Uterus transplantation has proven to be a successful treatment for women with absolute uterine infertility, caused either by the absence of a uterus or the presence of a nonfunctioning uterus. We ...report the first birth of a healthy child following uterus transplantation in the United States, from a recipient of a uterus allograft procured from an altruistic living donor. Two major modifications from the previously reported live births characterized this uterus transplant. First, the transplanted uterus relied upon and sustained the pregnancy while having only the utero‐ovarian vein as venous outflow. The implication is a significantly simplified living donor surgery that paves the way for minimally invasive laparoscopic or robot‐assisted techniques for the donor hysterectomy. Second, the time from transplantation to embryo transfer was significantly shortened from prior protocols, allowing for an overall shorter exposure to immunosuppression by the recipient and lowering the risk for potential adverse effects from these medications.
Testa et al report the first live birth in the United States after uterus transplantation, with two major modifications from the previously reported live births: The transplanted uterus relied upon and sustained the pregnancy while having only the utero‐ovarian vein as venous outflow, and the time from transplantation to embryo transfer was significantly shortened from prior protocols.
Uterus transplantation is a vascularized composite allograft transplantation. It allows women who do not have a uterus to become pregnant and deliver a baby. In this paper, we analyze the first five ...cases of living donor uterus transplantation performed in the United States. The first three recipients lost their uterus grafts at days 14, 12, and 6, respectively, after transplant. Vascular complications, related to both inflow and outflow problems, were identified as the primary reason for the graft losses. Two recipients, at 6 and 3 mo, respectively, after transplant, have functioning grafts with regular menstrual cycles. Ultimate success will be claimed only after a live birth. This paper is an in‐depth analysis of evaluation, surgical technique, and follow‐up of these five living donor uterus transplants. The lessons learned were instrumental in allowing us to evolve from failure to technical and functional success. We aim to share our conclusions and build on knowledge in the evolving field of uterus transplantation.
This analysis of the first five living donor uterus transplantations in the United States and the lessons learned regarding surgical technique and postoperative follow‐up could facilitate the transition from initial failure to technical and functional success.
A multifunctional lab-on-a-chip platform for spectroscopic analysis of liquid samples based on an optofluidic jet waveguide is reported. The optofluidic detection scheme is achieved through the total ...internal reflection arising in a liquid jet of only 150 μm diameter, leading to highly efficient signal excitation and collection. This results in an optofluidic chip with an alignment-free spectroscopic detection scheme, which avoids any background from the sample container. This platform has been designed for multiwavelength fluorescence and Raman spectroscopy. The chip integrates a recirculation system that reduces the required sample volume. The evaluation of the device performance has been accomplished by means of fluorescence measurements performed on eosin Y in water solutions, achieving a limit of detection of 33 pM. The sensor has been applied in Raman spectroscopy of water-ethanol solutions, leading to a limit of detection of 0.18%. As additional application, analysis of riboflavin using fluorescence detection demonstrates the possibility of detecting this vitamin at the 560 pM level (0.21 ng l
). Although measurements have been performed by means of a compact and low-cost spectrometer, in both cases the micro-jet optofluidic chip achieved similar performances if not better than high-end benchtop based laboratory equipment. This approach paves the way towards portable lab-on-a-chip devices for high sensitivity environmental and biochemical sensing, using optical spectroscopy.
•The practical experience of hemp cultivation in Europe and China was reviewed.•Hemp holds a great potential in the frame of the developing bio-based economy.•Knowledge on the effects of G×M×E on ...hemp quality characteristics is limited.•New hemp varieties tailored to specific end-uses need to be developed.
Hemp (Cannabis sativa L.) is a multiuse, multifunctional crop that provides raw material to a large number of traditional and innovative industrial applications. A relatively simple, low input cultivation technique and the sustainability of its products are the main drivers for a future expansion of the hemp crop. In Europe, the large political support of bioenergy in recent years has fuelled numerous studies on the potential cultivation of hemp for bioenergy production. In China the main drivers for a renewed interest in hemp are its traditional applications. For any given destination, the main target of hemp cultivation is the maximization of biomass production, but each end-use destination has specific quality requirements in terms of properties of the bast fibre, characteristics of the oil and proteins in the seeds, or profile of secondary metabolites in the inflorescence.
In this paper, traditional and innovative end use destinations and cultivation systems for hemp are introduced, together with some notes on hemp botany, biology, and resource use efficiency. This information, together with a review of the practical experience of hemp cultivation in Europe and China and knowledge gathered form scientific literature, highlights the effect of agronomic factors in determining the yield potential and quality level of hemp for specific end use destinations. To conclude, future perspectives and recommendations for hemp cultivation and research are discussed.
To date more than 4000 compounds are recognized to belong to the class of flavonoids. These natural phenolic drugs are poorly soluble in water and are rapidly degraded and metabolized in the human ...body, but nevertheless are very promising for their potential contribution to the prevention and therapy of major chronic diseases, including cardiovascular and neurodegenerative diseases and cancer. In recent years a number of flavanols (e.g. catechins), flavonols (e.g. quercetin, myricetin) and isoflavones (e.g. genistein, daidzein) have been confirmed to possess strong antioxidant, anti-inflammatory, anti-proliferative and anti-aging activities. Incorporation into lipidic or polymer-based nanoparticles appears to markedly help the oral delivery of flavonoids, as these particles can protect the drug from degradation in the gastrointestinal tract and, by virtue of their unique absorption mechanism through the lymphatic system, also from first-pass metabolism in the liver. In addition, both oral and parenteral administration of flavonoids exploits a pharmacologic delivery route that guarantees sustained release of the active principle at the desired site of action. A comprehensive review of studies currently available on the in vitro and in vivo experimental administration of flavonoids by means of nanovectors may be of use as a foundation for the development of advanced delivery systems for these powerful compounds, in view of their adoption in primary and secondary disease prevention.
Notch signaling deregulation is linked to the onset of several tumors including T-cell acute lymphoblastic leukemia (T-ALL). Deregulated microRNA (miRNA) expression is also associated with several ...cancers, including leukemias. However, the transcriptional regulators of miRNAs, as well as the relationships between Notch signaling and miRNA deregulation, are poorly understood. To identify miRNAs regulated by Notch pathway, we performed microarray-based miRNA profiling of several Notch-expressing T-ALL models. Among seven miRNAs, consistently regulated by overexpressing or silencing Notch3, we focused our attention on miR-223, whose putative promoter analysis revealed a conserved RBPjk binding site, which was nested to an NF-kB consensus. Luciferase and chromatin immunoprecipitation assays on the promoter region of miR-223 show that both Notch and NF-kB are novel coregulatory signals of miR-223 expression, being able to activate cooperatively the transcriptional activity of miR-223 promoter. Notably, the Notch-mediated activation of miR-223 represses the tumor suppressor FBXW7 in T-ALL cell lines. Moreover, we observed the inverse correlation of miR-223 and FBXW7 expression in a panel of T-ALL patient-derived xenografts. Finally, we show that miR-223 inhibition prevents T-ALL resistance to γ-secretase inhibitor (GSI) treatment, suggesting that miR-223 could be involved in GSI sensitivity and its inhibition may be exploited in target therapy protocols.
•An integrated full polymeric platform based on microbottle resonators is proposed.•Fast self-assembling process is adopted for microbottle fabrication.•Evanescently coupled SU8 planar waveguide are ...used for interrogation system.•The proposed microbottles packaging improves robustness to external disturbances.
An integrated full polymeric sensing platform composed by a self-assembled bottle microresonators packaged with planar waveguide in a stable structure is presented. Microbottles made of SU-8 resist and NOA resins have been fabricated and characterized. The interrogation system is constituted by evanescently coupled planar waveguide fabricated in SU-8 on polymethyl methacrylate substrate. A simple and effective method for the packaging of the microbottle has been adopted. It provides high mechanical stability to avoid surrounding disturbance able to affect the coupling efficiency between the resonator and the waveguide. The choice of polymers as fabrication material enables the use of this method for low-cost lab-on-chip production. The viability of the platform has been demonstrated via refractometric sensing establishing a bulk sensitivity of 120 nm per refractive index unit.
Bowel inflammation, impaired intestinal epithelial barrier (IEB), and gut dysbiosis could represent early events in Parkinson's disease (PD). This study examined, in a descriptive manner, the ...correlation among enteric α-synuclein, bowel inflammation, impairments of IEB and alterations of enteric bacteria in a transgenic (Tg) model of PD before brain pathology. Human A53T α-synuclein Tg mice were sacrificed at 3, 6, and 9 months of age to evaluate concomitance of enteric inflammation, IEB impairments, and enteric bacterial metabolite alterations during the early phases of α-synucleinopathy. The molecular mechanisms underlying the interplay between α-synuclein, activation of immune/inflammatory responses and IEB alterations were investigated with in vitro experiments in cell cultures. Tg mice displayed an increase in colonic levels of IL-1β, TNF, caspase-1 activity and enteric glia activation since 3 months of age. Colonic TLR-2 and zonulin-1 expression were altered in Tg mice as compared with controls. Lipopolysaccharide levels were increased in Tg animals at 3 months, while fecal butyrate and propionate levels were decreased. Co-treatment with lipopolysaccharide and α-synuclein promoted IL-1β release in the supernatant of THP-1 cells. When applied to Caco-2 cells, the THP-1-derived supernatant decreased zonulin-1 and occludin expression. Such an effect was abrogated when THP-1 cells were incubated with YVAD (caspase-1 inhibitor) or when Caco-2 were incubated with anakinra, while butyrate incubation did not prevent such decrease. Taken together, early enteric α-synuclein accumulation contributes to compromise IEB through the direct activation of canonical caspase-1-dependent inflammasome signaling. These changes could contribute both to bowel symptoms as well as central pathology.
The uterus is the most recent addition to the list of organs that can be successfully transplanted in humans. This article analyzes living donor uterus transplantation according to the ethical ...principle of equipoise. A comparison is made between living donor uterus transplantation and gestational surrogate motherhood. Both are solutions to absolute uterine infertility that allow the transfer of genetic material from intended parents to a child. The analysis concludes that living donor uterus transplantation does not violate the ethical principle of equipoise and should be considered an ethically acceptable solution to absolute uterine infertility.
This viewpoint of the ethics of living donor uterus transplantation and surrogacy under the principle of clinical equipoise suggests that living donor uterus transplantation is comparable, if not superior, to surrogacy from an ethical point of view.
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