Gut Microbiome and Lipidome Signatures in Irritable Bowel Syndrome Patients from a Low-Income, Food-Desert Area: A Pilot Study.

Irritable bowel syndrome (IBS) is a common gastroenterological disorder with triggers such as fructose. We showed that our IBS patients suffering from socioeconomic challenges have a significantly high consumption of high-fructose corn syrup (HFCS). Here, we characterize gut microbial dysbiosis and fatty acid changes, with respect to IBS, HFCS consumption, and socioeconomic factors. Fecal samples from IBS patients and healthy controls were subjected to microbiome and lipidome analyses. We assessed phylogenetic diversity and community composition of the microbiomes, and used linear discriminant analysis effect size (LEfSe), analysis of compositions of microbiomes (ANCOM) on highly co-occurring subcommunities (modules), least absolute shrinkage and selection operator (LASSO) on phylogenetic isometric log-ratio transformed (PhILR) taxon abundances to identify differentially abundant taxa. Based on a Procrustes randomization test, the microbiome and lipidome datasets correlated significantly (p = 0.002). Alpha diversity correlated with economic factors (p < 0.001). Multiple subsets of the phylogenetic tree were associated with HFCS consumption (p < 0.001). In IBS patients, relative abundances of potentially beneficial bacteria such as Monoglobaceae, Lachnospiraceae, and Ruminococcaceae were lower (p = 0.007), and Eisenbergiella, associated with inflammatory disorders, was higher. In IBS patients, certain saturated fatty acids were higher and unsaturated fatty acids were lower (p < 0.05). Our study aims first to underscore the influence of HFCS consumption and socioeconomic factors on IBS pathophysiology, and provides new insights that inform patient care.

A Pilot Study Exploring Temporal Development of Gut Microbiome/Metabolome in Breastfed Neonates during the First Week of Life.

Purpose: Exclusive breastfeeding promotes gut microbial compositions associated with lower rates of metabolic and autoimmune diseases. Its cessation is implicated in increased microbiome-metabolome discordance, suggesting a vulnerability to dietary changes. Formula supplementation is common within our low-income, ethnic-minority community. We studied exclusively breastfed (EBF) neonates' early microbiome-metabolome coupling in efforts to build foundational knowledge needed to target this inequality. Methods: Maternal surveys and stool samples from seven EBF neonates at first transitional stool (0-24 hours), discharge (30-48 hours), and at first appointment (days 3-5) were collected. Survey included demographics, feeding method, medications, medical history and tobacco and alcohol use. Stool samples were processed for 16S rRNA gene sequencing and lipid analysis by gas chromatography-mass spectrometry. Alpha and beta diversity analyses and Procrustes randomization for associations were carried out. Results: Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the most abundant taxa. Variation in microbiome composition was greater between individuals than within (p=0.001). Palmitic, oleic, stearic, and linoleic acids were the most abundant lipids. Variation in lipid composition was greater between individuals than within (p=0.040). Multivariate composition of the metabolome, but not microbiome, correlated with time (p=0.030). Total lipids, saturated lipids, and unsaturated lipids concentrations increased over time (p=0.012, p=0.008, p=0.023). Alpha diversity did not correlate with time (p=0.403). Microbiome composition was not associated with each samples' metabolome (p=0.450). Conclusion: Neonate gut microbiomes were unique to each neonate; respective metabolome profiles demonstrated generalizable temporal developments. The overall variability suggests potential interplay between influences including maternal breastmilk composition, amount consumed and living environment.

Intensity-specific considerations for exercise for patients with inflammatory bowel disease.

The rising prevalence of inflammatory bowel disease (IBD) necessitates that patients be given increased access to cost-effective interventions to manage the disease. Exercise is a non-pharmacologic intervention that advantageously affects clinical aspects of IBD, including disease activity, immune competency, inflammation, quality of life, fatigue, and psychological factors. It is well established that exercise performed at low-to-moderate intensity across different modalities manifests many of these diseased-related benefits while also ensuring patient safety. Much less is known about higher-intensity exercise. The aim of this review is to summarize findings on the relationship between strenuous exercise and IBD-related outcomes. In healthy adults, prolonged strenuous exercise may unfavorably alter a variety of gastrointestinal (GI) parameters including permeability, blood flow, motility, and neuro-endocrine changes. These intensity- and gut-specific changes are hypothesized to worsen IBD-related clinical presentations such as diarrhea, GI bleeding, and colonic inflammation. Despite this, there also exists the evidence that higher-intensity exercise may positively influence microbiome as well as alter the inflammatory and immunomodulatory changes seen with IBD. Our findings recognize that safety for IBD patients doing prolonged strenuous exercise is no more compromised than those doing lower-intensity work. Safety with prolonged, strenuous exercise may be achieved with adjustments including adequate hydration, nutrition, drug avoidance, and careful attention to patient history and symptomatology. Future work is needed to better understand this intensity-dependent relationship so that guidelines can be created for IBD patients wishing to participate in high-intensity exercise or sport.

Probiotics for the Prevention of Antibiotic-Associated Diarrhea.

Several communities have started using probiotic-rich fermented foods as therapeutic options with presumed medicinal powers. We now know the importance of microbiome balance and how probiotics can restore imbalances in the microbiome. Probiotics have been tested for a number of clinical uses such as the prevention of antibiotic-associated diarrhea (AAD), the treatment of various diseases such as H. pylori infection, irritable bowel disease, vaginitis, the prevention of allergies, and necrotizing enterocolitis in newborns. AAD has been the most indicated therapeutic use for probiotics. AAD is a common side effect of antibiotic usage, which affects up to 30% of patients. The hypothesis behind using probiotics for AAD is that they help normalize an unbalanced flora. There are many potential mechanisms by which probiotics support intestinal health such as (i) boosting immunity, (ii) increasing gut barrier integrity, (iii) producing antimicrobial substances, (iv) modulating the gut microbiome, (v) increasing water absorption, and (vi) decreasing opportunistic pathogens. Many randomized-controlled trials including the strain-specific trials that use Lactobacillus and Saccharomyces and meta-analyses have shown the benefits of probiotics in addressing AAD. Although adverse events have been reported for probiotics, these are broadly considered to be a safe and inexpensive preventative treatment option for AAD and other gastrointestinal disorders.

Clinical Factors Implicated in Antibiotic Resistance in Helicobacter pylori Patients.

Helicobacter pylori is a common gastric pathogen associated with multiple clinical syndromes, including cancer. Eradication rates of H. pylori remain suboptimal despite the progress made in the past few decades in improving treatment strategies. The low eradication rates are mainly driven by antibiotic resistance of H. pylori. Non-invasive molecular testing to identify patients with antibiotic-resistant H. pylori represents a promising therapeutic avenue, however this technology currently remains limited by availability, costs, and lack of robust validation. Moreover, there is insufficient evidence to demonstrate that resistance-testing-based treatment approaches are superior to appropriately designed empiric strategies. Consensus guidelines recommend use of proven locally effective regimens; however, eradication data are inconsistently generated in several regions of the world. In this review, we describe several clinical factors associated with increased rates of antibiotic resistant H. pylori, including history of previous antibiotic exposure, increasing age, female gender, ethnicity/race, extent of alcohol use, and non-ulcer dyspepsia. Assessment of these factors may aid the clinician in choosing the most appropriate empiric treatment strategy for each patient. Future study should aim to identify locally effective therapies and further explore the clinical factors associated with antibiotic resistance.

Effects of Milkfat on the Gut Microbiome of Patients After Bariatric Surgery, a Pilot Study.

BACKGROUND: The efficacy of bariatric surgery may be in part attributed to altered metabolism via new gut microbiome. Milkfat may promote the growth of microbes that are beneficial in long-term weight loss. Understanding the specific gut microbiome changes after surgery and their relationship to milkfat consumption may yield important strategies for managing obesity after bariatric procedures. METHODS: In this pilot study, stool samples were collected from nine patients before and at the time of surgery, and at 1, 3, and 6 months post-surgery. At each time-point, dairy consumption was determined from dietary surveys. 16 s rRNA gene sequencing was performed followed by alpha diversity analysis. Comparisons of relative abundances of microbial taxa and analyses of fatty acids changes were performed. RESULTS: Bariatric surgery led to enrichment of (i) Roseburia, associated with weight loss and (ii) Christensenellaceae, inversely related to body mass index. High milk-fat consumption correlated with enrichment of Blautia, inversely associated with visceral fat accumulation. Faecalibacterium, possibly associated with obesity, increased in patients with low milk-fat consumption. Butter was associated with decreased alpha diversity in all subjects (p-value = 0.038) and the frequency of its use was associated with decreased alpha diversity in patients (correlation = - 0.68, p-value = 0.042). Low-milk-fat consumers showed higher concentration of saturated fatty acids. CONCLUSIONS: Our results suggest that incorporating dairy products in post-bariatric-surgery dietary plans may help cultivate a gut microbiome that is effective in regulating fat storage as well as digesting beneficial metabolites. These observations will be helpful for the management of obesity in general population as well.

Characterization of gut microbiome and metabolome in Helicobacter pylori patients in an underprivileged community in the United States.

BACKGROUND: Helicobacter pylori (H. pylori), a bacterium that infects approximately half of the world's population, is associated with various gastrointestinal diseases, including peptic ulcers, non-ulcer dyspepsia, gastric adenocarcinoma, and gastric lymphoma. As the burden of antibiotic resistance increases, the need for new adjunct therapies designed to facilitate H. pylori eradication and reduce negative distal outcomes associated with infection has become more pressing. Characterization of the interactions between H. pylori, the fecal microbiome, and fecal fatty acid metabolism, as well as the mechanisms underlying these interactions, may offer new therapeutic approaches. AIM: To characterize the gut microbiome and metabolome in H. pylori patients in a socioeconomically challenged and underprivileged inner-city community. METHODS: Stool samples from 19 H. pylori patients and 16 control subjects were analyzed. 16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2. Alpha and beta diversity analyses were performed in QIIME 2. Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry, which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters. Multi-dimensional scaling (MDS) was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates. RESULTS: Fecal microbiome analysis showed that alpha diversity was lowest in H. pylori patients over 40 years of age compared to control subjects of similar age group. Beta diversity analysis of the samples revealed significant differences in microbial community structure between H. pylori patients and control subjects across all ages. Thirty-eight and six taxa had lower and higher relative abundance in H. pylori patients, respectively. Taxa that were enriched in H. pylori patients included Atopobium, Gemellaceae, Micrococcaceae, Gemellales and Rothia (R. mucilaginosa). Notably, relative abundance of the phylum Verrucomicrobia was decreased in H. pylori patients compared to control subjects. Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets. Stool samples from H. pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids (PUFAs) 22:4n6, 22:5n3, 20:3n6 and 22:2n6, while decreases were noted in other fatty acids including the PUFA 18:3n6. The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis. CONCLUSION: This exploratory study demonstrates H. pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism. Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.

Designing strategies for eradication of Helicobacter pylori based on prevalence patterns of infection and antibiotic resistance in a low-income, medically underserved community in the United States.

BACKGROUND: Regional variation in Helicobacter pylori resistance patterns is a significant contributing factor for the ineffectiveness of traditional treatments. To improve treatment outcomes, we sought to create an individualized, susceptibility-driven therapeutic approach among our patient population, which is one of the poorest in the nation. It is medically underserved, minority-predominant and has high incidence of H pylori infection. METHODS: We compiled various factors involved in the antibiotic resistance of H pylori from literature. We then created a predictive model to customize therapies based on analyzed data from 2,014 H pylori patients with respect to several of these factors. The predictions of the model were further tested with analysis of patient stool samples. RESULTS: A clear pattern of H pylori prevalence and antibiotic resistance was observed in our patients. We observed that majority of H pylori patients were women (62%) and over the age of 40 years (80%). 30% and 36% of the H pylori patients were African American and Hispanic, respectively. A median household income of less than $54,000, past H pylori infection, previous use of certain antibiotics for any infection decreased the chance of eradication. Results of the stool testing were consistent with model predictions (90% accuracy). CONCLUSION: This model demonstrates the predictive accuracy of H pylori infection and antibiotic resistance based on patient attributes and previous treatment history. It will be useful to formulate customized treatments with predicted outcomes to minimize failures. Our community attributes may contribute toward broad applicability of model for other similar communities.

Patient Awareness of Reported Adverse Effects Associated with Proton Pump Inhibitors in a Medically Underserved Community.

Reports of adverse effects associated with proton pump inhibitors (PPIs) are concerning because of high usage and over-the-counter availability. We sought to determine the awareness of PPI adverse effects among our patient population, which is medically underserved, low-income, and racially diverse. A 21-item survey was administered to gastroenterology-clinic outpatients. It collected information about age, gender, education, race, specialty of the prescriber, specific PPI, indication, knowledge of dose, adherence, duration of use and awareness of any risks. Medical records were reviewed to verify survey responses pertaining to indication, dosing, and adherence. A vast majority (96%) of 101 participants were not aware of PPI adverse effects. In total, 63% of the patients completed a high school education or less, which was associated with a higher risk of long-term PPI use than completion of at least an undergraduate degree (p = 0.05). In contrast to other studies, the shockingly low patient awareness about PPI adverse effects in our patient population is particularly concerning, especially as it is tied to their demographic attributes. This may lead to long-term and high-dose PPI use. Our study highlights the need for effective provider-driven education regarding medication risks, especially in the communities with significant health disparities.

Comparative outcomes in different aortic valve stenosis surgeries and implications of TAVR surgery for cirrhotic patients: A retrospective cohort study.

BACKGROUND: Our hospital system is committed to service to medically underserved, low-income, and minority populations. It is located in a city wherein 37% of people live in poverty. Overall cost effectiveness is part of our patient care quality improvement. Cirrhotic patients are at higher risk for cardiac surgery as cardiopulmonary bypass triggers the release of substances that mimic the physiologic changes seen in cirrhosis. We compared outcomes of surgeries performed for the treatment of aortic valve stenosis, surgical aortic valve replacement (SAVR), mini-surgical valve replacement (mini-SVR), and transcatheter aortic valve replacement (TAVR) with attention to cirrhotic patients. METHODS: This retrospective cohort study looked at the medical records of 457 patients. Demographic data, substance abuse, pre-existing diagnoses, length of stay, outcomes, and lab values were collected for each patient pre- and post-surgery. Fisher's exact test or chi square was used to compare categorical characteristics and outcomes among groups. ANOVA for repeated measures was utilized to compare group differences of continuous measurements over time. RESULTS: Despite having the highest average age of patients and higher incidence of pre-existing comorbidities, post-operative complications such as arrhythmia, hyponatremia, and coagulopathy developed to a lesser extent in TAVR patients. The length of post-surgery hospital stay was also the least in TAVR patients. TAVR offered better post-operative outcomes in cirrhotic patients as well. CONCLUSIONS: TAVR showed better post-surgical outcomes and provide an option for cardiac surgery for cirrhotic patients. This data will be useful for enabling a patient-centered decision-making process in our population.

Shaping Perceptions of Basic Science Education by Utilizing Real Patient Encounters.

BACKGROUND: Integrating basic science into clinical teaching has been a struggle for medical schools. However, early exposure to clinical experience has been associated with an increased understanding of the importance of basic science, positive attitudes, and developing clinical skills faster. Furthermore, early clinical exposure can help students reconnect with what drove them into medicine in the first place, especially when they are starting to feel burned out by the volume of lecture material. As a result, increasing patient experience during the first year has become a goal of many medical schools. METHODS: At Rutgers Robert Wood Johnson Medical School, interprofessional case discussions (ICDs) begin with a lecture that explicitly integrates basic science with a disease, followed by a discussion with a patient, their family, the healthcare team, and first-year students. Our objective is to explore whether ICDs enhanced the learning experience of basic science. CONTEXT: ICD satisfaction was assessed using evaluations from two different courses (2013-2016). Responses were analyzed quantitatively using descriptive statistics and qualitatively using a grounded-theory-content analysis. Study 2: A follow-up measure with current third- and fourth-year students on long-term retention of basic science was analyzed using a Wilcoxon signed rank test. Relative rankings of three different case-based teaching modalities were assessed using chi-square. RESULTS: Students reported significantly higher satisfaction with ICDs (93%) for reinforcing concepts and integrating materials compared to Flipped Classrooms (66%) and Jigsaws (65%), x 2 = 120.9, p < .001. Student comments fit into five categories: enjoyment, learning/retention, the clinical usefulness of basic science, affirming passion to be in medicine, and others. The follow-up measure indicated significantly greater retention of the biochemical basis of diseases covered during ICDs. CONCLUSIONS: While other teaching modalities integrate basic science into a clinical context, ICDs go further by displaying interprofessional care and the manifestation of the disease on the patient and the lives of their family. As a result, ICDs lead to a positive learning environment in which students feel comfortable, have a sense of rapport with the patients and health care providers, and feel motivated to learn basic science.

Use of Real Patients and Patient-Simulation-Based Methodologies for Teaching Gastroenterology to Pre-Clinical Medical Students.

In recent years, there has been an increasing focus on the need to integrate formal knowledge with clinical experience in the pre-clinical years since the initial years of medical education play an important role in shaping the attitudes of medical students towards medicine and support the development of clinical reasoning. In this study, we describe approaches that involve real patients and patient-simulation-based methodologies to teach gastroenterology to second year medical students. Our goals were to (i) demonstrate bio-psychosocial aspects of clinical practice, (ii) demonstrate commonality of gastrointestinal ailments, and (iii) help understand complex gastroenterology concepts. We used two main approaches including brief, pre-prepared questions and answers discussing with the patients in various sessions throughout the course and a two-hour session that included patient participation, patient simulation modalities with high fidelity mannequins, a lightening round of interactive cases, and a Patient Oriented Problem Solving (POPS) session. The approaches improved the effectiveness of the delivery of the content-heavy, fast-paced GI course and provided opportunities for the students to think about gastroenterology from both basic and clinical points of view. The approaches involved peer teaching, which supports knowledge acquisition and comprehension. Very positive feedback and overall engagement of students suggested that these approaches were well-received.

Creation and implementation of a flipped jigsaw activity to stimulate interest in biochemistry among medical students.

Learner-centered pedagogical methods that are based on clinical application of basic science concepts through active learning and problem solving are shown to be effective for improving knowledge retention. As the clinical relevance of biochemistry is not always apparent to health-profession students, effective teaching of medical biochemistry should highlight the implications of biochemical concepts in pathology, minimize memorization, and make the concepts memorable for long-term retention. Here, we report the creation and successful implementation of a flipped jigsaw activity that was developed to stimulate interest in learning biochemistry among medical students. The activity combined the elements of a flipped classroom for learning concepts followed by a jigsaw activity to retrieve these concepts by solving clinical cases, answering case-based questions, and creating concept maps. The students' reception of the activity was very positive. They commented that the activity provided them an opportunity to review and synthesize information, helped to gage their learning by applying this information and work with peers. Students' improved performance especially for answering the comprehension-based questions correctly in the postquiz as well as the depth of information included in the postquiz concept maps suggested that the activity helped them to understand how different clinical scenarios develop owing to deviations in basic biochemical pathways. Although this activity was created for medical students, the format of this activity can also be useful for other health-professional students as well as undergraduate and graduate students. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:343-353, 2018.

Characterization of YjjJ toxin of Escherichia coli.

Reminiscent of eukaryotic apoptotic programmed cell death, bacteria also contain a large number of suicide genes, which are in general co-expressed with their cognate antitoxin genes. These systems called the toxin-antitoxin (TA) systems are associated with cellular dormancy, and play major roles in biofilm formation and persistent multidrug resistance of many human pathogens. In recent years, the study on TA system toxins has become a hot topic due to the health implications of these toxins by virtue of their role in bacterial pathogenicity. Here we report functional characterization of a hitherto uncharacterized Escherichia coli TA toxin, YjjJ. YjjJ exhibits several uncommon properties: (i) unlike the genes encoding most type II TA system toxins, the gene encoding YjjJ is present as a single gene and not in an operon, (ii) despite being a homolog of the well-characterized toxin HipA, YjjJ seems to have different cellular target(s), and (iii) HipB, the cognate antitoxin of HipA, also acts as an antitoxin for YjjJ. This forms a basis for an interesting next step in the study of TA systems with respect to cross-regulation between various TA systems and the evolutionary as well as clinical significance of these observations.

Irritable Bowel Syndrome: Clinical Manifestations, Dietary Influences, and Management.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by symptoms of chronic abdominal pain and altered bowel habits in the absence of an overtly identifiable cause. It is the most commonly diagnosed functional gastrointestinal disorder, accounting for about one third of gastroenterology visits. It generally presents as a complex of symptoms, including psychological dysfunction. Hypersensitivity to certain foods, especially foods that contain high amounts of fructose, plays a role in the pathophysiology of IBS. Elevated consumption of high-fructose corn syrup (HFCS) has been discussed in this aspect. The treatment options for IBS are challenging and varied. In addition to dietary restrictions for HFCS-induced IBS, such as low-FODMAP (Fermentable Oligosaccharides, Disaccharide, Monosaccharides, and Polyols) diets, existing drug therapies are administered based on the predominant symptoms and IBS-subtype. Patients with IBS are likely to suffer from issues, such as anxiety, depression, and post-traumatic-stress disorder. Biopsychosocial factors particularly socioeconomic status, sex, and race should, thus, be considered for diagnostic evaluation of patients with IBS.

An Interactive Session on Nutritional Pathologies for Health Professional Students.

Various studies have emphasized the need to improve the nutrition training of health professionals, which will help them to provide optimal patient care. Nutrition-based interactive sessions may serve as an efficient approach to instigate an interest in nutrition among the students. Here we report the reception and effectiveness of a nutrition-pathology based interactive activity that we designed and implemented in the gastroenterology course given to the second year students at our medical school. The activity involved team work, individual accountability and peer-teaching. Nutrition pathology case stems (Kwashiorkor, vitamin B-12 deficiency, zinc deficiency and zinc-induced copper deficiency) were posted on the course website for the students to read before the session. At the start of the session, all the groups (each made up of four members) took a pre-quiz. Each student was then given an information sheet describing one case. Each group discussed the four cases with students acting as the "teacher" for the case assigned to them. A post-quiz was administered to the groups to assess acquisition of knowledge as well as in-depth thinking about the nutrition aspects discussed. The efficacy of the session measured by pre (39% questions correctly answered in total) and post-quizzes (96% questions correctly answered in total) and the overwhelmingly positive student feedback indicated that the session was highly effective. Ninety-five percent of students thought that the session demonstrated the clinical relevance of nutrition, while 98% students found the peer teaching to be engaging.

Regression of solid tumors by induction of MazF, a bacterial mRNA endoribonuclease.

MazF from Escherichia coli is an endoribonuclease that specifically cleaves mRNAs at ACA sequences. Its induction in mammalian cells has been shown to cause programmed cell death. Here we explored if a bacterial MazF-MazE toxin-antitoxin system can be used for gene therapy. For this, we first constructed a tetracycline-inducible MazF expression system in human embryonic kidney cells (T-Rex 293-mazF). Solid tumors were formed by injecting T-Rex 293-mazF cells into nude mice. All 8 mice injected with the cells developed solid tumors, which regressed upon induction of MazF. In 4 mice, tumors completely regressed, while in the remaining 4 mice, tumors reappeared after apparent significant regression, which was found to be due to the lack of presence of functional MazF. Notably, the MazF-mediated regression of the tumors was counteracted by the expression of its cognate antitoxin MazE. These results indicate that a bacterial MazF-MazE toxin-antitoxin system may have potential to be used as a therapeutic tool.

An online guided e-journal exercise in pre-clerkship years: oxidative phosphorylation in brown adipose tissue.

The rationale for this mandatory, guided online e-journal exercise is to foster the ability of students to independently read medical and scientific literature in a critical manner and to integrate journal reading with their basic science knowledge. After a lecture on oxidative phosphorylation, students were assigned to read an article on brown adipose tissue published in New England Journal of Medicine and were guided to analyze the article by answering online questions. After two iterations, student surveys about the project, its key pedagogical features, and ways to improve it suggest that the students perceived these exercises as active learning, which is clinically relevant and built on their course material. Furthermore, students agreed that the e-journal project was useful for learning how to read an article, for reviewing the material learned in class, and for promoting evidence-based medicine. This online e-journal exercise models some aspects students will experience as future physicians, where it is essential to keep up with literature and extract relevant information on a tight physician's schedule. This study demonstrated the usefulness of guided e-journal exercises as a simple effective active teaching tool for preclinical medical students, which can also be used for prehealth undergraduate programs.

Characterization of LdrA (long direct repeat A) protein of Escherichia coli.

Reminiscent of apoptotic genes in higher systems, almost all bacteria contain 'suicide' genes, which encode toxins. Toxins inhibit cell growth and may cause cell death. These are coexpressed with their cognate antitoxins from a toxin-antitoxin (TA) operon in normally growing cells. The cellular targets of toxins are diverse. The study of the TA system is important as in addition to their involvement in the normal bacterial physiology, TA systems may also play a role in bacterial pathogenicity. The long direct repeat (Ldr) family of proteins belongs to one such TA system. Here we report characterization of LdrA, the prototypical protein of the Ldr family, and show that it is highly toxic for cell growth. The data suggests that LdrA may exert toxicity by inhibiting ATP synthesis, possibly due to its localization in the cell membrane. This inhibition of energy production leads to the inhibition of biosynthetic reactions in the cell such as DNA replication, transcription and translation, and eventually cell growth.

Over the counter drugs (and dietary supplement) exercise: a team-based introduction to biochemistry for health professional students.

For successful delivery of basic science topics for health-professional students, it is critical to reduce apprehension and illustrate relevance to clinical settings and everyday life. At the beginning of the Biochemistry course for Physician Assistants, a team-based assignment was designed to develop an understanding of the mechanism of action, effectiveness, and toxicity of five common over the counter (OTC) drugs and dietary supplements, and place these familiar medicines in a political and historical context. The objectives of this exercise were to stimulate interest in biochemistry; to provide basic information on enzymes and enzyme inhibitors related to these drugs to be expanded upon later in the course; and to encourage active and interactive learning. Teams of five students were formed, and each student was given an information sheet on aspirin, alpha-galactosidase, orlistat, dextromethorphan, or simvastatin, a low dose statin, which was previously available without prescription at pharmacies in the UK. After each member of the team acquired information on one OTC drug/dietary supplement by reading an assigned information sheet, the team was asked to go through a series of questions, and then submit answers to a quiz as a group. A high rate of success on the quiz, an overwhelmingly positive response on formal course evaluations, and enthusiastic exchanges during class suggested this team-based session accomplished its goals.