Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass. 相似文献
The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.
DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.
DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.
Apparent CLint values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CLint values for total metabolism (CYP and CES enzymes) per gram of adult human liver.
Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.
Schizophrenia is a chronic mental illness that affects the client, family, and community. Nurses are educated to use the nurse-patient relationship to provide health education and collaborative health decision-making. However, challenges abound for nurses and clients with schizophrenia to effectively utilize the relationship to reach these goals.
Problem
There is a lack of evidence-based information to assist nurses to meet the challenges of building effective therapeutic relationships with clients for whom schizophrenia hinders health education and decision-making.
Purpose
To examine current research findings on factors that influence therapeutic relationships in psychiatric treatment settings as an initial effort to provide empirically based guidance for psychiatric nurses who seek to better use the relationship to work with the client toward health-related goals.
Method
This integrative review of the literature follows Whittemore and Knafl's (2015) method, analyzes 15 studies from multiple databases between the years 2006–2017, and assesses the rigor of each.
Findings
Numerous methods are used to assess therapeutic relationships. Few studies included nurses. Provider perception of client symptoms can negatively affect provider assessment of quality of relationship; no such association was found on the part of clients. Providers and clients prioritize client needs differently, with providers influenced by treatment setting demands, but provider-training programs can have a beneficial effect on their relationships.
Conclusion
Nurses and nurse educators can use the findings to guide assessment of how perceptions and priorities influence relationships. Findings also provide the foundation for further study of nurses' perceptions of therapeutic relationship, in progress, to yield more detailed information on what nurses and educators need to strengthen therapeutic relationships. 相似文献
In an outpatient rehabilitation setting, both patients’ use and therapists’ knowledge of complementary and alternative medicine
(CAM) varies widely. Based on this observation and a recognition of CAM as an emerging practice area for rehabilitation professionals,
it was felt that a thorough and consistent approach to the education and orientation of physical therapists to the world of
CAM and integrative care was needed. This special interest paper will describe one center’s approach, development, and use
of a unique and comprehensive training manual designed to provide both a structured and standardized approach for educating
physical therapists about CAM and related therapeutic modalities. This innovative teaching tool allows for multiple methods
of content delivery within a multidisciplinary format and can be used for those who practice currently or desire to practice
in an integrative care environment. 相似文献
Tears of the retinal pigment epithelium (RPE) are a recognized complication of pigment epithelium detachments associated with age-related macular degeneration (ARMD). The RPE tears are often associated with a poor visual prognosis and typically do not occur with subretinal hemorrhage. We report the case of a 76-year-old man with ARMD who developed an RPE tear associated with subretinal hemorrhage, without a demonstrable subretinal neovascular membrane. Temporally, there was a marked decrease in his vision that returned to his earlier baseline visual acuity over the course of six months of observation. 相似文献
The present study examined the hypothesis that oxytocin (OT) may influence female sexual behavior in prairie voles (Microtus ochrogaster). The effectiveness of OT to induce sexual behavior was tested in ovariectomized females that were injected daily with estradiol benzoate (EB, 0.02 micrograms, twice), a dose insufficient for estrus induction. On the third day females received intracerebroventricular (ICV) injections of OT (1, 300, or 1000 ng) or saline vehicle. In the presence of minimal estrogen stimulation, OT did not induce sexual receptivity, or influence autogrooming or other social interactions. The behavioral effects of OT were examined in another group of ovariectomized females that received daily oil or EB injections (10 micrograms, twice) followed on the third day by either ICV (1, 300, or 1000 ng) or intraperitoneal (IP) (1, 3, or 10 micrograms) injections of OT. Among EB-treated females, only those in confirmed estrus, prior to ICV or IP injection, were included in these studies. There was a dose-related decrease in the percentage of females that remained in behavioral estrus after ICV OT. In those females that continued to show sexual behavior, lordosis frequencies and durations were unaffected by ICV OT. Nonsexual behavior did not differ between mated females and those exhibiting OT-inhibited sexual behavior. In females that were EB-treated, autogrooming and side-by-side behavior increased after ICV OT, while there was a decline in aggression. Female sexual and nonsexual behaviors were not significantly affected by IP OT.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献