Design and validation of a GMP stem cell manufacturing protocol for MPSII hematopoietic stem cell gene therapy.

Hematopoietic stem cell gene therapy (HSCGT) is a promising therapeutic strategy for the treatment of neurodegenerative, metabolic disorders. The approach involves the ex vivo introduction of a missing gene into patients' own stem cells via lentiviral-mediated transduction (TD). Once transplanted back into a fully conditioned patient, these genetically modified HSCs can repopulate the blood system and produce the functional protein, previously absent or non-functional in the patient, which can then cross-correct other affected cells in somatic organs and the central nervous system. We previously developed an HSCGT approach for the treatment of Mucopolysaccharidosis type II (MPSII) (Hunter syndrome), a debilitating pediatric lysosomal disorder caused by mutations in the iduronate-2-sulphatase (IDS) gene, leading to the accumulation of heparan and dermatan sulfate, which causes severe neurodegeneration, skeletal abnormalities, and cardiorespiratory disease. In HSCGT proof-of-concept studies using lentiviral IDS fused to a brain-targeting peptide ApoEII (IDS.ApoEII), we were able to normalize brain pathology and behavior of MPSII mice. Here we present an optimized and validated good manufacturing practice hematopoietic stem cell TD protocol for MPSII in preparation for first-in-man studies. Inclusion of TEs LentiBOOST and protamine sulfate significantly improved TD efficiency by at least 3-fold without causing adverse toxicity, thereby reducing vector quantity required.

Prescribing pre- and post-operative physical activity interventions for people undergoing breast cancer surgery: A qualitative systematic review.

INTRODUCTION: Undertaking physical activity, pre- and post-operatively, can benefit recovery time and improve post-surgical outcomes. One cohort of patients that have reported these benefits are those undergoing surgery for breast cancer. Yet, what remains unclear is the level to which physical activity interventions are implemented into standard surgical care for patients with breast cancer. AIMS: This systematic review aimed to examine existing qualitative evidence focusing on pre- and post-operative physical activity interventions to better understand the benefits and shortcomings of physical activity within the surgical journey. METHODS: A systematic literature search was undertaken in November 2022, across five databases: MEDLINE, PsycINFO, Embase, CINAHL, and Scopus. Qualitative studies involving people with breast cancer who had undertaken a physical activity intervention, either pre- and/or post-operatively, were included for analysis. The review was registered on PROSPERO: CRD42022372466 and performed according to PRISMA guidelines. The Critical Appraisal Skills Programme qualitative study checklist was used to assess study quality. RESULTS: Fourteen studies were included, comprising the perspectives of 418 people receiving surgery for breast cancer. One study implemented preoperative physical activity interventions; the remaining studies focused on post-operative interventions. A narrative systematic review was undertaken due to heterogeneity in reported results. Four themes were developed by thematic analysis, centring on: (1) factors promoting engagement with physical activity interventions; (2) factors preventing engagement with physical activity interventions; (3) the impact of pre- and post-operative interventions on physical and psychological health; and (4) participant recommendations for pre- and post-operative interventions. CONCLUSION: Pre- and post-operative physical activity interventions were well-accepted. Patients recognised factors which promoted or prevented engagement with interventions, as well as pre- and post-operative physical and psychological benefits that arose as a result. Evidence based co-design studies may further inform successful implementation of prescribed physical activity into standard care for surgical breast cancer patients.

Medicine plus mindset: A mixed-methods evaluation of a novel mindset-focused training for primary care teams.

OBJECTIVES: Patient mindsets influence health outcomes; yet trainings focused on care teams' understanding, recognizing, and shaping patient mindsets do not exist. This paper aims to describe and evaluate initial reception of the "Medicine Plus Mindset" training program. METHODS: Clinicians and staff at five primary care clinics (N = 186) in the San Francisco Bay Area received the Medicine Plus Mindset Training. The Medicine Plus Mindset training consists of a two-hour training program plus a one-hour follow-up session including: (a) evidence to help care teams understand patients' mindsets' influence on treatment; (b) a framework to support care teams in identifying specific patient mindsets; and (c) strategies to shape patient mindsets. RESULTS: We used a common model (Kirkpatrick) to evaluate the training based on participants' reaction, learnings, and behavior. Reaction: Participants rated the training as highly useful and enjoyable. Learnings: The training increased the perceived importance of mindsets in healthcare and improved self-reported efficacy of using mindsets in practice. Behavior: The training increased reported frequency of shaping patient mindsets. CONCLUSIONS: Development of this training and the study's results introduce a promising and feasible approach for integrating mindset into clinical practice. Practice Implications Mindset training can add a valuable dimension to clinical care and should be integrated into training and clinical practice.

Physician weight influences responses to a public health message about the genetics of obesity.

OBJECTIVE: Many patients prefer lean physicians to physicians with obesity and place higher credence in their weight management advice. Because genetic information about weight can be viewed as self-serving for individuals with overweight or obesity, physicians with obesity may be discounted when sharing such information. As provision of genetic information regarding weight becomes increasingly common in public health messaging, could a physician's own weight influence how these messages are received by the public? METHODS: In an online survey, 967 participants were randomly assigned a physician profile (lean v. has obesity) with a media interview transcript discussing genetic factors of a common health condition (obesity v. osteoporosis). RESULTS: Participants perceived the physician with obesity who discussed genetic factors in obesity as less trustworthy and less credible. Participants were also less likely to anticipate following her advice on weight-related issues. Participants with higher BMI had less negative perceptions of this physician. CONCLUSION: Physicians with obesity, when providing public health messaging regarding genetic information about obesity, may be met with distrust and negative attitudes toward the physician. PRACTICAL IMPLICATIONS: Future research should investigate health communication strategies that address this form of weight stigma while accurately conveying genetic factors that contribute to weight.

"Harnessing the placebo effect: Exploring the influence of physician characteristics on placebo response": Correction.

Reports an error in "Harnessing the placebo effect: Exploring the influence of physician characteristics on placebo response" by Lauren C. Howe, J. Parker Goyer and Alia J. Crum (Health Psychology, 2017[Nov], Vol 36[11], 1074-1082). In the original article, changes were needed to clarify the timeframe over which allergic reactions were measured after the skin prick test (SPT) and the administration of the placebo cream, which was erroneously misrepresented in some cases being "0 to 6 minutes after cream application" when it should have stated "3 to 9 minutes after cream application." Corrections have been made to reflect this in the "Analytic Strategy for Physiological Results" section and in Figures 2 and 3 and the Figure Notes that accompany them. An additional supplemental figure (Figure S7) has also been added to the supplemental material available online to further clarify the timing of measurements, both in terms of time post-SPT and time post-cream application. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2017-10534-001). OBJECTIVE: Research on placebo/nocebo effects suggests that expectations can influence treatment outcomes, but placebo/nocebo effects are not always evident. This research demonstrates that a provider's social behavior moderates the effect of expectations on physiological outcomes. METHODS: After inducing an allergic reaction in participants through a histamine skin prick test, a health care provider administered a cream with no active ingredients and set either positive expectations (cream will reduce reaction) or negative expectations (cream will increase reaction). The provider demonstrated either high or low warmth, or either high or low competence. RESULTS: The impact of expectations on allergic response was enhanced when the provider acted both warmer and more competent and negated when the provider acted colder and less competent. CONCLUSION: This study suggests that placebo effects should be construed not as a nuisance variable with mysterious impact but instead as a psychological phenomenon that can be understood and harnessed to improve treatment outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

White patients' physical responses to healthcare treatments are influenced by provider race and gender.

The healthcare workforce in the United States is becoming increasingly diverse, gradually shifting society away from the historical overrepresentation of White men among physicians. However, given the long-standing underrepresentation of people of color and women in the medical field, patients may still associate the concept of doctors with White men and may be physiologically less responsive to treatment administered by providers from other backgrounds. To investigate this, we varied the race and gender of the provider from which White patients received identical treatment for allergic reactions and measured patients' improvement in response to this treatment, thus isolating how a provider's demographic characteristics shape physical responses to healthcare. A total of 187 White patients experiencing a laboratory-induced allergic reaction interacted with a healthcare provider who applied a treatment cream and told them it would relieve their allergic reaction. Unbeknownst to the patients, the cream was inert (an unscented lotion) and interactions were completely standardized except for the provider's race and gender. Patients were randomly assigned to interact with a provider who was a man or a woman and Asian, Black, or White. A fully blinded research assistant measured the change in the size of patients' allergic reaction after cream administration. Results indicated that White patients showed a weaker response to the standardized treatment over time when it was administered by women or Black providers. We explore several potential explanations for these varied physiological treatment responses and discuss the implications of problematic race and gender dynamics that can endure "under the skin," even for those who aim to be bias free.

Normative appeals motivate people to contribute to collective action problems more when they invite people to work together toward a common goal.

A common method to promote behavior change, particularly in contexts related to collective action, is to reference a social norm and ask people to comply with it. We argue that such appeals will be more effective when they couch the norm as an invitation to work with others toward a common goal. In six experiments, we found that working-together normative appeals, which invited people to "join in" and "do it together," increased interest in (Experiments 1, 4, and 5) and actual charitable giving (Experiment 2), reduced paper-towel use in public restrooms (Experiment 3), and increased interest in reducing personal carbon emissions (Experiment 6). By contrast, normative-information appeals, which included the same normative information but no reference to working together, did not affect interest or behavior. Mediation analyses suggest that working-together normative appeals were more effective because they fostered a feeling in participants that they were working together with others, which increased motivation, while inducing less social pressure, which undermined effectiveness. Results show how the very collective nature of collective action problems can be leveraged to promote personal behavior change and help solve societal problems. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Changing mindsets about side effects.

Given research showing that the very act of communicating side effects can increase their likelihood, how can providers inform patients about side effects while upholding their oath to do no unnecessary harm? An emerging approach provides a potential solution: truthfully describe certain minor side effects as a sign the treatment is active and working in the body. This approach focuses on instilling adaptive mindsets about the meaning of side effects while still keeping patients informed. This article describes existing research suggesting that this approach can be helpful in improving experience and outcomes in treatments for pain, hypertension and allergy. Compared with control groups given a standard, empathetic message about side effects, patients who were informed that side effects are a sign treatment is working were less anxious about side effects and rated them as less threatening and intense. A longitudinal, randomised controlled trial of this approach in patients receiving oral immunotherapy for food allergies found that describing side effects as a sign treatment was working reduced the rate at which patients contacted providers with concerns about side effects and led to greater increases in a biomarker of allergic tolerance from pretreatment to post-treatment (peanut-specific blood IgG4). In unveiling this approach, this article also raises important issues regarding which treatments and symptoms this approach should be applied to. Finally, we outline questions future research should address to further understand and leverage this approach.

Lower Limb Asymmetry After Anterior Cruciate Ligament Reconstruction in Adolescent Athletes: A Systematic Review and Meta-Analysis.

OBJECTIVES: To identify reported (1) common biomechanical asymmetries in the literature after anterior cruciate ligament (ACL) reconstruction in adolescents during landing and (2) timescales for asymmetry to persist postsurgery. DATA SOURCES: We identified sources by searching the CINAHL, PubMed, Scopus, and SPORTDiscus electronic databases using the following search terms: asymmetry OR symmetry AND landing AND biomechanics OR kinematics OR kinetics. STUDY SELECTION: We screened the titles and abstracts of 85 articles using our inclusion criteria. A total of 13 articles were selected for further analysis. DATA EXTRACTION: Three reviewers independently assessed the methodologic quality of each study. We extracted the effect sizes directly from studies or calculated them for biomechanical variables assessing asymmetry between limbs of participants with ACL reconstruction. We conducted meta-analyses on variables that were assessed in multiple studies for both double- and single-limb landings. DATA SYNTHESIS: Asymmetry was more commonly identified in kinetic than kinematic variables. Anterior cruciate ligament reconstruction appeared to have a large effect on asymmetry between limbs for peak vertical ground reaction force, peak knee-extension moment, and loading rate during double-limb landings, as well as mean knee-extension moment and knee energy absorption during both double- and single-limb landings. CONCLUSIONS: Our findings suggested that return-to-sport criteria after ACL reconstruction should incorporate analysis of the asymmetry in loading experienced by each limb rather than movement patterns alone.

Qualitative Evaluations of mHealth Interventions: Current Gaps and Future Directions.

Psycho-social factors are often addressed in behavioral health studies. While the purpose of many mHealth interventions is to facilitate behavior change, the focus is more prominently on the functionality and usability of the technology and less on the psycho-social factors that contribute to behavior change. Here we aim to identify the extent to which mHealth interventions for patient self- management address psychological factors. By understanding users' motivations, facilitators, and mindsets, we can better tailor mHealth interventions to promote behavior change.

When Your Doctor "Gets It" and "Gets You": The Critical Role of Competence and Warmth in the Patient-Provider Interaction.

Background: Research demonstrates that the placebo effect can influence the effectiveness of medical treatments and accounts for a significant proportion of healing in many conditions. However, providers may differ in the degree to which they consciously or unconsciously leverage the forces that produce placebo effects in clinical practice. Some studies suggest that the manner in which providers interact with patients shapes the magnitude of placebo effects, but this research has yet to distill the specific dimensions of patient-provider interactions that are most likely to influence placebo response and the mechanisms through which aspects of patient-provider interactions impact placebo response. Methods: We offer a simplifying and unifying framework in which interactions that boost placebo response can be dissected into two key dimensions: patients' perceptions of competence, or whether a doctor "gets it" (i.e., displays of efficiency, knowledge, and skill), and patients' perceptions of warmth, or whether a doctor "gets me" (i.e., displays of personal engagement, connection, and care for the patient). Results: First, we discuss how this framework builds on past research in psychology on social perception of competence and warmth and in medical literature on models of effective medical care, patient satisfaction, and patient-provider interactions. Then we consider possible mechanisms through which competence and warmth may affect the placebo response in healthcare. Finally, we share original data from patients and providers highlighting how this framework applies to healthcare. Both patient and provider data illustrate actionable ways providers can demonstrate competence and warmth to patients. Discussion: We conclude with recommendations for how researchers and practitioners alike can more systematically consider the role of provider competence and warmth in patient-provider interactions to deepen our understanding of placebo effects and, ultimately, enable providers to boost placebo effects alongside active medications (i.e., with known medical ingredients) and treatment in clinical care.

Changing Patient Mindsets about Non-Life-Threatening Symptoms During Oral Immunotherapy: A Randomized Clinical Trial.

BACKGROUND: Oral immunotherapy (OIT) can lead to desensitization to food allergens, but patients can experience treatment-related symptoms of allergic reactions that cause anxiety and treatment dropout. Interventions to improve OIT for patients are needed. OBJECTIVE: To determine whether fostering the mindset that non-life-threatening symptoms during OIT can signal desensitization improves treatment experience and outcomes. METHODS: In a randomized, blinded, controlled phase II study, 50 children/adolescents (28% girls, aged 7-17 years, M = 10.82, standard deviation = 3.01) completed 6-month OIT for peanut allergies. Patients and their parent(s) had monthly clinic visits at the Sean N. Parker Center for Allergy and Asthma Research between January 5, 2017, and August 3, 2017. All families received identical symptom management training. In a 1:1 approach, 24 patients and their families were informed that non-life-threatening symptoms during OIT were unfortunate side effects of treatment, and 26 patients and their families were informed that non-life-threatening symptoms could signal desensitization. Families participated in activities to reinforce these symptom mindsets. RESULTS: Compared with families informed that symptoms are side effects, families informed that symptoms can signal desensitization were less anxious (B = -0.46, 95% confidence interval [CI]: -0.76 to -0.16; P = .003), less likely to contact staff about symptoms (5/24 [9.4%] vs 27/154 [17.5%] instances; P = .036), experienced fewer non-life-threatening symptoms as doses increased (BInteraction = -0.54, 95% CI: -0.83 to -0.27; P < .001), less likely to skip/reduce doses (1/26 [4%] vs 5/24 [21%] patients; P = .065), and showed a greater increase in patient peanut-specific blood IgG4 levels (BInteraction = 0.76, 95% CI: 0.36 to 1.17; P < .001). CONCLUSIONS: Fostering the mindset that symptoms can signal desensitization improves OIT experience and outcomes. Changing how providers inform patients about non-life-threatening symptoms is a promising avenue for improving treatment.

Harnessing the placebo effect: Exploring the influence of physician characteristics on placebo response.

OBJECTIVE: Research on placebo/nocebo effects suggests that expectations can influence treatment outcomes, but placebo/nocebo effects are not always evident. This research demonstrates that a provider's social behavior moderates the effect of expectations on physiological outcomes. METHODS: After inducing an allergic reaction in participants through a histamine skin prick test, a health care provider administered a cream with no active ingredients and set either positive expectations (cream will reduce reaction) or negative expectations (cream will increase reaction). The provider demonstrated either high or low warmth, or either high or low competence. RESULTS: The impact of expectations on allergic response was enhanced when the provider acted both warmer and more competent and negated when the provider acted colder and less competent. CONCLUSION: This study suggests that placebo effects should be construed not as a nuisance variable with mysterious impact but instead as a psychological phenomenon that can be understood and harnessed to improve treatment outcomes. (PsycINFO Database Record

Healthier than thou? "Practicing what you preach" backfires by increasing anticipated devaluation.

[Correction Notice: An Erratum for this article was reported in Vol 112(5) of Journal of Personality and Social Psychology (see record 2017-17124-001). In the article, the beginning phrase of the second paragraph of the Internal Meta-Analysis of Studies 3 Through 5 section is incorrect. It should instead begin as follows: Across the three studies. The Monin et al. (2014) reference in both the References list and in text is included in error. The correct citation should read as follows: Monin, B., & Oppenheimer, D. M. (2014). The limits of direct replications and the virtues of stimulus sampling: Commentary on Klein et al., 2014. Social Psychology, 45, 299-300.] Should experts always practice what they preach? When an expert displays exemplary behavior, individuals who fear negative devaluation sometimes anticipate that this expert will look down on them. As a result, displays of excellence can paradoxically turn off the very people they are trying to inspire. Five studies document this in the medical domain, showing that individuals who are overweight or obese and concerned about their weight avoid physicians who advertise their fitness, for fear that these doctors will judge them negatively. People (erroneously) believe that doctors have healthier habits than other individuals (Study 1), doctors advertise healthy habits (Study 2), and overweight individuals anticipate devaluation from, and thus avoid and feel less comfortable with, doctors who portray themselves as fitness-focused (Study 3). Studies 4 and 5 test strategies for physicians to emphasize their own fitness without turning off weight-sensitive patients. This work demonstrates that it is critical to take into account ego-defensive processes when attempting to lead by example. (PsycINFO Database Record

Attitude Strength.

Attitude strength has been the focus of a huge volume of research in psychology and related sciences for decades. The insights offered by this literature have tremendous value for understanding attitude functioning and structure and for the effective application of the attitude concept in applied settings. This is the first Annual Review of Psychology article on the topic, and it offers a review of theory and evidence regarding one of the most researched strength-related attitude features: attitude importance. Personal importance is attached to an attitude when the attitude is perceived to be relevant to self-interest, social identification with reference groups or reference individuals, and values. Attaching personal importance to an attitude causes crystallizing of attitudes (via enhanced resistance to change), effortful gathering and processing of relevant information, accumulation of a large store of well-organized relevant information in long-term memory, enhanced attitude extremity and accessibility, enhanced attitude impact on the regulation of interpersonal attraction, energizing of emotional reactions, and enhanced impact of attitudes on behavioral intentions and action. Thus, important attitudes are real and consequential psychological forces, and their study offers opportunities for addressing behavioral change.

Changes in Self-Definition Impede Recovery From Rejection.

Previous research highlights how adept people are at emotional recovery after rejection, but less research has examined factors that can prevent full recovery. In five studies, we investigate how changing one's self-definition in response to rejection causes more lasting damage. We demonstrate that people who endorse an entity theory of personality (i.e., personality cannot be changed) report alterations in their self-definitions when reflecting on past rejections (Studies 1, 2, and 3) or imagining novel rejection experiences (Studies 4 and 5). Further, these changes in self-definition hinder post-rejection recovery, causing individuals to feel haunted by their past, that is, to fear the recurrence of rejection and to experience lingering negative affect from the rejection. Thus, beliefs that prompt people to tie experiences of rejection to self-definition cause rejection's impact to linger.