Intraretinal analysis of the a-wave of the electroretinogram (ERG) in dark-adapted intact cat retina

It has often been assumed that the recovery of the a-wave from its trough is caused by the intrusion of the b-wave. This study examined the recovery following the a-wave trough using intraretinal recordings in dark-adapted intact cat retina. Adult cats were anesthetized and paralyzed. The vitreal ERG was recorded between the vitreous humor and a reference electrode near the eye. Intraretinal recordings were made by referencing a microelectrode to the vitreal electrode. Bright flashes of diffuse white light were used to elicit a- and b-waves. Intravitreal injections of 2-amino-4-phosphonobutyrate (APB), cis 2,3-piperidine dicarboxylic acid (PDA), and kynurenic acid (KYN) were used to block the responses of bipolar and horizontal cells. Intravitreal injections of UL-FS 49 or DK-AH 269 were used to block Ih, a hyperpolarization-activated potassium current. Since the microelectrode was referenced to the vitreal electrode, recordings from the inner retina showed only the oscillatory potentials and b-waves. In the inner retina, the potential was flat until the b-wave became measurable, approximately 17 ms from the onset of the flash. The a-wave started to appear as the microelectrode reached the photoreceptors and its amplitude increased with depth until the microelectrode reached the choroid. The a-wave peaked at approximately 8 ms in response to flashes that saturated its amplitude and then began to recover well before any inner retinal responses were apparent. After injections of APB, PDA, and KYN, vitreal and intraretinal recordings showed only the a-wave, which consisted of an increase to peak at approximately 10 ms followed by a recovery to a plateau which was reached at approximately 25 ms. Blockers of Ih reduced the recovery, but did not eliminate it. The a-wave peaks and partially recovers before the b-wave intrudes. Both phases survive blockers of second-order neurons which implies that the photoreceptors generate both the rising and recovery phase of the a-wave. The recovery phase may be due to a current generated by the inner segment of photoreceptors.     

Resigned professionalism? Non-acute inpatients and resident education

A growing group of inpatients on acute clinical teaching units have non-acute needs, yet require attention by the team. While anecdotally, these patients have inspired frustration and resource pressures in clinical settings, little is known about the ways in which they influence physician perceptions of the learning environment. This qualitative study explored residents’ and attending physicians’ perceptions of caring for these patients, including their educational value. Using constructivist grounded theory, we conducted seven homogeneous focus groups and three interviews with residents and attending physicians from neurology and general internal medicine. A constant comparative analytical approach was employed alongside data collection, using theoretical sampling to explore emergent themes. Residents consistently described non-acute patients as non-educational, uninteresting, but still in need of care. Some attending physicians echoed this view, while others described multiple learning opportunities presented by non-acute patients. Both groups described residents as engaging with non-acute patients in a professional capacity, but not as learners. This engagement in a professional capacity could be considered diligent disinterest, or resigned professionalism. A constructivist understanding of the dynamics which influence learning in the workplace was used to explore the reasons why the residents in our study did not recognize the learning opportunities presented by non-acute patients. Our results resonate with Billett’s theory of workplace affordances, which offers an explanation as to why learners may not identify or take advantage of potential learning opportunities. Overall, our study assists our understanding of the sociocultural factors that influence learners’ choices to engage with particular clinical learning opportunities.     

Insulinemic and Inflammatory Dietary Patterns and Risk of Prostate Cancer

BackgroundHyperinsulinemia and inflammation are inter-related pathways that link diet with the risk of several chronic diseases. Evidence suggests that these pathways may also increase prostate cancer risk.ObjectiveTo determine whether hyperinsulinemic diet and inflammatory diet are associated with prostate cancer incidence and mortality.Design, setting, and participantsWe prospectively followed 41 209 men in the Health Professionals Follow-up Study (1986–2014). Scores for two validated dietary patterns were calculated from food frequency questionnaires at baseline and updated every 4 yr.Outcome measurements and statistical analysisTotal, advanced, and lethal prostate cancer outcomes were assessed. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for associations between two empirical hypothesis-oriented dietary patterns—empirical dietary index for hyperinsulinemia and empirical dietary inflammatory pattern—and prostate cancer risk estimated using Cox proportional hazard regression.Results and limitationsDuring 28 yr of follow-up, 5929 incident cases of total prostate cancer, including 1019 advanced and 667 fatal, were documented. In multivariable-adjusted models, there was a 7% higher risk of advanced prostate cancer (HR: 1.07; 95% CI: 1.01–1.15) and a 9% higher risk of fatal prostate cancer (HR: 1.09; 95% CI: 1.00–1.18) per standard deviation (SD) increase in the hyperinsulinemic diet. When stratified by age, the hyperinsulinemic diet was associated with only earlier-onset aggressive prostate cancer (men under 65 yr), with per SD HRs of 1.20 (95% CI: 1.06–1.35) for advanced, 1.22 (1.04–1.42) for fatal, and 1.20 (1.04–1.38) for lethal. The inflammatory diet was not associated with prostate cancer risk in the overall study population, but was associated with earlier-onset lethal prostate cancer (per SD increase HR: 1.16; 95% CI: 1.00–1.35).ConclusionsHyperinsulinemia and inflammation may be potential mechanisms linking dietary patterns with the risk of aggressive prostate cancer, particularly earlier-onset disease.Patient summaryAvoiding inflammatory and hyperinsulinemic dietary patterns may be beneficial for the prevention of clinically relevant prostate cancer, especially among younger men.     

A prospective study of pregravid oral contraceptive use in relation to fetal growth

OBJECTIVE: Because oral contraceptives are so widely used, any health consequences may have substantial public health implications. Whether pregravid oral contraceptives could affect subsequent pregnancies has not been adequately studied. The study objectives were to examine whether pregravid oral contraceptive use affects fetal growth and pregnancy hormone levels. DESIGN: A prospective study of pregnant women followed through pregnancy. SETTING: A major teaching hospital in Boston, USA. POPULATION: Two hundred and sixty Caucasian pregnant women, with a mean age of 31, and a parity of no more than two. Seventy-nine percent of the women were pregravid oral contraceptive users. METHODS: Exposure and covariate data were collected through structured questionnaires. Blood was drawn for hormonal analysis during the 16th and 27th gestational week. Information on pregravid oral contraceptive use included duration and recency of use, and oral contraceptive formulation. Multivariate regression models were used to examine the effect of pregravid oral contraceptive use on birth outcomes and the studied pregnancy hormones. MAIN OUTCOME MEASURES: Birthweight, placental weight, gestational age, pregnancy hormone levels of oestriol and progesterone at 16th and 27th gestational week. RESULTS: Adjusting for confounders, pregravid oral contraceptive use increased birthweight (mean difference =+207.3 g, 95% CI =+77.6 to +337.1) and placental weight (mean difference =+64.9 g, 95% CI =+13.0 to +116.9) compared with never use. Women with prior oral contraceptive use had higher levels of serum progesterone (P= 0.002) and oestriol (P= 0.12) at the 27th gestational week measurement. The effect on birthweight, placental weight and hormones was stronger among those using oral contraceptives in the previous year and those using a high progestin/high oestrogen potency preparation. CONCLUSIONS: Pregravid oral contraceptive use is positively associated with fetal growth, and this effect may be mediated through oestriol and progesterone.     

Lifestyle and dietary factors in the prevention of lethal prostate cancer

The prevention of lethal prostate cancer is a critical public health challenge that would improve health and reduce suffering from this disease. In this review, we discuss the evidence surrounding specific lifestyle and dietary factors in the prevention of lethal prostate cancer. We present a summary of evidence for the following selected behavioral risk factors: obesity and weight change, physical activity, smoking, antioxidant intake, vitamin D and calcium, and coffee intake.