A molecularly imprinted polymer-based detection platform confirmed through molecular modeling for the highly sensitive and selective analysis of ipratropium bromide.

This study presented a new method to design a MIP-based electrochemical sensor that could improve the selective and sensitive detection of ipratropium bromide (IPR). The polymeric film was designed using 2-hydroxyethyl methacrylate (HEMA) as the basic monomer, 2-hydroxy-2-methylpropiophenone as the initiator, ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and N-methacryloyl-L-aspartic acid (MAAsp) as the functional monomer. The presence of MAAsp results in the functional groups in imprinting binding sites, while the presence of poly(vinyl alcohol) (PVA) allows the generation of porous materials not only for sensitive sensing but also for avoiding electron transport limitations. Electrochemical characterizations of the changes at each stage of the MIP preparation process were confirmed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). In addition, morphological characterizations of the developed sensor were performed using scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurements. Theoretical calculations were also performed to explain/confirm the experimental results better. It was found that the results of the calculations using the DFT approach agreed with the experimental data. The MAAsp-IPR@MIP/GCE sensor was developed using the photopolymerization method, and the sensor surface was obtained by exposure to UV lamp radiation at 365 nm. The improved MIP-based electrochemical sensor demonstrated the ability to measure IPR for standard solutions in the linear operating range of 1.0 × 10-12-1.0 × 10-11 M under optimized conditions. For standard solutions, the limit of detection (LOD) and limit of quantification (LOQ) were obtained as 2.78 × 10-13 and 9.27 × 10-13 M, respectively. The IPR recovery values for the inhalation form were calculated as 101.70 % and 100.34 %, and the mean relative standard deviations (RSD) were less than 0.76 % in both cases. In addition, the proposed modified sensor demonstrated remarkable sensitivity and selectivity for rapid assessment of IPR in inhalation forms. The sensor's unique selectivity is demonstrated by its successful performance even in the presence of IPR impurities.

Molecular imprinted based microcryogels for thrombin purification.

In addition to understanding and explaining the functions of proteins, the need for low-cost, easy and efficient purification methods has been increasing in the field of protein purification, which is also important for enzyme production. In this context, an alternative approach has been developed for the purification of thrombin, which has a crucial role in the hemostatic process, via thrombin imprinted microcryogels that allow reuse and have high selectivity. The characterization studies of the microcryogels were accomplished with micro-computed tomography (µCT), scanning electron microscopy (SEM), optical microscope, surface area measurements (BET analyses) and swelling test measurements. By scanning various parameters affecting thrombin adsorption, the maximum thrombin adsorption capacity (Qmax) was found to be 55.86 mg/g. Also, the selectivity of microcryogels was investigated with the competitive agents and reusability studies were performed. The purity of thrombin was evaluated by Fast Performance Liquid Chromatography (FPLC) method. Experimental results indicated that adsorption of thrombin by the developed microcryogels fit the Langmuir isotherm model (Qmax: 55.86 mg/g, R2: 0.9505) and pseudo-second order for three different thrombin concentrations (R2: 0.9978, R2: 0.9998, R2: 0.9999).

MIP-on-a-chip: Artificial receptors on microfluidic platforms for biomedical applications.

Lab-on-a-chip (LOC) as an alternative biosensing approach concerning cost efficiency, parallelization, ergonomics, diagnostic speed, and sensitivity integrates the techniques of various laboratory operations such as biochemical analysis, chemical synthesis, or DNA sequencing, etc. on miniaturized microfluidic single chips. Meanwhile, LOC tools based on molecularly imprinted biosensing approach permit their applications in various fields such as medical diagnostics, pharmaceuticals, etc., which are user-, and eco-friendly sensing platforms for not only alternative to the commercial competitor but also on-site detection like point-of-care measurements. In this review, we focused our attention on compiling recent pioneer studies that utilized those intriguing methodologies, the microfluidic Lab-on-a-chip and molecularly imprinting approach, and their biomedical applications.

Human serum albumin depletion based on dye ligand affinity chromatography via magnetic microcryogels.

One of the primary purposes of proteomic studies is to analyze the proteins in the blood to be considered as biomarkers. Albumin, which constitutes the majority of total serum proteins, complicates the discovery of low-density proteins that are important for the diagnosis of diseases. Based on this, an alternative approach for albumin depletion was developed in this study by covalently attached Cibacron Blue 3GA (CB) to magnetic microcryogels. After detailed characterization of CB attached magnetic microcryogels synthesized via a microstencil array chip, albumin adsorption studies were performed to examine the optimum depletion conditions. In the presented study, the maximum albumin adsorption capacity (Qmax) was calculated as 149.25 mg/mL in pH 5.0 acetate buffer solution, which is the optimum pH value for albumin. Experimental studies have demonstrated that CB-attached magnetic microcryogels can be reused without loss of performance for albumin depletion after 10 adsorption-desorption cycles.

Total Aplasia of Paranasal Sinus Associated With a Syndromic Condition.

Total aplasia of paranasal sinus (TAPS) is extremely rare, although the fact that partial aplasia is very common. TAPS seems to be limited to only 5 case reports in the literature until now. We present the case of a 29-year-old patient who has a syndromic face appearance but whose TAPS was detected incidentally. The maxillary, sphenoid, ethmoid, and frontal sinuses were totally aplastic. Furthermore, clinodactyly and high-arched palate were observed. The patient's appearance was consistent with a syndromic face because of some findings on inspection such as hypertelorism, shortening of the palpebral fissure, protruded and wide nasal base, high arched palate and zygomatic hypoplasia. The patient's profile was more suitable for Teacher-Collins syndrome than other syndromes, however, a certain diagnosis was not made genetically. To the best of our knowledge, this is the first reported association between TAPS and a syndromic condition.

Quartz Crystal Microbalance-Based Aptasensors for Medical Diagnosis.

Aptamers are important materials for the specific determination of different disease-related biomarkers. Several methods have been enhanced to transform selected target molecule-specific aptamer bindings into measurable signals. A number of specific aptamer-based biosensors have been designed for potential applications in clinical diagnostics. Various methods in combination with a wide variety of nano-scale materials have been employed to develop aptamer-based biosensors to further increase sensitivity and detection limit for related target molecules. In this critical review, we highlight the advantages of aptamers as biorecognition elements in biosensors for target biomolecules. In recent years, it has been demonstrated that electrode material plays an important role in obtaining quick, label-free, simple, stable, and sensitive detection in biological analysis using piezoelectric devices. For this reason, we review the recent progress in growth of aptamer-based QCM biosensors for medical diagnoses, including virus, bacteria, cell, protein, and disease biomarker detection.

Inspirations of Biomimetic Affinity Ligands: A Review.

Affinity chromatography is a well-known method dependent on molecular recognition and is used to purify biomolecules by mimicking the specific interactions between the biomolecules and their substrates. Enzyme substrates, cofactors, antigens, and inhibitors are generally utilized as bioligands in affinity chromatography. However, their cost, instability, and leakage problems are the main drawbacks of these bioligands. Biomimetic affinity ligands can recognize their target molecules with high selectivity. Their cost-effectiveness and chemical and biological stabilities make these antibody analogs favorable candidates for affinity chromatography applications. Biomimetics applies to nature and aims to develop nanodevices, processes, and nanomaterials. Today, biomimetics provides a design approach to the biomimetic affinity ligands with the aid of computational methods, rational design, and other approaches to meet the requirements of the bioligands and improve the downstream process. This review highlighted the recent trends in designing biomimetic affinity ligands and summarized their binding interactions with the target molecules with computational approaches.

The creation of selective imprinted cavities on quartz crystal microbalance electrode for the detection of melamine in milk sample.

Molecularly imprinted polymer based nanofilms specific to melamine were synthesized on quartz crystal microbalance (QCM) electrode surface. Contact angle measurements, atomic force microscopy, ellipsometry and scanning electron microscopy were used for characterizations process. Some of the findings of the study are as follows: pH 6.0 was found as optimal working pH for melamine detection. Prepared MIP QCM electrode showed a linearity of 99.53% in the concentration range of 50-1000 ng/mL. Langmuir-Freundlich hybrid model was the best fitted isotherm for whole concentration range. The performance of MIP QCM electrode was also confirmed by determining of melamine in melamine spiked milk samples. As a conclusion, the results figured out that not only QCM nanosensor for specific melamine detection but also polymerization strategy were classified as an intriguing alternative for developing new melamine sensing platforms. Limit of detection (LOD) and limit of quantification (LOQ) were calculated as 2.3 ng/mL and 7.8 ng/mL, respectively.

Bilateral Petrous Apex Cephalocele Associated with a Wide Sella.

ABSTRACT: Petrous apex cephalocele (PAC) is a rare type of cephalocele. It is usually asymptomatic. It can be unilateral or bilateral. Bilateral cases are less common. They are etiologically and clinically different entities from unilateral ones. A 56-year-old female patient presented to the hospital with the complaint of a severe nonspecific headache. She has been examined in ear nose throat, ophthalmology, and finally neurology clinics. Bilateral PAC was incidentally found in magnetic resonance imaging (MRi) examination. Headache was associated with PAC because no additional pathology could explain the clinical symptomatology. There is a proven relationship between empty sella and PAC. Regarding PAC less than 50 cases are known. Our paper aims to contribute to the literature by exhibiting etiologic and clinic differences between unilateral and bilateral PAC. It highlights the relationship between PAC and broad sella that is a different entity from empty sella and shows this remarkable radiological appearance. The authors presented our case accompanied by clinical and MRi findings.

A porous molecularly imprinted nanofilm for selective and sensitive sensing of an anticancer drug ruxolitinib.

A novel methodology has been applied to generate a porous molecularly imprinted material for highly selective and sensitive recognition of Janus kinase inhibitor ruxolitinib (RUX). The porous material-based nucleobase-derivative functional monomer was developed by a photopolymerization method. The thymine methacrylate (ThyM) as a functional monomer was synthesized and copolymerized with 2-hydroxyethyl methacrylate (HEMA) in the presence of ethylene glycol dimethacrylate (EGDMA) onto the glassy carbon electrode [glassy carbon electrode/molecularly imprinted polymer@poly(2-hydroxyethyl methacrylate-co-thymine methacrylate), (GCE/MIP@PHEMA-ThyM)] for the first time. The presence of ThyM results in the functional groups in imprinting binding sites, while the presence of poly(vinyl alcohol) (PVA) allows to generate porous materials for sensitive sensing. The characterization of GCE/MIP@PHEMA-ThyM was investigated by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and impedance spectroscopy technique. Then, the porous MIP modified glassy carbon electrode was optimized with effecting parameters including removal agent, removal time, and incubation time to get a better response for RUX. Under well-controlled optimum conditions, the GCE/MIP@PHEMA-ThyM linearly responded to the RUX concentration up to 0.01 pM at the limit of detection (LOD) of 0.00191 pM. The non-imprinted polymer (NIP) was also prepared to serve as a control in the same way but without the template. The proposed method improves the accessibility of binding sites by generating the porous material resulting in highly selective and sensitive recognition of drugs in the pharmaceutical dosage form and synthetic human serum samples.

Borate mineral loading into acrylic bone cements to gain cost-effectivity, enhanced antibacterial resistivity, and better cellular integration properties.

Polymethyl methacrylate (PMMA), called as bone cement, has been used in implant surgery, initially in dental practices, then in arthroplasty surgery for decades. Bone cement is a highly preferred chemical in the field of orthopedics due to its bone-like hardness and mechanical strength. Meanwhile, antibiotic-loaded cements are used in joints and similar surgeries are generally due to the risk of infection. In this study, we aimed to demonstrate the effects of borate mineral loading into bone cement on enhancing the antibacterial resistivity and cell integration as well as retaining mechanical properties. Moreover, the incorporation of minerals into bone cements makes them much more cost-friendly biomaterials for surgical operations. Herein, antibacterial properties were evaluated by using vancomycin- and gentamycin-susceptible strains of Enterococcus faecalis and Staphylococcus aureus whereas cell viability tests were performed by osteoblast cell lines. Three sets of the bone cements, plain, calcium borate-, and sodium borate-loaded, were prepared through commercial procedures and subjected to mechanical, antibacterial and cell viability tests. Percentage deformation determined by compression tests under 0.100 MPa pressure was determined in the range of 12.58%-10.67% in respect to the amount of sodium borate mineral loaded whereas that was determined in the range of 12.54%-9.87% in respect to the amount of calcium borate mineral loaded. Micro-CT results also supported good mineral integration and structural features of the composite bone cements. Furthermore, mineral incorporation enhanced the cell viability, in other words, cellular integrity, up to 101.28% for sodium borate-loaded (NB75, 7.5 g mineral) and 72.04% for calcium borate-loaded (CB75, 7.5 g mineral) bone cement according to the negative control group, fresh culture medium. As a conclusion, both of these minerals could be classified as promising alternatives for developing bone cements with better antibacterial resistivity and cellular integration properties.

Reliability of 2 Smartphone Applications for Cobb Angle Measurement in Scoliosis

Background@#As mobile technology has evolved, smartphone applications have been used for radiographic angle measurements in daily clinical practice. This study aimed to assess the reliability of 2 smartphone applications (iPinPoint and Cobbmeter) in measuring scoliosis Cobb angles compared with picture archiving and communication system (PACS) tools. @*Methods@#Anteroposterior whole spinal digital radiographs of 50 patients were retrospectively analyzed. Four observers measured Cobb angles of predetermined major structural curves using the tools in the PACS software and 2 smartphone applications. The inter- and intraobserver reliabilty were measured using intraclass correlation coefficients (ICC). @*Results@#Very good interobserver agreement was seen with PACS, iPinPoint, and Cobbmeter measurements (ICC, 0.991, 0.980, and 0.991, respectively). Intraobserver reliability of the 4 observers was also very good for all techniques (ICC > 0.9 for all observers). @*Conclusions@#Both smartphone applications were reliable in measuring scoliosis Cobb angles, with reference to PACS tools. They may be useful when digital or manual mesurement tools are not available.

Interface imprinted polymers with well-oriented recognition sites for selective purification of hemoglobin.

In this study, we introduced a new strategy to design interface imprinted polymers for a novel aspect of molecular imprinting technique, utilization of sacrificial metal oxide particles. In the first step, bovine hemoglobin (BHb) was adsorbed on zinc oxide (ZnO) particles, which were then used to synthesize polyacrylic acid-based molecular imprinting membrane by bulk polymerization in the presence of ethylene glycol dimethacrylate as a cross-linking agent. After polymerization terminated, BHb-ZnO particles were removed to leave effective imprint sites onto the bulk polymeric network which is responsible for the formation of template orientation. The characterization of membranes was investigated by using Fourier transform infrared (FTIR), Raman spectroscopy (RS), scanning electron microscopy (SEM), surface area measurements (BET analyses) and thermogravimetric analysis (TGA). The interface molecularly imprinted membranes (iMIMs) have a relatively high specific rebinding capacity of 65.98 mg/g and excellent selectivity towards BHb with a separation factor of 6.78. The equilibrium adsorption isotherms fitted well to Langmuir isotherms (R2 = 0.9944) and the value of adsorption capability (Qmax) and equilibrium constant (b) were estimated to be 73.53 mg/g and 1.36 mg/mL for the iMIM, respectively. The kinetics of adsorption fitted best to pseudo-second order (R2 = 0.9912). The ZnO particles were used not only to ensure the preservation of the imprint cavities in the polymer network but also to lead to high template removal and better rebinding kinetics. This novel design with multiple recognition sites is quite simple and suitable for the separation of biomacromolecules.

Skin Cancers of the Auricle: A Retrospective Analysis of 41 Patients.

OBJECTIVE: Skin cancers of the auricle usually present with challenges because of the unique anatomy and topography of the auricle and the behavior of the tumor. The purpose of this study was to evaluate the clinical and histopathological characteristics and the surgical outcomes in patients with skin cancer of the auricle. METHODS: Medical records of patients who underwent surgery for a skin cancer of the auricle at two different tertiary medical centers during 2010 to 2020 were reviewed retrospectively. Sociodemographic data of patients, tumor location and size, histopathological type and subtype, T-stage, recurrence, and reconstructive technique were evaluated. RESULTS: The study included 41 patients with skin cancers of the auricle. Thirty-six (87.8%) were male and five (12.2%) were female; with a male-to-female ratio of 7.2:1. The mean age of the patients was 71.4 (46-92) years. Eighteen (43.9%) tumors were basal cell carcinoma (BCC) and 17 (41.5%) tumors were cutaneous squamous cell carcinoma (cSCC). The most common subunit for tumor location was the helix (n=17, 41.5%). Wedge resection plus primary closure was the most common surgical technique (58.5%). Recurrent disease was detected in five patients (12.1%). CONCLUSION: The frequency of the skin cancers of the auricle was remarkably high in men, and the helix was the most common subunit. Both BCC and cSCC were the most common histopathological types. Poor prognostic factors such as lymph node metastasis, perineural invasion, and recurrence were relatively common in patients with cSCC of the auricle.

Molecularly imprinted polymer integrated plasmonic nanosensor for cocaine detection.

A molecularly imprinted polymeric nanofilm was prepared for cocaine detection and applied to plasmonic nanosensor for real-time kinetic, selectivity and reusability analyses. The sensing polymeric surface was fabricated by synthesizing a selective and specific nanofilm on the gold plasmonic nanosensor surface. After characterization experiments with atomic force microscopy, ellipsometer, and contact angle measurements, the kinetic studies of cocaine detection in aqueous solutions in a wide concentration range between 0.2-100 µg/mL were applied to plasmonic nanosensor system at 24 °C with a low limit of detection (0.1 µg/L) and quantification values (0.3 µg/L) and the results showed that this molecularly imprinted polymeric nanofilm integrated plasmonic nanosensor is providing a model for the fastest, most accurate and most precise identification of the cocaine molecule which constitutes a large part of the workload of forensic laboratories.

Surface plasmon resonance based biomimetic sensor for urinary tract infections.

Tailor-made Escherichia coli (E. coli) receptors were created with microcontact imprinted technique and binding events of E. coli were carried out by a surface plasmon resonance (SPR) sensor in aqueous solution and in urine mimic in real time and label-free. N-methacryloyl-(l)-histidine methyl ester (MAH) was selected as a functional monomer to design tailor-made E. coli receptors on the polymeric film and during the formation of the polymeric film on a chip surface, Ag nanoparticles (AgNPs) were entrapped into the polymer mixture in order to lower the detection limit of biomimetic SPR based sensor. The polymeric film was characterized with atomic force microscopy (AFM), scanning electron microscopy (SEM), ellipsometer and contact angle measurements. Limit of detection (LOD) was found 0.57 CFU/mL and feasibility of the biomimetic sensor was investigated in urine mimic.

A repertoire of biomedical applications of noble metal nanoparticles.

Noble metals comprise any of several metallic chemical elements that are outstandingly resistant to corrosion and oxidation, even at elevated temperatures. This group is not strictly defined, but the tentative list includes ruthenium, rhodium, palladium, silver, osmium, iridium, platinum and gold, in order of atomic number. The emerging properties of noble metal nanoparticles are attracting huge interest from the translational scientific community and have led to an unprecedented expansion of research and exploration of applications in biotechnology and biomedicine. Noble metal nanomaterials can be synthesised both by top-down and bottom up approaches, as well as via organism-assisted routes, and subsequently modified appropriately for the field of use. Nanoscale analogues of gold, silver, platinum, and palladium in particular, have gained primary importance owing to their excellent intrinsic properties and diversity of applications; they offer unique functional attributes, which are quite unlike the bulk material. Modulation of noble metal nanoparticles in terms of size, shape and surface functionalisation has endowed them with unusual capabilities and manipulation at the chemical level, which can lead to changes in their electrical, chemical, optical, spectral and other intrinsic properties. Such flexibility in multi-functionalisation delivers 'Ockham's razor' to applied biomedical science. In this feature article, we highlight recent advances in the adaptation of noble metal nanomaterials and their biomedical applications in therapeutics, diagnostics and sensing.

Quartz crystal microbalance based histidine sensor.

Herein, quartz crystal microbalance (QCM) biosensor is prepared for the detection of l-histidine by attachment of l-histidine imprinted poly(EGDMA-MAH/Cu(II)) nanoparticles on QCM electrode. The imprinted nanoparticles with the size of 86.43 nm were synthesized via miniemulsion polymerization reaction. Prepared QCM sensors were characterized with ellipsometer, contact angle measurements and FTIR. The thickness measurements demonstrated that the particle thin films were almost monolayer. l-histidine solutions with a concentration range between 6.44 µM and 225.6 µM were introduced to QCM system to determine the adsorption kinetics. Selectivity of the l-histidine imprinted nanoparticles were examined using d-histidine and l-tryptophan as competitor molecules. l-histidine imprinted QCM biosensors was also used for RNAase, lysozyme, cytochrome-C and BSA to investigate the competitive adsorption of surface histidine exposed proteins.

Turkish validity and reliability of Eustachian tube dysfunction questionnaire-7.

INTRODUCTION: During clinical evaluations, in order to interpret patients' complaints caused by Eustachian tube dysfunction and to monitor the success of the treatment, standardized and disease-related scales are necessary. OBJECTIVE: The aim of this study was to investigate the validity and reliability of the Turkish version of Eustachian tube dysfunction questionnaire-7. METHODS: Forty patients diagnosed with Eustachian tube dysfunction and 40 healthy individuals were enrolled for the study. After language validation of the Eustachian tube dysfunction questionnaire-7 for Turkish, a scale was completed by the both Eustachian tube dysfunction and control groups. Two weeks after the first evaluation, 15 of the cases filled out the scale again without any treatment intervention. Known-groups method was used in validity analysis. Floor-ceiling effect, test-retest method, item-total score correlation and internal consistency analysis were used in reliability analyses. RESULTS: Cronbach's alpha coefficient was 0.714 for the entire questionnaire. The test-retest reliability coefficient for the total scale was determined as 0.792, indicating correlation between the two questionnaires completed by the same patient over time. In the Eustachian tube dysfunction group, total and each item scores were found significantly higher than the control group (p<0.001). CONCLUSION: The Turkish version of Eustachian tube dysfunction questionnaire-7 was found to be highly valid and reliable. This scale is recommended to use for screening of Eustachian tube dysfunction and evaluating treatment outcome.

Hemodynamic Changes in Paramedian Forehead Flap.

Paramedian forehead flap is a workhorse for nasal reconstruction. However, vascular complications may lead to flap failure. The purpose of this study was to evaluate the blood flow objectively and determine the hemodynamic changes in paramedian forehead flap with respect to influential factors of age, gender, and smoking. Thirty patients who had paramedian forehead flap were followed up prospectively between 2010 and 2013. The blood flow was assessed by resistance index using Color Duplex-Doppler Ultrasonography. Resistance index was measured at the proximal and distal ends of each flap on the postoperative first day, first week, and second week. All data were analyzed using SPSS 15.0 for Windows. Fifteen patients were female and the mean of age was 60.9 years. Our results demonstrated statistically significant differences with gradual decreases in resistance to blood flow, when the resistance index values at the proximal and distal ends of paramedian forehead flap were compared (P < 0.001 and P < 0.001). Age, gender, and smoking did not have a negative impact on the resistance index values of paramedian forehead flap. To the best of our knowledge, this is the first study in which resistance in blood flow and hemodynamic changes of paramedian forehead flap were objectively determined using Color Duplex-Doppler Ultrasonography. The resistance index gradually decreases, although it is considerably high at the early postoperative interval. Age, gender, and smoking do not adversely influence the blood flow in a well-designed paramedian forehead flap.