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
PurposeAlthough an adult model of patient-provider mutual exchange of information has been proposed, there is no guiding model for adolescents or measurement methodology. Our purpose was to develop a new scale of patient-provider interaction for adolescents accessing reproductive health care and at risk for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV), and assess the reliability and validity of the scale.MethodsThe Adolescent Patient-Provider Interaction Scale (APPIS) was developed from the Roter and Hall theory of doctor-patient relationships, previously validated adolescent satisfaction and communication scales, and focus group and individual elicitation interviews. To assess construct validity, the new nine-item APPIS was compared with the satisfaction scale used by the Young Adult Health Care Survey (YAHCS), and Kahn’s Provider Communication Scale. Pearson correlation coefficients were used to examine convergence across scales, and factor analysis of the APPIS was performed.ResultsThe study recruited 192 African American girls aged 17.9 ± 1.7 years (range 15–21 years) from three sites: a county STD clinic (n = 51), urban adolescent clinic (n = 99), and a family planning clinic (n = 42). Most participants (85%) rated their overall health care highly (≥ 7 on a 10-point scale); 49% felt that both the provider and patient were “in charge” of the visit, and 88% “strongly agreed” or “agreed” that there was an equal “exchange of information” during the visit. The APPIS showed good internal consistency (Cronbach alpha = .75), and moderate convergence with the six-item YAHCS scale (r = .57, p < .001) and seven-item Kahn scale (r = .48, p < .001). Three factors emerged from exploratory factor analyses, supporting our conceptualization of patient-provider interaction as being multi-dimensional.ConclusionsA new theory-based scale of adolescent patient-provider interaction compares favorably with previous scales of health care satisfaction and communication. The new APPIS may be useful for evaluating approaches to improve health care outcomes for adolescents at-risk for STDs and HIV. 相似文献
OBJECTIVE: To investigate whether the addition of 3,5,3'-triiodothyroacetic acid (TRIAC) to thyroxine (T4) treatment can suppress TSH secretion without inducing thyrotoxicosis at the periphery. DESIGN: Thyroid cancer patients were studied with different treatment modalities: T4 at supraphysiologic dose (2.5 +/- 0.3 micrograms/kg/day) and after reduction to a physiologic dose (1.8 +/- 0.3 micrograms/kg/day); then with the addition of TRIAC 500 or 1000 micrograms/day to the physiologic T4 treatment dose. PATIENTS: Twenty-two patients who had total thyroid ablation for differentiated thyroid carcinoma. MEASUREMENTS: Clinical and biological parameters of thyroid hormone action studied included heart rate, serum creatine phosphokinase, testosterone-oestradiol binding globulin, procollagen III and osteocalcin levels. RESULTS: The addition of TRIAC induced a significant and dose-dependent decrease in serum TSH levels and parallel effects on peripheral tissues. Compared to the suppressive T4 treatment dose, the addition of TRIAC to the physiologic T4 dose resulted in greater inhibition of TSH secretion in only 50% of the patients. The effects at the periphery of both treatment modalities were similar for a comparable level of TSH suppression. CONCLUSIONS: Even at low dose and when combined with T4, TRIAC has parallel effects on the pituitary and peripheral tissues. There is no justification for the use of TRIAC as suppressive treatment in thyroid cancer patients. 相似文献