Effect of Immunosuppression on the Immune Response to SARS-CoV-2 Infection and Vaccination.

Immunosuppressive treatment in patients with rheumatic diseases can maintain disease remission but also increase risk of infection. Their response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is frequently blunted. In this study we evaluated the effect of immunosuppression exposure on humoral and T cell immune responses to SARS-CoV-2 infection and vaccination in two distinct cohorts of patients; one during acute SARS-CoV-2 infection and 3 months later during convalescence, and another prior to SARS-CoV-2 vaccination, with follow up sampling 6 weeks after vaccination. Results were compared between rituximab-exposed (in previous 6 months), immunosuppression-exposed (in previous 3 months), and non-immunosuppressed groups. The immune cell phenotype was defined by flow cytometry and ELISA. Antigen specific T cell responses were estimated using a whole blood stimulation interferon-γ release assay. A focused post-vaccine assessment of rituximab-treated patients using high dimensional spectral cytometry was conducted. Acute SARS-CoV-2 infection was characterised by T cell lymphopenia, and a reduction in NK cells and naïve CD4 and CD8 cells, without any significant differences between immunosuppressed and non-immunosuppressed patient groups. Conversely, activated CD4 and CD8 cell counts increased in non-immunosuppressed patients with acute SARS-CoV-2 infection but this response was blunted in the presence of immunosuppression. In rituximab-treated patients, antigen-specific T cell responses were preserved in SARS-CoV-2 vaccination, but patients were unable to mount an appropriate humoral response.

"Having cancer is very expensive": A qualitative study of patients with ovarian cancer and PARP inhibitor treatment.

OBJECTIVE: To examine patient barriers and facilitators to PARP inhibitor (PARP-I) maintenance therapy in ovarian cancer. PARP-I improves survival in ovarian cancer, but these multi-year therapies cost around $100,000 annually and are under-prescribed. METHODS: We recruited patients with ovarian cancer treated with PARP-I maintenance therapy at an academic health system for a semi-structured interview. Patient demographics, including genetics and PARP-I cost, were self-reported. We assessed patient experiences with barriers and facilitators of PARP-I usage. Two team members used a thematic approach to analyze and identify key themes. RESULTS: In May 2022, we interviewed 10 patients (mean age = 65 years; 80% White; 60% with a germline genetic mutation). Patients paid on average $227.50 monthly for PARP-I, straining resources for some participants. While sampled patients were insured, all patients identified having no or inadequate insurance as a major barrier to PARP-I. At the same time, all participants prioritized clinical effectiveness over costs of care. Patients identified PARP-I delivery from specialty pharmacies, separate and different from other medications, as a potential barrier, but each had been able to navigate delivery. Patients expressed significant initial side effects of PARP-I as a potential barrier yet reported clinician communication and prompt dose reduction as facilitating continuation. CONCLUSIONS: Patients identified cost, restrictive pharmacy benefits, and initial side effects as barriers to PARP-I usage. Having insurance and a supportive care team were identified as facilitators. Enhancing communication about PARP-I cost and side effects could improve patient experience and receipt of evidence-based maintenance therapy in ovarian cancer.

Exploring the determinants of successful implementation of a preventive mental health and wellness intervention for Afghan refugee families: a qualitative analysis.

Many refugee children experience trauma in early childhood. Effective, tailored interventions are needed to improve refugee children's access to preventive mental health. We interviewed refugee-serving stakeholders and parents participating in an evidence-based preventive mental health and wellness intervention adapted for Afghan refugee children and families who may have experienced trauma. Interview guide development was informed by two implementation science frameworks: the Consolidated Framework for Implementation Research and the Model for Adaptation Design and Impact. A three-person team coded transcripts via rapid qualitative analysis, and the study team reached consensus on themes. Six refugee-serving facilitators and five refugee parents discussed key determinants of successful implementation. Themes included: (i) modeling cultural humility to promote communication about emotions; (ii) needed linguistic support and referral networks to avoid miscommunications and missed communications; (iii) bridging connections between children, families and schools; (iv) different takeaways, or differing goals and expectations between facilitators and participants; and (v) timely, specific cultural considerations to overcome participation barriers. Overall, we found key determinants of successful implementation of a preventive mental health and wellness intervention for refugee children and families included adaptations to enhance cultural humility and sensitivity to cultural context while strengthening communication among facilitators, children and families.

"Cancer's a demon": a qualitative study of fear and multilevel factors contributing to cancer treatment delays.

PURPOSE: Delays initiating cancer therapy are increasingly common, impact outcomes, and have implications for health equity. However, it remains unclear (1) whether patients' beliefs regarding acceptable diagnostic to treatment intervals align with current guidelines, and (2) to what degree psychological factors contribute to longer intervals. We conducted a qualitative study with patients and cancer care team members ("providers"). METHODS: We interviewed patients with several common solid tumors as well as providers. Interviews were analyzed using an interpretive approach, guided by modified grounded theory. RESULTS: Twenty-two patients and 12 providers participated. Half of patients had breast cancer; 27% waited >60 days between diagnosis and treatment. Several themes emerged. (1) Patients felt treatment should begin immediately following diagnosis, while providers' opinion on the goal timeframe to start treatment varied. (2) Patients experienced psychological distress while waiting for treatment. (3) Participants identified logistical, social, and psychological sources of delay. Fear related to multiple aspects of cancer care was common. Emotion-driven barriers could manifest as not taking steps to move ahead, or as actions that delayed care. (4) Besides addressing logistical challenges, patients believed that education and anticipatory guidance, from their care team and from peers, may help overcome psychological barriers to treatment and facilitate the start of therapy. CONCLUSIONS: Patients feel an urgency to start cancer therapy, desiring time frames shorter than those included in guidelines. Psychological distress is frequently both a contributor to, and a consequence of, treatment delays. Addressing multilevel barriers, including psychological ones, may facilitate timely treatment and reduce distress.

Early Engagement in HIV Research: Evaluation of the Penn CFAR Scholars Program Aimed at Increasing Diversity of the HIV/AIDS Workforce.

BACKGROUND: Demographic diversity is not represented in the HIV/AIDS workforce. Engagement of underrepresented trainees as early as high school may address this disparity. METHODS: We established the Penn Center for AIDS Research (CFAR) Scholars Program, a mentored research experience for underrepresented minority (URM) trainees spanning educational stages from high school to medical school. The program provides participants with tailored educational programming, professional skill building, and mentored research experiences. We conducted qualitative interviews with scholar, mentor, and leadership groups to evaluate the program's impact. RESULTS: Eleven participants were selected to partake in 1 of 5 existing mentored research programs as CFAR scholars. Scholars attended an 8-week HIV Seminar Series that covered concepts in the basic, clinical, behavioral, and community-based HIV/AIDS research. Program evaluation revealed that scholars' knowledge of HIV pathophysiology and community impact increased because of these seminars. In addition, they developed tangible skills in literature review, bench techniques, qualitative assessment, data analysis, and professional network building. Scholars reported improved academic self-efficacy and achieved greater career goal clarity. Areas for improvement included clarification of mentor-mentee roles, expectations for longitudinal mentorship, and long-term engagement between scholars. Financial stressors, lack of social capital, and structural racism were identified as barriers to success for URM trainees. CONCLUSION: The Penn CFAR Scholars Program is a novel mentored research program that successfully engaged URM trainees from early educational stages. Barriers and facilitators to sustained efforts of diversifying the HIV/AIDS workforce were identified and will inform future program planning.

The role of lipids in vitiligo and schizophrenia.

The pathogenesis of vitiligo and schizophrenia has not been adequately clarified. We explore the role of lipids in these diseases. Both conditions have been associated with stress in several observations and studies. Research data indicate complex interactions between oxidative stress and metabolic syndrome-with lipid abnormalities being a significant component of the latter-in these diseases. The impaired membrane lipid homeostasis mechanism is related to the increased phospholipid remodeling caused by excessive oxidative stress in schizophrenia. We indicate that sphingomyelin is possibly involved in the pathogenesis of these diseases. Statins have anti-inflammatory and immunomodulating effects and an effect against oxidative stress. Preliminary clinical studies show that these agents may be beneficial in both vitiligo and schizophrenia, but their therapeutic value should be studied further.

Through the looking glass: Skin signs that help diagnose eating disorders.

Eating disorders (EDs) such as anorexia nervosa and bulimia nervosa have a plethora of skin manifestations. They can be categorized into skin signs of self-purging, skin signs of starvation, skin signs related to drug abuse, skin signs of psychiatric comorbidity, and miscellaneous signs. "Guiding signs" are valuable because they are pointers to the diagnosis of an ED. They include hypertrichosis (lanugo-like hair), Russell's sign (knuckle calluses), self-induced dermatitis, and perimylolysis (tooth enamel erosion). Practitioners should recognize such skin signs promptly, as this helps to diagnose early, which may improve the prognosis of ED. Management requires a multidisciplinary approach that focuses on psychotherapy combined with attention to medical complications, nutritional needs, and nonpsychiatric findings such as cutaneous manifestations. Psychotropic medications that are currently used in EDs include pimozide and atypical antipsychotic agents, such as aripiprazole and olanzapine, fluoxetine, and lisdexamfetamine.

16p12.1 Deletion Orthologs are Expressed in Motile Neural Crest Cells and are Important for Regulating Craniofacial Development in Xenopus laevis.

Copy number variants (CNVs) associated with neurodevelopmental disorders are characterized by extensive phenotypic heterogeneity. In particular, one CNV was identified in a subset of children clinically diagnosed with intellectual disabilities (ID) that results in a hemizygous deletion of multiple genes at chromosome 16p12.1. In addition to ID, individuals with this deletion display a variety of symptoms including microcephaly, seizures, cardiac defects, and growth retardation. Moreover, patients also manifest severe craniofacial abnormalities, such as micrognathia, cartilage malformation of the ears and nose, and facial asymmetries; however, the function of the genes within the 16p12.1 region have not been studied in the context of vertebrate craniofacial development. The craniofacial tissues affected in patients with this deletion all derive from the same embryonic precursor, the cranial neural crest, leading to the hypothesis that one or more of the 16p12.1 genes may be involved in regulating neural crest cell (NCC)-related processes. To examine this, we characterized the developmental role of the 16p12.1-affected gene orthologs, polr3e, mosmo, uqcrc2, and cdr2, during craniofacial morphogenesis in the vertebrate model system, Xenopus laevis. While the currently-known cellular functions of these genes are diverse, we find that they share similar expression patterns along the neural tube, pharyngeal arches, and later craniofacial structures. As these genes show co-expression in the pharyngeal arches where NCCs reside, we sought to elucidate the effect of individual gene depletion on craniofacial development and NCC migration. We find that reduction of several 16p12.1 genes significantly disrupts craniofacial and cartilage formation, pharyngeal arch migration, as well as NCC specification and motility. Thus, we have determined that some of these genes play an essential role during vertebrate craniofacial patterning by regulating specific processes during NCC development, which may be an underlying mechanism contributing to the craniofacial defects associated with the 16p12.1 deletion.

Pilot Wellness Program With Adapted Social-Emotional Learning and COVID-19 Curriculum for Refugee Youth.

Refugee children are less likely than their non-refugee peers to receive timely diagnoses and treatment for mental and/or behavioral health problems, despite facing multiple risk factors including potential exposure to trauma during premigration, migration, and postmigration experiences. Social-Emotional Learning offers preventive mental health education for children through well-established, evidenced-based curricula. Although there are clear benefits of Social-Emotional Learning curricula, which can help children achieve long-term success emotionally and academically, Social-Emotional Learning curricula are not easily accessible for refugee children, often because of language and socioeconomic barriers. In this pilot study, we evaluated the feasibility and acceptability of an adapted Social-Emotional Learning program that included culturally specific, multilingual, trauma-informed wellness, and physical education during the COVID-19 pandemic: EMPOWER (Emotions Program Outside the Clinic With Wellness Education for Refugees). We used the Intervention Mapping framework which guided the (1) planning, (2) program development, and (3) mixed-method evaluation of the feasibility and acceptability of the EMPOWER pilot. We found that this adaptation was well-received by Afghan refugee families and that COVID-19 safety measures were well-understood after participation. Challenges emerged around videoconferencing connectivity and around finding a common language for discussing emotions. Future iterations of the program and evaluations will require continued partnerships with community members and organizations. As we continue and expand EMPOWER, we aim to evaluate short-term improvement in Social-Emotional Learning competence as well as long-term mental and behavioral health outcomes for children and their families.

Psychodermatology of acne: Psychological aspects and effects of acne vulgaris.

INTRODUCTION: Acne is a chronic inflammatory skin condition seen commonly in adolescence and young adulthood. Despite being a frequent and nonthreatening life condition, acne has a significant psychological impact and comorbidity. AIMS: This review will describe prevalence, common clinical features, different clinical presentations, differential diagnoses, and treatment recommendation. Special focus has been put on psychological aspects. METHODS: We conducted a literature search on PubMed from January 2001 to June 2020 with the search terms of Acne vulgaris, psychological, adolescents, anxiety, suicide, mood disorders. Reference lists of identified articles were examined for further relevant studies. The search was limited to English language articles. No specified quality criteria were used for study inclusion. RESULTS: The clinical manifestations of acne are very important in the differential diagnosis and its psychological implications. CONCLUSION: Through this article, we conclude that despite being a frequent and nonthreatening life condition, acne has a significant psychological impact which requires effective treatment to improve the patient's skin and self-esteem.

Nonpharmacological treatment approach in trichotillomania (hair-pulling disorder).

Trichotillomania (TTM) is a fairly common psychodermatological disorder. This is characterized by recurrent urges to pull hair from hair-containing parts of the body and produces bald patches on scalp. Besides scalp, eye lashes, eyebrows, and pubic area may be involved. Clinically two types are recognized, the automatic and focused types. Currently, this is classified into obsessive- and compulsive-related disorder. Most common psychiatric manifestations include anxiety, depression, and low self-esteem. It has bimodal distribution in children and adolescents and adults. No recognized treatment is available. Pharmacological treatment is based on limited trials and case reports. Psychotherapies are mainstay of treatment. This review mainly focuses on evidence-based psychotherapeutic techniques used in the treatment of TTM.

Psychotropic drugs in dermatology: A dermatologist's approach and choice of medications.

Psychiatric symptoms in dermatology practice are increasingly being recognized. The use of psychiatric medications by dermatologist is dealt with caution and uncertainty in several psychodermatological conditions. Several skin conditions are associated with anxiety, depression, and obsessive-compulsive symptoms. Some conditions such as delusion of parasitosis require antipsychotic medication treatment. Keeping in mind the importance of psychotropic medications and its use in dermatology, following brief review will familiarize dermatologists about the ease of understanding and prescribing psychotropic medications to help their patients with psychiatric symptoms and increase the compliance in treatment.

Psychological aspects of COVID-19.

BACKGROUND: COVID-19 pandemic has affected the world from every aspect. Individuals are drained from social, financial, and emotional percussion of this pandemic. Psychosocial consequences are far greater than are being perceived. It is anticipated that once the pandemic is over the psycho-emotional turbulence would shake the whole populations of affected countries. AIMS AND OBJECTIVES: To review the psychological consequences of COVID-19 pandemic. METHODS: A literature search was conducted on major databases from January 2020 to April 2020 with the search terms of Covid-19, Corona virus, psychological, depression, anxiety, phobias, obsessive behaviors, paranoia, parental relationship, marital life and maternal and fetal bond. CONCLUSION: Patients with COVID-19 infection are more likely to suffer from a myriad of psychological consequences, and this infection may have profound effect on parenting, relationships, marital life, elderly, and maternal-fetal bond.

Quantification of thrombus formation in malapposed coronary stents deployed in vitro through imaging analysis.

Stent thrombosis is a major complication of coronary stent and scaffold intervention. While often unanticipated and lethal, its incidence is low making mechanistic examination difficult through clinical investigation alone. Thus, throughout the technological advancement of these devices, experimental models have been indispensable in furthering our understanding of device safety and efficacy. As we refine model systems to gain deeper insight into adverse events, it is equally important that we continue to refine our measurement methods. We used digital signal processing in an established flow loop model to investigate local flow effects due to geometric stent features and ultimately its relationship to thrombus formation. A new metric of clot distribution on each microCT slice termed normalized clot ratio was defined to quantify this distribution. Three under expanded coronary bare-metal stents were run in a flow loop model to induce clotting. Samples were then scanned in a MicroCT machine and digital signal processing methods applied to analyze geometric stent conformation and spatial clot formation. Results indicated that geometric stent features play a significant role in clotting patterns, specifically at a frequency of 0.6225 Hz corresponding to a geometric distance of 1.606 mm. The magnitude-squared coherence between geometric features and clot distribution was greater than 0.4 in all samples. In stents with poor wall apposition, ranging from 0.27 mm to 0.64 mm maximum malapposition (model of real-world heterogeneity), clots were found to have formed in between stent struts rather than directly adjacent to struts. This early work shows how the combination of tools in the areas of image processing and signal analysis can advance the resolution at which we are able to define thrombotic mechanisms in in vitro models, and ultimately, gain further insight into clinical performance.

Vessel centerline reconstruction from non-isocentric and non-orthogonal paired monoplane angiographic images.

PURPOSE: Three-dimensional reconstruction of a vessel centerline from paired planar coronary angiographic images is critical to reconstruct the complex three-dimensional structure of the coronary artery lumen and the relative positioning of implanted devices. In this study, a new vessel centerline reconstruction method that can utilize non-isocentric and non-orthogonal pairs of angiographic images was developed and tested. METHODS: Our new method was developed in in vitro phantom models of bifurcated coronary artery with and without stent, and then tested in in vivo swine models (twelve coronary arteries). This method was also validated using data from six patients. RESULTS: Our new method demonstrated high accuracy (root mean square error = 0.27 mm or 0.76 pixel), and high reproducibility across a broad imaging angle (20°-130°) and between different cardiac cycles in vitro and in vivo. Use of this method demonstrated that the vessel centerline in the stented segment did not deform significantly over a cardiac cycle in vivo. In addition, the total movement of the isocenter in each image could be accurately estimated in vitro and in vivo. The performance of this new method for patient data was similar to that for in vitro phantom models and in vivo animal models. CONCLUSIONS: We developed a vessel centerline reconstruction method for non-isocentric and non-orthogonal angiographic images. It demonstrated high accuracy and good reproducibility in vitro, in vivo, and in clinical setting, suggesting that our new method is clinically applicable despite the small sample size of clinical data.

Psychocutaneous disease: Clinical perspectives.

Psychocutaneous disease, defined in this review as primary psychiatric disease with skin manifestations, is commonly encountered in dermatology. Dermatologists can play an important role in the management of psychocutaneous disease because patients visit dermatology for treatment of their skin problems but often refuse psychiatric intervention. This review describes common psychocutaneous syndromes, including delusional, factitious, obsessive-compulsive and related, and eating disorders, as well as psychogenic pruritus, cutaneous sensory (pain) syndromes, posttraumatic stress disorder, and sleep-wake disorders. The updated classification of these disorders in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition is included. Strategies for management are reviewed.

Psychocutaneous disease: Pharmacotherapy and psychotherapy.

Building a strong therapeutic alliance with the patient is of utmost importance in the management of psychocutaneous disease. Optimal management of psychocutaneous disease includes both pharmacotherapy and psychotherapy. This article reviews psychotropic medications currently used for psychocutaneous disease, including antidepressants, antipsychotics, mood stabilizers, and anxiolytics, with a discussion of relevant dosing regimens and adverse effects. Pruritus management is addressed. In addition, basic and complex forms of psychotherapy, such as cognitive-behavioral therapy and habit-reversal training, are described.