Cre/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype.

Kisspeptin and its receptor, Kiss1r, act centrally to stimulate reproduction. Recent evidence indicates that kisspeptin is also important for body weight and metabolism, as whole-body Kiss1r KO mice, developed with gene trap technology, display obesity and reduced metabolism. Kiss1r is expressed in brain and multiple peripheral tissues, but it is unknown which is responsible for the metabolic phenotype. Here, we sought to confirm that 1) the metabolic phenotype of the gene trap Kiss1r KOs is due to disruption of kisspeptin signaling and not off-target effects of viral mutagenesis, and 2) the Kiss1r flox line is suitable for creating conditional KOs to study the metabolic phenotype. We used Cre/lox technology (Zp3-Cre/Kiss1r flox) to develop a new global Kiss1r KO ("Kiss1r gKO") to compare with the original gene trap KO phenotype. We confirmed that deleting exon 2 of Kiss1r from the entire body induces hypogonadism in both sexes. Moreover, global deletion of Kiss1r induced obesity in females, but not males, along with increased adiposity and impaired glucose tolerance, similar to the gene trap Kiss1r KOs. Likewise, Kiss1r gKO females had decreased VO2 and VCO2, likely underlying their obesity. These findings support that our previous results in gene trap Kiss1r KOs are due to disrupted kisspeptin signaling, and further highlight a role for Kiss1r signaling in energy expenditure and metabolism besides controlling reproduction. Moreover, given Kiss1r expression in multiple cell-types, our findings indicate that the Kiss1r flox line is viable for future investigations to isolate specific target cells of kisspeptin's metabolic effects

The relationship between engineering bachelor qualifications and occupational status in Australia

Internationally, the importance of science, technology, engineering and mathematics (STEM) for innovation and competition drives concerns about the adequacy of national STEM workforces. Data from the UK, USA and Australia suggest that, even immediately post-graduation, a significant proportion of engineering bachelor graduates do not work in engineering roles. Using the 2011 Australian census data, we present an investigation into the relationship between educational qualifications and occupational status of Australian engineering bachelor graduates, and how this status varies specifically with graduate age. We consider the implications of these findings and present recommendations for the recruitment and education of Australian engineering undergraduates. We conclude that engineering students would be better informed about, and equipped for, the world of post-graduation work if they were exposed to the likely options for their career trajectory. Likewise, secondary school students and others considering engineering undergraduate study would be more honestly advised if they were informed about the full range of career possibilities for engineering graduates and the probability that they are just as likely to work out of engineering as in it

Effects of Selective Deletion of Tyrosine Hydroxylase from Kisspeptin Cells on Puberty and Reproduction in Male and Female Mice.

The neuropeptide kisspeptin, encoded by Kiss1, regulates reproduction by stimulating GnRH secretion. Kiss1-syntheizing neurons reside primarily in the hypothalamic anteroventral periventricular (AVPV/PeN) and arcuate (ARC) nuclei. AVPV/PeN Kiss1 neurons are sexually dimorphic, with females expressing more Kiss1 than males, and participate in estradiol (E2)-induced positive feedback control of GnRH secretion. In mice, most AVPV/PeN Kiss1 cells coexpress tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis (in this case, dopamine). Dopamine treatment can inhibit GnRH neurons, but the function of dopamine signaling arising specifically from AVPV/PeN Kiss1 cells is unknown. We generated a novel TH flox mouse and used Cre-Lox technology to selectively ablate TH specifically from Kiss1 cells. We then examined the effects of selective TH knock-out on puberty and reproduction in both sexes. In control mice, 90% of AVPV/PeN Kiss1 neurons coexpressed TH, whereas in mice lacking TH exclusively in Kiss1 cells (termed Kiss THKOs), TH was successfully absent from virtually all Kiss1 cells. Despite this absence of TH, both female and male Kiss THKOs displayed normal body weights, puberty onset, and basal gonadotropin levels in adulthood, although testosterone (T) was significantly elevated in adult male Kiss THKOs. The E2-induced LH surge was unaffected in Kiss THKO females, and neuronal activation status of kisspeptin and GnRH cells was also normal. Supporting this, fertility and fecundity were normal in Kiss THKOs of both sexes. Thus, despite high colocalization of TH and Kiss1 in the AVPV/PeN, dopamine produced in these cells is not required for puberty or reproduction, and its function remains unknown

Masculinity at work: The experiences of men in female dominated occupations

This paper presents the findings of a research project on the implications of men's non-traditional career choices for their experiences within the organization and for gender identity. The research is based on 40 in-depth interviews with male workers from four occupational groups: librarian-ship, cabin crew, nurses and primary school teachers. Results suggest a typology of male workers in female dominated occupations: seekers (who actively seek the career), finders (who find the occupation in the process of making general career decisions) and settlers (who settle into the career after periods of time in mainly male dominated occupations). Men benefit from their minority status through assumptions of enhanced leadership (the assumed authority effect), by being given differential treatment (the special consideration effect) and being associated with a more careerist attitude to work (the career effect). At the same time, they feel comfortable working with women (the zone of comfort effect). Despite this comfort, men adopt a variety of strategies to re-establish a masculinity that has been undermined by the 'feminine' nature of their work. These include re-labeling, status enhancement and distancing from the feminine. The dynamics of maintaining and reproducing masculinities within the non-traditional work setting are discussed in the light of recent theorising around gender, masculinity and work

Imager Evaluation of Diabetic Retinopathy at the Time of Imaging in a Telemedicine Program

Objective: To evaluate the ability of certified retinal imagers to identify presence versus absence of sight-threatening diabetic retinopathy (stDR) (moderate nonproliferative diabetic retinopathy or worse or diabetic macular edema) at the time of retinal imaging in a telemedicine program. Research Design and Methods: Diabetic patients in a primary care setting or specialty diabetes clinic received Joslin Vision Network protocol retinal imaging as part of their care. Trained nonphysician imagers graded the presence versus absence of stDR at the time of imaging. These gradings were compared with masked gradings of certified readers. Results: Of 158 patients (316 eyes) imaged, all cases of stDR (42 eyes [13%]) were identified by the imagers at the time of imaging. Six eyes with mild nonproliferative diabetic retinopathy were graded by the imagers to have stDR (sensitivity 1.00, 95% CI 0.90–1.00; specificity 0.97, 0.94–0.99). Conclusions: Appropriately trained imagers can accurately identify stDR at the time of imaging

The appropriation of hegemonic masculinity within selected research on men's health

Connell's hegemonic masculinity thesis (HMT) has occupied a relatively dominant position within contemporary research exploring the lives of men. Messerschmidt has conducted a review of recent literature that purports to use HMT, he describes in detail some of the ways Connell's work has been appropriated. Taking Messerschmidt's lead, this paper explores a small selection of men's health research that employ HMT as a central organising theme. Such a narrow focus and limited sample enables the theoretical, conceptual and empirical contributions of engagements with Connell's work to be critically explored in detail. This paper provides colleagues with clear examples of ways in which reified and reductive account of masculinity, are still being reproduced in contemporary analyses of men's lives. In calling for researchers to critically reflect upon their usage of Connell's thesis in more detail, my aim is to increase the subtlety and sophistication of such works. A further hope is that by highlighting specific examples of the need to appraise the relevance and adequacy of HMT as a conceptual frame of lived experiences, we might encourage researchers to access the multitude of different theoretical positions that speak to the lives of men

A qualitative study on the effects of psychoactive substance use upon artistic creativity

Background: Psychoactive substance use has often been claimed to help generate and facilitate the artistic creative process. Aims: The present study explored the role of artists’ substance use in their creative processes and their efforts to balance between enhancement and relaxation. Methods: Semi-structured interviews concerning the artistic creative process and the role of psychoactive substance use were recorded with 72 artists and analyzed using content analysis. The participants were classified according to their substance use in three groups (Cannabis Group, Alcohol Group, and Control Group). Results: Results show that both alcohol and cannabis were used to facilitate creativity and the emotional states that are necessary for the artistic creative process. Participants in the Control group reported that listening to music might function as a mind-altering tool. It was also found that for some artists, substance use is not only characteristic to creation, but it is also part of their everyday lives. Conclusion: Artists are aware of the balancing phenomenon during the artistic creative process. Whether psychoactive substance(s) or other environmental stimuli (such as music) are used to reach the required effect appears to depend upon the individual

A feasibility study of a microgravity enhancement system for Space Station Freedom

The current low frequency microgravity requirements for Space Station Freedom (SSF) call for a level of less than 1 micro-g over 50 percent of all the laboratory racks for continuous periods of 30 days for at least 180 days per year. While this requirement is attainable for some of the laboratory modules for the Permanently Manned Configuration (PMC), it can not be met for the Man-Tended Configuration (MTC). In addition, many experiments would prefer even lower acceleration levels. To improve the microgravity environment, the Microgravity Enhancement System (MESYS) will apply a continuous thrust to SSF, to negate the disturbing gravity gradient and drag forces. The MESYS consists of a sensor, throttle-able thrusters and a control system. Both a proof mass system and accelerometer were evaluated for use as the sensor. The net result of the MESYS will be to shift the microgravity contours from the center of mass to a chosen location. Results indicate the MESYS is not feasible for MTC since it will require 5,073 kg of hydrazine fuel and 7,660 watts of power for 30 days of operation during average atmospheric conditions. For PMC, the MESYS is much more practical since only 4,008 kg of fuel and 5,640 watts of power are required

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Contains fulltext : 70104tjan-heijnen.pdf (publisher's version ) (Open Access)BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker

Why are family carers of people with dementia dissatisfied with general hospital care?: a qualitative study

Background Families and other carers report widespread dissatisfaction with general hospital care for confused older people. Methods We undertook a qualitative interviews study of 35 family carers of 34 confused older patients to ascertain their experiences of care on geriatric and general medical, and orthopaedic wards of a large English hospital. Transcripts were analysed using a grounded theory approach. Themes identified in interviews were categorised, and used to build a model explaining dissatisfaction with care. Results The experience of hospital care was often negative. Key themes were events (illness leading to admission, experiences in the hospital, adverse occurrences including deterioration in health, or perceived poor care); expectations (which were sometimes unrealistic, usually unexplored by staff, and largely unmet from the carers’ perspective); and relationships with staff (poor communication and conflict over care). Expectations were influenced by prior experience. A cycle of discontent is proposed. Events (or ‘crises’) are associated with expectations. When these are unmet, carers become uncertain or suspicious, which leads to a period of ‘hyper vigilant monitoring’ during which carers seek out evidence of poor care, culminating in challenge, conflict with staff, or withdrawal, itself a crisis. The cycle could be completed early during the admission pathway, and multiple cycles within a single admission were seen. Conclusion People with dementia who have family carers should be considered together as a unit. Family carers are often stressed and tired, and need engaging and reassuring. They need to give and receive information about the care of the person with dementia, and offered the opportunity to participate in care whilst in hospital. Understanding the perspective of the family carer, and recognising elements of the ‘cycle of discontent’, could help ward staff anticipate carer needs, enable relationship building, to pre-empt or avoid dissatisfaction or conflict