsy specimen. The Ad-MSCs were grown and expanded under current Good Manufacturing Practice manufacturing conditions. The cells were then seeded onto a polyurethane fiber mesh scaffold (Cellspan scaffold) and cultured in a custom bioreactor to manufacture the final CEI graft. The cell-seeded scaffold was then shipped to the surgical site for surgical implantation. After removal of a tumor mass and a full circumferential 4 cm segment of the esophagus that was invaded by the tumor, the CEI was implanted by suturing the tubular CEI graft to both ends of the remaining native esophagus using end-to-end anastomosis. RESULTS: In this case report, we found that a clinical-grade, tissue-engineered esophageal graft can be used for segmental esophageal reconstruction in a human patient. This report reveals that the graft supports regeneration of the esophageal conduit. Histologic analysis of the tissue postmortem, 7.5 months after the implantation procedure, revealed complete luminal epithelialization and partial esophageal tissue regeneration. CONCLUSIONS: Autologous Ad-MSC seeded onto a tubular CEI tissue-engineered graft stimulates tissue regeneration following implantation after a full circumferential esophageal resection

Percutaneous septal ablation for left mid-ventricular obstructive hypertrophic cardiomyopathy: a case report

BACKGROUND: Mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHC) is a rare type of cardiomyopathy. The diagnosis is based on the hourglass appearance on the left ventriculogram and the presence of pressure gradient between apical and basal chamber of the ventriculum on the hemodynamic assessment. CASE PRESENTATION: The present case represents successful percutaneous treatment with septal ablation to patient with MVOHC associated with systolic anterior motion of the mitral valve and obstruction at both the mid-ventricular and outflow levels. CONCLUSION: Alcohol septal ablation has been proposed as less invasive alternatives to surgery in patients with MVOHC

Prox1 Regulates the Notch1-Mediated Inhibition of Neurogenesis

During development of the spinal cord, Prox1 controls the balance between proliferation and differentiation of neural progenitor cells via suppression of Notch1 gene expression