Teaching spirituality to medical students: a systematic review.

PURPOSE: Though it has become increasingly clear that religion and spirituality are important aspects of whole patient care, little is known about how this topic is taught to medical students. This systematic review examined the structure of courses teaching spirituality to medical students and assessed their impact on reported student outcomes. METHODS: In October 2020, the authors conducted a systematic review of the literature from 1926 to 2020 to identify published articles describing medical school spirituality curricula. Included studies were English-language articles that described spirituality courses predominantly designed for medical students, specified a curricular structure, and evaluated outcomes of the course. The authors used the Medical Education Research Study Quality Instrument (MERSQI) to assess the quality of the included studies and summarized course structures, curricular content, and study outcomes. RESULTS: Nineteen publications of the 1889 reviewed met the inclusion criteria. These studies were of moderate quality (mean MERSQI = 9.9). The majority of curricula were taught in United States medical schools. Courses were evenly split between mandatory versus elective classes, with mandatory courses having a shorter duration and higher total student participation. Most studies with clear student outcome evaluation had a pre- and post-test design. Common themes throughout the curricula included teaching how to take a spiritual history, delineating differences between spirituality and religion, and experience shadowing chaplains interacting with patients. CONCLUSIONS: This broad systematic review of the literature revealed a small but growing number of studies describing specific course structure and curricula for teaching spirituality at the medical student level. For the most concise approach, one short, mandatory didactic session followed by application with standardized or hospital patients can be an effective method of introducing students to the importance of spirituality. Important topics to address include the differences between religion and spirituality, recognizing spiritual distress, how to take a spiritual history, and the relevance of spirituality to student well-being. Measured student outcomes should encompass behavioral changes during patient care in addition to changes in knowledge and attitudes. Suggested methods of evaluation include reflective writing and adding a standardized patient case in which the patient is in spiritual distress in an Objective Structured Clinical Examination (OSCE).

What organizational and business models underlie the provision of spiritual care in healthcare organizations? An initial description and analysis.

Two-thirds of American hospitals have chaplains. This article explores the organizational and business models that underlie how chaplains are integrated into hospitals. Based on interviews with 14 chaplain managers and the 11 healthcare executives to whom they report at 18 hospitals in 9 systems, we identify three central findings. First, there is significant variation in how spiritual care programs are staffed and integrated into their hospitals. Second, executives and chaplain managers see the value of chaplains in terms of their quality of care, reliability and responsivity to emergent patient and staff needs, and clinical training and experience working within a complex environment. Third, few departments rely on empirical data when making decisions about staffing, tending instead to default to the budgetary status quo. These findings provide the basis for a larger more systematic study.

Magnetic Patterning of Vorticella convallaria in a Microfluidic Device.

We describe an inexpensive magnetic cell patterning method as a tool for protozoologists. The ciliate Vorticella convallaria is useful for various biofluidics applications. Here, we show that V. convallaria will ingest metal beads and that permanent magnets can be used to pattern cells in Petri dishes or a microfluidic device. Patterning is reversibly achieved by placing magnets at the point of desired cell attachment. Analogous magnetic manipulation could be performed using other phagocytic cells.

The personal utility of cfDNA screening: Pregnant patients' experiences with cfDNA screening and views on expanded cfDNA panels.

Prenatal cell-free DNA screening (cfDNA) provides more genetic risk information about the fetus than has ever been possible. At the same time, the rapid expansion of new cfDNA panels raises important questions about how to structure patient-centered discussions that best support patients' decision-making about its use. To address this question, we conducted interviews with pregnant patients to identify decision-making needs and preferences with respect to cfDNA in patient-centered healthcare discussions, given its evolving capability to identify a range of fetal variants. Personal utility was a core concept guiding decision-making. Participants spoke of how their deeply personal values and beliefs about maternal responsibility, actionability, and tolerance of uncertainty framed their view of the personal utility of cfDNA screening. While discussing their notions of personal utility with their healthcare provider, participants also had concerns about potential ramifications for the provider-patient relationship and shared decision-making when disclosing values and preferences regarding disability, quality of life, and termination-particularly as it becomes possible to identify variants with different disease-associated severity and outcomes. The complexities associated with the introduction of genomics in prenatal care present unique challenges to structuring effective shared decision-making discussions between patients and their healthcare providers. While efforts are underway to determine how to best educate patients about the medical aspects of cfDNA, it is equally important to develop approaches in healthcare communication that enable patients to make informed, values-based decisions about the use of cfDNA and its impact on their pregnancy.

Engineering Synthetic Chromosomes by Sequential Loading of Multiple Genomic Payloads over 100 Kilobase Pairs in Size.

Gene delivery vehicles currently in the clinic for treatment of monogenic disorders lack sufficient carrying capacity to efficiently address complex polygenic diseases. Thus, to engineer multifaceted genetic circuits for bioengineering human cells as a therapeutic option for polygenic diseases, we require new tools that are currently in their infancy. Mammalian artificial chromosomes, or synthetic chromosomes, represent a viable approach for delivery of large genetic payloads that are mitotically stable and remain independent of the host genome. Previously, we described a mammalian synthetic chromosome platform, termed the ACE system, that requires a single unidirectional integrase for the introduction of multiple genes onto the ACE platform chromosome. In this report, we provide a proof of concept that the ACE synthetic chromosome bioengineering platform is amenable to sequential delivery of off-the-shelf large genomic fragments. Specifically, large genomic clones spanning the human solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1 or GLUT1, 169 kbp), and human monocarboxylate transporter 1 (SLC16A1 or MCT1, 144 kbp) genetic loci were engineered onto the ACE platform and demonstrated to express and correctly splice both gene transcripts. Thus, the ACE system provides a facile and tractable engineering platform for the development of gene-based therapeutic agents targeting polygenic diseases.

Investigating Parent Needs, Participation, and Psychological Distress in the Children's Hospital.

BACKGROUND AND OBJECTIVES: Greater parent participation in a child's hospital care is associated with better child outcomes in the hospital and after discharge. This study examined the relationships between perceived need fulfillment for parents, parent participation in hospital care, and parent psychological distress. We hypothesized that greater perceived need fulfillment would be associated with greater participation in hospital care and decreased psychological distress. METHODS: In this prospective cohort study, 166 parents completed questionnaires on a pediatric (nonintensive care) floor. Eligible parents were fluent in English and had a child who was hospitalized ≥2 nights. Previously validated questionnaires were used to assess parent participation in hospital care and psychological distress (defined here as symptoms of anxiety/depression). A modified version of the Bereaved Parent Needs Assessment was used to assess perceived need fulfillment. The association between perceived need fulfillment and each outcome variable was examined using multiple linear regression analyses. RESULTS: Of 186 eligible parents, 166 were enrolled (1 declined, 19 missed/not present). In multivariable analyses, greater perceived need fulfillment was associated with greater participation in hospital care and fewer symptoms of depression, even after controlling for relevant covariates. Exploratory analyses identified needs that were differentially important within groups of parents at risk for distress. CONCLUSIONS: This study suggests that assessing and supporting parent needs during a child's hospitalization may improve parent and child outcomes by increasing parents' ability to participate in hospital care and decreasing psychological distress. Future research is needed to investigate the impact of interventions targeting specific parent needs.

Trypanosome Lytic Factor-1 Initiates Oxidation-stimulated Osmotic Lysis of Trypanosoma brucei brucei.

Human innate immunity against the veterinary pathogen Trypanosoma brucei brucei is conferred by trypanosome lytic factors (TLFs), against which human-infective T. brucei gambiense and T. brucei rhodesiense have evolved resistance. TLF-1 is a subclass of high density lipoprotein particles defined by two primate-specific apolipoproteins: the ion channel-forming toxin ApoL1 (apolipoprotein L1) and the hemoglobin (Hb) scavenger Hpr (haptoglobin-related protein). The role of oxidative stress in the TLF-1 lytic mechanism has been controversial. Here we show that oxidative processes are involved in TLF-1 killing of T. brucei brucei. The lipophilic antioxidant N,N'-diphenyl-p-phenylenediamine protected TLF-1-treated T. brucei brucei from lysis. Conversely, lysis of TLF-1-treated T. brucei brucei was increased by the addition of peroxides or thiol-conjugating agents. Previously, the Hpr-Hb complex was postulated to be a source of free radicals during TLF-1 lysis. However, we found that the iron-containing heme of the Hpr-Hb complex was not involved in TLF-1 lysis. Furthermore, neither high concentrations of transferrin nor knock-out of cytosolic lipid peroxidases prevented TLF-1 lysis. Instead, purified ApoL1 was sufficient to induce lysis, and ApoL1 lysis was inhibited by the antioxidant DPPD. Swelling of TLF-1-treated T. brucei brucei was reminiscent of swelling under hypotonic stress. Moreover, TLF-1-treated T. brucei brucei became rapidly susceptible to hypotonic lysis. T. brucei brucei cells exposed to peroxides or thiol-binding agents were also sensitized to hypotonic lysis in the absence of TLF-1. We postulate that ApoL1 initiates osmotic stress at the plasma membrane, which sensitizes T. brucei brucei to oxidation-stimulated osmotic lysis.

The ACPE supervisory education process: an historical perspective.

As the number of Clinical Pastoral Education students increases, supervisors in the Association for Clinical Pastoral Education (ACPE) are in short supply due to retirements. We explore factors associated with this supply problem, reporting here four results from our survey of active and retired supervisors. We identify the ages of the current supervisory pool, the ages at which supervisors were certified and the length of time spent in the supervisory education program across the decades. The survey results also identify what supervisors perceive as the most helpful components of their supervisory education. These four results identify trends across the decades that may be associated with the present and future shortages of supervisors.

Do health and education agencies in the United States share responsibility for academic achievement and health? A review of 25 years of evidence about the relationship of adolescents' academic achievement and health behaviors.

PURPOSE: The United States Centers for Disease Control and Prevention monitors health-risk behaviors of adolescents in United States, which include (1) violence; (2) tobacco use; (3) alcohol and other drug use; (4) sexual behaviors contributing to unintended pregnancy and sexually transmitted diseases; (5) inadequate physical activity; and (6) unhealthy dietary behaviors. We reviewed original research published in peer-reviewed journals between 1985 and 2010 to synthesize evidence about the association of adolescent health-risk behaviors and academic achievement. METHODS: Using predetermined selection criteria, 122 articles were included that used at least one variable for health-risk behaviors and also for academic achievement. RESULTS: For all six health-risk behaviors, 96.6% of the studies reported statistically significant inverse relationships between health-risk behaviors and academic achievement. CONCLUSIONS: With this persuasive evidence about the interrelationship of health-risk behaviors and academic achievement, it is imperative that leaders in education and health act together to make wise investments in our nation's school-age youth that will benefit the entire population. A unified system that addresses both health behavior and academic achievement would have reciprocal and synergistic effects on the health and academic achievement not only of children and adolescents, but also of adults in the United States.

Molecular characterizations of Nop16 in murine mammary tumors with varying levels of c-Myc.

NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated gene in in vitro studies, hence coexpression levels were strongly correlated. Importantly, high expression of NOP16 was associated with poor clinical outcome in breast cancer patients. However, coexpression of NOP16, MYC and estrogen receptor (ESR1) varied widely in tumors and cell lines suggesting that transcriptional regulation differed according to pathological environments. The goal of this study was to determine the expression patterns of Nop16, Myc and Esr1 in murine mammary tumors with disparate histopathological and molecular features. We hypothesized that tumor environments with relatively high Myc levels would have different coexpression patterns than tumor environments with relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein in tumors from WAP-c-myc mice that were of high grade and metastasized frequently. In contrast, Myc and Nop16 mRNA and proteins levels were significantly lower in the less aggressive tumors that developed in NRL-TGFα mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1 mRNA levels correlated positively with Myc levels in both models. However, Myc and Nop16 transcript levels correlated positively only in tumors from NRL-TGFα mice. We identified prominent NOP16 protein in nuclei and less prominent staining in the cytoplasm of luminal cells of ducts and lobules from normal mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFα mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear staining was faint or absent and cytoplasmic staining more pronounced. In summary, the regulation of expression and localization of NOP16 varies in tumor environments with high versus low MYC levels and demonstrate the importance of stratifying clinical breast cancers based on MYC levels.

Downstream bioengineering of ACE chromosomes for incorporation of site-specific recombination cassettes.

Advances in mammalian artificial chromosome technology have made chromosome-based vector technology amenable to a variety of biotechnology applications including cellular protein production, genomics, and animal transgenesis. A pivotal aspect of this technology is the ability to generate artificial chromosomes de novo, transfer them to a variety of cells, and perform downstream engineering of artificial chromosomes in a tractable and rational manner. Previously, we have described an alternative artificial chromosome technology termed the ACE chromosome system, where the ACE platform chromosome contains a multitude of site-specific, recombination sites incorporated during the creation of the ACE platform chromosome. In this chapter we review a variant of the ACE chromosome technology whereby site-specific, recombination sites can be integrated into the ACE chromosome following its de novo synthesis. This variation allows insertion of user-defined, site-specific, recombination systems into an existing ACE platform chromosome. These bioengineered ACE platform chromosomes, containing user-defined recombination sites, represent an ideal circuit board to which an array of genetic factors can be plugged-in and expressed for various research and therapeutic applications.

Short-term prophylactic tamoxifen reduces the incidence of antiestrogen-resistant/estrogen receptor-positive/progesterone receptor-negative mammary tumors.

Although many estrogen receptor-positive (ER+) breast cancers are effectively treated with selective estrogen receptor modulators and down-regulators (SERM/SERD), some are highly resistant. Resistance is more likely if primary cancers are devoid of progesterone receptors (PR-) or have high levels of growth factor activity. In this study, a transgenic mouse line that expresses transforming growth factor-alpha (NRL-TGFalpha mice) and that develops ER+/PR- mammary tumors was used to assess the possible effects of (a) therapeutic delivery of the SERM, tamoxifen, or SERD, ICI I82,780 (ICI), on the growth of established tumors and (b) short-term prophylactic tamoxifen administration on the initial development of new mammary tumors. To determine the therapeutic effects of tamoxifen and ICI on the growth of established tumors, mice were exposed to 3 weeks of drug treatment. Neither drug influenced tumor growth or glandular pathology. To determine if early prophylactic tamoxifen could alter tumorigenesis, a 60-day tamoxifen treatment was initiated in 8-week-old mice. Compared with placebo-treated mice, tamoxifen reduced tumor incidence by 50% and significantly decreased the degree of mammary hyperplasia. Prophylactic tamoxifen also significantly extended the life span of tumor-free mice. These data show that in this mouse model, established ER+/PR- mammary tumors are resistant to SERM/SERD treatment but the development of new mammary tumors can be prevented by an early course of tamoxifen. This study validates the utility of NRL-TGFalpha mice for (a) identifying candidate biomarkers of efficacious tamoxifen chemoprevention and (b) modeling the evolution of tamoxifen resistance.

Mechanisms of occupational asthma: Not all allergens are equal.

Asthma is a heterogeneous lung disorder characterized by airway obstruction, inflammation and eosinophil infiltration into the lung. Both genetics and environmental factors influence the expression of asthma, and not all asthma is the result of a specific immune response to allergen. Numerous asthma phenotypes have been described, including occupational asthma, and therapeutic strategies for asthma control are similar regardless of phenotype. We hypothesized that mechanistic pathways leading to asthma symptoms in the effector phase of the disorder differ with the inciting allergen. Since route of allergen exposure can influence mechanistic pathways, mice were sensitized by identical routes with a high molecular weight occupational allergen ovalbumin and a low molecular weight occupational allergen trimellitic anhydride (TMA). Different statistical methods with varying selection criteria resulted in identification of similar candidate genes. Array data are intended to provide candidate genes for hypothesis generation and further experimentation. Continued studies focused on genes showing minimal changes in the TMA-induced model but with clear up-regulation in the ovalbumin model. Two of these genes, arginase 1 and eotaxin 1 are the focus of continuing investigations in mouse models of asthma regarding differences in mechanistic pathways depending on the allergen. Microarray data from the ovalbumin and TMA model of asthma were also compared to previous data usingAspergillus as allergen to identify putative asthma 'signature genes', i.e. genes up-regulated with all 3 allergens. Array studies provide candidate genes to identify common mechanistic pathways in the effector phase, as well as mechanistic pathways unique to individual allergens.

Impact of macrophage and dendritic cell subset elimination on antiviral immunity, viral clearance and production of type 1 interferon.

We report herein that vesicular stomatitis virus (VSV) induced a concurrent primary Th1 (T helper 1) and Th2 cytokine response detectable ex vivo. Liposome-encapsulated clodronate-mediated elimination of CD8- marginal dendritic cells (DCs) and splenic macrophages (m Phi), but not CD8+ interdigitating DCs, prior to infection resulted in a markedly diminished chemokine and Th1 (IL-2, interferon-gamma) cytokine response, although the Th2 response (IL-4) remained relatively intact. Repopulation with marginal DCs and marginal metallophilic macrophages (MMM) restored Th1 cytokine profiles but did not restore chemokine responsiveness or reduce VSV-induced morbidity/mortality. Chemokine competency returned approximately 4 weeks post-depletion, which correlated temporally with repopulation of the spleen with marginal zone macrophages (MZM) and red pulp macrophages (RPM). Unexpectedly, virus-induced morbidity persisted for over 1 month post-depletion and was associated with virus dissemination and distinctive histological lesions in the liver. Depletion of interferon-producing plasmacytoid dendritic cells did not account for virus-induced morbidity because serum levels of type I interferon were not diminished in Cl2MBP-liposome-treated mice. Thus, distinct m Phi subsets are critical for chemokine production and viral clearance, and, in their absence, VSV disseminates even in the presence of high titers of interferon.

Arginase activity differs with allergen in the effector phase of ovalbumin- versus trimellitic anhydride-induced asthma.

Both trimellitic anhydride (TMA), a small molecular weight chemical, and ovalbumin (OVA), a reference protein allergen, cause asthma with eosinophilia. To test the hypothesis that different allergens elicit symptoms of asthma via different effector pathways, gene expression was compared in lungs of Balb/c mice sensitized with either TMA or OVA, followed by intratracheal challenge with TMA conjugated to mouse serum albumin (TMA-MSA) or OVA, respectively. Sensitized animals challenged with mouse serum albumin (MSA) alone were controls. Seventy-two hours after challenge, lung eosinophil peroxidase indicated that both allergens caused the same significant change in eosinophilia. Total RNA was isolated from lung lobes of 6-8 animals in each of four treatment groups and hybridized to Affymetrix U74Av2 GeneChips. False discovery rates (q-values) were calculated from an overall F test to identify candidate genes with differences in expression for the four groups. Using a q-value cutoff of 0.1, 853 probe sets had significantly different expression across the four treatment groups. Of these 853 probe sets, 376 genes had an Experimental/Control ratio of greater than 1.2 or less than 1/1.2 for either OVA- or TMA-treated animals, and 249 of the 376 genes were uniquely up- or down-regulated for OVA or TMA (i.e., differentially expressed with the allergen). qRT-PCR analysis of selected transcripts confirmed the gene expression analysis. Increases in both arginase transcript and enzyme activity were significantly greater in OVA-induced asthma compared to TMA-induced asthma. These data suggest that pathways of arginine metabolism and the importance of nitric oxide may differ in OVA- and TMA-induced asthma.

A mammalian artificial chromosome engineering system (ACE System) applicable to biopharmaceutical protein production, transgenesis and gene-based cell therapy.

Mammalian artificial chromosomes (MACs) provide a means to introduce large payloads of genetic information into the cell in an autonomously replicating, non-integrating format. Unique among MACs, the mammalian satellite DNA-based Artificial Chromosome Expression (ACE) can be reproducibly generated de novo in cell lines of different species and readily purified from the host cells' chromosomes. Purified mammalian ACEs can then be re-introduced into a variety of recipient cell lines where they have been stably maintained for extended periods in the absence of selective pressure. In order to extend the utility of ACEs, we have established the ACE System, a versatile and flexible platform for the reliable engineering of ACEs. The ACE System includes a Platform ACE, containing >50 recombination acceptor sites, that can carry single or multiple copies of genes of interest using specially designed targeting vectors (ATV) and a site-specific integrase (ACE Integrase). Using this approach, specific loading of one or two gene targets has been achieved in LMTK(-) and CHO cells. The use of the ACE System for biological engineering of eukaryotic cells, including mammalian cells, with applications in biopharmaceutical production, transgenesis and gene-based cell therapy is discussed.