23-year-old woman • fever, fatigue, and sore throat • Scleral icterus and hepatosplenomegaly • Dx?

► fever, fatigue, and sore throat ► Scleral icterus and hepatosplenomegaly.

Effects of active musical engagement during physical exercise on anxiety, pain and motivation in patients with chronic pain.

The experience of anxiety is central to the development of chronic pain. Music listening has been previously shown to exert analgesic effects. Here we tested if an active engagement in music making is more beneficial than music listening in terms of anxiety and pain levels during physical activity that is often avoided in patients with chronic pain. We applied a music feedback paradigm that combines music making and sports exercise, and which has been previously shown to enhance mood. We explored this method as an intervention to potentially reduce anxiety in a group of patients with chronic pain (N = 24, 20 female and 4 men; age range 34-64, M = 51.67, SD = 6.84) and with various anxiety levels. All participants performed two conditions: one condition, Jymmin, where exercise equipment was modified with music feedback so that it could be played like musical instruments by groups of three. Second, a conventional workout condition where groups of three performed exercise on the same devices but where they listened to the same type of music passively. Participants' levels of anxiety, mood, pain and self-efficacy were assessed with standardized psychological questionnaires before the experiment and after each condition. Results demonstrate that exercise with musical feedback reduced anxiety values in patients with chronic pain significantly as compared to conventional workout with passive music listening. There were no significant overall changes in pain, but patients with greater anxiety levels compared to those with moderate anxiety levels were observed to potentially benefit more from the music feedback intervention in terms of alleviation of pain. Furthermore, it was observed that patients during Jymmin more strongly perceived motivation through others. The observed diminishing effects of Jymmin on anxiety have a high clinical relevance, and in a longer term the therapeutic application could help to break the Anxiety Loop of Pain, reducing chronic pain. The intervention method, however, also has immediate benefits to chronic pain rehabilitation, increasing the motivation to work out, and facilitating social bonding.

Enhanced Short-Term Memory Function in Older Adults with Dementia Following Music-Feedback Physical Training: A Pilot Study.

Prior research demonstrates that music making, physical exercise, and social activity have unique, positive effects on cognition and mood. One intervention, "Jymmin®", was developed incorporating these approaches and found effective for decreased pain perception and increased endurance, self-efficacy, mood, and muscle efficiency. Previously, Jymmin was not piloted with older adults with dementia. The current study is a randomized pilot study of the Jymmin® with an older adult population in a long-term care facility (n = 38), evaluated across dementia levels (mild, moderate, or severe). Results found significant improvements in scores on a confrontation naming task across all conditions (p = 0.047) and a significant interaction effect for short-term memory scores (p = 0.046), suggesting higher scores at Time 2 for the experimental group and at Time 3 for the control group. There were no significant changes in mood ratings. Findings are discussed in the context of neural activity and musical agency.

Corrigendum: Musical feedback system Jymmin® leads to enhanced physical endurance in the elderly-A feasibility study.

[This corrects the article DOI: 10.3389/fspor.2022.915926.].

Musical feedback system Jymmin® leads to enhanced physical endurance in the elderly-A feasibility study.

Background and objectives: Active music-making in combination with physical exercise has evoked several positive effects in users of different age groups. These include enhanced mood, muscular effectivity, pain threshold, and decreased perceived exertion. The present study tested the applicability of this musical feedback system, called Jymmin ®, in combination with strength-endurance exercises in a population of healthy older adults. Research design and methods: Sixteen healthy, physically inactive older adults (5 males, 11 females) at the mean age of 70 years performed physical exercise in two conditions: A conventional work-out while listening passively music and a Jymmin ® work-out, where musical sounds were created with one's work-out movements. According to the hypothesis that strength-endurance is increased during musical feedback exercise, parameters relating to strength-endurance were assessed, including exercise duration, number of repetitions, perceived exertion (RPE), and participants' mental state (Multidimensional Mood State Questionnaire; MDMQ). Results: Results show that participants exercised significantly longer while doing Jymmin ® (Mdn = 248.75 s) as compared to the conventional work-out (Mdn = 182.73 s), (Z = 3.408, p = 0.001). The RPE did not differ between conventional work-out and the Jymmin ® condition, even though participants worked out significantly longer during the Jymmin ® condition (Mdn = 14.50; Z = -0.905; p = 0.366). The results of the MDMQ showed no significant differences between both conditions (Z = -1.037; p = 0.300). Discussion and implications: Results show that participants could work out longer while showing the same perceived exertion, relating to increased physical endurance. Music feedback work-out encouraged a greater degree of isometric contractions (muscle actively held at fixed length) and, therefore, less repetitions in this condition. In addition to the previously described effect on muscle effectivity, this non-stereotypic contraction pattern during music feedback training may have enhanced endurance in participants supporting them to better proportion energetic reserves during training (pacing). Clinical trial registration: Identifier: DRKS00023645.

Components of Active Music Interventions in Therapeutic Settings-Present and Future Applications.

Musical interventions in therapy have become increasingly relevant for rehabilitation in many clinics. What was long known for physiotherapy training-that the agency of the participant is crucial and moving is much more efficient for rehabilitation success than being moved-has over recent years also been shown to be true for music therapy. Accumulating evidence suggests that active musical interventions are especially efficient at helping rehabilitation success. Here, we review various approaches to active music therapy. Furthermore, we present several components that allow for manipulating musical expressiveness and physical engagement during active musical interventions, applying a technology-based music feedback paradigm. This paper will allow for a transfer of insights to other domains of music-based therapeutic interventions.

Advanced Multimodal Communication Curriculum for Pediatric Residents.

BACKGROUND: Medical educators juggle competing demands as they seek to integrate medical advancements and new technology with the call for earlier introduction to clinical experiences. Newer models of medical education place even greater emphasis on the importance of deliberate training of providers who can deliver compassionate patient-centered care. The need for adaptable, effective communication skills training has never been more relevant than now, in our high-tech and ever-evolving learning climate. METHODS: At a large pediatric academic center, we used Kern's six-step approach to complete a needs assessment, identify goals and learning preferences of trainees, and ultimately develop and evaluate a multimodal communication curriculum. This curriculum was rooted in the Accreditation Council for Graduate Medical Education's Pediatric Milestones, with the goal of enhancing knowledge, skills, and competency. Pediatric interns were randomized to either the new curriculum (n = 19) or the existing didactic-based communication training (n = 17) from 2019 to 2020. We evaluated the impact of the new and traditional curriculum through evaluations by expert facilitators, learner surveys, and faculty-assigned resident milestones. RESULTS: Many trainees self-identified performance gaps in communication skills at baseline. Eighteen residents attended 1 to 6 in-person deliberate practice workshops. Workshop participation by the residents varied over time due to a variety of factors. All residents, regardless of curricular exposure, showed statistically significant improvement in communication milestones from first to second year and those enrolled in the deliberate practice curriculum highly valued the workshops and coaching. DISCUSSION: Our curriculum demonstrates the value of deliberate practice opportunities for residents to gain skills in advanced communication. Residents appreciated this type of training and the time devoted to expand these skills. Lessons learned and barriers to implementation from this curriculum can be helpful for educators interested in integrating active, deliberate practice, simulation-based communication training into their current educational model.

Antenatal N-acetylcysteine to improve outcomes of premature infants with intra-amniotic infection and inflammation (Triple I): randomized clinical trial.

BACKGROUND: Intrauterine infection and/or inflammation (Triple I) is an important cause of preterm birth (PTB) and adverse newborn outcomes. N-acetylcysteine (NAC) is a Food and Drug Administration (FDA)-approved drug safely administered to pregnant women with acetaminophen toxicity. METHODS: We conducted a single-center, quadruple-blind, placebo-controlled trial of pregnant women with impending PTB due to confirmed Triple I. Participants (n = 67) were randomized to an intravenous infusion of NAC or placebo mimicking the FDA-approved regimen. Outcomes included clinical measures and mechanistic biomarkers. RESULTS: Newborns exposed to NAC (n = 33) had significantly improved status at birth and required less intensive resuscitation compared to placebo (n = 34). Fewer NAC-exposed newborns developed two or more prematurity-related severe morbidities [NAC: 21% vs. placebo: 47%, relative risk, 0.45; 95% confidence interval (CI) 0.21-0.95] with the strongest protection afforded against bronchopulmonary dysplasia (BPD, NAC: 3% vs. placebo: 32%, relative risk, 0.10; 95% CI: 0.01-0.73). These effects were independent of gestational age, birth weight, sex, or race. Umbilical cord plasma NAC concentration correlated directly with cysteine, but not with plasma or whole blood glutathione. NAC reduced the placental expression of histone deacetylase-2, suggesting that epigenetic mechanisms may be involved. CONCLUSIONS: These data provide support for larger studies of intrapartum NAC to reduce prematurity-related morbidity. IMPACT: In this randomized clinical trial of 65 women and their infants, maternal intravenous NAC employing the FDA-approved dosing protocol resulted in lower composite neonatal morbidity independent of gestational age, race, sex, and birthweight. Administration of NAC in amniocentesis-confirmed Triple I resulted in a remarkably lower incidence of BPD. As prior studies have not shown a benefit of postnatal NAC in ventilated infants, our trial highlights the critical antenatal timing of NAC administration. Repurposing of NAC for intrapartum administration should be explored in larger clinical trials as a strategy to improve prematurity-related outcomes and decrease the incidence of BPD.

Family-centered communication: A pilot educational intervention using deliberate practice and patient feedback.

OBJECTIVE: There are few opportunities in medical education dedicated to learning skills for effective communication in life altering patient scenarios. We therefore aimed to develop and assess a longitudinal advanced communication curriculum for pediatric residents using patient feedback and deliberate practice. METHODS: Pediatric residents at a large academic center were randomized into 2 groups. The intervention group received 6 educational sessions from 2019 to 2020, parent feedback of performance via the Communication Assessment Tool (CAT), and monthly communication tips. Communication skills of both groups were assessed at the end of the intervention. RESULTS: We collected 937 CAT assessments on 36 first-year residents. The intervention group demonstrated statistically significant improvement in communication skills from pre to post assessment (p = 0.0063, (odds ratio (OR) 1.76, 95 % confidence interval (CI) [1.17, 2.63]) compared to the control group (p = 0.080, OR 1.41, 95 % CI [0.96, 2.05]). CONCLUSIONS: There are patient and self-identified performance gaps in communication skills for pediatric residents, underscoring the need for formalized curricula dedicated to these skills. PRACTICE IMPLICATIONS: Our study highlights the value of deliberate practice and the integration of family feedback as an educational tool in communication skills development.

Dissonance in Music Impairs Spatial Gait Parameters in Patients with Parkinson's Disease.

BACKGROUND: It is known that music influences gait parameters in Parkinson's disease (PD). However, it remains unclear whether this effect is merely due to temporal aspects of music (rhythm and tempo) or other musical parameters. OBJECTIVE: To examine the influence of pleasant and unpleasant music on spatiotemporal gait parameters in PD, while controlling for rhythmic aspects of the musical signal. METHODS: We measured spatiotemporal gait parameters of 18 patients suffering from mild PD (50%men, mean±SD age of 64±6 years; mean disease duration of 6±5 years; mean Unified PD Rating scale [UPDRS] motor score of 15±7) who listened to eight different pieces of music. Music pieces varied in harmonic consonance/dissonance to create the experience of pleasant/unpleasant feelings. To measure gait parameters, we used an established analysis of spatiotemporal gait, which consists of a walkway containing pressure-receptive sensors (GAITRite®). Repeated measures analyses of variance were used to evaluate effects of auditory stimuli. In addition, linear regression was used to evaluate effects of valence on gait. RESULTS: Sensory dissonance modulated spatiotemporal and spatial gait parameters, namely velocity and stride length, while temporal gait parameters (cadence, swing duration) were not affected. In contrast, valence in music as perceived by patients was not associated with gait parameters. Motor and musical abilities did not relevantly influence the modulation of gait by auditory stimuli. CONCLUSION: Our observations suggest that dissonant music negatively affects particularly spatial gait parameters in PD by yet unknown mechanisms, but putatively through increased cognitive interference reducing attention in auditory cueing.

Increasing Divergent Thinking Capabilities With Music-Feedback Exercise.

Divergent thinking is an essential aspect of creativity and has been shown to be affected both by music and physical exercise. While it has been shown that making music and physical exercise can be beneficial for Divergent Thinking in isolation, it is unclear whether the effects can be combined. The present experiment investigated the relation of physical exertion and being in control of music on Divergent Thinking and the possibility of an interaction effect. Seventy-seven predominantly young, German participants were tested with measurements of Divergent Thinking collected after either (1) physical exercise with music listening, (2) making music with a knob setup without physical effort (music control only), or (3) making physical exercise with musical feedback (Jymmin™). Results showed greater increases in Divergent Thinking scores following music-feedback exercise compared to conditions of physical exercise with music listening and music control only. The data thus demonstrate that making music part of a physical exercise routine more strongly leads to the benefit of increased creative capacities, which we argue will be beneficial for athletes to prepare for certain types of competition/performance and as part of regeneration training.

Factors Associated with Neurodevelopmental Impairment in Bronchopulmonary Dysplasia.

OBJECTIVE: To identify factors associated with neurodevelopmental impairment (NDI) in patients with bronchopulmonary dysplasia (BPD). STUDY DESIGN: We identified 151 patients with moderate to severe BPD from 2010 to 2014 with complete Bayley Scales of Infant Development (BSID) scores at 24 months corrected age. We defined NDI as any diagnosis of cerebral palsy or ≥1 BSID composite scores of <80. RESULTS: The mean corrected age at BSID was 23 ± 1 months; 18% had a cognitive score of <80, 37% had a communication score of <80, and 26% had a motor score of <80. Cerebral palsy was diagnosed in 22 patients (15%); 84 (56%) patients did not have NDI. Patients with NDI had lower birth weight, but there was no difference in gestational age at birth, severe intraventricular hemorrhage (IVH), necrotizing enterocolitis, or patent ductus arteriosus ligation compared with patients with no NDI. Ventilator days were greater in patients with NDI than in patients without NDI. More patients with NDI received furosemide and systemic corticosteroids and the hospital length of stay was longer than in patients with no NDI. Logistic regression modeling demonstrated that for every additional 100 g of birth weight the odds of NDI decreased by 35% and for every additional hospital day the odds of NDI increased by 1.3%. CONCLUSIONS: In our cohort of patients with moderate to severe BPD, the majority had no NDI, and low birth weight and length of hospital stay were associated with increased risk of developing NDI. This finding suggests that there are potentially modifiable factors associated with better neurodevelopmental outcomes in patients with BPD that deserve further study.

Blame it on the bossa nova: Transfer of perceived sexiness from music to touch.

Emotion elicited through music transfers to subsequent processing of facial expressions. Music may accordingly function as a social technology by promoting social bonding. Here, we investigated whether music would cross-modally influence the perception of sensual touch, a behavior related to mating. A robot applied precisely controlled gentle touch to a group of healthy participants while they listened to music that varied with respect to its perceived sexiness. As the perceived sexiness of the music increased, so did the subjective sexiness of the touch stimulations. In short, the perception of sexiness transferred from music to touch. Because sensual touch is key to mating behavior and relates to procreation, this association has implications for the universality and evolutionary significance of music. (PsycINFO Database Record

Musical Agency during Physical Exercise Decreases Pain.

Objectives: When physical exercise is systematically coupled to music production, exercisers experience improvements in mood, reductions in perceived effort, and enhanced muscular efficiency. The physiology underlying these positive effects remains unknown. Here we approached the investigation of how such musical agency may stimulate the release of endogenous opioids indirectly with a pain threshold paradigm. Design: In a cross-over design we tested the opioid-hypothesis with an indirect measure, comparing the pain tolerance of 22 participants following exercise with or without musical agency. Method: Physical exercise was coupled to music by integrating weight-training machines with sensors that control music-synthesis in real time. Pain tolerance was measured as withdrawal time in a cold pressor test. Results: On average, participants tolerated cold pain for ~5 s longer following exercise sessions with musical agency. Musical agency explained 25% of the variance in cold pressor test withdrawal times after factoring out individual differences in general pain sensitivity. Conclusions: This result demonstrates a substantial pain reducing effect of musical agency in combination with physical exercise, probably due to stimulation of endogenous opioid mechanisms. This has implications for exercise endurance, both in sports and a multitude of rehabilitative therapies in which physical exercise is effective but painful.

The Band Effect-Physically Strenuous Music Making Increases Esthetic Appreciation of Music.

The esthetic appreciation of music is strongly influenced by cultural background and personal taste. One would expect that this would complicate the utilizability of musical feedback in paradigms, such that music would only be perceived as a reward if it complies to personal esthetic appreciation. Here we report data where we assessed esthetic appreciation of music after 1. a physically strenuous music improvisation and 2. after passive music listening (where participants esthetically assessed similar music). Data are reported from two experiments with different patient groups: 1. Drug abuse patients, and 2. Chronic pain patients. Participants in both experiments performed Jymmin, a music feedback method where exercise equipment is modified in such a way that it can be played like musical instruments by modulating musical parameters in a composition software. This combines physical exertion with musical performance in a fashion that has previously been shown to have a number of positive psychological effects such as enhanced mood and reduced perceived exertion. In both experiments esthetic appreciation of musical presentations during Jymmin and a control condition without musical agency were compared. Data show that both patient groups perceived the musical outcome of their own performance as more esthetically pleasing than similar music they listened to passively. This suggests that the act of making music (when combined with physical exertion) is associated with a positivity bias about the perceived esthetical quality of the musical outcome. The outcome of personal musical agency thus tends to be perceived as rewarding even if it does not comply with personal esthetic appreciation. This suggests that musical feedback interventions may not always have to be highly individualized because individual taste may not always be crucial. The results also suggest that the method applied here may be efficient at encouraging music listeners to actively explore new musical styles that they might otherwise be reluctant to listen to (e.g., avant-garde music). The results also hint toward a deeper understanding of why musicians, who exert themselves physically during musical performances to generate music and regardless of the type of music they are playing, typically find the physically demanding experience esthetically satisfying.

Benefits of listening to a recording of euphoric joint music making in polydrug abusers.

BACKGROUND AND AIMS: Listening to music can have powerful physiological and therapeutic effects. Some essential features of the mental mechanism underlying beneficial effects of music are probably strong physiological and emotional associations with music created during the act of music making. Here we tested this hypothesis in a clinical population of polydrug abusers in rehabilitation listening to a previously performed act of physiologically and emotionally intense music making. METHODS: Psychological effects of listening to self-made music that was created in a previous musical feedback intervention were assessed. In this procedure, participants produced music with exercise machines (Jymmin) which modulate musical sounds. RESULTS: The data showed a positive effect of listening to the recording of joint music making on self-efficacy, mood, and a readiness to engage socially. Furthermore, the data showed the powerful influence of context on how the recording evoked psychological benefits. The effects of listening to the self-made music were only observable when participants listened to their own performance first; listening to a control music piece first caused effects to deteriorate. We observed a positive correlation between participants' mood and their desire to engage in social activities with their former training partners after listening to the self-made music. This shows that the observed effects of listening to the recording of the single musical feedback intervention are influenced by participants recapitulating intense pleasant social interactions during the Jymmin intervention. CONCLUSIONS: Listening to music that was the outcome of a previous musical feedback (Jymmin) intervention has beneficial psychological and probably social effects in patients that had suffered from polydrug addiction, increasing self-efficacy, mood, and a readiness to engage socially. These intervention effects, however, depend on the context in which the music recordings are presented.

EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells.

EGF receptor (EGFR) promotes tumor growth as well as radio- and chemoresistance in various human malignancies including squamous cell carcinomas (SCC). In addition to deactivation of prosurvival signaling, cetuximab-mediated EGFR targeting might concomitantly induce self-attenuating signaling bypasses. Identification of such bypass mechanisms is key to improve the efficacy of targeted approaches. Here, we show great similarity of EGFR signaling and radiation survival in cetuximab-treated SCC cells grown in a more physiologic three-dimensional extracellular matrix and as tumor xenografts in contrast to conventional monolayer cell cultures. Using phosphoproteome arrays, we observed strong induction of JNK2 phosphorylation potentially resulting from cetuximab-inhibited EGFR through c-jun-NH(2)-kinase (JNK)-interacting protein-4 (JIP-4), which was identified using an immunoprecipitation-mass spectrometric approach. Inhibition of this signaling bypass by JIP-4 or JNK2 knockdown or pharmacologic JNK2 inhibition enhanced cetuximab efficacy and tumor cell radiosensitivity. Our findings add new facets to EGFR signaling and indicate signaling bypass possibilities of cancer cells to improve their survival on cetuximab treatment. By deactivation of cetuximab-self-attenuating JNK2-dependent signaling, the cytotoxicity, and radiosensitizing potential of cetuximab can be augmented.

Impact of atorvastatin treatment on platelet-activating factor acetylhydrolase and 15-F(2trans)-isoprostane in hypercholesterolaemic patients.

AIMS: Isoprostanes are the product of free radical oxidation of arachidonic acid, whose hydrolysis from phospholipids is presumably catalysed by phospholipases A(2) (PLA(2)s) such as group IIA or V PLA(2)s, or group VII PLA(2)[platelet-activating factor acetylhydrolase (PAF-AH), lipoprotein-associated phospholipase]. Atorvastatin reduces concentrations of low-density lipoprotein (LDL), with which PAF-AH is associated, and PLA(2)s' protein concentrations. We investigated the effect of atorvastatin on PLA(2)s and PAF-AH activity and the urinary excretion of 15-F(2trans)-isoprostane (15-F(2t)-IsoP, 8-iso-PGF(2alpha), iPF(2alpha)-III). METHODS: Twenty-four hypercholesterolaemic individuals naive to lipid-lowering therapy were randomized to atorvastatin 40 mg or placebo for 6 weeks. The 15-F(2t)-isoP urinary excretion (gas chromatography/mass spectrometry), PAF-AH and group IIA and V PLA(2) activities (photometry) were assessed at baseline and end-point. RESULTS: At end-point, 15-F(2t)-isoP urinary excretion concentrations as well as PLA(2)s' activity were unchanged under atorvastatin (mean change 0.21 +/- 1.79 ng h(-1), 95% confidence interval -0.92, 1.35 and 0.33 +/- 0.94 nmol min(-1) ml(-1), -0.27, 0.93) and under placebo (mean change 0.69 +/- 1.69 ng h(-1), -0.52, 1.90 and 1.29 +/- 2.16 nmol min(-1) ml(-1), -0.25, 2.84). Atorvastatin treatment decreased total (P < 0.001) and LDL-cholesterol (P < 0.001) but had no effect on high-density lipoprotein. PAF-AH activity was lowered in the atorvastatin group (mean change - 5.27+/- 1.96 nmol min(-1) ml(-1), -6.51, -4.03, P < 0.001) but not in the placebo group (mean change 1.02 +/- 1.64 nmol min(-1) ml(-1), 0.15, 2.20), and the change in PAF-AH activity was correlated with that in total (P = 0.03) and LDL-cholesterol (P = 0.03). CONCLUSION: Our results show a lowering effect of atorvastatin on PAF-AH activity associated with its lipid-lowering effect and exclude a key role of PAF-AH in the liberation of 15-F(2t)-isoP from phospholipids.