Microvascular complications. Retinopathy and nephropathy.

Diabetic retinopathy and diabetic nephropathy extract an enormous toll on patients with diabetes and an enormous burden on the health care system. With aggressive control of glycemia and blood pressure, coupled with aggressive use of laser photocoagulation and treatment of microalbuminuria, these problems can largely be eliminated. In the future, specific interventions may emerge that will allow interdiction of the pathophysiologic processes that lead to initiation and progression of these microvascular complications. The challenge for the primary care physician and diabetologist is to attain excellent glycemic control and aggressive control of blood pressure, while assuring that every patient has appropriate dilated fundus examinations at least annually, preferably by an ophthalmologist or retinal specialist, and regular screening for microalbuminuria. With such medical management, appropriate intervention can occur to reduce the risk of blindness and renal failure and to lessen the burden from diabetic retinopathy and nephropathy.     

“Bareback” Pornography Consumption and Safe-Sex Intentions of Men Having Sex with Men

Men having sex with men (MSM) commonly consume “bareback” pornography, which includes scenes of unprotected anal intercourse. Prior research on human imitative behavior suggests that these media might counteract efforts to promote safe-sex behaviors. To date, no studies have demonstrated a causal link between bareback pornography consumption and reduced safe-sex intentions. Study 1 utilized a correlational design conducted as an online survey. Study 2 was set in an actual MSM sex club, using a 2 × 2 mixed-factorial design to compare type of pornography (unprotected vs. protected anal intercourse) and age of actors (younger vs. older). As the main dependent variable in both studies, participants self-reported their inclinations toward unprotected versus protected intercourse, using a 100-point sliding scale (1 = unprotected, 100 = protected). In Study 1, more attention to unprotected sex acts on actual DVD film covers predicted lower safe-sex intentions, as compared to other elements of the film cover. In Study 2, safe-sex intentions after viewing unprotected-sex films were lower than after viewing protected-sex films. The results provide novel and ecologically valid evidence that “bareback” pornography consumption impacts viewer’s inclinations toward sexual risk-taking by lowering their intentions to use protected sex measures. Suggestions are given as to how these findings can be utilized for purposes of intervention and prevention of STI and HIV infections.     

Evaluating Adaptation and Olivocochlear Efferent Feedback as Potential Explanations of Psychophysical Overshoot

Masked detection threshold for a short tone in noise improves as the tone’s onset is delayed from the masker’s onset. This improvement, known as “overshoot,” is maximal at mid-masker levels and is reduced by temporary and permanent cochlear hearing loss. Computational modeling was used in the present study to evaluate proposed physiological mechanisms of overshoot, including classic firing rate adaptation and medial olivocochlear (MOC) feedback, for both normal hearing and cochlear hearing loss conditions. These theories were tested using an established model of the auditory periphery and signal detection theory techniques. The influence of several analysis variables on predicted tone-pip detection in broadband noise was evaluated, including: auditory nerve fiber spontaneous-rate (SR) pooling, range of characteristic frequencies, number of synapses per characteristic frequency, analysis window duration, and detection rule. The results revealed that overshoot similar to perceptual data in terms of both magnitude and level dependence could be predicted when the effects of MOC efferent feedback were included in the auditory nerve model. Conversely, simulations without MOC feedback effects never produced overshoot despite the model’s ability to account for classic firing rate adaptation and dynamic range adaptation in auditory nerve responses. Cochlear hearing loss was predicted to reduce the size of overshoot only for model versions that included the effects of MOC efferent feedback. These findings suggest that overshoot in normal and hearing-impaired listeners is mediated by some form of dynamic range adaptation other than what is observed in the auditory nerve of anesthetized animals. Mechanisms for this adaptation may occur at several levels along the auditory pathway. Among these mechanisms, the MOC reflex may play a leading role.     

Pancreatic Islet Autoantibodies as Predictors of Type 1 Diabetes in the Diabetes Prevention Trial�CType 1

OBJECTIVE

There is limited information from large-scale prospective studies regarding the prediction of type 1 diabetes by specific types of pancreatic islet autoantibodies, either alone or in combination. Thus, we studied the extent to which specific autoantibodies are predictive of type 1 diabetes.

RESEARCH DESIGN AND METHODS

Two cohorts were derived from the first screening for islet cell autoantibodies (ICAs) in the Diabetes Prevention Trial–Type 1 (DPT-1). Autoantibodies to GAD 65 (GAD65), insulinoma-associated antigen-2 (ICA512), and insulin (micro-IAA [mIAA]) were also measured. Participants were followed for the occurrence of type 1 diabetes. One cohort (Questionnaire) included those who did not enter the DPT-1 trials, but responded to questionnaires (n = 28,507, 2.4% ICA⁺). The other cohort (Trials) included DPT-1 participants (n = 528, 83.3% ICA⁺).

RESULTS

In both cohorts autoantibody number was highly predictive of type 1 diabetes (P < 0.001). The Questionnaire cohort was used to assess prediction according to the type of autoantibody. As single autoantibodies, ICA (3.9%), GAD65 (4.4%), and ICA512 (4.6%) were similarly predictive of type 1 diabetes in proportional hazards models (P < 0.001 for all). However, no subjects with mIAA as single autoantibodies developed type 1 diabetes. As second autoantibodies, all except mIAA added significantly (P < 0.001) to the prediction of type 1 diabetes. Within the positive range, GAD65 and ICA autoantibody titers were predictive of type 1 diabetes.

CONCLUSIONS

The data indicate that the number of autoantibodies is predictive of type 1 diabetes. However, mIAA is less predictive of type 1 diabetes than other autoantibodies. Autoantibody number, type of autoantibody, and autoantibody titer must be carefully considered in planning prevention trials for type 1 diabetes.Autoantibodies to islet cell antigens are known predictors of type 1 diabetes and are commonly present at its diagnosis (1–12). Islet cell autoantibodies (ICAs), the first identified (1,2), actually represent autoimmunity to several different antigens. More recently, autoantibodies specific to single tissue antigens, termed biochemical autoantibodies, have been identified (4,7,8,11–13). These include antibodies to GAD 65 (GAD65), the antibody to an insulinoma-associated antigen-2 (ICA512), and antibodies to insulin (IAA).Type 1 diabetes prevention trials have used autoantibodies to screen for individuals at increased risk who might be candidates for participation (14–16). The Diabetes Prevention Trial–Type 1 (DPT-1) assessed parenteral and oral insulin as potential prevention modalities. First- and second-degree relatives of type 1 diabetic patients were screened for the presence of ICA, which was required for eligibility. Although not relevant to the trials, biochemical autoantibodies were subsequently measured from screening samples to learn more about their prediction of type 1 diabetes. The prevalence of autoantibodies according to various subgroups has been reported for DPT-1 (17).We used two DPT-1 cohorts to examine the prediction of type 1 diabetes by ICA and biochemical autoantibodies, as few large-scale studies have examined the prediction of type 1 diabetes by a variety of single autoantibodies in large numbers of individuals of whom many ultimately developed type 1 diabetes. One cohort includes DPT-1 participants who participated in the trials (the Trials cohort), and the other cohort includes participants who did not participate in either trial but responded to questionnaires (the Questionnaire cohort) used to ascertain information regarding the diagnosis of type 1 diabetes. The differing perspectives of these two cohorts and the large number of individuals studied, almost 30,000, provide a unique opportunity for studying the prediction of type 1 diabetes by autoantibodies.     

Sex,social status,and CRF receptor densities in naked mole‐rats

Naked mole‐rats (Heterocephalus glaber) live in groups that are notable for their large size and caste structure, with breeding monopolized by a single female and a small number of males. Recent studies have demonstrated substantial differences between the brains of breeders and subordinates induced by changes in social standing. Corticotropin‐releasing factor (CRF) receptors—which bind the hormone CRF as well as related peptides—are important regulators of stress and anxiety, and are emerging as factors affecting social behavior. We conducted autoradiographic analyses of CRF₁ and CRF₂ receptor binding densities in female and male naked mole‐rats varying in breeding status. Both globally and in specific brain regions, CRF₁ receptor densities varied with breeding status. CRF₁ receptor densities were higher in subordinates across brain regions, and particularly in the piriform cortex and cortical amygdala. Sex differences were present in CRF₂ receptor binding densities, as is the case in multiple vole species. CRF₂ receptor densities were higher in females, both globally and in the cortical amygdala and lateral amygdalar nucleus. These results provide novel insights into the neurobiology of social hierarchy in naked mole‐rats, and add to a growing body of work that links changes in the CRF system with social behavior. J. Comp. Neurol. 524:228–243, 2016. © 2015 Wiley Periodicals, Inc.