Search Results (94)

Sickle cell disease (SCD) is the most common monogenic disorder worldwide and remains a major cause of morbidity and mortality. Sickle cell anemia (SCA), the homozygous HbSS genotype, represents the most severe and frequent form within the spectrum of SCD. Hydroxyurea (HU), a ribonucleotide reductase inhibitor, represents the first and most widely used disease-modifying therapy for SCA. This review summarizes current evidence on the mechanisms of action, clinical efficacy, systemic effects, and long-term safety of chronic HU therapy in patients with SCA. A comprehensive literature search was conducted in PubMed up to 2025 using the terms “sickle cell disease,” “sickle cell anemia”, “hydroxyurea,” and “children” or “paediatric.” Eligible studies included randomized controlled trials, cohort studies, and systematic reviews evaluating HU therapy in SCA. Literature analysis showed that HU exerts pleiotropic effects by inducing fetal hemoglobin (HbF) synthesis, improving red blood cell deformability, reducing leukocyte and platelet counts, and enhancing nitric oxide bioavailability. These mechanisms lead to decreased vaso-occlusive crises, acute chest syndrome, transfusion requirements, and overall mortality. Beyond hematologic improvement, HU confers neuroprotective benefits, modulates inflammatory and immune pathways, and supports normal growth and endocrine development in children. Adverse events, primarily mild bone marrow suppression, are dose-dependent and reversible with appropriate monitoring. No evidence supports an increased risk of malignancy with long-term use. In conclusion, chronic HU therapy is a safe, effective, and multifaceted treatment that substantially improves survival and quality of life in patients with SCA. Early initiation and individualized dosing maximize its therapeutic benefits and help prevent irreversible organ damage. Full article

In this study, a biodegradable Mg-Zn-Nd-Gd alloy was processed via multi-directional forging (MDF) to evaluate its microstructural evolution, mechanical performance, and corrosion behavior. Electron backscattered diffraction (EBSD) analysis was conducted to evaluate the influence of grain size and texture on mechanical strength and corrosion resistance. The average grain size decreased significantly from 118 ± 5 μm in the homogenized state to 30 ± 10 μm after six MDF passes, primarily driven by discontinuous dynamic recrystallization (DDRX). Remarkably, this magnesium (Mg) alloy exhibited a rare synergistic enhancement in both strength and ductility, with ultimate tensile strength (UTS) increasing by ~59%, yield strength (YS) by ~90%, while elongation improved by ~44% unlike conventional severe plastic deformation (SPD) techniques that often sacrifice ductility for strength. This improvement is attributed to grain refinement, dispersion strengthening from finely distributed Mg₁₂Nd and Mg₇Zn₃ precipitates, and texture weakening, which facilitated the activation of non-basal slip systems. Despite the mechanical improvements, electrochemical corrosion testing in Hank’s balanced salt solution (HBSS) at 37 °C revealed an increased corrosion rate from 0.1165 mm/yr in homogenized condition to 0.2499 mm/yr (after six passes of MDF. This was due to the higher fraction of low-angle grain boundaries (LAGBs), weak basal texture, and the presence of electrochemically active fine Mg₇Zn₃ particles. However, the corrosion rate remained within the acceptable range for bioresorbable implant applications, indicating a favorable trade-off between mechanical performance and degradation behavior. These findings demonstrate that MDF processing effectively enhances the strength–ductility synergy of Mg-rare earth alloys while maintaining a clinically acceptable degradation rate, thereby presenting a promising route for next-generation biomedical implants. Full article

The growing penetration of renewable energy sources requires resilient microgrids capable of providing stable and continuous operation. Hybrid energy storage systems (HESS), which integrate hydrogen-based storage systems (HBSS), battery storage systems (BSS), and supercapacitor banks (SCB), are essential to ensuring the flexibility and robustness of these microgrids. Accurate modelling of these microgrids is crucial for analysis, controller design, and performance optimization, but the complexity of HESS poses a significant challenge: simplified linear models fail to capture the inherent nonlinear dynamics, while nonlinear approaches often require excessive computational effort for real-time control applications. To address this challenge, this study presents a novel state space model with linear variable parameters (LPV), which effectively balances accuracy in capturing the nonlinear dynamics of the microgrid and computational efficiency. The research focuses on a high-voltage DC bus microgrid architecture, in which the BSS and SCB are connected directly in parallel to provide passive DC bus stabilization, a configuration that improves system resilience but has received limited attention in the existing literature. The proposed LPV framework employs recursive linearisation around variable operating points, generating a time-varying linear representation that accurately captures the nonlinear behaviour of the system. By relying exclusively on directly measurable state variables, the model eliminates the need for observers, facilitating its practical implementation. The developed model has been compared with a reference model validated in the literature, and the results have been excellent, with average errors, MAE, RAE and RMSE values remaining below 1.2% for all critical variables, including state-of-charge, DC bus voltage, and hydrogen level. At the same time, the model maintains remarkable computational efficiency, completing a 24-h simulation in just 1.49 s, more than twice as fast as its benchmark counterpart. This optimal combination of precision and efficiency makes the developed LPV model particularly suitable for advanced model-based control strategies, including real-time energy management systems (EMS) that use model predictive control (MPC). The developed model represents a significant advance in microgrid modelling, as it provides a general control-oriented approach that enables the design and operation of more resilient, efficient, and scalable renewable energy microgrids. Full article

In this study, a Ag/ZrO₂ hybrid coating prepared by the sol–gel method on a β-type Ti45Nb alloy was applied by the spin coating technique, and the microstructural, mechanical, electrochemical, and tribological properties of the surface were evaluated in a multi-dimensional manner. The hybrid solution was prepared using zirconium propoxide and silver nitrate and stabilized through a low-temperature two-stage annealing protocol. The crystal structure of the coating was determined by XRD, and the presence of dense tetragonal ZrO₂ phase and crystalline Ag phases was confirmed. SEM-EDS analyses revealed a compact coating structure of approximately 1.8 µm thickness with homogeneously distributed Ag nanoparticles on the surface. As a result of the electrochemical corrosion tests, it was determined that the open circuit potential shifted to more noble values, the corrosion current density decreased, and the corrosion rate decreased by more than 70% on the surfaces where the Ag/ZrO₂ coating was applied. In the tribological tests, a decrease in the coefficient of friction, narrowing of wear marks, and significant reduction in surface damage were observed in dry and physiological (HBSS) environments. The findings revealed that the Ag/ZrO₂ hybrid coating significantly improved the surface performance of the Ti45Nb alloy both mechanically and electrochemically and offers high potential for biomedical implant applications. Full article

Sickle-cell disease (SCD) is a group of inherited blood disorders in which a mutation in the β-globin (HBB) gene causes red blood cells to produce abnormal hemoglobin, known as Hb S. SCD is characterized by an autosomal-recessive pattern of inheritance, implying that for a child to manifest the condition, they must inherit an Hb S allele from both parents (HbSS) or one Hb S allele and another β-globin variant, such as Hb C or β-thalassemia (HbSC, HbS/β-thal). It has been observed that (heterozygote) carriers of one copy of the sickle-cell trait (HbAS) are typically healthy and can even gain partial protection from severe malaria. The term “severe and complicated malaria” is delineated based on specific clinical and laboratory characteristics in the presence of Plasmodium falciparum parasitemia. The prevalent forms of severe malaria among African children include cerebral malaria, respiratory distress, and severe malaria anemia. Cerebral malaria is a rare complication of malaria infection and is associated with a high mortality rate. Full article

Background: Sickle cell disease (SCD) significantly impacts diverse racial groups, particularly African American and Hispanic persons, who experience notable disparities in healthcare outcomes. Despite the extensive literature on SCD, studies focusing on in-hospital racial inequities remain limited. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) from 2016 to 2020, identifying adult hospitalizations for SCD (HbSS genotype). Hospitalizations were categorized by race—White, African American, Hispanic, and other, and analyzed for demographic variables, admission types, disposition outcomes, and complications. Statistical analyses included chi-square tests and multivariate logistic regression, adjusting for confounders. Results: Of the 1,089,270 identified hospitalizations, 90.31% were African American. African American and Hispanic patients exhibited significantly higher non-elective admissions compared to Whites (77.81%). In-hospital mortality was highest among Hispanics (0.82%). Multivariate regression analysis revealed that African Americans and others had higher odds of prolonged hospital stays (Adjusted Odds Ratio (AOR): 1.30 and 1.20, respectively). African Americans and Hispanics also had increased risks of in-hospital complications of SCD. Conclusions: This study highlights substantial racial disparities in SCD hospitalizations, with African Americans and Hispanics facing poorer outcomes compared to Whites. Hispanics also demonstrated increased mortality. These findings underscore the need for targeted healthcare interventions to address racial inequities in SCD management and improve outcomes for all affected populations. Full article

Kidney disorders significantly contribute to morbidity and mortality in sickle cell disease (SCD). Acute kidney injury (AKI), a major risk factor for chronic kidney disease (CKD), often arises from intravascular hemolysis, where plasma cell-free heme drives AKI through inflammatory and oxidative stress mechanisms. Hydroxyurea (HU), a well-established SCD-modifying therapy, improves clinical outcomes, but its effects on systemic heme and inflammatory mediators of kidney injury remain underexplored. This study evaluated HU’s impact on plasma heme, pro-inflammatory mediators, kidney injury, and renal histopathology in a sickle cell mouse model. Townes humanized sickle cell mice (HbSS) and non-sickle (HbAA) controls were treated with HU or vehicle for two weeks. HU significantly reduced total plasma heme, lactate dehydrogenase, and pro-inflammatory cytokines (CXCL10, VEGF-A, IFN-γ) in HbSS mice. HU reduced renal injury biomarkers (cystatin C, NGAL) and improved renal histopathology, evidenced by reduced vascular congestion, glomerulosclerosis, and tubular damage. Interestingly, HU did not alter the levels of kidney repair biomarkers (clusterin and EGF). These findings suggest that HU mitigates kidney injury by reducing the deleterious effects of circulating heme and inflammation, supporting its potential to slow or prevent progressive kidney injury in SCD. Full article

Background/Objectives: Dental avulsion involves the complete displacement of the tooth from its socket and falls into the most severe categories of the various types of traumatic dental injuries. Successful replantation of the tooth depends on various factors such as the time between the event and replantation, as well as the extra-alveolar storage medium and duration. The adoption of the correct handling measures and use of an appropriate storage medium are key factors that affect the long-term prognosis of the avulsed tooth following replantation. This systematic review and meta-analysis aim to determine if Hank’s Balanced Salt Solution (HBSS) is the most effective storage medium to preserve periodontal (PDL) cell viability following avulsion. Methods: A comprehensive review of the literature available was conducted on the 18 November 2024 across three databases, namely EBSCO (including PubMed-Medline), Scopus, and Web of Science. The review was written according to and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement created in 2009 and updated in 2020. The following PICO question was constructed for the systematic review: “In patients with avulsed permanent teeth, is Hank’s balanced salt solution more effective in preserving periodontal cell viability to increase the likelihood of a more successful replantation than any other storage media technique available?” A meta-analysis was also conducted with the selected studies, and the software used for this was R 4.3.1 (R Core Team (2018)). Results: A total number of 443 articles were found in the initial search. Of these 443, 9 articles were included in the final systematic review and meta-analysis. 6 out of the 9 articles conclude HBSS to be the most superior storage medium for the preservation of the PDL cells, whilst the other three concluded PDL cell preservation was higher in Morinda citrifolia juice, propolis, and coconut water, suggesting a suitable alternative to HBSS. Nonetheless, the meta-analysis indicated that PDL cell viability was significantly higher using HBSS compared to all other storage media. Conclusions: The systematic review and meta-analysis have provided adequate data in favor of the alternative hypothesis, indicating that Hank’s balanced salt solution is the most effective storage medium in the preservation of periodontal cell viability following the avulsion of permanent teeth. Full article

Mountain resilience is the ability of mountain regions to endure, adapt to, and recover from environmental, climatic, and anthropogenic stressors. Due to their steep topography, extreme weather conditions, and unique biodiversity, these areas are particularly vulnerable to climate change, natural hazards, and human activities. This paper examines how nature-based solutions (NbSs) can strengthen slope stability and geotechnical resilience, with a specific focus on Slovenia’s sub-Alpine regions as a case study representative of the Alps and similar mountain landscapes worldwide. The proposed Climate-Adaptive Resilience Evaluation (CARE) concept integrates geomechanical analysis with geotechnical planning, addressing the impacts of climate change through a systematic causal chain that connects climate hazards, their effects, and resulting consequences. Key factors such as water infiltration, soil permeability, and groundwater dynamics are identified as critical elements in designing timely and effective NbSs. In scenarios where natural solutions alone may be insufficient, hybrid solutions (HbSs) that combine nature-based and conventional engineering methods are highlighted as essential for managing unstable slopes and restoring collapsed geostructures. The paper provides practical examples, including slope stability analyses and reforestation initiatives, to illustrate how to use the CARE concept and how NbSs can mitigate geotechnical risks and promote sustainability. By aligning these approaches with regulatory frameworks and climate adaptation objectives, it underscores the potential for integrating NbSs and HbSs into comprehensive, long-term geotechnical strategies for enhancing mountain resilience. Full article

Qihe crucian carp Carassius auratus is one of the major economic aquacultural fish species in China. Due to environmental degradation and the impact of the reproduction mode of gynogenesis, the wild population of Qihe crucian carp exhibits an extremely low proportion of males. Therefore, it is imperative to develop the sperm preservation technology for Qihe crucian carp. In this study, the indicators, including sperm motility, sperm movement time, and sperm lifetime, were applied to evaluate the preservation effects of various extenders, cryoprotectant types and concentrations, and preservation manners, thus establishing the techniques of sperm short-term storage and cryopreservation for Qihe crucian carp. The results showed that HBSS was the most suitable extender solution, in which the sperm motility reached 93.00%. Under room temperature (26 °C), the sperm motility showed no significant differences across six different cryopreservation solutions. Under low temperature (4 °C), a 15% MeOH solution presented the most effective preservation effects of sperm in the short-term low-temperature storage. For cryopreservation in liquid nitrogen, the sperm activity in 20% DMSO was significantly higher than that in other solutions, representing the optimal cryopreservation solution. Furthermore, it was found that the sperm activity preserved by liquid nitrogen was significantly higher than that preserved by the ultra-freezer (−80 °C), indicating that the ultra-freezer cannot substitute for liquid nitrogen in cryopreservation. This is the first study to investigate the preservation of Qihe crucian carp sperm, providing valuable technical support for both genetic resource conservation and artificial breeding programs. Full article

Background: Sickle cell disease (SCD) is a rare autosomal recessive disorder that is common in countries with consanguineous marriages. It leads to various complications, including painful episodes, infections, delayed growth, stroke, and organ damage, which contribute to high healthcare utilization and costs. In Saudi Arabia, the prevalence of SCD is notably high, largely due to the frequency of consanguineous marriages. However, there has not yet been a study estimating the direct medical costs of managing SCD based on real-world data. This study aims to assess these costs in Saudi Arabia. Methods: Data were collected from electronic medical records (EMRs) at a university-affiliated tertiary care center. A micro-costing approach was used to estimate the direct medical costs (e.g., laboratory tests, imaging, emergency department visits, hospitalizations, prescription medications, outpatient visits, etc.) retrospectively over a 12-month follow-up period. The baseline characteristics of the patients were presented using frequencies and percentages. The costs of different healthcare services were analyzed using means and the 95% confidence intervals. A generalized linear model (GLM) with a gamma distribution was utilized to examine the association between the overall costs and patient characteristics (e.g., age, gender, duration of illness, surgeries, blood transfusions, etc.), allowing for the estimation of the adjusted mean costs. Results: A total of 100 patients met the inclusion criteria and were included in the analysis. The mean age of the patients was 10.21 years (±6.87 years); 53% were male, and a substantial majority (96%) had the HbSS genotype. Sixty-one percent of the patients had undergone at least one red blood cell (RBC) exchange transfusion, while 21% had undergone surgical procedures, including tonsillectomy, splenectomy, and cholecystectomy. Additionally, 45% had experienced at least one vaso-occlusive crisis (VOC), and 59% had been hospitalized at least once in the past 12 months. Factors such as the frequency of laboratory tests and imaging studies, the length of hospital stay (LOS), the rate of emergency department (ED) visits, surgical procedures, the number of prescription medications, and the frequency of blood transfusions were all significant predictors of higher direct medical costs (p < 0.05). The estimated mean annual direct medical costs per patient were USD 26,626.45 (95% CI: USD 22,716.89–USD 30,536.00). After adjusting for various factors, including age, gender, duration of illness, frequency of lab and imaging tests, LOS, ED visits, surgical procedures, number of prescription medications, rates of VOCs, and RBC exchange transfusions, the adjusted mean annual direct medical cost per patient was calculated to be USD 14,604.72 (95% CI: USD 10,943.49–USD 19,525.96). Conclusions: The results of this study emphasize the substantial direct medical costs linked to sickle cell disease (SCD), which are greatly affected by the frequency of related complications. These insights should motivate policymakers and healthcare researchers to assess both the national direct and indirect costs associated with SCD, especially given the significant number of SCD patients in Saudi Arabia. Full article

The Portuguese Newborn Screening Program currently includes 28 pathologies: congenital hypothyroidism, cystic fibrosis, 24 inborn errors of metabolism, sickle cell disease and spinal muscular atrophy. This pilot study for sickle cell disease newborn screening, including 188,217 samples, was performed between May 2021 and December 2023, with phase I, including 24,130 newborns, in the Lisbon and Setubal districts and phase II, including 164,087 newborns, in the whole country. DBS samples were analyzed through capillary electrophoresis. In phase I, a high birth incidence of sickle cell disease was found (1:928 NBs), resulting from the identification of 24 HbSS and 2 HbSC patients. This birth incidence decreased but remained significant when the pilot study for sickle cell disease newborn screening was expanded to a national level, with the identification of 67 sickle cell disease patients (59 HbSS and 8 HbSC), revealing a birth incidence of 1:2449 NBs. These data suggest that this condition is becoming increasingly relevant in Portugal, thus reflecting a general European trend, where sickle cell disease is already recognized as a public health problem. Therefore, it highlights the importance of its integration into the Portuguese National Newborn Screening Program panel in January 2024, thus allowing the early identification and clinical follow-up of these patients. Full article

Background and Clinical Significance: A brain abscess, defined as a localized intracranial infection that evolves into a purulent collection encased by a vascularized capsule, has higher prevalence among immunocompromised populations. Patients with sickle cell disease (SCD) are particularly vulnerable to bacterial infections due to their compromised immune systems, increasing their susceptibility to pathogens like Salmonella. While Salmonella is typically associated with gastroenteritis, osteomyelitis, and septicemia, its involvement in brain abscesses is exceedingly rare. There are few documented cases of Salmonella brain abscesses in the general population, and among patients with SCD, only one such case has been reported to date. In this report, we describe the second known case of a brain abscess caused by Salmonella infection in a patient with sickle cell disease, contributing to the limited literature on this rare and life-threatening condition. Case Presentation: A 32-year-old African American woman with sickle cell disease presented to the ER after a generalized seizure, reporting two weeks of worsening headaches, fevers, and left upper extremity weakness. Imaging revealed a right frontoparietal brain abscess, which was surgically drained, and cultures identified Salmonella enterica. After antibiotic treatment and a 23-day hospital stay, she was discharged. Four months later, she returned with another seizure during a sickle cell crisis, but follow-up MRI showed only minor scarring, and she was discharged on anticonvulsant therapy. Conclusions: This case emphasizes that Salmonella infections, though typically linked to osteomyelitis and sepsis, can also cause brain abscesses in immunocompromised patients like those with sickle cell disease. It highlights the need to consider infections alongside vascular causes in acute neurological cases and underscores the value of a multidisciplinary approach in managing such complex conditions. Full article

The advancing development in biomaterials and biology has enabled the extension of 3D printing technology to the bioadditive manufacturing of degradable hard tissue substitutes. One of the key advantages of bioadditive manufacturing is that it has much smaller design limitations than conventional manufacturing and is therefore capable of producing implants with complex geometries. In this study, three distinct blends of polylactic acid (PLA) and polyhydroxybutyrate (PHB) were produced using Fused Deposition Modeling (FDM) technology. Two of these blends were plasticized with oligomeric lactic acid (OLA) at concentrations of 5 wt% and 10 wt%, while the third blend remained unplasticized. Each blend was fabricated in two structural modifications: solid and porous. The biodegradation behavior of the produced specimens was examined through an in vitro experiment using three different immersion solutions: saline solution, Hank’s balanced salt solution (HBSS), and phosphate-buffered saline (PBS). All examined samples were also subjected to chemical analysis: atomic absorption spectroscopy (AAS), scanning electron microscopy (SEM), and energy-dispersive spectrometry (EDS). The results of the degradation experiments indicated a predominantly better absorption capacity of the samples with a porous structure compared to the full structure. At the same time, the blend containing a higher concentration of OLA exhibited enhanced pH stability over the evaluation period, maintaining relatively constant pH values before experiencing a minor decline at the end of the study. This observation indicates that the increased presence of the plasticizer may provide a buffering effect, effectively mitigating the acidification associated with material degradation. Full article

In the longstanding development of hydrate-bearing sediment (HBS) reservoirs, slow and permanent deformation of the formation will occur under the influence of stress, which endangers the safety of hydrate development projects. This paper takes hydrate-bearing sandy sediment (HBSS) as the research object and conducts triaxial compression creep tests at different saturation degrees (20%, 30%, and 40%). The results show that the hydrate-containing sandy sediments have strong creep characteristics, and accelerated creep phenomenon will occur under the long-term action of high stress. The longstanding destructive power of the specimen progressively raises with the increase in hydrate saturation, but the difference in the triaxial strength of the specimen progressively increases. This indicates that the damage to the hydrate structure during long-term loading is the main factor causing the strength decrease. Further, a new nonlinear creep constitutive model was developed by using the nonlinear Burgers model in series with the fractional-order viscoplastic body model, which can well describe the creep properties of HBSS at different saturation levels. Full article