PURPOSE OF REVIEWANKH is the human homolog of a gene whose dysfunction in a mutant mouse strain results in progressive ankylosis of the spine as well as soft tissue mineralization. ANKH mutations ...have been reported in inherited human disorders such as familial calcium pyrophosphate deposition disease (CPPD) and cranial metaphyseal dysplasia; however, research into the function of the ANKH protein has been more challenging. Progress has recently been made to understand the role of ANKH in the regulation of physiological and pathological mineralization.
RECENT FINDINGSANKH expression is regulated by intracellular levels of oxygen, phosphate and calcium as well as by the growth factor TGF-β. In addition, ANKH expression affects chondrogenesis, osteoblastogenesis and osteoclastogenesis. ANKH appears to interact with several cellular proteins, including the phosphate transporter PiT-1, and with proteins involved in NF-kappa β signaling, suggesting that ANKH may play an important non-PPi transporter role. ANKH has also been shown to regulate ATP efflux from chondrocytes.
SUMMARYANKH expression, as well as its potential non-PPi transporter functions, plays a variety of roles in the regulation of cellular events that surround differentiation and mineralization in bone and cartilage. Additional studies are warranted to further elucidate the contributions of ANKH to human health and disease, and to determine if ANKH deserves targeting for the treatment of diseases such as CPPD.
Calcium pyrophosphate deposition disease is defined by the presence of calcium pyrophosphate (CPP) crystals in articular cartilage and is the fourth most common type of arthritis in adults. Despite ...its high prevalence, the etiology of CPPD disease remains unclear and no specific therapies currently exist. It has been known for several decades that abnormalities of cartilage pyrophosphate metabolism are common in patients with CPPD disease, and this classic work will be reviewed here. Recent studies of rare familial forms of CPPD disease have provided additional novel information about its pathophysiology. This work suggests that CPPD disease occurs through at least two unique and potentially intertwined biomolecular pathways. We are hopeful that a detailed understanding of the components and regulation of these pathways will lead to improved therapies for this common disease.
ASHP Statement on Precepting as a Professional Obligation Wisniewski, Jennifer N; Williams, Charlene R; Carroll, Dana G ...
American journal of health-system pharmacy,
2024-Jan-01, 2024-01-01, 20240101, Letnik:
81, Številka:
1
Journal Article
Objective
The gene TNFRSF11B encodes for osteoprotegerin (OPG) and was recently identified as the CCAL1 locus associated with familial calcium pyrophosphate deposition disease (CPDD). While the CCAL1 ...OPG mutation (OPG‐XL) was originally believed to be a gain‐of‐function mutation, loss of OPG activity causes arthritis‐associated osteolysis in mice, which is likely related to excess subchondral osteoclast formation and/or activity. The purpose of the present study was to further explore the effect of OPG‐XL in osteoclastogenesis.
Methods
The effects of recombinant OPG‐XL and wild‐type (WT) OPG were determined in monoculture and coculture models of RANKL‐induced osteoclastogenesis. The effects of OPG‐XL on osteoclast survival as well as on TRAIL‐induced apoptosis were determined using standard in vitro assays and compared to WT OPG. The ability of OPG‐XL and WT OPG to bind to osteoblasts was measured with enzyme‐linked immunosorbent assay and flow cytometry using the osteoblastic MC3T3‐E1 cell line.
Results
OPG‐XL was less effective than WT OPG at blocking RANKL‐induced osteoclastogenesis in monoculture and coculture models. Osteoclast survival and inhibition of TRAIL‐induced apoptosis were similar in the presence of OPG‐XL and WT OPG. Compared to WT OPG, considerably less OPG‐XL bound to cells.
Conclusion
These findings indicate that OPG‐XL is a loss‐of‐function mutation as it relates to RANKL‐mediated osteoclastogenesis, and thus may permit increased osteoclast numbers and heightened bone turnover. Further studies are necessary to demonstrate how this mutation contributes to arthritis in individuals carrying this mutation.
Objective. To assess preceptor teaching challenges and development programming design preferences through a qualitative needs assessment of Doctor of Pharmacy student and resident preceptors.
...Methods. In 2018, 148 experiential education stakeholders across North Carolina (eg, preceptors, residency program directors, experiential faculty administrators, and practice site administrators) were invited to participate in a 60-minute semi-structured interview as part of a broad preceptor development needs assessment. Interview questions focused on: precepting challenges, positive and negative features of development programs, and preferences for program design. Interview transcripts were coded using thematic analysis.
Results. Forty-two participants completed interviews, including preceptors from various rotation types, residency program directors, experiential faculty administrators, and institution administrators. Participants identified numerous teaching challenges related to learners, preceptors, and institutional level factors. Participants often noted there was inadequate time, resources, and support to effectively teach. Desirable preceptor development program features included practical strategies, collaboration with preceptors, delivery by education and practice experts, and topics specific to precepting experience. Participants identified live, on-demand, and webinar formats as acceptable if collaboration and engagement were included. Participants also desired unique training opportunities such as online platforms, coaching programs, and simulated learning environments.
Conclusion. Preceptors for pharmacy students and residents face numerous challenges and require sufficient time, support, and resources to develop their skills. Participants requested training that included on-demand, frequent sessions delivered through various modalities, collaboration opportunities, a choice in topics and delivery formats, and sessions from educational and practice experts.
Pharmacist shortages in rural communities underscore the need to focus on increasing the pipeline of pharmacists practicing rurally. Experiential placement in rural communities is one method to ...approach this challenge. Regional pharmacy campuses may facilitate rural experiential placements. The objective of this study was to assess the effect of a regional campus on the number of rural experiential placements. This retrospective analysis compared experiential student placements in the five-year periods before and after the addition of a regional school of pharmacy campus. Experiential placements in the designated time periods were compared with respect to numbers of overall pharmacy practice experiences, experiences in rural locations, and rural counties with rotation sites. The average distance to rural sites was also compared. Differences in rural experiential placements were not statistically different. The number of rural counties with pharmacy experiential placements grew from eight to twelve, and driving distance increased. While institution of a regional campus contributed to an increase in the number of rural counties with experiential placements, overall rural experiential placements did not statistically differ versus suburban placements. Additional inquiry into factors that affect rural placement is needed to influence strategies to develop and maintain rural experiential sites and consistently place students at those sites.
Positive learner perceptions of learning experiences have been linked to better learning outcomes. More information is needed on learners' desired qualities of preceptors and learning experiences to ...inform preceptor development. Aligning learners' perceptions with a teaching framework, such as the Cognitive Apprenticeship (CA) framework, may be useful to guide preceptor self-assessment and development. However, information is lacking regarding whether the CA framework is consistent with learners' expectations. The purpose of this study was to determine pharmacy learner perspectives on desired preceptor behaviors and qualities and to evaluate their alignment with the CA framework to inform preceptor development.
Twenty-two learners (nine residents and 13 introductory and advanced pharmacy practice students) participated in nine focus group interviews. Data were analyzed qualitatively by inductive coding and pattern coding and then condensed into themes. After initial analysis, the CA framework was adapted into codes and applied to the data to explore the alignment of quality preceptor characteristics with CA.
Learners identified desired general preceptor characteristics, teaching behaviors, and qualities of sites and experience structure in their discussion. All four CA dimensions (Methods, Sociology, Sequencing, and Content) were represented in the described desired preceptor qualities. Most comments were connected to the Methods dimension.
This study supports the use of CA as a framework to guide preceptor development and assessment for desired precepting qualities, preceptor behaviors, and learning environments. Additional research is needed for best practices in implementing CA in preceptor assessment and professional development.
Objectives
Arthritis is a common clinical manifestation of hereditary hemochromatosis (HH), and HH is one of a handful of conditions linked to calcium pyrophosphate deposition (CPPD) in joints. The ...connection between these two types of arthritis has not yet been fully elucidated. In light of new pathogenic pathways recently implicated in CPPD involving bone, we reviewed the literature on the etiology of hemochromatosis arthropathy (HHA) seeking shared pathogenic mechanisms.
Results
Clinical observations reinforce striking similarities between HHA and CPPD even in the absence of CPP crystals. They share a similar joint distribution, low grade synovial inflammation, and generalized bone loss. Excess iron damages chondrocytes and bone cells in vitro. While direct effects of iron on cartilage are not consistently seen in animal models of HH, there is decreased osteoblast alkaline phosphatase activity, and increased osteoclastogenesis. These abnormalities are also seen in CPPD. Joint repair processes may also be impaired in both CPPD and HHA.
Conclusions
Possible shared pathogenic pathways relate more to bone and abnormal damage/repair mechanisms than direct damage to articular cartilage. While additional work is necessary to fully understand the pathogenesis of arthritis in HH and to firmly establish causal links with CPPD, this review provides some plausible hypotheses explaining the overlap of these two forms of arthritis.
Objectives/Hypothesis
Psychosocial distress is common among patients with head and neck cancer (HNC) and is associated with poorer quality of life and clinical outcomes. Despite these risks, distress ...screening is not widely implemented in HNC care. In this study, we investigated the prevalence of psychosocial distress and its related factors in routine care of patients with HNC.
Methods
Data from medical records between September 2017 and March 2020 were analyzed. Psychosocial distress was measured by the National Comprehensive Cancer Network's Distress Thermometer (DT), and a modified HNC‐specific problem list; depression and anxiety were assessed using the Patient Health Questionnaire‐4. Descriptive statistics and logistic regression were conducted to report prevalence of distress, depression and anxiety, and factors associated with clinical distress. Implementation outcomes, including rates of referrals and follow‐up for distressed patients, are also reported.
Results
Two hundred and eighty seven HNC patients completed the questionnaire (age 64.3 ± 14.9 years), with a mean distress score of 4.51 ± 3.35. Of those, 57% (n = 163) reported clinical distress (DT ≥ 4). Pain (odds ratio OR = 3.31, 95% CI = 1.75–6.26), fatigue (OR = 2.43, 95% CI = 1.1.7–5.05), anxiety (OR = 1.63, 95% CI = 1.30–2.05), and depression (OR = 1.51, 95% CI = 1.04–2.18) were significantly associated with clinical distress (P < .05). Of patients identified as distressed, 79% received same‐day psychosocial evaluation.
Conclusions
Clinical distress was identified in 57% of patients who completed the questionnaire, suggesting that an ultra‐brief psychosocial screening protocol can be implemented in routine ambulatory oncology care, and identifies patients whose distress might otherwise go unrecognized.
Level of Evidence
4 Laryngoscope, 132:1600–1608, 2022
The purpose of this study was to develop and assess an easily accessible interprofessional mobile web application to assist preceptors with challenging teaching and learning situations.
Phase 1 was a ...modified Delphi process of 48 advanced practice nursing, dentistry, medicine, and pharmacy preceptors to determine the content of the application. Phase 2 consisted of 12 preceptors from the 4 disciplines piloting a prototype to refine the tool using design-thinking principles. Feedback was analyzed using inductive coding and thematic analysis. Phase 3 evaluated the impact of the final tool on 80 preceptors’ satisfaction, knowledge, self-efficacy, and perception of behavior change.
Consensus on 10 topics was reached in the following 3 themes: feedback and communication, clinical and professional development of learners, and precepting efficiency. Preceptors rated the tool as efficient and applicable. Features perceived as useful included concise and applicable content that was easy to navigate with practical video examples. Features to improve included academic jargon, length of content, and lack of connectivity with other preceptors. Knowledge and self-efficacy improved after the use of the refined tool. Change in perceptions of behavior after 1 month was mixed, with a significant change in accessing resources to address challenging situations and regularly reflecting on challenging situations and no significant change in awareness, frequency, or success in managing challenging situations.
An interprofessional mobile web application for challenging teaching and learning situations developed through a modified Delphi process was deemed efficient and relevant and demonstrated positive knowledge and self-efficacy change.
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