[F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue.

Frequent low-impact exposure to THC during adolescence causes persistent sexually dimorphic alterations in the response to viral infection in mice.

Adolescent exposure to Δ-tetrahydrocannabinol (THC) has enduring effects on energy metabolism and immune function. Prior work showed that daily administration of a low-impact dose of THC (5 mg/kg, intraperitoneal) during adolescence alters transcription in adult microglia and disrupts their response to bacterial endotoxin or social stress. To explore the lasting impact of adolescent THC exposure on the brain's reaction to viral infection, we administered THC (5 mg/kg, intraperitoneal) in male and female mice once daily on postnatal day (PND) 30-43.

The Emmaus Project: Aging, Illness, and Dying Among Older Christians-A Qualitative Study.

Older patients have an increased risk of depression, neglect, and abuse. Studies demonstrate that spiritual and religious coping is important at times of personal crisis, but few studies explore the impact of religion on older persons' experiences of aging, illness, and impending death. This study set out to identify recurring spiritual and clinical themes shared by retirement home residents in the context of a Christian faith-based processing group.

Adipose Tissue and Metabolic Health.

In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health and highlight some recent developments in understanding and exploiting adipocyte biology. Adipose tissue plays critical roles in the regulation of systemic glucose and lipid metabolism and secretes bioactive molecules possessing endocrine, paracrine, and autocrine functions. Dysfunctional adipose tissue has a detrimental impact on metabolic health and is intimately involved in key aspects of metabolic diseases such as insulin resistance, lipid overload, inflammation, and organelle stress.

Practical wisdom in medicine through the eyes of medical students and physicians.

Background: Practical wisdom is considered a multidimensional virtue of enduring relevance to medicine. Though it has received increasing attention in recent years, proposed frameworks for practical wisdom can differ, and little is known about how medical students and physicians describe its dimensions and relevance.

Methods: We used structured interviews, employing open-ended and closed-ended questions, to describe how medical students and physicians understand practical wisdom and identify the kinds of clinical situations they believe require practical wisdom.

The Enhancing Life Research Laboratory: Tools for Addressing Orientational Distress in the Medical Profession.

Purpose: To explore distress in the medical profession and how it was highlighted by the ongoing COVID-19 pandemic. The term "orientational distress" was developed to name the experience of a breakdown in the patterns of moral self-understanding and one's capacity to navigate professional responsibilities.

Method: The Enhancing Life Research Laboratory at the University of Chicago convened a 5-session online workshop (total 10 hours, May-June 2021) to explore orientational distress and to promote collaboration between academics and physicians.

Regulation of beige adipocyte thermogenesis by the cold-repressed ER protein NNAT.

Objective: Cold stimuli trigger the conversion of white adipose tissue into beige adipose tissue, which is capable of non-shivering thermogenesis. However, what process drives this activation of thermogenesis in beige fat is not well understood. Here, we examine the ER protein NNAT as a regulator of thermogenesis in adipose tissue.

Screening chimeric GAA variants in preclinical study results in hematopoietic stem cell gene therapy candidate vectors for Pompe disease.

Pompe disease is a rare genetic neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency resulting in lysosomal glycogen accumulation and progressive myopathy. Enzyme replacement therapy, the current standard of care, penetrates poorly into the skeletal muscles and the peripheral and central nervous system (CNS), risks recombinant enzyme immunogenicity, and requires high doses and frequent infusions. Lentiviral vector-mediated hematopoietic stem and progenitor cell (HSPC) gene therapy was investigated in a Pompe mouse model using a clinically relevant promoter driving nine engineered GAA coding sequences incorporating distinct peptide tags and codon optimizations.

Sustaining the Intrinsic Motivations of the "Good Physician": A Content Analysis of Medical Students' and Physicians' Responses from Two National Surveys.

Objective: Physician motivation has been described as the reason, purpose, and force that drives people to pursue their work, and motivating factors include those that are intrinsic or extrinsic to the work. Social forces may contribute to motivational disparities between medical school and actual practice.

Methods: A secondary data analysis of two national surveys (medical students and practicing physicians from various specialties) was conducted.

CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway.

Background: Cystic fibrosis (CF) is characterized by reduced growth and lower body weight, which are multifactorial. CF mouse models lack key disease characteristics that predispose to a negative energy balance, such as pulmonary infections or exocrine pancreatic insufficiency, and yet they still exhibit a growth defect and an abnormally increased energy expenditure. Whether adipocyte thermogenesis contributes to the elevated resting energy expenditure in CF mice is unknown.

Gene Therapy Developments for Pompe Disease.

Pompe disease is an inherited neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). The most severe form is infantile-onset Pompe disease, presenting shortly after birth with symptoms of cardiomyopathy, respiratory failure and skeletal muscle weakness. Late-onset Pompe disease is characterized by a slower disease progression, primarily affecting skeletal muscles.

Adipose Mitochondrial Complex I Deficiency Modulates Inflammation and Glucose Homeostasis in a Sex-Dependent Manner.

Mitochondrial dysfunction in adipose tissue has been associated with type 2 diabetes, but it is unclear whether it is a cause or the consequence. Mitochondrial complex I is a major site of reactive oxygen species generation and a therapeutic target. Here we report that genetic deletion of the complex I subunit Ndufs4 specifically in adipose tissue results in an increased propensity to develop diet-induced weight gain, glucose intolerance, and elevated levels of fat inflammatory genes.

Moral Elevation, Physician Role Models, and Selected Markers of Professional Identity Formation and Well-Being: A Secondary Analysis from Two National Surveys.

Objectives: Moral elevation is the underlying emotion that arises when witnessing admirable acts, and it is theorized to be the psychological mechanism driving the impact that positive clinical role models have on medical students' professional identity formation (eg, growth in professional virtues, higher sense of meaning, and well-being). This proof-of-concept study explores the development of the Moral Elevation Scale in Medicine by testing the association of moral elevation with various markers of professional identity formation.

Methods: A secondary data analysis of two nationally representative samples of 960 medical students and 2000 physicians was performed.

Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1.

Manipulation of energy-dissipating adipocytes has the potential to produce metabolic benefits. To this end, it is valuable to understand the mechanisms controlling the generation and function of thermogenic fat. Here, we identify Letm1 domain containing 1 (Letmd1) as a regulator of brown fat formation and function.

Association of Intrinsic Motivating Factors and Joy in Practice: A National Physician Survey.

Objectives: In response to the need to identify positive measures that more accurately describe physician wellness, this study seeks to assess the validity of a novel joy in practice measure using validated physician well-being measures and test its association with certain intrinsic and extrinsic motivators.

Methods: Secondary data analysis using a nationally representative dataset of 2000 US physicians, fielded October-December 2011. Multivariable logistic models with survey design provided nationally representative individual-level estimates.

HIV proviral DNA integration can drive T cell growth ex vivo.

In vivo clonal expansion of HIV-infected T cells is an important mechanism of viral persistence. In some cases, clonal expansion is driven by HIV proviral DNA integrated into one of a handful of genes. To investigate this phenomenon in vitro, we infected primary CD4+ T cells with an HIV construct expressing GFP and, after nearly 2 mo of culture and multiple rounds of activation, analyzed the resulting integration site distribution.

"Can virtue be taught?": a content analysis of medical students' opinions of the professional and ethical challenges to their professional identity formation.

Background: Efforts have begun to characterize the ethical and professional issues encountered by medical students in their clinical years. By applying previously identified taxonomies to a national sample of medical students, this study seeks to develop generalizable insights that can inform professional identity formation across various clerkships and medical institutions.

Methods: In a national survey of medical students, participants answered an open-ended survey item that asked them to describe a clinical experience involving an ethical or professional issue.

Energy balance and obesity in individuals with cystic fibrosis.

This article reviews the significance of nutritional status in patients with cystic fibrosis (CF), and sheds light on the reasons behind the intense focus placed on perpetual weight gain and increased caloric intake by CF patients and their providers. The manuscript explores the potential mechanisms by which aberrant CFTR may contribute to increased resting energy expenditure (REE), and how correcting and potentiating its activity, possibly by reducing REE, among other intended and off-target effects, can contribute to weight gain in this patient population. The commentary also examines what is currently known about metabolic and vascular complications of obesity in patients with CF, and presents dietary, nutritional, pharmacologic and surgical approaches that may help obese patients with CF lose weight and build more lean body mass.

Male reproductive health in cystic fibrosis.

The impact of cystic fibrosis (CF) on male reproductive health is profound. The vast majority of men with CF are infertile due to obstructive azoospermia. Multiple factors associated with CF contribute to an increased prevalence of testosterone deficiency, which adversely affects muscle mass, bone density, and quality of life.

Moral Controversy and Working with Colleagues with a Shared Ethical/Moral Outlook: A National Survey of US Primary Care Physicians.

Objectives: This study assesses physicians' attitudes on the importance of working with colleagues who share the same ethical or moral outlook regarding morally controversial healthcare practices and examines the association of physicians' religious and spiritual characteristics with these attitudes.

Methods: We conducted a secondary data analysis of a 2009 national survey that was administered to a stratified random sample of 1504 US primary care physicians (PCPs). In that dataset, physicians were asked: "For you personally, how important is it to work with colleagues who share your ethical/moral outlook regarding morally controversial health care practices?" We examined associations between physicians' religious/spiritual characteristics and their attitudes toward having a shared ethical/moral outlook with colleagues.

Pulmonary embolism as the presenting symptom and a confounder in ACTH-secreting bronchial carcinoid.

Summary: Ectopic ACTH-secreting pulmonary neuroendocrine tumors are rare and account for less than 5% of endogenous Cushing’s syndrome cases. We describe an unusual case of metastatic bronchial carcinoid tumor in a young woman presenting with unprovoked pulmonary emboli, which initially prevented the detection of the primary tumor on imaging. The source of ectopic ACTH was ultimately localized by a Gallium-DOTATATE scan, which demonstrated increased tracer uptake in a right middle lobe lung nodule and multiple liver nodules.

Predictors of Empathic Compassion: Do Spirituality, Religion, and Calling Matter?

Objective: To determine whether physician spirituality, religion, and sense of calling toward medicine are predictors of self-reported empathic compassion.

Methods: We sampled 2000 practicing US physicians from all specialties and used self-reported measures of general and clinical empathic compassion taken from previous studies. Independent variables were single-item measures of calling, spirituality, and religiosity (importance of religion).