Emerging Concepts for Pelvic Organ Prolapse Surgery: What is Cure?

The objective of this review is to discuss emerging concepts in pelvic organ prolapse, in particular, “What is cure?” In a post-trial data analysis of the CARE (Colpopexy and Urinary Reduction Efforts) trial, treatment success varied tremendously depending on the definition used (19.2%–97.2%). Definitions that included the absence of vaginal bulge symptoms had the strongest relationships with the patients’ assessment of overall improvement and treatment success. As demonstrated by this study, there are several challenges in defining cure in prolapse surgery. Additionally, the symptoms of prolapse are variable. The degree of prolapse does not correlate directly with symptoms. There are many surgical approaches to pelvic organ prolapse. Multiple ways to quantify prolapse are used. There is a lack of standardized definition of cure. The data on prolapse surgery outcomes are heterogeneous. The goal of surgical repair is to return the pelvic organs to their original anatomic positions. Ideally, we have four main goals: no anatomic prolapse, no functional symptoms, patient satisfaction, and the avoidance of complications. The impact of transvaginal mesh requires thoughtful investigation. The driving force should be patient symptoms in defining cure of prolapse

Fanconi anemia manifesting as a squamous cell carcinoma of the hard palate: a case report

Fanconi Anemia is a rare autosomal recessive disorder characterized by various congenital malformations, progressive bone marrow failure at a very young age and of solid tumors development. The authors present a rare case of a squamous cell carcinoma of the hard palate in a Fanconi Anaemia patient. The atypical clinical manifestation rendered the diagnosis more difficult. This case, for age of appearance, sex and localization, is unique in international literature. We recommend a quarterly follow up of the oral-rhino-pharynx complex in FA patients and to consider as carcinomas, all oral lesions that last more than two weeks

Novel Naphthalene-Based Inhibitors of Trypanosoma brucei RNA Editing Ligase 1

African sleeping sickness is a devastating disease that plagues sub-Saharan Africa. Neglected tropical diseases like African sleeping sickness cause significant death and suffering in the world's poorest countries. Current treatments for African sleeping sickness either have high costs, terrible side effects, or limited effectiveness. Consequently, new medicines are urgently needed. RNA editing ligase 1 is an important protein critical for the survival of Trypanosoma brucei, the unicellular parasite that causes African sleeping sickness. In this paper, we describe our recent efforts to use advanced computer techniques to identify chemicals predicted to prevent RNA editing ligase 1 from functioning properly. We subsequently tested our predicted chemicals and confirmed that a number of them inhibited the protein's function. Additionally, one of the chemicals was effective at stopping the growth of the parasite in culture. Although substantial work remains to be done in order to optimize these chemicals so they are effective and safe to use in human patients, the identification of these parasite-killing compounds is nevertheless a valuable step towards finding a better cure for this devastating disease

Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments.

We report a technique to selectively and continuously label the proteomes of individual cell types in coculture, named cell type-specific labeling using amino acid precursors (CTAP). Through transgenic expression of exogenous amino acid biosynthesis enzymes, vertebrate cells overcome their dependence on supplemented essential amino acids and can be selectively labeled through metabolic incorporation of amino acids produced from heavy isotope-labeled precursors. When testing CTAP in several human and mouse cell lines, we could differentially label the proteomes of distinct cell populations in coculture and determine the relative expression of proteins by quantitative mass spectrometry. In addition, using CTAP we identified the cell of origin of extracellular proteins secreted from cells in coculture. We believe that this method, which allows linking of proteins to their cell source, will be useful in studies of cell-cell communication and potentially for discovery of biomarkers

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Soil warming accelerates decomposition of fine woody debris

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Plant and Soil 356 (2012): 405-417, doi:10.1007/s11104-012-1130-x.Soil warming from global climate change could increase decomposition of fine woody debris (FWD), but debris size and quality may mitigate this effect. The goal of this study was to investigate the effect of soil warming on decomposition of fine woody debris of differing size and quality. We placed FWD of two size classes (2 × 20 cm and 4 × 40 cm) and four species (Acer saccharum, Betula lenta, Quercus rubra and Tsuga canadensis) in a soil warming and ambient area at Harvard Forest in central Massachusetts. We collected the debris from each area over two years and measured mass loss and lignin concentration. Warming increased mass loss for all species and size classes (by as much as 30%), but larger debris and debris with higher initial lignin content decomposed slower than smaller debris and debris with lower initial lignin content. Lignin degradation did not follow the same trends as mass loss. Lignin loss from the most lignin-rich species, T. canadensis, was the highest despite the fact that it lost mass the slowest. Our results suggest that soil warming will increase decomposition of FWD in temperate forests. It is imperative that future models and policy efforts account for this potential shift in the carbon storage pool

Aging Skin: Nourishing from Out-In. Lessons from Wound Healing

Skin lesion therapy, peculiarly in the elderly, cannot be isolated from understanding that the skin is an important organ consisting of different tissues. Furthermore, dermis health is fundamental for epidermis integrity, and so adequate nourishment is mandatory in maintaining skin integrity. The dermis nourishes the epidermis, and a healthy epidermis protects the dermis from the environment, so nourishing the dermis through the epidermal barrier is a technical problem yet to be resolved. This is also a consequence of the laws and regulations restricting cosmetics, which cannot have properties that pass the epidermal layer. There is higher investment in cosmetics than in the pharmaceutical industry dealing with skin therapies, because the costs of drug registration are enormous and the field is unprofitable. Still, wound healing may be seen as an opportunity to “feed” the dermis directly. It could also verify whether providing substrates could promote efficient healing and test optimal skin integrity maintenance, if not skin rejuvenation, in an ever aging population

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits

Patterns of Loss and Regeneration of Tropical Dry Forest in Madagascar: The Social Institutional Context

Loss of tropical forests and changes in land-use/land-cover are of growing concern worldwide. Although knowledge exists about the institutional context in which tropical forest loss is embedded, little is known about the role of social institutions in influencing regeneration of tropical forests. In the present study we used Landsat images from southern Madagascar from three different years (1984, 1993 and 2000) and covering 5500 km(2), and made a time-series analysis of three distinct large-scale patterns: 1) loss of forest cover, 2) increased forest cover, and 3) stable forest cover. Institutional characteristics underlying these three patterns were analyzed, testing the hypothesis that forest cover change is a function of strength and enforcement of local social institutions. The results showed a minor decrease of 7% total forest cover in the study area during the whole period 1984–2000, but an overall net increase of 4% during the period 1993–2000. The highest loss of forest cover occurred in a low human population density area with long distances to markets, while a stable forest cover occurred in the area with highest population density and good market access. Analyses of institutions revealed that loss of forest cover occurred mainly in areas characterized by insecure property rights, while areas with well-defined property rights showed either regenerating or stable forest cover. The results thus corroborate our hypothesis. The large-scale spontaneous regeneration dominated by native endemic species appears to be a result of a combination of changes in precipitation, migration and decreased human population and livestock grazing pressure, but under conditions of maintained and well-defined property rights. Our study emphasizes the large capacity of a semi-arid system to spontaneously regenerate, triggered by decreased pressures, but where existing social institutions mitigate other drivers of deforestation and alternative land-use

Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors

BACKGROUND: PAX6 is a transcription factor playing a crucial role in the development of the eye and in the differentiation of the pancreatic endocrine cells as well as of enteroendocrine cells. Studies on the mouse Pax6 gene have shown that sequences upstream from the P0 promoter are required for expression in the lens and the pancreas; but there remain discrepancies regarding the precise location of the pancreatic regulatory elements. RESULTS: Due to genome duplication in the evolution of ray-finned fishes, zebrafish has two pax6 genes, pax6a and pax6b. While both zebrafish pax6 genes are expressed in the developing eye and nervous system, only pax6b is expressed in the endocrine cells of the pancreas. To investigate the cause of this differential expression, we used a combination of in silico, in vivo and in vitro approaches. We show that the pax6b P0 promoter targets expression to endocrine pancreatic cells and also to enteroendocrine cells, retinal neurons and the telencephalon of transgenic zebrafish. Deletion analyses indicate that strong pancreatic expression of the pax6b gene relies on the combined action of two conserved regulatory enhancers, called regions A and C. By means of gel shift assays, we detected binding of the homeoproteins PDX1, PBX and PREP to several cis-elements of these regions. In constrast, regions A and C of the zebrafish pax6a gene are not active in the pancreas, this difference being attributable to sequence divergences within two cis-elements binding the pancreatic homeoprotein PDX1. CONCLUSION: Our data indicate a conserved role of enhancers A and C in the pancreatic expression of pax6b and emphasize the importance of the homeoproteins PBX and PREP cooperating with PDX1, in activating pax6b expression in endocrine pancreatic cells. This study also provides a striking example of how adaptative evolution of gene regulatory sequences upon gene duplication progressively leads to subfunctionalization of the paralogous gene pair