Advanced Clinical Course Research Articles

Upregulated MUC2 Is an Unfavorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative CCRT.

For locally advanced rectal cancer patients, introducing neoadjuvant concurrent chemoradiotherapy (CCRT) before radical resection allows tumor downstaging and increases the rate of anus retention. Since accurate staging before surgery and sensitivity prediction to CCRT remain challenging, a more precise genetic biomarker is urgently needed to enhance the management of such situations. The epithelial mucous barrier can protect the gut lumen, but aberrant mucin synthesis may defend against drug penetration. In this study, we focused on genes related to maintenance of gastrointestinal epithelium (GO: 0030277) and identified mucin 2 (MUC2) as the most significantly upregulated gene correlated with CCRT resistance through a public rectal cancer transcriptome dataset (GSE35452). We retrieved 172 records of rectal cancer patients undergoing CCRT accompanied by radical resection from our biobank. We also assessed the expression level of MUC2 using immunohistochemistry. The results showed that upregulated MUC2 immunoexpression was considerably correlated with the pre-CCRT and post-CCRT positive nodal status (p = 0.001 and p < 0.001), advanced pre-CCRT and post-CCRT tumor status (p = 0.022 and p < 0.001), vascular invasion (p = 0.015), and no or little response to CCRT (p = 0.006). Upregulated MUC2 immunoexpression was adversely prognostic for all three endpoints, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) (all p < 0.0001), at the univariate level. Moreover, upregulated MUC2 immunoexpression was an independent prognostic factor for worse DSS (p < 0.001), LRFS (p = 0.008), and MeFS (p = 0.003) at the multivariate level. Collectively, these results imply that upregulated MUC2 expression is characterized by a more advanced clinical course and treatment resistance in rectal cancer patients undergoing CCRT, revealing the potential prognostic utility of MUC2 expression.

T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy

PurposeT2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course.MethodsThe volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping.ResultsT2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity.ConclusionIn late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.

Blackleg in inadequately immunized calves and their recovery following antibiotic therapy.

There is consensus regarding the importance of blackleg vaccination as a preventive measure, and proper immunization protocols are available. However, few studies have evaluated the effectiveness of vaccine protection against Clostridium chauvoei and the treatment of the disease in calves exhibiting early or advanced clinical courses. This study describes twelve blackleg cases in unvaccinated calves and in calves that received a single dose of the vaccine. It also reports the recovery of some calves after antibiotic therapy. Two necropsies of cattle dead from blackleg were performed. Fragments of skeletal muscle from these two cattle were immersed in paraffin for multiplex polymerase chain reaction (PCR) analysis. Twelve calves up to nine months of age developed signs of blackleg and eight died. Ten of those 9-month-old calves had received only the first dose of a blackleg vaccine at 4 months of age, but no booster. The last two affected calves belonged to a herd that had never been vaccinated. Four out of five calves treated with penicillin for 6-7 days recovered from the disease. The diagnosis of blackleg was based on necropsy, histopathological findings and detection of C. chauvoei in skeletal muscle samples of two necropsied calves using PCR. The occurrence of cases only in calves that did not receive a booster dose or were not vaccinated indicated that the vaccine used was effective when performed as recommended by the manufacturer. However, neglecting the booster resulted in casualties due to blackleg.

Using Skeletal Outlines and Illustrative Diagrams as a Teaching/Learning Strategy in a Baccalaureate Nursing Pharmacology Course

Knowledge of pharmacology is an important aspect of safe, effective and competent clinical nursing practice, yet it can be challenging to teach. Many academics within the discipline of nursing are concerned that current nursing curricula may not be preparing nurses to accept responsibilities related to pharmacological management and are inadequately prepared for their role in medication administration. Nursing faculty who teach advanced clinical nursing practice courses also report that students lack the foundational knowledge of pharmacology needed and required in advanced clinical courses. These concerns have led to a call for additional focus that must be placed on student knowledge acquisition of pharmacology content due to poor student performance on standardized tests. Within a four-year undergraduate Bachelor of Science in Nursing (BScN) curriculum, pharmacology content was taught to first-term, second year students within a nursing praxis course, over a 13-week period. Students were required to understand the foundational principles, concepts and content of pharmacology and to integrate this knowledge in a critical reflective manner in clinical practice. A teaching/learning approach was implemented within the classroom that aligned with the work of Bui and McDaniel (2015). This method utilized outlines, illustrative diagrams and mental models aimed to enhance student note-taking in the development of content knowledge and to assist students to internalize critical cognitive learning processes. Consequently, student comprehension and critical thinking of pharmacology content was increased. Establishing a solid foundation of pharmacology that is integrated in a critically manner is a major component of providing safe and competent patient care.

Metastatic small bowel adenocarcinoma in a 10-year-old Chinese girl

Small bowel adenocarcinoma is a rare entity in both adult and paediatric populations. Diagnosis is usually delayed due to vague symptoms. We report a case of ileal adenocarcinoma presented with multiple metastases. A 10-year-old Chinese girl presented with recurrent right lower quadrant pain developed intestinal obstruction. Computerized tomography showed terminal ileum wall thickening, a pelvic mass and suspicious pulmonary metastases. Laparotomy showed a terminal ileal tumour causing mechanical obstruction with metastases to the left ovarian and mesenteric lymph nodes. Palliative right hemi-colectomy with double-barrel ileostomy was performed. The pathology was reported to be ileocaecal adenocarcinoma with extensive lymphovascular permeation. She was the started on palliative chemotherapy with static disease. Diagnosis of small bowel adenocarcinoma remains a challenge to surgeons as the clinical presentation is subtle in spite of the advanced clinical course. Surgery plays a role in symptomatic treatment for patients with intestinal obstruction in advanced stage.

Post-hoc analysis on the cd14 c(-260)t promoter polymorphism and coronary heart disease

Functional C(-260)--> T polymorphism in the promoter of the CD14 gene has been reported to be associated with coronary heart disease (CHD). The functional role of the polymorphism, however, is still a matter of debate, since several studies have not proved its effect on clinical outcomes associated with atherosclerosis. Cardiovascular-related morbidity and mortality was assessed in a post-hoc approach four years after baseline characterization of patients (male/female n = 36/32) with angiographically proven coronary heart disease. CD14 C(-260)--> T promoter genotype was determined at baseline. Seventeen out of 20 CHD patients with non-lethal cardiovascular events carried at least one T-allele. CD14 T-260 allele carriers have a 3.59-fold (95 % confidence interval: 1.11-6.75) increased risk for non-lethal cardiovascular events (Kaplan-Meier plot: log rank test p = 0.029). All patients with lethal outcomes (n = 6) were also T-allele carriers. Multivariate logistic regression analysis among CHD patients including age, established risk factors and the C(-260)--> T polymorphism as covariates and non-lethal events as a dependent variable confirmed the independent prospective effect of the T-allele on cardiovascular outcomes in this subset. Further evidence is provided for the role of CD14 C(-260)--> T promoter polymorphism as a genetic susceptibility marker of atherosclerosis in patients with an advanced clinical course of the disease. Due to the small sample size and post-hoc character of the study large-scale prospective studies that monitor patients with proven CHD are needed to confirm these findings.

Tooth-colored restorations of posterior teeth in German dental education.

Optimizing the quality of tooth-colored restorations is one of the main topics of current research. But there is only little information available about university education in this field. The aim of this study was to collect and evaluate data about the different aspects of dental education in Germany concerning tooth-colored restorations. Based on the response to a questionnaire from 90% of all German dental schools in the fall of 1997 a detailed survey is given of the utilization, indications, practical procedure, problems and limitations of both direct and indirect tooth-colored restorations done by students. The results indicate a wide-spread use of directly inserted composite for posterior teeth in the different education programs. Indeed, the preferred preparation of the cavity margin differs from school to school. Rebuilding an adequate proximal contact and a precise fit at the gingival margin are looked upon as the main problems of class II composite fillings. Ceramic inlays are mainly inserted by students in advanced clinical courses with the insertion procedure being claimed as the main problem of this technique. The findings of this study mostly show the same limitations and difficulties of tooth-colored restorations in education as found by research. Partly different teaching concepts are reflected in the differing scientific results.

Doctoral programs in nursing: philosophy, curricula, and program requirements.

This study examined the philosophy, curricula, and program requirements of doctoral nursing programs in the United States. Forty-four doctoral nursing programs were solicited by mail and information about doctoral nursing programs was obtained. Of the programs, 31 offer the doctor of philosophy degree, 11 the doctor of nursing science degree, and 1 the doctor of education degree. Program philosophies could not be distinguished from one another. Eighteen doctoral programs offered advanced clinical courses and 22 programs focused on role preparation; 16 offered both clinical and role preparation. There was much variation in credit requirements, but the standard program was 60 credits in length, with 48 credits in nursing and 12 credits in cognates and electives. Approximately half the required credits focused on research. The similarity in the curricula of doctoral programs is striking. Discipline-specific values may be strong and account for the congruence in the types of curricula found in this study. Continued focus on research preparation, with varying degrees of emphasis on clinical or role development, is expected. The dominance of the doctoral degree as the terminal degree for nursing is likely to continue.

Guide for an Advanced Clinical Course in Orthopedic Nursing. New York, National League of Nursing Education, 1948. $0.60

Guide for an Advanced Clinical Course in Orthopedic Nursing. New York, National League of Nursing Education, 1948. $0.60