Fitting the data from embryo implantation prediction: Learning from label proportions

Machine learning techniques have been previously used to assist clinicians to select embryos for human-assisted reproduction. This work aims to show how an appropriate modeling of the problem can contribute to improve machine learning techniques for embryo selection. In this study, a dataset of 330 consecutive cycles (and associated embryos) carried out by the Unit of Assisted Reproduction of the Hospital Donostia (Spain) throughout 18 months has been analyzed. The problem of the embryo selection has been modeled by a novel weakly supervised paradigm, learning from label proportions, which considers all the available data, including embryos whose fate cannot be certainly established. Furthermore, all the collected features, describing cycles and embryos, have been considered in a multi-variate data analysis. Our integral solution has been successfully tested. Experimental results show that the proposed technique consistently outperforms an equivalent approach based on standard supervised classification. Embryos in this study were selected for transference according to the criteria of the Spanish Association for Reproduction Biology Studies. Obtained classification models outperform these criteria, specifically reordering medium-quality embryos

Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice

In chronic hepatitis B (CHB), failure to control hepatitis B virus (HBV) is associated with T cell dysfunction. HBV transgenic mice mirror many features of the human disease, including T cell unresponsiveness, and thus represent an appropriate model in which to test novel therapeutic strategies. To date, the tolerant state of CD8+ T cells in these animals could be altered only by strong immunogens or by immunization with HBV antigen-pulsed dendritic cells; however, the effectors induced were unable to suppress viral gene expression or replication. Because of the known stimulatory properties of alpha interferon (IFN-α) and interleukin-15 (IL-15), this study explored the therapeutic potential of liver-directed gene transfer of these cytokines in a murine model of CHB using adeno-associated virus (AAV) delivery. This combination not only resulted in a reduction in the viral load in the liver and the induction of an antibody response but also gave rise to functional and specific CD8+ immunity. Furthermore, when splenic and intrahepatic lymphocytes from IFN-α- and IL-15-treated animals were transferred to new HBV carriers, partial antiviral immunity was achieved. In contrast to previous observations made using either cytokine alone, markedly attenuated PD-L1 induction in hepatic tissue was observed upon coadministration. An initial study with CHB patient samples also gave promising results. Hence, we demonstrated synergy between two stimulating cytokines, IL-15 and IFN-α, which, given together, constitute a potent approach to significantly enhance the CD8+ T cell response in a state of immune hyporesponsiveness. Such an approach may be useful for treating chronic viral infections and neoplastic conditions

Development of a heptaplex PCR assay for identification of Staphylococcus aureus and CoNS with simultaneous detection of virulence and antibiotic resistance genes

Background Staphylococcal toxicity and antibiotic resistance (STAAR) have been menacing public health. Although vancomycin-resistant Staphylococcus aureus (VRSA) is currently not as widespread as methicillin-resistant S. aureus (MRSA), genome evolution of MRSA into VRSA, including strains engineered within the same patient under anti-staphylococcal therapy, may build up to future public health concern. To further complicate diagnosis, infection control and anti-microbial chemotherapy, non-sterile sites such as the nares and the skin could contain both S. aureus and coagulase-negative staphylococci (CoNS), either of which could harbour mecA the gene driving staphylococcal methicillin-resistance and required for MRSA-VRSA evolution. Results A new heptaplex PCR assay has been developed which simultaneously detects seven markers for: i) eubacteria (16S rRNA), ii) Staphylococcus genus (tuf), iii) Staphylococcus aureus (spa), iv) CoNS (cns), v) Panton-Valentine leukocidin (pvl), vi) methicillin resistance (mecA), and vii) vancomycin resistance (vanA). Following successful validation using 255 reference bacterial strains, applicability to analyse clinical samples was evaluated by direct amplification in spiked blood cultures (n = 89) which returned 100 % specificity, negative and positive predictive values. The new assay has LoD of 1.0x103 CFU/mL for the 16S rRNA marker and 1.0x104 CFU/mL for six other markers and completes cycling in less than one hour. Conclusion The speed, sensitivity (100 %), NPV (100 %) and PPV (100 %) suggest the new heptaplex PCR assay could be easily integrated into a routine diagnostic microbiology workflow. Detection of the cns marker allows for unique identification of CoNS in mono-microbial and in poly-microbial samples containing mixtures of CoNS and S. aureus without recourse to the conventional elimination approach which is ambiguous. In addition to the SA-CoNS differential diagnostic essence of the new assay, inclusion of vanA primers will allow microbiology laboratories to stay ahead of the emerging MRSA-VRSA evolution. To the best of our knowledge, the new heptaplex PCR assay is the most multiplexed among similar PCR-based assays for simultaneous detection of STAAR

Comparative study of PrPc expression in rat, monkey and cow gastrointestinal tract

ABSTRACT: The gastrointestinal tract (GIT) appears to be the main site of entry for the pathological isoform of prions (PrPsc). To understand how the PrPsc internalization process occurs, it is important to characterize the cell types that express normal prion protein (PrPc) along the GIT. To do so, we studied the distribution of PrPc in the rat, monkey, and cow GIT. Using Western blot analysis, we found that PrPc is expressed in all digestive regions of the three species. Immunoreactivity for PrPc was found throughout the GIT in epithelial cells sharing the neuroendocrine (NE) phenotype. Immunostained cells appeared scattered throughout the epithelium of fundic and pyloric glands as well as in intestinal villi and crypts

Comparative study of PrPc expression in rat, monkey and cow gastrointestinal tract

ABSTRACT: The gastrointestinal tract (GIT) appears to be the main site of entry for the pathological isoform of prions (PrPsc). To understand how the PrPsc internalization process occurs, it is important to characterize the cell types that express normal prion protein (PrPc) along the GIT. To do so, we studied the distribution of PrPc in the rat, monkey, and cow GIT. Using Western blot analysis, we found that PrPc is expressed in all digestive regions of the three species. Immunoreactivity for PrPc was found throughout the GIT in epithelial cells sharing the neuroendocrine (NE) phenotype. Immunostained cells appeared scattered throughout the epithelium of fundic and pyloric glands as well as in intestinal villi and crypts

Repigmentation of vitiligo by transplantation of autologous melanocyte cells cultured on amniotic membrane

SIR, Vitiligo is an acquired skin disease that affects 1% of the world’s population, and which significantly impacts the quality of life of patients. In patients with stable vitiligo, lack of effective medical therapies has led to the development of surgical treatment options using transplantation of autologous melanocytes. These techniques include split-thickness grafts, punch grafts and suction blister grafts, that do not require cell expansion.1,2 Transplantation methods include cultured mixed melanocyte–keratinocyte suspension with or without carrier, and cultured pure melanocyte suspension.3,4 To date, pure single-layer melanocyte cultures have not been reported in the treatment of vitiligo, nor has the use of amniotic membrane (AM) as a scaffold been documented. The AM, the inner part of the placenta, consists of a thick basement membrane of collagen type IV and laminin, and an avascular stroma. AM has been successfully used in skin transplantation5 and has been applied for ocular surface reconstruction in patients with severe corneal diseases.6 We treated a group of five patients (four men and one woman; age range 18–56 years, mean ± SD 29 ± 13Æ2) with either focal or generalized stable vitiligo using a graft of autologous melanocytes cultured on a denuded AM (Table 1). The technique of human amniotic processing and cryopreservation with Dulbecco’s modified Eagle’s medium and 50% glycerol recommended by the U.S. Food and Drug Administration renders all the amniotic cells nonviable.7 Immediately before use, AM was treated with 0Æ02% ethylenediamin

Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes

Background and aim: Leptin, a hormone mainly produced by fat cells, acts primarily on the hypothalamus regulating energy expenditure and food intake. Leptin receptors are expressed in several tissues and the possible physiological role of leptin is being extensively investigated, with the result that important peripheral actions of the hormone in the organism are being discovered. Recent studies have demonstrated leptin and leptin receptor expression in gastric epithelial cells. In the present study, we report the presence of the long leptin receptor isoform (OB-Rb) in human, rat, and mouse small intestine, supporting the hypothesis of leptin as a hormone involved in gastrointestinal function. Methods: The presence of the leptin receptor was determined by immunocytochemical methods using antibodies against the peptide corresponding to the carboxy terminus of the long isoform of the leptin receptor. Human duodenal biopsies from normal individuals undergoing gastrointestinal endoscopy, and intestinal fragments of Wistar rats and Swiss mice were processed for the study. Results: Immunoreactivity for the long leptin receptor isoform was observed in the three studied species. Staining was located throughout the cytoplasm of the enterocytes, of both villi and crypts, and in the basolateral plasma membrane. Immunolabelling for OB-Rb protein was also found in the brush border of human enterocytes of formol and paraformaldehyde fixed samples. Conclusion: This report demonstrates the presence of the long leptin receptor isoform in the absorptive cells of rat, mouse, and human small intestine, suggesting that leptin could have a physiological role in the regulation of nutrient absorption