From non-obese diabetic to Network for the Pancreatic Organ Donor with Diabetes: New heights in type 1 diabetes research

Since the discovery of therapeutic insulin in 1922 and the development of the non-obese diabetic spontaneous mouse model in 1980, the establishment of Network for the Pancreatic Organ Donor with Diabetes (nPOD) in 2007 is arguably the most important milestone step in advancing type 1 diabetes (T1D) research. In this perspective, we briefly describe how nPOD is transforming T1D research via procuring and coordinating analysis of disease pathogenesis directly in human organs donated by deceased diabetic and control subjects. The successful precedent set up by nPOD is likely to spread far beyond the confines of research in T1D to revolutionize biomedical research of other disease using high quality procured human cells and tissues.     

Novel benzo[b]thiophene derivatives as new potential antidepressants with rapid onset of action

We report benzo[b]thiophene derivatives synthesized according to a dual strategy. 8j, 9c, and 9e with affinity values toward 5-HT(7)R and 5-HTT were selected to probe their antidepressant activity in vivo using the forced swimming text (FST). The results showed significant antidepressant activity after chronic treatment. 9c was effective in reducing the immobility time in FST even after acute treatment. These findings identify these compounds as a new class of antidepressants with a rapid onset of action.     

Breast cancer awareness and barriers to symptomatic presentation among women from different ethnic groups in East London

Background:

During 2001 to 2005, 1-year breast cancer survival was low in ethnically diverse East London. We hypothesised that this was due to low breast cancer awareness and barriers to symptomatic presentation, leading to late stage at diagnosis in women from ethnic minorities. We examined ethnic differences in breast cancer awareness and barriers to symptomatic presentation in East London.

Methods:

We carried out a population-based survey of 1515 women aged 30+ using the Cancer Research UK Breast Cancer Awareness Measure. We analysed the data using logistic regression adjusting for age group and level of deprivation.

Results:

South Asian and black women had lower breast cancer awareness than white women. South Asian women, but not black women, reported more emotional barriers to seeking medical help than white women. White women were more likely than non-white women to report worry about wasting the doctor''s time as a barrier to symptomatic presentation.

Conclusion:

Interventions to promote early presentation of breast cancer for South Asian and black women should promote knowledge of symptoms and skills to detect changes, and tackle emotional barriers to symptomatic presentation and for white women tackle the idea that going to the doctor to discuss a breast symptom will waste the doctor''s time.     

Simvastatin is the statin that most efficiently protects against kainate-induced excitotoxicity and memory impairment

Statins have recently been shown to act as protectants against several neuropathological conditions. They have received special attention in the field of Alzheimer's disease (AD), where epidemiological studies indicating a lower prevalence of AD/dementia in statin-prescribed populations. Excitotoxicity, which derives from the overstimulation of glutamate receptors, is a major cause of neuron death in several neurological diseases, including AD and epilepsy. We have carried out a comparative study to investigate the effects of all the commercially available statins (simvastatin, lovastatin, fluvastatin, pravastatin, and atorvastatin) on neuron damage and memory impairment. To this end, we studied neurodegeneration in a mouse model by systemic administration of kainate. Simvastatin was the most effective statin in reducing the deleterious effects caused by kainate, including the severity of seizures, excitotoxicity, oxidative damage, neuritic dystrophy and apoptosis in the hippocampus and other limbic structures of the brain cortex. Lovastatin was the second most efficient statin in preventing seizures and histopathological signs of excitotoxicity, whilst fluvastatin, pravastatin, and atorvastatin showed neither antiepileptic nor neuroprotective effects. Only simvastatin enhanced episodic-like memory. To the best of our knowledge this is the first in vivo study to analyze the neuroprotective effect of all the commercially available statins. Our results suggest that both simvastatin and lovastatin (but especially simvastatin) may well have therapeutic potential in the treatment of neurodegenerative diseases involving excitotoxicity and memory impairment, including AD.     

A new electrocardiographic marker for sympathetic nerve stimulation: modulation of repolarization by stimulation of stellate ganglia

Activation of cardiac sympathetic nerves alters ventricular repolarization; however, these changes remain poorly characterized. The goal of this study was to examine effects of sympathetic stimulation on repolarization to identify electrocardiographic markers of sympathetic activation. Pigs underwent median sternotomy and bilateral thoracotomy to expose the stellate ganglia. Changes in T-wave duration, amplitude, repolarization vector, and time from peak to end (Tp-Te) were continuously monitored. Within 15 seconds of unilateral left or right stellate ganglion (LSG/RSG) stimulation, T-wave amplitude increased 6- and 4.5-fold, respectively, in lead aVF. T-wave duration and Tp-Te both increased 200% during LSG stimulation but only 50% and 30%, respectively, with RSG stimulation. During LSG stimulation, frontal and horizontal T-wave vectors, respectively, changed from 1.9° ± 22.8° and 333.8° ± 9.7° at baseline to 83.4° ± 3.9° (inferiorly) and 306.7° ± 1.8° (posteriorly). During RSG stimulation, frontal and horizontal T-wave vectors changed from 348.2° ± 21.6° and 333.8° ± 10.3° before stimulation to 280.7° ± 4.6° (superiorly) and 118.1° ± 5.6° (anteriorly). During stellate stimulation, T-wave vectors are displaced to angles specific for LSG activation (posteroinferiorly) or RSG activation (anterosuperiorly); T-wave amplitude, duration, and Tp-Te increase; and ST-duration decreases. Displaced repolarization vector and changes in T-wave morphometrics provide a novel marker of unilateral sympathetic nerve stimulation.     

Acceptability of male circumcision for prevention of HIV infection among men and women in Uganda

In the last decade, three randomized controlled trials in Kenya, South Africa, and Uganda have shown that medical male circumcision (MMC) reduces the sexual transmission of HIV from women to men. Objectives of this assessment were to measure acceptability of adult MMC and circumcision of children to inform policies regarding whether and how to promote MMC as an HIV prevention strategy. This mixed-method study, conducted across four Ugandan districts, included a two-stage household survey of 833 adult males and 842 adult females, focus group discussions, and a health provider survey. Respondents' acceptability of MMC was positive and substantial after being informed about the results of recent randomized trials. In uncircumcised men, between 40% and 62% across the districts would consider getting circumcised. Across the four districts between 60% and 86% of fathers and 49% and 95% of mothers were supportive of MMC for sons. Widespread support exists among men and women in this study for promoting MMC as part of Uganda's current 'ABC + ' HIV prevention strategy.