The Stanford Leisure-Time Activity Categorical Item (L-Cat): a single categorical item sensitive to physical activity changes in overweight/obese women.

BACKGROUND: Physical activity is essential for chronic disease prevention, yet <40% of overweight/obese adults meet the national activity recommendations. For time-efficient counseling, clinicians need a brief, easy-to-use tool that reliably and validly assesses a full range of activity levels, and, most importantly, is sensitive to clinically meaningful changes in activity. The Stanford Leisure-Time Activity Categorical Item (L-Cat) is a single item comprising six descriptive categories ranging from inactive to very active. This novel methodological approach assesses national activity recommendations as well as multiple clinically relevant categories below and above the recommendations, and incorporates critical methodological principles that enhance psychometrics (reliability, validity and sensitivity to change). METHODS: We evaluated the L-Cat's psychometrics among 267 overweight/obese women who were asked to meet the national activity recommendations in a randomized behavioral weight-loss trial. RESULTS: The L-Cat had excellent test-retest reliability (κ=0.64, P<0.001) and adequate concurrent criterion validity; each L-Cat category at 6 months was associated with 1059 more daily pedometer steps (95% CI 712-1407, ß=0.38, P<0.001) and 1.9% greater initial weight loss at 6 months (95% CI -2.4 to -1.3, ß=-0.38, P<0.001). Of interest, L-Cat categories differentiated from each other in a dose-response gradient for steps and weight loss (Ps<0.05) with excellent face validity. The L-Cat was sensitive to change in response to the trial's activity component. Women increased one L-Cat category at 6 months (M=1.0±1.4, P<0.001); 55.8% met the recommendations at 6 months whereas 20.6% did at baseline (P<0.001). Even among women not meeting the recommendations at both baseline and 6 months (n=106), women who moved 1 L-Cat categories at 6 months lost more weight than those who did not (M=-4.6%, 95% CI -6.7 to -2.5, P<0.001). CONCLUSIONS: Given strong psychometrics, the L-Cat has timely potential for clinical use such as tracking activity changes via electronic medical records, especially among overweight/obese populations who are unable or unlikely to reach national recommendations.

Assessing complexity and dynamics in epidemics: geographical barriers and facilitators of foot-and-mouth disease dissemination.

Introduction: Physical and non-physical processes that occur in nature may influence biological processes, such as dissemination of infectious diseases. However, such processes may be hard to detect when they are complex systems. Because complexity is a dynamic and non-linear interaction among numerous elements and structural levels in which specific effects are not necessarily linked to any one specific element, cause-effect connections are rarely or poorly observed. Methods: To test this hypothesis, the complex and dynamic properties of geo-biological data were explored with high-resolution epidemiological data collected in the 2001 Uruguayan foot-and-mouth disease (FMD) epizootic that mainly affected cattle. County-level data on cases, farm density, road density, river density, and the ratio of road (or river) length/county perimeter were analyzed with an open-ended procedure that identified geographical clustering in the first 11 epidemic weeks. Two questions were asked: (i) do geo-referenced epidemiologic data display complex properties? and (ii) can such properties facilitate or prevent disease dissemination? Results: Emergent patterns were detected when complex data structures were analyzed, which were not observed when variables were assessed individually. Complex properties-including data circularity-were demonstrated. The emergent patterns helped identify 11 counties as 'disseminators' or 'facilitators' (F) and 264 counties as 'barriers' (B) of epidemic spread. In the early epidemic phase, F and B counties differed in terms of road density and FMD case density. Focusing on non-biological, geographical data, a second analysis indicated that complex relationships may identify B-like counties even before epidemics occur. Discussion: Geographical barriers and/or promoters of disease dispersal may precede the introduction of emerging pathogens. If corroborated, the analysis of geo-referenced complexity may support anticipatory epidemiological policies.

Clinical and acquired immunologic responses to West Nile virus infection of domestic chickens (Gallus gallus domesticus).

Numerous bird species are highly susceptible to North American strains of West Nile virus (WNV), and although domestic chickens are relatively resistant to WNV-associated disease, this species currently represents the most practical avian model for immune responses to WNV infection. Knowledge of the immunomodulation of susceptibility to WNV in birds is important for understanding taxonomic differences in infection outcomes. While focusing on immunophenotyping of CD3(+), CD4(+), CD8(+), and CD45(+) lymphocyte subpopulations, we compared lymphocyte subpopulations, blood chemistries, cloacal temperatures, IgM and IgG antibody titers, and differential whole-blood cell counts of WNV-infected and uninfected hens. Total blood calcium and lymphocyte numbers were lower in WNV-infected chickens compared with uninfected chickens. The heterophil-to-lymphocyte ratio increased over time from 2 to 22 d postinoculation (DPI) in uninfected chickens and from 2 to 8 DPI in WNV-infected chickens, although levels declined from 8 to 22 DPI in the latter group. No significant differences were found in the remaining immunological and hematological variables of the WNV-infected and uninfected groups. Our results reaffirm that chickens are resistant to WNV infection, and demonstrated that the heterophil-to-lymphocyte ratio differed between groups, allowing for sorting of infection status. Similar patterns in immune responses over time in both infected and uninfected hens may be related to age (i.e., 10 wk) and associated immune development.

Incidence and severity of acute cellular rejection in recipients undergoing adult living donor or deceased donor liver transplantation.

Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the adult-to-adult living donor liver transplantation (A2ALL) retrospective cohort study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow-up was 778 and 713 days, respectively. Rates of clinically treated and biopsy-proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with >/=1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had >/=1 biopsy-proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (p = 0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy-proven rejection (p = 0.97) and graft loss due to rejection (p = 0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique posttransplant immunosuppression protocols for LDLT recipients.

Unilateral soft palate palsy secondary to blunt neck trauma: a case report.

Unilateral soft palate paralysis is rare. No cases of unilateral soft palate paralysis with associated velopharyngeal insufficiency (VPI) secondary to minor blunt neck trauma have been reported to date. This case details the presentation of a man with isolated unilateral soft palate paralysis and associated velopharyngeal insufficiency following a collision with an opponent when playing soccer.

Recipient morbidity after living and deceased donor liver transplantation: findings from the A2ALL Retrospective Cohort Study.

Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than two-fold higher when centers had performed 40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT.

Experience with low-dose valganciclovir prophylaxis in adult liver transplant recipients.

Valganciclovir (VGCV) is considered the agent of choice after organ transplant for cytomegalovirus (CMV) prophylaxis. The purpose of this retrospective study was to determine the effectiveness and safety of a low-dose regimen after liver transplant (OLT). Eighty-five patients who underwent OLT between August 2002 and August 2004 were included. All patient data for the first 12 months after transplant were collected. Patients received VGCV 450 mg once daily for 3 months posttransplant. CMV infection was based on detection of CMV virus or viral proteins in blood. CMV disease was defined by the presence of positive antigenemia/viremia and evidence of clinical symptoms and/or tissue findings. Patients were D+R+ (54%) and D-R+ (29%), D+R-(11%) and D-R-(6%). Overall, CMV infection and disease occurred in 13% (11/85). CMV infection and disease occurred in 7% and 6%, respectively. CMV infection and disease occurred in 44% (D+R-), 13% (D+R+), 4% (D-R+) patients. The mean time to onset of CMV infection and disease was 103 days (14 to 312 days). Overall, 82% of patients received antibody therapy. The most common adverse events associated with VGCV were leukopenia (16%), thrombocytopenia (4%), anemia (<1%), and neurotoxicity (<1%). Low-dose VGCV was not an effective means to prevent CMV infection in high-risk (D+R-) patients, especially those who received antibody induction. High-risk patients may require a high-dose regimen, such as 900 mg daily, and/or a longer period of prophylaxis, and/or reduction in the use of potent antibody treatments after liver transplant.

[In vitro evidence for pancreatic lineage: Ngn3 positive cells are endocrine progenitors derived from cultured islets].

OBJECTIVE: Further studies have been conducted to evaluate the roles of Ngn3 in adult islet maintenance and renewal. METHODS: Islets were isolated from 6 - 8 week old male C57BL/6 mice. After common bile duct cannulation, the pancreas was resected and digested in collagenase V (2.5 mg/ml). Islets were then handpicked and 10 - 12 islets were plated in 60 mm culture dish and cultivated with RPMI-1640, which contained 12.5 mmol/L HEPES, 5.2 mmol/L glucose and 2% fetal bovine serum (FBS). Islet cells were analyzed by immunocytochemistry methods for A6, insulin, glucagon, nestin, Ngn3 and 5-bromo-2'-deoxy-uridine (BrdU). RESULTS: The results of these studies indicated that less than 15 percent of proliferated islet cells were Ngn3 expressing cells, in which about one third of the Ngn3 positive cells co-expressed A6. The existence of Ngn3 in cultured islet cells is consistent with the results from other's findings both in embryogenesis and adult islet studies. A significant finding of our study is that the existence of A6 and Ngn3 co-expressing cells in the cultured islet. A6 is a marker for identifying bile duct epithelial cell oriented hepatic progenitor cells. Islet-derived A6 cells are possibly born in the adult pancreatic duct and migrate into islets. A6 cells co-express Ngn3 when these cells commit to endocrine lineage within the islets. More interestingly, islet-derived A6 positive cells have the potential to transdifferentiate into hepatic cells. CONCLUSION: The presence of Ngn3(+) and A6(+) cells in the cultured islets suggests that the four established islet cell types arise from a common endocrine lineage residing within the adult islets. A6 and Ngn3 are useful markers for understanding intra-islet adult stem cell lineages in our future studies. This approach may allow for significant advances in understanding the IPC proliferation and differentiation, and open the possibility of using intra-islet adult stem cells for diabetes treatment.

Systems Biology and Ratio-Based, Real-Time Disease Surveillance.

Most infectious disease surveillance methods are not well fit for early detection. To address such limitation, here we evaluated a ratio- and Systems Biology-based method that does not require prior knowledge on the identity of an infective agent. Using a reference group of birds experimentally infected with West Nile virus (WNV) and a problem group of unknown health status (except that they were WNV-negative and displayed inflammation), both groups were followed over 22 days and tested with a system that analyses blood leucocyte ratios. To test the ability of the method to discriminate small data sets, both the reference group (n = 5) and the problem group (n = 4) were small. The questions of interest were as follows: (i) whether individuals presenting inflammation (disease-positive or D+) can be distinguished from non-inflamed (disease-negative or D-) birds, (ii) whether two or more D+ stages can be detected and (iii) whether sample size influences detection. Within the problem group, the ratio-based method distinguished the following: (i) three (one D- and two D+) data classes; (ii) two (early and late) inflammatory stages; (iii) fast versus regular or slow responders; and (iv) individuals that recovered from those that remained inflamed. Because ratios differed in larger magnitudes (up to 48 times larger) than percentages, it is suggested that data patterns are likely to be recognized when disease surveillance methods are designed to measure inflammation and utilize ratios.

Pharmaceutical industry interactions of psychiatric trainees from 20 European countries.

BACKGROUND: Interactions between the pharmaceutical industry (PI) and psychiatrists have been under scrutiny recently, though there is little empirical evidence on the nature of the relationship and its intensity at psychiatry trainee level. We therefore studied the level of PI interactions and the underlying beliefs and attitudes in a large sample of European psychiatric trainees. METHODS: One thousand four hundred and forty-four psychiatric trainees in 20 European countries were assessed cross-sectionally, with a 62-item questionnaire. RESULTS: The total number of PI interactions in the preceding two months varied between countries, with least interactions in The Netherlands (M (Mean)=0.92, SD=1.44, range=0-12) and most in Portugal (M=19.06, SD=17.44, range=0-100). Trainees were more likely to believe that PI interactions have no impact on their own prescribing behaviour than that of other physicians (M=3.30, SD=1.26 vs. M=2.39, SD=1.06 on a 5-point Likert scale: 1 "completely disagree" to 5 "completely agree"). Assigning an educational role to the pharmaceutical industry was associated with more interactions and higher gift value (IRR (incidence rate ratio)=1.21, 95%CI=1.12-1.30 and OR=1.18, 95%CI=1.02-1.37). CONCLUSIONS: There are frequent interactions between European psychiatric trainees and the PI, with significant variation between countries. We identified several factors affecting this interaction, including attribution of an educational role to the PI. Creating alternative educational opportunities and specific training dedicated to PI interactions may therefore help to reduce the impact of the PI on psychiatric training.

HIV infection and risk factors among the armed forces personnel stationed in Kinshasa, Democratic Republic of Congo.

Despite recent declines in HIV incidence, sub-Saharan Africa remains the most heavily affected region in the global HIV/AIDS epidemic. Estimates of HIV prevalence in African military personnel are scarce and inconsistent. We conducted a serosurvey between June and September 2007 among 4043 Armed Forces personnel of the Democratic Republic of Congo (FARDC) stationed in Kinshasa, Democratic Republic of Congo (DRC) to determine the prevalence of HIV and syphilis infections and describe associated risk behaviours. Participants provided blood for HIV and syphilis testing and responded to a demographic and risk factor questionnaire. The prevalence of HIV was 3.8% and the prevalence of syphilis was 11.9%. Women were more likely than men to be HIV positive, (7.5% vs. 3.6% respectively, aOR: 1.66, 95% C.I: 1.21-2.28, p < 0.05). Factors significantly associated with HIV infection included gender and self-reported genital ulcers in the 12 months before date of enrollment. The prevalence of HIV in the military appears to be higher than the general population in DRC (3.8% vs. 1.3%, respectively), with women at increased risk of infection.

A potent, nonpeptidyl 1H-quinolone antagonist for the gonadotropin-releasing hormone receptor.

Extensive development of the structure-activity relationships of a screening lead determined three important pharmacophores for gonadotropin-releasing hormone (GnRH) receptor antagonist activity. Incorporation of the 3,4,5-trimethylphenyl group at the 3-position, 2-(2(S)-azetidinyl)ethoxy group at the 4-position, and N-4-pyrimidinylcarboxamide at the 6-position of the quinolone core resulted in the identification of 4-(2-(azetidin-2(S)-yl)ethoxy)-7-chloro-2-oxo-3-(3,4,5-trimethylphenyl)-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (1) as a potent antagonist of the GnRH receptor. A 10(4)-fold increase in in vitro binding affinity is observed for the GnRH receptor as compared to the initial screening lead. Compound 1 exhibits nanomolar binding activity and functional antagonism at the human receptor and is 7-fold less active at the rhesus receptor. Intravenous administration of compound 1 to rhesus monkeys results in a significant decrease of the serum levels of downstream hormones, luteinizing hormone (79% decrease in area under the curve) and testosterone (92% decrease in area under the curve), at a dose of 3 mg/kg. Quinolone 1 is a potent nonpeptidyl antagonist for the human GnRH receptor that is efficacious for the suppression of luteinizing hormone and testosterone in primates.

A statewide, population-based, time series analysis of access to liver transplantation.

While the number of patients listed for liver transplant has increased, the pool of donor organs has remained constant. Questions have arisen regarding equitable access to organs. The purpose of this study was to analyze factors associated with access to liver transplantation (LT) using a large, population-based, hospital discharge database. The primary hypothesis was that a variety of factors other than medical need could be associated with access to LT. The rate of LT was defined as the number of liver transplants per admission for liver disease. The data sources were selected to allow a population-based, time-series analysis of all patients admitted with liver disease and those receiving liver transplants in all 157 nonfederal hospitals in North Carolina from 1988 to 1993. The hypotheses of this study were that age, gender, payment source, type of liver disease, distance from the transplant center, and rural county of residence were associated with patients' likelihood of access to LT. During the six years studied, 56,803 patients were admitted with liver disease and 126 underwent liver transplantation (LT). The rate of LT increased from 0.07% to 0.27%. Age, gender, source of payment, type of liver disease, rural county of residence, and distance of residence from the transplant center were associated with rates of transplantation. In the multivariate model, source of payment appeared to have the strongest association with the likelihood of LT. These findings raise important questions associated with equitable access to health care, need for physician education, and transplant center regionalization.

Growth, developmental stability and immune response in juvenile Japanese quails (Coturnix coturnix japonica).

Stresses are environmental factors which restrict growth or cause a potentially adverse change in an organism. The exposure of developing organisms to environmental stresses may have several physiological consequences including a decrease in immunocompetence. However, mounting an immune response against a foreign antigen may in itself constitute a cost for developing organisms. This cost has potentially long-term consequences for adult function and fitness. This study examines the growth and developmental stability of Japanese quail++ chicks challenged by three non-pathogenic antigens: sheep red blood cells, which assess T-cell-dependent immune responses, and Mycoplasma synoviae and Newcastle disease virus, which assess T-cell-independent responses. Increases in both body mass and wing length were significantly reduced in antigen-challenged birds compared to control birds. Fluctuating asymmetry (FA) in the masses of primary feathers increased from the innermost (1) to the outermost (10) position on the wing. In addition, antigen challenge by M. synoviae and sheep red blood cells was associated with an increase in FA. The cell-mediated response measured by reaction to phytohaemagglutinin was significantly depressed in M. synoviae-challenged birds. White blood cell counts, except for monocytes, were elevated in response to all three antigen treatments. Total plasma protein and haematocrit also differed between treatments but exhibited no clear relationship to antigen challenge. Immune responses clearly impose a stress on developing chicks. Additional research will be required to determine the long-term consequences of developmental stress and assess the selective forces that influence the strength of the immune responses of chicks.

Hepatic progenitors and strategies for liver cell therapies.

Liver cell therapies, including liver cell transplantation and bioartificial livers, are being developed as alternatives to whole liver transplantation for some patients with severe liver dysfunction. Hepatic progenitors are proposed as ideal cells for use in these liver cell therapies given their ability to expand extensively, differentiate into all mature liver cells, have minimal immunogenicity, be cryopreservable, and reconstitute liver tissue when transplanted. We summarize our ongoing efforts to develop clinical programs of hepatic progenitor cell therapies with a focus on hepatic stem cell biology and strategies that have emerged in analyzing that biology.

A model utilizing adult murine stem cells for creation of personalized islets for transplantation.

Clinical islet cell transplantation has demonstrated great promise for diabetes treatment. Two major obstacles are the organ donor shortage and the immunoresponse. The purpose of this study was to create a model using the patient's own adult stem cell sources, possibly in combination with non-self cells, such as pancreatic, hepatic, or embryonic stem cells, to create "personalized" islets. We hypothesize that the reconstructed islets have the normal capability to produce insulin and glucagon with reduced immunoresponses after transplantation. Stem cells are a proliferating population of master cells that have the ability for self-renewal and multilineage differentiation. The recently developed photolithograph-based, biologic, microelectromechanic system (BioMEMS) technique supplies a useful tool for biomedical applications. Our lab has developed a novel method that integrates the adult stem cell and BioMEMS to reconstruct personalized islets. We selected islet-derived progenitor cells (IPC) for repairing and reconstructing STZ-diabetic islets. A6(+)/PYY(+) or A6(+)/ngn3(+) cells were selected to manipulate the neoislets. After 3 to 4 weeks in culture, the reconstructed cells formed islet-like clusters containing insulin or glucagon producing cells. The pilot results showed the ability of these reconstructed islets to correct hyperglycemia when transplanted into a STZ-diabetic isograft mouse model. Although several technical problems remain with the mouse model, namely, the difficulty to collect enough islets from a single mouse because of animal size, the mouse isograft model is suitable for personalized islet development.

Trace metals in ancient hair from the Karluk Archaeological Site, Kodiak, Alaska.

Considerable interest exists in characterizing the extent of changes in methylmercury exposures from preindustrial to modern-day times. Hair is often preserved over centuries and has been useful in determining the extent of dietary trace metal exposures, particularly methylmercury. We examined 16 human hair samples taken from human hair bundles buried in the soil of the Karluk One Archaeological site located near the current Karluk village on the Kodiak Archipelago of Alaska. Hair samples were analyzed for total mercury, methylmercury, selenium, and cadmium. The mean total mercury level was 1.33 ppm (SD = 1.09). The mean methylmercury level, however, was considerably lower than the total mercury concentration: the mean methylmercury level was 0.03 ppm (SD = 0.02). The mean cadmium level was 0.15 ppm (SD = 0.14) and the mean selenium level was 5.22 ppm (SD = 5.73). While the concentration of total mercury in the Karluk hair samples is comparable to those observed in ancient hair from other locations, direct methylmercury quantization demonstrated that methylmercury levels were less than 2% of the total mercury in these hair samples. Because the hair was subjected to a variety of environmental influences over the centuries, the possibility of degradation of methylmercury in the hair over the last 400 to 800 years cannot be ruled out. The use of hair from remains found in more protected frozen or dry environments may provide the best evidence for the extent of preindustrial exposures to methylmercury and other trace metals.

Anesthesia for thoracoscopy: an overview.

Advances in technology have provided the means to reduce the length of stay for some surgical patients while offering increased quality of care. Videoscopic surgery is a rapidly expanding technology with increasing applications. When used in place of open thoracotomy, thoracoscopy offers the patient a less traumatic treatment modality. This procedure presents challenges to the anesthetist in choosing anesthetic technique, patient monitoring, and maintenance of cardiorespiratory function in the presence of pneumothorax and a variety of coexisting disease states.

Quick splint for acute boutonniére injuries.

Injuries to the proximal interphalangeal (PIP) joint are common in athletes, especially in contact and ball sports(1). Most PIP injuries involve disruption of the volar plate or dorsal dislocation. Less common is the "boutonniére" injury, which, if left undiagnosed and untreated, results in a boutonniére deformity. This deformity is difficult to manage and often requires prolonged immobilization and/or surgery to regain function(2).

Exercise management.

Aerobic exercise is receiving increasing emphasis as an important health promoting behavior. This paper provides a model for assessment and management of the healthy exercising adult. A data base is presented that enables the practitioner to determine the presence of risk factors and/or disease, to identify health problems which might modify exercise prescription and to collect information to individualize the prescription. The remainder of the paper details the elements of exercise prescription with a specific focus on patient education.