Nursing science is heavily dependent on nurse scientists with adequate funding. Nurse scientists should be aware of organizations' research agendas and, to the extent possible, align research with ...stated research priorities. Current information on the demographics of nurse scientists, their projects, and the alignment to known priorities is illusive.
To describe areas of inquiry pursued by PhD-prepared nurses and congruence with the research agendas of nursing organizations.
A descriptive, exploratory approach was undertaken with PhD-prepared nurse scientists to gather data about their PhD program, dissertation topic, current work status, productivity, and future recommendations.
Key findings were that dissertation topics were broad and aligned with research priorities. Elements influencing research productivity are described.
Understanding current nursing science stewardship and intentionally strategizing for the future of research, academia, and clinical practice will enhance our ability to tailor PhD programs accordingly.
Internal ribosome entry site (IRES) elements found in the 5' untranslated region of mRNAs enable translation initiation in a cap-independent manner, thereby representing an alternative to ...cap-dependent translation in cell-free protein expression systems. However, IRES function is largely species-dependent so their utility in cell-free systems from different species is rather limited. A promising approach to overcome these limitations would be the use of IRESs that are able to recruit components of the translation initiation apparatus from diverse origins. Here, we present a solution to this technical problem and describe the ability of a number of viral IRESs to direct efficient protein expression in different eukaryotic cell-free expression systems. The IRES from the intergenic region (IGR) of the Cricket paralysis virus (CrPV) genome was shown to function efficiently in four different cell-free systems based on lysates derived from cultured Sf21, CHO and K562 cells as well as wheat germ. Our results suggest that the CrPV IGR IRES-based expression vector is universally applicable for a broad range of eukaryotic cell lysates. Sf21, CHO and K562 cell-free expression systems are particularly promising platforms for the production of glycoproteins and membrane proteins since they contain endogenous microsomes that facilitate the incorporation of membrane-spanning proteins and the formation of post-translational modifications. We demonstrate the use of the CrPV IGR IRES-based expression vector for the enhanced synthesis of various target proteins including the glycoprotein erythropoietin and the membrane proteins heparin-binding EGF-like growth factor receptor as well as epidermal growth factor receptor in the above mentioned eukaryotic cell-free systems. CrPV IGR IRES-mediated translation will facilitate the development of novel eukaryotic cell-free expression platforms as well as the high-yield synthesis of desired proteins in already established systems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Fraser S, Roberts L, Murphy E. Cauda equina syndrome: a literature review of its definition and clinical presentation. Objective To review the current evidence for the signs and symptoms of ...cauda equina syndrome (CES). Data Sources Relevant literature sourced through Medline, Embase, and CINAHL using the key search words “cauda equina syndrome” combined with “definition,” “clinical presentation,” “signs and symptoms,” “pathology,” and “etiology.” Study Selection Not applicable. Data Extraction Not applicable. Data Synthesis Three reviewers independently extracted data on CES from the literature specific to its definition, clinical presentation, and etiology. Of 111 articles, 105 were included for review, and relevant information on CES was synthesized into a framework structured as per a clinical consultation. A content analysis was then conducted using the method adopted by the Chartered Society of Physiotherapy whereby the level of consensus for each sign and symptom of CES was determined by its percentage coverage within the literature: 100% coverage equals unanimity, 75% to 99% equals consensus, 51% to 74% equals majority view, and 0% to 50% equals no consensus. This enabled the frequency of each reported sign and symptom to be ranked. Articles that included specific definitions for CES were divided into 3 categories: those that (1) included generalized statements, (2) stated a pathomechanical basis, and (3) defined the syndrome by its clinical presentation. Throughout this review, the frequencies of specific etiologies and pathologies were noted. Together with details of clinical presentation, this enabled a comprehensive review of CES. No single aspect of CES within the literature achieved unanimity or consensus; however, a majority view indicated that there would be bladder and sensory disturbance (74% and 66% of all articles, respectively). The most commonly cited pathology resulting in CES was identified as the disk (45% of all articles reviewed). Conclusions There are marked inconsistencies in the current evidence base surrounding the etiology and clinical presentation of CES, with 17 definitions identified. Subclassifications of the definition of CES are ambiguous and should be avoided. From reviewing 105 articles, a single definition of CES is proposed. For a diagnosis of CES, one or more of the following must be present: (1) bladder and/or bowel dysfunction, (2) reduced sensation in the saddle area, and (3) sexual dysfunction, with possible neurologic deficit in the lower limb (motor/sensory loss, reflex change).
Mountain biking is an increasingly popular outdoor activity on the extreme sport continuum. Extreme and high-risk sports have been investigated using a variety of motivational theories with sensation ...seeking a dominant theme; however, behavioral and motivational homogeneity within these types of populations should not be assumed. Recent studies have highlighted the therapeutic potential of extreme sports and similar outdoor activities. The aim of this study was to describe the characteristics of mountain biking participants, their engagement methods, and perceived benefits to mental health and well-being. This was a cross-sectional survey and participants were recruited via social media. An online questionnaire specific to the domain of mountain biking was developed. Analysis of the full sample (
= 1,484) and of three independent paired sub-samples was conducted using SPSS. The sub-samples compared the results of males and females; younger and older riders; and those who have recently engaged in downhill mountain biking and those who have not. The results have succeeded in identifying some disparities in mountain biker characteristics and engagement methods. The results suggest that some riders found pleasure in higher risk engagement. The study proposes various explanations for the disproportion of women in mountain biking. Irrespective of the confounding factors related to rider characteristics or engagement methods, mountain bikers reported copious benefits to mental health and well-being related to their engagement. There was a high reported usage of mountain biking as a coping strategy. As such, this study provides insights that could inform the development of outdoor activities as interventions for mental health.
Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have ...received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges.
In order to gain a more comprehensive insight into the nature of venetoclax resistance mechanisms, we evaluated the changes in the BCL-2 family members at the genetic and expression levels in seven different venetoclax-resistant derived leukemia and lymphoma cell lines.
Gene and protein expression analyses identified a number of different alterations in the expression of pro- and anti-apoptotic BCL-2 family members. In the resistant derived cells, an increase in either or both the anti-apoptotic proteins BCL-X
or MCL-1, which are not targeted by venetoclax was observed, and either concomitant or exclusive with a decrease in one or more pro-apoptotic proteins. In addition, mutational analysis also revealed a mutation in the BH3 binding groove (F104L) that could potentially interfere with venetoclax-binding. Not all changes may be causally related to venetoclax resistance and may only be an epiphenomenon. For resistant cell lines showing elevations in BCL-X
or MCL-1, strong synergistic cell killing was observed when venetoclax was combined with either BCL-X
- or MCL-1-selective inhibitors, respectively. This highlights the importance of BCL-X
- and MCL-1 as causally contributing to venetoclax resistance.
Overall our study identified numerous changes in multiple resistant lines; the changes were neither mutually exclusive nor universal across the cell lines tested, thus exemplifying the complexity and heterogeneity of potential resistance mechanisms. Identifying and evaluating their contribution has important implications for both patient selection and the rational development of strategies to overcome resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Declining cognitive functions in older individuals have enormous emotional, clinical, and public health consequences. Thus, therapeutics for preserving function and keeping older adults ...living independently are imperative. Aging is associated dysbiosis, defined as a loss of number and diversity in gut microbiota, which has been linked with various aspects of cognitive functions. Therefore, the gut microbiome has the potential to be an important therapeutic target for symptoms of cognitive impairment. In this review, we summarize the current literature regarding the potential for gut-targeted therapeutic strategies for prevention/treatment of the symptoms of cognitive impairment. Specifically, we discuss four primary therapeutic strategies: wild-type and genetically modified probiotics, fecal microbiota transplantation, physical exercise, and high-fiber diets and specifically link these therapies to reducing inflammation. These strategies may hold promise as treatment paradigm symptoms related to cognitive impairment.
Background
Intestinal (i.e., “gut”) permeability may be related to cardiovascular disease (CVD) risk, but biomarkers for gut permeability are limited and associations with CVD risk are ...unknown—particularly among older adults.
Aims
This cross-sectional study aimed to determine if serum biomarkers related to gut permeability intestinal fatty acid-binding protein (iFABP) and bacterial toxin clearing cluster of differentiation 14 (CD14), lipopolysaccharide binding protein (LBP) are associated with CVD risk among older adults.
Methods
Older adults (
n
= 74, 69.6 ± 6.5-years-old) were stratified by CVD risk category. One-way ANOVAs determined differences in each biomarker by risk category, and associations with risk score were evaluated with Pearson correlations.
Results
LBP (
p
= 0.007), but not iFABP and CD14, was significantly different between CVD risk categories. Post-hoc tests indicated LBP was higher in moderate risk and high-moderate risk compared to the high risk category (
p
< 0.005). Evaluation of LBP and individual components in the risk score demonstrated a moderate, negative correlation of LBP with age and systolic blood pressure (
r
= − 0.335 and
r
= − 0.297) and a small positive correlation between LBP and total cholesterol and LDL cholesterol (
r
= 0.204 and
r
= 0.220).
Discussion/Conclusion
Lower risk for CVD was associated with higher circulating concentrations of LBP, lower iFABP, and lower systemic inflammation in older adults. Further, there were small positive relationships between total and LDL cholesterol and circulating levels of LBP. These data suggest LBP may be a key component in reducing CVD risk in older adults.
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