Research Note: Bovine lactoferrin in chickens: an investigation into its viability as an antibiotic alternative.

Finding effective antibiotic alternatives is crucial to managing the re-emerging health risk of Clostridium perfringens (CP) type A/G-induced avian necrotic enteritis (NE), a disease that has regained prominence in the wake of governmental restrictions on antibiotic use in poultry. Known for its antimicrobial and immunomodulatory effects, the use of bovine lactoferrin (bLF) in chickens is yet to be fully explored. In this study, we hypothesized that bLF can accumulate in the small intestines of healthy chickens through gavage and intramuscular supplementation and serves as a potential antibiotic alternative. Immunohistochemistry located bLF in various layers of the small intestines and ELISA testing confirmed its accumulation. Surprisingly, sham-treated chickens also showed the presence of bLF, prompting a western blotting analysis that dismissed the notion of cross-reactivity between bLF and the avian protein ovotransferrin. Although the significance of the route of administration remains inconclusive, this study supports the hypothesis that bLF is a promising and safe antibiotic alternative with demonstrated resistance to the degradative environment of the chicken intestines. Further studies are needed to determine its beneficial pharmacological effects in CP-infected chickens.

Evaluation of the Patterns of Learning in the Labor Cervical Examination.

OBJECTIVE: The aim of the study was to evaluate patterns of skill acquisition in the labor cervical examination in novice providers, such as the change in accuracy and overestimation and underestimation over time and the impact of dilation and effacement on accuracy. METHODS: In this descriptive longitudinal study, medical students each performed 120 simulated cervical examinations. Accuracy and how often students overestimated and underestimated dilation and effacement during was determined for each set of 10 repetitions. Accuracy data were grouped and compared by dilation (1-3, 4-6, and 7-10 cm) and effacement (90%, 75%, 50%, and 25%). RESULTS: Student accuracy in dilation significantly improved throughout the course of the study (P < 0.001). At the beginning of the study, students more often overestimated dilation, but this decreased over time (P < 0.001). In addition, the accuracy of the students' estimations was 84%, 62%, and 52% for dilations of 1-3, 4-6, and 7-10 cm, respectively (P < 0.001). Student accuracy in effacement significantly improved throughout the course of the study (P < 0.001). At the beginning of the study, students more often overestimated effacement, but as training progressed, more students tended to overestimate and underestimate equally often (P < 0.001). In addition, accuracy of the students' estimations was 93%, 88%, 81%, and 35% for effacements of 90%, 75%, 50%, and 25%, respectively (P < 0.001). CONCLUSIONS: Knowing that students tend to overestimate cervical dilation and effacement early in training and that cervices of high dilation and low effacement are more difficult to assess will be helpful in designing more efficient cervical examination training regimens.

Prognosis Communication in Late-Life Disability: A Mixed Methods Study.

IMPORTANCE: Long-term prognosis informs clinical and personal decisions for older adults with late-life disability. However, many clinicians worry that telling patients their prognosis may cause harm. OBJECTIVE: To explore the safety of and reactions to prognosis communication in late-life disability. DESIGN: Participants estimated their own life expectancy and were then presented their calculated life expectancy using a validated prognostic index. We used a semi-structured interview guide to ask for their reactions. Qualitative data were analyzed using constant comparative analysis. Potential psychological and behavioral outcomes in response to receiving one's calculated prognosis were recorded and re-assessed 2-4 weeks later. SETTING: Community-dwelling older adults age 70+ residing in the San Francisco Bay Area. PARTICIPANTS: Thirty five older adults with a median age of 80 requiring assistance with ≥1 Activity of Daily Living. RESULTS: Self-estimates of life expectancy were similar to calculated results for 16 participants. 15 estimated their life expectancy to be longer than their calculated life expectancy by >2 years, while 4 shorter by >2 years. An overarching theme of, "fitting life expectancy into one's narrative" emerged from qualitative analysis. Discussing life expectancy led participants to express how they could alter their life expectancy (subtheme "locus of control"), how they saw their present health (subtheme "perceived health"), and their hopes and fears for the remaining years of their lives (subtheme "outlook on remaining years"). Feelings of anxiety and sadness in reaction to receiving calculated prognosis were rare. CONCLUSIONS AND RELEVANCE: About half of the disabled older adults' self-estimates of prognosis were similar to calculated estimates. Evidence of sadness or anxiety was rare. These data suggest that in most cases, clinicians may offer to discuss prognosis.

Heterogeneity of Scaffold Biomaterials in Tissue Engineering.

Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal.

Tissue-Engineering Approaches to Restore Kidney Function.

Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized.

Active immunotherapy using dendritic cells in the treatment of glioblastoma multiforme.

OBJECTIVE: Glioblastoma multiforme, the most common malignant brain tumor still has a dismal prognosis with conventional treatment. Therefore, it is necessary to explore new and/or adjuvant treatment options to improve patient outcomes. Active immunotherapy is a new area of research that may be a successful treatment option. The focus is on vaccines that consist of antigen presenting cells (APCs) loaded with tumor antigen. We have conducted a systematic review of prospective studies, case reports and clinical trials. The goal of this study was to examine the efficacy and safety in terms of complications, median overall survival (OS), progression free survival (PFS) and quality of life. METHODS: A PubMed search was performed to include all relevant studies that reported the characteristics, outcomes and complications of patients with GBM treated with active immunotherapy using dendritic cells. Reported parameters were immune response, radiological findings, median PFS and median OS. Complications were categorized based on association with the craniotomy or with the vaccine itself. RESULTS: A total of 21 studies with 403 patients were included in our review. Vaccination with dendritic cells (DCs) loaded with autologous tumor cells resulted in increased median OS in patients with recurrent GBM (71.6-138.0 wks) as well as those newly diagnosed (65.0-230.4 wks) compared to average survival of 58.4 wks. CONCLUSIONS: Active immunotherapy, specifically with autologous DCs loaded with autologous tumor cells, seems to have the potential of increasing median OS and prolonged tumor PFS with minimal complications. Larger clinical trials are needed to show the potential benefits of active immunotherapy.

Health-related quality of life of children with epilepsy in Hong Kong: how does it compare with that of youth with epilepsy in Canada?

OBJECTIVE: The primary aim of our study was to compare the health-related quality of life (HRQL) of children with epilepsy in Hong Kong with that of children with epilepsy in Canada, and to explore possible factors affecting these findings. A second interest was to determine agreement between proxy reports and self-ratings among children with epilepsy in Hong Kong, compare these with findings in Canada, and identify factors that influence the concordance. METHODS: Child self-report and parent-proxy questionnaires on an epilepsy-specific HRQL measure, appropriately translated and validated in Chinese, were administered to 266 Hong Kong children and their parents. An unpaired t test was used to compare the scores with published results from 381 Canadian children and their parents, who used the original English version of the measure. Demographic characteristics of the two groups were compared using t tests, chi2 tests, and Fisher's exact tests. Agreement between parents' and children's scores was evaluated with intraclass correlation coefficients (ICCs) and standardized response means (SRMs). The total HRQL score differences between parents and children in Hong Kong were compared with those in Canada using an unpaired t test. Factors that might affect the parent-child score difference were studied using Pearson correlation analysis, chi2 test, and analysis of variance. Factors studied included: sex, current age, age at diagnosis, duration of epilepsy, number of antiepileptic drugs used, type of seizure, seizure severity, cognition of the child, the type of school attended, presence of neurological problems, presence of behavioral problems, recent health care usage, education and employment status of both parents, housing status of the family, and relationship of the proxy respondent to the child. RESULTS: (1) In contrast to the Canadian sample, Hong Kong children with epilepsy were older (P<0.01), had a longer duration of epilepsy (P<0.01) and less severe seizures (P<0.01), and were more likely to attend normal schools (P<0.01). Children in Hong Kong reported more interpersonal/social difficulties (P<0.01), more worries (P<0.01), and more secrecy about their epilepsy (P<0.01). Parents in Hong Kong believed that their children perceived more worries (P<0.01) and were more secretive about their epilepsy (P<0.01). (2) Moderate to good agreement between parent-proxy response scores and child self-report scores was demonstrated (ICC=0.50-0.69, SRM=0.19-0.33). The total HRQL score differences between parent and child in Hong Kong were not different from those in Canada. None of the factors studied were related to the parent-child score difference. CONCLUSIONS: Youth with epilepsy in Hong Kong and their parents reported poorer quality of life than children with epilepsy in Canada. Further studies are necessary to identify the determinants of HRQL in children with epilepsy in different cultures. Acceptable agreement between the two ratings suggests that proxy reports can be used when child self-reports cannot be obtained.

Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups.

BACKGROUND & AIMS: Screening of high-risk groups for pancreatic cancer has not been adopted because of concerns regarding specificity and sensitivity. Suitability of a combination of 3 novel molecular screening techniques was investigated. METHODS: Pancreatic juice was extracted from 146 patients with pancreatic ductal adenocarcinoma, chronic pancreatitis, or biliary tract stones. p53 mutations were analyzed by using a modified yeast functional assay, K-ras status was analyzed using mutation-specific real-time PCR and the proportion of p16(INK4a) promoter methylation was estimated using comparative methylation-specific real-time PCR. RESULTS: p53 mutations were detected in 20 of 48 (42%) cancer cases, none of 49 controls, and 2 of 49 (4%) patients with pancreatitis. K-ras mutations were detected in 31 of 57 (54%) cancer patients, 13 of 61 (21%) controls, and 23 of 67 (34%) patients with pancreatitis. Twenty-six of 42 (62%) cancer patients had promoter methylation levels > 12%, compared with 3 of 24 (13%) controls, and 2 of 26 (8%) with pancreatitis. Mutations in p53 or high-level p16(INK4a) promoter methylation occurred in 29 of 36 (80%) patients with cancer, 3 of 24 (13%) controls, and 3 of 22 (13%) with pancreatitis. Three patients (8%) of 36 with cancer; 14 of 24 (58%) controls, and 13 of 22 (59%) patients with pancreatitis had no marker. The gallstone disease patients had a high rate of positive K-ras mutations, possibly reflecting the fact that they were not disease free. CONCLUSIONS: Combination molecular analysis increased the discrimination between patients with malignant and benign disease. This level of discrimination would allow patients in high-risk groups to be stratified from negligible risk to over 50% probability of an early cancer.