Thermal energy and electro-osmotic for biomimetic artificial olfactory cilia in tri-hybrid nanofluids: entropy-defying approaches.

Biomimetic artificial olfactory cilia have demonstrated potential in identifying specific volatile organic compounds linked to various diseases, including certain cancers, metabolic disorders, and respiratory conditions. These sensors may facilitate non-invasive disease diagnosis and monitoring. Cilia Motility is the coordinated movement of cilia, which are hair-like projections present on the surface of particular cells in different species. Cilia serve an important part in several biological functions, including motility, fluid movement, and sensory reception. Cilia motility is a complicated process that requires the coordinated interaction of structural components and molecular pathways. Cilia are made up of a highly structured structure known as the axoneme, which is made up of microtubules grouped in a unique pattern. The axoneme is made up of nine outer doublet microtubules and a core pair of singlet microtubules. This arrangement offers structural support and serves as a scaffold for the proteins involved in ciliary movement. Our latest endeavors investigate these Multiphysics phenomena in ciliary beating flows that are inspired by biology, utilizing copper, gold, and titania nanoparticles. We examine their functions in biological systems such as peristaltic transport computationally. Our models give precise two- and three-dimensional velocity, temperature, and concentration solutions by integrating transverse magnetohydrodynamics with laser heating. Furthermore, at the channel wall expressions, the skin friction coefficient, Sherwood number, Nusselt number and optimization of entropy generation are acquired and analyzed. Important properties of the velocity and scalar profiles are revealed by a thorough analysis of dimensionless parameters. The simplified examination provides more insight into the trapping patterns that result from the complex interaction between nanofluid rheology and optics. These findings greatly contribute to our knowledge and improvement of nanofluidic transport technologies in a variety of fields supporting industry, sustainability, and medicine. Our combined computational and experimental methodology clarifies the complex dynamics in these systems and provides design guidance for the engineering of improved fluidic devices that make use of multifunctional nanomaterial interfaces and peristaltic motion.

Unsteady boundary-layer flow over jerked plate moving in a free stream of viscoelastic fluid.

This study aims to investigate the unsteady boundary-layer flow of a viscoelastic non-Newtonian fluid over a flat surface. The plate is suddenly jerked to move with uniform velocity in a uniform stream of non-Newtonian fluid. Purely analytic solution to governing nonlinear equation is obtained. The solution is highly accurate and valid for all values of the dimensionless time 0 ≤ τ < ∞. Flow properties of the viscoelastic fluid are discussed through graphs.

Incorporation of Calcimimetics into ESRD Bundle: Changes in Etelcalcetide Utilization and PTH Control Following End of TDAPA Designation.

INTRODUCTION: Calcimimetics, including intravenous etelcalcetide and oral cinacalcet, are often prescribed to hemodialysis patients to prevent complications of elevated parathyroid hormone (PTH) levels. In January 2021, US dialysis reimbursement policy switched from the transitional drug add-on payment adjustment (TDAPA) to an increased bundled payment, with $10.09 per session added for all hemodialysis patients to cover the expense for calcimimetics, whether or not patients are administered etelcalcetide. We leveraged this natural experiment to investigate the impact of this policy change. METHODS: This analysis included 713 US in-center hemodialysis patients enrolled in the United States Dialysis Outcomes and Practice Patterns Study (US-DOPPS) who discontinued etelcalcetide during the TDAPA transition period (December 2020 - April 2021). Within a self-matched longitudinal design, within-patient changes in mean PTH, calcium, and phosphorus were assessed in the six months pre- vs. post- etelcalcetide discontinuation, using linear regression adjusted for potential confounders. RESULTS: Etelcalcetide use in US-DOPPS decreased 58%, from 12% to 5% from July 2020 to July 2021; 73% of etelcalcetide discontinuers switched to cinacalcet within six months. Comparing the six months pre- vs. post- etelcalcetide discontinuation, mean PTH levels increased by 107 (95% CI: 80, 133) pg/mL, and the prevalence of PTH >600 pg/mL increased by 15% (95% CI: 11%, 19%), from 28% to 43% overall, and increased from 26% to 49% among Black patients. Mean serum calcium and phosphorus levels increased by 0.42 and 0.16 mg/dL, respectively. CONCLUSION: Etelcalcetide use decreased substantially after TDAPA ended in January 2021, with most patients switching to cinacalcet. The subsequent increase in PTH levels was swift and sustained, and especially pronounced among Black patients, raising concerns about disparities and potential downstream impact on clinical outcomes. Despite the spirit of the policy change, the flat per-treatment increased payment may have inadvertently created a financial incentive to restrict patient access to a more effective therapy, and potentially stifle drug innovation.

Entropic analysis of cilia-modulated slip flow of trimetallic nanofluid through electroosmotic corrugated pump in the presence of inclined magnetic field.

An incredible eradication of thermal indulgence is required to enhance the flow and heat transfer enhancement in micro/nanofluidic devices. In addition, the rapid transport and instantaneous mixing of colloidal suspensions of metallic particles at nanoscale are exceptionally crucial at ascendency of inertial and surface forces. To address these challenges, the present work is intended to investigate the role of trimetallic nanofluid comprising of three kinds of nano-sized granules (titanium oxide, Silica and Aluminium dioxide) with pure blood through a heated micropump in the presence of inclined magnetic field and axially implemented electric field. To ensure rapid mixing in unidirectional flow, the pump internal surface is lined-up with mimetic motile cilia with slip boundary. The embedded cilia whip in pattern due to dynein molecular motion controlled by time and produce a set of metachronal waves along the pump wall. The shooting technique is executed to compute the numerical solution. In a comparative glance it is revealed that the trimetallic nanofluid exhibits 10% higher heat transfer efficiency as compared to bi-hybrid and mono nanofluids. Moreover, the involvement of electroosmosis results in almost 17% decrease in the heat transfer rate if it values jumps from 1 to 5. The fluid temperature in case of trimetallic nanofluid is higher and thus keeps the heat transfer entropy and the total entropy lower. Furthermore, involvement of thermal radiated and momentum slip significantly contribute in reducing heat losses.

Entropy generation in thermally radiated hybrid nanofluid through an electroosmotic pump with ohmic heating: Case of synthetic cilia regulated stream.

Synthetic cilia-regulated transports through micro and nanofluidic devices guarantee an efficient delivery of drugs and other biological substances. Entropy analysis of cilia stimulated transport of thermally radiated hybrid nanofluid through an electroosmotic pump is conducted in this study. Joint effects of applied Lorentz force and Ohmic heating on the intended stream are also studied. Metachronal arrangements of cilia field coating channel inner side, are liable to generate current in the fluid. After using the lubrication and the Debye-Huckel estimations, numerical solutions of the envisioned problem are obtained. For pressure rise per metachronal wavelength, the pressure gradient is numerically integrated. The analysis reveals that high electric potential results in reducing the heat transfer effects in the flow system. The enhancement of flow is noticed near the channel surface for higher electroosmotic parameters. The irreversibility in the channel decreases when the Helmholtz-Smoluchowski velocity is applied in the opposite direction of the flow and thus produces the fluid friction irreversibility.

Entropy Production in Electroosmotic Cilia Facilitated Stream of Thermally Radiated Nanofluid with Ohmic Heating.

No thermal process, even the biological systems, can escape from the long arms of the second law. All living things preserve entropy since they obtain energy from the nutrition they consume and gain order by producing disorder. The entropy generation in a biological and thermally isolated system is the main subject of current investigation. The aim is to examine the entropy generation during the convective transport of a ciliated nano-liquid in a micro-channel under the effect of a uniform magnetic field. Joint effects of electroosmosis and thermal radiation are also brought into consideration. To attain mathematical simplicity, the governing equations are transformed to wave frame where the inertial parts of the transport equations are dropped with the use of a long-wavelength approximation. This finally produces the governing equations in the form of ordinary differential equations which are solved numerically by a shooting technique. The analysis reports that the cilia motion contributes to enhance the flow and heat transfer phenomena. An enhancement in the flow is observed near the channel surface for higher cilia length and for smaller values of the electroosmotic parameter. The entropy generation in the ciliated channel is observed to be lessened by intensifying the thermal radiation and decreasing the Ohmic heating. The extended and flexible cilia structure contributes to augment the volumetric flow rate and to drop the total entropy generation in the channel.

Impact of partial slip and lateral walls on peristaltic transport of a couple stress fluid in a rectangular duct.

The impact of lateral walls and partial slip with different waveforms on peristaltic pumping of couple stress fluid in a rectangular duct with different waveforms has been discussed in the current article. By means of a wave frame of reference the flow is explored travelling away from a fixed frame with velocity c. Peristaltic waves generated on horizontal surface walls of rectangular duct are considered using lubrication technique. Mathematical modelling of couple fluid for three-dimensional flow are first discussed in detail. Lubrication approaches are used to simplify the proposed problem. Exact solutions of pressure gradient, pressure rise, velocity and stream function have been calculated. Numerical and graphical descriptions are displayed to look at the behaviour of diverse emerging parameters.

Benefits of fracture liaison services (FLS) in four Latin American countries: Brazil, Mexico, Colombia, and Argentina.

AIMS: Fracture liaison services (FLS) use a multidisciplinary approach to treat patients who have experienced an osteoporotic fracture to reduce the risk of subsequent fractures. To date, there has been minimal FLS implementation in Latin America where fractures continue to be undertreated. This study aims to estimate the number of fractures averted, bed days avoided, and costs saved resulting from universal FLS implementation in Brazil, Mexico, Colombia, and Argentina. MATERIALS AND METHODS: A calculator was developed to estimate the annual benefits of FLS programs in Brazil, Mexico, Colombia, and Argentina from a public hospital perspective. It was assumed all patients with a hip, vertebral, or wrist fracture were referred to an FLS program. Country-specific data were obtained from a previous systematic review and interviews with osteoporosis experts. Hospitalization and post-hospitalization costs were expressed in 2019 USD without discounting. Costs of FLS implementation were not considered. RESULTS: In 2019, the number of FLS patients prevented from having a subsequent hip, vertebral, or wrist fracture was estimated as 15,607 in Brazil, 8,168 in Mexico, 5,190 in Argentina, and 2,435 in Colombia with total bed days saved of 142,378 in Brazil, 75,877 in Mexico, 52,301 in Argentina, and 21,725 in Colombia. The annual cost savings in 2019 were highest in Argentina (28.1 million USD), followed by Mexico (19.6 million USD), Brazil (7.64 million USD) and Colombia (3.04 million USD). Over five years (2019-2023) the cumulative cost savings were 145 million USD in Argentina, 106 million USD in Mexico, 40.5 million USD in Brazil, and 16.1 million USD in Colombia. CONCLUSION: Universal FLS implementation in Brazil, Mexico, Colombia, and Argentina was predicted to prevent 31,400 fractures, avoid 292,281 bed days, and save 58.4 million USD in 2019, though caution is warranted in the interpretation of these results due to high uncertainty. Increased implementation of FLS programs in Latin American countries may help to realize these benefits.

Ten-Year Simulation of the Effects of Denosumab on Bone Remodeling in Human Biopsies.

Postmenopausal osteoporosis is a disease manifesting in degradation of bone mass and microarchitecture, leading to weakening and increased risk of fracture. Clinical trials are an essential tool for evaluating new treatments and may provide further mechanistic understanding of their effects in vivo. However, the histomorphometry from clinical trials is limited to 2D images and reflects single time points. Biochemical markers of bone turnover give global insight into a drug's action, but not the local dynamics of the bone remodeling process and the cells involved. Additionally, comparative trials necessitate separate treatment groups, meaning only aggregated measures can be compared. In this study, in silico modeling based on histomorphometry and pharmacokinetic data was used to assess the effects of treatment versus control on µCT scans of the same biopsy samples over time, matching the changes in bone volume fraction observed in biopsies from denosumab and placebo groups through year 10 of the FREEDOM Extension trial. In the simulation, treatment decreased osteoclast number, which led to a modest increase in trabecular thickness and osteocyte stress shielding. Long-term bone turnover suppression led to increased RANKL production, followed by a small increase in osteoclast number at the end of the 6-month-dosing interval, especially at the end of the Extension study. Lack of treatment led to a significant loss of bone mass and structure. The study's results show how in silico models can generate predictions of denosumab cellular action over a 10-year period, matching static and dynamic morphometric measures assessed in clinical biopsies. The use of in silico models with clinical trial data can be a method to gain further insight into fundamental bone biology and how treatments can perturb this. With rigorous validation, such models could be used for informing the design of clinical trials, such that the number of participants could be reduced to a minimum to show efficacy. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The burden of osteoporosis in Turkey: a scorecard and economic model.

The burden of osteoporosis in Turkey is not well characterized. Our results indicate that osteoporosis is undertreated in Turkey with 1.35 million fractures predicted to occur from 2019 to 2023 at an associated cost of 2.42 billion USD. Interventions are needed to close the treatment gap and minimize the economic burden. PURPOSE: The number of osteoporotic fractures is expected to increase as populations age, posing a major risk to health systems and patients. We created a scorecard summarizing the burden of disease, policy framework, service provision, and service uptake for osteoporosis in Turkey and estimated the economic burden of osteoporotic fractures in Turkey. METHODS: A systematic review of osteoporosis in Turkey was performed. Gaps in the literature were supplemented by surveys with osteoporosis experts. The findings were used to populate a scorecard and burden of illness model focused on adults aged 50 to 89 years in Turkey. The scorecard provided a visual representation of osteoporosis burden and management using a traffic light color coding system. The model quantified osteoporosis-related fracture costs (2019 USD) including hospitalizations, dual-energy x-ray absorptiometry testing, hip fracture surgery, prescription drugs, and patient productivity losses. RESULTS: The scorecard showed that osteoporosis is undertreated in Turkey. Despite timely access to diagnosis, > 75% of high-risk patients fail to initiate on appropriate therapies. In 2019, the economic model predicted that 255,183 osteoporosis-related fractures would occur in Turkey with an associated annual cost of approximately 455 million USD and an average burden per 1000 at risk of 23,987 USD. The cumulative 5-year cost of 1,354,817 fractures was 2.42 billion USD. CONCLUSIONS: Approximately 1.35 million fragility fractures are predicted to occur in Turkey during the next 5 years with costs of 2.42 billion USD. Closing the treatment gap will be imperative for preventing these fractures and minimizing the burden of osteoporosis in Turkey.

The burden of osteoporosis in Saudi Arabia: a scorecard and economic model.

Objectives: Aging populations are contributing to an increased volume of osteoporotic fractures. The goals of this study were to (1) develop a scorecard on epidemiological burden, policy framework, service provision, and service uptake for osteoporosis in Saudi Arabia and (2) estimate the direct costs of managing osteoporotic fractures in Saudi Arabia.Methods: Osteoporosis data specific to Saudi Arabia were collected through a systematic literature review and surveys with osteoporosis experts. The data were used to build a scorecard, as done previously for the European Union and select Latin American countries. The scorecard applied traffic light colour coding to identify areas of risk in Saudi Arabia's management of osteoporosis. The data were also used to parameterize a burden of illness model. The model estimated the direct medical costs of fractures among adults aged 50-89 years in Saudi Arabia. The model included hospitalization, testing, hip fracture surgery, and drug costs.Results: In Saudi Arabia, the Ministry of Health was aware of impending increases in the number of fractures and had prioritized osteoporosis on the national agenda. Accordingly, reimbursement restrictions for osteoporosis diagnosis and treatment were minimal. However, a national fracture registry and unified system for monitoring care were not in operation. This represents a critical gap in care that will continue to contribute to the underdiagnosis and undertreatment of osteoporosis if not addressed. In total, 174,225 osteoporosis-related fractures were estimated to occur in Saudi Arabia in 2019, with an annual cost of SR2.38 billion ($636 million USD; $1.55 billion PPP). Hospitalization was the primary cost driver.Conclusions: In 2019, Saudi Arabia was expected to incur SR2.38 billion ($636 million USD; $1.55 billion PPP) in costs owing to 174,225 osteoporosis-related fractures. The establishment of a national fracture registry and implementation of fracture liaison services will be paramount to reducing the fracture burden.

Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia.

Development of BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for patients diagnosed with chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. However, resistance or intolerance to these TKIs still leaves some patients without many treatment options. One point mutation in particular, the T315I mutation, has been shown to be resistant to first and second generation TKIs. The third generation TKI, ponatinib, may provide an option for these patients. Ponatinib (Iclusig®), an orally available, pan-tyrosine kinase inhibitor has a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. A Phase II study evaluated ponatinib in patients who were resistant or intolerant to nilotinib or dasatinib or patients who had the T315I mutation. In the Phase II study, ponatinib produced a major cytogenetic response in 54% of chronic phase chronic myeloid leukemia patients. It further achieved major hematologic response in 52% of patients in the accelerated phase, 31% of patients in the blast phase, and 41% of Philadelphia chromosome positive acute lymphoblastic leukemia patients. Ponatinib also showed efficacy in patients with the T315I mutation. Serious adverse events included arterial thrombosis, hepatotoxicity, cardiovascular risks, pancreatitis, hemorrhage, fluid retention, myelosuppression, rash, abdominal pain, and embryo-fetal toxicity. Due to the risk of these adverse events and potential drug interactions, the use of ponatinib must be carefully weighed against the benefits in treating patients who have limited treatment options.