Endogenous Angiotensin II‐induced p44/42 Mitogen‐Activated Protein Kinase Activation Mediates Sodium Appetite but not Thirst or Neurohypophysial Secretion in Male Rats

The renin–angiotensin–aldosterone system makes a critical contribution to body fluid homeostasis, and abnormalities in this endocrine system have been implicated in certain forms of hypertension. The peptide hormone angiotensin II (AngII) regulates hydromineral homeostasis and blood pressure by acting on both peripheral and brain targets. In the brain, AngII binds to the angiotensin type 1 receptor (AT1R) to stimulate thirst, sodium appetite and both arginine vasopressin (AVP) and oxytocin (OT) secretion. The present study used an experimental model of endogenous AngII to examine the role of p44/42 mitogen‐activated protein kinase (MAPK) as a signalling mechanism to mediate these responses. Animals were given a combined treatment of furosemide and a low dose of captopril (furo/cap), comprising a diuretic and an angiotensin‐converting enzyme inhibitor, respectively, to elevate endogenous AngII levels in the brain. Furo/cap induced p44/42 MAPK activation in key brain areas that express AT1R, and this effect was reduced with either a centrally administered AT1R antagonist (irbesartan) or a p44/42 MAPK inhibitor (U0126). Additionally, furo/cap treatment elicited water and sodium intake, and irbesartan markedly reduced both of these behaviours. Central injection of U0126 markedly attenuated furo/cap‐induced sodium intake but not water intake. Furthermore, p44/42 MAPK signalling was not necessary for either furo/cap‐ or exogenous AngII‐induced AVP or OT release. Taken together, these results indicate that p44/42 MAPK is required for AngII‐induced sodium appetite but not thirst or neurohypophysial secretion. This result may allow for the discovery of more specific downstream targets of p44/42 MAPK to curb sodium appetite, known to exacerbate hypertension, at the same time as leaving thirst and neurohypophysial hormone secretion undisturbed.     

Advanced Pharmacy Practice Experiences in Pharmacogenomics Offered by US Pharmacy Programs

Objective. To characterize advanced pharmacy practice experiences (APPEs) with a primary focus in pharmacogenomics at schools and colleges of pharmacy in the United States.Methods. This was a cross-sectional, multicenter, observational study of pharmacogenomics APPEs at US pharmacy schools. Directors of experiential education at 146 accredited schools of pharmacy were contacted by phone and asked if their school offered a pharmacogenomics APPE. The preceptors of pharmacogenomics APPEs identified by this phone screen were sent an email with a link to an online survey that asked about their APPE offerings.Results. Of the 142 schools of pharmacy that were successfully reached via phone, 40 (28%) offered an APPE with a primary focus in pharmacogenomics. Thirty unique APPEs with pharmacogenomics as a primary focus were identified. The total number of preceptors involved in the pharmacogenomics APPEs was 33: 19 (58%) faculty preceptors and 14 (42%) non-faculty preceptors. Twenty-three of the 30 pharmacogenomics APPEs completed the survey (77% response rate). The APPE sites were diverse and included academic medical centers, community health systems, pharmacogenomic testing laboratories, and schools of pharmacy. Each pharmacogenomics APPE accommodated an average of six students per year. The APPE activities varied across sites.Conclusion. Only a small number of US pharmacy schools offer an APPE with a primary focus in pharmacogenomics. These rotations are diverse in scope and precepted by faculty or non-faculty pharmacists. The Academy should pursue opportunities to increase experiential education in pharmacogenomics.     

Relationships Between Health Care Disparities and Coverage Policies for Breast,Colon, and Lung Cancer Screening

Disparities in outcomes exist for breast, colon, and lung cancer among diverse populations, particularly racial and ethnic underrepresented minorities (URMs) and individuals from lower socioeconomic status. For example, blacks experience mortality rates up to about 42% higher than whites for these cancers. Furthermore, although overall death rates have been declining, the differential access to screening and care has aggravated disparities. Our purpose is to assess how the coverage policies of CMS and the United States Preventive Services Task Force (USPSTF) influence these disparities. Additionally, barriers are often encountered in accessing screening tests and receiving prompt treatment. To narrow, and potentially eliminate, outcomes disparities, CMS and USPSTF could consider revising their decision-making processes regarding coverage. Some options include (1) extending their evidence base to include observational studies that involve groups at higher risk; (2) lowering the threshold ages for screening to encompass differences in incidence; (3) CMS approving screening CT colonography coverage, which can even increase compliance with other screening tests; (4) clarifying and streamlining guidelines; (5) supporting research on improving access to screening; and (6) encouraging the development of more navigation services for URMs.     

Laser and electron‐beam powder‐bed additive manufacturing of metallic implants: A review on processes,materials and designs

Additive manufacturing (AM), also commonly known as 3D printing, allows the direct fabrication of functional parts with complex shapes from digital models. In this review, the current progress of two AM processes suitable for metallic orthopaedic implant applications, namely selective laser melting (SLM) and electron beam melting (EBM) are presented. Several critical design factors such as the need for data acquisition for patient‐specific design, design dependent porosity for osteo‐inductive implants, surface topology of the implants and design for reduction of stress‐shielding in implants are discussed. Additive manufactured biomaterials such as 316L stainless steel, titanium‐6aluminium‐4vanadium (Ti6Al4V) and cobalt‐chromium (CoCr) are highlighted. Limitations and future potential of such technologies are also explored. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:369–385, 2016.     

Pannexin‐1 and P2X7‐Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes

Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin‐1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find‐me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue‐loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF‐κB ligand (RANKL) expression and osteoclastic bone resorption in wild‐type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X₇R in ATP release; thus, we examined P2X₇R‐deficient mice and WT mice treated with P2X₇R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find‐me signal. P2X₇RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X₇RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X₇R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process. © 2016 American Society for Bone and Mineral Research.     

Serum adiponectin is independently associated with the metabolic syndrome in Hong Kong,Chinese women with polycystic ovary syndrome

Objective: To evaluate the association of serum adiponectin level with the metabolic syndrome in Chinese women with polycystic ovary syndrome (PCOS).

Methods: This was a cross-sectional study carried out in Hong Kong Chinese women with PCOS at a university-affiliated tertiary hospital between January 2010 and January 2011. Clinical and biochemical parameters of the women were analysed. Prediction of the metabolic syndrome was determined by receiver–operator characteristic (ROC) curves, univariate and multivariate logistic regression analyses.

Results: A total of 116 women diagnosed to have PCOS were analysed. The area under the ROC curve of adiponectin for the prediction of metabolic syndrome was 0.820, 95% confidence interval (CI) 0.737–0.886. Univariate binary logistic regression showed that testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), waist circumference, body mass index (BMI), quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and adiponectin were significantly associated with the metabolic syndrome. On multivariate logistic regression analysis, adiponectin (p?= 0.020), HOMA-IR, age (p?= 0.011) and BMI (p?= 0.019) were independently associated with the metabolic syndrome, but not FAI (p?= 0.256).

Conclusions: Serum adiponectin is independently associated with the metabolic syndrome in Chinese women with PCOS. Further longitudinal follow-up studies are needed to determine whether serum adiponectin adds to the prediction of long-term cardiometabolic morbidity conferred by age, BMI and measures of insulin resistance.     

A follow-up study of women who donated oocytes to known recipient couples for altruistic reasons

BACKGROUND: Current legislation in Canada allows for only altruistic gamete donation. Limited clinical data are available on the emotional and psychological impact of altruistic oocyte donation on known donors. METHODS: Seventeen women who had donated oocytes to known parties without financial compensation agreed to receive the oocyte donation questionnaire (ODQ) to explore the psychological domains of altruistic oocyte donation. RESULTS: Thirteen ODQ were returned, giving a response rate of 76%. All subjects indicated that they were primarily motivated by a 'desire to give and help' the recipient couple. Most subjects did not find the donation decision difficult but some found the post-donation psychological adjustments challenging. Subjects also indicated that mandatory counselling on the psychological implications of oocyte donation was an important component of cycle preparation. The majority of subjects had disclosed the donation to others and felt that disclosure to the presumptive child was essential. CONCLUSIONS: The findings provide clinical materials for conceptualizing the dynamics entailed by known altruistic oocyte donation, with regards to motivation, relationship implications, donor satisfaction and plans for disclosure. The data support the provision of psycho-social support services to help donors dealing with any residual emotional difficulties regardless of the outcome of oocyte donation.