Search Results (57)

Background: Congenital Insensitivity to Pain and Anhidrosis (CIPA) is a rare autosomal recessive disorder characterized by congenital analgesia, anhidrosis, and multisystem involvement affecting the musculoskeletal, cutaneous, oral, and para-oral structures. This case report describes the oral phenotype and multidisciplinary clinical management of a child with CIPA. Case Description: A 9-year-old boy presented with poor oral hygiene, multiple severely damaged teeth, masticatory difficulty, limited mouth opening, impaired bolus control, and para-oral traumatic injuries. Medical and orthopedic history indicated recurrent painless fractures, self-inflicted injuries, cutaneous scarring, and recurrent hyperpyrexia. Oral self-injury associated with CIPA was suspected and supported by the Nociception Assessment Test and Minor’s Iodine–Starch Test. Although the clinical findings were suggestive of CIPA, the diagnosis remained presumptive due to the absence of confirmatory molecular or histopathological testing. Management: A wearable wireless continuous temperature-monitoring device was prescribed to assist in tracking hyperpyrexia associated with CIPA (RHA-CIPA). A conservative, staged, multidisciplinary treatment was planned rather than full-mouth extraction, emphasizing prevention of dental sepsis and mitigation of future self-injury. Dental procedures were performed under local anesthesia to manage discomfort related to tactile hyperesthesia. To reduce nocturnal biting and oral trauma, a hard acrylic occlusal protector was fabricated using an intraoral scanner and a 3D-printed cast. The patient was followed for 12 months. Outcomes: At the 12-month follow-up, clinical improvement was observed, with particularly notable gains in cheek elasticity and soft tissue resilience. Conclusions: This case highlights the considerable challenges involved in the interdisciplinary management of children with CIPA, including oral self-injury prevention, limited mouth opening, and the necessity of close coordination with medical specialties. These findings are descriptive observations of a single case and do not establish efficacy or generalizability of any intervention. Full article

The widespread contamination of aquatic systems by ciprofloxacin (CIP)—a persistent fluoroquinolone antibiotic—poses severe ecological risks due to its antibacterial resistance induction. Conventional sulfate radical-based advanced oxidation processes (SR-AOPs) suffer from inefficient catalyst synthesis, exemplified by low-yield ZIF-67 precursors (typically <25%). To address this, a nitrogen-doped carbon composite Co₃O₄/N@C was synthesized via ammonia-assisted ligand exchange followed by pyrolysis, using N-doped ZIF-67 as a self-sacrificial template. The ammonia incorporation quadrupled precursor yield compared to ammonia-free methods. This catalyst activated peroxydisulfate (PDS) to degrade 95% CIP within 90 min under the optimized conditions (0.5 g/L catalyst, 2 mmol/L PDS, pH 5), representing a 30% enhancement over non-ammonia analogs. Mechanistic studies identified singlet oxygen (¹O₂) as the dominant reactive species, facilitated by N-doped carbon-mediated electron transfer. This strategy overcomes the scalability barrier of MOF-derived catalysts for practical antibiotic wastewater remediation. Full article

In today’s dynamic tourism industry, shaped by globalization and digitalization, understanding destination competitiveness is crucial for crafting sustainable development policies. This paper explores Romania’s competitive advantage as a tourist destination through both theoretical and practical perspectives. The present research aims to diagnose Romania’s level of competitiveness by identifying tourist attributes perceived as relevant by visitors and evaluating their performance relative to other similar European destinations. A quantitative questionnaire-based survey was conducted to achieve this goal. The survey included 235 respondents, gathered through non-probability convenience and snowball sampling. Romania’s competitiveness was assessed using the Competitive Importance-Performance Analysis (CIPA) method, which allowed for the strategic mapping of the country’s position based on the relative performance of essential attributes. These attributes included cultural heritage, the diversity of natural landscapes, the digitalization of tourism services, and staff hospitality. The results highlighted that Romania possesses significant strengths in natural landscapes, gastronomy, accommodation quality, and outdoor activities. However, the study identified major negative gaps in critical areas such as service digitalization, tourist staff attitude, and the quality of cultural events. These findings underscore a latent competitive advantage based on authentic resources, which is currently underexploited from the perspective of modern management and infrastructure. The practical implications of this research provide a solid basis for optimizing tourism marketing policies, efficient resource allocation, and strengthening Romania’s positioning as an authentic, sustainable, and competitive destination within the European landscape. Full article

New approach methodologies (NAMs), including microphysiological systems (MPSs), can recapitulate structural and functional complexities of organs. Vanoxerine was reported to induce cardiac adverse events, including torsade de points (TdP), in a Phase III clinical trial. Despite earlier nonclinical animal models and Phase I–II clinical trials, events of QT prolongation or proarrhythmia were not observed. Here, we utilized cardiac NAMs to evaluate the functional consequences of vanoxerine treatment on human cardiac excitation–contraction coupling. The cardiac MPS used in this study was a microfabricated fluidic culture platform with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) capable of evaluating voltage, intracellular calcium handling, and contractility. Likewise, the hiPSC-CM comprehensive in vitro proarrhythmia assay (CiPA) was employed based on multielectrode array (MEA). Vanoxerine treatment delayed repolarization in a concentration-dependent manner and induced proarrhythmic events in both NAM platforms. The complex cardiac MPS displayed a frequency-dependent vanoxerine response such that EADs were eliminated at a faster pacing rate (1.5 Hz). Moreover, exposure analysis revealed a 99% vanoxerine loss in the cardiac MPS. TdP risk analysis demonstrated high to intermediate TdP risk at clinically relevant concentrations of vanoxerine and frequency-independent EAD events in the hiPSC-CM CiPA model. These findings demonstrate that nonclinical cardiac NAMs can recapitulate clinical outcomes, including detection of vanoxerine-induced delayed repolarization and proarrhythmic effects. Moreover, this work provides a foundation to evaluate the safety and efficacy of novel compounds to reduce the dependence on animal studies. Full article

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare genetic disorder, often leading to injuries and serious infections. In 2018, we established a multidisciplinary clinic (MDC) to provide structured, proactive care. We assessed the MDC’s impact on hospitalizations, surgeries, and infection rates. Methods: A retrospective study of genetically confirmed CIPA patients, treated from 2014 to 2024. Data from electronic medical records were compared between the pre-MDC (2014–2017) and post-MDC (2018–2024) periods. The core MDC team includes an infectious disease specialist, orthopedic surgeon, and nurses. The patients are stratified according to their carriage of resistant organisms and are managed using strict infection control measures. Follow-ups are scheduled routinely or as needed. Treatment is guided by clinical findings and culture results. Results: A total of 59 patients were included in the study. The baseline age did not differ significantly between the two periods. Hospitalization rates declined by 30.7% (from 57.7 to 40.0 per 1000 days), and clinic visits decreased by 42.9% (25.5 to 14.6). Overall surgical rates remained stable (2.8 to 2.7), with a 61.9% decrease in eye surgeries and a 130.5% increase in elective tooth extractions. Infection rates increased by 52% (from 6.6 to 10.1 per 1000 days). Conclusions: The implementation of the MDC bundle led to reduced hospitalizations, clinic visits, and eye surgeries, alongside the increased use of elective tooth extractions and culture testing. Closer monitoring and early infection management contributed to fewer severe complications. These findings support the value of structured, proactive multidisciplinary care in improving outcomes for children with CIPA. Full article

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive syndrome caused by loss-of-function mutations in the Neurotrophic Tyrosine Kinase Receptor 1 gene, characterized by recurrent episodes of infections and unexplained fever, anhidrosis, absence of reactions to noxious stimuli, intellectual disability, self-mutilating behaviors, and damage to many body organs, including the eyes. Main text: We systematically searched the Medline/PubMed, Scopus, and Web of Science databases from their inception until March 2025 for papers describing the clinical manifestations of patients with CIPA. The inclusion criterion was papers reporting ocular manifestations of patients diagnosed with CIPA. We excluded non-English papers or those reporting ocular manifestations of patients diagnosed with syndromes other than CIPA. Also, we excluded review articles, clinical trials, gray literature, or any paper that did not report ocular manifestations of patients with CIPA or that reported patients with previous ocular surgeries. Out of 6243 studies, 28 were included in the final analysis, comprising 118 patients. The mean age was 7.37 years, and males represented 63.5% (n = 75). Of the patients, fifty-six had bilateral ocular manifestations. The most common ocular manifestations were the absence of corneal reflex in 56 patients (47.5%, bilateral in 56), whereas corneal ulcerations were the second most common manifestation in 46 patients (38.98%, bilateral in 8), followed by corneal opacity in 32 patients (27.11%, bilateral in 19). Topical lubricants, topical antibiotics, and lateral tarsorrhaphy were common management modalities for these patients. Absent corneal sensitivity, corneal ulcers, and corneal opacities, among other manifestations, are common ocular presentations in patients with CIPA. Conclusions: Self-mutilation, intellectual disability, decreased lacrimation, and absence of the corneal reflex are factors that may explain the development of these manifestations in CIPA. The early detection of these manifestations can improve patient conditions and prevent further complications, in addition to helping to guide the clinical diagnosis of CIPA in these patients. Full article

In this study, a methacrylic derivative of xylan (XYLMA) was synthesized through transesterification reactions, with the aim of evaluating its physicochemical behavior and its interaction with kaolinite particles. Structural characterization by FT-IR and NMR spectroscopy confirmed the incorporation of methacrylic groups into the xylan (XYL) structure, with a degree of substitution of 0.67. Thermal analyses (TGA and DSC) showed a decrease in melting temperature and enthalpy in XYLMA compared to XYL, attributed to a loss of structural rigidity. Thermal analyses (TGA and DSC) revealed a decrease in the melting temperature and enthalpy of XYLMA compared to XYL, which is attributed to a loss of structural rigidity and a reduction in the crystalline order of the biopolymer. Aggregation tests in solution revealed that XYLMA exhibits amphiphilic behavior, forming micellar structures at a critical aggregation concentration (CAC) of 62 mg L⁻¹. In adsorption studies on kaolinite, XYL showed greater affinity than XYLMA, especially at acidic pH, due to reduced electrostatic forces and a greater number of hydroxyl groups capable of forming hydrogen bonds with the mineral surface. In contrast, modification with methacrylic groups in XYLMA reduced its adsorption capacity, probably due to the formation of supramolecular aggregates. These results suggest that interactions between xylan and kaolinite clay are key to understanding the role that hemicelluloses play in increasing copper recovery when added to flotation cells during the processing of copper sulfide ores with high clay content. Full article

Wastewater treatment plants (WWTPs) are recognised as key hotspots for the dissemination of antimicrobial-resistant bacteria and antimicrobial resistance genes (ARGs). However, studies addressing the role of domestic WWTPs in the spread of resistance traits in tropical regions remain limited. This study evaluated a domestic WWTP during dry and rainy seasons to examine its role as a reservoir and dissemination hub for ARGs and potential bacterial pathogens. The WWTP demonstrated stable physicochemical removal efficiencies, although its performance slightly decreased during the rainy season. Notably, the relative abundance of ARGs measured by qPCR was higher in the effluent than in the influent of the WWTP. Metagenomic analysis of activated sludge revealed that chromosomally encoded ARGs conferred resistance to macrolides, aminoglycosides, rifamycin, sulphonamides, and tetracyclines. In contrast, plasmid-associated ARGs were primarily linked to resistance against quaternary ammonium compounds (QACs), indicating the presence of a potential conjugative plasmid facilitating the mobility and persistence of QAC resistance genes within the microbial community. Furthermore, pathobiome analysis identified a high relative abundance of potential pathogens, including genera Gordonia, Acidovorax, Pseudomonas, and Mycobacterium members. These findings highlight the role of domestic WWTPs as reservoirs and potential amplifiers of antimicrobial resistance in tropical environments. Full article

Spent coffee grounds (SCG) are produced in large quantities during coffee brewing, contributing to environmental concerns. Additionally, cationic dyes from textile, paper, and leather wastewater pose a major pollution issue. This study explores SCG as an adsorbent for methylene blue (MB) dye. A novel comparison of SCG cleaning methods with warm water, accelerated solvent extraction (ASE), supercritical fluid extraction (SFE), and ultrasound-induced cavitation (US) is presented. In addition, the chemical modifications of SCG using acetylation, acid (HNO₃), and base (KOH) treatment that have not been reported before are presented. ATR-FTIR confirmed the inclusion of functional groups, for example, the nitro group in SCG treated with HNO₃, and an increase in carboxylic groups in the samples treated with KOH and HNO₃. SEM analysis revealed a consistent porous texture across samples, with SCG-SFE, SCG-US, and SCG-HNO₃ showing smaller pores, and SCG-ASE displaying elongated cavities. Adsorption isotherm tests followed the Freundlich and Langmuir models, indicating favorable adsorption. The Langmuir maximum adsorption capacity (q_max) varied among cleaning methods from 65.69 mg/g (warm water) to 93.32 mg/g (SFE). In contrast, in base- and acid-treated SCG, a three- to four-fold increase in adsorption capacity was observed, with q_max values of 171.60 mg/g and 270.64 mg/g, respectively. These findings demonstrate that SCG washed with warm water and chemically treated achieves adsorption capacities comparable to other biosorbents reported in the literature. Therefore, SCG represents a promising, low-cost, and sustainable material for removing cationic dyes from wastewater, contributing to waste valorization and environmental protection. Full article

Indium tin oxide (ITO) is a transparent conducting material with exceptional electrical and optical properties, widely used in biosensing and bioelectronics. Functionalization of ITO with linker molecules enables covalent attachment of biomolecules, allowing for dual-mode optical and electrochemical detection. Carbonic anhydrase IX (CA IX), a transmembrane enzyme overexpressed in hypoxic tumors, is a promising biomarker for cancer diagnostics due to its restricted expression in normal tissues. However, conventional detection methods are time-intensive and unsuitable for point-of-care applications. In this study, ITO surfaces were functionalized using silane-based chemistry to immobilize CA IX-specific antibodies, creating a novel biosensing platform. The biosensor utilized a secondary horseradish peroxidase (HRP)-conjugated antibody to catalyze the oxidation of luminol in the presence of hydrogen peroxide, producing a chemiluminescent and electrochemical signal. Characterization of the biosensor via a dual-mode optical and electrochemical approach revealed efficient antibody immobilization. Due to the high variation observed in the optical approach, limit of detection (LOD) experiments were conducted exclusively with electrochemistry, yielding an LOD of 266.4 ng/mL. These findings demonstrate the potential of ITO-based electrochemical biosensors for sensitive and selective CA IX detection, highlighting their applicability in cancer diagnostics and other biomedical fields. Full article

Background: Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is an exceedingly rare genetic disorder characterized by the inability to perceive pain, inability to sweat, and various neurological and orthopaedic complications. Case Presentation: This is a case report of a 3-year-old female patient as the first case in Latvia diagnosed with CIPA syndrome who repeatedly presented to Children’s Clinical University Hospital (CCUH) in Riga, Latvia, with severe orthopaedic manifestations. The patient had repeated fractures, several surgeries, and extensive spread of the disease throughout the left leg, which caused significant functional impairment and decreased quality of life. Despite aggressive orthopaedic interventions, including surgical interventions and physical therapy, the patient’s condition remained challenging to manage due to the inherent limitations posed by the insensitivity to pain. The Surgeon–Radiologist Council of Doctors discussed the patient’s condition and clinical sequalae, deciding that reconstructive surgery is not feasible, and amputation is recommended. Conclusions: Through this case report, we aim to highlight the unique orthopaedic challenges encountered in the management of CIPA patients, emphasizing the importance of a multidisciplinary approach involving orthopaedic surgeons, paediatricians, geneticists, and physiotherapists. Additionally, we discuss the need for further research to elucidate optimal management strategies and improve outcomes in this rare and complex patient population. Full article

The occurrence of pharmaceutical pollutants in aquatic matrices has been reported as an increasing concern around the world. Sustainable and feasible water treatment technologies are necessary to mitigate water pollution. In this study, we developed an environmentally friendly biochar electro-degradative system using biomass derived through green technologies. The system demonstrated exceptional removal efficiency, achieving over 99% removal of acetaminophen, sulindac, and carbamazepine following biochar electro-degradative treatment. Similar results were achieved from the mixture of the three compounds. The biochar column reusability confirmed the system stability, even after repeating the degradation cycles. Our findings highlight the potential of this novel electro-degradative system as an effective solution for the removal of pharmaceutical residues from wastewater. Full article

Silica aerogels are highly porous materials known for their low density and extensive surface area, making them ideal for applications in thermal insulation, catalysis, and environmental remediation. This study investigates the structural changes of functionalized hydrophobic silica aerogels used as carriers of the LCC ICCG enzyme. The aerogels were synthesized using the sol-gel method, with trimethylethoxysilane (TMES) as a functionalizing agent to enhance hydrophobicity. The enzyme-encapsulated aerogels were characterized using hyperpolarized ¹²⁹Xe NMR, ²⁹Si NMR, nitrogen sorption analysis, TEM, contact angle measurements, and FT-IR spectroscopy to evaluate their structural and chemical properties. The results confirmed successful encapsulation of the enzyme, as indicated by changes in the pore structure and network morphology. These findings demonstrate that functionalized silica aerogels can effectively support LCC ICCG immobilization, offering a promising approach for plastic degradation applications. Full article

This study evaluated the stability and reusability of amino-functionalized nanocellulose aerogels as CO₂-adsorbent materials. The modified aerogels, synthesized via a controlled silylation using N-[3-(trimethoxysilyl) propyl] ethylenediamine (DAMO), demonstrated excellent thermal stability up to 250 °C (TGA) and efficient CO₂ adsorption through chemisorption, which was the main adsorption mechanism. The performance of the aerogels was assessed using both adsorption isotherms and the decay pressure technique, revealing that CO₂ adsorption capacity increased with higher amino group loading (4.62, 9.24, and 13.87 mmol of DAMO). At 298 K and 4 bar, CO₂ adsorption capacity increased proportionally with the amino group concentration, reaching values of 3.17, 5.98, and 7.86 mmol of CO₂ g⁻¹ polymer, respectively. Furthermore, over 20 adsorption/desorption cycles, the aerogels maintained 95% CO₂ desorption at ambient temperature, indicating their potential for industrial use. These findings highlight the aerogels suitability as stable, reusable materials for large scale CO₂ capture and storage technologies. Full article

Extracellular vesicles (EVs) are promising biomarkers for diagnosing complex diseases such as cancer and neurodegenerative disorders. Yet, their clinical application is hindered by challenges in isolating cancer-derived EVs efficiently due to their broad size distribution in biological samples. This study introduces a microfluidic device fabricated using off-stoichiometry thiol-ene and cyclic olefin copolymer, addressing the absorption limitations of polydimethylsiloxane (PDMS). The device streamlines a standard laboratory assay into a semi-automated microfluidic chip, integrating sample mixing and magnetic particle separation. Using the microfluidic device, the binding kinetics between EVs and anti-CD9 nanobodies were measured for the first time. Based on the binding kinetics, already after 10 min the EV capture was saturated and comparable to standard laboratory assays, offering a faster alternative to antibody-based immunomagnetic protocols. Furthermore, this study reveals the binding kinetics of EVs to anti-CD9 nanobodies for the first time. Our findings demonstrate the potential of the microfluidic device to enhance clinical diagnostics by offering speed and reducing manual labor without compromising accuracy. Full article