Knowledge priorities on climate change and water in the Upper Indus Basin: a horizon scanning exercise to identify the top 100 research questions in social and natural sciences

River systems originating from the Upper Indus Basin (UIB) are dominated by runoff from snow and glacier melt and summer monsoonal rainfall. These water resources are highly stressed as huge populations of people living in this region depend on them, including for agriculture, domestic use, and energy production. Projections suggest that the UIB region will be affected by considerable (yet poorly quantified) changes to the seasonality and composition of runoff in the future, which are likely to have considerable impacts on these supplies. Given how directly and indirectly communities and ecosystems are dependent on these resources and the growing pressure on them due to ever-increasing demands, the impacts of climate change pose considerable adaptation challenges. The strong linkages between hydroclimate, cryosphere, water resources, and human activities within the UIB suggest that a multi- and inter-disciplinary research approach integrating the social and natural/environmental sciences is critical for successful adaptation to ongoing and future hydrological and climate change. Here we use a horizon scanning technique to identify the Top 100 questions related to the most pressing knowledge gaps and research priorities in social and natural sciences on climate change and water in the UIB. These questions are on the margins of current thinking and investigation and are clustered into 14 themes, covering three overarching topics of “governance, policy, and sustainable solutions”, “socioeconomic processes and livelihoods”, and “integrated Earth System processes”. Raising awareness of these cutting-edge knowledge gaps and opportunities will hopefully encourage researchers, funding bodies, practitioners, and policy makers to address them

Knowledge Priorities on Climate Change and Water in the Upper Indus Basin: A Horizon Scanning Exercise to Identify the Top 100 Research Questions in Social and Natural Sciences

River systems originating from the Upper Indus Basin (UIB) are dominated by runoff from snow and glacier melt and summer monsoonal rainfall. These water resources are highly stressed as huge populations of people living in this region depend on them, including for agriculture, domestic use, and energy production. Projections suggest that the UIB region will be affected by considerable (yet poorly quantified) changes to the seasonality and composition of runoff in the future, which are likely to have considerable impacts on these supplies. Given how directly and indirectly communities and ecosystems are dependent on these resources and the growing pressure on them due to ever-increasing demands, the impacts of climate change pose considerable adaptation challenges. The strong linkages between hydroclimate, cryosphere, water resources, and human activities within the UIB suggest that a multi- and inter-disciplinary research approach integrating the social and natural/environmental sciences is critical for successful adaptation to ongoing and future hydrological and climate change. Here we use a horizon scanning technique to identify the Top 100 questions related to the most pressing knowledge gaps and research priorities in social and natural sciences on climate change and water in the UIB. These questions are on the margins of current thinking and investigation and are clustered into 14 themes, covering three overarching topics of ‘governance, policy, and sustainable solutions’, ‘socioeconomic processes and livelihoods’, and ‘integrated Earth System processes’. Raising awareness of these cutting-edge knowledge gaps and opportunities will hopefully encourage researchers, funding bodies, practitioners, and policy makers to address them

Oocyte cryopreservation in oncological patients: different stimulation protocols

The study is a retrospective analysis about 21 cancer patients occur to our center, Department of Reproductive Medicine of The University of Pisa, in order to preserve their fertility before cancer treatment. We investigate the use of different stimulation protocol, according to different phases of menstrual cycle and according to cancer disease. Patients were divided into two group depending on the phase of menstrual cycle, follicular or luteal phase, at the moment of first examination. Standard stimulation protocol with gonadotropins is admistered in the follicular group, whereas in the second group we use GnRH-anatgonist before gonadotropins somministration in order to have a rapid luteolysis. Among the 21 cancer patients, two are affected by breast cancer. These patients receive a controlled ovarian stimulation with a combined letrozole-gonadotropins protocol after GnRH-antagonist induced luteolysis. The outcome measures are number of days needed before starting procedure, duration of stimulation, cumulative dosage of gonadotropins number of oocyte retrieved and percentage of mature oocytes. We focus our attention also on estradiol levels during ovarian stimulation. The results don’t show any differences between two groups if we consider days of stimulation, total amount of gonadotropins administered and the number of good mature quality oocytes retrieved. Moreover estradiol levels in letrozole group are lower than those in other patients. This study suggests that oocytes can be obtained before cancer treatment irrespective of menstrual cycle phase without compromising the efficacy of procedure. Moreover starting ovarian stimulation anytime during menstrual cycle allows to patients to not postpone the beginning of cancer treatment. Different stimulation protocols, according to different kinf of diasese, are available in order to obtain the maximum results without any complication for patients

CANCER&PREMATURE OVARIAN FAILURE: NEW STRATEGIES TO PREVENT OVARIAN LOSS DURING CHEMOTHERAPY

Cancer can be a devastating diagnosis. Despite the considerable advances done and the extensive knowledge acquired over time, it remains a major health problem with repercussions not only on a physical level, but also on the psychological and social spheres. Increases in the number of individuals diagnosed with cancer each year, due in large part to aging and growth of the population, as well as improving survival rates, have led to an ever-increasing number of “cancer survivors”. This denomination is used to describe any person who has been diagnosed with cancer, from the time of diagnosis through the balance of life. The goal of treatment is to ‘‘cure’’ the cancer, or prolong survival in patients with advanced disease, meanwhile preserving the highest possible quality of life in both the long and short term. Many survivors, even among those who are cancer free, must cope with the long-term effects of treatment, as well as psychological concerns such as fear of recurrence. Loss of fertility is one of the most devastating consequences of radio- or cytotoxic therapy for these young patients who, having overcome their disease, have expectations of a normal reproductive life. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. Fertility preservation and the ability to maintain future parenthood are issues that present and persist from the moment of a cancer diagnosis and they are essential components of a comprehensive approach to cancer treatment. In female cancer patient, various strategies have been used for fertility preservation. The combining use of GnRH agonist or oral contraceptive during chemotherapy is common but not so effective in order to protect ovary and fertility. To date, embryo cryopreservation is the only method widely used for fertility preservation. However, if it is not allowed or not available both oocyte cryopreservation and ovarian tissue banking followed by tissue transplant have also been successful. Each approach has associated advantages and disadvantages relating to current success rate, required delay in cancer treatment, sperm requirement, and risk of reintroducing cancer cells. chemotherapy and infertility The ovary is susceptible to chemotherapy-induced damage, particularly following treatment with alkylating agents such as cyclophosphamide. Ovarian damage is drug and dose-dependent and it’s related to age at the time of treatment, with progressively smaller doses required to produce ovarian failure with increasing age. The effect of chemotherapy on the ovary is not an “all or nothing” phenomenon and the number of surviving primordial follicles following exposure to chemotherapy correlates inversely with the dose of chemotherapy and the nature of agent. Histological studies of human ovaries have shown chemotherapy to cause ovarian atrophy and global loss of primordial follicles. A few human and animal studies have demonstrated that chemotherapy induces damage to ovarian pre-granulosa cells and that apoptosis occurs during oocyte and follicle loss. In addition, injury blood vessels and focal fibrosis of the ovarian cortex are further patterns of ovarian damage caused by chemotherapy. Study in animals show that the loss of inhibitory influence of small growing follicle on initiation of primordial follicle growth will result in increased activation of the resting pool of primordial follicles which will be further destroyed by chemotherapy. Recent studies have demonstrated that the aqueous extract of saffron (SE), rich in carotenoids, has antitumor effects and radical scavenger properties. By virtue of its antioxidant properties, we propose herein a possible role of SE in protecting ovary from chemotoxic effects in a mouse model

A novel system for single-port laparoscopic surgery: preliminary experience

Aims: To present preliminary data of single-access laparoscopic surgery with a new device for the treatment of benign adnexal pathologies. Methods: Ten women with benign adnexal pathologies underwent salpingectomy (n = 4) and ovarian/para-ovarian cyst enucleation (n = 6) using a laparo-endoscopic single-port approach with an innovative advanced multiport reusable trocar inserted transumbilically through a small wound retractor. Trocar introduction time, operative time, estimated blood loss, conversion to standard laparoscopy, peri- and postoperative complications, hospital stay and Visual Analog Scale score (as assessment of pain and cosmesis) were analyzed. Results: Port placement was successful in all patients. Mean trocar introduction time was 4.4 min (range 3.4-5.3 min) and no intra or postoperative complication occurred. The mean operating time was 50.0 ± 9.2 min and mean blood loss was 28.5 ± 8.8 ml. The mean hospital stay following surgery was 1.6 ± 0.5 days and convalescence was complete in 1 week. Neither scores for postoperative incisional pain nor cosmesis side effects have been observed in any subjects. Conclusion: We concluded that adnexal single-port surgery performed with this innovative advanced surgical instrumentation is a feasible, safe, and effective technique that drastically reduces postoperative pain and does not compromise cosmetic appearance. The isolation of the operative field by means of the drape prevents the contamination of the port site that occurs frequently, and mainly in adnexal pathologies of uncertain etiology. In addition, the ease of insertion and the conformation of the new port access also make the procedure feasible in obese patients

Premature ovarian insufficiency: current progress and future prospectives

Premature Ovarian Insufficiency (POI) is de- fined as the occurrence of hypergonadotrophic hypoestrogenic amenorrhea in women under the age of 40 years. POI represents the end of a gradual process of loss of primordial follicles that evolves silently to premature menopause. POI can be primary or induced by radiation, chemotherapy or surgery. The majority of spontaneous POI is idiopathic. No guidelines have been established regarding management of infertility in POI patients and currently no interventions have shown to remarkably in- crease the prospective of spontaneous concep- tion. As a consequence, in the majority of these patients the only opportunity of childbearing is eggs donation or adoption. Certainly, early di- agnosis is crucial to counsel POI patients about their future prospective of childbearing and possibly address them to oocytes cryopreservaion. The only possibility for patients to conceive with their own gametes, is when the diagnosis is made during the “transitional phase”, when amenorrhea and menopausal symptoms have not yet arisen. Although, some researchers have shown the persistence of meiosis and primordial follicles replenishment even during postnatal life in animal models, other researchers reported less optimistic results. Future research should focus on this topic and on the possibility to stop, or at least to slow down, ovarian ageing

Follicular fluid VEGF levels directly correlate with perifollicular blood flow in normoresponder patients undergoing IVF

It has become increasingly clear that the follicular microenvironment of the maturing human oocyte is a determining factor for the implantation potential of an embryo deriving from that oocyte. Indeed the quality and maturity of an oocyte are influenced by the level of intrafollicular oxygen content which, in turn, is proportional to the degree of follicular vascularity. The aim of the study was to establish whether there is a relationship between follicular fluid VEGF concentrations, perifollicular vascularity and reproductive outcome in normal responders under the age of 35 undergoing IVF. MATERIALS AND METHODS: Sixty-one consecutive patients, all at their first IVF cycle, were included in the study. All patients had primary infertility due to male factor or tubal factor. At oocyte retrieval, the perifollicular vascularity of two follicles per ovary was estimated qualitatively through power Doppler blood flow, for a total of two hundred forty-four follicles. The follicular fluid from the identified follicles was centrifuged and stored until VEGF assay. The maturity and fertilization rate of the corresponding oocytes as well as embryo quality and pregnancy rate were recorded. RESULTS: In our study, we found VEGF levels to be significantly correlated with grade of perifollicular vascularity. Oocytes obtained from follicles with the higher grade of vascularization also showed a higher rate of fertilization, embryos, a better quality and higher pregnancy rates were obtained in women with highly vascularized follicles. Perifollicular blood flow doppler indices seem to predict oocyte viability and quality. Moreover, VEGF may play a potential role in the development of the perifollicular capillary network. DISCUSSION: The ability of a given follicle to express VEGF and develop an adequate vascular network may be inter-related in patients under the age of 35. An adequate blood supply may be fundamental important in the regulation of intrafollicular oxygen levels and the determination of oocyte quality