Neuro-nutraceuticals: Natural products nourish the brain but be aware of contrary effects.

In this Special Issue on "Nutraceuticals: Molecular and Functional Insights into how Natural Products Nourish the Brain", the editors bring together contributions from experts in nutraceutical research to provide a contemporary overview of how select chemically identified molecules from natural products can beneficially affect brain function at the molecular level. Other contributions address the holistic benefit of herbal medicines and their multi-targeted actions, which improve brain function in diverse cellular and animal models of brain injury. Not only are new targets for nutraceuticals reported, but their benefits on neurobehavioural problems are elucidated in conditions as diverse as obesity and menopause. Inflammation in neuropathologies, including Alzheimer's disease (AD), remains a huge focus and diverse nutraceuticals demonstrate therapeutic applicability via glial-mediated actions. While contrary actions should be borne in mind in the search for novel neurotherapeutics, the great promise offered by herbal medicines and their newly identified active principles offers unique options for the management of diverse neurological and psychiatric conditions.

Targeting extracellular nutrient dependencies of cancer cells.

BACKGROUND: Cancer cells rewire their metabolism to meet the energetic and biosynthetic demands of their high proliferation rates and environment. Metabolic reprogramming of cancer cells may result in strong dependencies on nutrients that could be exploited for therapy. While these dependencies may be in part due to the nutrient environment of tumors, mutations or expression changes in metabolic genes also reprogram metabolic pathways and create addictions to extracellular nutrients. SCOPE OF REVIEW: This review summarizes the major nutrient dependencies of cancer cells focusing on their discovery and potential mechanisms by which metabolites become limiting for tumor growth. We further detail available therapeutic interventions based on these metabolic features and highlight opportunities for restricting nutrient availability as an anti-cancer strategy. MAJOR CONCLUSIONS: Strategies to limit nutrients required for tumor growth using dietary interventions or nutrient degrading enzymes have previously been suggested for cancer therapy. The best clinical example of exploiting cancer nutrient dependencies is the treatment of leukemia with l-asparaginase, a first-line chemotherapeutic that depletes serum asparagine. Despite the success of nutrient starvation in blood cancers, it remains unclear whether this approach could be extended to other solid tumors. Systematic studies to identify nutrient dependencies unique to individual tumor types have the potential to discover targets for therapy.

Immunomodulatory effects of dietary IMUNO-2865 in mice, pre-and post-vaccine challenge with parainfluenza virus 5.

Herbal remedies and nutraceuticals continue to be used as treatments for a variety of maladies ranging from joint disease to obesity. IMUNO-2865 is a natural nutraceutical supplement that has been advertised to modulate inflammation, boost cytokine activity promoting a robust immunity, but has yet to be evaluated as an adjuvant. In the present study, 4-week-old C57BL/6 female mice (n = 45) were fed 0, 5 or 50 mg/5 g tablet IMUNO-2865 (I-2865) in a tablet formulated feed. One group of mice (n = 15, 5 mice/diet) were placed on a feed diet for 14 days, while the other group of 30 mice (10 mice/diet) were placed on the diet for 28 days. Five mice from each diet group in the 28-day feeding trial were vaccinated on day 7 with a mouse recombinant parainfluenza virus to mimic viral challenge. On days 0, 14 and 28 blood samples were collected. Mice were humanely euthanized on days 14 and 28. Spleens were collected to analyze organ weight/body weight ratios, cell recovery, T cell and B cell phenotype, cell proliferation, antibody titers and cytokine production. Administration of dietary I-2865 for 14 days had no effect on murine immunity. In the 28-day dietary vaccine trial, I-2865 supplementation did not enhance vaccine response, based on vaccine antigen-specific IgG titers, nor did it alter T cell and B cell phenotype, function or cytokine response, but it did decrease splenocyte numbers in the vaccinated mice.

Intranasal immunization with aluminum salt-adjuvanted dry powder vaccine.

Intranasal vaccination using dry powder vaccine formulation represents an attractive, non-invasive vaccination modality with better storage stability and added protection at the mucosal surfaces. Herein we report that it is feasible to induce specific mucosal and systemic antibody responses by intranasal immunization with a dry powder vaccine adjuvanted with an insoluble aluminum salt. The dry powder vaccine was prepared by thin-film freeze-drying of a model antigen, ovalbumin, adsorbed on aluminum (oxy)hydroxide as an adjuvant. Special emphasis was placed on the characterization of the dry powder vaccine formulation that can be realistically used in humans by a nasal dry powder delivery device. The vaccine powder was found to have "passable" to "good" flow properties, and the vaccine was uniformly distributed in the dry powder. An in vitro nasal deposition study using nasal casts of adult humans showed that around 90% of the powder was deposited in the nasal cavity. Intranasal immunization of rats with the dry powder vaccine elicited a specific serum antibody response as well as specific IgA responses in the nose and lung secretions of the rats. This study demonstrates the generation of systemic and mucosal immune responses by intranasal immunization using a dry powder vaccine adjuvanted with an aluminum salt.

Modulation of innate immunity in Nile tilapia (Oreochromis niloticus) by dietary supplementation of Bacillus subtilis endospores.

Dietary supplementation of probiotics is growing as a scientifically valid alternative to antibiotics for enhancement of overall animal health and productivity in aquaculture. Strains of Bacillus subtilis are regarded as attractive probiotic candidates to the fish farming industry; however, there is a limited number of studies focused on the use of specific strains probiotics in tilapia, and therefore complicating replication. The objective of this study was to examine the effect of the strains NZ86 (NRRL B-50136) and O14VRQ (NRRL B-67221) of B. subtilis on various parameters of the innate immunity in Nile tilapia (Oreochromis niloticus) in a 51-day feeding trial. Supplementation of tilapia with either strain resulted in significant increases (p < 0.05) in plasma lysozyme concentration of varying degrees throughout the trial. Meanwhile, alternative complement activity was significantly elevated (p < 0.05) only after feeding of the NZ86 strain after 14 and 51 days. Conversely, supplementation with O14VRQ resulted in a significant increase (p < 0.05) in the percent of neutrophils in the peripheral blood of tilapia by day 28. At the end of the trial, there was a trend towards increased phagocytic and respiratory burst activities observed in immune organ derived leukocytes. Feeding with either probiotic appeared to have an up-regulation on the gene expression of both pro-inflammatory cytokines in the intestine, yet only O14VRQ was significantly different than the control. Moreover, the occurrence of these results could be associated with supplementation of the probiotic strains, given that Bacillus bacteria were observed to populate the intestines of the dietary treatment groups. These results suggest the potential roles of these B. subtilis probiotic candidates to stimulate immune responses both locally and systemically in tilapia.

The immunomodulatory effects of a commercial antiviral homeopathic compound in C57BL/6 mice, pre and post vaccine challenge.

Homeopathic remedies have been selectively employed in human medicine since Hahneman introduced the concept in 1828. While the use of homeopathy is regionally popular in both human and veterinary medicine, there is still a significant lack of scientific evidence supporting its efficacy. This is likely due to an absence of studies evaluating the mechanism of action of these compounds. Engystol® an FDA-approved antiviral agent, is a popular homeopathic commercial product. In select in vivo and in vitro observational studies, the drug showed a measureable innate immune therapeutic efficacy. The focus of the present study was to evaluate the innate and adaptive immunomodulatory effects of oral Engystol(®) (1 or 10 tablets/L water consumed), prior to and post antigenic challenge in a mouse model with a well-characterized and clinically measureable immune system. We first evaluated the murine immune response when oral Engystol(®) was given alone for 28days. Mice were then challenged with an antigen-specific H5N1 HA vaccine while on Engystol(®) for an additional 33days. Serum and supernatants from cultured splenic lymphocytes were collected and screened with a 32-cytokine panel. Serum vaccine epitope-specific IgG titers plus T cell and B cell phenotypes from splenic tissue were also evaluated. Preliminary results showed that Engystol(®) alone did not alter immunity; however, upon vaccine challenge, Engystol(®) decreased CD4(+)/CD8(+) ratios, altered select cytokines/chemokines, and anti-H5N1 HA IgG titers were increased in the 10 tablet/L group. Collectively, these data suggest that Engystol(®) can modulate immunity upon antigenic challenge.

Neuro-nutraceuticals: Further insights into their promise for brain health.

In this Special Issue on "Nutraceuticals: Molecular and Functional Insights into how Natural Products Nourish the Brain", the editors bring together contributions from experts in nutraceutical research to provide a contemporary overview of how select chemically identified molecules from natural products can beneficially affect brain function at the molecular level. Other contributions address key emergent issues such as bioavailability, neuronal health, inflammation and the holistic benefit of multi-targeted actions that impact upon how nutraceuticals ultimately leverage the brain to function better. In terms of the benefit of nutraceuticals it is clear that some naturally occurring molecules can be advantageous to both the young and aged brain, and that they have actions that ultimately can be directed to aid either in the improvement of cognition or in the management of debilitating neurodegenerative and neuropsychiatric conditions.

Neuro-nutraceuticals: The path to brain health via nourishment is not so distant.

In this Special Issue on "Nutraceuticals: Molecular and Functional Insights into how Natural Products Nourish the Brain", the editors bring together contributions from experts in nutraceutical research to provide a contemporary overview of how select chemically identified molecules can beneficially affect brain function at the molecular level. Other contributions address key emergent issues such as bioavailability, formulation, blood brain permeability, neuronal health and inflammation that impact upon how nutraceuticals ultimately leverage the brain to function better. Whilst nutraceutical is used as marketing term, it has no regulatory definition, and there is a continuing need for licensing authorities to ensure that adequate guidelines exist pertinent to the safety to guide consumers internationally. In terms of the benefit of nutraceuticals is it clear that some naturally occurring molecules can be advantageous to both the young and aged brain, and that they have actions that ultimately can be directed to aid either in the improvement of cognition or in the management of debilitating neurodegenerative and neuropsychiatric conditions.

A method of lyophilizing vaccines containing aluminum salts into a dry powder without causing particle aggregation or decreasing the immunogenicity following reconstitution.

Many currently licensed and commercially available human vaccines contain aluminum salts as vaccine adjuvants. A major limitation with these vaccines is that they must not be exposed to freezing temperatures during transport or storage such that the liquid vaccine freezes, because freezing causes irreversible coagulation that damages the vaccines (e.g., loss of efficacy). Therefore, vaccines that contain aluminum salts as adjuvants are formulated as liquid suspensions and are required to be kept in cold chain (2-8°C) during transport and storage. Formulating vaccines adjuvanted with aluminum salts into dry powder that can be readily reconstituted before injection may address this limitation. Spray freeze-drying of vaccines with low concentrations of aluminum salts and high concentrations of trehalose alone, or a mixture of sugars and amino acids, as excipients can convert vaccines containing aluminum salts into dry powder, but fails to preserve the particle size and/or immunogenicity of the vaccines. In the present study, using ovalbumin as a model antigen adsorbed onto aluminum hydroxide or aluminum phosphate, a commercially available tetanus toxoid vaccine adjuvanted with potassium alum, a human hepatitis B vaccine adjuvanted with aluminum hydroxide, and a human papillomavirus vaccine adjuvanted with aluminum hydroxyphosphate sulfate, it was shown that vaccines containing a relatively high concentration of aluminum salts (i.e., up to ~1%, w/v, of aluminum hydroxide) can be converted into a dry powder by thin-film freezing followed by removal of the frozen solvent by lyophilization while using low levels of trehalose (i.e., as low as 2% w/v) as an excipient. Importantly, the thin-film freeze-drying process did not cause particle aggregation, nor decreased the immunogenicity of the vaccines. Moreover, repeated freezing-and-thawing of the dry vaccine powder did not cause aggregation. Thin-film freeze-drying is a viable platform technology to produce dry powders of vaccines that contain aluminum salts.

An audit to determine if vitamin b12 supplementation is necessary after sleeve gastrectomy.

ABSTRACT: Sleeve gastrectomy has increased in popularity over the last five years and it is likely to supersede gastric banding. Nevertheless, it is unclear whether vitamin B12 supplementation is required after surgery. The aim of this short report is to identify any vitamin B12 deficiency and highlight the necessity of post laparoscopic sleeve gastrectomy vitamin B12 monitoring. PATIENTS AND METHODS: A review of 66 patients underwent LSG in our institution. 25 patients were excluded as they had no postoperative vitamin B12 screening. 41 patients were included as screened for vitamin B12 and other micronutrients including selenium, serum folate, ferritin, iron, zinc, copper, magnesium and vitamin D. RESULT: There were 5 male (12%) and 36 females (88%), 8/41 patients (20%) had Vitamin B12 deficiency, none of them developed macrocytic anaemia. 17/21 (81%) patient were vitamin D deficient and 9/21 (43%) exhibited low selenium. CONCLUSION: In this small group, a 20% prevalence of vitamin B12 was identified. As a consequence vitamin B12 monitoring and supplementation will be a standard of care in the early postoperative period after LSG at this institution.

Hyperkalemia and ventricular tachycardia after outpatient ureteral valve reimplantation: a case report.

OBJECTIVE: This study aimed to report on a toddler who presented with progressively worsening abdominal pain and obstructive uropathy 1 week after ureteral valve reimplantation. Acute renal failure resulted in critical hyperkalemia. METHODS: Chart review of presentation, physical examination, laboratory tests, and treatment. RESULTS: Initial potassium level was 10 mEq/L; ventricular tachycardia was observed and treated. CONCLUSIONS: More commonly, hyperkalemia results from overuse/overdose of supplementation or in patients with known renal failure. Although less common, obstructive uropathy should be considered in any patient with recent instrumentation of the urinary tract and coincident complications can be significant.

Systems analysis of genetic variation in MPTP neurotoxicity in mice.

We analyzed genetic variation in severity of neuronal damage using the known dopaminergic neurotoxicant, MPTP, as a prototypical chemical denervation agent. Male mice from ten members of the BXD family of recombinant inbred strains received 12.5 mg/kg MPTP s.c. (vs. saline) and 48 h later brains were taken for multiple related biochemical analyses. Striatal dopamine (DA) and its metabolites, DOPAC and HVA, and serotonin and its metabolite, 5-HIAAA, were analyzed by HPLC. DA turnover was assessed using DOPAC/DA and HVA/DA ratios. Striatal tyrosine hydroxylase (TH), glial fibrilary acidic protein (GFAP), and iron content in ventral midbrain were quantified. All dopamine measures, as well as TH and GFAP, demonstrated wide, genotype-dependent differences in response to MPTP. Serotonin was largely unaffected. Principal components analysis (PC) on difference values, saline minus MPTP, for DA, DOPAC, HVA, and TH, yielded a dominant principal component. The PC trait residuals for each genotype were compared against complementary expression data for striatum of the same strains. Three transcripts representing Mtap2, Lancl 1, and Kansl1l were highly correlated with the PC, as was the difference score, MPTP minus saline for GFAP. This systems approach to the study of environmental neurotoxicants holds promise to define individual genetic differences that contribute to variability in susceptibility to risk factors for diseases such as Parkinson's disease.

Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease.

There is increasing evidence that the consumption of flavonoid-rich foods can beneficially influence normal cognitive function. In addition, a growing number of flavonoids have been shown to inhibit the development of Alzheimer disease (AD)-like pathology and to reverse deficits in cognition in rodent models, suggestive of potential therapeutic utility in dementia. The actions of flavonoid-rich foods (e.g., green tea, blueberry, and cocoa) seem to be mediated by the direct interactions of absorbed flavonoids and their metabolites with a number of cellular and molecular targets. For example, their specific interactions within the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, have been shown to increase the expression of neuroprotective and neuromodulatory proteins and increase the number of, and strength of, connections between neurons. Concurrently, their effects on the vascular system may also lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus. Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid ß aggregation and effects on amyloid precursor protein processing through the inhibition of ß-secretase (BACE-1) and/or activation of α-secretase (ADAM10). Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance.

Chronic non-cancer pain: a siren for primary care--a report from the PRImary Care MultiEthnic Network (PRIME Net).

INTRODUCTION: Patients with chronic non-cancer pain (CNCP) are common and have a high degree of morbidity. Previous studies document clinician frustration and variability in CNCP management. We conducted this study to gather in-depth clinicians' views about factors that affect management of CNCP. METHODS: We conducted a survey in the Primary Care MultiEthnic Network, a consortium of PBRNs of primary care clinicians practicing in low-income, medically underserved communities, and in a network of private primary care offices. RESULTS: Of 792 clinicians surveyed, 497 (63%) participated. Responses and accompanying narrative comments clustered around 5 themes: (1) barriers to and uncertainties in optimal management; (2) the complex biopsychosocial nature of CNCP; (3) seriousness of prescription opioid abuse; (4) effort and burden required to properly manage CNCP; and (5) clinician commitment to provide care for CNCP patients and benefits of expanded care model for CNCP. One-third reported a severe outcome (death or life-threatening event) in a CNCP patient for whom they had prescribed opioids. Roughly one-third do not initiate prescribing of opioids. CONCLUSIONS: Guidelines and increased continuing medical education alone are unlikely to be the solutions to the challenges of CNCP management. Increased evidence for recommendations and resources for more comprehensive care management are needed.

Preclinical evaluation of tacrolimus colloidal dispersion for inhalation.

Substantial improvements in transplant therapy have been made in the past four decades resulting in the acceptance of organ transplantation as a viable treatment for late-stage disease and organ failure. More recently, lung transplantation has gained acceptance; however, high incidence of chronic rejection and opportunistic infections has limited success rates in comparison with other transplant procedures. To achieve more targeted therapy, pulmonary administration of nebulized tacrolimus (TAC) colloidal dispersion once daily for 28 consecutive days in Sprague Dawley (SD) rats has been investigated for safety and systemic elimination. A liquid dispersion of colloidal TAC and lactose (1:1 ratio by weight) was aerosolized using a vibrating mesh nebulizer and administered via a nose-only dosing chamber. Blood chemistry and histological comparisons to saline-dosed animals showed no clinically significant differences in liver and kidney function or lung tissue damage. Maximum blood and lung concentrations sampled 1h after the final dose showed TAC concentrations of 10.1 ± 1.4 ng/mL and 1758.7 ± 80.0 ng/g, respectively. Twenty-four hours after the final dose, systemic TAC concentrations measured 1.0 ± 0.5 ng/mL, which is well below clinically accepted trough concentrations (5-15 ng/mL) for maintenance therapy, and therefore, would not be expected to induce toxic side effects. The propensity for pulmonary retention seen when compared to single dose lung levels may be due to macrophage uptake and the lipophilic nature of TAC. Additionally, three month stability testing of TAC powder for reconstitution showed no changes in amorphous nature or drug potency when stored at ambient conditions. TAC colloidal dispersion proved to be non-toxic when administered by pulmonary inhalation to SD rats over 28 days while providing therapeutic concentrations locally. This delivery strategy may prove safe and effective for the prevention of lung allograft rejection in lung transplant recipients.

Can we rapidly identify traditional, complementary and alternative medicine users in the primary care encounter? A RIOS Net study.

OBJECTIVE: Pressed for time to address competing clinical demands within the brief clinical encounter, primary care clinicians often rely on observations of patients to select topics to address. Use of traditional, complementary, or alternative medicine (TM/CAM) may be an important topic for discussion with a patient, but identification of patients using TM/CAM is problematic. We conducted this study to determine if observable characteristics--among southwestern Hispanic and Native American persons--might suggest to the clinician that a patient is likely to use TM/CAM. DESIGN: A combination of clinic staff focus groups, patient and clinician interviews, and a clinician focus group was used to explore possible predictors of TM/CAM use among primary care patients in practices serving predominantly Hispanic and Native American communities. RESULTS: No easily observable characteristics were identified that clinicians might use to predict TM/CAM use in their patients. Less readily observable characteristics--identification with culture, family of origin, health condition--were more likely to be associated with TM/CAM use, but not infallibly so. CONCLUSIONS: Rather than attempt to predict TM/CAM use by an individual patient, clinicians may be better served by assuming its use by all, by applying strategies for rapid and effective communications with patients about the topic, by selecting which patients to discuss TM/CAM use with based on clinical circumstances, and/or by gathering information about TM/CAM use as part of routine initial database development.

The marriage of community-based participatory research and practice-based research networks: can it work? -A Research Involving Outpatient Settings Network (RIOS Net) study.

BACKGROUND: Interest in community-based participatory research (CBPR) has surged during the last several years because of its potential to enhance the quality and usefulness of research outcomes. Practice-based research networks (PBRNs) potentially can provide a bridge between the research endeavor and communities; PBRNs have been identified as a promising venue for CBPR. However, this marriage of CBPR and PBRNs faces many challenges, such as locus of project idea generation, time constraints, and funding limitations. METHODS: This was a case study of the application of the CBPR model and CBPR principles specific to PBRN research using a recent PBRN study of communication about traditional, complementary, and alternative medicines. RESULTS: Challenges (eg, added cost, time) and benefits (eg, improved research data collection process, enhanced data analysis) resulted from application of the CBPR model and are detailed. CONCLUSIONS: For practical and ethical reasons, PBRNs need to adopt the CBPR approach for certain types, if not all, of their research. This might require operational adaptations by the PBRN (eg, a community advisory board, community membership in the network board of directors, and outreach to community groups for input into network priorities) as well as dedicated time and funding.

'They don't ask me so I don't tell them': patient-clinician communication about traditional, complementary, and alternative medicine.

PURPOSE: Although high rates of traditional medicine and complementary and alternative medicine (TM/CAM) use have been well documented, there has been less attention to the factors influencing communication between patients and their primary care clinicians about TM/CAM. Such communication can be important in anticipating possible drug-herb interactions and in assuring agreement about therapeutic plans. METHODS: We used sequential, multistage, qualitative methods, including focus groups, in-depth interviews, and a video vignette, to explore communication about TM/CAM between patients and their primary care clinicians. The study was conducted in RIOS Net (Research Involved in Outpatient Settings Network), a Southwestern US practice-based research network, situated largely in Hispanic and American Indian communities where TM/CAM is an important part of self-care. RESULTS: One hundred fourteen patients, 41 clinic staff members, and 19 primary care clinicians in 8 clinic sites participated. The degree and nature of TM/ CAM communication is based on certain conditions in the clinical encounter. We categorized these findings into 3 themes: acceptance/nonjudgment, initiation of communication, and safety/efficacy. Perceived clinician receptivity to and initiation of discussion about TM/CAM strongly influenced patients' decisions to communicate; perceived clinician expertise in TM/CAM was less important. Clinicians' comfort with patients' self-care approaches and their level of concern about lack of scientific evidence of effectiveness and safety of TM/CAM influenced their communication about TM/CAM with patients. CONCLUSIONS: Specific communication barriers limit patient-clinician communication about TM/CAM. Clinicians who wish to communicate more effectively with their patients about these topics and better integrate the types of care their patients use can change the communication dynamic with simple strategies designed to overcome these barriers.

High bioavailability from nebulized itraconazole nanoparticle dispersions with biocompatible stabilizers.

A nebulized dispersion of amorphous, high surface area, nanostructured aggregates of itraconazole (ITZ):mannitol:lecithin (1:0.5:0.2, w/w) yielded improved bioavailability in mice. The ultra-rapid freezing (URF) technique used to produce the nanoparticles was found to molecularly disperse the ITZ with the excipients as a solid solution. Upon addition to water, ITZ formed a colloidal dispersion suitable for nebulization, which demonstrated optimal aerodynamic properties for deep lung delivery and high lung and systemic levels when dosed to mice. The ITZ nanoparticles produced supersaturation levels 27 times the crystalline solubility upon dissolution in simulated lung fluid. A dissolution/permeation model indicated that the absorption of 3 microm ITZ particles is limited by the dissolution rate (BCS Class II behavior), while absorption is permeation-limited for more rapidly dissolving 230 nm particles. The predicted absorption half-life for 230 nm amorphous ITZ particles was only 15 min, as a result of the small particle size and high supersaturation, in general agreement with the in vivo results. Thus, bioavailability may be enhanced, by decreasing the particle size to accelerate dissolution and increasing permeation with (1) an amorphous morphology to raise the drug solubility, and (2) permeability enhancers.

The virtual haptic back: a simulation for training in palpatory diagnosis.

BACKGROUND: Models and simulations are finding increased roles in medical education. The Virtual Haptic Back (VHB) is a virtual reality simulation of the mechanical properties of the human back designed as an aid to teaching clinical palpatory diagnosis. METHODS: Eighty-nine first year medical students of the Ohio University College of Osteopathic Medicine carried out six, 15-minute practice sessions with the VHB, plus tests before and after the sessions in order to monitor progress in identifying regions of simulated abnormal tissue compliance. Students palpated with two digits, fingers or thumbs, by placing them in gimbaled thimbles at the ends of PHANToM 3.0(R) haptic interface arms. The interface simulated the contours and compliance of the back surface by the action of electric motors. The motors limited the compression of the virtual tissues induced by the palpating fingers, by generating counterforces. Users could see the position of their fingers with respect to the back on a video monitor just behind the plane of the haptic back. The abnormal region varied randomly among 12 locations between trials. During the practice sessions student users received immediate feedback following each trial, indicating either a correct choice or the actual location of the abnormality if an incorrect choice had been made. This allowed the user to feel the actual abnormality before going on to the next trial. Changes in accuracy, speed and Weber fraction across practice sessions were analyzed using a repeated measures analysis of variance. RESULTS: Students improved in accuracy and speed of diagnosis with practice. The smallest difference in simulated tissue compliance users were able to detect improved from 28% (SD = 9.5%) to 14% (SD = 4.4%) during the practice sessions while average detection time decreased from 39 (SD = 19.8) to 17 (SD = 11.7) seconds. When asked in anonymous evaluation questionnaires if they judged the VHB practice to be helpful to them in the clinical palpation and manual medicine laboratory, 41% said yes, 51% said maybe, and 8% said no. CONCLUSION: The VHB has potential value as a teaching aid for students in the initial phases of learning palpatory diagnosis.