Intravenous injection of adipose-derived mesenchymal stromal cells benefits gait and inflammation in a spontaneous osteoarthritis model.

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published. Therefore, the aim of this study was to evaluate the short-term impact of intravenous (IV) delivery of allogeneic adMSCs in an established model of spontaneous OA, the Hartley guinea pig. Animals with moderate OA received once weekly injections of 2 × 106 adMSCs or vehicle control for 4 weeks in peripheral veins; harvest occurred 2 weeks after the final injection. Systemic administration of adMSCs resulted in no adverse effects and was efficacious in reducing clinical signs of OA (as assessed by computer-aided gait analysis) compared to control injected animals. Further, there were significant decreases in key inflammatory mediators (including monocyte chemoattractant protein-1, tumor necrosis factor, and prostaglandin E2 ) both systemically (liver, kidney, and serum) and locally in the knee (joint tissues and synovial fluid) in animals treated with IV adMSCs relative to controls (as per enzyme-linked immunosorbent assay and/or immunohistochemistry, dictated by tissue sample). Thus, systemic administration of adMSCs by IV injection significantly improved gait parameters and reduced both systemic and intra-articular inflammatory mediators in animals with OA. These findings demonstrate the potential utility of alternative delivery approaches for cellular therapy of OA, particularly for patients with multiple affected joints.

Phytochemical compound PB125 attenuates skeletal muscle mitochondrial dysfunction and impaired proteostasis in a model of musculoskeletal decline.

Impaired mitochondrial function and disrupted proteostasis contribute to musculoskeletal dysfunction. However, few interventions simultaneously target these two drivers to prevent musculoskeletal decline. Nuclear factor erythroid 2-related factor 2 (Nrf2) activates a transcriptional programme promoting cytoprotection, metabolism, and proteostasis. We hypothesized daily treatment with a purported Nrf2 activator, PB125, in Hartley guinea pigs, a model of musculoskeletal decline, would attenuate the progression of skeletal muscle mitochondrial dysfunction and impaired proteostasis and preserve musculoskeletal function. We treated 2- and 5-month-old male and female Hartley guinea pigs for 3 and 10 months, respectively, with the phytochemical compound PB125. Longitudinal assessments of voluntary mobility were measured using Any-MazeTM open-field enclosure monitoring. Cumulative skeletal muscle protein synthesis rates were measured using deuterium oxide over the final 30 days of treatment. Mitochondrial oxygen consumption in soleus muscles was measured using high resolution respirometry. In both sexes, PB125 (1) increased electron transfer system capacity; (2) attenuated the disease/age-related decline in coupled and uncoupled mitochondrial respiration; and (3) attenuated declines in protein synthesis in the myofibrillar, mitochondrial and cytosolic subfractions of the soleus. These effects were not associated with statistically significant prolonged maintenance of voluntary mobility in guinea pigs. Collectively, treatment with PB125 contributed to maintenance of skeletal muscle mitochondrial respiration and proteostasis in a pre-clinical model of musculoskeletal decline. Further investigation is necessary to determine if these documented effects of PB125 are also accompanied by slowed progression of other aspects of musculoskeletal dysfunction. KEY POINTS: Aside from exercise, there are no effective interventions for musculoskeletal decline, which begins in the fifth decade of life and contributes to disability and cardiometabolic diseases. Targeting both mitochondrial dysfunction and impaired protein homeostasis (proteostasis), which contribute to the age and disease process, may mitigate the progressive decline in overall musculoskeletal function (e.g. gait, strength). A potential intervention to target disease drivers is to stimulate nuclear factor erythroid 2-related factor 2 (Nrf2) activation, which leads to the transcription of genes responsible for redox homeostasis, proteome maintenance and mitochondrial energetics. Here, we tested a purported phytochemical Nrf2 activator, PB125, to improve mitochondrial function and proteostasis in male and female Hartley guinea pigs, which are a model for musculoskeletal ageing. PB125 improved mitochondrial respiration and attenuated disease- and age-related declines in skeletal muscle protein synthesis, a component of proteostasis, in both male and female Hartley guinea pigs.

Determinants of public health and interventions to address HIV infection among men who have sex with men in Miami-Dade County, Florida, USA.

Human immunodeficiency virus (HIV) among men who have sex with men (MSM) has been recognized as a public health problem in Miami-Dade County, Florida, USA. This was found to be a significant problem in our need assessment as evidenced by the HIV incidence rate of 28.4 per 100,000 population, which is higher than the average incidence reported for the state of Florida. MSM account for the mostly affected group, reaching 59% of all the new cases. A review of the HIV determinants was conducted using an ecological framework. At the individual level, sexual abuse, alcohol, and drug consumption were identified as determinants of HIV infection in this population. Family rejection was recognized as a determinant at the interpersonal level. Connection to the gay community can function as a protective factor but it can also be possible predictor of HIV infection. Among structural factors, poverty was found to be positively associated with HIV prevalence. Additionally, we highlighted the importance of sexual health education and especially pre-exposure prophylaxis (PrEP) as protective factors. By using systems thinking tools, we designed a causal loop diagram that illustrates visually the recognized determinants of public health. Finally, we presented several studies that evaluate evidence-based interventions to improve the uptake and retention in care of PrEP in MSM. We also described existing interventions implemented in Miami-Dade County, and reported studies that may contribute to the development of new HIV preventive strategies in the future.

Religion, Spirituality, and Ethics in Psychiatric Practice.

ABSTRACT: The interface of religion, spirituality, and psychiatric practice has long been of interest to the ethical psychiatrist. Some prominent early psychotherapists had a strained relationship with religion and spirituality. They posited that religion and spirituality were forms of mental illness, which discouraged the discussion of these values during treatment despite the fact that many patients subscribed to a religious or spiritual viewpoint. Contrarily, others supported a harmonious relationship with religion and spirituality and served as trailblazers for the incorporation of religion and spirituality into psychiatric treatment.As the field of psychiatry continues to evolve, additional dimensions of the relationship between religion, spirituality, and psychiatric practice must be explored. Today, many modern psychiatrists appreciate the importance of incorporating religion and spirituality into treatment, but questions such as whether it is ethical to practice psychiatry from a particular religious or spiritual viewpoint or for psychiatrists to advertise that they subscribe to a particular religion or spirituality and to engage in religious or spiritual practices with their patients remain nuanced and complex. In this resource document, the authors put forth and examine the ramifications of a bio-psycho-social-religious/spiritual model for psychological development and functioning, with this fourth dimension shifting the focus from symptom reduction alone to include other aspects of human flourishing such as resilience, meaning-making, and hope.

The Evolution of Forensic Psychiatry Ethics.

Developments in forensic psychiatry demonstrate evolving thinking about a profession negotiating legal and medical realms. Various approaches have attempted to balance the traditional ethics of medical practice with those of a legal system rooted in vigorous advocacy for one side or the other. Forensic psychiatry provides numerous models for navigating the complex social narratives that intersect Law and Psychiatry. Obligations to vulnerable persons and values underscore the proper ethical balance between forensic practitioners and institutions that are demonstrably unjust. It is the unifying ideas of culture, professionalism, dignity, and social goods that justify participation in a uniquely imperfect human enterprise.

Evaluation of electroacupuncture for symptom modification in a rodent model of spontaneous osteoarthritis.

OBJECTIVE: Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn. METHODS: Ten 12-month-old male Hartley guinea pigs-which characteristically have moderate to advanced OA at this age-were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression. RESULTS: Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups. CONCLUSION: This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.

Practice Resource for Forensic Training in General Psychiatry Residency Programs.

Full Document: Alonso-Katzowitz JS, Cardasis W, Cerny-Suelzer CA, et al: Practice Resource for Forensic Training in General Psychiatry Residency Programs. Journal of the American Academy of Psychiatry and the Law Online Supplement 2019, 47 (1). Available at: http://www.jaapl.org/content/47/1_Supplement.

Boundaries, Professionalism, and Malpractice in Psychiatry.

Boundary violations are an uncommon but nonetheless important cause of malpractice action against the psychiatrist. Although not all boundary crossings are boundary violations, boundary violations include various breaches ranging from sexual liaisons to inappropriate online behaviors. Sexual boundaries merit consideration not only with patients but also with former patients and family members of patients, partially because of the imbalance of power in the relationship. Some states have also imposed criminal penalties for certain types of boundary violations. Internet and e-mail boundaries also are critical for psychiatrists to consider. Online behaviors that are problematic or risky are explored. Questions for ethical self-reflection are posed. Recommendations are made throughout the article regarding avoiding boundary violations.

Professional Identity, the Goals and Purposes of Forensic Psychiatry, and Dr. Ezra Griffith.

Dr. Ezra Griffith's retirement as Editor of The Journal motivated this reflection on his contributions to forensic psychiatry. In 1998, Dr. Griffith published a response to Dr. Alan Stone's views and Dr. Paul Appelbaum's theory on ethics in forensic psychiatry. This response has been often labeled as the "cultural formulation" perspective. This article reviews some of the major contributors in the development of ethics and professionalism for forensic psychiatry and offers a perspective on Dr. Griffith's contributions in this evolving and relatively young sub-specialty within psychiatry. With his scholarly contributions to the field of ethics, Dr. Griffith has offered a bridge that connects past attempts to define our sub-specialty to a future formulation of the goals and purposes of forensic psychiatry, something that the author recommends as a next step.

Involuntary Treatment of Patients With Life-Threatening Anorexia Nervosa.

Anorexia nervosa has the highest mortality rate of any psychiatric illness. Predictors of mortality include chronicity of the illness, critically low body weight, and binging and purging behavior. Delusional beliefs body image, coupled with impaired judgment and cognition caused by starvation, often result in these patients adamantly resisting efforts to treat them. Guardianship, although useful in assisting with medical treatment decisions for patients with anorexia nervosa who are critically medically ill, is usually an inadequate intervention with respect to psychiatric treatment for these patients. Despite the severity and risk of the illness, there is often reluctance among providers to initiate involuntary treatment for patients with anorexia nervosa. Recent legal cases involving patients with anorexia nervosa have addressed the role of the committing court in authorizing treatment decisions and, in one case, opining that a patient was best served by receiving treatment in another state. Other related concerns addressed by the courts include ensuring that appropriate criteria are used for hospital admission, clarifying that the definition of grave disability as it pertains to anorexia does not require that the patient be close to death and that medications are often warranted in treating patients with the disease.

Unsolicited E-mails to Forensic Psychiatrists.

E-mail communication is pervasive. Since many forensic psychiatrists have their e-mail addresses available online (either on personal websites, university websites, or articles they have authored), they are likely to receive unsolicited e-mails. Although there is an emerging body of literature about exchanging e-mail with patients, there is little guidance about how to respond to e-mails from nonpatients. Therefore, we used a Delphi technique to develop a consensus about salient points for the forensic psychiatrist to consider regarding responding to e-mails from nonpatients and the risks entailed. Four scenarios are described, including e-mails from nonpatients and unknown others requesting advice or help. The potential ethics-related, legal, moral, and practical concerns for forensic psychiatrists are discussed. Finally, potential pitfalls for forensic psychiatrists are described.

Case reports: Publication standards in forensic psychiatry.

Psychiatrists who publish case reports are required to seek informed consent from their subjects on the basis of the ethics-related obligation to maintain patient confidentiality. Academic journals have developed editorial standards to fulfill this obligation. Forensic evaluations do not create a doctor-patient relationship in the traditional sense, and information obtained through a forensic evaluation may also be found in the public domain. This public exposure is particularly likely, given the development of open access publishing standards, online journals, and increasing professional involvement in social media. This article outlines the ethics of informed consent in published case reports for general and forensic psychiatry and offers recommendations for forensic case study publishing. The authors suggest changes in the current requirements stated in The Journal for publication of case reports.

Food insecurity, CD4 counts, and incomplete viral suppression among HIV+ patients from Texas Children's Hospital: a pilot study.

Determine the relationship between food insecurity and CD4 counts and viral suppression among pediatric HIV-positive patients. Food insecurity was assessed by validated survey. CD4 counts and viral load were abstracted from patients' charts. We used linear regression for the dependent variable of the natural log of CD4 counts and logistic regression for viral suppression, with backward deletion of covariates with p > 0.1. Food insecurity (ß = -0.23, 95 % CI [-0.40, -0.01]) was associated with lower CD4 counts and higher odds of incomplete viral suppression (OR = 4.07, 95 % CI [1.02, 13.92]). Food insecurity may adversely impact pediatric HIV outcomes.

Management of adults with Tetralogy of Fallot.

Tetralogy of Fallot is the most common form of cyanotic congenital cardiac disease. Patients with previously repaired tetralogy of Fallot are the most common patients seen in the Program for Adults with Congenital Heart Disease at The Johns Hopkins All Children's Heart Institute. Guidelines for the management of these patients are available from multiple sources including The American College of Cardiology (ACC) and The American Heart Association (AHA), The Canadian Cardiovascular Society, and The European Society of Cardiology (ESC). These guidelines describe multiple components related to the care for these patients including strategies for medical follow-up, the management of arrhythmias and electrophysiological diseases, and the treatment of chronic pulmonary insufficiency and stenosis. Several new strategies are available for replacement of the pulmonary valve including transcatheter replacement of the pulmonary valve and replacement of the pulmonary valve with a self-manufactured bicuspid polytetrafluoroethylene pulmonary valve.