A review of recent evidence relating to sugars, insulin resistance and diabetes

The potential impact on health of diets rich in free sugars, and particularly fructose, is of major concern. The focus of this review is the impact of these sugars on insulin resistance and obesity, and the associated risk of developing type 2 diabetes. Much of the concern is focussed on specific metabolic effects of fructose, which are argued to lead to increased fat deposition in the liver and skeletal muscle with subsequent insulin resistance and increased risk of diabetes. However, much of the evidence underpinning these arguments is based on animal studies involving very large intakes of the free sugars. Recent human studies, in the past 5 years, provide a rather different picture, with a clear dose response link between fructose intake and metabolic changes. In particular, the most marked effects are observed when a high sugars intake is accompanied by an excess energy intake. This does not mean that a high intake of free sugars does not have any detrimental impact on health, but rather that such an effect seems more likely to be a result of the high sugars intake increasing the chances of an excessive energy intake rather than it leading to a direct detrimental effect on metabolism

Stress Responses in Mental Disorders

1. The blood pressure responses to sympathetic and parasympathetic stimulation of 100 patients suffering from the commoner types of mental illness were recorded before and after treatment. The responses of 10 healthy male subjects were recorded for control purposes. 2. With the exception of hysteria, all the types of mental illness investigated showed abnormal autonomic patterns in terms of blood-pressure response but the individuals in each group showed a pattern which appeared to be characteristic of that group. 3. The possible reasons for the inconsistency in the observations of previous workers in this line of investigation were discussed. 4. Following treatment the tests revealed a relationship between clinical improvement and altered patterns of response in that the greater the improvement the nearer did the patterns approach 'normality' as judged by those of the controls. 5. The possible psychophysiological mechanisms involved in this relationship were discussed. 6. Suggestions were made on the influence of the autonomic pattern upon behaviour

Spam - solutions and their problems

We analyze the success of filtering as a solution to the spam problem when used alone or concurrently with sender and/or receiver pricing. We find that filters alone may exacerbate the spam problem if the spammer attempts to evade them by sending multiple variants of the message to each consumer. Sender and receiver prices can effectively reduce or eliminating spam, either on their own or when used together with filtering. Finally, we discuss the impli- cations for social welfare of using the different spam controls.Spam; filtering; email; receiver pricing; sender pricing

Existence Advertising, Price Competition, and Asymmetric Market Structure

We examine a two stage duopoly game in which firms advertise their existence to consumers in stage 1 and compete in prices in stage 2. Whenever the advertising technology generates positive overlap in customer bases the equilib- rium for the stage 1 game is asymmetric in that one firm chooses to remain small in comparison to its competitor. For a specific random advertising technology we show that one firm will always be half as large as the other. No equilibrium in pure price strategies exists in the stage 2 game and as long as there is some overlap in customer bases the mixed strategy equilibrium is far from the Bertrand equilibrium.Existence advertising; price dispersion; Bertrand paradox; information; duopoly

Current Concepts in the Treatment of Retinitis Pigmentosa

Inherited retinal degenerations, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), affect 1 in 4000 individuals in the general population. A majority of the genes which are mutated in these conditions are expressed in either photoreceptors or the retinal pigment epithelium (RPE). There is considerable variation in the clinical severity of these conditions; the most severe being autosomal recessive LCA, a heterogeneous retinal degenerative disease and the commonest cause of congenital blindness in children. Here, we discuss all the potential treatments that are now available for retinal degeneration. A number of therapeutic avenues are being explored based on our knowledge of the pathophysiology of retinal degeneration derived from research on animal models, including: gene therapy, antiapoptosis agents, neurotrophic factors, and dietary supplementation. Technological advances in retinal implant devices continue to provide the promise of vision for patients with end-stage disease

Spam: solutions and their problems

We analyze the success of filtering as a solution to the spam problem when used alone or concurrently with sender and/or receiver pricing. We find that filters alone may exacerbate the spam problem if the spammer attempts to evade them by sending multiple variants of the message to each consumer. Sender and receiver prices can effectively reduce or eliminating spam, either on their own or when used together with filtering. Finally, we discuss the implications for social welfare of using the different spam controls

A W:B4C multilayer phase retarder for broadband polarization analysis of soft x-ray radiation \ud

A W:B4C multilayer phase retarder has been designed and characterized which shows a nearly constant phase retardance between 640 and 850 eV photon energies when operated near the Bragg condition. This freestanding transmission multilayer was used successfully to determine, for the first time, the full polarization vector at soft x-ray energies above 600 eV, which was not possible before due to the lack of suitable optical elements. Thus, quantitative polarimetry is now possible at the 2p edges of the magnetic substances Fe, Co, and Ni for the benefit of magnetic circular dichroism spectroscopy employing circularly polarized synchrotron radiatio

Dose–response effect of a whey protein preload on within-day energy intake in lean subjects

The effect of consuming different amounts of whey protein on appetite and energy intake was investigated in two separate studies using randomised, crossover designs. Healthy-weight men and women (range: BMI 19·0–25·0 kg/m2, age 19·4–40·4 years) consumed one of four 400 ml liquid preloads, followed by an ad libitum test meal 90 min later. In study 1, preloads were 1675 kJ with 12·5, 25 or 50 % of energy from protein, and in study 2, preloads were 1047 kJ with 10, 20 or 40 % energy from protein. Flavoured water was used as the control in both the studies. Appetite ratings were collected immediately before 30, 60 and 90 min after consuming the preloads; and immediately, 30 and 60 min after consuming the test meal. In study 1, energy intake following the control preload (4136 (sem 337) kJ) was significantly higher than each of the 12·5 % (3520 (sem 296) kJ), 25 % (3384 (sem 265) kJ) and 50 % (2853 (sem 244) kJ) protein preloads (P < 0·05). Intake after the 12·5 % preload was significantly higher than following 25 and 50 % preloads (P < 0·05). In study 2, energy intake following the control preload (4801 (sem 325) kJ) was higher than following the 10 % (4205 (sem 310) kJ), 20 % (3988 (sem 250) kJ) and 40 % (3801 (sem 245) kJ) protein preloads (P < 0·05). There were no differences in subjective appetite ratings between preloads in either study. These findings indicate a dose–response effect of protein content of the preload on energy intake at a subsequent meal

Glutamate transporter dysfunction associated with nerve injury-induced pain in mice

Dysfunction at glutamatergic synapses has been proposed as a mechanism in the development of neuropathic pain. Here we sought to determine whether peripheral nerve injury-induced neuropathic pain results in functional changes to primary afferent synapses. Signs of neuropathic pain as well as an induction of glial fibrillary acidic protein in immunostained spinal cord sections 4 days after partial ligation of the sciatic nerve indicated the induction of neuropathic pain. We found that following nerve injury, no discernable change to kinetics of dl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) or N-methyl-d-aspartate receptor (NMDAR)-mediated evoked excitatory postsynaptic currents (eEPSCs) could be observed in dorsal horn (lamina I/II) neurons compared with those of naïve mice. However, we did find that nerve injury was accompanied by slowed decay of the early phase of eEPSCs in the presence of glutamate transporter inhibition by the competitive nontransportable inhibitor dl-threo-β-benzyloxyaspartic acid (TBOA). Concomitantly, expression patterns for the two major glutamate transporters in the spinal cord, excitatory amino acid transporters (EAAT) 1 and EAAT2, were found to be reduced at this time (4 days postinjury). We then sought to directly determine whether nerve injury results in glutamate spillover to NMDARs at dorsal horn synapses. By employing the use-dependent NMDAR blocker (±)MK-801 to block subsynaptic receptors, we found that although TBOA-induced spillover to extrasynaptic receptors trended to increased activation of these receptors after nerve injury, this was not significant compared with naïve mice. Together, these results suggest the development of neuropathic pain involves subtle changes to glutamate transporter expression and function that could contribute to neuropathic pain during excessive synaptic activity.NHMRC grant: 0569927 & 35144

Ocular Gene Therapy with Adeno-associated Virus Vectors: Current Outlook for Patients and Researchers

In this “Perspective”, we discuss ocular gene therapy – the patient’s perspective, the various strategies of gene replacement and gene editing, the place of adenoassociated virus vectors, routes of delivery to the eye and the remaining question - “why does immunity continue to limit efficacy?” Through the coordinated efforts of patients, researchers, granting agencies and industry, and after many years of pre-clinical studies, biochemical, cellular, and animal models, we are seeing clinical trials emerge for many previously untreatable heritable ocular disorders. The pathway to therapies has been led by the successful treatment of the RPE65 form of Leber congenital amaurosis with LUXTURNATM. In some cases, immune reactions to the vectors continue to occur, limiting efficacy. The underlying mechanisms of inflammation require further study, and new vectors need to be designed that limit the triggers of immunity. Researchers studying ocular gene therapies and clinicians enrolling patients in clinical trials must recognize the current limitations of these therapies to properly manage expectations and avoid disappointment, but we believe that gene therapies are well on their way to successful, widespread utilization to treat heritable ocular disorders