University of Illinois Chicago, Rockford campus

Cell culture has become an indispensable tool to help uncover fundamental biophysical and biomolecular mechanisms by which cells assemble into tissues and organs, how these tissues function, and how that function becomes disrupted in disease. Cell culture is now widely used in biomedical research, tissue engineering, regenerative medicine, and industrial practices. Although flat, two-dimensional (2D) cell culture has predominated, recent research has shifted toward culture using three-dimensional (3D) structures, and more realistic biochemical and biomechanical microenvironments. Nevertheless, in 3D cell culture, many challenges remain, including the tissue-tissue interface, the mechanical microenvironment, and the spatiotemporal distributions of oxygen, nutrients, and metabolic wastes. Here, we review 2D and 3D cell culture methods, discuss advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes, and suggest directions for future research.

BACKGROUND: Colonoscopy is commonly used to screen for neoplasia. To assess the performance of screening colonoscopy in everyday practice, we conducted a study of the rates of detection of adenomas and the amount of time taken to withdraw the colonoscope among endoscopists in a large community-based practice. METHODS: During a 15-month period, 12 experienced gastroenterologists performed 7882 colonoscopies, of which 2053 were screening examinations in subjects who had not previously undergone colonoscopy. We recorded the numbers, sizes, and histologic features of the neoplastic lesions detected during screening, as well as the duration of insertion and of withdrawal of the colonoscope during the procedure. We compared rates of detection of neoplastic lesions among gastroenterologists who had mean colonoscopic withdrawal times of less than 6 minutes with the rates of those who had mean withdrawal times of 6 minutes or more. According to experts, 6 minutes is the minimum length of time to allow adequate inspection during instrument withdrawal. RESULTS: Neoplastic lesions (mostly adenomatous polyps) were detected in 23.5% of screened subjects. There were large differences among gastroenterologists in the rates of detection of adenomas (range of the mean number of lesions per subject screened, 0.10 to 1.05; range of the percentage of subjects with adenomas, 9.4 to 32.7%) and in their times of withdrawal of the colonoscope from the cecum to the anus (range, 3.1 to 16.8 minutes for procedures during which no polyps were removed). As compared with colonoscopists with mean withdrawal times of less than 6 minutes, those with mean withdrawal times of 6 minutes or more had higher rates of detection of any neoplasia (28.3% vs. 11.8%, P<0.001) and of advanced neoplasia (6.4% vs. 2.6%, P=0.005). CONCLUSIONS: In this large community-based gastroenterology practice, we observed greater rates of detection of adenomas among endoscopists who had longer mean times for withdrawal of the colonoscope. The effect of variation in withdrawal times on lesion detection and the prevention of colorectal cancer in the context of widespread colonoscopic screening is not known. Ours was a preliminary study, so the generalizability and implications for clinical practice need to be determined by future studies.

CONTEXT: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. DESIGN: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.

Context: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. Objective: Toevaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. Design: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. Main Outcome Measure: HIV-1 status of the infant. Results: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%- 23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%- 6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p = .0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. Conclusion: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.

BACKGROUND: Constipation is a common, often chronic, gastrointestinal motility disorder characterized by such symptoms as straining, hard stool, and infrequent defecation. Published literature is limited regarding symptom prevalence, healthcare-seeking behaviour, and patient satisfaction with traditional therapies for chronic constipation. AIM: To assess the prevalence of chronic constipation among a random sample of Americans, to identify the frequency, severity and bothersomeness of their symptoms, and to assess satisfaction levels with traditional treatments. METHODS: All members (N = 37,004) of the Knowledge Networks Panel, representative of the US population, participated in a web-based survey. Eligibility was established using a six-question screener. RESULTS: Of the 24,090 panellists consenting to participate, 557 met eligibility requirements and took the 45-question survey. The most prevalent symptom was straining (79%). Hard stool and straining were the top two severe symptoms, and bloating, straining and hard stool were the top three bothersome symptoms. Symptoms affected quality of life of more than half (52%) the respondents. Among those who worked or went to school, 12% experienced reduced productivity and a mean of 2.4 days of absence in the month before the survey. Most respondents had used (96%) or were using (72%) constipation relief therapy; however, nearly half (47%) were not completely satisfied, mainly because of efficacy (82%) and safety (16%) concerns. CONCLUSIONS: Chronic constipation is common. Individual symptoms are often severe and bothersome, and many patients are dissatisfied with traditional treatment options, primarily because of lack of efficacy.

OBJECTIVE: Fecal incontinence represents an embarrassing social problem, the magnitude of which remains largely unknown. The present study prospectively examined the prevalence and demographic distributions of fecal incontinence. METHODS: demographic data, in addition to information regarding the reason for visit, bowel habits, and the frequency, type, and severity of fecal incontinence, were collected from individuals at the time of visits to their primary care physician or gastroenterologist. RESULTS: Eight hundred and eighty-one individuals 18 yr or older were included in the analysis. The overall prevalence of fecal incontinence was 18.4%. When stratified by frequency, 2.7, 4.5, and 7.1% of participants admitted to incontinence daily, weekly, or once per month or less, respectively. Incontinence increased progressively with age and was 1.3 times more common in males than females. Only one-third of individuals with fecal incontinence had ever discussed the problem with a physician. CONCLUSIONS: The prevalence of fecal incontinence appears to be more common than previously appreciated. Moreover, only a minority with a physician. It would seem important to more actively pursue this "silent affliction" particularly in patients who do not readily volunteer this information.

Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic-pituitary-adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer's and Parkinson's, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions.

OBJECTIVE: Despite studies suggesting that there is a higher prevalence of overweight or obese children in rural areas in the U.S., there are no national studies comparing the prevalence levels of overweight or obese rural to metropolitan children. The objective of this research was to examine the hypothesis that living in a rural area is a risk factor for children being overweight or obese. RESEARCH METHODS AND PROCEDURES: Using the National Survey of Children's Heath, the prevalence of overweight and/or obese rural children was compared with that of children in metropolitan settings. Multivariate analyses were performed on the data to detect if differences varied by health services use factors or demographic factors, such as household income, gender, and race. RESULTS: Multivariate analysis revealed that overweight or obese children >or=5 years of age were more likely to live in rural rather than metropolitan areas (odds ratio = 1.252; 95% confidence interval, 1.248, 1.256). Rural overweight U.S. children >or=5 years of age of age were more likely than their metropolitan counterparts to: be white, live in households <or=200% of the federal poverty level, have no health insurance, have not received preventive health care in the past 12 months, be female, use a computer for non-school work >3 hours a day, and watch television for >3 hours a day. In addition, they were more likely to have comorbidities. DISCUSSION: Living in rural areas is a risk factor for children being overweight or obese.

This study aimed to assess the literature available on the effects, on peri-implant tissues, of degradation products released from dental implants as a consequence of therapeutic treatment for peri-implantitis and/or of wear-corrosion of titanium. A literature review of the PubMed medline database was performed up to December 31, 2016. The following search terms were used: "titanium wear and dental implant"; "titanium corrosion and dental implant"; "bio-tribocorrosion"; "peri-implantitis"; "treatment of peri-implantitis"; "titanium particles release and dental implant"; and "titanium ion release and dental implant". The keywords were applied to the database in different combinations without limits of time period or type of work. In addition, the reference lists of relevant articles were searched for further studies. Seventy-nine relevant scientific articles on the topic were retrieved. The results showed that pro-inflammatory cytokines, infiltration of inflammatory response cells and activation of the osteoclasts activity are stimulated in peri-implant tissues in the presence of metal particles and ions. Moreover, degenerative changes were reported in macrophages and neutrophils that phagocytosed titanium microparticles, and mutations occurred in human cells cultured in medium containing titanium-based nanoparticles. Debris released from the degradation of dental implants has cytotoxic and genotoxic potential for peri-implant tissues. Thus, the amount and physicochemical properties of the degradation products determine the magnitude of the detrimental effect on peri-implant tissues.

Hispanic immigrants are increasingly residing in rural communities, including in the midwestern United States. Limitations in the ability of rural Hispanics to access and utilize health care contribute to patterns of poor health and health disparity. A conceptual model of "vulnerability" guides this community-based participatory assessment project designed to explore rural Hispanics' perceived barriers to accessing and utilizing health care. Findings from a series of 19 focus groups with 181 participants from three communities in the upper Midwest identified perceived barriers at the individual and health care system levels. The most commonly perceived barriers were the lack of and limitations in health insurance coverage, high costs of health care services, communication issues involving patients and providers, legal status/discrimination, and transportation concerns. Findings imply that these barriers could be addressed using multiple educational and health service delivery policy-related strategies that consider the vulnerable nature of this growing population.

How do boards of directors of large US corporations set the compensation levels for chief executive officers (CEOs)? Economic theories are based on the presumption that an independent board of directors will safeguard shareholders' interests and minimize opportunism on the part of management. Explicit in these formulations is the assumption that outside or independent directors (i.e. non-management directors) are more able to do this than insiders. But is this a reasonable assumption? Drawing on psychological theories of small group dynamics and social influence, we investigate the extent to which the board of directors may be influenced or captured by the CEO such that executives receive higher levels of compensation than performance or economic theories would predict. Results of a review of the descriptive evidence for the operation of boards and two empirical studies suggest that social influence may be responsible for significant increments in CEO compensation beyond what economic theories predict. The implications of these findings for both theories of governance and the operation of boards of directors is discussed.

In 2014, the Association of American Medical Colleges (AAMC) published a list of 13 Core Entrustable Professional Activities for Entering Residency (Core EPAs) that medical school graduates might be expected to perform, without direct supervision, on the first day of residency. Soon after, the AAMC commissioned a five-year pilot with 10 medical schools across the United States, seeking to implement the Core EPA framework to improve the transition from undergraduate to graduate medical education.In this article, the pilot team presents the organizational structure and early results of collaborative efforts to provide guidance to other institutions planning to implement the Core EPA framework. They describe the aims, timeline, and organization of the pilot as well as findings to date regarding the concepts of entrustment, assessment, curriculum development, and faculty development. On the basis of their experiences over the first two years of the pilot, the authors offer a set of guiding principles for institutions intending to implement the Core EPA framework. They also discuss the impact of the pilot, its limitations, and next steps, as well as how the pilot team is engaging the broader medical education community. They encourage ongoing communication across institutions to capitalize on the expertise of educators to tackle challenges related to the implementation of this novel approach and to generate common national standards for entrustment. The Core EPA pilot aims to better prepare medical school graduates for their professional duties at the beginning of residency with the ultimate goal of improving patient care.

INTRODUCTION: Regional or state studies in the USA have documented shortages of rural physicians and other healthcare professionals that can impact on access to health services. The purpose of this study was to determine whether rural hospital chief executive officers (CEOs) in the USA report shortages of health professions and to obtain perceptions about factors influencing recruiting and retention. METHODS: A nationwide US survey was conducted of 1031 rural hospital CEOs identified by regional/state Area Health Education Centers. A three-page survey was sent containing questions about whether or not physician shortages were present in the CEO's community and asking about physician needs by specialty. The CEOs were also asked to assess whether other health professionals were needed in their town or within a 48 km (30 mile) radius. Analyses from 335 respondents (34.4%) representative of rural hospital CEOs in the USA are presented. RESULTS: Primary care shortages based on survey responses were very similar to the pattern for all rural areas in the USA (49% vs 52%, respectively). The location of respondents according to ZIP code rurality status was similar to all rural areas in the USA (moderately rural, 29.3% vs 27.6%, respectively), and 69.1% were located in highly rural ZIP codes (vs 72.4% of highly rural ZIP codes for all USA). Physician shortages were reported by 75.4% of the rural CEOs, and 70.3% indicated shortages of two or more primary care specialties. The most frequently reported shortage was family medicine (FM, 58.3%) followed by general internal medicine (IM, 53.1%). Other reported shortages were: psychiatry (46.6%); general surgery (39.9%); neurology (36.4%); pediatrics (PEDS, 36.2%); cardiology (35%); and obstetrics-gynecology (34.4%). The three most commonly needed allied health professions were registered nurses (73.5%), physical therapists (61.2%) and pharmacists (51%). The percentage of CEOs reporting shortages of two or more primary care specialties (FM, IM or PEDS) was 70.3% nationally, with no statistically significant regional variation (p = .394), while higher for the New England through Virginia region (83.9%) than for all other regions. The CEOs reported the highest specialty care shortages for psychiatry (46.6%) followed by general surgery (39.9%), neurology (36.4%), cardiology (35.0%) and obstetrics-gynecology (34.4%). Major specialty shortages varied among regions and only for neurology and cardiology were regional differences statistically significant (p < .05). Marked variation between need for healthcare professionals were reported ranging from approximately 73% for registered nurses (RNs) to 16% for health educators. Reporting of need for RNs in rural areas was nearly 74% nationally and 35% reported a need for nurse practitioners. Differences for both RNs and nurse practitioners were not statistically significant among regions. Nationally, approximately 30% of CEOs reported a shortage of licensed practical nurses, which differed significantly among regions (p = .006). There was variation in physical therapist shortages among regions (p = .001), with 61.2% of CEOs reporting shortages nationally. Regional variation pattern was observed for pharmacists (p = .004) with approximately 50% of rural CEOs reporting a need for pharmacists nationally. The association between CEOs' reported shortages of two or more primary care doctors and their indication of the need for other health professionals was statistically significant for nurse practitioners, physician assistants, pharmacists, and dentists. The recruitment and retention attributes deemed to be of greatest importance were: (1) healthcare is a major part of the local economy; (2) community is a good place for family; (3) doctors are well-respected and supported; and (4) people in the community are friendly and supportive of each other. These were remarkably similar across 6 US geographic regions. CONCLUSIONS: Similarities in shortages and attributes influencing recruitment across regions suggest that major policy and program interventions are needed to develop a rural health professions workforce that will enable the benefits of recent US health reform insurance coverage to be realized. Substantial and targeted programs to increase rural healthcare professionals are needed.

BACKGROUND: c-Met and EGFR receptors are widely expressed on cancer cells; they are implicated in the development and progression of cancer through a plethora of effects on cell cycle progression, apoptosis, motility and metastasis and are potential targets for combination therapy. EGFR receptor tyrosine kinases are currently being targeted in a number of malignancies. METHODS: Apoptosis was studied by FACS analysis using propidium iodide. EGF and HGF signaling intermediates were studied by western blotting. Cell proliferation was determined by MTT assays. Cell motility was done by time lapse confocal microscopy. RESULTS: c-Met and EGFR were both expressed in A549, H1838, H2170, SW900, SW1573, H358, SKLU-1, and H1993 non small cell lung cancer (NSCLC) cell lines. Both EGF and HGF at 100 ng/ml in medium showed a synergistic effect on cell proliferation at 48-72 h as seen by a proliferation assay in A549, H1838, and SKMES cells. In A549 and H1838 cell lines, HGF (40 ng/ml) and EGF (5 ng/ml) induced synergistic phosphorylation on c-Met (Tyr 1003/1230/1234/1235). Additionally, synergistic phosphorylation of Akt (Ser-473) and phospho-ERK1+ERK2 (Thr202/Tyr204) was also seen indicating that EGF and HGF could induce synergistic phosphorylation of important signaling intermediates. Treatment with EGF and HGF at 100 ng/ml for 2 h also leads to an additive effect in inducing cell motility (especially membrane ruffling) in H1993 cells. A novel c-Met small molecule tyrosine kinase inhibitor SU11274 and EGFR tyrosine kinase inhibitors Tyrphostin AG1478 and gefitinib (Iressa) were tested to study their effect in combination on proliferation and apoptosis in lung cancer cells. Interestingly, a synergistic effect on inhibition of cell proliferation was seen in the presence of SU11274 and Tyrphostin AG1478. 0.5 microM Tyrphostin AG1478 and 2 microM SU11274 inhibited growth by 21% and 25%, respectively; a combination of both tyrosine kinase inhibitors inhibited growth by 65%. Interestingly, EGFR inhibitor (gefitinib, Iressa) and c-Met inhibitor (SU11274) also had a synergistic effect on apoptosis in H358 cells. CONCLUSION: There was a synergistic effect of EGF and HGF on proliferation, downstream activation of signal transduction and an additive effect seen on motility. These studies show that a combination of HGF and EGF tyrosine kinase inhibitors on NSCLC, could potentially be targeted in a synergistic fashion.

Morinda citrifolia (Noni) has been extensively used in folk medicine by Polynesians for over 2,000 years. It has been reported to have broad therapeutic effects, including anticancer activity, in both clinical practice and laboratory animal models. The mechanism for these effects remains unknown. The hypothesis that Morinda citrifolia possesses a cancer preventive effect at the initiation stage of carcinogenesis was studied. Our preliminary data indicated that 10% Tahitian Noni Liquid Dietary Supplement or Tahitian Noni Juice (TNJ), made from Morinda citrifolia fruit by Morinda Inc, in drinking water for one week was able to prevent DMBA-DNA adduct formation. The levels of DMBA-DNA adducts were reduced by 30% in the heart, 41% in the lung, 42% in the liver, and 80% in the kidney of female SD rats. Even more dramatic results were obtained in male C57 BL-6 mice: 10% TNJ was able to reduce DMBA-DNA adduct formation by 60% in the heart, 50% in the lung, 70% in the liver, and 90% in the kidney. In order to explore the mechanism of this preventive effect, the antioxidant activity of TNJ was examined in vitro by lipid hydroperoxide (LPO) and tetrazolium nitroblue (TNB) assays. In the LPO assay, LPO oxidizes leucomethylene blue to methylene blue in the presence of hemoglobin. The resultant blue color was quantified at 660 nm spectrophotometrically. In the TNB assay, superoxide anion radicals (SAR) reduce TNB into formazan blue that was also measured by absorption at 602 nm. TNJ showed a dose-dependent inhibition of both LPO and SAR in our system. The antioxidant activity of TNJ was compared to the effects of vitamin C, grape seed powder (GSP), and pycnogenol (PYC) at the daily dose per serving level recommended by U.S.RDAs or manufacturers. The results suggest that prevention of carcinogen-DNA adduct formation and the antioxidant activity of TNJ may contribute to the cancer preventive effect of Morinda citrifolia.

BACKGROUND: Analyses of a trial in constipated patients indicated that lubiprostone may be an effective treatment for irritable bowel syndrome with constipation. AIM: To assess the efficacy and safety of three lubiprostone doses for irritable bowel syndrome with constipation. METHODS: 195 irritable bowel syndrome with constipation patients received daily doses of 16 [8 microg twice daily (b.d.)], 32 (16 microg b.d.) or 48 microg (24 microg b.d.) lubiprostone or placebo b.d. for 3 months. Gastrointestinal parameters were recorded in diaries daily by patients. RESULTS: After 1 month, lubiprostone showed significantly greater improvements in mean abdominal discomfort/pain scores vs. placebo (P = 0.023). After 2 months, all lubiprostone groups showed significantly greater improvements in mean abdominal discomfort/pain scores (P < or = 0.039). After 3 months of treatment, the improvement in each lubiprostone arm was greater than placebo, but the test for trend was no longer significant. Treatment with lubiprostone showed significantly higher rates of gastrointestinal adverse events (P = 0.020), especially diarrhoea and nausea. CONCLUSION: Lubiprostone significantly improved gastrointestinal symptoms of irritable bowel syndrome with constipation at all doses. Higher doses of lubiprostone, especially the 48 microg/day group, were associated with more gastrointestinal adverse events. From these data, the 16 microg/day dose demonstrated the optimal combination of efficacy and safety. These results warrant further study of lubiprostone for treatment of irritable bowel syndrome with constipation patients.

Information processing theorists propose that traumatic events can lead to disruptions in the processing of information and to changes in beliefs. This study examined the relationships among trauma, posttraumatic stress disorder (PTSD), and religious beliefs. Participants included 120 individuals from community and clinical samples who participated in the DSM-IV Field Trial Study on PTSD. Results indicated that the PTSD group was more likely to report changes in religious beliefs following the first/only traumatic event, generally becoming less religious. PTSD status was not related to change in religious beliefs following the most recent event. Intrinsic religiosity was related to multiple victimization, but not PTSD. Results are discussed in terms of understanding the function of religiosity in participants' lives and future directions for research.

Between 1994 and 1996, three elephants from an exotic animal farm in Illinois died of pulmonary disease due to Mycobacterium tuberculosis. In October 1996, a fourth living elephant was culture-positive for M. tuberculosis. Twenty-two handlers at the farm were screened for tuberculosis (TB); eleven had positive reactions to intradermal injection with purified protein derivative. One had smear-negative, culture-positive active TB. DNA fingerprint comparison by IS6110 and TBN12 typing showed that the isolates from the four elephants and the handler with active TB were the same strain. This investigation indicates transmission of M. tuberculosis between humans and elephants.

When a rat navigates through space, head direction (HD) cells provide an ongoing signal of the rat's directional heading. It is thought that these cells rely, in part, on angular path integration of the rat's head movements. This integration requires that the HD cell system receive information about angular head movements and that this information be combined with the current directional signal, to generate the next "predicted" direction. Recent data suggest that the dorsal tegmental nucleus (DTN) may play a critical role in helping to generate the HD cell signal. To test this, recordings were made from cells in the DTN in freely moving rats. The following cell types were found: (a) "classic" HD cells, (b) angular velocity cells, and (c) cells that fired as a function of both head direction and angular velocity. Thus, DTN cells exhibit firing characteristics that are critical to the neural circuit hypothesized for generation of the HD cell signal.

Colonoscopy is increasingly used to screen for colorectal neoplasms and to remove benign adenomatous polyps before they become cancerous. This study, conducted at a large community-based gastroenterology practice, examined the proposal that endoscopists who take more time to examine the colorectal mucosa—prolonging withdrawal of the scope—detect more neoplasms. Twelve experienced gastroenterologists performed a total of 7882 colonoscopies during a 15-month period; 2053 of them were screening exams in persons having their first colonoscopy. Detection rates were compared for practitioners whose colonoscopic withdrawal times were less than 6 minutes and 6 minutes or longer. Experts believe that at least 6 minutes are needed to adequately inspect the colon and rectum. Nearly one in four of those examined (23.5%) were found to have adenomatous polyps. The mean withdrawal time was 6.3 minutes when no polyps were removed and 10.6 minutes when polyps were removed. Withdrawal times correlated closely with lesion detection rates, whether or not polyps or masses were manipulated. In cases where polyps were removed, withdrawal times correlated inversely with polyp size, and longer withdrawal times correlated positively with the removal of polyps less than 5 mm in diameter. Endoscopists taking 6 minutes or longer to withdraw the colonoscope had significantly higher rates of detection of all adenomas, advanced adenomas, and hyperplastic lesions. Those with relatively long withdrawal times detected nearly 4-fold more adenomas than endoscopists with relatively short withdrawal times. The rates of detection of advanced neoplasms were 6.4% and 2.6%, respectively, and of all neoplasms, 28.3% and 11.8%. The findings in this observational study are preliminary and therefore should be cautiously interpreted. Nevertheless, they may inform future attempts to find ways of preventing colorectal cancer.