A.A.L.S. Clinical Legal Education Panel: Evaluation and Assessment of Student Performance in a Clinical Setting

This article is adapted from a panel discussion held under the auspices of the Section on Clinical Legal Education of the Association of American Law Schools, presented at the annual meeting in Phoenix, Arizona on January 5, 1980. The participants were H. Russell Cort, Jack L. Sammons, Robert S. Catz, Ralph S. Tyler and Terence J. Anderson

Interaction between galectin-3 and cystinosin uncovers a pathogenic role of inflammation in kidney involvement of cystinosis.

Inflammation is involved in the pathogenesis of many disorders. However, the underlying mechanisms are often unknown. Here, we test whether cystinosin, the protein involved in cystinosis, is a critical regulator of galectin-3, a member of the β-galactosidase binding protein family, during inflammation. Cystinosis is a lysosomal storage disorder and, despite ubiquitous expression of cystinosin, the kidney is the primary organ impacted by the disease. Cystinosin was found to enhance lysosomal localization and degradation of galectin-3. In Ctns-/- mice, a mouse model of cystinosis, galectin-3 is overexpressed in the kidney. The absence of galectin-3 in cystinotic mice ameliorates pathologic renal function and structure and decreases macrophage/monocyte infiltration in the kidney of the Ctns-/-Gal3-/- mice compared to Ctns-/- mice. These data strongly suggest that galectin-3 mediates inflammation involved in kidney disease progression in cystinosis. Furthermore, galectin-3 was found to interact with the pro-inflammatory cytokine Monocyte Chemoattractant Protein-1, which stimulates the recruitment of monocytes/macrophages, and proved to be significantly increased in the serum of Ctns-/- mice and also patients with cystinosis. Thus, our findings highlight a new role for cystinosin and galectin-3 interaction in inflammation and provide an additional mechanistic explanation for the kidney disease of cystinosis. This may lead to the identification of new drug targets to delay cystinosis progression

Disruption of Saccadic Adaptation with Repetitive Transcranial Magnetic Stimulation of the Posterior Cerebellum in Humans

Saccadic eye movements are driven by motor commands that are continuously modified so that errors created by eye muscle fatigue, injury, or—in humans—wearing spectacles can be corrected. It is possible to rapidly adapt saccades in the laboratory by introducing a discrepancy between the intended and actual saccadic target. Neurophysiological and lesion studies in the non-human primate as well as neuroimaging and patient studies in humans have demonstrated that the oculomotor vermis (lobules VI and VII of the posterior cerebellum) is critical for saccadic adaptation. We studied the effect of transiently disrupting the function of posterior cerebellum with repetitive transcranial magnetic stimulation (rTMS) on the ability of healthy human subjects to adapt saccadic eye movements. rTMS significantly impaired the adaptation of the amplitude of saccades, without modulating saccadic amplitude or variability in baseline conditions. Moreover, increasing the intensity of rTMS produced a larger impairment in the ability to adapt saccadic size. These results provide direct evidence for the role of the posterior cerebellum in man and further evidence that TMS can modulate cerebellar function

Effectiveness of automated locomotor training in patients with acute incomplete spinal cord injury: A randomized controlled multicenter trial

<p>Abstract</p> <p>Background</p> <p>A large proportion of patients with spinal cord injury (SCI) regain ambulatory function. However, during the first 3 months most of the patients are not able to walk unsupported. To enable ambulatory training at such an early stage the body weight is partially relieved and the leg movements are assisted by two therapists. A more recent approach is the application of robotic based assistance which allows for longer training duration. From motor learning science and studies including patients with stroke, it is known that training effects depend on the duration of the training. Longer trainings result in a better walking function. The aim of the present study is to evaluate if prolonged robot assisted walking training leads to a better walking outcome in patients with incomplete SCI and whether such training is feasible or has undesirable effects.</p> <p>Methods/Design</p> <p>Patients from multiple sites with a subacute incomplete SCI and who are not able to walk independently will be randomized to either standard training (3-5 sessions per week, session duration maximum 25 minutes) or an intensive training (3-5 sessions per week, session duration minimum 50 minutes). After 8 weeks of training and 4 months later the walking ability, the occurrence of adverse events and the perceived rate of exertion as well as the patients' impression of change will be compared between groups.</p> <p>Trial registration</p> <p>This study is registered at clinicaltrials.gov, identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01147185">NCT01147185</a>.</p

Retigeric Acid B Exhibits Antitumor Activity through Suppression of Nuclear Factor-κB Signaling in Prostate Cancer Cells in Vitro and in Vivo

Previously, we reported that retigeric acid B (RB), a natural pentacyclic triterpenic acid isolated from lichen, inhibited cell growth and induced apoptosis in androgen-independent prostate cancer (PCa) cells. However, the mechanism of action of RB remains unclear. In this study, we found that using PC3 and DU145 cells as models, RB inhibited phosphorylation levels of IκBα and p65 subunit of NF-κB in a time- and dosage-dependent manner. Detailed study revealed that RB blocked the nuclear translocation of p65 and its DNA binding activity, which correlated with suppression of NF-κB-regulated proteins including Bcl-2, Bcl-xL, cyclin D1 and survivin. NF-κB reporter assay suggested that RB was able to inhibit both constitutive activated-NF-κB and LPS (lipopolysaccharide)-induced activation of NF-κB. Overexpression of RelA/p65 rescued RB-induced cell death, while knockdown of RelA/p65 significantly promoted RB-mediated inhibitory effect on cell proliferation, suggesting the crucial involvement of NF-κB pathway in this event. We further analyzed antitumor activity of RB in in vivo study. In C57BL/6 mice carrying RM-1 homografts, RB inhibited tumor growth and triggered apoptosis mainly through suppressing NF-κB activity in tumor tissues. Additionally, DNA microarray data revealed global changes in the gene expression associated with cell proliferation, apoptosis, invasion and metastasis in response to RB treatment. Therefore, our findings suggested that RB exerted its anti-tumor effect by targeting the NF-κB pathway in PCa cells, and this could be a general mechanism for the anti-tumor effect of RB in other types of cancers as well

Living in rural New England amplifies the risk of depression in patients with HIV

<p>Abstract</p> <p>Background</p> <p>The importance of depression as a complication of HIV infection is increasingly understood, and people living in rural areas are at increased risk for depression. However, it is not known whether living in rural areas amplifies the risk of depression in patients with HIV.</p> <p>Methods</p> <p>We compared the prevalence of depression between rural and metropolitan HIV patients seen at the Dartmouth-Hitchcock HIV Program in a retrospective cohort study. Using the validated Rural-Urban Commuting Area Score, we categorized patients as living in small town/rural areas, micropolitan or metropolitan towns. Then, using a multivariate logistic regression model to adjust for demographic factors that differed between rural and metropolitan patients, we estimated the impact of living in rural areas on the odds of depression.</p> <p>Results</p> <p>Among 646 patients with HIV (185 small town/rural, 145 micropolitan, 316 metropolitan), rural patients were older, white, male, and men who have sex with men (ANOVA, F-statistic < 0.05). The prevalence of depression was highest in rural patients (59.5 vs. 51.7 vs. 41.2%, F statistic < 0.001), particularly rural patients on antiretroviral therapy (72.4 vs. 53.5 vs. 38.2%, F-statistic < 0.001. A multivariate logistic regression model showed that the odds of depression in rural patients with HIV were 1.34 (P < 0.001).</p> <p>Conclusion</p> <p>HIV-infected patients living in rural areas, particularly those on antiretroviral therapy, are highly vulnerable to depression.</p

AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2

Activation of the serine/threonine kinase AKT is common in pancreatic cancer; inhibition of which sensitises cells to the apoptotic effect of chemotherapy. Of the various downstream targets of AKT, we examined activation of the NF-kappaB transcription factor and subsequent transcriptional regulation of BCL-2 gene family in pancreatic cancer cells. Inhibition of either phosphatidylinositol-3 kinase or AKT led to a decreased protein level of the antiapoptotic gene BCL-2 and an increased protein level of the proapoptotic gene BAX. Furthermore, inhibition of AKT decreased the function of NF-kappaB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway had little effect on the basal level of apoptosis in pancreatic cancer cells, but increased the apoptotic effect of chemotherapy. The antiapoptotic effect of AKT activation in pancreatic cancer cells may involve transcriptional induction of a profile of BCL-2 proteins that confer resistance to apoptosis; alteration of this balance allows sensitisation to the apoptotic effect of chemotherapy

Communicating genetic information: a difficult challenge for future pediatricians

<p>Abstract</p> <p>Background</p> <p>The role of the pediatrician as genetic counselor is ideal because pediatricians have medical knowledge and experience with genetic disorders (e.g. Down syndrome). Moreover, pediatricians can provide comprehensive care in a medical home to patients with genetic disorders. However, changes in the curriculum of the pediatric resident are necessary to address the future challenges of effectively communicating genetic information to patients. The objective of this study was to explore these challenges and make recommendations for training to adequately prepare pediatricians for their future role as genetic counselors.</p> <p>Methods</p> <p>Three reviewers independently searched PubMed, OVID, and Medline databases to identify articles describing the challenges of communicating genetic information to patients, published from 1960 to December 2005. After the publications were identified and reviewed, four major areas of interest were identified in order to categorize the findings.</p> <p>Results</p> <p>Twenty-five publications were identified during the literature search. From the review, the following categories were selected to organize the findings: (1) Inherent difficulties of communicating and comprehending genetic information; (2) Comprehension of genetic information by pediatricians; (3) Genetics training in residency programs; and (4) The effect of genetic information on the future role of pediatricians and potential legal implications.</p> <p>Conclusion</p> <p>Pediatricians and residents lack essential knowledge of genetics and communication skills for effective counseling of patients. The review indicated that successful communication of genetic information involves a number of important skills and considerations. It is likely that these skills and considerations are universally required for the communication of most complex specialized medical information. In the past, communication skills have not been considered a priority. Today, these skills have become a demanding professional and even legal obligation. However, the challenges involved in communicating complex medical information cannot be successfully addressed with universal, one-size-fits-all recommendations. Residency training programs require changes to adequately prepare future pediatricians for the growing challenge of communicating genetic information. Four important skills should be considered in the training of residents to improve the communication of complex information to patients. These skills are (1) discriminating, (2) understanding, (3) simplifying, and (4) explaining information.</p