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Background: Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs. Results: The microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon–Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray–Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts like Escherichia/Shigella, Acinetobacter or Stenotrophomonas was reduced by PERT. Conclusion: These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT., Finanziert über die DEAL-Vereinbarung mit Wiley 2019-2022.

All Medicaid programs pay for fluoride varnish applications during medical visits for infants and toddlers, but receipt of care varies considerably across states. Using 2006–2014 Medicaid data from 22 states, this study examined the association between Medicaid payment and receipt of fluoride varnish during pediatric medical visits. Among 3,393,638 medical visits, fewer than one in 10 visits included fluoride varnish. Higher Medicaid payment was positively associated with receipt of fluoride varnish during pediatric medical visits. As policymakers consider strategies for increasing young children’s access to preventive oral health services, as well as consider strategies for balancing budgets, attention should be paid to the effects of provider payment on access to pediatric oral health services.

It is important to better understand factors associated with physical activity (PA) levels in adolescents in rural areas. Cross-sectional data were used to obtain self-reported PA levels among adolescents in a school-based intervention in fall 2018. Demographic data, environmental variables, and cardiovascular fitness (PACER score) were also measured. Analyses included a two-sample t-test, ANOVA, a Chi-square test, and a linear regression model. Participants included 3799 7th graders. Male (p < 0.0001), white (p < 0.0001), and healthy weight (p < 0.0001) participants reported more days of PA. The correlation between school physical education (PE) and PACER was modest (r = 0.27, p < 0.0001). Multiple linear regression model showed significant effects of school PE (p = 0.0011), gender (p < 0.0001), race (p < 0.0001), and weight category (p < 0.0001) on self-reported PA. The percentage of students reporting 60 min of PA for 5 (p < 0.0001) or 7 (p = 0.0307) days per week tended to be higher with increased days per week of school PE. Policy changes that increase PA and PE in middle schools may present opportunities to improve PA levels in adolescents, with emphasis on being inclusive and mindful of minority and female youth.

Buprenorphine is an effective medication for the treatment of opioid use disorder (OUD), but the association between prior authorization policies and quality of care for individuals receiving buprenorphine treatment is not well-understood.Using 2006-2013 Medicaid Analytic eXtract (MAX) data from 34 states and the District of Columbia, we identified 294,031 episodes of buprenorphine treatment for OUD among individuals aged 14-64 years. We estimated generalized difference-in-differences models to examine the association between buprenorphine prior authorization policies and changes in buprenorphine treatment quality along four dimensions: (1) duration of at least 180 days, (2) dosage of at least 8 milligrams, and concurrent prescribing of (3) opioid analgesics and (4) benzodiazepines.Buprenorphine prior authorization policies were associated with an 11-percentage point reduction (p 0.01) in the likelihood of episodes with a duration of at least 180 days in the first four years after policy implementation. The policy was not associated with changes in effective dosage or concurrent prescribing of opioid analgesics or benzodiazepines.Buprenorphine prior authorization policies were associated with a sizeable and significant reduction in episodes of at least 180 days duration, underscoring the importance of identifying and removing barriers to effective and appropriate OUD care.

INTRODUCTION: Exotic dance clubs (EDCs) can play pivotal roles in the production of drug-related risks for female exotic dancers (FED). We aimed to characterize the structural and occupational factors associated with new drug initiation post-EDC entry among new FED (N = 117) in Baltimore, Maryland. MATERIALS AND METHODS: Logistic regression models tested the associations of new drug uptake, measured as initiating any illicit drug (including non-prescribed and diverted prescription narcotics) not used prior to EDC employment, with structural (e.g. debt sources, housing instability) and occupational (e.g. sex work, dancing as sole income source) vulnerabilities. RESULTS: Most FED were younger than 24 years-old (60%), identified as Black/African American (61%), and did not complete high school (56%). Twenty-nine (25%) reported using any new drug post-EDC entry, with cocaine (34%) cited most frequently among newly initiated substances. In multivariable analysis, drug initiation was significantly associated with cumulative debt sources (Adjusted Odds Ratio [AOR] = 1.82, 95% Confidence Interval [CI]: 1.19–2.77), dancing as only income source (AOR = 4.21, CI: 1.29–13.71), and sex work (AOR = 9.26, CI: 2.74–31.32). CONCLUSIONS: Our findings implicate co-occurring structural and occupational factors in FED’s initiation of illicit drugs proceeding EDC employment. Results demonstrate the coping role of drug use for FED in stressful working environments and the multiple vulnerabilities associated with illicit drug uptake. The study reinforces a need for harm reduction interventions (i.e. debt relief, employment connections, increased hourly pay) that consider the contribution of overlapping financial insecurities to the production of occupational risks motivating drug uptake.

This study examined the development of muscular fitness and coordination in children and adolescents with and without attention deficit hyperactivity disorder (ADHD) over a period of 11 years. Data was collected in three measurement waves as part of the longitudinal, representative Motorik-Modul (MoMo) study in Germany (2003–2006, 2009–2012, 2014–2017). The overall sample comprised 2988 participants (253 with ADHD, 65% males; 2735 non-ADHD, 47% males; mean age 9 years). Structural equation modeling was conducted, and the estimated models had a good fit. No differences in muscular fitness were observed between participants with and without ADHD. Participants with ADHD had a lower coordinative performance at first measurement than those without ADHD. The difference in coordinative performance persisted throughout the study period.

Lead exposure can cause substantial organ damage. Enteral lead absorption may be reduced by concomitant intake of clinoptilolite tuff, a zeolite from natural sources. This study aimed to assess the effect of purified clinoptilolite tuff (G-PUR) on enteral lead uptake in adults using stable lead isotope 204Pb as a tracer. In this randomized, placebo-controlled, double-blind, parallel-group study, 42 healthy participants were randomized to receive oral G-PUR 2.0 g, 2 * 2.0 g, or placebo, together with 2.5 µg of 204Pb in water. The enrichment of 204Pb caused by the tracer in blood and urine was measured by mass spectrometry. G-PUR was well tolerated. The mean maximum 204Pb enrichment of 0.505% of total blood lead was significantly higher (p 204Pb AUC0-192 was 86.5, 11.9, and 8.5% * h without and with G-PUR 2.0 g, and G-PUR 2 * 2.0 g, respectively (p 204Pb exposure was paralleled by a reduced urinary excretion in subjects receiving G-PUR. Concomitant oral intake of purified clinoptilolite tuff reduced enteral uptake of 204Pb in healthy humans by approximately 90%. The reduced bioavailability is demonstrable by a decrease of 204Pb tracer enrichment in blood and urine.Trial registration: clinicaltrials.gov identifier: NCT04138693, registered 24/10/2019.

BACKGROUND: To increase receipt of preventive oral health services, all state Medicaid programs have enacted policies to encourage non-dental providers to deliver preventive oral health services (POHS) in medical offices. This study examined if these Medicaid policies improved oral health, as measured by reductions in dental visits with treatment and preventable ED visits for non-traumatic dental conditions (NTDC). METHODS: Using data on children aged six months to up to six years from 38 state Medicaid programs during 2006–2014, we used a generalized difference-in-differences estimation approach to examine the probability of a child having, in a year, any dental visits with caries-related treatment and any ED visits for NTDC, conditional on length of policy enactment. Models included additional child- and county-level characteristics, state and year fixed effects, probability weights, and clustered standard errors. RESULTS: Among a weighted sample of 45,107,240 child/year observations, 11.7% had any dental visits with treatment and 0.2% had any ED visits for NTDC annually. Children in states with and without medical POHS policies had similar odds of having any dental visits with treatment, regardless of length of policy enactment. Children in states with medical POHS policies enacted for one or more years had significantly greater odds of having any ED visits for NTDC (P

Objective Patients with severe infection or sepsis require fast identification of the focus and prompt eradication. This study aims at investigating the role of body computed tomography (CT) and identifying outcome predictors in a general ward setting of patients with obscure infection. Methods We retrospectively identified 196 consecutive body CTs acquired in 179 patients with obscure infection, i.e. severe infection or sepsis from general wards with unclear focus, over 12-months in the year 2018. Reports were extracted using a full-text search in the radiological information system (RIS) of a large university medical center. CT reports were classified according to diagnostic confidence of the reader (i.e. certain, likely, possible, no focus), and correlated with clinical and laboratory parameters. The discharge diagnosis was set as the diagnostic reference standard. Contingency tables were prepared for statistical analysis with Chi-squared test amongst other analyses and the calculation of AUC statistics. Results In 133 out of 196 (67.9 %) body CTs from general wards with severe infection or sepsis, body CT identified an infectious focus. 90 % of the infections were located in the chest, abdomen, and genitourinary tract, in descending order. In 76.5 % (150 of 196) of examinations, CT correctly predicted the final infectious source. The positive predictive value (PPV) of a CT-detected focus was 84.2 % (95 % CI 79.0%–88.3%). A high diagnostic confidence of the reader resulted in a PPV of 96.4 % (95 % CI 87.4%–99.1%) while a low confidence resulted in a PPV of 63.3 % (95 % CI 48.2%–76.3%). Conclusion In patients with obscure infection treated in general wards, body CT detects the infectious source with a high positive predictive value. Focus detection accuracy highly depends on the diagnostic confidence of the CT reader.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide widely distributed in the nervous system, where it exerts strong neuroprotective effects. PACAP is also expressed in peripheral organs but its peripheral protective effects have not been summarized so far. Therefore, the aim of the present paper is to review the existing literature regarding the cytoprotective effects of PACAP in non-neuronal cell types, peripheral tissues, and organs. Among others, PACAP has widespread expression in the digestive system, where it shows protective effects in various intestinal pathologies, such as duodenal ulcer, small bowel ischemia, and intestinal inflammation. PACAP is present in both the exocrine and endocrine pancreas as well as liver where it reduces inflammation and steatosis by interfering with hepatic pathology related to obesity. It is found in several exocrine glands and also in urinary organs, where, with its protective effects being mainly published regarding renal pathologies, PACAP is protective in numerous conditions. PACAP displays anti-inflammatory effects in upper and lower airways of the respiratory system. In the skin, it is involved in the development of inflammatory pathology such as psoriasis and also has anti-allergic effects in a model of contact dermatitis. In the non-neuronal part of the visual system, PACAP showed protective effects in pathological conditions of the cornea and retinal pigment epithelial cells. The positive role of PACAP has been demonstrated on the formation and healing processes of cartilage and bone where it also prevents osteoarthritis and rheumatoid arthritis development. The protective role of PACAP was also demonstrated in the cardiovascular system in different pathological processes including hyperglycaemia-induced endothelial dysfunction and age-related vascular changes. In the heart, PACAP protects against ischemia, oxidative stress, and cardiomyopathies. PACAP is also involved in the protection against the development of pre-senile systemic amyloidosis, which is presented in various peripheral organs in PACAP-deficient mice. The studies summarized here provide strong evidence for the cytoprotective effects of the peptide. The survival-promoting effects of PACAP depend on a number of factors which are also shortly discussed in the present review.

Patients with cancer are vulnerable to Clostridium difficile infection (CDI); hospitals with larger oncology populations may have worse CDI performance. Among 71 academic hospitals studied, there were significant differences in oncology patient-days per 1,000 admissions across CDI standardized infection ratio categories of better, no different, and worse; worse hospitals had the greatest number of patient-days. Oncology patients' most commonly used high-risk CDI medications were quinolones, third- and fourth-generation cephalosporins, and proton pump inhibitors.

Scientific Abstracts These scientific abstracts are scheduled for presentation at the 2021 Society of Family Planning Annual Meeting. This year, 225 abstracts were submitted for consideration, of which 12 were selected for oral presentation and 84 were selected for poster presentation. The scientific abstract review was completed by the scientific reviewers and selectors

The Consolidated Framework for Implementation Research guided formative evaluation of the implementation of a redesigned interprofessional team rounding process. The purpose of the redesigned process was to improve health team communication about hospital discharge. Themes emerging from interviews of patients, nurses, and providers revealed the inherent value and positive characteristics of the new process, but also workflow, team hierarchy, and process challenges to successful implementation. The evaluation identified actionable recommendations for modifying the implementation process.

Hue perception has been shown to differ for the same stimulus when presented to the temporal and the nasal areas of the retina. The present study investigated perceptual differences in stimuli viewed binocularly or monocularly in the peripheral retina to determine how hue information combines across the two retinas for a stimulus falling on the temporal retina of one eye and the nasal retina of the other. A hue-scaling procedure was utilized to ascertain hue perception for three color- and binocular-normal observers viewing monochromatic stimuli (450–670 nm, 20 nm steps) ranging in size from 1.0° to 3.7°. Peripherally-presented binocular stimuli fell upon the nasal retina of one eye and the temporal retina of the other. Hue-scaling results indicated that peripheral binocular hue and saturation perceptions for smaller stimuli were more similar to those of stimuli falling on the temporal retina in the monocular condition. Hue-scaling data were also used to determine perceptive field sizes for the four elemental hues. Binocular perceptive field sizes were more similar to those obtained for stimuli falling on the temporal retina in the monocular conditions. Eye dominance did not appear to have an effect on hue perception. The results seem to indicate that visual information from the temporal retina is weighted more heavily when information from the two eyes is combined cortically. This finding may relate to differences in V1 cortical activation for stimuli presented to the nasal retina versus the temporal retina.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide with a widespread distribution throughout the entire body including the urinary system. PACAP exerts protective actions in different injury models related to several organ systems. Its protective effect is mainly based on its antiapoptotic, anti-inflammatory and antioxidant effects. The present review aims to summarize the effects of PACAP in pathologies associated with inflammation and oxidative stress-induced damage in the kidney. Both in vitro and in vivo data are available proving its protective actions against oxidative stress, hypoxia, renal ischemia/reperfusion, diabetic nephropathy, myeloma kidney injury, amyloidosis and different types of drug-induced nephropathies. Data showing the nephroprotection by PACAP emphasize the potential of PACAP’s therapeutic use in various renal pathologies.

BACKGROUND AND RATIONALE Poor communication between health team members can interfere with timely, coordinated preparation for hospital discharge. Research on daily bedside interprofessional health team rounds and nursing bedside shift handoff reports provides evidence that these strategies can improve communication. AIMS To improve health team communication and collaboration about hospital discharge; improve patient experience of discharge measured by patient-reported quality of discharge teaching, readiness for discharge, and postdischarge coping difficulty; and reduce readmissions and emergency department (ED) visits postdischarge. METHODS A two-sample pre- and postintervention design provided baseline data for redesign of health team communication processes and comparison data for evaluation of the new process' impact. Health team members (n = 105 [pre], n = 95 [post]) from two surgical units of an academic medical center in the midwestern United States provided data on discharge-related communication and collaboration. Patients (n = 413 [pre], n = 191 [post]) provided data on their discharge experience (quality of discharge teaching, readiness for discharge, postdischarge coping difficulty) and outcomes (readmissions, ED visits). Chi-square and t tests were used for unadjusted pre- and postintervention comparisons. Logistic regression of readmissions with a matched pre- and postintervention sample included adjustments for patient characteristics and hospitalization factors. RESULTS Readmissions decreased from 18% to 12% (p

The purpose of this study was to determine whether pituitary adenylate cyclase activating polypeptide (PACAP) could influence the neovascularization processes in hyperosmotic and oxidative stress in retinal pigment epithelial cells. Hyperosmotic conditions and oxidative stress were induced by 200 mM sucrose and 250 µM hydrogen peroxide (H2 O2 ), respectively. Morphology and elasticity of adult retinal pigment epithelial (ARPE-19) cells were measured by atomic force microscopy, while the investigation of junctional molecules, such as occludin and ZO-1, was carried out using immunofluorescence. For cell viability measurement, the MTT test was used. The effect of PACAP on the key angiogenic factors, such as vascular endothelial growth factor, angiogenin, and endothelin-1, was measured by an angiogenesis array and flow cytometry. Hyperosmotic stress-induced reorganization of the cytoskeleton and impairment of the junctions decreased cell viability and upregulated several angiogenic factors. In oxidative stress, we found that opening of the junctions decreased viability and upregulated the expression of angiogenic factors. PACAP was shown to be protective in both conditions. Retinal pigment epithelium cells play an important role in several diseases, such as diabetic retinopathy and macular edema. Therefore, protecting retinal pigment epithelial (RPE) cells with PACAP could be a novel and potential treatment in these diseases.

Purpose/objectives The purpose of this article is to describe an innovative approach to the integration of quality improvement and research processes. A project with the objective of improving health team communication about hospital discharge provides an exemplar case. Description of the project/program The TeamSTEPPS 10-step action planning guide provided the structure for planning, developing, and evaluating a redesign of interprofessional health team communication to improve hospital discharge led by 2 clinical nurse specialists. The redesign involved development of processes for team bedside rounding, registered nurse bedside shift reports, and briefing tools to support the rounding processes. Outcome Using the TeamSTEPPS process, a 4-phase combined quality improvement and research project was designed and implemented. Implementation is ongoing, supported by process evaluation for continuing process improvement. Longitudinal analysis of research outcomes will follow in the future. Conclusions Led by unit-based clinical nurse specialists, use of an integrated process of quality improvement and research creates evidence-based innovation to solve interprofessional practice problems. Incorporating research within the project design allows for data-based decisions to inform the clinical process improvement, as well as documentation of both the processes and outcomes of the local improvements that can inform replications in other sites.

Understanding the decision process underlying gaze control is an important question in cognitive neuroscience with applications in diverse fields ranging from psychology to computer vision. The decision for choosing an upcoming saccade target can be framed as a selection process between two states: Should the observer further inspect the information near the current gaze position (local attention) or continue with exploration of other patches of the given scene (global attention)? Here we propose and investigate a mathematical model motivated by switching between these two attentional states during scene viewing. The model is derived from a minimal set of assumptions that generates realistic eye movement behavior. We implemented a Bayesian approach for model parameter inference based on the model's likelihood function. In order to simplify the inference, we applied data augmentation methods that allowed the use of conjugate priors and the construction of an efficient Gibbs sampler. This approach turned out to be numerically efficient and permitted fitting interindividual differences in saccade statistics. Thus, the main contribution of our modeling approach is two--fold; first, we propose a new model for saccade generation in scene viewing. Second, we demonstrate the use of novel methods from Bayesian inference in the field of scan path modeling., Comment: 24 pages, 10 figures

Therapy for post-transplant relapse of paediatric ALL is limited. Standardised curative approaches are not available. We hereby describe our local procedure in this life-threatening situation. A total of 101 ALL patients received their first allogeneic stem cell transplantation (SCT) in our institution. After relapse, our primary therapeutic goal was to cure the patient with high-dose chemotherapy or specific immunotherapy (HDCHT/SIT) followed by a second SCT from a haploidentical donor (transplant approach). If this was not feasible, low-dose chemotherapy and donor lymphocyte infusions (LDCHT+DLI) were offered (non-transplant approach). A total of 23 patients suffered a post-transplant relapse. Eight patients received HDCHT/SIT, followed by haploidentical SCT in 7/8. Ten received LDCHT+DLI. The eight patients treated with a second transplant and the ten treated with the non-transplant approach had a 4-year overall survival of 56% and 40%, respectively (P=0.232). Prerequisites for successful treatment of post-transplant relapse by either a second transplant or experimental non-transplant approaches are good clinical condition and the capacity to achieve haematological remission by the induction treatment element.

To compare 2 different risk factor models for the prediction of shoulder dystocia.We performed a retrospective study of women with vaginal deliveries at a single institution over an 8-year period. Two distinct multivariable logistic regression models were used to evaluate the occurrence of shoulder dystocia: a traditional model used information based on birthweight and macrosomia, and a clinical model used information based on esti-mated fetal weight and suspected macrosomia.Of the 13,998 deliveries analyzed, there were 221 cases of shoulder dystocia (1.6%). In addition to the macrosomia or suspected macrosomia variables, the final models included prolonged second stage of labor, diabetes status, and oxytocin use. Neither model was highly sensitive or highly specific, and neither demonstrated a cutoff threshold that yielded a clinically viable PPV.Despite the presence of 1 or more risk factors for shoulder dystocia, its occurrence remains largely an unpredictable clinical event.

Although vaccination against the Human Papilloma Virus (HPV) reduces the risk of related morbidities, the vaccine uptake remains low in adolescents. This has been attributed to limited parental knowledge and misconceptions. In this cross sectional study, we assessed the (1) clarity of educational material informing Hispanic mothers about HPV, cervical cancer and the HPV vaccine, (2) determined vaccination acceptability and (3) identified predictors of vaccine acceptance in an underserved health setting. 418 Hispanic mothers received the educational material and completed an anonymous survey. 91 % of participants understood most or all of the information provided. 77 % of participants reported vaccine acceptance for their children; this increased to 84 % when only those with children eligible to receive vaccination were included. Significant positive predictors of maternal acceptance of the HPV vaccine for their children were understanding most or all of the provided information, older age and acceptance of the HPV vaccine for themselves. Concerns about safety and general dislike of vaccines were negatively associated with HPV vaccine acceptance. Prior knowledge, level of education, previous relevant gynecologic history, general willingness to vaccinate and other general beliefs about vaccines were not significantly associated with HPV vaccine acceptance. The majority of participants reported understanding of the provided educational material. Vaccine acceptability was fairly high, but was even higher among those who understood the information. This study documents a cost-effective way to provide Hispanic mothers with easy-to-understand HPV-related information that could increase parental vaccine acceptability and future vaccine uptake among their children.

Earthworm's innate immunity is maintained by cellular and humoral components. Our objective was to characterize the cytotoxicity leading to target cell death caused by earthworm coelomocytes. Coelomocyte lysates induced strong cytotoxicity in tumor cell lines. Transmission electron microscopy revealed cell membrane and intracellular damage in cells treated with coelomocyte lysates. Using TUNEL-assay, within 5 min of incubation we detected DNA fragmentation. Moreover, we found phosphatidylserine translocation in target cell-membranes. Furthermore, we detected dose-dependent Ca 2+ influx and decrease of mitochondrial membrane potential in coelomocyte lysate-treated cells. Interestingly, caspase 3/8 activation was undetectable in exposed tumor cells. One such cytotoxic molecule, lysenin identified in earthworms binds to sphingomyelin and causes target cell lysis in vertebrates. Pretreatment with our anti-lysenin monoclonal antibody rescued the majority but not all target cells from coelomocyte induced death. These data suggest that, not only lysenin but also other factors participate in the caspase-independent apoptosis induced by coelomocytes.

Objective We set out to test the hypothesis that infants born vaginally at ≤ 30 weeks gestation have less respiratory distress syndrome (RDS) than those born by cesarean delivery. Study Design We conducted a retrospective cohort study of 652 infants born between 24 and 30 6/7 weeks gestation from March 31, 1996 to May 31, 2014. Comparisons of neonatal outcomes by intended and actual mode of delivery were made using chi-square and t-tests (α = 0.05). Multiple logistic regression was performed to control for confounding variables. Results Neonates born by cesarean delivery were more likely to have RDS (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.10–2.90), require intubation (OR, 1.80; 95% CI, 1.12–2.88), and have longer neonatal intensive care unit stay (70.0 ± 37.1 vs. 57.3 ± 40.1 days, p = 0.02). Conclusion Compared with cesarean delivery, vaginal delivery is associated with a significant reduction in RDS among infants born at ≤ 30 weeks gestation.

Although previous research on advance care planning (ACP) has associated ACP with improved quality of care at the end of life, the appropriate use of ACP remains limited.To evaluate the impact of a pilot program using the "Honoring Choices Wisconsin" (HCW) model for ACP in a tertiary care setting, and to understand barriers to system-wide implementation.Retrospective review of prospectively collected data.Patients who received medical or surgical oncology care at Froedtert and the Medical College of Wisconsin.Patient demographics, disease characteristics, patient satisfaction, and clinical outcomes.Data from 69 patients who died following the implementation of the HCW program were reviewed; 24 patients were enrolled in the HCW program while 45 were not. Patients enrolled in HCW were proportionally less likely to be admitted to the ICU (12.5% vs. 17.8%) and were more likely to be "do not resuscitate" (87.5% vs. 80.0%), as well as have a completed ACP (83.3% vs. 79.1%). Furthermore, admission to a hospice was also higher among patients who were enrolled in the HCW program (79.2% vs. 25.6%), with patients enrolled in HCW more likely to die in hospice (70.8% vs. 53.3%). The HCW program was favorably viewed by patients, patient caregivers, and healthcare providers.Implementation of a facilitator-based ACP care model was associated with fewer ICU admissions, and a higher use of hospice care. System-level changes are required to overcome barriers to ACP that limit patients from receiving end-of-life care in accordance with their preferences.

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide having a widespread distribution both in the nervous system and peripheral organs including the gastrointestinal tract. It has been shown to exert actions on intestinal functions, mainly affecting glandular secretion and motility. PACAP has several different effects on cell survival depending on the cell type and the applied stimulus. Its influences on small intestinal epithelial cells are not yet elucidated, therefore the aim of the present study was to investigate the effects of PACAP on intestinal epithelial cells having high turnover (INT 407) against different harmful stimuli, such as oxidative stress, in vitro hypoxia and gamma radiation. We tested the effect of PACAP on proliferation and cell survival using MTT assay. Moreover, various cancer-related factors were evaluated by oncology array. PACAP did not influence the proliferation rate of INT 407 cells. Its cell survival-enhancing effect could be detected against oxidative stress, but not against in vitro hypoxia or gamma irradiation. Clonogenic survival assay was performed to analyze the effect of PACAP on clonogenic potential of cells exposed to gamma radiation. Surprisingly, PACAP enhanced the clone-forming ability decrease induced by irradiation. Western blot analysis of ERK1/2 phosphorylation was performed in order to obtain further information on the molecular background. Our data showed phospho-ERK1/2 suppression of PACAP in irradiated cells. Furthermore, the role of endogenous PACAP against oxidative stress was also investigated performing ADCYAP1 small interfering RNA transfection. We found significant difference in the cell vulnerability between cells undergoing silencing and cells without transfection suggesting the protective role of the endogenously present PACAP against oxidative stress in INT 407 cells. In summary, PACAP seems to be able to exert contradictory effects in INT 407 cells depending on the applied stressor, suggesting its regulatory role in the cellular household.

The wide range of psychological and cognitive symptoms associated with schizophrenia can often affect the level of independence that individuals with schizophrenia can achieve in their lives. Prospective memory (PM), or memory associated with future intentions, has been proposed as a useful indicator of select independent living skills. Currently, there is limited research with regards to prospective memory in schizophrenia. The current review systematically summarizes the literature focusing on prospective memory in schizophrenia and concludes that individuals with schizophrenia exhibited both an impairment in PM when compared to healthy controls and a general lack of awareness regarding these deficits. The existing research also suggests that PM deficits are not related to chronicity of illness or medications associated with schizophrenia. Limited findings suggest that PM deficits in individuals with schizophrenia may be associated with the ability to live independently and instrumental activities of daily living.

Objective: To compare the incidence of histopathological features in placentas from women with cholestasis of pregnancy to healthy individuals without ICP. Methods: Placentas from mothers with and without cholestasis of pregnancy were reviewed by a pathologist masked to the study group. Subjects were excluded if they had medical problems already associated with placental histopathology. Results: Twenty-four cases and 30 controls placentas were reviewed. Seventeen placental histopathological features were found. There was no statistically significant difference between the groups. Amongst patients with cholestasis, there was a decrease in villitis of unknown etiology in those treated with ursodeoxycholic acid. Conclusion: There is no difference in the placental histopathology in cholestasis of pregnancy compared to normal pregnancies, but treatment of patients with cholestasis of pregnancy with ursodeoxycholic acid may decrease findings of villitis of unknown etiology.

Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

The link between depression, obesity, and fertility status is poorly understood among Latina women. The Patient Health Questionnaire 9 (PHQ-9) is routinely administered in the Diabetes and Obesity in Reproductive Age women Clinic. We describe median PHQ-9 score and PHQ-9 score ≥10 [indicative of Major Depressive Disorder (MDD)] by fertility status. Of the 76 eligible new patients seen between June 2008 and 2009, 18.4% (n = 14) had PHQ-9 scores indicative of MDD. Infertile women had marginally significantly higher PHQ-9 scores than non-infertile women (p = 0.08). 26.5% of infertile women and 12.2% of non-infertile women had a PHQ-9 score indicative of MDD (p = 0.14). Number of previous births was inversely correlated with PHQ-9 score (R = -0.34, p = 0.002), those with no previous births had higher PHQ-9 scores (p = 0.001) and were more likely to have a PHQ-9 score indicative of MDD than those with previous births (28.6 vs. 9.8%, p = 0.04). Among non-infertile women, postpartum women had significantly lower PHQ-9 scores than non-postpartum women (p = 0.002). 4.6% of postpartum women and 21.1% of non-postpartum women had a PHQ-9 indicative of MDD (p = 0.19). Further investigation is needed to determine if reproductive success is protective against MDD among overweight and obese urban Latinas. Overall, depression is common among overweight and obese reproductive-age Latinas and thus routine screening is recommended.

Objective To evaluate the clinical utility of dilation and curettage (D&C) in diagnosing ectopic pregnancy (EP). Design Retrospective cohort study. Setting University hospital. Patient(s) Clinically stable women (n = 321) who underwent a diagnostic D&C with no visible intrauterine pregnancy (IUP) on transvaginal ultrasound or those with an abnormal hCG trend. Intervention(s) None. Main Outcome Measure(s) EP or IUP made by final pathologic review. Result(s) Overall, 73.2% of the patients were ultimately diagnosed with EP and 26.8% were found to have a nonviable IUP. Those with EPs had significantly lower initial hCGs than those with nonviable IUPs and were more likely to have had a history of an EP. On ultrasound, the overall impression, the presence of free fluid, and the endometrial echo complex correlated well with the final diagnoses but did not have 100% predictive value. Conclusion(s) D&C remains valuable to differentiate EP from nonviable IUP and to avoid misdiagnosis and unnecessary exposure to methotrexate. Low initial hCG values and ultrasound findings such as a thin endometrial echo complex and the presence of free fluid are associated with but are not diagnostic of an ectopic pregnancy.

The aim of the ‘Motorik-Modul’ (MoMo Basiserhebung, www.motorik-modul.de ) was to establish prevalence measurements on physical fitness and physical activity in German children and adolescents and to identify differences between age groups and genders. A total of 4,529 children and adolescents between the ages of 4–17 years from 167 cities across all states of the German Federation participated in this study. Sociodemographic parameters were recorded. Physical fitness was measured using endurance, strength, coordination and flexibility tests. Physical activity was assessed using a validated questionnaire, including aspects of physical activity participation (school/club/non-club), intensity of physical activity and type of activity. Chi-square tests and ANOVAS were used to compare groups and to detect age and gender effects, and data were compared with criterion-related guidelines by the WHO. For parameters describing physical fitness, age was the dominant influencing parameter. Many parameters showed increasing performance until the onset of puberty. Boys generally performed better than girls except in fine motor coordination during precision tasks and in flexibility. Physical activity was greater in older subjects with a greater intensity for adolescents who were physically active. The general activity level was similar to the data reported in the HBSC study by the WHO but lower than the recommended activity levels. With the results of this study, nationwide representative prevalence data on physical fitness and physical activity are available. These data contribute to the scientific knowledge on the prevalence and conditions of physical fitness and physical activity.

The variational approximation of posterior distributions by multivariate gaussians has been much less popular in the machine learning community compared to the corresponding approximation by factorizing distributions. This is for a good reason: the gaussian approximation is in general plagued by an [Formula: see text] number of variational parameters to be optimized, N being the number of random variables. In this letter, we discuss the relationship between the Laplace and the variational approximation, and we show that for models with gaussian priors and factorizing likelihoods, the number of variational parameters is actually [Formula: see text]. The approach is applied to gaussian process regression with nongaussian likelihoods.

To determine whether a newer commercially available antimüllerian hormone (AMH) enzyme-linked immunosorbent assay (picoAMH ELISA, AnshLabs) with a lower threshold of detection is predictive of successful ovarian stimulation in a population of women with diminished ovarian reserve (DOR).Retrospective case-control study.University-based IVF program.Cases were patients whose first IVF cycle was cancelled for lack of ovarian response (3 follicles; n = 24). Controls were patients with DOR (early follicular FSH of ≥10 IU/L), whose first cycle resulted in aspiration of at least 3 oocytes (n = 24).Frozen serum samples collected during routine clinical care between 2008 and 2012 before starting IVF were analyzed for AMH using the picoAMH ELISA.Serum AMH levels in patients who successfully reached oocyte retrieval compared with patients with a failed controlled ovarian hyperstimulation (COH) cycle. Receiver operator curve analysis was used to identify a predictive threshold AMH value.No demographic differences were found between groups. The successful group had a higher antral follicle count (8.5 vs. 6) and higher AMH levels (847 vs. 406 pg/mL). The AMH level correlated with the antral follicle count (R = 0.61). The AMH level of500 pg/mL had 83.3% sensitivity and 70.8% specificity to detect patients who proceeded to successful oocyte retrieval. Below AMH levels of 100 pg/mL, no patients achieved oocyte retrieval.Due to a lower threshold of detection, picoAMH may be able to predict successful ovarian stimulation among women with DOR using a threshold of 500 pg/mL, with good sensitivity and specificity.

We argue that leadership promotion in China's political elite relies on homophily for signals of trustworthiness and future cooperative behavior more than on economic performance. We first point to the limitation of the economic performance argument from within the framework of China's specific M-form state structure, and then we proffer a sociological explanation for why higher-level elites in China rely on homophilous associations in recruiting middle-level elites to the top positions of state. Using a unique dataset covering China's provincial leaders from 1979 to 2011, we develop a homophily index focusing on joint origin, joint education and joint work experience. We trace personal similarities in these respects between provincial leaders and members of China's supreme decision-making body, the Politbureau's Standing Committee. We then provide robust evidence confirming the persisting impact of homophilous associations on promotion patterns in post-reform China.

Staphylococcus aureus is one of the most significant pathogens causing nosocomial and community-acquired infections. Among the secreted staphylococcal virulence factors, there is a growing list of enterotoxins which can induce gastroenteric syndrome and toxic shock syndrome. Here, we developed a real-time fluorescence PCR assay (TaqMan PCR) for the detection of genes encoding staphylococcal enterotoxins A, B, C1, and D (SEA, SEB, SEC1, and SED) of S . aureus as well as the mecA gene encoding methicillin resistance and the femB gene as a specific genomic marker for S . aureus . SEA to SED were selected because they are the four classically described enterotoxins of S . aureus and because they were detected by latex agglutination. In order to evaluate the reliability of TaqMan PCR, we investigated 93 isolates of S . aureus derived from patients at our hospital over 5 months and compared the results with data obtained by a commerciall available reversed passive latex agglutination assay (SET-RPLA) for these isolates. Thirteen enterotoxin genes were detected by TaqMan PCR; however, no proteins expressed by these genes were detected by SET-RPLA. As a result, more isolates of S . aureus ( n = 44) were found positive by TaqMan PCR for one or more enterotoxin genes than by SET-RPLA for the respective proteins expressed by these genes ( n = 40). We conclude that TaqMan PCR is more sensitive because it offers the possibility for determining enterotoxins on a genotypic basis. Additionally, the assay allows the parallel detection of genes for SEA to SED and methicillin resistance in S . aureus . Furthermore, real-time PCR is well suited for screening large numbers of samples at the same time, allowing rapid, reliable, efficient, and cost-saving routine laboratory diagnosis.

It was previously reported that, compared to healthy individuals, patients with coronary heart disease (CHD) exhibit a higher proportion of platelets with lower densities and higher propensity to aggregate. Reasons for this increased tendency to aggregate were unknown but appeared to be independent of the patient's age, gender, or smoking habits. Sialic acid (N-acetyl-neuraminic acid), a negatively charged sugar and constituent of many glycoproteins and gangliosides, is known to confer the bulk of negative charges to mammalian cell surfaces. These negatively charged surfaces can help cells of the bloodstream to maintain a relative distance from each other due to repulsion of the same (negative) charges. In this study, we examined whether differences in platelet sialic acid are a potential pathogenic factor in patients with coronary heart disease. Upon isolating platelets, we found a significantly higher (p

To compare time to delivery between two induction procedures. The Foley balloon is a mechanical method for cervical ripening. However, the device may also result in endogenous prostaglandin release following separation of the chorionic membrane and decidua. Prolonged Foley placement may therefore be unnecessary for successful labor induction. Randomized controlled trial of labor induction at LAC+USC Medical Center between 2010 and 2013. Subjects were assigned to either (a) standard placement of the Foley balloon or (b) Foley balloon insufflation and immediate removal. Oxytocin was administered to all subjects not in active labor after 12 h. Delivery information and neonatal outcomes were documented and all patients were followed for 6 weeks for adverse events. A total of 79 women were included in the analysis (37 standard and 42 immediate). Induction time was 8.6 h longer in the immediate removal group (23.5 vs 32.1, P=0.002), but the difference in delivery within 24 h did not meet the statistical significance (46.0 vs 28.6%, P=0.11). Similar rates of cesarean delivery, epidural use and abnormal APGAR scores were observed. After controlling for number of vaginal exams and duration of rupture, a decreased risk of infection was observed in the immediate removal group (odds ratio=0.08, 95% confidence interval=0.007 to 0.93, P=0.04). Further, when the analysis was stratified by parity, differences in induction time only persisted in nulliparous women. Immediate removal of the Foley balloon may lead to longer overall induction time, but a lower risk of infection. Parous women may be particularly good candidates for this type of induction.

Foveal and peripheral hue-scaling data were obtained for a 1° foveal stimulus and a 3° stimulus presented at 10° retinal eccentricity under both bleach (reducing rod input) and no-bleach (permitting rod input) conditions. Uniform appearance diagrams (UADs) were generated from the data. Peripheral stimuli appeared more saturated than foveal stimuli (i.e., supersaturated), especially in the green–yellow region of the UADs. This effect was particularly pronounced for the peripheral bleach condition. The range of wavelengths perceived as green–yellow in the peripheral retina was expanded as compared to the fovea, while the range of wavelengths experienced as blue–green was compressed. This indicates that there are shifts in the unique hue loci with retinal location. While several factors can be ruled out as potential causes for these perceptual differences, the underlying mechanism of this supersaturation effect in the peripheral retina is unknown.

We derive a mean-field algorithm for binary classification with gaussian processes that is based on the TAP approach originally proposed in statistical physics of disordered systems. The theory also yields an approximate leave-one-out estimator for the generalization error, which is computed with no extra computational cost. We show that from the TAP approach, it is possible to derive both a simpler “naive” mean-field theory and support vector machines (SVMs) as limiting cases. For both mean-field algorithms and support vector machines, simulation results for three small benchmark data sets are presented. They show that one may get state-of-the-art performance by using the leave-one-out estimator for model selection and the built-in leave-one-out estimators are extremely precise when compared to the exact leave-one-out estimate. The second result is taken as strong support for the internal consistency of the mean-field approach.

Sleep deprivation (SD) has enriched our treatment programme for major depression. SD has been demonstrated to modify different host defence activities. There is some evidence that there are reciprocal relationships between immune function and increased hypothalamic-pituitary-adrenocortical (HPA) axis activity in depression. We therefore investigated the number of leukocytes, granulocytes, monocytes, lymphocytes, B cells, T cells, helper T cells, cytotoxic T cells, NK cells and salivary cortisol in 10 healthy men before and after total SD (TSD) as well as after recovery sleep. Blood samples were drawn on 3 consecutive days at 7 am, 1 pm and 7 pm, respectively. Comparison of the 7 am values by contrast analysis yielded significant differences for granulocytes (p = 0.044) and NK cells (p = 0.001) after SD and recovery sleep. NK cells decreased and granulocytes increased after SD and after recovery sleep. Significant differences between single points in time across the day were found for granulocytes (p = 0.022), monocytes (p = 0.031), T cells (p = 0.005), helper T cells (p = 0.004), cytotoxic T cells (p = 0.005) and NK cells (p = 0.017). No significant difference could be detected for leukocytes, lymphocytes and B cells counts. These results favour the thesis that SD and recovery sleep lead to changes in the distribution of peripheral leukocytes, especially in a reduction of NK cells after SD and recovery sleep. The cortisol rhythm was affected neither by SD nor recovery sleep.

The present study was conducted to investigate whether +/- pindolol antagonizes ipsapirone induced biobehavioral changes in a personality dependent way. Our previous work demonstrated that high impulsives show higher immune cell responses than low impulsive subjects upon treatment with ipsapirone. A total number of 80 healthy male volunteers received placebo (N = 20) or 10 mg ipsapirone (N = 20), 30 mg +/- pindolol (N = 20), or a combination of 30 mg +/- pindolol and 10 mg ipsapirone (N = 20). Each group consisted of 10 low and 10 high impulsive subjects. Since 5-HT related drugs induce thermoregulatory responses, the study took place in a climate chamber with a constant ambient temperature. Blood samples (for measurement of CD4+ cell counts) were drawn from an indwelling catheter invisibly for the subjects. The results clearly demonstrate that the ipsapirone induced decreases in body temperature and number of peripheral CD4+ cells are more pronounced in high impulsives. +/- Pindolol antagonizes thermoregulatory and CD4+ cell responses. The results are discussed with respect to mechanisms of alteration in 5-HT function related to impulsivity.

To compare the obstetrical outcomes of term pregnancies induced with one of four commonly used labor induction agents.This is a retrospective cohort study of induced deliveries between 1 August 1995 and 31 December 2007 occurring at the Los Angeles County + University of Southern California Medical Center. Viable, singleton, term pregnancies undergoing induction were identified. Exclusion criteria included gestational age less than 37 weeks, previous cesarean delivery, breech presentation, stillbirth, premature rupture of membranes, and fetal anomaly. Induction methods studied were oxytocin, misoprostol, dinoprostone and Foley catheter. Our primary outcome was cesarean delivery rate among the four induction agents. Secondary outcomes included rate of failed induction, obstetrical complications, and immediate neonatal complications.A total of 3707 women were included in the study (1486 nulliparous; 2221 multiparous). Outcomes were compared across induction methods using Chi-square Tests (Pearson or Fisher's, as appropriate). Among the nulliparous patients, there was no statistical difference among the four induction agents with regards to cesarean delivery rate (p = 0.51), frequency of failed inductions (p = 0.49), the cesarean delivery frequency for "fetal distress" (p = 0.82) and five minute Apgar score7 (p = 0.24). Among parous patients, the cesarean delivery rate varied significantly by induction method (p 0.001), being lowest among those receiving misoprostol (10%). Those receiving oxytocin and transcervical Foley catheter had cesarean rates of 22%, followed by dinoprostone at 18%. The rate of failed inductions was 2% among those receiving misoprostol, compared to 7-8% among those in the other groups (p 0.01). Although cases of "fetal distress" between the four induction agents was not significantly different amongst multipara women, the cesarean delivery indication for "fetal distress" was higher among multipara receiving misoprostol (p = 0.004). There was no difference among the different induction agents with regards to five minute Apgar7 (p = 0.34).Among nulliparous women, all induction methods have similar rate of cesarean delivery. The use of misoprostol appears to be associated with a lower risk of cesarean birth among parous women induced at our institution.

Objective To determine the preoperative pelvic ultrasonographic characteristics of postmenopausal women diagnosed with endometrial cancer (EC) at our institution. Methods Postmenopausal women with EC who underwent preoperative transvaginal pelvic ultrasound from 1999–2009 were identified from our institutional database. The histologic diagnosis was based on pathologic findings in the hysterectomy specimen. Endometrial echo complex (EEC) thickness was abstracted from ultrasound reports. In all instances, ultrasound preceded the biopsy by a maximum of 3months. Means with standard deviations were calculated for all categorical data. Differences between type 1 and type 2 ECs were determined using Mann–Whitney U tests and Chi squared/Fisher's exact tests, as appropriate. A p-value of Results Among 250 patients with postmenopausal EC, 156 had type 1 EC while 94 had type 2 EC. Thirty-six percent of the cohort had an EEC ≤4mm, including 37% of patients with type 1 EC and 34% of patients with type 2 EC (p=0.63). There were no significant differences between type 1 and type 2 ECs in any demographic characteristic, other than likelihood of postmenopausal bleeding. Conclusions Current expert opinion recommends no further diagnostic procedure in a woman with postmenopausal bleeding and an EEC ≤4mm. These results indicate that a sizable proportion of women with EC have EECs ≤4mm during their initial evaluation. An EEC ≤4mm does not completely rule out endometrial cancer and cannot supplant histologic evaluation.

Objective To evaluate the interobserver reliability of fetal heart rate (FHR) pattern definition and interpretation assessed by physicians at various levels of training using standard Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) definitions and standard principles of interpretation. Study Design We conducted an interrater reliability study of the intrapartum FHR tracings of 32 singleton term pregnancies at Los Angeles County–University of Southern California (LAC + USC) Medical Center. Analysis included the 5 hours immediately preceding delivery, divided into 10- minute segments. A medical student, resident, and three attending physicians evaluated the same set of FHR tracings. Interobserver agreement was assessed using the free-marginal kappa coefficient. Results Reviewers demonstrated substantial to excellent agreement on baseline rate (κ = 0.97), moderate variability (κ = 0.80), accelerations (κ = 0.62), decelerations (κ = 0.63), category (κ = 0.68), and the ability to identify the presence of either moderate variability or accelerations (κ = 0.82). Conclusions Interobserver agreement was significantly higher on all components of FHR definition and interpretation than previously expected. Standardization of FHR definitions and interpretation may improve interobserver reliability and patient safety.

INTRODUCTION The objective is to develop a low-fidelity total abdominal hysterectomy (TAH) model for resident training with the purpose to improve residents' knowledge of anatomy, instruments, instrument handling, suture selection, and steps of a TAH. METHODS A TAH model was created using products purchased from a crafts store. Obstetrics and gynecology residents (second-year residents and fourth-year residents) were subjected to a lecture followed by a simulated TAH. Before and after the course, subjects were given a survey to assess their confidence regarding the different surgical aspects of the TAH. Confidence was assessed regarding knowledge of anatomy, instruments, instrument handling, suture selection, incision site, steps of the TAH, and global confidence. Statistical analysis was performed using nonparametric tests. A P < 0.05 was considered significant. RESULTS A low-fidelity TAH model was created. Eight second-year residents and seven fourth-year residents were studied. As expected, second-year residents had a lower median number of hysterectomies performed as primary surgeon when compared with fourth-year residents [0.5 (0.0-1.75) vs. 51.0 (50.0-53.0); P < 0.05]. Despite this difference, after having undergone the course, both resident classes demonstrated either statistical trends or significantly increased surgical confidence in all areas studied. CONCLUSION Our novel, low-fidelity TAH simulation model and course improves obstetrics and gynecology residents' confidence in surgical skills and knowledge, particularly for those with less surgical experience. The total cost to make approximately 18 models was US $60.00.

The cDNA sequence encoding human beta-glucuronidase [Oshima, Kyle, Miller, Hoffmann, Powell, Grubb, Sly, Troplak, Guise and Gravel (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 685-689] was expressed in baby hamster kidney (BHK) cells. After purification from the culture supernatant in one step by use of immunoaffinity chromatography, the biochemical properties of the enzyme were examined. With a pH optimum of 4.0, a Km of 1.3 mM and thermal stability up to 68 degrees C, this protein has characteristics very similar to those described for beta-glucuronidase from human placenta [Brot, Bell and Sly (1978) Biochemistry 17, 385-391. However, the recombinant product has several structural properties not previously reported for beta-glucuronidase isolated from natural sources. First, recombinant beta-glucuronidase is synthesized as a tetramer consisting of two disulphide-linked dimers. As can be inferred from the cDNA sequence, the enzyme possesses five cysteine residues after cleavage of the signal peptide. By introducing a C-terminal truncation, we eliminated the last cysteine at position 644. In the mutant, covalent linkage between two monomers is no longer observed, indicating that Cys-644 is involved in intermolecular disulphide-bond formation. The functional role of the disulphide bond remains elusive, as it was shown that (i) intracellular transport of the mutant is not impaired and (ii) it is still able to form an enzymically active tetramer. A second feature that has not previously been observed for beta-glucuronidase from any origin is the existence of two enzymically active species for recombinant beta-glucuronidase, when examined by gel filtration on a TSK 3000 column. With apparent molecular masses of 380 kDa and 190 kDa we propose that they represent tetramers and dimers respectively. Partial N-terminal sequencing and electrophoresis under denaturing conditions revealed that the dimers consist of subunits that have been proteolytically processed at their C-terminus losing 3-4 kDa in peptide mass. Controlled proteolysis demonstrates that the enzyme's overall protein backbone as well as its activity are resistant to a number of proteases. Only the C-terminal portion is susceptible to protease action, and the disulphide-linked form is readily converted into non-disulphide-bonded subunits. Pulse-chase analysis shows that human beta-glucuronidase remaining intracellular in BHK cells after synthesis undergoes a similar proteolytic processing event, i.e. a reduction in mass of 3-4 kDa.(ABSTRACT TRUNCATED AT 400 WORDS)