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1.

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Methods and results

The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.

Conclusion

The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.  相似文献   
2.
Intersectionality theory calls for the understanding of race/ethnicity, sex/gender and class as interlinked. Intersectional analysis can contribute to public health both through furthering understanding of power dynamics causing health disparities, and by pointing to heterogeneities within, and overlap between, social groups. The latter places the usefulness of social categories in public health under scrutiny. Drawing on McCall we relate the first approach to categorical and the second to anti-categorical intersectionality. Here, we juxtapose the categorical approach with traditional between-group risk calculations (e.g. odds ratios) and the anti-categorical approach with the statistical concept of discriminatory accuracy (DA), which is routinely used to evaluate disease markers in epidemiology. To demonstrate the salience of this distinction, we use the example of racial/ethnic identification and its value for predicting influenza vaccine uptake compared to other conceivable ways of organizing attention to social differentiation. We analyzed data on 56,434 adults who responded to the NHFS. We performed logistic regressions to estimate odds ratios and computed the area under the receiver operating characteristic curve (AU-ROC) to measure DA. Above age, the most informative variables were education and household poverty status, with race/ethnicity providing minor additional information. Our results show that the practical value of standard racial/ethnic categories for making inferences about vaccination status is questionable, because of the high degree of outcome variability within, and overlap between, categories. We argue that, reminiscent of potential tension between categorical and anti-categorical perspectives, between-group risk should be placed and understood in relationship to measures of DA, to avoid the lure of misguided individual-level interventions.  相似文献   
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Identification of the association between tissue biomarkers, their surrogates in blood and clinical features, could provide new diagnostic tools and facilitate adequate choices of therapeutic interventions for selected patients suffering from CRS. The aim of present study was the assessment of macrophages in the polyp tissue and monocytes in the peripheral blood in the course of CRSwNP, and their functional immunophenotype. We analyzed 31 patients with CRSwNP. Nasal mucosa tissue was obtained via functional endoscopic sinus surgery (FESS). The control group included 10 patients with deviated nasal septum (DNS). Fluorochrome stained cells were proceed to acquisition using FACS Canto flow cytometer, and the results were analyzed using the software FACS Diva. In our study, we observed a significantly higher level of CD80, CD274, CD273 and TLR1 in nasal polyps compared to blood samples from patients with CRSwNP. This finding may suggest the importance of the PD-1 pathway as a therapeutic target in CRS and an important role for TLR1 in nasal polyp formation and maintenance. Our results may provide some insight into potential future targets of recurrent nasal polyp treatment and contribute to a better understanding of the inflammatory process in Chronic Rhinosinusitis.  相似文献   
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6.
Child abuse and neglect is any interaction or lack of interaction between a caregiver and a child resulting in nonaccidental harm to the child's physical and developmental state. Substance abuse is ingestion of any drug, which is capable of altering the mental functioning eventually leading to addiction. This paper presents a case report of a 12-year-old neglected girl with substance abuse for which she was physically abused by her mother.  相似文献   
7.
Many North American dental schools face the challenge of replacing the majority of their "boomer generation" clinical instructors over the next ten years as this cohort of faculty reaches retirement age. Developing a new cadre of clinical instructors poses a substantial faculty development challenge: what instructional techniques should be integrated into routine educational practice by the dental faculty of the future, and what aspects of the clinical learning environment should be addressed to improve the overall quality of the experience for patients, students, and the new cohort of instructors? To gain insight that might guide faculty development for new clinical instructors and enhance understanding of the learning environment in dental school clinics, this study addressed the following question: what are dental students' perceptions of their learning experiences in the clinical setting? The purpose of the study was to evaluate the effectiveness of the clinical instruction from the perspectives of the actual "consumer" of dental education: the student. This consumers' perspective was provided by 655 junior, senior, and graduate dental students at twenty-one North American dental schools who completed the Clinical Education Instructional Quality Questionnaire (ClinEd IQ) in 2003-04. The ClinED IQ examines four components of students' clinical experiences: 1) clinical learning opportunities, 2) involvement in specific learning activities, 3) interaction with clinical instructors, and 4) personal perceptions about clinical education. With the exception of inconsistent feedback and instruction and lack of continuous contact with the same instructors, juniors, seniors, and graduate students rated their interaction with clinical instructors favorably (mean=4.76 on a 6.00 scale), but provided lower ratings for clinical learning opportunities (mean=4.26 on a 6.00 scale) due to concerns about the efficiency of the dental clinic environment and lack of opportunity to treat patients in a variety of clinical settings. Analysis of more than 1,000 written comments provided by these students indicated four areas of concern: 1) inconsistent and sometimes insensitive (patronizing, rude) feedback from faculty; 2) excessive amounts of noneducational "legwork" such as billing, patient scheduling, phone calling, completing paperwork, and performing other clinic operations tasks; 3) limited access to faculty because of insufficient numbers of instructors on the clinic floor or difficulty locating faculty when they were needed for coaching, work evaluation, and chart signatures; and 4) concerns about the strategies employed to meet procedural requirements that some students saw as ethically questionable. Junior, senior, and graduate dental students at twenty-one North American dental schools perceived that the strongest aspect of their clinical education was their relationship with the faculty, but also reported that the dental school clinic was often an inefficient learning environment that hindered their opportunity to develop clinical competency. Students also sensed that faculty shortages, a growing crisis for dental education, hindered their progress in the clinic and made learning less efficient.  相似文献   
8.
This pilot study evaluated the experience of people with co-occurring disorders (mental illness and addiction) in relation to peer-led and professional-led group interventions. The study used a qualitative (phenomenological) approach to evaluate the experience of a convenience sample of 6 individuals with co-occurring disorders who participated in up to 8 sessions each of both peer-led and professional-led group interventions (with a similar rate of attendance in both groups). The semi-structured interview data were coded and thematically analyzed. We found 5 themes within and across the 2 interventions. In both groups, participants experienced a positive environment and personal growth, and learned, albeit different things. They were more comfortable in the peer-led group and acquired more knowledge and skills in the professional-led group. Offering both peer-led and professional-led group interventions to people with co-occurring disorders may be better than offering either alone  相似文献   
9.

Background

Surgeons have attempted to minimize postoperative anastomotic complications by employing intraoperative tests and manoeuvres to assess colorectal anastomotic integrity. These have evolved over time with improvement in operative technology and techniques. This systematic review aims to examine the impact of such intraoperative assessments.

Methods

A systematic review of studies assessing intraoperative anastomotic assessments and their impact on postoperative anastomotic complications was performed. Intraoperative measures undertaken as a result of intraoperative assessments and postoperative anastomotic complications were analysed.

Results

37 Studies were identified. 13 studies evaluated basic mechanical patency tests, ten studies evaluated endoscopic visualisation techniques and 14 studies evaluated microperfusion techniques. Postoperative anastomotic complications were significantly lower in patients tested with basic mechanical patency tests compared to those untested (non-RCT: 4.1 vs. 8.1 %, p = 0.03, RCTs: 5.8 vs. 16.0 %, p = 0.024). There were no differences in postoperative anastomotic complications between tested and non-tested cohorts in non-randomised cohort studies evaluating endoscopic visualisation techniques. However, intraoperative measures taken after abnormal intraoperative tests may have reduced the number of postoperative complications. Perfusion analysis techniques are not in routine widespread clinical practice as yet, but newer techniques such as fluorescent dyes and imaging under near infrared light show technical feasibility.

Conclusions

Intraoperative colorectal anastomotic assessment has evolved together with advancement of technology in the surgical setting. Moderate benefit in terms of lower postoperative anastomotic complications has been shown with basic mechanical patency testing and more recently with intraoperative endoscopic visualisation of colorectal anastomoses. The next advance and possible introduction into routine practice may include the use of microperfusion techniques. The latest in this group of techniques, which utilise autofluorescent dyes such as Indocyanine green, hold great potential. Well-planned controlled studies or ideally, randomised controlled trials need to be conducted to further assess the benefit of these latest techniques.  相似文献   
10.
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