Mindfulness-based stress reduction and health-related quality of life in a heterogeneous patient population

This study examined the effects of mindfulness-based stress reduction (MBSR) on health-related quality of life and physical and psychological symptomatology in a heterogeneous patient population. Patients (n=136) participated in an 8-week MBSR program and were required to practice 20 min of meditation daily. Pre- and post-intervention data were collected by using the Short-Form Health Survey (SF-36), Medical Symptom Checklist (MSCL) and Symptom Checklist-90 Revised (SCL-90-R). Health-related quality of life was enhanced as demonstrated by improvement on all indices of the SF-36, including vitality, bodily pain, role limitations caused by physical health, and social functioning (all P\u3c.01). Alleviation of physical symptoms was revealed by a 28% reduction on the MSCL (P\u3c.0001). Decreased psychological distress was indicated on the SCL-90-R by a 38% reduction on the Global Severity Index, a 44% reduction on the anxiety subscale, and a 34% reduction on the depression subscale (all P\u3c.0001). One-year follow-up revealed maintenance of initial improvements on several outcome parameters. We conclude that a group mindfulness meditation training program can enhance functional status and well-being and reduce physical symptoms and psychological distress in a heterogeneous patient population and that the intervention may have long-term beneficial effects

Mindfulness-based stress reduction lowers psychological distress in medical students

Background: Medical students confront significant academic, psychosocial, and existential stressors throughout their training. Mindfulness-based stress reduction (MBSR) is an educational intervention designed to improve coping skills and reduce emotional distress. Purpose: The purpose of this study was to examine the effectiveness of the MBSR intervention in a prospective, nonrandomized, cohort-controlled study. Methods: Second-year students (n = 140) elected to participate in a 10-week MBSR seminar. Controls (n = 162) participated in a didactic seminar on complementary medicine. Profile of Mood States (POMS) was administered preintervention and postintervention. Results: Baseline total mood disturbance (TMD) was greater in the MBSR group compared with controls (38.7 ± 33.3 vs. 28.0 ± 31.2; p \u3c .01). Despite this initial difference, the MBSR group scored significantly lower in TMD at the completion of the intervention period (31.8 ± 33.8 vs. 38.6 ± 32.8; p \u3c .05). Significant effects were also observed on Tension–Anxiety, Confusion–Bewilderment, Fatigue–Inertia, and Vigor–Activity subscales. Conclusion: MBSR may be an effective stress management intervention for medical students

Sensitivity of the human circadian system to short wavelength (420 nm) light

The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment, melanopsin. Nine action spectrum studies using rodents, monkeys, and human for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 nm to 484 nm, with some disagreement in short wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420 nm light for plasma melatonin suppression. Adult female (N=14) and male (N=12) subjects participated in two studies, each employing a within-subjects design. In a fluence-response study, subjects (N=8) were tested with eight light irradiances at 420 nm ranging over a four log unit photon density range of 1010 to 1014 photons/cm2/sec and one dark exposure control night. In the other study, subjects (N=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 1013 photons/cm2/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420 nm light and melatonin suppression (p\u3c0.001) with a half-saturation constant of 2.74 x 1011 photons/cm2/sec. The second study showed that 460 nm light is significantly stronger than 420 nm light for suppressing melatonin (p\u3c0.04). Together, the results clarify the visible short wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications

Gender Differences in Head Impacts Sustained by Collegiate Ice Hockey Players

Purpose—This study aims to quantify the frequency, magnitude, and location of head impacts sustained by male and female collegiate ice hockey players over two seasons of play. Methods—Over two seasons, 88 collegiate athletes (51 female, 37 male) on two female and male NCAA varsity ice hockey teams wore instrumented helmets. Each helmet was equipped with 6 single-axis accelerometers and a miniature data acquisition system to capture and record head impacts sustained during play. Data collected from the helmets were post-processed to compute linear and rotational acceleration of the head as well as impact location. The head impact exposure data (frequency, location, and magnitude) were then compared across gender. Results—Female hockey players experienced a significantly lower (p \u3c 0.001) number of impacts per athlete exposure than males (female: 1.7 ± 0.7; male: 2.9 ± 1.2). The frequency of impacts by location was the same between gender (p \u3e 0.278) for all locations except the right side of the head, where males received fewer impacts than females (p = 0.031). Female hockey players were 1.1 times more likely than males to sustain an impact less than 50 g while males were 1.3 times more likely to sustain an impact greater than 100 g. Similarly, males were 1.9 times more likely to sustain an impact with peak rotational acceleration greater than 5,000 rad/s2 and 3.5 times more likely to sustain an impact greater than 10,000 rad/s2. Conclusions—Although the incidence of concussion has typically been higher for female hockey players than male hockey players, female players sustain fewer impacts and impacts resulting in lower head acceleration than males. Further study is required to better understand th

Safety, pharmacodynamics, and antiviral activity of selgantolimod in viremic patients with chronic hepatitis B virus infection

Background &amp; Aims: Novel finite therapies for chronic hepatitis B (CHB) are needed, since lifelong treatment is usually required with current available oral antivirals. This phase II study (NCT03615066) evaluated the safety, pharmacodynamics, and antiviral activity of selgantolimod (a Toll-like receptor 8 agonist [TLR8]) with tenofovir alafenamide (TAF). Methods: Viremic patients with CHB not receiving treatment were stratified by HBeAg status and randomized 2:2:1 to TAF 25 mg/day with selgantolimod 3 mg orally once weekly (QW), selgantolimod 1.5 mg QW, or placebo. Combination therapy continued until week (W)24, followed by TAF monotherapy until W48; patients then discontinued TAF and were followed until W96 (treatment-free follow-up [TFFU] period). The primary efficacy endpoint was the proportion with ≥1 log10 IU/ml HBsAg decline at W24. Results: Sixty-seven patients received study drug; 27 were followed during TFFU. Nausea, headache, vomiting, fatigue, and dizziness were the most common adverse events. Most adverse events were grade 1. Alanine aminotransferase flares were not observed up to W48. Four patients experienced alanine aminotransferase and hepatitis flares during TFFU; all had HBV DNA increases. Selgantolimod increased serum cytokines and chemokines and redistributed several circulating immune cell subsets. No patients achieved the primary efficacy endpoint. Mean HBsAg changes were −0.12, −0.16, and −0.12 log10 IU/ml in the selgantolimod 3 mg, selgantolimod 1.5 mg, and placebo groups, respectively, at W48; HBV DNA declined in all groups by ≥2 log10 IU/ml as early as W2, with all groups rebounding to baseline during TFFU. No HBsAg or HBeAg loss or seroconversion was observed throughout TFFU. Conclusions: Selgantolimod up to 3 mg was safe and well tolerated. Pharmacodynamics and antiviral activity in viremic patients support continued study of selgantolimod in combination CHB therapies. Impact and implications: Novel therapeutics for chronic HBV infection are needed to achieve a functional cure. In this study, we confirmed the safety and tolerability of selgantolimod (formerly GS-9688, a TLR8) when administered with tenofovir alafenamide over 24 weeks in viremic patients with chronic HBV infection. Overall, declines in HBsAg levels with selgantolimod treatment were modest; subgroup analysis indicated that patients with alanine aminotransferase levels greater than the upper limit of normal had significantly greater declines compared to those with normal alanine aminotransferase levels (–0.20 vs. –0.03 log10 IU/ml; p &lt;0.001). These findings suggest a potential differential response to selgantolimod based on patients’ baseline HBV-specific immune response, which should be considered in future investigations characterizing the underlying mechanisms of selgantolimod treatment and in HBV cure studies using similar immunomodulatory pathways. Clinical trial number: NCT03615066 be found at https://www.gileadclinicaltrials.com/transparency-policy/.</p

Safety, pharmacodynamics, and antiviral activity of selgantolimod in viremic patients with chronic hepatitis B virus infection

Background &amp; Aims: Novel finite therapies for chronic hepatitis B (CHB) are needed, since lifelong treatment is usually required with current available oral antivirals. This phase II study (NCT03615066) evaluated the safety, pharmacodynamics, and antiviral activity of selgantolimod (a Toll-like receptor 8 agonist [TLR8]) with tenofovir alafenamide (TAF). Methods: Viremic patients with CHB not receiving treatment were stratified by HBeAg status and randomized 2:2:1 to TAF 25 mg/day with selgantolimod 3 mg orally once weekly (QW), selgantolimod 1.5 mg QW, or placebo. Combination therapy continued until week (W)24, followed by TAF monotherapy until W48; patients then discontinued TAF and were followed until W96 (treatment-free follow-up [TFFU] period). The primary efficacy endpoint was the proportion with ≥1 log10 IU/ml HBsAg decline at W24. Results: Sixty-seven patients received study drug; 27 were followed during TFFU. Nausea, headache, vomiting, fatigue, and dizziness were the most common adverse events. Most adverse events were grade 1. Alanine aminotransferase flares were not observed up to W48. Four patients experienced alanine aminotransferase and hepatitis flares during TFFU; all had HBV DNA increases. Selgantolimod increased serum cytokines and chemokines and redistributed several circulating immune cell subsets. No patients achieved the primary efficacy endpoint. Mean HBsAg changes were −0.12, −0.16, and −0.12 log10 IU/ml in the selgantolimod 3 mg, selgantolimod 1.5 mg, and placebo groups, respectively, at W48; HBV DNA declined in all groups by ≥2 log10 IU/ml as early as W2, with all groups rebounding to baseline during TFFU. No HBsAg or HBeAg loss or seroconversion was observed throughout TFFU. Conclusions: Selgantolimod up to 3 mg was safe and well tolerated. Pharmacodynamics and antiviral activity in viremic patients support continued study of selgantolimod in combination CHB therapies. Impact and implications: Novel therapeutics for chronic HBV infection are needed to achieve a functional cure. In this study, we confirmed the safety and tolerability of selgantolimod (formerly GS-9688, a TLR8) when administered with tenofovir alafenamide over 24 weeks in viremic patients with chronic HBV infection. Overall, declines in HBsAg levels with selgantolimod treatment were modest; subgroup analysis indicated that patients with alanine aminotransferase levels greater than the upper limit of normal had significantly greater declines compared to those with normal alanine aminotransferase levels (–0.20 vs. –0.03 log10 IU/ml; p &lt;0.001). These findings suggest a potential differential response to selgantolimod based on patients’ baseline HBV-specific immune response, which should be considered in future investigations characterizing the underlying mechanisms of selgantolimod treatment and in HBV cure studies using similar immunomodulatory pathways. Clinical trial number: NCT03615066 be found at https://www.gileadclinicaltrials.com/transparency-policy/.</p

Medical Student Professionalism Narratives: A Thematic Analysis and Interdisciplinary Comparative Investigation

<p>Abstract</p> <p>Background</p> <p>Professionalism development is influenced by the informal and hidden curriculum. The primary objective of this study was to better understand this experiential learning in the setting of the Emergency Department (ED). Secondarily, the study aimed to explore differences in the informal curriculum between Emergency Medicine (EM) and Internal Medicine (IM) clerkships.</p> <p>Methods</p> <p>A thematic analysis was conducted on 377 professionalism narratives from medical students completing a required EM clerkship from July 2008 through May 2010. The narratives were analyzed using established thematic categories from prior research as well as basic descriptive characteristics. Chi-square analysis was used to compare the frequency of thematic categories to prior research in IM. Finally, emerging themes not fully appreciated in the established thematic categories were created using grounded theory.</p> <p>Results</p> <p>Observations involving interactions between attending physician and patient were most abundant. The narratives were coded as positive 198 times, negative 128 times, and hybrid 37 times. The two most abundant narrative themes involved <it>manifesting respect </it>(36.9%) and <it>spending time </it>(23.7%). Both of these themes were statistically more likely to be noted by students on EM clerkships compared to IM clerkships. Finally, one new theme regarding <it>cynicism </it>emerged during analysis.</p> <p>Conclusions</p> <p>This analysis describes an informal curriculum that is diverse in themes. Student narratives suggest their clinical experiences to be influential on professionalism development. Medical students focus on different aspects of professionalism depending on clerkship specialty.</p

Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca2+ sparks in airway myocytes

Short-lived, localized Ca2+ events mediate Ca2+ signaling with high efficiency and great fidelity largely as a result of the close proximity between Ca2+-permeable ion channels and their molecular targets. However, in most cases, direct evidence of the spatial relationship between these two types of molecules is lacking, and, thus, mechanistic understanding of local Ca2+ signaling is incomplete. In this study, we use an integrated approach to tackling this issue on a prototypical local Ca2+ signaling system composed of Ca2+ sparks resulting from the opening of ryanodine receptors (RYRs) and spontaneous transient outward currents (STOCs) caused by the opening of Ca2+-activated K+ (BK) channels in airway smooth muscle. Biophysical analyses of STOCs and Ca2+ sparks acquired at 333 Hz demonstrate that these two events are associated closely in time, and approximately eight RYRs open to give rise to a Ca2+ spark, which activates ∼15 BK channels to generate a STOC at 0 mV. Dual immunocytochemistry and 3-D deconvolution at high spatial resolution reveal that both RYRs and BK channels form clusters and RYR1 and RYR2 (but not RYR3) localize near the membrane. Using the spatial relationship between RYRs and BK channels, the spatial-temporal profile of [Ca2+] resulting from Ca2+ sparks, and the kinetic model of BK channels, we estimate that an average Ca2+ spark caused by the opening of a cluster of RYR1 or RYR2 acts on BK channels from two to three clusters that are randomly distributed within an ∼600-nm radius of RYRs. With this spatial organization of RYRs and BK channels, we are able to model BK channel currents with the same salient features as those observed in STOCs across a range of physiological membrane potentials. Thus, this study provides a mechanistic understanding of the activation of STOCs by Ca2+ sparks using explicit knowledge of the spatial relationship between RYRs (the Ca2+ source) and BK channels (the Ca2+ target)

Ethnicity, sleep, mood, and illumination in postmenopausal women

BACKGROUND: This study examined how ethnic differences in sleep and depression were related to environmental illumination and circadian rhythms. METHODS: In an ancillary study to the Women's Health Initiative, 459 postmenopausal women were recorded for one week in their homes, using wrist monitors. Sleep and illumination experience were estimated. Depression was self-rated with a brief adjective check list. Affective diagnoses were made using the SCID interview. Sleep disordered breathing was monitored with home pulse oximetry. RESULTS: Hispanic and African-American women slept less than European-American women, according to both objective recordings and their own sleep logs. Non-European-American women had more blood oxygen desaturations during sleep, which accounted for 26% of sleep duration variance associated with ethnicity. Hispanic women were much more depressed. Hispanic, African-American and Native-American women experienced less daily illumination. Less daily illumination experience was associated with poorer global functioning, longer but more disturbed sleep, and more depression. CONCLUSIONS: Curtailed sleep and poor mood were related to ethnicity. Sleep disordered breathing was a factor in the curtailed sleep of minority women. Less illumination was experienced by non-European-American women, but illumination accounted for little of the contrasts between ethnic groups in sleep and mood. Social factors may be involved