Fertility preservation in pre-pubertal girls with cancer : the role of ovarian tissue cryopreservation

Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.With increasing numbers of survivors of cancer in young people future fertility and ovarian function are important considerations that should be discussed before treatment commences. Some young people, by nature of the treatment they will receive, are at high risk of premature ovarian insufficiency and infertility. For them, ovarian tissue cryopreservation (OTC) is one approach to fertility preservation that remains both invasive and for young patients experimental. There are important ethical and consent issues that need to be explored and accepted before OTC can be considered established in children with cancer. In this review we have discussed a framework for patient selection which has been shown to be effective in identifying those patients at high risk of premature ovarian insufficiency (POI) and who can be offered OTC safely.PostprintPeer reviewe

Human ovarian reserve from conception to the menopause

Current understanding is that the human ovary contains a fixed number of several million non-growing follicles (NGF), established by five months of gestational age, that declines with increasing age to the menopause when approximately 1,000 NGF remain at an average age of 50-51 years. With approximately 450 ovulatory monthly cycles in the normal human reproductive lifespan, this progressive decline in NGF numbers is attributed to follicle death by apoptosis. Individual histological studies have quantified NGF numbers over limited age ranges. However, no model describing the rate of establishment and decline of the NGF population from conception to menopause has been previously reported. Here we describe the best fitting model of the age-related NGF population in the human ovary from conception to menopause. Our model matches the log-adjusted NGF population to a five-parameter asymmetric double Gaussian cumulative (ADC) curve (r2 = 0.81). Furthermore we found that the rate of NGF recruitment into growing follicles for all women increases from birth until approximately age 14 years (coinciding with puberty) then decreases towards the menopause. The explanation for this new finding remains unclear but is likely to involve both paracrine and endocrine factors. We describe and analyse the best fitting model for the establishment and decline of human NGF; our model extends our current understanding of human ovarian reserve

Non-growing follicle density is increased following adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy in the adult human ovary

Funded by UK Medical Research Council Grants G0901839 and MR/L00299X/1.Study question: Do the chemotherapeutic regimens of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) or OEPA-COPDAC (combined vincristine, etoposide, prednisone, doxorubicin (OEPA) and cyclophosphamide, vincristine, prednisone, dacarbazine (COPDAC)) used to treat Hodgkin lymphoma (HL), affect the density, morphology and in vitro developmental potential of human ovarian follicles? Summary answer: Ovarian tissue from women treated with ABVD contained a higher density of non-growing follicles (NGFs) per cubic millimetre and increased numbers of multiovular follicles but showed reduced in vitro growth compared with patients with lymphoma who had not received chemotherapy, patients treated with OEPA-COPDAC, age-matched healthy women and age-related model-predicted values. What is known already: Chemotherapy regimens can cause a loss of follicles within the ovary that depends on the drugs given. Early stage HL is commonly treated by ABVD, a non-alkylating regimen which apparently has ovarian sparing qualities, thus it is important to investigate the histological appearance and distribution of follicles within ABVD-treated ovarian tissue. Study design, size, duration: Thirteen ovarian biopsies were obtained from HL patients (6 adolescents and 7 adults) and one biopsy from a non-HL patient. Two HL patients and the non-HL patient had received no treatment prior to biopsy collection. The remaining 11 HL patients received one of two regimens; ABVD or OEPA-COPDAC. Tissue was analysed histologically and compared to biopsies from healthy women, and in a sub-group of patients, tissue was cultured for 6 days in vitro. Participants/materials, setting, methods: Ovarian biopsies were obtained from patients undergoing ovarian cryopreservation for fertility preservation, and from healthy women at the time of Caesarian section (‘obstetric tissue’). Follicle number and maturity were evaluated in sections of ovarian cortical tissue, and compared to an age-related model of mean follicle density and to age-matched contemporaneous biopsies. The developmental potential of follicles was investigated after 6 days tissue culture. Main results and the role of chance: A total of 6877 follicles was analysed. ABVD-treated tissue contained a higher density of non-growing follicles/mm3 (230±17) (mean±SEM) than untreated (110±54), OEPA-COPDAC-treated (50±27 and obstetric tissue (20±4)(P< 0.01),with follicle density 9-21 standard deviations higher than predicted by an age-related model. Bi-ovular and binucleated non-growing follicles occurred frequently in ABVD-treated and in adolescent untreated tissue but were not observed in OEPA-COPDAC-treated or obstetric tissue, although OEPA-COPDAC-treated tissue contained a high proportion of morphologically abnormal oocytes (52% versus 23% in untreated, 22% in ABVD-treated and 25% in obstetric tissue; P< 0.001). Activation of follicle growth in vitro occurred in all groups, but in ABVD-treated samples there was very limited development to the secondary stage, whilst in untreated samples from lymphoma patients growth was similar to that observed in obstetric tissue (untreated; P< 0.01 versus ABVD-treated, ns versus obstetric). Large scale data: N/A Limitations, reasons for caution: Although a large number of follicles were analysed, these data were derived from a small number of biopsies. The mechanisms underpinning these observations have yet to be determined and it is unclear how they relate to future fertility. Wider implications of the findings: This study confirms that the number of NGFs is not depleted following ABVD treatment, consistent with clinical data that female fertility is preserved. Our findings demonstrate that immature follicle density can increase as well as decrease following at least one chemotherapy treatment. This is the first report of morphological and follicle developmental similarities between ABVD-treated tissue and the immature human ovary. Further experiments will investigate the basis for the marked increase in follicle density in ABVD-treated tissue.PostprintPeer reviewe

Permanent Draft Genome sequence for Frankia sp. strain CcI49, a Nitrogen-Fixing Bacterium Isolated from Casuarina cunninghamiana that Infects Elaeagnaceae

Frankia sp. strain CcI49 was isolated from Casuarina cunninghamiana nodules. However the strain was unable to re-infect Casuarina, but was able to infect other actinorhizal plants including Elaeagnaceae. Here, we report the 9.8-Mbp draft genome sequence of Frankia sp. strain CcI49 with a G+C content of 70.5 % and 7,441 candidate protein-encoding genes. Analysis of the genome revealed the presence of a bph operon involved in the degradation of biphenyls and polychlorinated biphenyls

MapMySmoke : feasibility of a new quit cigarette smoking mobile phone application using integrated geo-positioning technology, and motivational messaging within a primary care setting

This work was funded in part by an NHS Fife Research and Development Bursary Award to all authors. In addition, we have received funding from the University of St Andrews’ EPSRC Impact Acceleration Account. In 2013, Schick received a LEADERS award from the Scottish Universities Life Sciences Alliance that started this project.Background:  Approximately 11,000 people die in Scotland each year as a result of smoking-related causes. Quitting smoking is relatively easy; maintaining a quit attempt is a very difficult task with success rates for unaided quit attempts stubbornly remaining in the single digits. Pharmaceutical treatment can improve these rates by lowering the overall reward factor of nicotine. However, these and related nicotine replacement therapies do not operate on, or address, the spatial and contextual aspects of smoking behaviour. With the ubiquity of smartphones that can log spatial, quantitative and qualitative data related to smoking behaviour, there exists a person-centred clinical opportunity to support smokers attempting to quit by first understanding their smoking behaviour and subsequently sending them dynamic messages to encourage health behaviour change within a situational context. Methods:  We have built a smartphone app—MapMySmoke—that works on Android and iOS platforms. The deployment of this app within a clinical National Health Service (NHS) setting has two distinct phases: (1) a 2-week logging phase where pre-quit patients log all of their smoking and craving events; and (2) a post-quit phase where users receive dynamic support messages and can continue to log craving events, and should they occur, relapse events. Following the initial logging phase, patients consult with their general practitioner (GP) or healthcare provider to review their smoking patterns and to outline a precise, individualised quit attempt plan. Our feasibility study consists of assessment of an initial app version during and after use by eight patients recruited from an NHS Fife GP practice. In addition to evaluation of the app as a potential smoking cessation aid, we have assessed the user experience, technological requirements and security of the data flow. Results:  In an initial feasibility study, we have deployed the app for a small number of patients within one GP practice in NHS Fife. We recruited eight patients within one surgery, four of whom actively logged information about their smoking behaviour. Initial feedback was very positive, and users indicated a willingness to log their craving and smoking events. In addition, two out of three patients who completed follow-up interviews noted that the app helped them reduce the number of cigarettes they smoked per day, while the third indicated that it had helped them quit. The study highlighted the use of pushed notifications as a potential technology for maintaining quit attempts, and the security of collection of data was audited. These initial results influenced the design of a planned second larger study, comprised of 100 patients, the primary objectives of which are to use statistical modelling to identify times and places of probable switches into smoking states, and to target these times with dynamic health behaviour messaging. Conclusions:  While the health benefits of quitting smoking are unequivocal, such behaviour change is very difficult to achieve. Many factors are likely to contribute to maintaining smoking behaviour, yet the precise role of cues derived from the spatial environment remains unclear. The rise of smartphones, therefore, allows clinicians the opportunity to better understand the spatial aspects of smoking behaviour and affords them the opportunity to push targeted individualised health support messages at vulnerable times and places.Publisher PDFPeer reviewe

The Infrared Properties of Hickson Compact Groups

Compact groups of galaxies provide a unique environment to study the mechanisms by which star formation occurs amid continuous gravitational encounters. We present 2MASS (JHK), Spitzer IRAC (3.5-8 micron) and MIPS (24 micron) observations of a sample of twelve Hickson Compact Groups (HCGs 2, 7, 16, 19, 22, 31, 42, 48, 59, 61, 62, and 90) that includes a total of 45 galaxies. The near-infrared colors of the sample galaxies are largely consistent with being dominated by slightly reddened normal stellar populations. Galaxies that have the most significant PAH and/or hot dust emission (as inferred from excess 8 micron flux) also tend to have larger amounts of extinction and/or K-band excess and stronger 24 micron emission, all of which suggest ongoing star formation activity. We separate the twelve HCGs in our sample into three types based on the ratio of the group HI mass to dynamical mass. We find evidence that galaxies in the most gas-rich groups tend to be the most actively star forming. Galaxies in the most gas-poor groups tend to be tightly clustered around a narrow range in colors consistent with the integrated light from a normal stellar population. We interpret these trends as indicating that galaxies in gas-rich groups experience star formation and/or nuclear actively until their neutral gas consumed, stripped, or ionized. The galaxies in this sample exhibit a ``gap'' between gas-rich and gas-poor groups in infrared color space that is sparsely populated and not seen in the Spitzer First Look Survey sample. This gap may suggest a rapid evolution of galaxy properties in response to dynamical effects. These results suggest that the global properties of the groups and the local properties of the galaxies are connected.Comment: 34 pages, 26 figures, accepted for publication in AJ, higher quality images available in publicatio

Draft Genome Sequences of 10 Bacterial Strains Isolated from Root Nodules of Alnus Trees in New Hampshire

Here, we report the draft genome sequences obtained for 10 bacterial strains isolated from root nodules of Alnus trees. These members of the nodule microbiome were sequenced to determine their potential functional roles in plant health. The selected strains belong to the genera Rhodococcus, Kocuria, Rothia, Herbaspirillum, Streptomyces, and Thiopseudomonas

The Use of a Visual Motor Test to Identify Lingering Deficits in Concussed Collegiate Athletes

Background: Emerging evidence suggests neurophysiological deficits, such as visual motor coordination (VMC), may persist beyond clinical concussion recovery. Instrumented measurement of upper-limb VMC is critical for neurological evaluation post-concussion and may identify persistent deficits further elucidating persistent neurophysiological impairments not detected by the current clinical assessment battery. Aim: The aim of the study was to determine if a VMC test identifies persistent deficits in concussed collegiate student-athletes who have returned to baseline on clinical concussion assessments. Methods: Thirteen recently concussed intercollegiate student-athletes (male: 7, 18.9±0.7 years, 175.5±12.4 cm, 75.5±23.2 kg), and 13 matched control student-athletes (male: 7, 19.3±1.1 years, 173.5±11.9 cm, 75.8±19.9 kg) completed two testing sessions (T1: \u3c48 h after clinical recovery; T2: 30 days post-concussion) on a visual motor exam. The outcome measures were A* Average score (average number of lights hit on A* exam), simple visual reaction time (SVRT)-RT, and movement time (SVRT-MT) on the Dynavision D2. The dependent variables were compared with a 2 (group) × 2 (time) repeated measures ANOVAs. Results: There was no group interaction in A* average score (F(1,24)=0.036, P=0.849), SVRT-RT (F(1,22)=0.319, P=0.575), and SVRT-MT (F(1,22)=1.179, P=0.188). There was a main effect for time on A* average score (T1: 76.3±10.4 hits; T2: 82.7±11.2 hits; F(1,24)=38.1, P≤0.001) and SVRT-RT (T1: 0.31±0.04; T2: 0.29±0.04 s; F(1,22)=4.9, P=0.039). There was no main effect for SVRT-MT. There were no group differences at either time point. Conclusions: Among recently concussed collegiate student-athletes, no persistent deficits were identified in VMC beyond clinical recovery when assessed by Dynavision D2. This VMC exam may not provide a useful means of tracking recovery following concussion likely due to a substantial practice effect. Relevance for patients: While post-concussion neurophysiological deficits persist beyond clinical recovery, the laboratory based VMC assessment herein did not identify deficits at critical post-concussion time points. Therefore, other clinically translatable VMC assessments should be further investigated