Beyond the Scalpel: Advancing Strategic Approaches and Targeted Therapies in Nonexcisable Melanomas.

Melanoma in challenging anatomical locations such as the face, acral surfaces, and mucosal areas presents unique hurdles for surgical excision. This review examines alternative nonsurgical treatment modalities in the context of these complexities, addressing the gaps in current guidelines and the varied efficacy of existing therapies. A comprehensive literature search was conducted using PubMed, Embase, and Web of Science databases. The review focuses on peer-reviewed articles discussing nonsurgical treatment options for melanoma in complex anatomical locations. Articles were screened by three independent researchers, ensuring a broad analysis of topical agents, immunotherapies, radiotherapies, and targeted therapies. The review highlights significant advancements in localized treatments such as imiquimod and intralesional therapy with talimogene laherparepvec (T-VEC), which show promise in managing nonexcisable melanomas. BRAF and MEK inhibitors, as well as checkpoint inhibitors targeting CTLA-4 and PD-1/PD-L1 pathways, demonstrate improved survival rates but pose challenges with resistance and systemic side effects. Radiotherapy serves as an adjunctive strategy due to melanoma's inherent radioresistant properties. Despite advancements, there is a notable absence of comprehensive, evidence-based protocols to guide the treatment of melanoma in these critical areas. This paper underscores the need for standardized treatment guidelines that account for the efficacy, side effects, and psychosocial impacts of therapies. Future research should focus on refining existing treatments and exploring innovative modalities to enhance patient outcomes in the management of nonexcisable melanomas. Comprehensive guidelines and long-term efficacy studies are essential to optimize care and improve the quality of life for patients afflicted with melanoma in challenging anatomical locations.

A transdiagnostic group exercise intervention for mental health outpatients in Germany (ImPuls): results of a pragmatic, multisite, block-randomised, phase 3 controlled trial.

BACKGROUND: Globally, mental health conditions pose a substantial burden of disease. Despite the availability of evidence-based pharmacological and psychological treatments, the symptoms of a substantial subgroup of patients do not respond to these interventions, and only a minority of patients have access to them. This study aimed to assess the efficacy of ImPuls, a 6-month transdiagnostic group exercise intervention, plus treatment-as-usual, compared with treatment-as-usual alone in outpatients with various mental disorders. METHODS: In this pragmatic, two-arm, multisite, randomised controlled trial in Germany, ten outpatient rehabilitative and medical care facilities were involved as study sites. Participants were outpatients diagnosed according to ICD-10 with one or more of the following disorders based on structured clinical interviews: moderate or severe depression, primary insomnia, post-traumatic stress disorder (PTSD), panic disorder, or agoraphobia. Participants were required to be aged between 18 years and 65 years, insured by the health insurers Allgemeine Ortskrankenkasse Baden-Württemberg or Techniker Krankenkasse, fluent in German, and without medical contraindications for exercise. Blocks of six participants were randomly allocated to ImPuls plus treatment-as-usual or treatment-as-usual alone (allocation ratio: 1:1), stratified by study site. The randomisation sequence was generated by an external data manager. The team responsible for data collection and management was masked to the randomisation sequence. The ImPuls intervention comprised evidence-based outdoor exercises lasting 30 min, and aimed at achieving at least moderate intensity. It also incorporated behavioural change techniques targeting motivational and volitional determinants of exercise behaviour. Treatment-as-usual was representative of typical outpatient health care in Germany, allowing patients access to any standard treatments. The primary outcome was global symptom severity at 6 months after randomisation, measured using self-report on the Brief Symptom Inventory (BSI-18) and analysed in the intention-to-treat sample. No individuals with lived experience of mental illness were involved in conducting the study or writing the final publication. Safety was assessed in all participants. The trial was registered with the German Clinical Trials Register (DRKS00024152) with a completion date of June 30, 2024. FINDINGS: 600 patients provided informed consent, were recruited to the study, and underwent a diagnostic interview between Jan 1, 2021, and May 31, 2022. Following this, 199 were excluded on the basis of inclusion and exclusion criteria and one withdrew consent during the baseline assessment. Of the 400 eligible participants, 284 (71%) self-identified as female, 106 (27%) self-identified as male, and nine (2%) self-identified as other. The mean age was 42·20 years (SD 13·23; range 19-65). Ethnicity data were not assessed. 287 (72%) participants met the criteria for moderate or severe depression, 81 (20%) for primary insomnia, 37 (9%) for agoraphobia, 46 (12%) for panic disorder, and 72 (18%) for PTSD. 199 participants were allocated to the intervention group of ImPuls plus treatment-as-usual and 201 to the control group of treatment-as-usual alone. 38 (19%) participants did not receive the minimum ImPuls intervention dose. ImPuls plus treatment-as-usual demonstrated superior efficacy to treatment-as-usual alone in reducing global symptom severity, with an adjusted difference on BSI-18 of 4·11 (95% CI 1·74-6·48; d=0·35 [95% CI 0·14-0·56]; p=0·0007) at 6 months. There were no significant differences in the total number of adverse events or serious adverse events between the two groups. There was one serious adverse event (male, torn ligament) related to the intervention. INTERPRETATION: ImPuls is an efficacious transdiagnostic adjunctive treatment in outpatient mental health care. Our findings suggest that exercise therapy should be implemented in outpatient mental health care as an adjunctive transdiagnostic treatment for mental disorders such as depression, insomnia, panic disorder, agoraphobia, and PTSD. Transdiagnostic group exercise interventions might ameliorate the existing disparity in care provision between the many individuals in need of evidence-based treatment and the few who are receiving it. FUNDING: The German Innovation Fund of the Federal Joint Committee of Germany.

Body exposure and vocal analysis: validation of fundamental frequency as a correlate of emotional arousal and valence.

Introduction: Vocal analysis of fundamental frequency (f0) represents a suitable index to assess emotional activation. However, although f0 has often been used as an indicator of emotional arousal and different affective states, its psychometric properties are unclear. Specifically, there is uncertainty regarding the validity of the indices of f0mean and f0variabilitymeasures (f0dispersion, f0range, and f0SD) and whether higher or lower f0 indices are associated with higher arousal in stressful situations. The present study therefore aimed to validate f0 as a marker of vocally encoded emotional arousal, valence, and body-related distress during body exposure as a psychological stressor. Methods: N = 73 female participants first underwent a 3-min, non-activating neutral reference condition, followed by a 7-min activating body exposure condition. Participants completed questionnaires on affect (i.e., arousal, valence, body-related distress), and their voice data and heart rate (HR) were recorded continuously. Vocal analyses were performed using Praat, a program for extracting paralinguistic measures from spoken audio. Results: The results revealed no effects for f0 and state body dissatisfaction or general affect. F0mean correlated positively with self-reported arousal and negatively with valence, but was not correlated with HRmean/maximum. No correlations with any measure were found for any f0variabililtymeasures. Discussion: Given the promising findings regarding f0mean for arousal and valence and the inconclusive findings regarding f0 as a marker of general affect and body-related distress, it may be assumed that f0mean represents a valid global marker of emotional arousal and valence rather than of concrete body-related distress. In view of the present findings regarding the validity of f0, it may be suggested that f0mean, but not f0variabilitymeasures, can be used to assess emotional arousal and valence in addition to self-report measures, which is less intrusive than conventional psychophysiological measures.

Concept and study protocol of the process evaluation of a pragmatic randomized controlled trial to promote physical activity in outpatients with heterogeneous mental disorders-the ImPuls study.

BACKGROUND: Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial. METHODS: The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis. DISCUSSION: The results of our process evaluation will complement the evaluation of effectiveness and cost-effectiveness and will, for example, provide important information about mechanisms of impact, structural prerequisites, or provider qualification that may support the decision-making process of health policy stakeholders. It might contribute to paving the way for exercise programs like ImPuls to be made successively available for patients with heterogeneous mental disorders in the German outpatient mental health care system. TRIAL REGISTRATION: The parent clinical study was registered in the German Clinical Trials Register (ID: DRKS00024152, registered 05/02/2021, https://drks.de/search/en/trial/DRKS00024152 ).

Efficacy and mechanisms of change in exposure-based and cognitive stand-alone body image interventions in women with overweight and obesity.

OBJECTIVE: Body dissatisfaction is highly prevalent in overweight and obesity, while evidence for the efficacy of body image interventions is still scarce. This interventional pilot study investigates the efficacy and mechanisms of change of two stand-alone body image interventions in women with overweight and obesity. METHODS: Women with overweight and obesity (n = 76) were randomly assigned to five weekly sessions of either a mirror exposure (ME) or a cognitive restructuring intervention (CR) or to a wait-list control group (WCG). Primary outcome measures were self-reported body dissatisfaction and interview-based shape concerns; depression, self-esteem and emotional eating served as secondary outcome measures. Experimental paradigms were used prior to and after the interventions to analyze possible mechanisms of change: (a) Implicit Associations Tests to assess weight-related attitudes (b) eye-tracking experiments to assess visual processing of body pictures and (c) a thought-sampling procedure to assess body-related cognitions and arousal. RESULTS: According to intent-to-treat analyses using linear mixed-models, both interventions lead to significant improvements in body image, while there were no changes in the WCG. Different mechanisms of change were identified. CONCLUSIONS: Both types of interventions might be effective in the reduction of self-reported body dissatisfaction and interview-based shape concerns in overweight and obesity. However, as different mechanisms drive the effects, future research should clarify which individual might best benefit from which intervention.

Attentional processing of body images in women with overweight and obesity.

PURPOSE: Despite the claim to integrate body image interventions in obesity treatment, little is known about the mechanisms involved in maintaining body dissatisfaction in persons with overweight and obesity. Therefore, the present study sought to investigate attentional processing of body stimuli in women with overweight and obesity (OW). METHODS: Women with OW (n = 82) and normal weight controls (NW; n = 44) conducted two eye-tracking paradigms. In the first paradigm, fixation duration on the subjectively most beautiful and ugliest body part of one's own and a weight-matched control body were analyzed. In the second paradigm, picture pairs including the own and a control body or object were presented and initial fixation orientation was measured. Automatic and intentional processing of the body pictures was manipulated by either indicating on which side which stimuli would appear or not. RESULTS: Women with OW displayed a bias towards the ugliest as opposed to the most beautiful body part, whereas women with NW showed a balanced viewing pattern. Furthermore, both groups showed a preference for bodies relative to the object. However, only women with OW preferred their own relative to the control body during intentional processing. CONCLUSION: Taken together, results point towards a self-focused and deficit-oriented gaze pattern in women with overweight and obesity. Targeting these processes might help to improve obesity treatment outcomes. LEVEL OF EVIDENCE: Level I, experimental study.

Prenatal telemedicine during COVID-19: patterns of use and barriers to access.

OBJECTIVE: To evaluate patient experience with a prenatal telemedicine visit and identify barriers to accessing telemedicine among rural pregnant people in northern New England during the beginning of the COVID-19 pandemic. MATERIALS AND METHODS: We conducted a postvisit electronic survey of pregnant people who successfully participated in a prenatal telemedicine visit at a rural academic medical center in Northern New England. Nineteen questions were included in 5 domains: (1) engagement with prenatal care; (2) barriers to telemedicine and in person healthcare; (3) experience of prenatal care; (4) remote pregnancy surveillance tools; and (5) sources of COVID-19 information. RESULTS: Responses were obtained from 164 pregnant people. Forty percent of participants had participated in an audio-only telemedicine visit, and 60% in a video telemedicine visit. The visit was easy or somewhat easy for 79% of respondents and somewhat difficult or difficult for 6.8%. The most common barrier to accessing telemedicine was poor internet or phone connectivity, followed by childcare responsibilities, lack of equipment, and lack of privacy. Participants also engaged in additional remote prenatal care including phone calls with registered nurses (7.6%), communication with the obstetrics team through a secure health messaging portal (21.1%), and home health monitoring (76.3%). DISCUSSION AND CONCLUSIONS: In this survey, evaluating the experience of pregnant people participating in a prenatal telemedicine visit during the COVID-19 pandemic, respondents had a positive experience with telemedicine overall, but also identified significant barriers to participation including issues with connectivity and lack of equipment for the visit. Most participants used telemedicine in combination with other tools for remote self-care.

Vocal arousal: a physiological correlate of body distress in women with overweight and obesity.

PURPOSE: Numerous studies highlight the relevance of body image in the development and maintenance of overweight and obesity mostly using self-reported data. Given the importance of physiological assessment methods, the present study aimed at investigating vocally encoded emotional arousal as a correlate of body distress in women with overweight and obesity. METHODS: Cognitions of women with overweight and obesity (OW; n = 22) as well as normal weight controls (NW; n = 22) were assessed by means of a thought-sampling procedure during a mirror exposure and a control condition. Fundamental frequency (f0) as a marker of vocally encoded emotional arousal as well as verbalized body-related cognitions were analyzed during this experimental task. RESULTS: A stronger increase in f0 between the control and the mirror exposure condition was found in OW compared to NW. Furthermore, there were significant positive correlations between vocally encoded emotional arousal and various measures of body image. CONCLUSION: The findings support the utility of vocally encoded emotional arousal as an objective physiological correlate of the evaluative dimension of body image in women with overweight and obesity. LEVEL OF EVIDENCE: Level I, experimental study.

Cognitive-Emotional Involvement During Mirror Exposure Is Not Accompanied by Physiological Activation in Binge Eating Disorder.

Body image interventions have been shown to reduce self-reported cognitive-emotional facets of body image disturbance in binge eating disorder (BED). However, more objective assessment methods are required to evaluate the effects of these interventions. Therefore, the present study aimed at investigating the usefulness of vocally encoded emotional arousal as physiological correlate of body dissatisfaction during mirror exposure in women with BED. Women with BED (n = 60) and weight-matched controls (CG; n = 60) participated in an experimental thought-sampling procedure including a mirror exposure and a control condition in a repeated-measures design. Fundamental frequency as a vocal correlate of emotional arousal as well as negative, neutral, and positive body-related cognitions during both conditions were analyzed. In line with our hypotheses, the BED group verbalized more negative, and less positive and neutral body-related cognitions during the mirror exposure condition compared to the CG. Contrary to our hypotheses, though, there was a stronger increase in physiological arousal between the control and the mirror exposure condition in the CG relative to the BED group. Furthermore, a significant negative correlation between fundamental frequency and the severity of cognitive-emotional body image disturbances emerged. The findings indicate a cognitive-emotional over-involvement with physical appearance during mirror exposure in women with BED compared to weight-matched controls in the absence of a corresponding physiological pattern. Results are discussed in terms of an impaired ability of women with BED to show adequate physiological responses to body-related stress. In addition, methodological recommendations for future research are presented.

Efficacy of psychotherapies and pharmacotherapies for Bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN), a mental disorder that causes significant impairment, can be treated with psychological, pharmacological, nutrition-based and self-help interventions. We conducted a pre-registered meta-analysis of randomized-controlled trials (RCTs) to assess the efficacy of these interventions in up to 19 different interventions. METHODS: Database search terms were combined for BN and RCTs from database inception to March 2017. Abstinence from binge eating episodes, compensatory behaviors, the absence of a BN diagnosis and reduction of symptom severity were considered as primary outcome variables, reduction of self-reported eating pathology and depression served as secondary outcome variables. Retrieved RCTs were meta-analyzed using fixed and random effects models. RESULTS: RCT (79 trials; 5775 participants) effects post-treatment revealed moderate to large intervention effects for psychotherapy [mostly cognitive-behavioral therapy (CBT)] for primary outcome variables. Slightly reduced effects were obtained for self-help and moderate effects for pharmacotherapy. Similarly, psychotherapy yielded large to very large effects in regard to secondary outcome variables, while moderate to large effects were observed for self-help, Pharmacotherapy and combined therapies. Meta-analyses for the pre to post changes within group confirmed these findings. Additionally, follow-up analyses revealed the sustainability of psychotherapies in terms of large effects in primary outcome criteria, while these effects were moderate for self-help, pharmacotherapy, and combined therapies. CONCLUSIONS: Most psychological and pharmacological interventions revealed to be effective in BN treatment. Taking effect size, sustainability of the intervention, as well as the consistency of findings and available evidence into consideration, CBT can be recommended as the best intervention for the initial treatment of BN.

Multifaceted regulation of somatic cell reprogramming by mRNA translational control.

Translational control plays a pivotal role in the regulation of the pluripotency network in embryonic stem cells, but its effect on reprogramming somatic cells to pluripotency has not been explored. Here, we show that eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs), which are translational repressors, have a multifaceted effect on the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs). Loss of 4E-BP expression attenuates the induction of iPSCs at least in part through increased translation of p21, a known inhibitor of somatic cell reprogramming. However, MEFs lacking both p53 and 4E-BPs show greatly enhanced reprogramming resulting from a combination of reduced p21 transcription and enhanced translation of endogenous mRNAs such as Sox2 and Myc and can be reprogrammed through the expression of only exogenous Oct4. Thus, 4E-BPs exert both positive and negative effects on reprogramming, highlighting the key role that translational control plays in regulating this process.