Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer

Introduction  

Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active gene-dependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel–Biskis–Reilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK).     

Decreased insulin sensitivity during dietary sodium restriction is not mediated by effects of angiotensin II on insulin action

We have previously reported that modest dietary sodium restriction, as advocated in management guidelines for diabetes, may reduce insulin sensitivity. It has since been suggested that this effect may be mediated via cross-talk between insulin and angiotensin II (AII)-stimulated intracellular second messengers. In order to assess the effect of 5 days of modest sodium restriction (to <80 mmol/day target sodium intake) on insulin sensitivity, 15 healthy males underwent a double-blind, placebo-controlled, randomized, cross-over euglycaemic hyperinsulinaemic clamp study. One phase was supplemented with sodium tablets and the other with matched placebo. Insulin sensitivity (M) was reduced during dietary sodium restriction [median M value, 10.2 mg/kg per min (interquartile range 9.50-13.85) versus 12.8 mg/kg per min (interquartile range 9.60-14.30), P <0.05]. To elucidate potential mechanisms that may explain this observation, we investigated the effect of AII on insulin action in isolated adipocytes obtained from healthy females. No effect of AII on insulin-mediated glucose transport or suppression of lipolysis was observed. In conclusion, despite the observation that dietary sodium restriction was associated with a median 15% reduction in insulin sensitivity, we found no evidence of a direct effect of AII on insulin action in human adipocytes.     

Iatrogenic extreme corneal decompensation treated by sequential Descemet's Stripping Endothelial Keratoplasty surgeries six months apart

Descemet’s stripping endothelial keratoplasty (DSEK) is now the most common surgical procedure to treat endothelial dysfunction although it is known that endothelial cell survival is an issue of concern. We present a case whereby severe iatrogenic corneal decompensation caused by Descemet’s membrane detachment following premature disconnection of an infusion tube at the end of a trans pars plana vitrectomy and epiretinal membrane peel was successfully treated with two staged DSEK procedures six months apart. The patient was counselled that due to the severity of his extreme corneal oedema more than one DSEK procedure may be needed and the procedure was planned from the outset as a two-stage procedure. There was a measurable decrease in corneal thickness and increase in visual acuity following both the first and second procedures, which may be due to reinvigoration of the endothelial cell count following each procedure. We suggest that repeating the DSEK procedure, even when the first operation has gone well and the graft appears healthy, may be beneficial in obtaining further improvement in cases of severe corneal oedema.     

The relationship between visual function, duration and main causes of vision loss and falls in older people with low vision

Background  

Falls are an alarming health problem and a major cause of injury among the elderly. The healthcare cost associated with falls is considerable. Visual acuity has been found to be an independent risk factor for falls; however, the results are not unanimous. Moreover, other aspects of visual function such as visual field, contrast sensitivity and depth perception have not been adequately investigated in relation to falls. The aim of this study, therefore, was to determine the relationship between visual function, duration, and main causes of visual impairment, and falls in individuals with low vision.     

Multidisciplinary management of breast cancer concurrent with pregnancy.

The management of PABC is very difficult. The incidence of PABC is low, but may be increasing because of the number of women who are becoming pregnant at a later age. More investigation is needed to understand whether the biology of PABC is different from that of breast cancer in nonpregnant women. One exciting area of further research is the potential relationship between mutations in known breast cancer susceptibility genes and breast cancer development during pregnancy. Diagnosis or PABC remains challenging because of the anatomic and physiologic changes that occur in the breast during pregnancy. Understanding the generic influences on PABC may help physicians in diagnosing this disease earlier, and understanding the tumor-receptor characteristics of PABC can help physicians deliver effective treatment. The various modalities available for treatment of PABC and their risks and benefits must be discussed openly with patients and their families. Abortion is not usually recommended. Modified radical mastectomy is the recommended treatment for PABC diagnosed during the first trimester. Neoadjuvant or adjuvant chemotherapy can be given with minimal risks to the fetus during the second or third trimester. Radiation therapy is contraindicated during pregnancy because of the potential for injury to the fetus. Breast conservation therapy, with radiation treatments given after delivery or after neoadjuvant chemotherapy, is an option for women with PABC diagnosed late in pregnancy. Once the appropriate treatment modality is chosen, its implementation must not be delayed because of the pregnancy. Most of the literature shows that women with PABC have the same survival stage for stage as nonpregnant women with breast cancer. But some studies suggest that the prognosis is worse for patients who present with advanced-stage PABC. Finally, recurrence and survival in most patients previously treated for breast cancer do not appear to be adversely affected by subsequent pregnancy. Above all, the patient with breast cancer diagnosed during pregnancy is best served by early and continued involvement of a multidisciplinary cancer treatment team.