Glucocorticoid receptor signaling is essential for mesoderm formation and muscle development in zebrafish

Glucocorticoid receptor (GR) signaling is thought to play a key role in embryogenesis, but its specific developmental effects remain unclear. Cortisol is the primary ligand for GR activation in teleosts, and in zebrafish (Danio rerio), the prehatch embryo content of this steroid is of maternal origin. Using early zebrafish developmental stages, we tested the hypothesis that GR signaling is critical for embryo growth and hatching. In zebrafish, maternal GR mRNA is degraded quickly, followed by zygotic synthesis of the receptor. GR protein is widely expressed throughout early development, and we were able to knockdown this protein using morpholino oligonucleotides. This led to a more than 70% reduction in mRNA abundance of matrix metalloproteinase-13 (mmp13), a glucocorticoid-responsive gene. The GR morphants displayed delayed somitogenesis, defects in somite and tail morphogenesis, reduced embryo size, and rarely survived after hatch. This correlated with altered expression of myogenic markers, including myogenin, myostatin, and muscle-specific myosin heavy chain and troponin genes. A key finding was a 70-90% reduction in the mRNA abundance of bone morphogenetic proteins (BMP), including bmp2a, bmp2b, and bmp4 in GR morphants. Bioinformatics analysis confirmed multiple putative glucocorticoid response elements upstream of these BMP genes. GR morphants displayed reduced expression of BMP-modulated genes, including eve1 and pax3. Zebrafish GR mRNA injection rescued the GR morphant phenotype and reversed the disrupted expression of BMP and myogenic genes. Our results for the first time indicate that GR signaling is essential for zebrafish muscle development, and we hypothesize a role for BMP morphogens in this process.     

Embryo exposure to elevated cortisol level leads to cardiac performance dysfunction in zebrafish

In zebrafish (Danio rerio), de novo cortisol synthesis commences only after hatching, providing an interesting model to study the effects of maternal stress and abnormal cortisol deposition on embryo development and performance. We hypothesized that elevated cortisol levels during pre-hatch embryogenesis compromise cardiac performance in developing zebrafish. Cortisol was microinjected into one-cell embryos to elevate basal cortisol levels during embryogenesis. Elevated embryo cortisol content increased heart deformities, including pericardial edema and malformed chambers, and lowered resting heartbeat post-hatch. This phenotype coincided with suppression of key cardiac genes, including nkx2.5, cardiac myosin light chain 1, cardiac troponin type T2A, and calcium transporting ATPase, underpinning a mechanistic link to heart malformation. The attenuation of the heartbeat response to a secondary stressor post-hatch also confirms a functional reduction in cardiac performance. Altogether, high cortisol content during embryogenesis, mimicking increased deposition due to maternal stress, decreases cardiac performance and may reduce zebrafish offspring survival.     

Norms and practices within marriage which shape gender roles, HIV/AIDS risk and risk reduction strategies in Cabo Delgado, Mozambique

Despite increasing HIV/AIDS rates among married individuals, minimal research has been conducted on how men and women respond to risk in a marriage. This paper examines strategies used by married individuals to combat HIV/AIDS risk against prevailing gender norms. Qualitative data were gathered in four villages of Cabo Delgado province, Mozambique. Group discussions were held with 160 men and women to explore gender norms, HIV/AIDS knowledge and risk determinants. From the group discussions, 29 individuals were selected for further in-depth interviews to explore relationships between gender norms and risk reduction efforts within marriages. Findings illustrate how infidelity and social limitations placed on condom use not only increase HIV/AIDS risk but also entrench gender disparities. Although power differences between genders can make it difficult to negotiate safe sex, men and women are taking measures to reduce perceived HIV/AIDS risk in their marriage. Married men are reconstructing norms and taking responsibility to protect their family from HIV/AIDS by remaining faithful. For women, responses to HIV/AIDS risk in a marriage are more closely related to their ability to generate an income. Financially dependent women tend to leave a risky marriage altogether in contrast to financially autonomous women who will negotiate condom use with their husband. Factors such as experience with a risky partner, the desire to maintain a good social standing, fear of HIV/AIDS acquisition and parental guidance and support influence men and women to reduce perceived HIV/AIDS risk, despite constraining gender norms and power imbalances in a marriage. Nuanced understandings of the ways in which men and women are already taking measures to decrease noted HIV/AIDS risk, despite gender norms that make this a challenge, should be incorporated into localised responses.     

Does hyperoxia affect glucose regulation and transport in the newborn?

OBJECTIVE: Hyperglycemia has been found to occur in children placed on cardiopulmonary bypass. Our laboratory demonstrated that hyperoxia plays a role in this hyperglycemic response and also occurs in the absence of cardiopulmonary bypass. The purpose of this study was to elucidate potential mechanisms underlying the hyperoxic-induced hyperglycemia by examining glucagon, insulin, and epinephrine, which are important in glucose regulation and skeletal and cardiac glucose transporters (GLUT1 and GLUT4), which facilitate glucose entry. METHODS: Three-day-old piglets were anesthetized, intubated, and ventilated to normoxia. Animals were then randomly allocated to either 5 hours of normoxia (n = 4) or hyperoxia (n = 6). Measurements of oxygen, blood glucose, plasma glucagon, insulin, and epinephrine levels were made. Total GLUT1 and GLUT4 content in cardiac and skeletal muscle was measured using Western blotting analysis. RESULTS: A sustained hyperglycemic response (P <.001) was seen throughout the 5-hour ventilatory period. A significant twofold elevation in glucagon levels (P <.001) and a threefold elevation (P <.003) in plasma insulin levels occurred, despite no significant changes in plasma epinephrine. Total GLUT1 and GLUT4 content were significantly reduced in skeletal muscle by 66% and 59%, respectively, while no significant changes occurred in cardiac muscle. CONCLUSION: This study demonstrates that significant elevations in glucagon and insulin and reductions in total skeletal muscle GLUT1 and GLUT4 content all contribute to hyperoxia-induced hyperglycemia seen in newborns. To optimize postoperative recovery of newborns, consideration should be given to the levels of oxygen used to avoid the potential development of insulin resistance and subsequent decrease in glucose entry.     

An assessment of quality of sleep and the use of drugs with sedating properties in hospitalized adult patients

Background  

Hospitalization can significantly disrupt sleeping patterns. In consideration of the previous reports of insomnia and apparent widespread use of benzodiazepines and other hypnotics in hospitalized patients, we conducted a study to assess quality of sleep and hypnotic drug use in our acute care adult patient population. The primary objectives of this study were to assess sleep disturbance and its determinants including the use of drugs with sedating properties.     

Premature ventricular contractions arising from the pulmonary artery: the use of multielectrode array mapping and cryoablation

Premature ventricular contractions with a left bundle branch block-like morphology and inferior axis typically originate from the right ventricular outflow tract; however, they can also originate from the pulmonary artery. We report two patients with frequent premature ventricular contractions who underwent successful cryoablation of ectopics arising from the posterolateral region of the pulmonary artery. The safe and effective use of cryoablation within the pulmonary artery is discussed. We recommend the use of noncontact mapping with multielectrode array catheter in facilitating the technique and providing a more accurate localization of the ectopic focus within the pulmonary artery, compared with conventional pace mapping methods.     

Exchange of sex for resources: HIV risk and gender norms in Cabo Delgado,Mozambique

A qualitative analysis was carried out of data from 16 group discussions and 29 in-depth interviews conducted in rural and matrilineal areas of Cabo Delgado, Mozambique, to examine how the exchange of sex for resources – primarily money but also food, transportation, housing and gifts – is enacted and perceived in relation to HIV-related risk, and how prevalent gender norms are reflected in this practice. Findings reveal how gender norms shape access to resources differently for men and women as well as how variations in access to opportunities and income earning potential contribute to the emergence of sexual exchange for purposes of survival, but also as a means to ensure sexual and economic agency. Within this practice, individuals are confronting gender norms and re-defining their HIV-related risk. Some men refuse to spend scarce resources on other women by protecting their family from both financial insecurity and HIV acquisition. Among some women who engage in sexual transactions to obtain resources quickly, the resulting agency and decision making power gained are a trade-off to potential HIV risk. Nuanced understandings of gender dynamics and its influence on sexual risk taking and risk-reduction efforts in different local contexts are required.     

Going glass to digital: virtual microscopy as a simulation-based revolution in pathology and laboratory science

The recent technological advance of digital high resolution imaging has allowed the field of pathology and medical laboratory science to undergo a dramatic transformation with the incorporation of virtual microscopy as a simulation-based educational and diagnostic tool. This transformation has correlated with an overall increase in the use of simulation in medicine in an effort to address dwindling clinical resource availability and patient safety issues currently facing the modern healthcare system. Virtual microscopy represents one such simulation-based technology that has the potential to enhance student learning and readiness to practice while revolutionising the ability to clinically diagnose pathology collaboratively across the world. While understanding that a substantial amount of literature already exists on virtual microscopy, much more research is still required to elucidate the full capabilities of this technology. This review explores the use of virtual microscopy in medical education and disease diagnosis with a unique focus on key requirements needed to take this technology to the next level in its use in medical education and clinical practice.