Patient Turnover Research Articles

Impact of whole-body vibration exercise on physical performance and bone turnover in patients with monoclonal gammopathy of undetermined significance

ObjectiveMonoclonal Gammopathy of Undetermined Significance (MGUS) is a risk factor for reduced physical performance, osteoporosis, and fractures due to compromised musculoskeletal metabolism. In this condition it is unknown whether whole-body vibration (WBV) exercise favorably alters physical performance and bone metabolism. MethodsTo evaluate the effect of three-months WBV exercise (30 min; 2x/week) including an optional three-month extension on physical performance, bone metabolism and bone mineral density. Endpoints included functional assessments, bone turnover markers and bone mineral density assessed by peripheral quantitative computed tomography of the tibia. ResultsFifteen MGUS patients (median age 62.0, nine female) completed the first three months of which ten completed the three-month extension. Measures of physical functioning including chair rise test, timed up and go and 6-minute walk test improved (p = 0.007; p = 0.009; p = 0.005) after three and six months of WBV exercise. Total tibial bone mineral density remained unaltered (p > 0.05). WBV exercise tended to increase levels of sclerostin (p = 0.093) with a transient increase in osteoclast resorption markers (N-terminal telopeptide of collagen type 1, tartrate resistant acid phosphatase 5b) after three months while Dickkopf-1 (p = 0.093), procollagen I N-terminal propeptide (p = 0.074) and total alkaline phosphatase (p = 0.016) appeared to decline. No exercise-related adverse events were reported. ConclusionWBV exercise in MGUS patients improves indicators of physical performance. Observed trends in bone turnover markers and changes in distal tibial bone mineral density may indicate a regulatory effect of WBV exercise on bone metabolism and warrants further evaluation by large scale studies.

Bone turnover biomarkers, disease activity, and MRI changes of sacroiliac joints in patients with spondyloarthritis.

The lack of valid biomarkers in patients with spondyloarthritis (SpA) requires searching for additional options to increase sacroiliac joint (SIJ) evaluation effectiveness. We assessed the serum levels of bone turnover markers and their relationships with active and chronic changes in SIJs using magnetic resonance imaging (MRI), indices, and laboratory parameters of disease activity in SpA patients. 102 patients with SpA and 15 healthy subjects were included. Testing of serum levels of transforming growth factor-beta (TGF-β1), Wnt3, sclerostin, and Dickkopf-1 (Dkk-1) was conducted. Active inflammatory lesions in SIJs were evaluated using Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ score, and chronic changes using the Danish scoring method. Bath Ankylosing Spondylitis Disease Activity Index, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Ankylosing Spondylitis Disease Activity Scores with CRP, and ESR were used to assess disease activity. Serum levels of Dkk-1, TGF-β1, and sclerostin were significantly lower in SpA patients compared to healthy controls. The serum levels of Dkk-1 positively correlated with CRP. Dkk-1 had a significant negative correlation with Danish score. The sclerostin serum level had a weak negative correlation with the active inflammatory MRI SIJ lesions. There were positive correlations between TGF-β1 and sclerostin with Dkk-1, and negative correlation between Wnt3 and sclerostin. Dkk-1 positively correlated with CRP and negatively with chronic SIJ changes by Danish score. Sclerostin negatively correlated with the active SIJ lesions by SPARCC. This suggests that Dkk-1 and sclerostin are the most promising candidates to reveal inflammation and bone turnover in patients with SpA.

Primary Aldosteronism and Bone Metabolism: A Systematic Review and Meta-Analysis.

BackgroundCurrently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis.MethodsPubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient.ResultsA final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (MD=21.50 pg/ml, 95% CI (15.63, 27.37), P<0.00001) and slightly increased urinary calcium levels (MD = 1.65 mmol/24 h, 95% CI (1.24, 2.06), P < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery.ConclusionsPA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.

Interim Analysis of a Phase 2 Open-Label Trial Assessing Burosumab Efficacy and Safety in Patients With Tumor-Induced Osteomalacia

ABSTRACTPatients with tumor‐induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X‐linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti‐fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open‐label, intraindividual dose‐adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient‐reported outcomes. Safety was assessed based on treatment‐emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6‐minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment‐related TEAEs of grade ≥3 and no treatment‐related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Flow-Identified Site of Collapse During Drug-Induced Sleep Endoscopy: Feasibility and Preliminary Results

Flow-Identified Site of Collapse During Drug-Induced Sleep Endoscopy: Feasibility and Preliminary Results

Acceptability and Feasibility of Perioperative Music Listening: A Rapid Qualitative Inquiry Approach.

Perioperative music decreases pain, anxiety, and analgesia requirements while increasing patient satisfaction. We investigated the acceptability of perioperative music at a women's and children's hospital in Singapore, seeking to uncover barriers and facilitators to implementation in routine practice over a 12-week period. We used an undergraduate-led Rapid Qualitative Inquiry approach that includes data collection from multiple sources, iterative analysis, and additional data collection when necessary. Participants consisted of anesthesiologists and nurses working in the preoperative area, operating room, and postoperative recovery areas. In Stage 1, nurses and anesthesiologists answered a survey assessing attitudes and knowledge about perioperative music and attended a presentation introducing the intervention. In Stage 2, the results of the Stage 1 survey were disclosed, and nurses and anesthesiologists completed a second survey (Stage 1 survey questions with an additional query about implementation). Twenty-nine nurses were interviewed with semi-structured questions on barriers and facilitators to implementation. In Stage 3, nurses retook the Stage 2 survey after one month of implementation. The implementation of perioperative music was both acceptable and feasible in Singapore. The nurses' and anesthesiologists' acceptability increased over time with mostly positive qualitative feedback. Implementation barriers, including patient interest, timing of patient turnover, and added staff workload, appeared minor and could potentially be overcome by utilizing the intervention in the preoperative instead of postoperative area, deploying music in operating rooms with slower turnover, and evenly distributing staff workload. Local implementation stakeholders may make additional recommendations for scaling-up perioperative music interventions to fit other workflows while improving the patient experience.

Evolution of the environmental microbiota of a new neonatal intensive care unit (NICU) and implications for infection prevention and control.

To describe changes in the environmental microbiota of a new neonatal intensive care unit (NICU) and potential implications for infection prevention and control (IPC) efforts. Prospective observational study. A newly constructed level IV neonatal cardiac intensive care unit (NCICU) before and after patient introduction and the original NICU prior to patient transfer. Environmental samples were obtained from the original NICU prior to patient transfer to a new NCICU. Serial sampling of patient rooms and provider areas of the new NICU was conducted immediately prior to patient introduction and over an 11-month study period. Microbiota at each sampling point were characterized using Illumina sequencing of the V3/V4 region of the 16S rRNA gene. Microbiota characteristics (α and β diversity and differential abundance) were compared based on time, location, and clinical factors (room-level antibiotic use and patient turnover). An immediate increase in the environmental differential abundance of gut anaerobes were seen after patient introduction. There was an increase in the relative abundance of Staphylococcus spp, Klebsiella spp, Pseudomonas spp, and Streptococcus spp over time. The new NCICU consistently showed more diverse microbiota and remained distinct from the original NICU. The microbiota of the provider areas of the NCICU eventually formed a cluster separate from the patient rooms. Patient turnover increased room-level microbiota diversity. Microbiota characteristics of the new NICU were distinct from the original ICU despite housing similar patients. Patient and provider areas developed distinct microbiota profiles. Non-culture-based methods may be a useful adjunct to current IPC practice.

Exploring interprofessional teamwork at a tertiary public hospital in South Africa

ABSTRACT The landscape of health in South Africa has changed dramatically with the unprecedented rise in the burden of disease. Public health care facilities struggle to provide quality, patient-centered care to patients with complex health needs. Interprofessional teamwork is strongly advocated to improve the quality and patient-centeredness of care. This study explored the barriers and facilitators of interprofessional teamwork amongst health professionals working at a tertiary level public hospital in South Africa. The study employed a qualitative, descriptive, exploratory design. Data were collected during three focus group discussions with 14 purposively selected participants from several health professions. Barriers such as high patient turnover, lack of human resources, time, hierarchy, referral process, lack of knowledge of the roles and scopes of practice, negative attitudes, communication inefficiencies, language barriers, and professional jealousy were found to impede interprofessional teamwork. Facilitators of interprofessional teamwork included increased human resources, communication technology, respect, and relationship building. Although health professionals understand the barriers and facilitators of interprofessional teams in the provision of patient care, this study concludes that interprofessional capacity building is needed for successful interprofessional teamwork at a tertiary level public hospital setting.

The Performance of Deep Neural Networks in Differentiating Chest X-Rays of COVID-19 Patients From Other Bacterial and Viral Pneumonias.

Chest radiography is a critical tool in the early detection, management planning, and follow-up evaluation of COVID-19 pneumonia; however, in smaller clinics around the world, there is a shortage of radiologists to analyze large number of examinations especially performed during a pandemic. Limited availability of high-resolution computed tomography and real-time polymerase chain reaction in developing countries and regions of high patient turnover also emphasizes the importance of chest radiography as both a screening and diagnostic tool. In this paper, we compare the performance of 17 available deep learning algorithms to help identify imaging features of COVID19 pneumonia. We utilize an existing diagnostic technology (chest radiography) and preexisting neural networks (DarkNet-19) to detect imaging features of COVID-19 pneumonia. Our approach eliminates the extra time and resources needed to develop new technology and associated algorithms, thus aiding the front-line healthcare workers in the race against the COVID-19 pandemic. Our results show that DarkNet-19 is the optimal pre-trained neural network for the detection of radiographic features of COVID-19 pneumonia, scoring an overall accuracy of 94.28% over 5,854 X-ray images. We also present a custom visualization of the results that can be used to highlight important visual biomarkers of the disease and disease progression.

Is the Psychiatric History Losing Its Relevance?

One of the axioms of medical practice is that obtaining a good history is key to making a correct diagnosis and developing a treatment plan. This is particularly true in psychiatry, in which laboratory or imaging investigations are not typically of great value. Any factor that compromises a history may compromise care. This area of practice has not been formally studied, although it is widely believed to be true. In mental health settings, there are many factors that affect obtaining the history. Among these are the skills of the clinician in eliciting relevant information in a limited time, the clinician's philosophy regarding the importance of such history, and lack of formal training in history-taking. Nonphysician clinicians may be more likely than psychiatrists to confront these barriers. Practice settings may, in their effort to maximize access, patient turnover, and cost control, convey a here-and-now approach to patient care, implicitly downplaying the importance of a complete history. There may be some cultural factors at play as well, reflecting American society's gradually decreased interest in the study of history. Despite these understandable barriers, the need for a complete history is still the highest priority in an initial evaluation. Some suggestions are offered to support clinicians' and organizations' struggles to keep a comprehensive history at the forefront of care.

Topical anaesthesia plus intracameral lidocaine versus topical anaesthesia alone for phacoemulsification cataract surgery in adults

Background Phacoemulsification cataract surgery is usually performed in adults under local anaesthesia. Topical anaesthesia, which involves instilling anaesthetic drops to the ocular surface prior to and during surgery, has found large acceptance internationally. It is safe and allows for rapid patient turnover and visual recovery. Some surgeons have supplemented topical anaesthesia with intracameral lidocaine, reasoning that this may further reduce intraoperative pain, particularly during surgical stages involving manipulation of intraocular structures and rapid changes in fluid dynamics. This review, originally published in 2006 and updated in 2020, explores the efficacy and safety of using supplementary intracameral lidocaine in phacoemulsification cataract surgery.

Topical anaesthesia plus intracameral lidocaine versus topical anaesthesia alone for phacoemulsification cataract surgery in adults.

Topical anaesthesia plus intracameral lidocaine versus topical anaesthesia alone for phacoemulsification cataract surgery in adults.

Effects of COVID-19 Pandemic on Health and Wellbeing of Older People: A Comprehensive Review.

The pandemic is unavoidable; in addition to increased morbidity and mortality, they profoundly affect people and economies at every level. The negative effects of pandemics are more severe in marginalized populations such as older adults who have higher risks of acquiring infection, more disease-related complications, and increased risks of death. Furthermore, older people are affected by policy decisions and containment measures taken during pandemics. With rapid patient turnover and overwhelmed health care facilities, this older population may not receive proper medical care. In addition to poor clinical outcomes, such measures have profound negative effects on the mental health of older populations.

Assessment of the duration of surgery and patient turnover after the incorporation of a standardized intracameral combination of mydriatics and anesthetics for cataract surgery

To evaluate changes in clinical outcomes, duration, and workflow of cataract surgery, before and after the introduction of a commercially available intracameral combination of 2 mydriatics (phenylephrine, tropicamide) and 1 anesthetic (lidocaine) (ICMA). Service d'Ophtalmologie, Hôpital Bicêtre, Université Paris Sud., Le Kremlin-Bicêtre, France. Retrospective chart review. Three series of patients who underwent cataract surgery were grouped according to when they had surgery: just before ICMA was approved (early 2016, Series I); just after implementation of ICMA as the standard procedure for surgery (late 2016, Series II); and 21 months after using ICMA routinely for surgery (2018, Series III). Data were collected on patient turnover during the day of surgery and surgical outcomes. The study population comprised of 51, 47, and 51 patients in Series I, II, and III respectively. There were no statistical differences between series in the mean change in corrected distance visual acuity from preoperatively to 1 month postoperatively and in complications (P > .05, all comparisons). The mean duration of surgery was significantly shorter in Series III and II, compared with Series I (13.18 ± 4.05 and 13.62 ± 5.26 vs 15.82 ± 6.01 minutes; P = .023 and P = .041, respectively). The mean patient rotation was statistically significantly shorter in Series III compared with Series I (41.50 ± 8.31 vs 47.79 ± 14.66 minutes, respectively; P = .028). Implementing ICMA as a routine procedure in cataract surgery resulted in similar vision and safety outcomes than the usual topical eyedrop regimen, while significantly reducing the total surgery and rotation times. Hence, patient turnover during the surgical session was optimized while maintaining safety and efficacy of the procedure.

MiR-205 regulates bone turnover in elderly female patients with type 2 diabetes mellitus through targeted inhibition of Runx2.

The present study aimed to explore the expression of microribonucleic acid (microRNA) (miR)-205 in bone tissues and serum of elderly female patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP), and to investigate the effect of miR-205 on osteogenesis/adipogenesis of bone marrow mesenchymal stem cells (BMSCs) and its mechanism in elderly female mice with T2DM + OP. The bone tissues and serum of 24 female patients with T2DM + OP at the Third Affiliated Hospital of Qiqihar Medical University were collected as the research group, while those of 24 healthy people were collected as the control group. The expression level of miR-205 was detected in both groups via reverse transcription-polymerase chain reaction (RT-PCR). Then the elderly female mouse model of T2DM + OP was established as a model group, while normal mice of the same age were used as the control group. The mice in the model and control groups were transfected with miR-205 mimic, negative control (NC)-mimic, miR-205-inhibitor and NC-inhibitor. Alizarin red S (ARS) staining and RT-PCR were conducted after osteogenic induction for 21 days, and oil red O (ORO) staining and RT-PCR were performed after adipogenic induction for 24 days. The overexpression of miR-205 inhibited osteogenic differentiation and promoted adipogenic differentiation of BMSCs in elderly female mice with T2DM + OP, while knockdown of miR-205 promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs in elderly female mice with T2DM + OP. In addition, miR-205 was able to directly suppress the expression of its target gene RUNX family transcription factor 2 (Runx2). The expression level of miR-205 was obviously increased in female patients with T2DM + OP and the elderly female mouse model of T2DM + OP. In addition, miR-205 was able to regulate the osteogenic/adipogenic differentiation of BMSCs, and miR-205/Runx2 may be a new method and target for the treatment of female patients with T2DM + OP.

P0904EFFECT OF EMPAGLIFLOZIN ON SERUM MARKERS OF OSTEOCYTE AND OSTEOBLAST FUNCTION AND ALBUMINURIA IN DIABETIC AND NON-DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors are new class of oral antidiabetic drugs that show potent cardio- and nephroprotective actions. Despite having a favorable safety profile the treatment with SGLT2 inhibitors has been associated with several side-effects including increased risk of fractures. Although the pathomechanism of this complication has not been elucidated these drugs may inhibit tubular reabsorption of phosphate which may stimulate a secretion of fibroblast growth factor 23 (FGF23). The study was designed to assess the effect of SGLT2 inhibitor on markers of calcium-phosphate metabolism, bone turnover and early glomerular injury in diabetic and non-diabetic patients with stage 3 chronic kidney disease (CKD). Method 41 patients with chronic kidney disease including 23 without diabetes (13 M, 11F, age 52.9±0.7 years, estimated glomerular filtration rate (eGFR) 38.6±10.8 ml/min/1.73 m2) and 18 with type 2 diabetes (12 M, 6F, age 58.8±1.4 years, eGFR 38.8±7.7 ml/min/1.73 m2) were recruited. Main inclusion criteria were CKD stage 3 and urine albumin secretion &amp;gt;100 mg/g creatinine. All subjects received oral empagliflozin 10 mg once daily for 7 days. Serum calcium, phosphorus, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF23 and urine calcium, phosphate and albumin were measured at baseline and after 7 days of empagliflozin treatment. Results Plasma calcitriol, serum and urine calcium, phosphorus and BAP did not change significantly during the administration of empagliflozin. Urine phosphate/creatinine ratio was similar in both subgroups at baseline and did not change during empagliflozin administration. Plasma PTH was higher in non-diabetics than in diabetics both at baseline and after empagliflozin. The increase of PTH after empagliflozin tended to be higher in diabetic patients (p=0.07). There was only a trend towards an increase of serum FGF23 in both non-diabetic and diabetic subgroup (by 4.2±0.2 vs. 9.3±1.1 pg/mL, ns). BAP was significantly higher at baseline in diabetic patients but did not significantly change after empagliflozin in the subgroups. Albumin/creatinine ratio decrease after empagliflozin administration was significant only in non-diabetic patients (-62±17 vs. -2±8 mg/g in diabetic patients, p=0.03 for difference). Conclusion Our study showed no effect of short-time administration of empagliflozin on calcium-phosphate and bone metabolism markers in patients with both diabetic and non-diabetic CKD. Empagliflozin decreased albuminuria significantly only in non-diabetic CKD that may suggest a potentially greater nephroprotective effect of this SGLT2 inhibitor in non-diabetic than in diabetic nephropathy.

Changing paradigms of dermatology practice in developing nations in the shadow of COVID-19: Lessons learnt from the pandemic.

At present, routine dermatology practices stay mostly disrupted worldwide owing to the ongoing COVID‐19 pandemic. However, dermatology services need to be resumed in future and dermatologists especially in developing countries face a mammoth task of devising plans to tackle the upcoming surge of patients while still maintaining the precautions to avoid risk of infection to health care workers and our patients. Teledermatology practice is a viable alternative and there is need of starting functioning teledermatology centers at primary health care centers and training health care workers in telemedicine. Several steps like increasing the working hours of outpatient clinics, posting dermatologists and health staffs in shifts, encouraging online registration and payment, providing time slots to patients should be taken to prevent overcrowding at outpatient departments in hospitals of developing countries like India where the usual patient turnover during summers maybe around 600 to 800 per day. Once diagnosed by the dermatologist, a subsequent meticulous use of teledermatology can limit the number of follow‐up visits. To avoid student gatherings, the undergraduate and postgraduate teaching schedule should be replaced by online or virtual teaching in form of webinars and video conferencing. Above all, intense upgradation of health care infrastructure, recruitment, training of new health care staffs on mass level and huge investment in health care sector is required in all the developing countries.

Potential Biomarkers of the Turnover, Mineralization, and Volume Classification: Results Using NMR Metabolomics in Hemodialysis Patients

ABSTRACTBone biopsy is still the gold standard to assess bone turnover (T), mineralization (M), and volume (V) in CKD patients, and serum biomarkers are not able to replace histomorphometry. Recently, metabolomics has emerged as a new technique that could allow for the identification of new biomarkers useful for disease diagnosis or for the understanding of pathophysiologic mechanisms, but it has never been assessed in the chronic kidney disease–mineral and bone disorder (CKD–MBD) scenario. In this study, we investigated the association between serum metabolites and the bone TMV classification in patients with end‐stage renal disease by using serum NMR spectroscopy and bone biopsy of 49 hemodialysis patients from a single center in Brazil. High T was identified in 21 patients and was associated with higher levels of dimethylsulfone, glycine, citrate, and N‐acetylornithine. The receiver‐operating characteristic curve for the combination of PTH and these metabolites provided an area under the receiver‐operating characteristic curve (AUC) of 0.86 (0.76 to 0.97). Abnormal M was identified in 30 patients and was associated with lower ethanol. The AUC for age, diabetes mellitus, and ethanol was 0.83 (0.71 to 0.96). Low V was identified in 17 patients and was associated with lower carnitine. The association of age, phosphate, and carnitine provided an AUC of 0.83 (0.70 to 0.96). Although differences among the curves by adding selected metabolites to traditional models were not statistically significant, the accuracy of the diagnosis according to the TMV classification seemed to be improved. This is the first study to evaluate the TMV classification system in relation to the serum metabolome assessed by NMR spectroscopy, showing that selected metabolites may help in the evaluation of bone phenotypes in CKD–MBD. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Concentration and Duration of Indoxyl Sulfate Exposure Affects Osteoclastogenesis by Regulating NFATc1 via Aryl Hydrocarbon Receptor.

Indoxyl sulfate (IS) is a chronic kidney disease (CKD)-specific renal osteodystrophy metabolite that affects the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a transcription factor promoting osteoclastogenesis. However, the mechanisms underlying the regulation of NFATc1 by IS remain unknown. It is intriguing that the Aryl hydrocarbon receptor (AhR) plays a key role in osteoclastogenesis, since IS is an endogenous AhR agonist. This study investigates the relationship between IS concentration and osteoclast differentiation in Raw 264.7 cells, and examines the effects of different IS concentrations on NFATc1 expression through AhR signaling. Our data suggest that both osteoclastogenesis and NFATc1 are affected by IS through AhR signaling in both dose- and time-dependent manners. Osteoclast differentiation increases with short-term, low-dose IS exposure and decreases with long-term, high-dose IS exposure. Different IS levels switch the role of AhR from that of a ligand-activated transcription factor to that of an E3 ubiquitin ligase. We found that the AhR nuclear translocator may play an important role in the regulation of these dual functions of AhR under IS treatment. Altogether, this study demonstrates that the IS/AhR/NFATc1 signaling axis plays a critical role in osteoclastogenesis, indicating a potential role of AhR in the pathology and abnormality of bone turnover in CKD patients.

COVID-19 testing and patients in mental health facilities.

COVID-19 testing and patients in mental health facilities.