Galen Wagner,M.D., Ph.D. (1939–2016) as international mentor of young investigators in electrocardiology

This paper describes a substantial part of the international mentoring network of students and young investigators in electrocardiology that developed around Dr. Galen Wagner (1939–2016), including many experiences of his mentees and co-mentors.The paper is meant to stimulate thinking about international mentoring as a means to achieve important learning experiences and personal development of young investigators, to intensify international scientific cooperation, and to stimulate scientific production.     

Cervix Stimulation Evokes Predominantly Subthreshold Synaptic Responses in Mouse Thoracolumbar and Lumbosacral Superficial Dorsal Horn Neurons

IntroductionSensory input from the female reproductive tract (FRT) plays a pivotal role in coordinating reproductive reflexes. Additionally, a number of disorders, especially chronic pelvic pain, may be due to disturbances in sensory processing of signals from the FRT.AimsOur aim was to record synaptic responses in neurons from lumbar and sacral spinal cord segments during mechanical stimulation of the cervix.MethodsWe developed an in vivo preparation of the mouse spinal cord to record synaptic potentials from superficial dorsal horn (SDH) neurons under whole-cell patch clamp recording conditions.Main Outcome MeasuresWe analyzed the strength and distribution of excitatory postsynaptic potentials in SDH neurons evoked during mechanical stimulation of the cervix and cutaneous sites.ResultsResting membrane potential and neuronal input resistance was similar in thoracolumbar (TL, T13-L3) and lumbosacral (LS, L6-S2) segments. We elicited activity in 6/21 TL neurons and 15/39 LS neurons using mechanical stimulation of the cervix with a blunt probe. The majority of these neurons responded to cervix stimulation with bursts of subthreshold excitatory postsynaptic potentials (4/6 and 12/15 TL and LS neurons, respectively). The remainder responded with sufficient magnitude to generate action potentials (2/6 and 3/15 TL and LS neurons). Cutaneous synaptic inputs were also elicited in 11/21 TL neurons following stimulation of the flank/leg, 19/39 LS neurons by stimulation of the tail, and three LS neurons by perineal stimulation. Some neurons received convergent synaptic inputs from the cervix and cutaneous sites (4/6 TL and 4/15 LS).ConclusionThese data demonstrate that spinal projections of cervix afferents are widely dispersed in the SDH and considerable convergence exists between neurons innervating the cervix and cutaneous structures. Our results indicate that much of the synaptic activity evoked in SDH neurons following cervix stimulation is subthreshold. Jobling P, Graham BA, Brichta AM, and Callister RJ. Cervix stimulation evokes predominantly subthreshold synaptic responses in mouse thoracolumbar and lumbosacral superficial dorsal horn neurons.     

The association of comorbid anxiety and depression with asthma-related quality of life and symptom perception in adults

Background and objective:   There are limited data on the association and interaction between anxiety and depression comorbidity and asthma-related quality of life (AQOL) and symptom perception. This study evaluated these associations in patients subsequent to an emergency department (ED) visit for asthma.
Methods:   This was a cross-sectional study of 110 (38 male) adult asthma patients (mean age 42 years), who had visited an ED in the previous 18 months. Participants completed the hospital anxiety and depression scale, measures of AQOL and the asthma symptom checklist.
Results:   Depression symptoms independently showed a significant negative association with AQOL after controlling for depression/anxiety, age, gender, smoking status and ED visits in the previous 12 months (ED-12). Overall, anxiety and depression symptoms accounted for 28.3% of the variance in AQOL. Greater anxiety was associated with increased perception of asthma-specific panic-fear and hyperventilation symptoms during an asthma attack, irrespective of depression status. Categorical analyses of groups of patients, differentiated by psychometric properties on the hospital anxiety and depression scale (anxiety vs normal, anxiety and depression vs normal depression) confirmed most results. However, for the anxiety group there was a significant association with the AQOL domains of emotional functioning and response to environmental stimuli, after controlling for depression symptoms.
Conclusions:   The negative association of depression symptom scores with AQOL and of anxiety with increased panic-fear and hyperventilation symptoms suggests a potential role for interventions addressing this psychological comorbidity, in order to improve AQOL.     

Tissue selectivity of the anabolic steroid, 19-nor-4-androstenediol-3beta,17beta-diol in male Sprague Dawley rats: selective stimulation of muscle mass and bone mineral density relative to prostate mass

Stimulation of prostate growth is a major concern with testosterone therapy in older hypogonadal men. As a result, nonsteroidal selective androgen receptor modulators with anabolic activity but less prostate stimulation are being developed. Anabolic steroids might exhibit similar tissue selectivity. We hypothesized the anabolic steroid 19-nor-4-androstenediol-3beta,17beta-diol (3beta,19-NA) would increase muscle, lean body mass (LBM), and bone mineral density (BMD) with little stimulation of prostate growth. Male Sprague Dawley rats were implanted with SILASTIC brand (Dow Corning, Midland, MI) capsules containing 3beta,19-NA (4, 8, or 16 cm), dihydrotestosterone (DHT) (8 cm), 19-nortestosterone (16 cm), or four empty capsules after undergoing either a sham operation (intact) or orchidectomy (ORX). Serum gonadotropins, measured after 4, 8, or 24 wk of treatment, were significantly lower in 3beta,19-NA-treated vs. untreated, intact, and ORX rats (P < 0.05), and testosterone was lowered by 3beta,19-NA-treatment of intact animals. LBM and BMD were assessed after 20 wk, and 4 wk later, rats were killed for levator ani muscle and prostate weights. Compared with ORX rats, 3beta,19-NA-treated rats had dose-dependent higher levator ani muscle weights, LBM, and BMD, which were similar to intact and DHT-treated rats at the highest 3beta,19-NA dose. In contrast, prostate weights in all 3beta,19-NA-treated groups were similar to ORX rats and lower than intact and DHT- and 19-nortestosterone-treated rats even at the highest 3beta,19-NA dose. In summary, 3beta,19-NA increases muscle and bone mass without significant stimulation of prostate growth, suggesting it may have some properties of a steroidal selective androgen receptor modulator. Anabolic steroids such as 3beta,19-NA should be studied further to determine their mechanisms of tissue selectivity and effects in men.     

High rates of depressive symptoms among patients with systemic sclerosis are not explained by differential reporting of somatic symptoms

OBJECTIVE: Between 36% and 65% of patients with systemic sclerosis (SSc) report symptoms of depression above cutoff thresholds on self-report questionnaires. The objective of this study was to assess whether these high rates result from differential reporting of somatic symptoms related to the high physical burden of SSc. METHODS: Symptom profiles reported on the Center for Epidemiologic Studies Depression Scale (CES-D) were compared between a multicenter sample of 403 patients with SSc and a sample of respondents to an Internet depression survey, matched on total CES-D score, age, race/ethnicity, and sex. An exact nonparametric generalized Mantel-Haenszel procedure was used to identify differential item functioning between groups. RESULTS: Patients with SSc reported significantly higher frequencies (moderate to large effect size; P < 0.01) on 4 CES-D somatic symptom items: bothered, appetite, effort, and sleep. Internet respondents had higher item scores on 2 items that assessed interpersonal difficulties (unfriendly, large effect size; P < 0.01; disliked, large effect size; P < 0.01) and on 2 items that assessed lack of positive effect (happy, moderate effect size; P = 0.01; enjoy, large effect size; P < 0.01). Adjustment of standard CES-D cutoff criteria for potential bias due to somatic symptom reporting resulted in a reduction of only 3.6% in the number of SSc patients with significant symptoms of depression. CONCLUSION: High rates of depressive symptoms in SSc are not due to bias related to the report of somatic symptoms. The pattern of differential item functioning between the SSc and Internet groups, however, suggests some qualitative differences in depressive symptom presentation.