Fetal Medial Habenula Transplants: Innervation of the Rat Interpeduncular Nucleus

The effects of donor age and site of placement on the survival of fetal medial habenula (MH) transplants into adult rats hosts were examined. The innervation of the interpeduncular nucleus (IPN) in such cases was also examined. Explants of MH consisting of the medial-dorsal lip of the third ventricle were held in vitro for 1—2 days. Colloidal gold conjugated to wheat germ agglutinin was added for the last 18 hours to label the cells. Four of 16 cases with E19 derived transplants contained donor neurons. Markedly larger transplants were present in 95% of 20 cases with E16 derived transplants. Sites in the ventral midbrain were successful, while limited or no survival occurred at sites more remote from IPN. Retrograde labeling of transplant neurons was present in each case studied with HRP injection into host IPN. Colloidal gold-labeled macrophages, some oriented capillaries and GFAP-positive processes marked the donor-host interface. In EM the interface was evident only by the difference in tissue elements in the transplant versus host. Numerous synapses of Gray types I and II were present in the transplant. Excellent survival of MH neurons, donor/host interfaces, innervation of IPN by the transplant and fine structure in and around the transplants, all suggest that such preparations are suitable for further experimental analysis of the habenulo-interpeduncular system

RNA aptamer delivery through intact human skin

It is generally recognised that only relatively small molecular weight (typically 100,000-fold) and aptamer integrity was confirmed using an oligonucleotide precipitation assay. A Th17 response was stimulated in freshly excised human skin resulting in significantly upregulated IL-17f, and 22; topical application of the IL-23 aptamer decreased both IL-17f and IL-22 by approximately 45% but did not result in significant changes to IL-23 mRNA levels, confirming that the aptamer did not globally suppress mRNA levels. This study demonstrates that very large molecular weight RNA aptamers can permeate across the intact human skin barrier to therapeutically relevant levels into both the epidermis and dermis and that the skin penetrating aptamer retains its biologically active conformational structure capable of binding to endogenous IL-23

Exploring the facilitators and barriers to using an online infertility risk prediction tool (FoRECAsT) for young women with breast cancer: A qualitative study protocol

INTRODUCTION: As cancer treatments may impact on fertility, a high priority for young patients with breast cancer is access to evidence-based, personalised information for them and their healthcare providers to guide treatment and fertility-related decisions prior to cancer treatment. Current tools to predict fertility outcomes after breast cancer treatments are imprecise and do not offer individualised prediction. To address the gap, we are developing a novel personalised infertility risk prediction tool (FoRECAsT) for premenopausal patients with breast cancer that considers current reproductive status, planned chemotherapy and adjuvant endocrine therapy to determine likely post-treatment infertility. The aim of this study is to explore the feasibility of implementing this FoRECAsT tool into clinical practice by exploring the barriers and facilitators of its use among patients and healthcare providers. METHODS AND ANALYSIS: A cross-sectional exploratory study is being conducted using semistructured in-depth telephone interviews with 15-20 participants each from the following groups: (1) premenopausal patients with breast cancer younger than 40, diagnosed within last 5 years, (2) breast surgeons, (3) breast medical oncologists, (4) breast care nurses (5) fertility specialists and (6) fertility preservation nurses. Patients with breast cancer are being recruited from the joint Breast Service of three affiliated institutions of Victorian Comprehensive Cancer Centre in Melbourne, Australia-Peter MacCallum Cancer Centre, Royal Melbourne Hospital and Royal Women's Hospital, and clinicians are being recruited from across Australia. Interviews are being audio recorded, transcribed verbatim and imported into qualitative data analysis software to facilitate data management and analyses. ETHICS AND DISSEMINATION: The study protocol has been approved by Melbourne Health Human Research Ethics Committee, Australia (HREC number: 2017.163). Confidentiality and privacy are maintained at every stage of the study. Findings will be disseminated through peer-reviewed scholarly and scientific journals, national and international conference presentations, social media, broadcast media, print media, internet and various community/stakeholder engagement activities

Abuse and Diversion of Buprenorphine Sublingual Tablets and Film

Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants\u27 Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ( unique recipients of a dispensed drug, URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned

Observations of a diapycnal shortcut to adiabatic upwelling of Antarctic Circumpolar Deep Water

In the Southern Ocean, small-scale turbulence causes diapycnal mixing which influences important water mass transformations, in turn impacting large-scale ocean transports such as the Meridional Overturning Circulation (MOC), a key controller of Earth'sclimate. We present direct observations of mixing over the Antarctic continental slope between water masses that are part of the Southern Ocean MOC. A 12-hour time-series of microstructure turbulence measurements, hydrography and velocity observations off Elephant Island, north of the Antarctic Peninsula, reveals two concurrent bursts of elevated dissipation of O(10–6Wkg–1, resulting in heat fluxes ~10 times higher than basin-integrated Drake Passage estimates. This occurs across the boundary between adjacent adiabatic upwelling and downwelling overturning cells. Ray tracing and topography show mixing between 300-400 m consistent with the breaking of locally-generated internal tidal waves. Since similar conditions extend to much of the Antarctic continental slope where these water masses outcrop, their transformation may contribute significantly to upwelling

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents

Introduction. Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation across adolescence. Methods. Mega-analysis of pooled genetically informative data on smoking initiation was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N=19 313 pairs) between age 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the US, Europe and Australia. Results. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of smoking initiation across developed countries. The estimate of additive genetic contributions to liability of smoking initiation increased from approximately 15% to 45% from age 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to smoking initiation at age 13 (70%) and gradually less by age 19 (40%). Conclusions. Both additive genetic and shared environmental factors significantly contribute to variance in smoking initiation throughout adolescence. The present study, the largest genetic epidemiological study on smoking initiation to date, found consistent results across 11 studies for the etiology of smoking initiation. Environmental factors, especially those shared by siblings in a family, primarily influence smoking initiation variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. IMPLICATIONS: This is the first study to find evidence of genetic factors in liability to smoking initiation at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment

Practical nutritional recovery strategies for elite soccer players when limited time separates repeated matches

Specific guidelines that aim to facilitate the recovery of soccer players from the demands of training and a congested fixture schedule are lacking; especially in relation to evidence-based nutritional recommendations. The importance of repeated high level performance and injury avoidance while addressing the challenges of fixture scheduling, travel to away venues, and training commitments requires a strategic and practically feasible method of implementing specific nutritional strategies. Here we present evidence-based guidelines regarding nutritional recovery strategies within the context of soccer. An emphasis is placed on providing practically applicable guidelines for facilitation of recovery when multiple matches are played within a short period of time (i.e. 48 h). Following match-play, the restoration of liver and muscle glycogen stores (via consumption of ~1.2 gkg-1h-1 of carbohydrate) and augmentation of protein synthesis (via ~40 g of protein) should be prioritised in the first 20 minutes of recovery. Daily intakes of 6-10 gkg-1 body mass of carbohydrate are recommended when limited time separates repeated matches while daily protein intakes of >1.5 gkg-1 body mass should be targeted; possibly in the form of multiple smaller feedings (e.g., 6 x 20-40 g). At least 150% of the body mass lost during exercise should be consumed within 1 h and electrolytes added such that fluid losses are ameliorated. Strategic use of protein, leucine, creatine, polyphenols and omega-3 supplements could also offer practical means of enhancing post-match recovery. Keywords: soccer, nutrition, recovery, polyphenols, omega-3, creatine, fixture, congestio

Omega-3 fatty acids and vitamin D in immobilisation: Part A - Modulation of appendicular mass content, composition and structure

Objectives: Muscle size decreases in response to short-term limb immobilisation. This study set out to determine whether two potential protein-sparing modulators (eicosapentaenoic acid and vitamin D) would attenuate immobilisation-induced changes in muscle characteristics. Design: The study used a randomised, double-blind, placebo-controlled design. Setting: The study took part in a laboratory setting. Participants: Twenty-four male and female healthy participants, aged 23.0±5.8 years. Intervention: The non-dominant arm was immobilised in a sling for a period of nine waking hours a day over two continuous weeks. Participants were randomly assigned to one of three groups: placebo (n=8, Lecithin, 2400 mg daily), omega-3 (ω-3) fatty acids (n=8, eicosapentaenoic acid (EPA); 1770 mg, and docosahexaenoic acid (DHA); 390 mg, daily) or vitamin D (n=8, 1,000 IU daily). Measurements: Muscle and sub-cutaneous adipose thickness (B-mode ultrasonography), body composition (DXA) and arm girth (anthropometry) were measured before immobilisation, immediately on removal of the sling and two weeks after re-mobilisation. Results: Muscle thickness (-5.4±4.3%), upper and lower arm girth (-1.3±0.4 and -0.8±0.8%, respectively), lean mass (-3.6±3.7%) and bone mineral content (BMC) (-2.3±1.5%) decreased significantly with limb immobilisation in the placebo group (P0.05) towards attenuating the decreases in muscle thickness, upper/lower arm girths and BMC observed in the placebo group. The ω-3 supplementation group demonstrated a non-significant attenuation of the decrease in DXA quantified lean mass observed in the placebo group. Sub-cutaneous adipose thickness increased in the placebo group (P<0.05). ω-3 and vitamin D both blunted this response, with ω-3 having a greater effect (P<0.05). All parameters had returned to baseline values at the re-mobilisation phase of the study. Conclusion: Overall, at the current doses, ω-3 and vitamin D supplementation only attenuated one of the changes associated with non-injurious limb immobilisation. These findings would necessitate further research into either a) supplementation linked to injury-induced immobilisation, or b) larger doses of these supplements to confirm/refute the physiological reserve potential of the two supplements