Ultrasound Education in an Elective Course in the Undergraduate Medical Curriculum Improves Students' Subjective Learning and Clinical Rotation and Residency Preparedness.

Objectives: Studies have demonstrated that students are able to improve their understanding of anatomy, physical exam skills, and clinical knowledge when ultrasound is incorporated into their education. This study investigates whether students enrolled in an elective with significant use of ultrasound (ACS) in their preclinical years subjectively improved their preparedness for clinical rotations, residency, and learning in several subjects. Methods: This was a retrospective analysis of an anonymous online needs assessment survey sent to 384 third- and fourth-year medical students. Survey items included Likert scales analyzed with a student's t-test or Chi-Square analysis and yes/no questions analyzed with Chi square, as well as demographic information. Results: 201 students responded to the survey (52.3% response rate). ACS participants reported feeling more prepared for their clinical rotations than their non-ACS peers (3.5 vs. 2.33, p < 0.001 ) and felt more prepared for residency (3.12 vs 1.91, p < 0.001). ACS students also found ultrasound significantly more helpful in understanding the physical exam (69.3% vs. 53.2%, p = 0.02) and anatomy (94.7% vs. 81%, p = 0.012). Conclusions: Student respondents expressed a desire for more ultrasound education throughout medical school. Students who participated in ACS reported feeling more prepared for their clinical rotations and residency than their non-ACS peers and were more likely to feel that ultrasound improved their understanding of anatomy and the physical exam. This study adds to the literature suggesting that increasing the quantity of ultrasound in preclinical medical education may improve students' satisfaction, learning and clinical preparedness. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01800-4.

Telling Stories with Data.

The fidelity provided by rich, nuanced ethics consult narratives does not proscribe efforts to advance the profession by using data to assess performance and demonstrate value. While these two approaches have been described as in conflict with one another, the former sets the bar to which the latter should aim; to achieve this, consult data should, minimally, do two things: (1) tell the story of the case, as best as possible, in language easily accessible to both ethicists and non-ethicists alike; and (2) do so in a way that elements of interest can be aggregated, disambiguated, and analyzed. Here we present a three-component system designed with that in mind. First, the Armstrong Clinical Ethics Coding System (ACECS) produces a set of six codes that tell a simplified story of the case. These six codes form a meta narrative, which, like meta data, can be aggregated, disambiguated, and analyzed. Second, we use a data model to uncover the stories those data tell. The results allow us to understand relationships, recognize patterns, and reveal insights that are otherwise not discoverable when using narratives alone. Third, due to tremendous heterogeneity among cases, we represent findings visually using techniques borrowed from data storytelling, a powerful means to demonstrate the value of a consult service to administrators and others. The ability to derive meta narratives from an aggregate of case narratives allows us to describe, in detail, the work of our consult service in a manner directly comparable to other services that use the system while we preserve unprecedented case-level nuance. If adopted broadly, this functionality suggests a means to undergird the legitimacy of the ethics consult practice itself in an evidence-based manner similar to that which undergirds other domains of healthcare.

Lacticaseibacillus rhamnosus HN001 alters the microbiota composition in the cecum but not the feces in a piglet model.

The probiotic Lacticaseibacillus rhamnosus strain HN001 has been shown to have several beneficial health effects for both pediatric and maternal groups, including reduced risk of eczema in infants and gestational diabetes and postnatal depression in mothers. While L. rhamnosus HN001 appears to modify immune and gut barrier biomarkers, its mode of action remains to be fully elucidated. To gain insights into the role of HN001 on the infant microbiome, the impacts of L. rhamnosus HN001 supplementation was studied in 10-day old male piglets that were fed either infant formula, or infant formula with L. rhamnosus HN001 at a low (1.3 × 105 CFU/ml) or high dose (7.9 × 106 CFU/ml) daily for 24 days. The cecal and fecal microbial communities were assessed by shotgun metagenome sequencing and host gene expression in the cecum and colon tissue was assessed by RNA-seq. Piglet fecal samples showed only modest differences between controls and those receiving dietary L. rhamnosus HN001. However, striking differences between the three groups were observed for cecal samples. While total lactobacilli were significantly increased only in the high dose L. rhamnosus HN001 group, both high and low dose groups showed an up to twofold reduction across the Firmicutes phylum and up to fourfold increase in Prevotella compared to controls. Methanobrevibacter was also decreased in HN001 fed piglets. Microbial genes involved in carbohydrate and vitamin metabolism were among those that differed in relative abundance between those with and without L. rhamnosus HN001. Changes in the cecal microbiome were accompanied by increased expression of tight junction pathway genes and decreased autophagy pathway genes in the cecal tissue of piglets fed the higher dose of L. rhamnosus HN001. Our findings showed supplementation with L. rhamnosus HN001 caused substantial changes in the cecal microbiome with likely consequences for key microbial metabolic pathways. Host gene expression changes in the cecum support previous research showing L. rhamnosus HN001 beneficially impacts intestinal barrier function. We show that fecal samples may not adequately reflect microbiome composition higher in the gastrointestinal tract, with the implication that effects of probiotic consumption may be missed by examining only the fecal microbiome.

Social media and the practice of pediatric physical medicine and rehabilitation in the COVID-19 pandemic: A new era in patient-care.

Social media represents a significant source of health information for the public, especially during the COVID-19 pandemic where gatherings are limited. It is important for pediatric physical medicine and rehabilitation physicians to understand how their patients use these platforms in order to educate the public and provide sound medical advice on social media. Given the lack of current guidelines on medical education through social media, the purpose of this paper is to provide an overview of various online social media platforms and describe how they can be utilized to enhance pediatric patient education. It is necessary to understand the different educational functions and limitations of the various social media platforms. This text provides a comprehensive overview of different social media platforms, their educational uses, limitations, and sample accounts. Relevant to the COVID-19 pandemic, social media can improve the efficiency of educational delivery and clinic workflow. Although social media is not meant to replace physician-patient relationships, it can be used as a surrogate for health information and improve- even start- physician-patient relationships. Despite the benefits of social media, pediatric physiatrists may be hesitant to utilize these platforms for several reasons. This text provides an overview of common barriers to social media usage by physicians and recommendations to overcome them. Given that the pandemic has led to increased social media usage, physicians should be aware of its implications on patient care and how they can be used to enhance the practice of pediatric physical medicine and rehabilitation. As social media usage by both patients and physicians grows, more research is needed to create recommendations on how pediatric physiatrists can best utilize social media to educate the public in an enjoyable manner while maintaining a professional image.

Impacts of Formula Supplemented with Milk Fat Globule Membrane on the Neurolipidome of Brain Regions of Piglets.

The milk fat globule membrane (MFGM) appears to play an important role in infant neurocognitive development; however, its mechanism(s) of action remains unclear. This study aimed to investigate the role of a dietary MFGM supplement on the lipid profiles of different neonatal brain regions. Ten-day-old male piglets (4−5 kg) were fed unsupplemented infant formula (control, n = 7) or an infant formula supplemented with low (4%) or high (8%) levels of MFGM (n = 8 each) daily for 21 days. Piglets were then euthanized, and brain tissues were sectioned. Untargeted liquid chromatography-mass spectrometry lipidomics was performed on the cerebellum, hippocampus, prefrontal cortex, and the rest of the brain. The analyses identified 271 and 171 lipids using positive and negative ionization modes, respectively, spanning 16 different lipid classes. MFGM consumption did not significantly alter the lipidome in most brain regions, regardless of dose, compared to the control infant formula. However, 16 triacylglyceride species were increased in the hippocampus (t-test, p-value < 0.05) of the high-supplemented piglets. Most lipids (262 (96.7%) and 160 (93.6%), respectively) differed significantly between different brain regions (ANOVA, false discovery rate corrected p-value < 0.05) independent of diet. Thus, this study highlighted that dietary MFGM altered lipid abundance in the hippocampus and detected large differences in lipid profiles between neonatal piglet brain regions.

Utilizing learning communities to deliver an integrated undergraduate medical education curriculum.

AIM: Learning communities (LCs) have been identified as a structure to support student wellness as well as create a positive learning environment and have been increasingly adopted in undergraduate medical education (UGME). In 2016, Michigan State University College of Human Medicine made curricular changes which integrated basic, social, and clinical sciences. One of the major strategies adopted to deliver this integrated curriculum was to create LCs that served as a central scaffold for students' academic development. Our primary aim is to describe how the school utilized LC faculty to deliver this core integrated curriculum. METHODS: Students were surveyed about their perceptions of the effectiveness of the LCs in delivering an integrated science curriculum. Student academic performance in the new curriculum was compared to that of students from the legacy curriculum as a measure of the effectiveness of the curricular changes. RESULTS: The percentage of students in each class who responded to surveys ranged between 78.7% and 95.8%. Mean Likert responses (1 = strongly disagree; 5 = strongly agree) for statements 'the Faculty Fellow is effective in helping me learn the scholar group content', 'the Faculty Fellow is an effective teacher in our scholar group', and 'the Faculty Fellow is well prepared for our scholar group' ranged from 4.37 to 4.78, 4.72 to 4.76, and 4.81 to 4.86, respectively. In addition, a comparison of summative exam scores of the new curriculum's students to the legacy curriculum's students demonstrated comparable or better performances in the new curriculum. CONCLUSIONS: Utilizing LCs to deliver an integrated science curriculum is an underutilized strategy in UGME. Surveys on student satisfaction and academic performance are encouraging. Additional outcome measures are planned to continually evaluate this innovative multifaceted integration.

A Polyphenol Enriched Variety of Apple Alters Circulating Immune Cell Gene Expression and Faecal Microbiota Composition in Healthy Adults: A Randomized Controlled Trial.

Polyphenols within fruits and vegetables may contribute to health benefits due to their consumption, with the anthocyanin sub-set also adding colour. The Lemonade™ apple variety has green skin and white flesh, with low anthocyanin content, while some apple varieties have high anthocyanin content in both the skin and flesh. Effects of red compared with white-fleshed apples were studied in healthy human subjects in a randomized, placebo-controlled, cross-over intervention trial. Twenty-five healthy subjects consumed dried daily portions of the red-fleshed or placebo (white-fleshed) apple for two weeks, followed by one-week washout and further two-week crossover period. During the study, volunteers provided faecal samples for microbiota composition analysis and blood samples for peripheral blood mononuclear cell (PBMC) gene expression analysis. Subtle differences were observed in the faecal microbiota of subjects that were fed the different apples, with significant (p < 0.05) reductions in relative abundances of Streptococcus, Ruminococcus, Blautia, and Roseburia, and increased relative abundances of Sutterella, Butyricicoccus, and Lactobacillus in subjects after consuming the red apple. Changes in PBMC gene expression showed 18 mRNA transcripts were differentially expressed between the two groups, of which 16 were immunoglobulin related genes. Pathway analysis showed that these genes had roles in pathways such as immunoglobulin production, B cell-mediated immunity, complement activation, and phagocytosis. In conclusion, this study shows that anthocyanin-rich apples may influence immune function compared to control apples, with changes potentially associated with differences in the faecal microbiota.

Comparison Is Not a Zero-Sum Game: Exploring Advanced Measures of Healthcare Ethics Consultation.

BACKGROUND: Studies across the healthcare spectrum consistently show that sharing and comparing data across institutions improves the quality of patient care. Whether comparing data about healthcare ethics consultation (HCEC) would similarly improve quality is unknown due to the lack of research on HCEC data sharing and comparison. Methods: To explore this possibility, we analyzed data from two academic medical centers in the Central-Southern United States that both employ a shared, robust coding system for ethics consultations (N = 703 cases total over 2.5 years) using descriptive and chi-square statistics, correlation coefficients and logistic regressions. Results: Our findings relate to patient age, care location, requestor role, and ethical themes, which together contribute to an improved evidence base for explanatory analyses and quality improvement initiatives. Conclusions: We conclude it is possible to analyze and compare HCEC activities across separate institutions using a standardized approach to data gathering, that this approach is consistent with concurrent narrative case review and assessment, and that cross-institutional comparisons are meaningful. Our results suggest future comparative analyses will require additional standardization of advanced measures for describing and analyzing HCEC activities.

Cohort Profile: The Christchurch IBS cOhort to investigate Mechanisms FOr gut Relief and improved Transit (COMFORT).

BACKGROUND AND AIMS: This cross-sectional observational case-control study was initiated in July 2016 with the aim of increasing an understanding of the underlying disease mechanisms in functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS), functional diarrhoea (FD), and functional constipation (FC). Specific areas of interest include the effect of food, microbiome, host and microbial genetics, metabolome, and psychological variables on unexplained chronic gastrointestinal (GI) symptoms. METHODS: This study recruited consecutive patients who were attending one of two endoscopy centres in Christchurch, New Zealand, for colonoscopy and a subgroup of participants from the general public who did not undergo colonoscopy. Participants with known GI disease other than an FGID were excluded. Those with symptoms were recruited as cases, whilst those without symptoms were recruited as controls. In the days prior to preparation for colonoscopy, or an agreeable time for those not undergoing colonoscopy, demographic, symptom, psychological, dietary, and health data were collected in addition to biological samples (breath, faeces, blood, and urine). Colonic biopsies were taken at the time of colonoscopy from participants in the colonoscopy subgroup. RESULTS: Between July 2016 and December 2018, 349 participants were recruited, 315 of whom completed the study, 220 participants were from the colonoscopy subgroup, and 95 from the non-colonoscopy subgroup. This included 129 controls and 186 cases (57 IBS-diarrhoea predominant, 30 IBS-constipation predominant, 41 IBS-mixed, 42 FC, and 16 FD). The mean age of FGID cases was 53.4 years and controls 54.4 years. Cases (149/186, 80.1%) and controls (57/72, 55.8%) were predominantly female. Education levels were similar across the cohort. Smoking and alcohol rates were also similar. Biological samples were collected as planned from participants. CONCLUSIONS: The COMFORT cohort is a unique clinical cohort of FGID cases and controls with a wide range of demographic, dietary, clinical, psychological, and health data in addition to biological samples. Future research will aim to use a systems biology approach to establish the potential role of diet, host-microbiome interactions, and other factors in the pathogenesis of FGIDs.

Neuromodulating Influence of Two Electroacupuncture Treatments on Heart Rate Variability, Stress, and Vagal Activity.

Introduction: Although the clinical use of electro-acupuncture is widespread, the neuromodulating influence of various applied frequencies is not well established. Objectives: Heart rate variability (HRV), stress and parasympathetic recovery are closely related to health, longevity and vitality in humans. This study was undertaken to determine the influence of different electro-therapy frequencies on various autonomic nervous system markers when applied to a Battlefield Acupuncture Protocol (BFA). Design: A detailed comparison of autonomic nervous system (ANS) response to low frequency (LF) 2.5 Hz electro-acupuncture and mid-frequency (MF) 15 Hz electro-acupuncture applied by point stimulation to acupuncture points was undertaken on 2 groups of 12 patients. Interventions: Both LFEA and MFEA were applied to Battlefield Acupuncture protocol, consisting of five (5) key acupuncture ear (auricular) points that isolate the autonomic nervous system (ANS) and central nervous system's role in the chronic/acute pain cycle. Evaluations entailed an advanced status of autonomic nervous system (ANS) function through Electro-Cardiogram (ECG) baseline markers reflecting: sympathetic stress (SI); parasympathetic vagal tone (high frequency [HF]) and heart rate variability (HRV = total power). All were repeated subsequent to electro-therapy using 2 separate electro-modalities of low-frequency (2.5 Hz) electro-acupuncture (LFEA) and Mid-Frequency (15 Hz) electro-acupuncture (MFEA). All 24 patients received one (1) elector-acupuncture session. Results: The autonomic nervous system response to LFEA (2.5 Hz) reflected a statistically significant pre-post improvement in three of the markers collected: heart rate variability (HRV) improved by 61% [p = 0.002]; sympathetic stress (SI) reduced 42% [p = 0.002]; and parasympathetic vagal tone (HF) increased 56% [p = 0.017]. In contrast, MFEA (15 Hz) showed positive but non-significant changes in outcomes in all nervous system markers. Conclusions: The autonomic nervous system response with LFEA showed a measurable reduction in sympathetic stress with subsequent improvement in vagal tone, and HRV. This positive sympathetic nervous system deactivation from LFEA application shown in this study could have a major impact on other pathologies related to human health and longevity. Further cohort studies are warranted to determine the validity of these outcomes.

Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity.

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation.

Microcurrent Point Stimulation Applied to Lower Back Acupuncture Points for the Treatment of Nonspecific Neck Pain.

OBJECTIVES: Although acupuncture and microcurrent are widely used for chronic pain, there remains considerable controversy as to their therapeutic value for neck pain. We aimed to determine the effect size of microcurrent applied to lower back acupuncture points to assess the impact on the neck pain. DESIGN: This was a cohort analysis of treatment outcomes pre- and postmicrocurrent stimulation, involving 34 patients with a history of nonspecific chronic neck pain. SUBJECTS AND SETTINGS: Consenting patients were enrolled from a group of therapists attending educational seminars and were asked to report pain levels pre-post and 48 hours after a single MPS application. INTERVENTIONS AND MEASUREMENTS: Direct current microcurrent point stimulation (MPS) applied to standardized lower back acupuncture protocol points was used. Evaluations entailed a baseline visual analog scale (VAS) pain scale assessment, using a VAS, which was repeated twice after therapy, once immediately postelectrotherapy and again after a 48-h follow-up period. All 34 patients received a single MPS session. Results were analyzed using paired t tests. Results and Outcomes: Pain intensity showed an initial statistically significant reduction of 68% [3.9050 points; 95% CI (2.9480, 3.9050); p = 0.0001], in mean neck pain levels after standard protocol treatment, when compared to initial pain levels. There was a further statistically significant reduction of 35% in mean neck pain levels at 48 h when compared to pain levels immediately after standard protocol treatment [0.5588 points; 95% CI (0.2001, 0.9176); p = 0.03], for a total average pain relief of 80%. CONCLUSIONS: The positive results in this study could have applications for those patients impacted by chronic neck pain.

Comparative innate immune interactions of human and bovine secretory IgA with pathogenic and non-pathogenic bacteria.

Secretory IgA (SIgA) from milk contributes to early colonization and maintenance of commensal/symbiotic bacteria in the gut, as well as providing defence against pathogens. SIgA binds bacteria using specific antigenic sites or non-specifically via its glycans attached to α-heavy-chain and secretory component. In our study, we tested the hypothesis that human and bovine SIgA have similar innate-binding activity for bacteria. SIgAs, isolated from human and bovine milk, were incubated with a selection of commensal, pathogenic and probiotic bacteria. Using flow cytometry, we measured numbers of bacteria binding SIgA and their level of SIgA binding. The percentage of bacteria bound by human and bovine SIgA varied from 30 to 90% depending on bacterial species and strains, but was remarkably consistent between human and bovine SIgA. The level of SIgA binding per bacterial cell was lower for those bacteria that had a higher percentage of SIgA-bound bacteria, and higher for those bacteria that had lower percentage of SIgA-bound bacteria. Overall, human and bovine SIgA interacted with bacteria in a comparable way. This contributes to longer term research about the potential benefits of bovine SIgA for human consumers.

Short communication: Early-lactation, but not mid-lactation, bovine lactoferrin preparation increases epithelial barrier integrity of Caco-2 cell layers.

Bovine lactoferrin is an important milk protein with many health-promoting properties, including improving intestinal barrier integrity. Dysfunction of this barrier, commonly referred to as "leaky gut," has been linked to inflammatory and autoimmune diseases. With some processing techniques, lactoferrin isolated from milk collected at the start of the milking season (early lactation) may have lower purity than that isolated from milk collected during the rest of the milking season (mid-lactation) and could result in differences in bioactivity based on the stage of lactation. We compared reversed-phase HPLC chromatographs of early-lactation and mid-lactation preparations and found that both had large chromatograph peaks at the time predicted for lactoferrin. The notable difference between the 2 chromatographs was a much larger peak in the early-lactation lactoferrin sample that was determined to be angiogenin. Angiogenin was first identified due to its ability to induce new blood vessel formation, but is now known to be involved in numerous physiological processes. Then, we compared the effects of early-lactation and mid-lactation lactoferrin preparations in 2 bioassays: trans-epithelial electrical resistance (TEER), a measure of intestinal barrier integrity, and peripheral blood mononuclear cell cytokine secretion, a measure of immune-stimulatory properties. We found that early-lactation lactoferrin increased TEER across Caco-2 cell layers compared with control from 10 to 48 h, mid-lactation lactoferrin did not alter TEER. We also found that early-lactation lactoferrin reduced the amount of IL-8 produced by peripheral blood mononuclear cells (compared with those treated with control medium) to a greater extent than mid-lactation lactoferrin. A pro-inflammatory chemokine, IL-8 is also known to decrease barrier function. These results suggest that the decrease in IL-8 production in the presence of early-lactation lactoferrin may be the mechanism by which it increases TEER. The anti-inflammatory effect of early-lactation lactoferrin may be related to the presence of angiogenin, which is known to suppress inflammatory responses. This work indicates that products rich in angiogenin may have intestinal health benefits, and further work to investigate this is warranted.

DC Electroacupuncture Effects on Scars and Sutures of a Patient with Postconcussion Pain.

Introduction: This case study offers a detailed comparative analysis of the effects of direct-current electroacupuncture (DC-EA) on the autonomic nervous system (ANS), when DC-EA was applied to the cranial sutures and scars of a patient with a history of ischemic stroke and postconcussion syndrome (PCS) pain. Case: A 56-year-old female suffering from severe tremors and debilitating headaches requested acupuncture after conventional biomedicines failed to relieve her symptoms. Evaluations were performed to check the status of 27 ANS functions. These detailed evaluations were performed to obtain a baseline status of ANS function on this patient, who had a history of ischemic stroke, PCS, and chronic pain. All evaluations were repeated pre-post her DC-EA treatment. Results: This patient experienced significant relief from her symptoms after DC-EA treatment. An analysis of this patient's risk for ANS complications showed improvements in four key homeostatic markers post treatment. Conclusions: The ANS response of a patient with ischemic stroke, PCS, and chronic pain, who received electrical nerve stimulation using DC-EA reflected a measurable improvement in sympathetic tone, along with reductions in pain levels and PCS symptoms. The positive results in this case study could have applications to other pathologies that can be affected by the sympathetic nervous system activation on the body.

Connecting Patients to Prescription Assistance Programs: Effects on Emergency Department and Hospital Utilization.

BACKGROUND: Manufacturer prescription assistance programs (PAPs) have been developed to provide medications at little or no cost to eligible patients. There are over 200 PAPs available from pharmaceutical companies, and each may have different eligibility requirements and assistance guidelines. A formalized community-based patient prescription coordinator can help patients navigate these programs by reviewing an applicant's financial information and medication requirements to identify which PAPs are most appropriate. Little is known, however, about whether providing such guidance is associated with a reduction in acute care utilization. OBJECTIVE: To evaluate changes in emergency department and hospital utilization among patients who received care coordination and financial assistance with prescribed medications. METHODS: This single-cohort interrupted time-series study included participants in eastern Washington state who enrolled in the Spokane Prescription Assistance Network (SPAN) program between March 1, 2009, and August 31, 2012. Referrals to the SPAN patient prescription coordinator were made by a social service agency or medical provider for patients who may have difficulty paying for prescribed medications. Initial patient contact occurred while the patient was still being treated in a clinic or hospital or through a direct visit to the coordinator's community-based office. Participants were contacted 6 months after the initial appointment and then annually thereafter to review current medications and health status. A review of electronic health records provided information on hospitalizations and emergency department visits in the 12 months before and after program entry. RESULTS: Among SPAN participants (n = 310), emergency department and hospital encounters declined from 0.38 per participant in the year before enrollment to 0.20 encounters in the year following program entry. A repeated-measures mixed-effects model indicated SPAN participation was associated with a 51% decline in the rate of emergency department and hospital utilization (incidence rate ratio [IRR] = 0.49; 95% CI = 0.31-0.77; P = 0.002). Observed effects differed by prescription class. Factor interactions revealed significant reductions in utilization for participants with prescribed pulmonary medications (IRR = 0.58; 95% CI = 0.37-0.92; P = 0.019). Assistance with mental health (psychotropic) medications was associated with increased incidence of utilization (IRR = 2.07; 95% CI = 1.32-3.24; P = 0.001). At the time of SPAN enrollment, 60% of participants had prescriptions for psychotropic medications. CONCLUSIONS: A formalized patient prescription coordinator can help patients access prescribed medications at low cost and remain compliant with treatment plans. In a study of a coordination pilot program, reductions in hospital admissions and emergency department visits were observed following program participation. DISCLOSURES: This study was not supported by any outside funding. The authors declare no conflicts of interest. Study design was created by Burley, McPherson, and Daratha. Burley Daratha, Selinger, and Armstrong collected the data, with interpretation performed by Burley, Daratha, and Tuttle, assisted by McPherson. The manuscript was written by Burley, Daratha, and Selinger, with assistance from White, and revised by Burley, White, and Selinger, with assistance from Daratha and Tuttle.

Lactobacillus fermentum AGR1487 cell surface structures and supernatant increase paracellular permeability through different pathways.

Lactobacillus fermentum is commonly found in food products, and some strains are known to have beneficial effects on human health. However, our previous research indicated that L. fermentum AGR1487 decreases in vitro intestinal barrier integrity. The hypothesis was that cell surface structures of AGR1487 are responsible for the observed in vitro effect. AGR1487 was compared to another human oral L. fermentum strain, AGR1485, which does not cause the same effect. The examination of phenotypic traits associated with the composition of cell surface structures showed that compared to AGR1485, AGR1487 had a smaller genome, utilized different sugars, and had greater tolerance to acid and bile. The effect of the two strains on intestinal barrier integrity was determined using two independent measures of paracellular permeability of the intestinal epithelial Caco-2 cell line. The transepithelial electrical resistance (TEER) assay specifically measures ion permeability, whereas the mannitol flux assay measures the passage of uncharged molecules. Both live and UV-inactivated AGR1487 decreased TEER across Caco-2 cells implicating the cell surfaces structures in the effect. However, only live AGR1487, and not UV-inactivated AGR1487, increased the rate of passage of mannitol, implying that a secreted component(s) is responsible for this effect. These differences in barrier integrity results are likely due to the TEER and mannitol flux assays measuring different characteristics of the epithelial barrier, and therefore imply that there are multiple mechanisms involved in the effect of AGR1487 on barrier integrity.

Human oral isolate Lactobacillus fermentum AGR1487 reduces intestinal barrier integrity by increasing the turnover of microtubules in Caco-2 cells.

Lactobacillus fermentum is found in fermented foods and thought to be harmless. In vivo and clinical studies indicate that some L. fermentum strains have beneficial properties, particularly for gastrointestinal health. However, L. fermentum AGR1487 decreases trans-epithelial electrical resistance (TEER), a measure of intestinal barrier integrity. The hypothesis was that L. fermentum AGR1487 decreases the expression of intestinal cell tight junction genes and proteins, thereby reducing barrier integrity. Transcriptomic and proteomic analyses of Caco-2 cells (model of human intestinal epithelial cells) treated with L. fermentum AGR1487 were used to obtain a global view of the effect of the bacterium on intestinal epithelial cells. Specific functional characteristics by which L. fermentum AGR1487 reduces intestinal barrier integrity were examined using confocal microscopy, cell cycle progression and adherence bioassays. The effects of TEER-enhancing L. fermentum AGR1485 were investigated for comparison. L. fermentum AGR1487 did not alter the expression of Caco-2 cell tight junction genes (compared to L. fermentum AGR1485) and tight junction proteins were not able to be detected. However, L. fermentum AGR1487 increased the expression levels of seven tubulin genes and the abundance of three microtubule-associated proteins, which have been linked to tight junction disassembly. Additionally, Caco-2 cells treated with L. fermentum AGR1487 did not have defined and uniform borders of zona occludens 2 around each cell, unlike control or AGR1485 treated cells. L. fermentum AGR1487 cells were required for the negative effect on barrier integrity (bacterial supernatant did not cause a decrease in TEER), suggesting that a physical interaction may be necessary. Increased adherence of L. fermentum AGR1487 to Caco-2 cells (compared to L. fermentum AGR1485) was likely to facilitate this cell-to-cell interaction. These findings illustrate that bacterial strains of the same species can cause contrasting host responses and suggest that food-safe status should be given to individual strains not species.

Mismatching amodal redundancy inhibits operant learning in 5-month-old infants.

The current study examined the functional role redundant amodal information plays in an operant learning task in 5-month-old human infants. Prior studies have suggested that both simple and complex learning processes (discrimination, associative conditioning) are facilitated when amodal information is presented redundantly across sensory modalities. These studies, however, did not test whether the amodal information had to be similar across modalities for facilitation to occur. The current study examined how both matching and mismatching redundant amodal information about the shape of an object would influence learning of an operant response in human infants. Infants learned an operant kick response to move a mobile of cylinders while either holding a cylinder, a rectangular cube, or no object. Kick rate served as the dependent measure. The results showed that infants given mismatching redundant amodal information (e.g., viewed cylinders while holding a rectangular cube) showed inhibited operant learning. These results extend the Intersensory Redundancy Hypothesis by demonstrating that amodal redundancy can function in some instances to inhibit complex learning processes.

Identification of novel androgen-regulated pathways and mRNA isoforms through genome-wide exon-specific profiling of the LNCaP transcriptome.

Androgens drive the onset and progression of prostate cancer (PCa) by modulating androgen receptor (AR) transcriptional activity. Although several microarray-based studies have identified androgen-regulated genes, here we identify in-parallel global androgen-dependent changes in both gene and alternative mRNA isoform expression by exon-level analyses of the LNCaP transcriptome. While genome-wide gene expression changes correlated well with previously-published studies, we additionally uncovered a subset of 226 novel androgen-regulated genes. Gene expression pathway analysis of this subset revealed gene clusters associated with, and including the tyrosine kinase LYN, as well as components of the mTOR (mammalian target of rapamycin) pathway, which is commonly dysregulated in cancer. We also identified 1279 putative androgen-regulated alternative events, of which 325 (∼25%) mapped to known alternative splicing events or alternative first/last exons. We selected 30 androgen-dependent alternative events for RT-PCR validation, including mRNAs derived from genes encoding tumour suppressors and cell cycle regulators. Of seven positively-validating events (∼23%), five events involved transcripts derived from alternative promoters of known AR gene targets. In particular, we found a novel androgen-dependent mRNA isoform derived from an alternative internal promoter within the TSC2 tumour suppressor gene, which is predicted to encode a protein lacking an interaction domain required for mTOR inhibition. We confirmed that expression of this alternative TSC2 mRNA isoform was directly regulated by androgens, and chromatin immunoprecipitation indicated recruitment of AR to the alternative promoter region at early timepoints following androgen stimulation, which correlated with expression of alternative transcripts. Together, our data suggest that alternative mRNA isoform expression might mediate the cellular response to androgens, and may have roles in clinical PCa.