Effects of aging on vasopressin production in a kindred with autosomal dominant neurohypophyseal diabetes insipidus due to the DeltaE47 neurophysin mutation

Postmortem examinations of the hypothalamus of patients with autosomal dominant neurohypophyseal diabetes insipidus (adNDI), which have been reported only on persons dying between the ages of 37-87 yr, reveal the presence of the arginine vasopressin (AVP)-producing parvocellular neurons but the absence of 95% of the expected AVP-producing magnocellular neurons. To determine whether the clinical course of adNDI is compatible with the hypothesis that the neuropathologic findings are attributable to a progressive loss of magnocellular neurons beginning in early life, we performed posterior pituitary magnetic resonance imaging and water deprivation tests, including plasma ACTH measurements, on 17 affected members of a kindred with the deltaE47 neurophysin mutation whose ages ranged from 3 months to 54 yr. Nine adult nonaffected members (ages, 20-56 yr) underwent these tests as controls. All six children undergoing magnetic resonance imaging demonstrated a posterior pituitary hyperintense signal (PPHS). Eight of nine affected adults showed an absent or barely visible PPHS, whereas eight of nine age-matched nonaffected adults produced a normal size PPHS. During water deprivation tests, infants concentrated their urine normally, and a 3-month-old infant produced a high plasma AVP level of 15.7 pmol/liter. By school age, affected children were no longer able to concentrate their urine or prevent hypernatremia. Affected adults became dehydrated; their median plasma AVP level was less than 1.0 pmol/liter, but their median fasting plasma ACTH was 2-fold greater than the level of nonaffected adults (10.0 vs. 5.0 pmol/liter; P = 0.008). These results suggest that adNDI is a progressive disease associated with chronic loss of the magnocellular neurons that supply AVP to the posterior pituitary but preservation of the parvocellular neurons that supply AVP and CRH to the median eminence and stimulate ACTH production during hypernatremia.     

A randomized trial of strategies for assessing eligibility for long-term domiciliary oxygen therapy

RATIONALE: Restricting oxygen administration to those who benefit is desirable. OBJECTIVE: To determine the impact of alternative strategies for assessing eligibility for domiciliary oxygen on funded oxygen use, quality of life, and costs. METHODS: We randomized applicants for domiciliary oxygen therapy to an assessment system that relied on data collected by oxygen providers at the time of application and judgments by Home Oxygen Program personnel (conventional assessment) or to a system of data collection by a respiratory therapist that included, in patients unstable at the time of initial assessment, a repeat assessment after 2 months of stability (alternative assessment). MEASUREMENTS AND MAIN RESULTS: A total of 276 applicants were allocated to the conventional arm and 270 to the alternative assessment. In the year after application, oxygen use was lower in the alternative arm with no between-group differences in mortality, quality of life, or resource use in the community. Although alternative assessment applicants had on average higher assessment costs by dollars Canadian 155 per applicant, these costs were more than offset by decreased Home Oxygen Program costs of dollars Canadian 596 per applicant using Canadian cost weights. The comparable U.S. dollar figures were dollars US 309 and dollars US 432, respectively, and the difference in cost between strategies was therefore smaller using U.S. cost weights. CONCLUSIONS: Reassessment of applicants for domiciliary oxygen after several months of stability identifies an appreciable portion of initially eligible patients who are no longer eligible, thus reducing program costs to public funders without adverse consequences on quality of life, mortality, or other resource use.     

Anomalous right coronary artery originating from the distal left circumflex artery: single coronary artery with choronic atrial fibrillation

This report describes a patient with a single coronary artery in whom the right coronary artery originated from the distal left circumflex artery. Single coronary artery is a rare congenital anomaly of the coronary circulation which is often associated with other congenital cardiac malformations. This anomaly is thought to be clinically significant especially in patients with atrial fibrillation, although no other associated cardiac anomaly was detected.     

Perceptual reversals of Necker stimuli during intermittent presentation with limited attentional resources

During prolonged viewing of ambiguous stimuli, such as Necker cubes, sudden perceptual reversals occur from one perceptual interpretation to another. The role of attention in such reversals is not clear. We tested whether perceptual reversals depend on attentional resources by manipulating perceptual load and recording event‐related potentials (ERPs) during intermittent presentation of Necker stimuli. The results did not reveal any influence for perceptual load on the frequency of reversals. The ERPs showed that perceptual load influenced electrophysiological activity over parieto‐central areas in the P1 time window (110–140 ms), but load did not modify the early enhancements of positivity (30–140 ms), which correlated with perceptual reversals at occipito‐temporal sites. We conclude that disambiguation of ambiguous figures is based on early mechanisms that can work efficiently with only a minimal amount of attentional resources.     

Body-image dissatisfaction is strongly associated with chronic dysphoria

Background

Individual depressive symptoms may contribute to the risk of chronic depression. This study aimed to explore which symptoms predict chronic dysphoria, a hallmark of depression.

Methods

1057 participants from the population-based Young Finns study were examined for four times during a 16-year period. Those with a modified Beck’s Depression Inventory score in the upper third at all four screenings were considered to have chronic dysphoria (n=135). Participants with only one high depression score formed the reference group of transient dysphoria (n=179). Individual items of the Inventory were analyzed in terms of their association with dysphoria status and chronicity, controlling for potential confounding factors, such as personality assessed using the Temperament and Character Inventory.

Results

Body-image dissatisfaction was strongly associated with chronically elevated dysphoria (Bonferroni-corrected p=0.006). The degree of body-image dissatisfaction was associated with the probability for chronic dysphoria in a dose–response manner, with the estimated probability ranging from 0.01 to 0.60 as a function of item response. The association remained after adjustments for a wide range of personality characteristics.

Limitations

The study relied on self-reports of mood and personality, and lacked information on external opinion on participants appearances. The requirement of full time-series data may have resulted in attrition-related bias.

Conclusions

Body-image dissatisfaction was a strong predictor of chronic depression characterized by dysphoria. This finding suggests that dysfunctional attitude towards oneself might represent a potentially important target for cognitive therapies and preventive interventions.     

Learning Curve of Speech Recognition

Speech recognition (SR) speeds patient care processes by reducing report turnaround times. However, concerns have emerged about prolonged training and an added secretarial burden for radiologists. We assessed how much proofing radiologists who have years of experience with SR and radiologists new to SR must perform, and estimated how quickly the new users become as skilled as the experienced users. We studied SR log entries for 0.25 million reports from 154 radiologists and after careful exclusions, defined a group of 11 experienced radiologists and 71 radiologists new to SR (24,833 and 122,093 reports, respectively). Data were analyzed for sound file and report lengths, character-based error rates, and words unknown to the SR’s dictionary. Experienced radiologists corrected 6 characters for each report and for new users, 11. Some users presented a very unfavorable learning curve, with error rates not declining as expected. New users’ reports were longer, and data for the experienced users indicates that their reports, initially equally lengthy, shortened over a period of several years. For most radiologists, only minor corrections of dictated reports were necessary. While new users adopted SR quickly, with a subset outperforming experienced users from the start, identification of users struggling with SR will help facilitate troubleshooting and support.     

Differential effects of estradiol and progesterone on human T cell activation in vitro

Estradiol (E2) and progesterone (P4) are steroid hormones important for the regulation of immune responses during pregnancy. Their increasing levels coincide with an improvement of T cell-mediated diseases such as multiple sclerosis (MS). Although immune-endocrine interactions are involved in this phenomenon, the relative contribution of hormones is not known. We here report a direct comparison of E2- and P4-mediated effects on human CD4⁺ T cells, key cells in immune regulation. T cells were stimulated to obtain different activation levels and exposed to a broad range of hormone concentrations. Activation level was assessed by CD69/CD25 expression by flow cytometry, and secreted proteins (n = 196) were measured in culture supernatants using proximity extension assay and electrochemiluminescence immunoassay. We found that in low activated cells, pregnancy-relevant E2 concentrations increased activation and the secretion of several immune- and inflammation-related proteins. P4, on the other hand, showed a biphasic pattern, where serum-related concentrations upregulated activation and protein secretion while placenta-relevant concentrations induced a prominent dampening irrespective of the initial activation level. Our results demonstrate the importance of P4 as a major hormone in the immune modulation of T cells during pregnancy and emphasize the need to further evaluate its potency in the treatment of diseases like MS.